[0001] Embodiments generally relate to sensor devices for detecting pathogens, such as respiratory pathogens.

Background

[0002] Respiratory pathogens can be difficult to detect. In most cases, sophisticated equipment is required in order to be able to determine the existence or type of a particular pathogen carried by a person or existing in a space or on a surface.

[0003] Further, determining the existence of such pathogens in a particular location or carried by a particular person usually takes time and is not practical to determine in real time. For example, samples may be forwarded to a lab. Even at relatively high efficiency, such processing in a laboratory can often take at least 24 hours to determine the presence or absence of the pathogen

[0004] It is desired to address or ameliorate one or more shortcomings or disadvantages associated with prior techniques for detecting respiratory pathogens, or to at least provide a useful alternative thereto.

[0005] Throughout this specification the word "comprise", or variations such as "comprises" or "comprising", will be understood to imply the inclusion of a stated element, integer or step, or group of elements, integers or steps, but not the exclusion of any other element, integer or step, or group of elements, integers or steps.

[0006] Any discussion of documents, acts, materials, devices, articles or the like which has been included in the present specification is not to be taken as an admission that any or all of these matters form part of the prior art base or were common general knowledge in the field relevant to the present disclosure as it existed before the priority date of each of the appended claims. Summary

[0007] Some embodiments relate to an access system, comprising: an access portal separating a first area from a second area; an access actuator to control access to the second area from the first area via the access portal; a reader device in communication with the access actuator and configured to provide an access signal to the access actuator to allow access via the access portal; an access object carrying a sensor device for detecting a pathogen, the sensor device including: a flexible carrier substrate having a first side and an opposite second side; at least one sensor portion on the carrier substrate, the at least one sensor portion including: a carrier matrix carrying a first custom imprinted molecular polymer (CIMP) exposed or exposable to fluid and disposed on the first side of the carrier substrate, wherein the first CIMP is designed to interact with a first pathogen by geometric and chemical binding, a first pair of electrodes disposed in or adjacent the carrier matrix so that electrical potential between the electrodes of the first pair is affected by binding of the first CIMP with the first pathogen; a processor on the flexible carrier substrate and configured to receive an output signal from the first pair of electrodes indicative of a presence or absence of the first pathogen on the carrier matrix; and a coil disposed on the flexible carrier substrate to energise to act as a power source of the sensor device when the coil is positioned in proximity to an excitation field; and an antenna in communication with the processor to transmit a sensor output from the processor to the reader device; wherein the reader device is configured to generate the access signal based on the sensor output.

[0008] The access object may include an access card carrying the sensor device. The access object may include a cover layer defining an aperture on the first side on the carrier substrate, the aperture being sized and positioned to expose the CIMPs to the fluid through the aperture.

[0009] The first pathogen may be a respiratory pathogen. The first pathogen may be one of: rhinoviruses, coronaviruses, influenza viruses (A&B) and tuberculosis. The first pathogen may be SARS-CoV2.

[0010] The first pathogen may be one of: ebola, arenavirus, Mycobacterium leprae, adenovirus, Group A haemolytic streptococci, parainfluenza, Streptococcus pneumonia, Mycoplasma pneumonia, Klebsiella pneumonia, Herpes simplex virus, Candida Albicans, haemophilus influenza, Legionella, E.Coli, Aspergillus, Legionnaires disease and Cytomegalovirus.

[0011] Some embodiments relate to a pathogen detection system, comprising: a sensor housing mounted on a surface in an enclosed or encloseable space; a fan configured to draw air into the housing through an inlet aperture defined by the housing and to expel air through an outlet aperture defined by the housing; a sensor device disposed in the sensor housing for detecting a pathogen in air drawn into the sensor housing, the sensor device including: a flexible carrier substrate having a first side and an opposite second side; at least one sensor portion on the carrier substrate, the at least one sensor portion including: a carrier matrix carrying a first custom imprinted molecular polymer (CIMP) exposed or exposable to air and disposed on the first side of the carrier substrate, wherein the first CIMP is designed to interact with a first pathogen by geometric and chemical binding; a first pair of electrodes disposed in or adjacent the carrier matrix so that electrical potential between the electrodes of the first pair is affected by binding of the first CIMP with the first pathogen; a processor on the flexible carrier substrate and configured to receive an output signal from the first pair of electrodes indicative of a presence or absence of the first pathogen on the carrier matrix; a transmitter in communication with the processor to transmit a sensor output from the processor to a reader device.

[0012] The transmitter may include a wireless transmitter, and the sensor device may include an excitation coil on the carrier substrate for powering the sensor device in response to an excitation field.

[0013] The surface may be a wall surface. The surface may be a static surface of a movable object. The surface may be a movable surface. [0014] The first pathogen may be a respiratory pathogen. The first pathogen may be one of: rhinoviruses, coronaviruses, influenza viruses (A&B) and tuberculosis. The first pathogen may be SARS-CoV2.

