JP7449333B2 - Field-effect device gated by polar fluid - Google Patents

Description

Cross-reference to related applications This application is filed on June 30, 2016 with the title “DETECTION OF IONIC CONCENTRATION IN FLUID USING NANOSCAL.”
US Provisional Patent Application No. 62/356,729 entitled “MATERIALS VIA A CAPACITIVE RESPONSE” and “LACTATE-OXIDASE-FUNCTIONALIZED GRAPHENE POLYMER C” filed on June 30, 2016. OMPOSITES FOR LABEL-FREE DETECTION OF LACTATE IN SWEAT 62/356,742, each of which is hereby incorporated by reference in its entirety. It is used in

FIELD OF THE INVENTION The invention disclosed herein relates generally to the design, fabrication, and applications of polar fluid gated nanoscale field effect transistors (NFETs), and in particular graphene field effect transistors (GFETs). The present disclosure also relates generally to chemical and biological sensing using field effect transistors, and more particularly to chemical and biological sensing using field effect transistors with biochemically sensitive channels including graphene. Also related to chemical sensing.

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

The source (S) is where the carrier enters the channel. The drain (D) is where the carrier leaves 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 the source and drain is controlled.

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

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

In one aspect, a field effect transistor is disclosed herein. A field effect transistor includes 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. the scale material layer and the channel are created by a nanoscale material layer extending between and electrically connected to a drain electrode and a source electrode, and a polar fluid exposed to the nanoscale material layer; and a polar fluid induced gate terminal. In some embodiments, the polar fluid includes the 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 versus channel current characteristics of the field effect transistor in response to the target analyte.

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

In some embodiments, the nanoscale material is graphene, CNT, _MoS2 , boron nitride, metal dichalcogenide, phosphorene, nanoparticle, quantum dot, fullerene, 2D nanoscale material, 3D nanoscale material, 0D nanoscale material , 1D nanoscale materials, or any combination thereof.

In some embodiments, the polar fluid includes 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, plasma, biological fluids, chemical fluids, air samples, gas samples, or combinations thereof. The field effect transistor according to any one of the items.

In some embodiments, target analytes include electrolytes, glucose, lactate, IL6, cytokines, HER2, cortisol, ZAG, cholesterol, vitamins, proteins, drug molecules, metabolites, peptides, amino acids, DNA, RNA, aptamers, including enzymes, biomolecules, chemical molecules, synthetic molecules, or combinations thereof.

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

In some embodiments, the receptor is pyreneboronic acid (PBA), pyrene N-hydroxysuccinimide ester (pyrene-NHS), an organic chemical, an aromatic molecule, a cyclic molecule, an enzyme, a protein, an antibody, a virus, a single chain Includes DNA (ssDNA), aptamers, inorganic materials, synthetic molecules, and biomolecules.

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

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

In one aspect, disclosed herein is a method for sensing a target analyte in a polar fluid. The method includes exposing a polar fluid sample to a field effect transistor, the field effect transistor having a drain electrode; a source electrode; an electrically insulating substrate; an electrically conductive and chemically sensitive substrate disposed on the substrate; a nanoscale material layer at least partially defining a channel, the nanoscale material layer and the channel extending between and electrically connected to a drain electrode and a source electrode; a polar fluid-induced gate terminal created by a polar fluid exposed to a layer of nanoscale material, the polar fluid containing the target analyte and detecting the analyte by controlling the gate voltage versus channel current of the field effect transistor; 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 a concentration of a target analyte in the polar fluid based on the first and second source-drain voltages.

In some embodiments, the nanoscale materials include graphene, CNTs, MoS, 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, where the receptor layer includes a receptor that targets the target analyte.

In some embodiments, the receptor is pyreneboronic acid (PBA), pyrene N-hydroxysuccinimide ester (pyrene-NHS), an organic chemical, an aromatic molecule, a cyclic molecule, an enzyme, a protein, an antibody, a virus, a single chain Includes DNA (ssDNA), aptamers, inorganic materials, synthetic molecules, and biomolecules.

In some embodiments, target analytes include electrolytes, glucose, lactate, IL6, cytokines, HER2, cortisol, ZAG, cholesterol, vitamins, proteins, drug molecules, metabolites, peptides, amino acids, DNA, RNA, aptamers, including enzymes, biomolecules, chemical molecules, synthetic molecules, or combinations thereof.

