Non-enzymatic biosensor

Abstract

Various biosensors for detecting biomolecules, biosensing devices including the biosensors and systems including the biosensing devices are described herein. The biosensors include a first electrode and a second electrode, and a piezoelectric layer placed between the first electrode and the second electrode. The first electrode includes one or more regions coated with one or more molecularly imprinted polymer (MIP) coatings, each configured to bind a molecule of interest. The biosensor is configured to detect a concentration of each of the molecules of interest by determining a resonant frequency of the piezoelectric layer when the one or more regions of the first electrode are in contact with a solution. The biosensor has a microwave-based configuration or an acoustic wave-based configuration.

Description

NON-ENZYMATIC BIOSENSORFIELD OF THE INVENTION

[0001] The described embodiments relate generally to biosensors and in particular, to a non-enzymatic biosensor.BACKGROUND

[0002] Individuals with various health conditions such as diabetes, cardiovascular diseases or respiratory disorders often need frequent monitoring of their physical conditions. Traditionally, this involves periodic hospital or clinic appointments overseen by a qualified healthcare professional. However, frequent appointments can be inconvenient or burdensome for individuals, leading to inadequate monitoring, in addition to requiring significant healthcare resources.

[0003] Remote biosensing devices have been developed as an alternative to frequent hospital / clinic appointments. Remote biosensing devices in the form of physical activity trackers can also be used by healthy individuals to assist in forming and maintaining healthy habits. Remote biosensing devices allow individuals to selfmonitor certain biomarkers, chemical or physiological parameters at home, which can be used to provide personalized, more precise and actionable health insights. In some cases, these devices can also allow medical professionals to monitor a patient’s health remotely, allowing for timely intervention and for treatment plans to be adjusted. Some of these remote biosensing devices can also allow for continuous, real-time monitoring, providing a more comprehensive understanding of an individual’s health.

[0004] However, these devices are often costly, bulky, unstable and their performance is often affected by changes in environmental conditions. Further, these devices can typically only detect one type of biomarker or chemical or physiological parameter. There is a need for improved biosensing devices.SUMMARY

[0005] The following summary is intended to introduce the reader to various aspects of the detailed description, but not to define or delimit any invention.

[0006] In accordance with one aspect of this disclosure, there is provided a biosensor for detecting biomolecules. The biosensor includes a first electrode and a second electrode; and a piezoelectric layer placed between the first electrode and thesecond electrode; the first electrode comprising one or more regions coated with a corresponding one or more molecularly imprinted polymer (MIP) coating, each MIP coating configured to bind a molecule of interest. The biosensor is configured to detect a concentration of each of the molecules of interest by determining a resonant frequency of the piezoelectric layer when the one or more regions of the first electrode are in contact with a solution.

[0007] In at least one embodiment, detecting the concentration of the molecules of interest comprises: determining a voltage value associated with the resonant frequency and a voltage value associated with a reference resonant frequency; determining a change in the voltage value; and correlating the change in the voltage value to the concentration of the molecules of interest.

[0008] In at least one embodiment, the MIP is produced through one of thermal polymerization, electrochemical polymerization and ultraviolet (UV) polymerization.

[0009] In at least one embodiment, the biosensor has one of a microwavebased configuration and an acoustic wave-based configuration.

[0010] In accordance with another aspect of this disclosure, there is provided a biosensing device comprising a transceiver coupled to the biosensor described herein, wherein the transceiver is configured to transmit sensor data obtained by the biosensor to an external device.

[0011] In accordance with another aspect of this disclosure, there is provided a system for obtaining a health-related output for an individual comprising the biosensing device described herein; and an analysis system in communication with the biosensing device configured to process sensor data received from the biosensing device to determine a health-related output.

[0012] In at least one embodiment, the health-related output is a concentration of the molecule of interest.

