CN115753941A

CN115753941A - Polar fluid gated field effect device

Info

Publication number: CN115753941A
Application number: CN202211200989.1A
Authority: CN
Inventors: 拉杰特希·R·古迪班德; 萨乌拉博·拉达克里希南; 安东尼·加兰德; 米特·沃拉
Original assignee: Graphwear Technologies Inc
Current assignee: Graphwear Technologies Inc
Priority date: 2016-06-30
Filing date: 2017-06-30
Publication date: 2023-03-07
Also published as: WO2017216641A3; WO2017216641A2; EP3472607A2; CN109642888A; JP2024055954A; JP7449333B2; JP7129405B2; JP2022121664A; KR20240045375A; KR102653287B1; KR20190027828A; EP3472607A4; JP2019525200A; CN109642888B

Abstract

Nanoscale Field Effect Transistors (NFETs), such as graphene-based field effect transistors (GFETs), that do not have a physical gate are disclosed herein. Instead, they are gated by polar fluids. Systems and methods of using such transistors are also disclosed.

Description

Polar fluid gated field effect device

The application is a divisional application of a Chinese patent application with an application date of 2017, 30.06 months and an application number of 201780050922.5, entitled "polar fluid-gated field effect device" (which corresponds to a PCT application with an application date of 2017, 30 months and 06 months and an application number of PCT/IB 2017/001003).

Cross Reference to Related Applications

The present application claims priority from U.S. provisional patent application No. 62/356,729 entitled DETECTION OF ion connectivity IN FLUID USE, NANCTIONALIZE MATERIALS VIA A CAPACITIVE RESPONSE, filed on 30.6.2016 AND U.S. provisional patent application No. 62/356,742 entitled LACTATE-OXIDAE-FUNCTIONALIZED GRAPHINE POLYMER COMPOSITE FOR BELAL-FREE DETECTION OF LACTATE IN SWEAT AND OTHER BODIPLY FLUDS, filed on 30.6.2016, each OF which is incorporated herein by reference IN its entirety.

Technical Field

The invention disclosed herein relates generally to the design, fabrication, and application of Nanoscale Field Effect Transistors (NFETs), particularly Graphene Field Effect Transistors (GFETs), gated by polar fluids. The present 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 involving graphene.

Background

A Field Effect Transistor (FET) is a transistor that uses an electric field to control the electrical behavior of a device. Typically, a FET has three terminals (e.g., 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 carriers enter 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) to control the current between the source and drain.

Nanoscale Field Effect Transistors (NFETs), such as Graphene Field Effect Transistors (GFETs), are widely used in many applications, such as bioprobes, implants, and the like.

What is needed in the art are better FET designs and new methods of using them.

Disclosure of Invention

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, the nanoscale material layer partially defining an electrically conductive and chemically sensitive channel, the nanoscale material layer and channel extending between and electrically connected to the drain electrode and the source electrode; the gate terminal induced by the polarized fluid is created by the polar fluid exposed to the nanoscale material layer. In some embodiments, the polar fluid comprises a target analyte. In further embodiments, the polar fluid has a charge concentration sufficient to induce a polar fluid gate voltage that optimizes the gate voltage according to channel current characteristics of the (vers) field effect transistor in response to the target analyte.

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

In some embodiments, the nanoscale material comprises graphene, CNT, moS ₂ Boron nitride, a metal disulfide, a phospholene, a nanoparticle, a quantum dot, a fullerene, a 2D nanoscale material, a 3D nanoscale material, a 0D nanoscale material, a 1D nanoscale material, or any combination thereof.

In some embodiments, wherein 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 polar fluid comprises sweat, breath, saliva, cerumen, urine, semen, plasma, biological fluid, chemical fluid, air sample, gas sample, or combinations thereof

In some embodiments, the target analyte comprises an electrolyte, glucose, lactate, IL6, cytokine, HER2, cortisol, ZAG, cholesterol, vitamin, protein, drug molecule, metabolite, polypeptide, amino acid, DNA, RNA, aptamer, enzyme, biomolecule, chemical molecule, synthetic molecule, or a combination thereof.

In some embodiments, the field effect transistor further comprises: a receptor layer deposited on the nanoscale material layer, wherein the receptor layer comprises a receptor targeted to a target analyte.

In some embodiments, the receptor comprises 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.

In some embodiments, the field effect transistor further comprises: a back 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 back 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, a method for sensing a target analyte in a polar fluid is disclosed herein. The method comprises the following steps: exposing the polar fluid sample to a field effect transistor, wherein the field effect transistor comprises: 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 channel extending between and electrically connected to the drain electrode and the source electrode; a polar fluid induced gate terminal resulting from exposure of a polar fluid to the nanoscale material layer, wherein the polar fluid includes a target analyte and has a charge concentration sufficient to induce a polar fluid gate voltage that optimizes the gate voltage according to channel current characteristics of the field effect transistor for detection of the analyte; measuring a first source-drain voltage at a first point in time and a second source-drain voltage at a second and subsequent point in time; based on the first and second source-drain voltages, a concentration of a target analyte in the polar fluid is determined.

In some embodiments, the field effect transistor is functionalized with a receptor layer deposited on the nanoscale material layer, and wherein the receptor layer comprises a receptor targeted to a target analyte.

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 method further includes calculating a small change between the first source-drain voltage and the second source-drain voltage.

In some embodiments, the method further comprises: a constant current is applied between the source electrode and the drain electrode of the field effect transistor.

In some embodiments, the method further comprises: a constant voltage is applied between the source and drain electrodes of the field effect transistor.

In some embodiments, the method further comprises: a back polymer layer below the nanoscale material layer to provide support for additional mechanical, electrical, chemical, biological functions, or combinations thereof.

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

a constant current source or a constant voltage source electrically connected to the 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, the nanoscale material layer partially defining an electrically conductive and chemically sensitive channel, the nanoscale material layer and channel extending between and electrically connected to the drain electrode and the source electrode; the polarized fluid induced gate terminal is created by the polar fluid exposed to the nanoscale material layer. In some embodiments, the polar fluid comprises 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 according to 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 the field effect transistor.

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

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

In some implementations, the digital platform includes a smartphone, a tablet computer, a smart watch, an in-vehicle entertainment system, a notebook 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.

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

Drawings

Those skilled in the art will appreciate that the drawings described below are for illustration purposes only. The drawings are not intended to limit the scope of the present teachings in any way.

Fig. 1A depicts a prior art embodiment, showing a graphene field effect transistor (gFET).

Fig. 1B depicts a prior art embodiment, showing the current flow between source and drain controlled by the gate voltage.

An exemplary embodiment is depicted at 2A in fig. 2, demonstrating a gate-less graphene field effect (g-gFET).

An exemplary embodiment is depicted at 2B in FIG. 2, which illustrates a g-gFET.

An exemplary embodiment is depicted at 2C in fig. 2, which illustrates a g-gFET.

An exemplary embodiment is depicted at 2D in fig. 2, illustrating a g-gFET.

An exemplary embodiment is depicted at 3A in fig. 3, showing a Polar Fluid Gate Terminal (PFGT) in which the polar fluid has no movement.

Fig. 3B depicts an exemplary embodiment, showing a polar fluid gate terminal, wherein the polar fluid flows in a first direction.

