Sensors and methods of manufacturing therein

Abstract

Described herein is a biomarker sensor and methods of manufacturing the same. The biomarker sensor can use a nanomaterial strip. The biomarker sensor can measure biomarker without using the blood of a patient. The biomarker sensor can use sweat. The nanomaterial can be processed before being used in the biomarker sensor. The biomarker sensor can be manufactured through the use of electrodes, a nanomaterial channel, and an electrical connection between the two. The functional layers of the biomarker sensor can be located between a base substrate and a top cover.

Description

SENSORS AND METHODS OF MANUFACTURING THEREINBACKGROUND

[0001] Approximately 38 million people in the U.S., or 11.6% of the U.S. population, have diabetes. A large majority have type II diabetes, which is characterized by high blood sugar. People with diabetes may monitor their blood sugar levels with daily finger pricking, three-month blood tests, and other blood draw methods.SUMMARY

[0002] Listed herein is a set of clauses providing the devices, systems, and methods described herein.

[0003] The disclosed invention relates to methods and devices for fabricating high-sensitivity nanomaterial-based sensors, particularly gated field-effect transistor (FET) sensors, capable of detecting a wide range of biochemical analytes. The method includes providing a substrate, adding gate electrodes, forming a nanomaterial layer such as graphene or M0S2, and integrating source and drain electrodes spaced apart to form an active sensing channel. A material, such as a hydrogel or functional polymer, fluidically connects the nanomaterial to the gate electrodes and may also transfer biochemical signals or hold the sensor structure in place.

[0004] Optional elements include a support layer positioned between the substrate and nanomaterial, a top cover to isolate components from the skin, and functionalization layers — such as enzymes, aptamers, or antibodies — deposited on the gate electrodes to enable selective analyte detection. The invention further incorporates nanostructures like nanoparticles or redox mediators to enhance performance and sensitivity. The resulting sensor system can be tuned for diverse targets including glucose, cytokines, and hormones, making it highly adaptable for wearable health monitoring, biochemical detection, or diagnostic platforms.

[0005] 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 disclosure are shown and described. As will be realized, the present disclosure is capable of other and different embodiments, and its several details are 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

[0006] 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. U.S. Patent No. 9,930,777 is incorporated herein by reference. PCT / US2019 / 023255 is incorporated herein by reference. PCT / IB2017 / 001003 is incorporated herein by reference. PCT / US2015 / 027193 is incorporated herein by reference.BRIEF DESCRIPTION OF THE DRAWINGS

[0007] The novel features of the present disclosure are set forth with particularity in the appended claims. A better understanding of the features and advantages of the present disclosure will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the present disclosure are utilized, and the accompanying drawings (also "Figure" and "FIG." herein), of which:

[0008] FIG. 1 illustrates a top-down view of a process diagram for creating an example sensor in accordance with embodiments described herein.

[0009] FIG. 2 illustrates a side view of an example construction of layers during an intermediate step of nanomaterial processing in accordance with embodiments described herein.

[0010] FIG. 3 illustrates a graph of current versus voltage of an example electrode gate in accordance with embodiments described herein.

[0011] FIG. 4 illustrates a side view of an example cutter in accordance with embodiments described herein.

[0012] FIG. 5 illustrates a perspective view of the use of an example cutter in accordance with embodiments described herein.

[0013] FIG. 6 illustrates a perspective view of an example cut strip of nanomaterial that can be used in an example in accordance with embodiments described herein.

[0014] FIG. 7A illustrates a side view of an example cutter in accordance with embodiments described herein.

[0015] FIG. 7B illustrates a side view of another example cutter in accordance withembodiments described herein.

[0016] FIG. 8A illustrates a perspective view of an example cutter in accordance with embodiments described herein.

[0017] FIG. SB illustrates a perspective view of the use of the example cutter in accordance with embodiments described herein.

[0018] FIG. 9 illustrates a top down view and a side view of an example base layer for an example sensor in accordance with embodiments described herein.

[0019] FIG. 10 illustrates a top down view of an example sensor after a fifth manufacturing step in accordance with embodiments described herein.

[0020] FIG. 11 illustrates a top down view of an example sensor after a sixth manufacturing step in accordance with embodiments described herein.

[0021] FIG. 12 illustrates a top down view of an example sensor after a seventh manufacturing step in accordance with embodiments described herein.

[0022] FIG. 13 illustrates a top down view of an example sensor after a eighth manufacturing step in accordance with embodiments described herein.

[0023] FIG. 14 illustrates a top down view of an example sensor after a ninth manufacturing step in accordance with embodiments described herein.

[0024] FIG. 15 illustrates a perspective view of a base layer of an example sensor in accordance with embodiments described herein.

[0025] FIG. 16 illustrates a perspective view of an inner layer of an example sensor in accordance with embodiments described herein.

[0026] FIG. 17 illustrates a top down view of the inside of an example sensor in accordance with embodiments described herein.DETAILED DESCRIPTION

[0027] A large population in the U.S. suffers from diabetes, especially type II diabetes. In addition to daily blood pricks or three-month summary blood tests, a doctor may recommend continual monitoring over a period of time. This may be done by inserting a biomarkermonitoring device into the arm and measuring blood directly and continuously. The devices later need to be removed.