[0013] Other features and advantages of the present application will become apparent from the following detailed description taken together with the accompanying drawings. It should be understood, however, that the detailed description and the specific examples, while indicating preferred embodiments of the application, are given by way of illustration only, since various changes and modifications within the spirit and scope of the application will become apparent to those skilled in the art from this detailed description.DRAWINGS

[0014] Several embodiments will be described in detail with reference to the drawings, in which:

[0015] FIG. 1A shows a perspective view of an example non-enzymatic biosensor, in accordance with an embodiment;

[0016] FIG. 1 B shows a cross-sectional view of the biosensor of FIG. 1A;

[0017] FIG. 2 shows a schematic diagram of a mode of operation of a MIP layer.

[0018] FIG. 3A shows a cross-sectional view of an example bulk acoustic wave(BAW) resonator sensor;

[0019] FIG. 3B shows a cross-sectional view of another example BAW resonator sensor;

[0020] FIG. 3C shows a cross-sectional view of another example BAW resonator sensor;

[0021] FIG. 4A shows the biosensor of FIGS. 1 A-1 B in communication with an analysis system in accordance with an embodiment; and

[0022] FIG. 4B shows a biosensor device including the biosensor of FIGS.1A- 1 B in communication with an external device, in accordance with an embodiment.

[0023] The drawings, described below, are provided for purposes of illustration, and not of limitation, of the aspects and features of various examples of embodiments described herein. For simplicity and clarity of illustration, elements shown in the drawings have not necessarily been drawn to scale. The dimensions of some of the elements may be exaggerated relative to other elements for clarity. It will be appreciated that for simplicity and clarity of illustration, where considered appropriate, reference numerals may be repeated among the drawings to indicate corresponding or analogous elements or steps.DETAILED DESCRIPTION

[0024] Unless otherwise indicated, the definitions and embodiments described in this and other sections are intended to be applicable to all embodiments and aspects of the present application herein described for which they are suitable as would be understood by a person skilled in the art.

[0025] In understanding the scope of the present application, the term “comprising” and its derivatives, as used herein, are intended to be open ended terms that specify the presence of the stated features, elements, components, groups,integers, and / or steps, but do not exclude the presence of other unstated features, elements, components, groups, integers and / or steps. The foregoing also applies to words having similar meanings such as the terms, “including”, “having” and their derivatives. The term “consisting” and its derivatives, as used herein, are intended to be closed terms that specify the presence of the stated features, elements, components, groups, integers, and / or steps, but exclude the presence of other unstated features, elements, components, groups, integers and / or steps. The term “consisting essentially of”, as used herein, is intended to specify the presence of the stated features, elements, components, groups, integers, and / or steps as well as those that do not materially affect the basic and novel characteristic(s) of features, elements, components, groups, integers, and / or steps.

[0026] Terms of degree such as “substantially”, “about” and “approximately” as used herein mean a reasonable amount of deviation of the modified term such that the end result is not significantly changed. These terms of degree should be construed as including a deviation of at least ±5% of the modified term if this deviation would not negate the meaning of the word it modifies.

[0027] In addition, as used herein, the wording “and / or” is intended to represent an inclusive-or. That is, “X and / or Y” is intended to mean X or Y or both, for example. As a further example, “X, Y, and / or Z” is intended to mean X or Y or Z or any combination thereof.

[0028] As used in this application, the singular forms “a”, “an” and “the” include plural references unless the content clearly dictates otherwise.

[0029] As used herein and in the claims, two or more elements are said to be “coupled”, “connected”, “attached”, or “fastened” where the parts are joined or operate together either directly or indirectly (i.e. , through one or more intermediate parts), so long as a link occurs. As used herein and in the claims, two or more elements are said to be “directly coupled”, “directly connected”, “directly attached”, or “directly fastened” where the element are connected in physical contact with each other. None of the terms “coupled”, “connected”, “attached”, and “fastened” distinguish the manner in which two or more elements are joined together.

[0030] The terms "an embodiment," "embodiment," "embodiments," "the embodiment," "the embodiments," "one or more embodiments," "some embodiments,"and "one embodiment" mean "one or more (but not all) embodiments of the present invention(s)," unless expressly specified otherwise.

