Systems and devices for sensing

Abstract

The present disclosure provides an electrochemical sensor, the electrochemical sensor comprising: a gate electrode; a source electrode; a drain electrode; and an field communication layer, wherein the field communication layer is configured to allow diffusion of an analyte into the field communication layer, wherein the analyte undergoes a reaction proximate the gate electrode and within the field communication layer to produce an electrical response, and wherein the electrical response is configured to facilitate current flow between the source electrode and the drain electrode.

Description

SYSTEMS AND DEVICES FOR SENSINGBACKGROUND

[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.SUMMARY

[0002] The present disclosure relates to an electrochemical sensor for detecting analytes, particularly from biological surfaces such as human skin. The sensor includes a gate electrode, a source electrode, a drain electrode, and a field communication layer that facilitates analyte diffusion and subsequent electrochemical reactions near the gate electrode. These reactions produce an electrical response that modulates current flow between the source and drain electrodes. The field communication layer may include hydrophilic, hygroscopic, hydrophobic, or structural materials to aid analyte transport, moisture collection, and signal conduction. In some embodiments, the layer is held in place by a scaffold with a window for targeted analyte entry. The sensor may also include a wicking material to draw moisture from the skin, enabling analyte detection without external sampling. Analytes may include biomarkers such as glucose, electrolytes, proteins, DNA, RNA, hormones, or drugs. The sensor can be activated by various means, including liquid application or exposure to pre-treated materials. The system may further include a conduction station for hydration and a computing component for data processing and analysis. The sensor architecture may incorporate field-effect transistor designs and nanoscale materials such as graphene or carbon nanotubes to enhance sensitivity.Additional aspects and advantages of the present disclosure will become readily apparent to those skilled in this art from the following detailed description, wherein only illustrative embodiments of the present discl osure are shown and described. As will be real ized, the present disclosure is capable of other and different embodiments, and its several detailsare capable of modifications in various obvious respects, all without departing from the disclosure. Accordingly, the drawings and description are to be regarded as illustrative in nature, and not as restrictive.INCORPORATION BY REFERENCE

[0003] 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.BRIEF DESCRIPTION OF THE DRAWINGS

[0004] 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:

[0005] FIG. 1 illustrates a perspective view of a conduction station, which is used to maintain conduction in accordance with embodiments described herein.

[0006] FIG. 2 shows a graph of current vs. time for an electrochemical sensor exposed to different levels of H202 in accordance with embodiments described herein.

[0007] FIG. 3 shows a graph of a fully functionalized electrochemical sensor exposed to increasing levels of glucose in accordance with embodiments described herein.

[0008] FIG.4 shows a graph of an agar gate response in accordance with embodiments described herein.

[0009] FIG. 5 shows a graph of a nanomaterial field effect transistor in accordance with embodiments described herein.

[0010] FIG. 6 shows a graph of a nanomaterial field effect transistor measured over time in accordance with embodiments described herein.

[0011] FIG. 7 shows a graph of the sensor for 20 hours ex-vivo wear in accordance with embodiments described herein.

[0012] FIG. 8 shows a graph of current vs. blood glucose for ex-vivo wear in accordance with embodiments described herein.

[0013] FIG. 9 shows a perspective view of an electrospun mesh in accordance with embodiments described herein.

[0014] FIG. 10 illustrates a graph of current versus voltage of an example electrode gate in accordance with embodiments described herein.

[0015] FIG. 11 illustrate a top-down view of a process diagram for creating an example sensor in accordance with embodiments described herein.

[0016] FIG. 12 illustrates a top down view and a side view of an example base layer for an example sensor in accordance with embodiments described herein.

[0017] FIG. 13 illustrates a top down view of an example sensor after a fifth manufacturing step in accordance with embodiments described herein.

[0018] FIG. 14 illustrates a top down view of an example sensor after a sixth manufacturing step in accordance with embodiments described herein.

[0019] FIG. 15 illustrates a top down view of an example sensor after a seventh manufacturing step in accordance with embodiments described herein.

[0020] FIG. 16 illustrates a top down view of an example sensor after an eighth manufacturing step in accordance with embodiments described herein.

[0021] FIG. 17 illustrates a top down view of an example sensor after a ninth manufacturing step in accordance with embodiments described herein.

[0022] FIG. 18 illustrates a perspective view of a base layer of an example sensor in accordance with embodiments described herein.

[0023] FIG. 19 illustrates a perspective view of an inner layer of an example sensor in accordance with embodiments described herein.

[0024] FIG. 20 illustrates a top down view of the inside of an example sensor in accordance with embodiments described herein.DET AILED DESCRIPTION

[0025] 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.

[0026] 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.

[0027] 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.

[0028] 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.

[0029] 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.

[0030] Large populations in the United States and worldwide suffer from diabetes, a disease where an individual has excess glucose in the blood. Diabetes can cause severe health problems, including cardiovascular disease, nerve damage, kidney damage, eye damage, foot damage, and / or skin and mouth conditions. Monitoring a diabetic individual's level of blood glucose can be important for diabetes treatment and care. An individual may need to self-monitor his or her blood glucose. Current biomarker self-monitoring devices frequently require a blood sample, which an individual generally must obtain by pricking his or her own skin. There is thus a need for low- cost biomarker self-monitoring devices that are simple and easy for a diabetic individual to use that do not require a blood prick or other invasive techniques.

[0031] Described herein are devices for measuring one or more biomarkers in a non-invasive manner by detecting their presence in excreted bodily fluids of an individual. The bodily fluids may include, but are not limited to, sweat, urine, saliva, interstitial fluid, tears, and water vapor from respiration. This invention is about adding a layer of material or materials to an electrochemical system to achieve several utilities.

[0032] The first layer may be referred to as a field communication layer and completes the system by connecting the cathode to the anode through a conductive pathway that enables current flow. In particular, the field communication layer connects an anode that comprises a functional element of interest and a cathode that comprises a field effect transistor (FET).In this configuration the anode becomes the gating element ofthe FET and the salt bridge also exhibits a dielectric utility by enabling the formation of an electric double layer above the anode and above the cathode.

[0033] Another utility of interest of this layer will be referred to as "conduction" and pertains to the above-mentioned electric double layers. To ensure the reliable performance of the transistor in question, the electric double layers must remain stable, and the subjacent layers must sustain effective ionic and / or electronic conduction. The materials and the design of the layer in question are specifically selected for their conducting and release properties, such that the conduction is continuously maintained above the desired threshold throughout the life cycle of the system.

[0034] Another utility derived from the layer of interest will be referred to as "sample transport." The layer in question readily conforms to the skin ofthe user and provides a medium through which the samples of interest can diffuse and accumulate. Hence, the layer enables the system to transport the analytes from the skin ofthe user to the functional elements of the system.

[0035] By carefully selecting the materials that comprise the layer, a utility referred to as "selective blocking" can be engineered. One of the requirements of the system is to selectively measure analytes with minimal to no false positive results (or spurious readings unrelated to the analyte of interest). The layer in question acts as a selective blocking element that can allow the diffusion of the desired analyte while blocking or limiting the diffusion of interferent substances that could confound the readings.

[0036] The present invention relates to a novel layer designed for integration into electrochemical systems, providing multiple functionalities to enhance system performance and reliability.

[0037] One aspect of the invention involves the introduction of a specialized layer, termed herein as the field communication layer, which serves as a conduit connecting the cathode and anode within the system. Notably, this field communication layer facilitates current flow while also enabling the anode to function as a gating element for a field -effect transistor (FET). Additionally, the field communication layer contributes to the formation of stable electric double layers above both the anode and cathode.

