Systems and methods of calibrating a sensor

Abstract

Disclosed herein are methods and systems for calibrating a biosensor with the optional addition of peripherals to aid in the calibration. Methods and systems of the disclosure can be used advantageously to improve biosensor function, use-life and reliability.

Description

SYSTEMS AND METHODS OF CALIBRATING A SENSORBACKGROUND OF THE INVENTION

[0001] As of 2021, millions of Americans were affected by chronic diseases such as diabetes, cardiovascular, neurodegenerative, and autoimmune disorders. These conditions involve biological dysregulation leading to severe complications or death, and remain a major cause of mortality and healthcare burden in the U.S.

[0002] Conventional electrochemical systems often face challenges related to signal acquisition, material degradation, and noise interference, which can impact their performance and reliability.SUMMARY OF THE INVENTION

[0003] In an aspect, disclosed herein is a method of operating a biosensor comprising inputs, outputs, and processing steps, including but not limited to signal acquisition, feature extraction, signal processing, calibration, correction, or normalization, the method comprising: providing a field effect transistor comprising one or more control electrodes; measuring an electrical signal (e.g., source-drain current or electrical response, source-drain voltage, gate current, impedance, or capacitance) associated with one or more parameters of sensor operation, including but not limited to analyte concentration, environmental conditions, sensor stability, or electronic drift; applying a biasing sequence to at least one control electrode to induce a electrical response; measuring the electrical response; and extracting at least one signal or calibration parameter based at least in part on the response. In some embodiments, further comprising measuring one or more additional electrical signals (e.g., source-drain current or electrical response, source-drain voltage, impedance, or capacitance) of the field effect transistor under different control electrode biasing conditions. In some embodiments, wherein one or more counter electrodes is a reference electrode. In some embodiments, wherein one or more of the electrodes is functionalized with a receptor for a biomarker. In some embodiments, wherein the at least one signal is based at least in part on a capacitance measured between one or more electrodes. In some embodiments, wherein the at least one signal is based at least in part on electrode response or a source-drain response or a gate response or transient source-drain current or electrical response or a transient source-drainvoltage. In some embodiments, wherein the at least one signal is based at least in part on an electrode response or source-drain current or electrical response or a source-drain voltage measured while one or more gate electrodes are unactivated. In some embodiments, wherein the at least one signal is based at least in part on: calculating a dirac point based at least in part on a capacitance measured between one or more electrodes; calculating a measure of drift in the capacitance based at least in part of the dirac point; and subtracting the measure of drift from the capacitance at least one of the electrodes of the two or more electrodes to produce a measure of capacitance. In some embodiments, further comprising providing one or more sensor parameters selected from group consisting of: a sensor area, a counterion concentration, a diffusivity of the counterion, and a resistance of a channel of the field effect transistor. In some embodiments, wherein one or more gate electrodes comprise at least one sensitive electrode and at least one non-sensitive electrode. In some embodiments, wherein the at least one sensitive electrode comprises a plurality of sensitive electrodes configured to detect a plurality of analytes. In some embodiments, wherein the at least one sensitive electrode and the one or more non-sensitive electrode are utilized by the field effect transistor as gates. In some embodiments, wherein one or more source-drain current or electrical response or source-drain voltage is alternated or pulsed or varied across the one or more non- sensitive electrode and the one or more sensitive electrode. In some embodiments, wherein the second source-drain current or electrical response or source-drain voltage is alternated across the at least one non-sensitive electrode and the at least one sensitive electrode. In some embodiments, wherein the measuring is performed at a steady interval. In some embodiments, wherein the measuring of are performed in an alternating pattern. In some embodiments, wherein the measuring of are performed at a random interval. In some embodiments, wherein the measuring of electrical responses are performed at a fluctuating interval. In some embodiments, wherein the steady interval is approximately between 0.01 milliseconds and 10 minutes. In some embodiments, wherein the random interval is approximately between 0.01 milliseconds and 10 minutes. In some embodiments, wherein the fluctuating interval is approximately between 0.01 milliseconds and 10 minutes. In some embodiments, wherein the one or more electrode or source-drain current or electrical response or source drain voltage is a square- wave. In some embodiments, wherein the response of the one or more source or drain or gate is of mostly identical magnitude. In some embodiments, wherein the response of the one or more source or drain or gate is of different magnitude. In some embodiments, whereinthe magnitude is between about 0 and 1 volt. In some embodiments, wherein the extracting comprises a machine learning model. In some embodiments, wherein the machine learning model comprises at least one of a linear regression model, a logistic regression model, a decision tree, a clustering algorithm, a random forest, a gradient boosted tree ensemble, a support vector machine, a neural network, a multilayer perceptron, a nai:ve bayes method, a k- nearest neighbors method, a k-means method, hierarchical clustering, principal component analysis, independent component analysis, or any combination thereof.

[0004] In another aspect, disclosed herein is a method of operating a sensor, the method comprising: providing a field effect transistor comprising one or more control electrodes; acquiring electrical signals under varying biasing conditions; and processing the acquired signals to extract sensor output, calibration parameters, or device performance metrics;

[0005] measuring a electrode response, gate response or source-drain current or electrical response or source-drain voltage of the field effect transistor, wherein the source-drain current or electrical response or source-drain voltage is related to a concentration of a biomarker; providing at least one sensor of a distinct sensor modality from the field effect transistor; and adjusting the measuring the source-drain current or electrical response or source-drain voltage of the field effect transistor in (b) based at least in part on a reading from the at least one sensor. In some embodiments, where in the at least one sensor comprises at least one of a galvanometer, a thermometer, an accelerometer, an electrical heart sensor, an optical heart sensor, an altimeter, a gyroscope, an ambient light sensor, an anemometer, a bolometer, a heat flux sensor, a water sensor, a humidity sensor, a temperature sensor or any combination thereof. In some embodiments, wherein a measure of impedance is used to monitor components of the sensor. In some embodiments, wherein the measure of impedance is electrochemical impedance spectroscopy. In some embodiments, wherein the measure of impedance is performed using a frequency sweep of components of the sensor. In some embodiments, wherein the measure of impedance is performed in near real-time. In some embodiments, wherein the measure of impedance is performed in-situ. In some embodiments, wherein the device is configured to monitor a biological state. In some embodiments, where in the biological state is a measure of one or more molecules. In some embodiments, wherein the molecule is a sugar. In some embodiments, wherein the molecule is a salt. In some embodiments, wherein the molecule is an acid. In some embodiments, wherein the molecule is a lipid. In some embodiments, whereinthe sugar is glucose. In some embodiments, wherein the acid is lactic acid. In some embodiments, wherein the biological state is a disease. In some embodiments, wherein the disease is diabetes. In some embodiments, wherein the disease is cancer. In some embodiments, wherein the disease is heart disease. In some embodiments, wherein the disease is high cholesterol. In some embodiments, wherein the disease is high cholesterol. In some embodiments, wherein the disease is respiratory failure. In some embodiments, wherein the disease is liver disease. In some embodiments, wherein the disease is kidney disease. In some embodiments, wherein the biological state is stress. In some embodiments, wherein the disease is fatigue. In some embodiments, wherein the disease is high cholesterol.

[0006] In another aspect, herein disclosed is a sensor the sensor comprising: a field effect transistor comprising one or more control electrodes; at least one sensor, wherein the at least one sensor is of a different sensing modality than the field effect transistor; and a processor communicatively coupled to the field effect transistor and the at least one sensor, wherein the processor is configured to: measure a signal from the field effect transistor; measure a signal from the at least one sensor; and adjust the signal from the field effect transistor based at least on the signal from the at least one sensor. In some embodiments, wherein the processor is communicably coupled to a transmitter. In some embodiments, wherein the processor is communicably coupled to a signal receiver. In some embodiments, wherein the processor is communicably coupled to a display. In some embodiments, wherein the communicatively coupling is via WIFI, via Bluetooth, via a wired connection, via a z- wave connection, via an intermediate component, via a motherboard, via a radio signal, via a fiberoptic fiber, via a plurality of fiber optic fibers, via a server. In some embodiments, wherein the at least one sensor comprises at least one of a galvanometer, a thermometer, an accelerometer, an electrical heart sensor, an optical heart sensor, an altimeter, a gyroscope, an ambient light sensor, an anemometer, a bolometer, a heat flux sensor, a water sensor, a humidity sensor, a temperature sensor or any combination thereof. In some embodiments, further comprising a housing comprising: a mechanical attachment configured to fix the device to a skin of a subject; and an opening through which the device may contact the skin of the subject. In some embodiments, wherein the mechanical attachment is an adhesive coupled to the housing and oriented such that the adhesive faces and may be fixed to the skin of a subject. In some embodiments, wherein the mechanical attachment is a strap coupled to the housing. In someembodiments, wherein the strap comprises a buckle coupled to the strap on one end and a series of elements the buckle may be reversibly coupled.INCORPORATION BY REFERENCE

[0007] All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference. To the extent publications and patents or patent applications incorporated by reference contradict the disclosure contained in the specification, the specification is intended to supersede and / or take precedence over any such contradictory material. PCT / IB2025 / 055775 and PCT / IB2025 / 055773 is incorporated herein by reference.BRIEF DESCRIPTION OF THE DRAWINGS

[0008] The novel features of the invention are set forth with particularity in the appended claims. A better understanding of the features and advantages of the present invention will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the invention are utilized, and the accompanying drawings (also "Figure" and "FIG." herein), of which:

[0009] FIG. 1 illustrates a non-limiting example of a schematic for integrating signals and calibrating said signals.

