Portable electrochemical-sensor system for analyzing user health conditions and method thereof

Abstract

To analyze health conditions of a user.SOLUTION: An electrochemical sensor structure has a substrate and a nanostructured sensing surface receiving a volume of sample fluid. A sample region of an electrochemical sensor structure for receiving the sample fluid volume is sized such that the volume of the sample fluid is sufficient to operatively cover a portion of the sample region of the electrochemical sensor structure including the nanostructured sensing surface. The electrochemical sensor structure is connectable to a portable point-of-care (PoC) device. The PoC device may detect the energy properties of the sample fluid from the sample region of the electrochemical sensor structure, to produce a signal comprising a fluid reading, wherein the fluid reading is related to the energy properties of a biomarker in the sample fluid, thereby indicating the presence, the absence, or the quantity of the biomarker in the sample fluid.SELECTED DRAWING: Figure 23

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of U.S. Provisional Patent Application No. 62 / 755,148, filed November 2, 2018, U.S. Provisional Patent Application No. 62 / 786,180, filed December 28, 2018, and U.S. Provisional Patent Application No. 62 / 875,131, filed July 17, 2019, the contents of each of which are incorporated herein by reference in their entirety.

[0002] The present disclosure relates generally to portable electrochemical sensor systems and methods for analyzing and monitoring a user's health status, and specifically to a portable electrochemical sensor system having a point-of-care (PoC) device and a disposable electrochemical sensor for analyzing and monitoring a user's health status by detecting one or more biomarkers and / or disease analytes in a patient's bodily fluid received in an electrochemical sensor structure. The PoC device is also related to providing geospatial medical care to patients. In the event of an emergency, the PoC device may transmit geospatial information to the nearest emergency services or share the user's emergency contacts and information. [Background technology]

[0003] The focus of diagnostic medicine has shifted from hospital-based testing to simple at-home testing, resulting in increased awareness of patients' lifestyles. Portable health monitoring devices, such as blood pressure monitors, blood glucose meters, and smart watches with heart rate monitors, are widely used to monitor patients' health without having to go to clinics, medical laboratories, and / or hospitals for testing and diagnosis. Such portable health monitoring devices enable at-home testing, significantly saving patients time from visiting doctors and medical laboratories, thereby improving their quality of life. Such portable health monitoring devices also significantly save resources for clinics, medical laboratories, and hospitals.

[0004] The portable health monitoring device may be a handheld device that allows for convenient analysis of a user's health status. Examples of portable health monitoring devices include the Ascensia™ BREEZE™ Diabetes Care System (Ascensia and BREEZE are trademarks of Ascensia Diabetes Care Holdings AG, Basel, Switzerland) and the GLUCOMETER ELITE® Blood Glucose Meter (GLUCOMETER ELITE is a trademark of Ascensia Diabetes Care Holdings AG, Basel, Switzerland).

[0005] Some types of portable health monitoring devices, such as blood glucose meters, diagnose and monitor a patient's health condition by detecting and measuring the amount of a biomarker (such as glucose) or disease analyte (such as a protein, nucleic acid molecule, ionic metabolite, etc.) in a sample of the patient's body fluid. A biomarker is one or more specific compounds in a patient's body fluid that are indicative of a particular health condition.

[0006] Multiple biomarkers exist in human bodily fluids. However, in a home testing environment, the amount of bodily fluid sample that can be processed by a portable health monitoring device is usually limited. Furthermore, the amount of a particular biomarker in a fluid sample may be very small. Therefore, collecting, detecting, and measuring biomarkers found in bodily fluids with sufficient accuracy to determine the patient's health status has always been a challenge for portable health monitoring devices and sampling structures.

[0007] Furthermore, existing portable health monitoring devices, such as glucose monitoring devices, can only detect a single biomarker from a bodily fluid sample, but there is a need for portable health monitoring devices that can detect more than one biomarker for patient convenience and to reduce patient medical costs.

[0008] Diagnostic biosensing devices (hereinafter also referred to as point-of-care (PoC) devices) are also needed to reduce the burden on existing healthcare systems and improve patient access to healthcare. Furthermore, there is a need for PoC devices that can be used by untrained consumers for home testing of physiological fluids to effectively diagnose or predict disease and enhance disease management. More specifically, there is a high demand for on-demand, portable, reliable, intuitive, and low-cost PoC devices for home testing for disease diagnosis and prognosis.

[0009] For example, the standard of care for heart failure in the art is retroactive rather than proactive in the delivery of medical services. After being diagnosed with heart failure, patients typically need to visit their healthcare provider (HCP) periodically for laboratory testing. This is time-consuming and burdensome for patients and ineffective because it potentially puts patients at risk between visits.

[0010] While desperately needed, portable, at-home testing is only part of a complete solution. To meaningfully impact patient health, especially in emergencies, patients must have the option to access emergency medical services, as acute issues such as heart failure can lead to progressively debilitating conditions and sudden, life-threatening events. Therefore, solutions are needed to improve emergency access, including patient location, patient history data, and communication if the patient is unresponsive. However, current diagnostic devices have limited communication with emergency services, even in situations where urgent medical attention is required, potentially exposing patients to life-threatening risks in emergency situations.

[0011] U.S. Patent No. 9,869,669 to Han et al. teaches a sensor platform including a substrate, a plurality of nanochannels disposed on the substrate, a plurality of electrodes, a waveguide disposed on the substrate, and an analysis chamber and a reference chamber disposed on the substrate. Each electrode extends substantially across the width of the plurality of nanochannels. At least one analysis optical resonator is disposed in the analysis chamber and optically coupled to at least a portion of the waveguide. The at least one analysis optical resonator is in fluid communication with at least one of the plurality of nanochannels. At least one reference optical resonator is disposed in the reference chamber and optically coupled to at least a portion of the waveguide. The at least one reference optical resonator is in fluid communication with at least one other of the plurality of nanochannels.

[0012] Sharma et al., US Patent Application Publication No. 2016 / 0202250A1, teaches a metal nanoparticle / single-walled carbon nanotube (MNP / SWCNT) hybrid-based chemiresistive biosensor for the quantitative detection of human cardiac biomarkers, troponin I (cTnI) and myoglobin (Mb). Highly specific cardiac antibodies, anti-cTnI (Ab-cTnI) or anti-Mb (Ab-Mb), were covalently immobilized to site-specific carboxyl groups on MNPs immobilized on SWCNT devices. The biosensor device was characterized by source / drain current-voltage measurements. The device performance was investigated using the change in conductance of the SWCNT channel upon exposure to cTnI in human serum. The MNPs induced charge density on the SWCNTs, providing a large surface area for high protein loading and improved electrical signal, resulting in highly sensitive low-level detection of cTnI and Mb.

[0013] U.S. Patent Application Publication No. 2015 / 0083613A1 to Lee et al. teaches an electrochemical biosensor for measuring blood glucose with improved hematocrit measurement accuracy. According to U.S. Patent Application Publication No. 2015 / 0083613, an electrochemical biosensor including a first electrode portion for correcting the measured hematocrit value and a second electrode portion for measuring glucose concentration is effective in improving the accuracy of the measured hematocrit value and further improving the accuracy of the measured blood glucose concentration using the measured hematocrit value for correction. This is because the insulating cover is thinner than the working electrode and auxiliary electrode, so the areas of the first working electrode and first auxiliary electrode of the first electrode portion exposed to the blood sample are equal, the distance between the first working electrode and the second working electrode is constant, and the electrode area is always maintained by the insulating cover, even if positioning errors occur during printing.

[0014] U.S. Patent No. 7,045,054 B1 to Buck et al. teaches a sensor and a method for detecting an analyte. Each sensor includes a volume of a hydrophilic medium that holds an amount of analyte proportional to the concentration of the analyte in the biological fluid, an electrode and an oxidoreductase in contact with the medium, and an electron transfer mediator. The fluid contacts the sensor, and initially, at predetermined intervals, a potential sufficient to oxidize the mediator is intermittently applied to the electrode, and the current through the electrode is sensed as a function of the duration of the applied potential. The applied mediator oxidizing potential is maintained for a period sufficient to determine the rate of change of the current through the electrode over time. The current flow is correlated with the current flow of a known concentration of analyte in the medium.

[0015] U.S. Patent Application Publication No. 2018 / 0067071A1 to Wu et al. teaches a biosensor system including a measurement device and a test sensor including at least three independently addressable electrodes, at least two of which are substantially chemically separated. One or more working electrodes may be combined with two or more counter electrodes. The two or more counter electrodes may operate at different potentials to provide multi-analyte electrochemical analysis. An analytical method for performing multi-analyte electrochemical analysis is provided, and a test sensor is provided that is resistant to chemical mixing between secondary analysis regions.

[0016] U.S. Patent No. 7,723,099 B2 to Miller et al. teaches an interference-reduced electrochemical immunosensor system comprising: a first immunosensor that generates an electrochemical signal based on the formation of a sandwich between an immobilized antibody, a target analyte, and a labeled antibody, where a portion of the signal arises from nonspecific binding of the labeled antibody in a region of the first immunosensor; and a second immunosensor that acts as an immunoreference sensor and generates a signal that is the same as or predictably related to the degree of nonspecific binding occurring in the first immunosensor, and that has an immune complex between the immobilized antibody and an endogenous or exogenous protein in the sample that is not the target analyte.

[0017] U.S. Patent Application Publication No. 2013 / 0183243 to Labelle et al. teaches a diagnostic device and method of use for a diagnostic assay to monitor the presence of a biological sample, the device enabling the determination of at least two assay components on a single sensor. More specifically, U.S. Patent Application Publication No. 2013 / 0183243 relates to a multi-marker electrochemical impedance spectroscopy sensor with multiple molecular recognition elements, the sensor including multiple different molecular recognition element types tuned to alter the frequency of one molecular recognition element type to be at a frequency that is detectably different from the frequency of another molecular recognition element type on the same sensor.

[0018] U.S. Patent No. 7,910,352 B2 to Miller et al. teaches an interference-reduced electrochemical immunosensor system that includes a first immunosensor that generates an electrochemical signal based on the formation of a sandwich between an immobilized antibody, a target analyte, and a labeled antibody, where a portion of the signal arises from nonspecific binding of the labeled antibody in a region of the first immunosensor, and a second immunosensor that acts as an immunoreference sensor, generates a signal that is the same as or predictably related to the degree of nonspecific binding occurring in the first immunosensor, and has an immune complex between the immobilized antibody and an endogenous or exogenous protein in the sample that is not the target analyte.

[0019] U.S. Patent Application Publication No. 2019 / 0076068A1 to Yang et al. teaches a diagnostic electrochemical impedance spectroscopy (EIS) procedure applied to measure values ​​of impedance-related parameters for one or more sensing electrodes. The parameters may include real impedance, imaginary impedance, impedance magnitude, and / or phase angle. The impedance-related parameter measurements are then used to perform sensor diagnostics, calculate reliable fusion sensor blood glucose levels based on signals from multiple redundant sensing electrodes, calibrate the sensor, detect interferents in the immediate vicinity of one or more sensing electrodes, and inspect the surface area characteristics of electroplating electrodes. Impedance-related parameters that are substantially glucose-independent over specific frequency ranges can be defined. Application-specific integrated circuits (ASICs) enable the implementation of EIS-based diagnostics, fusion algorithms, and other processes based on the measurement of EIS-based parameters.

[0020] U.S. Patent No. 8,653,833 B2 to Chodavarapu et al. discloses a system including: (a) a signal generator for generating a probe signal having at least one predetermined characteristic and including at least a digital-to-analog converter; (b) a signal converter for generating a digital representation of at least one analog input signal of a plurality of analog input signals and including at least one of an analog-to-digital converter and a multiplexer; (c) a sensor including at least a first electrical contact and a second electrical contact; (d) a reference impedance; (e) a switch for receiving a probe signal from the signal generator and applying the probe signal at least one of continuously and selectively to at least one of the first electrical contact of the sensor and the reference impedance; and (f) an impedance connecting circuit including at least a switch for selectively connecting at least one of the second electrical contact of the sensor and the reference impedance to the signal converter. (g) an analysis circuit for receiving at least a digital representation of a generated probe signal and a digital representation of the at least one analog input signal, performing a first process on the digital representation of the generated probe signal to determine at least a characteristic of the probe signal, performing a second process on the digital representation of the at least one analog input signal to generate at least one real and imaginary component of the digital representation of the at least one analog input signal depending on at least the determined characteristic of the probe signal, applying a correction to at least the imaginary component, and determining an impedance of the sensor depending on at least a reference impedance and at least one of the real and imaginary components of the digital representation of the at least one analog input signal; and (h) a first memory for storing the determined impedance for subsequent retrieval.

[0021] U.S. Patent No. 8,663,442 B2 to Burke et al. teaches a method for measuring an analyte in a biological fluid, which includes applying an excitation signal having a DC component and an AC component. The AC and DC responses are measured. A corrected DC response is determined using the AC response. The concentration of the analyte is determined based on the corrected DC response.

[0022] US Pat. No. 8,158,430 B1 to Roy et al. teaches fluidic devices and systems that allow for the detection of analytes from biological fluids to provide point-of-care testing for a variety of medical applications.

[0023] EP 2,967,451 B1 to Johnson et al. teaches a point-of-care sensor system including a portable reader and a disposable cartridge for receiving and analyzing a sample. The cartridge may include one or more sensor channels, each containing one or more sensors. After providing a sample to the cartridge, the cartridge can be inserted into a reader, which interacts with the cartridge to perform detection on the cartridge and receive a signal indicating the presence and / or amount of one or more targets in the sample. Examples of cartridges may include cardiac panels, sepsis panels, etc. In some embodiments, the same sensor hardware may be configured for multiple measurements of different targets performed over different time frames. Storage and delivery mechanisms for solid and liquid reagents on the cartridge are also disclosed therein.

[0024] U.S. Patent Application Publication No. 2016 / 0057565A1 to Gold teaches systems and methods for sensing, communicating, and processing one or more physiological parameters of a user, such as when the user is in proximity to an object of interest. The object may be a product, a place, or another person. One embodiment thereof enables users, designers, manufacturers, marketers, and sellers to secure valuable information about how an object (or many objects) is perceived and used by a user (or many users). Various embodiments thereof may be used in conjunction with smart objects (e.g., internet-connected objects) and dumb objects (e.g., objects without internet or other network connectivity).

[0025] U.S. Patent Application Publication No. 2015 / 0371350A1 to Zebarjadi et al. teaches a system that allows patients to request medical services from a patient computing device. Physicians may be matched with patients seeking or needing medical care. Patients may register or become members of the system using a computing device. Using the same or a different computing device, patients may request medical care at a specific location. Physicians may be matched with patent requests for medical services. Physician / patient matching may be based on location information, the patient's medical needs, the physician's medical practice, gender, language skills, or other criteria. The physician may accept or reject the patient's request for medical services. Two-way, at least partially anonymous, communication may be initiated to enable the physician to assess the patient's medical needs. Computing devices associated with the patient and / or physician may be used in conjunction with a coordination component to collect relevant information, record medical records, manage communications, process claims, navigate to the patient's location, and / or for other purposes.

[0026] Frey's U.S. Patent No. 9,080,883 B2 teaches a method for dynamically outputting information, particularly for evacuating a person from a building, to a portable device based on the device's current location data determined by a location determination system. The current availability of evacuation routes located within the building is determined by a sensor system. Evacuation information is determined by a control unit based on the current availability of the evacuation routes and the device's current location and output to the portable device. Thus, in an emergency, a person's dedicated evacuation information can be determined and output on the person's mobile device (e.g., smartphone, PDA) as a function of the person's location and respective hazardous situation, thereby enabling, among other things, rapid and efficient evacuation of a building or premises.

[0027] U.S. Patent Application Publication No. 2017 / 0024531A1 to Malaviya teaches a healthcare information system for providing near-real-time or real-time contact tracing. The system includes a location data receiver unit configured to receive location data related to one or more entities associated with a healthcare facility, and a context profile management unit configured to utilize the received location data to generate, maintain, or update one or more context profiles, each corresponding to one or more entities. Devices, systems, and methods related to the use of near-real-time or real-time contact tracing in applications such as infection control, infection pathway development, and the like are provided.

[0028] U.S. Patent No. 8,249,547 B1 to Fellner teaches a wearable emergency alert device including a wearable member and a separately encased mobile phone member selectively attachable to the wearable member. The wearable member includes an attachment member for attaching the wearable member to a user's body part, a first transmitter for transmitting a first signal to the mobile phone member, a power source for the first transmitter, and a user-operable first actuator for activating the first transmitter to transmit the signal to the mobile phone member. The mobile phone member includes a mobile phone transceiver for establishing a first communication link between the mobile phone transceiver and the first transmitter and a second communication link between the mobile phone transceiver and the remote receiver for transmitting and receiving at least one of data, voice, and messages between the mobile phone transceiver and the remote receiver. An attachment member is provided for selectively and removably attaching the mobile phone member to the wearable member, enabling the mobile phone member to engage the first actuator to activate the emergency signal. Summary of the Invention

[0029] FIELD OF THE INVENTION The embodiments disclosed herein relate to portable electrochemical sensor systems and methods for analyzing and monitoring the health of a user. In some embodiments, the portable electrochemical sensor system uses a biosensor to detect the presence of one or more analytes or biomarkers from bodily fluids.

