JP2024055954A - Polar fluid-gated field-effect devices - Google Patents

Abstract

Disclosed herein are nanoscale field effect transistors (NFETs), e.g., graphene-based field effect transistors (GFETs), that do not have a physical gate. Instead of a physical gate, the field effect transistors are gated by a polar fluid. Systems and methods using such transistors are also disclosed. In one aspect, a field effect transistor is disclosed herein.
[Selected Figure] Figure 4A

Description

CROSS-REFERENCE TO RELATED APPLICATIONS This application is related to “DETECTION OF IONIC CONCENTRATION IN FLUID USING NANOSCALE”, filed on June 30, 2016.
No. 62/356,729, filed Jun. 30, 2016, entitled "LABEL-FREE DETECTION OF LACTATE IN SWEAT AND OTHER BODILY FLUIDS," each of which is hereby incorporated by reference in its entirety.

FIELD OF THEINVENTION The inventions disclosed herein generally relate to the design, fabrication, and application of nanoscale field effect transistors (NFETs), particularly graphene field effect transistors (GFETs), gated by polar fluids. The disclosure also relates generally to chemical and biological sensing using field effect transistors, and more particularly to biochemical sensing using field effect transistors with biochemically sensitive channels that include graphene.

Background A field effect transistor (FET) is a transistor that uses an electric field to control the electrical behavior of the device. In general, a FET has three terminals (e.g., a source, a drain, and a gate) and an active channel through which charge carriers (electrons or holes) flow from the source to the drain, for example through an active channel formed by a semiconductor material.

The source (S) is where carriers enter the channel. The drain (D) is where carriers leave the channel. The drain-to-source voltage is VDS and the source-to-drain current is IDS. The gate (G) modulates the channel conductivity by applying a gate voltage (VG) so that the current between the source and drain is controlled.

Nanoscale field effect transistors (NFETs), such as graphene field effect transistors (GFETs), are widely used in numerous applications such as bioprobes, implants, and the like.

What is needed in the art are better designs for FETs and new ways to use them.

In one aspect, a field effect transistor is disclosed herein. The field effect transistor includes a drain electrode, a drain electrode, a source electrode, an electrically insulating substrate, a nanoscale material layer disposed on the substrate and partially defining an electrically conductive and chemically sensitive channel, the nanoscale material layer and said channel extending between and electrically connected to the drain electrode and the source electrode, and a polar fluid-induced gate terminal created by a polar fluid exposed to the nanoscale material layer. In some embodiments, the polar fluid includes a target analyte. In some embodiments, the polar fluid has a charge concentration sufficient to induce a polar fluid gate voltage that optimizes the gate voltage vs. channel current characteristics of the field effect transistor in response to the target analyte.

In some embodiments, the constant current or voltage is provided by a constant current source or a constant voltage source and is applied between the source and drain electrodes.

In some embodiments, the nanoscale material comprises graphene, CNT, _MoS2 , boron nitride, metal dichalcogenides, phosphorene, nanoparticles, quantum dots, fullerenes, 2D nanoscale materials, 3D nanoscale materials, 0D nanoscale materials, 1D nanoscale materials, or any combination thereof.

In some embodiments, the polar fluid comprises a solution having polar molecules, a gas having polar molecules, a target sensing analyte, or a combination thereof.

In some embodiments, the field effect transistor of any one of claims 1 to 4, wherein the polar fluid comprises sweat, breath, saliva, earwax, urine, semen, blood plasma, a biological fluid, a chemical fluid, an air sample, a gas sample, or a combination thereof.

In some embodiments, the target analyte comprises an electrolyte, glucose, lactate, IL6, cytokine, HER2, cortisol, ZAG, cholesterol, vitamins, proteins, drug molecules, metabolites, peptides, amino acids, DNA, RNA, aptamers, enzymes, biomolecules, chemical molecules, synthetic molecules, or combinations thereof.

In some embodiments, the field effect transistor further includes a receptor layer deposited on the nanoscale material layer, the receptor layer including a receptor that targets the target analyte.

In some embodiments, the receptor includes pyrene boronic acid (PBA), pyrene N-hydroxysuccinimide ester (pyrene-NHS), organic chemicals, aromatic molecules, cyclic molecules, enzymes, proteins, antibodies, viruses, single-stranded DNA (ssDNA), aptamers, inorganic materials, synthetic molecules, and biomolecules.

In some embodiments, the field effect transistor further comprises a backside polymer layer below the nanoscale material layer to provide support for additional mechanical, electrical, chemical, biological functionality, or a combination thereof.

In some embodiments, the backside polymer layer includes: carbon polymer, biopolymer, PMMA, PDMS, flexible glass, nanoscale material, silica gel, silicone, ink, printed polymer, or any combination thereof.

In one aspect, disclosed herein is a method for sensing a target analyte in a polar fluid, the method including exposing a polar fluid sample to a field effect transistor including a drain electrode, a source electrode, an electrically insulating substrate, a nanoscale material layer disposed on the substrate and at least partially defining an electrically conductive and chemically sensitive channel, the nanoscale material layer and the channel extending between and electrically connected to a drain electrode and a source electrode, and a polar fluid-induced gating terminal created by a polar fluid exposed to the nanoscale material layer, the polar fluid including the target analyte and having a charge concentration sufficient to induce a polar fluid gating voltage that optimizes a gate voltage versus channel current characteristic of the field effect transistor for detecting the analyte, measuring a first source-drain voltage at a first time point and a second source-drain voltage at a second and subsequent time point, and determining a concentration of the target analyte in the polar fluid based on the first and second source-drain voltages.

In some embodiments, the nanoscale material includes graphene, CNT, MoS2, boron nitride, metal dichalcogenides, phosphorene, nanoparticles, quantum dots, fullerenes, 2D nanoscale materials, 3D nanoscale materials, 0D nanoscale materials, 1D nanoscale materials, or any combination thereof.

In some embodiments, the field effect transistor is functionalized with a receptor layer deposited on the nanoscale material layer, the receptor layer including a receptor that targets a target analyte.

In some embodiments, the receptor includes pyrene boronic acid (PBA), pyrene N-hydroxysuccinimide ester (pyrene-NHS), organic chemicals, aromatic molecules, cyclic molecules, enzymes, proteins, antibodies, viruses, single-stranded DNA (ssDNA), aptamers, inorganic materials, synthetic molecules, and biomolecules.

In some embodiments, the target analyte comprises an electrolyte, glucose, lactate, IL6, cytokine, HER2, cortisol, ZAG, cholesterol, vitamins, proteins, drug molecules, metabolites, peptides, amino acids, DNA, RNA, aptamers, enzymes, biomolecules, chemical molecules, synthetic molecules, or combinations thereof.

In some embodiments, the polar fluid comprises a solution containing polar molecules, a gas containing polar molecules, a target sensing analyte, or a combination thereof.

In some embodiments, the method further includes calculating a fractional rate of change between the first and second source-drain voltages.

In some embodiments, the method further includes applying a constant current between a source electrode and a drain electrode of the field effect transistor.

In some embodiments, the method further includes applying a constant voltage between the source and drain electrodes of the field effect transistor.

In some embodiments, the polar fluid comprises sweat, breath, saliva, earwax, urine, semen, plasma, biological fluids, chemical fluids, air samples, gas samples, or combinations thereof.

In some embodiments, the method further includes a backside polymer layer beneath the nanoscale material to provide support for additional mechanical, electrical, chemical, biological functionality, or a combination thereof.

In some embodiments, the backside polymer layer comprises a carbon polymer, a biopolymer, PMMA, PDMS, flexible glass, a nanoscale material, a silica gel, a silicone, an ink, a printed polymer, or any combination thereof.

In one aspect, the present specification discloses a field effect transistor and a system that includes:

A constant current or voltage source electrically connected to a field effect transistor. The field effect transistor includes a drain electrode; a source electrode; an electrically insulating substrate; a nanoscale material layer disposed on the substrate and at least partially defining an electrically conductive and chemically sensitive channel, the nanoscale material layer and the channel extending between and electrically connected to the drain and source electrodes; and a polar fluid-induced gate terminal created by a polar fluid exposed to the nanoscale material layer. In some embodiments, the polar fluid includes a target analyte. In some embodiments, the polar fluid has a charge concentration sufficient to induce a polar fluid gate voltage that optimizes the gate voltage for the channel current characteristics of the field effect transistor in response to the target analyte.