Exemplary embodiments are depicted at 3C in fig. 3, showing a polar fluid gate terminal, wherein the polar fluid flows in a second direction.

Fig. 4A depicts an exemplary embodiment showing the basic device with dielectric and gate metal as shown in fig. 2. The gate potential is measured between the gate metal and ground.

Fig. 4B depicts an exemplary embodiment showing the basic device with an added metal electrode in the PFGT as shown in fig. 2. The gate potential is measured between the metal electrode and ground.

Fig. 4C depicts an exemplary embodiment, showing the basic device enhanced with dielectric and gate metal and metal electrodes in a PFGT as shown in fig. 2. Two gate potentials are measured as shown.

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

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

Fig. 6 shows an exemplary embodiment demonstrating selective measurement of NaCl response in DI (deionized) water.

FIG. 7 shows an exemplary embodiment demonstrating sensitivity measurement of NaCl response in DI water.

Fig. 8 shows an exemplary embodiment demonstrating chloride response in sweat.

Fig. 9 illustrates an exemplary embodiment demonstrating selective measurement of glucose response in DI water.

Fig. 10 shows an exemplary embodiment demonstrating the glucose response in NaCl versus the glucose response in DI water.

FIG. 11 shows an exemplary embodiment demonstrating selective measurement of glucose response in NaCl water.

Fig. 12 illustrates an exemplary embodiment demonstrating the sensitivity measurement of the D-glucose response in DI water.

Fig. 13 illustrates an exemplary embodiment, demonstrating the functionalized step of making visualization through a GFET.

FIG. 14 shows an exemplary embodiment demonstrating the D-glucose response in sweat.

FIG. 15 shows an exemplary embodiment demonstrating the D-glucose response in blood.

Fig. 16 illustrates an exemplary embodiment demonstrating the measurement correlation between blood glucose and sweat glucose.

Fig. 17 shows an exemplary embodiment demonstrating selective measurement of lactate response in DI water.

Fig. 18 shows an exemplary embodiment demonstrating selective measurement of lactate response in various solutions.

Fig. 19 shows an exemplary embodiment demonstrating the response of lactic acid in NaCl versus that in DI water.

Fig. 20 shows an exemplary embodiment illustrating the lactic acid functionalization step visualized by GFET manufacturing.

Fig. 21 shows an exemplary embodiment illustrating a model of sensor correlation with sweat sodium concentration.

Fig. 22 shows an exemplary embodiment, demonstrating a model of the correlation of a sensor to sweat glucose concentration.

Fig. 23 shows an exemplary embodiment, illustrating the transconductance curves of PFTs.

Detailed Description

Nanoscale field effect transistors and methods of making and using the same are disclosed herein.

Overview of graphene field effect transistors

Graphene has significant mechanical resistance; this allows the thickness of the monolayer or bilayer to withstand significant mechanical stress without losing its primary electrical properties. This mechanical strength makes graphene an ideal candidate to replace the current generation Transparent Conducting Oxide (TCO) guided 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 costs. 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 atomic layers with little transparency above 90% and sheet resistance below 100%.

As shown in FIG. 1A, graphene FETs are typically covered with SiO ₂ The Si wafer of the layer is fabricated and the graphene forms the transistor channel. The graphene transistor consists of three terminals: source and drain metal electrodes in contact with the graphene channel and a global back gate realized by a doped Si substrate. These features contribute to the characteristic bipolar transport behavior of graphene in a Grat-FET, achieving both n-type and p-type transport when biased at an appropriate gate voltage on the substrate. GFET can be manufactured by any suitable method, including, for example, international patent publicationInformation disclosed in WO 2015/164,552, the entire contents of which are incorporated herein by reference.

Fig. 1B shows the current between source and drain controlled by the gate voltage. By changing the direction and magnitude of the gate voltage, the resulting curve of current flow through the source and drain is "V" shaped. At the tip of the V-shaped curve, a small change in gate voltage results in a channel current (I) _DS ) And tends to be smooth at both ends of the V-shaped curve.

Non-grid field effect transistor

In one aspect, a novel Field Effect Transistor (FET) without a physical gate is disclosed herein.

Fig. 2 depicts various embodiments of a FET without a physical gate. Fig. 2A depicts an exemplary graphene-based FET 210 comprising a substrate 1, a source electrode 2, a drain electrode 3, a receptor 4, a graphene layer 5, and a back polymer 6. As disclosed herein, the substrate 1 may be polyamide, PET, PDMS, PMMA, other plastics, silica, silicon, glass, alumina, sapphire, germanium, gallium arsenide, indium phosphide, alloys of silicon and germanium, fabric, textile, wire, paper, cellulose-backed material, insulators, metals, semiconductors, may be rigid, flexible, or any combination thereof. In some embodiments, the substrate 1 may be a silicon carbide substrate, and the graphene layer 5 may be epitaxially grown on the silicon carbide substrate directly by sublimation of silicon from the silicon carbide substrate (2B in fig. 2).

The source electrode 2 is an electrode region in the field effect transistor, and the majority carriers flow from the electrode region into the inter-electrode conduction path. Exemplary materials that can be used as the source electrode include, but are not limited to, silver, gold, carbon, graphite ink, conductive fabric, conductive textile, metal, conductive material, conductive polymer, conductive gel, ionic gel, conductive ink, non-metallic conductive material.

The drain electrode 3 is an electrode on the opposite side to the source electrode 2. Exemplary materials that may be used as the source electrode include, but are not limited to, silver, gold, carbon, graphite ink, conductive fabric, conductive textile, metal, conductive material, conductive polymer, conductive gel, ionic gel, conductive ink, non-metallic conductive material.

In some embodiments, the graphene layer 5 may have one or more graphene monolayers of uniform thickness, preferably of a predetermined thickness. Since the thickness affects electrical characteristics such as band gap, carrier concentration, etc., a uniform and preferably predetermined thickness provides control of the sensing characteristics and enables the formation of reproducible devices with low variability between individual sensors.

In some embodiments, the graphene layer 5 may be an epitaxial layer, and the graphene layer substrate may be a substrate on which the graphene layer is epitaxially grown. By leaving the graphene layer on the substrate on which it is grown, it is generally not necessary to process the nanoscale graphene layer and structure. Furthermore, when the graphene layer may remain on the substrate, the risk of damaging the thin graphene layer during the manufacture of the transistor is also reduced.

In some embodiments, the graphene layer 5 may be surface treated with the receptor 4 to obtain selectivity such that only selected types of analytes are detected by the graphene layer. Exemplary receptors 4 include, but are not limited to, 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, biomolecules.

In some embodiments, the graphene layer 5 and/or certain types of chemical species are prevented from reaching the chemically sensitive channels. The surface treatment may include deposition of metal particles and/or polymers.

The back polymer 6 is used to provide mechanical support for the graphene. And when doped, a new mode can be added for the sensing response. For example, the post-polymer may be doped with biomolecules that may also bind to a specific target and contribute to the resistance change of the transistor channel.

Device 220, device 230, and device 240 are variations of device 210. In the device 220, the back polymer layer 6 is omitted. In the device 230, the acceptor layer 4 is omitted. In the device 240, the back polymer layer 6 and the acceptor layer 4 are omitted.

As disclosed herein, a device or base device may be any of

devices

210, 220, 230, and 240.

