U.S. patent application number 17/518006 was filed with the patent office on 2022-03-10 for database and machine learning in response to parallel serial dual microfluidic chip.
The applicant listed for this patent is RELIANT IMMUNE DIAGNOSTICS, INC.. Invention is credited to HENRY JOSEPH LEGERE, III, JOVAN HUTTON PULITZER.
Application Number | 20220076847 17/518006 |
Document ID | / |
Family ID | |
Filed Date | 2022-03-10 |
United States Patent
Application |
20220076847 |
Kind Code |
A1 |
PULITZER; JOVAN HUTTON ; et
al. |
March 10, 2022 |
DATABASE AND MACHINE LEARNING IN RESPONSE TO PARALLEL SERIAL DUAL
MICROFLUIDIC CHIP
Abstract
A microfluidic chip device includes a reservoir for holding a
biologic sample containing a predetermined biologic material. A
first plurality of parallel pathways each testing one of one or
more treatment-agents and analyzing a first efficacy for each of
the one or more treatment agents applied to the predetermined
biologic material within the biologic sample. A multiplexer
provides a portion of the biologic sample into each of the first
plurality of parallel pathways from the reservoir. A second
plurality of parallel pathways each test a plurality of different
dosage levels of the one or more treatment agents and analyzes a
second efficacy of the plurality of different dosage levels with
respect to the predetermined biologic material. The multiplexer
further provides a second portion of the biologic sample into a
selected at least one of the second plurality of parallel pathways
responsive to a control input indicating the treatment agent
providing a highest efficacy.
Inventors: |
PULITZER; JOVAN HUTTON;
(FRISCO, TX) ; LEGERE, III; HENRY JOSEPH; (AUSTIN,
TX) |
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Applicant: |
Name |
City |
State |
Country |
Type |
RELIANT IMMUNE DIAGNOSTICS, INC. |
AUSTIN |
TX |
US |
|
|
Appl. No.: |
17/518006 |
Filed: |
November 3, 2021 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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16186516 |
Nov 10, 2018 |
11200986 |
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17518006 |
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62584678 |
Nov 10, 2017 |
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International
Class: |
G16H 50/70 20060101
G16H050/70; G16H 20/10 20060101 G16H020/10; G16H 10/60 20060101
G16H010/60; G16H 40/63 20060101 G16H040/63 |
Claims
1. A method for determining an efficacy of a treatment agent,
comprising: holding a biologic sample containing a predetermined
biologic material within a reservoir of a microfluidic chip device,
pumping a portion of the biologic sample into each of a first
plurality of parallel pathways of the microfluidic chip device from
the reservoir using a first pump; applying one or more treatment
agents each within one of the first plurality of parallel pathways
to the portion of the biologic sample within the parallel pathway;
analyzing a first efficacy of each of the applied one or more
treatment agents to the portion of the biologic sample within each
of the plurality of parallel pathways; pumping a second portion of
the biologic sample into a selected at least one second parallel
pathway of a second plurality of parallel pathways from the
reservoir using a second pump; applying one of the one or more
treatment agents at a plurality of different dosage levels within
the selected at least one second parallel pathway to the second
portion of the biologic sample within the selected at least one
second parallel pathway; and analyzing a second efficacy of each of
the plurality of different dosage levels within each of the
selected at least one second parallel pathway.
2. The method of claim 1, wherein the step of pumping a second
portion of the biologic sample further comprises pumping the second
portion of the biologic sample into a plurality of parallel
pathways, each of the plurality of parallel pathways applying a
different dosage level of the plurality of different dosage
levels.
3. The method of claim 1, wherein the step of pumping a second
portion of the biologic sample further comprises pumping the second
portion of the biologic sample into a single parallel pathway, the
single parallel pathway applying a different dosage level of the
plurality of different dosage levels at different serial locations
in the single parallel pathway.
4. The method of claim 1 further including the step of applying
affinity labels to cells within the biologic sample.
5. The method of claim 1, wherein the step of applying the one or
more treatment agents further comprise passing the portion of the
biologic sample through a serpentine microchannel to apply the
treatment agent to the biologic sample.
6. The method of claim 1, wherein the step of analyzing the first
efficiency and the second efficiency further comprise displaying
the biologic sample having the treatment agent applied thereto in a
viewing reservoir.
7. The method of claim 1, wherein the first plurality of parallel
pathways of the microfluidic chip device are each associated with
testing a first type of medical issue.
8. A microfluidic chip device, comprising: a reservoir for holding
a biologic sample containing a predetermined biologic material; a
first plurality of parallel pathways each for testing one of one or
more treatment agents and for analyzing a first efficacy for each
of the one or more treatment agents applied to the predetermined
biologic material within the biologic sample; a first pump for
pumping a portion of the biologic sample into each of the first
plurality of parallel pathways from the reservoir; a second
plurality of parallel pathways each for testing a plurality of
different dosage levels of the one or more treatment agents and for
analyzing a second efficacy of the plurality of different dosage
levels with respect to the predetermined biologic material; and a
plurality of second pumps each associated with one of the second
plurality of parallel pathways for pumping a second portion of the
biologic sample into a selected at least one of the second
plurality of parallel pathways responsive to a control input
indicating the treatment agent providing a highest efficacy.
9. The method of claim 8, wherein the plurality of second pumps the
second portion of the biologic sample into a plurality of parallel
pathways, each of a plurality of parallel pathways of the second
plurality of parallel pathways to apply a different dosage level of
the plurality of different dosage levels.
10. The microfluidic chip device of claim 8, wherein the plurality
of second pumps pump the second portion of the biologic sample into
a single parallel pathway of the plurality of parallel pathways,
the single parallel pathway applying a different dosage level of
the plurality of different dosage levels at different serial
locations in the single parallel pathway.
11. The microfluidic chip device of claim 8 further including a
medium contained within the reservoir containing various affinity
labels for applying affinity labels to cells within the biologic
sample.
12. The microfluidic chip device of claim 8, wherein the first
plurality of pathways each further includes a first serpentine
microchannel for applying the treatment agent to the biologic
sample.
13. The microfluidic chip device of claim 8, wherein the second
plurality of pathways each further includes a second serpentine
microchannel for applying the treatment agent to the biologic
sample at the predetermined dosage.
14. The microfluidic chip device of claim 8, wherein the first
plurality of pathways and the second plurality of pathways further
include a viewing reservoir for analyzing the first efficiency and
the second efficiency.
15. The microfluidic chip device of claim 8, wherein the first
plurality of parallel pathways of the microfluidic chip device are
each associated with testing a first type of medical issue.
16. A microfluidic chip device, comprising: a reservoir for holding
a biologic sample containing a predetermined biologic material; a
first plurality of parallel pathways each for testing one of one or
more treatment agents and for analyzing a first efficacy for each
of the one or more treatment agents applied to the predetermined
biologic material within the biologic sample; a multiplexer for
providing a portion of the biologic sample into each of the first
plurality of parallel pathways from the reservoir; a second
plurality of parallel pathways each for testing a plurality of
different dosage levels of the one or more treatment agents and for
analyzing a second efficacy of the plurality of different dosage
levels with respect to the predetermined biologic material; and
wherein the multiplexer further provides a second portion of the
biologic sample into a selected at least one of the second
plurality of parallel pathways responsive to a control input
indicating the treatment agent providing a highest efficacy.
17. The microfluidic chip device of claim 16, wherein the
multiplexer provides the second portion of the biologic sample into
a plurality of parallel pathways, each of a plurality of parallel
pathways of the second plurality of parallel pathways to apply a
different dosage level of the plurality of different dosage
levels.
18. The microfluidic chip device of claim 16, wherein the
multiplexer provides the second portion of the biologic sample into
a single parallel pathway of the plurality of parallel pathways,
the single parallel pathway applying a different dosage level of
the plurality of different dosage levels at different serial
locations in the single parallel pathway.
19. The microfluidic chip device of claim 8, wherein the first
plurality of pathways each further includes a first serpentine
microchannel for applying the treatment agent to the biologic
sample.
20. The microfluidic chip device of claim 8, wherein the first
plurality of parallel pathways of the microfluidic chip device are
each associated with testing a first type of medical issue.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a Continuation of U.S. patent
application Ser. No. 16/186,516, filed Nov. 10, 2018, entitled
DATABASE AND MACHINE LEARNING IN RESPONSE TO PARALLEL SERIAL DUAL
MICROFLUIDIC CHIP (Atty. Dkt. No. RIDL60-34407), which claims
priority to and the benefit of U.S. Provisional Application No.
62/584,678, filed Nov. 10, 2017, and entitled DATABASE AND MACHINE
LEARNING IN RESPONSE TO PARALLEL SERIAL DUAL MICROFLUIDIC CHIP
(Atty. Dkt. No. RIDL60-33873), the contents of which are
incorporated by reference herein in their entirety.
TECHNICAL FIELD
[0002] The following disclosure relates to a system connecting
various participants in a medical system to exchange information
regarding research and test results.
BACKGROUND
[0003] The emergence and spread of antibiotic-resistant bacteria
are aggravated by incorrect prescription and use of antibiotics.
Courts have this problem is the fact that there is no sufficiently
fast diagnostic test to guide correct antibiotic prescription at
the point of care. Currently, some fluid sample is retrieved from a
patient and forwarded to a lab for testing to determine a specific
treatment regimen. As a safeguard, the patient is sometimes
initially given large doses of a general antibiotic until a more
specific antibiotic can be determined to target the specific
bacteria. This can take upwards of two or three days, as the
process requires growing the bacteria in some culture medium and
observing its response to various antibiotics.
SUMMARY
[0004] The present invention, as disclosed and described herein, in
one aspect thereof, comprises a microfluidic chip device includes a
reservoir for holding a biologic sample containing a predetermined
biologic material. A first plurality of parallel pathways each
testing one of one or more treatment-agents and analyzing a first
efficacy for each of the one or more treatment agents applied to
the predetermined biologic material within the biologic sample. A
multiplexer provides a portion of the biologic sample into each of
the first plurality of parallel pathways from the reservoir. A
second plurality of parallel pathways each test a plurality of
different dosage levels of the one or more treatment agents and
analyzes a second efficacy of the plurality of different dosage
levels with respect to the predetermined biologic material. The
multiplexer further provides a second portion of the biologic
sample into a selected at least one of the second plurality of
parallel pathways responsive to a control input indicating the
treatment agent providing a highest efficacy.
BRIEF DESCRIPTION OF THE DRAWINGS
[0005] For a more complete understanding, reference is now made to
the following description taken in conjunction with the
accompanying Drawings in which:
[0006] FIG. 1 illustrates a high-level view of a microfluidics chip
of the present disclosure;
[0007] FIGS. 2A-2C illustrate detailed views of the multiple stages
of analysis provided by the microfluidics chip of FIG. 1;
[0008] FIGS. 3A-3D illustrate diagrammatic views of the various
cell capture regions and the interspersed pumps for the
microfluidics chip of FIG. 1;
[0009] FIGS. 4A-4G illustrates detailed views of the first viewing
stage;
[0010] FIG. 5 illustrates a detailed view of the first parallel
driving stage;
[0011] FIGS. 5A and 5B illustrate details of the coating applied to
the micro channels in the first driving stage;
[0012] FIG. 6 illustrates a detail of the serial driving stage;
[0013] FIGS. 7A-7D illustrate detailed views of a valveless
nozzle/diffuser micropump;
[0014] FIG. 8 illustrates a detailed view of a piezoelectric
micropump;
[0015] FIG. 9 illustrates a detailed view of a multi-chamber
micropump with check valves;
[0016] FIG. 10 illustrates a flowchart for the high-level operation
of the microfluidics chip;
[0017] FIG. 11 illustrates a flowchart for the initial loading
operation of the fluid sample;
[0018] FIG. 12 illustrates a flowchart for the viewing or cell
counter stage of analysis;
[0019] FIGS. 13A-13C illustrate diagrammatic use for the cell
counter;
[0020] FIG. 14 illustrates a flowchart for the main parallel stage
of analysis;
[0021] FIG. 15 illustrates the serial stage of analysis;
[0022] FIG. 16 illustrates a simple fight diagrammatic view of the
microfluidics chip;
[0023] FIG. 17 illustrates a simplified diagrammatic view of a
parallel module;
[0024] FIG. 18 illustrates simplified diagrammatic view of a serial
module;
[0025] FIG. 19 illustrates a simplified diagrammatic view of a
serial module arranged in parallel;
[0026] FIGS. 20A and 20B illustrated a diagrammatic view of an
embodiment utilizing a chemostat;
[0027] FIG. 21 illustrates a diagrammatic you have the
microfluidics chip utilizing valves;
[0028] FIGS. 22A-22B illustrate cross-sectional views of a micro
valve
[0029] FIG. 23 illustrates a diagrammatic view of preparing a
biologic sample and disposing it in the well on the microfluidic
chip;
[0030] FIG. 24 illustrates a cross-sectional view of an RT-lamp
interfaced with a cell phone;
[0031] FIG. 25 illustrates a perspective view of the RT lamp
interfaced with a microfluidic chip and a cell phone;
[0032] FIG. 26 illustrates a side view of a cell phone interfacing
with the micro fluidic chip;
[0033] FIG. 27 illustrates a window view of the camera and the
alignment process;
[0034] FIGS. 28A-28H illustrate multiple views of a diagram of the
microfluidic chip in schematic form and various loading and
analysis steps associated there with;
[0035] FIG. 29 illustrates a flowchart for the overall analysis
process utilizing the microfluidic chip;
[0036] FIG. 30 illustrates a flowchart to pick in the details of
the test path.
[0037] FIG. 31 illustrates a diagrammatic view of a biofluidic
triggering system in accordance with various embodiments of the
present disclosure;
[0038] FIG. 32 illustrates a diagrammatic view of an analog testing
device to a digital format and unique identifier conversion
process;
[0039] FIG. 33 illustrates one example of a unique identifier 302
in accordance with various embodiments of the present
disclosure;
[0040] FIG. 34A illustrates an embodiment in which one of the data
streams of the unique identifier is a test identification, TID
field;
[0041] FIG. 34B illustrates an embodiment in which one of the data
streams of the unique identifier is a unique device identification,
or UDID field;
[0042] FIG. 34C illustrates an embodiment which includes a SOID
(self/other identification) field;
[0043] FIG. 34D illustrates an embodiment which includes a data
stream which contains demographic information;
[0044] FIG. 34E illustrates an embodiment in which the unique
identifier contains a data stream which indicates whether or not
the user has supplied their personal email address;
[0045] FIG. 34F illustrates an embodiment of a data stream for a
unique identifier which contains a timestamp of when a completed
medical test is scanned or photographed by the mobile
application;
[0046] FIG. 34G illustrates a data stream for an embodiment in
which a unique identifier contains information related to the
results of a medical test;
[0047] FIG. 34H illustrates a data stream for an embodiment in
which a unique identifier includes an indication of whether or not
the user wishes to have the test results sent to a healthcare
provider;
[0048] FIG. 34I illustrates a data stream for an embodiment in
which a unique identifier includes information identifying the
user's healthcare provider; and
[0049] FIG. 34J illustrates a data stream for an embodiment in
which a unique identifier includes information relating to a retail
suggestion;
[0050] FIG. 34K illustrates a data stream for an embodiment in
which a unique identifier includes information identifying the
user's insurance I.D.;
[0051] FIGS. 35A and 35B illustrate systems for transmitting
prescriptions to a pharmacy using telemedicine;
[0052] FIG. 36 illustrates an embodiment of a system which utilizes
a remote diagnostic test to initiate a medical escalation and
intervention;
[0053] FIG. 37 illustrates an example of a table which would be
found in the database of a central office and which contains
criteria for when to initiate a medical intervention based on the
results of a remote diagnostic test;
[0054] FIG. 38 illustrates an embodiment which includes mapping a
diagnostic test to an individual user to create a unique profile on
a remote database;
[0055] FIG. 39 illustrates an example of a unique biologic ID
database table;
[0056] FIG. 40 illustrates an embodiment which includes mapping
diagnostic tests to individual users to create unique profiles;
[0057] FIG. 41 illustrates a flowchart for an embodiment which
includes mapping a diagnostic test to an individual user to create
a unique profile on a remote database;
[0058] FIG. 42 illustrates a diagrammatic view of a medical test
results, trends, and response system;
[0059] FIG. 43 illustrates information that may be recorded in a
patient record;
[0060] FIG. 44 illustrates a flowchart of a patient record
update/creation process;
[0061] FIG. 45 illustrates a sequence diagram of a test results and
treatment regimen enactment process;
[0062] FIG. 46 illustrates a diagrammatic view of a trends engine
in accordance with various embodiments of the present
disclosure;
[0063] FIG. 47 illustrates one embodiment of database tables
showing a particular trend;
[0064] FIG. 48 illustrates a sequence diagram of a research and
trends feedback process;
[0065] FIG. 49 illustrates a medical condition trend activation
process; and
[0066] FIG. 50 illustrates a diagrammatic view of one embodiment of
a system device that may be used within the environment described
herein.
