U.S. patent application number 17/033427 was filed with the patent office on 2021-01-21 for methods and systems for analyte information processing.
The applicant listed for this patent is Biological Dynamics, Inc.. Invention is credited to Iryna CLARK, Juan Pablo HINESTROSA SALAZAR, Robert KOVELMAN, Rajaram KRISHNAN, David LIU, Robert TURNER.
Application Number | 20210020275 17/033427 |
Document ID | / |
Family ID | 1000005131773 |
Filed Date | 2021-01-21 |
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United States Patent
Application |
20210020275 |
Kind Code |
A1 |
KRISHNAN; Rajaram ; et
al. |
January 21, 2021 |
METHODS AND SYSTEMS FOR ANALYTE INFORMATION PROCESSING
Abstract
Systems, devices, media, methods, and kits are disclosed to
integrate and exchange information of analyte analysis kits.
Analyte analysis can be performed and presented using in
association with advertising or questions.
Inventors: |
KRISHNAN; Rajaram; (San
Diego, CA) ; CLARK; Iryna; (Del Mar, CA) ;
TURNER; Robert; (San Diego, CA) ; KOVELMAN;
Robert; (La Jolla, CA) ; HINESTROSA SALAZAR; Juan
Pablo; (San Diego, CA) ; LIU; David; (San
Diego, CA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Biological Dynamics, Inc. |
San Diego |
CA |
US |
|
|
Family ID: |
1000005131773 |
Appl. No.: |
17/033427 |
Filed: |
September 25, 2020 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
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15974591 |
May 8, 2018 |
10818379 |
|
|
17033427 |
|
|
|
|
62503174 |
May 8, 2017 |
|
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
G01N 27/44791 20130101;
B01L 2300/023 20130101; G16H 30/20 20180101; B01L 3/5027 20130101;
B01L 3/502715 20130101; B01L 2400/0424 20130101; G01N 33/53
20130101; G16H 10/40 20180101; G16H 10/20 20180101 |
International
Class: |
G16H 10/40 20060101
G16H010/40; G16H 10/20 20060101 G16H010/20; G01N 27/447 20060101
G01N027/447; B01L 3/00 20060101 B01L003/00; G01N 33/53 20060101
G01N033/53; G16H 30/20 20060101 G16H030/20 |
Claims
1. A computer-implemented system comprising: a) a digital
processing device comprising: at least one processor, a memory, a
display, and an operating system configured to perform executable
instructions; b) an analyte analysis apparatus reversibly accepting
and positioning the digital processing device and an analyte
analysis cartridge configured to receive a biological material of
an individual; and c) a computer program stored in the memory of
the digital processing device, the computer program including
instructions executable by the digital processing device to create
an application comprising: i) a software module controlling the
cartridge to perform an analyte analysis of the biological material
to generate a result; ii) a software module presenting the result
on the display of the digital processing device; and iii) a
software module selecting one or more ads from a population of ads
or one or more questions from a population of questions to present
in association with the result.
2. The system of claim 1, wherein the analyte analysis apparatus
positions the digital processing device and an analyte analysis
cartridge relative to each other to perform the analyte
analysis.
3. The system of claim 2, wherein the digital processing device
further comprises a camera and wherein the analyte analysis
apparatus positions the analyte analysis cartridge such that the
camera of the digital processing device can capture an image of a
result field of the cartridge.
4. The system of claim 3, wherein the cartridge is a
dielectrophoresis (DEP) cartridge.
5. The system of claim 1, wherein the one or more ads or the one or
more questions are selected based on a user profile of the
individual, the analyte, the result, a location of the digital
processing device, or a combination thereof.
6. The system of claim 1, wherein a response by the individual to
the one or more ads or the one or more questions is added to a user
profile of the individual.
7. The system of claim 1, wherein the software module selecting the
one or more ads or the one or more questions receives instructions
from a remote server to select the one or more ads or the one or
more questions, wherein the selection is based on analysis
performed by the remote server.
8. The system of claim 1, wherein the one or more ads or the one or
more questions are provided by a third-party ad network.
9. The system of claim 1, wherein the application further comprises
a software module providing an interface allowing upload of the
result to an online database.
10. The system of claim 1, wherein the application further
comprises a software module providing a query interface allowing
search of the online database.
11. The system of claim 1, wherein the application further
comprises a software module providing at least one of a treatment
recommendation and a healthcare provider recommendation generated
by a machine learning algorithm based on a user profile of the
individual, the analyte, the result, a location of the digital
processing device, historical treatment outcome data for a cohort
of patients matched to the individual, healthcare provider
information, or a combination thereof.
12. The system of claim 1, wherein the result is geo-tagged with a
location of the digital processing device and uploaded to a
database.
13. A computer-implemented method comprising: a) transmitting, by a
digital processing device, a control signal to a cartridge of an
analyte analysis apparatus to perform an analyte analysis of a
biological material of an individual to generate a result; b)
presenting, by the digital processing device, the result on a
display; and c) selecting, by the digital processing device, one or
more ads from a population of ads or one or more questions from a
population of questions to present in association with the
result.
14. The method of claim 13, wherein the cartridge is configured to
receive the biological material of the individual.
15. The method of claim 13, wherein the analyte analysis apparatus
reversibly accepts and positions the digital processing device and
the cartridge.
16. The method of claim 15, wherein the digital processing device
comprises a camera and wherein the analyte analysis apparatus
positions the analyte analysis cartridge such that the camera of
the digital processing device can capture an image of a result
field of the cartridge.
17. The method of claim 13, wherein the digital processing device
or the analyte analysis apparatus provides power to the
cartridge.
18. The method of claim 17, wherein the cartridge is a
dielectrophoresis (DEP) cartridge.
19. The method of claim 13, wherein the one or more ads or the one
or more questions are selected based on a user profile of the
individual, the analyte, the result, a location of the digital
processing device, or a combination thereof.
20. The method of claim 13, wherein the digital processing device
receives instructions from a remote server to select the one or
more ads or the one or more questions, wherein the selection is
based on analysis performed by the remote server.
21. The method of claim 13, further comprising providing at least
one of a treatment recommendation and a healthcare provider
recommendation generated by a machine learning algorithm based on a
user profile of the individual, the analyte, the result, a location
of the digital processing device, historical treatment outcome data
for a cohort of patients matched to the individual, healthcare
provider information, or a combination thereof.
22. The method of claim 13, wherein the result is geo-tagged with a
location of the digital processing device and uploaded to a
database.
23. Non-transitory computer readable storage media encoded with a
program including instructions executable by at least one processor
of a digital processing device to create an application comprising:
a) a software module transmitting a control signal to a cartridge
of an analyte analysis apparatus to perform an analyte analysis of
a biological material of an individual to generate a result; b) a
software module presenting the result on a display; and c) a
software module selecting one or more ads from a population of ads
or one or more questions from a population of questions to present
in association with the result.
24. The media of claim 23, wherein the one or more ads or the one
or more questions are selected based on a user profile of the
individual, the analyte, the result, a location of the digital
processing device, or a combination thereof.
25. The media of claim 23, further comprising a software module
providing at least one of a treatment recommendation and a
healthcare provider recommendation generated by a machine learning
algorithm based on a user profile of the individual, the analyte,
the result, a location of the digital processing device, historical
treatment outcome data for a cohort of patients matched to the
individual, healthcare provider information, or a combination
thereof.
26. The media of claim 23, wherein the result is geo-tagged with a
location of the digital processing device.
27. The media of claim 23, wherein the cartridge is configured to
receive the biological material of the individual.
28. The media of claim 23, wherein the analyte analysis apparatus
reversibly accepts and positions the digital processing device and
the cartridge.
29. The media of claim 28, wherein the digital processing device
comprises a camera and wherein the analyte analysis apparatus
positions the analyte analysis cartridge such that the camera of
the digital processing device can capture an image of a result
field of the cartridge.
30. A computer-implemented method comprising: a) transmitting, by a
digital processing device, a control signal to a cartridge of an
analyte analysis apparatus to perform an analyte analysis of a
biological material of an individual to generate a result; b)
presenting, by the digital processing device, the result on a
display; c) selecting, by the digital processing device, at least
one first ad from a population of ads or at least one first
question from a population of questions to present in association
with the result; d) providing, by the digital processing device, an
interface allowing upload of the result to an online database; e)
providing, by the digital processing device, a query interface
allowing search of the online database; and f) selecting, by the
digital processing device, at least one second ad from the
population of ads or at least one second question from the
population of questions to present in association with one or more
results in response to a search performed in the query interface.
Description
CROSS-REFERENCE
[0001] This application is a continuation of U.S. application Ser.
No. 15/974,591, filed May 8, 2018, which claims the benefit of U.S.
Provisional Application Ser. No. 62/503,174, filed May 8, 2017,
each of which is incorporated herein by reference in its
entirety.
BACKGROUND OF THE INVENTION
[0002] Identification and quantification of analytes is important
in diagnosing and treating many conditions that impair human
health. Further data analysis on the usage of analytes aids
clinical management.
SUMMARY OF THE INVENTION
[0003] The present technologies fulfill a need for improved methods
of analyzing biological samples. Particular attributes of certain
aspects provided herein include methods of analyzing usage of
analyte kits and assisting clinical management.
[0004] The technologies disclosed herein provide an innovative
solution to various challenges facing traditional medical testing.
Traditional medical testing is a time-consuming process typically
requiring a subject to visit a clinic or hospital to provide a
biological sample. The sample is delivered to a test facility,
oftentimes at a different location, where the actual sample
analysis is performed. The subject then must wait for the test
results, which may take days or even weeks. Even in emergency
situations when rush testing is requested, a subject may be forced
to wait for hours in the emergency room due to various factors
beyond his or her control such as the availability of testing
resources and personnel at the particular medical location.
Alternatively, a subject may collect the sample at home and mail
the sample to a test facility. Aside from simple tests that do not
require data analysis or specialized equipment and can be performed
at home (e.g. home pregnancy test), these routine and conventional
medical testing approaches are time-consuming and unpredictable in
terms of when the results will be provided.
[0005] Accordingly, the systems, devices, media, and methods
disclosed herein overcome the limitations of the conventional
approach by providing a new paradigm for carrying out analyte
testing, analysis, and result sharing.
[0006] One advantage provided by the present disclosure is the
ability to carry out portable testing that is not limited to the
clinic setting unlike conventional testing methods. For example, an
analyte analysis apparatus and cartridge can be sized for
portability. In addition, the apparatus can be configured for use
with another electronic device such as, for example, a mobile
phone. The electronic device can then supply the apparatus with
power and optionally a camera for use in performing the analyte
testing. In addition, the processing power of the electronic device
can be leveraged to carry out the analysis of the analyte testing.
Alternatively, the apparatus or the electronic device may have a
network component enabling access to a network such as the
Internet, which allows the testing results to be uploaded to the
network (e.g. a cloud computing network via the Internet) for
analysis. Finally, the electronic device typically has a display
screen that can be used to show the results of the test along with
any advertisements or questions. By off-loading power, test
equipment (e.g. the camera), and data analysis onto electronic
devices or a network, the design of the analyte analysis apparatus
may be stream-lined or simplified for greater portability.
Alternatively, or in combination, the apparatus may utilize
batteries as a primary or secondary power source such as in case of
the electronic device being low in battery power. The portability
of this testing system is further enhanced through the use of a
disposable cartridge, thus avoiding potential challenges in
cleaning the apparatus outside of the clinic setting.
[0007] Another advantage provided by the present disclosure is the
ability to obtain results in real-time, often within minutes of
initiating analyte analysis. Whereas conventional medical testing
requires a series of steps carried out by multiple personnel with
the actual testing typically performed off-site at a test facility
or lab, the analyte analysis in the present disclosure can be
performed in real-time on location (e.g. at home or the
point-of-care). The analyte analysis apparatus can be used by a
subject to carry out the testing. The testing data may be
automatically uploaded to an electronic device and/or a cloud
platform for data analysis. Finally, the results of the analysis
may be provided to the subject or a user via the electronic
device.
[0008] Another advantage provided by the present disclosure is the
ability for a single individual to carry out the testing.
Conventional medical testing requires multiple personnel in
addition to the subject such as the nurse obtaining a biological
sample, a technician running the analyte testing, and a doctor
explaining the results. This can lead to mislabeling or delays due
to the number of personnel involved. In contrast, a subject can use
the technologies disclosed herein to conduct solo testing using his
or her own sample and be able to access the results without
requiring a middleman. Alternatively, in some cases, a healthcare
provider may run the test with the subject's sample and access the
results immediately such as through a web portal or a software
application on an electronic device without requiring a
technician.
[0009] Another advantage provided by the present disclosure is the
integration of subject test data with a network such that the
subject, healthcare providers, and optionally third parties are
able to access the information in a HIPAA compliant manner upon
proper authorization. Thus, regardless of whether the test is
conducted at home by the subject or by a healthcare provider at a
clinic, the test data/results may be provisioned on a network
platform that enables access by both the subject and the healthcare
provider. For example, a subject may personally conduct testing at
home, and then provide authorization to his family doctor to view
the results via a secured online web portal. This presents a
significant advantage over conventional systems in which the
healthcare provider maintains records of its testing on a
proprietary server or database which are available upon patient
request. In such conventional systems, there is inadequate means
for a subject to share test results with his healthcare provider,
and typically requires the subject to physically bring the results
to a doctor's visit. Moreover, the combination of mobile or
portable on-site testing with network data integration and sharing
with authorized healthcare providers or third parties provides an
innovative solution to disease management. For example, such
testing systems can be distributed to an at-risk population to test
for a particular disease, and as real-time data is uploaded onto
the network, disease investigators can track the spread of the
disease and plan accordingly. This implementation contrasts with
the conventional approach that requires healthcare workers to be
on-location to test and monitor the disease, which can skew the
results (e.g. primarily obtaining data from population centers
where testing is conducted) and put these healthcare workers at
risk of infection.
[0010] Another advantage provided by the present disclosure is the
provisioning of advertisements and/or survey questions/information
prompts in combination with point-of-care or at-home testing. While
the analyte analysis apparatus carries out the testing, the
capabilities of the electronic device are leveraged to provide a
subject with entertainment or useful information in the form of ads
and/or questions. Typically, users can view ads on their personal
devices such as smartphones. The conventional approach to
advertising involves displaying ads on the phone based on user
activity on the phone such as a website visited or a selected
video. In contrast, the ads and questions disclosed herein may be
presented by the electronic device in conjunction with analyte
testing by the analyte analysis apparatus, which is a new and
unconventional approach. In some cases, the ads or questions are
designed to be shown during the analyte testing and/or analysis for
efficient time use. For example, the ads or survey questions may be
configured to take no more time than the time required for analyte
testing and/or analysis (e.g. a movie trailer is limited to the 2
minute time period required to perform a particular analyte
testing). Moreover, the ads or survey questions can be directed to
alternative devices aside from the electronic device helping to
perform the analyte testing such as, for example, a laptop
computer, a tablet, or a TV in communication with the electronic
device. In some cases, the ads or survey questions are targeted
based on prior analyte testing results (e.g. ads for treatment
options available for the condition or disorder indicated by the
test results).
[0011] In one aspect, disclosed herein are systems comprising: a
digital processing device comprising: at least one processor, a
memory, a display, and an operating system configured to perform
executable instructions; an analyte analysis apparatus reversibly
accepting and positioning the digital processing device and an
analyte analysis cartridge configured to receive a biological
material of an individual; a computer program stored in the memory
of the digital processing device, the computer program including
instructions executable by the digital processing device to create
an application comprising: a software module controlling the
cartridge to perform an analyte analysis of the biological material
to generate a result; a software module presenting the result on
the display of the digital processing device; and a software module
selecting one or more ads from a population of ads or one or more
questions from a population of questions to present in association
with the result. In some embodiments, the analyte analysis
apparatus positions the digital processing device and an analyte
analysis cartridge relative to each other to perform the analyte
analysis. In some embodiments, the digital processing device
further comprises a camera and wherein the analyte analysis
apparatus positions the analyte analysis cartridge such that the
camera of the digital processing device can capture an image of a
result field of the cartridge. In some embodiments, the image is
analyzed by a machine learning algorithm to generate the result. In
some embodiments, the digital processing device or the analyte
analysis apparatus provides power to the cartridge. In some
embodiments, the cartridge is a dielectrophoresis (DEP) cartridge.
In some embodiments, the biological material is a biological fluid.
In some embodiments, the biological fluid is whole blood, plasma,
serum, saliva, cerebrospinal fluid, lymph fluid, urine, sweat,
tears, amniotic fluid, aqueous humor, vitreous humor, pleural
fluid, mucus, synovial fluid, exudate, interstitial fluid,
peritoneal fluid, pericardial fluid, sebum, semen, or bile. In some
embodiments, the one or more ads are selected based on a user
profile of the individual, the analyte, the result, a location of
the digital processing device, or a combination thereof. In some
embodiments, the user profile comprises medical information. In
some embodiments, the user profile comprises information pertaining
to adherence to treatment regimen. In some embodiments, the one or
more ads are targeted to the individual based on the individual
undergoing a current treatment. In some embodiments, the software
module selecting one or more ads receives instructions from a
remote server to select the one or more ads, wherein the selection
is based on analysis performed by the remote server. In some
embodiments, a response by the individual to the one or more ads is
added to a user profile of the individual. In some embodiments, the
one or more ads are provided by a third-party ad network. In some
embodiments, the application further comprises a software module
providing an interface allowing upload of the result to an online
database. In some embodiments, the application further comprises a
software module providing a query interface allowing search of the
online database. In some embodiments, the online database is
searchable by a biotechnology or pharmaceutical company. In some
embodiments, the online database is accessible to authorized third
parties. In some embodiments, a user profile for the individual is
stored on the online database. In some embodiments, the online
database is encrypted. In some embodiments, third party
applications are prevented from accessing private information
stored in the online database. In some embodiments, the application
further comprises a software module selecting one or more questions
from a population of questions to present in association with the
result. In some embodiments, the application further comprises a
software module providing at least one of a treatment
recommendation and a healthcare provider recommendation generated
by a machine learning algorithm based on a user profile of the
individual, the analyte, the result, a location of the digital
processing device, historical treatment outcome data for a cohort
of patients matched to the individual, healthcare provider
information, or a combination thereof. In some embodiments, the
software module selecting one or more questions receives
instructions from the remote server to select the one or more
questions, wherein the selection is based on analysis performed by
the remote server. In some embodiments, the application provides
the individual with a choice between the one or more ads and the
one or more questions. In some embodiments, a response by the
individual to the one or more questions is added to a user profile
of the individual. In some embodiments, the result is geo-tagged
with a location of the digital processing device and uploaded to a
database. In some embodiments, analyte analysis comprises analyte
capture, image acquisition, and data analysis. In some embodiments,
data analysis is performed remotely through cloud computing. In
some embodiments, the digital processing device sends a
communication over a network to another device of the user. In some
embodiments, the communication comprises one or more ads displayed
on another device. In some embodiments, the another device is a
cell phone, a smart phone, a tablet, a laptop, a television, an
electronic reader (E-reader), a projector, or a monitor. In some
embodiments, the communication comprises an alert that user
interaction is needed. In some embodiments, the user interaction is
selecting one or more ads for display by the digital processing
device, selecting one or more questions for display by the digital
processing device, viewing one or more ads, viewing one or more
questions, or viewing the result. In some embodiments, the
communication comprises one or more questions for display on
another device. In some embodiments, the system further comprises a
software module for obtaining usage statistics for the digital
processing device. In some embodiments, the usage statistics are
shared with a third party.
[0012] Additionally provided herein are computer-implemented
systems comprising: a digital processing device comprising: at
least one processor, a memory, and an operating system configured
to perform executable instructions; an analyte analysis apparatus
reversibly accepting and positioning the digital processing device
and an analyte analysis cartridge configured to receive a
biological material of an individual; a computer program stored in
the memory of the digital processing device, the computer program
including instructions executable by the digital processing device
to create an application comprising: a software module controlling
the cartridge to perform an analyte analysis of the biological
material to generate a result; a software module transmitting the
result to an online database, the online database searchable via a
query interface; and a software module selecting one or more ads
from a population of ads or one or more questions from a population
of questions to present in association with one or more results in
response to a search performed in the query interface by a data
consumer.
[0013] Further provided herein are computer-implemented systems
comprising: a digital processing device comprising: at least one
processor, a memory, a display, and an operating system configured
to perform executable instructions; an analyte analysis apparatus
reversibly accepting and positioning the digital processing device
and an analyte analysis cartridge configured to receive a
biological material of an individual; a computer program stored in
the memory of the digital processing device, the computer program
including instructions executable by the digital processing device
to create an application comprising: a software module controlling
the cartridge to perform an analyte analysis of the biological
material to generate a result; a software module presenting the
result on the display of the digital processing device; a software
module selecting at least one first ad from a population of ads to
present in association with the result; a software module
transmitting the result to an online database, the online database
searchable via a query interface; and a software module selecting
at least one second ad from the population of ads to present in
association with one or more results in response to a search
performed in the query interface by a data consumer.
[0014] Also provided herein are computer-implemented methods. Such
methods comprising transmitting, by a digital processing device, a
control signal to a cartridge of an analyte analysis apparatus to
perform an analyte analysis of a biological material of an
individual to generate a result; presenting, by the digital
processing device, the result on a display of a digital processing
device; and selecting, by the digital processing device, one or
more ads from a population of ads or one or more questions from a
population of questions to present in association with the
result.
[0015] Also provided herein are non-transitory computer readable
storage media encoded with a program including instructions
executable by at least one processor of a digital processing device
to create an application comprising: a software module transmitting
a control signal to a cartridge of an analyte analysis apparatus to
perform an analyte analysis of a biological material of an
individual to generate a result; a software module presenting the
result on a display; and a software module selecting one or more
ads from a population of ads or one or more questions from a
population of questions to present in association with the
result.
[0016] Additionally provided herein are computer-implemented method
comprising: transmitting, by a digital processing device, a control
signal to a cartridge of an analyte analysis apparatus to perform
an analyte analysis of a biological material of an individual to
generate a result; providing, by the digital processing device, an
interface allowing upload of the result to an online database;
providing, by the digital processing device, a query interface
allowing search of the online database; and selecting, by the
digital processing device, one or more ads from a population of ads
or one or more questions from a population of questions to present
in association with one or more results in response to a search
performed in the query interface.
[0017] Also provided herein are non-transitory computer readable
storage media encoded with a program including instructions
executable by at least one processor of a digital processing device
to create an application comprising: a software module transmitting
a control signal to a cartridge of an analyte analysis apparatus to
perform an analyte analysis of a biological material of an
individual to generate a result; a software module providing an
interface allowing upload of the result to an online database; and
a software module selecting one or more ads from a population of
ads or one or more questions from a population of questions to
present in association with the result.
[0018] Further provided herein are computer-implemented methods
comprising: transmitting, by a digital processing device, a control
signal to a cartridge of an analyte analysis apparatus to perform
an analyte analysis of a biological material of an individual to
generate a result; presenting, by the digital processing device,
the result on a display; selecting, by the digital processing
device, at least one first ad from a population of ads to present
in association with the result; providing, by the digital
processing device, an interface allowing upload of the result to an
online database; providing, by the digital processing device, a
query interface allowing search of the online database; and
selecting, by the digital processing device, at least one second ad
from the population of ads to present in association with one or
more results in response to a search performed in the query
interface.
[0019] Also provided herein are non-transitory computer readable
storage media encoded with a program including instructions
executable by at least one processor of a digital processing device
to create an application comprising: a software module transmitting
a control signal to a cartridge of an analyte analysis apparatus to
perform an analyte analysis of a biological material of an
individual to generate a result; a software module presenting the
result on a display; a software module selecting at least one first
ad from a population of ads to present in association with the
result; a software module providing an interface allowing upload of
the result to an online database; a software module providing a
query interface allowing search of the online database; and a
software module selecting at least one second ad from the
population of ads to present in association with one or more
results in response to a search performed in the query
interface.
