JP7129405B2 - Field-effect devices gated by polar fluids - Google Patents

Description

CROSS-REFERENCE TO RELATED APPLICATIONS This application is based on U.S. Provisional Patent Application Serial No. 62/356,729, entitled "DETECTION OF IONIC CONCENTRATION IN FLUID USING NANOSCALE MATERIALS VIA A CAPACITIVE RESPONSE," filed June 30, 2016; and U.S. Provisional Patent Application No. 6, 62/3 entitled "LACTATE-OXIDASE-FUNCTIONALIZED GRAPHENE POLYMER COMPOSITES FOR LABEL-FREE DETECTION OF LACTATE IN SWEAT AND OTHER BODILY FLUIDS" filed June 30, 2016, No. 642/3. Claiming priority, each of these provisional patent applications is hereby incorporated by reference in its entirety.

FIELD OF THE INVENTION The invention disclosed herein relates generally to the design, fabrication, and application of polar fluid-gated nanoscale field effect transistors (NFETs), particularly graphene field effect transistors (GFETs). The present disclosure also relates generally to chemical and biological sensing using field effect transistors, and more particularly to biosensing using field effect transistors with biochemically sensitive channels comprising graphene. It also relates to chemical sensing.

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

The source (S) is where the carrier enters the channel. The drain (D) is where the carriers leave the channel. The drain-source voltage is VDS and the source-drain current is IDS. The gate (G) modulates the channel conductivity by applying a gate voltage (VG) such that the current between 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 of FETs and new methods of using them.

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

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

In some embodiments, the nanoscale materials are graphene, CNTs, MoS2, boron nitride, metal dichalcogenides, phosphorenes, 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 with polar molecules, a gas with polar molecules, a target sensing analyte, or a combination thereof.

In some embodiments, the polar fluid comprises sweat, breath, saliva, earwax, urine, semen, blood plasma, biological fluids, chemical fluids, air samples, gas samples, or combinations thereof. A field effect transistor according to any one of the preceding claims.

In some embodiments, the target analyte is electrolytes, glucose, lactate, IL6, cytokines, 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 comprises a receptor layer deposited on the nanoscale material layer, the receptor layer comprising a receptor targeted to the target analyte.

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

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

In some embodiments, the backside polymer layer comprises: carbon polymers, biopolymers, PMMA, PDMS, flexible glass, nanoscale materials, silica gel, silicones, inks, printed polymers, or any combination thereof.

In one aspect, disclosed herein is a method for sensing a target analyte in a polar fluid. The method comprises exposing a polar fluid sample to a field effect transistor, the field effect transistor comprising a drain electrode; a source electrode; an electrically insulating substrate; a nanoscale material layer that at least partially defines a channel, wherein the nanoscale material layer and the channel extend between and are electrically connected to a drain electrode and a source electrode; the polar fluid-induced gate terminal created by the polar fluid exposed to the nanoscale material layer, where the polar fluid contains the target analyte and the gate voltage versus channel current of the field effect transistor to detect the analyte; a polar fluid induced gate terminal having a charge concentration sufficient to induce a polar fluid gate voltage that optimizes performance; measuring a second source-drain voltage at the time; and determining the concentration of the target analyte in the polar fluid based on the first and second source-drain voltages.

In some embodiments, the nanoscale materials are graphene, CNTs, 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 comprising receptors that target target analytes.

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

In some embodiments, the target analyte is electrolytes, glucose, lactate, IL6, cytokines, 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 comprises calculating a fractional rate of change between the first and second source-drain voltages.

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

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

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

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

In some embodiments, the backside polymer layer comprises carbon polymers, biopolymers, PMMA, PDMS, flexible glass, nanoscale materials, silica gel, silicones, inks, printed polymers, or any combination thereof.

In one aspect, disclosed herein is a field effect transistor and a system including:

A constant current source or constant voltage source electrically connected to the field effect transistor. A field effect transistor is a drain electrode; a source electrode; an electrically insulating substrate; and the channel extends between and is electrically connected to the drain and source electrodes; and a polar fluid-induced and a gate terminal. In some embodiments, the polar fluid contains target analytes. 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, a constant current source maintains a constant current through a field effect transistor.

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

In some embodiments, the voltage or current output is communicated to the digital platform through wired or wireless transmission.

