U.S. patent application number 14/873115 was filed with the patent office on 2016-01-28 for method for electronic biological sample analysis.
This patent application is currently assigned to Nanomedical Diagnostics, Inc.. The applicant listed for this patent is Nanomedical Diagnostics, Inc.. Invention is credited to BRETT GOLDSMITH.
Application Number | 20160025675 14/873115 |
Document ID | / |
Family ID | 54334529 |
Filed Date | 2016-01-28 |
United States Patent
Application |
20160025675 |
Kind Code |
A1 |
GOLDSMITH; BRETT |
January 28, 2016 |
METHOD FOR ELECTRONIC BIOLOGICAL SAMPLE ANALYSIS
Abstract
A biological sample analysis device includes a casing that
encloses a biological sample delivery system hydraulically coupled
to a sensor, wherein the sensor includes a plurality of Graphene
transistors and each transistor covalently bonds with a biomarker
causing the electrical properties of the transistor to measurably
change when the biomarker is exposed to corresponding antibodies
within an infected biological sample.
Inventors: |
GOLDSMITH; BRETT; (San
Diego, CA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Nanomedical Diagnostics, Inc. |
SAN DIEGO |
CA |
US |
|
|
Assignee: |
Nanomedical Diagnostics,
Inc.
SAN DIEGO
CA
|
Family ID: |
54334529 |
Appl. No.: |
14/873115 |
Filed: |
October 1, 2015 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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14263954 |
Apr 28, 2014 |
|
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14873115 |
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Current U.S.
Class: |
205/780.5 |
Current CPC
Class: |
B01L 2300/0645 20130101;
G01N 33/54373 20130101; B01L 3/502707 20130101; B01L 3/502715
20130101; B01L 2200/027 20130101; Y02A 50/57 20180101; G01N 27/4145
20130101; G01N 27/4146 20130101; B01L 2300/0636 20130101 |
International
Class: |
G01N 27/414 20060101
G01N027/414 |
Claims
1. The method for electronic biological sample analysis comprising:
introducing a biological sample to a sample chamber, the sample
chamber comprising a sensor configured to output a first current
range when the sample sensor is exposed to a sterile liquid and a
second current range when the sensor is exposed to predetermined
antibodies; applying a voltage to the sensor; measuring a current
output from the sensor; and determining if the current output is
within the first current range or the second current range.
2. The method of claim 1, wherein the sensor comprises one or more
Graphene transistors and applying a voltage to the sensor comprises
applying a drain-source voltage and a gate-source bias.
3. The method of claim 1, wherein the biological sample is blood,
serum, urine, or cerebral fluid.
4. The method of claim 1, wherein the measuring the current output
from the sensor is performed at regular intervals.
5. The method of claim 3, further comprising plotting the current
output over time and analyzing a trend.
6. The method of claim 1, further comprising flushing the
biological sample from the sample chamber with a sterile
solution.
7. The method of claim 6, further comprising re-introducing the
biological sample to the sample chamber.
8. The method of claim 7, further comprising repeating for a
plurality of cycles the flushing the biological sample from the
sample chamber with a sterile solution and re-introducing the
biological sample to the sample chamber and calculating a
statistical average current output when the biological sample is in
the sample chamber.
9. The method of claim 1, further comprising returning a "test
positive" signal if the current output is within the second current
range.
10. The method for electronic biological sample analysis
comprising: introducing a biological sample to a sample chamber,
the sample chamber including a sensor comprising one or more
Graphene transistors, the sensor configured to output a first
current range when the sample sensor is exposed to a sterile liquid
and a second current range when the sensor is exposed to
predetermined antibodies; applying a voltage to the sensor;
measuring a current output from the sensor; determining if the
current output is within the first current range or the second
current range; and returning a "test positive" signal if the
current output is within the second current range.
11. The method of claim 10, wherein applying a voltage to the
sensor comprises applying a drain-source voltage and a gate-source
bias.
12. The method of claim 10, wherein the biological sample is blood,
serum, urine, or cerebral fluid.
13. The method of claim 10, wherein measuring the current output
from the sensor is performed at regular intervals.
14. The method of claim 13, further comprising plotting the current
output over time and analyzing a trend.
15. The method of claim 10, further comprising flushing the
biological sample from the sample chamber with a sterile
solution.
16. The method of claim 15, further comprising re-introducing the
biological sample to the sample chamber.
17. The method of claim 16, further comprising repeating for a
plurality of cycles the flushing the biological sample from the
sample chamber with a sterile solution and re-introducing the
biological sample to the sample chamber and calculating a
statistical average current output when the biological sample is in
the sample chamber.
Description
TECHNICAL FIELD
[0001] The present disclosure is directed towards electronic
biological sample analysis.
BACKGROUND
[0002] Diagnostic technologies directed towards detecting viral or
bacterial infections, or other ailments, within a biological sample
generally do not have the sensitivity to directly detect the
presence of infectious agents such as a bacteria, virus, or
diseased tissue (e.g. cancer) before an immune response occurs.
Thus, most diagnostic technologies detect such infections or
ailments through detection of antibodies created by a patient's
immune system in response to the particular condition. For example,
these antibody detection techniques are currently not capable of
detecting many diseases within the first month of infection (e.g.
Lyme disease). There are laboratory scale analytical and sample
treatment techniques capable of detecting markers at an early stage
of infection. However, these laboratory techniques require time,
expertise and material that prevent common clinical use. One of
these laboratory scale sensors is based on direct detection using
carbon nanotube devices. Such sensors have been developed in
academic labs worldwide. A related material, Graphene, has seen
less academic development, but is widely understood to have similar
potential use. However, these specialized nanoelectronics lab
technologies have yet to be converted into a practical diagnostic
systems or methods.
[0003] Generally, biological sample analysis to determine the
presence of antibodies may be performed on blood or urine samples.
Current blood diagnostic systems rely on technologies including
enzyme-linked immunoassay (ELISA), gel electrophoresis and blood
culture. These are all proven, mature technologies. All three of
these tests require significant time to run, from several hours to
several days.
[0004] ELISA and gel electrophoresis tests generally measure an
immune system response to a disease (e.g. the presence of
antibodies), rather than presence of the disease itself. Most
diagnostic tests, including ELISA and gel electrophoresis tests,
require detection of a reporter molecule or molecular label. In
these tests a reporter or amplifier molecule is required to
generate a measurable signal.
[0005] All of these tests require either significant expertise or
very expensive automation equipment to run. This is partly due to
the multiple steps and specialized reagents required. For example,
ELISA tests are particular complicated. ELISA tests include coating
a measurement well or surface with a copy of a chemical marker
created by an infectious agent known as an antigen, incubating a
biological sample (e.g. blood, serum, urine, or cerebrospinal
fluid), and exposing the measurement well to the biological sample
to allow the antibody, if present, to bind to the antigen. The
binding process is subject to thermodynamic laws of probability and
is not perfect such that some antibodies will bind incorrectly or
fail to bind where they should. The ELISA test further includes
washing the patient sample from the well, adding a solution with a
reporting antibody intended to bind to antibodies bound to the well
wall, rinsing the well a second time, and adding a reporting dye to
the intended to change colors in the presence of reporting dye.