DETAILED DESCRIPTION
[0067] Referring now to the drawings, wherein like reference
numbers are used herein to designate like elements throughout, the
various views and embodiments of a microfluidic testing system with
cell capture/analysis regions for processing a parallel and serial
manner is illustrated and described, and other possible embodiments
are described. The figures are not necessarily drawn to scale, and
in some instances the drawings have been exaggerated and/or
simplified in places for illustrative purposes only. One of
ordinary skill in the art will appreciate the many possible
applications and variations based on the following examples of
possible embodiments.
[0068] Referring now to FIG. 1, there is illustrated a diagrammatic
view of a microfluidics chip 102 at a high-level view. There is
provided in the microfluidics chip 102 an input stage 104 that is
operable to receive a biological specimen. As used herein, a
"sample" must be capable of flowing through microfluidic channels
of the system embodiments described hereinbelow. Thus, any sample
consisting of a fluid suspension, or any sample that be put into
the form of a fluid suspension, that can be driven through
microfluidic channels can be used in the systems and methods
described herein. For example, a sample can be obtained from an
animal, water source, food, soil, air, etc. If a solid sample is
obtained, such as a tissue sample or soil sample, the solid sample
can be liquefied or solubilized prior to subsequent introduction
into the system. If a gas sample is obtained, it may be liquefied
or solubilized as well. The sample may also include a liquid as the
particle. For example, the sample may consist of bubbles of oil or
other kinds of liquids as the particles suspended in an aqueous
solution.
[0069] Any number of samples can be introduced into the system for
analysis and testing, and should not be limited to those samples
described herein. A sample can generally include any suspensions,
liquids, and/or fluids having at least one type of particle,
cellular, droplet, or otherwise, disposed therein. In some
embodiments, a sample can be derived from an animal such as a
mammal. In a preferred embodiment, the mammal can be a human.
Exemplary fluid samples derived from an animal can include, but are
not limited to, whole blood, sweat, tears, ear flow, sputum, bone
marrow suspension, lymph, urine, brain fluid, cerebrospinal fluid,
saliva, mucous, vaginal fluid, ascites, milk, secretions of the
respiratory, intestinal and genitourinary tracts, and amniotic
fluid. In other embodiments, exemplary samples can include fluids
that are introduced into a human body and then removed again for
analysis, including all forms of lavage such as antiseptic,
bronchoalveolar, gastric, peritoneal, cervical, athroscopic,
ductal, nasal, and ear lavages. Exemplary particles can include any
particles contained within the fluids noted herein and can be both
rigid and deformable. In particular, particles can include, but are
not limited to, cells, alive or fixed, such as adult red blood
cells, fetal red blood cells, trophoblasts, fetal fibroblasts,
white blood cells, epithelial cells, tumor cells, cancer cells,
hematopoeitic stem cells, bacterial cells, mammalian cells,
protists, plant cells, neutrophils, T lymphocytes, CD4+, B
lymphocytes, monocytes, eosinophils, natural killers, basophils,
dendritic cells, circulating endothelial, antigen specific T-cells,
and fungal cells; beads; viruses; organelles; droplets; liposomes;
nanoparticles; and/or molecular complexes. In some embodiments, one
or more particles such as cells, may stick, group, or clump
together within a sample.
[0070] In some embodiments, a fluid sample obtained from an animal
is directly applied to the system described herein at the input
stage, while in other embodiments, the sample is pretreated or
processed prior to being delivered to a system. For example, a
fluid drawn from an animal can be treated with one or more reagents
prior to delivery to the system or it can be collected into a
container that is preloaded with such a reagent. Exemplary reagents
can include, but are not limited to, a stabilizing reagent, a
preservative, a fixant, a lysing reagent, a diluent, an
anti-apoptotic reagent, an anti-coagulation reagent, an
anti-thrombotic reagent, magnetic or electric property regulating
reagents, a size altering reagent, a buffering reagent, an
osmolality regulating reagent, a pH regulating reagent, and/or a
cross-linking agent.
[0071] At this point in the process, a finite amount of biofluids
is disposed in the reservoir ready for transferring to subsequent
stages. This amount of fluid is then transferred to another stage
via a driving stage 106 in order to transfer this biofluid to
another reservoir, that associated with a viewing stage 108. At
this stage, a technician can examine the biofluid and determine the
makeup of the biofluid, discriminate cells, etc. in order to make
certain decisions as to going forward with remaining tests. The
microfluidic chip then transfers the biofluid at the viewing stage
108 to a parallel analysis stage 115 through a parallel driving
stage 110 wherein the biofluid is divided among a plurality of
parallel path this for analysis of the reaction of the material in
the biofluid with different reagents in a reading. This requires a
certain amount of the biofluid to be transferred to this analysis
stage. Thereafter, a decision is made as to whether to transfer the
remaining biofluid from the viewing stage 108, in order to perform
more testing and/or analysis on the biofluid. At this stage the
process, only one of the multiple second stage or serial stage path
is selected. One reason for this is that there is only a finite
amount of biofluid available and there is no need for testing along
paths that are associated with previous decisions indicating that
the results will be negative along these paths. Each of these
serial passes associated with one of the parallel paths. Thus, if
there are five parallel paths, there will be five serial paths.
Note that the term "serial path" is a term meaning that it is
within the serial decision tree and it need not actually be a
plurality of serial paths that are linked together in a serial
manner, although they could be and are in some embodiments
described hereinbelow. It is necessary to perform the
testing/analysis along each of the five parallel paths, but a
decision at this point indicates that only one of the serial paths
will be required for the testing/analysis purpose. This will be
described in more detail hereinbelow.
[0072] Referring now to FIGS. 2A-2C, there are illustrated
diagrammatic views of the various stages of the process. With
specific reference to FIG. 2A, there is illustrated a diagrammatic
view of first viewing stage, wherein the amount of biofluid stored
in the input stage reservoir 104 is driven to the viewing stage 108
reservoir. At this stage, optical device 202, for example, can be
used to view the cells disposed within the medium. This medium
could actually be the actual biofluid that was provided in the
sample from the human/animal or could be some diluted version
thereof. However, this biofluid will contain some cellular material
or some particulate of interest. This can be viewed with the out
device 202 and then passed to a processor 204, or a human could
analyze the results. With utilization of the processor 204, the
actual form of biofluid, and analog form, is transferred to a
digital form. This could be in the form of cell counting for
verification of a particular cell. As will be described
hereinbelow, affinity labels can be associated with each of the
cells or particulates in the biofluid and this could facilitate
visual recognition of different characteristics or different types
of cells, such as proteins, bacteria, etc. Each of these cellular
materials can have a particular affinity label associated there
with that allows it to be visually identified via some
characteristics such as florescence or even magnetic properties
associated with the affinity label. Again, this will be described
hereinbelow. Although an optical device 202 was illustrated and
described, any other type of device for analyzing the
characteristics of a particular affinity labeled cell can be
utilized, such as some type of magnetometer, etc.
[0073] Referring now to FIG. 2B, there is illustrated the next
parallel drive stage. At this stage, a micropump is utilized in the
parallel drive stage 110 to pump at least a portion of the biofluid
stored in the reservoir associated with the viewing stage 108 is
transferred to all of the parallel reading/analysis paths. In this
step, it can be seen that a portion of the biofluid in the
reservoir associated with the viewing stage 108 and is biofluid
exists in each of these parallel paths for analysis. There is an
indication in one of these parallel paths, associated with the
reservoir 210, that shows a positive indication of a reaction of
some type that is viewable. If, for example, this were bacteria,
one reagent could be an antibiotic in a large dosage that would
destroy the particular target bacteria and this would be recognized
by an observer. The other three paths, associated with reservoirs
214, 216 and 218 (an example of 4 paths), would have no reaction
and, as such, would not have affected the bacteria associated
therewith. In this example, a high level of concentrated antibiotic
is provided that would destroy the bacteria, but at this level of
analysis, there is no indication provided as to the actual dosage
of that antibiotic that would destroy the bacteria, other than the
fact that a large dosage of this particular antibiotic will destroy
the target bacteria. It is important to keep in mind that this
particular biofluid may have multiple and different bacteria,
proteins, etc. contained therein.
[0074] Referring now to FIG. 2C, there is illustrated a
diagrammatic view of the final serial stage of analysis/testing.
Since the first stage of testing/analysis transferred some of the
biofluid from the viewing stage 108 to the parallel stages 114,
there is still some biofluid remaining in the viewing stage 108.
This is a selectively transferred to one of the serial paths, that
associated with the testing reservoir 210. There are provided a
plurality of bypass channels 220 associated with each of the serial
paths and only the bypass channel 220 associated with the reservoir
210 in the parallel path 114 will be selected for transferring
biofluid to this particular serial path associated with the
reservoir 210 for testing. It will first be pumped to be a
micropump in a serial drive stage 222 to a first serial reservoir
224 for testing/analysis. If the test is negative, it can then be
passed to a subsequent serial driving stage 226 to a subsequent
serial reservoir 228 for testing/analysis and so on. As will be
described hereinbelow, there can be provided a single bypass path
220 which is connected to a manifold associated with each of the
serial paths and each of the manifolds can be associated with each
of the different reservoirs for testing, i.e., at this point the
testing is parallel to all of the subsequent testing reservoirs. In
the mode illustrated in this FIG. 2C, it is necessary to transfer
all of the necessary biofluid, i.e., typically the remaining
biofluid in the viewing stage reservoir 108, to the reservoir 224
and pass all of that biofluid to the next reservoir 228 and so on.
Thus, at each stage, all of the biofluid transferred in the
subsequent stages is tested at each subsequent stage. In a parallel
configuration, the remaining biofluid in the viewing stage 108
would be required to be divided among the different testing
reservoirs at each of the subsequent stages. This will be described
in more detail hereinbelow.
[0075] Referring now to FIGS. 3A-3D, there are illustrated
diagrammatic views of the process and fluid flow. In FIG. 3A come
there is illustrated an overall process flow for the embodiment
described hereinabove. This embodiment, there is provided an input
well 302 for receiving the biologic sample indicated by numeral
303. This constitutes a finite volume that must be transferred via
a micropump to a viewing reservoir 306. At this point,
substantially all of the biofluid is transferred from the reservoir
302 to the viewing reservoir 306. This is the first stage of the
process. The second stage of the process is illustrated as
providing three separate testing reservoirs 308, 310, 312, attached
at one to a microchannel manifold 314. Each of the testing
reservoirs 308, 310, 312, as will be described hereinbelow, is
comprised of a serpentine microchannel 316 attached at one end to
the manifold 314 and at the other end to a viewing reservoir 318. A
micropump 320 is provided for transferring biofluid from the
viewing reservoir 306 to the manifold 314. This will be divided
among the three testing reservoirs 308, 310, 312 and substantially
even amounts. The biofluid will traverse the serpentine
microchannel 316, which is coated with a particular reagent, one
example being an antibiotic. In this example, the antibiotic is at
a very high concentrated level, each of the testing reservoirs 308,
310 and 312 having a different antibiotic associated there with.
Only a portion of the biofluid in the viewing reservoir 306 will be
transferred to these three testing reservoirs 308, 310 and 312 for
testing/analysis and viewing at the associated viewing reservoir
318. The serpentine shape, when used with a medium containing cells
such as in a biologic sample, facilitates and enhances mixing due
to the increased interfacial contact area between the cells within
the biofluid sample.
[0076] The next step of testing/analysis will be selected only upon
a positive test occurring within one of the three testing
reservoirs 308, 310 and 312. However, each of the testing
reservoirs 308, 310 and 312 has associated there with a subsequent
group of testing reservoirs. In this embodiment, each of the
subsequent testing reservoirs is comprised of a plurality of sub
reservoirs 330, each of the sub reservoirs 330 being configured
identical to the testing reservoirs 308, 310 and 312, with a
serpentine microchannel region 316 and a viewing reservoir 318. A
single bypass microchannel 220 is provided to connect viewing
reservoir 306 to a sub reservoir manifold 332. Each of the
particular sub reservoir paths have associated there with a
separate micropump 334. Only one of these micropumps 334 is
selected for transferring the remaining portion of the biofluid
stored in the viewing reservoir 306 to the selected path. In this
embodiment, the remaining portion of the biofluid is transferred to
the first reservoir 330 bypassing the biofluid through the
serpentine microchannel 316 to the associated viewing reservoir
318. This particular microchannel will have coating of antibiotic,
in this example above, at a relatively low dose. If the bacteria,
for example, do not react accordingly with this level of
antibiotic, it can be recognized as such in the viewing reservoir
318. It is noted that the antibiotic associated with the coating on
the walls of the microchannel 330 at this dosage will not be picked
up by the bacteria and, as such, the bacteria in the viewing
reservoir 318 for the first sub reservoir 330 in the selected path
will still be intact. It can then be pumped from the reservoir 318
associated with the first testing reservoir 330 in the chain to a
subsequent testing reservoir 330 with a subsequent micropump 336.
This subsequent sub reservoir will have a concentration of
antibiotic in its serpentine microchannel 316 that is at a higher
level. As the level increases, a gradient is tested for, such that
the dosage can be gradually increased until the bacteria are
destroyed. If, for example, the bacteria were associated with an
affinity label that made it fluoresce, this would be recognized. It
could also be that there are multiple bacterial types contained
within the biofluid that are each associated with a different
affinity label and this could be recognized. It could, in fact, the
case that one type of bacteria perfected at a first dosage level of
the antibiotic and a second bacteria were affected at a another
dosage level of the antibiotic.
[0077] Referring now to FIG. 3B, there is illustrated a
diagrammatic view of an alternate process flow. This will work
substantially identical to the embodiment of FIG. 3A, come up until
the operation at the manifold 332 associated with the sub
reservoirs. In this embodiment, the three micropumps 334 each feed
a sub reservoir manifold 340. Each of the sub reservoir manifolds
340 is connected to a plurality of the sub reservoirs 330
associated with each path. In this embodiment, there are only
illustrated three sub reservoirs 330 for each of the sub reservoir
manifolds 340, although each path could have a different number of
sub reservoirs 330 associated therewith. The difference between
these two embodiments is that, at this point, the amount of
biofluid remaining in the viewing reservoir 306 now must be divided
amongst all of the sub reservoirs attached on one end thereof to
the associated sub reservoir manifold 340 selected by the activated
one of the micropumps 334. This will result in potentially less
biofluid being available for the testing/analysis step. This will
also mean that each of the viewing reservoirs 318 associated there
with will have a smaller volume associated therewith.
[0078] Referring now to FIG. 3C, there is illustrated a
diagrammatic view that provides a simplified diagram of the
transfer from reservoir to reservoir. In this illustration, the
input stage is illustrated as an input reservoir 350 labeled R0. A
micropump 352 is operable to transfer the contents of this input
reservoir, the biofluid, to a second reservoir, a viewing reservoir
354, labeled R1. A portion of the contents of this reservoir are
then transferred via a micropump 356 to a plurality of parallel
stage reservoirs 358 labeled R2. This is the first testing/analysis
stage. After this stage, the remaining contents of the viewing
reservoir 354 are transferred to the subsequent serial stage
reservoirs via a pump 360 via a bypass path and microchannel 362.
The serial stage reservoirs are labeled R3, R4, etc. This
illustration sets forth how the entire contents of the input
reservoir R0 are transferred down the chain. This is best
illustrated in FIG. 3D. In this illustration, it can be seen that
entire contents of reservoir R0 are transferred to reservoir R1. At
this point, only a portion of the contents are transferred to
reservoir R2. The remaining contents are sequentially transferred
to R3, R4, and so on. For this illustration, the entire remaining
contents of the reservoir 354, R1, will be transferred down the
chain entirely to reservoir R3, then to reservoir R4, and so on. In
the alternate embodiment, as described hereinabove, and not
illustrated in FIG. 3D, the bypass 362 could be connected to each
of the reservoirs R3, R4, etc. in parallel, noting that the
remaining contents of the reservoir R1 will then be divided amongst
the parallel connected reservoirs R3, R4, etc.
[0079] Referring now to FIGS. 4A-4G, there are illustrated
diagrammatic views of the initial processing section associated
with the viewing stage 108. There is provided a substrate 402 upon
the surface of which are formed a plurality of wells and
microchannels. A first well 404 is provided for receiving the
biofluid sample in this well has a finite volume associated there
with. At the bottom of this well a microchannel 406 extends outward
and up to the surface to an opening 408. The purpose of this
microchannel 406 extending to the bottom of the well 404 is to
ensure that the biofluid can be completely pumped from the well
404. For the formation of this microchannel 406, it might be that
the microchannel is formed through the surface of the substrate 402
and then a cover plate (not shown) having a surface that extends
down into the open microchannel. An adjacent channel 410 is
disposed proximate the opening 408 to provide another opening
therefore in order to accommodate a micropump 412 (shown in
phantom) interface with the opening 408 and the one end of the
microchannel 410 for transferring fluid from the well 404 to the
microchannel 410. The microchannel 410 extends along the surface of
substrate 402 in order to interface with a viewing well/reservoir
412. As the biofluid passes through the microchannel 410 and the
viewing well 412, a desired analysis can be performed on the
contents of the biofluid. As described hereinabove, in one example,
various cells in the biofluid might consist of different types of
bacteria, proteins, etc. and each of these may have associated
there with a specific affinity label, which is optically
detectable. There are, of course, other means by which affinity
labels can be detected. As the cells contained within the biofluid
pass through the viewing well/reservoir 414, they can be examined.
