U.S. patent application number 14/884705 was filed with the patent office on 2016-02-25 for chemically differentiated sensor array.
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 | 20160054312 14/884705 |
Document ID | / |
Family ID | 55348112 |
Filed Date | 2016-02-25 |
United States Patent
Application |
20160054312 |
Kind Code |
A1 |
GOLDSMITH; Brett |
February 25, 2016 |
CHEMICALLY DIFFERENTIATED SENSOR ARRAY
Abstract
A chemically differentiated sensor array system includes a
plurality of environmentally-gated transistors and an environmental
gate, wherein the environmental gate includes a liquid solution and
each environmentally-gated transistor includes a drain, a source,
and a Carbon-based substrate channel, the drain electrically
couples to a first location on the substrate channel, the source
electrically couples to a second location on the substrate channel
separated by a gap from the first location on the substrate
channel, the environmental gate covers and contacts the substrate
channel, a first insulating layer covers and separates the drain
from the environmental gate, and a second insulating layer covers
and separates the source from the environmental gate.
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: |
55348112 |
Appl. No.: |
14/884705 |
Filed: |
October 15, 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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14884705 |
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14684283 |
Apr 10, 2015 |
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14263954 |
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Current U.S.
Class: |
506/39 |
Current CPC
Class: |
G01N 33/493 20130101;
G01N 33/49 20130101; G01N 33/4836 20130101; C12Q 1/6869 20130101;
G01N 27/4148 20130101; G01N 33/5438 20130101; G01N 33/02 20130101;
G01N 27/4145 20130101 |
International
Class: |
G01N 33/543 20060101
G01N033/543 |
Claims
1. A chemically differentiated sensor array system comprising: a
plurality of environmentally-gated transistors and an environmental
gate, wherein the environmental gate comprises a liquid solution
and each environmentally-gated transistor comprises: a drain, a
source, and a substrate channel; wherein the substrate channel
comprises Carbon, the drain electrically couples to a first
location on the substrate channel, the source electrically couples
to a second location on the substrate channel separated by a gap
from the first location on the substrate channel, the environmental
gate covers and contacts the substrate channel, a first insulating
layer covers and separates the drain from the environmental gate,
and a second insulating layer covers and separates the source from
the environmental gate.
2. The system of claim 1, wherein the drain electrically couples to
a drain lead, the source electrically couples to a source lead, the
environmental gate electrically couples to a gate electrode, and
the gate electrode, source lead, and drain lead each electrically
couple to a power supply.
3. The system of claim 2, wherein the substrate channel comprises
Graphene or Carbon nanotubes.
4. The system of claim 2, wherein the environmental gate comprises
a water, alcohol, or metal.
5. The system of claim 2, wherein the environmental gate comprises
a biological sample.
6. The system of claim 5, wherein the biological sample comprises
blood, urine, bacterial growth media, or food.
7. The system of claim 2, wherein one or more of the
environmentally-gated transistors further comprises a sensitization
layer, wherein the sensitization layer covers and separates the
substrate channel from the environmental gate.
8. The system of claim 7, wherein the sensitization layer comprises
a polymer or a protein.
9. The system of claim 2, wherein a first one of the
environmentally-gated transistors further comprises a first
sensitization layer covering and separating the substrate channel
of the first one of the environmentally-gated transistors from the
environmental gate and a second one of the environmentally-gated
transistors further comprises a second sensitization layer covering
and separating the substrate channel of the second one of the
environmentally-gated transistors from the environmental gate.
10. The system of claim 2, further comprising an electrical
measurement device electrically coupled to the source lead or drain
lead of each environmentally-gated transistors, the electrical
measurement device configured to measure voltage, on-site
resistance, or transconductance.
11. The system of claim 10, further comprising a computing module,
wherein the computing module is configured to receive an output
signal from the electrical measurement device indicating an
electrical measurement value, and the identify a composition of the
environmental gate based on the output signal.
12. An environmentally-gated transistor comprising: a drain, a
source, a substrate channel, and an environmental gate; wherein the
substrate channel comprises a first semiconducting material; the
drain electrically couples to a first location on the substrate
channel; the source electrically couples to a second location on
the substrate channel separated by a gap from the first location on
the substrate channel; the environmental gate covers and contacts
the substrate channel; a first insulating layer covers and
separates the drain from the environmental gate; a second
insulating layer covers and separates the source from the
environmental gate; and the environmental gate electrically couples
to a gate electrode.
13. The environmentally-gated transistor of claim 12, wherein the
substrate channel comprises Graphene or Carbon nanotubes.
14. The environmentally-gated transistor of claim 12, wherein the
environmental gate comprises a water, alcohol, or metal.
15. The environmentally-gated transistor of claim 12, wherein the
environmental gate comprises a biological sample.
16. The environmentally-gated transistor of claim 15, wherein the
biological sample comprises blood, urine, bacterial growth media,
or food.
17. The environmentally-gated transistor of claim 12, further
comprising a sensitization layer, wherein the sensitization layer
covers and separates the substrate channel from the environmental
gate.
18. The environmentally-gated transistor of claim 17, wherein the
sensitization layer comprises a polymer or a protein.
19. A system of environmentally-gated transistors comprising: a
plurality of environmentally-gated transistors, wherein each
environmentally-gated transistor comprises: a drain, a source, a
substrate channel, and an environmental gate; wherein the substrate
channel comprises a first semiconducting material; the drain
electrically couples to a first location on the substrate channel;
the source electrically couples to a second location on the
substrate channel separated by a gap from the first location on the
substrate channel; the environmental gate covers and contacts the
substrate channel; a first insulating layer covers and separates
the drain from the environmental gate; a second insulating layer
covers and separates the source from the environmental gate; and
the environmental gate electrically couples to a gate
electrode.
20. The system of claim 19, wherein each environmentally-gated
transistor electrically couples to a power supply and an electrical
measurement device.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation-in-part and claims the
benefit of U.S. patent application Ser. No. 14/263,954, filed Apr.
28, 2014 and Ser. No. 14/684,283, filed Apr. 10, 2015, both of
which are hereby incorporated by reference in their entireties.
