Measurement system and associated technique for sensing electrical characteristics of sensor

Abstract

To provide an improved system, apparatus, and method for a measuring circuit that senses the electrical characteristics of a sensor.SOLUTION: Provided is an apparatus that senses the electrical characteristics of a sensor, and the apparatus comprises: a sense resistor configured to be connected to the sensor; a first amplifier having a first input part, a second input part, and an output part, the first amplifier connected with the sense resistor between the second input part and the output part; and a second amplifier. The second amplifier has a first input part connected to the output part of the first amplifier, a second input part connected to the first input part of the first amplifier, and an output part configured to supply a voltage indicating the electrical characteristics of the sensor.SELECTED DRAWING: Figure 5

Description

[Technical Field]

[0001] (Related Applications) This application claims priority under 35 U.S.C. §119(e) to U.S. Provisional Application No. 62 / 991,515, filed March 18, 2020, and entitled "Measurement Systems and Associated Techniques for Sensing Electrical Characteristics of a Sensor," the entire contents of which are incorporated herein by reference.

[0002] The present application relates generally to systems, devices, and methods for sensing electrical properties of one or more sensors, and more particularly to systems, devices, and methods suitable for sensing electrical properties to detect characteristics of bodily fluids. [Background technology]

[0003] Sensors can be used to detect one or more characteristics of bodily fluids. One method of detecting a characteristic is to use a measurement circuit connected to the sensor and capable of sensing the electrical properties of the sensor. However, some sensors have undesirably low sensitivity to the analyte of interest. As a result, the signal provided to the measurement circuit may be too weak to be useful for detecting the characteristic. Therefore, an improvement in the measurement circuit is needed. Summary of the Invention

[0004] A general description of sensors, associated components, and associated methods is provided.

[0005] Some embodiments of the present disclosure relate to an apparatus for sensing an electrical characteristic of a sensor, the apparatus may include a sense resistor configured to couple to the sensor, a first amplifier having a first input, a second input, and an output, the sense resistor coupled between the second input and the output, and a second amplifier, the second amplifier having a first input coupled to the output of the first amplifier, a second input coupled to the first input of the first amplifier, and an output configured to provide a voltage indicative of the electrical characteristic of the sensor.

[0006] In some embodiments, the electrical property may include the conductance of the sensor.

[0007] In some embodiments, the sensor may include a nanowire sensor.

[0008] In some embodiments, the device may further comprise a nanowire sensor configured such that the conductance indicates the presence of one or more analytes at a surface of the nanowire sensor.

[0009] In some embodiments, the surface of the nanowire sensor may have binding entities for biomarkers of brain injury.

[0010] In some embodiments, the surface of the nanowire sensor has binding entities for biomarkers, which may be selected from the group consisting of GFAP, UCH-L1, S100β, ICH, and NFL-1.

[0011] In some embodiments, the surface of the nanowire sensor may have binding entities for one or more biomarkers of infectious disease pathogens.

[0012] In some embodiments, the surface of the nanowire sensor may have binding entities for biomarkers of sepsis.

[0013] In some embodiments, the apparatus may further include a transimpedance amplifier (TIA) comprising the sense resistor and the first amplifier, and the TIA may be configured to generate a sense voltage indicative of the current flowing through the sensor.

[0014] In some embodiments, the second amplifier may comprise at least one member of the group consisting of an instrumentation amplifier, a difference amplifier, and an operational amplifier.

[0015] In some embodiments, the TIA may be contained in a single integrated circuit package.

[0016] In some embodiments, the TIA may include multiple discrete components.

[0017] In some embodiments, the plurality of discrete components may include field effect transistors (FETs).

[0018] Some embodiments of the present disclosure may relate to a system comprising a printed circuit board (PCB) having the device described above and at least one electrical connector mounted thereon, the electrical connector configured to electrically connect the device to the sensor.

[0019] In some embodiments, the electrical connector may be configured to removably connect the device to the sensor.

[0020] Some embodiments of the present disclosure relate to an apparatus for sensing an electrical characteristic of a sensor, the apparatus may include a sense amplifier having a first input and an output, the sense amplifier configured to generate a voltage at the output indicative of the electrical characteristic, and a transimpedance amplifier (TIA), the TIA having a first input coupled to the first input of the sense amplifier and a second input configured to couple to the sensor.

[0021] In some embodiments, the electrical property may include the conductance of the sensor.

[0022] In some embodiments, the sensor may include a nanowire sensor.

[0023] In some embodiments, the device may further comprise a nanowire sensor configured such that the conductance indicates the presence of one or more analytes at a surface of the nanowire sensor.

[0024] In some embodiments, the surface of the nanowire sensor may have binding entities for biomarkers.

[0025] In some embodiments, the biomarker may be a biomarker for brain injury.

[0026] In some embodiments, the surface of the nanowire sensor has binding entities for biomarkers, which may be selected from the group consisting of GFAP, UCH-L1, S100β, ICH, and NFL-1.

[0027] In some embodiments, the biomarkers may be biomarkers for one or more infectious disease pathogens.

[0028] In some embodiments, the biomarker may be a biomarker for sepsis.

[0029] In some embodiments, the TIA may have an output electrically connected to the second input of the sense amplifier, and the TIA may be configured to generate a sense voltage at the output of the TIA that is indicative of the current through the sensor.

[0030] In some embodiments, the TIA may be further configured to receive an input voltage signal at the first input of the TIA and apply the input voltage signal to the sensor via the second input of the TIA.

[0031] In some embodiments, the TIA may further include a sense resistor electrically connected between the first input of the TIA and the output of the TIA, and configured to generate the sense voltage when the current flows through the sense resistor.

[0032] In some embodiments, the sense amplifier may comprise at least one member of the group consisting of an instrumentation amplifier, a differential amplifier, and an operational amplifier.

[0033] Some embodiments of the present disclosure may relate to a system including a printed circuit board (PCB) having the above-described device and at least one electrical connector mounted thereon, the electrical connector configured to electrically connect to the sensor.

[0034] In some embodiments, the electrical connector may be configured to removably connect to the sensor.

[0035] Some embodiments of the present disclosure relate to a system for sensing an electrical characteristic of a sensor, which may include a transimpedance amplifier (TIA) configured to supply an alternating current (AC) voltage to the sensor, and a sense amplifier configured to generate a voltage indicative of the electrical characteristic in response to detecting a current flowing between the sensor and ground.

[0036] In some embodiments, the TIA may be configured to receive the AC voltage from an AC voltage source having a frequency between 0.1 Hz and 1 kHz.

[0037] In some embodiments, the TIA may be configured to receive the AC voltage from an AC voltage source having a frequency between 500 Hz and 700 Hz.

[0038] In some embodiments, the TIA may be configured to receive the AC voltage from an AC voltage source having a frequency of 600 Hz.

[0039] In some embodiments, the electrical property may include the conductance of the sensor.

[0040] In some embodiments, the sensor may include a nanowire sensor.

[0041] In some embodiments, the system may further comprise a nanowire sensor, configured such that the conductance indicates the presence of one or more analytes at the surface of the nanowire sensor.

[0042] In some embodiments, the nanowire sensor can be configured to generate an impedance greater than 0.5 MΩ when at least some analyte is disposed on the surface of the nanowire sensor.

[0043] In some embodiments, the nanowire sensor can be configured to generate an impedance greater than 50 MΩ when at least some analytes are disposed on the surface of the nanowire sensor.

[0044] In some embodiments, the nanowire sensor can be configured to generate an impedance greater than 75 MΩ when at least some analytes are disposed on the surface of the nanowire sensor.