[0031] In embodiments comprising an “additional” or “second” component, the second component as used herein is physically different from the other components or first component. A “third” component is different from the other, first, and second components, and further enumerated or “additional” components are similarly different.

[0032] The term “and / or” as used herein means that the listed items are present, or used, individually or in combination. In effect, this term means that “at least one of” or “one or more” of the listed items is used or present.

[0033] Chronic conditions often require frequent or constant monitoring. Typically, these conditions are monitored by healthcare professionals, by collecting bodily fluid samples, such as blood tests, or urine samples, that must then be analyzed using specialized laboratory equipment. Attending frequent appointments can, however, be inconvenient or burdensome and can be impractical for individuals who lack transportation or who live in areas where the necessary medical installations are not available. This can lead to poor monitoring of these chronic conditions, which can be detrimental to individuals’ health.

[0034] Many conditions, however, can be monitored remotely, through the use of self-monitoring devices such as remote biosensing devices, which have been developed to allow individuals to self-monitor certain biomarkers or physiological parameters and to allow healthcare providers to monitor their patients remotely. These remote biosensing devices can sometimes provide continuous and real-time monitoring, which can allow an individual’s health to be monitored more closely and in a more comprehensive manner.

[0035] For example, by obtaining and analyzing real-time data, healthcare providers can tailor treatment plans and interventions based on an individual's specific health needs, improving overall outcomes. The remote monitoring and early intervention enabled by these remote biosensing devices can reduce healthcare costs associated with hospitalizations, emergency room visits, and complications resulting from undetected health issues. Some of these remote biosensing devices can also be integrated into physical activity trackers to assist individuals in forming and maintaining healthy habits.

[0036] Continuous glucose monitors and ketone monitors have emerged as a type of remote biosensing device. These devices use a small sensor that is inserted under the skin to continuously monitor glucose and ketone levels. The sensor measures glucose and ketone in the interstitial fluid that surrounds the body's cells, using enzymatic methods. Enzymatic methods however are typically costly, can be unstable and are susceptible to changes in environmental conditions, causing them to sometimes be unreliable for monitoring an individual’s glucose or ketone levels. These devices also typically require a battery to power the sensor which can require recharging or replacing, making them inconvenient.

[0037] Other biosensor devices also exist. However, similar to continuous glucose monitors and ketone monitors, these devices tend to be costly and unstable and tend to be bulky, rendering them inconvenient for continuous monitoring. Further, these sensors can typically only sense one type of biomarker or one physiological parameter. Individuals wanting to monitor more than one biomarker or physiological parameter accordingly often require more than one sensing device.

[0038] The present application provides a small non-enzymatic biosensor that can sense biomarkers such as, but not limited to, glucose, lactate, ketone, creatine and cortisol. The biosensor can sense biomarkers through the use of molecularly imprinted polymer (MIP) coatings applied to the sensor. As will be described, MIPs are synthetic polymers created through molecular imprinting that can selectively recognize and bind to specific target molecules. The sensor can be a wireless sensor that can communicate sensor data to an external system for analysis and / or display. The sensor can be used for remote monitoring of health conditions.

[0039] The biosensor can be a microwave-based sensor that has a microstripbased resonator, a coplanar waveguide (CPW) based resonator or a coaxial-based resonator configuration. The resonator of the biosensor can be open-circuited, short- circuited or can be a capacitively-loaded resonator. The configuration of the biosensor can be selected according to the application of the biosensor and the bandwidth required for the application.

[0040] Alternatively, the biosensor can be an acoustic wave-based sensor. For example, the biosensor can have a film bulk acoustic resonator (FBAR) configuration, in which the transducer of the biosensor is made of a film bulk acoustic resonator. Reference is briefly made to FIGS. 3A-3C, which show example acoustic wave-basedresonator configurations of a biosensor 300. As shown in FIG. 3A, the biosensor 300A can have a membrane-type FBAR configuration. As shown in FIG. 3B, the biosensor 300B can have an air gap-type FBAR configuration. As shown in FIG. 3C, the biosensor 300C can have a solidly mounted resonator (SMR)-type configuration. As shown in FIG. 3A-3C, the biosensor 300 includes a substrate 302, electrodes 308, a support layer 312 and a piezoelectric film 314. In the air gap-type FBAR configuration of FIG. 3B, the support layer 312 is positioned over an air gap 318. In the SMR-type configuration of FIG. 3C, Bragg reflectors 320 are arranged between the substrate 302 and the electrodes 308.