[0038] Another aspect pertains to the "conduction" function of the field communication layer, ensuring the maintenance of stable electric double layers and the continuous conduction across subjacent layers critical for optimal system operation. Materials are selected for their ability to sustain effective conduction levels above a predefined threshold over the system's operational lifespan.

[0039] Furthermore, the field communication layer facilitates "sample transport" by conforming to the user's skin, allowing analytes to diffuse and accumulate efficiently. This feature enables the transportation of analytes from the skin to the functional elements of the system, thereby enhancing its analytical capabilities.

[0040] Lastly, the field communication layer offers "selective blocking" capabilities by carefully engineering material composition. This allows for the diffusion of target analytes while inhibiting the passage of interfering substances, thereby minimizing false positive readings and ensuring accurate measurements.

[0041] The multifunctional field communication layer described herein enhances the performance, reliability, and selectivity of electrochemical systems, offering benefits such as improved analyte detection, efficient sample transport, and stable electric double layer formation.

[0042] The present invention is a method to activate the sensor system by activating it with a solution before use. The solution to be used can be: deionized water, tap water, saline buffer (PBS, DPBS) in IX to 10 X concentrations, or an analyte solution prepared in any of the above solution of a given concentration. The solution can be glucose (0.01 mg / dL to Ig / dL) or lactic acid (0.01 mg / dL to Ig / dL).

[0043] The purpose of the method to activate the sensor system is: activate the different layers of the system that require being conductive to function; promote skin contact and analyte extraction, diffusion, and capture; enable electrical and / or ionic contact between the different electrodes; establish a sensing baseline to adjust calibration by measuring the sensor responseto a known biomarker concentration; provide a means to maintain conduction when the sensor is not being used, to prevent degradation of the layers; preserve the field communication layer’s integrity.

[0044] Activation can be accomplished by: adding a drop of the desired activating solution on the biosensor using a dropper; activating the biosensor by submerging / dunking sensor in a bath of the desired solution; activating the biosensor by place a preactivated sponge on the biosensor allowing for uniform activating; or by spraying the solution on the biosensor.

[0045] The present disclosure pertains to the design of a sensor and / or a device with a specific purpose of promoting and sequestering moisture at the skin interface with the area of interest on the sensor and / or device.

[0046] The device is designed to attach onto the skin of a user through elastic bands / straps or an adhesive patch in such a way that a light pressure is applied to the skin at all times. The area of interest may be recessed into a cavity either on the device or on the sensor. The walls of the cavity may be vertical or slightly slanted. In some embodiments, the cavity may comprise a soft material (e.g., rubber, silicone, polymer, or plastic) gasket on its periphery to strengthen the seal. In some embodiments, the area of interest may be coated with a wicking material to transport all available moisture to the area. In some embodiments, the wicking material is itself hygroscopic and is activated with an activation solution comprising any aqueous, polar, or non- polar solution to interface with the skin with minimal impedance, allowing molecules of interest to naturally diffuse into the activated layer to reach the area of interest.

[0047] Activating materials may be hydrophilic, hygroscopic (e.g., PVA, nylon, hydrated hydrogel, or desiccated hydrogel). Wicking materials may be patterned with hydrophobic areas to control and drive transport (e.g., paper microfluidics).

[0048] The top cover functions as a structural support and protective barrier for the field communication layer and underlying sensor elements, such as the channel. In some embodiments, the top cover may define a recessed region or form a mold-like enclosure to contain or guide the deposition of the field communication layer. It may selectively expose one or more functional areas, such as the gate region, while shielding other regions from mechanical interference. The top cover may be fabricated from one or more rigid or semi-rigid materials and can be coupled to the sensor substrate using various attachment or alignment means. In some implementations, features of the top cover may facilitate the shaping, positioning, or stabilization of internal layers prior to or during use.Electrospinning techniques may be used to create a moisture -wicking layer that facilitates connectivity betweenthe gate and the channel while maintaining stability in aqueous environments. In some embodiments, a fibrous film composed of nanoscale fibers is deposited onto the sensor substrate using a charged polymer solution under appropriate processing conditions. This fibrous network may provide directional fluid transport or enhanced surface area while being structurally stable in contact with moisture. The choice of polymer formulation, deposition environment, and substrate configuration may be selected based on the desired wicking, adhesion, and mechanical properties of the final film.

[0049] Other materials suitable for electrospinning may include, but are not limited to, synthetic or natural polymers, copolymers, or blends thereof that possess hydrophilic, hydrophobic, or surface- modifiable properties. Examples include polyvinyl alcohol (PVA), polycaprolactone (PCL), polyvinyl butyral (PVB), hydrophilic-coated hydrophobic fibers, and naturally hydrophilic fibers. Materials may be selected based on desired mechanical strength, porosity, wettability, biocompatibility, or responsiveness to activation or functionalization processes.

[0050] FIG. 1 illustrates a view of a conduction device that may be used to keep the layers of the electrochemical sensor activated. The device may comprise a bottle with a fluid in it. The device may comprise a portion for receiving the electrochemical sensor. The fluid may be transferred from the bottle to the electrochemical sensor to hydrate the electrochemical sensor.

[0051] FIG. 2 illustrates a representative graph of a sensor covered with a hydrogel -based field communication. The sensor was exposed to increasing concentrations of an analyte, such as hydrogen peroxide (H2O2), within a general range (e.g., from about 5 pM to about 100 pM). The graph presents the sensor's current response over time. A trend of decreasing current with increasing analyte concentration was observed, which aligns with expected sensor behavior. The graph further illustrates the channel signal, which is indicative of proper conduction through the field communication layer and confirms the operational integrity of the sensor system.

[0052] FIG. 3 illustrates a representative graph of a fully-functionalized sensor exposed to increasing concentrations of a biomarker, such as glucose. The signal from the gate electrode was monitored over time as the biomarker concentration increased within a range of approximately 0.01 mg / dL to 1 mg / dL. The sensor demonstrated a measurable sensitivity across the tested concentration range, exhibiting a generally linear increase in signal response relative to the increasing concentration of the biomarker. This result supports the sensor’s effective functionality in detecting and quantifying varying biomarker levels.

[0053] FIG. 4 illustrates a graph of an agar gate response. Current was measured at different concentrations of agar between 0 and 1 mg / dL. The sensor displayed a linear increase in current with increasing agar concentration.

[0054] FIG. 5 illustrates a graph of multiple nanomaterial field effect transistor (FET) curves for an electrochemical sensor described herein. The curves displayed a V-shape typical of nanomaterial- based FETs, which indicated that the transistor was complete. The X axis here is the swept voltage at the gate, while the Y axis is the measured current in the channel. The results showed the transistor working as intended.

[0055] FIG. 6 illustrates a graph of nanomaterial FETs when time is allowed to pass. As the field communication layer dried with time passing, the V-shape as seen in FIG. 5 diminished and tended toward a flat line. This indicated that the field communication layer was losing performance as it became deactivated. These results indicated that conduction is necessary for preserving sensor function.

[0056] FIG. 7 illustrates a graph of current, voltage, galvanometer magnitude, and glucose levels over time for an electrochemical sensor worn outside the body for 20 hours with a top cover.This ex-vivo wear showed stable conduction for up to 20 hours during wear. This suggests that the agar did not delaminate and that top cover provided the mechanical stability desired for the sensor.