INCORPORATION BY REFERENCE
[0020] All publications, patents, and patent applications mentioned
in this specification are herein incorporated by reference to the
same extent as if each individual publication, patent, or patent
application was specifically and individually indicated to be
incorporated by reference.
BRIEF DESCRIPTION OF THE DRAWINGS
[0021] The novel features of the invention are set forth with
particularity in the appended claims. A better understanding of the
features and advantages of the present invention will be obtained
by reference to the following detailed description that sets forth
illustrative embodiments, in which the principles of the invention
are utilized, and the accompanying drawings of which:
[0022] FIG. 1 illustrates an example data analysis flow chart.
[0023] FIG. 2 illustrates an alternative example analysis flow
chart.
[0024] FIG. 3 illustrates an example ad and/or question selection
flow chart.
[0025] FIG. 4 illustrates an example ad selection flow chart.
[0026] FIG. 5 schematically illustrates a computer control system
that is programmed or configured to implement methods provided
herein.
[0027] FIG. 6A illustrates an exemplary display of an electronic
device showing options for viewing a test result.
[0028] FIG. 6B illustrates an exemplary display of an electronic
device showing a survey question presented in association with a
test result.
[0029] FIG. 6C illustrates an exemplary display of an electronic
device allowing a user to view the results of a completed test.
[0030] FIG. 6D illustrates an exemplary display of an electronic
device showing the results of a completed test and an accompanying
recommendation.
[0031] FIG. 6E illustrates another exemplary display of an
electronic device showing the results of a completed test and an
accompanying recommendation.
[0032] FIG. 6F illustrates an exemplary display of an electronic
device showing a user portal.
DETAILED DESCRIPTION OF THE INVENTION
[0033] The technologies disclosed herein relate to a need for
improved computer-implemented methods of analyzing and managing
usage of analyte tests. Particular attributes of certain aspects
provided herein include methods of analyzing and sharing results of
analyte tests and assisting clinical management.
Data Analysis Overview
[0034] In various embodiments, the computing systems, media,
method, or kit disclosed herein includes data analysis, realized
based on software application or computing hardware or both. An
analysis application or system comprises at least a data processing
module. FIG. 1 illustrates an overview of a data processing flow.
In step 101, a system or a method comprises collecting user
information to develop a user profile. In some embodiments, user
information comprises one or more of a user name, a user ethnic
background, a user age, a user height and weight, and medical
information, such as a diagnosis and one or more symptoms. In some
embodiments, user information comprises health information or
health data. If applicable, standard HIPAA (Health Insurance
Portability and Accountability Act of 1996) will govern how this
information is stored and disseminated. For example, in some
embodiments, health data comprises a "limited data set" of
identifiable patient information as defined by HIPAA (e.g., for
purposes of protecting patient confidentiality and/or privacy). In
some embodiments, the health data is anonymized to remove all
identifying information. In some embodiments, patient information
is stored on a database. In some embodiments, the database is
encrypted. In some embodiments, the database prevents access to
patient information by applications unrelated to the systems and
methods disclosed herein (e.g. mobile applications installed on a
phone).
[0035] Referring again to FIG. 1, in some embodiments, operation
102 tests a user sample for the presence of an analyte. In some
embodiments, the user sample is tested using an analyte kit. In
some embodiments, the analyte kit comprises an analyte analysis
apparatus and a cartridge (e.g. a dielectrophoresis and fluidics
cartridge). In some embodiments, the analyte kit is configured to
interface with a digital processing device utilizing the analyte
analysis apparatus and cartridge to carry out imaging of an analyte
or sample, analysis of the image or data, provide a power supply to
the analyte analysis apparatus, or any combination thereof. In some
embodiments, the analyte kit comprises the digital processing
device. In some embodiments, the analyte kit isolates an analyte
using an assay, such as an immunoassay or a nucleic acid or protein
assay. The assay comprises a method of isolating and measuring an
analyte. In some cases, the assay is conducted using
dielectrophoresis, which allows the analyte to be detected by a
probe visualized creating an electrical signal to be detected by
one or more sensors. The analyte kit summarizes patterns of the one
or more electrical signals. The analyte kit transmits the patterns,
or the one or more electrical signals, or both, to the data
processing module. In operation 103 the system or the method
estimates a health condition of the user based on the user profile
101 and the test results 102. In operation 111, the system or the
method assists a physician to manage the subject's health. In
operation 112, the system or the method displays the user health
condition with one or more ads selected based on the user
information and/or the test results. In some embodiments, the
systems, devices, and methods described herein further provide one
or more recommendations based on the user information and/or test
results. In some embodiments, the recommendations comprise an
identified local healthcare provider or service near the user
(current location and/or user's home/work address) based on test
results indicating the user is suffering from a health condition,
disease, or disorder. As an illustrative example, a diabetic user
performs self-testing using the analyte analysis apparatus and
cartridge in combination with his smartphone, and the test results
indicate he is suffering from a healthcare condition such as low
blood sugar. Accordingly, based on his user profile indicating his
diabetic condition and the test result indicating low blood sugar,
his smartphone displays the test results, information on treating
the condition (e.g. eat some carbohydrates), and identifies a
nearby emergency room the user can visit or call for help along
with a button for immediately placing a call to the emergency
room.
[0036] FIG. 2 illustrates an alternate overview of a data
processing flow. In step 201, a system or a method comprises
collecting user information to develop a user profile. In some
embodiments, user information comprises one or more of a user name,
a user ethnic background, a user age, a user height and weight, and
medical information, such as a diagnosis and one or more symptoms.
In some embodiments, operation 202 tests a user sample for the
presence of an analyte. In some embodiments, the user sample is
tested using an analyte kit. The analyte kit isolates an analyte
using an assay, such as an immunoassay or a nucleic acid or protein
assay. The assay comprises a method of isolating and measuring an
analyte. In some cases, the assay is dielectrophoresis, which
allows the analyte to be detected by a probe visualized creating an
electrical signal to be detected by one or more sensors. The
analyte kit summarizes patterns of the one or more electrical
signals. The analyte kit transmits the patterns, or the one or more
electrical signals, or both, to the data processing module. In
operation 203 the system or the method estimates a health condition
of the user based on the user profile 201 and the test results 202.
In operation 211, the system or the method assists a physician to
manage the subject's health. In operation 212, the system or the
method transmits the user profile and the test results to a
database. In operation 213, the system or the method displays the
user health condition with one or more ads selected based on the
user information and/or the test results.
[0037] In certain aspects, described herein are systems and methods
coordinating the use of a diagnostic device (e.g. an analyte
analysis apparatus) with targeted advertisements and/or a database
of users and their results. In some embodiments, the diagnostic
device is a consumer-facing device that is usable outside of a
clinic setting such as at home. In some embodiments,
consumer-operated devices are configured to be compact and/or
portable and adapted to be used in combination with a digital
processing device such as a mobile phone. For example, a diagnostic
device adapted for consumer use can allow for the use of a
smartphone comprising a camera for capturing an image of the
analyte, a processor for performing data analysis, a hard drive for
data storage or communication interface for uploading data for
storage via a network, and a display for showing the results of the
analysis and optionally ads and/or questions. By offloading these
various functions onto the smartphone, the analyte analysis
apparatus or diagnostic device can be manufactured using fewer
resources so as to be more affordable to consumers. This design
also enables the apparatus to be streamlined for greater
portability and durability (e.g. more rugged design with thicker
outer shell and/or having fewer parts that can break). In addition,
the reduction in complexity helps accelerate safety testing for new
iterations of the analyte analysis apparatus and overall testing
system since they would have already been tested for use with the
electronic device such as the smartphone. By limiting the apparatus
to the essential test equipment, the apparatus may be environment
agnostic. For example, the apparatus can simply plug into a phone
that is already configured for the local environment (e.g. adapted
for 110 AC or 220 AC), and thus can have universal compatibility
with local electric grids and networks since those functions are
offloaded onto the electronic device. Moreover, performing the
analysis and displaying the results off of the apparatus helps
address any potential language barriers since the electronic device
would present such information in the local language or dialect
(e.g. using translation services such as Google translate).
[0038] Another advantage of this innovative setup is that an
existing iteration of the analyte analysis apparatus (e.g. an early
generation model) can achieve improved performance over time as the
electronic device (e.g. smartphones) is updated such as with better
cameras providing superior resolution and/or clarity. Thus, an
analyte analysis apparatus or diagnostic device can extend its
lifespan by piggybacking on improvements to the electronic device
of the user. Furthermore, this testing system can also offload
functions onto a remote server or cloud-based computing system or
network. For example, the battery life of the apparatus and/or
electronic device can be extended by uploading the testing data for
remote analysis. In addition, the speed of analysis may be improved
through remote analysis in case the electronic device has low
processing power. In some embodiments, a software application (e.g.
installed on the electronic device) decides whether to perform the
analysis locally on the electronic device or remotely via the
network. In some embodiments, this decision is based on at least
one of battery life of the electronic device, processing power of
the electronic device, estimated time of analysis by the electronic
device, estimated time of analysis of the network, and a user
selected setting (e.g. user can specify how analysis is to be
carried out by adjusting a setting on the user profile). In some
embodiments, the systems and methods disclosed herein utilize
suitable electronic devices such as smartphones or other devices
providing network audiovisual communications to provide telehealth.
For example, a user who has obtained the analysis of his/her test
results may wish to speak with a physician or expert for further
explanation (e.g. has questions beyond what is addressed in the
analysis presented through the electronic device). Accordingly, in
certain embodiments, the electronic device comprises a software
module allowing a user to communicate with a healthcare provider
such as by text messaging, email, phone call, video call, or other
digital communications.
[0039] In some embodiments, the diagnostic device is adapted for
use by a healthcare provider such as in the hospital or clinical
setting (as used herein, healthcare provider refers not just to
individual healthcare providers such as doctors or nurses but also
to healthcare providing organizations and businesses such as
hospitals, clinics, and healthcare centers). In some embodiments,
the diagnostic device is in communication with one or more
computing systems and/or databases of the healthcare provider or
organization. In some embodiments, the diagnostic device uploads
data obtained from imaging the analyte onto a remote server or
cloud-based network, which optionally performs analysis of the
image(s) and provides the results of the analysis to the healthcare
provider. In some embodiments, the results are provided through a
web portal. In some embodiments, the results are provided through a
software application via an application programming interface (API)
of a remote server or cloud-based computing system. In some
embodiments, the web portal or software application provides
secured user login for the healthcare provider and access to
encrypted patient data uploaded from the diagnostic device. In some
embodiments, the patient data is anonymized to remove identifying
information (e.g. name, address, etc). In some embodiments, the web
portal or software application provides tools for parameter-based
searching and/or sorting of uploaded data. In some embodiments, the
healthcare provider enters information for a (healthcare provider)
user profile. The information can include basic identifying
information such as name, address, and services offered. In some
cases, the healthcare provider enters information useful to
promoting the ecosystem maintained by the healthcare platform
described herein. Such information can include provider type, type
and/or size of practice group(s) or employee categories, location,
size, and insurance accepted.
[0040] In some embodiments, provided herein is a healthcare
platform providing an interactive ecosystem comprising users (e.g.
test subjects, patients), healthcare providers (e.g. hospitals,
doctors), and third parties (e.g. insurance companies,
pharmaceutical companies, universities, health research
organizations, etc). In some embodiments, testing is carried out
using the systems, devices, and methods described herein, and the
results of said testing are uploaded for storage within one or more
databases on the platform. In some embodiments, the testing
results, analyses, user profile, responses to ads/questions, and
any other information stored on the database(s) is encrypted to
protect user identity. In some embodiments, the platform comprises
a web portal or software application interface (e.g. an app on the
user electronic device) allowing a user to review the user profile,
testing results, and other information. In some embodiments, the
web portal or application interface provides tools for the user to
authorize other parties to access information such as testing
results. In some embodiments, the tools provide a user with options
to select parties to be given authorization to view or access user
information, and options to select the type of user information
that authorized parties can view or access. In some embodiments,
the tools provide a user with the ability to anonymize his
information for use by third parties such as, for example, in a
research study by a University research group or for patient
selection/screening for clinical trials by a pharmaceutical
company.
[0041] In some embodiments, the web portal or software application
provides tools for generating a provider profile for the healthcare
provider required to access uploaded data. In some embodiments, the
provider profile comprises information about the healthcare
provider such as provider type (e.g. hospital, clinic, family
doctor), type and/or size of practice group(s) or employee
categories (e.g. number of nurse, pediatrician, radiologist, etc),
location (e.g. address, city, town, county, state, country), size
(e.g. number of employees, doctors, nurses), and insurance
accepted. In some embodiments, the provider profile is associated
with information obtained from ads and/or questions posed to
healthcare providers utilizing the systems described herein. In
some embodiments, the healthcare provider is presented with one or
more ads selected from a plurality of ads in order to view the
results of an analysis as with the consumer-facing diagnostic
devices. Examples of ads that may be presented to a healthcare
provider include advertisements of drugs, therapies, surgical
tools, hospital equipment, medical malpractice insurance, medical
business consulting, and political ads relating to healthcare
legislation. In some embodiments, the healthcare provider is
presented with one or more questions selected from a plurality of
questions in order to view the results of an analysis. Examples of
questions that may be presented to a healthcare provider include
questions as to number of patients processed (e.g. in a day or
week), frequency of various reasons for patient visits (e.g. cold
symptoms, injury, heart condition, surgery, etc), price of various
services, commonly prescribed drugs, preferred medications (e.g.
favors prescribing brand-name vs generic), and willingness to
change service/prescriptions based on factors such as price or
effectiveness. In some embodiments, the ads presented to a
healthcare provider are personalized based on the provider profile
information and/or information gathered from previously viewed ads
and/or answered questions. As an example, a personalized ad may be
an advertisement for a generic drug touting that it is 10 times
cheaper than the name-brand formulation while being just as
effective based on the provider's response to a question indicating
a willingness to switch to a generic prescription based on price so
long as efficacy is equal. In some embodiments, multiple ads for
the same product or service can be configured, each having a
different angle or hook such as price, effectiveness, reputation,
or other advertising approaches. The ad for the product or service
may then be personalized by choosing one of the various approaches
based on correlating the response rate of the ads (e.g. click,
purchase, or conversion rate) to historical data. For example,
analysis of historical ad/question response data for all or related
healthcare providers may reveal that certain data predict increased
susceptibility to particular advertising approaches than others. In
some embodiments, the questions presented to a healthcare provider
are personalized based on the provider profile information and/or
information gathered from previously viewed ads and/or answered
questions. As an example, a personalized question may ask the
healthcare provider the reason the provider prescribes a name-brand
medication instead of the generic formulation based on previous
answers or profile information indicating this preference. In some
embodiments, the healthcare provider is prompted to provide
information while running a test using the diagnostic device. For
example, the healthcare provider may be prompted to indicate the
frequency, timing, and/or nature of the test (e.g. the 4.sup.th
daily test performed for a patient undergoing chemotherapy). In
some embodiments, the diagnostic device automatically uploads
metadata to the remote server or cloud-based network. In some
embodiments, the metadata is linked to the healthcare provider
and/or the patient whose biological sample is being tested. In some
embodiments, the metadata is linked to the provider or patient
anonymously such that the provider or patient identity cannot be
determined. In some embodiments, anonymity is provided using
encryption (e.g. asymmetric encryption).
[0042] In some embodiments, the diagnostic device is configured for
use in a commercial setting such as, for example, in a pharmacy or
retail stores (e.g. supermarket, department store, mall, etc). As
an example, the diagnostic device may be configured as a kiosk or
health station similar to the blood pressure health stations
frequently placed in pharmacies. In some embodiments, a diagnostic
device health station comprises an analyte analysis apparatus, one
or more cartridges, and a digital processing device and/or
communication interface. In some embodiments, the diagnostic device
health station comprises multiple disposable cartridges that are
discarded upon each use. In some embodiments, the diagnostic device
health station comprises a digital processing device in
communication with the analyte analysis apparatus for locally
storing data, performing data analysis, communicating with a remote
server or cloud-based network, selecting ads to present to the
user, or any combination thereof. Alternatively, in some
embodiments, the diagnostic device health station comprises a
communication interface that communicates with a remote server or
cloud-based network for storing data, performing data analysis,
selecting ads to present to the user, or any combination thereof.
In some embodiments, the diagnostic device health station comprises
at least one display for showing a result of the analyte or data
analysis, ads, questions/surveys, or other digital information.
Data Analysis Algorithms and Machine Learning Methods
[0043] In some embodiments, one or more computing devices carry out
data analysis. In some embodiments, data analysis is performed
using a computer program. In some embodiments, a computer program
comprises a data analysis module configured to analyze signals of
an assayed biological sample. In further embodiments, analyzing the
signals comprises a use of a statistical analysis. In some cases,
analyzing the signals comprises comparing the signals with a signal
template. There are various analyses, which can be combined to
assemble an analysis module in the computer program. Examples of
analyzing the signals include: analyzing strength of the signals,
analyzing a frequency of the signals, identifying a spatial
distribution pattern of the signals, identifying a temporal pattern
of the one or more signals, detecting a discrete fluctuation in the
signals corresponding to a chemical reaction event, inferring a
pressure level, inferring a temperature level, inferring a light
intensity, inferring a color intensity, inferring a conductance
level, inferring an impedance level, inferring a concentration of
ions, analyzing patterns of one or more AC electrokinetic high
field regions and one or more AC electrokinetic low field regions,
and analyzing a chemical reaction event. In still further
embodiments, a chemical reaction event comprises one or more of the
following: a molecular synthesis, a molecular destruction, a
molecular breakdown, a molecular insertion, a molecular separation,
a molecular rotation, a molecular spinning, a molecular extension,
a molecular hybridization, a molecular transcription, a sequencing
reaction, and a thermal cycling.
[0044] In some embodiments, the data analysis module is configured
to detect signals of an assayed biological sample. The signals can
comprise one or more images taken of the assayed biological sample.
The one or more images can comprise pixel image data. The one or
more images can be received as raw image data. The data detection
module can be configured to receive pixel image data from a mobile
computing device. The pixel image data can be from an image
captured by a camera on the mobile computing device. In various
embodiments, the data analysis module performs image processing
upon the pixel image data. A pixel in an image may be produced by a
signal that is a combination of photons produced by the assayed
sample and a background signal. Background signal can come from
photons emitted or reflected by external light sources. In some
cases, certain auto-fluorescent materials can interfere with
fluorescence-based assays. Accordingly, measurements of optical
signals using the unprocessed pixels may overestimate the signal of
the assay. Image processing can be used to reduce noise or filter
an image. Image processing can be used to improve signal quality.
In various embodiments, the data analysis module performs
calibration in order to correct for background noise level using a
reference signal (e.g., a null sample). In various embodiments, the
data analysis module processes the image to normalize contrast
and/or brightness. The data analysis module may perform gamma
correction. In some embodiments, the data analysis module converts
the image into grayscale, RGB, or LAB color space.
[0045] In various embodiments, the data analysis module processes
the pixel image data using data processing algorithms to convert
the data into a distribution of numerical values based on signal
intensity. The pixel image data can comprise spatial information
and intensity for each pixel. In various embodiments, the data
analysis module selects one or more subfields within the image to
be used in determining the result. This process may be necessary in
some circumstances. For example, the signal being detected may not
fill up the entire field of view of a camera or may be out of
position due to misalignment between the camera lens and the
assayed biological sample (e.g., the sample may be off-center in
the camera's field of view). The one or more subfields can be
selected based on the distribution of numerical values. For
example, the one or more subfields can be selected based on having
a distribution of the highest numerical values. In some
embodiments, the data analysis module divides an image into a
plurality of subfields and selects one or more subfields to be used
in determining the result (e.g., positive or negative detection of
cell-free circulating tumor DNA). The data analysis module can use
an algorithm to locate a sub-field having an area that comprises a
distribution of numerical values representing the highest signal
intensity out of a plurality of possible sub-fields. As an
illustrative example, an assay that utilizes a fluorescent dye to
detect an analyte can produce a fluorescent signal of a certain
frequency or color. The data analysis module then divides the image
into sub-fields and locates a sub-field having the highest signal
intensity. The sub-field having the highest signal intensity may
then be used for calculating whether the result is positive or
negative for the presence of the analyte. In various embodiments,
signal intensity for a sub-field is calculated based on an average,
median, or mode of signal intensity for all pixels located within
the sub-field. The spatial intensity of the signal can be captured
as an image by a camera of a mobile computing device. The image can
be converted into a distribution of numerical values based on
signal intensity. In various embodiments, the data analysis module
normalizes the pixel image set. In various embodiments, the data
analysis module receives multiple images or sets of pixel image
data corresponding to said multiple images for an assayed
biological sample. The data analysis module can analyze the
multiple images to generate a more accurate result than analyzing a
single image. In some embodiments, the data analysis module
analyzes at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 30, 40, or 50
images for an assayed biological sample.
[0046] Various algorithms can be used to generate models that
predict a result of the analyte testing. In some instances, machine
learning methods are applied to the generation of such models (e.g.
trained classifier). Such models can be generated by providing a
machine learning algorithm with training data in which the expected
output is known in advance.
[0047] Various algorithms can also be used to predict treatment
and/or healthcare options for a user. In some embodiments, the
systems, devices, and methods herein comprise a software module
providing one or more recommendations to a user. In some
embodiments, the software module provides a recommendation in
response to a query entered by the user. Alternatively, or in
combination, a user is presented with the results of analyte
testing along with one or more recommendations based on the results
and/or user profile. For example, the one or more recommendations
can suggest the nearest hospital with the requisite facilities or
resources for treating the specific disorder the user is suffering
from (according to the test results and/or user profile
information). In some embodiments, an algorithm utilizes a web
crawler and/or database to identify the resources available at
specific healthcare providers. In some embodiments, treatment
information for users who follow the recommendation(s) are analyzed
and incorporated to update the algorithm. For example, a user who
obtains a positive test result for a highly infectious disease
travels to the nearest hospital, for which no information is known
according to the algorithm. However, during the course of the
visit, the hospital turns out to have a quarantine space and
established quarantine protocols that successfully resolve the
potential outbreak. This information is uploaded to the platform's
online databases along with other treatment information for the
user. The algorithm then updates its decision making based on this
information such that, for example, this hospital may be
recommended for future users who require treatment for an
infectious disease (pursuant to other relevant conditions such as
proximity to the user or availability of comparable facilities). In
some embodiments, the algorithm is a machine learning algorithm
that is trained using previous treatment results. For example, a
user suffering from a particular disease may be provided with a
recommended treatment and/or healthcare provider based on a machine
learning algorithm trained with data sets comprising data for
subjects having similar conditions and outcome data for available
treatments and/or healthcare providers. Thus, a user suffering from
condition A may be provided with a recommendation to visit hospital
B based on an algorithm trained using outcome data for the matched
cohort of patients who also suffered from condition A and visited
hospitals B, C, and D (e.g. the hospitals within a certain driving
distance of the user). In some cases, a user may be matched against
a cohort of patients based on any of age, gender, disease or
condition, duration of disease or condition, symptoms, and other
relevant factors. In some embodiments, the algorithm provides one
or more recommendations based on the user's own medical history.
For example, the algorithm may provide a treatment recommendation
based on the user's past responses to various treatments (e.g. a
treatment option is removed from consideration because of past
instances when the user experienced no effect or an adverse
reaction to the treatment). In some embodiments, recommendations
are only provided for predictions having an area under curve of at
least about 0.6, about 0.7, about 0.8, about 0.9, about 0.95, or
about 0.99 when assessed for predictive accuracy using data not
used for training. In some embodiments, the systems, devices, and
methods described herein comprise an application comprising a
software module providing at least one of a treatment
recommendation and a healthcare provider recommendation generated
by a machine learning algorithm based on a user profile of the
individual, the analyte, the result, a location of the digital
processing device, historical treatment outcome data for a cohort
of patients matched to the individual, healthcare provider
information, or a combination thereof. In some embodiments, the
software application comprises a software module receiving a user
query to provide the one or more recommendations. In some
embodiments, the software application comprises a software module
automatically generating and providing the one or more
recommendation along with the results of the analyte testing.