[0028] There exists a need for devices that can measure blood biomarker levels without inflicting harm on the patient and without involving minor surgeries. In summary, there exists a need to measure blood biomarker levels without drawing blood.

[0029] Provided herein are devices and methods for manufacturing biomarker sensors that do not rely on blood to measure biomarker levels in the body. Described herein are wearable biomarker sensors that measure biomarkers from the surface of the skin, for example sweat. In some cases, biomarkers can be measured from 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 cases, sweat from the surface of the skin comes into direct or indirect contact with the gate of a gated field-effect transistor. The gate may have receptors, enzymes, and reactants that break down the glucose into hydrogen peroxide and a gluconolactone ion. The gate may have enzymes and reactants that break down the hydrogen peroxide into two electrons. The two electrons may be passed through the channel of the gated field- effect transistor and detected. All or substantially all of the biomarker in the sweat that contacts the gate, directly or indirectly, can be captured by the gate and converted to electrons due to the relatively higher concentration of enzymes and receptors on the gate than the amount of biomarker that contacts the gate, directly or indirectly.

[0030] Described herein are devices and methods for manufacturing biomarker sensors that use nanomaterial paper. In some cases, nanomaterial paper forms the channel of the gated field-effect transistor. The gated field-effect transistor can be a polar fluid gated field-effect transistor (PFGFET). In some cases, the nanomaterial used in the device can first be processed into the paper form. In some cases, the processing nanomaterial may comprise doping with metal salts, such as gold chloride or palladium chloride. Processing nanomaterial may comprise cutting the nanomaterial into desired sizes. Processing nanomaterial may comprise using a backing layer to improve the rigidity of the nanomaterial without a loss of electron mobility.

[0031] Although the application will describe the application of nanomaterial, hexagonal boron nitride (h-BN) has many similar properties and can be substituted for the nanomaterial at any of these steps.Methods

[0032] Provided herein are methods of processing nanomaterial and methods of using the processed nanomaterial to manufacture a biomarker sensor that does not use blood to measure biomarker levels. FIG. 1 illustrates steps in manufacturing a biomarker sensor and will be further described below.Methods of Processing Nanomaterial

[0033] Nanomaterial is a sheet of carbon atoms one atom thick that occurs in a honeycomb lattice. Nanomaterial has unique and impressive electrical properties, such as mobilities of 200,000 cm2 / V -s and ballistic transport on the micrometer scale at room temperature. However, nanomaterial is very delicate, and many attempts at using it have resulted in sub-par results due to bending, crinkling, or other deformations in the nanomaterial during the manufacturing process. Nanomaterial may be grown on copper by chemical vapor deposition (CVD) at either atmospheric or low pressure, and is frequently sold on copper sheets. However, due to the delicate nature of both the nanomaterial and the copper, graphene may be removed from the copper during the processing of graphene. Although frequently sold on copper, graphene can also be sold on nickel. As such, any use of copper throughout may be substituted by nickel.

[0034] Described herein are methods of processing nanomaterial comprising adding a backing layer onto nanomaterial, removing the copper sheet that the nanomaterial is commercially sold on, doping the nanomaterial, and cutting or singulating the nanomaterial paper.Adding a Backing Laver

[0035] In some cases, nanomaterial can be stabilized by adding a backing layer. In some cases, addition of a backing layer can allow for the fabrication of nanoscale systems on the macroscale level. A backing layer can provide mechanical structure and stability to the nanoscale material, rendering it easier to handle and to further process while preventing damage and preserving its intrinsic properties and characteristics. For nanomaterial, a backing layer may provide rigidity and allow the nanomaterial to preserve its electrical properties.

[0036] A backing layer may also enable efficient transfer of the nanoscale material (e.g., CVD graphene) from their growth substrate to their final layer in one step, with no or few subsequent transfers. The backing layer can be bonded to the nanomaterial.

[0037] Carefully selecting the polymer to be used as part of the bonded backing layer may enable the nanoscale material to be bonded to a "final" substrate that has or has not been previously treated to increase its affinity to the backing layer, to ensure easy bonding through "gentle" conditions (low temp, pressure), thereby preserving the nanoscale properties. The backing layer can comprise polymers with different properties depending on the goal of the transfer. The backing layer may comprise thermoset, thermoplastic, elastomeric, glassy materials, such as polyurethane, ethylene-vinyl acetate (EVA), silicone (e.g., polydimethylsiloxane (PDMS), etc.), epoxies, polyvinyl alcohol (PVA), nylon, polymethyl methacrylate (PMMA), parylene, acrylonitrile butadiene styrene (ABS), nylon, polyethylene terephthalate (PET), or any combinations thereof.

[0038] In addition to the main polymers, there may be additives, fillers, or both added to the backing layer to tune its mechanical, electrical and chemical properties for ease of singulation or further processing. The additives or fillers can be carbon based materials, such as carbon black, graphene oxide, reduced graphene oxide, or activated charcoal; or dielectric materials such as alumina, titanate compounds (Ti02, etc.), fumed silica or metal oxides, or any combination thereof.