[0030] As one skilled in the art will understand, an analyte is a chemical moiety, component, or species of interest in an analytical procedure performed on a sample. The term "analyte" often refers to a relatively simple element or molecule, such as serum chloride or a liver enzyme, that is detectable in an analytical process.

[0031] Those skilled in the art will also understand that a biomarker is a biological molecule typically found in blood, other body fluids, or tissues that can be used as an indication of normal or abnormal processes, or of a condition or disease. A biomarker has a detectable property that may be objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacological responses to therapeutic intervention. The term "biomarker" often refers to a marker for detecting or diagnosing a specific disease or group of diseases, which may be malignant or non-malignant, such as cardiovascular disease.

[0032] Notwithstanding the above differences, those skilled in the art will understand that the electrochemical sensor systems and methods described herein may be adapted to detect any suitable analyte and / or biomarker in various embodiments. Accordingly, in the following description, the terms "analyte" and "biomarker" may be used interchangeably.

[0033] According to one aspect of the present disclosure, a portable electrochemical sensor system includes a point-of-care (PoC) device and a disposable electrochemical sensor structure for analyzing and monitoring the health status of a user or patient.

[0034] In some embodiments, the PoC device cooperates with a disposable electrochemical sensor structure to detect and gather information from biomarkers found in a mammalian body fluid sample.

[0035] In some embodiments, the electrochemical sensor structure includes a sample region for receiving a patient's bodily fluid sample. The electrochemical sensor structure may be inserted into an otherwise coupled PoC device. The PoC device then detects and measures the amount of one or more biomarkers and / or disease analytes indicative of a health condition in the received bodily fluid sample by measuring the energy characteristics of the sample fluid. In some embodiments, the analyte concentration is quantified electrochemically, and noise from undesired proteins is reduced by the introduction of a filtration unit.

[0036] The portable electrochemical sensor systems disclosed herein can be used to diagnose certain diseases without meeting a doctor in person, allowing users to avoid visiting a clinic or hospital for simple diagnostic tests such as fingerstick blood tests, thereby reducing the user's wait time at the clinic and the time spent by medical professionals performing such simple diagnostic tests.

[0037] The portable electrochemical sensor systems disclosed herein are suitable for use by untrained users for at-home testing of physiological fluids to effectively diagnose or predict disease and enhance disease management.

[0038] The portable electrochemical sensor systems disclosed herein are effective for monitoring the health of a patient by detecting one or more analytes in a bodily fluid received in an electrochemical sensor structure. Related methods and components of the portable electrochemical sensor systems for accurately detecting the analytes are also disclosed.

[0039] According to one aspect of the present disclosure, a portable electrochemical sensor system includes a PoC device that functions as a reader and a sensor strip.

[0040] In various embodiments, the sensing strip may include a single or multiple working electrodes (WE) along with corresponding counter and reference electrodes (CE and RE, respectively). A separation unit HF-PSC skilled in capturing cellular components from bodily fluids is also disclosed herein. The electrochemical sensor is connected to a portable PoC device. The PoC device can detect the energy characteristics of the sample fluid from the sample region of the electrochemical sensor structure to generate a signal including a fluid reading, which is related to the energy characteristics of biomarkers in the sample fluid and thereby indicates the presence, absence, or amount of an analyte in the sample fluid.

[0041] The PoC devices disclosed herein measure the amount of specific biomarkers in bodily fluids that are indicative of health conditions. By using the PoC devices, users may diagnose certain diseases without meeting a doctor in person.

[0042] In some embodiments, an electrochemical sensor structure or strip includes one or more electrodes, a flexible substrate, a top cover layer, and a hydrophobic insulating layer. A sample fluid may be placed in a sample region of the strip, and the strip is then inserted into a PoC device. The PoC device determines the presence and / or amount of a particular analyte in the sample fluid by measuring the energy characteristics of the sample fluid.

[0043] According to one aspect of the present disclosure, there is disclosed an apparatus for analyzing a bodily fluid sample of a user, the apparatus comprising: a housing with at least one first port for receiving an electrochemical sensor structure, the electrochemical sensor structure comprising a first circuit having a first set of electrodes for contacting a bodily fluid sample; an identification circuit for identifying one or more biomarkers analyzable using the electrochemical sensor structure; an analysis circuit comprising a set of coupling electrodes for electrically coupling to the first set of electrodes of the electrochemical sensor structure for analyzing the identified one or more biomarkers in the bodily fluid sample; a control circuit coupled to the identification and analysis circuit for determining a set of biosensing parameters based on the identified one or more biomarkers and for controlling the analysis circuit to analyze the identified one or more biomarkers in the bodily fluid sample based on the set of biosensing parameters; and an output for outputting an analysis result of the analysis of the identified one or more biomarkers in the bodily fluid sample.

[0044] In some embodiments, the identification circuit is for identifying one or more biomarkers by measuring the impedance of a second circuit of the electrochemical sensor structure, the resistance of the second circuit encoding the identity of the one or more biomarkers.

[0045] In some embodiments, the second circuit comprises a second set of electrodes.

[0046] In some embodiments, the identification circuit is for identifying the one or more biomarkers by reading a radio frequency identification (RFID) tag that encodes identification information of the one or more biomarkers of the electrochemical sensor structure.

[0047] In some embodiments, the RFID tag is on the electrochemical sensor structure or on a shipping vial containing the electrochemical sensor structure.

[0048] In some embodiments, the device further comprises an imaging component, and the identification circuit is for identifying the one or more biomarkers by using the imaging component to scan an image that encodes identification information of the one or more biomarkers.

[0049] In some embodiments, the identification circuitry is for instructing a device having an imaging component and operably coupled to the apparatus to use the imaging component to scan an image encoding identification information of the one or more biomarkers to identify the one or more biomarkers.

[0050] In some embodiments, the image is a one-dimensional or two-dimensional barcode.

[0051] In some embodiments, the image is on the electrochemical sensor structure or on a delivery vial containing the electrochemical sensor structure.

[0052] In some embodiments, the analysis circuit is configured to measure one or more impedances, one or more currents, and / or one or more voltages of the first circuit to analyze the identified one or more biomarkers in the bodily fluid sample.

[0053] In some embodiments, the analysis circuit comprises at least one potentiostat circuit for electrically coupling to the first circuit for analyzing the identified one or more biomarkers in the bodily fluid sample.

[0054] In some embodiments, the at least one potentiostat circuit comprises a direct current (DC) potentiostat circuit, an alternating current (AC) potentiostat circuit, or a combination thereof.

[0055] In some embodiments, the set of coupled electrodes includes at least a coupled RE, a coupled CE, and a coupled WE for electrically coupling to a reference electrode (RE), a control electrode (CE), and a working electrode (WE) of an electrochemical sensor structure.

[0056] In some embodiments, the set of coupled electrodes includes at least a coupled RE, a coupled CE, and a plurality of WEs for electrically coupling to the RE, CE, and a plurality of WEs of the electrochemical sensor structure.

[0057] In some embodiments, the set of coupled electrodes includes at least a coupled RE, a coupled CE, and three or more coupled WEs for electrically coupling the RE, CE, and three or more WEs of the electrochemical sensor structure.

[0058] In some embodiments, at least one first set of coupled WEs is for electrically coupling to a first set of WEs of an electrochemical sensor structure supersaturated with a first set of one or more capture ligands, at least one second set of coupled WEs is for electrically coupling to a second set of WEs of the electrochemical sensor structure cross-linked with a predetermined concentration of a second set of one or more capture ligands, and the analytical circuit is for analyzing the identified one or more biomarkers in the bodily fluid sample by calculating an analyte concentration based on a difference in charge transfer resistance (RCT) between the first and second sets of WEs of the electrochemical sensor structure.

[0059] In some embodiments, the analysis circuit is for calculating an analyte concentration based on a difference in charge transfer resistance (RCT) between the first set and the second set of WEs of the electrochemical sensor structure and for analyzing the identified one or more biomarkers in the bodily fluid sample by using statistical methods.

[0060] In some embodiments, the output comprises a screen for displaying the results of the analysis.

[0061] In some embodiments, the screen is a touch screen for displaying analysis results and receiving input from a user.

[0062] In some embodiments, the output comprises a speaker for outputting the analysis results.

[0063] In some embodiments, the apparatus further comprises a networking module for communicating with one or more remote devices.

[0064] In some embodiments, the networking module is a BLUTOOTH module.

[0065] In some embodiments, the output comprises a networking module for outputting the analysis results to one or more remote devices.

[0066] In some embodiments, the one or more remote devices include an artificial intelligence (AI) system for determining the health status of the user based on the analysis results.

[0067] In some embodiments, the device further comprises one or more buttons for receiving input from a user.

[0068] In some embodiments, the one or more buttons comprise an SOS button for initiating emergency communication with one or more emergency services.

[0069] In some embodiments, the housing comprises a front wall, a rear wall, a top wall, a bottom wall, and two opposing side walls, with one or more buttons distributed on at least one of the side walls.

[0070] In some embodiments, the at least one first port is located on the upper wall or the lower wall.

[0071] In some embodiments, the device further comprises an adapter for electrically and removably coupling to the device, the adapter comprising a plurality of second ports for receiving a plurality of additional electrochemical sensor structures.

[0072] In some embodiments, the multiple additional electrochemical sensor structures have the same mechanical and / or electrical specifications.

[0073] In some embodiments, the multiple additional electrochemical sensor structures have different mechanical and / or electrical specifications.

[0074] In some embodiments, the device comprises a plurality of first ports.

[0075] In some embodiments, the multiple first ports have the same mechanical and / or electrical specifications.

[0076] In some embodiments, the multiple first ports have different mechanical and / or electrical specifications.

[0077] In some embodiments, the device further comprises a battery for powering at least the identification circuitry, the analysis circuitry, and the control circuitry, and a second port for electrically coupling to a power source for charging the battery.

[0078] In some embodiments, the second port is a Universal Serial Bus (USB) port.

[0079] In some embodiments, the device further comprises a third port for physically and electrically coupling to a smartphone.

[0080] In some embodiments, the analytical and / or control circuitry comprises an electrochemical module for detecting and analyzing N-terminal pro-B-type natriuretic peptide (NT-pro-BNP), a fluorescence module, a polymerase chain reaction (PCR) module for detecting and analyzing aptamer-based ligands, and an absorption module for metabolite analysis.

[0081] In some embodiments, the analysis circuitry and / or the control circuitry further comprises a memory having stored therein a calibration curve for determining the concentration of one or more identified biomarkers.

[0082] In some embodiments, the device further comprises one or more Global Positioning System (GNSS) components for obtaining geospatial information of the device, and the output is for outputting the analysis results and the geospatial information.

[0083] In some embodiments, the one or more remote devices are for evaluating the analysis results to obtain an assessment of the user's health status; storing the analysis results, the geospatial information, and the assessment of the user's health status; notifying the user about further actions if the assessment of the user's health status is above a first threshold but below a second threshold; and initiating an emergency protocol if the assessment of the user's health status is above the second threshold.

[0084] According to one aspect of the present disclosure, there is disclosed an apparatus for analyzing a bodily fluid sample of a user. The apparatus includes a housing with at least one first port for receiving an electrochemical sensor structure, the electrochemical sensor structure including a first circuit having a first set of electrodes for contacting the bodily fluid sample, an analysis circuit including a set of coupling electrodes for electrically coupling to the first set of electrodes of the electrochemical sensor structure for analyzing one or more biomarkers in the bodily fluid sample, and an output for outputting an analysis result of the analysis of the identified one or more biomarkers in the bodily fluid sample. The set of coupling electrodes includes at least a reference electrode (RE), a control electrode (CE), and a plurality of working electrodes (WE) for electrically coupling to a reference electrode (RE), a control electrode (CE), and a plurality of working electrodes (WE) of the electrochemical sensor structure.

[0085] In some embodiments, the set of coupled electrodes includes at least a coupled RE, a coupled CE, and three or more coupled WEs for electrically coupling the RE, CE, and three or more WEs of the electrochemical sensor structure.

[0086] In some embodiments, at least one first set of coupled WEs is for electrically coupling to a first set of WEs of an electrochemical sensor structure supersaturated with a first set of one or more capture ligands, at least one second set of coupled WEs is for electrically coupling to a second set of WEs of the electrochemical sensor structure cross-linked with a predetermined concentration of a second set of one or more capture ligands, and the analytical circuit is for analyzing the identified one or more biomarkers in the bodily fluid sample by calculating an analyte concentration based on a difference in charge transfer resistance (RCT) between the first and second sets of WEs of the electrochemical sensor structure.

[0087] In some embodiments, the analysis circuit is for calculating an analyte concentration based on a difference in charge transfer resistance (RCT) between the first set and the second set of WEs of the electrochemical sensor structure and for analyzing the identified one or more biomarkers in the bodily fluid sample by using statistical methods.

[0088] According to one aspect of the present disclosure, an electrochemical sensor structure is disclosed that includes a substrate, a first circuit that includes a first set of electrodes dispersed on the substrate and extending into a sampling area of ​​the substrate for contacting a bodily fluid sample, and an identification structure for identifying one or more biomarkers in the bodily fluid sample that can be analyzed using the electrochemical sensor structure.

[0089] In some embodiments, the substrate comprises a polymer.

[0090] In some embodiments, the polymer comprises polystyrene, polyester, polycarbonate, or polyamide.

[0091] In some embodiments, the substrate is a porous substrate.

[0092] In some embodiments, the substrate is a track-etched membrane having a porosity of 30% or greater.

[0093] In some embodiments, the substrate comprises a poly(methyl methacrylate) (PMMA) film.

[0094] In some embodiments, the identification structure comprises a second circuit having a predetermined impedance that encodes the identity of one or more biomarkers of the electrochemical sensor structure.

[0095] In some embodiments, the identification structure comprises a radio frequency identification (RFID) tag that encodes the identity of one or more biomarkers of the electrochemical sensor structure.

[0096] In some embodiments, the identification structure includes an image that encodes the identity of one or more biomarkers of the electrochemical sensor structure.

[0097] In some embodiments, the image includes a one-dimensional or two-dimensional barcode that encodes the identity of one or more biomarkers of the electrochemical sensor structure.

[0098] In some embodiments, the first set of electrodes includes at least a reference electrode (RE), a control electrode (CE), and a working electrode (WE).

[0099] In some embodiments, the first set of electrodes includes at least a RE, a CE, and a plurality of WEs.

[0100] In some embodiments, the first set of electrodes includes at least a RE, a CE, and three or more WEs.

[0101] In some embodiments, at least one first set of WEs is supersaturated with a first set of one or more capture ligands, and at least one second set of WEs is cross-linked with a predetermined concentration of the second set of one or more capture ligands.

[0102] In some embodiments, the first set of one or more capture ligands comprises the same capture ligand.

[0103] In some embodiments, the first set of one or more capture ligands comprises different capture ligands.

[0104] In some embodiments, the second set of one or more capture ligands comprises the same capture ligand.

[0105] In some embodiments, the second set of one or more capture ligands comprises different capture ligands.

[0106] In some embodiments, the first set of one or more capture ligands is the same as the second set of one or more capture ligands.

[0107] In some embodiments, the first set of one or more capture ligands is different from the second set of one or more capture ligands.

[0108] In some embodiments, each of the first set of electrodes includes a layer of chromium (Cr) and a layer of gold (Au) on the Cr layer.

[0109] In some embodiments, at least one WE further comprises a layer of a conductive nanomaterial on the Au layer.

[0110] In some embodiments, at least one WE further comprises a layer of sensing element over the layer of conductive nanomaterial.

[0111] In some embodiments, the CE extends along at least two edges of the sampling region, thereby surrounding the remainder of the first set of electrodes.

[0112] In some embodiments, the electrochemical sensor structure further includes a hydrophobic intermediate layer having a distal end opening forming a sampling port for receiving a bodily fluid sample into the sampling region, and a protective layer over the hydrophobic intermediate layer and covering the sampling region.

[0113] In some embodiments, the sampling region of the substrate comprises one or more introduction channels around its edge for introducing a bodily fluid sample using capillary effect, a heterophilic plasma separation component (HF-PSC) unit adjacent to the one or more introduction channels for receiving the bodily fluid sample therefrom and filtering interfering components of the bodily fluid sample, and an analyte drop chamber intermediate the HF-PSC and the first electrode set, which receives the filtered bodily fluid sample from the HF-PSC to allow the filtered bodily fluid sample to contact the first electrode set.