[0041] The transducer of the biosensor can have electrodes coated with one or more MIP coatings. The use of multiple MIP coatings can allow the biosensor to detect more than one biomarker / physiological parameter at a time. Since a MIP sensorallows for non-enzymatic measurement, the biosensor described herein can avoid disadvantages typically associated with enzymatic biosensors, such as high costs associated with enzymes and enzyme degradation. The biosensor can be a passive biosensor (i.e., a sensor which does not need any additional energy source), which can eliminate the need for costly and hazardous batteries typically required for operating biosensors.

[0042] Referring to FIGS.1 A-1 B, shown therein is a non-enzymatic sensor 100, in accordance with an embodiment. As described, the sensor 100 is configured for detecting biomarkers, for example, biomarkers in biological fluid such as interstitial fluid. In the example sensor of FIGS. 1A-1 B, the biosensor 100 is an acoustic wavebased sensor that has a film bulk acoustic resonator (FBAR) configuration, though as explained, the biosensor 100 can have a microwave-based configuration. As is commonly known to those skilled in the art of sensors, FBARs are a type of acoustic wave-based resonator that use piezoelectric materials to generate an electric charge in response to detecting mechanical vibrations. The sensor can be a standalone sensor and can be implemented as a patch that can be placed on the surface of a user’s skin. Alternatively, the sensor 100 can be integrated into, attached to or placed in close adhesion to a device, for example but not limited to, a wearable device such as an infusion pump.

[0043] The high-frequency stability and low insertion loss of FBAR can provide particular advantages to the biosensor 100. For example, the high-frequency stabilityof the biosensor 100 can allow the biosensor 100 to operate at higher frequencies which can allow the biosensor 100 to more easily detect small changes in the properties of the biological fluid being sensed by the biosensor 100 and in turn allows small amounts of a biomarker to be detected in the fluid. The biosensor can be operable in the gigahertz range. By operating at a higher frequency, the size of the biosensor can also be reduced. The biosensor 100 can accordingly be smaller in size than traditional biosensors.

[0044] As explained, the biosensor 100 can be a passive sensor that does not require a physical external energy source (e.g., battery) for detecting biomolecules.

[0045] As shown, the sensor 100 consists of a substrate 102 providing structural support, one or more reflector layers 104, a thin film piezoelectric layer 106 and electrodes 108. The substrate can be made of any appropriate biocompatible, high frequency substrate material, including, but not limited to a silicon layer. One or more reflector layers 104 can consist of a one or more high impedance layers and one or more low impedance layers. The piezoelectric layer can be made of any piezoelectric material, including but not limited to Aluminum Nitride (AIN), zinc oxide (ZnO) and lead zirconate titanate (PZT).

[0046] In embodiments where the biosensor is a microwave-based sensor, the substrate can be made of any appropriate biocompatible, high frequency substrate material and in at least one embodiment, the substrate is made of a polytetrafluoroethylene-alumina composite.

[0047] As shown in FIG. 1 B, a first electrode layer 108 can be placed underneath the piezoelectric layer 106, above the reflector layers 104 and a second electrode layer 108 can be placed on the top surface of the piezoelectric layer 106 so that the piezoelectric layer 106 is placed between two electrode layers 108. When an alternating electrical signal is applied across these electrodes 108, an electric field that induces mechanical vibrations in the piezoelectric layer 106 is induced. The first and second electrode layers 108 can be placed under the skin of the user, for example, at a depth of about 5mm-9mm. The electrodes 108 can be coupled to an oscillator circuit that can generate an alternating electric signal. The oscillator circuit can oscillate at a predetermined frequency. The electrode layers 108 can be made of any conducting material, for example, copper, aluminum, molybdenum, etc. and coated with a layer of gold.