Polar Fluid Gate Terminal (PFGT)

Graphene is an allotrope of carbon in the form of a hexagonal lattice at two-dimensional atomic scale, with one atom forming each vertex. Graphene is the basic structural element of other allotropes, including graphite, charcoal, carbon nanotubes, and fullerenes. Graphene can be considered as an infinite aromatic molecule, the limiting case of flat polycyclic aromatics. In some embodiments, the graphene is a monolayer of carbon atoms. Each carbon atom in graphene has four electrons. With three of these electrons, the carbon atom combines with the three nearest neighbors to form a hexagonal lattice. For each atom, the fourth electron is delocalized across the entire graphene layer, which allows conduction of an electron current.

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

An exemplary embodiment is depicted at 3A in fig. 3, showing a polar fluid gate terminal in which the polar fluid has no motion. As shown, the charge of the polar or ionic component is redistributed in the polar fluid to produce a Polar Fluid Gate Terminal (PFGT) and an induced fluid gate Voltage (VGT) _FG ). This voltage can result in a shift of the V-shaped current from the x-axis (voltage) in the fluid gate voltage curve. As described above, at the tip of the V-shaped curve, a small change in gate voltage may result in a channel current (I) _DS ) And tends to plateau at both ends of the V-shaped curve. A shift towards the tip of the V-shaped curve may result in enhanced sensitivity: very small voltage changes in response to current changes can be detected. Similarly, very small current changes in response to voltage changes may also be detected.

As mentioned above, a shift towards the tip of the V-shaped curve may result in better sensitivity. This offset may be caused by the gate voltage induced by the polar liquid. In some embodiments, the gate voltage induced by the polar liquid is related to the concentration of charged particles within the polar fluid. In some embodiments, the concentration may reflect the total amount of all negatively charged particles or all positively charged particles. The variation of the V-shaped curve can be associated with a wide range of charged particle concentrations. In some embodiments, the offset is associated with a charged particle concentration as low as 1 femtogram/liter (e.g., naCl). In some embodiments, the offset is associated with a charged particle concentration of up to 300 grams/liter (e.g., naCl). The results show that the current sensing system is flexible and can withstand a wide range of charge concentrations.

Fig. 3B depicts an exemplary embodiment, showing a polar fluid gate terminal, wherein the polar fluid flows in a first direction. Gate potential (V) _FG ) Will be proportional to the flow rate of the polar fluid. V _FG Depending on the direction of flow of the polar fluid; for example, along and through the source and drain terminals. For example, if the gate voltage is positive in the source-drain direction, it is negative in the reverse direction, and vice versa. When a polar fluid flows through the source-drain voltage, if the gate voltage is positive in the Y-direction, it is negative in the-Y-direction, and vice versa. When the direction of the polar fluid flow changes, the direction of the gate voltage will also change.

An exemplary embodiment is depicted at 3C in fig. 3, showing a polar fluid gate terminal in which the polar fluid flows in a second direction opposite the first direction.

Detecting gate voltage of polar fluid gate terminal

Fig. 4A to 4C show the arrangement by which the gate voltage at the Polar Fluid Gate Terminal (PFGT) is determined.

Fig. 4A depicts an exemplary embodiment showing a base device with a dielectric layer 7 and a gate metal 8. Here, the base device may be any device depicted in fig. 2, 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 underlying device, e.g. substrate 1 as shown in fig. 2. A gate metal 8 is added under the dielectric layer 7. The gate metal 8 is added only to measure the induced gate voltage, and no voltage is applied through the gate metal 8. In some embodiments, vg1 may vary in a non-linear manner depending on PFGT device characteristics and channel type. For example, if the channel is graphene (bipolar), vg1 may follow the transconductance response typical of graphene devices.

Fig. 4B depicts an exemplary embodiment showing the basic device as shown in fig. 2 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 may vary in a non-linear manner depending on PFGT device characteristics and channel type. For example, if the channel is graphene (bipolar), vg2 will follow the transconductance response typical of graphene devices (see, e.g., fig. 23).

Fig. 4C depicts an exemplary embodiment showing the basic device as shown in fig. 2 enhanced with a dielectric and gate metal, and a metal electrode in a PFGT. Two gate potentials are measured as shown. The two gate potentials (Vg 1 and Vg 2) are electrical outputs that are adjusted using source-drain current/voltage and induced PFG. The simultaneous measurement of Vg1 and Vg2 creates a triple-gated structure that can be used to develop next generation microprocessors, logic gates, computational circuits, radio Frequency (RF) devices, sensors, and the like.

Fig. 4C depicts an exemplary embodiment showing the basic device as shown in fig. 2 enhanced with a dielectric and gate metal, and a metal electrode in a PFGT. Two gate voltages (e.g., vg1 and Vg 2) are provided to the PFGT to adjust the overall electrical characteristics of the PFGT device for the desired application. The simultaneous modulation of Vg1 and Vg2 results in a triple-gated structure that can be used to convert device operation to desired electrical performance in a more controlled manner using minimal energy. Such devices may be used in the development of next generation microprocessors, logic gates, computing circuits, radio Frequency (RF) devices, sensors, and the like.

Figure 5A depicts an exemplary embodiment of the present invention,a circuit for sensor readout via a Polar Fluid Graphene Field Effect Transistor (PFGFET) is shown. In FIG. 5A, the current (I) is constant _C ) Is supplied to the PFGFET. Reading an output voltage (V) from across a PFGFET using a voltage divider and a current limiting resistor (R) _OUT ). The voltage output is then calibrated to the concentration of the analyte being sensed.

Fig. 5B depicts an exemplary embodiment showing another circuit for sensor readout via a PFGFET. Here, constant voltage (V) _S ) Is provided to the PFGFET. Reading current or charge (I) from a PFGFET using a current limiting resistor (R) _OUT ). The current output is then calibrated to the concentration of the analyte being sensed.

Having described the invention in detail, it will be readily understood that modifications, variations, and equivalents may be made thereto without departing from the scope of the invention defined in the appended claims. Furthermore, it should be understood that all examples in the present invention are provided as non-limiting examples.

The present invention provides embodiments including, but not limited to:

1. a 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 partially defining an electrically conductive and chemically sensitive channel, the nanoscale material layer and the channel extending between and electrically connected to the drain electrode and the source electrode; and

a polar fluid induced gate terminal resulting from exposure of a polar fluid to the nanoscale material layer,

wherein:

the polar fluid comprises a target analyte; and

the polar fluid has a charge concentration sufficient to induce a gate voltage of the polar fluid,

the polar fluid gate voltage optimizes a gate voltage according to channel current characteristics of the field effect transistor in response to the target analyte.

2. The field effect transistor according to embodiment 1, wherein a constant current supplied from a constant current source or a constant voltage supplied from a constant voltage source is applied between the source electrode and the drain electrode.

3. The field effect transistor of

embodiment

1 or 2, wherein the nanoscale material comprises graphene, CNT, moS ₂ Boron nitride, a metal disulfide, a phospholene, a nanoparticle, a quantum dot, a fullerene, a 2D nanoscale material, a 3D nanoscale material, a 0D nanoscale material, a 1D nanoscale material, or any combination thereof.

4. The field effect transistor of any of embodiments 1-3, wherein the polar fluid comprises a solution having polar molecules, a gas having polar molecules, a target sensing analyte, or a combination thereof.