[0114] In some embodiments, at least one of the one or more introduction channels is funnel-shaped, with an opening adjacent the edge of the sampling region that tapers toward the HF-PSC unit.

[0115] In some embodiments, at least one of the one or more introduction channels is imprinted on the substrate.

[0116] In some embodiments, at least one of the one or more introduction channels is formed by a gap in a coating on the substrate.

[0117] In some embodiments, the HF-PSC units comprise symmetric and / or asymmetric pores of various pore sizes.

[0118] In some embodiments, the electrochemical sensor structure further includes one or more capillary channels each including an inlet within or around the analyte drop chamber and extending from the analyte drop chamber to the first set of electrodes, at least one of the one or more capillary channels being hydrophilic to the bodily fluid sample and including an abrupt expansion at a distance to the inlet for controlling the volume of the bodily fluid sample therein, and at least one WE extending to at least one of the one or more capillary channels at a location intermediate the inlet and its expansion for interacting with the bodily fluid sample therein.

[0119] and one or more capillary channels each including an inlet within or around the analyte drop chamber and extending from the analyte drop chamber to the first set of electrodes, at least one of the one or more capillary channels being hydrophobic to the bodily fluid sample and including an abrupt tapering portion at a distance to the inlet for controlling the volume of bodily fluid therein, and at least one WE extending to at least one of the one or more capillary channels at a location intermediate the inlet and its tapered portion for interacting with the bodily fluid sample therein.

[0120] According to one aspect of the present disclosure, an electrochemical sensor structure is disclosed, comprising: a substrate; and a first circuit comprising a first set of electrodes dispersed on the substrate and extending into a sampling region of the substrate for contacting a bodily fluid sample, the first set of electrodes including at least a reference electrode (RE), a control electrode (CE), and a plurality of working electrodes (WE).

[0121] In some embodiments, the plurality of WEs includes three or more WEs.

[0122] In some embodiments, at least one first set of WEs is supersaturated with a first set of one or more capture ligands, and at least one second set of WEs is cross-linked with a predetermined concentration of the second set of one or more capture ligands.

[0123] According to one aspect of the present disclosure, an electrochemical sensor structure is disclosed, comprising: a substrate; a first circuit comprising a first set of electrodes dispersed on the substrate and extending into a sampling region of the substrate for contacting a bodily fluid sample; the sampling region of the substrate comprising one or more inlet channels around its edge for introducing the bodily fluid sample using capillary effect; a heterophilic plasma separation component (HF-PSC) unit adjacent to the one or more inlet channels for receiving the bodily fluid sample therefrom and filtering interfering components of the bodily fluid sample; and an analyte drop chamber intermediate the HF-PSC and the first set of electrodes for receiving the filtered bodily fluid sample from the HF-PSC to allow the filtered bodily fluid sample to contact the first set of electrodes.

[0124] In some embodiments, at least one of the one or more introduction channels is funnel-shaped, with an opening adjacent the edge of the sampling region that tapers toward the HF-PSC unit.

[0125] According to one aspect of the present disclosure, an electrochemical sensor structure is disclosed that includes a substrate, a first circuit having a first set of electrodes dispersed on the substrate and extending into a sampling region of the substrate for contacting a bodily fluid sample, and one or more capillary channels, each extending from an inlet to the first set of electrodes, at least one of the one or more capillary channels being at a distance to the inlet and including an area-changing portion having a varied cross-sectional area for controlling a volume of the bodily fluid sample therein, and at least one WE extending to at least one of the one or more capillary channels at a location intermediate the inlet and its area-changing portion for interacting with the bodily fluid sample therein.

[0126] In some embodiments, at least one of the one or more capillary channels is hydrophilic to the bodily fluid sample, and the area-changing portion of at least one of the one or more capillary channels is a portion downstream of at least one WE with an increased cross-sectional area.

[0127] In some embodiments, at least one of the one or more capillary channels is hydrophobic to the bodily fluid sample, and the area-changing portion of at least one of the one or more capillary channels is a portion downstream of the at least one WE that has a reduced cross-sectional area.

[0128] According to one aspect of the present disclosure, a system for analyzing a bodily fluid sample of a user is disclosed. The system includes an electrochemical sensor structure for receiving the bodily fluid sample thereon and a test device in cooperation with the electrochemical sensor structure for analyzing the bodily fluid sample. The electrochemical sensor structure includes a substrate, a first circuit including a first set of electrodes dispersed on the substrate and extending into a sampling area of ​​the substrate for contacting the bodily fluid sample, and an identification structure for identifying one or more biomarkers in the bodily fluid sample that can be analyzed using the electrochemical sensor structure. The testing device comprises a housing with at least one first port for receiving an electrochemical sensor structure, the electrochemical sensor structure comprising a first circuit having a first set of electrodes for contacting a bodily fluid sample; an identification circuit for identifying one or more biomarkers analyzable using the electrochemical sensor structure; an analysis circuit comprising a set of coupling electrodes for electrically coupling to the first set of electrodes of the electrochemical sensor structure for analyzing the identified one or more biomarkers in the bodily fluid sample; a control circuit coupled to the identification and analysis circuit for determining a set of biosensing parameters based on the identified one or more biomarkers and for controlling the analysis circuit to analyze the identified one or more biomarkers in the bodily fluid sample based on the set of biosensing parameters; and an output section for outputting analysis results of the analysis of the identified one or more biomarkers in the bodily fluid sample.

[0129] The present invention can be better understood with reference to the following drawings and description. The components in the drawings are not necessarily to scale, emphasis instead being placed upon illustrating the principles of the invention. Moreover, the figures indicate corresponding parts throughout the various views, as referenced. [Brief explanation of the drawings]

[0130] [Figure 1A] 1A-1C are schematic perspective and plan views, respectively, of a health monitoring system and a portable health monitoring system including a portable point-of-care (PoC) device and an electrochemical sensor structure, according to some embodiments of the present disclosure; [Figure 1B] 1A-1C are schematic perspective and plan views, respectively, of a health monitoring system and a portable health monitoring system including a portable point-of-care (PoC) device and an electrochemical sensor structure, according to some embodiments of the present disclosure; [Figure 2] 1B is a schematic plan view of an electrochemical sensor structure of the health monitoring system shown in FIG. 1A, the electrochemical sensor structure including a plurality of electrodes. [Figure 3A] 3 is a schematic diagram of the circuitry of the PoC device shown in FIG. 2 for electrically coupling to electrodes of an electrochemical sensor structure for measuring one or more biomarkers in a bodily fluid sample on the electrochemical sensor structure. [Figure 3B] 3 is a schematic diagram of the circuitry of the PoC device shown in FIG. 2 for electrically coupling to electrodes of an electrochemical sensor structure for measuring one or more biomarkers in a bodily fluid sample on the electrochemical sensor structure. [Figure 4A] FIG. 1B is a perspective view of an electrochemical sensor structure of the health monitoring system shown in FIG. 1A. [Figure 4B] 4B is a cross-sectional view of the electrochemical sensor structure shown in FIG. 4A taken along section line AA. [Figure 4C] 4B is a cross-sectional view of the electrochemical sensor structure shown in FIG. 4A taken along section line BB. [Figure 4D] 4B is a cross-sectional view of the electrochemical sensor structure shown in FIG. 4A taken along section line CC. [Figure 5A] 4B is a schematic diagram of the electrochemical sensor structure shown in FIG. 4A having a substrate and multiple electrodes including a reference electrode (RE), a control electrode (CE), and a working electrode. [Figure 5B] 4B is a schematic diagram of the electrochemical sensor structure shown in FIG. 4A, showing the substrate and the WE, which includes a nanostructured sensing surface with ZnO nanorods. [Figure 6A] 1 illustrates a process for fabrication of an electrochemical sensor structure with ZnO nanorods. [Figure 6B] 1 illustrates a process for fabrication of an electrochemical sensor structure with ZnO nanorods. [Figure 6C] 1 illustrates a process for fabrication of an electrochemical sensor structure with ZnO nanorods. [Figure 6D] 1 illustrates a process for fabrication of an electrochemical sensor structure with ZnO nanorods. [Figure 6E] 1 illustrates a process for fabrication of an electrochemical sensor structure with ZnO nanorods. [Figure 6F] 1 illustrates a process for fabrication of an electrochemical sensor structure with ZnO nanorods. [Figure 7A] 4B illustrates a process for fabricating the electrochemical sensor structure shown in FIG. 4A according to some embodiments of the present disclosure. [Figure 7B] 4B illustrates a process for fabricating the electrochemical sensor structure shown in FIG. 4A according to some embodiments of the present disclosure. [Figure 7C] 4B illustrates a process for fabricating the electrochemical sensor structure shown in FIG. 4A according to some embodiments of the present disclosure. [Figure 7D] 4B illustrates a process for fabricating the electrochemical sensor structure shown in FIG. 4A according to some embodiments of the present disclosure. [Figure 7E] 4B illustrates a process for fabricating the electrochemical sensor structure shown in FIG. 4A according to some embodiments of the present disclosure. [Figure 8] 1B is a schematic plan view of an electrochemical sensor structure of the health monitoring system shown in FIG. 1A, according to some embodiments of the present disclosure. FIG. [Figure 9A] 1 illustrates a PoC device having a radio frequency identification (RFID) reader and a transport vial having an RFID tag, according to some embodiments of the present disclosure, where the PoC device determines the type of biomarker associated with the electrochemical sensor structure in the transport vial by reading information on the RFID tag of the transport vial. [Figure 9B] 1 illustrates a PoC device having a one-dimensional barcode scanner and a transport vial having a one-dimensional barcode, according to some embodiments of the present disclosure, where the PoC device determines the type of biomarker associated with the electrochemical sensor structure in the transport vial by reading information in the one-dimensional barcode of the transport vial. [Figure 10] 1 illustrates a PoC device having a connection port for physically and electrically coupling to a smartphone, according to some embodiments of the present disclosure. [Figure 11] 11 illustrates a PoC device as shown in FIG. 10 coupled to a smartphone, using the smartphone's camera to read information on the two-dimensional barcode of the transport vial to determine the type of biomarker in the electrochemical sensor structure in the transport vial, according to some embodiments of the present disclosure. [Figure 12] 11 illustrates a PoC device as shown in FIG. 10 coupled to a smartphone, using the smartphone's camera to read information on the two-dimensional barcode of the transport vial to determine the type of biomarker in the electrochemical sensor structure in the transport vial, according to some embodiments of the present disclosure. [Figure 13] 1 illustrates a strip adapter for accommodating different types of electrochemical sensor structures manufactured according to different specifications, according to some embodiments of the present disclosure. [Figure 14] FIG. 14 is an electrical circuit diagram of the strip adapter shown in FIG. 13. [Figure 15A] 1B is a schematic plan view of a portion of an electrochemical sensor structure of the health monitoring system shown in FIG. 1A, according to some embodiments of the present disclosure. FIG. [Figure 15B]1B is a schematic plan view of a portion of the electrochemical sensor structure of the health monitoring system shown in FIG. 1A according to further embodiments of the present disclosure. [Figure 16] 1B is a schematic plan view of a portion of the electrochemical sensor structure of the health monitoring system shown in FIG. 1A according to further embodiments of the present disclosure. [Figure 17A] 1B shows a schematic diagram of an exemplary manufacturing process for screen-printing electrodes of the electrochemical sensor structure of the health monitoring system shown in FIG. 1A, according to further embodiments of the present disclosure. [Figure 17B] 1B shows a schematic diagram of an exemplary fabrication process for sputtered electrodes of the electrochemical sensor structure of the health monitoring system shown in FIG. 1A, according to further embodiments of the present disclosure. [Figure 18A] 1B illustrates the progression of a deposition process for fabricating electrodes of the electrochemical sensor structure of the health monitoring system shown in FIG. 1A, according to further embodiments of the present disclosure. [Figure 18B] 1B illustrates the progression of a deposition process for fabricating electrodes of the electrochemical sensor structure of the health monitoring system shown in FIG. 1A, according to further embodiments of the present disclosure. [Figure 18C] 1B illustrates the progression of a deposition process for fabricating electrodes of the electrochemical sensor structure of the health monitoring system shown in FIG. 1A, according to further embodiments of the present disclosure. [Figure 18D] 1B illustrates the progression of a deposition process for fabricating electrodes of the electrochemical sensor structure of the health monitoring system shown in FIG. 1A, according to further embodiments of the present disclosure. [Figure 18E] 1B illustrates the progression of a deposition process for fabricating electrodes of the electrochemical sensor structure of the health monitoring system shown in FIG. 1A, according to further embodiments of the present disclosure. [Figure 18F] 1 is a graph showing measurements of strip quality, including the quality of deposited or immobilized biosensors, organic chemicals, biolinkers, and nanorods. [Figure 19]FIG. 1B is a top view of an electrochemical sensor structure of the health monitoring system shown in FIG. 1A according to further embodiments of the present disclosure, the electrochemical sensor structure comprising an introduction channel followed by a heterophilic plasma separation component (HF-PSC) unit adjacent to the electrode. [Figure 20] 19A and 19B are schematic diagrams of the electrochemical sensor structure shown in FIG. 19, illustrating the fluid sample passing through the inlet channel and HF-PSC unit and into the analyte drop chamber for contacting the electrodes. [Figure 21] A working schema for quantifying analytes from body fluids is shown for an electrode assembly of a two to six working electrode system. [Figure 22] FIG. 1B is a block diagram illustrating the modular structure of the PoC device of the health monitoring system shown in FIG. 1A for body fluid analysis. [Figure 23] 1B is a block diagram illustrating a modular structure of a PoC device of the health monitoring system shown in FIG. 1A for body fluid analysis, according to some embodiments of the present disclosure. FIG. [Figure 24A] 1B illustrates a hybrid design of the electrochemical sensor structure of the health monitoring system shown in FIG. 1A with flow stability and volume control of the fluid sample received within its sampling region, according to some embodiments of the present disclosure. [Figure 24B] 1B illustrates a hybrid design of the electrochemical sensor structure of the health monitoring system shown in FIG. 1A with flow stability and volume control of the fluid sample received within its sampling region, according to some embodiments of the present disclosure. [Figure 25A] 1B illustrates an electrochemical sensor structure of the health monitoring system shown in FIG. 1A with control of the stability and volume of the fluid sample flow received within its sampling region, according to further embodiments of the present disclosure. [Figure 25B] 1B illustrates an electrochemical sensor structure of the health monitoring system shown in FIG. 1A with control of the stability and volume of the fluid sample flow received within its sampling region, according to further embodiments of the present disclosure. [Figure 25C]1B illustrates an electrochemical sensor structure of the health monitoring system shown in FIG. 1A with control of the stability and volume of the fluid sample flow received within its sampling region, according to further embodiments of the present disclosure. [Figure 26] 1B is a flowchart illustrating a process performed by a PoC device of the health monitoring system shown in FIG. 1A for body fluid analysis, according to some embodiments of the present disclosure. [Figure 27] 1B is a flowchart illustrating a process performed by a PoC device of the health monitoring system shown in FIG. 1A for analyzing body fluids, according to further embodiments of the present disclosure. [Figure 28] 10 is a flowchart illustrating a process for analyzing body fluids according to further embodiments of the present disclosure. [Figure 29A] 1A and 1B are schematic and plan views, respectively, of a health monitoring system according to some embodiments of the present disclosure; [Figure 29B] 1A and 1B are schematic and plan views, respectively, of a health monitoring system according to some embodiments of the present disclosure; DETAILED DESCRIPTION OF THE INVENTION

[0131] overview Embodiments disclosed herein generally relate to portable electrochemical sensor systems for monitoring a user's health. More specifically, some embodiments disclosed herein relate to on-demand, portable, reliable, intuitive, and low-cost biosensing devices, such as point-of-care (PoC) devices for at-home testing for disease diagnosis and prognosis. In some embodiments, the portable electrochemical sensor system includes a diagnostic biosensing device and a sampling structure, such as a disposable electrochemical sensor structure, for monitoring a patient's health by detecting various analytes, such as proteins and other molecules, in a sample of the patient's bodily fluid received in the electrochemical sensor structure. The presence, absence, or variations in the amount of specific analytes in the bodily fluid may be used as an indicator or predictor of disease.

[0132] In some embodiments, the electrochemical sensor structure includes a sample receiving area for receiving a sample of a patient's bodily fluid. The sample receiving area of ​​the electrochemical sensor structure may include a substrate including a plurality of electrodes and having one or more sensing elements thereon suitable for detecting one or more analytes.

[0133] In some embodiments, the substrate may be made of a flexible polymeric material, such as a flexible modified / unmodified (treated or untreated) acrylic or polymeric membrane strip with one or more detection elements thereon for detecting one or more analytes.