[0057] FIG. 8 illustrates a graph of current and blood glucose over time for an electrochemical sensor worn ex-vivo with a top cover. This ex-vivo data shows that the top cover is providing ample protection of the channel from mechanical forces during wear because we don't see any point spike events or sharp changes in baseline in over 5 hours of data using the ABS top cover.

[0058] FIG. 9 illustrates a perspective view of an electrospun mesh used as a wicking material for an electrochemical sensor as described herein. This electrospun mesh was moisture wicking and hydrophilic.

[0059] The present disclosure provides an electrochemical sensor, the electrochemical sensor comprising: a gate electrode; a source electrode; a drain electrode; and an field communication layer, wherein the field communication layer is configured to allow diffusion of an analyte into the field communication layer, wherein the analyte undergoesa reaction proximate the gate electrode and within the field communication layer to produce an electrical response, and wherein the electrical response is configured to facilitate current flow between the source electrode and the drain electrode. In some embodiments, the field communication layer comprises one or more hydrophilic materials. In some embodiments, the analyte is delivered from a surface to be measured, optionally, wherein the surface to be measured is the skin of a user. In some embodiments, the electrochemical sensor is placed on the skin of the user to detect one or more analytes. In some embodiments, the one or more biological analytes comprise 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 reaction is configured to form one or more products, optionally, wherein the one or more products comprises peroxide, and the one or more products are configured to form one or more charged particles, the one or more charged particles configured to produce the electrical response.

[0060] The present disclosure provides an electrochemical sensor, the electrochemical sensor comprising: a gate electrode; a source electrode; a drain electrode; an field communication layer; and a scaffold for the field communication layer, wherein the scaffold is configured to cover a channel between the source and the drain, wherein the scaffold comprises a window configured to allow diffusion of an analyte into the field communication layer, wherein the analyte is configured to produce a gating potential, and wherein the gating potential is configured to facilitate current flow between the source electrode and the drain electrode. In some embodiments, the scaffold comprises a plastic structure that holds the field communication layer in place within the electrochemical sensor. In some embodiments, the plastic structure comprises acrylonitrile butadiene styrene, polyetherimide, polyether ether ketone, polyethylene terephthalate, or a plastic with a high flexural modulus.

[0061] The present disclosure provides an electrochemical sensor, the electrochemical sensor comprising: a gate electrode; a source electrode; a drain electrode; an field communication layer; and an area coated with a wicking material, the wicking material configured to interface with a skin of a user and to transport availabl e moisture on the skinto the area, wherein the available moisture comprises an analyte, wherein the analyte is configured to produce a gating potential, and wherein the gating potential is configured to facilitate current flow between the source electrode and the drain electrode. In some embodiments, the wicking material comprises a hygroscopic material. In some embodiments, the hygroscopic material comprises PVA, nylon, or a hydrogel. In some embodiments, the wicking material is patterned with hydrophobic areas to control and drive transport. In some embodiments, the wicking material is activated with a solution. In some embodiments, the solution may include any suitable aqueous, polar, or non-polar solution capable of promoting conduction, molecular transport, or interfa ce formation with the skin or target surface. In some embodiments, the area coated with the wicking material is recessed into a cavity on the electrochemical sensor. In some embodiments, the cavity further comprises a soft material gasket on a periphery of the cavity. In some embodiments, the soft material gasket comprises rubber or silicone. In some embodiments, the field communication layer comprises a hydrogel, a saccharide polymer, nylon, or polyvinyl alcohol. In some embodiments, the hydrogel comprises agar or agarose. In some embodiments, the field communication layer further comprises one or more hydrophobic materials or treatment that direct or enhance sample transport. In some embodiments, the field communication layer is treated or mixed with one or more additional hygroscopic materials. In some embodiments, the one or more additional hygroscopic materials comprise hyaluronic acid, titanate salts, urea, glycerol, polyethylene glycol, polysorbate 20, polysorbate 60, or Triton X- 100. In some embodiments, the field communication layer comprises one or more salts. In some embodiments, the one or more salts comprise PBS, sodium chloride, choline chloride, or lithium. In some embodiments, the field communication layer further comprises one or more structural materials. In some embodiments, the one or more structural materials comprise plastics, polymers, composites, biomaterials, nanomaterials, or other structurally supportive materials suitable for maintaining the integrity and function of the device. In some embodiments, the field communication layer is treated chemically, mechanically, or through energy exposure. In some embodiments, the energy exposure comprises plasma treatment, ozone treatment, or abrasion. In some embodiments, the field communication layer is mixed with a blocking material, a blocking chemical, mesh, one or more filters, or one or more pores to prevent transport of undesired species. In some embodiments, the blocking materialcomprises one or more materials selected from polymers, biomaterials, nanomaterials, composites, or other functional materials designed to restrict or regulate molecular transport. In some embodiments, the field communication layer (previously referred to as the field communication layer) further comprises a hydrophobic coating, which may include hydrophobic polymers, nanomaterials, or other water-repellent materials. In some embodiments, the hydrophobic coating comprises one or more materials selected from hydrophobic polymers, nanomaterials, plastics, elastomers, or combinations thereof. In some embodiments, liquid is added to the field communication layer to facilitate conduction of the electrochemical sensor. In some embodiments, the gate, source, or drain electrode comprises one or more conductive or semiconductive materials, including but not limited to nanomaterials such as zero-dimensional (OD), one-dimensional (ID), and two-dimensional (2D) materials, polymers, composites, and other suitable advanced materials. In some embodiments, the field communication layer comprises a solvent. In some embodiments, the field communication layer comprises a layer of material added to the electrochemical sensor. In some embodiments, the field communication layer enables a formation of an electric double layer above the source electrode and the drain electrode. In some embodiments, the layer of material conforms to the skin of the user and provides a medium through which samples can diffuse or accumulate, thereby transporting analytes from the skin of the user to the drain electrode. In some embodiments, the layer of material is synthesized as ceramic, polymer, or composite. In some embodiments, the layer of material is synthesized in a glassy or fibrous manner. In some embodiments, the electrochemical sensor is activated by adding a drop of a desired activating solution to the electrochemical sensor using a dropper. In some embodiments, the electrochemical sensor is activated by submerging or dunking the electrochemical sensor in a bath of a desired activating solution. In some embodiments, the electrochemical sensor is activated by placing a preactivated sponge on the electrochemical sensor, thereby allowing for uniform activating of the electrochemical sensor. In some embodiments, the electrochemical sensor is activated by spraying a desired activating solution onto the electrochemical sensor. In some embodiments, the source electrode, the drain electrode, the one or more gate electrodes and the channel collectively form a field effect transistor. Optionally, the gate electrode may be configured to operate as a control electrode. In some embodiments, the channel comprises a nanoscale material. In some embodiments, the nanoscale materialcomprises nanomaterial. 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.

[0062] The present disclosure provides a conduction station, the conduction station configured to receive the electrochemical sensor and to wet the field communication layer of the electrochemical sensor.Nanomaterial PG FET Description

[0063] The following application are incorporated by reference herein for all purposes: WO201 9 / 183279, WO2017 / 216641, and WO2015164552.Nanomaterial Field Effect Transistors in General

[0064] Nanomaterial possesses a remarkable mechanical resistance; this enables thicknesses on the order of a monolayer or bilayer to be subjected 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.

[0065] 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 substrate. 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 substrate. Any applicable method can be applied to fabricate a GFET, including, for example, theinformation disclosed in International Patent Publication No. WO 2015 / 164,552, which is hereby incorporated by reference in its entirety.