[0015] The first pathogen may be one of: ebola, arenavirus, Mycobacterium leprae, adenovirus, Group A haemolytic streptococci, parainfluenza, Streptococcus pneumonia, Mycoplasma pneumonia, Klebsiella pneumonia, Herpes simplex virus, Candida Albicans, haemophilus influenza, Legionella, E.Coli, Aspergillus, Legionnaires disease and Cytomegalovirus.

[0016] Some embodiments relate to a sensor device for detecting a pathogen, including: a carrier substrate having a first side and an opposite second side; at least one sensor portion on the carrier substrate, the at least one sensor portion including: a carrier matrix carrying a first custom imprinted molecular polymer (CIMP) exposed or exposable to air and disposed on the first side of the carrier substrate, wherein the first CIMP is designed to interact with a first pathogen by geometric and chemical binding; a first pair of electrodes disposed in or adjacent the carrier matrix so that electrical potential between the electrodes of the first pair is affected by binding of the first CIMP with the first pathogen; a processor on the flexible carrier substrate and configured to receive an output signal from the first pair of electrodes indicative of a presence or absence of the first pathogen on the carrier matrix; and an antenna in communication with the processor to transmit a sensor output from the processor to a probe device. [0017] Some embodiments relate to a sensor device for detecting a respiratory pathogen, including: a flexible carrier substrate having a first side and an opposite second side; at least one sensor portion on the carrier substrate, the at least one sensor portion including: a carrier matrix carrying a first custom imprinted molecular polymer (CIMP) exposed or exposable to air and disposed on the first side of the carrier substrate, wherein the first CIMP is designed to interact with a first pathogen by geometric and chemical binding; a first pair of electrodes disposed in or adjacent the carrier matrix so that electrical potential between the electrodes of the first pair is affected by binding of the first CIMP with the first pathogen; a processor on the flexible carrier substrate and configured to receive an output signal from the first pair of electrodes indicative of a presence or absence of the first pathogen on the carrier matrix; an attachment structure on at least part of the second side to attach the sensor to an object; and an antenna in communication with the processor to transmit a sensor output from the processor to a probe device.

[0018] The sensor device may further include an excitation coil on the carrier substrate for powering the sensor device in response to an excitation field. The sensor device may be free of a built-in power source.

[0019] The at least one sensor portion may include a second CIMP carried by the carrier matrix and a second pair of electrodes disposed in or adjacent the carrier matrix, wherein the second CIMP is designed to interact with a second pathogen by geometric and chemical binding and wherein electrical potential between the electrodes of the second pair is affected by binding of the second CIMP with the second pathogen.

[0020] The at least one sensor portion may include a second CIMP carried by the carrier matrix and a second pair of electrodes disposed in or adjacent the carrier matrix, wherein the second CIMP is designed to interact with the first pathogen by geometric and chemical binding and wherein electrical potential between the electrodes of the second pair is affected by binding of the second CIMP with the first pathogen.

[0021] The processor may be configured to receive an output signal from each pair of electrodes of the at least one sensor portion. The sensor output may include a unique identifier of the sensor device.

[0022] The attachment structure may include a bonding layer. The sensor device may further include a removable backing layer to expose the bonding layer for bonding by attachment to the object. The sensor device may further include a cover layer to cover and seal the first side of the carrier substrate other than the carrier matrix of each at least one sensor portion.

[0023] Some embodiments relate to an object carrying the sensor device according to embodiments described herein.

[0024] Some embodiments relate to an object having affixed thereto the sensor device according to embodiments described herein.

[0025] Some embodiments relate to use of the sensor device according to embodiments described herein to detect the presence of a pathogen.

[0026] Some embodiments relate to a system comprising: at least one of the sensor device according to embodiments described herein disposed in a built environment; a reader device configured to communicate with the processor of each at least one sensor device to identify whether each at least one sensor device has detected the presence of a pathogen in the built environment.

[0027] The system may further comprise a server in communication with the reader device, the server having access to storage for storing data relating to each at least one sensor.

[0028] Some embodiments relate to a system comprising: a reader device configured to communicate with the processor of at least one of the sensor device of any one of claims 17 to 26 disposed in a built environment, and configured to identify whether each at least one sensor device has detected the presence of a pathogen in the built environment.