[0039] The advantages of the backing layer to the nanomaterial include structure, transferability, ease of handling, affinity-based bonding to a final substrate at a lower temperature and pressure to minimize damage to the system and allowing for additives or fillers to tune the mechanical properties of nanomaterial for ease of later singulation. The backing later can be composed of a single homogeneous layer or of several layers. It can be modified with functional groups to tune its surface energy. Functional groups can be used to dope up the nanoscale material to control the desired properties of the system. The backing layer can also be used to enhance the trans- conductive properties of semiconducting nano and macro materials. The backing layer can also be used to enable and control electrochemical reactions. The backing layer can control access to or hold fluids containing ions, molecules, microbes, bacteria, biomarkers, etc. by tuning its surface properties The backing layer can act as a shock absorber and enhance the stability of nanomaterials.

[0040] The backing layer can be added to the nanoscale material through one or more of adding pressure, applying rollers, applying heat, thermobonding, dropcasting, spincoating, electrospining, lamination, compression, electrodeposition, screen or stencil printing, atomiclayer deposition (ALD), sputtering, chemical vapor deposition (CVD), direct ink write, or any combination thereof.

[0041] In some cases, there may be a filler layer between the backing layer and the nanomaterial. The filler layer can comprise one or more of graphene oxide, carbon black, alumina, silica, fumed silica, titanium dioxide, ferrous oxide, or any combination thereof.

[0042] In some cases, the backing layer can comprise multiple polymers or materials. When the backing layer comprises multiple polymers or materials, the materials may first be combined into a single backing layer through one or more of adding pressure, applying rollers, applying heat, thermos-bonding, or any combination thereof. Once the backing layer has been formed, the backing layer can be added to the nanoscale material through the methods described above.

[0043] When the filler layer comprises multiple polymers or materials, the materials may likewise first be combined into a single filler layer.

[0044] FIG. 2 shows the combined materials in use. At this point in the nanomaterial processing stage, the nanomaterial construction comprises the original layer the nanomaterial was sold on 50, the nanomaterial layer itself 52, the filler layer 54, and the backing layer 56 comprising the two materials 57 and 58.Nanomaterial Doping and Passivation

[0045] During the nanomaterial transfer process from the copper to the backing layer, for example during or after removal of the copper, nanoparticles can be added onto the nanomaterial. These nanoparticles can shift the Dirac point, the voltage where the current is the lowest. FIG. 3 illustrates an example Dirac point 60 on a current vs. voltage graph. To avoid decreased sensitivity to glucose at high levels of biomarker, the biomarker sensor may function in the linear region of the current vs. voltage graph of the current between source and drain as controlled by gate voltage, as shown by the area with many circles in FIG. 3.

[0046] Described herein is a method for doping nanomaterial with nanoparticles, for example nanoparticles, such that the biomarker sensor remains sensitive to biomarker at both high and low levels of glucose in biomarkers released from the skin. Nanomaterial doping can be done by increasing the number of available charges for current flow. This can also increase the gate current output onto the PFGFET. Nanoparticle doping of the nanomaterial channel can increase the gate current biomarker response magnitude (see Example 2 below). One method to improvethe amount of gold that can be added to nanomaterial can be to increase the charge transfer efficiency from the solution containing the gold to the nanomaterial channel.

[0047] Adding nanoparticles to nanomaterial (e.g., nanomaterial doping) can be done to increase a number of available charges for current flow across the gated nanomaterial field-effect transistor. Adding nanoparticles to nanomaterial (e.g., nanomaterial doping) can be done to increase a current output from a gate in the gated nanomaterial field-effect transistor.

[0048] The diameter of the deposited nanoparticles can be between about 100 nm to about 500 nm. The diameter of the deposited nanoparticles can be less than about 100 nm, less than about 200 nm, less than about 300 nm, less than about 400 nm, or less than about 500 nm. The diameter of the deposited nanoparticles can be greater than about 100 nm, greater than about 200 nm, greater than about 300 nm, greater than about 400 nm, or greater than about 500 nm.

[0049] Once the channel has been doped with the nanoparticles, it can be important to prevent nanoparticle delamination from the channel. In some cases, nanoparticles may induce a cytotoxic response in a patient wearing the device. To prevent this, the channel may be passivated so to prevent nanoparticle delamination from the channel and subsequent migration through a field communication layer onto the skin surface.Singulating / Cutting Nanomaterial Paper

[0050] After adding a backing layer, removing the original copper, and doping the nanomaterial to a desirable Dirac point, the nanomaterial paper can be cut or singulated. Described herein are methods to cut nanomaterials, for example nanomaterial, into patterns and shapes through mechanical, thermal, or thermomechanical processes without introducing defects in the material and affecting its intrinsic properties. These techniques may be used on the macroscale.

[0051] The cutting can be done mechanically by using a blade, scissors and other cutting tools, as shown in FIGS. 7A-7B. The cutting can be done thermally by using localized heating. The cutting can be done thermos-mechanically using heated blades, heated wires, heated knives, heated scissors and other combination of localized heating associated with a mechanical edge. By using mechanical, thermal, or thermomechanical processes, a clean room or expensive tools and process are may be avoided. These methods may also be low cost. These methods may allow for cutting into any form or shape as desired.