[0048] The electrode layers 108 can be coupled directly or indirectly to a signal generator generating the alternating electric signal. For example, the electrode layers 108 can be connected to an electronic oscillator circuit. The signal generator can be proximate to the sensor 100. For example, when the sensor 100 is a standalone sensor implemented as a patch, the signal generator can be on the patch. In operation, the piezoelectric layer 106 vibrates at its resonant frequency when the applied electrical signal matches the natural frequency of the piezoelectric layer 106, generating acoustic waves that propagate through the sensor. In an FBAR, the thickness of the piezoelectric layer 106 determines the resonant frequency of the FBAR and accordingly, the resonant frequency of the FBAR can be precisely tuned during fabrication, by controlling the thickness of the piezoelectric layer 106.

[0049] In the embodiment shown in FIGS. 1A-1 B, as shown, the sensor 100 includes a first MIP-coated region 110a for detecting a first biomarker and a second MIP-coated region 110b for detecting a second biomarker. For example, the first MIP- coated region 110a can be sensitive to glucose (i.e., it can bind glucose molecules), while the second MIP-coated region 110b can be sensitive to lactate (i.e., it can bind lactate molecules). As shown, the MIP can be placed on or can coat a portion of the electrode 108. The MIP coating can be formed through a polymerization process, for example, using thermal polymerization, electrochemical polymerization or UV polymerization, as those techniques are commonly known in the art of polymerization. The different MIP-coated regions 110 can enable the sensor 100 to detect multiple target molecules, simultaneously.

[0050] To form the MIP coating, a functional monomer and the molecule of interest serving as a template molecule are mixed to form a solution. This solution is then combined with a solution of cross-linking agents. The functional monomer is selected based on its ability to interact with the functional groups of the target molecule.

[0051] The solution is then polymerized, for example, using thermal polymerization, electrochemical polymerization or UV polymerization. During polymerization, the functional monomer and cross-linking agents undergo polymerization where the functional monomer surrounds the template molecule, creating a polymer matrix with specific binding sites that mirror the shape, size, and functional groups of the template molecule.

[0052] The bulk polymer obtained is then applied to the surface of an electrode 108 of the sensor 100. Since the solution rapidly vaporizes, a thin layer of MIP is formed on the surface of the sensor.

[0053] In some embodiments, the bulk polymer is washed with water to remove any non-polymerized monomers and solvents and dried in an oven prior to being applied to the surface of the electrode 108.

[0054] In some embodiments the bulk polymer is milled to produce a fine powder and mixed with an adhesion solution before being applied to the surface of the electrode 108.

[0055] In some embodiments, the sensor with MIP formed on the surface of the sensor is dried in the oven to evaporate any remaining solvent.

[0056] Once the MIP is applied to the biosensor 100, the template molecule is then removed from the MIP by washing the coated sensor with deionized water, leaving behind cavities (as shown by 202, 204 in FIG. 2) that are complementary to the molecular structure of the template molecule (i.e. , imprints) as shown in FIG. 2

[0057] The resulting MIP formed is a MIP that has specific binding sites that can selectively recognize and bind to the template molecule or molecules with similar structural features. As shown in FIG. 2, when the target molecule of interest 220 comes into contact with the MIP 200, the MIP 200 binds to the molecule 220 and does not bind to other molecules 210 (i.e., molecules which are not the target molecule of interest).

[0058] The process can be repeated for each target molecule of interest. For example, the MIP for each target molecule can be prepared separately and applied to different portions of the electrode of the sensor to produce a sensor that is sensitive to more than one target molecule.