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

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

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

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

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

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

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

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

A constant current or constant voltage source that is electrically connected to a field effect transistor. A field effect transistor comprises: a drain electrode; a source electrode; an electrically insulating substrate; a nanoscale material layer disposed on the substrate that at least partially defines an electrically conductive and chemically sensitive channel; and a nanoscale material layer, wherein the channel extends between and is electrically connected to the drain and source electrodes; and a gate terminal. In some embodiments, the polar fluid includes the target analyte. In some embodiments, the polar fluid has a charge concentration sufficient to induce a polar fluid gate voltage that optimizes the gate voltage for 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, a constant voltage source maintains a constant voltage across a 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 processes a smartphone, tablet computer, smart watch, in-car entertainment system, laptop computer, desktop computer, computer terminal, television system, e-book reader, wearable device, or digital input. including any other type of computing device.

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

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

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

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

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

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

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

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

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

FIG. 3B illustrates an exemplary embodiment showing a polar fluid gate terminal with polar fluid flowing in a first direction.

FIG. 3C illustrates an exemplary embodiment showing a polar fluid gate terminal with polar fluid flowing in a second direction.

FIG. 4A illustrates an exemplary embodiment showing the base device illustrated in FIGS. 2A-2D with a 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. The 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 a 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 response in DI water.

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

FIG. 8 illustrates an exemplary embodiment showing 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 D-glucose responses 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 response in various solutions.

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

FIG. 20 illustrates an exemplary embodiment showing the lactic acid functionalization step visualized by GFET fabrication.

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

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

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

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

Graphene possesses significant mechanical resistance, which allows monolayer or bilayer thicknesses to be subjected to significant 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 offered 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), with transparency higher than 90% and better than 100% after proper processing. It also results in fewer atomic layers with lower sheet resistance.

As illustrated in FIG. 1A, graphene FETs are generally fabricated on a Si wafer covered with a SiO2 layer, and the graphene forms the transistor channel. The graphene transistor consists of three terminals, source and drain metal electrodes that contact the graphene channel, and a global backgate enabled by a doped Si substrate. These features facilitate graphene's characteristic ambipolar transport behavior in Grat-FETs - achieving both n-type and p-type transport when biased with the proper gate voltage at the substrate. Any applicable method can be applied to fabricate 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 varying the direction and magnitude of the gate voltage, the resulting current curve between the source and drain takes a "V" shape. Small changes in gate voltage at the tip of the V-curve result in significant and detectable changes in the channel current ( _IDS ), which tends to flatten out at the two end points of the V-curve.
gateless field effect transistor

In one aspect, a new type of field effect transistor (FET) without a physical gate is disclosed herein.

2A through 2D illustrate various embodiments of FETs without physical gates. FIG. 2A illustrates an exemplary graphene-based FET 210 including a substrate 1 , a source electrode 2 , a drain electrode 3 , a receptor 4 , a graphene layer 5 , and a backside polymer 6 . As disclosed herein, the substrate 1 can be made of polyamide, PET, PDMS, PMMA, other plastics, silicon dioxide, silicon, glass, aluminum oxide, sapphire, germanium, gallium arsenide, indium phosphide, silicon. It can be an alloy with germanium, a fabric, a textile, a silk, a paper, a cellulose-based material, an insulator, a metal, a semiconductor, 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 interelectrode 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 Includes, but is not limited to, gels, conductive inks, and non-metallic conductive materials.

The drain electrode 3 is an electrode on the opposite side of the source electrode 2. Exemplary materials that can be used as 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, and non-metallic conductive materials.

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

In some embodiments, the graphene layer 5 may be an epitaxial layer, and the substrate for the graphene layer may be a substrate on which the graphene layer is epitaxially grown. By leaving the graphene layer on the substrate for growth, we do not necessarily have to deal with typically nano-thin graphene layers and structures. The risk of damaging the thin graphene layer during transistor fabrication is also reduced if the graphene layer can remain 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, graphene layer 5 and/or certain types of chemicals are thus prevented from reaching the chemically sensitive channels. Surface treatment may include deposition of metal particles and/or polymers.