In some embodiments, the constant current source maintains a constant current through a field effect transistor.

In some embodiments, a constant voltage source maintains a constant voltage across a field effect transistor.

In some embodiments, the voltage or current output is transmitted to a digital platform via wired or wireless transmission.

In some embodiments, the digital platform includes a smartphone, a tablet computer, a smartwatch, an in-car entertainment system, a laptop computer, a desktop computer, a computer terminal, a television system, an e-book reader, a wearable device, or any other type of computing device that processes digital input.

As known to one of ordinary skill in the art, any embodiment disclosed herein may be used in conjunction with any aspect of the present invention, either alone or in combination with other embodiments.

Those skilled in the art will appreciate that the drawings provided below are for illustrative purposes only. The drawings are not intended to limit the scope of the teachings of the present invention.

FIG. 1A illustrates a prior art embodiment illustrating a graphene field effect transistor (gFET).

FIG. 1B illustrates a prior art embodiment showing the current between the source and drain as controlled by the gate voltage.

FIG. 2A illustrates an exemplary embodiment showing a gateless graphene field effect (ggFET).

FIG. 2B illustrates an exemplary embodiment showing a ggFET.

FIG. 2C illustrates an exemplary embodiment showing a ggFET.

FIG. 2D illustrates an exemplary embodiment showing a ggFET.

FIG. 3A illustrates an exemplary embodiment showing a polar fluid gate terminal (PFGT) with no polar fluid moving.

FIG. 3B illustrates an exemplary embodiment showing a polar fluid gate terminal through which a polar fluid flows in a first direction.

FIG. 3C illustrates an exemplary embodiment showing a polar fluid gate terminal through which the polar fluid flows in a second direction.

4A illustrates an exemplary embodiment showing the base device illustrated in Figures 2A-2D with a dielectric and a gate metal. The gate potential is measured between the gate metal and ground.

4B illustrates an exemplary embodiment showing the base device illustrated in Figures 2A-2D with an additional metal electrode in a PFGT. The gate potential is measured between the metal electrode and ground.

4C illustrates an exemplary embodiment showing the base device illustrated in FIGS. 2A-2D augmented with a dielectric and gate metal and metal electrodes into a PFGT. The two gate potentials are measured as indicated.

FIG. 5A illustrates an exemplary embodiment showing a GFET used in conjunction with a constant current source.

FIG. 5B illustrates an exemplary embodiment showing a GFET used in conjunction with a constant voltage source.

FIG. 6 illustrates an exemplary embodiment showing selectivity measurements of NaCl response in DI water.

FIG. 7 illustrates an exemplary embodiment showing sensitivity measurements for NaCl response in DI water.

FIG. 8 illustrates an exemplary embodiment showing the chloride response in sweat.

FIG. 9 illustrates an exemplary embodiment showing selectivity measurements of glucose response in DI water.

FIG. 10 illustrates an exemplary embodiment showing glucose response in DI water versus glucose response in NaCl.

FIG. 11 illustrates an exemplary embodiment showing selectivity measurements of glucose response in NaCl water.

FIG. 12 illustrates an exemplary embodiment showing sensitivity measurements of D-glucose in DI water.

FIG. 13 illustrates an exemplary embodiment showing the functionalization steps visualized by GFET fabrication.

FIG. 14 illustrates an exemplary embodiment showing D-glucose response in sweat.

FIG. 15 illustrates an exemplary embodiment showing D-glucose response in blood.

FIG. 16 illustrates an exemplary embodiment showing correlation of measurements between blood glucose and sweat glucose.

FIG. 17 illustrates an exemplary embodiment showing selectivity measurements of lactate response in DI water.

FIG. 18 illustrates an exemplary embodiment showing selectivity measurements of lactate response in various solutions.

FIG. 19 illustrates an exemplary embodiment showing lactate response in NaCl versus lactate response in DI water.

FIG. 20 illustrates an exemplary embodiment showing the lactate functionalization steps visualized by GFET fabrication.

FIG. 21 illustrates an exemplary embodiment showing a model for correlation of the sensor to sodium concentration in sweat.

FIG. 22 illustrates an exemplary embodiment showing a model for correlation of the sensor to glucose concentration in sweat.

FIG. 23 illustrates an exemplary embodiment showing the transconductance curve for a PFT.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS Disclosed herein are nanoscale field effect transistors and methods for making and using same.
A typical graphene field-effect transistor

Graphene possesses remarkable mechanical resistance, which allows it to be subjected to considerable mechanical stresses at thicknesses of the order of monolayers or bilayers without losing its primary electrical properties. Such mechanical strength makes graphene an ideal candidate to replace the current generation of transparent conductive oxides (TCOs) offered by indium tin oxide (ITO). Unlike graphene, ITO is brittle and susceptible to mechanical stresses; however, its low sheet resistance and high transparency are sufficient to offset its high material cost. On the other hand, the production of large-area and low-sheet-resistance graphene sheets is a relatively simple and scalable process using chemical vapor deposition (CVD), which, after proper processing, results in a few atomic layers with transparency higher than 90% and sheet resistance lower than 100.

As illustrated in FIG. 1A, graphene FETs are typically fabricated on a Si wafer covered with a SiO2 layer, with graphene forming the transistor channel. A graphene transistor consists of three terminals, source and drain metal electrodes that contact the graphene channel, and a global backgate enabled by a doped Si substrate. These features facilitate the characteristic ambipolar transport behavior of graphene in Grat-FETs—achieving both n-type and p-type transport when biased with the proper gate voltage at the substrate. Any applicable method can be applied to fabricate GFETs, including, for example, the information disclosed in International Patent Publication No. WO 2015/164,552, which is incorporated herein by reference in its entirety.

1B illustrates the current between the source and drain as controlled by the gate voltage. By changing the direction and magnitude of the gate voltage, the resulting current curve between the source and drain takes on a "V" shape. Small changes in the gate voltage at the extremities of the V-shaped curve result in significant and detectable changes in the channel current (I _DS ), which tends to flatten out at the two endpoints of the V-shaped curve.
Gateless Field-Effect Transistor

In one aspect, the present specification discloses a new type of field effect transistor (FET) that does not have a physical gate.

2A through 2D illustrate various embodiments of FETs without a physical gate. FIG. 2A illustrates an exemplary graphene-based FET 210, including a substrate 1, a source electrode 2, a drain electrode 3, a receptor 4, a graphene layer 5, and a backside polymer 6. As disclosed herein, the substrate 1 can be polyamide, PET, PDMS, PMMA, other plastics, silicon dioxide, silicon, glass, aluminum oxide, sapphire, germanium, gallium arsenide, indium phosphide, alloys of silicon and germanium, fabrics, textiles, silk, paper, cellulose-based materials, insulators, metals, semiconductors, and can be rigid, flexible, or any combination thereof. In some embodiments, the substrate 1 can be a silicon carbide substrate, and the graphene layer 5 can be epitaxially grown directly on the silicon carbide substrate by sublimation of silicon from the silicon carbide substrate (FIG. 2B).

The source electrode 2 is the electrode region of the field effect transistor from which the majority of carriers flow into the interelectrode conductive channel. Exemplary materials that can be used as the source electrode include, but are not limited to, silver, gold, carbon, graphite ink, conductive fabrics, conductive textiles, metals, conductive materials, conductive polymers, conductive gels, ionic gels, conductive inks, and non-metallic conductive materials.

The drain electrode 3 is an electrode on the opposite side of the source electrode 2. Exemplary materials that can be used as the source electrode include, but are not limited to, silver, gold, carbon, graphite ink, conductive fabrics, conductive textiles, metals, conductive materials, conductive polymers, conductive gels, ionic gels, conductive inks, and non-metallic conductive materials.