[0010] FIG. 2 illustrates a non-limiting example of a time series with a signal being calibrated using a peripheral.

[0011] FIG. 3 illustrates a non-limiting example of a square wave read off two electrodes.

[0012] FIG. 4 illustrates a non-limiting example of a gate current changing in response to a solute concentration.

[0013] FIG. 5 illustrates a non-limiting example of a time series with a signal and a reading from a glucometer.

[0014] FIG. 6 illustrates a non-limiting example of a time series with a signal beingcalibrated.

[0015] FIG. 7 illustrates a non-limiting example of a time series with a current.

[0016] FIG. 8 illustrates a graph of current versus voltage of an example electrode gate in accordance with embodiments described herein.

[0017] FIG. 9 illustrates a non-limiting example of a time series with a signal and a peripheral signal from an accelerometer.DETAILED DESCRIPTION OF THE INVENTION

[0018] While various embodiments of the invention have been shown and described herein, it will be obvious to those skilled in the art that such embodiments are provided by way of example only. Numerous variations, changes, and substitutions may occur to those skilled in the art without departing from the invention. It should be understood that various alternatives to the embodiments of the invention described herein may be employed.

[0019] Whenever the term "at least," "greater than," or "greater than or equal to" precedes the first numerical value in a series of two or more numerical values, the term "at least," "greater than" or "greater than or equal to" applies to each of the numerical values in that series of numerical values. For example, greater than or equal to 1, 2, or 3 is equivalent to greater than or equal to 1, greater than or equal to 2, or greater than or equal to 3.

[0020] Whenever the term "no more than," "less than," or "less than or equal to" precedes the first numerical value in a series of two or more numerical values, the term "no more than," "less than," or "less than or equal to" applies to each of the numerical values in that series of numerical values. For example, less than or equal to 3, 2, or 1 is equivalent to less than or equal to 3, less than or equal to 2, or less than or equal to 1.

[0021] Certain inventive embodiments herein contemplate numerical ranges. When ranges are present, the ranges include the range endpoints. Additionally, every sub range and value within the range is present as if explicitly written out.

[0022] The term "about" or "approximately" may mean within an acceptable error range for the particular value, which will depend in part on how the value is measured or determined, e.g., the limitations of the measurement system. For example, "about" may mean within 1 or more than 1 standard deviation, per the practice in the art. Alternatively, "about" may mean a range of up to 20%, up to 10%, up to 5%, or up to 1% of a given value. Where particular values are described in the application and claims, unless otherwise stated the term "about" meaning within an acceptable error range for the particular value may be assumed.

[0023] The present invention relates to novel electrical architectures, methods of operation, and data acquisition frameworks for integration with electrochemical and biosensing systems, encompassing inputs, outputs, signal acquisition, processing, and control functions, and providing enhanced performance, flexibility, and scalability compared to conventional circuit designs or signal handling approaches.

[0024] One key aspect of the invention involves the use of one or more electrodes, which may or may not be different, that are alternatively biased through waves (eg. square wave) with identical or different periodicities and magnitudes. The low frequency of the waves allows the system to measure the step response in both transient and steady-state regimes, leading to the acquisition of two distinct signals of interest from the electrochemical sensor - one from the initial transient and another from the steady-state.

[0025] Furthermore, by modeling how the transient state settles into the steady-state, valuable information can be derived regarding the physical and chemical state of the electrochemical system, providing a third signal of interest and enabling the understanding of the system's evolution, including its sensitivity.

[0026] The electrochemical system incorporates sensitive material layers, such as enzymes, proteins, or DNA, onto electrodes. Prolonged excitation of the underlying electrodes can lead to degradation of these materials through unwanted annealing, Joule heating, and the introduction of energy into a fragile environment. By cycling the electrodes through a tuned frequency or low-frequency wave, the present invention allows the material layers to relax and recover, leading to an extended use life of the electrochemical system. This leads to advantageous properties of this design where the measurements are improved, the performance of the physical system is improved and the subsequent readings are more accurate while also prolonging the life of the components.

[0027] Additionally, prolonged excitation of either electrode in the electrochemical system can result in low-frequency noise "drift" that affects the nature of the signal of interest. Advantageously, the cycling of the electrodes, as proposed in this invention, reduces this effect and enables the system to report a more pristine signal.

[0028] For systems intended to be used as electrochemical sensors, where the electrodes constitute the sensing elements, the ability to switch or cycle between different electrodes enables the implementation of multiple sensors on the same board, benefiting from the advantages of the present invention. For example, one electrode might measure glucose, another could measure lactic acid, and so on. Furthermore, one electrode might be rendered nonsensitive and used to collect "background" data, enabling the system to remove artifacts unrelated to the signals of interest, such as humidity, temperature, or interferents. Additionally, multiple electrodes can be used for the same analyte to increase the system's use life and enhance data confidence through sensor fusion.

[0029] The transient signal acquired by the system corresponds to the capacitive current, while the steady-state signal represents the faradaic current. The modeling of the transient to steady-state transition follows electrochemical kinetics and contains information about activation, analyte concentration, dielectric constants, and enzyme activity, among other parameters.

[0030] This novel electric design and data acquisition method can be integrated into electrochemical systems, providing enhanced signal acquisition, extended use life of sensitive materials, reduced noise interference, and the ability to implement multiple sensors on a single board, ultimately improving the overall performance and reliability of the electrochemical system.

[0031] FIGS. 1 through 9 illustrate exemplary system architectures and signal processing frameworks for sensor platforms. As shown in FIG. 1, the system may include one or more sensing elements configured to generate electrical responses under various biasing conditions, with signals processed through analog-to-digital conversion (ADC), microcontroller units (MCU), and algorithmic processing pipelines. FIGS. 2 depict alternative configurations of signal acquisition and processing circuitry. FIGS. 3 through 9 present additional embodiments of control and processing pathways, including data acquisition modules, feature extractionunits, signal correction and normalization modules, and calibration engines. Electrical responses may include current, voltage, impedance, capacitance, transient responses, and steady-state signals. The system may further incorporate auxiliary sensors, such as accelerometers, temperature sensors, or additional physiological or environmental sensors, to support artifact rejection, multi-signal calibration, or enhanced data integration. Collectively, the figures illustrate multiple embodiments of flexible biosensor signal acquisition, processing, and calibration pipelines that may be implemented across various device architectures.Peripherals

[0032] Peripherals / modules may be added to an embedded system dedicated to the accurate measurement of a signal or signals of interest. The purpose of the additional / optional peripherals is to measure and monitor the state of the sensor, environment, and detect spurious signals that may affect the accuracy of the signals of interest. They provide:1. The ability to measure the characteristics of a transistor or other component of the sensing system, through measurement of its transconductance (known as IVg). It measures the current response across the source and drain of the transistor through a voltage sweep of its gate. It gives us information regarding the resistance of the sensor, the amplification / gain and the current direction of the signal (hole vs electron conduction). It also allows us to confirm the proper electrical ionic connection between the 3 elements.2. The ability to measure the impedance of the different parts and the whole of the system, through electrochemical impedance spectroscopy. This measurement(s), through a frequency sweep of the different components allows us to measure in situ and in real time the different capacitance, resistance, inductance and other electrical components -physical or apparent of the system.3. The ability to monitor / quantify the activation (eg. activation) of the sensor through galvanometry or potentiometry or other electrical measurement between dedicated electrodes. It also allows us to confirm the proper electrochemical connection between the circuit elements.4. The ability to measure, quantify and qualify the motions that the system issubject to through the use of accelerometry and / or gyroscope.

[0033] The information collected by these peripherals allows for the measurement of the state of the system at any given time, advantageously. Those signals to remove or correct for spurious artifacts (eg. motion artifacts, like bumping into a wall or table, etc) to preserve and obtain an accurate reading from the signal(s) of interest.

[0034] Advantageously, those signals allow for the tuning and modification the calibration setting of the system (as the actual state of the electrical components, activation) affect the sensitivity of the sensor. By knowing them it is possible to correct the sensitivity to maintain the accuracy of the sensor output.

[0035] The present invention relates to a novel electric design and data acquisition method for integration into an electrochemical system, providing multiple improvements to the typical circuitry.