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

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, with one atom forming each vertex. It is the basic structural element of other allotropes, including graphite, charcoal, carbon nanotubes, and fullerenes. It can be thought of as an infinitely large aromatic molecule, the final case of the family of flat polycyclic aromatic hydrocarbons. In some embodiments, graphene is a single layer of carbon atoms. Each carbon atom in graphene has four electrons. Through three of these electrons, the carbon atom bonds to its three nearest neighbors, forming a hexagonal lattice. For each atom, four electrons are delocalized over the entire graphene layer, allowing conduction of electron current.

When a polar fluid is deposited on the graphene layer, the special electronic properties of graphene will cause charge rearrangement in the polar fluid to form a liquid-induced gate voltage, which increases the voltage 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 moving. As illustrated, the charge of the polar or ionic component is redistributed within 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 noted, at the tip of the V-curve, a small change in gate voltage can result in a significant and detectable change in the channel current ( _IDS ), which flattens out at the two end points of the V-curve. There is a tendency to A shift toward the tip of the V-curve can result in increased sensitivity, allowing very small changes in voltage to be detected in response to changes in current. Similarly, very small changes in current in response to changes in voltage can also be detected.

As mentioned above, a shift towards the tip of the V-curve can result in better sensitivity. Such a shift can be caused by polar liquid induced gate voltage. In some embodiments, the polar liquid-induced gate voltage is related to the concentration of charged particles in the polar fluid. In some embodiments, the concentration can reflect the total amount of all negatively charged particles or all positively charged particles. The shift in the V-shaped curve can be correlated to a wide range of charged particle concentrations. In some embodiments, the shift is correlated to charged particle concentrations as low as 1 femtog/L (eg, NaCl). In some embodiments, the shift correlates to 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 with polar fluid flowing in a first direction. The magnitude of the gate potential (V _FG ) is directly proportional to the polar fluid flow rate. The sign or direction of V _FG depends on the direction in which the polar fluid flows; eg, along and across the source-drain terminal. For example, if the gate voltage is positive along the source-drain direction, it becomes negative in the opposite direction, and vice versa. When the polar fluid flows across the source drain voltage, if the gate voltage is positive along the Y direction, it becomes negative along the Y direction and vice versa. When the polar fluid flow direction changes, the gate voltage direction may also change.

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

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 a dielectric layer 7 and a gate metal 8. FIG. Here, the base device can be any illustrated in FIGS. 2A-2D, such as 210, 220, 230, and 240. Gate potential is measured between the gate metal and ground. A dielectric layer 7 is added under the substrate of the base device (eg substrate 1 as illustrated in FIGS. 2A to 2D). Gate metal 8 is added below dielectric layer 7 . Gate metal 8 is applied only to measure the induced gate voltage; no voltage is applied through gate metal 8. In some embodiments, Vg1 can be varied non-linearly depending on the PFGT device characteristics and the type of channel. 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. The gate potential is measured between the metal electrode and ground. Vg2 is the top gate voltage formed by the double layer capacitance between the added metal electrode and the active channel. Vg2 can vary non-linearly depending on PFGT device characteristics and channel type. For example, if the channel is graphene (ambipolar), 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 source-drain current/voltage and induced PFG. Simultaneous measurements of Vg1 and Vg2 can be achieved using tri-gated structures, which 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 applied to the PFGT to modulate the overall electrical characteristics of the PFGT device to suit 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, computing circuits, radio frequency (RF) devices, sensors, and the like.

FIG. 5A illustrates an exemplary embodiment showing a circuit 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 concentration of the analyte being sensed.

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

Although the invention has been described in detail, it will be apparent that modifications, variations, and equivalent embodiments are possible without departing from the scope of the invention as defined in the appended claims. It will 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. Those skilled in the art will appreciate that the techniques disclosed in the examples that follow represent techniques that have been found to work satisfactorily in carrying out the invention, and therefore constitute examples of the mode for carrying out the invention. You should understand that you can. However, those skilled in the art, in light of this disclosure, may make many changes in the specific embodiments disclosed without departing from the spirit and scope of the invention and still obtain the same or similar results. That 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 deposited onto the graphene, typically less than 0.5 mm thick, 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 opposite 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 graphene layers.