[0045] In some embodiments, the nanowire sensor can be configured to generate an impedance greater than 100 MΩ when at least some analytes are disposed on the surface of the nanowire sensor.

[0046] In some embodiments, the surface of the nanowire sensor may have binding entities for biomarkers.

[0047] In some embodiments, the biomarker may be a biomarker for brain injury.

[0048] In some embodiments, the surface of the nanowire sensor may have binding entities for biomarkers, and the biomarkers may be selected from the group consisting of GFAP, UCH-L1, S100β, ICH, and NFL-1.

[0049] In some embodiments, the biomarkers may be biomarkers for one or more infectious disease pathogens.

[0050] In some embodiments, the biomarker may be a biomarker for sepsis.

[0051] In some embodiments, an input of the TIA may be configured to receive the current and an output of the TIA may be configured to provide a sense voltage to the sense amplifier.

[0052] In some embodiments, the TIA may further comprise a sense resistor configured to generate the sense voltage when the current flows through a sense resistor.

[0053] In some embodiments, the sense amplifier may comprise at least one member of the group consisting of an instrumentation amplifier, a differential amplifier, and an operational amplifier.

[0054] In some embodiments, the system may further include a printed circuit board (PCB) having the TIA, a sense amplifier, and at least one electrical connector mounted thereon, the electrical connector being configured to electrically connect with the sensor.

[0055] Other advantages and features of the present application will become apparent from the following detailed description of various non-limiting embodiments of the present application, when considered in conjunction with the accompanying figures. In the event that this application and a document incorporated by reference include conflicting and / or inconsistent disclosure, the present application shall control. In the event that two or more documents incorporated by reference include conflicting and / or inconsistent disclosure with respect to each other, the document having the later effective date shall control. [Brief explanation of the drawings]

[0056] Non-limiting embodiments of the present invention are illustratively described with reference to the accompanying drawings, which are schematic and not intended to be drawn to scale. In these drawings, each of the identical or nearly identical components shown is typically represented by a single numeral. For clarity, not every component is labeled in every drawing, nor is every component of each embodiment of the present invention shown unless illustration is necessary for those skilled in the art to understand the invention.

[0057] [Figure 1] FIG. 1 illustrates an exemplary system for sensing an electrical property of a sensor, according to some embodiments. [Figure 2] 2 illustrates an exemplary sensor that may be included in the system of FIG. 1, according to some embodiments. [Figure 3] 2 illustrates an exemplary controller that may be included in the system of FIG. 1, according to some embodiments. [Figure 4] 2 illustrates an exemplary measurement device with which the system of FIG. 1 may be equipped, according to some embodiments. [Figure 5] 5 is a circuit diagram of exemplary components of the measurement device of FIG. 4, according to some embodiments. [Figure 6] FIG. 1 shows an example of a sensor comprising a wire bonding composition disposed on a portion of each electrode of a pair of electrodes, according to some embodiments. [Figure 7] FIG. 1 illustrates an example of a sensor comprising a blocking layer disposed above a nanowire that electrically connects a pair of electrodes, but that is not present in other portions of the sensor, according to some embodiments. [Figure 8] FIG. 2 illustrates a non-limiting embodiment of a sensor comprising a pair of electrodes, further comprising a back-gate electrode, a water-gate electrode, and a ground electrode, according to some embodiments. [Figure 9]1 illustrates a graph of the signal-to-noise ratio (SNR) of the voltage at the output of a measurement device versus the voltage applied across a sensor by the measurement device, according to some embodiments. DETAILED DESCRIPTION OF THE INVENTION

[0058] Systems, devices, and methods for sensing an electrical property of a sensor are generally provided. The measurement devices described herein can be configured to improve sensitivity in sensing an electrical property of a sensor.

[0059] In some embodiments, the sensors described herein may be configured to generate a signal indicative of the sensor's environment when a bias signal (e.g., a voltage) is applied to the sensor. For example, the signal may indicate an electrical characteristic of the sensor. As an example, a nanowire sensor may generate a current when a bias voltage is applied to the nanowire sensor, the current indicating the impedance of the nanowire sensor, which may vary according to the nanowire sensor's environment. When such a sensor is placed in proximity to a bodily fluid, the impedance of the sensor can indicate the presence of one or more analytes in the bodily fluid in proximity to the sensor. Exemplary applications of the sensing systems described herein include detecting biomarkers of diseases, conditions, or injuries, such as traumatic brain injury. For example, one or more surfaces of the nanowire sensor may have binding entities for biomarkers thereon, as described in more detail below. The binding entities may be attached to the surface of the nanowire sensor, for example, by covalent, non-covalent, and / or similar bonds.

[0060] However, signals from such sensors are typically very small (e.g., between 10 picoamperes (pA) and 1 microampere (μA)), requiring very sensitive measurement systems to make the data from the sensors usable. For example, if a system is not sensitive enough to the sensed signal, interference from noise, distortion, and / or other factors may overwhelm the sensed signal, making it impossible to identify the signal beyond the interference. Therefore, it is desirable to increase the sensitivity of such measurement systems to detect even very small signals.

[0061] Improving the sensitivity of a measurement system presents challenges. For example, when sensing very small currents, one way to increase the sensitivity of the measurement device in the system is to use a large sense resistor to generate a large sense voltage indicative of the sensed current. However, a large sense resistor generates a voltage even when current noise generated in the system enters the sense path and adds to the sensed current. As a result, much of the sense voltage generated across the sense resistor corresponds to noise rather than signal. In some applications, the added noise can negate the increased sensitivity achieved by a large sense resistor. Similar challenges arise when sensors are biased with an alternating current (AC) signal. Parasitic capacitance in the measurement system creates a nonlinear impedance in the sense path, adding distortion to the sense voltage that affects the system's ability to determine electrical characteristics.

[0062] In some aspects described herein, the inventors have developed techniques for implementing a measurement device that reduces the effects of current noise and distortion generated by components of a measurement system when sensing an electrical characteristic of a sensor. In some embodiments, the device for sensing an electrical characteristic of a sensor may include a first amplifier and a second amplifier. The second amplifier has inputs connected to the input and output of the first amplifier, respectively. A sense resistor may be connected between the second input of the first amplifier and the output of the first amplifier, and the output of the second amplifier may be configured to provide (output) a voltage indicative of the electrical characteristic of the sensor. In some embodiments, the device for sensing an electrical characteristic of a sensor may include a sense amplifier configured to generate a voltage indicative of the electrical characteristic at its output, and a transimpedance amplifier (TIA) having a first input connected to the input of the sense amplifier and a second input configured to connect to the sensor. The inventors have discovered that such an amplifier interconnection configuration reduces the effects of current noise in the system, for example, by limiting the amount of current noise to which the sense path is exposed. Such a configuration also makes it easier to equip the measurement device with a larger sense resistor, thereby increasing the sensitivity of the system.

[0063] The techniques described herein can also facilitate the use of alternating current (AC) bias signals for sensing, since they reduce the effects of distortion on AC signals. In some embodiments, a system for sensing an electrical characteristic of a sensor can include a TIA configured to provide an alternating current (AC) voltage to the sensor and a sense amplifier configured to generate a voltage indicative of the electrical characteristic in response to detecting a current flowing between the sensor and ground. Furthermore, the techniques described herein can also facilitate connecting the sensor between a measurement device and ground, improving protection against overvoltage events such as electrostatic discharge (ESD), as the sensor can be configured to shunt ESD energy to ground, limiting the effects of the ESD event.