[0052] FIG. 4 illustrates a side view of a cutter device 70, for example a blade, heated blade,knife, or heated knife. FIG. 5 shows a cutting device 70 such as FIG. 4 being used to cut a long sheet of nanomaterial 80 into smaller strips of nanomaterial 85. FIG. 6 shows a magnified perspective view of the strip of nanomaterial 85.

[0053] FIG. 7 A illustrates an alternate cutting device 100 that can cut via localized heating or can comprise a bladed edge for mechanical or thermomechanical cutting. FIG. 7B illustrates a smaller cutter 102, The smaller cutter 102 is separate from cutting device 100 (e.g., smaller cutter 102 may not be inserted into the backing part of cutting device 100). The smaller cutter 102 can likewise cut via localized heating or can comprise a bladed edge for mechanical or thermomechanical cutting.

[0054] FIG. 8A illustrates a perspective view of a cutting device 110 that can cut mechanically via a wire or thermos-mechanically via a heated wire. It can cut, melt, or both a nanomaterial sheet that it is moved or dragged through. FIG. 8B illustrates a perspective view of the cutting device 110 cutting a nanomaterial sheet, for example a nanomaterial sheet.

[0055] The cutting can be performed free-standing by running a heated wire vertically through the nanomaterial to be cut, as shown in FIG. 8B. The force may be applied orthogonally or partially tangentially. For example, the force may be applied between about a 10 degree angle and about a 90 degree angle. The force can be applied at less than about a 10 degree angle, less than about a 20 degree angle, less than about a 30 degree angle, less than about a 40 degree angle, less than about a 50 degree angle, less than about a 60 degree angle, less than about a 70 degree angle, less than about a 80 degree angle, or less than about a 90 degree angle. The material to be cut can be placed onto a substrate such as, for example, hard surfaces including but not limited to glass, resin, metal, epoxy, or any combination thereof; soft substrates including but not limited to wood or plastic; or self-healing mats such as those made of silicone. The substrate can also be cooled down to provide a thermal shock, thereby facilitating the cutting.

[0056] If the cut is performed mechanically, the cutting motion may be performed by hand by moving the blade down or dragging the blade across the cut location. The cutting motion may be performed by an impulse shock akin to a hammer hitting the top of a blade that was previously positioned. The cutting motion may be performed by a pneumatically actuated blade to bring down and retract the blade.

[0057] A blade used for mechanical, thermal, or thermomechanical processes may compriseobsidian glass, stainless steel, diamond scribe, or any combination thereof. The cutting element can be scissors, angled blades, straight or flat blades, wires, grids of blade or wire frames, paper cutters, die cutters, or any combination thereof.

[0058] The heating element can be integrated into the cutting element. The heating element can be a dedicated heating grid, such as a grid of a material that can easily be heated through electric current. The heating element can be coiled around some part of the mechanical element to fully heat the latter.

[0059] The nanomaterial channel used in the biomarker sensor can be a thin strip. To get this strip, a nanomaterial sheet can be cut. The nanomaterial sheet can originally be about 6 inches squared with nanomaterial on one side and the backing layer on the other side for stability and rigidity. The 6-inches- squared sheet can be cut into strips of about 6 inches by about 6 mm. These strips can be cut into small strips of about 6 mm in length by about I mm in width.

[0060] In some cases, the biomarker sensor device may be larger or smaller. The nanomaterial channel may likewise be larger or smaller to accommodate the space in the biomarker sensor. In some cases, the nanomaterial sheet prior to cutting can be between about I inch and about IO inches. In some cases, the nanomaterial sheet prior to cutting can be less than about I cm, less than about 2 cm, less than about 3 cm, less than about 4 cm, less than about 5 cm, less than about 6 cm, less than about 7 cm, less than about 8 cm, less than about 9 cm, or less than about IO cm. In some cases, the nanomaterial sheet prior to cutting can be greater than about I cm, greater than about 2 cm, greater than about 3 cm, greater than about 4 cm, greater than about 5 cm, greater than about 6 cm, greater than about 7 cm, greater than about 8 cm, greater than about 9 cm, or greater than about 10 cm.

[0061] In some cases, the final nanomaterial strip can be between about 3 mm to 9 mm in length. In some cases, the final nanomaterial strip can be between about 3 mm to about 5 mm, about 3 mm to about 7 mm, about 3 mm to about 9 mm, about 5 mm to about 7 mm, about 5 mm to about 9 mm, or between about 7 mm to about 9 mm in length. In some cases, the final nanomaterial strip can be less than about 3 mm, less than about 5 mm, less than about 7 mm, or less than about 9 mm. In some cases, the final nanomaterial strip can be greater than about 3 mm, greater than about 5 mm, greater than about 7 mm, or greater than about 9 mm.