[0066] 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.

[0067] In one aspect, disclosed herein is a new type of field effect transistors (FETs) that do not have a physical gate.

[0068] 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.

[0069] 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.

[0070] 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.

[0071] In some embodiments, nanomaterial layer can have a uniform thickness, preferably a predetermined thickness of one or more monolayers of nanomaterial. As thethickness effects electrical properties, e.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.

[0072] 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.

[0073] In some embodiments, nanomaterial layer can be surface treated with receptors 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.

[0074] 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.

[0075] Nanomaterial 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, nanomaterial is a monolayer of carbon atoms. Each carbon atom in nanomaterial 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.

[0076] When a polar fluid is deposited on a nanomaterial layer, the electronic characteristics of nanomaterial and similar nanomaterials will cause re-organization of thecharges in the polar fluid and form a liquid induced gate voltage, which can modulate the current between the source and drain electrodes.

[0077] As shown in FIG. 10, 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 to plateau 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.

[0078] 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 / I- (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.

[0079] 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

[0080] Example 4 A through 4C are set ups by which gate voltage at a polar fluid gate terminal (PF GT) is determined.

[0081] Example 4A is an exemplary embodiment, with a base device with a dielectric layer and a gate metal . Gate potential is measured between the gate metal and the ground. Dielectric layer is added underneath the substrate of the base device (e.g., substrate ). Gate metal 8 is added underneath dielectric layer. Gate metal is added only to measure the induced gate voltage, no voltage will be applied through gate metal. 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 nanomaterial (ambipolar), Vgl can follow the transconductance response typical to a nanomaterial device.

[0082] 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 nanomaterial (ambipolar), thenVg2 will follow the transconductance response typical to a nanomaterial device.

[0083] 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.

[0084] 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.

[0085] Example 5A is an exemplary embodiment, with a circuit used for sensor readout via a polar fluid nanomaterial field effect transistor (PFGFET). In Example 5A, a constant current (le) is supplied to the PFGFET. Output voltages (VouT) 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.

[0086] 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.Wearable Sensor

[0087] Non-invasive, quick, and convenient ways of sensing 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 molecules of interest in real time from sweat or other bodily fluids such as saliva. Examples of such molecules include glucose, lactate, electrolytes, and cholesterol.

[0088] 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 bio-fluid, 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 DN A, an RNA, an aptamer, an enzyme, a biomolecule, a chemical molecule, a synthetic molecule, or combinations thereof.

[0089] The systems or devices may further be worn unobtrusively (e.g., everyday) inconvenient 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 of the user. The user may utilize the information provided by the devices to take further action as desired.

[0090] 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 / or magnets to facilitate attachment of a sensor to the transmitter.

[0091] The sensor may be removably coupled to the transmitter. The sensor comprises a sensor substrate, electrodes, and sensor elements such as nanomaterial. 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.

[0092] 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 , cure, conduction layer 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.

[0093] Embodiments disclosed herein provide devices, systems, and methods for monitoring physiological signals. Disposable or replaceable sensors may be utilized inmonitoring 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.

[0094] 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 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 sensing apparatus.

[0095] 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.

[0096] 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 same biomarker.

[0097] 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.

[0098] 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 capabl e 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.

[0099] 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.

[0100] 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 tothe 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.

[0101] 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 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.

[0102] 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.

[0103] 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 proteins, enzymes, aptamers, cholesterol, cancer biomarkers, and other diagnostically relevant molecules. 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 nanomaterial-based 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 isconfigured 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.

[0104] 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.

[0105] 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 theprocessing 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.

[0106] 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 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 for detecting 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.

[0107] 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 layerof 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.

[0108] In some embodiments, the receptor layer comprises a receptor selected from group consisting of pyrene boronic acid (PBA), pyrene N-hydroxysuccinimide ester (Pyrene- NIIS), 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, aDNA, anRNA, 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. 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.

[0109] 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 asurface 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.

[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 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 each comprises nanomaterial.

[0111] 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 plural ity 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.

[0112] 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.

[0113] 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 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 and store sensing signals from the modular sensor.

[0114] 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.

[0115] 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 agroup 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.

[0116] 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 nanomaterial-based 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.

[0117] 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 realtime 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.

[0118] 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 mechanismprovided 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.

[0119] Also disclosed is a wearable device. The wearable 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. 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.

[0120] In some embodiments, the processing module is configured to selectively activateat 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.

[0121] 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.

[0122] In some embodiments, the receptor layer comprises a receptor selected from group consisting of 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, and biological molecules. In some embodiments, the target analyte comprises an electrolyte, glucose, lactic acid, IL6, a cytokine, IIER2, Cortisol, ZAG, cholesterol, vitamins, a protein, a drug molecule, a metabolite, a peptides, an amino acid, a DNA, an RN A, 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 isflexible. 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.

[0123] In some embodiments, 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.

[0124] Accordingly, in one aspect, a disposable sensor may be provided. The disposable sensor 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.

[0125] In some embodiments, the volume is equal to or less than about 0.5 cm3. In some embodiments, the sensor element comprises nanomaterial. 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.

[0126] 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.

[0127] 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.

[0128] 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.Sensor with Field communication layer

[0129] FIG. 11 illustrates a top-down view of a process diagram for creating an example sensor in accordance with embodiments described herein.

[0130] Provided herein are methods of manufacturing a biomarker sensor shown in FIG. 11 illustrate and comprising adding a support layer, depositing nanoparticles, picking and placing nanoparticles strips onto the support layer, metallization, passivation, functionalization or tuning of the nanomaterial channel, addition of a spacer, addition of an field communication layer or matrix layer, addition of a top cover, and conduction of the field communication layer.

[0131] The biomarker sensor can comprise a polar fluid gated field-effect transistor (PFGFET). In some cases, the biomarker sensor can comprise one or more gate electrodes. The biomarker sensor can comprise a source electrode and a drain electrode. There can be a channel connecting the source electrode and the drain electrode. In some cases, the various electrodes can comprise conductive materials or conductive polymers. The various electrodes can comprise wires, squares, circles, or other shapes of metals.

[0132] FIG. 12 il lustrates a top-down and side view of the base substrate of the biomarker sensor, comprising the base substrate 121 with conductive pads 122. This can be the starting point for the method of manufacturing the biomarker sensor. The backbone of the biomarker sensor can be a base substrate 121 comprising conductive pads 122. In some cases, the conductive pads 122 can be preset on the base substrate. In some cases, thesubstrate 121 is a dark substrate or a black substrate. The substrate 121 can comprise one or more polymers that do not directly adhere to nanomaterial. In some cases, there can be four conductive pads 122. In some cases, the four conductive pads 122 can be arranged as four squares in a diamond shape, with one on the top, one on each side, and one on the bottom, as shown in FIG. 12. In some cases, there can be less than four conductive pads. In some cases, there can be greater than four conductive pads. The conductive pads can function as the bases for electrodes that may be printed on top of them. Some of the conductive pads can function as the bases for gate electrodes while others function as the bases for source or drain electrodes.

[0133] In some cases, the top and bottom conductive pads form the bases for source and the drain for the PFGFET. In some cases, the right and left conductive pads form the bases for a gate for the PFGFET. The gate can comprise conductive materials and nanoparticles. "Top” and "botom" refer to when the chip is viewed with the longer edge vertical, and "right and left" refer to when the chip is viewed with the longer edge vertical as in FIG. 1.