In some embodiments, the digital platform handles smartphones, tablet computers, smartwatches, in-car entertainment systems, laptop computers, desktop computers, computer terminals, television systems, e-book readers, wearable devices, or digital inputs. Including any other type of computing device.
In embodiments of the present invention, for example, the following items are provided.
(Item 1)
a drain electrode;
a source electrode;
an electrically insulating substrate;
a layer of nanoscale material disposed on the substrate and partially defining an electrically conductive and chemically sensitive channel, the nanoscale material layer and the channel extending between the drain and source electrodes; and a layer of nanoscale material electrically connected to the electrodes;
a polar fluid-induced gate terminal created by a polar fluid exposed to said nanoscale material layer;
A field effect transistor comprising
the polar fluid comprises a target analyte;
A field effect transistor, wherein said polar fluid has a charge concentration sufficient to induce a polar fluid gate voltage that optimizes gate voltage versus channel current characteristics of said field effect transistor in response to said target analyte.
(Item 2)
A field effect transistor according to item 1, wherein a constant current or constant voltage is provided by a constant current source or constant voltage source and applied between the source and drain electrodes.
(Item 3)
said nanoscale materials are 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 4)
4. The field effect transistor of any one of items 1-3, wherein the polar fluid comprises a solution with polar molecules, a gas with polar molecules, a target sensing analyte, or a combination thereof.
(Item 5)
5. Any one of items 1 to 4, wherein the polar fluid comprises sweat, breath, saliva, cerumen, urine, semen, blood plasma, biological fluids, chemical fluids, air samples, gas samples, or combinations thereof. Field effect transistor.
(Item 6)
The target analyte is electrolytes, glucose, lactate, IL6, cytokines, HER2, cortisol, ZAG, cholesterol, vitamins, proteins, drug molecules, metabolites, peptides, amino acids, DNA, RNA, aptamers, enzymes, biomolecules, chemical Field effect transistor according to any one of items 1 to 5, comprising a molecule, a synthetic molecule, or a combination thereof.
(Item 7)
7. A field effect transistor according to any one of items 1 to 6, further comprising a receptor layer deposited on said nanoscale material layer, said receptor layer comprising receptors targeting a target analyte.
(Item 8)
The receptor is pyreneboronic 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, biomolecules.
(Item 9)
9. Any one of items 1-8, further comprising a backside polymer layer under said nanoscale material layer to provide support for additional mechanical, electrical, chemical, biological functionality, or combinations thereof. A field effect transistor according to any one of the preceding paragraphs.
(Item 10)
10. The field effect transistor of item 9, wherein the backside polymer layer comprises carbon polymers, biopolymers, PMMA, PDMS, flexible glass, nanoscale materials, silica gel, silicones, inks, printed polymers, or any combination thereof.
(Item 11)
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 and at least partially defining an electrically conductive and chemically sensitive channel, the nanoscale material layer and the channel extending between the drain and source electrodes. a layer of nanoscale material and electrically connected to the electrodes;
a polar fluid-induced gate terminal created by the polar fluid exposed to the nanoscale material layer, the polar fluid containing the target analyte and of the field effect transistor to detect the analyte; a polar fluid-induced gate terminal with sufficient charge concentration to induce a polar fluid gate voltage that optimizes gate voltage versus channel current characteristics;
a step comprising
measuring a first source-drain voltage at a first time point and a second source-drain voltage at a second and subsequent time points; and
determining the concentration of the target analyte in the polar fluid based on the first and second source-drain voltages;
method including.
(Item 12)
said nanoscale materials are 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. According to any one of items 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. described method.
(Item 14)
The receptor is pyreneboronic 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, biomolecules.
(Item 15)
The target analyte is electrolytes, glucose, lactate, IL6, cytokines, HER2, cortisol, ZAG, cholesterol, vitamins, proteins, drug molecules, metabolites, peptides, amino acids, DNA, RNA, aptamers, enzymes, biomolecules, chemical 15. A method according to any one of items 11-14, comprising a molecule, a synthetic molecule, or a combination thereof.
(Item 16)
16. The method of any one of items 11-15, wherein the polar fluid comprises a solution with polar molecules, a gas with polar molecules, a target sensing analyte, or a combination thereof.
(Item 17)
17. The method of any one of items 11-16, further comprising calculating a fractional rate of change between the first and second source-drain voltages.
(Item 18)
applying a constant current between the source and drain electrodes of the field effect transistor;
18. The method of any one of items 11-17, further comprising:
(Item 19)
19. The method of any one of items 11 to 18, further comprising applying a constant voltage between the source and drain electrodes of the field effect transistor.
(Item 20)
20. Any one of paragraphs 11 to 19, wherein the polar fluid comprises sweat, breath, saliva, cerumen, urine, semen, blood plasma, biological fluids, chemical fluids, air samples, gas samples, or combinations thereof. Method.
(Item 21)
21. Any one of items 11-20, further comprising a backside polymer layer under said nanoscale material layer to provide support for additional mechanical, electrical, chemical, biological functionality, or combinations thereof. The method described in section.
(Item 22)
22. The method of item 21, wherein the backside polymer layer comprises carbon polymers, biopolymers, PMMA, PDMS, flexible glass, nanoscale materials, silica gel, silicones, inks, printed polymers, or any combination thereof.
(Item 23)
field effect transistor and
With a constant current source or constant voltage source electrically connected to a field effect transistor
A system comprising
The field effect transistor is
a drain electrode;
a source electrode;
an electrically insulating substrate;
a layer of nanoscale material disposed on the substrate and partially defining an electrically conductive and chemically sensitive channel, the nanoscale material layer and the channel extending between the drain and source electrodes; and a layer of nanoscale material electrically connected to the electrodes;
a polar fluid-induced gate terminal created by a polar fluid exposed to said nanoscale material layer;
including
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 gate voltage versus channel current characteristics of the field effect transistor in response to the target analyte.
(Item 24)
24. The system of item 23, wherein the constant current source maintains a constant current through the field effect transistor.
(Item 25)
24. The system of item 23, wherein the constant voltage source maintains a constant voltage on the field effect transistor.
(Item 26)
24. The system of item 23, wherein the voltage or current output is communicated to the digital platform through wired or wireless transmission.
(Item 27)
The digital platform is a smart phone, tablet computer, smartwatch, in-car entertainment system, laptop computer, desktop computer, computer terminal, television system, e-book reader, wearable device, or any other type that processes digital input. 27. The system of item 26, comprising a computing device.

Any of the embodiments disclosed herein, alone or in combination with other embodiments, can be used in conjunction with any aspect of the present invention, as known to those skilled in the art.

Those skilled in the art will appreciate that the drawings, shown below, are for illustration purposes only. The drawings are not intended to limit the scope of the teachings of the 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 (g-gFET).