[0048] The classifier or trained machine learning algorithm of the
present disclosure can comprise one feature space. In some cases,
the classifier comprises two or more feature spaces. The two or
more feature spaces may be distinct from one another. Each feature
space can comprise types of information about a case, such as
biomarker expression or the presence of genetic mutations. The
accuracy of the classification may be improved by combining two or
more feature spaces in a classifier instead of using a single
feature space. The patient and treatment information generally make
up the input features of the feature space and are labeled to
indicate the classification of each test result for the given set
of input features corresponding to that case. In many cases, the
classification is the outcome of the test analysis. The training
data is fed into the machine learning algorithm which processes the
input features and associated outcomes to generate a model. In some
cases, the machine learning algorithm is provided with training
data that includes the classification (e.g., diagnostic or test
result), thus enabling the algorithm to "learn" by comparing its
output with the actual output to modify and improve the model. This
is often referred to as supervised learning. Alternatively, the
machine learning algorithm can be provided with unlabeled or
unclassified data, which leaves the algorithm to identify hidden
structure amongst the cases (referred to as unsupervised learning).
Sometimes, unsupervised learning is useful for identifying the
features that are most useful for classifying raw data into
separate cohorts.
[0049] One or more sets of training data may be generated and used
to train a machine learning algorithm. An algorithm may utilize a
predictive model such as a neural network, a decision tree, a
support vector machine, or other applicable model. Using the
training data, an algorithm can form a classifier for classifying
the case according to relevant features. The features selected for
classification can be classified using a variety of viable methods.
The machine learning algorithm may be selected from the group
consisting of a supervised, semi-supervised and unsupervised
learning, such as, for example, a support vector machine (SVM), a
Naive Bayes classification, a random forest, an artificial neural
network, a decision tree, a K-means, learning vector quantization
(LVQ), self-organizing map (SOM), graphical model, regression
algorithm (e.g., linear, logistic, multivariate, association rule
learning, deep learning, dimensionality reduction and ensemble
selection algorithms. In some embodiments, the machine learning
algorithm is selected from the group consisting of: a support
vector machine (SVM), a Naive Bayes classification, a random
forest, and an artificial neural network. Machine learning
techniques include bagging procedures, boosting procedures, random
forest algorithms, and combinations thereof. Illustrative
algorithms for analyzing the data include but are not limited to
methods that handle large numbers of variables directly such as
statistical methods and methods based on machine learning
techniques. Statistical methods include penalized logistic
regression, prediction analysis of microarrays (PAM), methods based
on shrunken centroids, support vector machine analysis, and
regularized linear discriminant analysis.
[0050] In some embodiments, the data analysis module performs
feature extraction using a feature extraction algorithm to obtain
relevant information about the signal while leaving out irrelevant
information. Some examples of feature extraction algorithms include
histogram of oriented gradients (HOG), scale-invariant feature
transform (SIFT), and speeded up robust feature (SURF). Feature
extraction algorithms can be used in image processing for threshold
detection (thresholding), edge detection, corner detection, blob
detection, and ridge detection. In view of the disclosure provided
herein, those of skill in the art will recognize that many
algorithms are available for performing feature extraction.
[0051] In some embodiments, the data analysis module uses a trained
algorithm to determine a result for the sample (e.g., positive or
negative detection of an analyte or microparticulate). The trained
algorithm of the present disclosure as described herein can
comprise one feature space. The trained algorithm of the present
disclosure as described herein can comprise two or more feature
spaces. The two or more feature spaces may be distinct from one
another. Each feature space can comprise types of information about
a sample, such as presence of a nucleic acid, protein,
carbohydrate, lipid, or other macromolecule. Algorithms can be
selected from a non-limiting group of algorithms including
principal component analysis, partial least squares regression, and
independent component analysis. Algorithms can include methods that
analyze numerous variables directly and are selected from a
non-limiting group of algorithms including methods based on machine
learning processes. Machine learning processes can include random
forest algorithms, bagging techniques, boosting methods, or any
combination thereof. Algorithms can utilize statistical methods
such as penalized logistic regression, prediction analysis of
microarrays, methods based on shrunken centroids, support vector
machine analysis, or regularized linear discriminant analysis. The
algorithm may be trained with a set of sample data (e.g., images or
pixel image data) obtained from various subjects. The sample data
may be obtained from a database described herein such as, for
example, an online database storing the results of analyte
analyses. A set of samples can comprise samples from at least 10,
20, 30, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250, 300, 350, 400,
450, 500, 600, 700, 800, 900, or 1000 or more subjects. The trained
algorithm can be tested using independent samples to determine its
accuracy, specificity, sensitivity, positive predictive value,
negative predictive value, or any combination thereof. The trained
algorithm can have an accuracy of at least 80, 90, 95, or 99%% for
a set of at least 100 independent samples. The trained algorithm
can have a positive predictive value of at least 80, 90, 95, or 99%
for a set of at least 100 independent samples. The trained
algorithm can have a specificity of at least 80, 90, 95, or 99% for
a set of at least 100 independent samples.
[0052] As an example, in the case of algorithms providing treatment
or healthcare provider recommendations, examples of features
include the analyte, the result, a healthcare condition, age,
gender, and other factors affecting the outcome. In some
embodiments, the treatment and/or healthcare provider is
pre-selected based on location and/or resource availability. For
example, a user may enter constraints on treatment by limiting
healthcare providers to within a 30 mile radius of the current
device location. Next, the available healthcare providers within
this radius are identified, their information extracted (e.g. using
webcrawlers or existing databases), and then converted into data
corresponding to the features of the algorithm. The data are fed
into the algorithm to generate an output (e.g. a predicted outcome
between 1.0 corresponding to positive outcome and 0.0 corresponding
to negative outcome) for each healthcare provider. The providers
are then ranked based on the outcome prediction, and the highest
ranked provider is presented to the user as the recommended
healthcare provider.
[0053] In some embodiments, various algorithms are applied to
generate predictions or recommendations for third parties or
healthcare providers rather than the user. In some embodiments, the
recommendations include identified locations having specific
healthcare needs. In some embodiments, machine learning algorithms
can reveal areas having high clusters of specific types of medical
needs (e.g. high rate of a certain infectious). For example, third
parties such as epidemiologists can use this information to
identify potential outbreaks. In addition, healthcare providers or
government health organizations can identify areas requiring
increased resources for responding to such healthcare needs. As
another example, various algorithms can analyze uploaded user data
to determine the fastest growing healthcare needs. Such information
can be made accessible to healthcare providers or third parties who
receive appropriate authorization. In some embodiments, access to
this data is monetized to help make the testing systems, devices,
and apparatuses described herein available to the patient
population.
[0054] In some embodiments, the systems and methods described
herein utilize one or more algorithms to perform patient data
analytics. As an example, patient data may be analyzed using
machine learning algorithm(s) to determine susceptibility to
different diseases based on various factors (e.g. age, location,
ethnicity, gender, etc). Accordingly, patients who are identified
as having a predicted susceptibility to a certain disease may be
provided with recommendations to see a doctor, obtain testing, or
presented with questions directed to other risk factors or symptoms
of the disease. In some embodiments, patient data is sorted into
different cohorts based on such factors, allowing matching cohorts
to be used to generate personalized recommendations or analyses for
individual subjects. For example, ads for a certain treatment
popular with a matched cohort of patients having similar
demographics as an individual may be selected for presentation to
that individual when carrying out analyte testing according to the
systems and methods described herein. Similarly, unsupervised
machine learning may be applied to a data set to carry out cluster
analysis for identifying patient clusters that may be receptive to
common treatment modalities. Individuals who are grouped into
specific clusters may be targeted with certain ads or questions
based on the common characteristics of the cluster.
[0055] In some embodiments, machine learning algorithms utilized
herein comprise artificial neural networks, which mimic networks of
neurons based on the neural structure of the brain. They process
input data by comparing the classification of a specific case (e.g.
a patient) with the known actual classification of the case (e.g.
an outcome such as adverse event). Artificial neural networks are
typically organized in layers comprising an input layer, an output
layer, and at least one hidden layer, wherein each layer comprises
one or more neurons or nodes. Each node in a given layer is
connected to the nodes in the preceding layer and the nodes in the
subsequent layer. A given node receives input from the nodes in the
preceding layer, changes its internal state based on the value of
the received input, and generates an output based on the input and
activation. This output is sent to the nodes in the subsequent
layer, and the process continues until the output layer generates
the final output which may be a prediction. As a result, the input
propagates through the layers of the neural network to generate a
final output classification such as, for example, a value
corresponding to a classification such as a known outcome
represented by neurons in the output layer. As an example, the
output layer may comprise a node corresponding to healthcare
provider A or healthcare provider B in the case of an algorithm
determining the provider to recommend a individual to for
treatment. The output can be ranked according to the values of
these respective nodes (which may be normalized to a value between
0 and 1). In a case where the node corresponding to healthcare
provider A has a value of 0.9 while the node corresponding to
healthcare provider B has a value of 0.1, the output can be ranked
with provider A as the number one option and provider B as the
number two option. In some cases, treatment options are not ranked
and/or presented when they fall below a minimum significance
threshold.
Systems
[0056] In certain aspects, computer-implemented systems, devices,
media, and methods described herein function to coordinate use of a
diagnostic device (e.g. an analyte analysis apparatus) with
targeted advertisements and optionally a database of users and
their results.
[0057] In some embodiments, the diagnostic device is an analyte
detection system, for example, a dielectrophoresis and fluidics
cartridge for isolating and detecting one or more analytes
associated with a medical condition. In some embodiments, the
diagnostic device comprises an analyte analysis apparatus, a
cartridge, or both. In some embodiments, targeted advertisements
are selected based on one or more of the user information such as
user age, user height and weight, and user medical information. In
some embodiments, the database is searchable by a user or patient.
In some embodiments, the database is searchable by a research
professional. In some embodiments, the database is searchable by a
physician. In some embodiments, the database is searchable by a
biotechnology or pharmaceutical company. In some embodiments, the
online database is accessible to authorized third parties.
[0058] Provided herein are computer-implemented systems. Some such
systems comprising: a digital processing device comprising: at
least one processor, a memory, a display, and an operating system
configured to perform executable instructions; an analyte analysis
apparatus reversibly accepting and positioning the digital
processing device and an analyte analysis cartridge configured to
receive a biological material of an individual; a computer program
stored in the memory of the digital processing device, the computer
program including instructions executable by the digital processing
device to create an application comprising: a software module
controlling the cartridge to perform an analyte analysis of the
biological material to generate a result; a software module
presenting the result on the display of the digital processing
device; and a software module selecting one or more ads from a
population of ads to present in association with the result. In
some embodiments, the analyte analysis apparatus positions the
digital processing device and an analyte analysis cartridge
relative to each other to perform the analyte analysis. In some
embodiments, the digital processing device further comprises a
camera and wherein the analyte analysis apparatus positions the
analyte analysis cartridge such that the camera of the digital
processing device can capture an image of a result field of the
cartridge. In some embodiments, the image is analyzed by a machine
learning algorithm to generate the result. In some embodiments, the
digital processing device or the analyte analysis apparatus
provides power to the cartridge. In some embodiments, the cartridge
is a dielectrophoresis (DEP) cartridge. In some embodiments, the
biological material is a biological fluid. In some embodiments, the
biological fluid is whole blood, plasma, serum, saliva,
cerebrospinal fluid, lymph fluid, urine, sweat, tears, amniotic
fluid, aqueous humor, vitreous humor, pleural fluid, mucus,
synovial fluid, exudate, interstitial fluid, peritoneal fluid,
pericardial fluid, sebum, semen, or bile. In some embodiments, the
one or more ads are selected based on a user profile of the
individual, the analyte, the result, a location of the digital
processing device, or a combination thereof. In some embodiments,
the user profile comprises medical information. In some
embodiments, the user profile comprises information pertaining to
adherence to treatment regimen. In some embodiments, the one or
more ads are targeted to the individual based on the individual
undergoing a current treatment. In some embodiments, the software
module selecting one or more ads receives instructions from a
remote server to select the one or more ads, wherein the selection
is based on analysis performed by the remote server. In some
embodiments, a response by the individual to the one or more ads is
added to a user profile of the individual. In some embodiments, the
one or more ads are provided by a third-party ad network. In some
embodiments, the application further comprises a software module
providing an interface allowing upload of the result to an online
database. In some embodiments, the application further comprises a
software module providing a query interface allowing search of the
online database. In some embodiments, the online database is
searchable by a biotechnology or pharmaceutical company. In some
embodiments, the online database is accessible to authorized third
parties. In some embodiments, a user profile for the individual is
stored on the online database. In some embodiments, the online
database is encrypted. In some embodiments, third party
applications are prevented from accessing private information
stored in the online database. In some embodiments, the application
further comprises a software module selecting one or more questions
from a population of questions to present in association with the
result. In some embodiments, the application further comprises a
software module providing at least one of a treatment
recommendation and a healthcare provider recommendation generated
by a machine learning algorithm based on a user profile of the
individual, the analyte, the result, a location of the digital
processing device, historical treatment outcome data for a cohort
of patients matched to the individual, healthcare provider
information, or a combination thereof. In some embodiments, the
software module selecting one or more questions receives
instructions from the remote server to select the one or more
questions, wherein the selection is based on analysis performed by
the remote server. In some embodiments, the application provides
the individual with a choice between the one or more ads and the
one or more questions. In some embodiments, a response by the
individual to the one or more questions is added to a user profile
of the individual. In some embodiments, the result is geo-tagged
with a location of the digital processing device and uploaded to a
database. In some embodiments, analyte analysis comprises analyte
capture, image acquisition, and data analysis. In some embodiments,
data analysis is performed remotely through cloud computing. In
some embodiments, the digital processing device sends a
communication over a network to another device of the user. In some
embodiments, the communication comprises one or more ads displayed
on another device. In some embodiments, the another device is a
cell phone, a smart phone, a tablet, a laptop, a television, an
electronic reader (E-reader), a projector, or a monitor. In some
embodiments, the communication comprises an alert that user
interaction is needed. In some embodiments, the user interaction is
selecting one or more ads for display by the digital processing
device, selecting one or more questions for display by the digital
processing device, viewing one or more ads, viewing one or more
questions, or viewing the result. In some embodiments, the
communication comprises one or more questions for display on
another device. In some embodiments, the system further comprises a
software module for obtaining usage statistics for the digital
processing device. In some embodiments, the usage statistics are
shared with a third party.
[0059] Additionally provided herein are computer-implemented
systems comprising: a digital processing device comprising: at
least one processor, a memory, and an operating system configured
to perform executable instructions; an analyte analysis apparatus
reversibly accepting and positioning the digital processing device
and an analyte analysis cartridge configured to receive a
biological material of an individual; a computer program stored in
the memory of the digital processing device, the computer program
including instructions executable by the digital processing device
to create an application comprising: a software module controlling
the cartridge to perform an analyte analysis of the biological
material to generate a result; a software module transmitting the
result to an online database, the online database searchable via a
query interface; and a software module selecting one or more ads
from a population of ads or one or more questions from a population
of questions to present in association with one or more results in
response to a search performed in the query interface by a data
consumer. In some embodiments, the analyte analysis apparatus
positions the digital processing device and an analyte analysis
cartridge relative to each other to perform the analyte analysis.
In some embodiments, the digital processing device further
comprises a camera and wherein the analyte analysis apparatus
positions the analyte analysis cartridge such that the camera of
the digital processing device can capture an image of a result
field of the cartridge. In some embodiments, the image is analyzed
by a machine learning algorithm to generate the result. In some
embodiments, the digital processing device or the analyte analysis
apparatus provides power to the cartridge. In some embodiments, the
cartridge is a dielectrophoresis (DEP) cartridge. In some
embodiments, the biological material is a biological fluid. In some
embodiments, the biological fluid is whole blood, plasma, serum,
saliva, cerebrospinal fluid, lymph fluid, urine, sweat, tears,
amniotic fluid, aqueous humor, vitreous humor, pleural fluid,
mucus, synovial fluid, exudate, interstitial fluid, peritoneal
fluid, pericardial fluid, sebum, semen, or bile. In some
embodiments, the online database interfaces with a social network
or other online community. In some embodiments, the query interface
allows the data consumer to search by individual, by analyte, by
result, or by a combination thereof. In some embodiments, the
online database is searchable by a biotechnology or pharmaceutical
company. In some embodiments, the online database is accessible to
authorized third parties. In some embodiments, a user profile for
the individual is stored on the online database. In some
embodiments, the online database is encrypted. In some embodiments,
third party applications are prevented from accessing private
information stored in the online database. In some embodiments, the
one or more ads are selected based on a user profile of the
individual, the analyte, the result, a location of the digital
processing device, or a combination thereof. In some embodiments,
the user profile comprises medical information. In some
embodiments, the user profile comprises information pertaining to
adherence to treatment regimen. In some embodiments, the one or
more ads are targeted to the individual based on the individual
undergoing a current treatment. In some embodiments, the software
module selecting one or more ads receives instructions from a
remote server to select the one or more ads, wherein the selection
is based on analysis performed by the remote server. In some
embodiments, the one or more ads are provided by a third-party ad
network. In some embodiments, the application further comprises a
software module selecting one or more questions from a population
of questions to present in association with one or more results in
response to a search performed in the query interface by the data
consumer. In some embodiments, the software module selecting one or
more questions receives instructions from a remote server to select
the one or more questions, wherein the selection is based on
analysis performed by the remote server. In some embodiments, the
application provides the data consumer with a choice between the
one or more ads and the one or more questions. In some embodiments,
the result is geo-tagged with a location of the digital processing
device and uploaded to a database. In some embodiments, analyte
analysis comprises analyte capture, image acquisition, and data
analysis. In some embodiments, data analysis is performed remotely
through cloud computing. In some embodiments, the digital
processing device sends a communication over a network to another
device of the user. In some embodiments, the communication
comprises one or more ads displayed on another device. In some
embodiments, the another device is a cell phone, a smart phone, a
tablet, a laptop, a television, an electronic reader (E-reader), a
projector, or a monitor. In some embodiments, the communication
comprises an alert that user interaction is needed. In some
embodiments, the user interaction is selecting one or more ads for
display by the digital processing device, selecting one or more
questions for display by the digital processing device, viewing one
or more ads, viewing one or more questions, or viewing the result.
In some embodiments, the communication comprises one or more
questions for display on another device. In some embodiments, the
system further comprises a software module for obtaining usage
statistics for the digital processing device. In some embodiments,
the usage statistics are shared with a third party.
[0060] Further provided herein are computer-implemented systems
comprising: a digital processing device comprising: at least one
processor, a memory, a display, and an operating system configured
to perform executable instructions; an analyte analysis apparatus
reversibly accepting and positioning the digital processing device
and an analyte analysis cartridge configured to receive a
biological material of an individual; a computer program stored in
the memory of the digital processing device, the computer program
including instructions executable by the digital processing device
to create an application comprising: a software module controlling
the cartridge to perform an analyte analysis of the biological
material to generate a result; a software module presenting the
result on the display of the digital processing device; a software
module selecting at least one first ad from a population of ads to
present in association with the result; a software module
transmitting the result to an online database, the online database
searchable via a query interface; and a software module selecting
at least one second ad from the population of ads to present in
association with one or more results in response to a search
performed in the query interface by a data consumer. In some
embodiments, the at least one first ad and the at least one second
ad are provided by one or more third-party ad networks.
[0061] In some embodiments, disclosed herein are non-transitory
computer readable storage media encoded with a program including
instructions executable by at least one processor of a digital
processing device to create an application carrying out the methods
or steps described herein.
Methods
[0062] Computer-implemented methods herein coordinate use of an at
home diagnostic device with targeted advertisements and optionally
a database of users and their results. In some embodiments, the at
home diagnostic device comprises a dielectrophoresis and fluidics
cartridge for isolating and detecting one or more analytes
associated with a medical condition. In some embodiments, targeted
advertisements are selected based on one or more of the user
information such as user age, user height and weight, and user
medical information. In some embodiments, the database is
searchable by a user. In some embodiments, the database is
searchable by a research professional. In some embodiments, the
database is searchable by a physician. In some embodiments, the
database is searchable by a biotechnology or pharmaceutical
company.
[0063] Also provided herein are computer-implemented methods. Such
methods comprising transmitting, by a digital processing device, a
control signal to a cartridge of an analyte analysis apparatus to
perform an analyte analysis of a biological material of an
individual to generate a result; presenting, by the digital
processing device, the result on a display of a digital processing
device; and selecting, by the digital processing device, one or
more ads from a population of ads or one or more questions from a
population of questions to present in association with the result.
In some embodiments, the cartridge is configured to receive the
biological material of the individual. In some embodiments, the
analyte analysis apparatus reversibly accepts and positions the
digital processing device and the cartridge. In some embodiments,
the analyte analysis apparatus positions the digital processing
device and an analyte analysis cartridge relative to each other to
perform the analyte analysis. In some embodiments, the digital
processing device comprises a camera and wherein the analyte
analysis apparatus positions the analyte analysis cartridge such
that the camera of the digital processing device can capture an
image of a result field of the cartridge. In some embodiments, the
image is analyzed by a machine learning algorithm to generate the
result. In some embodiments, the digital processing device or the
analyte analysis apparatus provides power to the cartridge. In some
embodiments, the cartridge is a dielectrophoresis (DEP) cartridge.
In some embodiments, the biological material is a biological fluid.
In some embodiments, the biological fluid is whole blood, plasma,
serum, saliva, cerebrospinal fluid, lymph fluid, urine, sweat,
tears, amniotic fluid, aqueous humor, vitreous humor, pleural
fluid, mucus, synovial fluid, exudate, interstitial fluid,
peritoneal fluid, pericardial fluid, sebum, semen, or bile. In some
embodiments, the one or more ads are selected based on a user
profile of the individual, the analyte, the result, a location of
the digital processing device, or a combination thereof. In some
embodiments, the user profile comprises medical information. In
some embodiments, the user profile comprises information pertaining
to adherence to treatment regimen. In some embodiments, the one or
more ads are targeted to the individual based on the individual
undergoing a current treatment. In some embodiments, the digital
processing device receives instructions from a remote server to
select the one or more ads, wherein the selection is based on
analysis performed by the remote server. In some embodiments, a
response by the individual to the one or more ads is added to a
user profile of the individual. In some embodiments, the one or
more ads are provided by a third-party ad network. In some
embodiments, the method further comprises providing, by the digital
processing device, an interface allowing upload of the result to an
online database. In some embodiments, the method further comprises
providing, by the digital processing device, a query interface
allowing search of the online database. In some embodiments, the
online database is searchable by a biotechnology or pharmaceutical
company. In some embodiments, the online database is accessible to
authorized third parties. In some embodiments, a user profile for
the individual is stored on the online database. In some
embodiments, the online database is encrypted. In some embodiments,
third party applications are prevented from accessing private
information stored in the online database. In some embodiments, the
method further comprises selecting, by the digital processing
device, one or more questions from a population of questions to
present in association with the result. In some embodiments, the
method further comprises providing, by the digital processing
device, at least one of a treatment recommendation and a healthcare
provider recommendation generated by a machine learning algorithm
based on a user profile of the individual, the analyte, the result,
a location of the digital processing device, historical treatment
outcome data for a cohort of patients matched to the individual,
healthcare provider information, or a combination thereof. In some
embodiments, the digital processing device receives instructions
from a remote server to select the one or more questions, wherein
the selection is based on analysis performed by the remote server.
In some embodiments, the digital processing device provides the
individual with a choice between the one or more ads and the one or
more questions. In some embodiments, a response by the individual
to the one or more questions is added to a user profile of the
individual. In some embodiments, the result is geo-tagged with a
location of the digital processing device and uploaded to a
database. In some embodiments, analyte analysis comprises analyte
capture, image acquisition, and data analysis. In some embodiments,
data analysis is performed remotely through cloud computing. In
some embodiments, the digital processing device sends a
communication over a network to another device of the user. In some
embodiments, the communication comprises one or more ads displayed
on another device. In some embodiments, the another device is a
cell phone, a smart phone, a tablet, a laptop, a television, an
electronic reader (E-reader), a projector, or a monitor. In some
embodiments, the communication comprises an alert that user
interaction is needed. In some embodiments, the user interaction is
selecting one or more ads for display by the digital processing
device, selecting one or more questions for display by the digital
processing device, viewing one or more ads, viewing one or more
questions, or viewing the result. In some embodiments, the
communication comprises one or more questions for display on
another device. In some embodiments, the method further comprises
obtaining usage statistics for the digital processing device. In
some embodiments, the usage statistics are shared with a third
party.