The viewing well/reservoir 414 on the other side thereof is
connected to one side of a microchannel 416, the other side thereof
connected to a reservoir 418. Since the micropump 412 must force
the biofluid through the microchannels and the viewing
well/reservoir 414, there is required the necessity for a holding
reservoir 418 to be present. However, initially, this reservoir
418, the microchannel 410 and the viewing well/reservoir 414 will
have air disposed therein. This air must be removed. This can be
done with a negative pressure of some sort or just a waste gate
output to the atmosphere. This is provided by a waste gate
microchannel 420 that is connected to an opening 422 through the
cover glass (not shown) or to the side of substrate 402. A valve
423 could be provided above the opening 422. As biofluid enters the
reservoir 418, air will be pushed out through the microchannel 420.
It is desirable for this microchannel 422 to have as low a profile
as necessary such that only air exits therefrom. Depending upon the
size of the cells contained within the biofluid, the microchannel
420 can be significantly smaller and have a lower profile than the
microchannels 410 and 416. Is important to note that, once the
micropump 412 transfers the biofluid from the well 404, the volume
transferred will be spread between the two microchannels 410 and
416, the viewing well 414 and the reservoir 418. Thus, the
reservoir 418 has a significantly larger volume that any of the
microchannels 410 and 416 and the viewing well/reservoir 414.
Additionally, it may be that the depth of the wells/reservoirs 404
and 418, as well as the viewing well reservoir 414 are also as
shallow as the microchannels 410 and 416 but significantly wider to
accommodate the required volume.
[0080] The outlet of the reservoir 418 is connected from the bottom
thereof through a microchannel 426 to an opening 428 on the upper
surface of the substrate 402. This is interfaced with a micropump
430 (in phantom) to an adjacent microchannel 432 for subsequent
processing. These micropumps 412 and 430, although illustrated as
being flush with the substrate, will typically be disposed above
the cover plate (not shown) with holes disposed through the cover
plate. The opening 428 will be a horizontal microchannel associated
with the manifold 314 described hereinabove. This will be
associated with a plurality of micropumps 430 for each of the
parallel paths or the bypass path. A cross-sectional view of the
embodiment of FIG. 4A is illustrated in FIG. 4B, with a cover plate
440 disposed over the substrate 402 with an opening 442 disposed
above the well 404 for receiving the biofluid sample.
[0081] FIGS. 4C and 4D illustrate top view and cross-sectional
views of the reservoir 418 illustrating how the microchannel 416
feeds biofluid into the top of the reservoir 418, and the flow path
for the biofluid from the reservoir 418 through the microchannel
426 from the bottom of the reservoir 418. However, it may be that,
with capillary action, the depth of the reservoir 418 could be
equal to that of the microchannels 416 and 426 such that they are
all at the surface of the substrate 402 for ease of manufacturing.
When a negative pressure is placed upon the reservoir 418, air will
be pulled into the microchannel 426 through the microchannel 420.
It is possible in this mode that the micropump 412 could be
operated to actually create a positive pressure in the microchannel
416 to force the biofluid in the reservoir 418 into the opening 428
through the microchannel 426. Again, the microchannel 420 would
preferably have a dimension that was smaller than the smallest cell
size within the biofluid.
[0082] Referring now to FIGS. 4E and 4F, there are illustrated top
view and cross-sectional views of the reservoir 418 with an
alternate embodiment illustrating microchannel 426' as being
beneath the bottom of the reservoir 418 to allow more complete
emptying of the reservoir 418.
[0083] Referring now to FIG. 4G, there is illustrated an alternate
embodiment of inlet wells for receiving the biofluid sample. There
is provided the well 404 for receiving the biofluid sample and a
second well 464 receiving an additional fluid sample. This fluid
sample in well 460 could be some type of dilutant or it could be a
medium containing various affinity labels. As noted hereinabove,
the fluid sample could have associated there with affinity labels
prior to the biofluid sample being disposed in the well 404.
However, it is possible that the microfluidic chip have disposed in
the well 460 a medium containing affinity labels, for example. The
well 460 would be interfaced through a microchannel 462 to an
opening 464 adjacent the opening 408. A two input, one output,
micropump 412' that interfaces with the microchannel 410.
[0084] Referring now to FIG. 5, there is illustrated a diagrammatic
view of the microchannel structure associated with the parallel
stage of operation. The microchannel 426 is interfaced with a
microchannel manifold 502 which corresponds to the opening 428.
This microchannel manifold 502 is interfaced with a plurality of
micropumps 504, corresponding to the micropump 430. These
micropumps 504 are disposed in pairs, each pair associated with one
testing reagent. As noted hereinabove, there are provided a
plurality of parallel paths, each associated with a reservoir 312
having a serpentine microchannel 316 and a viewing reservoir 318.
The first micropump 504 in the pair of micropumps 504 is connected
to one end of the associated serpentine microchannel 316. When this
micropump 504 is activated, biofluid from the reservoir 418 is
passed through the manifold microchannel 502 and through the
serpentine microchannel 316 to the viewing reservoir 318. As was
the case above, there is provided a waste microchannel 506 for each
of the reservoirs 318 to allow air to escape therefrom as biofluid
is forced through the microchannel 316. The micropump 504
associated with this serpentine microchannel 316 will be operated
for a sufficient amount of time to transfer sufficient biofluid
from the reservoir 418 through the serpentine a channel 316 and
finally into the reservoir 318 to fill the reservoir 318. The
microchannel 506 can have some type of valve associated with the
opening thereof to prevent the escape of any biofluid therefrom or,
alternatively, the dimensions of that microchannel 506 could be
small enough to prevent any appreciable amount of cells escaping
therefrom. Although not illustrated, the one of the pair of
micropumps 504 associated with the parallel stage of operation and
associated reservoirs 312 will also be operated to fill the
associated serpentine microchannel 316 and reservoir 318.
[0085] Referring now to FIGS. 5A and 5B, there are illustrated
cross-sectional views of the serpentine microchannel 316. As
described hereinabove, the sides of these channels 316 are coated
with some type of reagent. For example, if a Urinary Tract
Infection (UTI) were suspected and were being tested for in the
microfluidic chip, the sensitivity for common antimicrobial agents
for UTI treatment might include ampicillin (AMP), ciprofloxacin
(CIP), and trimethoprim/sulfamethoxazole (SXT), these being three
agents that could be tested for and three different paths. The
bacteria that might exist within the urine samples from an
individual could be any of uropathogenic E. coli strains (EC132,
EC136, EC137, and EC462). Some prior research has shown that,
through antimicrobial resistance profiles of these pathogens that
EC132 is resistant to AMP and CIP but not SXT. EC136 is resistant
to AMP only. EC137 is sensitive to all the antibiotics tested.
EC462 is resistant to AMP and SXT but not CIP. In order to coat
sides of the serpentine microchannels 316, one technique would to
have a certain amount of the antibiotic dissolved in sterile water
to the serpentine microchannels 316 at different levels.
Subsequently, the diluted antibiotic is dried by incubation at a
desired temperature and desired time. The original diluted
antibiotic has a starting concentration of a predetermined g/ml
concentration. The surface area is sufficiently covered such that,
when the biofluid passes thereover, it will interact with
reagent.
[0086] Referring now to FIG. 6, there is illustrated a microchannel
diagram of the reservoir 330 on the surface of the chip 402. This
is connected by the microchannel 507 from the associated one of the
micropumps 504. After the results in the viewing reservoir 318 have
been determined to yield a positive result, for that particular
path in the parallel analysis/testing operation, the other of the
pair of micropumps 504 is activated and the remaining amount of
micro-fluid from the reservoir 418 is transferred to the reservoir
330. This will be passed through the serpentine microchannel 316
and stored in the reservoir 318, labeled 602 in FIG. 6. This is
substantially larger than the reservoir 318 associated with the
reservoir 312. Thus, for this embodiment, the remaining portion of
the biofluid from the reservoir 418 will be substantially stored in
the reservoir 602. This will have associated there with a waste
microchannel 604 and an outlet microchannel 608 that extends
outward from the bottom of the reservoir 602 and up to an opening
610 in the surface of the substrate for interface with the
micropump 336. The micropump 336 is operable, at the next stage of
the testing/analysis, to move the contents of the reservoir 602
over to the next reservoir 330 for testing at that next
concentration level associated with the next reservoir 330 in the
sequence.
[0087] Referring now to FIGS. 7A-7D, there is illustrated an
example of a valveless MEMS micropump. The micropump includes a
body 702 with two pumping chambers 704 and 706. At the inlet side
of each of the chamber 704 and 706 is disposed a conical inlet 710
and 712, respectively. The conical inlets 710 and 712 are wider at
the pump chamber side and narrower at the inlet side thereof. The
inlet sides of conical inlet 710 and 712 are connected to
respective inlet channel 714 and 716. The outlet side of the
chambers 704 and 706 are interfaced with conical outlets 718 and
720, respectively, the conical outlets 718 and 720 having a
narrower portion at the outlet of the respective pump chamber 704
and 706 and a wider portion at the respective outlet thereof
interfacing with respective outlet channels 722 and 724. The
conical inlets 710 and 712 and outlets 718 and 720 are frustro
conical in shape. A piezoelectric membrane and actuator 726 is
dispose between the two pumping chambers 704 and 706 and is
operable to be extended up into one of the chambers 704 and 706 at
one time to increase the pressure therein and at the same time
extend away from the other of the chambers 704 and 706 to decrease
the pressure therein. The operation is then reversed.
[0088] The piezoelectric membrane and actuator 726 is comprised of
a piezoelectric disc 740 on one side of a membrane 742 and a
piezoelectric disc 744 on the other side thereof. Each of the
piezoelectric discs 740 and 744 are formed by stratifying a layer
of use electric material 748 between two layers of conducting
material 750. Piezoelectric material 748 can be made with Piezo
Material Lead Zirconate Titanate (PZT-SA), although other
piezoelectric materials can be used. The conducting material 60 may
be composed of an epoxy such as commercially available EPO-TEK H31
epoxy. The epoxy serves as a glue and a conductor to transmit power
to the piezoelectric discs 750. The piezoelectric discs 750 are
secured to the surface of the intermediate layer 748, so that when
a voltage is applied to the membrane 742, a moment is formed to
cause the membrane 742 to deform.
[0089] The operation of the micropump will be described with
reference to FIG. 7D. At rest, the upper chamber 704 and the lower
chamber 706 are separated by a diaphragm pump membrane 742. The
diffuser elements 710, 712, 718 and 720 are in fluid communication
with each respective chamber. Diffuser elements are oriented so
that the larger cross-sectional area end of one diffuser element is
opposite the smaller cross-sectional area end of the diffuser
element on the other side of the chamber. This permits a net
pumping action across the chamber when the membrane is
deformed.
[0090] The piezoelectric discs are attached to both the bottom and
the top of the membrane. Piezoelectric deformation of the plates is
varied by varying the applied voltage so as to excite the membrane
with different frequency modes. Piezoelectric deformation of the
cooperating plates puts the membrane into motion. Adjustments are
made to the applied voltage and, if necessary, the choice of
piezoelectric material, so as to optimize the rate of membrane
actuation as well as the flow rate. Application of an electrical
voltage induces a mechanical stress within the piezoelectric
material in the pump membrane 742 in a known manner. The
deformation of the pump membrane 742 changes the internal volume of
upper chamber 704 and lower chamber 706. As the volume of the upper
chamber 704 decreases, pressure increases in the upper chamber 706
relative to the rest state. During this contraction mode, the
overpressure in the chamber causes fluid to flow out the upper
chamber 704 through diffuser elements on both sides of the chamber.
However, owing to the geometry of the tapered diffuser elements,
specifically the smaller cross-sectional area in the chamber end of
the left diffuser element relative to the larger cross-sectional
area of the right diffuser element, fluid flow out of the left
diffuser element is greater than the fluid flow out the right
diffuser element. This disparity results in a net pumping of fluid
flowing out of the chamber to the left.
[0091] At the same time, the volume of the lower chamber 706
increases with the deformation of the pump member 742, resulting in
an under pressure in the lower chamber 706 relative to the rest
state. During this expansion mode, fluid enters the lower chamber
706 from both the left and the right diffuser elements. Again owing
to the relative cross-sectional geometry of the tapered diffuser
elements, fluid flow into the lower chamber 706 through the right
diffuser element is greater than the fluid drawn into the lower
chamber 706 through the left diffuser element. This results in a
net fluid flow through the right diffuser element into the chamber,
priming the chamber for the pump cycle.
[0092] Deflection of the membrane 742 in the opposite direction
produces the opposite response for each chamber. The volume of the
upper chamber 704 is increased. Now in expansion mode, fluid flows
into the chamber from both the left and right sides, but the fluid
flow from the right diffuser element is greater than the fluid flow
from the left diffuser element. This results in a net intake of
fluid from the right diffuser element, priming the upper chamber
704 for the pump cycle. Conversely, the lower chamber 706 is now in
contraction mode, expelling a greater fluid flow from the lower
chamber 706 through the left diffuser element than the right
diffuser element. The result is a net fluid flow out of the lower
chamber 706 to the left.
[0093] Referring now to FIG. 8, there is illustrated a
cross-sectional view of a piezoelectric micropump with check
valves. Membrane 802 is disposed within a pump chamber 804 and
secured to a body 806. A piezoelectric disc 808 is disposed beneath
the membrane 802 and electrode 810 is disposed below the
piezoelectric disc 808. Deformation of the membrane 802 with the
piezoelectric disc at the appropriate frequency will cause a volume
of the pumping chamber 804 to change. An inlet valve 811 allows
fluid to flow into the chamber 804 and an outlet valve 812 allows
fluid to flow out of the chamber 804.
[0094] Referring now to FIG. 9, there is illustrated a micropump
960 in which a nanofabricated or microfabricated fluid flow pathway
is formed between structures. A first reservoir 961 terminates with
a first gate valve 966 which permits or restricts fluid flow
between the first reservoir 961 and a second reservoir 971. An
electrolytic pump 985 drives a first diaphragm 965 which is
communication with the second reservoir 971, to close the first
gate valve 966, and pulls a second diaphragm 969, which opens a
second gate valve 968 to drive fluid from the second reservoir 971
to a third reservoir 973. The electrolytic pump 985 is driven by
electrowetting of a first membrane 964 on the first gate valve 966
side of the pump. By switching to electrowetting of a second
membrane 963 fluid within the third reservoir 973 is emitted from
an exit opening 970 by actuation of the second diaphragm 969.
[0095] Referring now to FIG. 10, there is illustrated a flowchart
depicting the overall operation of the system. The process is
initiated at a Start block 1002 and then proceeds to a block 1004,
wherein the biofluid sample is loaded. The process enclosed a block
1006, wherein the biofluid is transferred to the viewing window or
the cell counter. The process then flows to a decision block 1008
to determine when the counting operation is done, i.e., when the
cells have been discriminated. As noted hereinabove, each of these
cells could be associated with, depending on upon the type, a
particular affinity label to allow them to be discriminated between
within the viewing window. The process then flows to a block 1010
in order to pump the biofluid material to the next phase, that
associated with the parallel testing/analysis step. A decision is
then made at a block 1012 as to whether this is a positive state,
i.e., has any of the biofluid material interacted with a particular
reagent to give a positive result. If not, the process is
terminated at a block 1014 and, if so, the process flows to a block
1016 in order to capture the biofluid material in a secondary
reservoir. Once the path is selected, the appropriate micropump is
activated and the biofluid material is pumped to the next reservoir
along the secondary path, as indicated by a block 1018. The process
then flows to a block 1020 in order to analyze the results at each
secondary reservoir and, if there is a positive result, as
indicated by block 1022, the process is terminated at a block 1024.
If the result is not positive, the process then flows to a block
1026 to determine if that is the last testing reservoir and, if so,
the process flows to the terminate block 1024. If there are more
testing/analysis blocks through which to process the biofluid
material, the process then flows to block 1028 and back to the
input of a block 1018 to pump the biofluid serial to the next
testing reservoir.
[0096] Referring now to FIG. 11, there is illustrated a flowchart
for the loading operation, which is initiated at a block 1101 and
then flows to a block 1102 wherein the sample is placed in the well
and then to a decision block 1104 to determine if this is a process
wherein the biofluid sample is to be mixed with some other diluted
product or an affinity label. If it is to be mixed, the process
flows to a block 1106 to mix the biofluid sample and, if not, the
process bypasses this step. The process then flows to a block 1108
in order to activate the pump and transferred the biofluid material
after mixing to the next reservoir in the process.
[0097] Referring now to FIG. 12, there is illustrated a flowchart
for the process of the cell counting operation, i.e., the operation
at the viewing reservoir. This is initiated at a block 1202
proceeds to a block 1204 in order to transfer the biofluid material
to the viewing chamber. The process enclosed a block 1206 in order
to view the cells in real time as they pass through the various
microchannels and viewing window. The process then flows to a block
1208 in order to count the cells. At this stage, the cells can have
various affinity labels associated there with such that the target
cells can be viewed and discriminated between based upon the
affinity labels associated therewith. If, for example, there were
multiple types of bacteria contained within the biofluid sample and
each of these types of bacteria had associated therewith different
affinity label that clips arrest at a different color, they killed
be discriminated between. Additionally, proteins would have a
different affinity label than a bacteria and this would also allow
discrimination between the two types of cells. The process then
flows to a block 1210 to store the transferred biofluid in the
reservoir and into a block 1212 to terminate.