5. The field effect transistor of any of embodiments 1-4, wherein the polar fluid comprises sweat, breath, saliva, cerumen, urine, semen, plasma, biological fluid, chemical fluid, air sample, gas sample, or a combination thereof.

6. The field effect transistor of any of embodiments 1-5, wherein the target analyte comprises an electrolyte, glucose, lactate, IL6, cytokine, HER2, cortisol, ZAG, cholesterol, vitamin, protein, drug molecule, metabolite, polypeptide, amino acid, DNA, RNA, aptamer, enzyme, biological molecule, chemical molecule, synthetic molecule, or a combination thereof.

7. The field effect transistor according to any one of embodiments 1 to 6, further comprising:

a receptor layer deposited on the nanoscale material layer, wherein the receptor layer comprises a receptor targeted to the target analyte.

8. The field effect transistor of embodiment 7, wherein the acceptor comprises 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.

9. The field effect transistor according to any one of embodiments 1 to 8, further comprising:

a back polymer layer below the nanoscale material layer to provide support for additional mechanical, electrical, chemical, biological functions, or a combination thereof.

10. The field effect transistor of embodiment 9, wherein the back polymer layer comprises: carbon polymers, biopolymers, PMMA, PDMS, flexible glass, nanoscale materials, silicone gel, silicone, inks, printed polymers, or any combination thereof.

11. A method for sensing a target analyte in a polar fluid, comprising:

exposing the polar fluid sample to a field effect transistor, wherein the field effect transistor comprises:

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; and

a polar fluid induced gate terminal resulting from the polar fluid exposed to the nanoscale material layer, wherein the polar fluid includes a target analyte and has a charge concentration sufficient to induce a polar fluid gate voltage that optimizes a gate voltage according to channel current characteristics of the field effect transistor for detection of the analyte;

measuring a first source-drain voltage at a first point in time and a second source-drain voltage at a second and subsequent point in time; and

determining a concentration of the target analyte in the polar fluid based on the first source-drain voltage and the second source-drain voltage.

12. The method of embodiment 11, wherein the nanoscale material comprises graphene、CNT、MoS ₂ Boron nitride, a metal disulfide, a phospholene, a nanoparticle, a quantum dot, a fullerene, a 2D nanoscale material, a 3D nanoscale material, a 0D nanoscale material, a 1D nanoscale material, or any combination thereof.

13. The method of embodiment 11 or 12, wherein the field effect transistor is functionalized with a receptor layer deposited on the nanoscale material layer, and wherein the receptor layer comprises a receptor targeted to the target analyte.

14. The method of embodiment 13, wherein the receptor comprises 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.

15. The method of any of embodiments 11-14, wherein the target analyte comprises an electrolyte, glucose, lactate, IL6, cytokine, HER2, cortisol, ZAG, cholesterol, vitamin, protein, drug molecule, metabolite, polypeptide, amino acid, DNA, RNA, aptamer, enzyme, biological molecule, chemical molecule, synthetic molecule, or a combination thereof.

16. The method of any one of embodiments 11-15, wherein the polar fluid comprises a solution having polar molecules, a gas having polar molecules, a target sensing analyte, or a combination thereof.

17. The method of any of embodiments 11-16, further comprising:

calculating a small change between the first source-drain voltage and the second source-drain voltage.

18. The method of any of embodiments 11-17, further comprising:

applying a constant current between the source electrode and the drain electrode of the field effect transistor.

19. The method of any one of embodiments 11-18, further comprising:

applying a constant voltage between the source electrode and the drain electrode of the field effect transistor.

20. The method of any one of embodiments 11-19, wherein the polar fluid comprises sweat, breath, saliva, cerumen, urine, semen, plasma, biological fluid, chemical fluid, air sample, gas sample, or a combination thereof.

21. The method of any of embodiments 11-20, further comprising: a back polymer layer below the nanoscale material layer to provide support for additional mechanical, electrical, chemical, biological functions, or a combination thereof.

22. The method of embodiment 21, wherein the back polymer layer comprises: carbon polymers, biopolymers, PMMA, PDMS, flexible glass, nanoscale materials, silicone gel, silicone, inks, printed polymers, or any combination thereof.

23. A system, comprising:

a field effect transistor; and

a constant current source or a constant voltage source electrically connected to the field effect transistor, wherein the field effect transistor includes:

a drain electrode;

a source electrode;

an electrically insulating substrate;

a polar fluid induced gate terminal resulting from exposure of the polar fluid to the nanoscale material layer, wherein:

the polar fluid comprises a target analyte; and

the polar fluid has a charge concentration sufficient to induce a polar fluid gate voltage that optimizes a gate voltage according to channel current characteristics of the field effect transistor in response to the target analyte.

24. The system of embodiment 23, wherein the constant current source maintains a constant current through the field effect transistor.

25. The system of embodiment 23, wherein the constant voltage source maintains a constant voltage across the field effect transistor.

26. The system of embodiment 23, wherein the voltage output or the current output is transmitted to a digital platform via wired or wireless transmission.

27. The system of embodiment 26, wherein the digital platform comprises a smartphone, a tablet computer, a smart watch, an in-vehicle entertainment system, a notebook 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.

Examples

The following non-limiting examples are provided to further illustrate the embodiments of the invention disclosed herein. It should be appreciated by those of skill in the art that the techniques disclosed in the embodiments that follow represent methodologies that have been found to function well in the practice of the invention, and thus can be considered to constitute examples of modes for its practice. However, those of skill in the art should, in light of the present disclosure, appreciate that many changes can be made in the specific embodiments which are disclosed and still obtain a like or similar result without departing from the spirit and scope of the invention.

Example 1

Experimental conditions for nano field effect transistor

Devices are fabricated with graphene as the carrier channel of a two-terminal NFET without a physical gate terminal.

The polymer is disposed on graphene, typically less than 0.5mm thick, and then separated from the catalytic substrate on which the graphene is grown. A flexible polymer platform for a sensing system is used for a graded graphene polymer composite and two metal electrical contacts. The graphene polymer composite is bonded to a flexible polymer platform. A solution of the desired linker molecules is deposited on the graphene polymer complex for incubation. Removing the excess linking group molecule solution from the graphene polymer composite material; and two metal electrical contacts are deposited on two edges of the graphene polymer composite.

The graphene polymer composite is then placed on a polymer substrate, such as polytetrafluoroethylene, polyimide, etc., and then heated at 80-150 degrees celsius for 1-10 minutes to remove any impurities.

The GFET sensor is then ready for use. In some cases, receptors for a particular analyte are deposited on the graphene layer.

A sensor system for analyte sensing by sweat, wherein the sensor comprises:

o a flexible polymer platform made of (polyimide);

the o-graphene polymer composite is bonded to a flexible polymer platform;

the source and drain electrodes in the sensor configuration located on opposite edges of the graphene polymer composite layer are also bonded to the flexible polymer platform;

o each of the source electrode and the drain electrode is composed of a conductive metal;

the o-graphene polymer composite layer is functionalized with linker molecules for the desired analyte biosensing between the two electrodes; and

the o-sensor system is analyzed in close proximity to the original sweat source.