[0036] The system comprises one or more different electrodes that are alternatively biased through a wave of identical or different periodicity / magnitudes. The use of low frequency of the waves (eg. square) essentially allows the systems to measure the step response in both transient and steady state regimes leading to the acquisition of one or more different signals of interest (from the initial transient and the steady state) from the electrochemical sensor. Further modeling how the transient settles into the steady states yields information regarding the state (physical, chemical) of the electrochemical system and provides a third way of deriving a signal of interest, including understanding the evolution of the system, pertaining to its sensitivity for example.

[0037] The larger system incorporates sensitive material layers, such as -but not limited to- enzymes, proteins, DNA onto metal electrodes. The prolonged excitation of the subjacent electrodes leads to degradation of those materials, through unwanted annealing, Joule heating and otherwise introduction of energy into a fragile environment. By cycling the electrodes through a low frequency square wave, this design allows for the material layers in question to relax and recover, leading to a longer use life of the electrochemical system.

[0038] Prolonged excitation of either electrode in the electrochemical system leads to low frequency noise "drift" that affects the nature of the signal of interest. The cycling of theelectrodes reduces this effect and enables the system to report a more pristine signal.

[0039] Further, for a system that is meant to be used as an electrochemical sensor, for which the electrodes in question constitute the sensing element, having the possibility to switch / cycle between the different electrodes enables the implementation of several different sensors on the same board, benefiting from the above invention. For example, an electrode might measure glucose, another one might measure lactic acid, one might also be rendered non sensitive and will be used to collect the "background" to enable the system to remove artifacts that are unrelated to the signals of interest (for example: humidity, temperature, interference). Also, the use of several electrodes for the same analyte may increase use life and increase confidence in data through fusion.

[0040] The methods and devices disclosed herein describe the ability to determine a transient signal based on capacitive current, a steady state based on faradaic current, and allows for the ability to model of transient to steady state based on follows electrochemical kinetics and contains information about activation, analyte concentration, dielectric constants, enzyme activity for example.Example 1: Values

[0041] The invention may be developed and tested using the following values and parameters

[0042] Waveform: square wave

[0043] Amplitude p2p: O to 10 V

[0044] Period: 0 - 10 min

[0045] Number of electrodes: 2 to 100Nanomaterial PFGFET Description

[0046] The following application are incorporated by reference herein for all purposes: WO2019 / 183279, WO2017 / 216641, and WO2015164552.

[0047] The field-effect transistor (FET) is a transistor that uses an electric field to control the electrical behavior of the device. In general, a FET has three terminals (e.g., source, drain, and gate) and an active channel. Though the active channel, e.g., formed by a semi-conductivematerial, charge carriers (electrons or holes) flow from the source to the drain.

[0048] Source (S) is where the carriers enter the channel. Drain (D) is where the carriers leave the channel. Drain-to-source voltage is VDS, and source to drain current is IDS. Gate (G) modulates the channel conductivity by applying a gate voltage (VG) to control a current between source and drain.

[0049] Nanoscale field effect transistors (NFETs) such as polar fluid gated field effect transistors (PFGFETs) are widely used in numerous applications such as in bioprobes, implants, and etc.

[0050] What is needed in the field are better designs of FETs and new ways of using them.

[0051] In one aspect, disclosed herein is a field effect transistor. The field effect transistor comprises: a drain electrode; a drain electrode; a source electrode; an electrically insulating substrate; a nanoscale material layer arranged on the substrate, the nanoscale material layer partially defining an electrically conducting and chemically sensitive channel, the nanoscale material layer and the channel extending between and being electrically connected to the drain electrode and source electrode; and a polar fluid induced gate terminal created by a polar fluid exposed to the nanoscale material layer. In some embodiments, the polar fluid comprises the 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 versus channel current characteristics of the field effect transistor in response to the target analyte

[0052] In some embodiments, a constant current or a constant voltage is applied at or between the electrodes or source and drain electrodes, provided by a constant current source or a constant voltage source.

[0053] In some embodiments, the nanoscale material comprises , CNTs, MoS2, boron nitride, metal dichalcogenides, phosphorene, nanoparticles, quantum dots, fullerene, 2D nanoscale material, 3D nanoscale material, OD nanoscale material, ID nanoscale material or any combination thereof

[0054] In some embodiments, wherein the polar fluid comprises a solution with polar molecules, a gas with polar molecules, a target sensing analyte, or combinations thereof.

[0055] In some embodiments, the polar fluid comprises sweat, breath, saliva, earwax, urine, semen, blood plasma, a bio-fluid, a chemical fluid, an air sample, a gas sample, or a combination thereof

[0056] In some embodiments, the target analyte comprises an electrolyte, glucose, lactic acid, IL6, a cytokine, HER2, cortisol, ZAG, cholesterol, vitamins, a protein, a drug molecule, a metabolite, a peptides, an amino acid, a DNA, an RNA, an aptamer, an enzyme, a biomolecule, a chemical molecule, a synthetic molecule, or combinations thereof

[0057] In some embodiments, the field effect transistor, further comprises: a receptor layer deposited on the nanoscale material layer, wherein the receptor layer comprises receptors targeting the target analyte.

[0058] In some embodiments, the receptors comprise pyrene boronic acid (PBA), pyrene N- hydroxysuccinimide ester (Pyrene-NHS), organic chemicals, aromatic molecules, cyclic molecules, enzymes, proteins, antibodies, viruses, single stranded DNAs (ssDNAs), aptamers, inorganic materials, synthetic molecules, biological molecules.

[0059] In some embodiments, the field effect transistor, further comprises: a back polymer layer under the nanoscale material layer to provide support for additional mechanical, electrical, chemical, biological functionality or combinations thereof.

[0060] In some embodiments, the back polymer layer comprises: carbon polymers, bio polymers, PMMA, PDMS, flexible glass, nanoscale materials, silica gel, silicone, inks, printed polymers or any combination thereof.

[0061] In one aspect, disclosed herein is a method for sensing a target analyte in a polar fluid. The method comprises: exposing the polar fluid sample to a field effect transistor, where the field effect transistor comprises: a drain electrode; a source electrode; an electrically insulating substrate; a nanoscale material layer arranged on the substrate, the nanoscale material layer at least partially defining an electrically conducting and chemically sensitive channel, the nanoscale material layer and the channel extending between and being electrically connected to the drain electrode and source electrode; and a polar fluid induced gate terminal created by the polar fluid exposed to the nanoscale material layer, wherein the polar fluid comprises the target analyte and has charge concentration sufficient to induce a polar fluid gate voltage thatoptimize the gate voltage versus channel current characteristics of the field effect transistor for detecting the analyte; measuring a first source-drain or control electrode voltage or current at a first time point and a second source-drain or control electrode voltage or current at a second and subsequent time point; and determining a concentration of the target analyte in the polar fluid based on the first and second source-drain voltages.

[0062] In some embodiments, the nanoscale material comprises graphene, CNTs, MoS2, boron nitride, metal dichalcogenides, phosphorene, nanoparticles, quantum dots, fullerene, 2D nanoscale material, 3D nanoscale material, OD nanoscale material, ID nanoscale material or any combination thereof

[0063] 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 receptors targeting the target analyte.

[0064] In some embodiments, the receptors comprise pyrene boronic acid (PBA), pyrene N- hydroxysuccinimide ester (Pyrene-NHS), organic chemicals, aromatic molecules, cyclic molecules, enzymes, proteins, antibodies, viruses, single stranded DNAs (ssDNAs), aptamers, inorganic materials, synthetic molecules, biological molecules.

[0065] In some embodiments, the target analyte comprises an electrolyte, glucose, lactic acid, IL6, a cytokine, HER2, cortisol, ZAG, cholesterol, vitamins, a protein, a drug molecule, a metabolite, a peptides, an amino acid, a DNA, an RNA, an aptamer, an enzyme, a biomolecule, a chemical molecule, a synthetic molecule, or combinations thereof.

[0066] In some embodiments, the polar fluid comprises a solution with polar molecules , gas with polar molecules, target sensing analyte or combinations thereof.

[0067] In some embodiments, the method further comprises calculating a fractional change between the first and second source-drain voltages.

[0068] In some embodiments, the method further comprises: applying a constant current between the source and drain electrodes of the field effect transistor.

[0069] In some embodiments, the method further comprises: applying a constant voltage between the source and drain electrodes of the field effect transistor.

[0070] In some embodiments, the polar fluid comprises sweat, breath, saliva, earwax, urine, semen, blood plasma, a bio-fluid, a chemical fluid, an air sample, a gas sample, or a combination thereof

[0071] In some embodiments, the method further comprises: a back polymer layer under the nanoscale material layer to provide support for additional mechanical, electrical, chemical, biological functionality or combinations thereof.

[0072] In some embodiments, the back polymer layer comprises: carbon polymers, bio polymers, PMMA, PDMS, flexible glass, nanoscale materials, silica gel, silicone, inks, printed polymers or any combination thereof.

[0073] In one aspect, disclosed herein is a system comprising: a field effect transistor; and

[0074] a constant current source or a constant voltage source electrically connected with the field effect transistor. The field effect transistor comprises: a drain electrode; a source electrode; an electrically insulating substrate; a nanoscale material layer arranged on the substrate, the nanoscale material layer partially defining an electrically conducting and chemically sensitive channel, the nanoscale material layer and the channel extending between and being electrically connected to the drain electrode and source electrode; and a polar fluid induced gate terminal created by a polar fluid exposed to the nanoscale material layer. In some embodiments, the polar fluid comprises 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.