[0098] Referring now to FIGS. 13A-13C from their illustrated
various configurations for the cell counting operation. In the
first embodiment of FIG. 13A, there are provided a three-part
microchannel 1302, a middle section microchannel 1304 and an outlet
microchannel section 1306 the middle section 1304 has a diameter
that is slightly larger than the largest cell that could be
contained within the biofluid. This allows the cells to be
transferred in a more orderly manner. The cell viewing would be
performed at this middle section microchannel 1304. In the
embodiment of FIG. 13B, there are provided three varying diameter
middle microchannel sections 1308, 1310 and 1312, each with
different diameters to allow different size cells to flow
therethrough. This type of embodiment may facilitate some selection
in the cells for viewing. In the embodiment of FIG. 13C, there is
illustrated the above disclose embodiment wherein the microchannel
416 empties into the reservoir 418 and the viewing is basically
performed upon the cells within the reservoir 418.
[0099] Referring now to FIG. 14 come there is illustrated a
flowchart for the parallel cell capture in the first
testing/analysis stage. This is initiated at a block 1402 and a
process and proceeds to a block 1406 in order to preload all of the
cell capture areas having reagent associated there with, such that
the portion of the biofluid stored in the reservoir 418 is
transferred to the reservoirs associated with the parallel cell
capture areas. The process enclosed a block 1408 wherein the pump
is activated to fill all of the cell capture wells associated with
this stage of testing/analysis. The process then flows to a block
1410 to possibly allow the cells to slowly go through the
microchannels in order to interact with the reagent. If so, this
requires a certain amount of time and this would result in the
micropumps operating at a lower rate to allow sufficient time for
the cells to flow through the serpentine microchannels 316 to
interface with the particular coating on the surfaces thereof. This
basically is the amount of time required for the micropumps to fill
up the reservoir 318 associated there with. The length of the
serpentine microchannel 316 would determine the amount of time
required to fill up the reservoir 318. Once the reservoir has been
filled, as indicated by a block 1412, then the viewing window in
the reservoir 318 is analyzed, as indicated by a block 1414. The
path from the block 1410 to the input of the block 1414 indicates a
path by which the micropumps can be run at a higher rate. The
process then is terminated at a block 1416.
[0100] Referring now to FIG. 15, there is illustrated flowchart for
the second phase of the analysis, provided that the first phase
indicated a positive result for one of the cell capture areas and
the associated reagent. This is initiated a block 1502 and then
proceeds to a block 1504 to preload all of the secondary cell
capture areas with reagent and into a function block 1506 to pump
all of the remaining biofluid material from the reservoir 418 into
the first reservoir in the secondary reservoirs 330. This also goes
through and incubate step to allow the micropumps to pump at a
slower rate to allow the biofluid material to go through the
serpentine microchannel 316 at a slower rate before it enters the
associated reservoir 318. When the reservoir 318 is filled, as
indicate a by block 1510, the contents of the reservoir 318 are
analyzed at a block 1512. If the pump can be run at a faster rate,
this is provided by a path around the block 1510. If the result is
positive, as indicated by a block 1514, then the process is
terminated at a block 1516. If not, the process flows from the
block 1514 to a block 1518 in order to the next reservoir 330 in
the back to the input of the serpentine microchannel 316 and then
float the input of the block 1508.
[0101] Referring now to FIG. 16, there is illustrated a simplified
diagrammatic view of the microfluidics chip for processing a
plurality of modules. The sample 303 is input to the well 302 and
then pumped into the viewing window 306. A waste microchannel 1602
is provided an interface to the viewing window 306 that is
interfaced with a micro valve 1604 to allow air to escape, or any
bubbles that may be present, from the viewing window 306.
Additionally, the waste microchannel 1602 could interface with an
external vacuum source aid in fluid flow. A cell
counter/discriminator 1606 is provided for optically viewing the
contents of the viewing window 306, the output thereof processed
via a processor 1608. The outlet of the viewing window 306 is
interfaced with a manifold microchannel 1610 through a connecting
channel 1612. At this point, the micro valve 1604 is closed such
that the biofluid contained within the viewing window 306 and the
interfaced with microchannel manifold 1610 to allow fluid to be
pump therefrom to a plurality of distribution paths along
distribution microchannels 1614. It may be that pump 304 would need
to be activated in order to reduce the pressure at the upper end of
the viewing channel 306 or, alternately, a microchannel 1618
interfaced with a micro valve 1620 could be provided to, when open,
relieve the pressure in the upper end of the viewing window 306 to
allow biofluid to be pumped therefrom to the microchannel manifold
1610.
[0102] Each of the distribution microchannels 1614 is interfaced
with a separate module via an associated distribution pump 1624 to
interface with and associated one of modules 1625, labeled A-Z, for
example. There can be any number of modules provided. However, each
module 1625 has associated there with a finite capacity and,
therefore, the number of modules 1625 that can be interfaced to the
viewing window 306 is a function of the volume of biofluid
contained therein and the capacity of the reservoirs of each of the
individual modules 1625, each of the individual modules 1625
potentially having a different capacity, depending upon the
configuration thereof. However, selecting among the various
distribution pump 1624 can allow desired tests to be done with the
available biofluid contained within the viewing window 306.
[0103] Referring now to FIG. 17 there is illustrated a diagrammatic
view of one of the modules 1625 associated with the parallel
testing configuration, wherein biofluid is loaded into a plurality
of testing reservoirs. The distribution pump 1624 associated there
with transfers fluid from the distribution microchannels 1614 to an
intermediate microchannel manifold 1702 which is then interface
with a plurality of testing reservoirs 312, as described
hereinabove. Each of these testing reservoirs has a serpentine
microchannel 316 and a viewing window 318 associated there with. As
described hereinabove, each of these testing reservoirs can have a
different volume and a different configuration mechanically and can
be associated with a different test. They can each have a
particular coating of reagent, such as an antibiotic, to interact
with the biofluid for testing purposes to determine if there is any
reaction of the biofluid in the cells contained therein to the
material coated on the sides of the serpentine microchannels 316.
In the operation of this particular module 1625, all of these
testing reservoirs 312 are associated with different reagents and
will be loaded in parallel. For this embodiment, will be desirable
for each of the reservoir 312 to have the same volume. If, however,
they had different volumetric capacities, it would be necessary to
have some type of waste gate with a micro valve to allow all of the
viewing windows 318 to achieve full capacity.
[0104] Referring now to FIG. 18, there is illustrated a
diagrammatic view of the serially configured wherein a plurality of
testing reservoirs 330 our arranged in a series configuration. In
this configuration, the associated distribution pump 1624 will
transfer biofluid from the microchannel manifold 1610 through the
distribution microchannels 1614 to the first of the testing
reservoirs 330. The biofluid will be contained within the viewing
chamber 318 and, as noted hereinabove, there will be possible be
some type of waste microchannel associated micro valve to allow
air/bubbles to escape during filling of the viewing window 318.
Thereafter, a second serial pump 1706 is activated to transfer the
contents of the viewing window 318 to a second testing reservoir
330 in the associated serpentine microchannel 316 and viewing
window 318. In this transfer, there may be required a relief
microchannel (not shown) at the inlet end thereof to reduce the
pressure therein during the pumping operation. This will continue
until all of the tests have been done. Each of the serpentine
microchannels 316 associated with each of the testing reservoirs
330 will have a graduated increase in the particular reagent to
determine the dosage, in this example. It may be that, upon being
exposed to the dosage of the reagent in the first testing reservoir
330 that cellular material in the biofluid is somewhat affected by
the reagent, i.e., the antibiotic, for example. By moving to a
higher concentration of the reagent in the next sequential testing
reservoir 330, this could be accounted for in the overall analysis.
It may be that the actual concentration in the next sequential
testing chamber 330 is not an exact incremental increase in the
reagent. For example, if it was desired to expose the biofluid to
reagent increments of 10%, 20%, 30%, etc. in 10% increments, it may
be that the first testing chamber 330 has a concentration of 10%
and then the second testing chamber has a concentration of possibly
16%, accounting for the fact that the accumulated effect of passing
through the 10% testing chamber 330 and the 16% testing chamber 330
effectively provides a 20% accumulated exposure in the second
testing chamber 330 and so on.
[0105] Referring now to FIG. 19, there is illustrated a
diagrammatic view of a configuration for providing parallel loading
of the serial configuration for the incremental testing. This is
similar to the embodiment of FIG. 17, except that the testing
chambers 330 are all interfaced with the associated distribution
pump 1624 through a microchannel manifold 1902 in a parallel
configuration, such that they are all loaded at the same time, with
each having a different concentration of reagent associated there
with. In this configuration, however, since all of the testing
chambers 330 will be loaded in parallel, there are required to be a
sufficient volume of biofluid contained within the viewing window
306 initially to facilitate complete filling of each of the
associated viewing windows 318.
[0106] Referring now to FIGS. 20A-20B come there is illustrated a
diagrammatic view of chemostat, wherein the associated distribution
pump 1624 transfers biofluid from the distribution microchannel
1614 to a chemostat 2002. The details of the chemostat 2002 are
illustrated in FIG. 20B. A main microchannel 2004 is interfaced on
one and thereof with the output of the distribution pump 1624
associated there with, with the other end of the microchannel 2004
interfaced with a waste gate via a micro valve (not shown). There
are a plurality of cell storage microchannels 2006 connected
between one surface of the main microchannel 2004 and a waste
microchannel 2008. Each of these cell storage microchannels 2006
associated there with a filter 2010 disposed at the end thereof
proximate to the waste microchannel 2008. Each of the cell storage
microchannels 2006 has a size that will receive a particular target
cell having a particular dimension, such that the target cell will
flow into the cell storage microchannel and cells of smaller size
will pass through the associated filter 2010, which filter 2010 is
a microchannel with a diameter that is smaller than that of the
target cell. This waste material will flow out through the waste
gate or micro valve (not shown) associated with the waste
microchannel 2008. By maintaining a pressure differential between
the main microchannel 2004 and the waste microchannel 2008, the
target cells will be stored within the cell storage channels 2006.
Larger cells than the target cells in the main microchannel 2004
will bypass the cell storage microchannels 2006 and pass out of the
waste gate associated with the main microchannel 2004, keeping in
mind that there is required to be a lower pressure within the waste
microchannel 2008 as compared to the main microchannel 2004.
[0107] Referring now to FIG. 21, there is illustrated an embodiment
of the microfluidic chip utilizing micro valves as opposed to
intermediate micropumps. In this embodiment, there are illustrated
a plurality of input wells 2102 for interfacing with an initial
micropump 2104 to pump fluid through a viewing window 2106 to a
first reservoir 2108. Having multiple wells 2102 allows multiple
samples to be input through the viewing window 2106 or to actually
mix two different materials together for flowing through the
viewing window 2106 to the reservoir 2108. The waste gate 2110 can
be provided at the reservoir connected thereto via a waste
microchannel 2112 to allow air/bubbles to escape. A micropump 2114
is operable to pump fluid from the reservoir 2108 to a main
microchannel manifold 2116. During this pumping operation, some
type of pressure relief is required which can either be provided
via one of the pumps 2104 being activated or a relief micro valve
2118 Interface with the input end of the viewing window 2106
through a relief microchannel 2120.
[0108] Interfaced with the main microchannel manifold 2116 is a
plurality of distribution micro valves 2124. These distribution
micro valves 2124 can be interfaced with various modules, as
described above herein with respect to FIGS. 17-20A/B. The only
difference is that the associated distribution pump 1624 has been
replaced by a distribution valve 2124. Additionally, each of the
parallel loaded testing reservoirs 312 can be individually
associated with one of the distribution valves 2124 to selectively
certain ones thereof for testing. Since each one of these testing
reservoirs 312, after selection, is required to be completely
filled, by allowing individual selection of the testing reservoirs
312, certain ones thereof can be eliminated. It may be that, in
pre-analyzing the biofluid sample, it can be predetermined that
certain ones of the associated reagents in the reservoir 312 are
not required the testing/analysis step and can therefore be
eliminated from the step of filling. This is opposed to the
embodiment of FIG. 17, wherein all of the testing reservoirs 312
are complete the filled.
[0109] Referring now to FIGS. 22A-22B, there is illustrated
cross-sectional views of a micro valve in an open and a closed
position. The substrate 402 has cover plate 440 disposed on top
thereof. There are provided to microchannels 2202 and 2204 that are
to be connected together with the micro valve. The microchannel
2202 is interfaced with a hole 2006 to the surface of the cover
plate 440 to an opening 2208. The microchannel 2204 is interfaced
to a hole 2210 to an opening 2212 in the cover plate 440. The micro
valve has a fixed body 2214 with a membrane 2216 disposed on the
surface there above to define a pumping chamber 2218. The pumping
chamber 2218 has a hole 2220 interfacing the pumping chamber 2218
with the opening 2208 on the cover plate 440. Similarly, the hole
2212 is interfaced to the pumping chamber 2218 through a hole 2222.
The membrane 2216 is operable to reciprocate away from the surface
of the fixed body 2214 exposing the top of the hole 2220 in the
pumping chamber 2218 to allow fluid to flow through the pumping
chamber 2218 and down through the opening 2222 through the cover
plate 440 and through to the microchannel 2204. In the closed
position, the membrane 2216 is forced down against the upper end of
the hole 2220. A pneumatic cavity 2230 is disposed above the
membrane 2216 in a housing 2232 and interfaces with a pneumatic
source through a hose 2234. Thus, by drawing a vacuum in the
pneumatic cavity 2230, the membrane 2216 will be pulled away from
the hole 2220 to allow fluid to flow and, when pressurized air is
forced into the pneumatic cavity 2230, and the membrane 2216 is
forced down to the surface of the fixed body 2214 to seal the
opening 2224 in a closed position.
[0110] Referring now to FIG. 23, there is illustrated a process
flow for preparing the biologic sample for the microfluidic chip
102. The preparation of the biologic sample can take many forms. In
this example, the raw biologic sample can be preprocessed,
depending upon the type of sample that is being considered. For
example, if blood is being tested, the Complete Blood Count (CBC)
can be determined, as well as the White Blood Cell Count (WBC), the
liver functions and the kidney functions. For urinalysis, the
sample can be prepared for testing for WBC's and nitrates, as well
as proteins and Bilirubin. There are many well-known processes for
preparing biologic samples prior to testing. Once the biologic
sample has been prepared a, affinity labels are attached thereto.
Typically, there will be a vial 2302 provided with the biologic
sample that is mixed with affinity labels in a vial 2303 resulting
in the vial 2304 containing a labeled sample. These labels are
sometimes referred to as "affinity labels" or "microspheres." These
functional polymeric microspheres typically have a diameter of less
than 5 .mu.m and have been developed for use with immunological
methods. The reagents were initially used as visual markers to
identify specific cell types and analyze the distribution of cell
surface antigens by scanning electron microscopy. They have also
been used, due to their inherent properties, two separate labeled
from unlabeled cells by techniques such as centrifugation, a
electrophoresis, magnetic chromatography and fluorescence cell
sorting. The cells contained within the biologic sample are
basically cells bearing defined antigens or receptors, ligands
which bind with a high degree of selectivity an affinity to these
cell surface sites. The microspheres interact with the specific
ligand, which can allow for separation based upon the
characteristic properties of the microspheres. This allows for
displaying of these labeled cells with the target receptor or
antigen with antibiotics or other ligands directly or indirectly
bound to the microspheres. Specific types of microspheres or
affinity labels can be the type that will fluoresce at a particular
wavelength. Thus, specific cells can be identified the optical
techniques to identify target cells or differentiate between
various types of, for example, bacterial cells and proteins, etc.
This labeled sample is then disposed within the well 302 on the
microfluidic chip 102 for later processing.
[0111] Referring now to FIG. 24, there is illustrated a side
cross-sectional view of an RT-lamp. The RT-lamp is a Reverse
Transcription Loop-mediated isothermal Amplification device, which
is a technique for the amplification of RNA. This combines the
advantages of the reverse transcription without of the LAMP
technique. The LAMP technique is a single to technique for the
application of DNA. This technique is an isothermal nucleic acid
application technique, in which a chain reaction is carried out at
a constant temperature and does not require a thermal cycler. The
target sequences animal five at a constant temperature using either
two or three sets of primers and polymerase with high strand
displacement activity in addition to a replication activity. The
addition of the reverse transcription phase allows for the
detection of RNA and provides a one-step nucleic acid amplification
method that is used to diagnose infectious diseases caused by
bacteria or viruses.
[0112] FIG. 24 illustrates an example in which a multimode
instrument 2401 is coupled to a smartphone 2402. The smartphone
2402 includes an LED 2404 and a camera 2406. The camera 2406
includes an image sensor, such as a CCD. The instrument 2401
includes a sample chamber 2408 for receiving an optical assay
medium. The optical assay medium comprises the labeled biologic
sample disposed within the viewing window 306 on the microfluidic
chip 102. The sample chamber 2408 may include a door 2432 that
prevents stray light from entering.