[0059] When a MIP-coated region 110 of the electrode 108 is exposed to a biomolecule of interest that the MIP can bind, for example, when a solution containing the biomarker comes into contact with the MIP-coated region 110 of the electrode 108, the MIP-coated region 110 binds the biomolecule of interest, resulting in a change in the mass of the electrode 108, which in turns results in a change in the resonant frequency of the piezoelectric layer 106. The acoustic waves generated by thepiezoelectric layer 106 can be converted into voltage measurements by an oscillator coupled to the biosensor 100, and the voltage measurements can be recorded and transmitted to an external system for analysis. Based on the recorded resonant frequency of the piezoelectric layer 106, the concentration of the biomolecule in the sample can be determined, for example, by comparing the recorded voltage value and a reference voltage value of the piezoelectric layer 106. The reference voltage value of the piezoelectric layer 106 can correspond to the voltage associated with the resonant frequency of the piezoelectric layer 106 when the electrode layer 108 adjacent to the piezoelectric layer is not coated with a MIP layer, for example, when the electrode layer 108 is coated with a non-molecularly imprinted polymer (NIP) (i.e., a polymer that does not include binding sites for the molecule(s) of interest).

[0060] The change in resonant frequency or voltage can be correlated with a biomarker concentration. For example, each resonant frequency or voltage value can be associated with a concentration of the biomarker of interest.

[0061] Although FIGS. 1A-1 B show two MIP-coated regions 110a, 110b, the sensor 100 can have more than two MIP-coated regions, and each region can be configured to detect a different biomarker, allowing the sensor 100 to detect multiple biomarkers simultaneously. In such cases, the resonant frequency of each region can be determined to determine a concentration of each biomarker of interest.

[0062] Referring now to FIG. 4A, shown therein is a block diagram of the sensor 100 coupled with an external device 430 which is in communication with an analysis system 400 via a network 404. Reference is simultaneously made to FIG. 4B, which shows the sensor 100 in communication with the external device 430. Though only one sensor 100 is shown, the analysis system 400 may be in communication with a plurality of sensors 100 (via one or more external devices 430). The analysis system 400 can receive raw sensor data (e.g., voltage measurements) from the sensor 100 via the external device 430. The analysis system 400 may then process or evaluate the raw sensor data to determine various characteristics of the sensor data. For example, the analysis system 400 can determine a concentration of a biomarker.

[0063] The analysis system 400 may include a processor, a data storage, and a communication interface. The analysis system 400 can include computer-executable instructions stored in the data storage that can be executed by the processor to configure the processor to perform various analysis processes. The analysis system 400 may be provided using various computing devices such as, for example, anelectronic tablet device, a personal computer, workstation, server, portable computer, mobile device, personal digital assistant, laptop, smart phone, WAP phone, an interactive television, video display terminals, gaming consoles, and portable electronic devices etc. In some cases, the analysis system 400 can be provided by multiple components over a wide geographic area.

[0064] The analysis system 400 can process and / or analyze the sensor data to generate an output that is viewable by a user, for example, the individual whose biomarkers are being assessed or a healthcare professional monitoring the condition of the individual. For example, the analysis system 400 can generate an output that is viewable on a smartphone, smartwatch, or other device having a graphical user interface for viewing the output. The output can be for example, a level of a biomarker of interest, a level of the biomarker of interest over time, a graphical representation of the level of biomarker overtime or over a predetermined time window, etc. In some embodiments, the analysis system 400 is configured to process the sensor data to provide insights about the user’s health. For example, the analysis system 400 can determine that a user’s level of a biomolecule of interest is high and accordingly that the user should monitor their level of that biomolecule of interest more closely.

[0065] The sensor 100 can transmit sensor data to the analysis system 400 in real time via a transmitter coupled to the sensor 100 and the analysis system 400 can process and / or analyze the sensor data in real time or in near real time.