FIG. 2B illustrates an exemplary embodiment showing a g-gFET.

FIG. 2C illustrates an exemplary embodiment showing a g-gFET.

FIG. 2D illustrates an exemplary embodiment showing a g-gFET.

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

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

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

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

FIG. 4B illustrates an exemplary embodiment showing the base device illustrated in FIGS. 2A-2D with additional metal electrodes within the PFGT. Gate potential is measured between the metal electrode and ground.

FIG. 4C illustrates an exemplary embodiment showing the base device illustrated in FIGS. 2A-2D augmented with dielectric and gate metal and metal electrodes within the PFGT. 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 responses 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 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 NaCl versus glucose response in DI water.

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

FIG. 12 illustrates an exemplary embodiment showing sensitivity measurements for 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 the D-glucose response in sweat.

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

FIG. 16 illustrates an exemplary embodiment showing the correlation of measurements between blood sugar 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 responses 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 step visualized by GFET fabrication.

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

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

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

DETAILED DESCRIPTION OF THE INVENTION Disclosed herein are nanoscale field effect transistors and methods of making and using the same.
General graphene field effect transistor

Graphene possesses remarkable mechanical resistance, which allows thicknesses on the order of monolayers or bilayers to be subjected to considerable mechanical stress without losing its primary electrical properties. Such mechanical strength makes graphene an ideal candidate to replace the transparent conducting oxide (TCO) current generation provided by indium tin oxide (ITO). Unlike graphene, ITO is brittle and susceptible to mechanical stress; 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, yields greater than 90% transparency and greater than 100% transparency. yields fewer atomic layers with even lower sheet resistance.

As illustrated in FIG. 1A, graphene FETs are typically fabricated on a Si wafer covered with a SiO2 layer, with the graphene forming the transistor channel. A graphene transistor consists of three terminals, source and drain metal electrodes contacting the graphene channel, and a global back gate enabled by a doped Si substrate. These features facilitate the characteristic ambipolar transport behavior of graphene in Grat-FETs - realizing both n-type and p-type transport when biased with appropriate gate voltages at the substrate. Any applicable method can be applied to fabricate the GFET, including, for example, the information disclosed in International Patent Publication No. WO2015/164,552, which is incorporated herein by reference in its entirety.

FIG. 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 source and drain takes on a "V" shape. A small change in gate voltage at the tip of the V-curve produces a significant and detectable change in the channel current (I _DS ), which tends to plateau at the two endpoints of the V-curve.
gateless field effect transistor

In one aspect, disclosed herein is a new type of field effect transistor (FET) that does not have a physical gate.

Figures 2A through 2D illustrate various embodiments of FETs without physical gates. FIG. 2A illustrates an exemplary graphene-based FET 210 including substrate 1, source electrode 2, drain electrode 3, receptor 4, graphene layer 5, and backside polymer 6. FIG. As disclosed herein, the substrate 1 may include polyamide, PET, PDMS, PMMA, other plastics, silicon dioxide, silicon, glass, aluminum oxide, sapphire, germanium, gallium arsenide, indium phosphide, silicon and It can be an alloy with germanium, fabric, fabric, silk, paper, cellulose-based materials, insulators, metals, semiconductors, and can be rigid, flexible, or any combination thereof. In some embodiments, substrate 1 can be a silicon carbide substrate and 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 inter-electrode conductive channel. Exemplary materials that can be used as source electrodes include silver, gold, carbon, graphite ink, conductive fabrics, conductive textiles, metals, conductive materials, conductive polymers, conductive gels, ionic Including but not limited to gels, conductive inks, non-metallic conductive materials.

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

In some embodiments, the graphene layer 5 can have one or more monolayers of graphene of uniform thickness, preferably a predetermined thickness. Since thickness affects electrical properties such as bandgap, carrier concentration, etc., a uniform and preferably predetermined thickness provides control over sensing properties and results in reproducible devices with low variability between individual sensors. allow formation.

In some embodiments, the graphene layer 5 can be an epitaxial layer and the substrate of the graphene layer can be the substrate on which the graphene layer is epitaxially grown. By leaving the graphene layer on the growth substrate, typically nano-thin graphene layers and structures do not necessarily have to be dealt with. 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 pyreneboronic 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 thus certain types of chemicals are prevented from reaching the chemically sensitive channels. Surface treatments may include deposition of metal particles and/or polymers.

A backside polymer 6 is used to provide mechanical support to the graphene. Also, new modalities can be added to the sensing response when doped. For example, the backside polymer can be doped with biomolecules that can also bind to specific targets and participate in resistance changes in transistor channels.

Devices 220 , 230 and 240 are variations of device 210 . In device 220, backside polymer layer 6 is omitted. In device 230, receptor layer 4 is omitted. In device 240, both backside polymer layer 6 and 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, one atom of which forms each vertex. It is the basic structural element of graphite, charcoal, carbon nanotubes, and other allotropes, including fullerenes. It can be thought of as the final case in the family of planar polycyclic aromatic hydrocarbons as infinitely large aromatic molecules. In some embodiments, graphene is a monolayer of carbon atoms. Each carbon atom in graphene has four electrons. Through three of these electrons, the carbon atom bonds to the three closest carbon atoms forming a hexagonal lattice. For each atom, four electrons are delocalized on the entire graphene layer, allowing electron current conduction.

When a polar fluid is deposited on the graphene layer, the special electronic properties of graphene will lead to charge reorganization in the polar fluid to form a liquid-induced gate voltage, resulting in a voltage drop between the source and drain electrodes. Current can be modulated.