[0134] In some embodiments, the PoC device may include one or more potentiostat circuits for monitoring the electrochemical reaction between the analyte in the bodily fluid sample and the sensing element.

[0135] The potentiostat circuit may comprise a DC potentiostat circuit, the use of which may be limited to chronoamperometry and voltammetry, and when used in conjunction with a frequency response analyzer may be used as an impedance analysis system.

[0136] In particular, the components of the system disclosed herein may be used to stimulate a sample with AC, DC, or a combination thereof. In some embodiments, the signal may comprise an AC amplitude with a specific frequency offset from the DC signal. Test signals may also be generated in different combinations. For example, one embodiment may simply use a DC signal for sample testing to pass a current in either direction, thereby enabling substrate characterization, recognition, or analysis. More specifically, the system uses a range of frequencies to measure criteria related to, but not limited to, the quality of the substrate, the conductance of the electrodes, the quality of the biosensor immobilized on the electrode, and the binding efficiency of the analyte to the biosensor.

[0137] In some embodiments, diagnostics of electrochemical impedance spectroscopy (EIS) systems may be performed through domain recognition aided by the resulting Nyquist plot analysis. For example, by relying on Nyquist plot pre-characterization of the capture ligands on the strip, newly scanned data may be used in comparison to gauge the quality of the immobilization layer after a period of storage or before use.

[0138] In these embodiments, the PoC device may include three electrodes used by a DC potentiostat circuit coupled to a frequency response analyzer. For example, the system may include four stages: current-to-voltage conversion by a multiplexer, an amplifier to accommodate additional electrodes in the system, a gain stage, and a final frequency response analyzer integrated circuit (IC). In design variations, the multiplexer may be used to switch the system between a calibration mode and one or more multi-electrode modes (e.g., a three-electrode mode, a four-electrode mode, ..., and an eight-electrode mode).

[0139] When a bodily fluid sample is placed in the sample region of the electrochemical sensor structure, an electrochemical interaction between the analyte in the bodily fluid sample and the sensing element occurs, causing an energy change. The electrochemical sensor structure is interfaced with an ex vivo PoC device that imparts energy to the sample fluid and measures the energy characteristics of the sample to generate a sample fluid reading indicative of the concentration of a particular compound in the sample fluid. The sample volume may be as small as about 10 microliters (μL) to about 20 μL. The applied energy may be electrical energy, and the measured energy characteristic may be a potential difference, a current, or an impedance.

[0140] Because analytes often have an affinity and specificity for a particular sensing element, electrochemical sensor structures generally must be specially fabricated to detect a particular type of analyte.

[0141] Antibodies, nucleic acid aptamers, and enzymes are often used as sensing elements in biosensing devices due to their high specificity and affinity for their respective biomarkers. Given the high specificity of sensing elements for specific analytes, the sampling region of the device may contain only one type of sensing element and may be used to detect a single analyte. Furthermore, different analytes have different energy characteristics. Therefore, a PoC device needs to be calibrated for a specific analyte to measure its energy characteristics. Therefore, in some embodiments, a PoC device for measuring multiple analytes may include a calibration feature to adjust its settings to accommodate each of the multiple analytes.

[0142] In some embodiments, one or more potentiostat circuits may be calibrated by using diluted human plasma / serum / blood / fluid samples with known concentrations of target disease analytes (such as, but not limited to, N-terminal pro-B-type natriuretic peptide (NT-pro-BNP), troponin, ck-mb, D-dimer, creatinine, electrolytes, etc.) obtained anonymously from a suitable source such as a medical laboratory. The potentiostat circuits of the PoC device may then be calibrated using samples of various analyte concentrations.

[0143] In some embodiments, the PoC device uses an electrochemical sensor structure or an identification element on its carrier vial to determine the biomarker being analyzed. The identification element may include a detection electrode, a radio frequency identification (RFID) tag, a one-dimensional barcode, a two-dimensional barcode such as a quick response (QR) code, etc.

[0144] In some embodiments, a portable electrochemical sensor system may be configured to monitor heart failure (HF) by detecting and quantifying HF-related analytes, such as NT-proBNP, cardiac troponin (cTn), etc., from small volumes of bodily fluid samples, such as blood samples obtained by simple sampling processes, such as fingerstick collection.

[0145] cTn is a sensitive and specific biomarker of myocardial injury. cTn guides the triage and management of patients with symptoms suggestive of acute coronary syndrome. Meanwhile, B-type natriuretic peptide (BNP) levels are also elevated in acute myocardial infarction and are a quantitative biochemical marker associated with the extent of infarction and left ventricular systolic dysfunction. Therefore, BNP has prognostic value. The most potent inducer of BNP gene transcription is left ventricular (LV) wall stretch due to increased pressure or volume. The hormone precursor (proBNP) is cleaved into BNP and NT-proBNP, providing serologic evidence of BNP, NT-proBNP, and proBNP. While conventional BNP assays detect proBNP and BNP, as well as various degradation fragments of BNP, NT-proBNP assays detect NT-proBNP and proBNP. Although BNP and NT-pro-BNP are passively cleared by many organs, including the kidneys, the half-life of BNP is significantly shorter than that of NT-pro-BNP (e.g., approximately 20 min vs. 60–120 min). Therefore, NT-pro-BNP is considered a very promising candidate biomarker for home or ambulatory heart failure prognosis applications.

[0146] Detection of analyte binding signals can be based on electrochemical, optical (chemiluminescence, reflectance, etc.), or magnetic transduction signals. Such electrochemical detection methods rely on either voltage or current to detect analyte binding and are suitable for implementation in miniaturized electrical biosensor devices. These methods monitor the change in electrical impedance that occurs when the analyte binds to the capture ligand, which is then correlated with the concentration of the target analyte.

[0147] The main challenge in the electrochemical detection and quantification of HF biomarkers (e.g., NT-pro-BNP, cTn, etc.) is their low blood concentrations and therefore the amplification of biomolecular binding events (cutoff value: <0.125 nanograms per milliliter (ng / mL) = exclusion of non-acute heart failure).

[0148] Improved sensitivity (e.g., less than 1 ng / mL) may be achieved using methods that utilize nanostructured sensing surfaces to amplify biomolecule binding signals. The sensing surfaces have nanoscale dimensions that are matched in size to target troponin molecules with increased surface area-to-volume ratios and structural morphologies to provide selective functionalization sites for analytes that bind with corresponding capture ligands.

[0149] Description of Various Embodiments 1A and 1B, an electrochemical sensor system for monitoring a user's health condition is shown and generally identified using the reference numeral 100. The portable electrochemical sensor system 100 includes a diagnostic device 102 and a sampling structure 104, such as a disposable electrochemical sensor structure.

[0150] In these embodiments, the diagnostic apparatus 102 may be a portable PoC device such as a Philos™ PoC device (Philos is a trademark of CardiAI Technologies Ltd. of Calgary, Alberta, Canada) and may have a size suitable for personal use (e.g., 5 centimeters (cm) by 7.5 cm by 2 cm in one embodiment). The PoC device 102 in these embodiments includes a screen 106, a user input structure for receiving user input, a strip receiving port 110 for accepting the electrochemical sensor structure 104, and a control structure (not shown) such as an RFduino microcontroller offered by RFduino Inc. of Hermosa Beach, California, USA, and associated circuitry. The PoC device 102 also includes a power source such as a battery for powering the various components.

[0151] The user input structure may include one or more buttons 108 and / or a touch-sensitive screen (such as the touch-sensitive screen 106 in some embodiments) for receiving user input such as user commands (e.g., turning the PoC device 102 on or off, starting a diagnostic process, displaying readings taken in a diagnostic process, displaying previous diagnostic readings, etc.) and / or user data (e.g., the user's age, gender, weight, height, etc.).

[0152] The circuitry may include analytical circuitry, such as potentiostat circuitry for biosensing (described in more detail below), as well as monitoring circuitry for other tasks, such as executing user-commanded operations, detecting insertion of the electrochemical sensor structure 104, reading and displaying measured levels of biomarkers, storing the measured data, transmitting the measured data to a remote device for trend tracking, etc. The potentiostat circuitry may be designed to correspond to the circuitry of the electrochemical sensor structure 104.

[0153] As shown in Figure 2, the electrochemical sensor structure 104 may comprise multiple electrodes 124-132 dispersed on a biocompatible substrate 122 that allows fluid to flow thereover. Parameters related to the effective conductance and / or impedance of the substrate can be used to reveal or derive characteristic information about a single entity or the interaction between two or more entities. The entities may include, but are not limited to, a monolayer, a stack of monolayers, a protein, an oligonucleotide, an enzyme, or any combination thereof.

[0154] In particular, the electrochemical sensor structure 104 of this embodiment includes a reference electrode (RE) 124, a control electrode (CE) 126, and a working electrode (WE) 128, all of which extend into its sampling region 134 for measuring the energetic characteristics of a bodily fluid sample (not shown) received therein. The surfaces of the electrodes may be modified or otherwise treated with a mediator to mediate electron transfer from the electrodes to the bodily fluid.

[0155] The electrochemical sensor structure 104 also includes a pair of identification electrodes 130 and 132 coupled by traces having a predetermined resistance or a predetermined impedance to indicate the type of biomarker that the electrochemical sensor structure 104 is suitable for detecting. The electrodes 124-132 may be made of or include a conductive or semiconductive metal, such as gold (Au), chromium (Cr), titanium, platinum, silver, or the like.

[0156] With such an electrochemical sensor structure 104 , the analysis circuitry correspondingly includes a set of mating electrodes within the strip receiving port 110 for electrically engaging the electrodes 124 - 132 of the electrochemical sensor structure 104 .

[0157] As shown in FIGS. 3A and 3B, the PoC device 102 includes a plurality of circuits 142 and 144 for electrically engaging the electrodes 124-132 when the electrochemical sensor structure 104 is inserted into the strip receiving port 110.

[0158] 3A, a first circuit 142 in the form of a voltage divider is used to determine the type of biomarker. As noted above, the identification electrodes 130 and 132 have a predetermined resistance between them, represented by resistor R1. The resistance of R1 is predefined and indicates the type of biomarker that the electrochemical sensor structure 104 is suitable for detecting. A second circuit 144 is electrically engaged with the identification electrodes 130 and 132 and couples a voltage V REG (e.g., 3.3 V) is applied to the voltage signal V Detect is output from between R1 and R2. Therefore, V Detect =V REG R1 / (R1+R2), and the resistance of R1 and then the type of biomarker, V Detect V REG may be obtained by comparing with

[0159] 3B, a second circuit 144 in the form of a direct current (DC) potentiostat circuit is used to control the voltage between WE 128 and RE 124. Herein, the body fluid sample on the electrochemical sensor structure 104 serves as an electrolyte between WE 128 (which serves as the cathode), RE 124 (which serves as the anode), and CE 126. Due to the nature of operational amplifier 148, RE 124 and U dの Current is supplied through CE126 until the voltages are equal. d Determine the voltage of the electrolyte and determine if the voltage is too low. d too low U may not be able to produce sufficient measurement resolution d may trigger an inferential response or surface property change, thus determining the accuracy of biomarker measurements.

[0160] Thus, in circuit 144, the three-electrode configuration is connected to a DC potentiostat circuit in which a constant DC voltage is regulated and applied to the WE 128 and RE 124 of the electrochemical sensor structure 104. Circuit 144 may be used to determine the energetic characteristics of a sample fluid for analysis of the sample fluid by detecting and determining impedance measurements. Those skilled in the art will appreciate that circuit 144 can also be used for amperometric-type measurements commonly used in glucose detection. Furthermore, potentiometric-type measurements may also be implemented using the three-electrode configuration. In this configuration, an alternating current (AC) wave of a predetermined frequency is applied to stimulate a bodily fluid sample while measuring the forward (e.g., increasing voltage) and reverse (e.g., increasing voltage) currents to generate a differential current (forward-reverse).

[0161] As shown in FIG. 3B, a control structure 152 (e.g., a microcontroller) controls V Detect V REG Then, the microcontroller 152 compares the biosensing parameters (U d, etc.) to suit the determined type of biomarker, and measure the voltage of the WE 128. In this embodiment, an amplifier circuit 154 including an amplifier 156, a resistor R3, and a capacitor C is used to amplify the signal of the WE 128. In this manner, the energy characteristics of the biomarkers in the bodily fluid sample on the electrochemical sensor structure 104 are measured and used to determine the health status of the patient.

[0162] U d While the voltage of the electrolyte determines the accuracy of the biomarker measurements, the physical and electrochemical structure of the electrochemical sensor structure 104 also determines the accuracy of the biomarker measurements. Additionally, the physical and electrochemical structure of the electrochemical sensor structure 104 also determines other necessary features such as dust resistance, electrode robustness, ease of use, and manufacturing cost.

[0163] 4A-4D illustrate the physical and electrochemical structure of some embodiments of an electrochemical sensor structure 104. As shown, the electrochemical sensor structure 104 comprises a substrate 122 having electrodes 124-132 deposited, printed, or otherwise coupled to the same side thereof. As one skilled in the art will appreciate, providing all of the electrodes 124-132 on the same side of the electrochemical sensor structure 104 facilitates miniaturization of the electrochemical sensor structure 104, thereby providing for elegant connector designs, ease of user handling, and ease of sampling of bodily fluids.

[0164] The identification electrodes 130 and 132 are located around the proximal end 172 of the electrochemical sensor structure 104 (the end for insertion into the strip-receiving port 110 of the PoC device 102) and are electrically connected by a predetermined resistance R1. The electrodes RE124, CE126, and WE128 extend from the proximal end 172 of the electrochemical sensor structure 104 to its distal end 174. As shown in FIG. 4B , the distal electrodes RE124′, CE126′, and WE128′ (corresponding to and connected to RE124, CE126, and WE128, respectively) are laterally spaced apart the same distance. The electrode RE124′ has a much larger surface than the surfaces of the electrodes CE126′ or WE128′. For example, in some embodiments, the surface area ratio of WE128′, CE126′, and RE124′ may be approximately 1:1:4.

[0165] The electrochemical sensor structure 104 in these embodiments also includes a hydrophobic intermediate layer 176 that covers a distal portion of the electrochemical sensor structure 104 (also identified using reference numeral 174), except for the sampling region 134 around the distal electrodes RE 124', CE 126', and WE 128'. The hydrophobic intermediate layer 176 has a distal end opening 178 that forms a rearward-facing sampling port (also identified using reference numeral 178) for receiving a bodily fluid sample into the sampling region 134 and contacting the distal electrodes RE 124', CE 126', and WE 128'. The electrochemical sensor structure 104 further includes a protective layer 180 on top of the hydrophobic intermediate layer 176, covering the distal portion 174 (including the sampling region 134). In these embodiments, the protective layer 180 is made of a suitable material, such as glass or plastic.

[0166] In some embodiments, the substrate 122 may be made of a flexible polymer material, such as a flexible polyimide film strip having one or more sensing elements thereon for detecting one or more biomarkers. In some embodiments, the flexible substrate 122 may be made of a modified or unmodified polymer substrate, including, but not limited to, a track-etched film, a treated or untreated acrylic substrate, etc. In some embodiments, the track-etched film 122 may be a porous polyimide film.

[0167] In some embodiments, the track-etched membrane 122 may have a porosity of 30% or greater. As used herein, the porosity of a material is defined as the ratio of the volume of voids or empty spaces to the total volume of the material. In some embodiments, the track-etched membrane 122 may have a porosity of 50% or greater.

[0168] In some embodiments, the pore size, shape, and density of the track-etched membrane can be varied in a controllable manner, resulting in the fabrication of membranes with selected transport and retention properties. Because of the precisely determined structure of track-etched membranes, using track-etched membranes as substrates 122 can offer distinct advantages over conventional membranes. For example, in some embodiments, the pore size, shape, and density of the track-etched membrane 122 can be varied in a controllable manner, resulting in the fabrication of membranes with selected transport and retention properties. A membrane 122 with a higher pore density allows for a rougher surface to bond to the metal layer, which in turn allows for increased capacity to accommodate a larger amount of three-dimensional (3D) nanorods (described below) that are subsequently grown on the membrane surface. More nanorods correspond to more available binding sites for antibody molecules, which in turn increases the overall sensitivity of the electrochemical sensor structure 104. Furthermore, a membrane 122 with a higher pore density also facilitates the flow of a bodily fluid sample thereover.

[0169] 5A is a schematic diagram of electrochemical sensor structure 104 showing substrate 122 and electrodes RE 124', CE 126', and WE 128'. FIG. 5B is a schematic diagram of electrochemical sensor structure 104 showing substrate 122 and electrode WE 128'. As shown, electrochemical sensor structure 104 comprises a nanostructured sensing surface at its sampling region 134 to amplify the amount of biomarker that binds to electrochemical sensor structure 104 to achieve improved sensitivity.