TECHNICAL FIELD
[0002] The present disclosure is directed towards electronic
sensors for sample analysis, and more particularly, to a chemically
differentiated sensor array.
BACKGROUND
[0003] Individual electronic chemical sensors may be designed to be
specific for a single target chemical, broadly responsive to a
class of chemicals, or have enhanced sensitivity for particular
chemical interactions. Generally, there is a trade-off in making
these design decisions. It may be difficult or impossible to create
a single sensor with the desired chemical specificity and
sensitivity. To overcome this challenge, it is common to use
multiple sensors together in an array.
[0004] Creating a chemically differentiated sensor array is more
complex than creation of a single sensor. This increase in
complexity drives electronic sensor array design toward simpler
types of sensors such as resistive or capacitive sensors. Such
sensors are less sensitive than transistors or other "gated"
sensors. Arrays of transistor-based chemical sensors incorporate
internal gating structures such as floating gates, split gates, or
back gates. This design increases manufacturing cost and
complexity.
[0005] Typically, modern transistors comprise semiconducting
material on a single solid or connected piece of material. There is
usually a solid mechanical connection between the transistor
channel, the material forming the connection for the source and
drain of the transistor, the gate dielectric material, and the gate
material. When incorporating transistors into sensors, this
structure is usually maintained. In an ion-sensitive field effect
transistor (ISFET) geometry, the gate material itself may be a
liquid that is not mechanically bound to the chip. However, these
types of transistors have generally included a dielectric or
insulating layer mechanically bound to the transistor conduction
channel to prevent unwanted chemical reactions and current flow
from the gate to the transistor conduction channel. For example,
silicon reacts spontaneously with oxygen when exposed to air or
water, so a layer of metal oxide may be used to prevent reactions
in the conduction channel. These chemically protective layers also
separate the conduction channel of a transistor from the local
environment when used as a sensor. This decreases the sensitivity
of transistor-based chemical sensors by creating a physical barrier
to interaction of the local environment to be sensed and the
conduction electrons. Furthermore, these barrier layers are applied
uniformly across the sensor array, limiting the available chemical
differentiation between different sensors in the array.
[0006] One method of increasing chemical coupling to a sensor
channel has been to reduce the insulating dielectric to a small,
non-zero thickness that still chemically protects the conduction
channel. This approach can be done through control of material
deposition, use of specialty materials, or removal of excess gate
dielectric material. This generally requires additional
manufacturing steps and does not completely solve the problem.
[0007] Another method employs the use of "high-k" dielectrics such
as halfnium oxide. These materials lead to a larger capacitance
between the sensing environment and the conduction channel, without
decreasing the thickness of the dielectric material, but again
results in a chemically uniform approach that only mitigates the
problem.
[0008] Another method involves creating a conductive "floating
gate" that may comprise metal or some material that closely
coordinates with the chemicals targeted for sensing. This approach
allows for close coupling of the sensing environment to a material
which is coupled to the conduction channel, but is complicated to
manufacture and still requires an intermediary material to
translate chemical changes to the transistor conduction
channel.
SUMMARY OF EMBODIMENTS
[0009] The present disclosure is directed towards electronic
sensors for sample analysis, and more particularly, to a chemically
differentiated sensor array. In particular, the present disclosure
is directed towards chemically differentiated sensor arrays
comprising transistor-based sensors that each include an
environmental gate without the need for a barrier layer or
universal gate dielectric.
[0010] As disclosed herein, an environmental gate may be a liquid
material that comes into contact with the transistor, has a
controlled voltage, but is applied or exposed to the transistor
only part of the sensing measurement. It may be a material such as
water based solutions, alcohol based solutions, battery
electrolyte, blood or blood derivatives, urine, bacterial growth
media, food, ionic solvents, or liquid metals. The voltage of the
liquid compared to the transistor channel is controlled through an
external connection or through a connection elsewhere on the sensor
chip. The measurement signal of these sensors is a combination of
transistor transconductance, threshold voltage, and on-state
resistance. Using a graphene transistor in combination with an
environmental gate yields a transistor with a gate dielectric
formed from the electrochemical double layer that spontaneously
forms by a water when in contact with a surface. Charge transfer
between the liquid and the graphene is suppressed when the graphene
is clean and free of any intervening materials such as acrylic
residue or dielectric material. A sensitization layer such as a
polymer or protein may be applied to this clean graphene surface to
impart chemical selectivity to the transistor based sensor.
[0011] Multiple transistor-based sensors may be placed in an array
exposed to the same, or different environmental gates. For example,
the array may include two transistors, or may include thousands of
transistors. In this configuration, no barrier, protective layer or
sensitization layer is required between the environmental gate and
the transistor channel. However, different transistors within the
array may be differentiated by employing a different sensitization
layer. For example, a thick material such as an antibody layer may
be used, or a thin material such as a small molecule may also be
used. Each sensitization layer may be employed on a different
transistor located on the same chip, and sharing the same
environmental gate.
[0012] In some examples, different sensitization layers and
different types of sensitization layers may be employed, including
covalently and non-covalently bound materials, and incorporate them
all into different groups of transistors on the same chip and
sharing the same environmental gate. Signals generated by each of
the transistors may read out simultaneously or nearly
simultaneously (e.g., by measuring electrical properties such as
voltage or current across the transistor.
[0013] In some examples, a chemically differentiated sensor array
may be used as a system for biological sample analysis. For
example, a system for biological sample analysis may include an
electronic biological sample sensor system wherein the biological
sample sensor system includes one or more sensor chips
electronically coupled to an external connector wherein the sensor
chips includes one or more transistors. Sequencing probes are
associated with the transistors and configured such that if a
complimentary DNA sequence is present in a biological sample, such
as a suspension containing a DNA sample, the electrical properties
of the transistor will change. Based on this change, the DNA
sequence in the biological sample may be identified. The sensor
system may be enclosed in a case, wherein one or more sample wells
are disposed on one side, and each sample well is configured to
form a liquid-tight seal with one of the sensor chips.