[0062] In some cases, the final nanomaterial strip can be between about 0.5 mm to 2 mm inwidth. In some cases, the final nanomaterial strip can be between about 0.5 mm to about 1 mm, about 0.5 mm to about 1.5 mm, about 0.5 mm to about 2 mm, about 1 mm to about 1.5 mm, about 1 mm to about 2 mm, or between about 1.5 mm to about 2 mm in width. In some cases, the final nanomaterial strip can be less than about 0.5 mm, less than about 1 mm, less than about 1.5 mm, or less than about 2 mm. In some cases, the final nanomaterial strip can be greater than about 0.5 mm, greater than about 1 mm, greater than about 1.5 mm, or greater than about 2 mm.

[0063] In some cases, the edge profile of the nanomaterial strips or pieces may be indicative of cutting the nanomaterial versus separating it into pieces by other means.

[0064] After the cutting process completes, the nanomaterial strip channel is processed and ready to be applied to the biomarker sensor. The nanomaterial created by this process can be a mono-layer or few layer nanomaterial sheet. In some cases, the few levels of nanomaterial can help minimize the size of the device without impacting functionality. Additionally, the fewer the levels of nanomaterial, the better the flexibility and electrical properties can be. As such, few layers or a mono-layer can improve sensitivity of the biomarker sensor.Methods of Manufacture of a Biomarker Sensor

[0065] Provided herein are methods of manufacturing a biomarker sensor shown in FIG. 1 and comprising adding a support layer, depositing nanoparticles, picking and placing nanomaterial strips onto the support layer, metallization, passivation, functionalization or tuning of the nanomaterial channel, addition of a spacer, addition of an field communication layer, addition of a top cover, and activation of the field communication layer.

[0066] The biomarker sensor can comprise a polar fluid gated nanomaterial field-effect transistor (PFGFET). In some cases, the biomarker sensor can comprise one or more gate electrodes. The biomarker 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 copper or other metals. The various electrodes can comprise wires, squares, circles, or other shapes of metals. Optionally, the gate electrode may be configured to operate as a control electrode.

[0067] FIG. 9 illustrates 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 canbe 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, the substrate 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. 9. 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.

[0068] 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 carbon materials and nanoparticles. "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.

[0069] A support layer comprising a similar material to the nanomaterial backing layer can be added on top of the substrate. The support layer 130 can comprise different polymers than substrate. The support layer 130 can cover substantially all of the base substrate 121 except the conductive pads 122. The support layer 130 can leave open the conductive pads 122 to be formed into electrodes by ink printing conductive materials in subsequent steps. The similar material of the support layer 130 can allow nano-material 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 thermos-bonding, dropcasting, spin-coating, 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.

[0070] In some cases, nanoparticles can be used to add receptors to the biomarker sensor. Insome 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.

[0071] 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., graphene). The nanomaterial can be attached to a backing layer. The nanoscale material or nanomaterial can be picked up mechanically. The nanomaterial can be picked up using pliers, a vacuum seal, suction, adhesive, or any combination thereof. 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.

[0072] In some cases, more generally, the nanomaterial can be lowered on an alternate substrate. In some cases, as described above, the support layer may comprise similar polymers as the nanomateriars backing layer, such that the backing layer can adhere to the support layer. 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.

[0073] In some cases, the metal used in metallization comprises one or more conductive materials, such as metals, metal alloys, metal nanomaterials, or conductive composites. These materials can be added to one or more of the top or bottom conductive pads to form the source and drain electrodes. The conductive material can be deposited using methods such as ink printing, sputtering, evaporation, or other deposition techniques.

[0074] The metal can be used to physically or mechanically connect the nanomaterial layer tothe 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 below the 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.

[0075] 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.

[0076] In some cases, the metal can have cytotoxic properties. This can include the metallization applied as a connector and the doped nanomaterial. It can be important to prevent nanoparticle or silver nanoparticle delamination from the sensor. To prevent a cytotoxic response in the wearer, the doped nanomaterial channel and metal connector may be passivated so to prevent nanoparticle delamination and subsequent migration through a field communication layer onto the skin surface.

[0077] The doped nanomaterial channel and metal connector can be passivated via electrodeposition, as shown in FIG. 10. FIG. 10 illustrates a top-down of a sensor comprising base substrate 121, support layer 130, conductive treated gate electrodes 140, nanomaterial channel 150, metalized source and drain electrodes 160, and passivation layer 170. 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.

[0078] 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. Alternate or additional methods can include spin coating or drop casting. Example 2 below further describes the methods.

[0079] As discussed above, passivation of the doped nanomaterial channel can occur soon after nanomaterial doping. Alternatively, or in addition, passivation of the doped nanomaterial channel can be done at the same time as passivation of the metal connector.Functionalization

[0080] Once the nanomaterial channel of the PFGFET is electrically connected to the source and drain electrodes, the sensor can be tuned or functionalized. FIG. 11 illustrates a top-down ofa sensor comprising base substrate 121, support layer 130, functionalized conductive material treated gate electrodes 180, nanomaterial channel 150, metalized source and drain electrodes 160, and passivation layer 170. As indicated by the number on the left side, functionalizing the gate electrodes can comprise a sixth step in the manufacturing method described herein.

[0081] 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.