A method of determining analyte concentration by sweat comprising the steps of:

applying a constant bias voltage to the functionalized graphene polymer composite sensor with the conductive channel;

o measuring a first source-drain voltage across the sensor;

exposing the conductive pathway to the primary sweat by placing the conductive pathway in proximity to a source of sweat;

the analyte binds to the linker molecule by releasing electrons into the channel through the linker, resulting in a change in the potential on the channel;

o measuring a second source-drain voltage across the sensor;

determining the concentration of the analyte based on a small change between the first source-drain voltage and the second source-drain voltage.

During analysis, a fixed current or voltage is passed through the sensor. The electrical response of the GFET sensor to analytes in polar solution was recorded using the analyte in Deionized (DI) water as a negative control. DI water response on the functionalized GFET was also measured. Analytes include NaCl, D-glucose and lactate.

Example 2

Analysis of NaCl samples

In these examples, a fixed current or voltage is passed through the GFET. The electrical response of the GFET sensor was recorded as follows: naCl concentration in DI water, or DI water response on functionalized GFET.

Selectivity is: the response of various NaCl concentrations in DI water was measured on a GFET to investigate the sensitivity of the sensor to NaCl. Solutions with varying concentrations of NaCl were prepared at 0 to 1g/L in DI water. The test started with the introduction of 2ul of the lowest concentration on the GFET, followed by the next higher concentration after 3 minutes, and so on; for example, in the example shown in FIG. 6, the ratio was changed from 0.05g/L to 0.1g/L. This continues until all concentrations are introduced into the GFET.

Fig. 6 shows that GFET did not respond significantly to DI water alone, but linearly to increasing NaCl concentration in DI water. The increased concentration changes the voltage on the channel, showing high selectivity to NaCl in DI water as a control.

Sensitivity of the probe: the response of various NaCl concentrations in DI water was also measured on a GFET to investigate the sensitivity range of the sensor to NaCl. Solutions with exponentially increasing NaCl concentrations were prepared, ranging from 0.1ng/dL to 10mg/dL in DI water. The test started with the introduction of 2ul of the lowest concentration on the GFET, followed by the next higher concentration after 3 minutes, and so on. Here, the concentration increases logarithmically, e.g., from 0.1ng/dl to lng/dl, then 10ng/dl, then 0.1ug/dl, and so on. This continues until all concentrations are introduced into the GFET.

Fig. 7 shows that GFET did not respond significantly to DI water alone, but started responding exponentially from the lowest to the highest concentration of NaCl in DI water. The increase in concentration changes the voltage on the channel, thereby showing a high sensitivity to NaCl in DI water at about 250 femtograms/liter as a control.

Chloride response in sweat: the chloride concentration in human sweat is measured with a human subject. The test requires the subject to perform a physical activity, such as running, and not to take water to moisturize.

GFET is worn by human subjects on the forearm and lower back (eccrine sweat glands). The electrical response due to chloride concentration in sweat is continuously transmitted and recorded (every 500 milliseconds) while the subject is engaged in intense physical activity (e.g., running). The observed change in chloride concentration in sweat is represented by a small change in voltage, as shown in fig. 8.

Figure 8 shows the real-time concentration of sweat osmolality for two human subjects using PFGFET attached to skin. Osmolality in sweat is directly related to the physical performance of the individual. Object 1 is a sprint and object 2 is a jogger. The sprint runner (object 1) runs the same distance at a faster speed (run 1) than the joggers (objects 2 and 2). The more intense the physical activity of the subject was observed, the higher the measured body weight osmolality. Peak body weight osmolality was observed during the most intense physical activity. A decrease in body weight osmolality during intense physical activity is also observed. This is caused in the event that the subject ingests too much water without sufficient supplementation of salt. In the data, when the slope of the curve goes towards 0, it indicates hyponatremia during which the body attempts to retain as much salt as possible (to maintain ionic balance), so the overall osmolarity changes very slowly.

The following novel results and/or features are observed.

High selectivity: GFET (NFET) regulated by PFGT produces a highly selective response to NaCl concentration in different control fluids: (>97％)。

High sensitivity: GFET functionalized with PBA has a high sensitivity to NaCl with a limit of detection (LOD) of 250 femtograms/liter. GFET sensors have high signal-to-noise ratios, have high selectivity, and are highly sensitive to surface area, surface and/or electrical field due to the high surface area for bondingThere is higher bonding between the molecules. All these factors act as great differences, making GFETs highly sensitive.

Gate modulation by polar molecules: in polar fluids (e.g., water, salt, etc.), polar molecules (e.g., ions, etc.) are observed to form a Polar Fluid Gate Terminal (PFGT) on the NFET. Polar molecules near the surface of the graphene induce a dielectric effect, thereby generating a charge transfer channel. The gating strength of PFGT depends on both the charge and the concentration of polar molecules in the fluid. This third Polar Fluid Gate Terminal (PFGT) modulates the electrical response of the NaCl concentration in the polar fluid.

Continuous monitoring: the concentration of ions in the fluid is continuously measured due to the modulation of the NFET channel current from the gate terminal of the induced polar fluid. Once the ionic solution is removed from the surface of the NFET, the electrical response of the polar fluid-gated NFET returns to the bare or initial value.

Induced motion of polarized fluid on NFET surface: it was observed that the polar fluid (such as NaCl in DI water) would attempt to repel or lift off the NFET surface immediately due to the increased hydrophobicity between the NFET surface and the polar fluid. The higher the concentration of polar molecules (e.g., naCl) in the fluid, the greater the strength of the PFGT and thus the greater the repulsive effect. This repulsion effect, combined with the modulation of the electrical response induced by PFGT by NaCl molecules on NFETs, allows for highly sensitive, selective and continuous monitoring of the electrolyte system.

Real-time continuous chloride monitoring in human sweat: for example, human subjects wear GFET on the forearm and lower back (eccrine sweat glands). Sweat is diluted and ultrafiltered blood. The electrical response due to the chloride concentration in sweat was continuously transmitted and recorded (every 500 milliseconds) while the subject was performing a) intense physical activity (exercise) b) without intense physical activity (such as sitting at a desk and eating). Background ion concentrations in sweat (mainly NaCl) were observed to form PFGT on both terminal GFET devices. From Cl ^- The ion-induced change in the gated strength of PFGT induced on GFET allows continuous non-invasive monitoring of Cl ion molecules in human sweat. Sweat was observed to be a very good electrodeSex fluid, the chloride concentration can be measured continuously because it is very dilute and ultrafiltered.

Example 3

Analysis of D-glucose samples

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

The electrical response of the GFET/PBA sensor is recorded as follows:

d-glucose concentration in oDI Water

D-glucose concentration in artificial sweat (DI + NaCl + lactic acid)

Concentration of D-glucose in DI Water on O-non-functionalized GFET

Lactose concentration in DI Water on o-functionalized device (control 1)

Concentration of Artificial sweat on o-functionalized devices (control 2)

DI water response on o-functionalized GFET

o measurement of glucose in human sweat: real-time continuous monitoring of glucose concentration in human sweat was performed using wearable GFET/PBA sensors. Correlating real-time continuous sweat glucose response to blood glucose measurement using a commercially available blood glucose meter

Functionalization: for example, graphene FETs are functionalized with linker molecules (locks) that specifically bind glucose molecules in the fluid. For example, GFET is functionalized with pyreneboronic acid (PBA). Pyreneboronic acid was bonded to the graphene surface using pi-pi bonding. PBA forms reversible boron-anion complexes with D-glucose. The preparation method comprises the following steps:

the polymer is placed on graphene, typically less than 0.5mm thick, and then separated from the catalytic substrate on which it is grown.