[0014] Also as disclosed herein, an example method for biological
sample analysis. A biological sample is introduced into one or more
sample wells configured to form a seal with a sensor. The sensor
has a plurality of sequencing probes, configured to bind with a
complementary sequence of nucleotides in a biological sample. A
voltage is applied to the sensor and the output current of the
sensor is measured to determine changes in the electrical
properties of the sensor chip, such as the transconductance and
resistance of the chip, resulting from changes in pH indicative of
DNA binding. The DNA sequence of the biological sample is then
identified based on the changes in the electrical properties caused
by the DNA binding process.
[0015] Also as disclosed herein, an example system for biological
sample analysis includes a sensing section including one or more
sensor chips, wherein each sensor chip comprises one or more
transistors and a plurality of sequencing probes; a plate section
including one or more biological sample wells, wherein each of the
one or more biological sample wells is configured to direct a
liquid sample to one of the one or more sensor chips; and a
processing section including a processing module.
BRIEF DESCRIPTION OF DRAWINGS
[0016] 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.
[0017] FIG. 1 illustrates a top view of a biological sample
analysis device consistent with embodiments disclosed herein.
[0018] FIG. 2 illustrates a side view of a biological sample
analysis device consistent with embodiments disclosed herein.
[0019] FIG. 3 illustrates a back view of a biological sample
analysis device consistent with embodiments disclosed herein.
[0020] FIG. 4 is a photograph of an example biological sample
analysis device consistent with embodiments disclosed herein.
[0021] FIG. 5 is a photograph of an electronic biological sample
sensor system from an example biological sample analysis device
consistent with embodiments disclosed herein.
[0022] 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.
[0023] 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.
[0024] 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.
[0025] FIG. 9 illustrates a top view of a lower cartridge assembly
from an example biological sample analysis device consistent with
embodiments disclosed herein.
[0026] FIG. 10 illustrates a side view of a lower cartridge
assembly from an example biological sample analysis device
consistent with embodiments disclosed herein.
[0027] FIG. 11 illustrates a back view of a lower cartridge
assembly from an example biological sample analysis device
consistent with embodiments disclosed herein.
[0028] FIG. 12 illustrates an upper view of an upper cartridge
assembly from an example biological sample analysis device
consistent with embodiments disclosed herein.
[0029] FIG. 13A illustrates a side view of an upper cartridge
assembly from an example biological sample analysis device
consistent with embodiments disclosed herein.
[0030] FIG. 13B illustrates a back view of an upper cartridge
assembly from an example biological sample analysis device
consistent with embodiments disclosed herein.
[0031] FIG. 14A illustrates a side view of a sample chamber from an
example biological sample analysis device consistent with
embodiments disclosed herein.
[0032] FIG. 14B illustrates a side view of a sample chamber from an
example biological sample analysis device including an O-ring used
to form a liquid-tight and sterile seal consistent with embodiments
disclosed herein.
[0033] FIG. 15 illustrates a top view of a liquid handling assembly
from an example biological sample analysis device consistent with
embodiments disclosed herein.
[0034] FIG. 16A illustrates a side view of a liquid handling
assembly from an example biological sample analysis device
consistent with embodiments disclosed herein.
[0035] FIG. 16B illustrates a front view of a liquid handling
assembly from an example biological sample analysis device
consistent with embodiments disclosed herein.
[0036] FIG. 17A illustrates a top view of an example biological
sample analysis sensor chip wirebonded in a chip carrier consistent
with embodiments disclosed herein.
[0037] 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.
[0038] 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.
[0039] 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.
[0040] FIG. 18 illustrates a top view of an example biological
sample analysis sensor chip consistent with embodiments disclosed
herein.
[0041] FIG. 19 is a process diagram illustrating a method for
electronically testing a biological sample consistent with
embodiments disclosed herein.
[0042] FIG. 20 is a process diagram illustrating a method for
electronic biological sample analysis consistent with embodiments
disclosed herein.
[0043] FIG. 21 is an example diagram illustrating the process of
binding of subjugate bases of DNA.
[0044] FIG. 22 illustrates a top view of an example DNA sequencing
device consistent with embodiments disclosed herein.
[0045] FIG. 23 is a block diagram illustrating another example DNA
sequencing device consistent with embodiments disclosed herein.
[0046] FIG. 24 is a process diagram illustrating a method for DNA
sequencing consistent with embodiments disclosed herein.
[0047] FIG. 25A is a cross-section diagram illustrating an example
transistor sensor with a buffer layer, but without a sensitization
layer.
[0048] FIG. 25B is a cross-section diagram illustrating an example
transistor sensor with a buffer layer and a sensitization
layer.
[0049] FIG. 26A is a cross-section diagram illustrating an example
environmentally gated transistor sensor without a buffer layer or a
sensitization layer, consistent with embodiments disclosed
herein.
[0050] FIG. 26B is a cross-section diagram illustrating an example
environmentally gated transistor sensor without a buffer layer, but
with a sensitization layer, consistent with embodiments disclosed
herein.
[0051] FIG. 27 is a top-down diagram illustrating an example
arrayed sensor consistent with embodiments disclosed herein.
[0052] FIG. 28 is a chart illustrating sensor array measurements of
a biological sample using different sensor groupings with different
sensitization layers.
[0053] FIG. 29 illustrates an example-computing module that may be
used to implement various features of the systems and methods
disclosed herein.
[0054] 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
[0055] Embodiments of the present disclosure are directed toward a
chemically differentiated sensor array. The array may include a
plurality of environmentally-gated transistors and an environmental
gate covering the transistors. For example, the environmental gate
may be a liquid, such as a solution or a liquid metal. The solution
may be water-based or alcohol-based. In some examples, the solution
is a biological sample, such as blood, DNA, urine, saliva, or a
cellular sample.
[0056] Each environmentally-gated transistor may include a drain, a
source, and a substrate channel. The substrate channel may include
a semiconductor material that is inert in air and water. For
example, the semiconductor material may be Carbon-based, such as
Graphene or Carbon nanotubes. The drain and source may also include
semiconductor materials. For example, the drain and source may both
be either n-type or p-type semiconductors. The drain and source may
each be located on (e.g., deposited on) and electrically couple to
the substrate channel. The drain and source are separated on the
substrate channel by a gap. An insulating layer may then be
deposited on, and thereby cover each of the source and the drain.