The sensor system for analyte sensing through sweat consisted of:
○ Flexible polymer platform made of (Kapton);
○ Graphene polymer composite bonded to a flexible polymer platform;
o Source and drain electrodes positioned within the sensor arrangement at opposite edges of the layer of graphene polymer composite, also bonded to the flexible polymer platform;
○ A source electrode and a drain electrode each made of a conductive metal;
○ The graphene polymer composite layer is functionalized with a linker molecule between the two electrodes for the desired analyte biosensing; and ○ The sensor system is placed in close proximity to the source of clean sweat to be analyzed. I let it and held it.

The method for determining analyte concentration through sweat included the following steps:
o Applying a constant bias voltage to the functionalized graphene polymer composite sensor having conduction channels;
o Measuring the first source-drain voltage via the sensor;
o Exposure to clean sweat by bringing the conduction channel in close proximity to the source of sweat;
o Binding the analyte to the linker molecule by releasing electrons through the linker into the channel, resulting in a change in potential across the channel;
o Measuring the second source-drain voltage via the sensor;
o Determining the analyte concentration based on the fractional rate of change between the first source-drain voltage and the second source-drain voltage.

During analysis, a fixed current or voltage was passed through the sensor. The electrical response of the GFET sensor was recorded for analyte in polar solution using analyte in deionized (DI) water as a negative control. The DI water response for the functionalized GFET was also measured. Analytes included NaCl, D-glucose, and lactic acid.
(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 for: NaCl concentration in DI water or DI water response on non-functionalized GFET.

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

Figure 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 concentration changed the voltage across the channel, which showed high selectivity for NaCl in DI water as a control.

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

Figure 7 shows that the GFET does not give a significant response to DI water alone, with an exponential response starting from the lowest concentration of NaCl in DI water to the highest concentration of NaCl. Increasing concentrations varied the voltage across the channel, thereby showing a high sensitivity of about 250 femtograms/liter towards NaCl in DI water as a control.

Sweat Chloride Response: Measurements of human sweat chloride concentrations were performed in human subjects. The test required subjects to perform physical activities such as running and occasionally use water to hydrate.

The GFET was worn by human subjects on the forearm and lower back (eccrine sweat glands). Electrical responses due to chloride concentration in sweat were transmitted and recorded continuously (every 500 milliseconds) while the subject performed strenuous physical activity (such as running). Changes in chloride concentration in sweat were observed as represented by the fractional rate of change of voltage, as illustrated in FIG.

FIG. 8 shows real-time concentration of sweat osmolality for two human subjects using a PFGFET attached to the skin. The osmolality 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) compared to a jogger (Subject 2 and Run 2). It was observed that the more intense the subject's physical activity, the higher the measured body osmolality concentration. The peak of body osmolarity was observed during periods of the most intense physical activity. Body osmolarity was also observed to decrease during periods of intense physical activity. This was caused when the subject consumed too much water without proper salt supplementation. In the data, a slope of the curve toward 0 indicates hyponatremia. During this period, the body tries to retain as much salt as possible (to maintain ionic balance), and therefore the overall body osmotic concentration changes very slowly.

The following novel results and/or characteristics were observed.

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

High sensitivity: The PBA functionalized GFET exhibited 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 the surface and molecules is stronger. All of these factors play a very differentiating role in making a GFET highly sensitive.

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

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

Induced motion of polar fluid on the surface of the NFET: Polar fluids (such as NaCl in DI water) are quickly repelled or removed 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 (eg, NaCl) in the fluid, the stronger the PFGT and therefore the greater the repulsive effect. This repulsive effect combined with the modulation of the PFGT-induced electrical response by NaCl molecules on the NFET enabled a selective and continuous monitoring electrolyte system with higher sensitivity.

Real-time continuous chloride monitoring in human sweat: As an example, a GFET was worn by a human subject on the forearm and lower back (eccrine sweat glands). Sweat is diluted and ultrafiltered blood. Electrical responses due to chloride concentrations in sweat are measured continuously during a) strenuous physical activity (training), b) less strenuous physical activity (such as sitting at an office desk and eating). (every 500 milliseconds) and recorded. Background ion concentrations in sweat (primarily 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 continuously measuring chloride concentration 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:
o D-glucose concentration in DI water o D-glucose concentration in artificial sweat (DI + NaCl + lactic acid) o D-glucose concentration in DI water on non-functionalized GFET o Lactose concentration in DI water on functionalized device (control 1)
○ Artificial sweat concentration on functionalized device (Control 2)
o DI Water Response with Functionalized GFET o Human Sweat Glucose Measurement: Real-time continuous monitoring of glucose concentration was performed in human sweat using a wearable GFET/PBA sensor. Real-time continuous sweat glucose responses were correlated to blood glucose measurements using a commercially available glucose meter.