[0064] Additionally provided herein are computer-implemented method
comprising: transmitting, by a digital processing device, a control
signal to a cartridge of an analyte analysis apparatus to perform
an analyte analysis of a biological material of an individual to
generate a result; providing, by the digital processing device, an
interface allowing upload of the result to an online database;
providing, by the digital processing device, a query interface
allowing search of the online database; and selecting, by the
digital processing device, one or more ads from a population of ads
or one or more questions from a population of questions to present
in association with one or more results in response to a search
performed in the query interface. In some embodiments, the
cartridge is configured to receive the biological material of the
individual. In some embodiments, the analyte analysis apparatus
reversibly accepts and positions a digital processing device and
the cartridge. In some embodiments, the analyte analysis apparatus
positions the digital processing device and an analyte analysis
cartridge relative to each other to perform the analyte analysis.
In some embodiments, the digital processing device comprises a
camera and wherein the analyte analysis apparatus positions the
analyte analysis cartridge such that the camera of the digital
processing device can capture an image of a result field of the
cartridge. In some embodiments, the image is analyzed by a machine
learning algorithm to generate the result. In some embodiments, the
digital processing device or the analyte analysis apparatus
provides power to the cartridge. In some embodiments, the cartridge
is a dielectrophoresis (DEP) cartridge. In some embodiments, the
biological material is a biological fluid. In some embodiments, the
biological fluid is whole blood, plasma, serum, saliva,
cerebrospinal fluid, lymph fluid, urine, sweat, tears, amniotic
fluid, aqueous humor, vitreous humor, pleural fluid, mucus,
synovial fluid, exudate, interstitial fluid, peritoneal fluid,
pericardial fluid, sebum, semen, or bile. In some embodiments, the
online database interfaces with a social network or other online
community. In some embodiments, the query interface allows the data
consumer to search by individual, by analyte, by result, or by a
combination thereof. In some embodiments, the online database is
searchable by a biotechnology or pharmaceutical company. In some
embodiments, the online database is accessible to authorized third
parties. In some embodiments, a user profile for the individual is
stored on the online database. In some embodiments, the online
database is encrypted. In some embodiments, third party
applications are prevented from accessing private information
stored in the online database. In some embodiments, the one or more
ads are selected based on a user profile of the individual, the
analyte, the result, a location of the digital processing device,
or a combination thereof. In some embodiments, the user profile
comprises medical information. In some embodiments, the user
profile comprises information pertaining to adherence to treatment
regimen. In some embodiments, the one or more ads are targeted to
the individual based on the individual undergoing a current
treatment. In some embodiments, the digital processing device
receives instructions from a remote server to select the one or
more ads, wherein the selection is based on analysis performed by
the remote server. In some embodiments, the one or more ads are
provided by a third-party ad network. In some embodiments, the
method further comprises selecting, by the digital processing
device, one or more questions from a population of questions to
present in association with one or more results in response to a
search performed in the query interface. In some embodiments, the
digital processing device receives instructions to select the one
or more questions from a remote server, wherein the selection is
based on analysis performed by the remote server. In some
embodiments, the digital processing device provides the individual
with a choice between the one or more ads and the one or more
questions. In some embodiments, the result is geo-tagged with a
location of the digital processing device and uploaded to a
database. In some embodiments, analyte analysis comprises analyte
capture, image acquisition, and data analysis. In some embodiments,
data analysis is performed remotely through cloud computing. In
some embodiments, the digital processing device sends a
communication over a network to another device of the user. In some
embodiments, the communication comprises one or more ads displayed
on another device. In some embodiments, the another device is a
cell phone, a smart phone, a tablet, a laptop, a television, an
electronic reader (E-reader), a projector, or a monitor. In some
embodiments, the communication comprises an alert that user
interaction is needed. In some embodiments, the user interaction is
selecting one or more ads for display by the digital processing
device, selecting one or more questions for display by the digital
processing device, viewing one or more ads, viewing one or more
questions, or viewing the result. In some embodiments, the
communication comprises one or more questions for display on
another device. In some embodiments, the method further comprises
obtaining usage statistics for the digital processing device. In
some embodiments, the usage statistics are shared with a third
party.
[0065] Further provided herein are computer-implemented methods
comprising: transmitting, by a digital processing device, a control
signal to a cartridge of an analyte analysis apparatus to perform
an analyte analysis of a biological material of an individual to
generate a result; presenting, by the digital processing device,
the result on a display; selecting, by the digital processing
device, at least one first ad from a population of ads to present
in association with the result; providing, by the digital
processing device, an interface allowing upload of the result to an
online database; providing, by the digital processing device, a
query interface allowing search of the online database; and
selecting, by the digital processing device, at least one second ad
from the population of ads to present in association with one or
more results in response to a search performed in the query
interface. In some embodiments, the at least one first ad and the
at least one second ad are provided by one or more third-party ad
networks.
[0066] In some embodiments, disclosed herein are non-transitory
computer readable storage media encoded with a program including
instructions executable by at least one processor of a digital
processing device to create an application carrying out the methods
or steps described herein.
Analyte Analysis Apparatus
[0067] Also provided herein are analyte analysis apparatuses for
use with detection methods herein, which are small enough to be
easily carried or transported and have very low power requirements.
In some embodiments, an analyte analysis apparatus is a compact
device. An exemplar compact device is described in
PCT/US2017/024149, which is incorporated in its entirety. In some
embodiments, the analyte analysis apparatus or compact device
reversibly accepts and positions the digital processing device and
an analyte analysis cartridge. In some embodiments, the analyte
analysis apparatus or compact device performs an analyte analysis.
In some embodiments, the compact device is used only for analyte
capture and image acquisition while analyte analysis is performed
remotely in the cloud. In some embodiments, digital processing
devices herein include a mobile computing device such as a mobile
phone, smartphone, tablet, wearable computing device (e.g.
smartwatch, head-mounted display), personal data assistant (PDA),
handheld gaming console, portable media player, personal navigation
device, mobile internet device (MID), or laptop computer. In some
embodiments, an analyte analysis apparatus integrates various
components described herein.
Size
[0068] In various embodiments, analyte analysis apparatuses herein
are sized to be easily carried by an average person with one hand.
In some embodiments, the size and shape of the apparatus is
variable depending on the type of mobile computing device to be
used in combination with the analyte analysis apparatus. In some
embodiments, an analyte analysis apparatus comprises a housing
frame to hold a mobile computing device, at least one microfluidic
channel, and a fluidic cartridge. In some embodiments, analyte
analysis apparatus sized to be used with a mobile computing device
is configured to be portable. In some embodiments, a analyte
analysis apparatus herein has a height ranging from about 130 mm to
about 320 mm, for example about 130, 140, 150, 160, 170, 180, 190,
200, 210, 220, 230, 240, 250, 260, 270, 280, 290, 300, 310, or 320
mm. In some embodiments, analyte analysis apparatuses herein have a
width ranging from about 60 mm to about 230 mm, for example about
60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190,
200, 210, 220, or 230 mm. In some embodiments, analyte analysis
apparatuses herein have a depth ranging from about 20 mm to about
100 mm, for example about 20, 30, 40, 50, 60, 70, 80, 90, or 100
mm. In some embodiments, the housing frame is adapted to hold a
range of possible mobile computing devices of varying sizes such
as, for example, a mobile phone, a mini tablet, or a tablet. In
some embodiments, the housing frame comprises one or more members
for holding the mobile computing device in place. In some
embodiments, the members are adjustable members. In some
embodiments, the housing frame comprises one or more adjustable
members positioned at a top and/or bottom of the mobile computing
device. In some embodiments, the housing frame comprises one or
more adjustable members positioned at a left and/or right side of
the mobile computing device. In some embodiments, the housing frame
comprises one or more adjustable members positioned at a front or
back of the mobile computing device. In some embodiments, the
members are adjustable via translational or axial movement,
rotation, or expansion. In some embodiments, a member is slidable.
In some embodiments, a member is flexible. In some embodiments, a
member comprises a clamp for gripping the mobile computing unit,
wherein the clamp is adjustable (e.g., claws of the clamp are
slidable relative to each other for opening and closing their
grip). In some embodiments, each member comprises a surface for
engaging with a surface of the mobile computing device. In some
embodiments, the surface of each member comprises a high friction
material (e.g. rubber, non-slip plastic, a textured fabric, foam,
polymers, etc.) to prevent sliding of the mobile computing device.
In some embodiments, the housing frame comprises a cradle for
receiving and positioning the mobile computing device.
[0069] In some embodiments, an analyte analysis apparatus is
configured to accept and position a mobile computing device so that
a camera of the mobile computing device is aligned with an optical
pathway to enable the device to take an image, photo, or video. In
some embodiments, the analyte analysis apparatus is configured to
accept and position a front facing camera of the mobile computing
device. In some embodiments, the analyte analysis apparatus is
configured to accept and position a rear facing camera of the
mobile computing device. In some embodiments, the analyte analysis
apparatus accepts and positions a mobile computing device so that a
camera of the device is aligned with an optical pathway while also
not obstructing a display screen of the device. This configuration
provides the advantage of allowing a user to watch ads, answer
questions, or otherwise use the device while the test or assay is
being performed. In some embodiments, the analyte analysis
apparatus comprises an optical pathway that blocks out external
light from entering the camera for taking the image. In some
embodiments, the device is connected and communicating via internal
network to other devices in user's environment, alerting user that
interaction needed (Ex: smart home, "the test is done" alert, with
ads being displayed on TV instead of phone etc, etc). In some
embodiments, the optical pathway comprises a light seal (e.g., a
foam light seal) that, upon engagement with the surface of the
device, prevents external light from entering the camera
aperture.
Power
[0070] In various embodiments, analyte analysis apparatuses
described herein have the feature of running on very low power, for
example on the power provided by a USB or micro USB port. In some
cases, the power is provided by the digital processing device. In
some cases, the power is provided by a battery pack. In some cases,
the power is provided by a solar charger. In some cases, the power
is provided by a wall outlet. In some cases, the power is provided
by a headphone jack.
[0071] In some embodiments, a power supply is embedded into a
digital processing device.
[0072] In some embodiments, it is contemplated that analyte
analysis apparatuses herein are configured to use multiple power
sources depending on the source that is available at the time.
[0073] Power provided by a USB port is typically understood to be
about 5 volts. The maximum current recommended to be drawn from a
USB port is about 500 mA. The maximum load of power to be generated
by a USB port is 2.5 Watts. Therefore, analyte analysis apparatuses
described herein, in some embodiments, have lower power
requirements than 5 volts, 500 mA, or 2.5 Watts. In some
embodiments, analyte analysis apparatuses herein are powered by a
battery pack or wall outlet and have larger power requirements, for
example about 2.5 to about 10 Watts. In some embodiments, analyte
analysis apparatuses herein have power requirements of less than
0.01 to 10 Watts. In some embodiments, analyte analysis apparatuses
herein require less than about 10, 9.5, 9.0, 8.5, 8.0, 7.5, 7.0,
6.5, 6.0, 5.9, 5.8, 5.7, 5.6, 5.5, 5.4, 5.3, 5.2, 5.1, 5.0, 4.9,
4.8, 4.7, 4.6, 4.5, 4.4, 4.3, 4.2, 4.1, 4.0, 3.9, 3.8, 3.7, 3.6,
3.5, 3.4, 3.3, 3.2, 3.1, 3.0, 2.9, 2.8, 2.7, 2.6, 2.5, 2.4, 2.3,
2.2, 2.1, 2.0, 1.9, 1.8, 1.7, 1.6, 1.5, 1.4, 1.3, 1.2, 1.1, 1.0,
0.9, 0.8, 0.7, 0.6, 0.5, 0.4, 0.3, 0.2, 0.1, 0.09, 0.08, 0.07,
0.06, 0.05, 0.04, 0.03, 0.02, or 0.01 Watts.
[0074] In some embodiments, analyte analysis apparatuses described
herein are contemplated to couple to a digital processing device
via a connection port, such as a USB connection port or a micro USB
connection port. Connection of the analyte analysis apparatuses to
the digital processing device, in some embodiments, allows the
analyte analysis apparatus to draw power and also allows the
digital processing device to control the analyte analysis
apparatus. In some embodiments, analyte analysis apparatuses herein
comprise more than one connection port. In some embodiments,
analyte analysis apparatuses herein comprise a connection port
adapter that allows a user to connect different digital processing
devices to the analyte analysis apparatus.
[0075] In some embodiments, max power that is drawn from a USB port
on a phone is 2.5 W. In some embodiments, the USB port provides 500
mA at 5V.
Communication
[0076] In various embodiments, the subject matter disclosed herein
includes a communication interface. In some embodiments, a
communication interface is embedded in a digital processing device.
In some embodiments, a communication interface operates on one or
more of the following transmission technologies: 3G communication
protocols, 4G communication protocols, 5G communication protocols,
IEEE 802.11 standards (e.g. Wi-Fi), Bluetooth protocols, short
range, RF communications, satellite communications, visible light
communications, and infrared communications. In some embodiments,
the analyte analysis apparatus communicates with a digital
processing device using one or more wired network protocols or
architectures.
[0077] In some embodiments, a communication interface is embedded
in an analyte analysis apparatus. In some embodiments, the analyte
analysis apparatus is configured to communicate with a digital
processing device such as a mobile phone, a tablet, a laptop, a
personal computer, a router, or other computing device. In some
embodiments, the analyte analysis apparatus is configured to
communicate wirelessly with a digital processing device. In some
embodiments, the analyte analysis apparatus is configured to
communicate with a digital processing device via a wired
connection. In some embodiments, the analyte analysis apparatus is
configured to communicate wirelessly with a remote server or
cloud-based network. The remote server or cloud-based can provide
data storage and/or data analysis, which can reduce energy usage by
the analyte analysis apparatus or the digital processing device.
Alternatively, in some embodiments, the data storage and/or data
analysis is performed by the analyte analysis apparatus or the
digital processing device. In some embodiments, data is temporarily
stored locally on the analyte analysis apparatus or digital
processing device, and optionally uploaded onto a database on a
remote server or cloud-based network. In some embodiments, data is
temporarily stored locally on the analyte analysis apparatus or
digital processing device when there is no network or internet
signal available for data uploading. In further embodiments, the
data is uploaded once the network or internet signal is
established, and the locally stored data is optionally deleted.
[0078] In some embodiments, a communication interface comprises a
wired communication interface. Examples include USB, microUSB,
Ethernet, lightning port, IEEE 1394 (e.g. FireWire), TCP/IP, RJ45,
serial ports, and parallel ports.
Optics
[0079] In various embodiments, the subject matter disclosed herein
includes a camera or an imaging device to obtain a measurement. In
some embodiments, the camera or imaging device obtains a
measurement by detecting and/or measuring light. In some
embodiments, the camera or imaging device captures an image. In
some embodiments, the camera or imaging device captures a photo
and/or video. In some embodiments, an image is processed to obtain
a measurement. For example, in some embodiments, a measurement
comprises quantification of an amount of signal such as light. In
some embodiments, a camera or an imaging device is embedded in a
digital processing device; for instance, a camera of a mobile
computing device, such as a camera on a phone, tablet, or laptop
computer. It is contemplated that analyte analysis apparatuses
described herein comprise at least one optical pathway through
which the camera of the mobile computing device can obtain an
image. Cameras on digital processing devices, in some embodiments
are integrated into the digital processing devices, such as a
camera on a phone, a tablet, or a laptop computer. In some
embodiments, external lenses can be adapted onto a camera on a
digital processing device to enable the camera to obtain a better
image. In some embodiments, the camera is a 12 megapixel camera. In
some embodiments, the camera is a 10, 9, 8, 7, 6, 5, 4, or 3
megapixel camera.
[0080] In some embodiments, analyte analysis apparatuses herein
comprise an optical pathway through which the camera on the mobile
computing device is able to obtain an image (e.g., of an assayed
biological sample). Optical pathways in analyte analysis
apparatuses herein, in some embodiments comprise a typical
epi-fluorescence optical pathway, known by those of skill in the
art, which detect fluorescent signals via a camera sensor in the
digital processing device or an external CMOS (complementary
metal-oxide-semiconductor) or CCD (charged coupled device) sensor
to determine a quantity of an analyte of interest in a sample. In
some embodiments, the optical pathway comprises a microscope
objective. In some embodiments, the optical pathway comprises an
endoscope objective.
[0081] In some embodiments, analyte analysis apparatuses herein
comprise a camera and an optical pathway through which the camera
is able to obtain an image. In some embodiments, an analyte
analysis apparatus is a stand-alone device that does not require a
digital processing device such as a smartphone to capture an image,
carry out analyte analysis, or upload data (e.g. captured image or
analyte analysis result) for storage. In some embodiments, the
analyte analysis apparatus comprises an optical sensor capable of
imaging the assayed biological sample. Optical pathways in analyte
analysis apparatuses herein, in some embodiments comprise a typical
epi-fluorescence optical pathway, known by those of skill in the
art, which detect fluorescent signals via a camera sensor in the
digital processing device or an external CMOS (complementary
metal-oxide-semiconductor) or CCD (charged coupled device) sensor
to determine a quantity of an analyte of interest in a sample. In
some embodiments, the optical pathway comprises a microscope
objective.
Fluidics
[0082] Analyte analysis apparatuses herein are capable of using a
variety of mechanisms for moving fluids through the device
including a syringe, a peristaltic pump, or a piezo pump. Fluids
move through the device using a compact fluidics chamber of a
fluidics cartridge. Exemplary fluidics cartridges are described
herein and in the case of analyte analysis apparatus, are sized and
shaped to fit inside or dock with the analyte analysis apparatus.
In some embodiments, the fluidics cartridge is inserted into the
analyte analysis apparatus. In some embodiments, the fluidics
cartridge is connected to the analyte analysis apparatus by a
hinge. In some embodiments, the fluidics cartridge comprises a
slider to cover the sample input port. In some embodiments, the
fluidics cartridge comprises a reservoir, for example a sample
reservoir, a buffer reservoir, and a waste reservoir. In some
embodiments, the fluidics cartridge comprises at least two
chambers, for example a test chamber and a control solution
chamber. In some embodiments, the fluidics cartridge comprises a
port, for example a sample input port, a sample reservoir port, a
waste reservoir port, and a buffer reservoir port. In some
embodiments, the buffer reservoir port also comprises a pump
interface location. In some embodiments, the fluidics cartridge
comprises a chip. In some embodiments, the fluidics cartridge
comprises two or more chips. In some embodiments, the fluidics
cartridge comprises a DEP chip. In some embodiments, the fluidics
cartridge and chip comprise an analyte analysis cartridge. In some
embodiments, the fluidics cartridge comprises a result field.
[0083] In some embodiments, disclosed herein are interchangeable or
disposable cartridges for use with the methods and devices
disclosed herein. In some embodiment, the cartridge comprises a
sample receiver. In other embodiments, the cartridge comprises at
least one fluidic channel. In yet other embodiments, the cartridge
comprises a sensor. Exemplary embodiments of analyte analysis
apparatuses (e.g. compact device) and cartridges that can be used
with the methods and devices disclosed herein can be found, for
example, in U.S. Provisional Application 62/313,120 entitled
"Disposable Fluidic Cartridge and Components," filed Mar. 24, 2016,
which is incorporated herein in its entirety for this
disclosure.
Electronics
[0084] In various embodiments, an analyte analysis apparatus
disclosed herein comprises an electronic chip to control the
analyte analysis apparatus. In some embodiments, an electronic chip
comprises a signal amplifier. In some designs, an electronic chip
comprises a differential amplifier.
[0085] In various embodiments, an electronic chip is configured to
control the cartridge to receive the biological sample. In further
embodiments, an electronic chip is configured to control the
cartridge to assay the biological sample.
[0086] In some embodiments, an electronic chip is configured to
energize the biological sample. In further embodiments, energizing
the biological sample comprises one or more of the following: an
ionization in the biological sample and applying an electric
current to the biological sample.
[0087] In some embodiments, an electronic chip is configured to
acquire signals from the assayed biological sample. Examples of
signals include, but not limited to, fluorescence,
non-fluorescence, electric, chemical, a current of ions, a current
of charged molecules, a pressure, a temperature, a light intensity,
a color intensity, a conductance level, an impedance level, a
concentration level (e.g., a concentration of ions), and a kinetic
signal.
[0088] In certain embodiments, signals comprise an alternating
current (AC) electrokinetic signal. In some cases, the signals
comprise one or more AC electrokinetic high field regions and one
or more AC electrokinetic low field regions.
Sensors
[0089] In various embodiments, the system, devices, and methods
described herein include one or more sensors, or use the same.
Examples of sensors include, but not limited to, RF tags, speed
sensors, acoustic sensors, water sensors, direction sensors,
temperature sensors, infrared sensors, liquid sensors, gas sensors,
carbon dioxide sensors, carbon monoxide sensors, oxygen sensors,
hydrogen sensors, ozone sensors, electrochemical gas sensors,
radiation sensors, breathalyzers, holographic sensors, motion
sensors, acceleration sensors, pressure sensors, torque sensors,
force sensors, gyroscopes, electric current sensors, and electric
voltage sensors.
[0090] In some embodiments, an array of sensors is implemented on a
device. In some embodiments, the sensors in the array are
connected. In some embodiments, two or more sensors in an array are
different types and/or shapes, or all sensors are the same
type/shape. In some embodiments, three or more sensors in an array
are a mix of sensors sharing the same type and/or shape and sensors
having different types and/or shapes.
[0091] In some applications, where multiple chip designs are
employed, it is advantageous to have a chip sandwich where two
devices are facing each other, separated by a spacer, to form a
flow cell. In various embodiments, devices are run sequentially or
in parallel. In some embodiments, multiple chip designs are used to
narrow the size range of material collected creating a band pass
filter. In some instances, current chip geometry (e.g., 80 um
diameter electrodes on 200 um center-center pitch (80/200) acts as
500 bp cutoff filter (e.g., using voltage and frequency conditions
around 10 Vpp and 10 kHz). In such instances, a nucleic acid of
greater than 500 bp is captured, and a nucleic acid of less than
500 bp is not. Alternate electrode diameter and pitch geometries
have different cutoff sizes such that a combination of chips should
provide a desired fragment size. In some instances, a 40 um
diameter electrode on 100 um center-center pitch (40/100) has a
lower cutoff threshold, whereas a 160 um diameter electrode on 400
um center-center pitch (160/400) has a higher cutoff threshold
relative to the 80/200 geometry, under similar conditions. In
various embodiments, geometries on a single chip or multiple chips
are combined to select for a specific sized fragments or particles.
For example, when a 600 bp cutoff chip leaves a nucleic acid of
less than 600 bp in solution, then that material is optionally
recaptured with a 500 bp cutoff chip (which is opposing the 600 bp
chip). This leaves a nucleic acid population comprising 500-600 bp
in solution. In some embodiments, size selection is accomplished
using a single electrode geometry, wherein nucleic acid of >500
bp is isolated on the electrodes, followed by washing, followed by
reduction of the ACEK high field strength (change voltage,
frequency, conductivity) in order to release nucleic acids of
<600 bp, resulting in a supernatant nucleic acid population
between 500-600 bp.