When the environmental gate is filled in the gap between the source
and the drain, the insulating layer separates, and thereby
electrically insulates, the source and drain from the environmental
gate.
[0057] The environmental gate may then electrically interact with
the substrate channel. A gate electrode may then be inserted in or
otherwise contact the environmental gate. Each of the source and
the drain may also couple to a source lead and drain lead,
respectively. A voltage may then be applied, via a power supply, to
the environmental gate with respect to either the source or the
drain. Based on a the type of environmental gate used, the
threshold voltage required to enable current flow through the
substrate channel may vary, thus enabling the environmentally-gated
transistor to identify the type of environmental gate, or
components of the environmental gate.
[0058] In some examples, one or more of the environmentally-gated
transistors includes a sensitization layer that covers and
separates the substrate channel from the environmental gate. For
example, the sensitization layer may be a polymer or a protein.
Different sensitization layers may be used to target different
types of environmental gate substances (i.e., to increase
sensitivity and specificity of a particular environmentally-gated
transistor to a particular sample(s) within the environmental
gate). By changing the composition or dimensions of the
sensitization layer, the environmental gate's interaction with the
channel substrate will change, and thus change the electrical
properties of the environmentally-gated transistor. By varying the
dimensions and compositions of the sensitization layers for
different environmentally-gated transistor's in the array, the
array can be sensitive to, and distinguish between many different
substances within the environmental gate (i.e., biological
molecules, antibodies, chemicals, etc.).
[0059] The system may also include an electrical measurement device
electrically coupled to the source lead or drain lead of each
environmentally-gated transistors. For example, the electrical
measurement device may be a voltmeter, an ampmeter, or other
electrical measurement device configured to measure voltage,
on-site resistance, or transconductance, or other electrical
properties of the transistor. One of skill in the art would
understand how to configure such an electrical measurement device
across an array of transistors. In some examples, the electrical
measurement device is also coupled to a computing module that is
configured to receive an output signal from the electrical
measurement device indicating an electrical measurement value, and
the identify a composition of the environmental gate based on the
output signal. The computing module may include a processor and
memory with a software program embedded thereon, the software being
configured to perform the measurement and identification steps
described above. In some examples, the computing module may also
include a display and a user input device (e.g., a keyboard, mouse,
etc.) to enable user interaction.
[0060] Various embodiments described below with reference to FIGS.
1-24 relate to biological sample analysis devices incorporating
similar Graphene-based substrate technology to detect and identify
biological samples contained within a liquid solution (similar to
the environmental gate described above). FIGS. 25A and 25B below
related to ion-sensitive field effect (ISFET) transistors with and
without sensitization layers. FIGS. 26A, 26B, 27, and 28 relate to
environmentally-gated transistors, and chemically differentiated
sensor arrays that incorporate environmentally-gated
transistors.
[0061] 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.
[0062] 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 watertight. 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.
[0063] 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.
[0064] 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.
[0065] 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.
[0066] 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.
[0067] 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.
[0068] 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 are 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 178.
[0069] 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.
[0070] 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.
[0071] 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 flange, 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).
[0072] 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.
[0073] 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 comprise 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.
[0074] 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.
[0075] 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.
[0076] 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.
[0077] 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.
[0078] 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.
[0079] 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.
[0080] FIG. 12 illustrates a top view of an 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.
[0081] 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.
[0082] 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.
[0083] 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.
[0084] FIG. 14A 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 to FIG. 14A, 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 to 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. FIG. 14B
illustrates the side view of a sample chamber similar to FIG. 14A
that further illustrates a sensor chip 1410 that may also be forced
or clamped against O-ring 1464 to form a liquid-tight and sterile
seal. As illustrated by FIG. 14B, tubing 1476 may be configured to
deliver a liquid biological sample into sample chamber 1400.
[0085] 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).
[0086] 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.
[0087] 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 FIGS. 14A and 14B.
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.
[0088] 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.a hybridized. Sp.sup.a
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.
[0089] 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.
[0090] 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, and 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.
[0091] 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.
[0092] 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:
[0093] Autoimmune Diseases [0094] Hashimoto's thyroiditis [0095]
Hyperthyroidism [0096] Multiple sclerosis [0097] Rheumatoid
arthritis
[0098] Bacterial Infections [0099] Bacillus anthracis (anthrax)
[0100] Escherichia coli (food poisoning) [0101] Haemophilus
influenzae (bacterial influenza) [0102] Neisseria gonorrhoeae
(gonorrhea) [0103] Neisseria meningitides (meningitis) [0104]
Plasmodium (malaria) [0105] Rickettsia prowazekii (typhus) [0106]
Salmonella enterica (food poisoning, typhoid) [0107] Staphylococcus
(food poisoning, staph) [0108] Streptococcus pneumonia (pneumonia)
[0109] Treponema pallidum (syphilis)
[0110] Viral Infections [0111] Ebola [0112] Epsein-Bar virus [0113]
Hepatitis A, B, C, D, E [0114] Herpes simplex virus (cold sore,
herpes) [0115] Herpes zoster (chickenpox, shingles) [0116] HIV
[0117] Human coronavirus (common cold) [0118] Influenza (common
cold) [0119] Norovirus [0120] Rhinovirus (common cold) [0121]
Rotavirus [0122] SARS coronavirus [0123] Variola virus
(smallpox)
[0124] Cancer Markers [0125] Alpha fetoprotein [0126]
beta-2-microglobulin [0127] beta-human chorionic gonadotropin
[0128] Calcitonin [0129] Cancer antigen 123 [0130] Cancer antigen
125 [0131] Cancer antigen 15-3 [0132] Cancer antigen 19-9 [0133]
Cancer antigen 27.29 [0134] Carcinoembryonic antigen [0135]
Chromogranin A [0136] Cytokeratin [0137] Human chorionic
gonadotropin [0138] Osteopontin [0139] Prostate specific
antigen
[0140] 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.
[0141] 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.
[0142] 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. 25 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.
[0143] 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-drain and source-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
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. 25 that includes a processor programmed
with one or more computer programs configured to perform the steps
disclosed herein.