In some embodiments, the graphene layer 5 can have one or more monolayers of graphene of uniform, preferably predetermined, thickness. Since thickness affects electrical properties, e.g., band gap, carrier concentration, etc., a uniform, preferably predetermined, thickness provides control over sensing properties and allows for the formation of reproducible devices with less variability between individual sensors.

In some embodiments, the graphene layer 5 may be an epitaxial layer, and the substrate of the graphene layer may be the substrate on which the graphene layer is epitaxially grown. By leaving the graphene layer on the substrate of growth, the typically nano-thin graphene layers and structures do not necessarily have to be handled. The risk of damaging the thin graphene layer during transistor fabrication is also reduced if the graphene layer can be left on the substrate.

In some embodiments, the graphene layer 5 can be surface treated with receptors 4 for selectivity, such that only selected types of analytes are detected by the graphene layer.
Exemplary receptors 4 include, but are not limited to, pyrene boronic acid (PBA), N-hydroxysuccinimide ester (pyrene-NHS), organic chemicals, aromatic molecules, cyclic molecules, enzymes, proteins, antibodies, viruses, single-stranded DNA (ssDNA), aptamers, inorganic materials, synthetic molecules, and biomolecules.

In some embodiments, the graphene layer 5 and/or therefore certain types of chemicals are prevented from reaching the chemically sensitive channels. Surface treatments may include deposition of metal particles and/or polymers.

The backside polymer 6 is used to provide mechanical support to the graphene and, when doped, can add new modalities to the sensing response. For example, the backside polymer can be doped with biomolecules that can both bind to specific targets and participate in the resistance change of the transistor channel.

Devices 220, 230, and 240 are variations of device 210. In device 220, the backside polymer layer 6 is omitted. In device 230, the receptor layer 4 is omitted. In device 240, both the backside polymer layer 6 and the receptor layer 4 are omitted.

As disclosed herein, the device or base device can be any of devices 210 , 220 , 230 , and 240 .
Polar Fluid Gate Terminal (PFGT)

Graphene is an allotrope of carbon that takes the form of a two-dimensional atomic-scale hexagonal lattice with one atom forming each vertex. It is the basic structural element of other allotropes, including graphite, charcoal, carbon nanotubes, and fullerenes. It can be thought of as the ultimate case of a family of flat polycyclic aromatic hydrocarbons, an infinitely large aromatic molecule. In some embodiments, graphene is a single layer of carbon atoms. Each carbon atom in graphene has four electrons. Through three of these electrons, the carbon atom is bonded to its three nearest neighbors to form a hexagonal lattice. For each atom, the four electrons are delocalized on the entire graphene layer, allowing the conduction of electron flow.

When a polar fluid is deposited on the graphene layer, the special electronic properties of graphene can cause charge reorganization in the polar fluid to form a liquid-induced gate voltage that can modulate the current between the source and drain electrodes.

FIG. 3A illustrates an exemplary embodiment showing a polar fluid gate terminal with no polar fluid in motion. As shown, the charge of the polar or ionic components is redistributed in the polar fluid, resulting in the creation of a polar fluid gate terminal (PFGT) and an induced fluid gate voltage (V _FG ). This voltage can result in a shift on the x-axis (voltage) in a V-shaped current versus fluid gate voltage curve. As noted, at the tip of the V-shaped curve, small changes in gate voltage can result in significant and detectable changes in the channel current (I _DS ), which tends to flatten out at the two endpoints of the V-shaped curve. The shift toward the tip of the V-shaped curve can result in increased sensitivity, allowing very small changes in voltage in response to changes in current to be detected. Similarly, very small changes in current in response to changes in voltage can also be detected.

As mentioned above, a shift towards the tip of the V-shaped curve can result in better sensitivity. Such a shift can be caused by a polar liquid-induced gate voltage. In some embodiments, the polar liquid-induced gate voltage is related to the concentration of charged particles in the polar fluid. In some embodiments, the concentration can reflect the total amount of all negatively charged particles or all positively charged particles. The shift of the V-shaped curve can be correlated to a wide range of charged particle concentrations. In some embodiments, the shift correlates to charged particle concentrations as low as 1 femto g/L (e.g., NaCl). In some embodiments, the shift correlates to charged particle concentrations as high as 300 g/L (e.g., NaCl). These results suggest that the current sensing system is resilient and can withstand a wide range of charge concentrations.

3B illustrates an exemplary embodiment showing a polar fluid gate terminal with a polar fluid flowing in a first direction. The magnitude of the gate potential (V _FG ) is directly proportional to the flow rate of the polar fluid. The sign or direction of V _FG depends on the direction in which the polar fluid flows; e.g., along or across the source-drain terminals. For example, if the gate voltage is positive along the source-drain direction, it will be negative in the reverse direction, and vice versa. When the polar fluid flows across the source-drain voltage, if the gate voltage is positive along the Y direction, it will be negative in the Y direction, and vice versa. When the direction of polar fluid flow changes, the direction of the gate voltage may also change.

FIG. 3C illustrates an exemplary embodiment showing a polar fluid gate terminal through which the polar fluid flows in a second direction opposite the first direction.
Sensing the gate voltage at the polar fluid gate terminal

Figures 4A through 4C illustrate configurations in which the gate voltage at the polar fluid gate terminal (PFGT) is determined.

Figure 4A illustrates an exemplary embodiment showing a base device with a dielectric layer 7 and a gate metal 8, where the base device can be any of those illustrated in Figures 2A-2D, such as 210, 220, 230, and 240. The gate potential is measured between the gate metal and ground. A dielectric layer 7 is added below the substrate of the base device (e.g., substrate 1 as illustrated in Figures 2A-2D). A gate metal 8 is added below the dielectric layer 7. The gate metal 8 is added only to measure the induced gate voltage, no voltage is applied through the gate metal 8. In some embodiments, Vg1 can be nonlinearly varied depending on the PFGT device characteristics and the type of channel. For example, if the channel is graphene (ambipolar), Vg1 can follow a transconductance response typical of graphene devices.

Figure 4B illustrates an exemplary embodiment showing the base device illustrated in Figures 2A-2D with an added metal electrode in the PFGT. The gate potential is measured between the metal electrode and ground. Vg2 is the top gate voltage formed by the double layer capacitance between the added metal electrode and the active channel. Vg2 can vary nonlinearly depending on the PFGT device characteristics and the type of channel. For example, if the channel is graphene (ambipolar), Vg2 follows the transconductance response typical of graphene devices (see, e.g., Figure 23).

Figure 4C illustrates an exemplary embodiment showing the base device illustrated in Figures 2A-2D with the dielectric and gate metal and metal electrodes in the PFGT enhanced. Two gate potentials are measured as indicated. The two gate potentials (Vg1 and Vg2) are the electrical outputs modulated using the source-drain current/voltage and induced PFG. The simultaneous measurement of Vg1 and Vg2 creates a tri-gated structure that can be used to develop next generation microprocessors, logic gates, computational circuits, radio frequency (RF) devices, sensors, and the like.

Figure 4C illustrates an exemplary embodiment showing the base device illustrated in Figures 2A-2D with an enhancement of the dielectric and gate metal and metal electrodes in the PFGT. Two gate voltages (e.g., Vg1 and Vg2) are supplied to the PFGT to modulate the overall electrical characteristics of the PFGT device for a desired application. Simultaneous modulation with Vg1 and Vg2 creates a tri-gated structure that can be used to shift the operation of the device to the desired electrical performance in a more controlled manner using minimal energy. Such devices can be used to develop next generation microprocessors, logic gates, computational circuits, radio frequency (RF) devices, sensors, and the like.

5A illustrates an exemplary embodiment showing the circuit used to read out the sensor via a polar fluidic graphene field effect transistor (PFGFET). In FIG. 5A, a constant current (I _C ) is supplied to the PFGFET. The output voltage (V _OUT ) is read through the PFGFET using a divider and a current resistor (R). The voltage output is then calibrated to the concentration of the analyte being sensed.

Figure 5B illustrates an exemplary embodiment showing another circuit used to read out the sensor via the PFGFET. Here, a constant voltage (Vs) is supplied to the PFGFET. A current or charger (Ian) is read from the PFGFET using a current resistor (R). The current output is then calibrated to the concentration of the analyte being sensed.