The graphene polymer composite is then placed on a polymer substrate, such as polytetrafluoroethylene, polyimide, etc., and heated at 80-150 degrees celsius for 1-10 minutes to remove any impurities.

The graphene polymer was then introduced into the PBA solution for 5-20 minutes to functionalize 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 a GFET to investigate the sensitivity of the functionalized sensor to D-glucose.

Solutions were prepared with different concentrations of D-glucose (0.1 to 100mg/dL in DI water) and different concentrations of lactose were prepared in DI water. The test started with the introduction of 5ul of the lowest concentration on the GFET, followed by the introduction of the next highest concentration after 3 minutes, and so on. This continues until all concentrations are introduced into the GFET.

Fig. 9 shows that GFET did not respond significantly to DI water or lactose solution, but exponentially to increased D-glucose concentration in DI water. The increased concentration changes the voltage on the channel, thereby exhibiting high selectivity to D-glucose versus DI water as a control.

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

Solutions with different concentrations of D-glucose from 0.1 to 100mg/dL were prepared in DI water and NaCl, respectively. The test started with the introduction of the lowest concentration of 5ul on the GFET, followed by the next higher concentration after 3 minutes, and so on. Here, the concentration increases logarithmically. This continues until all concentrations are introduced into the GFET.

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

Selective measurement of glucose response in NaCl solutions: the response of various D-glucose concentrations in NaCl was measured on a GFET to investigate the sensitivity of the functionalized sensor to D-glucose.

Solutions were prepared with varying concentrations of D-glucose (0.1 to 100 mg/dL) in NaCl solution, and varying concentrations of NaCl in DI water. The test started with the introduction of the lowest concentration of 5ul on the GFET, followed by the next higher concentration after 3 minutes, and so on. Here, the concentration increases logarithmically. This continues until all concentrations are introduced into the GFET.

Fig. 11 shows that GFET has no significant response to NaCl-only solutions, while the comparative increased NaCl concentration solution exhibits a linear response to the increased D-glucose concentration in the fixed NaCl concentration solution. The increase in concentration changes the voltage on the channel, thereby exhibiting high selectivity for D-glucose. GFET (NFET) functionalized with PBA produced a highly selective response (> 95%) to glucose concentration.

Fig. 11 gives the idea that the functionalized glucose sensor is not sensitive to NaCl (because the orange curve is rather flat), whereas the glucose curve increases with increasing concentration of glucose present in the NaCl solution.

Sensitivity measurement of D-glucose response in DI water: the response of various D-glucose concentrations in the DI was measured on a GFET to investigate the sensitivity range of the functionalized sensor to D-glucose.

Solutions were prepared with exponentially increasing glucose concentrations (250 ng/l to 100 ng/l in DI water). The test started with 3 rounds of 5ul DI water introduction every 3 minutes, followed by a minimum concentration of 5ul on the GFET, followed by the next higher concentration after 3 minutes, and so on. Here, the concentration increases logarithmically; for example, from 0.25pg/l, then 2.5pg/l, and so on. This continues until all concentrations are introduced into the GFET.

Fig. 12 shows that the GFET exhibited no significant response to DI water alone, but exhibited a linear response starting from the lowest concentration to the highest concentration, with the current in the channel changing as the concentration increased, thereby exhibiting about 250 femtograms/liter (i.e., 1.38 e) for D-glucose ^-12 mmol/l) of the sample.

Step of functionalization: shown in fig. 13 is the current response of the graphene sensor before functionalization, after functionalization, and after introduction of glucose on the sensor. This is useful for understanding each stage of the GFET manufacturing step and how the current response of the GFET changes after each stage. For example, as shown in fig. 13, the current response increased after functionalization (orange) compared to before functionalization (blue) because the linker molecule is bound by a pi-pi bondAnd the total charge on the graphene surface increases. The linker molecule, by using these charge clouds, attracts and binds the glucose molecule, thereby reducing the current on the GFET compared to its previous state.

D-glucose response in sweat and blood: glucose concentration in human sweat is measured with a human subject. The test requires the subject to perform physical activity, such as running, using a blood glucose meter every few minutes and to take a blood sample to measure blood glucose. GFET is worn by human subjects on the forearm and lower back (eccrine sweat glands). The electrical response due to the D-glucose concentration in sweat is continuously transmitted and recorded (every 500 milliseconds) while the subject is engaged in intense physical activity (e.g., running).

In this particular case, the physical activity is eating. As the subject begins to sit, his glucose will begin to rise, as can be seen from sweat and blood glucose. After the person finishes eating, the glucose level will begin to drop and stabilize.

In the case of running, when a person begins running, the body uses glucose and breaks it down to gain exercise energy. Therefore, you will see a decrease in glucose. However, after a period of time, your body insulin starts to work and the overall blood glucose level will start to rise again.

Fig. 14 shows the change in D-glucose concentration in sweat, represented by a small change in voltage.

The blood glucose data in fig. 15 is also plotted against time throughout the exercise period. The sweat glucose measurement is correlated to the blood glucose measurement. Here, sweat glucose values for corresponding blood glucose values are plotted against blood (blood versus sweat) to obtain a correlation R ² It provides an idea of how well sweat glucose matches blood glucose.

Fig. 16 also shows the measurement correlation between blood glucose and sweat glucose. Here, 3 different sensors are used for the same person at the same time. Over 150 sweat profiles were collected from 10 human subjects over the entire study periodAnd their blood glucose for correlation. The subject performs physical activity (exercise, running, etc.) or does not perform physical activity (sitting on a table, etc.). For these 150 curves, the calculated correlation between sweat and blood is R ² =84%, also shown in the figure

The following novel results and/or features are observed.

High selectivity: GFET (NFET) functionalized with PBA produces a highly selective response to glucose concentration in different control fluids: (>95％)。

High sensitivity: GFET functionalized with PBA exhibits high sensitivity to D-glucose with a limit of detection (LOD) of 250 femtograms/liter, i.e., 1.38e ^-12 mmol/l. The LOD of the existing glucometer is between 0.3 and 1.1 mmol/l. GFET functionalized with PBA is about 1010 times more sensitive than existing standard glucose measurement devices. GFET sensors have a high signal-to-noise ratio, have high selectivity, and, due to the high surface area for bonding, there is a higher bond between the surface and the receptor molecule. All these factors play a large differential role in making GFETs highly sensitive.

Gate modulation by polar molecules: in polar fluids (e.g., water, salt, etc.), polar molecules (e.g., ions) are observed to form a Polar Fluid Gate Terminal (PFGT) on the NFET. Polar molecules near the surface of the graphene induce a dielectric effect, thereby generating a charge transfer channel. The gating strength of PFGT depends on the charge and concentration of polar molecules in the fluid. This third Polar Fluid Gate Terminal (PFGT) regulates the electrical response from the glucose concentration in the polar fluid.

Continuous blood glucose monitoring: charge modulation greatly enhances the reversibility of PBA-glucose bonds on graphene surfaces due to the polar fluid gate terminal on NFETs formed in a polar fluid. The higher the concentration of polar molecules (e.g., ions, etc.) in the polar fluid, the greater the reversibility of the PBA-D-glucose bonds is observed. Once the concentration of glucose bound on the sensor is higher than that in sweat, the glucose molecules are detached from the PBA due to its Gibbs free energy, a reversible nature is observed,this is clearly seen in the electrical response recorded in fig. 14, as the concentration of glucose drops instantaneously. This allows for reusable real-time continuous monitoring of D-glucose molecules in polar fluids.