[0082] In some cases, an active layer, such as a layer comprising one or more functional biological or chemical agents, can be used to transform a target analyte into an intermediate or detectable species. The target analyte can include, for example, various biomolecules such as sugars, metabolites, or other small molecules of interest. The transformed substance may undergo one or more chemical or electrochemical reactions, resulting in the generation of detectable electrochemical signals, which can be measured by the sensor. 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 functionalization 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 functionalization 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 andcycle 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 functionalization 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 carbon 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.

[0083] 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.

[0084] Protective Steps

[0085] 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 an field communication layer, adding a top cover, and activating the field communication layer.

[0086] FIG. 12 illustrates a top-down of a sensor comprising base substrate 121, support layer 130, functionalized conductive material treated gate electrodes 180, nanomaterial channel 150, metalized source and drain electrodes 160, and spacer 190. Although not shown underneath the shaded area, there may still be conductive pads 122 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 nanomaterial channel by creating a layer of padding.

[0087] To efficiently transfer glucose molecules to the spaced and partly covered nanomaterialchannel, an field communication layer can be added on top of the spacer. FIG. 13 illustrates a top-down view of a sensor comprising base substrate 121, support layer 130, functionalized conductive material treated gate electrodes 180, nanomaterial channel 150, metalized source and drain electrodes 160, passivation layer, 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 an field communication layer can comprise an eighth step in the manufacturing method described herein. The bridge 200 can cover the gate electrodes 180, the source electrode, and the drain electrode. The bridge 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.

[0088] The field communication layer 200 can comprise one or more of genipin-based crosslinked enzyme aggregates (CLEAs), glutaraldehyde, tyramine, chitosan, agar or agarose hydrogel, poly (3,4-ethylenedioxythiophene): polystyrene sulfonate (PEDOT: PSS), or any combination thereof. The CLEAs may aggregate, leading to a higher density of the enzymes on the gate electrodes.

[0089] 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. 14 illustrates two top-down views and a side view of a sensor comprising base substrate 121, functionalized conductive material treated gate electrodes, nanomaterial channel, metalized source and drain electrodes 160, passivation layer, spacer, field communication layer 200, and top cover 210. The left top-down view shows a view from inside the top cover. The right or middle 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 a support layer under the spacer and top cover 210. As indicated by the number on the left side, adding a top cover can comprise a ninth step in the manufacturing method described herein. In some cases, the top cover 210 does not leave the nanomaterialchannel 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. The top cover may leave two gate electrodes open. In some cases, the top cover is the part of the device that touches the skin of a user.

[0090] 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 hydrated. Activation can make the field communication layer moist or wet to facilitate the transfer of ions across the bridge. Activation mediums can comprise one or more of polar fluids, non-polar fluids, viscous liquids, or any combination thereof. In some cases, the viscous liquids can reduce the loss of enzymatic activity and reduce fouling.Devices

[0091] 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 biomarker 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.

[0092] 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), an field communication 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.

[0093] FIG. 15 provides a magnified perspective view of the base substrate 1121 comprising conductive pads 1122. FIG. 16 provides a magnified perspective view of the support layer 1130. FIG. 17 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.

[0094] The sensor device can comprise a base substrate 1121 that forms the side farthest awayfrom 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 1122. The conductive pads 1122 can be preset in or on top of the base substrate 1121. The conductive pads 1122 can be separately added or adhered to the base substrate 1121. In some cases, there can be four conductive pads 1122. 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 1122 can function as the bases for electrodes that may be printed on top of them. Some of the conductive pads 1122 can function as the bases for gate electrodes while others function as the bases for source or drain electrodes.

[0095] 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.

[0096] 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 1122. The support layer 1130 can leave open the conductive pads 1122 to be formed into electrodes by ink printing conductive materials. 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, ethylenevinyl 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 1130 can assist with adhesion between the subsequent layers as well.

[0097] 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 1122 that peek through the support layer. The one or more gate electrodes 1140 can be formed by carbon printing. The gate electrodes 1140 can be disposed over the "right" and "left" conductive pads when viewing the device as in FIG. 1. 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.

[0098] Nanoparticles can comprise the catalytic layers. 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.

[0099] 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 strip 1150 can comprise the channel of the PFGFET of the sensor device. To fulfill its role as the channel, nanomaterial strip 1 150 can be doped. Nanomaterial strip 1 150 can be doped nanomaterial 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.

[0100] The sensor can comprise source and drain electrodes 1160. In some cases, the metal used in metallization comprises silver. Silver can be added to one or more of the top or bottom conductive pads to print the source and drain electrodes. The silver can be ink printed.

[0101] The electrodes 1160 can be used to physically or mechanically connect the nanomaterial layer 1150 to the two conductive pads 1122 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 1122 below the nanomaterial layer. The electrodes 1160 may receive electrons through the field communication layer 1200 from the gate.

[0102] 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.

[0103] 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 layer passivates the doped nanomaterial channel 1150 and one passivates the silver source and drain electrodes 1160. In some cases, the doped nanomaterial channel 1150 and silver source and drain electrodes 1160 can be passivated at the same time. In some cases, the doped nanomaterial channel 1150 can be passivated shortly after doping during the nanomaterial processing steps prior to being placed on the sensor, while the silver electrodes 1160 can be passivated once the silver is disposed on the conductive pads 1122. The passivation layers, or both 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.