These steps are also subject to variances in binding efficiency and
accuracy.
[0006] Gel electrophoresis tests are also complicated. In many
cases, ELISA is generally preferred for cost and difficulty. Not
all infectious agents can be detected by using a blood culture, for
example infection with Borelia burgdoferi is not generally
identified via blood culture. The complexity of these tests makes
them extremely operator dependent, creating the possibility for
variance in test result accuracy depending on the experience and
skill of the operator. Automation could improve accuracy and
decrease testing variance, but no such automated solutions are
readily available.
[0007] Another biological sample analysis technique is based on the
polymerase chain reaction (PCR), which clones targeted small
fragments of DNA. This is a highly sensitivity technique, but also
requires either significant expertise or very expensive automated
equipment to run properly, and requires several hours for each
test.
[0008] All of these currently available tests are costly, highly
operator dependent, and lack the sensitivity specificity to
accurately and reliably detect many diseases, particularly in the
disease's early states (e.g. Lyme disease).
SUMMARY OF EMBODIMENTS
[0009] The present disclosure is directed towards an electronic
biological sample analysis system and method. In particular, the
present disclosure is directed towards direct detection of disease
and/or infection using a nanoelectronic circuit by enabling bonding
of antibodies directly with an electronic circuit in the testing
device, exposing the testing device to a biological sample, and
measuring changes in electrical properties of the electronic
circuit-antibody system. The changes in electrical properties are
analyzed to determine the presence of infection in the sample. This
technique can be extraordinarily sensitive, and can be engineered
to drastically minimize the effects of improper antibody
binding.
[0010] As disclosed herein, an example system for electronic
biological sample analysis includes an electronic biological sample
sensor system wherein the biological sample sensor system includes
a sensor chip electronically coupled to an external connector
wherein the sensor chip includes one or more transistors, each
transistor includes one or more scattering sites, and each
scattering site includes one or more covalently bonded biomarkers.
In several embodiments, the transistors comprise Graphene. In some
examples, the transistors comprise sp.sup.2 hybridized Carbon and
sp.sup.3 hybridized Carbon, wherein at least sp.sup.3 hybridized
Carbon molecules covalently bond to biomarker molecules such that
the electrical properties of the transistor change when exposed to
biological samples from patients with infections or diseases
corresponding to the biomarker.
[0011] Some embodiments of the disclosure further include a liquid
handling system and a casing shaped to form a liquid-tight and
internally located sample chamber. The electronic biological sample
sensor system and the liquid handling system are encapsulated in
the casing. In some embodiments, the liquid delivery system
includes a sample chamber and one or more flanges hydraulically
coupled to the sample chamber, wherein the sample chamber forms a
liquid-tight seal against the sensor chip.
[0012] Also as disclosed herein, an example method for electronic
biological sample analysis includes introducing a biological sample
to an electronic biological sample analysis sensor, applying
voltage to the electronic biological sample analysis sensor,
measuring current from the biological sample analysis sensor,
comparing the measured current with a baseline current, and
returning a "test positive" if the change in current exceeds a
predetermined threshold. For example, the biological sample may be
a urine, blood, serum, or cerebral fluid sample. The steps of
introducing a biological sample, applying voltage, and measuring
current may be repeated and alternated in a cycle with flushing the
biological sample analysis sensor with a sterile solution.
Repeating these steps will increase the statistical significance of
the results and reduce sampling noise.
BRIEF DESCRIPTION OF DRAWINGS
[0013] The present disclosure, in accordance with one or more
various embodiments, is described in detail with reference to the
following figures. The figures are provided for purposes of
illustration only and merely depict typical or example embodiments
of the disclosure.
[0014] FIG. 1 illustrates a top view of a biological sample
analysis device consistent with embodiments disclosed herein.
[0015] FIG. 2 illustrates a side view of a biological sample
analysis device consistent with embodiments disclosed herein.
[0016] FIG. 3 illustrates a back view of a biological sample
analysis device consistent with embodiments disclosed herein.
[0017] FIG. 4 is a photograph of an example biological sample
analysis device consistent with embodiments disclosed herein.
[0018] FIG. 5 is a photograph of an electronic biological sample
sensor system from an example biological sample analysis device
consistent with embodiments disclosed herein.
[0019] FIG. 6 illustrates a top view of an electronic biological
sample sensor system from an example biological sample analysis
device consistent with embodiments disclosed herein.
[0020] FIG. 7 illustrates a side view of an electronic biological
sample sensor system from an example biological sample analysis
device consistent with embodiments disclosed herein.
[0021] FIG. 8 illustrates a back view of an electronic biological
sample sensor system from an example biological sample analysis
device consistent with embodiments disclosed herein.
[0022] FIG. 9 illustrates a top view of a lower cartridge assembly
from an example biological sample analysis device consistent with
embodiments disclosed herein.
[0023] FIG. 10 illustrates a side view of a lower cartridge
assembly from an example biological sample analysis device
consistent with embodiments disclosed herein.
[0024] FIG. 11 illustrates a back view of a lower cartridge
assembly from an example biological sample analysis device
consistent with embodiments disclosed herein.
[0025] FIG. 12 illustrates a upper view of an upper cartridge
assembly from an example biological sample analysis device
consistent with embodiments disclosed herein.
[0026] FIG. 13A illustrates a side view of an upper cartridge
assembly from an example biological sample analysis device
consistent with embodiments disclosed herein.
[0027] FIG. 13B illustrates a back view of an upper cartridge
assembly from an example biological sample analysis device
consistent with embodiments disclosed herein.
[0028] FIG. 14 illustrates a side view of a sample chamber from an
example biological sample analysis device consistent with
embodiments disclosed herein.
[0029] FIG. 15 illustrates a top view of a liquid handling assembly
from an example biological sample analysis device consistent with
embodiments disclosed herein.
[0030] FIG. 16A illustrates a side view of a liquid handling
assembly from an example biological sample analysis device
consistent with embodiments disclosed herein.
[0031] FIG. 16B illustrates a front view of a liquid handling
assembly from an example biological sample analysis device
consistent with embodiments disclosed herein.
[0032] FIG. 17A illustrates a top view of an example biological
sample analysis sensor chip wirebonded in a chip carrier consistent
with embodiments disclosed herein.
[0033] FIG. 17B illustrates a top view of an example biological
sample analysis sensor chip covered with a molded plastic cover
shaped to form a sample chamber consistent with embodiments
disclosed herein.