[0064] Referring now to the figures, FIG. 1 illustrates an exemplary system 100 for sensing an electrical property of a sensor, according to some embodiments. In FIG. 1, the system 100 includes a controller 102, a measurement device 104, and a sensor 106, which are shown electrically interconnected. In some embodiments, the sensor 106 may be disposed in proximity to one or more bodily fluids, and the electrical property of the sensor 106 may vary in response to one or more characteristics of the bodily fluids. For example, the electrical property may include the impedance (and / or admittance, conductance, etc.) of the sensor 106. In one example, the impedance of the sensor 106 can indicate the presence of one or more analytes in proximity to the sensor 106. For example, the sensor 106 may include a nanowire sensor having binding entities thereon for biomarkers. The measurement device 104 may be configured to sense the electrical property of the sensor 106 and provide an indication of the electrical property to the controller 102. In the above example, the controller 102 may be configured to analyze the electrical property to determine the presence of the analyte(s).

[0065] In some embodiments, the controller 102 may include a bias circuit configured to provide one or more bias signals (e.g., voltage and / or current) to the measurement device 104. The measurement device 104 may be configured to apply (e.g., directly or indirectly) the bias signal(s) to the sensor 106 and sense an electrical characteristic of the sensor 106 in response to applying the bias signal(s) to the sensor 106. For example, to determine the impedance of the sensor 106, the measurement device 104 may apply a voltage across the sensor 106 and sense a current passing through the sensor 106. The measurement device 104 may further be configured to provide an indication of the sensed electrical characteristic to the controller 102 for analysis. For example, the measurement device 104 may provide a signal to the controller 102 representing the current passing through the sensor 106. This signal is indicative of the impedance of the sensor 106. In this example, the controller 102 may determine the impedance of the sensor 106 using Ohm's Law. The controller 102 may also determine whether or how many analytes are in proximity to the sensor 106 based on the impedance.

[0066] It should be understood that in some embodiments, the measurement device 104 may be configured to generate a voltage and / or current based on the bias signal(s) from the controller 102 and supply the generated voltage and / or current, rather than the bias signal(s), to the sensor 106. Furthermore, it should be understood that in some embodiments, the system 100 may include a first controller configured to provide the bias signal(s) and a second controller configured to receive and process an indication of the sensed electrical property from the measurement device 104.

[0067] In some embodiments, the controller 102, the measurement devices 104, and the sensors 106 may be packaged together, such as disposed on the same circuit board (e.g., printed circuit board) and / or in the same housing. Alternatively, in some embodiments, the controller 102 and / or the measurement devices 104 may be packaged separately from the sensors 106. For example, the controller 102 and the measurement devices 104 may be disposed on a first circuit board and / or housed in a first integrated circuit package, and the sensors 106 may be disposed on a second circuit board and / or housed in a second integrated circuit package. For example, in this example, the circuit board having the controller 102 and the measurement devices 104 thereon may have electrical connectors configured to receive complementary electrical connectors for electrically connecting the measurement devices 104 and / or the controller 102 to the sensors 106.

[0068] 2 illustrates an exemplary nanowire sensor 206 that may be included in system 100, according to some embodiments. Sensor 206 is shown having electrodes 210, 230 connected to terminals of nanowire 220. Thus, when a voltage is applied to electrodes 210, 230, a voltage is applied across the terminals of nanowire 220. For example, the voltage may be provided by measurement device 104 in the manner described in connection with FIG. 1. According to various embodiments, the applied signal may include DC voltages and / or currents as well as AC voltages and / or currents.

[0069] In some embodiments, one of the terminals of the sensor 206 may be connected to a ground, such as a DC ground reference to which the DC and / or AC voltages are referenced and / or a DC voltage reference by which the AC signal applied to the other terminal operates. The inventors have discovered that grounding the terminal of the sensor 206 improves protection against overvoltage events, such as ESD events. For example, grounding the terminal of the sensor 206 provides a path for ESD charges to escape (dissipate). This can prevent the buildup of high voltages (e.g., on the order of kilovolts (kV)) and reduce the effects of ESD events.

[0070] In some embodiments, the nanowire 220 of the sensor 206 may be disposed in proximity to one or more bodily fluids, such that the presence or absence of an analyte in the bodily fluid(s) affects the impedance of the nanowire 220. For example, the presence of an analyte may lower the impedance of the nanowire 220. As a result, the nanowire 220 may conduct a higher current between the electrodes 210, 230 when more analyte is disposed in proximity to the nanowire 220 than when less analyte is present. In some embodiments, the nanowire sensor 206 may be configured to generate an impedance greater than 0.5 MΩ when at least some analyte is disposed on the surface of the nanowire sensor 206. In some embodiments, the nanowire sensor 206 may be configured to generate an impedance greater than 50 MΩ when at least some analyte is disposed on the surface of the nanowire sensor 206. In some embodiments, the nanowire sensor 206 may be configured to generate an impedance greater than 75 MΩ when at least some analyte is disposed on the surface of the nanowire sensor 206. In some embodiments, nanowire sensor 206 may be configured to generate an impedance greater than 100 MΩ when at least some analyte is disposed on the surface of nanowire sensor 206 .

[0071] In some embodiments, one or more surfaces of nanowire 220 may have binding entities for biomarkers. For example, the binding entities may be covalently attached to the surface of nanowire 220. Alternatively, the binding entities may be non-covalently and / or affinity-attached to the surface, such as by non-covalent attachment (e.g., by adsorption). In some applications, the biomarker may be associated with traumatic brain injury. In some such embodiments, the nanowire may have binding entities for biomarkers of brain injury. According to various embodiments, the biomarker may be glial fibrillary acidic protein (GFAP), UCH-L1, S100β, ICH, or NFL-1, small molecules, and / or lipids. Thus, one or more binding entities for one or more of GFAP, UCH-L1, S100β, ICH, NFL-1, and / or other suitable biomarkers may be present on the surface of the nanowire. In some embodiments, multiple binding entities for one or more biomarkers may be attached to one or more surfaces of nanowire 220 and / or to the surfaces of multiple nanowires of the same or multiple sensors in the measurement system. For example, in one set of embodiments, a first nanowire or set of first nanowires has a first binding entity for one of GFAP, UCH-L1, S100β, ICH, and NFL-1, and a second nanowire or set of second nanowires has a second binding entity for one of GFAP, UCH-L1, S100β, ICH, and NFL-1. In some embodiments, the first and second binding entities may be different and bind to different biomarkers. Other configurations are possible. Examples of bindings, binding entities, biomarkers, and other components are described in U.S. Application No. 62 / 953,140, ​​filed December 23, 2019, entitled "Sensor Systems and Methods," which is incorporated herein by reference in its entirety for all purposes.

[0072] In some embodiments, the sensors and / or nanowires described herein may have one or more binding entities for biomarkers other than biomarkers associated with brain injury. For example, such binding entities and / or biomarkers may include biomarkers associated with infectious agents, biomarkers for sepsis, or any other suitable biomarkers.

[0073] The sensors described herein may be suitable for sensing various analytes in various fluids. In some embodiments, the fluid is a bodily fluid. The sensors may be suitable for sensing analytes in human bodily fluids and / or non-human, animal bodily fluids. Non-limiting types of suitable bodily fluids include blood types (e.g., venous whole blood, capillary whole blood), blood components (e.g., plasma, serum), urine, saliva, tears, and / or cerebrospinal fluid. Bodily fluids may be obtained, for example, by finger stick. In some embodiments, the bodily fluid may include a throat or nasal swab in which at least a portion of the throat or nasal mucus is transferred to a buffer solution and incubated in the buffer solution.