Functionalization: As an example, a graphene FET was functionalized with a linker molecule (Lock) that specifically binds glucose molecules in a fluid. 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 deposited on the graphene, typically less than 0.5 mm thick, and then separated from the catalyst substrate on which it was grown.
o The graphene polymer composite was then placed on a polymer substrate such as Teflon, polyimide, etc. and heated at 80-150 degrees Celsius for 1-10 minutes to remove any impurities.
○ The graphene polymer was then introduced into a solution of PBA for 5-20 minutes for functionalization at room temperature.
o 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 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, followed by the next higher concentration 3 minutes later, and so on. This continued until all concentrations were introduced onto the GFET.

Figure 9 shows that the 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 concentration changed the voltage across the channel, which showed high selectivity for D-glucose with DI water as a control.

Glucose response in NaCl versus glucose response in DI water: The response of various D-glucose concentrations in DI water and NaCl solutions was measured on a GFET to determine the response for D-glucose in DI water versus D-glucose in NaCl. The sensitivity of the functionalized sensor was studied and the effect of NaCl solution was understood.

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 onto the GFET, followed by the next higher concentration 3 minutes later, and so on. Here, the concentration increased logarithmically. This continued until all concentrations were introduced onto the GFET.

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

Selectivity measurement of glucose response in NaCl solution: The response of various D-glucose concentrations in NaCl was measured on a 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 onto the GFET, followed by the next higher concentration 3 minutes later, and so on. Here, the concentration increased logarithmically. This continued until all concentrations were introduced into the GFET.

FIG. 11 shows that the GFET did not give a significant response to NaCl solutions alone, but showed a linear response to solutions of increasing D-glucose concentration at a fixed NaCl concentration versus solutions of increasing NaCl concentration. Increasing concentration changed the voltage across the channel, thereby demonstrating high selectivity for D-glucose. A GFET (NFET) functionalized with PBA gave a high selective response (95%) to glucose concentration.

Figure 11 shows that the functionalized glucose sensor is not sensitive to NaCl (as the orange curve is fairly flat), whereas the glucose curve increases as the concentration of glucose present in the NaCl solution increases. It gives an idea.

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

Solutions containing exponentially increasing concentrations of glucose ranging from 250 femtograms/L to 100 mg/L in DI water were prepared. The test started by introducing 5 ul of DI water over the GFET every 3 minutes, followed by the lowest concentration of 5 ul, followed by the next higher concentration 3 minutes later. , and so on. Here the concentration increased logarithmically; for example from 0.25 pg/l then 2.5 pg/l and so on. This continued until all concentrations were introduced onto the GFET.

Figure 12 shows that the GFET does not give a significant response to DI water alone, with a linear response starting from the lowest concentration to the highest concentration, and increasing concentration changes the current across the channel, thereby , a high sensitivity of about 250 femtograms/liter (ie 1.38e ⁻¹² mmol/l) for D-glucose was demonstrated.

Functionalization Step: Figure 13 shows the current response for the graphene sensor before functionalization, after functionalization, and after glucose is introduced onto the sensor. This helps understand each stage of the GFET fabrication steps and how the GFET's current response changes after each stage. For example, Figure 13 shows an increase in the current response after functionalization (orange) compared to before functionalization (blue), which indicates that the linker molecules are connected by π-π bonds and that the graphene surface This is caused by an increase in all the charges on the The linker molecule attracts the glucose molecule and binds to it by using these charge clouds, thereby reducing the current on the GFET compared to its previous state.