[0029] Some embodiments relate to a portable respiratory pathogen detector, comprising: a detector housing, the detector housing having an exhalation capture port and being of a size to be held in a human hand; a sensor device for detecting a respiratory pathogen, the sensor device disposed in the detector housing and positioned to be exposed to exhaled breath received through the exhalation capture port, the sensor device including: a carrier substrate having a first side and an opposite second side; at least one sensor portion on the carrier substrate, the at least one sensor portion including: a carrier matrix carrying a first custom imprinted molecular polymer (CIMP) exposed or exposable to air and disposed on the first side of the carrier substrate, wherein the first CIMP is designed to interact with a first pathogen by geometric and chemical binding; a first pair of electrodes disposed in or adjacent the carrier matrix so that electrical potential between the electrodes of the first pair is affected by binding of the first CIMP with the first pathogen; a sensor processor on the flexible carrier substrate and configured to receive an output signal from the first pair of electrodes indicative of a presence or absence of the first pathogen on the carrier matrix and to generate a sensor output based on the output signal; and a detector processor in the detector housing and configured to receive the sensor output, the detector processor being configured to determine a detection result based on the sensor output and to at least one of: cause the detection result to be displayed on a display of the detector housing, or to transmit the detection result to an external device.

[0030] Some embodiments relate to a face covering including the sensor device of embodiments described herein, wherein the sensor device is coupled to the face covering to detect the presence of a pathogen. The sensor device may be attached to a surface of the face covering. The sensor device may be positioned on the face covering to overly an area on or near the nose or mouth when the face covering is worn by a wearer.

[0031] In some embodiments, the sensor portion of the sensor device is configured so that, after a first detection of a pathogen, the sensor portion is treatable to allow for at least a second detection of the pathogen. Key to Sequence Listing

SEQ ID NO: 1 is an amino acid sequence of forkhead-associated protein (FHA)

SEQ ID NO: 2 is an amino acid sequence of SARS CoV-2 S2Pi ₂ os-FHA SEQ ID NO: 3 is an amino acid sequence of a flexible linker SEQ ID NO: 4 is an amino acid sequence of a poly His tag SEQ ID NO: 5 is an amino acid sequence of an Avi tag SEQ ID NO: 6 is an amino acid sequence of a modified receptor binding domain (RBD) of SARS-CoV2 virus spike protein

SEQ ID NO: 7 is an amino acid sequence of RBD ectodomain sequence

(amino acids 332-532) from the Wuhan Flu-1 isolate

SEQ ID NO: 8 is an amino acid sequence of a S glycoprotein ectodomain sequence (residues 16-1208) from the Wuhan Flu-1 isolate

Brief Description of Drawings

[0032] Embodiments are described in greater detail below, with reference to the accompanying drawings, in which:

[0033] Figure 1 is a block diagram of an example system employing sensors to detect respiratory pathogens;

[0034] Figure 2A is a perspective view of a sensor device for detecting respiratory pathogens according to some embodiments;

[0035] Figure 2B is a plan view of the sensor device of Figure 2 A;

[0036] Figure 3 is an exploded perspective view of the sensor device of Figure 2A;

[0037] Figure 4 is a schematic illustration of a sensor portion of the sensor device of Figure 2A; [0038] Figure 5A is a perspective view of a sensor chip forming part of the sensor device of some embodiments;

[0039] Figure 5B is a side elevation view of the sensor chip shown in Figure 5A;

[0040] Figure 5C is a plan view of the sensor chip shown in Figure 5A;

[0041] Figure 5D is an exploded prospective view of the sensor chip of Figure 5 A;

[0042] Figure 5E is a schematic illustration of a sensor chip according to further embodiments;

[0043] Figure 6 is a schematic illustration of a process of binding an antigen, such as a respiratory pathogen, to a sensor portion;

[0044] Figure 7 is a schematic illustration of binding antigens to a sensor portion of a sensor chip according to some embodiments;

[0045] Figure 8A is a schematic diagram to illustrate circuitry of the sensor device according to some embodiments;

[0046] Figure 8B is a circuit diagram of electrical circuitry of the sensor device according to some embodiments;

[0047] Figure 9A is a schematic illustration of an example access object carrying a sensor device on a front side of the access card according to some embodiments;

[0048] Figure 9B is a perspective view of a rear side of the access object of Figure 9A;

[0049] Figure 10 is a perspective view of a carrier including the access object of Figure 9A; [0050] Figure 11 A is an exploded view of a face mask including the sensor device according to some embodiments;

[0051] Figure 1 IB is a side view of the mask of Figure 11A, showing the sensor device disposed between fabric layers of the face mask;

[0052] Figure 12 is a schematic illustration of the face mask of Figure 11 A being worn by a person;

[0053] Figure 13 is a schematic illustration of part of an access system in which a carrier including the access object of Figure 9A is positioned close to a wireless reader device for authorising access to an access portal, such as a door;

[0054] Figure 14 is a schematic illustration of an access system for locking or unlocking the access portal, depending on interaction of the access object with the wireless reader as shown in Figure 13;