[0074] In some embodiments, the sensors described herein can sense analytes in a fluid through electrostatic interactions. For example, a charged analyte can be electrostatically attracted to a nanowire and / or a blocking layer disposed thereon. This electrostatic attraction can cause the analyte to deposit on the nanowire and / or the blocking layer. In some embodiments, the analyte is a charged molecule, such as a charged biopolymer and / or a charged biosmall molecule. Non-limiting examples of suitable analytes (e.g., charged analytes) include proteins (e.g., GFAP, UCH-L1, S100β, ICH, NFL-1), peptides, nucleic acids (e.g., DNA, RNA, PNA), lipids, carbohydrates, small molecules, and derivatives of the above.

[0075] Once the electrical properties of the sensor are sensed, a constant voltage may be applied (e.g., by measurement device 104) between electrodes 210, 230 such that changes in the current through nanowire 220 depend primarily on the presence or absence of analyte or the number of analytes in proximity to nanowire 220. Measurement device 104 may be configured to sense the current through nanowire 220 and provide an indication of the current to controller 102, as described in connection with FIG.

[0076] Further examples of sensors are shown in Figures 6-8. For example, Figure 6 shows an example of a nanowire sensor 606 comprising an electrode 122 and a nanowire 222 disposed on a surface layer 2022 of a substrate 922. The sensor 606 further comprises an insulating layer 5022 (e.g., an electrical insulating layer) and a wire bonding composition 6022. The insulating layer 5022 may be configured to insulate the electrode 122 from the surrounding environment. The wire bonding composition 6022 is shown disposed on a portion of each electrode of a pair of electrodes 122. The wire bonding composition 6022 may be configured to facilitate an electrical connection between the electrode 122 and the measurement device 104.

[0077] As shown in FIG. 6 , the wire bonding composition 6022 may be disposed directly on the electrode material of the electrode 122. It is also possible to dispose the wire bonding composition on the electrode such that one or more intervening components are present between the wire bonding composition and the electrode material. For example, the wire bonding composition may be disposed on a conductive material disposed on the electrode material, such as a conductive material that facilitates connection between the electrode material and the wire bonding composition. One example of a conductive material suitable for this purpose is an alloy of titanium and gold. When the wire bonding composition is disposed directly on a portion of the electrode material of the electrode and a passivation layer is disposed directly on a different portion of the electrode material, the electrode material of the electrode can be exposed for contact with the wire bonding composition by removing a portion of the passivation layer disposed on the electrode material. This can be accomplished, for example, by using photolithography techniques described elsewhere herein.

[0078] In some embodiments, the surface chemistry of one or more components of sensor 606 can be modified to promote desired interactions with one or more analytes of interest. For example, one or more types of molecules can be attached to the surface of nanowires 222. Such molecules can include those configured to bind to the analytes of interest (e.g., antibodies against an antigen of interest). The molecules of interest can be covalently attached to the nanowires. In some embodiments, covalent attachment of the molecules of interest to the nanowires can be facilitated through the use of silane derivatives. Silane derivatives containing functional groups suitable for binding with the molecules of interest (e.g., amino groups, such as primary amino groups, aldehyde groups, epoxy groups) can be covalently attached to the nanowires. The molecules of interest can then react with the silane derivatives to form covalent bonds therewith, optionally after activation to facilitate binding with the silane derivative. In some embodiments, it can be advantageous to modify the surface chemistry of multiple nanowires as a later step during sensor fabrication and / or after a step in which the molecules of interest may be decomposed (e.g., after any photolithography step, after any etching step).

[0079] In some embodiments, a blocking layer may be formed on one or more components of the sensor 606. The blocking layer may be located between these components and the environment external to the sensor. In some embodiments, the blocking layer mediates interactions with one or more components of the environment external to the sensor (e.g., one or more components, such as one or more samples to be analyzed and / or one or more analytes therein). For example, the blocking layer may reduce nonspecific interactions between the sample and / or components therein and one or more components of the sensor (e.g., multiple nanowires therein). A blocking layer suitable for this purpose may be formed from and / or include a material that does not readily bind sample components (e.g., proteins) other than the analytes of interest. As another example, the blocking layer may reduce electrostatic charge screening by a sample to be analyzed using one or more components of the sensor (e.g., multiple nanowires therein).

[0080] The blocking layer may be introduced to the sensor by a variety of suitable processes, one example of which involves dispersing a solution containing the components of the blocking layer onto the sensor and / or one or more components thereof, and then incubating the sensor with the solution disposed thereon to allow bonding between the components of the blocking layer and the sensor and / or components of the sensor.

[0081] If present, the blocking layer may be disposed on one or more discrete portions of the sensor, or may form a coating that covers a substantial portion of the sensor (e.g., the blocking layer may cover all or most of the portions of the sensor that are not in electrical communication with the external environment). Figure 7 shows an example of a sensor 706 that further includes a blocking layer 7024. The blocking layer 7024 is disposed over the nanowires 224 that electrically connect the electrodes 124, but is not present in other portions of the sensor.

[0082] In some embodiments, electrodes may be disposed elsewhere on the sensor, as described elsewhere herein in connection with FIGS. 6-7 . By way of example, the sensor may further include a back gate electrode, a water gate electrode, and / or a ground electrode. If present, these electrodes may be formed by a photolithography process (e.g., as described elsewhere herein). They may be performed in a single step or may be fabricated by separate steps. The steps employed to form these electrode(s) may be performed at any suitable time. In some embodiments, one or more of these electrodes may be formed simultaneously with the formation of one or more pairs of electrodes. For example, a photolithography process employed to form a pair of electrodes, as described elsewhere herein, may include simultaneously removing photoresist from the locations where the pair of electrodes are to be formed, and simultaneously depositing the material for forming the pair of electrodes on portions of the substrate exposed by this process, thereby forming one or more additional electrodes.

[0083] 8 illustrates one non-limiting embodiment of a sensor 806 that includes electrodes 126 as well as a back gate electrode 8026, a water gate electrode 9026, and a ground electrode 10026. If such additional electrodes are present, they may be directly exposed to the environment external to the sensor and / or may not have a passivation and / or electrical insulation layer disposed thereon. In other embodiments, one or more passivation and / or electrical insulation layers may be located between one or more of these electrodes and the external environment.

[0084] In some embodiments, the back gate electrode, water gate electrode, and / or ground electrode may be disposed on the substrate (e.g., substrate 926) such that they are in direct contact with the material that forms the bulk of the substrate (e.g., instead of a surface layer). By way of example, in some embodiments, the electrode (e.g., the back gate electrode) is deposited on the portion of the substrate from which the surface layer has been etched. Without wishing to be bound by any particular theory, it is believed to be advantageous for the back gate electrode to be disposed on the substrate such that it is in direct contact with the material that forms the bulk of the substrate. This arrangement is believed to increase the consistency of the gating provided by the back gate electrode, enable dry gating of multiple nanowires, and / or provide an easy way to ground the bulk substrate.

[0085] Returning to system 100, FIG. 3 illustrates an exemplary controller 302 that may be included in system 100, according to some embodiments. Controller 302 is shown to include bias circuitry 310 and processing circuitry 320. Bias circuitry 310 may be configured to provide one or more bias signals to measurement device 104 to sense an electrical characteristic of the sensor. Processing circuitry 320 may be configured to receive signals from measurement device 104 indicative of the electrical characteristic and determine the electrical characteristic from the received signals. In some embodiments, processing circuitry 320 may be configured to set the bias signal(s) that bias circuitry 310 is configured to provide, such as by providing a control signal to bias circuitry 310 indicative of the bias signal(s) to be generated by bias circuitry 310. In some embodiments, processing circuitry 320 may be configured to adjust the bias signal(s) to be generated by bias circuitry 310 using feedback received via measurement device 104 and / or bias circuitry 310.