[0104] The sensor can comprise one or more functionalization layers disposed on the catalytic layer 1220 and gate electrodes 1140. Although only shown for one of the gate electrodes 1140, the functionalization layer may be disposed on more than one gate electrodes, for example two or all gate electrodes 1140. Functionalization can comprise a functional layer of a sensor that isbuilt 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.

[0105] 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 functionalization 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 functionalization 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 functionalization 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 carbon 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 1existing 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.

[0106] The sensor can comprise a 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 nanomaterial 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 the base substrate 1121 and the top cover. The spacer can be between the support layer 1130 and the top cover. The spacer can be between the nanomaterial channel 1150 and the top cover.

[0107] The sensor can comprise a bridge 1200. The bridge can be an field communication layer. The bridge 1200 can cover the gate electrodes 1140, the source electrode, and the drain electrode. The bridge 1200 can cover the nanomaterial channel 1150. The field communication layer 1200 can carry one or more of biochemical, molecules, and charges (e.g., electrons) between the electrodes. As such, even if a glucose molecule from sweat contacts the area of the gate electrodes 1140, the electrons can still be moved to the nanomaterial channel 1150. The bridge 1200 can fluidically connect the nanomaterial channel 1150 and the gate electrodes 1140. The bridge 1200 can be between the spacer and the top cover 1210.

[0108] The field communication layer 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 CXEAs may aggregate, leading to a higher density of the enzymes on the gate electrodes.

[0109] 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 beable 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.

[0110] The sensor may comprise a activation layer. The activation layer may be thick if it comprises a viscous fluid, or may be thin if it comprises a non-viscous fluid. Activation can make the field communication layer moist or wet to facilitate the transfer of ions across the bridge. Activation mediums can comprise one or more of deionized water, phosphate buffered saline (PBS), viscous liquids, or any combination thereof. In some cases, the viscous liquids can reduce the loss of enzymatic activity and reduce fouling.

[0111] The activation layer can be in direct contact with the skin. In some cases, the activation layer covers the entirety of the skin-facing side of the device, such that only the activation layer is in direct contact with the skin. In some cases, the activation layer covers only two open "windows" in the top cover 121p that leave the gate electrodes 1140 open, and allow both the activation layer and the top cover to be in direction contact with the skin. In some cases, for example with non-viscous, absorbable fluids, the activation layer may be absorbed into the field communication layer, top cover, or both such that there is no discernable activation layer and the layer in direct contact with the skin is the top cover.Definitions

[0112] Unless defined otherwise, all terms of art, notations and other technical and scientific terms or terminology used herein are intended to have the same meaning as is commonly understood by one of ordinary skill in the art to which the claimed subject matter pertains. In some cases, terms with commonly understood meanings are defined herein for clarity and / or for ready reference, and the inclusion of such definitions herein should not necessarily be construed to represent a substantial difference over what is generally understood in the art.

[0113] Throughout this application, various embodiments may be presented in a range format. It should be understood that the description in range format is merely for convenience and brevity and should not be construed as an inflexible limitation on the scope of the disclosure. Accordingly, the description of a range should be considered to have specifically disclosed all the possible subranges as well as individual numerical values within that range. For example, description of a range such as from 1 to 6 should be considered to have specifically disclosedsubranges such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6 etc., as well as individual numbers within that range, for example, 1, 2, 3, 4, 5, and 6. This applies regard less of the brea dth of the range.

[0114] The ranges disclosed herein also encompass any and all overlap, sub-ranges, and combinations thereof. Language such as "up to," "at least," "greater than," "less than," "between," and the like includes the number recited. Numbers preceded by a term such as "approximately", "about", and "substantially" as used herein include the recited numbers, and also represent an amount close to the stated amount that still performs a desired function or achieves a desired result. 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, the terms "approximately", "about", and "substantially" may refer to an amount that is within less than 10% of, within less than 5% of, within less than 1% of, within less than 0.1% of, and within less than 0.01% of the stated amount. 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. As used herein, the term "about" a number refers to that number plus or minus 10% of that number. The term "about" a range refers to that range minus 10% of its lowest value and plus 10% of its greatest 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.

[0115] As used in the specification and claims, the singular forms "a", "an" and "the" include plural references unless the context clearly dictates otherwise. For example, the term "a sample" includes a plurality of samples, including mixtures thereof.

[0116] The terms "determining," "measuring," "evaluating," "assessing," "assaying," and "analyzing" are often used interchangeably herein to refer to forms of measurement. The terms include determining if an element is present or not (for example, detection). These terms can include quantitative, qualitative or quantitative and qualitative determinations. Assessing can be relative or absolute. "Detecting the presence of can include determining the amount of something present in addition to determining whether it is present or absent depending on the context.

[0117] The terms "subject," "individual," or "patient" are often used interchangeably herein. A"subject" can be a biological entity containing expressed genetic materials. The biological entity can be a plant, animal, or microorganism, including, for example, bacteria, viruses, fungi, and protozoa. The subject can be tissues, cells and their progeny of a biological entity obtained in vivo or cultured in vitro. The subj ect can be a mammal. The mammal can be a human. The subj ect may be diagnosed or suspected of being at high risk for a disease. In some cases, the subject is not necessarily diagnosed or suspected of being at high risk for the disease.