[0055] Figure 15A is a schematic illustration of a pathogen detection system including a wall-mounted sensor device for detecting respiratory pathogens in an enclosed space, such as an elevator, according to some embodiments;

[0056] Figure 15B illustrates an example location of the wall-mounted sensor device of Figure 15 A;

[0057] Figure 16 is a schematic illustration of a portable respiratory pathogen detector, shown in the exemplary form of a handheld breath detector including a sensor device according to some embodiments, configured to detect respiratory pathogens in an exhaled breath of a person;

[0058] Figure 17 is a flowchart of an example process executed by a processor of the sensor device according to some embodiments; [0059] Figure 18 is a graph of resistance change vs concentration of spike protein in a pathogen detection test;

[0060] Figure 19 is a graph of resistance change vs concentration of spike protein in another pathogen detection test;

[0061] Figure 20A is a graph illustrating the efficiency of reusing a sensor portion after treating with pure isopropyl alcohol according to some embodiments;

[0062] Figure 20B is a graph illustrating the efficiency of reusing a sensor portion after treating with acetic acid according to some embodiments;

[0063] Figure 21 is a schematic illustration of an example use case of a face mask including a sensor device;

[0064] Figure 22 is a graph illustrating the cross-selectivity of a sensor device according to some embodiments;

[0065] Figure 23A is a graph illustrating the detection efficiency of a sensor device for various pathogen variants according to some embodiments;

[0066] Figure 23B is a graph illustrating the detection efficiency of a sensor device for various pathogen variants according to some embodiments; and

Figure 24 is a graph illustrating the detection efficiency of a sensor device for various pathogen variants when utilising a spraying application method.

Detailed Description

[0067] Embodiments generally relate to sensor devices for detecting respiratory pathogens. The present disclosure describes the application of such sensor devices in various ways, such as by including the sensor devices in or on movable or static objects, so that respiratory pathogens present in a fluid contacting a sensing portion of the sensor device can be detected.

[0068] In particular, embodiments generally relate to sensor devices carrying custom imprinted molecular polymers (CIMP) that are designed or configured to interact with particular pathogens that can be carried through the air, for example, by being exhaled through a person’ s breath. The Sensor device may carry one or multiple sensor portions. Each sensor portion of the sensor device has a pair of electrodes disposed on or adjacent the carrier matrix, with the CIMP disposed between the electrodes, so that measurement of electrical potential between the electrodes can allow detection of binding of the CIMP with the pathogen to which it is configured to bind. In this way, respiratory pathogens contacting the CIMP on the carrier substrate from a fluid, such as air, saliva, vapour, liquid droplets or another carrier fluid, can be electrically detected.

[0069] Embodiments of the sensor device can be configured to have multiple sensing portions on the sensor device for providing multiple detection locations for the same respiratory pathogen or for detecting multiple different respiratory pathogens.

[0070] The sensor device can be used in a number of different scenarios in order to detect respiratory pathogens. For example, as is described below, some embodiments of sensor devices can be attached to a movable or manually portable object, such as a face mask or an access card. In further examples, sensor devices according to some embodiments can be attached to fixed objects, such as a seatback of an airplane, train or bus, a wall surface or a gate, in an area where it is desired to know whether a respiratory pathogen is present or absent in the vicinity of the object. In further examples, sensor devices can be attached to moveable objects, including carts, vehicles, clothing, similar objects or handheld detection devices.

[0071] Embodiments advantageously allow rapid electrical and electronic determination of whether a particular pathogen has come into fluid contact with the sensor device. This rapid pathogen presence determination technology has many potential applications, some of which are described herein. [0072] Referring now to Figure 1 , a sensing system 100 is described. Sensing system 100 includes at least one sensor device 120 and possibly many such sensor devices 120 in the same or different locations. Each sensor device 120 includes a processor 124, a first pathogen sensing portion 126, and in some embodiments multiple pathogen sensing portions, including a second pathogen sensing portion 128, each of which is configured to be electrically probed by the processor 124. In various embodiments, one or more sensor devices 120 in system 100 include an antenna 122 and coil 123 for wireless excitation and communication with a reading device. The antenna 122 and coil 123 can be used for near field communication (NFC) according to known techniques.

In other embodiments, where wireless excitation and communication with a reading device is not required, for example due to a wired connection being available, the antenna 122 and/or coil 123 may not be present as part of sensor 120.

[0073] Sensing system 100 further includes at least one sensor reader 119, which may form part of a computing device 110 or a standard wireless access card reader, for example. The sensor device 120 includes an excitation coil 123 responsive to an excitation field, such as an electric field, generated by a reader device according to existing technologies. The reader device may be, form part of or include any suitable device capable of generating an excitation field to induce current flow in the excitation coil 123 and communicate with the sensor 120 via the antenna. Where sensor device communicates in the manner of a (passive) NFC tag, the reader device may act as a NFC reader according to known techniques, for example.