[0086] In some embodiments, the bias circuit 310 may include one or more alternating current (AC) and / or direct current (DC) voltage sources configured to generate the bias signal(s). In some embodiments, the bias circuit 310 may include a battery and / or a voltage regulator configured to generate a DC voltage as the bias signal. For example, the bias circuit 310 may directly supply a DC voltage to the measurement device 104. Alternatively or additionally, the bias circuit 310 may include a modulation circuit configured to generate an AC waveform using a DC voltage, such as a square wave and / or a ramp wave. In some embodiments, the bias circuit may include an AC voltage source, such as a local oscillator, configured to generate an AC waveform as the bias signal. For example, the AC waveform may be generated directly from the output of the local oscillator or may be generated by mixing, filtering, integrating, or otherwise adjusting the output of the local oscillator. In some embodiments, the bias circuit 310 may be configured to generate an AC signal having a frequency between 0.1 Hz and 1 kHz. In some embodiments, the bias circuit 310 may be configured to generate an AC signal having a frequency between 500 Hz and 700 Hz. In some embodiments, the bias circuit 310 may be configured to generate an AC signal having a frequency of 600 Hz.

[0087] In some embodiments, bias circuit 310 may include digital-to-analog conversion (DAC) circuitry and / or amplification circuitry. For example, bias circuit 310 may be configured to generate a digital AC waveform (e.g., a square wave, etc.) and provide the AC waveform as an analog AC waveform (e.g., a sine wave and / or a triangle wave, etc.) to measurement device 104. Alternatively or additionally, bias circuit 310 may be configured to generate a bias signal at a low voltage level (e.g., on the order of millivolts), amplify the bias signal, and then provide the amplified bias signal to measurement device 104.

[0088] In some embodiments, processing circuitry 320 may be configured to determine an electrical characteristic of the sensor based on a signal received from measurement device 104. For example, the signal may be indicative of a current passing through the sensor, and processing circuitry 320 may be configured to determine the level of the current passing through the sensor. Alternatively or additionally, processing circuitry 320 may be configured to determine the impedance of the sensor, such as using the determined level of current. For example, processing circuitry 320 may be configured to divide the voltage applied to the sensor by the determined level of current. For example, processing circuitry 320 may be configured to store (e.g., in memory, a register, etc.) the value of the voltage applied to the sensor and / or calculate the value using settings provided to bias circuitry 310 to generate the bias signal(s). In some embodiments, processing circuitry 320 may include one or more processors (e.g., microprocessors, reduced instruction set processors, etc.) and / or digital logic circuits (e.g., field programmable gate arrays, application specific integrated circuits, etc.) configured to determine electrical characteristics, such as using stored instructions and / or other values ​​in memory, registers, latches, flip-flops, and / or other storage media.

[0089] In some embodiments, processing circuitry 320 may include analog-to-digital conversion (ADC) circuitry and / or amplification circuitry. For example, processing circuitry 320 may be configured to receive signals indicative of the electrical characteristics from measurement device 104 as analog signals, while processing circuitry 320 may be configured to determine the electrical characteristics in the digital domain, such as using processor(s) and / or digital logic circuitry of processing circuitry 320. Alternatively or additionally, amplification circuitry of processing circuitry 320 may be configured to amplify signals received from measurement device 104 to voltage levels suitable for determining the electrical characteristics.

[0090] In some embodiments having multiple controllers, a first controller may include bias circuitry 310 and a second controller may include processing circuitry 320. The first controller may also include some processing circuitry, such as for setting the bias signal(s) to be generated by bias circuitry 310. In some embodiments, bias circuitry 310 may be included in a first integrated circuit package and processing circuitry 320 may be included in a second integrated circuit package. For example, these two integrated circuit packages are located on the same PCB. In some embodiments, bias circuitry 310 and processing circuitry 320 may be included in a single integrated circuit package.

[0091] The present inventors have developed a measurement device configured to reduce and / or mitigate the effects of at least some electromagnetic noise on signals received via a sensor. This can improve the sensitivity of a system configured to sense the electrical properties of the sensor. In some embodiments, the present inventors have found that the sensitivity of a measurement device can be reduced by electromagnetic noise generated within the system, such as within the sensor, within system components connected to the measurement device, or even within the measurement device itself. In one example, an amplifier in a measurement device configured to connect to a sensor can generate input-referred noise, such as current noise, that can be superimposed on the signal received via the sensor. As a result, the signal from the sensor must have sufficient signal power to overcome the noise generated by the amplifier, thus affecting the ability of the measurement device to sense the electrical properties of the sensor and thereby reducing the sensitivity of the system. The level of noise generated by the amplifier is acceptable for some applications, such as applications with a current detection path having a relatively low impedance (e.g., 1 Ω) and a relatively large signal to be sensed (e.g., on the order of μA).

[0092] Similarly, if the impedance of the current detection path includes capacitance, the capacitance has little effect when the sensor is biased with a DC signal and the signal from the sensor indicating the electrical characteristic is at least substantially DC. However, if the impedance of the current detection path is relatively high (e.g., 0.5 MΩ, 50 MΩ, 75 MΩ, 100 MΩ, or higher) and / or the signal being detected is very small (e.g., on the order of pA), an otherwise tolerable level of noise can have a much higher effect. Similarly, if an AC signal biases the sensor and the signal from the sensor indicating the electrical characteristic is correspondingly AC, even a relatively small parasitic capacitance (e.g., on the order of pF) can increase the noise level of the sensed signal.

[0093] The measurement devices described herein may address the above problems, at least in part, by arranging and / or interconnecting components of the measurement device in a manner that reduces and / or mitigates the effects of electromagnetic noise generated by the measurement device components, sensors, and / or other system components.

[0094] FIG. 4 illustrates an exemplary measurement device 404 that may be included in the system 100, according to some embodiments. The measurement device 404 is shown to include a transimpedance amplifier (TIA) 410 and a sense amplifier 430. A first input of the TIA 410 is connected to an output of the controller 102 and also to a first input of the sense amplifier 430. A second input of the TIA 410 is connected to the output of the TIA 410, the sensor 106, and a second input of the sense amplifier 430. An output of the sense amplifier 430 is connected to the controller 102. In some embodiments, the TIA 410 may be configured to receive one or more bias signals from a bias circuit of the controller 102 and apply a bias voltage and / or current to the sensor 106 using the bias signals. The sense amplifier 430 may be configured to receive a signal via the TIA 410 and the sensor 106 and generate a signal indicative of an electrical characteristic of the sensor 106 at an output connected to the controller 102.

[0095] The inventors have discovered that interference, such as current noise and distortion generated by the sense amplifier, can interfere with the signal received from the sensor. For example, if the input terminals of a sense amplifier are connected across a sense resistor that receives current from the sensor, current noise generated by the sense amplifier can be added as noise to the current from the sensor. Furthermore, parasitic capacitance from system components can add nonlinear impedance to the sense path, distorting the received signal. One technique developed by the inventors to address this issue is to connect the inputs of the sense amplifier 430 to the inputs of the TIA 410 so that current noise from the sense amplifier 430 does not flow in a loop between its inputs. Furthermore, the parasitic capacitance of the sense amplifier 430 is isolated from the sense path, limiting the amount of distortion added to the sensed signal. As a result, the configuration of the measurement device 404 reduces the impact of current noise generated by the sense amplifier 430 on the signal received from the sensor 106. In some embodiments, the measurement device 404 may be configured to apply an AC voltage to the sensor 106, as the effects of distortion from parasitic capacitance are significantly mitigated. The illustrated configuration also facilitates grounding the terminals of the sensor 106, and therefore may provide improved protection against overvoltage events, as described herein.