[0092] In some embodiments, the devices and methods described
herein allow for selection of nucleic acids of about 100 bp to
about 1,000 bp. In some embodiments, the devices and methods
described herein allow for selection of nucleic acids of at least
about 100 bp. In some embodiments, the devices and methods
described herein allow for selection of nucleic acids of at least
about 100 bp, 150 bp, 200 bp, 250 bp, 300 bp, 350 bp, 400 bp, 450
bp, or about 500 bp. In some embodiments, the devices and methods
described herein allow for selection of nucleic acids of at most
about 1,000 bp. In some embodiments, the devices and methods
described herein allow for selection of nucleic acids of at most
about 250 bp, 300 bp, 350 bp, 400 bp, 450 bp, 500 bp, 550 bp, 600
bp, 650 bp, 700 bp, 750 bp, 800 bp, 850 bp, 900 bp, 950 bp, or
about 1,000 bp. In some embodiments, the devices and methods
described herein allow for selection of nucleic acids of about 100
bp to about 150 bp, about 100 bp to about 200 bp, about 100 bp to
about 250 bp, about 100 bp to about 300 bp, about 100 bp to about
400 bp, about 100 bp to about 500 bp, about 100 bp to about 600 bp,
about 100 bp to about 700 bp, about 100 bp to about 800 bp, about
100 bp to about 900 bp, about 100 bp to about 1,000 bp, about 150
bp to about 200 bp, about 150 bp to about 250 bp, about 150 bp to
about 300 bp, about 150 bp to about 400 bp, about 150 bp to about
500 bp, about 150 bp to about 600 bp, about 150 bp to about 700 bp,
about 150 bp to about 800 bp, about 150 bp to about 900 bp, about
150 bp to about 1,000 bp, about 200 bp to about 250 bp, about 200
bp to about 300 bp, about 200 bp to about 400 bp, about 200 bp to
about 500 bp, about 200 bp to about 600 bp, about 200 bp to about
700 bp, about 200 bp to about 800 bp, about 200 bp to about 900 bp,
about 200 bp to about 1,000 bp, about 250 bp to about 300 bp, about
250 bp to about 400 bp, about 250 bp to about 500 bp, about 250 bp
to about 600 bp, about 250 bp to about 700 bp, about 250 bp to
about 800 bp, about 250 bp to about 900 bp, about 250 bp to about
1,000 bp, about 300 bp to about 400 bp, about 300 bp to about 500
bp, about 300 bp to about 600 bp, about 300 bp to about 700 bp,
about 300 bp to about 800 bp, about 300 bp to about 900 bp, about
300 bp to about 1,000 bp, about 400 bp to about 500 bp, about 400
bp to about 600 bp, about 400 bp to about 700 bp, about 400 bp to
about 800 bp, about 400 bp to about 900 bp, about 400 bp to about
1,000 bp, about 500 bp to about 600 bp, about 500 bp to about 700
bp, about 500 bp to about 800 bp, about 500 bp to about 900 bp,
about 500 bp to about 1,000 bp, about 600 bp to about 700 bp, about
600 bp to about 800 bp, about 600 bp to about 900 bp, about 600 bp
to about 1,000 bp, about 700 bp to about 800 bp, about 700 bp to
about 900 bp, about 700 bp to about 1,000 bp, about 800 bp to about
900 bp, about 800 bp to about 1,000 bp, or about 900 bp to about
1,000 bp. As described herein, selection of nucleic acids of a
certain size or range indicate that at least 70%, 80%, 90%, 95%, or
99% of the selected nucleic acids are within that size or range. As
an illustrative example, selection of nucleic acids of about 300 bp
to about 600 bp can indicate that about 90% of the nucleic acids
are about 300 bp to about 600 bp. In some embodiments, sensor
readout is fully multiplexed. In further embodiments, multiplexing
is based on rows and/or columns. A multiplexing example is 5 bit by
4 bit--nine control lines and one additional signal line, resulting
in a total of ten lines.
[0093] In some embodiments, a DEP electrode I/O is advantageously
laid out as more than one line.
[0094] In some embodiments, a sensor comprises a surface
passivation organic layer.
[0095] In another embodiment, a destructive sensing method would be
to not implement a hydrogel coating on the chip surface, turn on
the DEP field, and allow the analytes of interest to burn or
denature on the surface of the electrodes (usually the hydrogel
layer is there as a protective layer to prevent this very thing
from occurring). As these analytes accumulate on the surface of the
electrodes, the electrical characteristics of the electrodes
(resistance, capacitance, impedance, or a combination thereof)
would change, and these changes are measurable by using sense
circuitry built into the analyte analysis apparatus. Alternatively,
in other embodiments discussed earlier herein, this method looks
for a change in impedance/resistance with the hydrogel layer still
on the surface of the chip.
[0096] In another embodiment, the hydrogel is functionalized with
different moieties that can be used for sensing such as RGD
peptides for cell adhesion, glucose sensor, ion sensors for water
purification, thermally responsive hydrogels for characterization
of biochemical reactions. By determining the ionic change in the
hydrogel, the rate or levels of activity can be determined.
Digital Processing Device
[0097] In various embodiments, the subject matter described herein
include a digital processing device, or use of the same. FIG. 5
shows a digital processing device 510 that is programmed or
otherwise configured to carry out executable instructions. In some
embodiments, the digital processing device is programmed to select
one or more ads and/or one or more questions based on user
information and/or setting information. In some embodiments, the
digital processing device is an electronic device of a user. In
some embodiments, the digital processing device is a computer
system that is remotely located with respect to the user (e.g., a
remote server). In some embodiments, the digital processing device
is a mobile computing device. In further embodiments, the digital
processing device includes one or more hardware central processing
units (CPU) 520 that carry out the device's functions. In still
further embodiments, the digital processing device further
comprises an operating system and/or application 560 configured to
perform executable instructions. In some embodiments, the operation
system or application 560 comprises one or more software modules
590 configured to perform executable instructions (e.g., a data
analysis module). In some embodiments, the digital processing
device is optionally connected a computer network 580. In further
embodiments, the digital processing device is optionally connected
to the Internet such that it accesses the World Wide Web. In still
further embodiments, the digital processing device is optionally
connected to a cloud computing infrastructure. In other
embodiments, the digital processing device is optionally connected
to an intranet. In other embodiments, the digital processing device
is optionally connected to a data storage device.
[0098] In accordance with the description herein, suitable digital
processing devices include, by way of non-limiting examples, server
computers, desktop computers, laptop computers, notebook computers,
sub-notebook computers, netbook computers, netpad computers,
set-top computers, handheld computers, Internet appliances, mobile
smartphones, tablet computers, personal digital assistants, video
game consoles, and vehicles. Those of skill in the art will
recognize that many smartphones are suitable for use in the system
described herein. Non-limiting examples of smartphones include
those using mobile operating systems such as Android, iOS, Tizen,
Sailfish OS, BlackBerry OS, Windows Mobile, Symbian, Bada, webOS,
Palm OS, and Ubuntu Touch. Those of skill in the art will also
recognize that select televisions, video players, and digital music
players with optional computer network connectivity are suitable
for use in the system described herein. Suitable tablet computers
include those with booklet, slate, and convertible configurations,
known to those of skill in the art.
[0099] In some embodiments, the digital processing device includes
an operating system 560 configured to perform executable
instructions. The operating system is, for example, software,
including programs and data, which manages the device's hardware
and provides services for execution of applications. Those of skill
in the art will recognize that suitable server operating systems
include, by way of non-limiting examples, FreeBSD, OpenBSD,
NetBSD.RTM., Linux, Apple.RTM. Mac OS X Server.RTM., Oracle.RTM.
Solaris.RTM., Windows Server.RTM., and Novell.RTM. NetWare.RTM..
Those of skill in the art will recognize that suitable personal
computer operating systems include, by way of non-limiting
examples, Microsoft.RTM. Windows.RTM., Apple.RTM. Mac OS X.RTM.,
UNIX.RTM., and UNIX-like operating systems such as GNU/Linux. In
some embodiments, the operating system is provided by cloud
computing.
[0100] In some embodiments, the device includes a storage 530
and/or memory device 550. The storage and/or memory device is one
or more physical apparatuses used to store data or programs on a
temporary or permanent basis. In some embodiments, the device is
volatile memory and requires power to maintain stored information.
In some embodiments, the device is non-volatile memory and retains
stored information when the digital processing device is not
powered. In further embodiments, the non-volatile memory comprises
flash memory. In some embodiments, the non-volatile memory
comprises dynamic random-access memory (DRAM). In some embodiments,
the non-volatile memory comprises ferroelectric random access
memory (FRAM). In some embodiments, the non-volatile memory
comprises phase-change random access memory (PRAM). In other
embodiments, the device is a storage device including, by way of
non-limiting examples, CD-ROMs, DVDs, flash memory devices,
magnetic disk drives, magnetic tapes drives, optical disk drives,
and cloud computing based storage. In further embodiments, the
storage and/or memory device is a combination of devices such as
those disclosed herein.
[0101] In some embodiments, the digital processing device includes
a display 540 to send visual information to a user. In some
embodiments, the display is a cathode ray tube (CRT). In some
embodiments, the display is a liquid crystal display (LCD). In
further embodiments, the display is a thin film transistor liquid
crystal display (TFT-LCD). In some embodiments, the display is an
organic light emitting diode (OLED) display. In various further
embodiments, on OLED display is a passive-matrix OLED (PMOLED) or
active-matrix OLED (AMOLED) display. In some embodiments, the
display is a plasma display. In other embodiments, the display is a
video projector. In some embodiments, the display is a touchscreen.
In still further embodiments, the display is a combination of
devices such as those disclosed herein.
[0102] In some embodiments, the digital processing device includes
an interface 570 for interacting with and/or receiving information
from a user. In some embodiments, the interface comprises a
touchscreen. In some embodiments, the interface comprises an input
device. In some embodiments, the input device is a keyboard. In
some embodiments, the input device is a pointing device including,
by way of non-limiting examples, a mouse, trackball, track pad,
joystick, game controller, or stylus. In some embodiments, the
input device is a touch screen or a multi-touch screen. In other
embodiments, the input device is a microphone to capture voice or
other sound input. In other embodiments, the input device is a
camera or video camera to capture motion or visual input. In still
further embodiments, the input device is a combination of devices
such as those disclosed herein.
[0103] In some embodiments, user data (e.g. user profile, user
information, and analyte analysis) stored in the digital processing
device is encrypted. In some embodiments, third party applications
are blocked from accessing private information stored on the
digital processing device.
User Interface
[0104] In various embodiments, the subject matter herein includes a
user interface for an individual to input information and select
analytes to be tested as well as to receive the results of the
assay.
[0105] In various embodiments, a user interface comprises one or
more interface elements allowing a user to interact with devices,
apparatuses, or systems described herein. In various embodiments,
the user interface comprises physical interactive elements such as
hard buttons (e.g., physically tangible buttons), knobs, sliders,
switches, a keypad, microphones, and/or cameras. In some
embodiments, physical interactive elements provide haptic or
tactile feedback in response to a touch action. In various
embodiments, a user interface comprises a display. In some
embodiments, the display is a touchscreen such as a resistive
touchscreen or a capacitive touchscreen. In some embodiments, a
touchscreen comprises one or more soft interface elements. In some
embodiments, a soft interface element on the touchscreen is a soft
button or icon for receiving user input or instructions. In some
embodiments, a touchscreen provides haptic or tactile feedback in
response to a touch action on the touchscreen. In some embodiments,
the interface provides a selection of assays or tests for the user
to select. In some embodiments, the interface displays a time to
completion for a selected assay or test. In some embodiments, the
interface displays a selection of ads for a user to select for
viewing. In some embodiments, the display 540 is part of the
interface 570.
[0106] In some embodiments, the interface comprises a security
protocol to prevent unauthorized access to user information. In
some embodiments, the interface requires user authentication before
allowing a user to view results of an analyte analysis. In some
embodiments, the interface requires user authentication before
allowing a user to open an analyte analysis program. In some
embodiments, user information is encrypted and requires user
authentication to be decrypted. In some embodiments, user
authentication is provided via at least one of biometric
authentication (e.g. fingerprint scanner, retina scanner), password
authentication, and security question authentication.
[0107] In some embodiments, the interface is a web portal allowing
user access to information. In some embodiments, the web portal
comprises HIPAA-compliant security protocols to protect user
information. In some embodiments, the web portal enables a user to
track information specific to the user. In some embodiments, the
web portal enables an authorized user to track information not
specific to the user (e.g. a doctor authorized to track information
for his patient).
Non-Transitory Computer Readable Storage Medium
[0108] In various embodiments, the subject matter disclosed herein
include one or more non-transitory computer readable storage media
encoded with a program including instructions executable by the
operating system of an optionally networked digital processing
device. In further embodiments, a computer readable storage medium
is a tangible component of a digital processing device. In still
further embodiments, a computer readable storage medium is
optionally removable from a digital processing device. In some
embodiments, a computer readable storage medium includes, by way of
non-limiting examples, CD-ROMs, DVDs, flash memory devices, solid
state memory, magnetic disk drives, magnetic tape drives, optical
disk drives, cloud computing systems and services, and the like. In
some cases, the program and instructions are permanently,
substantially permanently, semi-permanently, or non-transitorily
encoded on the media.
Computer Program
[0109] In various embodiments, the subject matter disclosed herein
include at least one computer program, or use of the same. A
computer program includes a sequence of instructions, executable in
the digital processing device's CPU, written to perform a specified
task. Computer readable instructions may be implemented as program
modules, such as functions, objects, Application Programming
Interfaces (APIs), data structures, and the like, that perform
particular tasks or implement particular abstract data types. In
light of the disclosure provided herein, those of skill in the art
will recognize that a computer program may be written in various
versions of various languages.
[0110] The functionality of the computer readable instructions may
be combined or distributed as desired in various environments. In
some embodiments, a computer program comprises one sequence of
instructions. In some embodiments, a computer program comprises a
plurality of sequences of instructions. In some embodiments, a
computer program is provided from one location. In other
embodiments, a computer program is provided from a plurality of
locations. In various embodiments, a computer program includes one
or more software modules. In various embodiments, a computer
program includes, in part or in whole, one or more web
applications, one or more mobile applications, one or more
standalone applications, one or more web browser plug-ins,
extensions, add-ins, or add-ons, or combinations thereof.
[0111] In some implementations, analyte analysis apparatuses herein
are controlled by a user using a computer program on a digital
processing device, such as a phone, tablet, or laptop computer.
Computer programs for analyte analysis apparatuses are also capable
of performing analysis of the output data.
[0112] In some embodiments, a computer program comprises a software
module comprising a data analysis module configured to analyze
signals of an assayed biological sample. In further embodiments,
analyzing the signals comprises a use of a statistical analysis. In
some cases, analyzing the signals comprises comparing the signals
with a signal template. There are various analyses, which can be
combined to assemble an analysis module in the computer program.
Examples of analyzing the signals include: analyzing strength of
the signals, analyzing a frequency of the signals, identifying a
spatial distribution pattern of the signals, identifying a temporal
pattern of the one or more signals, detecting a discrete
fluctuation in the signals corresponding to a chemical reaction
event, inferring a pressure level, inferring a temperature level,
inferring a light intensity, inferring a color intensity, inferring
a conductance level, inferring an impedance level, analyzing
patterns of one or more AC electrokinetic high field regions and
one or more AC electrokinetic low field regions, and analyzing a
chemical reaction event. In still further embodiments, a chemical
reaction event comprises one or more of the following: a molecular
synthesis, a molecular destruction, a molecular breakdown, a
molecular insertion, a molecular separation, a molecular rotation,
a molecular spinning, a molecular extension, a molecular
hybridization, a molecular transcription, a sequencing reaction,
and a thermal cycling. In some embodiments, a computer program
comprises a software module presenting a result obtained by the
data analysis module on a display of a digital processing device.
In some embodiments, a computer program comprises a software module
providing an interface to allow upload of a result to an online
database. In some embodiments, a computer module comprises a
software module providing a query interface allowing search of the
online database.
User Information, Ads, and Questions
[0113] In some embodiments, the systems and methods described
herein comprise a software module for collecting user information
to develop a user profile. In some embodiments, user information
comprises one or more of a user name, a user ethnic background, a
user age, a user height, a user weight, a user body fat percentage,
medical history, and other medical information, such as a diagnosis
and one or more symptoms. In some embodiments, medical information
includes one or more of a diagnosis, past or present treatment
regimen (e.g., dosage, frequency, duration, etc) and outcome, past
and/or present symptoms, genetic profile (including elevated risk
associations with certain diseases), family history of illness,
drug or other allergies, blood type, past injuries or illnesses,
surgery, past and/or current medication, mental health history, and
information pertaining to adherence to treatment regimen (e.g.,
pharmacy records indicating whether user regularly refills
prescription, self-reporting, physician reports, electronic
recordings, and blood or urine assays). In some embodiments, the
user profile includes price information for drug(s). In some
embodiments, price information for drug(s) is obtained from the
user (e.g., during setup of the user profile and/or via question(s)
presented to the user during analyte analysis). In some
embodiments, user information comprises non-medical information
such as one or more of user home address, user zip code, user
income, user family income, user job sector, user job function, any
owned or operated business, type of business, number of employees,
size and location(s) of the business, user credit rating, user
insurance coverage (e.g., health insurance, home insurance, vehicle
insurance, life insurance, etc.), education (e.g., degrees,
licenses, credentials, or certifications), marital status, number
and/or age of children, language(s), information on relatives of
the user (e.g., relationship with user, location, marital status,
number and/or age of children, or degree of contact), user interest
in various topics (e.g., entertainment, movies, sports,
automobiles, politics, economics, health, law, education, science,
or technology), user brand preferences, user spending information
(e.g., amount spent on traveling, food, entertainment, and/or
clothing in the past year), and social media information (e.g.,
Twitter handle, Facebook profile, user preference settings in
social media). In some embodiments, user information is obtained
through one or more methods as described herein such as, for
example, presenting questions to the user or accessing user
information from the digital processing device. In some
embodiments, user information is obtained by accessing publicly
available information. Publicly available information can include
type of home and price (e.g., based on latest recorded sale
obtained from a county recorder), social media postings, marriage
and/or divorce records, warrants and/or arrests, court cases,
obituaries, immigration records, professional licensing records,
and business licenses.
[0114] In some embodiments, the systems and methods described
herein comprise a software module for geo-tagging an analyte
analysis result with a current location of the digital processing
device where the analyte analysis takes place. In some embodiments,
the location of the digital processing device is obtained without
geo-tagging the analyte analysis. In some embodiments, the location
is a real-time location. As used herein, geo-tagging refers to the
process of adding geographical identification metadata. For
example, in some embodiments, a geo-tagged analyte analysis
comprises geographical location metadata indicating the analyte
analysis was carried out in a certain geographic location. In some
embodiments, the geographic location comprises one or more of a
continent, a nation, a state, a province, a territory, an island, a
city/town/village, an address, and coordinates (e.g. longitude and
latitude). In some embodiments, the geographic location is a
specific location or an area around a location. In some
embodiments, a result (e.g. of an analyte analysis) is
time-stamped. For example, an analyte analysis that is performed is
optionally time-stamped with the date and/or time when the result
was generated.
[0115] In some embodiments, the systems and methods described
herein comprise an online database. In some embodiments, the online
database stores information for an individual (e.g. test or analyte
analysis results, user profile, etc). In some embodiments, the
online database obtains information for an individual from the
social network or other online community. In some embodiments, the
online database provides information for the individual to the
social network or other online community. In some embodiments, an
online database interface allows an individual or user to transfer
information between the online database and the social network or
online community. For example, in some embodiments, an individual
posts a clean test result stored on the online database on a social
network. In some embodiments, the online database comprises a
social network or other online community.
[0116] In some embodiments, the systems and methods described
herein comprise a software module for obtaining usage statistics
(e.g. operating system, cellular network, Wi-Fi network) from the
digital processing device. In some embodiments, the software module
obtains usage statistics for one or more of email use, web
browsing, video streaming, web searching, app usage, online
shopping, ad views, and ad clicks. In some embodiments, usage
statistics are shared with a third party such as, for example, a
pharmaceutical company.
[0117] FIG. 3 provides an illustrative flow chart of one process
for selecting ads and/or questions suitable for presenting to a
user. In some embodiments, a user profile is developed using
information entered by a user 301 (e.g., when a user first sets up
a profile). A user profile is developed using information obtained
from the digital processing device of the user 302. For example, in
some embodiments, information stored on the device is accessed
after obtaining authorization from the user to access one or more
of a contact list, browsing history, social media, email, text
messages, or other user information on the digital processing
device. In further embodiments, a user optionally chooses to
authorize access in place of being presented with one or more ads
and/or one or more questions in association with a result (e.g., a
dielectrophoresis-based test result). In further embodiments,
authorization to access user information is limited to meta-data
and/or non-identifying information. In some embodiments, user
information is obtained from publicly available information such as
a social media profile and public postings by the user. In some
embodiments, a user profile is developed using publicly available
information about the user 303.
[0118] In some embodiments, a user is presented with one or more
ads in association with an assay or test (e.g., the user has to
watch one or more ads in order to obtain a test result generated
using the systems or methods described herein). In other
embodiments, a user is presented with one or more questions to be
answered in association with an assay or test. In some embodiments,
a user chooses between watching one or more ads and answering one
or more questions in association with an assay or test. In some
embodiments, the result of the assay or test is locked until the
user watches one or more ads or answers one or more questions
presented in association with the assay or test. In some
embodiments, the user has a choice of watching one or more ads,
answering one or more survey questions, or paying for the assay or
test. In some embodiments, the user makes this choice when
configuring a user profile. In some embodiments, a user is
presented with one or more ads and one or more questions in
association with an assay or test. FIGS. 6A-6F illustrate an
exemplar embodiment of the process by which a user utilizes the
systems and devices described herein to execute analyte testing and
view the test results. An exemplary embodiment of an application
interface or display of an electronic device is shown in FIG. 6A in
which the user is presented with several options for viewing the
test result. Once the user makes his choice, the display may then
show the selected choice such as the exemplary survey question
shown in FIG. 6B. In some cases, testing progress may be indicated
such as by a progress bar as shown. After the user has made a
choice and viewed or answered the ad or question, respectively, the
device may allow the user to view the test results (FIG. 6C). The
optional recommendations accompanying the test results may vary
(e.g. depending on user profile, past treatment information, etc)
such as shown in FIGS. 6D and 6E. Finally, the user may choose from
various options in a software application or web portal such as the
health portal shown in FIG. 6F. The health portal may provide
options to perform a test, view or configure the user profile, view
testing history (time and results of previous tests), data sharing,
search, ask anything, and settings. In various embodiments, the
health portal allows the user to conduct testing such as by the
analyte analysis apparatuses described herein. The data sharing
option can allow a user to give authorization to other entities or
persons such as healthcare providers or third parties to view
certain health data. In some cases, the search option allows a user
to search through his or her test results, identify healthcare
providers, find treatment options, and obtain other relevant
information. The "ask anything" option may leverage the algorithms
described herein to address user queries such as, for example,
utilizing a machine learning algorithm to identify a suggested
treatment based on the user profile, past treatment history, and
treatment availability. The settings may be used to setup user
preferences (e.g. whether to pay, view an ad, or answer a survey
question in order to view test results).
[0119] The one or more ads and one or more questions can be
presented at different stages during the assay or test. For
example, in some embodiments, a user is presented with an ad while
the assay or test is running, and then presented with a question in
order to unlock the result for viewing. In various embodiments, the
one or more ads or one or more questions are selected as suitable
for presenting to the user 304. In some embodiments, suitable ads
and/or questions are selected based on how the ads/questions (or
setting information for said ads/questions) match up with the user
profile as described throughout this application. In some
embodiments, the user response to the ads and/or questions is
stored and used to further develop the user profile 305. For
example, a negative response to a question of whether the user
likes horror movies can be added to the user profile to screen out
the user from receiving ads for horror movies in the future. As
another example, a user's decision to select a movie ad in order to
view an extended trailer associated with the ad is stored as an
indication of user interest in that movie, the movie genre, the
director, the actor(s), or other aspects of the movie. Accordingly,
the next selection of suitable ads or questions will be based on
the user profile enhanced with this additional information 306. In
some embodiments, the process of selecting suitable ads and/or
questions to be displayed to a user and then enhancing the user
profile with the responses is an iterative process that is further
enhanced as additional information about the user is obtained with
each cycle (305, 306). In various embodiments, the systems and
methods described herein provide data consumers with access to the
plurality of user profiles and/or the information they contain 307.