[0144] 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.
[0145] 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.
[0146] The technology of the present disclosure is applicable to
not only infection and disease detection, but for other analysis as
well. One such type of analysis is DNA sequencing. When subjugate
bases of DNA (or RNA) bind, the binding process releases ions into
the surrounding suspension. FIG. 21 illustrates an example of the
binding process. As illustrated, a DNA chain 2100 is shown with
subjugate base pairs. At one end 2110, only one side of the double
helix formation is present, with unpaired bases. Binding occurs in
the presence of a sequencing probe 2120--shown in FIG. 21 as
deoxyribose nucleoside triphosphate (dNTP). A sequencing probe is a
fragment of DNA (or RNA in the sequencing of DNA) used to detect
the presence of nucleotide sequences that are complimentary to the
sequence of the sequencing probe. If the dNTP compliments the next
exposed base (illustrated in area 2105), binding occurs and a
subjugate base pair is created (illustrated in area 2130). The
release of a hydrogen ion results in a change in the local pH of
the suspension. By knowing the dNTP being introduced into the
suspension, it is possible to determine which base--adenine,
thymine, guanine, or cytosine--was exposed and the precise
structure of the strand. If a chain of the same exposed base is
present (i.e., more than one of the same base is found
consecutively on a single-strand of the DNA molecule), more ions
will be released, resulting in a greater change in the pH of the
suspension. By measuring the change in the electrical properties of
transistors caused by changes in pH, it is possible to identify the
DNA sequence present in the suspension. Some current DNA sequencing
tools employ a silicon transistor pH meter, such as ion-sensitive
field-effect transistor (ISFET), to identify changes in the local
pH level indicative of DNA binding. The biological sample analysis
sensor chip discussed above is exceptionally suited for such DNA
testing.
[0147] FIG. 22 illustrates an example DNA sequencing device 2200 in
accordance with the present disclosure. The DNA sequencing device
2200 is substantially similar to the biological sample analysis
device described above with respect to FIGS. 1-18. The DNA
sequencing device 2200 includes a first cartridge half 2240 and a
second cartridge half 2250. The first cartridge half 2240 and the
second cartridge half 2250 may be attached in a manner similar to
the biological sample analysis device 100 discussed above with
respect to FIG. 1.
[0148] As shown in FIG. 22, the first cartridge half 2240 includes
an open-air well 2260. In various embodiments, a plurality of
open-air wells 2260 may be included in the first cartridge half
2240. In some embodiments, ninety-six (96) open-air wells 2260 may
be included in the first cartridge half 2240, similar to standard
DNA sequencing plates. The open-air well 2260 serves the same
function as the sample chamber 160 discussed above in FIG. 1. The
bottom of the open-air wells 2260 are aligned with the sensor chips
2210 such that the open-air wells 2260 are in fluidic communication
with the sensor chips 2210 to direct a suspension containing DNA
molecules to the sensor chip 2210. A suspension is a liquid
solution containing a DNA sample, for example cellular material
from a cheek swab. In some embodiments, open-air well 2260 may
include an O-ring groove on its outer rim, allowing a liquid-tight
seal to form with the sensor chip 2210, similar to the seal
discussed above with respect to FIG. 1. In various embodiments, a
gasket may be placed in between the open-air wells 2260 and the
sensor chips 2210 to seal the open-air wells 2260 and prevent the
suspension from seeping into the rest of the DNA sequencing device
2200. In some embodiments, a cover (not pictured) may be included
on the first cartridge half 2240. The cover may be configured to
enclose the one or more open-air wells 2260 such that no liquid
escapes if the DNA sequencing device 2200 is moved.
[0149] Still referring to FIG. 22, the second cartridge half 2250
may include a sensor chip 2210, a chip carrier 2212, a carrier
socket 2214, a circuit board 2216, and an external connector 2280.
For example, circuit board 2216 may be mounted or form fit inside
of the second cartridge half 2250 and may be electronically coupled
to external connector 2280. Circuit board 2216 may also support and
electronically couple to carrier socket 2214, which in turn may
support and electronically couple to chip carrier 2212. Chip
carrier 2212 may be configured to physically support and
electronically couple to sensor chip 2210. In various embodiments,
the electrical connector 2280 may be coupled to an amp meter,
voltmeter, multi-meter, or another external measurement device for
monitoring the change in current or voltage of the transistors. In
some embodiments, the electrical connector 2280 may be coupled to a
computing device designed to measure current and voltage changes in
the transistors due to changes in pH. In some embodiments, the
electrical connector 2280 may both provide electricity to the
circuit board 2216 and output signals to a device for monitoring,
such as a computing device.
[0150] Where a plurality of open-air wells are included in the
first cartridge half 2140, additional sensor chips 2210 may be
required. In such embodiments, the circuit board 2216 may include a
plurality of sensor chips 2210, chip carriers 2212, and carrier
sockets 2214. Each sensor chip 2210 corresponds to one of the
open-air wells 2260 included in the first cartridge half 2240. As
discussed above, each sensor chip 2210 is configured to form a
liquid-tight seal with one of the open-air wells 2260.
[0151] In various embodiments, sensor chip 2210 may be a Graphene
chip with one or more Graphene transistors, similar to the Graphene
chip discussed above in regards to FIGS. 17-18. Unlike traditional
silicon transistors, Graphene does not oxidize in air, is extremely
chemically inert, and thermally stable without the need for
disposing protective layers on the Graphene. Accordingly, less
material is necessary to construct the Graphene chip, and the
Graphene chip may be placed directly in contact with the sensing
environment.
[0152] The Graphene chip used as the sensor chip 2210 may comprise
a plurality of electronic scattering sites, with each scattering
site located on a particular Graphene transistor. Sequencing probes
may be associated with each scattering site and Graphene
transistor. In various embodiments, each scattering site may
include covalently bonded sequencing probes that are complimentary
to specific nucleotide sequences in the suspension. The sequencing
probe may be bonded to the Graphene using a linker such as EDC and
NHS, discussed above with regards to FIG. 18. In some embodiments,
the sequencing probes may not be covalently bonded to the
scattering sites, but instead immobilized through bonding to a
structure directly adjacent to the Graphene transistor. For
example, an immobilization layer of hydrogel or other adherent may
be disposed on the Graphene chip 2210, and the sequencing probes
may be disposed on the immobilization layer. Sensor chips capable
of sequencing all possible base pair possibilities in accordance
with the present disclosure can be constructed using high end
electronics fabrication techniques, such as the photolithography
fabrication process discussed above with regards to FIG. 18.