[0034] FIG. 17C illustrates a top view of an example biological
sample analysis sensor chip covered by a sample chamber that is
hydraulically coupled to sample deliver tubing consistent with
embodiments disclosed herein.
[0035] FIG. 17D illustrates a top view of an example biological
sample analysis sensor chip covered by a sample chamber and encased
in an external casing consistent with embodiments disclosed
herein.
[0036] FIG. 18 illustrates a top view of an example biological
sample analysis sensor chip consistent with embodiments disclosed
herein.
[0037] FIG. 19 is a process diagram illustrating a method for
electronically testing a biological sample consistent with
embodiments disclosed herein.
[0038] FIG. 20 is a process diagram illustrating a method for
electronic biological sample analysis consistent with embodiments
disclosed herein.
[0039] FIG. 21 illustrates an example computing module that may be
used to implement various features of the systems and methods
disclosed herein.
[0040] The figures are not intended to be exhaustive or to limit
the disclosure to the precise form disclosed. It should be
understood that the disclosure can be practiced with modification
and alteration, and that the disclosure can be limited only by the
claims and the equivalents thereof.
DETAILED DESCRIPTION
[0041] Embodiments of the present disclosure are directed toward
systems and methods for performing biological sample analysis. In
some examples, a system for biological sample analysis includes an
outer casing, a biological sample delivery system, and an
electronic biological sample sensor system. The biological sample
delivery system may be configured to deliver a liquid biological
sample externally located from the biological sample analysis
system to the biological sample sensor system via one or more tubes
coupled to a sample chamber, wherein at least one side of the
sensor chamber is exposed to a sensor chip in the electronic
biological sample sensor system. In several examples, the
electronic biological sample sensor system includes the sensor chip
and an electronic connector, electrically coupled to the sensor
chip, wherein the electronic connector is configured to deliver
source-drain voltage and source-gate bias to transistors in the
sensor chip, as well as to monitor current flow from the
transistors that corresponds to the presence of particular
antibodies (e.g. antibodies for Lyme disease) within the biological
sample.
[0042] FIG. 1 illustrates a top view of an example biological
sample analysis device. An example biological sample analysis
device 100 an outer casing comprising a first cartridge half 140
and a second cartridge half 150 configured to fit together to form
a sealed enclosure. First cartridge half 140 and second cartridge
half 150 may be aligned and secured together with screws, bolts,
tabs, dowels, or other fasteners inserted through mounting holes
152. For example, four mounting holes 152 in first cartridge half
140 may be aligned with four mounting holes 152 in second cartridge
half 150 to properly align the two cartridge halves, and then
fasteners may be inserted through the holes to secure the halves
together.
[0043] The external casing of biological sample analysis device
100, in general, is configured to encapsulate an electronic
biological sample sensor system enclosed therein. In some examples,
the external casing of biological sample analysis device 100 may
comprise an outer casing that is a single molded component wherein
the molded component comprises plastic, foam, rubber, acrylic, or
any other moldable material that is sufficiently water tight. In
other examples, the first cartridge half 140 may be hingedly
coupled to second cartridge half 150. First cartridge half 140 may
also snap fit, press fit, or lock in place when oriented in a
closed position with respect to second cartridge half 150 such that
the two cartridge halves together form a single cartridge. In some
examples, first cartridge half 140 and second cartridge half 150
are aligned using alignment pins or dowels protruding from either
the first or the second of the cartridge half, and inserting said
alignment pins into alignment holes 152 on the other cartridge
half. In one such example, the two cartridge halves may be snap
fit, form fit, or press fit together. Other methods of
manufacturing a watertight external cartridge casing that are
possible as would be known in the art, so long as the external
cartridge casing, at least, encloses sample chamber 160 and sensor
chip 110.
[0044] Still referring to FIG. 1, second cartridge half 150 may
further comprise a sensor chip 110, a chip carrier 112, a carrier
socket 114, a circuit board 116, and an external connector 180. For
example, circuit board 116 may be mounted or form fit inside of
second half casing 150 and may be electronically coupled to
external connector 180. Circuit board 116 may also support and
electronically couple to carrier socket 114, which in turn may
support and electronically couple to chip carrier 112. Chip carrier
112 may be configured to physically support and electronically
couple to sensor chip 110.
[0045] In some examples, sensor chip 110 is a Graphene chip with
one or more Graphene transistors, as disclosed herein. The Graphene
chip may comprise a plurality of electronic scattering sites
located on a top surface of the Graphene chip, wherein each
scattering site includes covalently bonded biomarkers that
correlate to particular antibodies generated by the human body in
reaction to particular infections or diseases (e.g. biomarkers
selected for their propensity to bond to antibodies generated by
the human body in response to Lyme disease). Further, each
scattering site is located on a particular Graphene transistor. The
scattering sites are further configured to change the electrical
properties of the particular Graphene transistor when the
scattering site is exposed to the antibody or antibodies that
correlate to the particular bonded biomarker. Accordingly, by
applying voltage across the source and drain of each transistor,
and properly biasing the source and gate voltage, each Graphene
transistor is configured to switch on and/or increase current flow
when exposed to a liquid sample containing the antibody or
antibodies that correlate to the particular biomarkers bonded to
the Graphene transistor's scattering site.
[0046] Sensor chip 110 may electrically couple to chip carrier 112.
For example, sensor chip 110 may be wire bonded to chip carrier
112. In several embodiments, chip carrier 112 also supports and
holds in place sensor chip 110.
[0047] Chip carrier 112 may electrically couple to carrier socket
114. In several embodiments, carrier socket 114 supports and holds
in place chip carrier 112. Chip carrier 112 may be further
configured to snap fit, form fit, or press fit into carrier socket
114 such that electrical leads extending from chip carrier 112 both
mechanically and electrically couple to carrier socket 114, but may
be mechanically released from carrier socket 114.
[0048] Carrier socket 114 may electrically couple to circuit board
116. In several embodiments, circuit board 116 supports and holds
in place carrier socket 114. Circuit board 116 may then
electrically couple to electrical connector 180. Other electrical
and mechanical orientations of sensor chip 110 with respect to
circuit board 116 are possible. For example, sensor chip 110 may
directly bond to circuit board 116 through a wire bonding,
soldering, flip chip solder ball, or other type of
electro-mechanical bond as known in the art. In some embodiments, a
wire harness or other electric coupling mechanism may facilitate
electric coupling of sensor chip 110 with electrical connector 180
such that circuit board 116 is not required.