[0113] The optical assay medium is positioned over a detection head
2412 in the sample chamber 2408. The instrument 2401 includes an
optical output path for receiving an optical output from the
optical assay medium in the sample chamber 2408 via the detection
head 2412. The optical output path may include a multimode fiber
2414 that directs light from the detection head 2412 to a
cylindrical lens 2416. The optical output path may further include
a wavelength-dispersive element, such as a diffraction grating
2418, that is configured to disperse the optical output into
spatially-separated wavelength components. The optical output path
may also include other optical components 2430, such as collimating
lenses, filters, and polarizers.
[0114] The instrument 2401 can include a mount for removably
mounting the smartphone 2402 in a working position such that the
camera 2406 is optically coupled to the optical path, for example,
in a predetermined position relative to the diffraction grating
2418. In this working position, the camera 2406 can receive at
least a portion of the dispersed optical output such that different
locations are received at different locations on the image
sensor.
[0115] The instrument 2401 may also include an input optical path
for directing light from a light source to the optical assay medium
in the sample chamber 2408, for example, through the detection head
2412. In some instances, the LED 2404 on the smartphone 2402 could
be used as the light source. To use the LED 2404 as the light
source, the input optical path may include a collimating lens 2420
that receives light from the LED 2404 when the smartphone 2402 is
mounted to the instrument 2401 in the working position. The input
optical path may further include a multimode fiber 2422 that
directs the light from the collimating lens 2420 to the detection
head 2412. The input optical path may also include other optical
components, such as collimating lenses, filters, and
polarizers.
[0116] The instrument 2401 may also include an additional input
optical path that directs light form an internal light source, such
as a laser 2424, to the optical assay medium in the sample chamber
2408. The additional input optical path may include a multimode
optical fiber 2426, as well as collimating lenses, filters,
polarizers, or other optical components 2428.
[0117] Referring now to FIG. 25, there is illustrated the view of
the RT-lamp 2401 with a microfluidics chip 102 disposed within the
sample chamber 2408.
[0118] Referring now to FIG. 26, there is illustrated a side view
of the smart phone 2402 interfaced with the microfluidic chip 102
four imaging the surface thereof, which is illustrated in a window
view in FIG. 27. This window view illustrates the viewing window as
a box 2702 in which the image of the microfluidic chip 102 is
displayed. The application automatically recognizes various markers
2704, 2706 and 2708 1 three corners thereof. This will allow
orientation of the window with respect to the application. A box
2710 shown in phantom dashes will be oriented by the application
running on the smart phone 2402. Once the box has been oriented
visually about the image of the microfluidic chip 102, then
processing can proceed. The processing is basically focusing upon
the chip to gain the best optical image of the target sites. The
target sites are storage reservoirs 312 and 330, for example. Each
of these will have a viewing well 318 associated there with and
these viewing wells 318 will have, in one example, a process
biologic sample having affinity labels associated there with that
fluoresce. By recognizing the florescence, the presence of the cell
can be determined. The lack of florescence indicates that the cell,
a bacteria for example, has been destroyed. This can be a positive
test. By examining at each stage of the testing process the chip, a
determination can be made as to results in essentially real time.
This will be described in more detail hereinbelow. Once the image
is believed to be in focus, the user can actually take the picture
or the application can automatically determine that the focus is
adequate and take that. This is very similar to character
recognition techniques that are utilized in recognizing faces in
camera images received by the phone.
[0119] Referring now to FIGS. 28A-28H, there are illustrated
various images of the microfluidic chip 102 at different stages,
this view being a diagrammatic view for simplicity. In this view,
there is provided the sample well 2802 which then feeds into the
viewing well 2804. As described hereinabove, there are multiple
pumps that allow fluid to be moved from the sample well 2802 over
to the viewing well 2804 and these are not shown for simplicity
purposes. There is provided a multiplexer 2806 which represents the
micropumps/valves described hereinabove. The multiplexer 2806 may
be associated with one bank 2808 of reservoirs 2802 for the
parallel processing stage. These reservoirs 2012 correspond to the
reservoirs 312. This requires that the multiplexer 2806 distribute
fluid to a microchannel manifold 2810 and one testing phase. The
multiplexer 2806 also is connected via a plurality of microchannels
to a bank of reservoirs 2814 associated with the serial processing
stage to selectively distribute fluid to one of the strings in a
second testing phase. This bank of reservoirs includes the
reservoirs 330 described hereinabove. Each of these reservoirs 330
is arranged in series such that each has a valve or pump 2816
disposed there between. The multiplexer 2806 also interfaces with a
bank 2820 of reservoirs, these, in this example, associated with
the serial testing/analysis stage and having reservoirs 330
associated there with. In this example, there are provided five
test reservoirs in the bank 2808, wherein each of these test
reservoirs has associated there with one serial string of test
reservoirs 330 in the bank 2814 and one parallel loaded string of
reservoirs 330 in the bank 2820. Additionally, there is a separate
testing reservoir 2824 which could correspond to the cell storage
area utilizing a chemostat described hereinabove, which is
interfaced with multiplexer 2806 through a microchannel 2826.
[0120] Referring now to FIGS. 28B-28H, there are illustrated
various stages of the loading and analysis. FIG. 28B illustrates
the first step in the process wherein the biologic sample is loaded
into the viewing window 2004. That the step in the process, the
microfluidic chip is disposed within the RT lamp 2401 and analyzed
to determine the number of cells and the type of cells. If, for
example, a certain bacteria were being tested for on this
particular microfluidic chip 102, the lack of bacteria cells, as
indicated by the particular affinity labels that would be attached
to these particular bacteria cells, would indicate that further
testing is not required. However, if the correct cells are labeled
and the number of cells is at an appropriate level for testing,
then the next step of the process is taken.
[0121] FIG. 28C illustrates a next step of the process wherein a
portion of the contents of the viewing well 2804 are transferred to
all of the reservoirs 2812 in the bank 2808, there being five
reservoirs 2812 disposed therein, it being noted that there could
be more reservoirs 2012 provided on the microfluidic chip 102.
There will be a certain amount of time required for the pump
associated with the multiplexer 2806 to actually move the desire
portion of the biologic sample through the manifold 2810 to the
reservoirs 2812. As noted hereinabove, each of the reservoirs 2812
corresponds to the reservoirs 312, each having a serpentine
microchannel 316 and a viewing reservoir 318 associated there with.
The micro pumps associated with the multiplexer 2806 in
communication with the very small widths of the microchannels can
require this process to take upwards of 10 or 20 minutes. After
this period of time, the microfluidic chip 102 can be imaged to
determine if the cells have been destroyed by the coating on the
surfaces of the serpentine channel 316. (It should be noted that
the viewing well 318 could also be coated). If the cells are
destroyed, this indicates that the reagent that coats the walls of
the microchannel associated with the reservoirs 312 reacted in a
manner indicating self-destruction. However, any visual indication
in the viewing wells that can be a vehicle for discrimination
between interaction with the particular reagent coating the walls
of the serpentine microchannels 316 will provide the ability for a
decision to be made as to which reagent is required for further
testing.
[0122] FIG. 28D illustrates the next phase of operation, which is
the phase in which the dosage level is determined. In the example
above, the middle reservoir in the bank 2808 provided a trigger
indication that triggered a decision to then test for dosage in the
middle string within the bank 2814. This will require a multiplexer
2806 to only transfer the remaining portion of the biologic sample
from the viewing reservoir 2804 into this particular string. As
described hereinabove, this process will involve first passing of
fluid to the first reservoir 330, which will take a certain amount
of time to actually pump the biologic sample through the
microchannels into the viewing window 318. This can be a multiphase
process, which requires viewing at each stage. In this particular
example, the third stage of testing in this middle string in the
bank of reservoirs 2814 resulted in a perceivable result, i.e., a
lack of florescence, for example. At this point, the image will
actually show the perceivable result in both the bank 2808 and in
the bank 2814. Thus, in the three phases of testing, the particular
cells have been a defined, an indication has been provided as to
which of multiple reagents that could possibly provide the desired
therapeutic results would be the best choice for the patient and
then the third phase of testing provides the actual dosage of that
determine reagent. It may be that for ten individuals that had
exactly the same symptoms and processed a similarly processed
biologic sample for testing in the same way with the microfluidic
chip and the RT-lamp 2401 came up with different results. Each
individual's particular physiology can vary and, as such, the
results could differ. In a typical medical environment, the
particular reagent of choice or drug of choice is determined by an
individual based upon various criteria. Since the medical
professional does not have the test directly in front of them, they
might just prescribe, for example, a broad based antibiotic. They
might follow that up with testing of a biologic sample in a lab,
which could take a number of days just to determine exactly what
bacteria is present and what would be the best antibiotic to use in
order to attack this particular bacteria. Of course, the
broad-spectrum antibiotic might have worked by the time the test
results come back. If not, these results might be useful to the
medical professional. However, these tests seldom if ever actually
focus in on the dosage that would be preferable for a particular
individual. If even the particular antibiotic could be identified
which was specific to that particular bacteria tested for and found
be present in the biologic sample, the dosage prescribed is
typically a medium or high dosage, depending upon the criteria that
the medical professional utilizes. However, the medical
professional typically generalizes the physiology of any individual
and maybe filters that based upon age, gender, etc. However, the
individual physiology is not taken into account.
[0123] With use of the present microfluidic chip 102, the entire
testing process can be performed at the Point of Care (POC) in a
relatively short amount of time. The result is not only the
identification of the best reagent to use but also the dosage. This
is all accomplished with a very small amount of biologic
sample.
[0124] FIG. 28E, there is illustrated a potential further
processing that can be provided. In this embodiment, the bank 2820
can have a different modification of the antibiotic that was
determined from the test associated with the bank 2808. This
modification could be associated with the pH of the antibiotic,
wherein it has been determined with respect to some antibiotics
that the pH of the antibiotic can affect the efficacy thereof. In
this example, it can be seen that the third reservoir with respect
to dosage is the one that is selected in the bank 2814 but in the
bank 2820, is the lowest dosage. Thus, the multiplexer 2806 needs
to first test the bank 2814 and then test the bank 2820. However,
it should be understood that both the bank 2814 and the bank 2020
could be identical, either serially loaded or parallel loaded, the
commonality being that they have a gradually increasing dose of
antibiotics that can be tested for.
[0125] FIGS. 28F-28G, there are illustrated two additional examples
of two different patients with substantially the same symptoms and
utilizing substantially the same process for preparing the biologic
sample. With respect to FIG. 28F, the fifth reservoir and the
antibiotic associated there with exhibited the highest efficacy at
the highest dose as to destroying the particular bacteria, in the
example of the bacteria. The associated dosage determined from
testing the biologic sample in the bank 2814 was considered to be
the second level of dosage. In the bank 2020, the third level of
dosage was considered to be the lowest dose. With respect to FIG.
28G, the first reservoir and the antibiotic associated there with
was considered to have the highest efficacy with respect to dealing
with the particular bacteria and it was the lowest dose in that
case when tested in the bank 2814, as compared to the fourth level
dosage in the bank 2820. It can be seen thus that different
patients will have different "fingerprints" associated with the
testing of the same biologic sample repaired and substantially same
way.
[0126] FIG. 28H, there is illustrated an alternate embodiment
wherein the test performed at the bank 2808 resulted in a slight
ambiguity in that the bacteria were killed in two other reservoirs.
In this case, the indication would be that either of these
antibiotics would work against this particular strain of bacteria.
Thus, the next phase the test would require the multiplexer 2806 to
distribute the contents of the reservoir 2804 through the
microchannels to actually two different strings. Thus, for this
type of test to be carried out, it is important that there be
sufficient volume in the viewing window 2804, i.e., sufficient
amount of biofluid introduced to the well 2802, in order to fill
both of these reservoirs and allow the testing to progress down to
the highest dosage level in either or both of the banks 2814 and
2820. The results of this test show that, for the rightmost
reservoir in the bank 2808 having been determined to be effective
at the highest dose, the next of the last dosage was required in
order to achieve the desired results, whereas the next to the left
reservoir in the bank 2808 having been determined to be effective
at the highest dose required only the smallest dose to achieve the
results. Therefore, this test shows that, although two antibiotics
would work, one would actually work with the lower dose.
[0127] It should also be understood that, in addition to the test
being different for the same strain of bacteria in a biologic
prepared men substantially the same way, it should also be
understood that this particular set of results could be different
for different strains of the same bacteria. It may be that, for one
strain, one antibiotic would work at a particular dose and, for
another strain of the same bacteria, a different antibiotic work or
just a different dose of the same antibiotic. The microfluidic chip
described and disclosed in the present disclosure allows this
determination to be made utilizing a single sample in a
parallel/serial testing method at the POC wherein the first step or
phase of selection is made among a plurality of potential
antibiotics that could arguably target different bacteria and, once
a determination is made at the first phase, then the next and
serial decision is made to determine dosage at a second phase.
[0128] Referring now to FIG. 29, there is illustrated a flowchart
depicting the overall analysis process. The process is initiated at
a block 2902 and then proceeds to a block 2904 wherein the biologic
sample is prepared. As described hereinabove, this preparation
involves labeling the cells within the biologic sample so that they
can be discriminated between or identified. It may be that there
are a number of different types of cells such as bacteria of
different strains and types, proteins, etc. Different affinity
labels can be applied such that multiple cells of different types
can be identified. The process then flows to a block 2906 wherein
the biologic sample is placed into the sample well and then passed
on to the viewing well. At this point, the microfluidic chip is
placed into the RT-lamp and optically analyzed, as indicated by
process block 2908. It is at this point in the testing phase that
the identification process will identify the potential target
cells. Since each of the microfluidic chips has a finite number of
reservoirs associated there with for the purpose of testing, the
coating is applied to these particular reservoirs for the specific
antibiotics or reagents to be tested may not be useful for testing
the particular cellular structures that have been identified at
this step in the process. However, it should be understood that the
number of different banks of testing reservoirs that can be
provided on a particular microfluidic chip can be expandable and
the could actually be provided for multiple different types of
reagents. For example, one set of testing banks may be associated
with UTI and another associated with streptococcal bacteria.
Recognizing these at this step in utilizing them with a
microfluidic chip that can test for both types of bacteria will
allow the particular biologic sample, which is quite small, to be
routed to the appropriate reservoirs for testing for that specific
identify bacteria.
[0129] The decision to proceed is determined at a decision block
2910 and, if testing can proceed with the current microfluidic
chip, the process proceeds to a block 2911 to select the particular
test that are to be performed. The process then proceeds to
sequence through the tests, as indicated by a block 2914. This
sequencing sequences through the various phases, with the initial
test being selected first, as indicated by block 2916. In the above
examples, this is the first parallel phase to determine which among
several reagents is most effective against the particular cellular
structure of interest. The process then proceeds to a block 2918 in
order to analyze the results of this initial test and then to a
decision block 2920 to determine if more tests are required or if
this is the only test. If the test is negative at this stage and
none of the reagents provides any effectiveness indication, the
process is terminated or, if this is the last test, the process is
terminated. The process, if continued, then selects the next test
in the sequence and proceeds back to the input of the block 2918 to
continue sequencing through the tests.
[0130] Referring now to FIG. 30, there is illustrated a flowchart
for the testing process. This is initiated at a block 3002 and then
proceeds to a block 3004 two first pump a portion of the biologic
sample stored in the viewing window through to the parallel
reservoirs and load all of the parallel reservoirs for
testing/analysis. This may take upwards of 10 or 20 minutes, due to
the fact that the micropumps utilized are relatively slow and the
diameter of the microchannels is small, thus restricting high flow
rates. The process then flows to decision block 3006 to determine
if there is been any positive result, i.e., is there any indication
that any of the reagents provide an effectiveness indication,
either through some color change or the lack of color indicating
the destruction of the cells. If there is no result, then the
process is terminated and the process flows to a function block
3008 to select the next test path that is associated with the
antibiotic having been tested as being effective in the first phase
of operation/testing. A process block 3010 and indicates that a
graded dosage test path is selected, either the one for loading
parallel or the one or loading serially. It should be understood
that the parallel loaded graded dosage test path requires all of
the reservoirs to be completely filled from the reservoir
associated with the viewing window. The serial path, by comparison,
allows all of the contents of the viewing window in the reservoir
associated there with to be disposed in each reservoir and then
sequentially transferred to the next reservoir down the chain and
at the higher dosage. However, it should be understood that the
system can be configured such that the first reservoir at the
lowest dosage is loaded with only a portion of the contents of the
viewing window and the reservoir associated there with, analyzed
and then a micro valve gate opened to allow the micropumps for
pumping fluid to the serial path to operate to continue pushing
more biofluid through the first reservoir, thus filling the second
and reservoir and so on. In this process, sufficient biofluid must
be contained within the viewing window and the reservoir associated
there with in order to allow for filling of all of the reservoirs
down to the highest dosage rate associated with that serial
string.