D-Glucose Response in Sweat and Blood: Measurements of human sweat glucose concentrations were performed in human subjects. The test required subjects to perform physical activities such as running, take blood samples, and measure their blood sugar every few minutes using a glucose meter. The GFET was worn by human subjects on the forearm and lower back (eccrine sweat glands). Electrical responses due to D-glucose concentrations in sweat were transmitted and recorded continuously (every 500 milliseconds) while the subject performed 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 eats a meal, glucose levels begin to drop and stabilize.

In the case of running, as you begin to run, your body uses glucose and breaks it down to obtain energy for your run. Therefore, a decrease in glucose is seen. However, after some point, the body's insulin begins to act and total glucose levels begin to rise again.

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

The blood glucose data in Figure 15 was also plotted against time over the entire period of training. Sweat glucose measurements were correlated with blood sugar measurements. Now, we plot the sweat glucose values against the corresponding blood sugar values again against the blood (blood vs. sweat) to obtain a correlation ^R2 , which is how well the sweat glucose matches the blood sugar. I 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 for the same amount of time. Over 150 curves for sweat glucose were collected and correlated from 10 human subjects, along with blood glucose over the entire duration of the study. Subjects performed physical activity (e.g., training, running) or no physical activity (e.g., 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 high selective responses (>95%) to glucose concentrations in various control fluids.

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

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

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 bond. When the concentration of glucose bound to the sensor becomes higher than the glucose concentration in sweat due to its Gibbs free energy, the glucose molecules become released from the PBA, and a reversible property is observed; This is clearly seen in the electrical response recorded in Figure 14 as the concentration of glucose momentarily drops. This allows reusable real-time continuous monitoring of D-glucose molecules in polar fluids.

Reusability of glucose sensors due to movement of polar fluid on the sensor surface: Movement of polar fluid (such as glucose in salt) on the NFET increases the removal of bound glucose molecules from the linker molecule 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 its original bare value.

Induced motion of polar fluid on the surface of NFET: Polar fluid (such as glucose in salt) is quickly repelled or removed 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 stronger the PFGT and therefore the greater the repulsion effect. This repulsive action, combined with the removal of bound glucose molecules (described in section e above), and the modulation of the electrical response due to the PFGT on the NFET, result in a more sensitive selective and continuous monitoring glucose system. made possible.

Real-time continuous glucose monitoring in human sweat: GFET functionalized with PBA
was worn on the forearm and lower back (eccrine sweat glands) by human subjects. Sweat is diluted and ultrafiltered blood. Electrical responses due to D-glucose concentrations in sweat are continuously measured while the subject engages in a) strenuous physical activity (training) and b) non-vigorous physical activity (such as sitting at an office desk and eating). The target was transmitted and recorded every 500 milliseconds. Sweat glucose responses were 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 due to PFGT on GFET has enabled continuous non-invasive monitoring of glucose molecules in human sweat. A correlation of 84% (R ² ) was calculated between blood glucose and sweat glucose measurements. Correlations were calculated for 150 sweat glucose responses collected from 10 human subjects under various physical activity conditions. It has been observed that sweat is a very good polar fluid for continuously measuring glucose because it is highly diluted and ultrafiltered.
(Example 4)
Analysis of lactic acid samples

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

Functionalization: Graphene FETs were functionalized with linker molecules (locks) that specifically bind lactic acid molecules in the fluid. As an example, GFETs were functionalized onto graphene surfaces using lactate oxidase (LOx) and intermediate pyrene-NHS coupling chemistry.
o The polymer is deposited on the graphene, typically less than 0.5 mm thick, and then separated from the catalyst substrate on which it is grown.
o The graphene polymer composite is then placed on a polymer substrate such as Teflon, polyimide, etc. and heated at 80-150 degrees Celsius for 1-10 minutes to remove any impurities.
o The graphene polymer is then introduced into a solution of pyrene-NHS for 5-20 minutes for functionalization at room temperature.
o The graphene polymer is then introduced into a solution of LOx for binding for 520 minutes at room temperature.
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)
○ DI water response in functionalized GFET.

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

Figure 17 shows that the GFET does not give a significant response to DI alone, and the polynomial response is to high lactate concentrations in DI water; increasing concentration changes the voltage across the channel; Thereby, high selectivity towards lactic acid in DI water was demonstrated using DI water as a control.

Selectivity measurement of lactate response in different solutions: The response of different lactate concentrations in different solutions is 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 onto the GFET, followed by the next higher concentration 3 minutes later, and so on. This was continued for each solution separately until all concentrations were introduced onto the GFET.