In some embodiments, one or more ads comprise at least 1, 2, 3, 4,
5, 6, 7, 8, 9, or 10 or more ads. In some embodiments, one or more
ads comprise no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more
ads. In some embodiments, one or more ads comprise between 1 and 5,
2 and 6, 3 and 7, 4 and 8, 5 and 9, or 6 and 10 ads. In some
embodiments, one or more questions comprise at least 1, 2, 3, 4, 5,
6, 7, 8, 9, or 10 or more questions. In some embodiments, one or
more questions comprise no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, or
10 or more questions. In some embodiments, one or more questions
comprise between 1 and 5, 2 and 6, 3 and 7, 4 and 8, 5 and 9, or 6
and 10 questions.
[0120] In some embodiments, one or more questions presented to a
user are configured to obtain additional health information. In
some embodiments, one or more questions presented to a user are
configured to obtain additional non-health information. In some
embodiments, the questions are based on user information and/or
test results. In some embodiments, the questions are configured as
multiple choice questions, fill in the blank, true or false, binary
choice, short answer, matching, preference rankings, or other
format. In some embodiments, a user is asked one or more questions
of varying question types (and sometimes in combination with ads)
in a progression over time as the user repeatedly uses the systems
or devices described herein. As an illustrative example, a user is
presented with a binary question on whether he or she is interested
in movies in order to access the first test result. If the user
answers yes, then the next question during a second test asks the
user to rank a preference for movie genres from highest to lowest
for action, romantic, drama, comedy, and horror. Based on these
choices, during the third test, the user is presented with an ad
for an upcoming movie release in the user's highest rated movie
genre. In some embodiments, a user is presented with a choice
between different ads to view. In some embodiments, the choice
includes a description of each ad. In some embodiments, a user is
presented with a choice between one or more ads or questions. As an
illustrative example, a user is presented with a choice between
watching an ad for a drug or an ad for a car and answering a
question about his sports preference. As another example, a user is
presented with a first question asking whether the user is taking a
particular medication, and if the user answers in the affirmative,
a second question is presented asking the price of the medication.
In some embodiments, one or more ads are presented to a user based
on a disease/condition and/or treatment (e.g. provided by a user
during user profile setup or answered in a question). For example,
in some embodiments, ads for a group of drugs commonly administered
together as part of a chemotherapeutic treatment regimen are
presented to a user who indicated he was just diagnosed with
cancer. In some embodiments, an ad comprises clinical trial
information and is presented to a user whose user profile
information makes the user an eligible clinical trial
participant.
[0121] In some embodiments, user profile information is used to
enhance treatment. For example, in some embodiments, user blood
type is used to identify potential organ donors for a user
suffering from or at risk for organ failure.
[0122] In some embodiments, one or more ads or questions are
presented to a user of the digital processing device based on the
location of the device. For example, a user uses a digital
processing device and an analyte analysis apparatus described
herein to perform an analyte analysis of a biological material of
an individual (in this case, the user himself). The analyte
analysis is geo-tagged with the location of the user and his device
based on GPS and/or Wi-Fi triangulation data obtained from the
device. The geo-tagged analyte analysis is then uploaded to a
database comprising a plurality of geo-tagged analyte analyses. In
some embodiments, the database is accessible to an authorized user.
For example, in some embodiments, an authorized user is a
governmental organization such as the CDC, a non-governmental
organization, an epidemiologist, a researcher or research
institution, or a drug company. In some embodiments, the authorized
user uses the geo-tagged analyte analyses to determine changes to a
disease, demand for a drug or treatment, spread of a disease,
and/or identify a need for aid in a geographic location.
[0123] In some embodiments, the location of the device/user is used
to select ad(s) and/or question(s) to present to a user. In some
embodiments, the location is matched against one or more ads or
questions to determine relevant ads or questions. For example, a
user uses a digital processing device and an analyte analysis
apparatus described herein to perform an analyte analysis of a
biological material. The device determines its location and
provides the location to a remote server. The remote server then
compares the location against a database of ads/questions to select
one or more ads or questions to present to the user. In this
example, the user is located in a particular geographic region
known for having a high UV index. Accordingly, the remote server
selects an ad for sunscreen and an ad for UV-protecting rash guards
for the digital processing device to present to the user. In some
embodiments, an algorithm automatically selects one or more ads or
questions based on location of the device without requiring human
input.
[0124] In some embodiments, an ad is targeted to a category or
demographic. In some embodiments, a demographic comprises one or
more of an age range, a gender, an ethnicity, a nationality,
household income, geographic location, home ownership,
disabilities, education, employment status, health status (e.g.
cancer diagnosis), children, type of car(s), marital status, and
credit rating. In some embodiments, an ad is targeted to a healthy
demographic (e.g. lacking a particular disease diagnosis). In some
embodiments, an ad for cancer screening and/or detection is
targeted to a healthy demographic.
[0125] In some embodiments, user information obtained using the
systems and methods described herein is used to build a user
profile (as used herein, user profile encompasses provider profile,
which is a type of user profile limited to healthcare providers).
In some embodiments, a plurality of user profiles is stored on one
or more databases accessible by a data consumer. In some
embodiments, a data consumer is a user (e.g., person who is getting
tested), a physician, a nurse, a healthcare worker, a
pharmaceutical company, an advertiser, a researcher or research
group, a university, a government agency, or other individual or
organization. In some embodiments, a data consumer pays for access
to the user and/or provider profiles. In some embodiments, a data
consumer is authorized to access user/provider profiles and/or data
associated with said profiles. For example, data associated with
said profiles can include metadata (e.g. timing/frequency of
certain tests performed by diagnostic devices). In some
embodiments, a data consumer agrees to view one or more ads and/or
answer one or more questions in exchange for accessing user
profiles. In some embodiments, the systems and methods described
herein comprise a software module for processing and curating the
user information and/or user profiles so that they allow searching
and/or filtering of data by data consumers. In some embodiments,
user profiles are anonymized to remove identifying information
and/or presented to data consumers in accordance with HIPAA
requirements (e.g., the "limited health data" described elsewhere
herein). In some embodiments, data consumers are divided into
paying and non-paying data consumers based on their classification.
For example, in some embodiments, a pharmaceutical company or large
organization pays to obtain access, while individuals (e.g., a user
utilizing the systems and methods herein to obtain test results)
view ads and/or answer questions to obtain access to the
information. In some embodiments, the user profile comprises health
information relevant to a data consumer such as, for example, a
pharmaceutical company. As an illustrative example, a
pharmaceutical company looking for ideal participants in a clinical
trial for a new breast cancer drug screens the plurality of
anonymized user profiles to select for early stage breast cancer
patients between the ages of 20 and 35 who do not smoke and are
indicated as having high adherence to treatment regimen (e.g.,
based on pharmacy refill records for a past treatment regimen). The
company then is able to send an anonymized message (i.e., company
does not know identities of the recipients) to eligible candidates
inviting them to participate in the clinical trial. In some
embodiments, the message comprises one or more questions presented
to each user. Alternatively, in another example, a pharmaceutical
company is interested in marketing a complementary therapy for
users being treated for a particular illness or condition.
Accordingly, the pharmaceutical company screens user profiles for
users who are currently being treated for the illness or condition
and have indicated (e.g., by answering questions) a willingness to
try complementary therapies with certain benefits such as, for
example, mitigating side effects of their main treatment regimen.
The company then targets ads for complementary therapies to this
group of users using the systems and methods described herein.
[0126] In some embodiments, a user profile comprises non-health
information that is useful to an advertiser. As an illustrative
example, a mortgage company wants to target home mortgage
re-financing ads to users who have recently bought a home. First,
the mortgage company screens the user profiles for users who have
purchased a home in the past five years. This information is
obtained either from the user directly answering the question or
from public records such as, for example, obtaining purchase
records for the property located at the user's home address. The
mortgage company further screens for users who exceed a minimum
income threshold or other factors relevant to suitability for home
mortgage re-financing. The company then targets home mortgage
re-financing ads to this user group.
[0127] In some embodiments, the systems and methods described
herein comprise a software module soliciting and/or receiving user
feedback on the performance or accuracy of the analyte analysis. In
some embodiments, user feedback is used in product development to
improve performance of the systems and methods for performing
analyte analysis.
[0128] In some embodiments, advertisers or third-party party ad
networks provide one or more ads to be presented to one or more
users. In some embodiments, the ads are targeted ads generated
based on user information from user profiles. In some embodiments,
advertisers provide one or more questions to be presented to one or
more users. In some embodiments, the one or more questions
presented to users are from surveys. In some embodiments, a survey
is broken up into separate rounds of questions presented to users
over time. As an illustrative example, a survey of 6 questions are
divided into groups of one or more questions that are presented
each time a user answers questions in association with the assay or
test. In some embodiments, surveys are market description surveys,
market profiling surveys, tracking surveys, purchase analysis
surveys, customer expectation surveys, new product concept surveys,
brand equity surveys, habits and uses surveys, or other
surveys.
[0129] In some embodiments, a computer program comprises a software
module that selects one or more ads from a population of ads. In
some embodiments, the selected ad is presented in association with
the result obtained by the data analysis module. In some
embodiments, the selected ad is presented prior to the performance
of an assay or test. In some embodiments, the selected ad is
presented during the performance of an assay or test. In some
embodiments, the selected ad is presented during a data analysis
step to obtain a result by the data analysis module. In some
embodiments, the ad is selected based on the individual. For
example, in some embodiments, the selected ad is targeted based on
user information for the individual (e.g., an ad for a local sports
team based on the individual's address). In some embodiments, the
ad is selected based on the analyte. For example, an ad for genome
sequencing is selected that includes sequencing a gene associated
with the analyte. In some embodiments, the ad is selected based on
the result. As an illustrative example, a health insurance ad is
selected when the result is a positive indication for a biomarker
associated with an illness. In some embodiments, the ad is
presented on a display of a digital processing device. In some
embodiments, the ad is provided by one or more third-party ad
networks.
[0130] FIG. 4 shows an illustrative embodiment of a process by
which advertisers configure ads to be displayed to users. In some
embodiments, a population of ads comprises ads configured by one or
more third-party ad networks (401, 402, 403). In some embodiments,
third-party ad networks are advertisers or advertising agencies. In
some embodiments, advertisers configure one or more ads with a
certain budget (e.g., a certain number of ad displays at a certain
rate per view and/or rate per click). In some embodiments, an ad is
configured with various information settings by the third-party ad
network. In some embodiments, information settings include one or
more of advertising type (e.g., product, service, and/or
informational), payment (price or free), product, or service type
(e.g., medication, entertainment, counseling, etc.). In some
embodiments, information settings include one or more advertiser
preferences such as, for example, target demographic information
such as age, gender, ethnicity, nationality, income, occupation,
marital status, and other user information as described elsewhere
herein. In some embodiments, an advertiser selects the target
population of user profiles to be presented with an ad (e.g., by
filtering the plurality of user profiles to arrive at a defined
target group of users). In other embodiments, an advertiser selects
advertiser preferences, and the ads are displayed to users based on
said preferences without being limited to a pre-defined user group.
As an illustrative example, an advertiser preference specifies that
an ad is to be displayed to users who fit a certain target
demographic profile or who select the ad when presented with two or
more choices. The configured ads are then pooled together into a
population of ads 404. In some embodiments, as users begin to use
the systems and methods described herein, configured ads are
selected as suitable for display based on user profile and the ad
information 405 (e.g., advertiser preferences, setting information,
ad content, etc.). In some embodiments, configured ads are no
longer selected once the associated advertising budget is depleted
406.
[0131] In some embodiments, one or more ads are selected based on
user information. In some embodiments, the ads are selected by
matching advertiser-configured information settings for the ads
against user information. In some embodiments, the systems and
methods described herein comprise a software module for performing
cohort analysis or behavioral analytics on the plurality of user
profiles stored on one or more databases. In some embodiments,
cohort analysis comprises dividing the plurality of user profiles
into groups or cohorts based on common user information shared
between members of each cohort (e.g., a cohort of cancer patients
who have stage I colon cancer). In some embodiments, cohort
analysis is used to help advertisers or data consumers better
understand user behavior. As an illustrative example, a
pharmaceutical company looking for participants in a clinical trial
for a cancer treatment does not have access to a sufficiently large
set of user profiles with information on adherence to treatment
regimen. In this example, the treatment has a strict dosage and
schedule that must be adhered to in order to result in a positive
outcome. Thus, the pharmaceutical company uses the systems and
methods described herein to perform cohort analysis using the
cohort of users who do have information on adherence to treatment
regimen to identify factors relevant to adherence. The company
discovers that certain user information correlates with adherence
to treatment regimen and is therefore able to use that information
to identify more potential clinical trial participants.
[0132] In some embodiments, an ad comprises a data link (e.g., an
Internet link) to additional content (e.g., a YouTube video, a
product website, or an online store). In some embodiments, an ad is
optionally selectable to cause the digital processing device to
access additional content. In various embodiments, the systems and
methods described herein comprise a software module for storing
information on selection and/or non-selection of ads by a user. In
some embodiments, the information is analyzed to estimate
responsiveness of the user to ads in general or to certain ad
categories. In some embodiments, user responsiveness is then used
to enhance future targeted ads. For example, a user who frequently
selects movie ads (e.g., clicks on the ad) will be directed to
additional content such as the movie website or an extended trailer
is assigned a high movie ad responsiveness score (e.g., as a
percentile amongst the plurality of user profiles). As a result,
some movie advertisers choose to target movie ads to users in the
top 50% of movie ad responsiveness out of the plurality of user
profiles.
[0133] In some embodiments, one or more of the result, the
individual, and the analyte is transmitted to a server or a
database, where an ad is selected from a population of ads provided
by one or more third-party ad networks. The ad is then configured
by selecting one or more ad content file(s) (e.g., text file,
graphics file, video file, and interactive file). In some
embodiments, the ad content file is selected based on user
profiles. For example, in the plurality of user profiles, some
users have a preference for watching video ads, while other users
have a preference for graphics files. Accordingly, in some
embodiments, an ad for the same product or service is shown to
different users using different content catered to the individual
preference of each user. In some embodiments, these preferences are
determined using user information from questions answered in
association with a test or assay. Alternatively, in some
embodiments, these preferences are determined by analyzing user
responsiveness to various ad types. For example, in some
embodiments, a user who predominantly (e.g., at least 50%, 60%,
70%, 80% or 90%) interacts with video file ads is determined to
prefer video content files to other forms of content files.
[0134] Many types of ad content files are suitable. In some
embodiments, suitable ad content files include text, documents,
e-books, audio, images (e.g., photographs, illustrations, etc.),
videos, multimedia (e.g., interactive elements, games, etc.), or
combinations of the same.
[0135] Many text formats are suitable including, by way of
non-limiting examples, Rich Text Format (RTF), TXT, ASCII, UTF-8,
and HTML formatted text. Many document formats are suitable
including, by way of non-limiting examples, Microsoft.RTM. Office
Word.RTM., Microsoft.RTM. Office PowerPoint.RTM., Microsoft.RTM.
Office Excel.RTM., DocBook, HTML, OpenDocument, PalmDoc, Portable
Document Format (PDF), Rich Text Format (RTF), and WordPerfect.
[0136] Many e-book formats are suitable including, by way of
non-limiting examples, plain text, hypertext markup language
(HTML), Amazon.RTM. Kindle.TM., Open Electronic Package,
TomeRaider, Arghos Diffusion, Flip Books, ANSI/NISO Z39.86 (DAISY),
FictionBook, Text Encoding Initiative, Plucker, Compressed HM,
Portable Document Format, PostScript, DjVu, Microsoft LIT, eReader,
Desktop Author, Newton eBook, Founder Electronics, Libris,
Mobipocket, EPUB, Broadband eBooks (BBeB), SSReader, TealDoc, IEC
62448, and Comic Book Archive file. Suitable e-books include those
formatted for viewing on, by way of non-limiting examples,
Apple.RTM. iPad.RTM., Amazon.RTM. Kindle.TM. Barnes & Noble
Nook.TM., Sony.RTM. Reader.TM., iRex iLiad, the Jinke Hanlin
eReader, Bookeen CyBook, Endless Ideas BeBook, and the Kobo.TM.
eReader.
[0137] Many audio formats are suitable including, by way of
non-limiting examples, MP3, WAV, AIFF, AU, Apple.RTM. Lossless,
MPEG-4, Windows Media.RTM., Vorbis, AAC, and Real Audio.RTM..
[0138] Many raster image formats are suitable including, by way of
non-limiting examples, Joint Photographic Experts Group (JPEG),
JPEG 2000, Exchangeable image file format (EXIF), Tagged Image File
Format (TIFF), RAW, Portable Network Graphics (PNG), Graphics
Interchange Format (GIF), Windows.RTM. bitmap (BMP), portable
pixmap (PPM), portable graymap (PGM), portable bitmap file format
(PBM), wireless bitmap (WBMP), and WebP. In some embodiments,
images are uncompressed (e.g., RAW format). In other embodiments,
images are compressed. Both lossy and lossless image CODECs are
suitable. Many vector image formats are suitable including, by way
of non-limiting examples, CGM and SWF. Both two-dimensional and
three-dimensional vector images are suitable.
[0139] Many video formats are suitable including, by way of
non-limiting examples, Windows.RTM. Media Video (WMV), Windows.RTM.
Media.RTM., Motion Picture Experts Group (MPEG), Audio Video
Interleave (AVI), Apple.RTM. QuickTime.RTM., RealMedia.RTM., Flash
Video, Motion JPEG (M-JPEG), WebM, and Advanced Video Coding High
Definition (AVCHD). In some embodiments, video is uncompressed
(e.g., RAW format). In other embodiments, video is compressed. Both
lossy and lossless video CODECs are suitable including, by way of
non-limiting examples, DivX.TM., Cineform, Cinepak, Dirac, DV,
FFV1, H.263, H.264, H.264 lossless, JPEG 2000, MPEG-1, MPEG-2,
MPEG-4, On2 Technologies (VPS, VP6, VP7, and VP8), RealVideo, Snow
lossless, Sorenson Video, Theora, and Windows Media Video
(WMV).
[0140] In some embodiments, image and/or video media are
standard-definition. In other embodiments, image and/or video media
are high-definition. In further embodiments, a high-definition
image or video frame includes at least 1280.times. about 720 pixels
or at least 1920.times. about 1080 pixels.
[0141] Many multimedia formats are suitable including, by way of
non-limiting examples, Adobe.RTM. Flash.RTM., Apple.RTM.
QuickTime.RTM., Microsoft.RTM. Silverlight.RTM., Java.TM., HTML 5,
XHTML 5, and Unity.RTM..
[0142] In some embodiments, an ad content file includes text and
graphics suitable for display on a user interface of a compact
electronic device.
[0143] In some embodiments, the systems and methods described
herein comprise a software module providing information on nearby
health systems. In some embodiments, a nearby health system is a
lab, a hospital, a doctor, a clinic, a test facility, or other
healthcare facility. In some embodiments, the information on a
nearby healthcare system comprises one or more of a location of a
healthcare system, service(s) offered, hours of operations, contact
information, and travel distance/time based on a current location
of the user.
[0144] In some embodiments, the systems and methods described
herein comprise a software module providing notifications and/or
reminders. In some embodiments, a reminder is provided to a user to
run a test. In some embodiments, a reminder is provided to a user
to take medication. In some embodiments, a notification is provided
to a user informing the user of doctor(s) and/or nearby support
group(s).
[0145] In some embodiments, the systems and methods described
herein comprise a software module providing a pay wall for a user
to obtain ad-free testing. In some embodiments, a user pays a flat
fee to obtain ad-free testing (e.g., ad-free and question-free). In
some embodiments, a user pays a subscription to obtain ad-free
testing.
Databases
[0146] In various embodiments, the subject matter disclosed herein
includes one or more databases, or use of the same to store
biological sequences, reference sequences, and test or assay
results. In view of the disclosure provided herein, those of skill
in the art will recognize that many databases are suitable for
storage and retrieval of the sequence information. In various
embodiments, suitable databases include, by way of non-limiting
examples, relational databases, non-relational databases, object
oriented databases, object databases, entity-relationship model
databases, associative databases, and XML databases. In some
embodiments, a database is internet-based. In further embodiments,
a database is web-based. In still further embodiments, a database
is cloud computing-based. In other embodiments, a database is based
on one or more local computer storage devices.
[0147] In some embodiments, a database comprises a network of
individuals or subjects. In some embodiments, the network of
individuals or subjects is a social network. In some embodiments,
the individuals are data consumers. In some embodiments, the
database comprises data analysis results obtained by the
individuals. In some embodiment, the database comprises a list of
analytes. In some embodiments, the individuals are anonymous. In
some embodiments, the database is searchable using a query
interface. In some embodiments, the database is searchable by an
individual. In some embodiments, the database is searchable by a
physician. In some embodiments, the database is searchable by a
researcher.
[0148] In some embodiments, the database stores user profiles
and/or user information associated with the test or assay results.
In some embodiments, the database is searchable by an advertiser.
The database can be searchable with varying restrictions based on
the party performing the search. For example, in some embodiments,
an advertiser is limited to anonymized user profile information
without having access to any health information, while the
physician of a user is able to access health information for that
user. Meanwhile, a researcher is able to access anonymized user
profile information and anonymized HIPAA-compliant health
information. In some embodiments, data stored in one or more
databases is encrypted. In some embodiments, third party
applications are blocked from accessing private information stored
in the one or more databases.
[0149] In some embodiments, the systems and methods described
herein comprise a first database having public access (e.g.,
members of the general public can access the database). In some
embodiments, the first database is anonymized and otherwise
HIPAA-compliant. In some embodiments, the first database provides
limited access to information or data stored within. For example,
in some embodiments, the first database only provides statistical
information such as prostate cancer rate in a certain age group,
and does not allow access to individual information. In some
embodiments, the systems and methods described herein comprise a
second database for non-public access. In some embodiments,
researchers or research institutions, corporations, healthcare
providers, or other non-public groups have access to the second
database. In some embodiments, the second database is anonymized
and otherwise HIPAA-compliant. In some embodiments, the second
database provides limited access to information or data stored
within. In some embodiments, one or more databases or phone
applications interface with healthcare system applications to share
and/or retrieve information. In some embodiments, one or more
databases connect to one or more exercise applications on a phone
to obtain user information (e.g., to add to the user profile).
Assays and Applications
[0150] In some embodiments, the methods described herein allow for
isolating and detecting an analyte using an assay, such as an
immunoassay or a nucleic acid or protein assay. In some
embodiments, the assay uses devices and systems suitable for
isolating or separating analytes from a fluid composition. In
various aspects, assays herein allow for a rapid procedure that
requires a minimal amount of material and/or results in a high
purity DNA isolated from biological samples. Assays and
applications herein comprise applying the biological sample to a
cartridge comprising an array of electrodes capable of generating
AC electrokinetic forces when the array of electrodes is energized.
In some embodiments a dielectrophoretic field is a component of AC
electrokinetic force effects. In some embodiments, the AC
electrokinetic force, including dielectrophoretic fields, comprises
high-field regions (positive DEP area where there is a strong
concentration of electric field lines due to a non-uniform electric
field) and/or low-field regions (negative DEP area where there is a
weak concentration of electric field lines due to a non-uniform
electric field). In some embodiments, the analyte comprises a
biomarker. In some embodiments, the analyte comprises a nucleic
acid. In some embodiments, the analyte comprises a protein.
[0151] In specific instances, the analytes are isolated in a field
region (e.g., a high field region) of the dielectrophoretic field.