[0131] In the process, the serial string will first select the
lowest graded dose reservoir and a process block 3012 and then pump
biofluid to the first reservoir and a process block 3014, analyze
the results a process block 3016, understanding that it could take
10 to 20 minutes to fill each reservoir. A determination is made at
a decision block 3018 as to whether there is a positive result,
i.e., was there and an effectiveness determination made at this
point, and, if so proceed to a decision block 3020 to determine if
there are any higher concentrations to be tested for. If so, the
next reservoir selected by opening gate or activating a micropump,
as indicated by a process block 3022, and the proceed back to the
process block 3014 in order to pump to this reservoir.
[0132] In the parallel process, a process block 3026 indicates an
operation wherein the micropump pumps sufficient biofluid material
to the parallel rated reservoirs to fill all of the reservoirs and
into a process block 3028 in order to analyze the results.
[0133] In some embodiments, a biological specimen (i.e. saliva,
blood, urine, semen, feces) may be provided by a user onto an
analog testing device. The analog testing device may be used for
testing strep (i.e. strep A, strep B, rapid strep), TP/INR, chronic
conditions, MERS (Middle Eastern Respiratory Syndrome), diabetes,
urinary tract infection and analysis, influenza, pregnancy, HIV,
malaria, immunology, blood glucose, hemoglobin, blood electrolytes,
cholesterol, fertility, troponin, cardiac markers, fecal analysis,
sperm viability, food pathogens, HemoCues, CRP (put them in),
dengue fever, HBA1C (put them in), Homocystein, salivary assay,
drugs of abuse, drug interaction, infectious diseases, viral loads,
tuberculosis, allergies (i.e. food and environment), Lyme disease,
Methacillian-resistent MRSA, staphylococcus areas, sexually
transmitted diseases, thyroid stimulating hormone (TSH), lipid
profile, INR (put them in), TEG, magnesium, lactate, transcutaneous
bilirubin, Helicobacter pylori, bacteria, cell count, cancer
markers, tumor markers, resistant staph aureus, antibiotic
resistance, stroke markers, sepias markers, DNA markers,
parathyroid, renal, or any other type of analog testing device that
utilizes a biological specimen to determine a user's disease,
disability, discomfort or dissatisfaction state of health. In some
embodiments, the analog testing device may be compact and
hand-held. In some embodiments, the analog testing device may be a
standard stand-alone device.
[0134] In some embodiments, the user may take a sample of the
biological specimen and transfer the biological specimen to an
input of the testing device. The input of the testing device may
include an input window that guides and holds the biological
specimen securely within the analog testing device. In some
embodiments, more than one window may be provided on the analog
testing device to accommodate more than one biological specimen.
For instance, the analog testing device may include two windows for
a pregnancy test, in which one window may be provided to receive
urine to test for the presence of HCG and a second window may be
provided to receive urine to test for urinary tract infection
bacteria. In some embodiments, multiple analog testing devices with
one or more input windows may be used to detect the biological
specimen. In some embodiments, the analog testing device may
include a results display window indicating a positive or negative
sign, a color spectrum, a line, a circle, a curve, a balloon, a
signature marker, or variance of the like. The results may be
mathematical, geometrical, color spectral, light spectrum, cell
multiplication, or the like. The display window may indicate the
completion of the test, an error, the test results or a combination
thereof.
[0135] In some embodiments, the user may capture the results on the
results display window via a mobile computing device, for instance
in the form of audio, video, photo, scan, or a combination thereof.
The mobile computing device may include one or more peripheral
devices, for instance, an image scanner, microphone, video
recorder, digital camera, speakers, and the like, to capture the
results from the analog testing device and convert the results into
a digital data package.
[0136] FIG. 31 illustrates a diagrammatic view of a biofluidic
analysis system 3100 in accordance with various embodiments of the
present disclosure. The system 3100 may include a mobile device
3102. The mobile device 3102 may be a mobile handheld user device,
such as a smart phone, tablet, or the like. The mobile device 3102
may include a processor 3104, a memory 3106, an input/output (I/O)
interface 3108, a display 3110, and a communication interface 3112
all connected via a bus 3114. The communication interface may
connect the mobile device 3102 to outside sources, such as a server
3116 having a database 3118 associated therewith, over a network
3120, i.e. a cellular network or Internet network. The memory 3106
may store an operating system 3122 and various special-purpose
applications, such as a browser by which webpages and
advertisements are presented, or special-purpose native
applications, such as weather applications, games,
social-networking applications, shopping applications, and the
like. The digital data package may provide data to a special
purpose native application 3124 stored in the memory 3106, the
application 3124 having associated therewith an application
programming interface (API) 3126. The digital data package may be
obtained by the mobile device 3102 by an test results capture
module 3128 connected to the processor 3104. The test results
capture module 3128 may capture an image, scan, video, or other
digital media of a testing device 3130, converting the analog
biologic sample testing device and the results presented on the
device to a digital format and to create a unique identifier that
can be used to trigger a plurality of events.
[0137] The unique identifier comprising the digital data package
may be analyzed by the application 3124 to determine the results
from the analog testing device. In some embodiments, the
determination of the test results, due to the type of analog
testing device, is not determined locally by the application 3124.
In some embodiments, the unique identifier may be transmitted to
the server 3116, via the network 3120, for remote analysis of the
data contained in the unique identifier. In some cases, results
from the analog testing device may be determined locally and
remotely. In some instances, the user of the mobile device 3102 may
not have cellular network or Internet connection, for instance, the
settings for connectivity on the mobile device 3102 is disabled,
turned off or a combination thereof. In this case, the transmission
of the unique identifier to the server 3116 may be postponed until
a connection is available.
[0138] In some embodiments, the mobile device 3102 may include a
location sensor, such as a global positioning system (GPS) sensor
or other components by which geographic location is obtained, for
instance, based on the current wireless environment of the mobile
device 3102, like SSIDs of nearby wireless base stations, or
identifiers of cellular towers in range. In some cases, geographic
locations are inferred by, for instance, an IP address through
which a given mobile device 3102 communicates via the Internet,
which may be a less accurate measure than GPS-determined locations.
In other cases, geographic location is determined based on a cell
tower to which a mobile device 3102 is wirelessly connected.
Depending on how the geographic data is acquired and subsequently
processed, that data may have better or less reliable quality and
accuracy.
[0139] FIG. 32 illustrates a diagrammatic view of an analog testing
device to a digital format and unique identifier conversion process
3200 in accordance with various embodiments of the present
disclosure. A testing device 3202 may provide medical test results
in an analog format, such as in a results display window 3204
indicating a positive or negative sign, a color spectrum, a line, a
circle, a curve, a balloon, a signature marker, or variance of the
like. A biologic specimen may be deposited into the testing device
3202 where the biologic may bind or react with particular reagents
specific to the type of test to which the testing device 3202
pertains. The testing device 3202 may also include a test type
identifier 3206, such as a code, graphic, symbol, or other
indicator on a surface of the testing device 3202.
[0140] A mobile device 3208, which may be the mobile device 3102
described herein, may include a capture device 3210. The mobile
device 3208 may convert use the capture device 3210, in addition to
other data known or otherwise obtained by the mobile device 3208,
to convert the analog data and biologic presented by the testing
device 3202 to a digital unique identifier 212. When digital media
such as an image, video, or other digital format of the testing
device 3202 is captured by the capture device 3210, certain
properties may be analyzed, processed, and stored into as a digital
data package. For instance, the test type associated with the
testing device 3202 may be determined by the mobile device 3208 by
identifying the particular test associated with the test type
identifier 3206 captured within the digital media.
[0141] Test results provided in the results display window 3204 or
elsewhere on the testing device 3202 may also be captured within
the digital media and analyzed. For example, in the case of a color
indicator as the result of the test, the RGB values of the pixels
contained in the digital media of the test results may be
determined in order to provide a digital value for the test
results. The test result may be stored in the digital data package
in a particular digital format, for instance, a positive or
negative test result value. The value may be a binary value, a
rating, a probability, or other type of result indicator. The
biologic specimen used to conduct the test may also be included in
the digital data package. The biologic specimen provided into the
testing device 3202 may be determined from the test type identifier
3206, since in many cases the specific test will dictate the
biologic to be used.
[0142] The data provided by the digital data package may also
include the type, manufacture and serial number of the testing
device 3202, and a timestamp for when the capture device 3210
captured the digital media. The manufacture, serial number and
cellular provider of the mobile device 3208 may also be included in
the digital data package. The application 3124 may then generate
the unique identifier 3212 from the data of the testing device 3202
and mobile device 3208, in combination with data of the user of the
mobile device 3208. Data of the user may be the user's name,
birthday, age, gender, social security number, height, weight,
race, diagnosis status, insurance information, medical codes, drug
codes, and the like, and a combination thereof.
[0143] In some embodiments, the unique identifier may be verified
by a verification server, such as the server 3116, to determine the
authentication of the biological specimen. In some cases, the user
may provide the analog testing device 3202 with a substance not
classified as a biological specimen. In this instance, an
application on the server 3116 will provide the application program
3124 with a message indicating an error, in which the user may be
required to provide a biological specimen to a different analog
testing device. In some embodiments, after verification of a
biological specimen, the local application program 124 or the
server 3116 via the user's application program 124 will provide the
user with a positive or negative outcome of the analog testing
device 3202. In some cases, the user is displayed a negative test
result and the application program 124 of the mobile device 3208
indicates that testing is completed. In other cases, the user is
displayed a positive test result by the application program 124 on
the display 3110 of the mobile device 3208.
[0144] The unique identifier 3212 may include of a plurality of
digital data streams 3214 used during creation of the unique
identifier 3212, such as information included within the digital
data package, or otherwise known or obtained by the mobile device
3208 or the server 3116. The plurality of digital data streams 3214
(D1, D2, D3, D4 . . . Dn) may be assembled together to create the
unique identifier 3212, and the mobile device 3208, the server
3116, or the authorized system components may parse or deconstruct
the unique identifier 3212 to analyze specific user properties or
test properties, and to trigger events based on the properties.
[0145] Creating a single unique identifier 3212 which contains many
different items of information is an efficient way of associating
many different types of information with a single biologic, user,
test, etc. Every time a test is conducted, a new unique identifier
3212 may be created. Each unique identifier created may include the
plurality of data streams 3214. Each one of the plurality of data
streams 3214 in the unique identifier 3212 stores a different type
of information. In some embodiments, the information stored in data
streams 3214 includes the test type, the test results, demographics
of the user, or an identification number, such as an IMSI number,
for the mobile device 3208. Different embodiments may include
different data streams 3214, as is described hereinbelow with
respect to FIGS. 4A-4K. In some embodiments, the unique identifier
3212 is set up in a structural format, such that each data stream
3214 is a subcomponent of the unique identifier 3212. In some
embodiments, unique identifier 3212 is a string of alphanumeric
characters, and the data streams 3214 which make up the unique
identifier 3212 are simply different portions of the character
string. In these embodiments, the format of the unique identifier
3212 is known to a database or server which can correctly parse the
unique identifier 3212 into the separate data streams 3214 for
analysis.
[0146] FIG. 33 illustrates one example of a unique identifier 302
in accordance with various embodiments of the present disclosure.
In this example, the plurality of data streams 3212 includes, but
is not limited to, test data, such as test type, biologic data,
such as biologic type or types used by the test, test results
obtained upon completion of the test, user data such as
demographics, and mobile device data, such as an IMSI number.
[0147] Referring now to FIG. 34A, there is illustrated an
embodiment in which one of the data streams 3214 of the unique
identifier 3212 is a test identification, TID data stream 3402. The
TID data stream 3402 identifies the type of test which the user is
conducting (pregnancy, HIV, peanut allergy, etc.). In the example
depicted in FIG. 34A, the TID data stream 3402 is a character
string of "F1A," which indicates that the test is for the flu, is
test version "1," and is a test of an example "A" type of flu
substrain. Different embodiments of TID data stream 3402 will have
different sizes of character strings, or will not be character
strings at all. In some embodiments, this information is obtained
when a user uses the mobile application to scans a barcode or image
from the test product, or when the user inputs an identification
code into the mobile application. In some embodiments, the data in
the TID data stream 3402 is used by the mobile application to
determine which database to access when processing the results of
the medical test.
[0148] Referring now to FIG. 34B, there is illustrated an
embodiment in which one of the data streams 3214 of the unique
identifier 3212 is a unique device identification, or UDID data
stream 3404. The UDID data stream 3404 contains information which
uniquely identifies the mobile device on which the application is
running. Many devices, such as mobile phones, have unique
identifiers built-in by the manufacturer, often in the form of long
character strings, such as an IMSI number. In some embodiments, the
UDID data stream 3404 is a character string which includes such an
identifier. In other embodiments, the UDID 3404 is generated by the
mobile application or the mobile application user.
[0149] Referring now to FIG. 34C, there is illustrated an
embodiment which includes a SOID (self/other identification) data
stream 3406. The SOID data stream 3406 is a data stream 3214 which
designates whether the medical test is being performed on the
mobile application user, or whether the test is being performed on
an individual other than the user. The SOID data stream 3406 also
identifies the relationship between the person being tested and the
mobile application user. Some embodiments also include basic
demographic data, such as gender or age range, in the SOID data
stream 3406. For example, if the person being tested is a small
child, then the actual user of the mobile application may be the
child's mother or father. In the example depicted in FIG. 34C, the
SIOD data stream 3406 is a character string which reads "CF3,"
which indicates that the person being tested is a child of the
mobile application user, is female, and is three-years-old.
Naturally, other embodiments will have different formats for the
SOID data stream 3406, and may not be character strings.
[0150] Referring now to FIG. 34D, there is illustrated an
embodiment which includes a data stream 2302 which contains
demographic information. A DEMZIP data stream 3408 (demographic/ZIP
code) contains information about the person being tested with the
medical test. In the example illustrated in FIG. 34D, the DEMZIP
data stream 3408 includes a character string which represents the
gender, age range, and geographic location (in the form of a ZIP
code) of the person being tested. For example, in FIG. 34D, the
DEMZIP data stream 3408 indicates that the test subject is a male,
in age range 4, who is located in the ZIP code 78237. In other
embodiments, the DEMZIP data stream 3408 will have additional
demographic traits included, such as height or weight. Some
embodiments will contain geographic location information in a
format other than ZIP code, such as city, state, or country names.
In some embodiments, such as is illustrated in FIG. 34D, the DEMZIP
data stream 3408 will be a character string, while in other
embodiments, it will take other forms.
[0151] Referring now to FIG. 34E, there is illustrated an
embodiment in which the unique identifier 3212 contains a data
stream 3214 which indicates whether or not the user has supplied
their personal email address. A personal email data stream 3410
does not actually contain the email address of the user, but it
does indicate whether or not the user has supplied an email address
to the mobile application. In some embodiments, if personal email
data stream 3410 indicates that the user has supplied an email
address, then when the unique identifier 3212 is passed to a remote
server, the remote server will link the unique identifier 3212 with
the email address of the user which has been stored in a separate
database. In some embodiments, such as illustrated in FIG. 34E, the
personal email data stream 3410 is a simple character string of "Y"
or "N" to indicate "yes" or "no" with regard to whether an email
has been supplied. Other embodiments will have a "1" or a "0" for
"yes" or "no" or may have other character strings or data
formats.
[0152] Referring now to FIG. 34F, there is illustrated an
embodiment of a data stream 3214 for a unique identifier 3212 which
contains a timestamp of when a completed medical test is scanned or
photographed by the mobile application. Knowing exactly when a
medical test was scanned by a mobile application can be very
important in different types of analysis. In this embodiment, the
DTS data stream (date/time stamp) 3412 indicates the time in a
YYMMDDHHMMSS format, that is, the first two characters indicate the
year, the next two indicate the month, the next two indicate the
day, the next two indicate the hour (in a 24-hour day format), the
next two indicate the minute, and the last two indicate the second.
Naturally, some embodiments will have other formats for the DTS
data stream other than a 12-character string, and will have
different levels of specificity with regard to the time.
[0153] Referring now to FIG. 34G, there is illustrated a data
stream 3214 for an embodiment in which a unique identifier 3212
contains information related to the results of a medical test.
These embodiments will have test results, or information related to
test results as part of the overall unique identifier 3212 as an
EVRK (Evaluation of Results and Ranking of the Diagnosis) data
stream 3414, as opposed to, or in addition to, the results being in
a totally separate file. In embodiments of the system which use
numerical values for test results, these values will be
incorporated into the EVRK data stream 3414. Some embodiments will
also include an escalation scale, which is a numerical indication,
as a number on a predetermined scale, of how urgent or serious a
potential medical problem might be. In the example illustrated in
FIG. 34G, the EVRK data stream 3414 is a character string and has a
value of "0982," with the first three digits representing the
results of the test and the last digit representing the escalation
scale value. Other embodiments will have other formats for the EVRK
data stream 3414 and will have the results indicated in other ways,
such as alphanumerically, rather than just numerically.