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 component 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 cause a shift in the x-axis (voltage) in the V-shaped current versus fluid gate voltage curve. As will be noted, at the tip of the V-curve, a small change in gate voltage can produce a significant and detectable change in the channel current (I _DS ), flattening out at the two endpoints of the V-curve. there is a tendency to A shift towards the tip of the V-shaped curve can result in increased sensitivity, allowing detection of very small changes in voltage in response to changes in current. Similarly, very small changes in current in response to changes in voltage can also be detected.

As noted above, a shift towards the tip of the V-shaped curve can result in better sensitivity. Such shifts can be induced by polar liquid-induced gate voltages. 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. A shift in the V-curve can be correlated to a wide range of charged particle concentrations. In some embodiments, the shift correlates with charged particle concentrations as low as 1 femto g/L (eg, NaCl). In some embodiments, the shift correlates with charged particle concentrations as high as 300 g/L (eg, NaCl). These results suggest that the current sensing system is resilient and can withstand a wide range of charge concentrations.

FIG. 3B illustrates an exemplary embodiment showing a polar fluid gate terminal through which polar fluid flows 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 _VFG depends on the direction in which the polar fluid flows; eg, along, 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 a polar fluid flows across the source-drain voltage, if the gate voltage is positive along the Y direction, it becomes negative in the Y direction and vice versa. When the direction of polar fluid flow changes, the direction of the gate voltage can also change.

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

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

FIG. 4A illustrates an exemplary embodiment showing a base device with dielectric layer 7 and gate metal 8 . The base device here can be any of those illustrated in FIGS. 2A-2D, such as 210, 220, 230 and 240. FIG. Gate potential is measured between the gate metal and ground. A dielectric layer 7 is applied under the substrate of the base device (eg, substrate 1 as illustrated in Figures 2A to 2D). A gate metal 8 is applied under the dielectric layer 7 . A 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 varied non-linearly depending on the PFGT device characteristics and channel type. For example, if the channel is graphene (ambipolar), Vg1 can follow the transconductance response typical of graphene devices.

FIG. 4B illustrates an exemplary embodiment showing the base device illustrated in FIGS. 2A-2D with metal electrodes added within the PFGT. 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 non-linearly depending on the PFGT device characteristics and channel type. For example, if the channel is graphene (bipolar), Vg2 follows the transconductance response typical of graphene devices (see, eg, FIG. 23).

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

FIG. 4C illustrates an exemplary embodiment showing the base device illustrated in FIGS. 2A-2D with enhanced dielectric and gate metal and metal electrodes within the PFGT. Two gate voltages (eg, Vg1 and Vg2) are supplied to the PFGT to modulate the overall electrical properties of the PFGT device for the desired application. Simultaneous modulation with Vg1 and Vg2 creates a tri-gated structure that can be used to shift device operation to 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.

FIG. 5A illustrates an exemplary embodiment showing circuitry used for sensor readout via a polar fluid 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 current resistor (R). The voltage output is then calibrated to the analyte concentration to be sensed.

FIG. 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. Current or charger (Ian) is read from the PFGFET using a current resistor (R). The current output is then calibrated to the analyte concentration to be sensed.

Having described the invention in detail, it will be apparent that modifications, variations, and equivalents are possible without departing from the scope of the invention as defined in the appended claims. let's be Furthermore, 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 embodiments of the invention disclosed herein. It will be appreciated by those of ordinary skill in the art that the techniques disclosed in the examples that follow represent techniques found to function well in the practice of the invention, and thus should be considered to constitute examples of modes for its implementation. It should be understood that However, one skilled in the art, in light of the present disclosure, can make many changes in the particular embodiments disclosed and still achieve similar or similar results without departing from the spirit and scope of the invention. It will be understood.
(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 catalyst substrate on which the graphene was grown. A flexible polymer platform for the sensing system was used for staging the graphene polymer composite and two metal electrical contacts. A graphene polymer composite was attached to a flexible polymer platform. A solution of the desired linker molecules is deposited onto 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 sensor was then ready for use. In some cases, receptors for specific analytes were deposited on the graphene layer.

A sensor system for analyte sensing through sweat consisted of:
o Flexible polymer platform made with (Kapton);
o Graphene polymer composites attached to a flexible polymer platform;
o Source and drain electrodes positioned within the sensor configuration on opposite edges of a layer of graphene polymer composite, also bonded to the flexible polymer platform;
o each of the source and drain electrodes constructed from a conductive metal;
o The graphene polymer composite layer is functionalized with linker molecules for the desired analyte biosensing between the two electrodes; and o The sensor system is in close proximity to the source of pristine sweat to be analyzed. let and held.

A method for determining analyte concentrations through sweat included the following steps:
o Applying a constant bias voltage to a functionalized graphene polymer composite sensor with conducting channels;
o measuring a first source-drain voltage via a sensor;
o Exposure of the conducting channels to pristine sweat by bringing them into close proximity to the sweat source;
o binding the analyte to the linker molecule by releasing electrons through the linker into the channel, resulting in a change in electrical potential across the channel;
o measuring a second source-drain voltage via the sensor;
o Determining the concentration of the analyte based on the fractional rate of change between the first source-drain voltage and the second source-drain voltage.

A fixed current or voltage was passed through the sensor during the analysis. The electrical response of the GFET sensor was recorded for analytes in polar solutions using analytes in deionized (DI) water as negative controls. DI water responses to functionalized GFETs were also measured. 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 the non-functionalized GFET.