[0049] Still referring to FIG. 1, a biological sample delivery
system may be configured to expose sensor chip 110 to a biological
sample. The biological sample delivery system may comprise one or
more tubes 176, one or more flanges 172 and 174, and sample chamber
160. Flanges 174 and 172 may hydraulically couple to sample chamber
160 through the one or more tubes 176 such that, if a biological
sample is introduced through either flange 172 or 174, the
biological sample will flow through the tubes 176, into sample
chamber 160, and then, if continued pressure is maintained through
one of the flanges 172 or 174, the biological sample may be forced
out of sample chamber 160 and out of the other flange or flanges
174 or 172. For example, if flanges 174 input flanges, the flange
172 may act as an exit flange. One of flanges 174 may be used to
flush the entire biological sample delivery system with a cleaning
solution. Tubes 176 may be hydraulically coupled together with
junction 176.
[0050] In several examples, sensor chip 110 forms a liquid-tight
seal with sample chamber 160. For example, an O-ring 162 may fit
within O-ring groove 164 on the outer rim of sample chamber 160,
such that when sensor chip 110 is pressed up against sample chamber
160 (e.g. when casing halves 140 and 150 are closed together),
O-ring 162 is compressed inside of O-ring groove 164 and against
both sample chamber 160 and sensor chip 110, creating a
liquid-tight seal.
[0051] FIG. 2 illustrates a side view of biological sample analysis
device 100. In the non-limiting embodiment illustrated by FIG. 2,
casing half 140 is a top half of the casing system and casing half
150 is the bottom half of the casing system. Sample chamber 160
protrudes downward from upper casing half 140 and into bottom
casing half 150 when the two halves are configured in the closed
position illustrated in FIG. 2. Further, sample chamber 160 is
sealed on a bottom side by sensor chip 110 such that, when a
biological sample is introduced through flanges 172 and/or 174, it
flows through tubes 176, into sample chamber 160, and contacts
sensor chip 110.
[0052] FIG. 3 illustrates a back view of a biological sample
analysis device 100. In the non-limiting example embodiment
illustrated by FIG. 3, three sample delivery flanges are located on
an external surface of the casing and are configured to
hydraulically couple to an external sample deliver system. In some
examples, flanges 174 may be input flanges and flange 172 may be an
exit flange. For example, one of flanges 174 may be a biological
sample input flanges, and one of flanges 174 may be a cleaning
solution input flange. In other examples, only two flanges may be
used, while in some examples, more than three flanges may be used.
Other mechanisms for delivering a biological sample to the sensor
chip may be used. For example, sensor chip 110 may be dipped in a
biological sample stored in a test tube, dewar, cup, catheter bag,
or other container. Alternatively, sensor chip 110 may be located
within a tube designed to carry the biological sample, or may be
configured on a test strip or card and passed directly through the
biological sample (e.g. similar to a pregnancy test strip).
[0053] FIG. 4 is a photograph of an example biological sample
analysis device. As illustrated by FIG. 4, the casing system may be
an acrylic casing or a plastic casing. In other embodiments, the
casing system may comprise composite materials, metal, rubber,
silicone, glass, resin, or other liquid tight materials as known in
the art.
[0054] FIG. 5 is a photograph of an electronic biological sample
sensor system from an example biological sample analysis device. As
illustrated by FIG. 5, a sensor chip may be wire bonded to a chip
carrier, the chip carrier may be coupled to a carrier socket, and
the carrier socket may be mounted on a circuit board (e.g. a bread
board). The circuit board may then couple to an electronic
connector. In some embodiments, the chip carrier is a 44-pin chip
carrier. The circuit board may be custom made to electrically
couple to the pins from the chip carrier to the connector. In many
embodiments, the electronic biological sample sensor system is
assembled such that each transistor from the sensor chip completes
an electrical circuit through the chip carrier, carrier socket,
circuit board, and/or electrical connector. For example, the
electrical connector may comprises connector leads for both
V.sub.DS and V.sub.GS, to supply drain-source voltage and
gate-source bias to each of the transistors on the sensor chip. The
electrical connector may further comprise multiple channel leads to
monitor and/or measure current flow across each of the transistors
independently, such that each channel monitors a different
transistor. In some examples, the connector is a sub-D
connector.
[0055] FIG. 6 illustrates a top view of an electronic biological
sample sensor system from an example biological sample analysis
device. As illustrated, an example electronic biological sample
sensor system 600 may comprise sensor chip 610, chip carrier 612,
carrier socket 614, circuit board 616, and electrical connector
680. Alternative embodiments may include just sensor chip 610 and
electrical connector 680. In some embodiments, an electronic
biological sample sensor system is a single integrated circuit
comprising one or more Graphene transistors, each transistor being
configured to expose the Graphene transistor gates to an external
environment (e.g. to a liquid sample resting on a top surface of
the Graphene transistor). The electronic biological sample sensor
system may further comprise V.sub.DS and V.sub.GS circuit
connections to supply drain-source voltage and gate-source bias to
each transistor, as well as at least one electrical channel for
monitoring and/or measuring current flow through each
transistor.
[0056] FIG. 7 illustrates a side view of an electronics assembly
from an example biological sample analysis device similar to the
device illustrated in FIG. 6. Referring to FIG. 7, circuit board
616 may provide electrical connections between electrical connector
680 and sensor chip 610 through chip carrier 612 and carrier socket
614, and may also provide structural support to sensor chip 610,
chip carrier 612, and/or carrier socket 614. For example, when
sensor chip 610 is bonded to chip carrier 612 and chip carrier 612
is inserted in socket 614, the structural bond between circuit
board 616 and carrier socket 612 provides a rigid base for and
maintains the structural location of chip carrier 612 and sensor
chip 610.
[0057] FIG. 8 illustrates a back view of an electronics assembly
from an example biological sample analysis device similar to the
device illustrated in FIGS. 6 and 7. Referring to FIG. 8, sensor
chip 610 may be centrally located with respect to circuit board
616, carrier socket 614, and/or chip carrier 612.
[0058] FIG. 9 illustrates a top view of a lower cartridge assembly
from an example biological sample analysis device. Lower cartridge
casing 950 may comprise molded or machined plastic, acrylic, glass,
ceramic, composite, rubber, metal, or other materials that would be
water tight and provide a sterile environment for a biological
sample. In some examples, lower cartridge casing 950 comprises
thermosetting plastics such as epoxy, polyester or polyurethane or
from thermoplastics such as acrylic, polyvinyl chloride or
polytetrafluoroethylene (Teflon). Mounting structures 952 may be
pins protruding from the casing to mount and align with an upper
cartridge assembly, or alternatively, may be holes to accept
alignment and/or mounting pins, posts, or screws from the upper
cartridge assembly. Other alignment and/or fastening mechanisms may
be used to align and secure the upper cartridge assembly with the
lower cartridge assembly.
[0059] FIG. 10 illustrates a side view of a lower cartridge
assembly from an example biological sample analysis device similar
to the device illustrated in FIG. 9. Referring to FIG. 10, example
mounting holes 952 may extend vertically through the lower
cartridge assembly.