[0154] Referring now to FIG. 34H, there is illustrated a data
stream 3214 for an embodiment in which a unique identifier 3212
includes an indication of whether or not the user wishes to have
the test results sent to a healthcare provider. In these
embodiments, the unique identifier 3212 includes a PDr (personal
doctor) data stream 3416. The PDr data stream 3416 is simply an
indication of whether or not the user wishes to have the test
results transmitted to the user's healthcare provider. In some
embodiments, a user inputs this preference into the mobile
application after completing the medical test, while in other
embodiments, this preference is input into the mobile application
separately from any particular test. In some embodiments, an
indication of wanting the results sent to the healthcare provider
will initiate a telemedicine session with the healthcare provider.
In some embodiments, such as that which is illustrated in FIG. 34H,
the PDr data stream 3416 is a short, simple character string, such
as "Y," "N," "1," or "0." Other embodiments will have different
formats.
[0155] Referring now to FIG. 34I, there is illustrated a data
stream 3214 for an embodiment in which a unique identifier 3212
includes information identifying the user's healthcare provider. In
these embodiments, the unique identifier 3212 includes a Healthcare
Provider data stream 3418. The Healthcare Provider data stream 3418
includes information which can be used in a storage database to
look up the healthcare providers identification and contact
information. This information would be used in situations where the
mobile application user indicates that they wish to have the
medical test results sent to the healthcare provider. In some
embodiments, the Healthcare Provider data stream 3418 contains a
code which is used to look up more detailed information from
another storage database, while in other embodiments, the
identification information and the contact email address or phone
number is stored in the data stream itself.
[0156] Referring now to FIG. 34J, there is illustrated a data
stream 3214 for an embodiment in which a unique identifier 3212
includes information relating to a retail suggestion. For these
embodiments, a Retail Suggestion data stream 3420 is included in
the unique identifier 3212. The Retail Suggestion data stream 3420
includes data which identifies a retailer or a product or service
which can be suggested (for example, through the mobile
application) to a user. In some embodiments, these suggestions are
based on the type of medical test performed. In other embodiments,
the suggestions are based on the results of the medical test. For
example, if the medical test is a pregnancy test which returns a
positive result, then the suggestion might be for a brand of baby
diapers. In the example illustrated in FIG. 34J, the Retail
Suggestion data stream 3420 provides a suggestion of Tylenol
("TYL") which can be purchased at Walgreens ("WAL"). In the example
illustrated in FIG. 34J, the Retail Suggestion data stream 3420 is
a character string. In other embodiments, the format of the Retail
Suggestion data stream 3420 will be different. In some embodiments,
the Retail Suggestion data stream is utilized in situations where
the PDr data stream 3416 indicates that the user does not wish to
have the test results communicated to a healthcare provider.
[0157] Referring now to FIG. 34K, there is illustrated a data
stream 3214 for an embodiment in which a unique identifier 3212
includes information identifying the user's insurance I.D. In these
embodiments, the unique identifier 3212 includes an insurance I.D.
data stream 3422. The insurance I.D. data stream 3422 includes
information which can be used in a storage database to look up a
user's insurance information. This information would be used in
situations where the mobile application user indicates that they
wish to have the medical test results sent to the healthcare
provider, pharmacy, or other entity to allow the user's insurance
to be used for a transaction, such as filling a prescription.
[0158] Referring now to FIG. 35A, there is illustrated an
embodiment of a system in which a prescription is transmitted to a
pharmacy using a medical test and telemedicine. In these
embodiments, rather than the patient needing to physically travel
to a pharmacy to drop off a prescription to be filled, the user
uses a mobile application to electronically transmit the
prescription information to the pharmacy. These embodiments improve
upon embodiments which use medical tests and telemedicine and take
advantage of the fact that the user is already engaged in a
telemedicine session with the user's healthcare provider through a
network 3502 such as the internet. In these embodiments, the user
engages in a telemedicine session with a healthcare provider as
described herein, via Path {circle around (1)}. When the user and
the healthcare provider complete the telemedicine session, the
healthcare provider can prescribe necessary medicine to the mobile
application user. However, since the user is not physically present
with the healthcare provider, the user does not pick up a physical
prescription slip. Instead, the healthcare provider transmits via
Path {circle around (2)} the prescription in electronic form either
to the user's mobile application, or to the pharmacy of the user's
choice. If the healthcare provider transmits the "electronic
prescription" to the user's mobile application, then the user can
then store the electronic prescription on his mobile device 3102 in
the mobile application until he is ready to get the prescription
filled. The user then uses the mobile application to send the
electronic prescription to the pharmacy via Path {circle around
(3)}. The pharmacy then fills the prescription as normal.
[0159] Referring now to FIG. 35B, there is illustrated another
embodiment of a system in which a prescription is transmitted to a
pharmacy using a medical test and telemedicine. These embodiments
are similar to those described herein with respect to FIG. 35A. The
system includes a user with a mobile device 3102 running a mobile
application, a healthcare provider, a pharmacy, and a remote server
or central office with a records database. In these embodiments,
the user participates in a telemedicine session with a healthcare
provider via Path {circle around (1)} as described herein. Next, if
the healthcare provider decides that a prescription is needed, the
healthcare provider creates a prescription record and transmits the
record through a network 3502 such as the internet to a central
office 3504 or remote server via Path {circle around (2)}. The
central office 3504 then stores the record in a records database
3506. When the user is ready to have their prescription filled,
they use the mobile application on the mobile device 3102 to
contact the central office 3504 via Path @. The central office 3504
then retrieves the prescription record from the database 3506 and
sends the prescription record to the pharmacy via Path {circle
around (4)} to have the prescription filled. With this method, the
healthcare provider does not have to worry about which pharmacy to
send the prescription to, and the fact that the prescription record
does not have to be stored on the mobile device 3102 means that the
user could potentially access the prescription record from another
mobile device or any other compatible device with network
access.
[0160] Referring now to FIG. 36, there is illustrated an embodiment
of a system which utilizes a remote diagnostic test to initiate a
medical escalation and intervention. In some situations, the result
of a medical diagnostic test will indicate that immediate or urgent
medical attention is needed for the patient. In some embodiments,
medical attention will be summoned automatically in these
situations. In these embodiments, the user performs a medical
medical test and uses a mobile application running on a mobile
device 3102 to capture an image of the test product, as described
herein. The mobile application then transmits, via Path {circle
around (1)}, the test information through a network 3602 to a
remote server or central office 3604. The central office 3604
accesses a database 3606 for the necessary information to generate
a result for the medical test. The central office 3604 may also
retrieve from the database 3606 criteria for determining whether or
not a medical escalation or intervention is warranted on the basis
of the test results. The central office 3604 generates a test
result and checks the criteria to determine if medical escalation
is needed. If no medical escalation is needed, the central office
3604 simply returns, via Path {circle around (2)}, the test results
to the mobile device 3102 through the network 3602. If, however,
the central office 3604 determines that some type of medical
escalation is warranted, then the central office transmits, though
the network 3602 via Path {circle around (3)}, the test and test
result information, along with information about the user (such as
any relevant personal, demographic and/or contact information
collected from the user) to a healthcare provider 3608.
Alternatively, instead of the healthcare provider 3608 being
contacted by the central office 3608, in some embodiments, the fact
that a medical escalation is needed is transmitted along with the
test results from the central office 3602 through the network 3602
via Path {circle around (2)} to the mobile device 3102 running the
mobile application. The mobile device 3102 then transmits the test
and test result information to a healthcare provider 3608 through
the network 3602 via Path {circle around (4)}.
[0161] The manner of the medical escalation or intervention varies
depending on the embodiment, and may vary depending on the type of
test and/or the test results. In some embodiments, the escalation
takes the form of notifying emergency medical personnel, rather
than a healthcare provider 3608, of an urgent medical situation. In
these embodiments, the central office may call 911 or in some other
way notify emergency services These embodiments would be useful,
for example, if a blood test shows that the medical test user has
near fatal levels blood sugar or that the user is having a heart
attack or stroke. In other embodiments, the medical escalation
takes the form of the mobile application on the mobile device
automatically initiating a telemedicine session with a healthcare
provider 3608. These embodiments are useful, for example, in
urgent, but not quite emergency, situations. For example, elevated
blood sugar or high blood pressure might not be immanently deadly
to a patient, but should still be addressed and brought to the
attention of a healthcare 3608 provider quickly. In other
embodiments which are most useful for urgent--but not quite
emergency--situations, the central office 3604 notifies the
healthcare provider 3608 of the test results, and leaves it up to
the healthcare provider to determine the best next course of action
to take with respect to the patient.
[0162] Referring now to FIG. 37, there is illustrated an example of
a table which would be found in the database of a central office
3606 and which contains criteria for when to initiate a medical
intervention based on the results of a remote diagnostic test. The
table 3702 includes several columns of information. In the example
embodiment depicted in FIG. 37, the diagnostic test is a
quantitative one which produces a numerical rating as part of the
test result, similar to the embodiments described herein. An
example of such a test could be a blood glucose test, wherein a
certain risk is generally associated with a range of glucose
levels. In this example, a low test result "rating" indicates a low
health risk for the condition being tested, while a higher "rating"
indicates a higher risk. In the some embodiments which use a table
such as table 3702, different types of medical intervention are
used for different test results. The first column 3704 of table
3702 specifies a range of test result "ratings," while the rest of
the columns 3704, 3706, and 3708 specify information correlating to
that rating range. Column 3706 specifies the health risk associated
with a particular test result rating from column 3704, and column
3708 specifies what type of medical intervention will be initiated
for a test result within a given range. For example, if a user
conducts the example medical test, and the central office 3604
generates a test result rating of 57 (which indicates a dangerous
health risk), then the central office will not only return the test
result to the user, it will also initiate an urgent medical
intervention, such as initiating a telemedicine session between the
user and a healthcare provider. If the central office 3604
generates a test result rating of 93 (which would indicate a deadly
health risk), then the central office will initiate an emergency
health intervention, such as notifying emergency medical services
of the user's condition. On the other hand, if the test result
rating is in the "NORMAL" or "ELEVATED" range, then no medical
intervention will be initiated, and the central office 3604 will
simply return the test results to the user and the mobile device
3102. Naturally, other embodiments will have different styles of
tables in the central office 3604 database. Some embodiments which
have qualitative rather than quantitative tests (for example,
testing simply "positive" or "negative" for a disease) will not
have various multiple different types of medical intervention.
[0163] Referring next to FIG. 38, there is illustrated an
embodiment which includes mapping a diagnostic test to an
individual user to create a unique profile on a remote database.
Each time a patient conducts a medical test, there is a change to
gather information about that patient and the patient's test.
Instead of each piece of information about a patient or a test
being regarded individually, multiple data points and pieces of
information for a common patient can be associated with each other,
providing a greater insight into and creating a detailed profile of
the patient. Referring to FIG. 38, there is illustrated a unique
profile record 3800. Each unique profile record 3800 is associated
with an individual patient or diagnostic test user and has a unique
ID 3802. The unique profile record 3800 contains information
associated with the patient/user, such as the patient name 3804,
the name of a healthcare provider 3806 associated with the patient,
or the name of a pharmacy 3808 associated with the patient.
Importantly, the unique profile record 3800 also includes the
biologic IDs 3810 associated with the user. Each biologic ID 3810
is the same ID as the biologic header 3902 in one of the unique
biologic ID database tables 3900. Thus, the unique profile record
3800 includes a "link" to the record of each biologic used by the
patient associated with the unique profile record. Each time a
diagnostic test is conducted on a biologic sample, the biologic
sample is associated with the unique profile record 3800, which
means the unique biologic ID database table 3900 (which includes
data about the test) is associated with the unique profile record
3800 and the user. This means that more information about the
patient is collected and accumulated.
[0164] Different embodiments will include different types of data
to be stored within each unique profile record 3800. In some
embodiments, the unique profile record 3800 includes information
about food or medications to which the patient is allergic. Some
embodiments of the unique profile record 3800 include records of
which illnesses which the patient has had. Virtually any type of
information related to the patient/user can be included in the
unique profile record 3800 in various embodiments, so long as it
contributes to construction a better "picture" of the
patient/user.
[0165] Referring now to FIG. 39, there is illustrated an example of
a unique biologic ID database table 3900. The table 3900 is
illustrative of the type of data stored in association with data
for a biologic transmitted by a mobile device 3102 for storage on
the database 3118. A biologic ID header 3902 is provided that shows
that the biologic sample has been given a unique ID. All data
concerning the biologic may be stored in association with the
unique biologic ID. The table 3900 also includes a biologic type
entry 3904. This designates what type of biologic that the biologic
associated with the unique ID is, such as blood, urine, stool,
saliva, sweat, or other biologics. The table 3900 also provides a
plurality of test ratings 3906, for various tests performed on the
biologic. In the example shown in FIG. 39, a blood biologic is
provided having an assigned ID of 2402, and having been testing for
pregnancy markers, the Zika virus, and for glucose levels. The
rating for pregnancy was a 99 rating, the rating for a Zika
infection was a 75, and the rating for glucose levels was a 10.
This would indicate that the test subject has an extremely high
likelihood of both a pregnancy and a Zika infection, which would
have resulted in a warning to seek medical attention at the
conclusion of the tests. Other information may also be stored in
the database in relation to the biologic, including other condition
ratings, time and date each test was performed, user information
such as ethnicity, gender, and age, and status indicators such as
whether a test subject visited a physician as a result of the
tests. The database 3118 thus provides the test subject with a
growing collection of information that may be accessed by the test
subject. This allows the test subject to present the test results
to her physician for medical attention or additional testing, and
allows for others who may access the database, such as disease
researchers, to have access to data on various biologic samples and
their markers.
[0166] Referring next to FIG. 40, there is illustrated an
embodiment which includes mapping diagnostic tests to individual
users to create unique profiles. The patient/user 4001 conducts a
medical test using a mobile device 3102. The first time the patient
4001 uses the mobile application on the mobile device 3102, the
application allows the patient to create a unique ID 3802 to be
assigned to the unique profile record 3800 associated with the
patient. In some embodiments, the unique ID 3802 is simply assigned
by the mobile application instead of being chosen by the user 4001.
After a test is conducted, the mobile application transmits the
biologic ID 3902 of the biologic tested along with the unique ID
3802 along Path {circle around (1)} through a network 4002, such as
the internet, to a remote server or central office 4004. Once the
biologic ID 3902 and the associated unique ID 3802 reaches the
central office server 4004, the central office server transmits the
biologic ID and the unique ID to a connected database 4006. Within
database 4006 are stored the unique profile records 3800 for each
patient/user 4001. Once the database 4006 receives the biologic ID
3902 and the unique ID 3802, the database uses the unique ID to
identify the correct unique profile record 3800 and then appends
the biologic ID 3902 to that unique profile record. If this is the
first test conducted for/by a particular patient/user 4001, then
the database 4006 creates a new unique profile record 3800 with the
provided unique ID 3802 and appends the biologic ID 3902. In this
way, each time a user 4001 conducts a diagnostic test, the unique
ID 3802 and the biologic ID 3902 are sent to the database 4006,
where the unique profile record is incrementally augmented with
additional information about the user/patient 4001. In some
embodiments, the biologic ID 3902 is not assigned by the
application on the mobile device 3102. Instead, the mobile device
sends the information relating to the biologic (test type, test
results, etc.) to the central office serve 4004 and database 4006,
which then assign a biologic ID 3902 to the biologic data and
associate it with the appropriate unique ID 3802.
[0167] Data for other users 4001 with other unique profiles 3802
will be handled similarly. Since each user 4001 has a unique
profile record 3800 associated with him or her, the database 4006
will be able to associated biologic IDs 3902 with the correct user.
In this way, the database 4006 will be populated with unique
profile records 3800, from which potentially vast amounts of data
can be obtained.
[0168] Referring now to FIG. 41, there is illustrated a flowchart
for an embodiment which includes mapping a diagnostic test to an
individual user to create a unique profile on a remote database.
The process starts at Start block 4102 and proceeds to function
block 4104, where the user launches the mobile application on the
mobile device 3102. The process then moves to decision block 4106.
If a unique ID 3802 for the user does not exist, the process moves
to function block 4108, where a unique ID is created by the mobile
application. The process then moves to function block 4110. If, at
block 4106, a unique ID 3802 for the user does exist, the process
skips block 4108 and moves to function block 4110. At block 4110,
the user conducts a diagnostic test with a testing device 3130 and
a mobile device 3102 as described herein. The process then moves to
block 4112, where the mobile application transmits the biologic ID
information 3902 (which will also link the user to data about the
type of diagnostic test) and the unique ID 3802 to the remote
server 4004. At step 4114, an ID is assigned to the biologic
information. The process then moves to decision block 4118. If a
unique profile record 3800 for the user does not exist, the process
moves to function block 4116, where a unique profile record is
created. The process then moves to function block 4120. If, at
decision block 4118, a unique profile record 3800 for the user
already exists, the process moves to block 4120. At block 4120, the
database 4006 appends the biologic ID information 3902 to the
unique profile record 3800. The diagnostic test performed by the
user is now mapped to the user's profile 3800 through the biologic
database ID table 3900. The process then ends at End block
4122.
[0169] In some embodiments, a medical test may be performed by a
doctor, lab technician, etc. and may use an automated testing
device to perform the test. In this scenario, the test may be used
to determine a treatment regimen for a patient based on the test
results. For instance, if the test is designed to determine the
proper medication and dosage level of that medication to
effectively treat a patient, this information may be added to a
patient file and transmitted to other parties to alert the other
parties to take action in order to enact the treatment plan.