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

FIG. 6 shows that the GFET does not give a significant response to DI water alone and the linear response is to high NaCl concentrations in DI water. Increasing concentrations changed the voltage across the channel, thereby demonstrating high selectivity to NaCl in DI water as a control.

Sensitivity: Responses of various NaCl concentrations in DI water were 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 the lowest concentration of 2 ul on the GFET, then the next higher concentration after 3 minutes, and so on. Here the concentration increased logarithmically, eg, 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.

FIG. 7 shows that the GFET gives no significant response to DI water alone, with an exponential response starting from the lowest concentration of NaCl to the highest concentration of NaCl in DI water. Increasing concentrations varied the voltage across the channel, thereby exhibiting a high sensitivity of approximately 250 femtograms/liter towards NaCl in DI water as a control.

Sweat Chloride Response: Human sweat chloride concentration measurements were performed in human subjects. This test required subjects to engage in physical activity such as running and occasionally use water for hydration.

GFETs were worn by human subjects on the forearms and hips (eccrine sweat glands). The electrical response due to chloride concentration in sweat was transmitted and recorded continuously (every 500 ms) while the subject underwent strenuous physical activity (such as running). Changes in chloride concentration in sweat were observed expressed by the fractional rate of change of voltage, as illustrated in FIG.

FIG. 8 shows the real-time concentration of sweat osmotic pressure in two human subjects using a PFGFET attached to the skin. The osmotic concentration in sweat was directly correlated to an individual's physical performance. Subject 1 was a sprinter and Subject 2 was a jogger. A sprinter (subject 1) ran the same distance at a faster pace (run 1) than a jogger (subject 2 and run 2). It was observed that the more intense the subject's physical activity, the higher the measured body osmolarity. A peak in body osmolality was observed during periods of most vigorous physical activity. Body osmotic pressure was also observed to decrease during periods of strenuous physical activity. This was caused when the subject consumed too much water without adequate salinity. The data indicate hyponatremia if the slope of the curve goes to zero. During this period, the body tries to retain as much salt as possible (to maintain ionic balance), so the overall body osmotic concentration changes very slowly.

The following novel results and/or characteristics were observed.

High selectivity: PFGT-modulated GFETs (NFETs) gave 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/liter. GFET sensors have a high signal-to-noise ratio, are highly sensitive, and due to the large surface area for binding, the binding between surface and molecule is stronger. All of these factors play a very large differentiating role in making GFETs highly sensitive.

Gate modulation due to polar molecules: In polar fluids (water, salt, etc.), polar molecules (such as ions) were observed to form polar fluid gate terminals (PFGTs) on NFETs. Polar molecules near the graphene surface induced dielectric effects and created channels for charge transfer. The gating strength of PFGT depended on both the charge and the concentration of polar molecules in the fluid. Such a third polar fluid gate terminal (PFGT) modulated the electrical response from NaCl concentration in the polar fluid.

Continuous monitoring: Concentrations of ions were measured continuously in the fluid by modulating the NFET channel current from the evoked polar fluid gate terminal. Once the ionic solution was removed from the surface of the NFET, the electrical response of the polar fluid gate NFET returned to its original bare or pristine value.

Induced motion of polar fluids on the surface of NFETs: Polar fluids (such as NaCl in DI water) are quickly repelled or expelled from the NFETs due to the high hydrophobicity between the NFET surface and the polar fluids. It is considered to be. The higher the concentration of polar molecules (eg, NaCl) in the fluid, the higher the strength of the PFGT and thus the greater the repulsive action. This repulsion, combined with the modulation of the PFGT-induced electrical response 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 forearms and hips (eccrine sweat glands). Sweat is diluted and ultrafiltered blood. The electrical response due to the chloride concentration in sweat was measured continuously while the subject was engaged in a) strenuous physical activity (training), b) non-vigorous physical activity (such as sitting at an office desk and eating). (every 500 ms) and recorded. Background ion concentrations in sweat (mainly NaCl) were observed to form PFGTs on two-terminal GFET devices. Changes in the gating strength of the induced PFGT on the GFET due to Cl ions enabled continuous non-invasive monitoring of Cl ion molecules in human sweat. It has been observed that sweat is a very good polar fluid for measuring chloride concentration on a continuous basis because 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 the non-functionalized GFET ○ Lactose concentration in DI water on the functionalized device (control 1)
○ Artificial sweat concentration on functionalized device (control 2)
o DI water response with functionalized GFET o Human sweat glucose measurements: Real-time continuous monitoring of glucose concentration was performed in human sweat using a wearable GFET/PBA sensor. Real-time continuous sweat glucose responses correlated with blood glucose measurements using a commercial glucose meter.

Functionalization: As an example, graphene FETs were functionalized with a linker molecule (Rock) that specifically binds to glucose molecules in fluids. As an example, a GFET was functionalized with pyreneboronic acid (PBA). Pyreneboronic 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 placed on the graphene, typically less than 0.5 mm thick, and then separated from the catalyst substrate it was grown on.
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 the solution of PBA for 5-20 minutes for functionalization at room temperature.
o After the functionalization step the sensor is ready for use.

Responses of various D-glucose concentrations in DI water were 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 DI water were prepared along with various concentrations of lactose in DI water. The test started by introducing the lowest concentration of 5 ul onto the GFET, then the next higher concentration after 3 minutes, and so on. This was continued until all concentrations were introduced onto the GFET.

FIG. 9 shows that GFET does not give a significant response to DI water or lactose solutions alone, and the exponential response is to high D-glucose concentrations in DI water. Increasing concentrations changed the voltage across the channel, thereby demonstrating high selectivity for D-glucose with DI water as a control.