[0170] More specifically, distal electrode WE 128′ comprises a nanostructured sensing surface 182 having a plurality of nanorods 184, such as zinc oxide (ZnO) nanorods. In some embodiments, ZnO nanorods can be synthesized by depositing ZnO onto distal electrode WE 128′ on a substrate (acting as a seed), and then immersing the substrate containing the coated electrode in a chemical bath consisting of zinc nitrate hexahydrate and hexamethylenetetramine at a temperature below the boiling point of water, preferably about 80° C. to “grow” the ZnO nanorods.

[0171] The nanorods 184 are coated with a particular type of sensing element 188, such as one or more immobilized capture ligands, such as antibodies, enzymes, nucleic acid aptamers, etc., to detect a particular biomarker 190 for which the sensing element 188 has high specificity and affinity. The nanorods 184 are also coated with bridging molecules 186 that immobilize the sensing element molecules 188 on the nanorods 184 for capturing and reacting with the corresponding biomarkers 190.

[0172] 6A-6F illustrate a process for fabricating an electrochemical sensor structure 104 with ZnO nanorods in these embodiments.

[0173] As shown in FIG. 6A, a track-etched porous polyimide film with a thickness of about 25 μm is provided as a substrate 122 .

[0174] 6B, a patterned stencil mask with 50 millimeter (mm) diameter exposures is applied to substrate 122 at the locations of electrodes RE 124, CE 126, and WE 128. Sputter coating or electron beam coating is then used to deposit 25 nanometers (nm) of Cr and 125 nm of Au at the electrode locations to form electrodes RE 124, CE 126, and WE 128.

[0175] 6C, a secondary stencil mask having a 50 mm diameter exposure at the location of electrode WE 128 is applied to substrate 122, and a ZnO seed layer 192 is selectively deposited on electrode WE 128 in a conventional RF magnetron sputtering process using 99.99% pure ZnO in an argon (Ar) plasma at 12 standard cubic centimeters per minute (sccm) at 50 watts (W) power without oxygen. Deposition is then carried out for approximately 30 minutes at a base pressure of 15 milliTorr (mTorr).

[0176] The thickness of the deposited ZnO seed layer is about 30±5 nm, which may be verified using a suitable profilometer such as a Dektak 8 profilometer provided by Veeco Instruments Inc., Plainview, NY, USA.

[0177] 6D, ZnO nanorods are then synthesized on the electrode WE 128 using a suitable hydrothermal method, for example, by immersing the electrode-formed substrate 112 in a chemical bath consisting of 50 millimolar (mM) equimolar zinc nitrate hexahydrate (Zn(NO3)2) and chamber (HMTA) for 30 minutes for nucleation at a temperature of approximately 80°C and 300 revolutions per minute (rpm) to "grow" ZnO nanorods 184. The processed substrate 112 is then rinsed with deionized water and air-dried.

[0178] As shown in Figures 6E and 6F, protein immobilization to electrode WE128 is performed by first using 10 mM dithiobis(succinimidyl propionate) (i.e., DSP) 196 in dimethyl sulfoxide (i.e., DMSO) for 2 hours, followed by 1 microgram per milliliter (µg / mL) anti-NT-pro-BNP antibody 198 in phosphate-buffered saline (PBS) for 15 minutes. Unbound DSP is blocked with a suitable protein blocking buffer, such as Thermo Scientific SuperBlock™ Blocking Buffer (SuperBlock is a trademark of Thermo Fisher Scientific Inc., Waltham, Massachusetts, USA).

[0179] Next, an electrochemical sensor structure 104 with ZnO nanorods is fabricated.

[0180] In some embodiments, metal oxide nanostructures may be synthesized by depositing metal oxides onto one or more WE electrodes via an electrochemical process.

[0181] 7A-7E illustrate processes for fabricating an electrochemical sensor structure 104 according to some alternative embodiments of the present disclosure. In these embodiments, ZnO nanorods are not used. Instead, highly conductive nanomaterials 206, such as carbon nanotubes, nano-sized gold particles, etc., are applied to the distal electrode WE 128′ to form a biosensor with increased surface area and therefore improved sensitivity.

[0182] 7A, a substrate 122 is first prepared. In this example, the substrate is made of or includes poly(methyl methacrylate) (i.e., PMMA) and track-etched polyamide, polyester, and / or polycarbonate.

[0183] PMMA is a transparent thermoplastic. Compared to other materials, such as polycarbonate, PMMA has high transmittance, high ultraviolet (UV) resistance (thus not yellowing over time), and high stiffness (thus making it more scratch-resistant). PMMA is well-suited for smooth laser cutting without yellowing or burning during laser cutting, and can be remolded and recycled without degradation. In comparison, polycarbonate can easily yellow and burn during laser cutting. PMMA is also easy to polish (e.g., to create smooth edges to prevent injury). Additionally, PMMA is cost-effective compared to other materials, such as polycarbonate.

[0184] As shown in FIG. 7B , electrodes WE128 / 128′, CE126 / 126′, and RE124 / 124′ are formed on substrate 122 by depositing a layer of Cr202 on substrate 122 and a layer of Au204 on Cr layer 202 using a suitable deposition method such as chemical vapor deposition (CVD), plasma vapor deposition (PVD), sputter coating, or electron beam, applying a first mask to substrate 122 to only expose the locations of the electrodes.

[0185] Although not shown, other electrodes such as identification electrodes 130 and 132 may also be formed in this step.

[0186] After deposition of the electrodes, scanning electron microscopy (SEM) and / or atomic force microscopy (AFM) can be used to characterize the deposited electrodes.

[0187] 7C, WE128 / 128' is functionalized by applying a layer of conductive nanomaterial 206 onto the Au layer 204 to form a biosensor with increased surface area and therefore improved sensitivity. For this step, a suitable deposition method such as CVD, PVD, sputter coating, e-beam, etc. may be used with a second mask applied to the electrode deposition substrate 122 that exposes only the distal electrode WE128'.

[0188] Characterization of the nanomaterial layer 206 may be performed by using an SEM, an energy dispersive X-ray analyzer (EDX), a transmission electron microscope (TEM), an AFM, or the like.

[0189] 7D, immunoglobulins or antibodies 208 are immobilized on the nanomaterial layer 206 of the WE128' forming the layer of the sensing element, and optimization of the antibody concentration and interaction time between the antibody and the antigen is performed. Characterization may then be performed using SEM and / or AFM.

[0190] As shown in FIG. 7E, a suitable biological material or blocking agent 212 is coated onto the antibody 208.

[0191] A hydrophobic intermediate layer 176 is then applied around the electrodes 124', 126', and 128' to form the sampling region 134. Fabrication of the electrochemical sensor structure 104 is complete after a protective layer 180 is bonded to the hydrophobic intermediate layer 176.

[0192] In these embodiments, the substrate 112 is made of a non-porous PMMA membrane, but the highly conductive nanocomposite deposited thereon provides ample available binding sites for antibody molecules compared to track-etched porous membranes.

[0193] Those skilled in the art will appreciate that other suitable materials, such as polyethylene terephthalate (PET), may be used to fabricate the substrate 112 in other embodiments.

[0194] In the above embodiment, the electrochemical sensor structure 104 includes identification electrodes 130 and 132 for indicating the type of biomarker associated therewith. When the electrochemical sensor structure 104 is inserted or otherwise coupled to the PoC device 102, the PoC device 102 checks the type of biomarker associated with the inserted electrochemical sensor structure 104. If the PoC device 102 determines that the electrochemical sensor structure 104 is incompatible with it, the PoC device 102 may present an alarm or warning (e.g., a beep and / or a warning on the screen 106).

[0195] 8, the electrochemical sensor structure 104 does not include an identification electrode. In the example shown in FIG. 8, the electrochemical sensor structure 104 includes only three electrodes RE 124, CE 126, and WE 128. In these embodiments, the portable electrochemical sensor system 100 may use other suitable methods for determining the type of biomarker that the electrochemical sensor structure 104 is suitable for detecting, as described below.

[0196] 9A, the PoC device 102 includes an RFID tag antenna 222 and an RFID reader 224 integrated into the back of the device. Similarly, the transport vial 226 (also referred to as a strip vial) containing the electrochemical sensor structure 104 includes an RFID tag antenna 228 and an RFID chip 230 that stores information about the type of biomarker associated with the electrochemical sensor structure 104 within the strip vial 226. The PoC device 102 may use the RFID reader 224 to read the information in the RFID chip 230 of the strip vial 226 to determine the type of biomarker that the electrochemical sensor structure 104 is capable of detecting.

[0197] Before each time the patient starts a new test, the PoC device 102 may ask the patient to place the transport vial 226 near the PoC device 102 to obtain identification information of the electrochemical sensor structure 104. Based on the information received by the RFID reader in the PoC device 102, the PoC device 102 determines whether the electrochemical sensor structure 104 is compatible with it (i.e., whether the PoC device 102 and the electrochemical sensor structure 104 are compatible to detect the same biomarkers). If the PoC device 102 determines that the electrochemical sensor structure 104 in the strip vial 226 is incompatible, the PoC device 102 may present an alarm or warning (e.g., a beep and / or a warning on the screen 106).

[0198] In some embodiments, instead of presenting an alarm or warning, the PoC device 102 may adjust the electrical parameters of the potentiostat circuit based on information detected from the strip vial 226 to suit the type of electrochemical sensor structure 104 contained in the strip vial 226 for accurate biomarker detection.

[0199] In another embodiment, each electrochemical sensor structure 104 may include an RFID chip that stores information about the type of biomarker associated with it. If the PoC device 102 determines that the electrochemical sensor structure 104 is incompatible, the PoC device 102 may present an alarm or warning (e.g., a beep and / or a warning on the screen 106). Alternatively, the PoC device 102 may adjust the electrical parameters of its potentiostat circuitry based on the information detected from the electrochemical sensor structure 104 to accommodate it for accurate biomarker detection.

[0200] 9B, the PoC device 102 includes an imaging component 232, such as a one-dimensional barcode scanner, for scanning one-dimensional barcodes. Similarly, the strip vial 226 includes a one-dimensional barcode 234 that stores, encodes, or otherwise indicates the identity or type of biomarker associated with, and capable of being analyzed by, the electrochemical sensor structure 104 within the strip vial 226.

[0201] The PoC device 102 may use a barcode scanner 232 to read the one-dimensional barcode 234 on the strip vial 226 to determine the type of biomarker that can be analyzed by using the electrochemical sensor structure 104. If the PoC device 102 determines that the electrochemical sensor structure 104 in the strip vial 226 is incompatible, the PoC device 102 may present an alarm or warning (e.g., a beep and / or warning on the screen 106) or adjust the electrical parameters of the potentiostat circuitry described above.

[0202] In another embodiment, each electrochemical sensor structure 104 may include a one-dimensional barcode (e.g., on its "bottom" side opposite the sampling area 134) that indicates the type of biomarker associated with it.

[0203] In one embodiment, the PoC device 102 includes a scanner or imaging component for scanning two-dimensional barcodes, such as matrix barcodes or QR codes. Similarly, the strip vial 226 includes a QR code indicating the type of biomarker associated with the electrochemical sensor structure 104 in the strip vial 226. The PoC device 102 may use the QR code scanner to read the QR code on the strip vial 226 to determine the type of biomarker the electrochemical sensor structure 104 is capable of detecting. If the PoC device 102 determines that the electrochemical sensor structure 104 in the strip vial 226 is incompatible, the PoC device 102 may issue an alarm or warning (e.g., a beep and / or a warning on the screen 106) or adjust electrical parameters of the potentiostat circuitry described above.

[0204] In another embodiment, each electrochemical sensor structure 104 may include a QR code (eg, on its back) that indicates the type of biomarker associated with it.

[0205] In some embodiments, the PoC device may have an infrared scanner that can be used to recognize the type of electrochemical sensor structure 104 inserted into its strip receiving port 110 and read a one-dimensional barcode or QR code located on a transport vial in which the electrochemical sensor structure 104 is stored.

[0206] 1A and 1B. However, the PoC device 102 in this embodiment does not include a screen. Instead, the PoC device 102 includes a connection port 242, such as a Universal Serial Bus (USB) port (e.g., a micro USB port or a USB Type-C port), for physically and electrically coupling to a host computing device, such as a smartphone, tablet, laptop computer, or desktop computer. The host computing device may execute a corresponding application program to control and cooperate with the PoC device 102 to perform tasks.

[0207] 11, the strip vial 226 includes a QR code 244 that indicates the type of biomarker associated with the electrochemical sensor structure 104 in the strip vial 226. The PoC device 102 is coupled to a smartphone 246 and uses a camera 248 of the smartphone 246 to read the QR code 244 on the strip vial 226 and determine the type of biomarker that the electrochemical sensor structure 104 is capable of detecting.

[0208] 12, the strip vial 226 includes a one-dimensional barcode 234 that indicates the type of biomarker associated with the electrochemical sensor structure 104 in the strip vial 226. The PoC device 102 is coupled to a smartphone 246 and uses a camera 248 of the smartphone 246 to read the one-dimensional barcode 234 on the strip vial 226 to determine the type of biomarker that the electrochemical sensor structure 104 is capable of detecting.

[0209] In some embodiments, the PoC device 102 may include only the potentiostat circuitry and / or the detection circuitry and may be operatively coupled to a computing device such as a smartphone. In these embodiments, the PoC device 102 may utilize the smartphone's processor, screen, inputs (e.g., touchscreen, physical buttons, virtual buttons, etc.), and camera for the computational power necessary to display information to the user and, if necessary, to scan external inputs such as QR codes or one-dimensional barcodes.

[0210] In some embodiments, the portable electrochemical sensor system 100 includes a strip adapter 252, as shown in FIG. 13. The strip adapter 252 includes a strip insert 254 with physical and electrical specifications suitable for insertion into the strip receiving port 110 of the PoC device 102. The strip insert 254 is electrically connected via electrical wiring 258 to multiple strip receivers 256, such as strip receivers 256A and 256B shown in FIG. 13. Each strip receiver 256A, 256B is configured to receive a corresponding type of electrochemical sensor structure 104A, 104B. In these embodiments, the different types of electrochemical sensor structures 104A, 104B may have different dimensions and may include different electrode configurations.

[0211] 14, electrochemical sensor structure 104A includes three electrodes RE124, CE126, and WE128 on all of its "top" sides, from its first side 262 to its second side 264. However, electrochemical sensor structure 104B includes three electrodes WE128, RE124, and CE126 on its first side 262 to its second side 264, with electrodes WE128 and CE126 on the "top" sides and electrode RE124 on the "bottom" side opposite the "top" side (represented using dashed lines).

[0212] Thus, as shown in FIG. 14, strip receiver 256A has three electrical terminals 124", 126", and 128" on its corresponding "top" side arranged in the same order as electrodes 124, 126, and 128 of electrochemical sensor structure 104A for proper engagement with its electrodes WE128, RE124, and CE126.

[0213] Strip receiver 256A has three electrical terminals 124", 126", and 128" arranged in the same order as electrodes 124, 126, and 128 of electrochemical sensor structure 104B, with electrical terminals 126" and 128" on the corresponding "top" side and electrical terminal 124" on the corresponding "bottom" side for proper engagement with its electrodes WE128, RE124, and CE126.

[0214] Thus, the strip adapter 252 allows the PoC device 102 to accommodate different types of electrochemical sensor structures 104 manufactured according to different specifications, such as electrochemical sensor structures 104 manufactured by different manufacturers.

[0215] In some embodiments, the strip adapter 252 does not include a strip insert 254. Rather, the strip adapter 252 includes a wireless communication module for wirelessly coupling to the PoC device 102 for transferring test data to the PoC device 102.

[0216] While in the above embodiment, the PoC device 102 includes only one strip-receiving port 110, in some alternative embodiments, the PoC device 102 may include multiple strip-receiving ports 110. The multiple strip-receiving ports 110 may have the same physical and electrical specifications. Alternatively, at least some of the multiple strip-receiving ports 110 may have different physical and electrical specifications for receiving different electrochemical sensor structures 104, in a manner similar to that described above.

[0217] In the above embodiment, the surface area ratio of WE128', CE126', and RE124' may be approximately 1:1:4, however, in some alternative embodiments, the surface area ratio of WE128', CE126', and RE124' may be determined based on the type of biomarker or antibody used on the electrochemical sensor structure 104 or by the analyte being targeted.

[0218] In some alternative embodiments, the surface area ratio of the WE 128', CE 126', and RE 124' may be determined based on the amount of sensing element applied to the nanostructured sensing surface of the electrochemical sensor structure.

[0219] In some alternative embodiments, the ratio between the surface area of ​​electrodes WE128', CE126', and RE124' and the surface area of ​​sample region 134 may be determined based on the electrochemical properties of the sensing element or biomarker for which electrochemical sensor structure 104 is specific.

[0220] In some embodiments, the ratio between the cross-sectional area of ​​the sampling port 178 and its height may be determined based on the electrochemical properties of the sensing element or biomarker for which the electrochemical sensor structure 104 is specific.