[0074] Figure 1 illustrates the computing device 110 as including a sensor reader 119 for communicating with the sensor device 120. Thus, computing device 110 is one example of a reader device. Further examples of reader devices are shown and described in relation to Figures 13 to 16.

[0075] Where the reader device is or forms part of a computing device 110, the sensing system 100 may include a remote server 130 for communication with the computing device 110 over a data communication network 140. Network 140 may be or include the Internet and/or other data communication networks, alone or in combination.

[0076] Each computing device 110 includes a processor 112, which may include multiple processing devices, memory 114, data storage 116 and a communication interface 118, for example. The memory 114 is accessible to the processor 112 and stores executable program code that, when executed by the processor 112, causes the computing device 110 to implement a sensor application 190. The processor 112 further has access to data storage 116 in order to store and retrieve sensor data 182 from sensor devices 120 with which the computing device 110 has interacted and received data. The communication interface 118 may include a wireless interface, such as a near field communication (NFC) interface, together with drivers and ports to enable such communication. The communication interface 118 may include sensor reader 119. The communication interface 118 may also include serial interfaces, such as USB interfaces to communicate with a separate or connected device that omits a suitable excitation field for interacting with sensor device 120, for example.

[0077] The sensor application 190 is defined by lines and groups of program code that are stored in memory 114 and executable to allow the processor 112 to execute various computing functions for operation of the sensor application 190. These functions are logically grouped in modules for performing related groups of functions, including a user interface module 192, a sensor data processing module 193 and a reporting module 194, as part of the sensor application 190, for example. The user interface module 192 may allow user interaction with a user, for example via a touch screen of the computing device 110, in order to trigger interaction of the computing device 110 with the sensor device 120 and display the results of detection signals received from the sensor device 120, for example. The sensor data processing module 193 may be configured to decode data received from a sensor device 120 in order to determine whether the received signals from sensor device 120 indicate the presence or absence of a pathogen detected by the sensor device 120. The sensor data processing module 193 may apply filter processes, calibration processes and/or thresholding processes to the received signals from sensor device 120. The sensor data processing module 193 provides a pathogen detection output as a result of such processes to the user interface module 192 and/or reporting module 194. The pathogen detection output may also be stored in sensor data 182. Reporting module 194 is configured to generate and send reports of pathogen detection data from each sensor device 120 with which the computing device 110 has interacted to remote server 130 or another device.

[0078] Remote server 130 includes a processor 132, which may include multiple processing devices, memory 134 and storage 136. The storage 136 may form part of the remote server 130 or may be part of a data store accessible to the remote server 130.

The memory 134 includes a reporting module 135 for generating reports and/or notifications (e.g. to client devices (not shown) over network 140) based on the sensor output received from one or multiple computing devices 110. As each sensor device 120 is encoded to have a unique identifier (e.g. stored in chip memory of processor 124), and each such unique identifier is received by the computing device 110 during interaction therewith, the computing device 110 can track sensor outputs from each sensor device 120 and provide these to the remote server 130. The remote server 130 may maintain device purchase and provenance records 138 for all sensor devices 120 in order to be able to track the purchase history of such sensor devices 120 and match it against sensor output data received from computing devices 110 based on the unique identifier of each sensor device 120.

[0079] The sensor outputs from each sensor device 120 identify the type of pathogen detectable by each sensing portion carried by the sensor device 120. Where a sensor device 120 includes multiple sensing portions, the data output from the sensor device 120 to the reader device includes an identifier for each sensing portion to identify the nature or type of pathogen that the sensing portion is configured to detect.

[0080] Some embodiments of sensor device 120 are free of any internal power source or supply. Embodiments of sensor device 120 may rely on power from current generated by excitation of the coil 123 by an external excitation field, according to existing technologies. Current from excitation of the coil 123 is generally sufficient to temporarily power the processor 124 of the sensor device 120 in order to sense the electrical potential across each pathogen sensing portion 126, 128 carried on the sensor device 120, and to transmit an output signal by the antenna 122. Thus, in some embodiments of sensor device 120, the device may be considered to be passive, not powered. In other embodiments of sensor device 120, the processor 124 may receive electrical power to operate from a constant power source 190, which may include a battery or other DC power supply, which may be derived from a mains power supply, for example.

[0081] Referring also to Figures 2 A, 2B, 3 and 4, some embodiments of a sensor device 120 will be described in further detail. The sensor device 120 may have a substantially flexible and thin carrier substrate 210. The carrier substrate 210 acts as a base to affix and carry other parts of the sensor device 120. Outer edges of the carrier substrate 210 substantially define the length and width dimensions of the sensor device 120. The carrier substrate 210 may have a thickness of between about 0.2mm and about 2mm, for example. The carrier substrate 210 may be approximately rectangular in outline, for example and may have a length of between 2 and 3 cm and a width of between 1 and 1.5cm, for example.