[0118] The section headings used herein are for organizational purposes only and are not to be construed as limiting the subject matter described.

Claims

CLAIMSWHAT IS CLAIMED IS:

1. A method of making a sensor, method comprising: providing a substrate; adding one or more gate electrodes on the substrate; providing a layer of a nanomaterial above the substrate; adding a first electrode at a first portion of the layer of nanomaterial and a second electrode at a second portion of the nanomaterial, wherein the first portion and the second portion are spaced at a distance; and providing a material on the substrate, wherein the material is configured to fluidically connect the nanomaterial and the one or more gate electrodes.

2. The method of claim 1, further comprising, subsequent to (a), forming a support layer, wherein the support layer is between the substrate and the layer of nanomaterial.

3. The method of claim 2, wherein the support layer covers substantially all of the substrate except the one or more gate electrodes, the first electrode, and the second electrode.

4. The method of claim 3, wherein the support layer covers substantially all of the substrate except the one or more gate electrodes, the first electrode, the second electrode, and a galvanometer.

5. The method of claim 3, wherein the support layer covers substantially all of the substrate except the one or more gate electrodes, the first electrode, the second electrode, and a reference electrode.

6. The method of claim 2, wherein the support layer is formed of substantially the same material as a backing layer of the nanomaterial layer.

7. A sensor, comprising:a substrate; one or more gate electrodes on the substrate; a layer of nanomaterial above the substrate; a first electrode at a first portion of the layer of nanomaterial and a second electrode at a second portion of the nanomaterial, wherein the first portion and the second portion are spaced at a distance; and a material on the substrate, wherein the material is configured to fluidically connect the nanomaterial and the one or more gate electrodes.

8. The sensor of claim 30, wherein the substrate comprises one or more polymers.

9. The sensor of claim 30, further comprising a support layer, wherein the support layer is between the substrate and the layer of nanomaterial.

10. The sensor of claim 32, wherein the support layer configured to bind to the nanomaterial layer.

11. The sensor of claim 32, wherein the support layer comprises one or more different polymers than one or more polymers comprising the substrate.

12. A sensor comprising a multiterminal structure comprising: a first terminal, one or more gate terminals, and a second terminal; a nanomaterial layer between the first terminal and the second terminal and configured to form one or more channels; and an active layerdisposed on the one or more gate terminals and configured to interact with an analyte proximate to the active layer.

13. A method of improving sensitivity of a sensor, the method comprising: providing a multiterminal structure comprising: a first terminal, one or more gate terminals, and a second terminal; providing a nanomaterial layer between the first terminal and the second terminal, wherein the nanomaterial layer is configured to form a channel;providing an active layer disposed on the one or more gate terminals; and contacting the active layer with the analyte, wherein the analyte is configured to interact with an analyte proximate to the active layer.

14. The method of claim 13, further comprising providing an intermediate layer proximate the active layer, wherein the intermediate layer and the active layer are collectively configured to increase an interaction of the analyte to the active layer15. The method of claim 13, further comprising transforming the analyte into a substance that can be broken down into an electrochemical substance using the active layer.

16. A device comprising: a field effect transistor, wherein a channel of the field effect transistor comprises nanomaterial; and a layer of metallic nanoparticles deposited on the nanomaterial, wherein the layer of metallic nanoparticles is configured to increase a performance of the field effect transistor as a sensor of an analyte.

17. The device of claim 16, further comprising: a processor configured to receive a signal from the FET, wherein signal comprises an indication of an analyte.

18. A method of manufacturing a sensor, the method comprising: providing a layer of nanomaterial; forming a plurality of contacts proximate the nanomaterial to form a gated fieldeffect transistor, wherein a channel of the gated field-effect transistor comprises nanomaterial; and depositing a layer of nanoparticles on a surface of the channel .

19. A workpiece comprising: a backing layer comprising one or more polymers; and a patterned layer of nanomaterial disposed on the backing layer;wherein the patterned layer of the nanomaterial comprises an electron mobility greater than 1000 cm2 / V-s, and wherein the patterned layer of the nanomaterial comprises an edge profile with an edge roughness, wherein the edge roughness is consistent with cutting.

20. A method of manufacturing a nanomaterial workpiece, the method comprising:(a) providing a patterned layer of nanomaterial;(b) applying a backing layer comprising one or more polymers to the patterned layer of nanomaterial, wherein the backing layer comprising the one or more polymers is disposed on the patterned layer of nanomaterial to form a layered structure; and(c) cutting the layered structure; wherein the patterned layer of the nanomaterial comprises an electron mobility greater than 1000 cm2 / V-s, and wherein the patterned layer of the nanomaterial comprises an edge profile with an edge roughness, wherein the edge roughness is consistent with cutting.

21. A workpiece comprising: a back polymer layer; and a nanomaterial layer disposed on the back polymer layer and mechanically supported by the back polymer layer, wherein the back polymer layer is configured to modulate an electrical property of the nanomaterial layer.

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