[0170] FIG. 42 illustrates a diagrammatic view of a medical test
results, trends, and response system 4200. The system 4200 includes
a centralized system 4202. The centralized system 4202 may include
or be connected to an actionable analytics database 4204, a trends
engine 4206, and a plurality of patient records 4208. The plurality
of patient records 4208 may include patient demographics and
personal information, medical history including test results,
doctor's notes, etc., medical information specific to the patient
such as DNA data, blood type, markers detected during tests on the
patient, or other types of information. The centralized system 4202
may act as a central hub of information for various entities
related to the medical industry. These various entities may be
interconnected with each other as well as with the centralized
system 4202.
[0171] For example, the system 4200 illustrated in FIG. 42 further
includes one or more of the following: a doctor's office 4210, a
test site 4212, a university of higher learning 4214, a research
database 4216, a research lab 4218, a hospital 4220, a compounding
pharmacy 4222, a retail pharmacy 4224, the centralized system 4202,
and other entities 4226. All these entities may be interconnected
over a network 4228 to share information and otherwise provide an
infrastructure for tracking medical test results, disease trends,
pharmaceutical effectiveness trends, triggering medical actions for
patients, etc. For example, test results generated by using the
microfluidic chip described herein may include drug efficacy and
proper dosage information pertaining to a patient. This information
may be passed from the entity in the system 4200 that performed the
test, such as a doctor's office 4210, a hospital 4220, a research
lab 4218, or any other test site 4212 or other entity 4226. The
results may then be received by the centralized system 4202 to
update a patient record 4208 stored in associated with the
centralized system 4202. The test results, test information,
patient information, and other data may be stored in the database
4204 or processed by the trends engine 4206 to evaluate overall
patient health, and to determine whether the patient is susceptible
to other medical conditions or whether the test results received
regarding the patient are indicative of trends or other medical
conditions concerning other patients whose information is stored in
the centralized system 4202. The results may also be utilized in
advancing medical research, such as by universities 4214, research
labs 4218, and by updating research databases 4216.
[0172] Referring now to FIG. 43, and still to FIG. 42, patient
records on file with any of the entities 4210-4226 may also be
updated to reflect the new information obtained as a result of the
test. FIG. 43 illustrates the types of information that may be
recorded in a patient record 4208, or in the database 4204, in
accordance with various embodiments of the present disclosure. FIG.
43 shows that a patient may have a patient record 4302. This
patient record may be stored as a document on the centralized
system 4202, such as a text file, PDF file, excel file, or other
document, or the data in the patient record 4302 may be stored in
the database 4204. Particular test types may have ID numbers
associated with the particular test types. The ID for the test type
may be stored in relation to a patient record when the test
associated with the test ID is performed on the patient associated
with the patient record. Results of the test performed on the
patient or on a patient's biologic specimen may also be stored in
relation to the patient.
[0173] For example, FIG. 43 shows that test results 4304 of a test
having a test ID of 10 are stored in relation to a patient having a
patient ID of 1002. Test information results, treatment plans, and
other information may be stored in relation to the patient. For
example, and as illustrated in FIG. 43, if a patient is found to be
positive for a bacterial infection, such as streptococcal bacteria,
and results from a test conducted using the microfluidic chip
described herein indicate that the most effective medication and
dosage to treat the infection is amoxicillin at 250 mg, this
information may be transmitted across the system 4200. The
centralized system 4202 may receive the test results and generate a
treatment plan or regimen that indicates that the patient should
take amoxicillin at 250 mg twice daily for two weeks. The treatment
regimen may be generated for the patient and this treatment regimen
may be transmitted to entities responsible for enacting the
treatment regimen, such as the doctor's office 4210, the
compounding pharmacy 4222 or the retail pharmacy 4224, etc.
[0174] Referring now to FIG. 44, there is illustrated a flowchart
of a patient record update/creation process 4400. The process
begins at step 4402 when a medical test is performed to determine a
treatment plan for a patient, such as a test using the microfluidic
chip described herein. At decision block 4404, an entity such as
the centralized system 4202 determines whether the patient is a new
patient, which may be done by querying the database 4204 for
personal information relating to the patient to determine if that
information already exists in the database such as a social
security number. If it is determined that the patient is a new
patient, the process flows to step 4406 to generate a new record
for the patient. The process then flows to step 4410. If at
decision block 4404 it is determined that the patient already has a
patient record stored, the process flows to step 4408 where the
existing patient record is updated with the results of the test
performed in step 4402. The process then flows to step 4410. At
step 4410, a treatment regimen is determined for the patient based
on the test results data. For instance, if a particular medication
at a particular dosage level was tested as effective against a
medical condition of the patient, a regimen of administration of
the medication may be generated.
[0175] The process then flows to step 4412 to save the treatment
regimen to the patient record. At step 4414, an overall patient
health report may be saved to the patient record. This health
report may include general information relating to the patient from
other office visits, such as weight, medical states such as
diabetes or other states, and may include the medical condition
with respect to the test conducted in step 4402, such as stating
the test date, severity of the condition, details regarding the
treatment regimen and drug interactions and side effects, etc. The
process then flows to step 4416. At step 4416, the treatment
regimen, overall health report, and other patient information may
be transmitted to entities that may use such information to treat
the patient, such as a doctor's office, hospital, or other
entity.
[0176] Referring now to FIG. 45, there is illustrated a sequence
diagram of a test results and treatment regimen enactment process
4500. At step 4502, a doctor sends a request to a test site to
schedule a test. The test site at step 4504 then performs the
scheduled test. At step 4506, a treatment plan is generated at the
test site. The test site may generate the treatment plan when
generation of the treatment plan is automated by the device
performing the test, or by a professional analyzing the test. In
some embodiments, the test results may be sent elsewhere for
determining the treatment plan, such as to the doctor or to the
centralized system.
[0177] At step 4508, the test site sends an update to the patient
record at the centralized system with test results and a treatment
plan. At step 4510, the centralized system transmits the test
results and treatment plan to the doctor's office. At step 4512,
the doctor's office confirms the treatment plan with the patient
and at step 4514 the doctor's office sends a confirmation of the
treatment plan and any written prescriptions to the centralized
system. At step 4516, the centralized system updates the overall
patient profile and database associations to that patient profile.
For example, if the patient is a Caucasian female, and the test
results were positive for Crohn's disease, such an association may
be made in the database as a potential trend or susceptibility, but
may wait for additional data before marking it as an active
trend.
[0178] At step 4518, the centralized system requests one or more
prescriptions from a pharmacy according to the treatment plan. At
step 4520, the pharmacy transmits a confirmation to the centralized
system that the prescriptions were delivered to or pickup by the
patient. At step 4522, a research database may request updated data
from the centralized system. The research database may utilize the
centralized system as a storehouse for a multitude of information
and data points related to diseases, patient demographics,
biological markers, or other information useful to medical research
and academia. At step 4524, the centralized system transmits the
requested data to the research database.
[0179] Referring now to FIG. 46, there is illustrated a
diagrammatic view of a trends engine 4602 in accordance with
various embodiments of the present disclosure. The trends engine
4602 may be a linear or non-linear deep learning neural network or
trained database. Neural networks are non-parametric methods used
for machine learning such as pattern recognition and optimization.
They are able to generate an output based on a weighted sum of
inputs, which is then passed through an activation function.
Typically, the activation function determines the output by summing
the inputs multiplied by the weights. A basic activation function
is that of y=f(.SIGMA.wx), where x is the vector of inputs, w is
the vector of weights, f(.) is the activation function, and y is
the output vector.
[0180] The inputs, weights, and outputs may be organized within a
multilayer perceptron (MLP), wherein there is an input layer, one
or more hidden layers, and an output layer. As shown in FIG. 46, a
plurality of inputs may be entered into the trends engine 4602. The
trends engine 4602 may include a series of weighted neurons that
pass the inouts through an activation function t generate one or
more outputs, or trends. The trends engine 4602 may be a
feedforward network network. Although there could be any number of
hidden layers, typically ranging from one to three, it will be
appreciated by those skilled in the art that a single hidden layer
can estimate differentiable functions, provided there are enough
hidden units. A higher number of hidden layers also increases
processing time and the amount of adjustments needed during neural
network training.
[0181] It will be understood by those skilled in the art that the
neural network would be trained in order for the neural network to
become more accurate. Various training methods exist, such as
supervised learning where random weights are fed into the neural
network and adjusted accordingly, backpropagation methods, or other
methods. Activation functions are applied to the weighted sum of
the inputs to generate a certain outcome. The weights may be set to
small random values initially. The input pattern may then be
applied and propagated through the network until a certain output
is generated for the hidden layer. Training results may be
collected including the number of true positives, true negatives,
false positives, and false negatives. If the number or percentage
of false positives and negatives appear too high, additional
training may be required.
[0182] The outputs of the hidden layer are used as entries for the
output layer. Weighted and summed up, they are passed through an
activation function to produce the final output. The way the
weights are modified to meet the desired results defines the
training algorithm and is essentially an optimization problem. When
the activation functions are differentiable, the error
backpropagation algorithm may be a good approach in progressing
towards the minimum of the error function. The errors are then
passed back through the network using the gradient, by calculating
the contribution of each hidden node and deriving the adjustments
needed to generate an output that is closer to the target value. It
will be understood by those skilled in the art that neural networks
can be set up and trained in various ways and that the above
description is illustrative of but one method. It will be
appreciated that the neural network may be organized in any way to
allow for the functionality disclosed herein.
[0183] In some embodiments, the trends engine 4602 may function on
a threshold system. For instance, if a certain number or percentage
of patients that are within a specific haplogroup also test
positive for a specific medical condition, this may indicate a
trend output by the trends engine 4602. As more positive results
are received for a particular medical condition, the trends engine
4602 may query the database 4206 to determine if there are any
demographical or other commonalities between patients that have
tested positive for the medical condition. For example, if the
threshold is set to 75%, and 80% of patients of African descent
have tested positive for a medical condition, the trend engine 4602
may communicate the trend to other entities within the system 4200,
or provide the trend when the centralized system 4202 is accessed
by other entities in the system 4200.
[0184] Referring now to FIG. 47, there is illustrated one
embodiment of database tables showing a particular trend. There is
shown a patient record 4702. The patient record 4702 includes
various data concerning the patient, such as the test IDs for tests
performed on the patient or a specimen from the patient. If a
patient has a DNA test performed, a patient's haplogroup may be
determined. Haplogroups may be Y-chromosomal or may be
mitochondrial haplogroups. The centralized system 4202 may keep
track of a patients' haplogroups to attempt to find trends among
patients that share a common ancestry. For example, FIG. 47
illustrates that patient ID #1002, in record 4702, is within
haplogroup C. Thus, the centralized system 4202 may link the
patient to data accumulated and test results obtained regarding all
patients that are within haplogroup C. Table 4704 illustrates that
the centralized system 4202 may count the number of positive
results for each test performed on a person of haplogroup C. In
this example, patient ID #1002 has may have tested positive for
test ID 10. The table 4704 shows that a large number of people in
haplogroup C have also tested positive for test ID #10. There is
also shown in patient record 4702 that the patient is susceptible
to prostate cancer. This may be determined from a trend similar to
that shown in 4704. For instance, if test ID #10 tested for
prostate cancer markers, and the 10,720 positive results
illustrated in FIG. 47 was above a threshold amount to activate a
trend, all patients in haplogroup C, such as patient ID #1002,
would have an entry added to his or her patient record noting a
trending susceptibility to prostate cancer.
[0185] Referring now to FIG. 48, there is illustrated a sequence
diagram of a research and trends feedback process 4800. At step
4802, a test site 4212 performs a medical test, such as a test
using the microfluidic chip disclosed herein. At step 4804, the
test site 4212 sends to the centralized system 4202 a patient
record update including test results and a treatment plan. At step
4806, the centralized system 4202 checks trends via the trend
engine 4206 and database 4204. At step 4808, the centralized system
4806 requests current research regarding the medical condition of
the patient from a research database 4216. At step 4810, the
requested research is transmitted from the research database 4216
to the centralized system 4202. At step 4812, the centralized
system 4202 transmits the test results, any trends regarding the
patient or others similar to the patient, the requested current
research, and any recommendations based on this data to the
doctor's office 4210. At step 4814, the doctor's office 4210
requests additional testing for the patient. The doctor may request
additional testing because of trends regarding the patient's
condition or research that was provided to the doctor in step 4812.
At step 4816, the test site performs the additional testing.
[0186] At step 4818, the test site sends an update to the patient
record including the test results for the additional testing and a
new or updated treatment plan for the patient based on the
additional testing. At step 4820, the test results are update
patient record and treatment plan are transmitted from the
centralized system 4202 to the doctor's office 4210. At step 4822,
the doctor's office 4210 sends confirmation of the updated
treatment plan to the centralized office 4822.
[0187] Referring now to FIG. 49, there is illustrated a medical
condition trend activation process 4900. The process 4900 begins at
step 4902, where patient information and the efficacy and dosage
for particular medications pertaining to a first patient produced
by a first test are obtained by an entity such as the centralized
server. At step 4904, patient information and the efficacy and
dosage for particular medications pertaining to a second patient
produced by a second test are obtained by an entity such as the
centralized server. At step 4906, the server compares patient
information of the second patient with the patient information of
the first patient. At decision block 4908, it is determined whether
there is any significant patient information matches. For example,
if the tests conducted on both patients were for Crohn's disease,
and both patients are of the same gender and ethnicity, then there
may be a significant patient information match. If there is no
significant patient information match the process flows to end
block 4910. If there is a match, the process flows to step 4912 to
store the potential trend.
[0188] A trend may be stored as a potential trend when there is a
correlating data point, but not enough data to activate it as an
active trend in the system. At step 4914, the system receives a
plurality of additional test results from a plurality of addition
conducted tests. The process then flows to decision block 4916 to
determine whether additional instances of the potential trend
stored in step 4912 is in an amount above a threshold. Such a
threshold may be a certain number, a percentage of all patients
related to the trend demographic or other data point (such as all
female patients of a particular ethnicity), or other threshold
types. If instance of the potential trend is not above the
threshold, the process flows back to step 4914 to receive more test
results. If at decision block 4916 it is determined that the
instances of the potential trend is above the threshold, the
process flows to step 4918. At step 4918, the system changes the
status of the potential trend to an active trend.
[0189] Referring to FIG. 50, one embodiment of a system device 5000
is illustrated. The system device 5000 is one possible example of a
device used by an end user, and/or a device such as the mobile
device or the server 4202. Embodiments include cellular telephones
(including smart phones), personal digital assistants (PDAs),
netbooks, tablets, laptops, desktops, workstations, telepresence
consoles, and any other computing device that can communicate with
another computing device using a wireless and/or wireline
communication link. Such communications may be direct (e.g., via a
peer-to-peer network, an ad hoc network, or using a direct
connection), indirect, such as through a server or other proxy
(e.g., in a client-server model), or may use a combination of
direct and indirect communications. It is understood that the
device may be implemented in many different ways and by many
different types of systems, and may be customized as needed to
operate within a particular environment.
[0190] The system 5000 may include a controller (e.g., a central
processing unit ("CPU")) 5002, a memory unit 5004, an input/output
("I/O") device 5006, and a network interface 5008. The components
5002, 5004, 5006, and 5008 are interconnected by a transport system
(e.g., a bus) 5010. A power supply (PS) 5012 may provide power to
components of the computer system 5000, such as the CPU 5002 and
memory unit 5004, via a power system 5014 (which is illustrated
with the transport system 5010 but may be different). It is
understood that the system 5000 may be differently configured and
that each of the listed components may actually represent several
different components. For example, the CPU 5002 may actually
represent a multi-processor or a distributed processing system; the
memory unit 5004 may include different levels of cache memory, main
memory, hard disks, and remote storage locations; the I/O device
5006 may include monitors, keyboards, and the like; and the network
interface 5008 may include one or more network cards providing one
or more wired and/or wireless connections to a network 5016.
Therefore, a wide range of flexibility is anticipated in the
configuration of the computer system 5000.
[0191] The system 5000 may use any operating system (or multiple
operating systems), including various versions of operating systems
provided by Microsoft (such as WINDOWS), Apple (such as Mac OS X),
UNIX, and LINUX, and may include operating systems specifically
developed for handheld devices, personal computers, servers, and
embedded devices depending on the use of the system 5000. The
operating system, as well as other instructions, may be stored in
the memory unit 5004 and executed by the processor 5002. For
example, the memory unit 5004 may include instructions for
performing some or all of the methods described herein.
[0192] It should be understood that the drawings and detailed
description herein are to be regarded in an illustrative rather
than a restrictive manner, and are not intended to be limiting to
the particular forms and examples disclosed. On the contrary,
included are any further modifications, changes, rearrangements,
substitutions, alternatives, design choices, and embodiments
apparent to those of ordinary skill in the art, without departing
from the spirit and scope hereof, as defined by the following
claims. Thus, it is intended that the following claims be
interpreted to embrace all such further modifications, changes,
rearrangements, substitutions, alternatives, design choices, and
embodiments.
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