[0221] In some embodiments, the sensing element and geometric parameters of the electrochemical sensing structure are determined for detecting NT-pro-BNP.

[0222] In some embodiments, the nanostructured sensing surface may be coated with a detection element that has high affinity and specificity for binding of the analyte.

[0223] In some embodiments, the nanostructured sensing surface may be coated with a detection element that has high affinity and specificity for binding to NT-pro-BNP.

[0224] In some embodiments, the electrochemical sensor system 100 may be used to analyze a sample fluid, which may be any fluid having a detectable biomarker.

[0225] In some embodiments, one or more portable PoC devices 102 may be used in a health monitoring computer network system, such as a computer network system having an artificial intelligence (AI)-based platform accessible via a software or firmware application running on a computer or mobile device to evaluate patient health data, rule out minor health issues, provide accessible personalized health management advice to the patient, and communicate serious patient-specific health concerns to a healthcare provider. The AI-based platform may utilize neural networks to process and analyze health data input from various selected sources and generate a personalized assessment of each patient's health status. Such a health monitoring system may be used as a communication and monitoring tool by both physicians and patients, streamlining access to healthcare and reducing strain on healthcare resources.

[0226] In some embodiments, the PoC device may comprise a communications module for connecting to the AI ​​platform using a suitable wired or wireless communications technology, such as Ethernet, WI-FI® (WI-FI is a registered trademark of the Wi-Fi Alliance, Austin, Texas, USA), BLUETOOTH® (BLUETOOTH is a registered trademark of Bluetooth SIG Inc., Kirkland, WY, USA), ZIGBEE® (ZIGBEE is a registered trademark of ZigBee Alliance Corp., San Ramon, California, USA), 3G, 4G, and / or 5G wireless mobile communications technology, for transmitting data collected from analysis of the bodily fluid sample on the sample area of ​​the electrochemical sensor structure.

[0227] In some embodiments, the PoC device 102 may transmit data to the AI ​​platform only if it obtains a valid reading of the data from a fluid sample applied to the sample area of ​​the electrochemical sensor structure.

[0228] In some embodiments, the PoC device 102 may further comprise other suitable peripheral components, such as one or more positioning modules.

[0229] In some embodiments, the one or more positioning modules may be one or more Global Navigation Satellite System (GNSS) components (e.g., one or more components for operation with the United States' Global Positioning System (GPS), the Global'naya Navigatsionnaya Sputnikovaya Sistema (Russia's GLONASS), the European Union's Galileo positioning system, and / or the Chinese Beidou system).

[0230] After user consent, the PoC device 102 may use one or more positioning modules to determine geospatial information such as location, city, country, etc. that may be used as the user's geospatial information. As one skilled in the art will appreciate, geospatial data provides situational context to the user's various biomarker information and, therefore, provides an overall assessment of the patient's health status.

[0231] The resulting geospatial information may be transmitted from the PoC device 102 to a server via a suitable communication technology, such as Wi-Fi, 3G, 4G, or 5G cellular communication technology.

[0232] The server can use the geospatial information collected from the PoC devices 102 for research into related areas such as the prevalence and incidence of heart failure, understanding healthcare resource utilization, areas of frequent readmissions, the impact of low socioeconomic status on cardiac health, and to aid in the development of clinical pathways to assist healthcare systems and policy makers.

[0233] In some embodiments, based on user consent, geospatial or geofencing tracking may be implemented on the PoC device 102 (with server cooperation) to delegate patient history, current patient status, and current patient location to first responders.

[0234] In some embodiments, the PoC device 102 can coordinate with other health monitoring devices and / or have additional health monitoring capabilities to provide a more comprehensive health monitoring solution. For example, in some embodiments, the GNSS-integrated PoC device 102 can be used to track patients suffering from or at high risk of having a cardiac event. For chronic conditions like HF, which require constant, if not intermittent, monitoring of biomarker levels, in the event of decompensation (from steady state to chronic health state), the "patient door to care" time becomes critical. This device shortens the "event-to-care" time by providing the patient's precise location in urban, rural, and remote areas.

[0235] In these embodiments, geospatial technology can be mission-critical to the PoC device 102. The primary value proposition geoinformatics offers is emergency communication with geolocation in the event of a sudden cardiac event. For example, if a patient is responsive but unable to make a call, the patient can press an SOS button on the PoC device 102. An emergency communication, such as an automated text report, is then sent to one or more emergency services.

[0236] Those skilled in the art will recognize that other embodiments are readily available.

[0237] 15A shows an electrochemical sensor structure 104 according to some embodiments of the present disclosure. In these embodiments, the electrochemical sensor structure 104 is similar to that described above, except that the electrochemical sensor structure 104 in these embodiments comprises two WEs 128-1 and 128-2 with an RE 124 intermediate therebetween and a CE 126 extending around the WEs 128-1 and 128-2.

[0238] 15B shows an electrochemical sensor structure 104 according to further embodiments of the present disclosure. In these embodiments, the electrochemical sensor structure 104 is similar to that shown in FIG. 15A, except that the CE 126 in the sampling region 134 includes a smooth passing trace, and the two WEs 128-1 and 128-2 include oval electrode terminals.

[0239] FIG. 15B illustrates an electrochemical sensor structure 104 according to further embodiments of the present disclosure. In these embodiments, the electrochemical sensor structure 104 is similar to that shown in FIG. 15A , except that the electrochemical sensor structure 104 of these embodiments includes an oval-shaped CE 126 with an RE 124 and six WEs 128 enclosed within the circle of the CE 126. The oval-shaped CE 126 is electrically connected only to a counter wire CW 302 (indicated by a dot overlapping both wires), and the electrochemical sensor structure 104 includes a separation or insulating layer (not shown) sandwiched between the electrode components to electrically isolate the CE 126 from the other electrodes (e.g., the REs 124 and WEs 128). Alternatively, the counter wire CW 302 may be on the side of the substrate opposite the side having the REs 124 and WEs 128.

[0240] The electrodes of the above electrochemical sensor structure 104 can be fabricated via screen printing or sputter deposition processes using conductive inks and conductive or semiconductive metals, respectively.

[0241] Figure 17A shows a schematic diagram of an exemplary screen-printed electrode fabrication process 310. Figure 17B shows a schematic diagram of an exemplary sputtered electrode fabrication process 340. In these examples, three or more electrodes (labeled base electrodes) are fabricated on a treated (i.e., modified) or untreated (i.e., unmodified) polymer substrate 332 and subsequently screen printed.

[0242] As shown in Figures 17A and 17B, a substrate 332 is first prepared (Figure 17A, step 312; Figure 17B, Fig. 342). Next, base electrodes (e.g., CE, WE1, WE2, and RE) are fabricated as single elements or layers with other elements of varying thickness using conductive or semiconductive materials such as titanium, platinum, gold, chromium, silver, etc. (Figure 17A, step 314; Figure 17B, Fig. 344).

[0243] The base electrode assembly can be sputter-coated with a metal oxide (e.g., ZnO) layer up to 100 nm thick (Figure 17A, step 316; Figure 17B, step 346). Highly organized metal oxide nanostructures can be electrochemically or hydrothermally fabricated on the seed layer (Figure 17A, step 318; Figure 17B, step 348). Next, capture ligands with affinity for specific analytes can be crosslinked onto the surface of the newly synthesized nanostructures (Figure 17A, step 320; Figure 17B, step 350). To avoid nonspecific binding of interfering components, general or novel blockers can be integrated into the sensing surface (Figure 17A, step 322; Figure 17B, step 352).

[0244] SEM, profilometry, TEM, and AFM techniques can be used to characterize the surface morphology and roughness of the fabricated electrodes and nanostructured components. Various electrochemical techniques, including but not limited to cyclic voltammetry, amperometry, and EIS, can be utilized to acquire electrochemical data and establish standards. Furthermore, Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) can be used to analyze the elemental composition of the assemblies.

[0245] 18A-18F show the progression of the deposition process, with FIG. 18A showing a test strip with a bare electrode 362, FIG. 18B showing a nanorod deposition 364 on the electrode 362, FIG. 18C showing a crosslinker 366 deposited on the nanorod deposition 364, FIG. 18D showing a blocking agent 368 deposited on the crosslinker 366, and FIG. 18E showing an antibody 370 deposited on the electrode 362.

[0246] Figure 18F is a graph showing measurements of the quality of an electrode-supported test strip, including the quality of the deposited or immobilized biosensor, organic chemical, biolinker, and nanorods, where the horizontal axis represents real impedance measurements and the vertical axis represents imaginary impedance measurements. Each of curves 372-378 is obtained from EIS measurements of strip 104 under different surface conditions. Curve 372 represents the ideal immobilization conditions shown in Figure 18E, including antibody 370, blocking agent 368, crosslinker 366, and nanorod layer 364 immobilized on electrode 362.

[0247] 19 is a schematic plan view of an electrochemical sensor structure 104 having an assembly 382 of multiple electrodes (e.g., a CE, an RE, and two to six WEs) according to some embodiments of the present disclosure. The electrochemical sensor structure 104 includes one or more inlet channels 384 for introducing a fluid sample into an adjacent heterophilic plasma separation component (HF-PSC) unit 386 using capillary effect. The HF-PSC unit 386 is proximate to the electrode assembly 382 and spaced apart from it with a gap therebetween forming an analyte drop chamber 388.

[0248] The one or more inlet channels 384 may be imprinted on the substrate 112, or alternatively may be formed by a suitable material coated on the substrate 112 with gaps therein that form the inlet channels 384. The one or more inlet channels 384 may have any suitable geometric shape or dimensions. In the example shown in FIG. 19 , the electrochemical sensor structure 104 includes one funnel-shaped inlet channel 384 adjacent the edge of the sampling region 134 and having an opening that tapers toward the HF-PSC unit 386.

[0249] As shown in FIG. 20, when the body fluid 402 is dripped into the introduction channel 384, this utilizes the surface tension properties of the dripped body fluid 402 for efficient flow dynamics, thus reducing the volume required for the quantification assay.

[0250] The inlet channel 384 channels the dripped body fluid 402, and the analyte, along with other fluid components, travels through the HF-PSC unit 386. The HF-PSC unit 386 is a separator component embedded with specific blocker components to filter out unwanted interfering components of the fluid 402 and to capture or retain interfering fluid components that may otherwise induce false-positive or false-negative results in the assay. The HF-PSC unit 386 can be modified and / or treated to capture interfering fluid components for improved sensitivity and selectivity. In various embodiments, the HF-PSC unit 386 can include symmetric and / or asymmetric pores with various pore sizes. In some embodiments, the HF-PSC unit 386 can alternatively be untreated, depending on the application of the assay.

[0251] The filtered fluid sample obtained in the HF-PSC unit 386 then enters the analyte drop chamber 388 to contact the electrode assembly 382, ​​which comprises a layered nanostructure and a base electrode with or without bridging capture ligands for specific analytes (WE, CE, and RE). In various embodiments, the number of WE electrodes can vary depending on the type of assay and the multiplexing of the assay.

[0252] FIG. 21 illustrates a working schema 420 for quantification of an analyte from a body fluid for an electrode assembly of a two to six working electrode system, showing one of the working electrodes embedded and supersaturated with a desired capture ligand, the interaction of body fluid components with the embedded supersaturated ligand, and a simplified conceptual EIS graph illustrating quantification of the analyte.

[0253] As shown, one of the WEs 128, such as WE128-2, is supersaturated with a capture ligand, while the other, WE128-1, is cross-linked with a predetermined concentration of a similar or different capture ligand (step 422). Quantification values ​​are derived from previously performed experiments that define standard curves for both the desired and interfering entities. The PoC device 102 then uses a mathematical model to calculate a final output value in terms of the EIS values ​​(obtained in steps 422 and 424) to determine the actual assay value for the analyte of interest, as follows: Analyte concentration = Rct WE2 -Rct WE1 where Rct WE1 and Rct WE2 are resistive to charge electron transfer between electrodes WE1 and WE2, respectively (RCT is also denoted as "charge transfer resistance").

[0254] 19-21, the electrochemical sensor structure 104 includes two WEs 128, one WE supersaturated with a capture ligand (referred to as the supersaturated WE) and the other WE crosslinked with a predetermined concentration of a similar or different capture ligand (referred to as the experimental WE). The analyte concentration is calculated based on the difference in RCT between the supersaturated WE and the experimental WE.

[0255] In some embodiments where the electrochemical sensor structure 104 includes three or more WEs 128 (e.g., as shown in FIG. 16 ), one or more WEs may be configured to be supersaturated WEs and other WEs may be configured to be experimental WEs. The concentration of the analyte is calculated based on the difference in RCT between the supersaturated WE and the experimental WE using a suitable statistical method, such as a maximum likelihood estimator, a least squares estimator, or a minimum mean square error (MMSE) estimator.

[0256] 22 is a block diagram illustrating a modular structure 440 of an electrochemical sensor system 100 for analyzing bodily fluids. As shown, analytes enter the electrochemical sensor structure 104 via an analyte inlet 442 (e.g., a capillary inlet for a blood sample as described above) and are processed by its analyte processing module 444, which may be provided through a substrate that results in mixing of the blood with the conjugates. Such processing results in final separation of plasma containing the conjugates, allowing for efficient downstream processing.

[0257] The output of the analyte processing module 444 is sent to a multi-module setup 446 of the PoC device 102, which includes an electrochemistry module 448, a fluorescence module 450, a polymerase chain reaction (PCR) module 452, and an absorbance module 454, which in some embodiments may be combined or otherwise integrated into a single miniaturized module. Here, the multi-module setup 446 allows a user to switch to a suitable one of the modules 448-454 for blood analysis. For example, NT-pro-BNP detection may require the electrochemistry module 448, the fluorescence module 450 and the PCR module 452 may work together to enable aptamer-based ligand recognition, and a metabolite panel may require the absorbance module 454.

[0258] The calibration curve module 456 may be memory of the PoC device 102 or memory on a secure central server that stores the calibration curve (i.e., calibrated data set). In some embodiments, the PoC device 102 may communicate with the central server to obtain the calibration curve associated with the lot / batch of strips 104.

[0259] In some embodiments, screen printing techniques can be used to create the electrode arrangement and provide impedance-coded identification of the lot / batch of strips. Using this code, the PoC device 102 can communicate with a central server to establish an accurate calibration curve prior to analyte analysis.

[0260] The raw data from the multi-module setup 446 is securely transmitted to memory 456 and compared to a calibration curve stored therein to obtain biologically relevant measurements (e.g., biomarker concentrations obtained through EIS) in appropriate units. The obtained measurements are then displayed on a display 458 of the PoC device 102 and / or transmitted via a suitable wired or wireless communication technology, such as BLUETOOTH®, to and displayed on an associated mobile device 460 (e.g., the user's mobile device and / or the physician's mobile device).

[0261] In some embodiments, values ​​obtained via EIS can also be used to diagnose the effectiveness of an immobilized biosensor. For example, in one embodiment, an EIS sweep can be performed to predict the "health" of a substrate before applying a fluid sample thereto.

[0262] 23 is a block diagram illustrating a modular structure 480 of a PoC device 102 for blood analysis, according to some embodiments of the present disclosure. As shown, the PoC device 102 can be used with multiple electrochemical sensor structures or disposable strips 104 for blood analysis, such as an NT-pro-BNP test strip 482 for detecting the NT-pro-BNP biomarker in a human blood sample, a glucose test strip 484, a creatinine test strip 486, and other suitable strips (e.g., strips for testing electrolytes, troponin, etc.). The strips 104 (e.g., strips 482-486) ​​have universal strip adapters for interfacing with the PoC device 102.

[0263] The PoC device 102 includes a programmable AC potentiostat circuit 488 and a programmable DC potentiostat circuit 490, which include voltage control and data storage and analysis, and are controlled by a control circuit 492 (e.g., an Arduino microcontroller) having necessary components such as a memory 494 and a communications module 496 (e.g., a Bluetooth module). The PoC device 102 also includes a light-emitting diode (LED) display 498 (or other suitable display) and a battery 500 for powering the various components.

[0264] Based on the type of test, the PoC device 102 can automatically use the programmable AC potentiostat circuit 488 or the programmable DC potentiostat circuit 490 for the test. The test results are transmitted to the control circuit 492 for analysis and stored in its memory 494. The analysis results are displayed on an LED display 498 and / or securely and wirelessly transmitted to and displayed on the mobile device 460.

[0265] In some embodiments, the fluid flow channel may function in concert with an electrode system. Prior art systems have used multiple electrodes to assess the amount of fluid present in the flow channel. To miniaturize the strip design, a combination of channel geometry and electrode design is used. As described in more detail below, in some embodiments, the channel or microchannel may be accessed through an inlet port. Opposite the inlet port, there may be a constriction across the entire cross section of the channel. In related embodiments, the substrate may be treated to be hydrophobic, which impedes fluid flow. The stability of the fluid flow may be assessed by measuring the change in current from the electrodes.