[0060] FIG. 11 illustrates a back view of a lower cartridge
assembly from an example biological sample analysis device similar
to the device illustrated in FIG. 9. Referring to FIG. 11, openings
in casing 950 may be located and configured to accept the
electronic biological sample sensor system described in FIGS.
6-8.
[0061] FIG. 12 illustrates a top view of a upper cartridge assembly
from an example biological sample analysis device. Upper cartridge
casing 1240 may comprise molded or machined plastic, acrylic,
glass, ceramic, composite, rubber, metal, or other materials that
would be water tight and provide a sterile environment for a
biological sample. In some examples, upper cartridge casing 950
comprises thermosetting plastics such as epoxy, polyester or
polyurethane or from thermoplastics such as acrylic, polyvinyl
chloride or polytetrafluoroethylene (Teflon). Mounting structures
1252 may be pins protruding from the casing to mount and align with
the lower cartridge assembly, or alternatively, may be holes to
accept alignment and/or mounting pins, posts, or screws from the
lower cartridge assembly. Other alignment and/or fastening
mechanisms may be used to align and secure the upper cartridge
assembly with the lower cartridge assembly.
[0062] Still referring to FIG. 12, upper cartridge assembly may
further comprise biological sample chamber 1260, O-ring groove
1262, O-ring 1264, and/or cartridge body alignment tab 1266. For
example, sample chamber 1260 may be configured to hold a liquid
biological sample when sealed on a bottom side by the sensor chip
from the electronic biological sensor system. O-ring 1264 may be
located inside O-ring groove 1262 and configured to form a seal
between sample chamber 1260 and the sensor chip when the upper and
lower cartridge assemblies are secured together. Cartridge body
alignment tab 1266 is shaped to fit inside a similarly shaped
socket on the lower cartridge assembly to align the upper and lower
cartridge assemblies.
[0063] FIG. 13A illustrates a side view of an upper cartridge
assembly from an example biological sample analysis device similar
to the device illustrated in FIG. 12. Referring to FIG. 13A, sample
chamber 1260 and cartridge body alignment tab 1266 may protrude
downward from the upper cartridge assembly.
[0064] FIG. 13B illustrates a back view of a top cartridge assembly
from an example biological sample analysis device similar to the
device illustrated in FIGS. 12 and 13A. Referring to FIG. 13B,
sample chamber 1260 and cartridge body alignment tab 1266 may be
centrally located within the upper cartridge assembly.
[0065] FIG. 14 illustrates a side view of a sample chamber epoxied
or molded onto a chip carrier from an example biological sample
analysis device clamped to a sensor chip from an example biological
sample analysis device. Referring FIG. 14, sample chamber 1400
comprises a molded solid material (e.g. molded plastic) 1490
configured to hold a liquid biological sample. Sensor chip 1410 is
located on a lower side of sample chamber 1400 to complete a seal
such that, if a liquid biological sample is placed in the sample
chamber, gravity will cause the liquid biological sample contact a
top surface of sensor chip 1410. Sensor chip 1410 may be secured in
sample chamber 1400 using epoxy, molded plastic, or another
moldable or formable solid material that may be configured to form
a liquid-tight and sterile seal with sensor chip 1410. Sensor chip
1410 may also be forced or clamped against O-ring 1464 to form a
liquid-tight and sterile seal. As illustrated by FIG. 14, tubing
1476 may be configured to deliver a liquid biological sample into
sample chamber 1400.
[0066] FIG. 15 illustrates a top view of a liquid handling assembly
from an example biological sample analysis device. Liquid handling
assembly 1500 may comprise one or more tubes 1576 and one or more
flanges 1572 and 1574. Flanges 1572 and 1574 are configured to
hydraulically connect liquid handling assembly 1500 to an external
liquid source. For example, flanges 1574 may accept input from a
liquid biological sample source and/or a cleaning source to enable
flushing of the liquid handling system with a cleaning solution
(e.g. saline). Flange 1572 may be a liquid exhaust flange to enable
liquid handling system 1500 to exhaust the biological sample or
cleaning solution. Flanges 1572 and 1574 may be Luer fittings, for
example. Tubes 1576 may be hydraulically coupled with one or more
junction connectors 1578. Liquid handling assembly 1500, and
biological sample chamber 1260 illustrated in FIGS. 12-14, may be
cleaned with a cleaning solution and/or with steam or chemical
sterilization (e.g. bleach, ozone, or hydrogen peroxide).
[0067] FIG. 16A illustrates a side view and FIG. 16B illustrates a
front view of a liquid handling assembly from an example biological
sample analysis device from an example biological sample analysis
device similar to the liquid handling assembly illustrated in FIG.
15. As illustrated, tube 1576 may couple to flanges 1574 and 1572
with a liquid-tight coupling mechanism such as a burr or form fit
coupling. Tubes 1576 also bend downward to deliver a liquid
biological sample into the sample chamber.
[0068] FIG. 17A illustrates a top view of an example biological
sample analysis sensor chip wirebonded in a chip carrier from an
electronic biological sensor system. Sensor chip 1710 may be a
Graphene chip with a plurality of Graphene transistors wherein each
transistor electrically couples through wire leads to chip carrier
1714. FIG. 17B illustrates a top view of sensor chip 1710 covered
with a molded plastic cover shaped to form a sample chamber similar
to sample chamber 1400 illustrated in FIG. 14. Accordingly, when a
liquid biological sample is introduced into the sample chamber,
gravity will cause the biological sample to contact sensor chip
1710. FIG. 17C illustrates a top view of sensor chip 1710, covered
with a sample chamber, and hydraulically coupled to tubes 1776
configured to deliver a liquid biological sample into sample
chamber 1400. FIG. 17D illustrates a top view sensor chip 1710
covered by a sample chamber and encased in an external casing
similar to external casings disclosed in FIGS. 1-4 and 6-14.
[0069] FIG. 18 illustrates a top view of an example biological
sample analysis sensor chip as used in an electronic biological
sample sensor system. For example, biological sample analysis
sensor chip 1800 may comprise one or more transistors 1810. Each
transistor 1810 may comprise Graphene. For example, each transistor
1810 may comprise sp.sup.2 hybridized Carbon (Csp.sup.2) that is a
single atomic layer thick, or just a few atomic layers thick. Each
Graphene transistor 1810 may further comprise one or more
electronic scattering sites, wherein each electronic scattering
site comprises Carbon that is sp.sup.3 hybridized. Sp.sup.3
hybridized Carbon enables covalent bonding with a biomolecule at
the Csp.sup.3 orbital. The covalently bonded molecules may act as
biomarkers wherein predetermined biomarkers will additionally bond
to predetermined antibodies generated by a living organism (e.g. a
human or a mammal) in response to a particular virus, bacteria,
disease, or illness. For example, the Graphene chip may be prepared
for chemical functionalization by chemical oxidation with Diazonium
salts, Sulfuric Acid, Potassium Permanganate or Hydrogen Peroxide.