[0134] The support layer can comprise different polymers than substrate. The support layer can cover substantially all of the base substrate except the conductive pads. The support layer 130 can leave open the conductive pads to be formed into electrodes by ink printing conductive material in subsequent steps. The simi lar material of the support layer can allow nanomaterial to adhere to the support layer. The support layer 130 can comprise one or more of thermoset, thermoplastic, elastomeric, or glassy materials, such as polyurethane, ethylene- vinyl acetate (EVA), silicone, epoxies, polyvinyl alcohol (PVA), nylon, polymethyl methacrylate (PMMA), parylene, acrylonitrile butadiene styrene (ABS), polyethylene terephthalate (PET), or any combinations thereof. The support layer 130 can bind to the nanomaterial paper through one or more of thermobonding, dropcasting, spincoating, electrospining, lamination, compression, electrodeposition, screen or stencil printing, atomic layer deposition (ALD), sputtering, chemical vapor deposition (CVD), direct ink write, or any combination thereof. The support layer 130 can assist with adhesion between the subsequent layers as well.

[0135] Nanoparticles can be deposited on one or more of the right or left conductive material-ink printed gates on the conductive pads. In some cases, nanoparticles can be used toadd receptors to the biomarker sensor. In some cases, the biomarker receptors and enzymes are present on the gate of the transistor. In some cases, the receptors can comprise one or more of glucose oxidase, lactic oxidase, antibodies, single- strand DNA, aptamers, glucose dehydrogenase, a cocktail of enzymes with different pH activity regions to enable sensitivity across an expected physiological pH, or any combination thereof. In some cases, the nanoparticles can further comprise one or more secondary receptors, for example a catalase, NAD and NADH, diaphorase, or any combination thereof. Catalase can be used to regenerated oxygen and remove hydrogen peroxide after biomarker has been broken down into hydrogen peroxide. NAD and NADH and cycle to provide energy to glucose dehydrogenase for a reaction. Diaphorase can be used to regenerate the NAD and NADH.

[0136] Disclosed herein is a method to pick up, move, and place nanomaterial without impacting its electrical properties or causing damage. In some cases, this method can be used to pick up and place a macroscale material of nanoscale design (e.g., nanomaterial). The nanomaterial can be attached to a backlayer. The nanoscale material or nanomaterial can be picked up mechanically. The picked-up nanomaterial can be moved to a new location for further processing or placement via robotic arm, mechanical arm, gantry, conveyor, or any combination thereof. The nanomaterial can be lowered onto the support layer and be released on top. The nanomaterial may be processed for adhesion or the support layer can be pretreated.

[0137] In some cases, more generally, the nanomaterial can be lowered on an alternate substrate. In some cases, the alternate substrate may comprise silicone paper. In some cases, the alternate substrate may be soft or hard. The alternate substrate may comprise materials made of, but not limited to, foam, ceramic, plastic, metals, rubber, or any combination thereof.

[0138] In some cases, the metal used in metallization comprises conductive material. Conductive material can be added to one or more of the top or bottom conductive pads to print the source and drain electrodes. The conductive material can be ink printed.

[0139] The metal can be used to physically or mechanically connect the nanomaterial layer to the two conductive pads below the nanomaterial layer. The metal may not hold the nanomaterial down against the two conductive pads below the nanomaterial layer. The metal may electrically connect the nanomaterial layer to the two conductive pads belowthe nanomaterial layer. The metal may conduct electrical signals between the nanomaterial layer and the two conductive pads below the nanomaterial layer. The metal may receive electrons through the field communication layer from the gate. In some cases, an additional layer may be added to block the metal from contacting the skin of a user.

[0140] In some cases, the metallization process can be used to form the electrodes and then connect the nanomaterial layer to the newly made electrodes. The metallization process can then likewise connect the nanomaterial to the electrodes electrically.

[0141] In some cases, the metal can have cytotoxic properties. This can include the metallization applied as a connector and the doped nanoscale layer. It can be important to prevent conductive material nanoparticle delamination from the sensor. To prevent a cytotoxic response in the wearer, the doped nanoscale layer channel and metal connector may be passivated so to prevent nanoparticle delamination and subsequent migration through a field communication layer onto the skin surface.

[0142] The doped nanoscale layer channel and metal connector can be passivated via electrodeposition, as shown in FIG. 13. FIG. 13 illustrates a top-down of a sensor comprising base substrate 121, support layer 130, nanomaterial treated gate electrodes 140, nanomaterial channel 150, metalized source and drain electrodes 160, and passivation layer 170. As shown in the side view, the passivation later can lay on, and passivate, one or both of the source and drain electrodes 160 or the doped nanoscale layer channel 150. Although not shown underneath the shaded area, there may still be conductive pads 122 in all four squares. As indicated by the number on the left side, passivating the source and drain electrodes, nanomaterial channel, or both can comprise a fifth step in the manufacturing method described herein.

[0143] An aqueous polymer solution can be placed onto the doped nanomaterial channel 150 or source and drain electrodes 160, and then chronoamperometry can be run using a three electrode setup with the channel or metal connector as the working electrode, a nanomaterial wire as the counter electrode, and silver or silver chloride as the reference electrode. The polymer can comprise the passivation layer 170. The channel or metal connector can then be cleaned with phosphate buffered saline (PBS). The polymer can be both conductive and non-conductive polymers, for example o-phenylenediamine (oPD), parylene, polypurrole, polyaniline, or any combination thereof.

[0144] As discussed above, passivation of the doped nanoscale layer channel can occur soon after nanomaterial doping. Alternatively, or in addition, passivation of the doped nanoscale layer channel can be done at the same time as passivation of the metal connector.Functional ation

[0145] Once the nanomaterial channel of the PFGFET is electrically connected to the source and drain electrodes, the sensor can be tuned or functionalized. FIG. 14 illustrates a top-down of a sensor comprising base substrate 121, support layer 130, functionalized nanomaterial treated gate electrodes 180, nanomaterial channel 150, metalized source and drain electrodes 160, and passivation layer 170. Although not shown underneath the shaded area, there may still be conductive pads in all four squares. As indicated by the number on the left side, functionalizing the gate electrodes can comprise a sixth step in the manufacturing method described herein.

[0146] Functionalization can comprise a functional layer of a sensor that is built to perform one or more of continuous, periodic, or one off measurements of one or more target analytes of interest. Functionalization can comprise a method to tune the properties of a sensor with different functional layers to achieve specific desired properties. In some cases, the layers are "active" electrochemically or biologically and can be used to convert some substance into another or convert a chemical into an electrical signature. In some cases, the layers may be inert and be used to block or prevent the movement or diffusion of some substance. The layers may be used as a structural matrix to bind and immobilize molecules or charges to create properties of interest or hold other layers in place. Functionalization can be used to tune the gate electrodes.