[0082] The carrier substrate 210 has electrical conductors disposed thereon in the form of a conductor layer 220 that includes the antenna 122 and coil 123. The conductor layer 220 is configured to receive processor 124 in the form of a processing chip and to receive or define other electrical components, including resistors, capacitors, amplifiers and other electrical circuit componentry to enable signal conduction and processing on the sensor device 120. Conductor layer 220 further defines sensor portion base conductive portions 251a, 251b for contacting and electrically coupling to a sensor chip 250 carried by the sensor device 120. Sensor chip 250 may be adhered to the base conductive portions 251a, 251b by an adhesive conductive paste, such as a suitable silver paste, for example. The sensor chip 250 has thereon at least one sensing portion 126, and if present, a second or further sensing portion 128, to carry the CIMPs. [0083] CIMPs are designed to act as artificial receptors with a predetermined designed selectivity and specificity for a given analyte. These artificial receptors can be used in place of antibodies or other binding moieties. An advantage that CIMPs have over biological antibodies is that CIMPs are fully synthetic molecules that do not degrade over time and can withstand sterilisation procedures, such as gamma irradiation or autoclaves, that are required for medical devices. Furthermore, CIMPs are designed to withstand solvents and storage at room temperature without degradation. This suitability for long term storage is an important consideration for devices that may need to be stored for decades in preparation for an outbreak, epidemic or pandemic.

[0084] CIMPs are a kind of polymer referred to in the art as Molecularly Imprinted Polymers (MIPs). Synthesis of such MIPs is described in International Patent Application No. PCT/GB 2006/001986, for example. The polymeric matrices obtained using existing molecular imprinting technology are robust molecular recognition elements able to mimic natural recognition entities. These synthetic receptors created by the polymeric matrices of the CIMPS are capable of binding to a target molecule, such as a pathogen. The target molecule fits into the binding site of the CIMP with high affinity and specificity. The interactions between the CIMP and the target molecule are similar to those between antibodies and antigens, consisting of electrostatic interactions, hydrogen bonds, Van der Waals forces, and hydrophobic interactions, for example. The CIMPs used in sensor devices 120 in the present disclosure are typically in the order of 50nm to 150nm in size. Such CIMPS may be referred to as Nano-MIPs (nanometre-scale molecularly imprinted polymers).

[0085] CIMPs are made through a process of producing an impression within a solid or a gel. The size, shape and charge distribution of the impression corresponds to a template molecule present during polymerisation, in the example here it would be the RBD (receptor binding domain) of SARS-CoV2 virus spike protein. An example CIMP described for use in sensor devices 120 of the present disclosure was developed using an amino acid polypeptide to the RBD region of the SARs-CoV2 virus. The process involves initiating the polymerisation of monomers in the presence of the template molecule i.e. RBD peptide that is extracted afterwards. The monomers belong to usually large libraries of molecules, the greater the library complexity the higher probability a CIMP of high binding affinity will be generated. The processes is initiated with dissolution of the template, functional monomers, cross linking agent and an initiator in a progenic solvent. The monomers which are spatially surrounding the template have usually been carefully preselected using computer modelling before cross linking occurs and they are fixed by copolymerisation. The template is then washed-out using solvents leaving a microporous matrix with microcavities that are complementary to the shape of the template. CIMPs are usually modified away from the binding region to contain linker molecules to functionalise them to surfaces, amine chemistry being a popular choice.

[0086] It would be typical for the CIMP to be characterised once established chemically by solid state nuclear magnetic resonance and morphologically by scanning electron microscopy. Functional characterisation is achieved using techniques such as dot blot for a crude target binding efficacy or surface plasma resonance to test the CIMPs binding dynamics. CIMPs are often modelled on specific binding regions of large proteins. These specific binding regions may be around 20-30 amino acids long. Accordingly, the functional characterisation tests may be complemented with the full length protein from which the binding regions is derived, as the full length protein may be spatially closer to the pathogen to be detected. In the case of the CIMP used in the present disclosure for binding the SARS-CoV2 virus, the template also underwent a viral titre test to determine its ability to bind live SARS-CoV2 virus.

[0087] Advantageously, CIMPs can generally withstand high enough temperatures to allow for sterilisation of the sensor device 120, if required, without appreciable functional degradation.