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

Lactate response in NaCl versus DI water: The response of various lactate concentrations in DI water and NaCl solutions was measured on a GFET to determine the sensitivity of the functionalized sensor to lactate in DI water versus lactate in NaCl. studied and understood the effect of NaCl solution. Solutions were prepared containing various concentrations of lactic acid ranging from 0.1 to 100 mg/dL in DI water and NaCl, respectively. The test started by introducing the lowest concentration of 2 ul onto the GFET, followed by the next higher concentration 3 minutes later, and so on. This continued until all concentrations were introduced onto the GFET.

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

Lactic acid functionalization steps visualized through GFET fabrication: The current response for the graphene sensor before functionalization, after functionalization, and after introducing lactic acid onto the sensor is illustrated in FIG. 20. This helps understand each stage of the GFET fabrication steps and how the GFET's current response 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 to the lactic acid molecule, thereby reducing the current on the GFET compared to its previous state.

The following novel results and/or characteristics were observed.

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

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

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

Induced movement of polar fluids on the surface of the NFET: Polar fluids (such as lactic acid in artificial sweat) are quickly repelled or removed from the NFET due to the high hydrophobicity between the NFET surface and the polar fluid. It is thought that it will become. The higher the concentration of polar molecules in the fluid, the stronger the PFGT and therefore the greater the repulsion effect. This repulsive effect combined with the modulation of the electrical response due to the PFGT on the NFET enabled a selective and continuous monitoring lactate system with higher sensitivity.
(Example 5)
Additional analysis

Sweat Salt Concentration Correlation: Figure 21 depicts the sweat sensor response with respect to 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 (e.g. 0.1 mg/dl), followed by the next higher concentration (e.g. 0.2 mg/dl), and so on for 3 minutes. Dropped at intervals. The corresponding fractional rate of change of 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 the corresponding voltage change.

Sweat Glucose Concentration Correlation: Figure 22 depicts sweat sensor responses with 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 begins by dropping 5 ul of the lowest concentration (e.g., 0.1 mg/dl), followed by the next higher concentration (e.g., 0.2 mg/dl), and so on for 3 minutes. It was 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 the corresponding voltage change.

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

A highly concentrated NaCl solution ranging from 0.1 ng/dl to 1 mg/dl is dripped onto the sensor every 3 minutes. The test begins by dropping the lowest concentration (e.g., 0.1 ng/dl) of 2 ul, 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, with both the Debye length and the gating effect being a function of the concentration of polar molecules. Regarding the initial concentration of the NaCl solution, DI occupies a larger proportion, due to which more holes are created and a voltage drop is seen. However, after a few drops, when the concentration of NaCl increases in the solution, it dominates and more electrons are created near the Debye layer, thereby exhibiting an increase in voltage.

This illustrates the transconductance properties of a polar fluid-gated graphene sensor.

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

Additionally, those skilled in the art will appreciate the applicability of various features from different embodiments. Similarly, the various elements, features, and steps discussed above, as well as other known equivalents of such elements, features, and steps, may be used to perform methods according to the principles described herein. They can be mixed and adapted by those skilled in the art. Among the various elements, features, and steps, various embodiments specifically include some and specifically exclude others.

Although the invention has been disclosed in the context of certain specific embodiments and examples, those skilled in the art will appreciate that embodiments of the invention extend beyond the specifically disclosed embodiments to other alternative embodiments and/or It will be understood that the use extends to modifications and equivalents thereof.

Many variations and alternative elements have been disclosed in embodiments of the invention. Still other variations and alternative elements 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 invention are referred to as " It should be understood that the term "about" is sometimes modified. Thus, in some embodiments, the numerical parameters set forth in the written description and appended claims are approximations that can vary depending on the desired properties sought to be obtained by a particular embodiment. It is. In some embodiments, numeric parameters should be interpreted in light of the reported number of significant digits and by applying normal rounding techniques. Although numerical ranges and parameters set forth in broad terms for some embodiments of the invention are approximations, the numbers set forth in specific examples are reported to be as precise as practicable. The numerical values presented in some embodiments of the invention may necessarily contain certain errors resulting from the standard deviations found in their respective test measurements.