Although the present invention has been described in detail, it will be apparent that modifications, variations, and equivalent embodiments are possible without departing from the scope of the invention as defined in the appended claims. Moreover, it should be understood that all examples in this disclosure are provided as non-limiting examples.

The following non-limiting examples are provided to further illustrate the embodiments of the invention disclosed herein. Those skilled in the art should understand that the techniques disclosed in the following examples represent methods found to work well in the practice of the invention and therefore can be considered to constitute examples of the embodiments for its implementation. However, those skilled in the art will understand in light of this disclosure that many changes can be made in the specific embodiments disclosed without departing from the spirit and scope of the invention and still obtain the same or similar results.
Example 1
Experimental conditions for nanoscale field-effect transistors

The device was fabricated with graphene as the carrier channel of a two-terminal NFET without a physical gate terminal.

The polymer was placed on the graphene, typically with a thickness of less than 0.5 mm, and then separated from the catalytic substrate on which the graphene was grown. A flexible polymer platform for the sensing system was used to stage the graphene polymer composite and two metal electrical contacts. The graphene polymer composite was bonded to the flexible polymer platform. A solution of the desired linker molecule was deposited on the graphene polymer composite and incubated. Excess linker molecule solution was removed from the graphene polymer composite; two metal electrical contacts were deposited on both edges of the graphene polymer composite.

The graphene polymer composite was then placed on a polymer substrate such as Teflon, polyimide, and the like, and then heated at 80-150 degrees Celsius for 1-10 minutes to remove any impurities.

The GFET sensors were then ready for use. In some cases, receptors for specific analytes were deposited on the graphene layer.

The sensor system for analyte sensing through sweat consisted of:
○ Flexible polymer platform made of (Kapton);
Graphene polymer composites bonded to flexible polymer platforms;
o source and drain electrodes positioned in a sensor configuration on opposing edges of a layer of graphene-polymer composite, also bonded to a flexible polymer platform;
○ each of a source electrode and a drain electrode comprised of a conductive metal;
o The graphene polymer composite layer was functionalized with linker molecules for biosensing of the desired analyte between the two electrodes; and o The sensor system was held in close proximity to a source of uncontaminated sweat to be analyzed.

The method for determining analyte concentration through sweat included the following steps:
o applying a constant bias voltage to a functionalized graphene polymer composite sensor having a conducting channel;
measuring a first source-drain voltage via a sensor;
o Exposing the conduction channels to uncontaminated sweat by bringing them into close proximity to the source of sweat;
o binding of the analyte to the linker molecule by releasing an electron through the linker into the channel, resulting in a change in electrical potential across the channel;
○ measuring, via a sensor, a second source-drain voltage;
Determining a concentration of an analyte based on the fractional rate of change between the first source-drain voltage and the second source-drain voltage.

During the analysis, a fixed current or voltage was passed through the sensor. The electrical response of the GFET sensor was recorded for analytes in polar solutions, using analytes in deionized (DI) water as a negative control. DI water responses were also measured for the functionalized GFET. Analytes included NaCl, D-glucose, and lactate.
Example 2
Analysis of NaCl samples

In these examples, a fixed current or voltage was passed through the GFET. The electrical response of the GFET sensor was recorded with respect to: NaCl concentration in DI water or DI water response on a non-functionalized GFET.

Selectivity: The response of various NaCl concentrations in DI water was measured on the GFET to study the sensitivity of the sensor to NaCl. Solutions containing various concentrations of NaCl ranging from 0 to 1 g/L in DI water were prepared. The test started by introducing 2 ul of the lowest concentration onto the GFET, followed by the next higher concentration after 3 minutes, and so on; for example, from 0.05 g/L to 0.1 in the example shown in Figure 6. This was continued until all concentrations had been introduced onto the GFET.

Figure 6 shows that the GFET gave no significant response to DI water alone, and a linear response to high NaCl concentrations in DI water. Increasing concentrations changed the voltage across the channel, thereby showing high selectivity for NaCl in DI water as a control.

Sensitivity: The response of various NaCl concentrations in DI water was also measured on the GFET to study the sensitivity of the sensor to NaCl. Solutions containing exponentially increasing concentrations of D-glucose ranging from 0.1 ng/dL to 10 mg/dL in DI water were prepared. The test started by introducing 2 ul of the lowest concentration onto the GFET, followed by the next higher concentration after 3 minutes, and so on. Here, the concentration increased logarithmically, e.g., from 0.1 ng/dL to lng/dL, then lOng/dL, then to 0.1 ug/dL, and so on. This was continued until all concentrations were introduced onto the GFET.

Figure 7 shows that the GFET gave no significant response to DI water alone, and an exponential response starting from the lowest concentration of NaCl in DI water to the highest concentration of NaCl. Increasing concentrations changed the voltage across the channel, thereby showing high sensitivity towards NaCl in DI water as a control, about 250 femtograms/liter.

Sweat chloride response: Measurements of human sweat chloride concentrations were performed in human subjects. The study required subjects to engage in physical activity such as running and to use water to hydrate at intervals.

GFETs were worn by human subjects on the forearm and lower back (eccrine sweat glands). The electrical response due to chloride concentration in sweat was continuously transmitted and recorded (every 500 ms) while the subjects engaged in vigorous physical activity (e.g., running). Changes in chloride concentration in sweat were observed, represented by the fractional rate of change of voltage, as illustrated in Figure 8.

Figure 8 shows the real-time concentration of sweat osmolality of two human subjects using skin-attached PFGFETs. The osmolality concentration in sweat correlated directly to the physical performance of the individual. Subject 1 was a sprinter and Subject 2 was a jogger. The sprinter (Subject 1) ran the same distance at a faster pace (Run 1) compared to the jogger (Subject 2 and Run 2). It was observed that the more intense the subject's physical activity, the higher the measured body osmolality concentration. The peak in body osmolality was observed during the most intense physical activity period. It was also observed that body osmolality decreased during the intense physical activity period. This was caused when the subject consumed too much water without properly replenishing salt. In the data, a slope of the curve towards zero indicates hyponatremia. During this period, the body tries to retain as much salt as possible (to maintain ionic balance) and therefore the overall body osmolality concentration changes very slowly.

The following novel results and/or characteristics were observed:

High selectivity: PFGT-modulated GFETs (NFETs) provided highly selective responses (>97%) to NaCl concentrations in various control fluids.

High sensitivity: GFET functionalized with PBA showed high sensitivity to NaCl with a limit of detection (LOD) of 250 femtograms per liter. The GFET sensor has a high signal-to-noise ratio, is sensitive, and due to the large surface area for binding, the binding between the surface and the molecules is stronger. All of these factors play a very differentiating role in making the GFET highly sensitive.

Gate modulation due to polar molecules: In polar fluids (water, salt, etc.), polar molecules (ions, etc.) were observed to form a polar fluidic gate terminal (PFGT) on the NFET. The polar molecules near the graphene surface induced a dielectric effect and created a channel for charge transfer. The gate strength of the PFGT depended on both the charge and the concentration of the polar molecules in the fluid. Such a third polar fluidic gate terminal (PFGT) modulated the electrical response from the NaCl concentration in the polar fluid.

Continuous monitoring: The concentration of ions was continuously measured in the fluid by modulation of the NFET channel current from the induced polar fluidic gate terminal. Once the ionic solution was removed from the surface of the NFET, the electrical response of the polar fluidic gated NFET returned to its original bare or initial value.

Induced movement of polar fluids at the surface of the NFET: It is believed that polar fluids (such as NaCl in DI water) become quickly repelled or removed from the NFET due to the high hydrophobicity between the NFET surface and the polar fluid. The higher the concentration of polar molecules (e.g., NaCl) in the fluid, the higher the strength of the PFGT and therefore the greater the repulsive effect. This repulsive effect combined with the modulation of the electrical response due to the PFGT by the NaCl molecules on the NFET enabled a more sensitive selective and continuous monitoring electrolyte system.