Glucose response in NaCl versus glucose response in DI water. The sensitivity of functionalized sensors was studied to understand the action of NaCl solutions.

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

FIG. 10 shows that the D-glucose response in NaCl is amplified over the D-glucose response in DI water. A polar solution providing PFGT over the GFET amplified the electrical response through the channel, thereby increasing sensitivity and providing reversibility.

Selectivity measurement of glucose response in NaCl solution: Responses of various D-glucose concentrations in NaCl were 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 the lowest concentration of 5 ul on the GFET, then the next higher concentration after 3 minutes, and so on. Here the concentrations increased logarithmically. This was continued until all concentrations were introduced into the GFET.

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

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

Sensitivity measurement of D-glucose response in DI water: Various D-glucose concentration responses in DI water were measured on the GFET to study the sensitivity range of functionalized sensors 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 started with 3 injections of 5 ul of DI water on the GFET every 3 minutes, followed by 5 ul of the lowest concentration, followed by the next higher concentration after 3 minutes. , and so on. Here the concentration increased logarithmically; eg from 0.25 pg/l, then 2.5 pg/l and so on. This was continued until all concentrations were introduced onto the GFET.

FIG. 12 shows that the GFET gave no significant response to DI water alone, with a linear response starting from the lowest concentration to the highest concentration, with increasing concentrations changing the current across the channel, thereby , indicating that a high sensitivity of about 250 femtograms/liter (ie 1.38e ⁻¹² mmol/l) was exhibited for D-glucose.

Functionalization Step: Figure 13 shows the current response for the graphene sensor before functionalization, after functionalization and after glucose was introduced onto the sensor. This aids in understanding each stage of the GFET fabrication steps and how the current response of the GFET changes after each stage. For example, FIG. 13 shows an increase in current response after functionalization (orange) compared to before functionalization (blue), because the linker molecules are linked by π-π bonds and the graphene surface It is caused by an increase in all charges above. The linker molecule attracts glucose molecules and binds to them by using these charge clouds, thereby reducing the current on the GFET compared to its previous state.

D-Glucose Response in Sweat and Blood: Human sweat glucose concentration measurements were performed in human subjects. The test required subjects to engage in physical activity such as running, take blood samples, and measure blood glucose every few minutes using a glucose meter. GFETs were worn by human subjects on the forearms and hips (eccrine sweat glands). Electrical responses due to D-glucose concentrations in sweat were transmitted and recorded continuously (every 500 ms) while the subject underwent strenuous physical activity (such as 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 a person has eaten, glucose levels begin to drop and stabilize.

In the case of running, as you start running, your body uses glucose and breaks it down to get energy for running. A drop in glucose is therefore seen. After some time, however, the body's insulin kicks in and total glucose levels begin to rise again.

FIG. 14 shows the change in sweat D-glucose concentration expressed by the fractional rate of change of voltage.

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

FIG. 16 further shows the correlation of measurements between blood sugar and sweat glucose. Here three different sensors were used on the same person at the same time. Over 150 curves for sweat glucose were collected from 10 human subjects and correlated with blood glucose over the course of their study. Subjects engaged in physical activity (training, running, etc.) or no physical activity (such as sitting at a desk). For these 150 curves, the calculated correlation was R ² =84% between sweat and blood, as shown in FIG.

The following novel results and/or characteristics were observed.

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

High sensitivity: GFET functionalized with PBA showed high sensitivity to D-glucose with a limit of detection (LOD) of 250 femtograms/liter or 1.38e ⁻¹² mmol/l. Existing glucose meters have LODs between 0.3 and 1.1 mmol/l. The PBA-functionalized GFET is approximately 10 times more sensitive than existing standard glucose-measuring devices. GFET sensors have a high signal-to-noise ratio, high sensitivity, and due to the large surface area for binding, the binding between the surface and receptor molecules is stronger. All of these factors play a very large differentiating role in making GFETs highly sensitive.

Gate modulation due to polar molecules: In polar fluids (water, salt, etc.), polar molecules (such as ions) were observed to form polar fluid gate terminals (PFGTs) on NFETs. Polar molecules near the graphene surface induced dielectric effects and created channels for charge transfer. The gating strength of PFGT depended on both the charge and the concentration of polar molecules in the fluid. Such a third polar fluid gate terminal (PFGT) modulated electrical responses from glucose concentrations in polar fluids.

Continuous glucose monitoring: The reversibility of the PBA-glucose bond 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 (such as ions) in the polar fluid, the greater the reversibility of the PBA-D-glucose binding. When the concentration of glucose bound to the sensor becomes higher than that in sweat due to its Gibbs free energy, glucose molecules become liberated from PBA and a reversible nature is observed; This is clearly seen in the electrical response recorded in FIG. 14 as the concentration of glucose drops momentarily. This enables reusable real-time continuous monitoring of D-glucose molecules in polar fluids.

Glucose sensor reusability due to movement of polar fluids on the sensor surface: movement of polar fluids (such as glucose in salt) over NFETs enhances removal of bound glucose molecules from linker molecules It was observed that As an example, when the glucose solution was removed from the graphene surface of the GFET, the electrical response of the GFET returned to the original bare value.

Induced motion of polar fluids on the surface of NFETs: Polar fluids (such as glucose in salt) are quickly repelled or expelled from the NFET due to the high hydrophobicity between the NFET surface and the polar fluid. It is considered to be. The higher the concentration of polar molecules in the fluid, the higher the strength of the PFGT and thus the greater the repulsive action. This repulsion, combined with the removal of bound glucose molecules (described in section e above), and the modulation of the electrical response caused by PFGTs on NFETs could lead to a more sensitive selective and continuous monitoring glucose system. made it possible.