[0066] As shown in FIG. 4B, which shows a biosensor device, the sensor 100 can be connected to a transceiver 420 which can transmit sensor data to the external device 430. In some embodiments, the transceiver receives signals from the external device 430. In some embodiments, the external device 430 can implement one or more features of the analysis system 400 of FIG. 4A. Alternatively, the external device 430 can be in communication with the analysis system 400. For example, the external device 430 can receive sensor data from the sensor 100 via the transceiver 420 and transmit the sensor data to the analysis system 400 for analysis. The transceiver 420 can be comprised within an antenna and the sensor data can be transmitted to the external device 430 via radio frequency (RF) signals. As shown, the sensor 100 can be implemented on a patch 410 and the transceiver 420 can be placed on the patch 410 in communication with the sensor 100.

[0067] In some embodiments, the biosensor 100 includes one or more means for energy harvesting. For example, the biosensor 100 can include means for harvesting kinetic energy, and / or energy produced by the electromagnetic field of the transducer of the biosensor 100. As another example, the biosensor 100 can include means for harvesting solar energy. For example, the patch 410 can include one or more means for harvesting energy. The energy harvested can be used to provide power to the oscillator circuit that applies the alternating electrical signal to the biosensor 100.

[0068] In some embodiments, the biosensor 100 includes devices for storing energy, including energy harvested and energy generated by components of the biosensor 100.

[0069] Returning to FIG. 4A, the network 404 may be any network capable of carrying data, including the Internet, Ethernet, plain old telephone service (POTS) line, public switch telephone network (PSTN), integrated services digital network (ISDN), digital subscriber line (DSL), coaxial cable, fiber optics, satellite, mobile, wireless (e.g. Wi-Fi, WiMAX), SS7 signaling network, fixed line, local area network, wide area network, and others, including any combination of these, capable of interfacing with, and enabling communication between, the sensor 100 and the analysis system 400.

[0070] While the present application has been described with reference to examples, it is to be understood that the scope of the claims should not be limited by the embodiments set forth in the examples, but should be given the broadest interpretation consistent with the description as a whole.

[0071] ITEMS

[0072] Item 1. A biosensor for detecting biomolecules comprising: a first electrode and a second electrode; and a piezoelectric layer placed between the first electrode and the second electrode; the first electrode comprising one or more regions coated with a corresponding one or more molecularly imprinted polymer (MIP) coating, each MIP coating configured to bind a molecule of interest; and wherein the biosensor is configured to detect a concentration of each molecule of interest by determining a resonant frequency of the piezoelectric layer when the one or more regions of the first electrode are in contact with a solution.

[0073] Item 2. The biosensor of any preceding item, wherein detecting the concentration of each molecule of interest comprises: determining a voltage valueassociated with the resonant frequency and a voltage value associated with a reference resonant frequency; determining a change in the voltage value; and correlating the change in the voltage value to the concentration of the molecules of interest.

[0074] The biosensor of any preceding item, wherein the MIP coating is produced through one of thermal polymerization, electrochemical polymerization and ultraviolet (UV) polymerization.

[0075] The biosensor of any preceding item, wherein the biosensor has a microwave-based configuration.

[0076] The biosensor of any preceding item, wherein the biosensor has a microstrip-based resonator.

[0077] The biosensor of any preceding item, wherein the biosensor has a coplanar waveguide (CPW) based resonator.

[0078] The biosensor of any preceding item, wherein the biosensor has a coaxial-based resonator.

[0079] The biosensor of any preceding item, wherein the biosensor has a capacitively-loaded resonator.

[0080] The biosensor of any preceding item, wherein the biosensor has an acoustic wave-based configuration.

[0081] The biosensor of any preceding item, wherein the biosensor has a film bulk acoustic resonator (FBAR).

[0082] The biosensor of any preceding item, further comprising a support layer below the second electrode and a substrate below at least a part of the support layer.

[0083] The biosensor of any preceding item, further comprising a support layer below the second electrode, a substrate below the support layer, and an air gap between the substrate and at least a portion of the support layer.

[0084] The biosensor of any preceding item, further comprising Bragg reflectors between a substrate and the second electrode.

[0085] The biosensor of any preceding item, wherein the one or more regions coated with a corresponding one or more MIP coating comprises a first MIP-coated region for detecting a first biomarker and a second MIP-coated region for detecting a second biomarker.