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

Groupings of alternative elements or embodiments of the invention disclosed herein are not to be construed as limiting. 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. In the event that any such inclusion or deletion occurs, this specification shall be construed as including the group as modified herein, and as such the written description of all Markush groups as used in the appended claims. satisfy the given explanation.

Preferred embodiments of the invention are described herein. Variations on those preferred embodiments will become apparent to those skilled in the art upon reading the foregoing description. It is contemplated that those skilled in the art will be able to employ such variations as appropriate, and that the invention may be practiced otherwise than as 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. Furthermore, any combination of the above-described elements in all their possible variations is encompassed by the invention, unless indicated otherwise herein or 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 individually incorporated herein by reference in their 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 used may be within the scope of the invention. Thus, by way of example and without limitation, alternative configurations of the invention may be utilized in accordance with the teachings herein. Therefore, the embodiments of the invention are not limited to the precise details shown and described.

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

Claims (21)

A field effect transistor,
a drain electrode;
a source electrode;
A substrate and
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 the nanoscale material layer, wherein the polar fluid-induced gate terminal creates an induced gate voltage in the channel to a polar fluid-induced gate terminal that allows the field effect transistor to function as an active device when a polar fluid is externally introduced into the channel;
a polymer layer bonded to the nanoscale material layer and positioned between the substrate and the nanoscale material layer, the polymer layer having additional mechanical, electrical, chemical functionality; a polymeric layer configured to provide biological functionality, biological functionality, or a combination thereof;
field effect transistors, including; 2. The field effect transistor of claim 1, wherein the polar fluid is externally introduced into the channel as droplets. 2. The field effect transistor of claim 1, wherein the polar fluid is externally introduced into the channel when the field effect transistor is brought into contact with a volume of the polar fluid. The field effect transistor of claim 1, wherein the active device is configured to be used 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 the field effect transistor does not include or require a permanent physical gate terminal formed on the substrate. 2. The field effect transistor of claim 1, wherein the induced gate voltage is related to a concentration of charged particles within the polar fluid. 2. The field effect transistor of claim 1, wherein the polar fluid-induced gate terminal is transient and is active only when the polar fluid is externally introduced into the channel. 2. The field effect transistor of claim 1, wherein the field effect transistor is not configured to function as the active device when the polar fluid is removed from the channel. Field effect transistor according to claim 1, wherein the channel is electrically conductive and chemically and/or biosensitive. 2. The field effect transistor of claim 1, wherein the nanoscale material layer is epitaxially grown. The nanoscale material may be graphene, CNT, MoS ₂ , boron nitride, metal dichalcogenide, phosphorene, nanoparticle, quantum dot, fullerene, 2D nanoscale material, 3D nanoscale material, 0D nanoscale material, 1D nanoscale material, or any combination thereof. The field effect transistor described in . 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, earwax, urine, semen, plasma, biological fluids, chemical fluids, air samples, gas samples, or combinations thereof. The polar fluid may include electrolytes, glucose, lactic acid, IL6, cytokines, HER2, cortisol, ZAG, cholesterol, vitamins, proteins, drug molecules, metabolites, peptides, amino acids, DNA, RNA, aptamers, enzymes, biomolecules, and chemical molecules. 2. The field effect transistor of claim 1, wherein the field effect transistor comprises one or more target analytes, including a synthetic molecule, a synthetic molecule, or a combination 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. The one or more receptors may be 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), an aptamer, an inorganic material, a synthetic molecule, or a biomolecule. 2. The field effect transistor of claim 1, wherein the polymer layer comprises carbon polymer, biopolymer, PMMA, PDMS, flexible glass, nanoscale material, silica gel, silicone, ink, printed polymer, or any combination thereof. The substrate may be made of polyimide, flexible printed circuit board (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 an alloy, fabric, textile, silk, paper, cellulose-based material, or any combination thereof. 2. The field effect transistor of claim 1, wherein the substrate is made of an electrically insulating material. 2. A biosensing system comprising a field effect transistor according to claim 1, wherein the biosensing system or a component thereof is configured to be attached to a subject, and wherein the field effect transistor is configured such that the polar fluid is A biosensing system configured to detect one or more target analytes in the polar fluid when externally introduced into the channel from the subject's body.