Real-time continuous glucose monitoring in human sweat: PBA-functionalized GFETs were worn by human subjects on the forearms and hips (eccrine sweat glands). Sweat is diluted and ultrafiltered blood. The electrical response due to the D-glucose concentration in sweat was measured continuously while the subject was engaged in a) strenuous physical activity (training) and b) non-vigorous physical activity (such as sitting at an office desk and eating). Targets (every 500 ms) were transmitted and recorded. The sweat glucose response was correlated to blood glucose readings obtained every few minutes using a blood glucose meter over the length of activity (typically 20 minutes to over 6 hours). Background ion concentrations in sweat (mainly NaCl) were observed to form PFGTs on two-terminal GFET/PBA devices. The increased reversibility between PBA and D-glucose binding resulting from PFGT on GFET enabled continuous noninvasive monitoring of glucose molecules in human sweat. A correlation of 84% (R ² ) was calculated between blood and sweat glucose measurements. Correlations were calculated for 150 sweat glucose responses collected from 10 human subjects under various physical activity conditions. It has been observed that sweat is 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 a linker molecule (Rock) that specifically binds to lactate molecules in fluids. As an example, a GFET was functionalized to the graphene surface using the intermediate pyrene-NHS linkage chemistry with lactate oxidase (LOx).
o The polymer is placed on the graphene, typically less than 0.5 mm thick, and then separated from the catalyst substrate grown on it.
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 bonding at room temperature for 520 minutes.
o 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 in non-functionalized GFET ○ Lactic acid concentration in NaCl in functionalized GFET ○ Artificial sweat concentration in functionalized device ( Control 2)
o DI water response in functionalized GFETs.

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

FIG. 17 shows that the GFET gives no significant response to DI alone and the polynomial response is to high lactate concentrations in DI water, with increasing concentrations changing the voltage across the channel, It showed high selectivity for lactic acid in DI water using DI water as a control.

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

FIG. 18 shows that GFET gave no significant response to NaCl and NaCl glucose controls alone, and gave polynomial responses 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 in the non-functionalized sensor for the lactate NaCl solution, further highlighting the sensor's selectivity and sensitivity to lactate.

Lactate response in NaCl versus lactate response in DI water: Responses of various lactate concentrations in DI water and NaCl solutions were measured on the GFET to determine the sensitivity of the functionalized sensor to lactate in DI water versus lactate in NaCl. studied and understood the action of NaCl solutions. Solutions containing various concentrations of lactic acid ranging from 0.1 to 100 mg/dL were prepared in DI water and NaCl, respectively. The test started by introducing the lowest concentration of 2 ul on the GFET, then the next higher 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.

Lactate functionalization step visualized through GFET fabrication: Current responses for the graphene sensor before functionalization, after functionalization, and after introduction of lactate onto the sensor are illustrated in FIG. This aids in understanding each stage of the GFET fabrication steps and how the current response of the GFET changes after each stage. For example, FIG. 20 shows that the current response decreases 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 relative to its previous state.

The following novel results and/or characteristics were observed.

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

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

Gate modulation due to polar molecules: In polar fluids (water, salt, etc.), polar molecules (such as ions) were observed to form polar fluid gate terminals (PFGTs) on NFETs. Polar molecules near the graphene surface induced dielectric effects and created channels for charge transfer. The gating strength of PFGT depended on both the charge and the concentration of polar molecules in the fluid. Such a third polar fluid gate terminal (PFGT) modulated the electrical response from lactate concentrations in polar fluids.

Induced motion of polar fluids on the surface of NFETs: Polar fluids (such as lactic acid in artificial perspiration) are likely to be quickly repelled or removed from the NFETs due to the high hydrophobicity between the NFET surface and the polar fluids. is considered to be The higher the concentration of polar molecules in the fluid, the higher the strength of the PFGT and thus the greater the repulsive action. This repulsion combined with the modulation of the electrical response due to PFGT on NFET enabled a more sensitive selective and continuous monitoring lactate system.
(Example 5)
Additional analysis

Correlation of Sweat Salt Concentration: FIG. 21 represents the sweat sensor response in terms of the corresponding sweat sodium concentration.

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

Correlation of Sweat Glucose Concentrations: FIG. 22 represents sweat sensor responses in terms of corresponding sweat glucose concentrations.

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

Transconductance Curve: FIG. 23 represents the transconductance curve for the PFGT device.

A high concentration NaCl solution ranging from 0.1 ng/dl to 1 mg/dl is dropped onto the sensor every 3 minutes. The test begins by dropping the lowest concentration of 2 ul (e.g. 0.1 ng/dl) followed by the next higher concentration (e.g. 1 ng/dl) and so on at 3 minute intervals. Dripped.

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

This demonstrates the transconductance properties of graphene sensors gated with polar fluids.

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

Furthermore, those skilled in the art will appreciate the applicability of various features from different embodiments. Likewise, the various elements, features, and steps discussed above, and other known equivalents for such elements, features, and steps, may be used so that the methods are performed in accordance with the principles described herein. It can be mixed and matched by those skilled in the art. 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, it will be appreciated by those skilled in the art that embodiments of the present invention extend beyond the specifically disclosed embodiments to other alternative embodiments and/or It will be understood that it extends to uses and modifications and equivalents thereof.