[0147] In some cases, an active layer such as a layer comprising an enzyme can be used to transform a molecule of interest into a different substance that can then be broken down into an electrochemical substance. The molecule of interest can be glucose. Glucose can be broken down into, among other compounds, hydrogen peroxide. Hydrogen peroxide can then be broken down into electrons. In some cases, two electrons can be generated from each molecule of hydrogen peroxide. The active enzymatic layer can comprise one or more of glucose oxidase, lactic oxidase, antibodies, single-strand DNA, aptamers, glucose dehydrogenase, a cocktail of enzymes with different pH activity regions to enable sensitivity across an expected physiological pH, or any combination thereof. The activeenzymatic layer can also comprise secondary receptors to increase the sensitivity of the nanomaterial sensor. The secondary receptors can comprise one or more of a catalase, NAD and NADH, diaphorase, or any combination thereof. Catalase can be used to regenerated oxygen and remove hydrogen peroxide after glucose has been broken down into hydrogen peroxide. NAD and NADH and cycle to provide energy to glucose dehydrogenase for a reaction. Diaphorase can be used to regenerate the NAD and NADH. The enzymatic reactions occurring due to the enzymatic layer can be facilitated or sped up by redox mediators and catalytic elements. The redox mediators can comprise Prussian blue, ferricyanide, or both. The catalytic elements can comprise one or more of gold, platinum, palladium, carbon, or any combination thereof. The conductive material can be used to minimize or prevent metallic diffusion. The catalytic elements can be used to increase the reaction speed or facilitate the second reaction to break down hydrogen peroxide into electrons. In some cases, the catalytic element can be the same as the element used to dope the nanomaterial channel. In some cases, the catalytic element can be different from the element used to dope the nanomaterial channel. In some cases, the catalytic elements can comprise a separate layer from the functionalization layer.

[0148] The active enzymatic layer may be supplemented by an inert protein layer that will block nonspecific binding site and only allow the molecule of interest to react. These inert proteins can be selected to synergize with the enzyme layer and increase its lifetime. A first inert layer can comprise, but is not limited to, one or more of casein or bovine serum albumin (BS A). A second inert layer may be used to trap the inert protein layer and active enzyme layer in close proximity and bind them to the surface of the nanomaterial sensor. This can be done through electrostatic chargers, physical hindrance, or both.

[0149] While described in view of deriving electrons from glucose, other molecules that release electrons upon one or multiple reactions can be used to activate the sensor.

[0150] After the gate electrodes have been functionalized or tuned, there may be multiple manufacturing steps geared towards protecting the skin of a user from any cytotoxic residues remaining after passivation. These steps may comprise adding a spacer onto the functionalized device, adding a field communication layer, adding a top cover, and activating the field communication layer.

[0151] FIG. 15 illustrates a top-down of a sensor comprising base substrate 121, supportlayer 130, functionalized nanomaterial treated gate electrodes 180, nanomaterial channel 150, metalized source and drain electrodes 160, passivation layer 170, and spacer 190. Although not shown underneath the shaded area, there may still be conductive pads in all four squares. Although not shown underneath the shaded area, there is still the support layer 130 under the spacer 190. As indicated by the number on the left side, adding a spacer can comprise a seventh step in the manufacturing method described herein. The spacer can comprise a substrate with adhesive on one end that only exposes the electrodes and the nanomaterial overlaying the electrodes. This can protect a user's skin from contacting the remainder of the doped nanoscale layer channel by creating a layer of padding.

[0152] To efficiently transfer glucose molecules to the spaced and partly covered nanomaterial channel, a field communication layer can be added on top of the spacer. FIG. 16 illustrates a top-down of a sensor comprising base substrate 121, support layer 130, functionalized nanomaterial treated gate electrodes 180, nanomaterial channel 150, metalized source and drain electrodes 160, spacer 190, and field communication layer 200. Although not shown underneath the small shaded area, there may still be conductive pads in all four squares. Although not shown underneath the large shaded area, there is still the support layer 130 under the spacer 190. As indicated by the number on the left side, adding a field communication layer or matrix layer can comprise an eighth step in the manufacturing method described herein. The field communication layer 200 can cover the gate electrodes 180, the source electrode, and the drain electrode. The field communication layer 200 can cover the nanomaterial channel 150. The field communication layer 200 can carry one or more of biochemical, molecules, and charges (e.g., electrons) between the electrodes. The field communication layer 200 can carry one or more of biochemical, molecules, and charges (e.g., electrons) to the nanomaterial channel 150. As such, even if a glucose molecule from sweat contacts the area of the gate electrodes, the electrons can still be moved to the nanomaterial channel. The field communication layer 200 can hold the nanomaterial layer 150 in place on the support layer 130.

[0153] The field communication layer 200 can comprise one or more of genipin-based cross-linked 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.

[0154] After adding the field communication layer, a top cover can be added to further protect a user's skin from contacting any metallic particles used in the device. FIG. 17 illustrates a top-down view of a sensor comprising base substrate 121, functionalized nanomaterial treated gate electrodes 180, field communication layer 200, and top cover 210. The top-down view shows a view from outside the top cover. Although not shown underneath the small shaded area, there may still be conductive pads in all four squares. Although not shown underneath the large shaded area, there is still the support layer under the spacer and top cover. In some cases, the top cover 210 does not leave the nanomaterial channel open. In some cases, the top cover 210 does not leave the source or the drain electrode open. In some cases, the top cover may leave the one or more gate electrodes open.

[0155] After covering the device with a top cover such that all functional parts of the device are disposed between the top cover and the base layer substrate, the field communication layer can be activated. Activation can make the field communication layer moist or wet to facilitate the transfer of ions across the field communication layer. Activation mediums can comprise one or more polar or non-polar fluids, or any combination thereof. In some cases, the viscous liquids can reduce the loss of enzymatic activity and reduce fouling.

[0156] Described herein is a device for measuring an analyte. The device can comprise a sensor. The analyte can comprise biomarker. The biomarker sensor can measure glucose without contacting a wearer's blood. The device can be worn on a wrist, arm, leg, or other location. The device can be worn on a band such as a wristband, ankle-band, bicep cuff, or a thigh band, or can be clipped onto undergarments to rest against the skin. Adhesives can also be used on the top cover to hold the device directly against the skin if proper precautions are taken to not injure the wearer.

[0157] Provided herein is a device comprising a bottom substrate and a top cover with various functional layers in between. The layers can comprise electrodes forming a gated field-effect transistor (FET), a field communication layer, a matrix layer, a FET channel, and electrical conductors. The device is designed to contact the skin of a wearer at the top cover. The top cover can be designed to protect the skin of the wearer from the functional layers of the device that may comprise cytotoxic nanoparticles. The top cover may be wet or moist to hydrate the field communication layer matrix layer.

[0158] FIG. 18 provides a magnified perspective view of the base substrate 1121 comprising conductive pads 1122. FIG. 19 provides a magnified perspective view of the support layer 1130. FIG. 20 shows a top-down view of the nanomaterial channel 1150, the gate electrodes 1140 and source and drain electrodes 1160, and the base substrate 1121 of the sensor.

[0159] The sensor device can comprise a base substrate 1121 that forms the side farthest away from the skin of a patient. In some cases, the substrate 1121 is a dark substrate or a black substrate. The substrate 1121 can comprise one or more polymers that do not directly adhere to nanomaterial. The base substrate 1121 can comprise conductive pads. The conductive pads can be preset in or on top of the base substrate 1121. The conductive pads can be separately added or adhered to the base substrate 1121. In some cases, there can be four conductive pads. In some cases, the four conductive pads can be arranged as four squares in a diamond shape, with one on the top, one on each side, and one on the bottom. In some cases, there can be less than four conductive pads. In some cases, there can be greater than four conductive pads. The conductive pads can function as the bases for electrodes that may be printed on top of them. Some of the conductive pads can function as the bases for gate electrodes while others function as the bases for source or drain electrodes.

[0160] In some cases, the top and bottom conductive pads form the bases for source and the drain for the PFGFET. In some cases, the right and left conductive pads form the bases for a gate for the PFGFET. "Top” and "bottom" refer to when the chip is viewed with the longer edge vertical, and "right and left" refer to when the chip is viewed with the longer edge vertical as in FIG. 1.