Real-time continuous chloride monitoring in human sweat: As an example, GFETs were worn by human subjects on the forearm and lower back (eccrine sweat glands). Sweat is diluted and ultrafiltered blood. The electrical response due to chloride concentration in sweat was continuously transduced and recorded (every 500 ms) while the subjects were engaged in a) vigorous physical activity (training) and b) non-vigorous physical activity (such as sitting at an office desk and eating). It was observed that background ion concentrations in sweat (mainly NaCl) formed a PFGT on the two-terminal GFET device. The change in gate strength of the induced PFGT on the GFET due to Cl ions allowed for continuous non-invasive monitoring of Cl ion molecules in human sweat. It was observed that sweat is a very good polar fluid for measuring chloride concentration continuously, since it is highly diluted and ultrafiltered.
Example 3
Analysis of D-glucose samples

In these examples, a fixed current or voltage was passed through the GFET.

The electrical response of the GFET/PBA sensor was recorded for:
○ D-glucose concentration in DI water ○ D-glucose concentration in artificial sweat (DI + NaCl + lactic acid) ○ D-glucose concentration in DI water on non-functionalized GFET ○ Lactose concentration in DI water on functionalized device (Control 1)
Artificial sweat concentration on functionalized devices (Control 2)
○ DI water response with functionalized GFETs ○ Human sweat glucose measurement: Real-time continuous monitoring of glucose concentration was performed in human sweat using a wearable GFET/PBA sensor. The real-time continuous sweat glucose response was correlated to blood glucose measurements using a commercial glucose meter.

Functionalization: As an example, graphene FETs were functionalized with a linker molecule (lock) that specifically binds to glucose molecules in the fluid. As an example, GFETs were functionalized with pyrene boronic acid (PBA). Pyrene boronic acid binds to the graphene surface using π-π bonds. PBA forms a reversible boron anion complex with D-glucose. The fabrication steps are as follows:
o The polymer was deposited on the graphene, typically to a thickness of less than 0.5 mm, and then separated from the catalytic substrate on which it was grown.
o The graphene polymer composite was then placed on a polymer substrate such as Teflon, polyimide etc. and heated at 80-150 degrees Celsius for 1-10 minutes to remove any impurities.
o The graphene polymer was then introduced into a solution of PBA for 5-20 minutes for functionalization at room temperature.
After the functionalization step the sensor is ready for use.

The response of various D-glucose concentrations in DI water was measured on the GFET to study the sensitivity of the functionalized sensor to D-glucose.

Solutions containing D-glucose in various concentrations ranging from 0.1 to 100 mg/dL in DI water were prepared along with various concentrations of lactose in DI water. The test started with 5 ul of the lowest concentration being introduced onto the GFET, followed by the next highest concentration after 3 minutes, and so on. This was continued until all concentrations had been introduced onto the GFET.

Figure 9 shows that the GFET gave no significant response to DI water or lactose solution alone, and an exponential response to high D-glucose concentrations in DI water. Increasing concentrations changed the voltage across the channel, thereby showing high selectivity for D-glucose with DI water as a control.

Glucose response in NaCl vs. glucose response in DI water: The response of various D-glucose concentrations in DI water and NaCl solutions was measured on the GFET to study the sensitivity of the functionalized sensor to D-glucose in DI water vs. D-glucose in NaCl and to understand the effect of NaCl solution.

Solutions containing various concentrations of D-glucose ranging from 0.1 to 100 mg/dL were prepared in DI water and NaCl, respectively. The test started by introducing 5 ul of the lowest concentration onto the GFET, followed by the next higher concentration after 3 minutes, and so on, where the concentrations increased logarithmically. This was continued until all concentrations had been introduced onto the GFET.

Figure 10 shows that the D-glucose response in NaCl is more amplified than the D-glucose response in DI water. The polar solution providing the PFGT on the GFET amplified the electrical response through the channel, thereby increasing sensitivity and providing reversibility.

Selectivity measurement of glucose response in NaCl solution: The response of various D-glucose concentrations in NaCl was measured on the GFET to study the sensitivity of the functionalized sensor to D-glucose.

Solutions containing various concentrations of D-glucose ranging from 0.1 to 100 mg/dL in NaCl solution were prepared along with various concentrations of NaCl in DI water. The test started by introducing 5 ul of the lowest concentration onto the GFET, followed by the next higher concentration after 3 minutes, and so on, where the concentrations increased logarithmically. This was continued until all concentrations had been introduced onto the GFET.

Figure 11 shows that the GFET gave no significant response to NaCl solutions alone, and showed a linear response to solutions of increasing NaCl concentration, but increasing D-glucose concentrations at a fixed NaCl concentration. Increasing concentration changed the voltage across the channel, thereby indicating high selectivity for D-glucose. The PBA-functionalized GFET (NFET) gave a highly selective response (95%) to glucose concentration.

Figure 11 gives an idea that the functionalized glucose sensor is insensitive to NaCl (since the orange curve is fairly flat), whereas the glucose curve rises as the concentration of glucose present in the NaCl solution increases.

Sensitivity measurement of D-glucose response in DI water: Various D-glucose concentration responses in DI were measured on the GFET to study the sensitivity range of the functionalized sensor to D-glucose.

Solutions containing exponentially increasing concentrations of glucose ranging from 250 femtograms/L to 100 mg/L in DI water were prepared. The test began with three 5 ul DI water injections over the GFET every 3 minutes, followed by 5 ul of the lowest concentration, followed by the next highest concentration after 3 minutes, and so on. Here, the concentrations increased logarithmically; e.g., from 0.25 pg/L, then 2.5 pg/L, and so on. This continued until all concentrations had been injected over the GFET.

FIG. 12 shows that the GFET gave no significant response to DI water alone, and a linear response changed the current across the channel with increasing concentration, starting from the lowest concentration to the highest, thereby demonstrating a high sensitivity of approximately 250 femtograms/liter (i.e., 1.38e ⁻¹² mmol/l) to D-glucose.

Functionalization steps: Figure 13 shows the current response for the graphene sensor before functionalization, after functionalization, and after glucose is introduced onto the sensor. This helps understand each step of the GFET fabrication steps and how the current response of the GFET changes after each step. For example, Figure 13 shows that the current response increases after functionalization (orange) compared to before functionalization (blue), which occurs because the linker molecules are attached by π-π bonds and the total charge on the surface of the graphene increases. The linker molecules attract and bind to the glucose molecule by using these charge clouds, thereby reducing the current on the GFET compared to its previous state.

D-Glucose Response in Sweat and Blood: Measurements of glucose concentration in human sweat were performed in human subjects. The test required the subjects to engage in physical activity such as running, draw blood samples, and measure blood glucose every few minutes using a glucose meter. GFETs were worn by the human subjects on the forearm and lower back (eccrine sweat glands). The electrical response due to D-glucose concentration in sweat was transmitted and recorded continuously (every 500 milliseconds) while the subjects engaged in vigorous physical activity (e.g. running).

In this particular case, the physical activity was eating food. As the subject begins to eat, the subject's glucose begins to rise, as seen in both sweat and blood glucose. After the person has eaten, glucose levels begin to drop and stabilize.

When you start running, your body uses glucose and breaks it down to get energy for running, so you see a drop in glucose. But after some point, your body's insulin kicks in and your total glucose levels start to rise again.

Figure 14 shows the change in D-glucose concentration in sweat, represented by the fractional rate of change in voltage.

The blood glucose data in Figure 15 was also plotted against time over the entire training period. The sweat glucose measurements were correlated to the blood glucose measurements. Here, the sweat glucose values against the corresponding blood glucose values were plotted again against blood (blood vs. sweat) to get the correlation ^R2 , giving an idea of how well the sweat glucose matches against blood glucose.

Figure 16 further shows the correlation of measurements between blood glucose and sweat glucose, where three different sensors were used at the same time on the same person. More than 150 curves for sweat glucose were collected and correlated from 10 human subjects with blood glucose for the entire duration of the study. The subjects were either physically active (training, running, etc.) or not (sitting at a desk, etc.). For these 150 curves, the calculated correlation was ^R2 = 84% between sweat and blood, as shown in Figure 16.