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

In some embodiments, numerical values representing amounts of components, properties such as molecular weights, reaction conditions, and the like, used to describe and claim certain embodiments of the present invention are referred to as " It is to be understood that it is optionally modified by the term "about". Accordingly, in some embodiments, the numerical parameters set forth in the written description and appended claims are approximations that may vary depending on the desired properties sought to be obtained by a particular embodiment. is. In some embodiments, numeric parameters should be interpreted in light of the reported number of significant digits and by applying normal rounding techniques. Notwithstanding that the numerical ranges and parameters setting forth the broad scope of some embodiments of the 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 this 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" are used in the context of describing particular embodiments of the invention (particularly in certain contexts of the claims below). , and similar references may be construed to include both singular and plural forms. Recitation of ranges of values herein is merely intended as a shorthand method of referring individually to each separate value falling within the range. Unless otherwise indicated herein, each individual value is incorporated herein as if it were individually recited herein. All methods described herein can be performed in any suitable order unless otherwise indicated herein or otherwise clearly contradicted by context. The use of any and all examples or exemplary language (eg, "such as") provided with respect to certain embodiments herein is intended solely to better illustrate the invention. and does not impose any limitation on the scope of any invention otherwise claimed. No language in the specification 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 limitations. Each group member 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 hereby deemed to contain the group as modified and thus all Markush groups used in the claims appended hereto. satisfies the description.

Preferred embodiments of the invention are described herein. Variations on those preferred embodiments may become apparent to those of ordinary skill in the art upon reading the foregoing description. It is contemplated that one skilled in the art may employ such variations as appropriate, and the invention may be practiced otherwise than specifically described herein. Accordingly, many embodiments of this 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 to patents and printed publications throughout this specification. The references and printed publications cited above are hereby individually incorporated by reference in their entirety.

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

Claims (20)

A field effect transistor,
a drain electrode;
a source electrode;
a substrate;
a layer of nanoscale material disposed on the substrate as a channel extending between and electrically connecting the source and drain electrodes;
A polar fluid-induced gate terminal formed when a polar fluid is exposed to said nanoscale material layer, wherein said polar fluid-induced gate terminal creates an induced gate voltage in said channel to cause said a polar fluid-induced gate terminal that enables the field effect transistor to function as an active device when a polar fluid is externally introduced into the channel;
wherein said polar fluid and said channel collectively function as said polar fluid-induced gate terminal;
Field effect transistor. 2. The field effect transistor of claim 1, wherein said polar fluid is externally introduced into said channel as droplets. 2. The field effect transistor of claim 1, wherein said polar fluid is externally introduced into said channel when said field effect transistor is in contact with a volume of said polar fluid. 2. The field effect transistor of claim 1, wherein said active device is configured for use as a sensing device. 5. The field effect transistor of Claim 4, wherein the active device is configured to be used for biosensing. 2. The field effect transistor of claim 1, wherein said field effect transistor does not include or require a persistent physical gate terminal formed on said substrate. 2. The field effect transistor of claim 1, wherein the induced gate voltage is related to the concentration of charged particles within the polar fluid. 2. The field effect transistor of claim 1, wherein said polar fluid-induced gate terminal is transient and active only when said polar fluid is externally introduced into said channel. 2. The field effect transistor of claim 1, wherein said field effect transistor is not configured to function as said active device when said polar fluid is removed from said channel. 2. The field effect transistor of claim 1, wherein said channel is electrically conductive and chemically and/or biologically sensitive. 2. The field effect transistor of claim 1, wherein said nanoscale material is epitaxially grown. said nanoscale materials are 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. 2. The field effect transistor of claim 1, wherein the polar fluid comprises a solution containing polar molecules or a gas containing polar molecules. 2. The field effect transistor of claim 1, wherein the polar fluid comprises sweat, breath, saliva, cerumen, urine, semen, blood plasma, biological fluids, chemical fluids, air samples, gas samples, or combinations thereof. The polar fluid contains electrolytes, glucose, lactate, IL6, cytokines, HER2, cortisol, ZAG, cholesterol, vitamins, proteins, drug molecules, metabolites, peptides, amino acids, DNA, RNA, aptamers, enzymes, biomolecules, chemical molecules. 2. The field effect transistor of claim 1, comprising one or more target analytes including, synthetic molecules, or combinations thereof. Further comprising a receptor layer coupled to the nanoscale material layer, the receptor layer comprising one or more receptors configured to target one or more target analytes in the polar fluid. A field effect transistor according to claim 1. wherein said one or more receptors are pyreneboronic acid (PBA), pyrene N-hydroxysuccinimide ester (pyrene-NHS), organic chemicals, aromatic molecules, cyclic molecules, enzymes, proteins, antibodies, viruses, single-stranded DNA 17. The field effect transistor of claim 16 , comprising (ssDNA), aptamers, inorganic materials, synthetic molecules, or biomolecules. The substrate is polyimide, flexible printed circuit (FPC), polyamide, polyurethane, PET, PDMS, PMMA, silicon dioxide, silicon, glass, aluminum oxide, sapphire, germanium, gallium arsenide, indium phosphide, silicon and germanium 2. The field effect transistor of claim 1, comprising alloys, fabrics, textiles, silk, paper, cellulose-based materials, or any combination thereof. 2. The field effect transistor of claim 1, wherein said substrate is made of an electrically insulating material. 10. A biosensing system comprising the field effect transistor of claim 1, wherein the biosensing system or component thereof is configured to be worn on a subject, and wherein the field effect transistor is configured such that the polar fluid A biosensing system configured to detect one or more targets in the polar fluid when externally introduced into the channel from the subject's body.

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