[0096] It should be understood that amplifiers 410 and / or 430 may include multiple outputs, such as in embodiments where amplifiers 410 and / or 430 are configured to generate and output a differential signal. It should also be understood that in some embodiments, measurement device 404 may be connected to multiple terminals of sensor 106, such as in embodiments configured to apply a differential signal to sensor 106 and / or in embodiments configured to apply a ground reference to sensor 106 in addition to biasing sensor 106.

[0097] In some embodiments, the TIA 410 may be included in a single integrated circuit package. Alternatively or additionally, in some embodiments, the sense amplifier 430 may be included in a single integrated circuit package. In some embodiments, the integrated circuit packages containing the TIA 410 and the sense amplifier 430 may be located on the same PCB. In some embodiments, the TIA 410 and the sense amplifier 430 may be included in the same integrated circuit package. In some embodiments, the components of the TIA 410 and / or the sense amplifier 430 may be discrete components, such as discrete field effect transistors (FETs).

[0098] 5 is a circuit diagram of an exemplary TIA 510 and sense amplifier 530 that may be included in the measurement device 404, according to some embodiments. The TIA 510 is shown to include an amplifier 512 and a sensing element 520, and the sense amplifier 530 is shown to include an amplifier 532. The amplifier 512 of the TIA 510 has a first input 514, a second input 516, and an output 518. The amplifier 532 of the sense amplifier 530 has a first input 534 connected to the output 518 of the amplifier 512, a second input 536 connected to the first input 514 of the amplifier 512, and an output 538. The sensor element 520 includes a sense resistor 522 and a sense capacitor 524 connected between the second input 516 and the output 518 of the amplifier 512. In some embodiments, the input 514 of the amplifier 512 and / or the output 538 of the amplifier 532 may be configured to connect to the controller 102. For example, in some embodiments, the TIA 510, the sense amplifier 530, and at least a portion of the controller 102 may be disposed on a single PCB, whereby conductive traces on the PCB may connect the TIA 510 and / or the sense amplifier 530 to the controller 102. The second input 516 of the amplifier 512 may be configured to connect to the sensor 106. For example, in some embodiments, the second input 516 of the amplifier 512 may be connected to an electrical connector configured for removably connecting to a complementary electrical connector of the sensor 106. In one example, the electrical connectors may be configured to repeatedly and / or non-permanently connect and disconnect from each other.

[0099] The amplifier 512 of the TIA 510 may be configured to bias the sensor 106. In some embodiments, the amplifier 512 may include an integrated circuit (e.g., an integrated circuit disposed in its own integrated circuit package). In some embodiments, the sensor element 520 may be disposed in the same integrated circuit package as the amplifier 512. In some embodiments, the components of the amplifier 512 may be discrete, such as including one or more discrete FETs. A first input 514 of the amplifier 512 may be configured to receive a bias signal from the controller 102. A second input 516 may be configured to bias the sensor 106 with the bias signal. For example, as shown, the output 518 of the amplifier 512 may be connected to the second input 516 through the sensor element 520, such that the amplifier 512 is configured to pull the voltage at the second input 516 to the voltage at the first input 514. As a result, the amplifier 512 may apply a voltage to the sensor 106 that is substantially equal to the voltage of the received bias signal.

[0100] The sensor element 520 may be configured to receive a signal from the sensor 106 via the second input 516 and generate a sense voltage. For example, the second input 516 may receive a current through the sensor 106 in response to a bias voltage applied to the sensor 106. The received current may produce a sense voltage across the sensor element 520. Thus, the second input 516 of the amplifier 512 may function as an output of the TIA 510, which is configured to generate a sense voltage indicative of the current through the sensor.

[0101] In some embodiments, the sensor element 520 may be configured to provide a transimpedance gain of at least 1 μV / pA, e.g., 5 μV / pA or more, at DC and / or the frequency of the applied bias signal (e.g., between 0.1 Hz and 1 kHz, between 500 Hz and 700 Hz, 600 Hz, etc.). According to various embodiments, the sense resistor 522 may have a resistance between 0.1 MΩ and 75 MΩ, e.g., between 0.25 MΩ and 50 MΩ, between 1 MΩ and 25 MΩ, between 25 MΩ and 50 MΩ, etc. It should be understood that other impedance elements may be provided and / or used in place of the sense resistor 522 and / or the sense capacitor 524.

[0102] The amplifier 532 of the sense amplifier 530 may be configured to receive the sense voltage via the TIA 410 and the sensor 106. In some embodiments, the sense amplifier 530 may include an amplifier such as an operational amplifier, an instrumentation amplifier, and / or a differential amplifier. In some embodiments, the components of the amplifier 532 may be discrete, such as including a discrete FET. A first input 534 and a second input 536 of the amplifier 532 may be configured to receive the sense voltage generated by the sensor element 520 in response to receiving a current from the sensor 106. For example, the first input 534 is connected to the output 518 of the amplifier 512 and the sensor element 520, and the second input 536 is connected to the input 514 of the amplifier 512. As shown in FIG. 5 , the second input 516 is configured to provide a voltage to the sensor 106 that is substantially the same as the voltage received from the controller 102 at the first input 514. Thus, the second input 536 of the amplifier 532 receives substantially the same voltage as if the second input 536 were connected to the second input 516 and the sensor element 520. Furthermore, because the second input 536 is connected to the first input 514, the effect of current noise (e.g., input bias current) generated in the amplifier 532 on the signal received via the sensor 106 can be mitigated, as described herein. The amplifier 530 may be configured to generate a signal indicative of an electrical characteristic at an output 538 for provision to the controller 102. In some embodiments, the amplifier 532 may be configured to amplify the signal received at the inputs 534, 536 by a set gain parameter and generate an amplified signal at the output 538. For example, as shown in FIG. 5, the gain of the amplifier 532 may be set by connecting a resistor across the gain setting input RG.

[0103] It should be appreciated that in some embodiments, the TIA 510 may be configured to apply the same bias signal received from the controller 102 to the terminals of the sensor. Alternatively, a voltage divider and / or diode may be connected between the second input 516 and the output 518 so that a voltage different from the voltage of the bias signal may be applied to the sensor. For example, the applied voltage may have a voltage offset and / or may be proportional to the voltage of the bias signal.

[0104] It should be understood that in some embodiments, the TIA 510 and / or sense amplifier 530 and the controller 102 may be located on different PCBs and / or in different housings. Alternatively or additionally, in some embodiments, the TIA 510 and / or sense amplifier 530 may be connected to the controller 102 using one or more electrical connectors. Alternatively or additionally, in some embodiments, the second input 516 may be connected to the sensor 106 by other means, such as conductive traces on one or more PCBs.

[0105] FIG. 9 illustrates a relationship between the SNR of the voltage at the output of the measurement device and the voltage V applied across the sensor by the measurement device, according to some embodiments. APPL 9 is a graph 900 of the measurement device having components configured in the manner described herein with respect to FIG. 5. The measurement device was placed in a system with a sensor configured in the manner described herein for sensor 206 with respect to FIG. 2. To evaluate the noise inherent in the measurement system, nanowire 220 of sensor 206 was modeled by a thin-film resistor having the resistance value indicated.

[0106] As shown in Figure 9, the measurement device measures voltages V between 10 mVRMS and 100 mVRMS. APPL was applied to the sensor 206 (via the input 516 of the TIA 510). APPLIn response to the application of the voltage, the measurement device generated an output voltage (at output 538 of sense amplifier 530). The output voltage corresponded to the sensed resistance of sensor 206 and contained a signal content and a noise content. The signal content included the voltage caused by the resistance of the sensor, and the noise content included the voltage caused by noise in the system.