[0075] In some embodiments, the constant current source maintains a constant current through the field effect transistor.

[0076] In some embodiments, the constant voltage source maintains a constant voltage over the field effect transistor.

[0077] In some embodiments, a voltage output or a current output is communicated, through a wired or wireless transmission, to a digital platform.

[0078] In some embodiments, the digital platform comprises a smart phone, a tablet computer,a smart watch, an in-car entertainment system, a laptop computer, desktop computers, a computer terminal, a television system, e-book reader, a wearable device, or any other type of computing device that processes digital input.Nanomaterial Field Effect Transistors in General

[0079] Nanomaterial possesses a remarkable mechanical resistance; this enables thicknesses on the order of a monolayer or bilayer to be subj ected to a substantial mechanical stress without losing its primary electrical properties. Such mechanical strength makes nanomaterial an ideal candidate to replace the current generation of transparent conductive oxides (TCO), led by Indium Tin Oxide (ITO). Unlike nanomaterial, ITO is brittle and susceptible to mechanical stress; however its low sheet resistance and high transparency are enough to offset its high material costs. The production of large area and low sheet resistance nanomaterial sheets, on the other hand, is a relatively straightforward and scalable process using chemical vapor deposition (CVD), yielding few atomic layers with transparency higher than 90% and sheet resistances lower than 100 after proper treatment.

[0080] Nanomaterial FETs are generally fabricated on a Si wafer covered with a Si02 layer, and nanomaterial forms the transistor channel. The nanomaterial transistor consists of three terminals: source and drain metal electrodes contacting the nanomaterial channel and a global back gate enabled by the doped Si sub strate. These features facilitate the characteristic ambipolar transport behavior of nanomaterial in the Grat-FETs - achieving both n-type and p-type transport when biased with a proper gate voltage at the sub strate. Any applicable method can be applied to fabricate a GFET, including, for example, the information disclosed in International Patent Publication No. WO 2015 / 164,552, which is hereby incorporated by reference in its entirety.

[0081] By varying on the direction and magnitude of the gate voltage, the resulting curve of current flow the source and drain takes a "V" shape. At the tip of the V-shaped curve, small changes in gate voltage result in significant and detectable changes in channel current (IDS), and tends to plateau out at the two ends of the V-shaped curve.Gateless Field Effect Transistors

[0082] In one aspect, disclosed herein is a new type of field effect transistors (FETs) that do not have a physical gate.

[0083] An example nanomaterial-based FET may include a substrate, a source electrode, a drain electrode, receptors , a nanomaterial layer, and back polymer. As disclosed herein, substrate can be polyamide, PET, PDMS, PMMA, other plastics, silicon dioxide, silicon, glass, aluminum oxide, sapphire, germanium, gallium arsenide, indium phosphide, an alloy of silicon and germanium, fabrics, textiles, silk, paper, cellulose based materials, insulator, metal, semiconductor, can be rigid, flexible or any combination thereof In some embodiments, substrate can be a silicon carbide substrate and nanomaterial layer can be epitaxially grown on the silicon carbide substrate directly by sublimation of silicon from the silicon carbide substrate.

[0084] Source electrode is the electrode region in a field-effect transitor from which majority carriers flow into the interelectrode conductivity channel. Exemplary material that can be used as a source electrode includes but is not limited to silver, gold, carbon, graphite ink, conductive fabrics, conductive textiles, metals, conductive materials, conductive polymers, conductive gels, ionic gels, conductive inks, non-metallic conductive materials.

[0085] Drain electrode is the electrode on the opposite side from source electrode. Exemplary material that can be used as a source electrode includes but is not limited to silver, gold, carbon, graphite ink, conductive fabrics, conductive textiles, metals, conductive materials, conductive polymers, conductive gels, ionic gels, conductive inks, non-metallic conductive materials.

[0086] In some embodiments, nanomaterial layer can have a uniform thickness, preferably a predetermined thickness of one or more monolayers of nanomaterial. As the thickness effects electrical properties, c.g.. band gap, carrier concentration etc., a uniform and preferably predetermined thickness provides control of the sensing properties and enables the formation of reproducible devices with low variability between individual sensors.

[0087] In some embodiments, nanomaterial layer can be an epitaxial layer and the nanomaterial layer substrate may be the substrate on which the nanomaterial layer was epitaxially grown. By letting the nanomaterial layer remain on the substrate of growth, it is not necessary to handle typically nano-thin nanomaterial layers and structures. Also the risk of damaging the thin nanomaterial layer during manufacturing of the transistor is reduced when the nanomaterial layer can remain on the substrate.

[0088] In some embodiments, nanomaterial layer can be surface treated with receptors 4 for selectivity so that only selected types of analytes are detected by the nanomaterial layer. Exemplary receptors 4 include but are not limited to pyrene boronic acid (PBA), N- hydroxysuccinimide ester (Pyrene-NHS), organic chemicals, aromatic molecules, cyclic molecules, enzymes, proteins, antibodies, viruses, single stranded DNAs (ssDNAs), aptamers, inorganic materials, synthetic molecules, biological molecules.

[0089] In some embodiments, nanomaterial layer and / or so that certain types of chemicals are prevented from reaching the chemically sensitive channel. The surface treatment may comprise deposition of metal particles and / or polymers.

[0090] Back polymer is used to provide mechanical support to the nanomaterial. And when doped, can add a new modality to the sensing response. For example, the back polymer can be doped with biomolecules that could also bind to specific targets and contribute to the resistance change of the transistor channel.Nanomaterial gate terminal (NFGT)

[0091] For example, Graphene is an allotrope of carbon in the form of a two-dimensional, atomic-scale, hexagonal lattice in which one atom forms each vertex. It is the basic structural element of other allotropes, including graphite, charcoal, carbon nanotubes and fullerenes. It can be considered as an indefinitely large aromatic molecule, the ultimate case of the family of flat polycyclic aromatic hydrocarbons. In some embodiments, graphene is a monolayer of carbon atoms. Each carbon atom in graphene has four electrons. Through three of these electrons the carbon atom binds to three nearest neighboring carbon atoms to form a hexagonal lattice. For each atom, a forth electron is delocalized on the whole nanomaterial layer, which allows the conduction of an electron current.

[0092] When a polar fluid is deposited on a nanomaterial layer, the electronic characteristics of nanomaterial and similar nanomaterials will cause re-organization of the charges in the polar fluid and form a liquid induced gate voltage, which can modulate the current between the source and drain electrodes.

[0093] As shown in FIG. 8, Charges of the polar or ionic components are redistribution in the polar fluid to create a polar fluid gate terminal (PF GT) and an induced fluid gate voltage (VFG). This voltage can result in a shift in the x-axis (voltage) in the V-shaped current vs. fluid gate voltage curve. As noted, at the tip of the V-shaped curve, small changes in gate voltage can result in significant and detectable changes in channel current (IDS), and tends toplateau out at the two ends of the V-shaped curve. A shift towards the tip of the V-shaped curve can lead to enhanced sensitivity: very small changes in voltage in response to change in current can be detected. Similarly, very small changes in current in response to change in voltage can also be detected.

[0094] As described above, a shift towards the tip of the V-shaped curve can lead better sensitivity. Such a shift can be caused by a polar liquid induced gate voltage. In some embodiments, the polar liquid induced gate voltage is associated with the concentration of charged particles within the polar fluid. In some embodiments, the concentration can reflect the total quantity of all negatively charged particles or all positively charged particles. The shift in the V-shaped curve can correlate with a wide range of charged particle concentrations. In some embodiments, a shift is correlated with a charged particle concentration as low as 1 femto g / L (e.g., NaCl). In some embodiments, a shift is correlated with a charged particle concentration as high as 300 g / L (e.g., NaCl). The results suggest that the current sensing system is resilient and can tolerate a wide range of charge concentrations.

[0095] The magnitude of the gate potential (VFG) will be directly proportional to the flow rate of the polar fluid. The sign or direction of VFG will depend on the direction of flow of the polar fluid; e.g., along the source drain terminal and across the source drain terminal. For example, if the gate voltage is positive along the source drain direction, it will be negative in the reverse direction, and vice versa. When the polar fluid is flowing across the source drain voltage, if the gate voltage is positive along the Y direction, it will be negative in the -Y direction and vice versa. When the direction of the polar fluid flow changes, the direction of the gate voltage would also change.Detecting Gate Voltage at Polar fluid gate terminal

[0096] Example 4A through 4C are set ups by which gate voltage at a polar fluid gate terminal (PFGT) is determined.