The following novel results and/or characteristics were observed:

High selectivity: PBA-functionalized GFETs (NFETs) provided highly selective responses (>95%) to glucose concentrations in various control fluids.

High sensitivity: PBA-functionalized GFETs showed high sensitivity to D-glucose with a limit of detection (LOD) of 250 femtograms/liter, i.e., 1.38e ^-12 mmol/l. Existing glucose meters have LODs between 0.3 and 1.1 mmol/l. PBA-functionalized GFETs are approximately 1010 times more sensitive than existing standard glucose measuring devices. GFET sensors have a high signal-to-noise ratio, are highly sensitive, and due to the large surface area for binding, the binding between the surface and the receptor molecules is stronger. All of these factors play a very differentiating role in making GFETs highly sensitive.

Gate modulation due to polar molecules: In polar fluids (water, salt, etc.), polar molecules (ions, etc.) were observed to form a polar fluidic gate terminal (PFGT) on the NFET. The polar molecules near the graphene surface induced a dielectric effect and created a channel for charge transfer. The gate strength of the PFGT depended on both the charge and the concentration of the polar molecules in the fluid. Such a third polar fluidic gate terminal (PFGT) modulated the electrical response from the glucose concentration in the polar fluid.

Continuous glucose monitoring: The reversibility of PBA-glucose binding on the graphene surface was greatly enhanced by charge modulation due to the polar fluid gate terminal on the NFET formed in the polar fluid. It was observed that the higher the concentration of polar molecules (e.g. ions) in the polar fluid, the greater the reversibility of PBA-D-glucose binding. When the glucose concentration bound to the sensor becomes higher than that in sweat due to its Gibbs free energy, the glucose molecules become released from PBA and a reversible nature is observed, which is clearly seen in the electrical response recorded in Figure 14 as the concentration of glucose drops momentarily. This allows for reusable real-time continuous monitoring of D-glucose molecules in polar fluids.

Reusability of glucose sensors due to the movement of polar fluids over the sensor surface: The movement of polar fluids (such as glucose in salt) over the NFET was observed to increase the removal of bound glucose molecules from the linker molecules. As an example, when the glucose solution was removed from the graphene surface of the GFET, the electrical response of the GFET reverted to its original bare value.

Induced movement of polar fluids on the surface of the NFET: It is believed that polar fluids (such as glucose in salt) become quickly repelled or removed from the NFET due to the high hydrophobicity between the NFET surface and the polar fluid. The higher the concentration of polar molecules in the fluid, the higher the strength of the PFGT and therefore the greater the repulsion effect. This repulsion effect, combined with the removal of bound glucose molecules (described in section e above), and the modulation of the electrical response due to the PFGT on the NFET, enabled a more sensitive selective and continuous monitoring glucose system.

Real-time continuous glucose monitoring in human sweat: PBA-functionalized GFETs
were worn by human subjects on the forearm and lower back (eccrine sweat glands). Sweat is diluted and ultrafiltered blood. Electrical responses due to D-glucose concentrations in sweat were continuously transmitted and recorded (every 500 ms) while subjects were engaged in a) vigorous physical activity (training) and b) non-vigorous physical activity (such as sitting at an office desk and eating). Sweat glucose responses were correlated to blood glucose readings obtained every few minutes using a blood glucose meter over the length of the activity (typically 20 min to over 6 h). Background ion concentrations in sweat (mainly NaCl) were observed to form a PFGT on the two-terminal GFET/PBA device. The increased reversibility between PBA and D-glucose binding due to the PFGT on the GFET enabled continuous non-invasive monitoring of glucose molecules in human sweat. A correlation of 84% (R ² ) was calculated between blood glucose and sweat glucose measurements. Correlations were calculated for 150 sweat glucose responses collected from 10 human subjects under various physical activity conditions. Sweat was observed to be a very good polar fluid for continuous glucose measurement because it is highly diluted and ultrafiltered.
Example 4
Analysis of Lactic Acid Samples

In these examples, a fixed current or voltage was passed through the GFET.

Functionalization: Graphene FETs were functionalized with linker molecules (locks) that specifically bind to lactate molecules in fluids. As an example, GFETs were functionalized with lactate oxidase (LOx) on the graphene surface using intermediate pyrene-NHS linking chemistry.
o The polymer is deposited on the graphene, typically to a thickness of less than 0.5 mm, and then separated from the catalytic substrate on which it was grown.
o The graphene polymer composite is then placed on a polymer substrate such as Teflon, polyimide etc. and heated at 80-150 degrees Celsius for 1-10 minutes to remove any impurities.
o The graphene polymer is then introduced into a solution of pyrene-NHS for 5-20 minutes for functionalization at room temperature.
o The graphene polymer is then introduced into a solution of LOx for binding at room temperature for 520 minutes.
After the functionalization step the sensor is ready for use.

The electrical response of the GFET/LOx sensor was recorded for:
Lactic acid concentration in DI water Lactic acid concentration in artificial sweat (DI+NaCl+glucose) Lactic acid concentration in NaCl on non-functionalized GFET Lactic acid concentration in NaCl on functionalized GFET Artificial sweat concentration on functionalized device (Control 2)
○ DI water response on functionalized GFETs.

Selectivity measurement of lactate response in DI water: The response of various lactate concentrations in DI was measured on the GFET to study the sensitivity of the functionalized sensor to lactate. Solutions of lactate with various concentrations ranging from 0 to 25 mM in DI water were prepared. The test started by introducing 2 ul of the lowest concentration onto the GFET, followed by the next higher concentration after 3 minutes, and so on. This was continued until all concentrations had been introduced onto the GFET.

Figure 17 shows that the GFET gave no significant response to DI alone, but a polynomial response to high lactate concentrations in DI water, with increasing concentration changing the voltage across the channel, thereby demonstrating high selectivity for lactate in DI water, using DI water as a control.

Selectivity measurement of lactate response in various solutions: The response of various lactate concentrations in various solutions was measured on the GFET to study the sensitivity of the functionalized sensor to lactate and the response on the non-functionalized sensor. Solutions containing various concentrations of lactate ranging from 0 to 25 mM in NaCl and NaCl glucose were prepared. The test started by introducing 2 ul of the lowest concentration onto the GFET, followed by the next higher concentration after 3 minutes, and so on. This was continued for each solution separately until all concentrations had been introduced onto the GFET.

Figure 18 shows that the GFET gave no significant response to NaCl and NaCl-glucose controls alone, and a polynomial response to increasing lactate concentrations in NaCl and NaCl-glucose solutions. Increasing concentrations changed the voltage across the channel, thereby demonstrating high selectivity for lactate. There was no significant response for the non-functionalized sensor with lactate-NaCl solution, further highlighting the selectivity and sensitivity of the sensor to lactate.

Lactate response in NaCl vs. lactate response in DI water: The response of various lactate concentrations in DI water and NaCl solutions was measured on the GFET to study the sensitivity of the functionalized sensor to lactate in DI water vs. lactate in NaCl and to understand the effect of NaCl solutions. Solutions containing various concentrations of lactate ranging from 0.1 to 100 mg/dL were prepared in DI water and NaCl, respectively. The test started by introducing 2 ul of the lowest concentration onto the GFET, followed by the next highest concentration after 3 minutes, and so on. This was continued until all concentrations were introduced onto the GFET.

Figure 19 shows that the lactate response in NaCl is less amplified than the lactate response in DI water.

Lactic acid functionalization steps visualized throughout the GFET fabrication: The current response for the graphene sensor before functionalization, after functionalization, and after introducing lactate onto the sensor is illustrated in FIG. 20. This helps understand each step of the GFET fabrication steps and how the current response of the GFET changes after each step. For example, FIG. 20 shows that the current response is reduced after functionalization (orange) compared to before functionalization (blue). The linker molecule attracts and binds to the lactate molecule, thereby reducing the current on the GFET compared to its previous state.

The following novel results and/or characteristics were observed:

High selectivity: LOx-functionalized GFETs (NFETs) provided highly selective responses (>94%) to lactate concentrations in various control fluids.