Antibody attachment may start by linking Carboxylic Acid groups on
the Graphene to amine groups on the antibody or linker using
1-Ethyl-3-(3-Dimethylaminopropyl)Carbodiimide (EDC) and
N-Hydroxysuccinimide (NHS). A linker molecule may be used when
direct attachment to the antibody is not possible. In one example,
Streptavidin is used to bind a Biotinylated protein or
Nitrotriacetic Acid is used to bind a His-tagged protein. Multiple
antibodies can be attached to a single chip by limiting the
reaction volume to sufficiently a small drop on top of a group of
transistors.
[0070] In several embodiments, the Graphene sensor chip may be
constructed using a photolithography fabrication process to form
Graphene transistors connected to metal contact leads. For example,
the Graphene may be a CVD Graphene on a plastic film that is placed
on a wafer (e.g. a silicon wafer) and exposed to a solvent (e.g.
acetone) to dissolve the plastic and leaving the Graphene on the
wafer. The Graphene may then be rinsed (e.g. with isopropyl
alcohol, methanol, and/or water) and heated to remove residue. In
some examples, the wafer with the Graphene layer is heated for
between 30 minutes and four hours. If a shorter time is used, than
the wafer with the Graphene layer may be exposed to heat of between
150 degrees C. to 300 degrees C., whereas if a longer heating time
is selected, than the wafer with the Graphene layer may be exposed
to air at room temperature. Other methods of depositing Graphene on
a wafer are possible, including standard material deposition
processes as would be known in the art.
[0071] One example method for constructing a Graphene sensor chip
includes depositing alignment marks and some wiring on a wafer
using photolithography, depositing a Graphene layer, then
depositing final wiring using photolithography. Another example
method for constructing a Graphene sensor chip includes depositing
Graphene and depositing all wiring in a single step. The steps
described are non-limiting and may be performed in any order. After
the deposition of the Graphene and wires, many examples include
dicing the wafers into chips, bonding the chips into chip carriers,
and loading the chips onto circuit boards. Several examples further
include electrically coupling a socket for the chips to an external
electrical connector. In some examples, the bonding of the chip to
the chip carrier is a wire bonding process. In some examples, the
chip carrier is a 44 pin ceramic or plastic chip carrier, but other
chip carrier formats are possible as would be known in the art.
[0072] In some examples, the circuit boards are configured such
that at least two pins are voltage inputs and the remaining pins
are measurement channels. For example, one voltage input may be
used to set the drain-source bias on the Graphene transistors
(V.sub.DS) and the other voltage input may be used to set the
gate-source bias on the Graphene transistors (V.sub.GS). The
V.sub.DS lead may electrically couple to the drain electrode on
each Graphene resistor, and V.sub.GS lead may electrically couple
to the gate and/or source electrodes of each Graphene resistor and
may be used to set the gate/source bias. Measurement channel leads
may then electrically couple to individual Graphene transistors to
measure current when the Graphene transistor is exposed to a liquid
sample. For example, when biomarkers bonded to the Graphene
transistor gate are selected for their bonding properties with
specific antibodies. When a specific biomarker bonds with the
specific antibody, the conductive properties of the Graphene
change, causing that particular transistor to switch on, and
allowing current to flow to the transistor's source and respective
measurement channel. Graphene transistors on any given sensor chip
may be configured with a uniform biomarker designed to bond with a
uniform antibody (e.g. an antibody for Lyme disease), or multiple
biomarkers may be used for the different Graphene transistors, such
that a single sensor chip may detect multiple antibodies present in
a single liquid sample.
[0073] Any biomarker that is known to bond to a particular antibody
may be used in the sensor chip to detect the presence of that
antibody. The following non-limiting list includes several example
diseases and infections with known antibody-to-biomarker
relationships:
[0074] Autoimmune Diseases [0075] Hashimoto's thyroiditis [0076]
Hyperthyroidism [0077] Multiple sclerosis [0078] Rheumatoid
arthritis
[0079] Bacterial Infections [0080] Bacillus anthracis (anthrax)
[0081] Escherichia coli (food poisoning) [0082] Haemophilus
influenzae (bacterial influenza) [0083] Neisseria gonorrhoeae
(gonorrhea) [0084] Neisseria meningitides (meningitis) [0085]
Plasmodium (malaria) [0086] Rickettsia prowazekii (typhus) [0087]
Salmonella enterica (food poisoning, typhoid) [0088] Staphylococcus
(food poisoning, staph) [0089] Streptococcus pneumonia (pneumonia)
[0090] Treponema pallidum (syphilis)
[0091] Viral Infections [0092] Ebola [0093] Epsein-Bar virus [0094]
Hepatitis A, B, C, D, E [0095] Herpes simplex virus (cold sore,
herpes) [0096] Herpes zoster (chickenpox, shingles) [0097] HIV
[0098] Human coronavirus (common cold) [0099] Influenza (common
cold) [0100] Norovirus [0101] Rhinovirus (common cold) [0102]
Rotavirus [0103] SARS coronavirus [0104] Variola virus
(smallpox)
[0105] Cancer Markers [0106] Alpha fetoprotein [0107]
beta-2-microglobulin [0108] beta-human chorionic gonadotropin
[0109] Calcitonin [0110] Cancer antigen 123 [0111] Cancer antigen
125 [0112] Cancer antigen 15-3 [0113] Cancer antigen 19-9 [0114]
Cancer antigen 27.29 [0115] Carcinoembryonic antigen [0116]
Chromogranin A [0117] Cytokeratin [0118] Human chorionic
gonadotropin [0119] Osteopontin [0120] Prostate specific
antigen
[0121] Still referring to FIG. 18, transistors 1810 may be
organized and/or located within wells 1868 to concentrate a
biological sample over the transistors. Wells 1868 may be formed
with well structure 1866 that may comprise capillary tubing
plastic, rubber, composite, silicon, or other structural materials
as known in the art. Each well 1868 may include one or more
transistors 1810, and each sensor chip 1800 may include one or more
wells 1868, wherein each well may include a homogeneous biomolecule
for detection of a particular antibody. In some examples, wells on
the same sensor chip may include different biomolecules such that a
single sensor chip may be configured to detect a plurality of
antibodies. All of the transistors 1810 and wells 1868 make up an
antibody detection surface on sensor chip 1800. As illustrated by
FIG. 18, the antibody detection surface may be enclosed within
O-ring 1864 and configured to be sealed within a sample chamber
with a liquid-tight seal. Bond pads, or leads 1812 electrically
couple to the transistors, and allow the sensor chip to
electrically couple to a chip carrier, carrier socket, circuit
board, and/or external electrical connector.