[0161] The sensor device can comprise a support layer 1130 disposed on the base substrate 1121. The support layer can comprise a similar material to a nanomaterial backlayer. The support layer 1130 can comprise different polymers than substrate 1121. The support layer 1130 can cover substantially all of the base substrate 1121 except the conductive pads. The support layer 1130 can leave open the conductive pads to be formed into electrodes by ink printing conductive material. The similar material of the support layer 1130 can allow nanomaterial to adhere to the support layer. The support layer 1130 can comprise one or more of thermoset, thermoplastic, elastomeric, or glassy materials, such as polyurethane, ethylene-vinyl acetate (EVA), silicone, epoxies, polyvinyl alcohol (PVA), nylon, polymethyl methacrylate (PMMA), parylene, acrylonitrile butadienestyrene (ABS), polyethylene terephthalate (PET), or any combinations thereof. The support layer 130 can bind to the nanomaterial paper through one or more of thermobonding, dropcasting, spincoating, electrospining, lamination, compression, electrodeposition, screen or stencil printing, atomic layer deposition (ALD), sputtering, chemical vapor deposition (CVD), direct ink write, or any combination thereof. The support layer 1130 can assist with adhesion between the subsequent layers as well.

[0162] The sensor device can comprise one or more gate electrodes 1140. The one or more gate electrodes 1140 can be disposed on one or more of the conductive pads that peek through the support layer. The one or more gate electrodes 1140 can be formed by conductive material printing. The gate electrodes 1140 can be disposed over the "right" and "left" conductive pads when viewing the device as in FIG. 1, or the "top" and "botom" conductive pads when viewing the device. These gate electrodes 1140 may not be covered by the top cover 1210, as discussed later. The gate electrodes may be a first point of reactive contact with the device.

[0163] The sensor can comprise nanoparticles deposited on one or more of the right or left conductive material-ink printed gates on the conductive pads (e.g., one or more of the gate electrodes 1140). Nanoparticles can comprise the catalytic layers 1220. In some cases, nanoparticles can be used to add receptors to the biomarker sensor. In some cases, the biomarker receptors and enzymes are present on the gate of the transistor. In some cases, the receptors can comprise one or more of glucose oxidase, lactic oxidase, antibodies, single-strand DNA, aptamers, glucose dehydrogenase, a cocktail of enzymes with different pH activity regions to enable sensitivity across an expected physiological pH, or any combination thereof. In some cases, the nanoparticles can further comprise one or more secondary receptors, for example a catalase, NAD and NADH, diaphorase, or any combination thereof. Catalase can be used to regenerated oxygen and remove hydrogen peroxide after glucose has been broken down into hydrogen peroxide. NAD and NADH and cycle to provide energy to glucose dehydrogenase for a reaction. Diaphorase can be used to regenerate the NAD and NADH.

[0164] The sensor device can comprise a nanomaterial layer 1150. The nanomaterial layer 1150 can have a backing layer, as described above. The nanomaterial layer 1150 can be a small strip cut from a larger piece of nanomaterial paper. The nanomaterial layer or strip1150 can comprise the channel of the PFGFET of the sensor device. To fulfill its role as the channel, nanomaterial strip 1150 can be doped. Nanomaterial strip 1150 can be nanoscale-doped to move the Dirac point and increase the sensitivity of the nanomaterial strip. The backlayer of the nanomaterial 1150 can bind to the support layer so that the nanomaterial itself is facing away from the support layer. The nanomaterial strip 1150 can be placed stretching from above the top conductive pad to above the bottom conductive pad. The word "above" can mean above from a side view of the device. The nanomaterial 1150 can be formed using the methods of processing nanomaterial described above.

[0165] The sensor can comprise source and drain electrodes 1160. Unlike the conductive material-ink printed gate electrodes 1140, these electrodes can be made by metallization. In some cases, the metal used in metallization comprises conductive material. Conductive material can be added to one or more of the top or bottom conductive pad to print the source and drain electrodes. The conductive material can be ink printed.

[0166] The electrodes 1160 can be used to physically or mechanically connect the nanomaterial layer 1150 to the two conductive pads below the nanomaterial layer. The electrodes 1160 may not hold the nanomaterial down against the two conductive pads below the nanomaterial layer 1150. The electrodes 1160 may hold the nanomaterial down against the two conductive pads below the nanomaterial layer 1150. The electrodes 1160 may electrically connect the nanomaterial layer 1150 to the two conductive pads below the nanomaterial layer. The electrodes 1160 may receive electrons through the field communication layer 1200 from the gate.

[0167] In some cases, the metal comprising the electrodes can have cytotoxic properties. It can be important to prevent nanoparticle delamination from the sensor. To prevent a cytotoxic response in the wearer, the metal electrodes 1160 may be passivated so to prevent nanoparticle delamination and subsequent migration through a field communication layer 1200 onto the skin surface.

[0168] The sensor can comprise one or more passivation layers. In some cases, an additional layer may be added to block the electrodes from contacting the skin of a user. This can be a passivation layer. In some cases, one set of passivation layers over placed on the nanomaterial over the region containing the electrodes 1160 can be sufficient. In some cases, the sensor may comprise more than one set of passivation layers, where one layerpassivates the doped nanoscale layer channel 1150 and one passivates the conductive material source and drain electrodes 1160. In some cases, the doped nanoscale layer channel 1150 and conductive material source and drain electrodes 1160 can be passivated at the same time. In some cases, the doped nanoscale layer channel 1150 can be passivated shortly after doping during the nanomaterial processing steps prior to being placed on the sensor, while the conductive material electrodes 1160 can be passivated once the conductive material is disposed on the conductive pads. The passivation layers can comprise one or more of conductive and non- conductive polymers, for example o-phenylenediamine (oPD), parylene, polypurrole, polyaniline, or any combination thereof. The passivation layers can comprise the same polymers or different polymers if two passivation layers are used.

[0169] Functionalization can comprise a functional layer of a sensorthat is built to perform one or more of continuous, periodic, or one off measurements of one or more target analytes of interest. Functionalization can comprise a method to tune the properties of a sensor with different functional layers to achieve specific desired properties. In some cases, the layers are '’active" electrochemically or biologically and can be used to convert some substance into another or convert a chemical into an electrical signature. In some cases, the layers may be inert and be used to block or prevent the movement or diffusion of some substance. The layers may be used as a structural matrix to bind and immobilize molecules or charges to create properties of interest or hold other layers in place. Functionalization can be used to tune the gate electrodes.