[0097] Example 4A is an exemplary embodiment, with a base device with a dielectric layer 7 and a gate metal 8. Here the base device can be any of the devices described herein such as 210, 220, 230 and 240. Gate potential is measured between the gate metal and the ground. Dielectric layer 7 is added underneath the substrate of the base device (e.g., substrate 1). Gate metal 8 is added underneath dielectric layer 7. Gate metal 8 is added only to measure theinduced gate voltage, no voltage will be applied through gate metal 8. In some embodiments, Vgl can vary in non-linear way depending on the PFGT device characteristics and type of channel. For example, if the channel is graphene (ambipolar), Vgl can follow the transconductance response typical to a graphene device.

[0098] Example 4B is an exemplary embodiment, showing a base device with an added metal electrode in the PFGT. Gate potential is measured between the metal electrode and the ground. Vg2 is the top gate voltage formed by the double layer capacitance between added metal electrode and active channel. Vg2 can vary in non-linear way depending on the PFGT device characteristics and type of channel. For example if the channel is graphene (ambipolar), thenVg2 will follow the transconductance response typical to a graphene device.

[0099] Example 4C is an exemplary embodiment, with a base device augmented with the dielectric and gate metal, and a metal electrode in the PFGT. Two gate potentials are measured as indicated. The two gate potentials (Vgl and Vg2) are electrical outputs that are modulated using the source drain current / voltage and the induced PFG. The simultaneous measurements of Vgl and Vg2 creates a tri-gated structure that can used develop next generation microprocessors, logic gates, computational circuits, radio frequency (RF) devices, sensors, and etc.

[0100] Example 4C is an exemplary embodiment, with a base device augmented with the dielectric and gate metal, and a metal electrode in the PFGT. Two gate voltages (e.g., Vgl and Vg2) are supplied to the PFGT to modulate the overall electrical characteristics of the PFGT device for a desired application. The simultaneous modulation by Vgl and Vg2 creates a trigated structure that can used to shift the device operation to a desired electrical performance in a more controlled fashion using minimal energy. Such a device can be utilized to develop next generation microprocessors, logic gates, computational circuits, radio frequency (RF) devices, sensors, and etc.

[0101] Example 5A is an exemplary embodiment, with a circuit used for sensor readout via a polar fluid gated field effect transistor (PFGFET). In Example 5A, a constant current (le) is supplied to the PFGFET. Output voltages (V ouT) are read from across the PFGFET using a divider and current limiting resistor (R). The electrical voltage output is then calibrated to the concentrations of the analyte being sensed.

[0102] Example 5B is an exemplary embodiment, with another circuit used for sensor readout via PFGFET. Here, a constant voltage (Vs) is supplied to the PFGFET. Currents or chargers (Ian) are read from the PFGFET using a current limiting resistor (R). The electrical current output is then calibrated to the concentrations of the analyte being sensed.W earable Sensor

[0103] Non-invasive, quick, and convenient ways ofsensing signals (e.g., physiological signals) may be desired. For example, there is a need for screening for diseases and / or generally monitoring body physiology without blood or urine for the general population, patients (e.g., diabetics), and athletes. The present disclosure provides devices, systems, and methods for monitoring for physiological signals non-invasively, quickly, and conveniently with high sensitivity and / or specificity. In one example, the systems or devices provided herein may sense biomarkers such as glucose level or body osmolality. For instance, the systems or devices may non-invasively measure glucose and / or electrolytes in real time from sweat, or other bodily fluids such as saliva.

[0104] Systems and methods of the present disclosure may detect a biological fluid. In some examples, the biological fluid comprises a solution with polar molecules, a gas with polar molecules, a target sensing analyte, or combinations thereof. In some examples, the biological fluid comprises sweat, breath, saliva, earwax, urine, semen, blood plasma, interstitial fluid, lung -originated water vapor, a biofluid, a chemical fluid, an air sample, a gas sample, or a combination thereof. In some embodiments, the target analyte comprises an electrolyte, glucose, lactic acid, IL6, a cytokine, HER2, Cortisol, ZAG, cholesterol, vitamins, a protein, a drug molecule, a metabolite, a peptide, an amino acid, a DNA, an RNA, an aptamer, an enzyme, a biomolecule, a chemical molecule, a synthetic molecule, or combinations thereof.

[0105] The systems or devices may further be worn unobtrusively (e.g., everyday) in convenient patch or strap form factors. The devices may be worn, synced (e.g., with a server), and be used to track in real time the health or general physical state ofthe user. The user may utilize the information provided by the devices to take further action as desired.

[0106] The system may use Bluetooth to transmit data and may interact with a user, for example, with a screen or one or more light emitting diodes (LEDS). The transmitter module of the system may comprise a processing module and optionally an outer housing. The housing may house a sensor write / readout assembly, associated electronics, communications devices and / ormagnets to facilitate attachment of a sensor to the transmitter.

[0106] The sensor may be removably coupled to the transmitter. The sensor a sensor substrate, electrodes, and sensor elements such as graphene. The weight of the biosensing system may be negligible, for example, equal to or less than about 500g, 400g, 300g, 200g, 150g, 120g, 100g, 80g, 60g, 40g, 30g, 20g, 10g, 5g, 4g, 3g, 2g, or 1g. Optionally, the sensor may be a disposable sensor. Alternatively or in addition, the sensor may be a replaceable sensor. For example, the sensor may be used, cleaned or processed, and be used again. While disposable sensors are primarily discussed herein, it is to be understood that details and / or descriptions discussed with respect to disposable sensors may be applicable to replaceable sensors.

[0107] As described throughout, the systems, devices, and methods provide non-invasive, quick, and convenient ways of sensing signals. This may be provided by a number of factors, including, but not limited to one or more of: 1) a replaceable magnetic sensor substrate, 2) a flexible printed circuit material with embedded sensor electrodes and metal vias folded around a magnetic iron sheet, 3) a sensor substrate with alternate hydrophobic and hydrophilic regions to facilitate sweat localization / absorption, 4) a metal contact and passivation layer thickness and method of application, 5) a dual conduction layer strategy - nanomaterial, conduction layer 1 , cure, conduction layer 2 and then passivation, 6) a constant current 5 to 200 micro Amps, across sensor and voltage readout 8 bit or higher / or 7) a wearable mount: band and patch.

[0108] Embodiments disclosed herein provide devices, systems, and methods for monitoring physiological signals. Disposable or replaceable sensors may be utilized in monitoring physiological signals with high sensitivity and / or specificity. Various physiological signals, including glucose or lactic acid may be monitored conveniently, and in real time with no inconvenience to a user. For example, a user may wear device (e.g., a patch or a small attachment such as a wrist strap) anywhere on their body (e.g., as a wrist band) and the device may monitor and detect sweat to screen for physiological signals. Small disposable or replaceable sensors may beneficially be provided that may be coupled and uncoupled from the device such that signals may be monitored accurately and conveniently.

[0109] According to some aspects of the disclosure, a modular sensor is disclosed. The modular sensor may comprise: a substrate; a plurality of contact electrodes provided on a surface of the substrate; and a plurality of sensing lines disposed between the plurality ofcontact electrodes to collectively form a plurality of sensor elements, wherein each sensor element comprises at least one sensing line extending longitudinally between a pair of contact electrodes, wherein the modular sensor is configured to be operably and releasably coupled to a device for use as a sensing apparatus.

[0110] In some embodiments, the modular sensor is configured to function as an active sensing unit when electronically coupled to the device. In some embodiments, the modular sensor is configured to fit within a recessed housing on the device. In some embodiments, the modular sensor is protected by the recessed housing. In some embodiments, the substrate comprises a ferrous metal or alloy, and the device comprises a magnetic material. In some embodiments, the modular sensor is configured to be coupled and held in place on the device via an attractive force between the magnetic material and the ferrous metal or alloy.

[0111] In some embodiments, at least one of the plurality of sensing lines comprises a nanoscale material. In some embodiments, at least one of the plurality of sensing lines comprises nanomaterial. In some embodiments, the plurality of sensing lines each comprises nanomaterial. In some embodiments, the plurality of sensor elements is configured to detect one or more markers in a fluid. In some embodiments, the plurality of sensor elements is configured to detect one or more biomarkers in a biological fluid of a subject. In some embodiments, the plurality of sensor elements is configured to detect a same biomarker.

[0112] In some embodiments, the biological fluid comprises sweat or interstitial fluid obtained via the surface of the skin. In some embodiments, the biological fluid comprises breath or lung originated water vapor obtained from exhaling on the device. In some embodiments, each of the plurality of sensor elements is configured to detect a different biomarker. In some embodiments, the plurality of sensor elements is configured operate in a multichannel multiplexed configuration. In some embodiments, the one or more biomarkers comprises an electrolyte, glucose, lactic acid, IL6, a cytokine, HER2, Cortisol, ZAG, cholesterol, vitamins, a protein, a drug molecule, a metabolite, a peptide, an amino acid, a DNA, an RNA, an aptamer, an enzyme, a biomolecule, a chemical molecule, a synthetic molecule, or combinations thereof. In some embodiments, the one or more biomarkers comprises an electrolyte, glucose, and lactic acid.