[0122] FIG. 19 is a process diagram illustrating a method for
electronically testing a biological sample (e.g. using a biological
sample analysis device). A method for electronically testing a
biological sample 1900 may include introducing a biological sample
into a sample chamber at step 1910. For example, the biological
sample may be urine or blood and the sample chamber may be a
biological sample chamber and sensor chip similar to embodiments
disclosed in FIGS. 1-18. Method 1900 may further include applying a
voltage to the sensor chip at step 1920. For example, a voltage may
be applied to connector leads electronically coupled to transistors
within the sensor chip to supply a drain-source voltage and a
gate-source bias. Method 1900 may further include measuring current
on sensor measurement channels at step 1930. For example, each
sensor measurement channel may be monitored through connector leads
electronically coupled to corresponding transistors. Method 1900
may further include monitoring a change in current over time at
step 1940, and comparing the change in current with a baseline
measurement at step 1950 (e.g. a current measurement taken when the
sensor chip was exposed to only saline or another control liquid).
Method 1900 may further include returning a "test positive" signal
at step 1960 if a threshold change in current over baseline is
reached, indicating the presence of an antibody-biomolecule bond at
one or more scattering sites as disclosed in FIG. 18.
[0123] The steps of measuring current on sensor measurement
channels 1930, monitoring changes in current over time 1940,
comparing the changes with a baseline measurement 1950, and
returning a "test positive" signal may be performed by an
electronic biological sample testing module. For example, a
biological sample testing module may be a computer module as
disclosed in FIG. 21 that includes a processor programmed with one
or more computer programs configured to perform the steps disclosed
herein. Other steps of method 1900 may be similarly performed by a
computer module.
[0124] FIG. 20 is a process diagram illustrating a method for
electronic biological sample analysis. A method for electronic
biological sample analysis 2000 includes flushing a sample chamber
with a clean buffer at step 2010. For example, the sample chamber
may be a biological sample chamber similar to embodiments disclosed
herein and the clean buffer may be a saline solution or other
sterile solution as known in the art. Method 2000 further includes
applying voltage to an electronic biological sample sensor system
at step 2020. For example, voltage may be applied across the source
and drain and source and gate of transistors in a sensor chip.
Method 2000 further includes introducing a sample to the sample
chamber at step 2030, applying a voltage to the sensor, and
monitoring current changes at step 2030. The applied voltage will
cause current to vary from a baseline if the biological sample
includes antibodies that correspond to biomolecules bonded to
scattering sites in the sensor chip transistors. Steps 1910 through
1940 may be repeated multiple times at step 2045 to increase
statistical significance of the measurements. Method 2000 may
further include returning a "test positive" signal at step 2050 if
a the average change in current over baseline exceeds a
predetermined threshold level. The steps disclosed in method 2000
may be performed by an electronic biological sample testing module.
For example, a biological sample testing module may be a computer
module as disclosed in FIG. 21 that includes a processor programmed
with one or more computer programs configured to perform the steps
disclosed herein.
[0125] In some examples, all of the applied and measured voltages
are referenced to a common ground. A single device measurement may
include applying a voltage (e.g between 0.1V and 1V) to the drain
of all of the Graphene transistors (V.sub.DS) and a voltage (e.g
between -1V and 1V) to the liquid in the sensing chamber
(V.sub.GS). The resulting liquid voltage (V.sub.REF) can be
monitored through a reference electrode. The electrical baseline of
each of the sensors on the chip can be measured by recording the
current on all of the sensor measurement channels when V.sub.REF is
0V. V.sub.GS can be controlled such that if V.sub.REF changes up or
down (e.g in a range from -1V to 1V) while holding V.sub.DS steady.
The current can be measured on all of the sensor measurement
channels. For each measurement channel, the resulting data, when
considered with a Y-axis of current and an X-axis V.sub.REF, can be
fit with a line. The slope and X-axis intercept of the line can be
calculated where the electrical baseline current, slope, and
intercept of the fit line form three data points in a measurement
vector for each sensor in a device measurement. To increase
statistical significance, a device measurement can be repeated
multiple times (e.g. 3 to 5 times) to obtain an average value and
statistical variance for the measurement vector for each sensor.
This process can be automated using a computer module as disclosed
herein.
[0126] In some examples, a method for electronic biological sample
analysis includes connecting a system for electronic biological
sample analysis to an electrical system, flushing the system for
electronic biological sample analysis with clean serum or buffer,
and measuring a baseline device measurement to obtain a baseline
set of measurement vectors. The method may further include
injecting a biological sample into the system and measuring a
device measurement at regular intervals over an incubation period
(e.g. every minute for 10, 20, or 30 minutes). The method may
further include flushing the system with clean serum or buffer and
measuring a device measurement at a regular interval (e.g. every
minute for 1, 5, or 10 minutes). The system may then be flushed
with clean serum or buffer again and repeating measuring a device
measurement at a regular interval. The method may further include
comparing the measurement vectors before, during, and after
exposing the system to the biological sample and analyzing the date
for a significant change in the measurement vector for many
similarly functionalized sensors indicating a binding event, which
can be reported as a positive identification.
[0127] FIG. 21 illustrates an example computing module that may be
used to implement various features of the systems and methods
disclosed herein. In one embodiment, the computing module includes
a processor and a set of computer programs residing on the
processor. The set of computer programs may be stored on a
non-transitory computer readable medium having computer executable
program code embodied thereon. The computer executable code may be
configured to perform one or more steps of the method for
electronically testing a biological sample 1900 disclosed in FIG.
19, and/or one or more steps of the method for electronic
biological sample analysis 2000 disclosed in FIG. 20.
[0128] As used herein, the term module might describe a given unit
of functionality that can be performed in accordance with one or
more embodiments of the present application. As used herein, a
module might be implemented utilizing any form of hardware,
software, or a combination thereof. For example, one or more
processors, controllers, ASICs, PLAs, PALs, CPLDs, FPGAs, logical
components, software routines or other mechanisms might be
implemented to make up a module. In implementation, the various
modules described herein might be implemented as discrete modules
or the functions and features described can be shared in part or in
total among one or more modules. In other words, as would be
apparent to one of ordinary skill in the art after reading this
description, the various features and functionality described
herein may be implemented in any given application and can be
implemented in one or more separate or shared modules in various
combinations and permutations. Even though various features or
elements of functionality may be individually described or claimed
as separate modules, one of ordinary skill in the art will
understand that these features and functionality can be shared
among one or more common software and hardware elements, and such
description shall not require or imply that separate hardware or
software components are used to implement such features or
functionality.
[0129] Where components or modules of the application are
implemented in whole or in part using software, in one embodiment,
these software elements can be implemented to operate with a
computing or processing module capable of carrying out the
functionality described with respect thereto. One such example
computing module is shown in FIG. 21. Various embodiments are
described in terms of this example-computing module 2100. After
reading this description, it will become apparent to a person
skilled in the relevant art how to implement the application using
other computing modules or architectures.