Reusability of glucose sensors due to movement of polar fluids on the sensor surface: it was observed that the movement of a polar fluid (such as glucose in salt) on the NFET enhanced the removal of bound glucose molecules from the linker molecules. As an example, when the glucose solution is removed from the graphene surface in the GFET, the electrical response of the GFET returns to a bare value.

Induced motion of polarized fluid on NFET surface: it was observed that the polar fluid (e.g., glucose in salt) would attempt to repel or lift off the NFET surface immediately due to the increased hydrophobicity between the NFET surface and the polar fluid. The higher the concentration of polar molecules in the fluid, the greater the strength of the PFGT and therefore the greater the repulsive effect. This repulsive effect, combined with the removal of bound glucose molecules (described above in section e) and the modulation of the electrical response due to PFGT on NFETs, allows for highly sensitive, selective and continuous monitoring of the glucose system.

Real-time continuous blood glucose monitoring in human sweat: GFET functionalized with PBA was worn by human subjects on the forearms and lower back (eccrine sweat glands). Sweat is diluted and ultrafiltered blood. The electrical response due to glucose concentration in sweat is continuously transmitted and recorded (every 500 milliseconds) while the subject is performing: a) Intense physical activity (exercise) and b) no intense physical activity (such as eating in front of a desk). Sweat glucose response is related to blood glucose readings taken every few minutes using a blood glucose meter over the length of the activity (typically 20 minutes to over 6 hours). Background ion concentrations (mainly NaCl) in sweat were observed to form PFGT on both terminal GFET/PBA devices. The enhanced reversibility between PFGT, PBA and D-glucose bonds on GFET allows continuous non-invasive monitoring of glucose molecules in human sweat. Calculate 84% (R) between blood glucose and sweat glucose measurements ² ) The correlation of (c). Computing at various physical activitiesCorrelation of more than 150 sweat glucose responses collected from 10 human subjects under conditions. Sweat is observed to be a very good polar fluid, allowing continuous glucose measurement because it is very dilute and ultrafiltered.

Example 4

Analysis of lactic acid samples

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

Functionalization: graphene FETs are functionalized with linker molecules (locks) that specifically bind lactic acid molecules in the fluid. For example, GFET was functionalized with lactate oxidase (LOx) to the graphene surface using the intermediate pyrene-NHS ligation chemistry.

The o-polymer is disposed on graphene, typically less than 0.5mm thick, and then separated from the catalytic substrate on which the graphene is grown.

The graphene polymer composite is then placed on a polymer substrate, such as polytetrafluoroethylene, polyimide, etc., and heated at 80-150 ℃ for 1-10 minutes to remove any impurities.

o then the graphene polymer was introduced into the pyrene-NHS solution for 5-20 minutes to functionalize at room temperature.

o graphene polymer was then introduced into the LOx solution and combined for 520 minutes at room temperature.

After the functionalization step, the sensor is ready for use.

The electrical response of the GFET/LOx sensor is recorded as follows:

lactic acid concentration in oDI Water

Concentration of lactic acid in artificial sweat (DI + NaCl + glucose)

o lactic acid concentration in NaCl on non-functionalized GFET

o lactic acid concentration in NaCl on functionalized GFET

Concentration of Artificial sweat on o-functionalized devices (control 2)

DI water response on o-functionalized GFET

Selective measurement of lactate response in DI Water: the response of various lactate concentrations in the DI was measured on a GFET to investigate the sensitivity of the functionalized sensor to lactate. Preparation in DI waterSolutions with varying concentrations of lactic acid ranging from 0 to 25mM were prepared. The test started with the introduction of 2ul of the lowest concentration on the GFET, followed by the introduction of the next highest concentration after 3 minutes, and so on. This continues until all concentrations are introduced into the GFET.

Fig. 17 demonstrates that GFET does not respond significantly to DI water alone and that the polynomial response to the increase in lactic acid concentration in DI water, which changes the voltage across the channel, demonstrates high selectivity to lactic acid in DI water, using DI water as a control.

Selective measurement of lactate response in various solutions: the response of various concentrations of lactate in various solutions was measured on a GFET to study the sensitivity of functionalized sensors to lactate and the response to non-functionalized sensors. Solutions with different concentrations of lactic acid of 0-25mM were prepared in NaCl and NaCl-glucose. The test started with the introduction of 2ul of the lowest concentration on the GFET, followed by the next highest concentration after 3 minutes, and so on. This continues until all concentrations are introduced into the GFET, separately for each solution.

Fig. 18 shows that GFET did not respond significantly to NaCl only or NaCl-glucose controls, while exhibiting a polynomial response to increasing lactate concentrations in NaCl and NaCl-glucose solutions. The increase in concentration changes the voltage across the channel, thereby exhibiting high selectivity to lactic acid. The non-functionalized sensor did not respond significantly to the lactate NaCl solution, further emphasizing the selectivity and sensitivity of the sensor to lactate.

Lactic acid response in NaCl vs. DI Water: the response of various lactate concentrations in DI water and NaCl solution was measured on a GFET to investigate the sensitivity of the functionalized sensor to lactate in DI water and lactate in NaCl, and to understand the effect of NaCl solution. Solutions of lactic acid (0.1 to 100 mg/dL) were prepared at different concentrations in DI water and NaCl, respectively. The test started with the introduction of 2ul of the lowest concentration on the GFET, followed by the next higher concentration after 3 minutes, and so on. This continues until all concentrations are introduced into the GFET.

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

Lactic acid functionalization step by GFET fabrication visualization: the current response of the graphene sensor before functionalization, after functionalization and after incorporation of lactate into the sensor is shown in fig. 20. This is useful for understanding each stage of the GFET manufacturing step and how the current response of the GFET changes after each stage. 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 the lactic acid molecule compared to its previous state, thereby reducing the current on the GFET.

The following novel results and/or features are observed.

High selectivity: GFET (NFET) functionalized with LOx produces a highly selective response to lactate concentration in different control fluids: (>94％)。

High sensitivity: GFET functionalized with pyrene NHS has high sensitivity to lactic acid with a limit of detection (LOD) of 250 femtograms/liter; i.e. 2.78e ^-12 mmol/l. The LOD of the existing lactic acid meter is between 0.001 and 10 mmol/l. GFET functionalized with pyrene NHS is about 108 times more sensitive than existing standard lactate measurement devices. GFET sensors have a high signal-to-noise ratio, have high selectivity, and, due to the high surface area for bonding, there is a higher bond between the surface and the receptor molecule. All these factors play a great differential role in making GFETs highly sensitive.

Gate modulation by polar molecules: in polar fluids (e.g., water, salt, etc.), polar molecules (e.g., ions) are observed to form a Polar Fluid Gate Terminal (PFGT) on the NFET. Polar molecules near the surface of the graphene induce a dielectric effect, thereby generating a charge transfer channel. The gating strength of PFGT depends on the charge and concentration of polar molecules in the fluid. This third Polar Fluid Gate Terminal (PFGT) modulates the electrical response from the concentration of lactic acid in the polar fluid.