[0113] In some embodiments, the biological fluid sample comprises sweat, breath, saliva,earwax, urine, semen, blood plasma, a bio-fluid, a chemical fluid, an air sample, a gas sample, or a combination thereof. In some embodiments, the biological fluid sample comprises sweat or breath. In some embodiments, the plurality of sensor elements is configured to detect the one or more biomarkers when in contact with the biological fluid sample. In some embodiments, the plurality of sensor elements is capable of detecting the one or more biomarkers in a non- invasive manner, without requiring penetration of the subject's skin to extract the biological fluid sample.

[0114] In some embodiments, the plurality of sensor elements is configured to detect a presence and concentration of the one or more biomarkers substantially in real-time when the device is being worn on the subject or in proximity to the subject. In some embodiments, data indicative of the presence and concentrations of the one or more biomarkers is collected and stored by the device. In some embodiments, the data is collected and stored on the device over a time period that the device is being worn on the subject or in proximity to the subject. In some embodiments, the modular sensor is configured to be operably and releasably coupled to the device without the use of tools. In some embodiments, the modular sensor is configured to be operably and releasably coupled to the device in less than 10 seconds.

[0115] Also disclosed is a sensing apparatus. A sensing apparatus may comprise: a plurality of modular sensors configured to detect one or more biomarkers in a biological fluid sample of a subject when the device is being worn by the subject or in proximity to the subject; and a device configured to interchangeably and releasably couple to a modular sensor selected from the plurality of modular sensors, wherein the device is configured to receive, store, and send sensing signals from the modular sensor.

[0116] In some embodiments, the device comprises a transmitter configured to transmit the sensing signals over a network. In some embodiments, the transmitter is configured to transmit the sensing signals to a mobile device that is associated with and in proximity to the subject. In some embodiments, the device comprises a recessed housing configured to receive and support the modular sensor. In some embodiments, the device is releasably coupled to the modular sensor via a magnetic attachment mechanism. In some embodiments, the magnetic attachment mechanism comprises a magnetic material provided on at least one of the modular sensor and the device, and a ferrous metal or alloy provided on at least one of the modular sensor and the device. In some embodiments, the device is configured to bereleasably coupled to a strap or patch, wherein the strap or patch is configured to be worn on a portion of the subject's body. In some embodiments, the plurality of modular sensors comprises at least one nanomaterial-based sensor.

[0117] Also disclosed is a device. The device may comprise: a processing module configured to operably couple to at least one sensor selected from a group consisting of a plurality of discrete biological or chemical sensors, wherein two or more different sensors for detecting two or more different target analytes are interchangeably and releasably attachable to the device, depending on a type(s) of target analytes to be detected from a sample of a subject collected on the device when the subject is wearing the device or in proximity to the device.

[0118] In some embodiments, the sample comprises sweat, saliva, breath, blood, or other biological fluids of the subject. In some embodiments, the different target analytes comprise different biomarkers and / or chemical agents. In some embodiments, the biomarkers are selected from the group consisting of electrolytes, glucose, and lactic acid. In some embodiments, at least one of the sensors is configured to measure a pH or ionic concentration of the sample. In some embodiments, at least one of the sensors comprises a nanomaterialbased sensor. In some embodiments, the plurality of discrete sensors are heterogeneous sensors comprising (i) at least one nanomaterial-based sensor and (ii) at least one non nanomaterial-based sensor. In some embodiments, the processing module is configured to detect and monitor levels of a first target analyte when a first sensor specific to the first target analyte is attached to the device. In some embodiments, the processing module is configured to switch to detection and monitoring of a second target analyte when the first sensor is detached from the device and replaced by a second sensor specific to the second target analyte. In some embodiments, the processing module is located onboard the device, and configured to process sensor data substantially in real-time as the data is being collected by the at least one sensor, in order to detect and monitor levels of one or more target analytes. In some embodiments, the device comprises a graphical display for displaying the detected levels of the one or more target analytes. In some embodiments, the processing module is configured to transmit the processed sensor data to a remote device, server or third party entity. In some embodiments, the processing module comprises a recommendation engine configured to prescribe certain corrective or mitigative actions to the subject, based on the detected levels of the one or more target analytes.

[0119] In some embodiments, a modular sensing kit is disclosed. The modular sensing kit may comprise (1) the device and (2) the plurality of discrete biological or chemical sensors of claim on any aspect or embodiment. In some embodiments, a quick release mechanism provided on the device allows different discrete sensors to be manually attached and detached from the device without the use of tools. In some embodiments, the plurality of discrete sensors are provided separately from the device. In some embodiments, one or more of the discrete sensors is configured for a single use with the device, and discarded after each use encounter by the subject. In some embodiments, one or more of the discrete sensors is configured for multiple uses with the device, and capable of being recycled and reused in multiple use encounters by the subject. In some embodiments, the plurality of discrete sensors have different sensitivities to a same target analyte or different target analytes. In some embodiments, the plurality of discrete sensors comprises a first sensor and a second sensor both configured to detect a target analyte, wherein the first sensor has a higher sensitivity than the second sensor. In some embodiments, the first sensor is capable of detecting a substantially lower level or concentration of the target analyte compared to the second sensor.

[0120] Also disclosed is a device. The device may comprise: a processing module operably coupled to three or more different discrete biological or chemical sensors, wherein the processing module is configured to selectively activate the three or more different discrete biological or chemical sensors in different multiplexed configurations depending on desired type(s) of sensing application of a subject.

[0121] In some embodiments, the different multiplexed configurations permit a plurality of different target analytes to be detected from a sample of the subj ect collected on the device when the subject is wearing the device or in proximity to the device. In some embodiments, the different multiplexed configurations enable increased sensitivity in the detection and monitoring of different target analytes. In some embodiments, the processing module is configured to selectively activate a fewer number of the biological or chemical sensors to reduce power consumption of the device. In some embodiments, the processing module is configured to selectively activate a greater number of the biological or chemical sensors to enhance sensitivity in the detection and monitoring of different target analytes. In some embodiments, the three or more discrete sensors comprises a first sensor for detecting a first target analyte, a second sensor for detecting a second target analyte, and a third sensor fordetecting a third target analyte. In some embodiments, the processing module is configured to selectively activate at least two out of the first, second and third sensors. In some embodiments, the processing module is configured to selectively activate (1) the first and second sensors in a first multiplexed configuration, (2) the second and third sensors in a second multiplexed configuration, or (3) the first and third sensors in a third multiplexed configuration. In some embodiments, the processing module is capable of detecting (1) the presence and (2) concentrations ranging from 1 fg / L and above of two or more different target analytes in a sample having a volume of less than 1 pL collected from the subject on the device when the subject is wearing the device or in proximity to the device. In some embodiments, the device is capable of detecting the presence and concentrations of the two or more different target analytes in less than 1 second.

[0122] Also disclosed is a method of fabricating a modular sensor. The method may comprise: providing a sensor substrate comprising at least two electrodes disposed on a surface of the substrate; depositing a layer of nanomaterial on the surface of the sensor substrate between the at least two electrodes; metallizing at least a portion of the layer of nanomaterial at or near the at least two electrodes; passivating at least a portion of the layer of nanomaterial with a passivation polymer; and optionally, functionalizing at least a portion of the layer of nanomaterial, wherein functionalizing the layer of nanomaterial with a receptor layer, wherein the receptor layer is sensitive to a target analyte.

[0123] In some embodiments, the receptor layer comprises a receptor selected from group consisting of pyrene boronic acid (PBA), pyrene N-hy dr oxy succinimide ester (Pyrene-NHS), organic chemicals, aromatic molecules, cyclic molecules, enzymes, proteins, antibodies, viruses, single stranded DNAs (ssDNAs), aptamers, inorganic materials, synthetic molecules, and biological molecules. In some embodiments, the target analyte comprises an electrolyte, glucose, lactic acid, IL6, a cytokine, HER2, Cortisol, ZAG, cholesterol, vitamins, a protein, a drug molecule, a metabolite, a peptides, an amino acid, a DNA, an RNA, an aptamer, an enzyme, a biomolecule, a chemical molecule, a synthetic molecule, or combinations thereof. In some embodiments, the substrate comprises polyamide, Polyethylene terephthalate (PET), polydimethylsiloxane (PDMS), Poly(methyl methacrylate) (PMMA), other plastics, silicon dioxide, silicon, glass, aluminum oxide, sapphire, germanium, gallium arsenide, indium phosphide, an alloy of silicon and germanium, fabrics, textiles, silk, paper, cellulose basedmaterials, insulator, metal, semiconductor, or a combination thereof. In some embodiments, the substrate is flexible. In some embodiments, the passivation polymer comprises Acrylic, PMMA, silicone, polysilicone, PDMS, rubber, hotmelt co- polymers, EVA co polymers, ethylene acrylate, PET, Polyamide, PTFE, fluoropolymer, thermoplastics, gels, hydrogels, polypropylene, polyethylene, Polyolefins, polyvinyl chloride, polyesters, polyurethanes, Styrene block copolymers, Polycaprolactone, Polycarbonates, Fluoropolymers, Silicone rubbers, Thermoplastic elastomers, Polypyrrole, or a combination thereof. In some embodiments, the passivation polymer is polyurethane. In some embodiments, the depositing the nanomaterial layer comprises heating the substrate beyond a fusing temperature of a functional back polymer disposed between the nanomaterial layer and the substrate. In some embodiments, the method further comprises functionalizing a first portion of the substrate near the nanomaterial layer with a hydrophilic material. In some embodiments, a second portion ofthe substrate near the nanomaterial layer is not functionalized with the hydrophilic material. In some embodiments, the second portion ofthe substrate is functionalized with a hydrophobic material.