[0130] Referring now to FIG. 21, computing module 2100 may
represent, for example, computing or processing capabilities found
within desktop, laptop, notebook, and tablet computers; hand-held
computing devices (tablets, PDA's, smart phones, cell phones,
palmtops, smart-watches, smart-glasses etc.); mainframes,
supercomputers, workstations or servers; or any other type of
special-purpose or general-purpose computing devices as may be
desirable or appropriate for a given application or environment.
Computing module 2100 might also represent computing capabilities
embedded within or otherwise available to a given device. For
example, a computing module might be found in other electronic
devices such as, for example, digital cameras, navigation systems,
cellular telephones, portable computing devices, modems, routers,
WAPs, terminals and other electronic devices that might include
some form of processing capability.
[0131] Computing module 2100 might include, for example, one or
more processors, controllers, control modules, or other processing
devices, such as a processor 2104. Processor 2104 might be
implemented using a general-purpose or special-purpose processing
engine such as, for example, a microprocessor, controller, or other
control logic. In the illustrated example, processor 2104 is
connected to a bus 2102, although any communication medium can be
used to facilitate interaction with other components of computing
module 2100 or to communicate externally.
[0132] Computing module 2100 might also include one or more memory
modules, simply referred to herein as main memory 2108. For
example, preferably random access memory (RAM) or other dynamic
memory, might be used for storing information and instructions to
be executed by processor 2104. Main memory 2108 might also be used
for storing temporary variables or other intermediate information
during execution of instructions to be executed by processor 2104.
Computing module 2100 might likewise include a read only memory
("ROM") or other static storage device coupled to bus 2102 for
storing static information and instructions for processor 2104.
[0133] The computing module 2100 might also include one or more
various forms of information storage mechanism 2110, which might
include, for example, a media drive 2112 and a storage unit
interface 2120. The media drive 2112 might include a drive or other
mechanism to support fixed or removable storage media 2114. For
example, a hard disk drive, a solid state drive, a magnetic tape
drive, an optical disk drive, a CD or DVD drive (R or RW), or other
removable or fixed media drive might be provided. Accordingly,
storage media 2114 might include, for example, a hard disk, a solid
state drive, magnetic tape, cartridge, optical disk, a CD or DVD,
or other fixed or removable medium that is read by, written to or
accessed by media drive 2112. As these examples illustrate, the
storage media 2114 can include a computer usable storage medium
having stored therein computer software or data.
[0134] In alternative embodiments, information storage mechanism
2110 might include other similar instrumentalities for allowing
computer programs or other instructions or data to be loaded into
computing module 2100. Such instrumentalities might include, for
example, a fixed or removable storage unit 2122 and a storage
interface 2120. Examples of such storage units 2122 and storage
interfaces 2120 can include a program cartridge and cartridge
interface, a removable memory (for example, a flash memory or other
removable memory module) and memory slot, a PCMCIA slot and card,
and other fixed or removable storage units 2122 and storage
interfaces 2120 that allow software and data to be transferred from
the storage unit 2122 to computing module 2100.
[0135] Computing module 2100 might also include a communications
interface 2124. Communications interface 2124 might be used to
allow software and data to be transferred between computing module
2100 and external devices. Examples of communications interface
2124 might include a modem or softmodem, a network interface (such
as an Ethernet, network interface card, WiMedia, IEEE 802.XX or
other interface), a communications port (such as for example, a USB
port, IR port, RS232 port Bluetooth.RTM. interface, or other port),
or other communications interface. Software and data transferred
via communications interface 2124 might typically be carried on
signals, which can be electronic, electromagnetic (which includes
optical) or other signals capable of being exchanged by a given
communications interface 2124. These signals might be provided to
communications interface 2124 via a channel 2128. This channel 2128
might carry signals and might be implemented using a wired or
wireless communication medium. Some examples of a channel might
include a phone line, a cellular link, an RF link, an optical link,
a network interface, a local or wide area network, and other wired
or wireless communications channels.
[0136] In this document, the terms "computer program medium" and
"computer usable medium" are used to generally refer to transitory
or non-transitory media such as, for example, memory 2108, storage
unit 2120, media 2114, and channel 2128. These and other various
forms of computer program media or computer usable media may be
involved in carrying one or more sequences of one or more
instructions to a processing device for execution. Such
instructions embodied on the medium are generally referred to as
"computer program code" or a "computer program product" (which may
be grouped in the form of computer programs or other groupings).
When executed, such instructions might enable the computing module
2100 to perform features or functions of the present application as
discussed herein.
[0137] The presence of broadening words and phrases such as "one or
more," "at least," "but not limited to" or other like phrases in
some instances shall not be read to mean that the narrower case is
intended or required in instances where such broadening phrases may
be absent. The use of the term "module" does not imply that the
components or functionality described or claimed as part of the
module are all configured in a common package. Indeed, any or all
of the various components of a module, whether control logic or
other components, can be combined in a single package or separately
maintained and can further be distributed in multiple groupings or
packages or across multiple locations.
[0138] Additionally, the various embodiments set forth herein are
described in terms of exemplary block diagrams, flow charts and
other illustrations. As will become apparent to one of ordinary
skill in the art after reading this document, the illustrated
embodiments and their various alternatives can be implemented
without confinement to the illustrated examples. For example, block
diagrams and their accompanying description should not be construed
as mandating a particular architecture or configuration.
[0139] While various embodiments of the present disclosure have
been described above, it should be understood that they have been
presented by way of example only, and not of limitation. Likewise,
the various diagrams may depict an example architectural or other
configuration for the disclosure, which is done to aid in
understanding the features and functionality that can be included
in the disclosure. The disclosure is not restricted to the
illustrated example architectures or configurations, but the
desired features can be implemented using a variety of alternative
architectures and configurations. Indeed, it will be apparent to
one of skill in the art how alternative functional, logical or
physical partitioning and configurations can be implemented to
implement the desired features of the present disclosure. Also, a
multitude of different constituent module names other than those
depicted herein can be applied to the various partitions.
Additionally, with regard to flow diagrams, operational
descriptions and method claims, the order in which the steps are
presented herein shall not mandate that various embodiments be
implemented to perform the recited functionality in the same order
unless the context dictates otherwise.
[0140] Although the disclosure is described above in terms of
various exemplary embodiments and implementations, it should be
understood that the various features, aspects and functionality
described in one or more of the individual embodiments are not
limited in their applicability to the particular embodiment with
which they are described, but instead can be applied, alone or in
various combinations, to one or more of the other embodiments of
the disclosure, whether or not such embodiments are described and
whether or not such features are presented as being a part of a
described embodiment. Thus, the breadth and scope of the present
disclosure should not be limited by any of the above-described
exemplary embodiments.
* * * * *