[0266] In some embodiments, the dimensions of the microchannel are predetermined to achieve a predetermined volume to allow complete filling of the fluid.

[0267] 24A and 24B show a hybrid design of an electrochemical sensor structure 104 with control over the stability and amount of fluid sample flow received within its sampling region, according to some embodiments of the present disclosure.

[0268] As shown in FIG. 24A, the electrochemical sensor structure 104 has an inlet or inlet opening 512 in or around the analyte drop chamber 388 and includes one or more capillary channels 510 (also referred to as microchannels or microfluidic channels) extending from the analyte drop chamber 388 to the electrode region.

[0269] One or more capillary channels 510 can be imprinted or otherwise formed on the substrate 122 and can be hydrophilic to the fluid sample. Each microchannel 510 includes a substantially abrupt expansion 514 (i.e., a substantially abrupt increase in width and / or its cross-sectional area), with the distance between the inlet 512 and the expansion 514 predetermined based on fluid volume requirements.

[0270] An electrode 518, such as a WE, extends into the microchannel 510 at a location intermediate the inlet 512 and the extension 514 (i.e., the electrode 518 is downstream of the inlet 512 and upstream of the extension 514) and can directly interact with the fluid sample therein. Thus, the electrode 518 can be used to interrogate the sample via a DC potentiostat circuit, an AC potentiostat circuit, or a combination thereof.

[0271] During sampling of a bodily fluid, a fluid stream enters and flows through the microchannel 510 at the inlet 512. Figure 24A shows the flow front 516 approaching the electrode 518. Figure 24B shows the flow front 516 passing the electrode 518.

[0272] The abrupt expansion 514 and its associated surface tension effects impede the flow front of the fluid within the microchannel 510, thus controlling the volume of the fluid. When the flow front 516 is not approaching the electrode 518, the impedance scanned by the electrode 518 is low. As the flow front 516 passes the electrode 518, the impedance scanned by the electrode 518 may steadily increase, thereby indicating the passage of the flow front 516.

[0273] In some embodiments, the abrupt expansion 514 and its associated surface tension effects may also be used to control fluid velocity.

[0274] The electrodes 518 can be electrically coupled to a DC potentiostat circuit 490 (see FIG. 23), which applies a DC voltage to the electrodes 518 and monitors the rate of current change. If the rate of current is zero for a high impedance measurement (e.g., greater than a predetermined impedance threshold), it means that the microchannel 510 is receiving blood therein but is not flowing. If the rate of current is non-zero for a high impedance measurement (e.g., greater than a predetermined impedance threshold) for more than a predetermined period, it means that the amount of blood in the microchannel 510 is sufficient for a strip test.

[0275] 25A-25C illustrate an electrochemical sensor structure 104 that controls the flow stability and volume of a fluid sample received in its sampling region, according to further embodiments of the present disclosure.

[0276] 24A and 24B, and includes one or more microchannels 510 having an inlet or inlet opening 512 in or around the analyte drop chamber 388 and extending from the analyte drop chamber 388 to an electrode region. The one or more capillary channels 510 may be imprinted or otherwise formed on the substrate 122 and may be hydrophobic to the fluid sample.

[0277] As shown, each microchannel 510 includes a substantially abrupt taper 514' (i.e., a substantially abrupt decrease in width and / or cross-sectional area) for controlling fluid volume. The distance between the inlet 512 and the taper 514' is predetermined based on the fluid volume requirements.

[0278] An electrode 518, such as a WE, extends into the microchannel 510 at a location intermediate the inlet 512 and the tapered portion 514′ (i.e., the electrode 518 is downstream of the inlet 512 and upstream of the tapered portion 514′) and can directly interact with the fluid sample therein. The electrode 518 can be used to interrogate the sample via a DC potentiostat circuit, an AC potentiostat circuit, or a combination thereof.

[0279] 26 is a flowchart illustrating a process 600 performed by the PoC device 102 for analyzing body fluids, according to some embodiments of the present disclosure. As shown, the signal generator 602 of the PoC device 102 outputs a signal (e.g., an AC signal) to the WEs 606-612 via a multiplexer / demultiplexer (mux / demux) 604. The signal from the WEs 606-612 is fed to a multi-channel current-to-voltage converter 614, which outputs a voltage signal to either a DC potentiostat circuit 618 or an AC potentiostat circuit 620 via a multiplexer / demux 616. The output of the DC potentiostat circuit 618 and / or the AC potentiostat circuit 620 is analyzed by a data analysis module 622. The analysis results of the data analysis module 622 are read, displayed, and / or stored in an output module 624.

[0280] 27 is a flowchart illustrating a process 700 performed by the PoC device 102 for bodily fluid analysis, according to some embodiments of the present disclosure. The process 700 begins when a user selects the type of test and strip 104 to use (step 702). When the strip 104 is inserted into the PoC device 102, the PoC device 102 diagnoses the strip 104 for substrate quality and biosensor component integrity (step 704). If the test is impedance-based, the PoC device 102 automatically calibrates itself to an impedance range appropriate for the biomarker being tested (step 706). The PoC device 102 also checks the type of strip 104 and adjusts its parameters to match the strip 104 (step 708).

[0281] The PoC device 102 may test the strip 104 using a combination of impedance, voltage, and current. If the PoC device 102 determines that the strip 104 is not usable (the "No" branch of step 710), the process 700 proceeds to step 702, where the PoC device 102 requests the user to replace the strip 104. If the PoC device 102 determines that the strip 104 is viable (the "Yes" branch of step 710), then the PoC device 102 requests the user to provide a blood sample (step 712).

[0282] Upon receiving the blood sample, the PoC device 102 assesses the stability of the flow (step 714) and monitors changes in the current from the electrodes (step 716) as described above (see also Figures 24A and 24B). If the current is changing (the "Yes" branch of step 718), the process 700 returns to step 716 for further monitoring of the current change.

[0283] Once the current change stops ("NO" branch of step 718), a timer is started to record the interaction period (step 720), and the PoC device 102 begins measuring impedance after the predetermined interaction period has expired (step 722). The PoC device 102 then compares the raw measurements to a calibration curve (step 724) and displays the results in terms of concentration (step 726). Quantitative or qualitative data is also uploaded to a server (step 730). The test session then ends (step 732).

[0284] 28 is a flowchart illustrating a process 800 for analyzing body fluids according to some embodiments of the present disclosure. The process 800 begins when a patient initiates a test using a PoC device 102 (step 802). The PoC device 102 is operatively coupled to a health monitoring network system and is in communication with a server as described above.

[0285] Similar to process 700, the user selects the type of biomarker for the test (step 804), inserts the appropriate biomarker strip 104 into the PoC device 102 (step 806), and administers a fingertip blood sample to the strip 104 (step 808). The PoC device 102 then quantifies the biomarker levels and registers its geolocation using its GNSS component (e.g., its GPS component) (step 810). At step 812, the test and geolocation data are aggregated and evaluated to obtain an assessment of the user's health status.

[0286] In these embodiments, the PoC device 102 includes multiple thresholds for comparison with the test data, for example, a first threshold above which indicates an abnormal health condition and a second threshold above which indicates a serious health condition.

[0287] If, in step 814, the PoC device 102 determines that the user's health condition assessment is above the first threshold but below the second threshold (i.e., an abnormal but not serious health condition), the PoC device 102 then communicates with the health monitoring network system and enables the health monitoring network system to contact the patient for further action (step 816). Next, process 800 proceeds to step 822.

[0288] If, at step 814, the PoC device 102 determines that the user's health status assessment is below the first threshold (i.e., normal health status), the PoC device 102 then displays the user's health status assessment and records the test data and the user's health status assessment (step 818). Next, process 800 proceeds to step 822.

[0289] If, in step 814, the PoC device 102 determines that the user's health status assessment exceeds a second threshold (i.e., a serious health status), the PoC device 102 then communicates with the health monitoring network system to initiate an emergency protocol (step 820). The patient can also initiate an emergency via the PoC device 102 (step 828). The patient's report file (e.g., having the user's history, biomarker data, geographic location, health status assessment, etc.) is then sent to an emergency contact (e.g., the patient's physician) and / or service (step 824). Process 800 then proceeds to step 822.

[0290] The patient report file is stored on the health monitoring network system server at step 822. The process 800 ends (step 826).

[0291] As one skilled in the art will appreciate, the PoC devices 102 disclosed herein may have a variety of form factors, such as being handheld or desktop devices. The PoC devices 102 may be used to monitor suitable biomarkers or analytes derived from bodily fluids, such as whole blood, plasma, serum, urine, and similar biological specimens, and provide physiologically relevant information. The physiologically relevant information may be securely transmitted to healthcare professionals, physicians, clinical and / or hospital administrative networks, including, but not limited to, public and / or private healthcare systems.

[0292] The PoC device 102 may be designed and implemented in a modular manner and may include multiple detection modules for detecting different analytes. Each detection module may employ a specific technology to confirm the concentration of the analyte. The PoC device 102 may also include additional modules, such as a module for initiating communication with external devices (e.g., a mobile phone, a hard drive, a data center, a computer cloud, etc.).

[0293] In the above embodiments, the PoC device 102 includes one or more buttons 108 next to the screen 106 for receiving user input. In some alternative embodiments shown in Figures 29A and 29B, the PoC device 102 in these embodiments is similar to that shown in Figure 1A. However, in these embodiments, the PoC device 102 may include a touchscreen 106 on its front wall 902, a strip-receiving port 110 on its top wall 904 for receiving a strip 104, and one or more buttons 108 on its two opposing side walls 906. The buttons 108 can be used to receive user input and perform various functions. For example, a first one of the buttons 108 may be used to activate or wake the PoC device 102 from sleep mode, a second one of the buttons 108 may be used to start a test, and a third one of the buttons 108 may be used to adjust the volume of a speaker integrated into the PoC device 102 when a user selects to play test results through the speaker (e.g., when the PoC device is "reading" the test results). As one skilled in the art will appreciate, arranging one or more buttons 108 on one or two side walls 906 of the PoC device 102 may facilitate a user's convenient operation of the PoC device 102 with one hand.

[0294] The strip receiving port 110 may preferably be located in any suitable location on the PoC device 102 that will not interfere with one-handed operation of a user. For example, in some embodiments, the strip receiving port 110 may be on the bottom wall 908 of the PoC device 102. In some other embodiments, the strip receiving port 110 may be on one of the side walls 906 of the PoC device 102.

[0295] In some embodiments in which the PoC device 102 includes multiple strip receiving ports 110, the multiple strip receiving ports 110 may preferably be arranged on the PoC device 102 in any location that would not interfere with one-handed operation of the user.

[0296] In some embodiments, the PoC device 102 may include a USB port (e.g., a micro USB port or a USB Type-C port) or any suitable port for connecting to a power source for charging the battery of the PoC device 102.

[0297] In some embodiments, the PoC device 102 may include a connection port, such as a USB port, for receiving a strip adapter 252 similar to that shown in Figure 13, but having a strip insert 254 with suitable physical and electrical specifications for insertion into the connection port. In these embodiments, the PoC device 102 may or may not include a strip receiving port 110, depending on the implementation.

[0298] 2, the PoC device 102 measures the resistance of a pair of identification electrodes 130 and 132 to identify one or more biomarkers analyzable using an electrochemical sensor structure 104 inserted therein. In some alternative embodiments, the electrochemical sensor structure 104 comprises an identification circuit with predetermined electrical characteristics indicative of the one or more analyzable biomarkers.

[0299] Similarly, the PoC device 102 includes circuitry for coupling to the identification circuit of the electrochemical sensor structure 104 when the electrochemical sensor structure 104 is inserted therein and determining predetermined electrical characteristics for identifying one or more analyzable biomarkers.

[0300] For example, in some embodiments, the identification circuit may be a circuit having a predetermined capacitance indicative of one or more analyzable biomarkers, and the PoC device 102 includes circuitry for determining the predetermined capacitance for identifying the one or more analyzable biomarkers.

[0301] In some other embodiments, the identification circuit may be a circuit having a predetermined inductance indicative of one or more analyzable biomarkers, and the PoC device 102 includes circuitry for determining the predetermined inductance for identifying the one or more analyzable biomarkers.

[0302] In yet some other embodiments, the identification circuit may be a circuit that stores a code indicative of one or more analyzable biomarkers (e.g., an IC chip that stores a code indicative of one or more analyzable biomarkers), and the PoC device 102 includes reader circuitry for reading the code from the IC chip to determine a predetermined inductance for identifying the one or more analyzable biomarkers.

[0303] In some of the above embodiments, the PoC device 102 uses an imaging component (such as a camera) to scan an image (such as a one-dimensional or two-dimensional barcode) on the electrochemical sensor structure 104 or on a transport vial containing the electrochemical sensor structure 104 to identify one or more analyzable biomarkers. Those skilled in the art will understand that in some embodiments, other suitable images encoding the identity of one or more analyzable biomarkers may also be used to identify one or more analyzable biomarkers as described above.

[0304] In some embodiments, the PoC device 102 can assess the stability and volume of the flow of the fluid sample on the strip 104 .

[0305] In some embodiments, the PoC device 102 may include one or more components to support the voltage and current signals that are read or transmitted to the strip 104 .

[0306] In some embodiments, the PoC device 102 can connect to a central server that allows for secure two-way communication of information, such as calibration curves, test results, strip information, lot information, batch information, geospatial information, software information, etc.

[0307] Although embodiments have been described above with reference to the accompanying drawings, those skilled in the art will appreciate that variations and modifications can be made without departing from the scope thereof as defined by the appended claims.

Claims

1. 1. A device for analyzing a bodily fluid sample of a user, comprising: a housing having at least one first port for receiving an electrochemical sensor structure, the electrochemical sensor structure including a first circuit having a first set of electrodes for contacting the bodily fluid sample; an identification circuit for identifying one or more biomarkers analyzable using the electrochemical sensor structure; an analysis circuit comprising a set of coupling electrodes for electrically coupling to the first set of electrodes of the electrochemical sensor structure for analyzing the identified one or more biomarkers in the bodily fluid sample; a control circuit coupled to the identification and analysis circuit for determining a set of biosensing parameters based on the identified one or more biomarkers and for controlling the analysis circuit to analyze the identified one or more biomarkers in the bodily fluid sample based on the set of biosensing parameters; an output for outputting an analysis result of the analysis of the identified one or more biomarkers in the bodily fluid sample.

2. 2. The device of claim 1, wherein the identification circuit is for identifying the one or more biomarkers by measuring the impedance of a second circuit of the electrochemical sensor structure, the resistance of the second circuit encoding identification information of the one or more biomarkers.

3. The device of claim 2 , wherein the second circuit comprises a second set of electrodes.

4. 10. The device of claim 1, wherein the identification circuit is for identifying the one or more biomarkers by reading a radio frequency identification (RFID) tag that encodes identification information of the one or more biomarkers in the electrochemical sensor structure.

5. The device of claim 2 , wherein the RFID tag is on the electrochemical sensor structure or on a shipping vial containing the electrochemical sensor structure.

6. further comprising an imaging component; 10. The device of claim 1, wherein the identification circuitry is for identifying the one or more biomarkers by scanning an image using the imaging component that encodes identification information of the one or more biomarkers.

7. 10. The apparatus of claim 1, wherein the identification circuitry is for instructing a device having an imaging component and operatively coupled to the apparatus to use the imaging component to scan an image encoding identification information of the one or more biomarkers to identify the one or more biomarkers.

8. 8. The apparatus according to claim 6 or 7, wherein the image is a one-dimensional or two-dimensional barcode.

9. The apparatus of any one of claims 6 to 8, wherein the image is on the electrochemical sensor structure or on a delivery vial containing the electrochemical sensor structure.

10. 10. The device of claim 1, wherein the analysis circuit is configured to measure one or more impedances, one or more currents, and / or one or more voltages of the first circuit to analyze the identified one or more biomarkers in the body fluid sample.

11. 11. The device of claim 1, wherein the analysis circuit comprises at least one potentiostat circuit for electrically coupling to the first circuit for analyzing the identified one or more biomarkers in the bodily fluid sample.

12. 12. The apparatus of claim 11, wherein the at least one potentiostat circuit comprises a direct current (DC) potentiostat circuit, an alternating current (AC) potentiostat circuit, or a combination thereof.

13. 13. The device of claim 1, wherein the set of coupled electrodes includes at least a reference electrode (RE), a control electrode (CE), and a working electrode (WE) for electrically coupling to a reference electrode (RE), a control electrode (CE), and a working electrode (WE) of the electrochemical sensor structure.

14. The device of any one of claims 1 to 12, wherein the set of coupled electrodes includes at least a coupled RE, a coupled CE, and a plurality of WEs for electrically coupling to the RE, CE, and a plurality of WEs of the electrochemical sensor structure.