[0124] According to some aspects of the disclosure, a modular sensor is provided. The modular sensor may comprise a substrate; a plurality of contact electrodes provided on a surface of the substrate; and a plurality of sensing lines disposed between the plurality of contact electrodes to collectively form a plurality of sensor elements, wherein each sensor element comprises at least one sensing line extending longitudinally between a pair of contact electrodes, wherein the modular sensor is configured to be operably and releasably coupled to a device for use as a wearable sensing apparatus.

[0125] In some embodiments, the modular sensor is configured to function as an active sensing unit when electronically coupled to the device. In some embodiments, the modular sensor is configured to fit within a recessed housing on the device. In some embodiments, the modular sensor is protected by the recessed housing when the device is being worn by a subject. In some embodiments, the substrate comprises a ferrous metal or alloy, and the device comprises a magnetic material. In some embodiments, the modular sensor is configured to be coupled and held in place on the device via an attractive force between the magnetic material and the ferrous metal or alloy. In some embodiments, at least one of the plurality of sensing lines comprises nanomaterial. In some embodiments, the plurality of sensing lines eachcomprises nanomaterial.

[0126] In some embodiments, the plurality of sensor elements is configured to detect one or more biomarkers in a biological fluid sample of a subject when the device is being worn by the subject. In some embodiments, the plurality of sensor elements is configured to detect a same biomarker. In some embodiments, each of the plurality of sensor elements is configured to detect a different biomarker. In some embodiments, the plurality of sensor elements is configured operate in a multichannel multiplexed configuration. In some embodiments, the one or more biomarkers comprises an electrolyte, glucose, lactic acid, IL6, a cytokine, HER2, Cortisol, ZAG, cholesterol, vitamins, a protein, a drug molecule, a metabolite, a peptide, an amino acid, a DNA, an RNA, an aptamer, an enzyme, a biomolecule, a chemical molecule, a synthetic molecule, or combinations thereof. In some embodiments, the one or more biomarkers comprises an electrolyte, glucose, and lactic acid. In some embodiments, the biological fluid sample comprises sweat, breath, saliva, earwax, urine, semen, blood plasma, a bio-fluid, a chemical fluid, an air sample, a gas sample, or a combination thereof. In some embodiments, the biological fluid sample comprises sweat or breath. In some embodiments, the plurality of sensor elements is configured to detect the one or more biomarkers when in contact with the biological fluid sample.

[0127] In some embodiments, the plurality of sensor elements is capable of detecting the one or more biomarkers in a non-invasive manner, without requiring penetration of the subject's skin to extract the biological fluid sample. In some embodiments, the plurality of sensor elements is configured to detect a presence and concentration of the one or more biomarkers substantially in real-time when the device is being worn on the subject. In some embodiments, data indicative of the presence and concentrations of the one or more biomarkers is collected and stored by the device. In some embodiments, the data is collected and stored on the device over a time period that the device is being worn on the subject. In some embodiments, the modular sensor is configured to be operably and releasably coupled to the device without the use of tools. In some embodiments, the modular sensor is configured to be operably and releasably coupled to the device in less than 10 seconds.

[0128] Also disclosed is a wearable sensing apparatus. The wearable sensing apparatus may comprise a plurality of modular sensors configured to detect one or more biomarkers in a biological fluid sample of a subject when the device is being worn by the subject; and a deviceconfigured to interchangeably and releasably couple to a modular sensor selected from the plurality of modular sensors, wherein the device is configured to receive and store sensing signals from the modular sensor.

[0129] In some embodiments, the device comprises a transmitter configured to transmit the sensing signals over a network. In some embodiments, the transmitter is configured to transmit the sensing signals to a mobile device that is associated with and in proximity to the subject. In some embodiments, the device comprises a recessed housing configured to receive and support the modular sensor. In some embodiments, the device is releasably coupled to the modular sensor via a magnetic attachment mechanism. In some embodiments, the magnetic attachment mechanism comprises a magnetic material provided on at least one of the modular sensor and the device, and a ferrous metal or alloy provided on at least one of the modular sensor and the device. In some embodiments, the device is configured to be releasably coupled to a strap, wherein the strap is configured to be worn on a portion of the subject's body. In some embodiments, the plurality of modular sensors comprises at least one nanomaterial-based sensor.

[0130] Also disclosed is a wearable device. The wearable device may comprise a processing module configured to operably couple to at least one sensor selected from a group consisting of a plurality of discrete biological or chemical sensors, wherein two or more different sensors for detecting two or more different target analytes are interchangeably and releasably attachable to the wearable device, depending on a type(s) of target analytes to be detected from a sample of a subject collected on the wearable device when the subject is wearing the device.

[0131] In some embodiments, the sample comprises sweat, saliva, breath, blood, or other biological fluids of the subject. In some embodiments, the different target analytes comprise different biomarkers and / or chemical agents. In some embodiments, the biomarkers are selected from the group consisting of electrolytes, glucose, and lactic acid. In some embodiments, at least one of the sensors is configured to measure a pH or ionic concentration of the sample. In some embodiments, at least one of the sensors comprises a nanomaterialbased sensor. In some embodiments, the plurality of discrete sensors are heterogeneous sensors comprising (i) at least one nanomaterial-based sensor and (ii) at least one non nanomaterial-based sensor.

[0132] In some embodiments, the processing module is configured to detect and monitor levels of a first target analyte when a first sensor specific to the first target analyte is attached to the wearable device. In some embodiments, the processing module is configured to switch to detection and monitoring of a second target analyte when the first sensor is detached from the wearable device and replaced by a second sensor specific to the second target analyte. In some embodiments, the processing module is located onboard the wearable device, and configured to process sensor data substantially in real-time as the data is being collected by the at least one sensor, in order to detect and monitor levels of one or more target analytes. In some embodiments, the wearable device comprises a graphical display for displaying the detected levels of the one or more target analytes.In some embodiments, the processing module is configured to transmit the processed sensor data to a remote device, server or third party entity. In some embodiments, the processing module comprises a recommendation engine configured to prescribe certain corrective or mitigative actions to the subject, based on the detected levels of the one or more target analytes.

[0133] Also disclosed is a modular sensing kit. The modular sensing kit may comprise (1) the wearable device and (2) the plurality of discrete biological or chemical sensors of any embodiment disclosed herein. In some embodiments, a quick release mechanism provided on the wearable device allows different discrete sensors to be manually attached and detached from the wearable device without the use of tools. In some embodiments, the plurality of discrete sensors are provided separately from the wearable device. In some embodiments, one or more of the discrete sensors is configured for a single use with the wearable device, and discarded after each use encounter by the subject. In some embodiments, one or more of the discrete sensors is configured for multiple uses with the wearable device, and capable of being recycled and reused in multiple use encounters by the subject. In some embodiments, the plurality of discrete sensors have different sensitivities to a same target analyte or different target analytes. In some embodiments, the plurality of discrete sensors comprises a first sensor and a second sensor both configured to detect a target analyte, wherein the first sensor has a higher sensitivity than the second sensor. In some embodiments, the first sensor is capable of detecting a substantially lower level or concentration of the target analyte compared to the second sensor.

[0134] Also disclosed is a wearable device. The wearable device may comprise a processingmodule operably coupled to three or more different discrete biological or chemical sensors, wherein the processing module is configured to selectively activate the three or more different discrete biological or chemical sensors in different multiplexed configurations depending on desired type(s) of sensing application of a subject. In some embodiments, the different multiplexed configurations permit a plurality of different target analytes to be detected from a sample of the subject collected on the wearable device when the subject is wearing the device. In some embodiments, the different multiplexed configurations enable increased sensitivity in the detection and monitoring of different target analytes. In some embodiments, the processing module is configured to selectively activate a fewer number of the biological or chemical sensors to reduce power consumption of the wearable device. In some embodiments, the processing module is configured to selectively activate a greater number of the biological or chemical sensors to enhance sensitivity in the detection and monitoring of different target analytes. In some embodiments, the three or more discrete sensors comprises a first sensor for detecting a first target analyte, a second sensor for detecting a second target analyte, and a third sensor for detecting a third target analyte.