[0107] The ratio of signal content to noise content in the output voltage was determined by converting the output voltage to a digital signal using a 24-bit ADC circuit and then performing lock-in amplifier processing on the digital signal in a processor to calculate the output voltage amplitude. Once the output voltage amplitude was calculated, the noise content in the output voltage was determined by calculating the standard deviation of the signal. The signal content was calculated as the average value of the signal. In the first set of measurements, labeled with a circular dot (●) in Figure 9, the nanowire 220 of the sensor 206 had an indicated resistance of 10 MΩ. In the second set of measurements, labeled with a triangle (▲) in Figure 9, the nanowire 220 had an indicated resistance of 1 MΩ.

[0108] As shown in FIG. 9, the measurement device measures a voltage V between 10 mVRMS and 100 mVRMS applied to a sensor 206 having a resistance of 1 MΩ. APPL The measurement device achieved an SNR of over 20,000 for a voltage V between 10 mVRMS and 100 mVRMS applied to a sensor 206 with a resistance of 10 MΩ. APPL A SNR of over 5,000 was achieved for voltages V between 30mVRMS and 100mVRMS. APPL SNR of over 10,000 for a 100mVRMS voltage V APPL It included an SNR of over 20,000.

[0109] While several embodiments of the present technology have been described and illustrated herein, those skilled in the art will readily envision various other means and / or structures for carrying out the functions and / or results and / or one or more advantages described herein, and each such variation and / or modification is deemed to be within the scope of this application.

[0110] For example, while measurement devices having analog components have been described herein, it should be understood that digital components may be used as alternative or additional parts of the measurement devices described herein. Also, while discrete FET components of amplifiers have been described herein, such discrete components may alternatively or additionally include bipolar components and / or high electron mobility transistors, according to various embodiments. Also, while nanowire sensors have been described as an example of sensors that may be used in accordance with the techniques described herein, other sensors, such as nanotube sensors, may be used.

[0111] For example, the plurality of nanowires generally includes nanowires having a desired chemical composition. As one example, the nanowires may be formed from and / or include a material that can be functionalized with one or more chemicals of interest (e.g., one or more chemicals that have a desired interaction with the analyte of interest and / or chemicals that can further react with molecules that have a desired interaction with the analyte of interest). As another example, the nanowires may be formed from and / or include a material that has a desired electrical conductivity and / or equivalent surface potential (e.g., from a semiconductor, from a material that changes electrical conductivity upon exposure to the analyte of interest, and / or from a material that changes equivalent surface potential upon exposure to the analyte of interest). Non-limiting examples of materials having this property include selected elements (e.g., silicon), ceramics (e.g., gallium nitride, gallium arsenide, indium oxide, indium phosphide, molybdenum disulfide, tungsten disulfide), polymers (e.g., semiconducting polymers), one-dimensional materials (e.g., carbon nanotubes, one-dimensional materials comprising one or more of the above materials), and two-dimensional materials (e.g., graphene, two-dimensional materials comprising one or more of the above materials). In some embodiments, the nanowires are formed from and / or comprise one or more of the above materials in single-crystal form (e.g., single-crystal silicon). Further features of nanowires and sensors are described in U.S. Application No. 62 / 953,140, ​​filed December 23, 2019, entitled "Sensor Systems and Methods," which is incorporated herein by reference in its entirety for all purposes.

[0112] More generally, those skilled in the art will readily appreciate that all parameters, dimensions, materials, and configurations described herein are meant to be exemplary, and that the actual parameters, dimensions, materials, and / or configurations will depend on the particular application or applications for which the teachings of the present disclosure are employed. Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments of the technology described herein. Accordingly, it will be understood that the foregoing embodiments are presented by way of example only, and that within the scope of the appended claims and their equivalents, aspects of the technology may be practiced otherwise than as specifically described and claimed. This application relates to each individual feature, system, article, material, kit, and / or method described herein. Furthermore, any combination of two or more such features, systems, articles, materials, kits, and / or methods is within the scope of this application, provided that such features, systems, articles, materials, kits, and / or methods are not mutually inconsistent.

[0113] All definitions defined and used herein should be understood to control over dictionary definitions, definitions in documents incorporated by reference, and / or ordinary meanings of the defined terms.

[0114] The indefinite articles "a" and "an" as used in this specification and claims, unless expressly indicated to the contrary, should be understood to mean "at least one."

[0115] The term "and / or," as used in the specification and claims, should be understood to mean "either or both" of the elements so coordinated, i.e., elements that are conjunctively present in some cases and disjunctively present in other cases. Multiple elements listed with "and / or" should be construed in the same manner, i.e., to refer to "one or more" of the elements so coordinated. Other elements can optionally be present other than the elements specifically identified by the "and / or" clause, whether related or not to the elements specifically identified. Thus, as a non-limiting example, the phrase "A and / or B," when used in conjunction with open-ended language such as "comprising," can refer in one embodiment to A only (optionally including elements other than B); in another embodiment to B only (optionally including elements other than A); in yet another embodiment to both A and B (optionally including other elements), etc.

[0116] As used herein and in the claims, "or" should be understood to have the same meaning as "and / or" as defined above. For example, when separating items in a list, "or" or "and / or" shall be interpreted as being inclusive, i.e., including at least one element of a plurality or list of elements, but also including more than one element, and optionally, additional items not in the list. Terms clearly indicating the contrary, such as "only one of" or "exactly one of," or, when used in the claims, "consisting of," refer to the inclusion of exactly one element of a plurality or list of elements. In general, the term "or" as used herein shall be interpreted as indicating exclusive alternatives (i.e., "one or the other, but not both") only when preceded by terms of exclusivity, such as "either," "one of," "only one of," or "exactly one of." When used in the claims, "consisting essentially of" shall have its ordinary meaning as used in the field of patent law.

[0117] As used in this specification and claims, the phrase "at least one," in reference to a list of one or more elements, should be understood to mean at least one element selected from any one or more elements in the list of elements, but not necessarily including at least one of each and every element specifically listed in the list of elements, and not excluding any combination of elements in the list of elements. Also, within this definition, elements other than those specifically identified in the list of elements to which the phrase "at least one" refers can optionally be present, whether related to the specifically identified elements or not. Thus, as a non-limiting example, "at least one of A and B" (or, synonymously, "at least one of A or B," or, synonymously, "at least one of A and / or B") can refer in one embodiment to at least one (optionally multiple) A's in the absence of B (and optionally including elements other than B); in another embodiment to at least one (optionally multiple) B's in the absence of A (and optionally including elements other than A); in yet another embodiment to at least one (optionally multiple) A's and at least one (optionally multiple) B's (and optionally including other elements); and so on.

[0118] Also, unless expressly indicated to the contrary, in any method claimed herein including multiple steps or acts, it should be understood that the order of the method steps or acts is not necessarily limited to the order of the method steps or acts described.

[0119] In the claims, as in the foregoing specification, all transitional phrases such as "comprising," "including," "carrying," "having," "containing," "involving," "holding," "composed of," and the like, are to be understood as open-ended, i.e., including but not limited to. Only the transitional phrases "consisting of" and "consisting essentially of" are closed or semi-closed transitional phrases, respectively, as set forth in Section 2111.03 of the United States Patent Office Manual of Patent Examining Procedures.