In some embodiments, the assay further includes one or more of the
following steps: concentrating cells of interest in a first
dielectrophoretic field region (e.g., a low field DEP region),
lysing cells in the first dielectrophoretic field region, and/or
concentrating nucleic acid in a second dielectrophoretic field
region (e.g., a high field DEP region). In other embodiments, the
assay includes one or more of the following steps: concentrating
cells in a first dielectrophoretic field region (e.g., a low field
DEP region), concentrating nucleic acid in a second
dielectrophoretic field region (e.g., a high field DEP region), and
washing away the cells and residual material. The assay also
optionally includes devices and/or systems capable of performing
one or more of the following steps: washing or otherwise removing
residual (e.g., cellular) material from the nucleic acid (e.g.,
rinsing the array with water or buffer while the nucleic acid is
concentrated and maintained within a high field DEP region of the
array), degrading residual proteins (e.g., residual proteins from
lysed cells and/or other sources, such degradation occurring
according to any suitable mechanism, such as with heat, a protease,
or a chemical), flushing degraded proteins from the nucleic acid,
and collecting the nucleic acid. In some embodiments, the result of
the assays described herein is an isolated nucleic acid, optionally
of suitable quantity and purity for enzymatic reactions, such as
PCR or DNA sequencing.
[0152] In some embodiments, the methods described herein allow for
performing enzymatic reactions. In other embodiments, the methods
described herein allow for performing polymerase chain reaction
(PCR), isothermal amplification, ligation reactions, restriction
analysis, nucleic acid cloning, transcription or translation
assays, or other enzymatic-based molecular biology assay.
[0153] In some embodiments, the methods described herein are
performed in a short amount of time. In some embodiments, the
period of time is short with reference to the "procedure time"
measured from the time between adding the fluid to the device and
detecting changes in the analyte. In some embodiments, the
procedure time is less than 3 hours, less than 2 hours, less than 1
hour, less than 30 minutes, less than 20 minutes, less than 10
minutes, or less than 5 minutes. In another aspect, the period of
time is short with reference to the "hands-on time" measured as the
cumulative amount of time that a person must attend to the
procedure from the time between adding the fluid to the device and
measuring the changes in the analyte. In some embodiments, the
hands-on time is less than 20 minutes, less than 10 minutes, less
than 5 minute, less than 1 minute, or less than 30 seconds.
[0154] In some embodiments, the methods described herein comprise
amplifying the isolated nucleic acid by polymerase chain reaction
(PCR). In some embodiments, the device or system comprise a heater
and/or temperature control mechanisms suitable for thermocycling.
PCR is optionally done using traditional thermocycling by placing
the reaction chemistry analytes in between two efficient
thermoconductive elements (e.g., aluminum or silver) and regulating
the reaction temperatures using TECs. Additional designs optionally
use infrared heating through optically transparent material like
glass or thermo polymers. In some instances, designs use smart
polymers or smart glass that comprise conductive wiring networked
through the substrate. This conductive wiring enables rapid thermal
conductivity of the materials and (by applying appropriate DC
voltage) provides the required temperature changes and gradients to
sustain efficient PCR reactions. In certain instances, heating is
applied using resistive chip heaters and other resistive elements
that will change temperature rapidly and proportionally to the
amount of current passing through them.
[0155] In some embodiments, the methods described herein are used
in conjunction with traditional fluorometry (CCD, pmt, other
optical detector, and optical filters), fold amplification is
monitored in real-time or on a timed interval. In certain
instances, quantification of final fold amplification is reported
via optical detection converted to AFU (arbitrary fluorescence
units correlated to analyze doubling) or translated to electrical
signal via impedance measurement or other electrochemical
sensing.
[0156] In some instances, light delivery schemes are utilized to
provide the optical excitation and/or emission, and/or detection of
fold amplification. In certain embodiments, this includes using the
flow cell materials (thermal polymers like acrylic (PMMA) cyclic
olefin polymer (COP), cyclic olefin co-polymer, (COC), etc.) as
optical wave guides to remove the need to use external components.
In addition, in some instances light sources--light emitting
diodes--LEDs, vertical-cavity surface-emitting lasers--VCSELs, and
other lighting schemes are integrated directly inside the flow cell
or built directly onto the micro electrode array surface to have
internally controlled and powered light sources. Miniature PMTs,
CCDs, or CMOS detectors can also be built into the flow cell. This
minimization and miniaturization enables compact devices capable of
rapid signal delivery and detection while reducing the footprint of
similar traditional devices (e.g. a standard bench top
PCR/QPCR/Fluorometer).
[0157] In some embodiments, the isolated sample disclosed herein is
further utilized in a variety of assay formats. For instance, in
some embodiments, devices which are addressed with nucleic acid
probes or amplicons are utilized in dot blot or reverse dot blot
analyses, base-stacking single nucleotide polymorphism (SNP)
analysis, SNP analysis with electronic stringency, or in STR
analysis. In addition, such methods described herein are utilized
in formats for enzymatic nucleic acid modification, or
protein-nucleic acid interaction, such as, e.g., gene expression
analysis with enzymatic reporting, anchored nucleic acid
amplification, or other nucleic acid modifications suitable for
solid-phase formats including restriction endonuclease cleavage,
endo- or exo-nuclease cleavage, minor groove binding protein
assays, terminal transferase reactions, polynucleotide kinase or
phosphatase reactions, ligase reactions, topoisomerase reactions,
and other nucleic acid binding or modifying protein reactions.
[0158] In addition, in some embodiments, the methods described
herein are useful in immunoassays. For instance, in some
embodiments, some of the methods described herein are used with
antigens (e.g., peptides, proteins, carbohydrates, lipids,
proteoglycans, glycoproteins, etc.) in order to assay for
antibodies in a bodily fluid sample by sandwich assay, competitive
assay, or other formats. Alternatively, in some embodiments, the
locations of the device are addressed with antibodies, in order to
detect antigens in a sample by sandwich assay, competitive assay,
or other assay formats. In some embodiments, the isolated nucleic
acids are useful for use in immunoassay-type arrays or nucleic acid
arrays.
Enzymes
[0159] In some embodiments, the method includes introduction of
enzymes to the sample. In some embodiments, the enzyme is a
restriction enzyme. Non limiting examples of a restriction enzyme
are AcII, HindIII, SspI, MIuCI Tsp509I, PciI, AgeI, BspMI, BfuAI,
SexAI, MIuI, BceAI, HpyCH4IV, HpyCH4III, Bael, BsaXI, AF1III, SpeI,
BsrI, BmrI, BglII, AfeI, AluI, StuI, ScaI, ClaI, PI-SceI, NsiI,
AseI, SwaI, CspCI, MfeI, BssSI, BmgBI, PmII, DraIII, AleI, EcoP15I,
PvuII, AlwNI, BtsIMutI, TspRI, NdeI, NlaIII, CviAII, FatI, MsII,
FspEI, XcmI, BstXI, PflMI, BccI, NcoI, BseYI, FauI, SmaI, XmaI
TspMI, Nt, CviPII, LpnPI, AciI, SacII, BsrBI, MspI HpaII, ScrFI,
BssKi StyD4I, BsaJI, BsII, BtgI, NciI, AvrII, MnII, BbvCI,
Nb.BbbCI, Nt.BbvCI, SbfI, BpU10I, Bsu36I, EcoNI, HpyAV, BstNI,
PspGI, StyI, BcgI, PvuI BstUI, EagI, RsrII, BbiEI, BsiWI, BsmBI,
Hpy99I, MspA1I, MspJI, SgrAI, BfaI, BspCNI, XhoI, EarI, AcuI, PstI,
BpmI, DdeI, SfcI, AfiII, BpuEI, SmII, Aval BsoBI, MboII, BbsI,
XmnI, BsmI, Nb.BsmI, EcoRI, HgaI, AarII, ZraI, Tth111IPfIFI, PshAI,
AhdI, DrdI, Eco53kI, SacI, BseRI, PleI, Nt.BstNBI, MlyI, HinfI,
EcoRV, MboI Sau3AI, DpnI, BsaBI, TfiI, BsrDI, Nb.BsrDI, BbvI, BtsI,
Nb.BtsI, BstAPI, SfaNI, SphI, SrfI, MneAIII, NaeI, NgoMIV, BgII,
AsiSI, BtgZI, HinPlI, HhaI, BssHII, NotI, Fnu4HI, Cac8I, MwoI,
NheI, BmtI, SapI, Nt.BspQI, BlpI, Tsel ApeKI, Bsp1286I, AlwI,
Nt.AlwI, BamHI, FokI, BtsCI, HaeIII, FseI, SfiI, NarI, KasI, SfoI
PluTI, AscI, EciI, BsmFI, ApaI, PspOMI, Sau96I, NlaIV, KpnI,
Acc651, BsaI, HphI, BstEII, AvaII, BanI, BaeGI, BsaHI, BanII, RsaI,
CviQI BstZ17I, BciVI, SaII, Nt.BsmAI, BsmAI BcoDI, ApaLI, BsgI
AccI, Hpy166II, Tsp45I, Hpal, PmeI, HincII, BsiHKAI, ApoI, NspI,
BsrFI, BstYI, HaeII, CviKI-1, EcoO109I, PpuMI, I-CeuI SnaBI,
I-SceI, BspHI, BspEI, MmeI, Taq-I, Nrul, Hpy188I, Hpy188III, Xbal,
BeII, HpyCH4V, FspI, PI-PspI, MscI, BsrGI, MseI MacI, PsiI, BstBI,
DraI, PspXI, BsaWI, BsaAI, and EaeI.
[0160] In other embodiments, the enzyme is an exonuclease. Non
limiting examples of an exonuclease are Lambda Exonuclease, T7
Exonuclease, Exonuclease III, RecJ.sub.f, Exonuclease I,
Exonuclease I, Exonuclease V, Nuclease BAL-31, Mung Bean Nuclease,
DNase I, Micrococcal Nuclease, T7 Endonuclease I, and T5
Exonuclease.
[0161] In other embodiments, the enzyme is a protease. Non limiting
examples of a protease are Achromopeptidase, Aminopeptidase,
Ancrod, Angiotensin Converting Enzyme, Bromelain, Calpain, Calpain
I, Calpain II, Carboxypeptidase A, Carboxypeptidase B,
Carboxypeptidase G, Carboxypeptidase P, Carboxypeptidase W,
Carboxypeptidase Y, Caspases (general), Caspase 1, Caspase 2,
Caspase 3, Caspase 4, Caspase 5, Caspase 6, Caspase 7, Caspase 8,
Caspase 9, Caspase 10, Caspase 11, Caspase 12, Caspase 13,
Cathepsin B, Cathepsin C, Cathepsin D, Cathepsin E, Cathepsin G,
Cathepsin H, Cathepsin L, Chymopapain, Chymase, Chymotrypsin,
Clostripain, Collagenase, Complement Clr, Complement Cls,
Complement Factor D, Complement factor I, Cucumisin, Dipeptidyl
Peptidase IV, Elastase leukocyte, Elastase pancreatic,
Endoproteinase Arg-C, Endoproteinase Asp-N, Endoproteinase Glu-C,
Endoproteinase Lys-C, Enterokinase, Factor Xa, Ficin, Furin,
Granzyme A, Granzyme B, HIV Protease, IGase, Kallikrein tissue,
Leucine Aminopeptidase (General), Leucine aminopeptidase, cytosol,
Leucine aminopeptidase, microsomal, Matrix metalloprotease,
Methionine Aminopeptidase, Neutrase, Papain, Pepsin, Plasmin,
Prolidase, Pronase E, Prostate Specific Antigen, Protease,
Alkalophilic from Streptomyces griseus, Protease from Aspergillus,
Protease from Aspergillus saitoi, Protease from Aspergillus sojae,
Protease (B. licheniformis) (Alkaline), Protease (B. licheniformis)
(Alcalase), Protease from Bacillus polymyxa, Protease from Bacillus
sp, Protease from Bacillus sp (Esperase), Protease from Rhizopus
sp., Protease S, Proteasomes, Proteinase from Aspergillus oryzae,
Proteinase 3, Proteinase A, Proteinase K, Protein C, Pyroglutamate
aminopeptidase, Renin, Rennin, Streptokinase, Subtilisin,
Thermolysin, Thrombin, Tissue Plasminogen Activator, Trypsin,
Tryptase, and Urokinase
[0162] In other embodiments, the enzyme is a lipase. Non limiting
examples of a lipase are biological lipases such as bile
salt-dependent lipase, pancreatic lipase, lysosomal lipase, hepatic
lipase, lipoprotein lipase, hormone-sensitive lipase, gastric
lipase, endothelial lipase, pancreatic lipase related protein,
pancreatic lipase related protein 1, lingual lipase, lipase members
H, I, J, K, M and N, monoglyceride lipase, dicylglycerol lipase
alpha, diacylglycerol lipase beta, and carboxyl ester lipase.
Removal of Residual Material
[0163] In some embodiments, following isolation of the analytes,
the method includes optionally flushing residual material from the
isolated analytes. In some embodiments, the methods described
herein optionally and/or comprise a reservoir comprising a fluid
suitable for flushing residual material from the analytes.
"Residual material" is anything originally present in the sample,
originally present in the cells, added during the procedure,
created through any step of the process including but not limited
to cells (e.g. intact cells or residual cellular material), and the
like. For example, residual material includes intact cells, cell
wall fragments, proteins, lipids, carbohydrates, minerals, salts,
buffers, plasma, and the like. In some embodiments, a certain
amount of analyte is flushed with the residual material.
[0164] In some embodiments, the residual material is flushed in any
suitable fluid, for example in water, TBE buffer, or the like. In
some embodiments, the residual material is flushed with any
suitable volume of fluid, flushed for any suitable period of time,
flushed with more than one fluid, or any other variation. In some
embodiments, the method of flushing residual material is related to
the desired level of isolation of the analyte, with higher purity
analyte requiring more stringent flushing and/or washing. In other
embodiments, the method of flushing residual material is related to
the particular starting material and its composition. In some
instances, a starting material that is high in lipids requires a
flushing procedure that involves a hydrophobic fluid suitable for
solubilizing lipids.
[0165] In some embodiments, the method includes degrading residual
material including residual protein. For example, proteins are
degraded by one or more of chemical degradation (e.g. acid
hydrolysis) and enzymatic degradation. In some embodiments, the
enzymatic degradation agent is a protease. In other embodiments,
the protein degradation agent is Proteinase K. The optional step of
degradation of residual material is performed for any suitable
time, temperature, and the like. In some embodiments, the degraded
residual material (including degraded proteins) is flushed from the
isolated analytes.
[0166] In some embodiments, the agent used to degrade the residual
material is inactivated or degraded. In some embodiments, an enzyme
used to degrade the residual material is inactivated by heat (e.g.,
50 to 95.degree. C. for 5-15 minutes). For example, enzymes
including proteases, (for example, Proteinase K) are degraded
and/or inactivated using heat (typically, 15 minutes, 70.degree.
C.). In some embodiments wherein the residual proteins are degraded
by an enzyme, the method further comprises inactivating the
degrading enzyme (e.g., Proteinase K) following degradation of the
proteins. In some embodiments, heat is provided by a heating module
in the device (temperature range, e.g., from 30 to 95.degree.
C.
[0167] The order and/or combination of certain steps of the method
can be varied. In some embodiments, the methods are capable of
performing certain steps in any order or combination. For example,
in some embodiments, the residual material and the degraded
proteins are flushed in separate or concurrent steps. That is, the
residual material is flushed, followed by degradation of residual
proteins, followed by flushing degraded proteins from the isolated
analytes. In some embodiments, the residual proteins are first
degraded, and then both the residual material and degraded proteins
are flushed from the analytes in a combined step.
[0168] In some embodiments, the analytes are used in PCR, enzymatic
assays, or other procedures that analyze, characterize or amplify
the analytes.
[0169] For example, in some embodiments, the isolated analyte is a
nucleic acid, and the methods described herein are capable of
performing PCR or other optional procedures on the isolated nucleic
acids. In other embodiments, the nucleic acids are collected and/or
eluted from the device. In some embodiments, the methods described
herein are capable of allowing collection and/or elution of nucleic
acid from the device or system. Exemplary eluents include water,
TE, TBE, and L-Histidine buffer.
[0170] In some embodiments, isolated nucleic acids will be in
native state, e.g. still associated with proteins or trapped in
exosomes, in comparison to other isolation techniques where
digestion/lysis steps are taken in order to isolate the nucleic
acids.
[0171] Isolated protein components can also be called
immuno-proteins with clinical application such as CEA, CA-125, PAS,
CA 27.29, CA15-3, Cyfra-21, AFP, BHCG, etc. Since the isolation
occurs selectively thru antibody binding, the protein will be free
of other aggregates and will be in a solution such as to prevent
aggregation and denaturation.
Samples
[0172] In some embodiments, the sample comprises a fluid or a
sample fluid. In one aspect, the sample is a biological sample. In
one aspect, the sample is a biological material. In one aspect, the
biological material is a biological fluid. In one aspect, the
biological fluid is blood. In one aspect, the sample comprises
cells or other particulate material. In some embodiments, the
sample does not comprise cells. In another aspect, the sample is an
environmental sample.
[0173] In some embodiments, the sample is a liquid, optionally
water, an aqueous solution, or dispersion. In some embodiments, the
sample is a bodily fluid. Exemplary bodily fluids include whole
blood, plasma, serum, saliva, cerebrospinal fluid, lymph fluid,
urine, sweat, tears, amniotic fluid, aqueous humor, vitreous humor,
pleural fluid, mucus, synovial fluid, exudate, interstitial fluid,
peritoneal fluid, pericardial fluid, sebum, semen, bile, and the
like. In some embodiments, analytes are measured within bodily
fluids using the methods described herein are part of a medical
therapeutic or diagnostic procedure, device, or system. In some
embodiments, the sample is tissues and/or cells solubilized and/or
dispersed in a fluid medium. For example, the tissue can be a
cancerous tumor from which analytes, such as nucleic acids, can be
isolated using the methods, devices, or systems described
herein.
[0174] In some embodiments, the sample is an environmental sample.
In some embodiments, the environmental sample is assayed or
monitored for the presence of a particular nucleic acid sequence
indicative of a certain contamination, infestation incidence, or
the like. The environmental sample can also be used to determine
the source of a certain contamination, infestation incidence or the
like using the methods, devices, or systems described herein.
Exemplary environmental samples include municipal wastewater,
industrial wastewater, water or fluid used in or produced as a
result of various manufacturing processes, lakes, rivers, oceans,
aquifers, ground water, storm water, plants or portions of plants,
animals or portions of animals, insects, municipal water supplies,
and the like.
[0175] In some embodiments, the sample is a food or beverage. The
food or beverage can be assayed or monitored for the presence of a
particular analyte indicative of a certain contamination,
infestation incidence, or the like. The food or beverage can also
be used to determine the source of a certain contamination,
infestation incidence or the like using the methods described
herein. In various embodiments, the methods described herein can be
used with one or more of bodily fluids, environmental samples, and
foods and beverages to monitor public health or respond to adverse
public health incidences.
[0176] In some embodiments, the sample is a growth medium. The
growth medium can be any medium suitable for culturing cells, for
example lysogeny broth (LB) for culturing E. coli, Ham's tissue
culture medium for culturing mammalian cells, and the like. The
medium can be a rich medium, minimal medium, selective medium, and
the like. In some embodiments, the medium comprises or consists
essentially of a plurality of clonal cells. In some embodiments,
the medium comprises a mixture of at least two species. In some
embodiments, the cells comprise clonal cells, pathogen cells,
bacteria cells, viruses, plant cells, animal cells, insect cells,
and/or combinations thereof.
[0177] In some embodiments, the sample is water.
[0178] In some embodiments, the sample comprises other particulate
material. In some embodiments, such particulate material are, for
example, inclusion bodies (e.g., ceroids or Mallory bodies),
cellular casts (e.g., granular casts, hyaline casts, cellular
casts, waxy casts and pseudo casts), Pick's bodies, Lewy bodies,
fibrillary tangles, fibril formations, cellular debris, or other
particulate material. In some embodiments, particulate material is
an aggregated protein (e.g., beta-amyloid).
[0179] In some embodiments, the sample is a small volume of liquid
including less than 10 ml. In some embodiments, the sample is less
than 8 ml. In some embodiments, the sample is less than 5 ml. In
some embodiments, the sample is less than 2 ml. In some
embodiments, the sample is less than 1 ml. In some embodiments, the
sample is less than 500 .mu.l. In some embodiments, the sample is
less than 200 .mu.l. In some embodiments, the sample is less than
100 .mu.l. In some embodiments, the sample is less than 50 .mu.l.
In some embodiments, the sample is less than 10 .mu.l. In some
embodiments, the sample is less than 5 .mu.l. In some embodiments,
the sample is less than 1 .mu.l.
[0180] In some embodiments, the quantity of sample used in the
method comprises less than about 100,000,000 cells. In some
embodiments, the sample comprises less than about 10,000,000 cells.
In some embodiments, the sample comprises less than about 1,000,000
cells. In some embodiments, the sample comprises less than about
100,000 cells. In some embodiments, the sample comprises less than
about 10,000 cells. In some embodiments, the sample comprises less
than about 1,000 cells.
[0181] In some embodiments, isolation of an analyte from a sample
methods described herein takes less than about 30 minutes, less
than about 20 minutes, less than about 15 minutes, less than about
10 minutes, less than about 5 minutes or less than about 1 minute.
In other embodiments, isolation of an analyte from a sample with
methods described herein takes no more than 30 minutes, no more
than about 20 minutes, no more than about 15 minutes, no more than
about 10 minutes, no more than about 5 minutes, no more than about
2 minutes, or no more than about 1 minute. In additional
embodiments, isolation of an analyte from a sample with the methods
described herein takes less than about 15 minutes, less than about
10 minutes, or less than about 5 minutes.
[0182] In some embodiments, the analyte is a macroscale
analyte.
[0183] In some embodiments, the methods described herein are used
to obtain, isolate, or separate any desired analyte. In some
embodiments, the analyte is a nucleic acid. In other embodiments,
the nucleic acids isolated by the methods described herein include
DNA (deoxyribonucleic acid), RNA (ribonucleic acid), and
combinations thereof. In some embodiments, the analyte is protein
fragments. In some embodiments, the nucleic acid is isolated in a
form suitable for sequencing or further manipulation of the nucleic
acid, including amplification, ligation, or cloning.
[0184] In some embodiments, the sample consists of a combination of
micron-sized entities or cells, larger nanoparticulates, and
smaller nanoparticulates or biomolecules. In some embodiments, the
micron-sized entities comprise blood cells, platelets, bacteria,
and the like. In some embodiments, larger nanoparticulates comprise
particulates in the range of about 10 nm and about 900 nm effective
stokes diameter, and comprise exosomes, high mw nucleic acids,
including high mw DNA, oligo-nucleosome complexes, aggregated
proteins, vesicle bound DNA, cell membrane fragments, and cellular
debris dispersed in the sample. In some embodiments, smaller
nanoparticulates 10 nm effective stokes diameter) comprise proteins
such as immunoglobulins, human serum albumin, fibrinogen and other
plasma proteins, smaller apoptotic DNA, and free ions.
[0185] In some embodiments, the assays and methods disclosed herein
are capable of selectively isolating target particulates, including
micron-sized entities, larger nanoparticulates, and/or smaller
nanoparticulates. In some embodiments, the assays and methods
disclosed herein are capable of selectively isolating target
particulates, including micron-sized entities, larger
nanoparticulates, and/or smaller nanoparticulates in complex
biological or environmental samples. The target particulates are
isolated in different field regions at or near the surface of the
array or cartridge, allowing non-target particulates or
particulates that are not isolated at or near the surface of the
array or cartridge to be flushed from the array or cartridge.