[0170] In some cases, an active layer such as a layer comprising an enzyme can be used to transform a molecule of interest into a different substance that can then be broken down into an electrochemical substance. The molecule of interest can be glucose. Glucose can be broken down into, among other compounds, hydrogen peroxide. Hydrogen peroxide can then be broken down into electrons. In some cases, two electrons can be generated from each molecule of hydrogen peroxide. The active enzymatic layer can comprise one or more of glucose oxidase, lactic oxidase, antibodies, single-strand DNA, aptamers, glucose dehydrogenase, a cocktail of enzymes with different pH activity regions to enable sensitivity across an expected physiological pH, or any combination thereof. The active enzymatic layer can also comprise secondary receptors to increase the sensitivity of the nanomaterial sensor. The secondary receptors can comprise one or more of a catalase,NAD and NADH, diaphorase, or any combination thereof. Catalase can be used to regenerated oxygen and remove hydrogen peroxide after glucose has been broken down into hydrogen peroxide. NAD and NADH and cycle to provide energy to glucose dehydrogenase for a reaction. Diaphorase can be used to regenerate the NAD and NADH. The enzymatic reactions occurring due to the enzymatic layer can be facilitated or sped up by redox mediators and catalytic elements. The redox mediators can comprise Prussian blue, ferricyanide, or both. The catalytic elements can comprise one or more of gold, platinum, palladium, carbon, or any combination thereof. The conductive material can be used to minimize or prevent metallic diffusion. The catalytic elements can be used to increase the reaction speed or facilitate the second reaction to break down hydrogen peroxide into electrons. In some cases, the catalytic element can be the same as the element used to dope the nanomaterial channel. In some cases, the catalytic element can be different from the element used to dope the nanomaterial channel. In some cases, the functionalization layer uses the existing catalytic layers. The functionalization layer can have the same catalytic elements as the existing catalytic layers. The functionalization layer can have different catalytic elements from the existing catalytic layers.

[0171] The active enzymatic layer may be supplemented by an inert protein layer that will block nonspecific binding site and only allow the molecul e of interest to react. These inert proteins can be selected to synergize with the enzyme layer and increase its lifetime. A first inert layer can comprise, but is not limited to, one or more of casein or bovine serum albumin (BS A). A second inert layer may be used to trap the inert protein layer and active enzyme layer in close proximity and bind them to the surface of the nanomaterial sensor. This can be done through electrostatic chargers, physical hindrance, or both. The trapping can combine the layers into one functionalization layer that can be deposited on either a separate catalytic layer or onto the gate electrodes, or a combination of both.

[0172] The sensor can comprise spacer. The spacer can comprise a substrate with adhesive on one end that only exposes the electrodes and the nanomaterial 1150 overlaying the electrodes. This can protect a user's skin from contacting the remainder of the doped nanoscale layer channel 1150 by creating a layer of padding. The spacer may or may not be able to adhere to nanomaterial, so can comprise materials similar to the support layer 1130 that can adhere to nanomaterial, or materials similar to the base substrate layer 1121 that may not adhere to nanomaterial. The spacer can be between thebase substrate 1121 and the top cover. The spacer can be between the support layer 1130 and the top cover 1210. The spacer can be between the nanomaterial channel 1150 and the top cover.

[0173] The sensor can comprise a field communication layer. The field communication layer can be a field communication layer matrix layer. The field communication layer can be a field communication layer. The field communication layer can cover the gate electrodes 1140, the source electrode, and the drain electrode. The field communication layer can cover the nanomaterial channel 1150. The field communication layer can carry one or more of biochemical, molecules, and charges (e.g., electrons) between the electrodes. As such, even if a molecule from bodily fluids contacts the area of the gate electrodes 1140, the electrons can still be moved to the nanomaterial channel 1150. The field communication layer can fluidically connect the nanomaterial channel 1150 and the gate electrodes 1140. The field communication layer can be between the spacer and the top cover.

[0174] The field communication layer 1200 can comprise one or more of polymers, composites, nanomaterials, enzymes, biomaterials, nanoparticles, proteins, or any combination thereof. The CLEAs may aggregate, leading to a higher density of the enzymes on the gate electrodes.

[0175] The sensor can comprise a top cover. The top cover can be added to further protect a user's skin from contacting any metallic particles used in the device. In some cases, the top cover does not leave the nanomaterial channel open. In some cases, the top cover does not leave the source or the drain electrode open. In some cases, the top cover may leave the one or more gate electrodes open. The top cover may leave two gate electrodes 1140 open. In some cases, the top cover is the part of the device that touches the skin of a user. The top cover may or may not be able to adhere to nanomaterial, so can comprise materials similar to the support layer 1130 that can adhere to nanomaterial, or materials similar to the base substrate layer 1121 that may not adhere to nanomaterial.

[0176] The sensor may comprise a conduction layer. The conduction layer may be thick if it comprises a viscous fluid, or may be thin if it comprises a non-viscous fluid. Conduction can make the field communication layer moist or wet to facilitate the transfer of ions across the field communication layer. Conduction mediums can comprise one or more of aqueous, polar,or non-polar solutions, or any combination thereof. In some cases, the viscous liquids can reduce the loss of enzymatic activity and reduce fouling.

[0177] The conduction layer can be in direct contact with the skin. In some cases, the conduction layer covers the entirety of the skin-facing side of the device, such that only the conduction layer is in direct contact with the skin. In some cases, the conduction layer covers only two open "windows" in the top cover 121p that leave the gate electrodes 1140 open, and allow both the conduction layer and the top cover to be in direction contact with the skin. In some cases, for example with non-viscous, absorbable fluids, the conduction layer may be absorbed into the field communication layer, top cover, or both such that there is no discernable conduction layer and the layer in direct contact with the skin is the top cover.

[0178] While preferred embodiments of the present 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. It is not intended that the invention be limited by the specific examples provided within the specification. While the invention has been described with reference to the aforementioned specification, the descriptions and illustrations of the embodiments herein are not meant to be construed in a limiting sense. Numerous variations, changes, and substitutions will now occur to those skilled in the art without departing from the invention. Furthermore, it shall be understood that all aspects of the invention are not limited to the specific depictions, configurations or relative proportions set forth herein which depend upon a variety of conditions and variables. It should be understood that various alternatives to the embodiments of the invention described herein may be employed in practicing the invention. It is therefore contemplated that the invention shall also cover any such alternatives, modifications, variations, or equivalents. 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 C AIMED IS:

1. An electrochemical sensor, said electrochemical sensor comprising: a gate electrode; a source electrode; a drain electrode; and an field communication layer, wherein said field communication layer is configured to allow diffusion of an analyte into said field communication layer, wherein said analyte undergoes a reaction proximate said gate electrode and within said field communication layer to produce an electrical response, and wherein said electrical response is configured to facilitate current flow between said source electrode and said drain electrode.

2. The electrochemical sensor of claim 1, wherein said field communication layer comprises one or more hydrophilic materials.

3. The electrochemical sensor of claim 1, wherein said electrochemical sensor is placed on said skin of said user to detect one or more analytes.

4. An electrochemical sensor, said electrochemical sensor comprising: a gate electrode; a source electrode; a drain electrode; an field communication layer; and a scaffold for said field communication layer, wherein said scaffold is configured to cover a channel between said source and said drain, wherein said scaffold comprises a window configured to allow diffusion of an analyte into said field communication layer, wherein said analyte is configured to produce a gating potential , and wherein said gating potential is configured to facilitate current flow between said source electrode and said drain electrode.

5. The electrochemical sensor of claim 4, wherein said scaffold comprises a plastic structure that holds said field communication layer in place within said electrochemical sensor.

6. An electrochemical sensor, said electrochemical sensor comprising: a gate electrode; a source electrode; a drain electrode; an field communication layer; and an area coated with a wicking material, said wicking material configured to interface with a skin of a user and to transport available moisture on said skin to said area, wherein said available moisture comprises an analyte, wherein said analyte is configured to produce a gating potential, and wherein said gating potential is configured to facilitate current flow between said source electrode and said drain electrode.

7. The electrochemical sensor of claim 6, wherein said wicking material comprises a hygroscopic material.

8. A conduction station, said conduction station configured to receive said electrochemical sensor of any preceding claim and to wet said field communication layer of said electrochemical sensor.

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