[0153] In various embodiments, the sensitivity of the sensor chip
2210 may be tailored by employing a similar protein binding method
discussed above with respect to FIG. 18. Through tailoring the
sensitivity of the sensor chip 2210, the DNA sequencing device 2200
may be optimized for a particular pH range. In various embodiments,
the voltage shift measurements described above may be used. In some
embodiments, the suspension itself may be optimized for a more
sensitive reading by selecting solutions that interact more closely
with the sensor chip 2210.
[0154] In various embodiments, additional calculations may be used
to determine the effect of pH change and, accordingly, conduct DNA
sequencing. Due to the unique properties of the Graphene used in
creating the sensor chip 2210, the effects of pH changes on
Graphene are more complex than those seen with typical
semiconductor sensors, such as the ISFET. This complexity arises
from the fact that the sensor chip 2210 is in direct contact with
the sensing environment. In addition, the unique electronic
structure of Graphene also contributes to the complexity. Graphene
acts as a bipolar transistor, showing electronic characteristics of
both n-type and p-type semiconductors. In some embodiments, changes
in the transconductance of the Graphene may be used to determine
the pH change. Transconductance is the ratio of the current
variation at an output to the voltage variation at an input. The
transconductance of a transistor is different at different pH
levels. In some embodiments, changes in the resistance of the
Graphene may be used. In other embodiments, a combination of one or
more of the changes in current, transconductance, or resistance due
to changes in pH may be used to identify the DNA sequence present
in a suspension.
[0155] In various embodiments, it may be beneficial to include some
additional processing functionality within the DNA sequencing
device itself. FIG. 23 is a block diagram illustrating another
example DNA sequencing device 2300 in accordance with the present
disclosure. As shown in FIG. 23, the DNA sequencing device 2300
includes a plate section 2310, which includes one or more open-air
wells 2302, similar to the open-air wells 2260 described above with
regards to FIG. 22. In some embodiments, the plate section 2310 may
include ninety-six (96) open-air wells, similar to standard DNA
sequencing plates. In some embodiments, the plate section 2310 may
include a cover to seal the open-air wells 2302. In various
embodiments, the cover may be attached to the plate section 2310
permanently. In other embodiments, the cover may be removable from
the plate section 2310. In some embodiments, the cover may comprise
individual strips configured to seal one or more open-air wells
2302 within a single column or row. In some embodiments, the plate
section 2310 may be removable from the DNA sequencing device 2300.
By removing the plate section 2310, cleaning the open-air wells
2302 and the sensor chips 2304 may be accomplished easier. In
addition, if the plate section 2310 was to be damaged, but the rest
of the device was unaffected, a user may be able to swap out an
undamaged plate section for the damages section.
[0156] Each of the one or more open-air wells 2302 is configured to
sit on top of a sensor chip 2304 embodied in a sensing section
2320. When situated on top of one of the sensor chips 2304, a
suspension containing a DNA strand may be directed into the
open-air well 2302 and the suspension can contact the sensor chip
2304, similar to the configuration discussed above with regards to
FIG. 22. A liquid-tight seal 2306 is formed between each open-air
well 2302 and sensor chip 2304. This liquid-tight seal 2306 may be
formed in a similar manner as the seal discussed above with regards
to FIG. 22. As configured, each sensor chip 2304 can sense changes
in current and resistance in the suspension directed into the
open-air well 2302 when a nucleotide sequence in the DNA is present
that is complimentary to the sequencing probe associated with the
transistor.
[0157] The output from each sensor chip 2304 may be fed into a data
acquisition module (DAQ) 2315. The DAQ 2215 may serve the same
purpose as the external amp meter, voltmeter, or multi-meter
discussed above with regards to the electrical connector in FIG.
22. The DAQ 2215 may include a multiplexer module (MUX) 2322. The
MUX enables analysis of multiple samples to occur using a single
DNA sequencing device 2300 by allowing a user to select which of
the samples to analyze by selecting the specific open-air well 2302
and sensor chip 2304 combination. In some embodiments, the DAQ may
include a current module 2324 and a voltage module 2328. The
current module 2324 may be configured to identify the change in
current over time based on the output signal of one of the sensor
chips 2304. The voltage module may be configured to identify the
change in voltage over time based on the output signal of one of
the sensor chips 2304. In various embodiments, the current module
2324 and the voltage module 2328 may convert the analog signals
received from the sensor chips 2304 into digital signals for
processing. In some embodiments, the DAQ may include an output
module 2326 to combine the output from the current module 2324 and
the voltage module 2328 and output the data to a digital I/O module
2332 embodied in the processing section 2330. In some embodiments,
the output module 2326 may convert the output from the current
module 2324 and the voltage module 2328 into digital signals. In
some embodiments, the MUX 2322 of the DAQ 2315 may also communicate
with the digital I/O module 2332.
[0158] In addition to the digital I/O module 2332, the processing
section may include a processing module 2334 and an interface
module 2336. The digital I/O module 2332 may provide a connection
between the DAQ 2315 and the processing module 2334. The processing
module may be configured to process the received digital signals
from the digital I/O module 2332. In some embodiments, the
processing module 2334 may be configured to determine the
transconductance of the sensor chip 2304 for the sample being
analyzed. In other embodiments, the processing module 2334 may be
configured to determine the resistance of the sensor chip 2304. In
some embodiments, the processing module 2334 may be configured to
identify a DNA sequence present in a suspension based on the
changes in the electrical properties of a transistor with an
associated sequencing protein. The change in electrical properties
indicates the presence of DNA binding, indicating that the
complimentary nucleotide sequence to the particular sequencing
protein is in the suspension. In some embodiments, the processing
module 2334 may be configured to plot the change in pH over time
against one or more of the change in current, voltage,
transconductance, and resistance. In some embodiments, the
processing module 2334 may include a memory configured to store the
instructions relevant to each of the above described processing
functions for the processing module 2334.