Claims

1. 1. An apparatus for sensing an electrical property of a sensor, the apparatus comprising: a sense resistor configured to connect to the sensor; a first amplifier having a first input, a second input, and an output, the sense resistor connected between the second input and the output; a second amplifier; The second amplifier is a first input connected to the output of the first amplifier; a second input connected to the first input of the first amplifier; an output configured to provide a voltage indicative of the electrical characteristic of the sensor.

2. The apparatus of claim 1 , wherein the electrical property comprises a conductance of the sensor.

3. The apparatus of claim 2 , wherein the sensor comprises a nanowire sensor.

4. further comprising a nanowire sensor; The apparatus of claim 3 , wherein the nanowire sensor is configured such that the conductance indicates the presence of one or more analytes at a surface of the nanowire sensor.

5. The device of claim 4 , wherein the surface of the nanowire sensor has binding entities for biomarkers of brain injury.

6. a surface of the nanowire sensor having binding entities for biomarkers; 5. The device of claim 4, wherein the biomarker is selected from the group consisting of GFAP, UCH-L1, S100β, ICH, and NFL-1.

7. The device of claim 4 , wherein the surface of the nanowire sensor has binding entities for one or more biomarkers of infectious disease pathogens.

8. The device of claim 4 , wherein the surface of the nanowire sensor has binding entities for biomarkers of sepsis.

9. 10. The apparatus of claim 1, further comprising a transimpedance amplifier (TIA) comprising the sense resistor and the first amplifier, the TIA configured to generate a sense voltage indicative of a current flowing through the sensor.

10. 10. The apparatus of claim 1, wherein the second amplifier comprises at least one member of the group consisting of an instrumentation amplifier, a differential amplifier, and an operational amplifier.

11. The apparatus of claim 1 , wherein the TIA is contained in a single integrated circuit package.

12. The apparatus of claim 1 , wherein the TIA comprises a plurality of discrete components.

13. The apparatus of claim 12 , wherein the plurality of discrete components comprises field effect transistors (FETs).

14. a printed circuit board (PCB), the printed circuit board comprising: The device of claim 1; at least one electrical connector mounted on the printed circuit board; The system, wherein the electrical connector is configured to electrically connect the device to the sensor.

15. The system of claim 14 , wherein the electrical connector is configured to removably connect the device to the sensor.

16. 1. An apparatus for sensing an electrical property of a sensor, said apparatus comprising: a sense amplifier having a first input and an output, the sense amplifier configured to generate a voltage at the output indicative of the electrical characteristic; a transimpedance amplifier (TIA), The TIA is a first input connected to the first input of the sense amplifier; a second input configured to connect to the sensor.

17. The apparatus of claim 16 , wherein the electrical property comprises a conductance of the sensor.

18. The apparatus of claim 17 , wherein the sensor comprises a nanowire sensor.

19. further comprising a nanowire sensor; 20. The apparatus of claim 18, wherein the nanowire sensor is configured such that the conductance indicates the presence of one or more analytes at a surface of the nanowire sensor.

20. 20. The device of claim 19, wherein the surface of the nanowire sensor has binding entities for biomarkers.

21. 21. The device of claim 20, wherein the biomarker is a biomarker for brain injury.

22. a surface of the nanowire sensor having binding entities for biomarkers; 20. The device of claim 19, wherein the biomarker is selected from the group consisting of GFAP, UCH-L1, S100β, ICH, and NFL-1.

23. 21. The device of claim 20, wherein the biomarkers are biomarkers for one or more infectious disease pathogens.

24. 21. The device of claim 20, wherein the biomarker is a biomarker for sepsis.

25. the TIA having an output electrically coupled to the second input of the sense amplifier; 17. The apparatus of claim 16, wherein the TIA is configured to generate a sense voltage at the output of the TIA that is indicative of a current through the sensor.

26. 26. The apparatus of claim 25, wherein the TIA is further configured to receive an input voltage signal at the first input of the TIA and apply the input voltage signal to the sensor via the second input of the TIA.

27. 17. The apparatus of claim 16, wherein the TIA further comprises a sense resistor electrically connected between the first input of the TIA and the output of the TIA, the sense resistor being configured to generate a sense voltage when current flows through the sense resistor.

28. 17. The apparatus of claim 16, wherein the sense amplifier comprises at least one member of the group consisting of an instrumentation amplifier, a differential amplifier, and an operational amplifier.

29. a printed circuit board (PCB), the printed circuit board comprising:

17. An apparatus according to claim 16; at least one electrical connector mounted on the printed circuit board; and The electrical connector is configured to electrically connect with the sensor.

30. 30. The system of claim 29, wherein the electrical connector is configured to removably connect to the sensor.

31. 1. A system for sensing an electrical property of a sensor, the system comprising: a transimpedance amplifier (TIA) configured to supply an alternating current (AC) voltage to the sensor; a sense amplifier configured to generate a voltage indicative of the electrical characteristic in response to detecting a current flowing between the sensor and ground; A system comprising:

32. 32. The system of claim 31, wherein the TIA is configured to receive the AC voltage from an AC voltage source having a frequency between 0.1 Hz and 1 kHz.

33. 32. The system of claim 31, wherein the TIA is configured to receive the AC voltage from an AC voltage source having a frequency between 500 Hz and 700 Hz.

34. 32. The system of claim 31, wherein the TIA is configured to receive the AC voltage from an AC voltage source having a frequency of 600 Hz.

35. 32. The system of claim 31, wherein the electrical property comprises a conductance of the sensor.

36. 36. The system of claim 35, wherein the sensor comprises a nanowire sensor.

37. further comprising a nanowire sensor; 37. The system of claim 36, wherein the nanowire sensor is configured such that the conductance indicates the presence of one or more analytes at a surface of the nanowire sensor.

38. 38. The system of claim 37, wherein the nanowire sensor is configured to generate an impedance greater than 0.5 MΩ when at least some analyte is disposed on a surface of the nanowire sensor.

39. 38. The system of claim 37, wherein the nanowire sensor is configured to generate an impedance greater than 50 MΩ when at least some analyte is disposed on a surface of the nanowire sensor.

40. 38. The system of claim 37, wherein the nanowire sensor is configured to generate an impedance greater than 75 MΩ when at least some analyte is disposed on a surface of the nanowire sensor.

41. 38. The system of claim 37, wherein the nanowire sensor is configured to generate an impedance greater than 100 MΩ when at least some analyte is disposed on a surface of the nanowire sensor.

42. 38. The system of claim 37, wherein the surface of the nanowire sensor has binding entities for biomarkers.

43. 43. The system of claim 42, wherein the biomarker is a biomarker for brain injury.

44. a surface of the nanowire sensor having binding entities for biomarkers; 38. The system of claim 37, wherein the biomarker is selected from the group consisting of GFAP, UCH-L1, S100β, ICH, and NFL-1.

45. 43. The system of claim 42, wherein the biomarkers are biomarkers for one or more infectious disease pathogens.

46. 43. The system of claim 42, wherein the biomarker is a biomarker for sepsis.

47. an input of the TIA configured to receive the current; 32. The system of claim 31, wherein an output of the TIA is configured to provide a sense voltage to the sense amplifier.

48. 48. The system of claim 47, wherein the TIA further comprises a sense resistor configured to generate the sense voltage when the current flows through a sense resistor.

49. 32. The system of claim 31, wherein the sense amplifier comprises at least one member of the group consisting of an instrumentation amplifier, a differential amplifier, and an operational amplifier.

50. further comprising a printed circuit board (PCB); the printed circuit board having the TIA, a sense amplifier, and at least one electrical connector mounted on the printed circuit board; 32. The system of claim 31, wherein the electrical connector is configured to electrically connect with the sensor.

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