[0086] The biosensor of any preceding item, wherein at least one of the first MIP-coated region and the second MIP-coated region is sensitive to glucose molecules.

[0087] The biosensor of any preceding item, wherein at least one of the first MIP-coated region and the second MIP-coated region is sensitive to lactate molecules.

[0088] The biosensor of any preceding item, wherein the first MIP-coated region is sensitive to glucose molecules and the second MIP-coated region is sensitive to lactate molecules.

[0089] A biosensing device comprising a transceiver coupled to the biosensor of any preceding item, wherein the transceiver is configured to transmit sensor data obtained by the biosensor to an external device.

[0090] A system for obtaining a health-related output for an individual comprising: the biosensing device of any preceding item; and an analysis system in communication with the biosensing device configured to process sensor data received from the biosensing device to determine a health-related output.

[0091] The system of any preceding item, wherein the health-related output is a concentration of the molecule of interest.

Claims

Claims:1 . A biosensor for detecting biomolecules comprising: a first electrode and a second electrode; and a piezoelectric layer placed between the first electrode and the second electrode; the first electrode comprising one or more regions coated with a corresponding one or more molecularly imprinted polymer (MIP) coating, each MIP coating configured to bind a molecule of interest; and wherein the biosensor is configured to detect a concentration of each molecule of interest by determining a resonant frequency of the piezoelectric layer when the one or more regions of the first electrode are in contact with a solution.

2. The biosensor of claim 1 , wherein detecting the concentration of each molecule of interest comprises: determining a voltage value associated with the resonant frequency and a voltage value associated with a reference resonant frequency; determining a change in the voltage value; and correlating the change in the voltage value to the concentration of the molecules of interest.

3. The biosensor of claims 1 or 2, wherein the MIP coating is produced through one of thermal polymerization, electrochemical polymerization and ultraviolet (UV) polymerization.

4. The biosensor of any one of claims 1 to 3, wherein the biosensor has a microwavebased configuration.

5. The biosensor of claim 4, wherein the biosensor has a microstrip-based resonator.

6. The biosensor of claim 4, wherein the biosensor has a coplanar waveguide (CPW) based resonator.

7. The biosensor of claim 4, wherein the biosensor has a coaxial-based resonator.

8. The biosensor of any one of claims 4 to 7, wherein the biosensor has a capacitively- loaded resonator.

9. The biosensor of any one of claims 1 to 3, wherein the biosensor has an acoustic wave-based configuration.

10. The biosensor of claim 9, wherein the biosensor has a film bulk acoustic resonator (FBAR).

11. The biosensor of claim 10, further comprising a support layer below the second electrode and a substrate below at least a part of the support layer.

12. The biosensor of claim 10, further comprising a support layer below the second electrode, a substrate below the support layer, and an air gap between the substrate and at least a portion of the support layer.

13. The biosensor of claim 10, further comprising Bragg reflectors between a substrate and the second electrode.

14. The biosensor of any one of claims 1 to 13, wherein the one or more regions coated with a corresponding one or more MIP coating comprises a first MIP-coated region for detecting a first biomarker and a second MIP-coated region for detecting a second biomarker.

15. The biosensor of claim 14, wherein at least one of the first MIP-coated region and the second MIP-coated region is sensitive to glucose molecules.

16. The biosensor of claim 14, wherein at least one of the first MIP-coated region and the second MIP-coated region is sensitive to lactate molecules.

17. The biosensor of claim 14, wherein the first MIP-coated region is sensitive to glucose molecules and the second MIP-coated region is sensitive to lactate molecules.

18. A biosensing device comprising a transceiver coupled to the biosensor of claim 1 , wherein the transceiver is configured to transmit sensor data obtained by the biosensor to an external device.

19. A system for obtaining a health-related output for an individual comprising: the biosensing device of claim 18; and an analysis system in communication with the biosensing device configured to process sensor data received from the biosensing device to determine a health-related output.

20. The system of claim 19, wherein the health-related output is a concentration of the molecule of interest.

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