15. The device of any one of claims 1 to 12, wherein the set of coupled electrodes includes at least a coupled RE, a coupled CE, and three or more coupled WEs for electrically coupling to the RE, CE, and three or more WEs of the electrochemical sensor structure.

16. a first set of at least one of the coupled WEs for electrically coupling to a first set of WEs of the electrochemical sensor structure supersaturated with a first set of one or more capture ligands; a second set of at least one of the coupled WEs for electrically coupling to a second set of WEs of the electrochemical sensor structure cross-linked with a second set of one or more capture ligands at a predetermined concentration; 16. The device of claim 14 or 15, wherein the analysis circuit is for analyzing the identified one or more biomarkers in the bodily fluid sample by calculating an analyte concentration based on a difference in charge transfer resistance (RCT) between the first and second sets of WEs of the electrochemical sensor structure.

17. 17. The device of claim 16, wherein the analysis circuit is for calculating an analyte concentration based on a difference in charge transfer resistance (RCT) between the first and second sets of WEs of the electrochemical sensor structure and analyzing the identified one or more biomarkers in the bodily fluid sample by using statistical methods.

18. The apparatus of any one of claims 1 to 17, wherein the output comprises a screen for displaying the analysis results.

19. 20. The device of claim 18, wherein the screen is a touch screen for displaying the analysis results and receiving input from the user.

20. The apparatus according to any one of claims 1 to 19, wherein the output unit comprises a speaker for outputting the analysis results.

21. The apparatus of any one of claims 1 to 20, further comprising a networking module for communicating with one or more remote devices.

22. 22. The device of claim 21, wherein the networking module is a Bluetooth module.

23. 23. The apparatus of claim 21 or 22, wherein the output comprises the networking module for outputting the analysis results to the one or more remote devices.

24. 24. The apparatus of claim 23, wherein the one or more remote devices comprise an artificial intelligence (AI) system for determining a health status of the user based on the analysis results.

25. The device of any preceding claim, further comprising one or more buttons for receiving input from the user.

26. 26. The device of claim 25, wherein the one or more buttons comprise an SOS button for initiating emergency communications with one or more emergency services.

27. the housing comprising a front wall, a rear wall, a top wall, a bottom wall, and two opposing side walls; 27. The device of claim 26, wherein the one or more buttons are distributed on at least one of the side walls.

28. 28. The device of claim 27, wherein the at least one first port is located on the upper wall or the lower wall.

29. 29. The device of any one of claims 1 to 28, further comprising an adapter for electrically and removably coupling to the device, the adapter comprising a plurality of second ports for receiving a plurality of additional electrochemical sensor structures.

30. 30. The apparatus of claim 29, wherein the plurality of additional electrochemical sensor structures have the same mechanical and / or electrical specifications.

31. 30. The apparatus of claim 29, wherein the plurality of additional electrochemical sensor structures have different mechanical and / or electrical specifications.

32. The device of any preceding claim, wherein the device comprises a plurality of first ports.

33. 33. The apparatus of claim 32, wherein the plurality of first ports have the same mechanical and / or electrical specifications.

34. 33. The apparatus of claim 32, wherein the plurality of first ports have different mechanical and / or electrical specifications.

35. a battery for powering at least the identification circuit, the analysis circuit, and the control circuit; The device of any one of claims 1 to 34, further comprising: a second port for electrically coupling to a power source for charging the battery.

36. 36. The device of claim 35, wherein the second port is a Universal Serial Bus (USB) port.

37. 37. The device of any one of claims 1 to 36, further comprising a third port for physically and electrically coupling to a smartphone.

38. 38. The device of any one of claims 1 to 37, wherein the analytical circuitry and / or the control circuitry comprises an electrochemical module for detecting and analyzing N-terminal pro-B-type natriuretic peptide (NT-pro-BNP), a fluorescence module, a polymerase chain reaction (PCR) module for detecting and analyzing aptamer-based ligands, and an absorption module for metabolite analysis.

39. 39. The apparatus of claim 38, wherein the analytical circuitry and / or the control circuitry further comprises a memory having stored therein a calibration curve for determining the concentration of the identified one or more biomarkers.

40. further comprising one or more Global Positioning System (GNSS) components for acquiring geospatial information of the device; The apparatus of any one of claims 1 to 40, wherein the output is for outputting the analysis results and the geospatial information.

41. the one or more remote devices: evaluating the analysis results to obtain an assessment of the user's health status; storing the analysis results, the geospatial information, and the assessment of the user's health status; notifying the user about further action if the assessment of the user's health status is above a first threshold but below a second threshold; 41. The device of claim 40, when recited in claim 23, for initiating an emergency protocol if the assessment of the user's health state exceeds the second threshold.

42. 1. A device for analyzing a bodily fluid sample of a user, comprising: a housing having at least one first port for receiving an electrochemical sensor structure, the electrochemical sensor structure including a first circuit having a first set of electrodes for contacting the bodily fluid sample; an analysis circuit comprising a set of coupling electrodes for electrically coupling to the first set of electrodes of the electrochemical sensor structure for analyzing one or more biomarkers in the bodily fluid sample; an output unit for outputting an analysis result of the analysis of the identified one or more biomarkers in the bodily fluid sample; The device, wherein the set of coupled electrodes includes at least a reference electrode (RE), a control electrode (CE), and a plurality of working electrodes (WE) for electrically coupling to a reference electrode (RE), a control electrode (CE), and a plurality of working electrodes (WE) of the electrochemical sensor structure.

43. 43. The apparatus of claim 42, wherein the plurality of WEs includes three or more coupling WEs for electrically coupling to three or more WEs of the electrochemical sensor structure.

44. a first set of at least one of the coupled WEs for electrically coupling to a first set of WEs of the electrochemical sensor structure supersaturated with a first set of one or more capture ligands; a second set of at least one of the coupled WEs for electrically coupling to a second set of WEs of the electrochemical sensor structure cross-linked with a second set of one or more capture ligands at a predetermined concentration; 44. The device of claim 42 or 43, wherein the analysis circuit is for analyzing the identified one or more biomarkers in the bodily fluid sample by calculating an analyte concentration based on a difference in charge transfer resistance (RCT) between the first and second sets of WEs of the electrochemical sensor structure.

45. 45. The device of claim 44, wherein the analysis circuit is for calculating an analyte concentration based on a difference in charge transfer resistance (RCT) between the first and second sets of WEs of the electrochemical sensor structure and analyzing the identified one or more biomarkers in the bodily fluid sample by using statistical methods.

46. 1. An electrochemical sensor structure comprising: A substrate; a first circuit comprising a first set of electrodes dispersed on the substrate and extending into a sampling area of ​​the substrate for contacting a bodily fluid sample; an identification structure for identifying one or more biomarkers in the bodily fluid sample that can be analyzed using the electrochemical sensor structure.

47. 47. The electrochemical sensor structure of claim 46, wherein the substrate comprises a polymer.

48. 48. The electrochemical sensor structure of claim 47, wherein the polymer comprises polystyrene, polyester, polycarbonate, or polyamide.

49. 47. The electrochemical sensor structure of claim 46, wherein the substrate is a porous substrate.

50. 50. The electrochemical sensor structure of claim 49, wherein the substrate is a track-etched membrane having a porosity of 30% or greater.

51. 47. The electrochemical sensor structure of claim 46, wherein the substrate comprises a poly(methyl methacrylate) (PMMA) film.

52. 52. The electrochemical sensor structure of any one of claims 46 to 51, wherein the identification structure comprises a second circuit having a predetermined impedance that encodes identification information of the one or more biomarkers of the electrochemical sensor structure.

53. 52. The electrochemical sensor structure of any one of claims 46 to 51, wherein the identification structure comprises a radio frequency identification (RFID) tag encoding identification information of the one or more biomarkers of the electrochemical sensor structure.

54. The electrochemical sensor structure of any one of claims 46 to 51, wherein the identification structure comprises an image encoding the identity of the one or more biomarkers of the electrochemical sensor structure.

55. 55. The electrochemical sensor structure of claim 54, wherein the image comprises a one-dimensional or two-dimensional barcode encoding the identity of the one or more biomarkers of the electrochemical sensor structure.

56. 56. The electrochemical sensor structure of any one of claims 46 to 55, wherein the first set of electrodes comprises at least a reference electrode (RE), a control electrode (CE), and a working electrode (WE).

57. 56. The electrochemical sensor structure of any one of claims 46 to 55, wherein the first set of electrodes comprises at least an RE, a CE, and a plurality of WEs.

58. 56. The electrochemical sensor structure of any one of claims 46 to 55, wherein the first set of electrodes comprises at least an RE, a CE, and three or more WEs.

59. 59. The electrochemical sensor structure of claim 57 or 58, wherein at least one first set of the WEs is supersaturated with a first set of one or more capture ligands and at least one second set of the WEs is cross-linked with a predetermined concentration of a second set of one or more capture ligands.

60. 60. The electrochemical sensor structure of claim 59, wherein the first set of one or more capture ligands comprises the same capture ligand.

61. 60. The electrochemical sensor structure of claim 59, wherein the first set of one or more capture ligands comprises different capture ligands.

62. 60. The electrochemical sensor structure of claim 59, wherein the second set of one or more capture ligands comprises the same capture ligand.

63. 60. The electrochemical sensor structure of claim 59, wherein the second set of one or more capture ligands comprises different capture ligands.

64. 64. The electrochemical sensor structure of any one of claims 59 to 63, wherein the first set of one or more capture ligands is the same as the second set of one or more capture ligands.

65. 64. The electrochemical sensor structure of any one of claims 59 to 63, wherein the first set of one or more capture ligands is different from the second set of one or more capture ligands.

66. 66. The electrochemical sensor structure of any one of claims 56 to 65, wherein each of the first set of electrodes comprises a layer of chromium (Cr) and a layer of gold (Au) on the Cr layer.

67. 67. The electrochemical sensor structure of claim 66, wherein at least one WE further comprises a layer of conductive nanomaterial on the Au layer.

68. 68. The electrochemical sensor structure of claim 67, wherein the at least one WE further comprises a layer of sensing element over the layer of conductive nanomaterial.

69. 69. The electrochemical sensor structure of any one of claims 56 to 68, wherein the CE extends along at least two edges of the sampling region, thereby surrounding the remainder of the first set of electrodes.

70. a hydrophobic middle layer having a distal end opening forming a sampling port for receiving the bodily fluid sample into the sampling region; 70. The electrochemical sensor structure of any one of claims 46 to 69, further comprising a protective layer over the hydrophobic intermediate layer and covering the sampling area.

71. The sampling area of ​​the substrate is one or more introduction channels around its periphery for introducing said bodily fluid sample using capillary effect; a heterophile plasma separation component (HF-PSC) unit adjacent to the one or more input channels for receiving the body fluid sample therefrom and filtering interfering components from the body fluid sample; 70. The electrochemical sensor structure of any one of claims 46 to 69, comprising: an analyte drop chamber intermediate the HF-PSC and the first set of electrodes, the analyte drop chamber receiving the filtered bodily fluid sample from the HF-PSC to allow the filtered bodily fluid sample to contact the first set of electrodes.

72. 72. The electrochemical sensor structure of claim 71, wherein at least one of the one or more introduction channels is funnel-shaped, with an opening adjacent the edge of the sampling region and tapering toward the HF-PSC unit.

73. 73. The electrochemical sensor structure of claim 71 or 72, wherein at least one of the one or more introduction channels is imprinted on the substrate.

74. 73. An electrochemical sensor structure according to claim 71 or 72, wherein at least one of the one or more introduction channels is formed by a gap in a coating on the substrate.

75. 75. The electrochemical sensor structure of any one of claims 71 to 74, wherein the HF-PSC unit comprises symmetric and / or asymmetric pores of various pore sizes.

76. further comprising one or more capillary channels each including an inlet within or around the analyte drop chamber and extending from the analyte drop chamber to the first set of electrodes; at least one of the one or more capillary channels is hydrophilic to the bodily fluid sample and includes an abrupt expansion at a distance to the inlet to control the volume of the bodily fluid sample therein; 76. The electrochemical sensor structure of any one of claims 71 to 75, wherein at least one WE extends to the at least one of the one or more capillary channels at a location intermediate the inlet and its extension for interacting with the bodily fluid sample therein.

77. further comprising one or more capillary channels each including an inlet within or around the analyte drop chamber and extending from the analyte drop chamber to the first set of electrodes; at least one of the one or more capillary channels is hydrophobic to the bodily fluid sample and includes an abrupt taper in a distance to the inlet to control the volume of the bodily fluid sample therein; 76. The electrochemical sensor structure of claim 71, wherein at least one WE extends to the at least one of the one or more capillary channels at a location intermediate the inlet and its tapered portion for interacting with the bodily fluid sample therein.

78. 1. An electrochemical sensor structure comprising: A substrate; a first circuit comprising a first set of electrodes dispersed on the substrate and extending into a sampling area of ​​the substrate for contacting a bodily fluid sample; The electrochemical sensor structure, wherein the first set of electrodes includes at least a reference electrode (RE), a control electrode (CE), and a plurality of working electrodes (WE).

79. 79. The electrochemical sensor structure of claim 78, wherein the plurality of WEs comprises three or more WEs.

80. 80. The electrochemical sensor structure of claim 78 or 79, wherein at least one first set of the WEs is supersaturated with a first set of one or more capture ligands and at least one second set of the WEs is cross-linked with a predetermined concentration of a second set of one or more capture ligands.

81. 1. An electrochemical sensor structure comprising: A substrate; a first circuit comprising a first set of electrodes dispersed on the substrate and extending into a sampling area of ​​the substrate for contacting a bodily fluid sample; The sampling area of ​​the substrate is one or more introduction channels around its periphery for introducing said body fluid sample using capillary effect; a heterophile plasma separation component (HF-PSC) unit adjacent to the one or more input channels for receiving the body fluid sample therefrom and filtering interfering components from the body fluid sample; and an analyte drop chamber intermediate the HF-PSC and the first set of electrodes, the analyte drop chamber receiving the filtered bodily fluid sample from the HF-PSC to allow the filtered bodily fluid sample to contact the first set of electrodes.

82. 82. The electrochemical sensor structure of claim 81, wherein at least one of the one or more introduction channels is funnel-shaped, with an opening adjacent the edge of the sampling region and tapering toward the HF-PSC unit.

83. 1. An electrochemical sensor structure comprising: A substrate; a first circuit comprising a first set of electrodes dispersed on the substrate and extending into a sampling area of ​​the substrate for contacting a bodily fluid sample; one or more capillary channels each extending from an inlet of the sampling region to the first set of electrodes; at least one of the one or more capillary channels includes a varying area portion at a distance to the inlet, the varying area portion having a varying cross-sectional area for controlling a volume of the bodily fluid sample therein; An electrochemical sensor structure, wherein at least one WE extends to the at least one of the one or more capillary channels at a location intermediate the inlet and its area-changing portion for interacting with the body fluid sample therein.

84. the at least one of the one or more capillary channels is hydrophilic to the bodily fluid sample; 84. The electrochemical sensor structure of claim 83, wherein the area-changing portion of the at least one of the one or more capillary channels is a portion downstream of the at least one WE that has an increased cross-sectional area.

85. the at least one of the one or more capillary channels is hydrophobic with respect to the bodily fluid sample; 84. The electrochemical sensor structure of claim 83, wherein the area-changing portion of the at least one of the one or more capillary channels is a portion downstream of the at least one WE that has a reduced cross-sectional area.

86. 1. A system for analyzing a bodily fluid sample of a user, comprising: an electrochemical sensor structure for receiving the bodily fluid sample thereon; a test device in communication with the electrochemical sensor structure for analyzing the bodily fluid sample; the electrochemical sensor structure substrate, a first circuit comprising a first set of electrodes dispersed on the substrate and extending into a sampling area of ​​the substrate for contacting a bodily fluid sample; an identification structure for identifying one or more biomarkers in the bodily fluid sample analyzable using the electrochemical sensor structure; The inspection device a housing having at least one first port for receiving the electrochemical sensor structure, the electrochemical sensor structure comprising a first circuit having a first set of electrodes for contacting the bodily fluid sample; an identification circuit for identifying one or more biomarkers analyzable using said electrochemical sensor structure; an analysis circuit comprising a set of coupling electrodes for electrically coupling to the first set of electrodes of the electrochemical sensor structure for analyzing the identified one or more biomarkers in the bodily fluid sample; a control circuit coupled to the identification and analysis circuit for determining a set of biosensing parameters based on the identified one or more biomarkers and for controlling the analysis circuit to analyze the identified one or more biomarkers in the bodily fluid sample based on the set of biosensing parameters; and an output for outputting an analysis result of the analysis of the identified one or more biomarkers in the bodily fluid sample.

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