High sensitivity: The pyrene-NHS functionalized GFET showed high sensitivity to lactate with a limit of detection (LOD) of 250 femtograms/liter, i.e., 2.78e ^-12 mmol/l. Existing lactate meters have LODs between 0.001 and 10 mmol/l. The pyrene-NHS functionalized GFET is about 108 times more sensitive than the existing standard lactate measuring device. The GFET sensor has a high signal-to-noise ratio, is highly sensitive, and due to the large surface area for binding, the binding between the surface and the receptor molecules is stronger. All of these factors play a very differentiating role in making the GFET highly sensitive.

Gate modulation due to polar molecules: In polar fluids (water, salt, etc.), polar molecules (ions, etc.) were observed to form a polar fluidic gate terminal (PFGT) on the NFET. The polar molecules near the graphene surface induced a dielectric effect and created a channel for charge transfer. The gate strength of the PFGT depended on both the charge and the concentration of the polar molecules in the fluid. Such a third polar fluidic gate terminal (PFGT) modulated the electrical response from the lactate concentration in the polar fluid.

Induced movement of polar fluids on the surface of the NFET: It is believed that polar fluids (such as lactate in artificial sweat) become quickly repelled or removed from the NFET due to the high hydrophobicity between the NFET surface and the polar fluid. The higher the concentration of polar molecules in the fluid, the higher the strength of the PFGT and therefore the greater the repulsive effect. This repulsive effect combined with the modulation of the electrical response due to the PFGT on the NFET enabled a more sensitive selective and continuous monitoring lactate system.
Example 5
Further analysis

Correlation of sweat salt concentration: Figure 21 shows the sweat sensor response with respect to the corresponding sweat sodium concentration.

Increasing concentrations of NaCl (0.1 mg/dl to 100 mg/dl) were added to the graphene sensor every 3 minutes. The test started with dropping 2 ul of the lowest concentration (e.g., 0.1 mg/dl), followed by the next higher concentration (e.g., 0.2 mg/dl), and so on, at 3 minute intervals. The corresponding fractional rate of change in voltage was measured. This was repeated for 10 different sensors, with a maximum error of 15% observed. This serves as a model for the correlation between sweat sodium and the corresponding voltage change.

Correlation of sweat glucose concentration: Figure 22 shows the sweat sensor response with respect to the corresponding sweat glucose concentration.

Increasing concentrations of glucose (0.1 mg/dl to 100 mg/dl) were added to the graphene sensor every 3 minutes. The test started with dropping 5 ul of the lowest concentration (e.g., 0.1 mg/dl), followed by the next higher concentration (e.g., 0.2 mg/dl), and so on, at 3 minute intervals, and the corresponding fractional change in voltage was measured. This was repeated on 10 different sensors, with a maximum error of 5% observed. This serves as a model for the correlation between sweat glucose and the corresponding voltage change.

Transconductance curves: Figure 23 shows the transconductance curves for the PFGT device.

NaCl solutions of increasing concentrations, ranging from 0.1 ng/dl to 1 mg/dl, are dripped onto the sensor every 3 minutes. The test begins with dripping 2 ul of the lowest concentration (e.g., 0.1 ng/dl), followed by the next highest concentration (e.g., 1 ng/dl), and so on, at 3 minute intervals.

As the polar fluid is introduced, a Debye layer forms on the graphene sensor and a gating effect is observed, with both the Debye length and the gating effect being functions of the concentration of the polar molecules. For the initial concentration of NaCl solution, the DI dominates and hence more holes are created and a voltage drop is observed. However, after a few drops, when the concentration of NaCl increases in the solution, it dominates and more electrons are created near the Debye layer, thereby indicating an increase in voltage.

This demonstrates the transconductance properties of the graphene sensor gated by a polar fluid.

The various methods and techniques described above provide several ways of implementing the present invention. Of course, it will be understood that not all of the described objectives or advantages may be realized in accordance with any particular embodiment described herein. Thus, for example, one skilled in the art will understand that a method may be implemented to achieve or optimize one advantage or group of advantages as taught herein without necessarily achieving other objectives or advantages as may be taught or presented herein. Various advantageous and disadvantageous alternatives are described herein. It will be understood that some preferred embodiments specifically include one, another, or several advantageous features, while others specifically exclude one, another, or several disadvantageous features, while still others specifically mitigate an adverse feature of the present invention by including one, another, or several advantageous features.

Furthermore, one of ordinary skill in the art will understand the applicability of various features from different embodiments. Similarly, the various elements, features, and steps discussed above, as well as other known equivalents for such elements, features, and steps, can be mixed and matched by one of ordinary skill in the art to perform methods in accordance with the principles described herein. Of the various elements, features, and steps, some are specifically included and others are specifically excluded in various embodiments.

Although the present invention has been disclosed in the context of certain specific embodiments and examples, those skilled in the art will appreciate that the embodiments of the present invention extend beyond the specifically disclosed embodiments to other alternative embodiments and/or uses and their modifications and equivalents.

Many variations and alternative elements have been disclosed in the embodiments of the present invention. Still other variations and alternative elements will be apparent to those skilled in the art.

It should be understood that in some embodiments, the numerical values expressing amounts of components, properties such as molecular weight, reaction conditions, and the like, used to describe and claim certain embodiments of the present invention are in some cases modified by the term "about". Thus, in some embodiments, the numerical parameters set forth in the written description and appended claims are approximations that can vary depending on the desired properties sought to be obtained by a particular embodiment. In some embodiments, the numerical parameters should be construed in light of the number of reported significant digits and by applying ordinary rounding techniques. Notwithstanding that the numerical ranges and parameters setting forth the broad scope of some embodiments of the present invention are approximations, the numerical values set forth in the specific examples are reported as precisely as practicable. The numerical values presented in some embodiments of the present invention may necessarily contain certain errors resulting from the standard deviation found in their respective testing measurements.

In some embodiments, the terms "a" and "an" and "the" and similar references used in the context of describing certain embodiments of the invention (particularly in certain contexts of the claims below) can be construed to include both the singular and the plural. The recitation of ranges of values herein is merely intended as a shorthand way of individually referring to each separate value encompassed within that range. Unless otherwise indicated herein, each of the individual values is incorporated herein as if individually recited herein. All methods described herein can be performed in any suitable order unless otherwise indicated herein or clearly contradicted by context. The use of any and all examples or exemplary language (e.g., "such as") presented with respect to certain embodiments herein is intended merely to better illustrate the invention and does not impose limitations on the scope of the invention as otherwise claimed. No language herein should be construed as indicating any non-claimed element essential to the practice of the invention.

Groupings of alternative elements or embodiments of the invention disclosed herein are not to be construed as limiting. The members of each group may be referred to and claimed individually or in any combination with other members of the group or other elements found herein. One or more members of a group may be included in or deleted from a group for reasons of convenience and/or patentability. When any such inclusion or deletion occurs, the specification is deemed to contain the group as modified herein, and thus satisfies the written description of all Markush groups used in the appended claims.

Preferred embodiments of the invention are described herein. Variations on those preferred embodiments will become apparent to those of skill in the art upon reading the foregoing description. Those skilled in the art will be able to employ such variations as appropriate, and it is contemplated that the invention may be practiced otherwise than as specifically described herein. Accordingly, many embodiments of the invention include all modifications and equivalents of the subject matter recited in the claims appended hereto as permitted by applicable law. Moreover, any combination of the above-described elements in all possible variations thereof is encompassed by the invention unless otherwise indicated herein or otherwise clearly contradicted by context.

Additionally, numerous references have been made throughout this specification to patents and printed publications. The above cited references and printed publications are individually incorporated herein by reference in their entireties.

Finally, it is to be understood that the embodiments of the invention disclosed herein are illustrative of the principles of the invention. Other modifications that may be employed are within the scope of the invention. Thus, by way of example, and not of limitation, alternative configurations of the invention may be utilized in accordance with the teachings herein. Thus, the embodiments of the invention are not limited to that precisely as shown and described.