[0135] In some embodiments, the processing module is configured to selectively activate at least two out of the first, second and third sensors. In some embodiments, the processing module is configured to selectively activate (1) the first and second sensors in a first multiplexed configuration, (2) the second and third sensors in a second multiplexed configuration, or (3) the first and third sensors in a third multiplexed configuration.In some embodiments, the processing module is capable of detecting (1) the presence and (2) concentrations ranging from 1 femtogram per liter (fg / L) and above of two or more different target analytes in a sample having a volume of less than 1 microliters (pL) collected from the subject on the wearable device when the subject is wearing the device. In some embodiments, the wearable device is capable of detecting the presence and concentrations of the two or more different target analytes in less than 1 second.

[0136] Also disclosed is a method of fabricating a modular sensor. The method may comprise: providing a sensor substrate comprising at least two electrodes disposed on a surface of the substrate; depositing a layer of nanomaterial on the surface of the sensor substrate between the at least two electrodes; metallizing at least a portion of the layer of nanomaterial at or near the at least two electrodes; passivating at least a portion of the layer of nanomaterial with apassivation polymer; and optionally, functionalizing at least a portion of the layer of nanomaterial, wherein functionalizing the layer of nanomaterial with a receptor layer, wherein the receptor layer is sensitive to a target analyte.

[0137] In some embodiments, the receptor layer comprises a receptor selected from group consisting of pyrene boronic acid (PBA), pyrene N-hydroxy succinimide ester (Pyrene-NHS), organic chemicals, aromatic molecules, cyclic molecules, enzymes, proteins, antibodies, viruses, single stranded DNAs (ssDNAs), aptamers, inorganic materials, synthetic molecules, and biological molecules. In some embodiments, the target analyte comprises an electrolyte, glucose, lactic acid, IL6, a cytokine, HER2, Cortisol, ZAG, cholesterol, vitamins, a protein, a drug molecule, a metabolite, a peptides, an amino acid, a DNA, an RNA, an aptamer, an enzyme, a biomolecule, a chemical molecule, a synthetic molecule, or combinations thereof. In some embodiments, the substrate comprises polyamide, Polyethylene terephthalate (PET), polydimethylsiloxane (PDMS), Poly(methyl methacrylate) (PMMA), other plastics, silicon dioxide, silicon, glass, aluminum oxide, sapphire, germanium, gallium arsenide, indium phosphide, an alloy of silicon and germanium, fabrics, textiles, silk, paper, cellulose based materials, insulator, metal, semiconductor, or a combination thereof. In some embodiments, the substrate is flexible. In some embodiments, the passivation polymer comprises Acrylic, PMMA, silicone, polysilicone, PDMS, rubber, hotmelt co- polymers, EVA co polymers, ethylene acrylate, PET, Polyamide, PTFE, fluoropolymer, thermoplastics, gels, hydrogels, polypropylene, polyethylene, Polyolefins, polyvinyl chloride, polyesters, polyurethanes, Styrene block copolymers, Polycaprolactone, Polycarbonates, Fluoropolymers, Silicone rubbers, Thermoplastic elastomers, Polypyrrole, or a combination thereof. In some embodiments, the passivation polymer is polyurethane.

[0138] In some embodiments, the depositing the nanomaterial layer comprises heating the substrate beyond a fusing temperature of a functional back polymer disposed between the nanomaterial layer and the substrate. In some embodiments, the method further comprises functionalizing a first portion of the substrate near the nanomaterial layer with a hydrophilic material. In some embodiments, a second portion of the substrate near the nanomaterial layer is not functionalized with the hydrophilic material. In some embodiments, the second portion of the substrate is functionalized with a hydrophobic material.

[0139] Accordingly, in one aspect, a disposable sensor may be provided. The disposablesensor may comprise: a substrate; two or more contact electrodes disposed on a surface of the substrate; and a sensor element disposed between the two or more contact electrodes, wherein the substrate comprises a volume equal to or less than about 5 cm3.

[0140] In some embodiments, the volume is equal to or less than about 0.5 cm3. In some embodiments, the sensor element comprises graphene. In some embodiments, the sensor is configured to detect glucose, lactic acid, or other biomarkers. In some embodiments, the sensor is configured to contact sweat, saliva, or breath to screen for disease or micronutrient information. In some embodiments, the sensor comprises a contact area configured to come into contact with a user's fingers. In some embodiments, the sensor comprises magnets.

[0141] In another aspect, a transmitter may be provided. The transmitter may comprise: a receiving port for receiving a disposable sensor, wherein the receiving port comprises a mechanism for coupling to the disposable sensor; a processor operably coupled to the receiving port; and an outer housing.

[0142] In some embodiments, the mechanism comprises magnets. In some embodiments, the transmitter comprises a volume equal to or less than about 100 cm3. In some embodiments, the transmitter comprises a volume equal to or less than about 50 cm3. In some embodiments, the transmitter comprises a coupling mechanism for coupling with a strap. In some embodiments, the strap is a wrist strap. In some embodiments, the processor is configured to receive signals from the disposable sensor and screen for disease or micronutrient information. In some embodiments, the processor is configured to screen for disease or micronutrient information in real time.

[0143] In another aspect, a system for sensing signals is provided. The system may comprise: a disposable sensor; a transmitter comprising a sensor receiving portion for receiving the disposable sensor; and an attachment comprising a transmitter receiving portion for receiving the transmitter. A field communication layer can comprise one or more of genipin-based crosslinked enzyme aggregates (CLEAs), glutaraldehyde, tyramine, chitosan, agar or agarose hydrogel, poly(3,4- ethylenedioxythiophene): polystyrene sulfonate (PEDOT:PSS), or any combination thereof. The CLEAs may aggregate, leading to a higher density of the enzymes on the gate electrodes.

[0144] While preferred embodiments of the present invention have been shown and describedherein, it will be obvious to those skilled in the art that such embodiments are provided by way of example only. Numerous variations will now occur to those skilled in the art without departing from the invention. It should be understood that various alternatives to the embodiments of the invention described herein may be employed in practicing the invention. It is intended that the following claims define the scope of the invention and that methods and structures within the scope of these claims and their equivalents be covered thereby.

Claims

CLAIMSWHAT IS CLAIMED IS:

1. A method of calibrating a sensor the method comprising:(a) providing a field effect transistor comprising at least two gate electrodes;(b) measuring a first source-drain current or electrical response or source- drain voltage of the field effect transistor, wherein the first source-drain current or electrical response or source-drain voltage is related to a concentration of a biomarker, wherein during (b), a first gate electrode of the at least two gate electrodes is on and a second gate electrode of the at least two gate electrodes is off.(c) subsequent to (b), measuring a transient discharge of the first gate electrode; and(d) extracting at least one calibration signal of the field effect transistor based at least in part on the transient discharge.

2. The method of claim 1, further comprising, subsequent to (d), measuring a second source-drain current or electrical response or source-drain voltage of the field effect transistor, the first gate electrode of the at least two gate electrodes is off and the second gate electrode of the at least two gate electrodes is on.

3. The method of claim 1, wherein the at least one calibration signal is based at least in part on a capacitance measured between one of the at least two gate electrodes and a source electrode or a drain electrode.

4. The method of claim 1, wherein the at least one calibration signal is based at least in part on a transient source-drain current or electrical response decay or a transient source-drain voltage decay.

5. The method of claim 1, wherein the at least one calibration signal is based at least in part on a baseline source-drain current or a baseline source-drain voltage measured while both the first gate electrode and the second gate electrode are off.

6. The method of claim 1, wherein the at least one calibration signal is based at leastin part on:(a) calculating a dirac point based at least in part on a capacitance measured between the first electrode and a source electrode or a drain electrode;(b) calculating a measure of drift in the capacitance based at least in part of the dirac point; and(c) subtracting the measure of drift from the capacitance at least one of the electrodes of the two or more electrodes to produce a calibrated measure of capacitance.

7. A method of calibrating a sensor, the method comprising:(a) providing a field effect transistor comprising at least two gate electrodes;(b) measuring a source-drain current or electrical response or source-drain voltage of the field effect transistor, v iereinthe source-drain current or electrical response or source-drain voltage is related to a concentration of a biomarker;(c) providing at least one sensor of a distinct sensor modality from the field effect transistor; and(d) adjusting the measuring the source-drain current or electrical response or source-drain voltage of the f ield effect transistor in (b) based at least in part on a reading from the at least one sensor.

8. The method of claim 7, where in the at least one sensor comprises at least one of a galvanometer, a thermometer, an accelerometer, an electrical heart sensor, an optical heart sensor, an altimeter, a gyroscope, an ambient light sensor, an anemometer, a bolometer, a heat flux sensor, a water sensor, a humidity sensor, a temperature sensor or any combination thereof.

9. A sensor, the sensor comprising:(a) a field effect transistor comprising at least two gate electrodes;(b) at least one sensor, wherein the at least one sensor is of a different sensing modality than the field effect transistor; and(c) a processor communicatively coupled to the field effect transistor and the at least one sensor, wherein the processor is configured to:• measure a signal from the field effect transistor;• measure a signal from the at least one sensor; and• adjust the signal from the field effect transistor based at least on the signal from the at least one sensor.

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