[0186] In some embodiments, the larger nanoparticulate molecular
target includes exosomes, high mw nucleic acids, including high mw
DNA, oligo-nucleosome complexes, aggregated proteins, vesicle bound
DNA, cell membrane fragments, and cellular debris. In other
embodiments, the target circulating cell-free biomarker includes
mutations, deletions, rearrangements or methylated nucleic acid of
circulating, cell-free DNA, micro RNA, RNA from microvesicles, or a
combination thereof. In still other embodiments, the detection of
the cell-free biomarker provides information useful for cancer
diagnosis, cancer prognosis or treatment response in a patient. In
yet other embodiments, the tumor cell-free biomarker is associated
with CNS tumors, neuroblastoma, gliomas, breast cancer, endometrial
tumors, cervical tumors, ovarian tumors, hepatocellular carcinoma,
pancreatic carcinoma, esophageal tumors, Stoch tumors, colorectal
tumors, head and neck tumors, nasopharyngeal carcinoma, thyroid
tumors, lymphoma, leukemia, lung cancer, non-small cell lung
carcinoma, small cell lung carcinoma, testicular tumors, kidney
tumors, prostate carcinoma, skin cancer, malignant melanoma,
squamous cell carcinoma or a combination thereof. In some
embodiments, the tumor cell-free biomarker is GFAP, VEGF, EGFR,
b-FGF, KRAS, YKL-40, MMP-9, or combinations thereof.
[0187] In other embodiments, the target biomarker is chosen from
the group consisting of proteins, lipids, antibodies, high
molecular weight DNA, tumor cells, exosomes, nucleosomes and
nanosomes. In still other embodiments, the bound nucleic acid is
eluted from the first chamber for further characterization. In yet
other embodiments, the eluted nucleic acid is amplified or
sequenced.
[0188] In various embodiments, the analyte is a composition that is
free from at least 99% by mass of other materials, free from at
least 99% by mass of residual cellular material, free from at least
98% by mass of other materials, free from at least 98% by mass of
residual cellular material, free from at least 95% by mass of other
materials, free from at least 95% by mass of residual cellular
material, free from at least 90% by mass of other materials, free
from at least 90% by mass of residual cellular material, free from
at least 80% by mass of other materials, free from at least 80% by
mass of residual cellular material, free from at least 70% by mass
of other materials, free from at least 70% by mass of residual
cellular material, free from at least 60% by mass of other
materials, free from at least 60% by mass of residual cellular
material, free from at least 50% by mass of other materials, free
from at least 50% by mass of residual cellular material, free from
at least 30% by mass of other materials, free from at least 30% by
mass of residual cellular material, free from at least 10% by mass
of other materials, free from at least 10% by mass of residual
cellular material, free from at least 5% by mass of other
materials, or free from at least 5% by mass of residual cellular
material.
[0189] In various embodiments, the analyte has any suitable purity.
For example, if an enzymatic assay requires analyte samples having
about 20% residual cellular material, then isolation of the analyte
to 80% is suitable. In some embodiments, the isolated analyte
comprises less than about 80%, less than about 70%, less than about
60%, less than about 50%, less than about 40%, less than about 30%,
less than about 20%, less than about 10%, less than about 5%, or
less than about 2% non-analyte cellular material and/or protein by
mass. In some embodiments, the isolated analyte comprises greater
than about 99%, greater than about 98%, greater than about 95%,
greater than about 90%, greater than about 80%, greater than about
70%, greater than about 60%, greater than about 50%, greater than
about 40%, greater than about 30%, greater than about 20%, or
greater than about 10% analyte by mass.
Nucleic Acids
[0190] The analytes are isolated in any suitable form including
unmodified, derivatized, fragmented, non-fragmented, and the like.
In some embodiments, when the analyte is a nucleic acid, the
nucleic acid is collected in a form suitable for sequencing. In
some embodiments, the nucleic acid is collected in a fragmented
form suitable for shotgun-sequencing, amplification, or other
manipulation. In some embodiments, the nucleic acid is collected in
a solution comprising reagents used in, for example, a DNA
sequencing procedure, such as nucleotides as used in sequencing by
synthesis methods.
[0191] When the analyte is a nucleic acid, the nucleic acid
isolated using the methods described herein is high-quality and/or
suitable for DNA sequencing, nucleic acid amplification, such as
PCR, or other nucleic acid manipulation, such as ligation, cloning
or further translation or transformation assays. In some
embodiments, the collected nucleic acid comprises at most 0.01%
protein. In some embodiments, the collected nucleic acid comprises
at most 0.5% protein. In some embodiments, the collected nucleic
acid comprises at most 1% protein. In some embodiments, the
collected nucleic acid comprises at most 2% protein. In some
embodiments, the collected nucleic acid comprises at most 3%
protein. In some embodiments, the collected nucleic acid comprises
at most 4% protein. In some embodiments, the collected nucleic acid
comprises at most 5% protein
Protein
[0192] When the analyte is a protein or protein fragment, the
protein or protein fragment isolated using the methods described
herein is high-quality and/or suitable for using directly in
downstream procedures. In some embodiments, the collected protein
or protein fragment comprises at most 0.01% non-target protein. In
some embodiments, the collected protein or protein fragment
comprises at most 0.5% non-target protein. In some embodiments, the
collected protein or protein fragment comprises at most 0.1%
non-target protein. In some embodiments, the collected protein or
protein fragment comprises at most 1% non-target protein. In some
embodiments, the collected protein or protein fragment comprises at
most 2% non-target protein. In some embodiments, the collected
protein or protein fragment comprises at most 3% non-target
protein. In some embodiments, the collected protein or protein
fragment comprises at most 4% non-target protein. In some
embodiments, the collected protein or protein fragment comprises at
most 5% non-target protein.
Detection and Characterization of Cancer Using Cell-Free
Biomarkers
[0193] In some embodiments, assays are performed on circulating
cell-free high molecular weight DNA (>300 bp) and other target
cell-free biomarkers isolated using the methods and devices
disclosed herein to characterize cancer in patients using target
specific cell-free biomarkers. "Characterization" of cancer
includes, but is not limited to, detection and diagnosis of cancer,
prognosis of disease, treatment response monitoring and other
actions related to cancer analysis and treatment therein.
[0194] In some embodiments, the characterization is performed via
molecular profiling of cell-free biomarkers. The profiling
includes, but is not limited to, enumeration of analytes, specific
detection of analytes, including, but not limited to, proteins,
lipids, antibodies, tumor DNA, tumor cells, exosomes, nucleosomes,
nanosomes detection of specific gene sequences, detection of mutant
gene sequences, detection of loss of heterozygosity, determination
of methylation status, detection of alterations, detection of
deletions, and other molecular profiling assays used in the
analysis and characterization of physical and/or biochemical status
of a patient or subject.
[0195] Cell-free biomarkers can be derived from proteins or
molecules associated with cellular exocytosis, necrosis, or
secretion processes. Examples of biomarkers include: high molecular
weight DNA (>300 bp), nucleosomes, exosomes, aggregated
proteins, cell membrane fragments, mitochondria, cellular vesicles,
extracellular vesicles, and other markers related to cellular
exocytosis, necrosis, or secretion.
[0196] Examples of candidates for circulating cell-free biomarkers
include, but are not limited to, cell-free circulating tumor DNA
(ctDNA), including mutations or deletions, rearrangement,
methylated nucleic acid, loss of heterozygosity, and other DNA
alterations. In some embodiments, RNA is also used, including, but
not limited to, micro RNA (miRNA), RNA from microvesicles and other
RNA forms that provide useful information with regards to the
characterization of, for example, cancer diagnosis, prognosis, and
treatment response in a patient. In some embodiments, tumor cells
are directly monitored, as well as cell free proteins, including,
but not limited to, GFAP, VEGF, EGFR, b-FGF, KRAS, YKL-40, and
MMP-9.
[0197] The methods and devices disclosed herein for
characterization of, for example, cancer patients and subjects uses
AC Electrokinetics to isolate cell free target biomarkers directly
from whole blood, serum, plasma, or other bodily fluid or sample.
The methods and devices disclosed herein use minimal amounts of
sample, for example, up to 10 .mu.l, up to 20 .mu.l, up to 30
.mu.l, up to 40 .mu.l, up to 50 .mu.l, up to 60 .mu.l, up to 70
.mu.l, up to 80 .mu.l, up to 90 .mu.l, up to 100 .mu.l, up to 200
.mu.l, up to 300 .mu.l, up to 400 .mu.l, up to 500 .mu.l, or more
of sample. In some embodiments, the methods and devices disclosed
herein use less than 500 .mu.l, less than 400 .mu.l, less than 300
.mu.l, less than 200 .mu.l, less than 100 .mu.l, less than 90
.mu.l, less than 80 .mu.l, less than 70 .mu.l, less 60 .mu.l, less
than 50 .mu.l, less than 40 .mu.l, less than 30 .mu.l, less than 20
.mu.l, less than 10 .mu.l, or less than 5 .mu.l of sample. In some
embodiments, the methods and devices disclosed herein use between
about 50 .mu.l of sample and about 500 .mu.l of sample.
[0198] The methods and devices disclosed herein for
characterization of, for example, cancer patients and subjects use
intercalating dyes, antibody labeling, or other traditional
staining techniques to enable direct quantification using
fluorescence microscopy or other detection techniques. In some
embodiments, the methods and devices disclosed herein also use
DNA/RNA hybridization techniques to detect specific alleles
implicated in cancer. In some embodiments, the methods and devices
disclosed herein also use Quantitative Real Time PCR, including of
nuclear or mitochondrial DNA or other target nucleic acid molecule
markers, enzyme-linked immunosorbent assays (ELISA), direct SYBR
gold assays, direct PicoGreen assays, or loss of heterozygosity
(LOH) of microsatellite markers, optionally followed by
electrophoresis analysis, including, but not limited to, capillary
electrophoresis analysis, sequencing and/or cloning, including next
generation sequencing, methylation analysis, including, but not
limited to, modified semi-nested or nested methylation specific
PCR, DNA specific PCR (MSP), quantification of minute amounts of
DNA after bisulfitome amplification (qMAMBRA), as well as
methylation on beads, mass-based analysis, including, but not
limited to, MALDI-ToF (matrix-assisted laser desorption/ionization
time of flight analysis, optionally in combination with PCR, and
digital PCR.
[0199] In some embodiments, the methods and devices disclosed
herein employ dyes, including intercalating dyes, antibody
labeling, stains and other imaging molecules that enable direct
quantification of the cell-free biomarker materials directly on or
in use with the embodied devices, including the use of fluorescence
microscopy. Examples of fluorescent labeling of nucleic acids (e.g.
DNA and RNA) include, but are not limited to, cyanine dimers
high-affinity stains (Life Technologies). Among them YOYO.RTM.-1,
YOYO.RTM.-3, POPO.TM.-1, POPO.TM.-3, TOTO.RTM.-1, and TOTO.RTM.-3
are optionally chosen staining dyes. Fluorescent labeling of
protein for detection and quantitation in conjunction with the
methods and devices disclosed herein include, but are not limited
to, Quanti-iT.TM. protein quantitation assay, NanoOrange.TM.
protein quantitation assay, CBQCA protein quantitation assay (Life
Technologies). In some embodiments, fluorescent quantitation of
other cancer biomarkers is used including mitochondria, labelling
dyes such as MitoTracker.RTM. Green FM.RTM. and MitoTracker.RTM.
Red FM.RTM..
[0200] In some embodiments, the methods and devices disclosed
herein are used in conjunction with DNA/RNA hybridization
techniques to detect specific alleles implicated in cancer. In some
embodiments, specific electrodes and corresponding electrode trace
lines can be designed to individually control separate electrodes
so as to achieve a unique electric field distribution. In some
embodiments, by designing non-uniform electric field distribution,
specific DNA/RNA are manipulated.
[0201] Additionally, in some embodiments, the microelectrode arrays
disclosed herein are further functionalized, for example, by
covering the array with a reactive hydrogel. In some embodiments,
the hydrogel comprises binding partners, including biotin binding
protein; alternatively, the hydrogel is functionalized by acylation
or by surface modification to chemisorb oligonucleotides on the
surface. In some embodiments, the methods and devices disclosed
herein are manipulated to attain control of hybridization and
detection of specific alleles, for example, through the use of a
Complimentary Metal-Oxide Semiconductor (CMOS) device that controls
the microelectrode array in a manner that allows for multiple use
of the array and high-throughput screening of matching
oligonucleotides.
[0202] In some embodiments, the methods and devices disclosed
herein enable elution of circulating cell-free target biomarkers
such as nucleosomes, high molecular weight DNA, exosomes and
proteins for post-genetic analysis and for quantification and
further analysis using quantitative PCR, reverse transcriptase (RT)
PCR, and sequencing analytical techniques for identifying proteins
or nucleic acids of interest in the isolated and eluted sample DNA.
Post-genetic analysis is performed on nucleosomal or nucleoprotein
complexed dsDNA (greater than 300 bp), on exosomal dsDNA or RNA
(greater than 100 bp), and/or on mitochondrial DNA.
Certain Terminology
[0203] The articles "a", "an" and "the" are non-limiting. For
example, "the method" includes the broadest definition of the
meaning of the phrase, which can be more than one method.
[0204] As used herein, the term "about" a particular value refers
to a range of 10% above the value to 10% below the value. For
example, "about 100" refers to 90 to 110.
EXAMPLES
[0205] While preferred embodiments of the present invention have
been shown and described herein, it will be obvious to those
skilled in the art that such embodiments are provided by way of
example only. Numerous variations, changes, and substitutions will
now occur to those skilled in the art without departing from the
invention. It should be understood that various alternatives to the
embodiments of the invention described herein are employed in
practicing the invention. It is intended that the following claims
define the scope of the invention and that methods and structures
within the scope of these claims and their equivalents be covered
thereby.
Example 1: Detecting Nanoscale Analytes in Complex Biological
Samples
[0206] Using the devices and methods disclosed herein, 50 uL sample
of blood from a subject is inserted into a cartridge and the cells
are lysed using a 100 milli-second 100V DC pulse using an HP 3245A
function generator. The nucleic acids from the blood cells are then
gathered on the electrode surface using 10 kHz, 10Vp-p.
Example 2: Monitoring a Disease State in an Individual
[0207] An individual who is being treated for lung cancer wishes to
monitor treatment progress using a portable device. The portable
device is powered by and controlled by a mobile phone. An
application on the mobile phone is used to run the diagnostic
assay. The individual creates a user profile in the application
that includes a medical diagnosis, treatment regimen, and
demographic information. The individual obtains a 50 .mu.l sample
of blood, inputs the sample into the device, and selects an assay
appropriate to monitor treatment progress for lung cancer. The
assay carried out by the portable device uses dielectrophoresis to
isolate cell free nucleic acid particles from larger cellular
particles in the blood. The cell free nucleic acid particles are
visualized and quantitated using the camera of the mobile phone.
While the assay is carried out, the user interface of the
application shows advertisements targeted to the individual based
on the user profile and the assay selected. When the assay is
complete, the individual is given a result. The result is also
transmitted to the individual's healthcare provider.
Example 3: Monitoring a Disease State in an Population
[0208] A population of individuals treated for lung cancer wish to
monitor treatment progress using a portable device. The portable
device is powered by and controlled by a mobile phone. An
application on the mobile phone is used to run the diagnostic
assay. Each individual creates a user profile in the application
that includes a medical diagnosis, treatment regimen, and
demographic information. Each individual obtains a 50 .mu.l sample
of blood, inputs the sample into the device, and selects an assay
appropriate to monitor treatment progress for lung cancer. The
assay carried out by the portable device uses dielectrophoresis to
isolate cell free nucleic acid particles from larger cellular
particles in the blood. The cell free nucleic acid particles are
visualized and quantitated using the camera of the mobile phone.
While the assay is carried out, the user interface of the
application shows advertisements targeted to each individual based
on the user profile and the assay selected. When the assay is
complete, each individual is given a result. The result is also
transmitted to each individual's healthcare provider and to an
online database. Each individual's user profile and results are
present in the online database which is searchable by each
individual, each individual's healthcare provider, and medical
researchers. The online database provides a resource to monitor
treatment results in a population of individuals undergoing
treatment. The online database also provides a resource for
individuals undergoing treatment to compare their results and to
connect with other individuals and other healthcare providers.
Example 4: Choice of Advertising or Answering Questions
[0209] An individual who is being treated for lung cancer is
provided with a portable device for monitoring treatment progress
free of charge by his healthcare provider. The portable device is
an analyte analysis apparatus powered by and controlled by a
tablet. The portable device has an adapter that accounts for the
larger size of the table relative to mobile phones when positioning
the tablet to run the diagnostic assay. An application on the
tablet is used to run the diagnostic assay. The individual creates
a user profile in the application that includes a medical
diagnosis, treatment regimen, and demographic information. The user
profile is also enhanced with social media information and
preferences imported from the individual's Facebook profile. Every
week, the individual uses the portable device to monitor his
treatment progress. The individual obtains a 50 .mu.l sample of
blood, inputs the sample into the device, and selects an assay
appropriate to monitor treatment progress for lung cancer. The
assay carried out by the portable device uses dielectrophoresis to
isolate cell free nucleic acid particles from larger cellular
particles in the blood. The cell free nucleic acid particles are
visualized and quantitated using the camera of the tablet. While
the assay is carried out, the user interface of the application
presents a choice of answering questions or watching advertisements
targeted to the individual based on the user profile and the assay
selected. The questions are from a paid survey provided by a
third-party. The individual selects survey and answers the
questions. When the assay is complete, the individual is given a
result. The result is also transmitted to the individual's
healthcare provider. The next week, the individual runs the
diagnostic assay again. Because the individual indicated his cancer
diagnosis and treatment regimen in his user profile, a remote
server compares this information against a database of ads to
determine a pool of relevant ads, and then selects from this pool
an ad for a novel lung cancer treatment to present to the user. The
healthcare provider receives payment for the targeted ad. Over
time, repeated payments for ads/questions over time serves to
offset the cost of the portable device for the healthcare provider,
thereby allowing the individual access to the portable device for
self-monitoring of treatment progress without being required to pay
for the device.
Example 5: Selection of Advertisements and Questions
[0210] An individual who is being treated for lung cancer wishes to
monitor treatment progress on a weekly basis using a portable
device. The portable device is powered by and controlled by a
mobile phone. An application on the phone is used to run the
diagnostic assay. The individual creates a user profile in the
application that includes a medical diagnosis, treatment regimen,
and demographic information. The user profile is uploaded to a
remote server storing a plurality of user profiles. A first
software module at the server analyzes the user profile and
compares it against a population of ads configured by advertisers
to determine one or more ads suitable for display. The first
software module selects an ad for an action movie based on the user
age and gender falling within an advertiser preference for males
aged between 18 and 35 for the ad. A second software module
analyzes the user profile and compares it against a population of
questions to determine one or more questions suitable for
presenting to the individual. The second software module selects a
set of three questions asking about the individual's taste in
movies based on the individual's answer to a question during a
previous test that he is interested in movies. The selection of ads
and questions are provided by the remote server to the application
of the device. The individual loads a sample into the portable
device. While the assay is being carried out by the device, the
user interface of the application presents a choice of answering
the selected questions or watching the selected advertisement. The
individual selects the advertisement, which is then displayed as a
movie teaser on a display of the mobile phone. The individual then
selects the movie teaser, which opens a link to a website
containing a full length movie trailer. The individual's decision
to select the movie teaser is added to the person's user profile on
the remote server. When the assay is complete, the individual is
given a result. The result is also transmitted to the individual's
healthcare provider. The first and second software modules analyze
the updated user profile and compare it against the population of
ads and the population of questions to determine suitable ads
and/or questions.
Example 6: Monitoring a Disease State in a Population
[0211] Portable devices for monitoring malaria infections are
distributed throughout medical clinics in a third world country.
Individuals who receive treatment at the clinics monitor their
response to treatment using the portable devices, which upload
geo-tagged and time-stamped analyte analysis results to an
encrypted database. Epidemiologists at an infectious disease
research institute are granted permission to access anonymized,
HIPAA-compliant information in the database as authorized users.
They analyze the geographic distribution of the results over time
to determine that the malaria infection rate in an eastern
geographic region has increased substantially over the past 6
months. The epidemiologists contact a non-governmental organization
involved in combating malaria and provide this information. The
non-governmental organization then deploys personnel and resources
to the eastern geographic region to deliver additional mosquito
netting and repellent as well as anti-malarial medication. The
epidemiologists continue monitoring the situation over the next 6
months and determine that the humanitarian efforts by the NGO have
halted the increased malaria infection rate.
Example 7: Targeted Advertising to a Healthy Individual
[0212] An otherwise healthy individual without any disease
diagnosis obtains a portable device to monitor her health. The
individual generates a user profile using her digital processing
device and authorizes access to her social media accounts on
Facebook and Twitter to build her user profile. The individual also
provides a detailed family health history including a history of
breast cancer on her mother's side of the family. Based on this
information, when she uses the portable device to conduct a test,
she is presented with a targeted ad for early breast cancer
screening.
Example 8: Treatment Recommendation in Association with Analyte
Testing
[0213] An individual who is diabetic selects a portable device for
periodically monitoring the blood plasma concentration of a
medication he is taking. The selected portable device is an
implantable medication monitor configured with a network element
for communicating with the individual's smartphone. The monitor has
been adapted to have minimal hardware and software components to
minimize the resources needed for manufacture, and has been
provided to the individual for free. As such, the monitor comprises
a sensor and any hardware needed to conduct the testing, and the
network element, but lacks a user interface (aside from a power
switch), a display, or other conventional features present in
diagnostic devices. After the individual implants the monitor and
turns it on, the device automatically pairs with the individual's
smartphone via the network element. An application on the phone
communicates with the monitor and sends instructions to the monitor
to conduct analyte testing according to a treatment regimen
provided by the individual when setting up his profile on the user
portal (FIG. 6F). The user profile is setup to include the
medication, the disease or condition treated by the medication,
treatment regimen, address, and demographic information.
[0214] Following profile setup, the individual selects the "perform
test" option in the user portal on his smartphone. The phone sends
instructions to the monitor to begin testing and presents the user
with the option to pay for the testing, watch an advertisement, or
answer a survey question in order to view the result (FIG. 6A). The
individual selects the option to answer the survey question and is
presented with a question targeted towards the medication he is
monitoring (FIG. 6B). The individual selects "dizziness" as a side
effect of the medication. After answering the question, the
individual is given the ability to view his test results once the
testing has been completed (FIG. 6C). The test results are then
shown indicating that the user's current medication level is high.
These test results are also uploaded to a remote server for further
analysis and generation of one or more recommendations accompanying
the test result. Since the treatment regimen is known, an algorithm
analyzes the dosing frequency and dosage to calculate a dosage
reduction for reducing the blood plasma concentration to normal
levels. This recommendation is then transmitted to the individual's
smartphone and presented on the phone's display (FIG. 6D). In
addition, another algorithm has analyzed the outcome data for a
matched cohort of subjects who also have taken the same medication
for treating the same condition to generate a prediction of an
adverse response requiring medical attention based upon similar
blood plasma concentrations. Although the individual did not select
any of the more serious symptoms requiring medical attention in
answering the survey question, this algorithm determines that there
is a moderate risk of adverse response and provides a warning to
see a doctor in case the individual notices more serious symptoms
(FIG. 6E).
[0215] About six hours later, the individual begins experiencing
abdominal pain while traveling. Recalling the warning presented on
his smartphone, he opens up the user portal on his phone and
selects the "search" function (FIG. 6F). He uses the search
function to identify a healthcare provider in proximity to his
location. In response to his search query, an algorithm is executed
on a remote server that filters healthcare providers for capability
to deal with overdoses and symptoms related to the individual's
medication. The algorithm then computes estimated times to
treatment as the sums of estimated times to arrival to the
healthcare provider locations and the estimated wait times using
current traffic conditions and historical wait times for the
providers. The providers are then listed in order of estimated time
to treatment. The individual selects the provider, a nearby
emergency room, with the shortest estimated time to treatment, and
his phone opens up a map application with directions to the
provider's location. The individual visits emergency room and
receives treatment. During the visit, the individual selects the
"Ask anything" function on his phone's application portal and
requests to communicate with his doctor who prescribed the
medication. The portal lists options to send a text message, email,
audio message, or video message. The individual chooses to send a
message to his doctor informing him of his condition. A few days
later, while using the monitor to test himself, he is prompted with
a survey question inquiring about whether he has suffered any
adverse response due to the previous high blood plasma
concentration of his medication. The individual answers that he has
had to visit the hospital for treatment due to abdominal pain. This
information is then anonymized, and uploaded onto an encrypted
database in a remote server.
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