According to a preferred embodiment of the present invention, for example, the following is provided:
(Item 1)
A drain electrode;
A source electrode;
An electrically insulating substrate;
a nanoscale material layer disposed on the substrate, the nanoscale material layer partially defining an electrically conductive and chemically sensitive channel, the nanoscale material layer and the channel extending between and electrically connected to the drain and source electrodes;
a polar-fluid-induced gate terminal created by a polar fluid exposed to the nanoscale material layer,
the polar fluid comprises a target analyte;
A field effect transistor, wherein the polar fluid has a charge concentration sufficient to induce a polar fluid gate voltage that optimizes a gate voltage versus channel current characteristic of the field effect transistor in response to the target analyte.
(Item 2)
Item 3. The field effect transistor according to item 1, wherein a constant current or voltage is provided by a constant current source or a constant voltage source and is applied between the source electrode and the drain electrode.
The nanoscale material may be graphene, CNT, _MoS2 , boron nitride, metal dichalcogenides, phosphorene, nanoparticles, quantum dots, fullerenes, 2D nanoscale materials, 3D nanoscale materials,
3. The field effect transistor of claim 1 or 2, comprising 0D nanoscale materials, 1D nanoscale materials, or any combination thereof.
(Item 4)
4. The field effect transistor of any one of claims 1 to 3, wherein the polar fluid comprises a solution having polar molecules, a gas having polar molecules, a target sensing analyte, or a combination thereof.
(Item 5)
5. The field effect transistor of any one of claims 1 to 4, wherein the polar fluid comprises sweat, breath, saliva, earwax, urine, semen, blood plasma, a biological fluid, a chemical fluid, an air sample, a gas sample, or a combination thereof.
(Item 6)
6. The field effect transistor of any one of claims 1 to 5, wherein the target analyte comprises an electrolyte, glucose, lactate, IL6, a cytokine, HER2, cortisol, ZAG, cholesterol, a vitamin, a protein, a drug molecule, a metabolite, a peptide, an amino acid, DNA, RNA, an aptamer, an enzyme, a biomolecule, a chemical molecule, a synthetic molecule, or a combination thereof.
(Item 7)
7. The field effect transistor of any one of claims 1 to 6, further comprising a receptor layer deposited on the nanoscale material layer, the receptor layer comprising a receptor that targets a target analyte.
(Item 8)
8. The field effect transistor according to item 7, wherein the receptor comprises pyrene boronic acid (PBA), pyrene N-hydroxysuccinimide ester (pyrene-NHS), an organic chemical, an aromatic molecule, a cyclic molecule, an enzyme, a protein, an antibody, a virus, a single-stranded DNA (ssDNA), an aptamer, an inorganic material, a synthetic molecule, or a biomolecule.
(Item 9)
9. The field effect transistor of any one of claims 1 to 8, further comprising a backside polymer layer beneath the nanoscale material layer to provide support for additional mechanical, electrical, chemical, biological functionality, or a combination thereof.
(Item 10)
10. The field effect transistor of claim 9, wherein the backside polymer layer comprises a carbon polymer, a biopolymer, PMMA, PDMS, flexible glass, a nanoscale material, a silica gel, a silicone, an ink, a printed polymer, or any combination thereof.
(Item 11)
1. A method for sensing a target analyte in a polar fluid, comprising:
exposing the polar fluid sample to a field effect transistor, said field effect transistor comprising:
A drain electrode;
A source electrode;
An electrically insulating substrate;
a nanoscale material layer disposed on the substrate, the nanoscale material layer at least partially defining an electrically conductive and chemically sensitive channel, the nanoscale material layer and the channel extending between and electrically connected to the drain and source electrodes;
a polar-fluid-induced gating terminal created by the polar fluid exposed to the nanoscale material layer, the polar fluid containing the target analyte and having a charge concentration sufficient to induce a polar-fluid gating voltage that optimizes a gate voltage vs. channel current characteristic of the field effect transistor for detecting the analyte;
The method includes the steps of measuring a first source-drain voltage at a first time point and a second source-drain voltage at a second and subsequent time point, and determining a concentration of the target analyte in the polar fluid based on the first and second source-drain voltages.
(Item 12)
12. The method of claim 11, wherein the nanoscale material comprises graphene, CNT, _MoS2 , boron nitride, metal dichalcogenides, phosphorene, nanoparticles, quantum dots, fullerenes, 2D nanoscale materials, 3D nanoscale materials, 0D nanoscale materials, 1D nanoscale materials, or any combination thereof.
(Item 13)
13. The method of any one of claims 11 or 12, wherein the field effect transistor is functionalized with a receptor layer deposited on the nanoscale material layer, the receptor layer comprising a receptor that targets a target analyte.
(Item 14)
14. The method according to claim 13, wherein the receptor comprises pyrene boronic acid (PBA), pyrene N-hydroxysuccinimide ester (pyrene-NHS), an organic chemical, an aromatic molecule, a cyclic molecule, an enzyme, a protein, an antibody, a virus, a single-stranded DNA (ssDNA), an aptamer, an inorganic material, a synthetic molecule, or a biomolecule.
(Item 15)
15. The method of any one of claims 11 to 14, wherein the target analyte comprises an electrolyte, glucose, lactate, IL6, a cytokine, HER2, cortisol, ZAG, cholesterol, a vitamin, a protein, a drug molecule, a metabolite, a peptide, an amino acid, DNA, RNA, an aptamer, an enzyme, a biological molecule, a chemical molecule, a synthetic molecule, or a combination thereof.
(Item 16)
16. The method of any one of claims 11 to 15, wherein the polar fluid comprises a solution having polar molecules, a gas having polar molecules, a target sensing analyte, or a combination thereof.
(Item 17)
17. The method of any one of clauses 11 to 16, further comprising the step of calculating a fractional rate of change between the first and second source-drain voltages.
(Item 18)
18. The method of any one of claims 11 to 17, further comprising the step of applying a constant current between the source and drain electrodes of the field effect transistor.
(Item 19)
19. The method of any one of claims 11 to 18, further comprising the step of applying a constant voltage between the source and drain electrodes of the field effect transistor.
(Item 20)
20. The method of any one of claims 11 to 19, wherein the polar fluid comprises sweat, breath, saliva, earwax, urine, semen, blood plasma, a biological fluid, a chemical fluid, an air sample, a gas sample, or a combination thereof.
(Item 21)
21. The method of any one of claims 11 to 20, further comprising a backside polymer layer beneath the nanoscale material layer to provide additional mechanical, electrical, chemical, biological functionality, or combinations thereof.
(Item 22)
22. The method of claim 21, wherein the backside polymer layer comprises a carbon polymer, a biopolymer, PMMA, PDMS, flexible glass, a nanoscale material, a silica gel, a silicone, an ink, a printed polymer, or any combination thereof.
(Item 23)
A system including a field effect transistor and a constant current or voltage source electrically connected to the field effect transistor,
The field effect transistor is
A drain electrode;
A source electrode;
An electrically insulating substrate;
a nanoscale material layer disposed on the substrate, the nanoscale material layer partially defining an electrically conductive and chemically sensitive channel, the nanoscale material layer and the channel extending between and electrically connected to the drain and source electrodes;
a polar-fluid-induced gating terminal created by a polar fluid exposed to the nanoscale material layer;
the polar fluid comprises a target analyte;
The system, wherein the polar fluid has a charge concentration sufficient to induce a polar fluid gate voltage that optimizes a gate voltage vs. channel current characteristic of the field effect transistor in response to the target analyte.
(Item 24)
24. The system of claim 23, wherein the constant current source maintains a constant current through the field effect transistor.
(Item 25)
24. The system of claim 23, wherein the constant voltage source maintains a constant voltage on the field effect transistor.
(Item 26)
24. The system of claim 23, wherein the voltage output or current output is transmitted to a digital platform via wired or wireless transmission.
(Item 27)
27. The system of claim 26, wherein the digital platform comprises a smartphone, a tablet computer, a smartwatch, an in-car entertainment system, a laptop computer, a desktop computer, a computer terminal, a television system, an e-book reader, a wearable device, or any other type of computing device that processes digital input.

Claims (1)

The invention as depicted in the drawings .