[0088] Example respiratory pathogens for which CIMPs can be created and which the sensor device 120 can be configured to detect include: rhinoviruses, coronaviruses (and SARS-CoV2 in particular), influenza viruses (A&B) and tuberculosis. Further example pathogens for which CIMPs can be created and which the sensor device 120 can be configured to detect include: ebola, arenavirus, Mycobacterium leprae, adenovirus, Group A haemolytic streptococci, parainfluenza, Streptococcus pneumonia (pneumococcus), Mycoplasma pneumonia, Klebsiella pneumonia, Herpes simplex virus, Candida Albicans (fungus), haemophilus influenza, Legionella, E.Coli, Aspergillus (fungi), Legionnaires disease and Cytomegalovirus.

[0089] To measure the detection limits of the sensor device 120, 10pL of known concentration of SARS-CoV-2 spike protein solution in artificial saliva was drop casted on the CIMPs immobilised on a sensing portion 126 for 10 min. The protein solution was removed from the sensor device, dried under N2 gas and the resistance measurements were obtained (R). Three resistance measurements were obtained for each sensor device 120 after antigen immobilisation with a bias set at 1.8 V (to be compatible with the existing circuitry). The resistance of the (3-glycidyloxypropyl) trimethoxy silane (GPS) silanised sensing portions used was 10 kC-200 kC. Data collection time in each measurement was 60 s. Change in resistance was measured as follows: AR(%) = (R0-R)/R0 x 100%. R =Resistance after antigen addition, R0 = Resistance before antigen addition. Results of the testing using artificial saliva are shown in Figure 19.

[0090] The same conditions were used to conduct detection measurements of SARS- CoV-2-targeting CIMP immobilised sensing portions by drop-casting 10pL of known concentration of SARS-CoV-2 spike protein solution in phosphate-buffered saline (PBS) was drop casted on the CIMPs immobilised on a sensing portion 126 for 10 min. Change in resistance was measured as follows: AR(%) = (R-R0)/R0 x 100%. Results of the testing using PBS are shown in Figure 18.

[0091] Sensing portions containing SARS-CoV-2-targeting immobilised CIMPs successfully detected SARS-CoV-2 spike proteins in both PBS and artificial saliva. The detection limit in both solvents is around 0.1 ng/mL (i.e. 10 ⁷ mg/mL). Both solvents displayed an increase in resistance change with increased protein concentration and a reverse polarity in resistance change with respect to the increased protein concentration. Hence, the contribution from the solvent in the measurements is negligible. [0092] The test results as shown in Figures 18 and 19 show that SARS-CoV-2- targetting CIMP immobilised sensing portions according to embodiments described herein successfully detected SARS-CoV-2 spike proteins in both PBS and artificial saliva. The relevance of detecting the spike protein lies within its function in infection. A coronavirus contains four structural proteins, including spike (S), envelope (E), membrane (M), and nucleocapsid (N) proteins. Among them, S protein plays the most important role in viral attachment, fusion and entry by binding to human and bat angiotensin-converting enzyme 2 (ACE2) receptors. Within SARS-CoV-2, the RBD resides at 331 to 524 of S protein and it is this region that exhibits the strongest binding to ACE2.

[0093] The measurements of change in resistance of the tested sensing portions exhibit a close to log-linear relationship between protein concentration and resistance in either solvent. Hence, the contribution from the solvent in the measurements is negligible. The contribution of either solvent is an important consideration because the virus may be in aerosolised saliva from a cough or the sensor may be deployed in a controlled lab environment where PBS is the solvent of choice. The implication of the overall sensitivity is that the sensor device 120 will perform well enough to detect clinically relevant amounts of virus in the scenarios it is currently considered for deployment in. The detection limit suggests the sensor will accurately detect only a few viral particles i.e. an amount that will likely cause an infection. Higher threshold limits may miss clinically relevant virus. Hence it is helpful for the sensor to be accurate for concentrations as low as 0.1 ng/mL.

[0094] The carrier substrate 210 has a body formed of a suitable flexible plastic. The substrate body may have cut outs that define gaps between parts of the interior of the body. For example, a gap 218 may be formed between a first substrate body end 211 and an opposite substrate body end 212. The gap 218 may also be defined as an interior gap or space by an outer portion 214 that extends around an outside edge of the body between the first end 211 and the second end 212. Extending inwardly from the second end 212, the body may have a chip carrying portion 213. Extending toward the first end 211 from the chip carrying portion 213 (but separated therefrom by gap 218) is a substrate sensor portion base 215 to receive and support the sensor chip 250.

[0095] The sensor device 120 further includes a cover layer 230 to cover over the conductor layer 220. The cover layer may be or include a suitable plastic film or other material that can seal and protect the conductor layer 220 and also allow for formation of the aperture 235. The cover layer 230 covers and seals the sensor portion across all front surfaces of the carrier substrate 210 and conductor layer 220, other than where an aperture 235 is formed in the cover layer 230. The aperture 235 is sized and positioned to allow passage of air or other fluids from an external environment to each sensor portion 126, 128 carried by the sensor chip 250. The aperture 235 may define an opening of between about 4 mm ² and about 20 mm ² , for example.