[0159] The interface module 2336 may be configured to output the
data from the processing module 2336 to the user. In some
embodiments, the interface module 2336 may include a connector
configured to connect with a computing device. For example, in some
embodiments, the interface module may include a USB connector, a
VGA connector, a parallel port connector, or some other connector
configured to transmit data to a computing device. In other
embodiments, the interface module 2336 may include components for
wireless transmission of data, such as Wi-Fi or Bluetooth. The user
may control and interact with the DNA sequencing device 2300
through the interface module 2336.
[0160] In various embodiments, the processing section 2330 may be
included on the same circuit board as the sensing section 2320. In
other embodiments, the sensing section 2320 may be embodied on a
first circuit board, and the processing section 2330 may be
embodied on a section circuit board. In such embodiments, the
sensing section 2320 circuit board may be connected to the
processing section 2330 circuit board through pin headers. In other
embodiments, the two boards may be connected directly by disposing
pin headers on both boards configured to mate with each other. In
other embodiments, a connecting cable may be used to connect one
pin header on the sensing section 2320 with a pin header on the
processing section 2330. One of ordinary skill would appreciate
that any acceptable method of connecting the two circuit boards
together may be utilized, depending on the design of the DNA
sequencing device 2300.
[0161] FIG. 24 is a process diagram illustrating an example method
of identifying DNA sequences (e.g. utilizing a DNA sequencing
device). A method of identifying DNA sequences 2400 may include
introducing a suspension into a sample well including a sensor chip
at step 2410. The suspension may be DNA material, such as cellular
material from a cotton swab, suspended in a liquid buffer as is
known in the art. The sample well and sensor chip may be similar to
the embodiments disclosed in FIGS. 22 and 23. Method 2400 may
further include applying a voltage to the sensor chip at step 2420.
In some embodiments, the voltage across the sensor chip may be held
constant while the voltage across the liquid gate is varied during
the measurement period. In other embodiments, the liquid gate
voltage may be held constant, while the voltage across the sensor
chip is varied.
[0162] In some embodiments, the voltage applied at step 2420 may be
used to denature the DNA molecules within the suspension, if
necessary. Method 2400 may further include measuring the current of
the sensor chip on sensor measurement channels at step 2430. For
example, each sensor measurement channel may be monitored through
connector leads electronically coupled to corresponding
transistors. In some embodiments, the method 2400 may be preceded
by a calibration step, whereby solutions of known pH are introduced
into the sample wells in order to determine the baseline reading
for the sensor chip. Method 2400 may further include determining
any change in the electrical properties of the sensor chip over
time at step 2440. Changes in the transconductance and the
resistance of the sensor chip indicates a release of a hydrogen ion
around the sensor chip, changing the pH level. Method 2400 may
further include identifying a DNA sequence of the DNA molecule in
the suspension based on the change in electrical properties of the
sensor chip at step 2450. The DNA sequence of a DNA molecule in a
suspension is determinable by identifying the sequencing probe
associated with the sensor chips in which the electrical properties
changed over time, indicating a DNA binding process by the change
in the pH.
[0163] The steps of measuring current on sensor measurement
channels 2430, determine change in electrical properties over time
2440, and identifying the DNA sequence in the suspension 2460 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. 25 that includes a processor programmed
with one or more computer programs configured to perform the steps
disclosed herein. Other steps of method 2400 may be similarly
performed by a computer module.
[0164] FIG. 25A is a cross-section diagram illustrating a
transistor sensor with a buffer layer, but without a sensitization
layer. As illustrated, source 2502 and drain 2504 are layered on
channel 2506. Each of source 2502 and drain 2504 are fabricated
from a semiconductor material (i.e., n-type or p-type
semiconductors) and covered by an insulating material, as would be
known in the art. Channel 2506, also fabricated from a
semiconductor material, is layered on gate dielectric 2508, and
gate dielectric 2508 is layered on back gate 2510. In this type of
configuration, the channel 2506 generally will react with air or
water, and thus a barrier layer (not shown) is typically deposited
on top of the channel. For example, the barrier may be a metal
oxide to prevent reactions in the channel. This barrier layer
decreases the sensitivity of the transistor. In an array of this
type of transistor illustrated in FIG. 25A, the barrier layer is
generally deposited uniformly across the entire array of
transistors. Environmental gate 2520 may be a water solution or
alcohol solution, for example, that incorporates a biological or
chemical sample.
[0165] FIG. 25B is a cross-section diagram illustrating a
transistor sensor with a buffer layer and a sensitization layer.
The structure of this transistor is the same as the structure
illustrated in FIG. 25A, except a sensitization layer 2512 is
layered on top of channel 2506 to increase sensitivity to targeted
environmental gate solutions.
[0166] FIG. 26A is a cross-section diagram illustrating an
environmentally gated transistor sensor without a buffer layer or a
sensitization layer. The structure illustrates incorporates a
channel substrate 2606 that fabricated from a semiconductor
material that is chemically inert to air or water, with a source
2602 and drain 2604 layered thereon. For example, source 2602 and
drain 2604 may each be fabricated from a semiconductor material
(i.e., a n-type or p-type semiconductor), and the channel substrate
2606 may be fabricated from a Carbon-based semiconductor material
such as Graphene or Carbon nanotubes. Environmental gate 2620 may
be a liquid, such as a water-based solution, an alcohol-based
solution, or a liquid metal, as disclosed herein. Source 2602 and
drain 2604 are covered by an insulator to electrically insulate
them from environmental gate 2620. Under this construction, no
barrier layer is required, as the Carbon-based semiconductor is
chemically inert to air and water. Source 2602 and drain 2604 are
separated by a gap.
[0167] Based on electrical principles of transistors, when a
sufficient threshold voltage is applied across the environmental
gate 2620 and the source 2602, or the environmental gate 2620 and
the drain 2604, current flow increases through channel 2606 and can
be measured across leads (not shown) coupled to source 2602 and
drain 2604. A gate electrode may be placed in, or in contact with
environmental gate 2620 to apply a gate voltage. In some
embodiments, the gate electrode may also be used as a sense
electrode, e.g., to monitor changes in electrical properties of the
environmental gate as gate voltage is applied.