Induced motion of polarized fluid on NFET surface: it was observed that the polar fluid (such as lactic acid in artificial sweat) would attempt to repel or break away from the NFET surface immediately due to the increased hydrophobicity between the NFET surface and the polar fluid. Flow ofThe higher the concentration of polar molecules in the body, the greater the strength of the PFGT and therefore the greater the repellent effect. This repulsive effect, combined with the modulation of the electrical response caused by PFGT on the NFET, allows for highly sensitive, selective and continuous monitoring of the lactic acid system.

Example 5

Other analysis

Sweat salt concentration correlation: figure 21 shows the response of a sweat sensor 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. At the start of the test 2ul of the lowest concentration (e.g. 0.1 mg/dl) was added dropwise, followed by the next higher concentration (e.g. 0.2 mg/dl) and so on at 3 minute intervals. The corresponding small change in voltage is measured. This procedure was repeated for 10 different sensors, with a maximum error of 15% being observed. This serves as a model for the correlation between sodium sweat and the corresponding voltage change.

Sweat glucose concentration correlation: fig. 22 shows the response of a sweat sensor 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 starts with the addition of 5ul 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 small change in voltage is measured. This procedure was repeated for 10 different sensors, with a maximum error of 5% being observed. This serves as a model for the correlation between sweat glucose and the corresponding voltage change.

Transconductance curve: fig. 23 shows the transconductance curves of a PFGT device.

NaCl solutions at concentrations ranging from 0.1ng/dl to 1mg/dl were added dropwise to the sensor every 3 minutes. The test started with the addition of 2ul of the lowest concentration (e.g. 0.1 ng/dl) and then the next higher concentration (1 ng/dl) was decreased and so on for a 3 minute interval.

When a polar fluid is introduced, a debye layer is formed on the graphene sensor and a gating effect is observed, both the debye length and the gating effect being a function of the polar molecule concentration. For the initial concentration of NaCl solution, DI was more dominant, thereby generating more holes and we seen a voltage drop. However, after a few drops, as the NaCl concentration in the solution increases, it becomes more dominant and more electrons are generated near the debye layer, exhibiting an increase in voltage.

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

The various methods and techniques described above provide a number of ways to implement the present invention. Of course, it is to be understood that all of the objects or advantages described may be achieved in accordance with any particular embodiment described herein. Thus, for example, those skilled in the art will recognize that the methods may be performed in a manner that achieves or optimizes one advantage or group of advantages as taught herein without necessarily achieving other objectives or advantages as may be taught or suggested herein. Various advantageous and disadvantageous alternatives are mentioned herein. It should be understood that some preferred embodiments specifically include one, another or several advantageous features, while other preferred embodiments specifically exclude one, another or several disadvantageous features, while other preferred embodiments specifically mitigate one existing disadvantageous feature, another or several advantageous features by including one.

Furthermore, the skilled person will recognise the applicability of various features from different embodiments. Similarly, various elements, features and steps discussed above, as well as other known equivalents for each such element, feature or step, can be mixed and matched by one of ordinary skill in this art to perform methods in accordance with principles described herein. Among the various elements, features and steps, some will be specifically included and others will be specifically excluded in different embodiments.

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

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

In some embodiments, numbers expressing quantities of ingredients, properties such as molecular weight, response conditions, and so forth, used to describe and claim certain embodiments of the invention are to be understood as being modified in certain instances by the term "about". Accordingly, in some embodiments, the numerical parameters set forth in the written description and attached claims are approximations that may vary depending upon the desired properties sought to be obtained by a particular embodiment. In some embodiments, 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 invention are approximations, the numerical values set forth in the specific embodiments are reported as precisely as possible. Numerical values presented in some embodiments of the invention may include certain errors necessarily 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 particular embodiments of the invention (especially in the context of certain of the following claims) may be construed to cover both the singular and the plural. Recitation of ranges of values herein are merely intended to serve as a shorthand method of referring individually to each separate value falling within the range. Unless otherwise indicated herein, each individual value is incorporated into the specification 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 (e.g., "such as") provided with respect to certain embodiments herein, is intended merely to better illuminate the invention and does not pose a limitation on the scope of the invention claimed. No language in the specification should be construed as indicating any non-claimed element as 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 make any combination of references and requirements, alone or with other members of the group or other elements found herein. One or more group members may be included in or deleted from the group for reasons of convenience and/or patentability. When any such inclusion or deletion occurs, the specification is considered herein to include the modified group, thereby enabling the written description of all markush groups used in the appended claims.

Preferred embodiments of the present invention are described herein. Variations of those preferred embodiments may become apparent to those of ordinary skill in the art upon reading the foregoing description. It is contemplated that skilled artisans may employ such variations as appropriate, and 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.

In addition, throughout the specification, many references have been made to patents and printed publications. Each of the references and printed publications cited above is incorporated by reference herein in its entirety.

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 may be 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. Thus, embodiments of the invention are not limited to those precisely as shown and described.

Claims

1. A field effect transistor, comprising:

a drain electrode;

a source electrode;

an electrically insulating substrate;

a polar fluid induced gate terminal resulting from exposure of the polar fluid to the nanoscale material layer,

wherein:

the polar fluid comprises a target analyte; and

2. The field effect transistor of claim 1, wherein a constant current supplied by a constant current source or a constant voltage supplied by a constant voltage source is applied between the source electrode and the drain electrode.

3. The field effect transistor of claim 1 or 2, wherein the nanoscale material comprises graphene, CNT, moS ₂ Boron nitride, a metal disulfide, a phospholene, a nanoparticle, a quantum dot, a fullerene, a 2D nanoscale material, a 3D nanoscale material, a 0D nanoscale material, a 1D nanoscale material, or any combination thereof.

4. The field effect transistor of any of claims 1-3, wherein the polar fluid comprises a solution having polar molecules, a gas having polar molecules, a target sensing analyte, or a combination thereof.

5. The field effect transistor of any of claims 1-4, wherein the polar fluid comprises sweat, breath, saliva, cerumen, urine, semen, plasma, biological fluid, chemical fluid, air sample, gas sample, or a combination thereof.

6. The field effect transistor of any of claims 1-5, wherein the target analyte comprises an electrolyte, glucose, lactate, IL6, cytokine, HER2, cortisol, ZAG, cholesterol, vitamin, protein, drug molecule, metabolite, polypeptide, amino acid, DNA, RNA, aptamer, enzyme, biological molecule, chemical molecule, synthetic molecule, or a combination thereof.

7. The field effect transistor of any of claims 1-6, further comprising:

8. The field effect transistor of claim 7, wherein the acceptor comprises 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.

9. A method for sensing a target analyte in a polar fluid, comprising:

a drain electrode;

a source electrode;

an electrically insulating substrate;

a polar fluid induced gate terminal resulting from the polar fluid being exposed to the nanoscale material layer, wherein the polar fluid includes a target analyte and has a charge concentration sufficient to induce a polar fluid gate voltage that optimizes a gate voltage as a function of channel current characteristics of the field effect transistor for detection of the analyte;

10. A system, comprising:

a field effect transistor; and

a constant current source or a constant voltage source electrically connected to the field effect transistor, wherein the field effect transistor comprises:

a drain electrode;

a source electrode;

an electrically insulating substrate;

the polar fluid comprises a target analyte; and