[0168] FIG. 26B is a cross-section diagram illustrating an
environmentally gated transistor sensor without a buffer layer,
like the transistor illustrated in FIG. 26A, but also including a
sensitization layer 2612. For example, the sensitization layer 2612
may be a polymer or a protein. Different sensitization layers may
be used to target different types of environmental gate substances
(i.e., to increase sensitivity and specificity of a particular
environmentally-gated transistor to a particular sample(s) within
the environmental gate). By changing the composition or dimensions
of the sensitization layer, the environmental gate's interaction
with the channel substrate will change, and thus change the
electrical properties of the environmentally-gated transistor. By
varying the dimensions and compositions of the sensitization layers
for different environmentally-gated transistor's in the array, the
array can be sensitive to, and distinguish between many different
substances within the environmental gate (i.e., biological
molecules, antibodies, chemicals, etc.).
[0169] FIG. 27 is a top-down diagram illustrating an example
arrayed sensor. As illustrated, electrical connections 2720 connect
to the source and drain leads for environmentally gated transistors
2710. As illustrated, many (from just two, to thousands or more)
environmentally gated transistors may be fabricated on a single
array on the same Carbon-based substrate. One of ordinary skill in
the art would appreciate that the example illustrated in FIG. 27 is
only one type of possible layout for the environmentally-gated
transistor array, and many other layouts and configurations are
possible.
[0170] As discussed above, the system may also include an
electrical measurement device (not shown) electrically coupled to
the source lead or drain lead of each environmentally-gated
transistors. For example, the electrical measurement device may be
a voltmeter, an ampmeter, or other electrical measurement device
configured to measure voltage, on-site resistance, or
transconductance, or other electrical properties of the transistor.
One of skill in the art would understand how to configure such an
electrical measurement device across an array of transistors. In
some examples, the electrical measurement device is also coupled to
a computing module that is configured to receive an output signal
from the electrical measurement device indicating an electrical
measurement value, and the identify a composition of the
environmental gate based on the output signal. The computing module
may include a processor and memory with a software program embedded
thereon, the software being configured to perform the measurement
and identification steps described above. In some examples, the
computing module may also include a display and a user input device
(e.g., a keyboard, mouse, etc.) to enable user interaction.
[0171] FIG. 28 is a chart illustrating sensor array measurements of
a biological sample using different sensor groupings with different
sensitization layers. For example, a similar chart may be generated
using the computing module described above. Referring to FIG. 28,
the y-axis of the chart is normalized transconductance and the
x-axis is time. An environmental gate solution containing multiple
bacterial biomarkers is exposed to the array of
environmentally-gated transistors, wherein environmentally-gated
transistors in sensor group 1 includes a first sensitization layer
2612 sensitive to a first type of biomarker, environmentally-gated
transistors in sensor group 2 includes a second sensitization layer
2612 sensitive to a second type of biomarker, and
environmentally-gated transistors in sensor group 3 includes a
third sensitization layer 2612 sensitive to a third type of
biomarker. Example transconductance measurements across the sensor
array for all three sensor groups over time are illustrated on the
chart, demonstrating the ability of the array to quickly detect and
identify different biomarkers.
[0172] FIG. 29 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, one or more steps of the method for electronic biological
sample analysis 2000 disclosed in FIG. 20, and/or one or more steps
of the method for DNA sequencing 2400 disclosed in FIG. 24. The
computer executable code may further be configured to measure,
detect, and identify environmental gate compositions based on
measured electrical properties across a chemically differentiated
sensor array, consistent with the environmentally-gated transistors
and array illustrated in FIGS. 26A, 26B, and 27.
[0173] 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.
[0174] 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. 29. Various embodiments are
described in terms of this example-computing module 2900. 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.
[0175] Referring now to FIG. 29, computing module 2900 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 2900 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.
[0176] Computing module 2900 might include, for example, one or
more processors, controllers, control modules, or other processing
devices, such as a processor 2904. Processor 2904 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 2904 is
connected to a bus 2902, although any communication medium can be
used to facilitate interaction with other components of computing
module 2900 or to communicate externally.
[0177] Computing module 2900 might also include one or more memory
modules, simply referred to herein as main memory 2908. For
example, preferably random access memory (RAM) or other dynamic
memory, might be used for storing information and instructions to
be executed by processor 2904. Main memory 2908 might also be used
for storing temporary variables or other intermediate information
during execution of instructions to be executed by processor 2904.
Computing module 2900 might likewise include a read only memory
("ROM") or other static storage device coupled to bus 2902 for
storing static information and instructions for processor 2904.
[0178] The computing module 2900 might also include one or more
various forms of information storage mechanism 2910, which might
include, for example, a media drive 2912 and a storage unit
interface 2920. The media drive 2912 might include a drive or other
mechanism to support fixed or removable storage media 2914. 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 2914 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 2912. As these examples illustrate, the
storage media 2914 can include a computer usable storage medium
having stored therein computer software or data.
[0179] In alternative embodiments, information storage mechanism
2910 might include other similar instrumentalities for allowing
computer programs or other instructions or data to be loaded into
computing module 2900. Such instrumentalities might include, for
example, a fixed or removable storage unit 2922 and a storage
interface 2920. Examples of such storage units 2922 and storage
interfaces 2920 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 2922 and storage
interfaces 2920 that allow software and data to be transferred from
the storage unit 2922 to computing module 2900.
[0180] Computing module 2900 might also include a communications
interface 2924. Communications interface 2924 might be used to
allow software and data to be transferred between computing module
2900 and external devices. Examples of communications interface
2924 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 2924 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 2924. These signals might be provided to
communications interface 2924 via a channel 2928. This channel 2928
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.
[0181] 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 2908, storage
unit 2920, media 2914, and channel 2928. 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
2900 to perform features or functions of the present application as
discussed herein.
[0182] 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.
[0183] 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.
[0184] 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.
[0185] 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.
* * * * *