[0096] In some embodiments, the sensor device 120 includes a backing layer 240 on a back side of the carrier substrate 210 opposite to the front side that receives the conductor layer 220. The backing layer 240 may include an adhesive layer on a backside of the carrier substrate 210 in order to adhere the sensor device 120 to an object. The backing layer 240 may have a peel off outer layer to expose adhesive for attachment of the sensor device 120 to an object, for example. Although adhesive is contemplated as a suitable means for attachment of the sensor device 120 to an object, other suitable attachment mechanisms can be employed. The backing layer 240 may include, be integrated with or coupled to other layers and such other layers may have adhesive or attachment mechanisms provided thereon. Such attachment mechanisms may include mechanical connectors, clips, pins or other suitable fasteners, for example. The backing layer 240 may have the same length and width as the carrier substrates in some embodiments and in other embodiments may have substantially larger length and width dimensions in order to allow greater area for attachment of the sensor device 120 to an object.

[0097] As shown in Figure 4, which is not to scale, each sensing portion 126 includes an electrode pair including a first electrode 352a and a second electrode 352b arranged to face each other in parallel while remaining separated by a small electrode gap 355. The first electrode 352a is electrically coupled to a connecting conductor 351a to electrically couple the first electrode 352a to the sensor portion base conductive portion 251a. The second electrode 352b is electrically coupled to a connecting conductor 351b to electrically couple the second electrode 352b to the second sensor portion base conductive portion 251b. The first electrode 352a and the second electrode 352b collectively comprise an electrode pair 352. The first and second electrodes 352a, 352b are disposed in or on an upper layer of the sensing portion, which may be a ZnO layer, for example. On top of the upper layer is disposed a carrier matrix and the CIMP is disposed in the carrier matrix in the gap 355. The carrier matrix may be or include GPS (y-glycidoxy propyl trimethoxy silane), for example. A separation (x) between the first and second electrodes 352a, 352b may be between around 20 microns and 100 microns, optionally around 40 microns, for example. A length across which the gap 355 extends between the first and second electrodes 352a, 352b may be around 4mm, for example. The active sensing area of each sensing portion 126, 128, as defined by the length multiplied by the separation (x) of the gap 355, may be approximately 400,000 to around 80,000 square microns, for example.

[0098] Figures 5A to 5D show the sensing chip 250 in further detail. The sensing chip 250 has first and second electrodes 510a, 510b on opposed ends of an upper face of the sensing chip 250. The electrodes 510a, 510b are disposed on top of an upper chip layer 520. The upper chip layer 520 may be formed of zinc oxide and have a thickness of around 100 nanometres, for example. The thickness of the electrodes 510a, 510b may be around 5 nanometres where the electrodes 510a, 510b are formed of chromium, or around 50 nanometres where the electrodes 510a, 510b are formed of gold, for example. The upper layer 520 may be disposed on top of an intermediate layer 530.

The intermediate layer 530 may be formed of silicon dioxide and have a thickness of around 300 nanometres, for example. The intermediate layer 530 may be disposed on a silicon wafer layer 540, which may have a thickness in microns to suit requirements. The silicon wafer may have a thickness in the range of 280-460 microns, for example. In some embodiments, electrodes 510a and 510b may be formed of titanium (Ti)/gold (Au). The electrodes 510a and 510b may be manufactured photolithographically, for example. [0099] The exposed upper surface 522 of the upper layer 520 may carry the sensing portions 126, 128, as shown in Figure 5A. The upper surface 522 has a carrier matrix, such as a GPS (y-glycidoxy propyl trimethoxy silane) matrix layer, thereon for binding the CIMPs to the sensing portion 126, 128. The first electrode 510a and the second electrode 510b collectively comprise an electrode pair 510 of the sensing chip 250. Conductors 511 may be used to electrically couple the electrodes 510a, 510b to the sensing portion 126.

[0100] Where the sensing chip 250 includes multiple sensing portions 126, 128, an example of which is shown in Figure 5A, then the electrodes 510a, 510b may be separated into multiple electrically separate electrodes for separate electrical signalling between each sensing portion 126, 128 and the processor 124. In such embodiments, first conductors 511a may be used to electrically couple a first separate pair of electrodes 510a, 510b with a first sensing portion 126, while electrically separate second conductors 511b may be used to electrically couple a second separate pair of electrodes 510a, 510b with a second sensing portion 128. Where multiple sensing portions 126, 128 are present on the sensing chip 250, the processor 124 (or circuitry intermediate the processor 124 and the sensing chip 250) may include a multiplexer to allow selective polling of the sensing portions 126, 128 by the processor 124.

[0101] Figure 5E is a schematic diagram of further embodiments of the sensor chip 250. In such embodiments, multiple sensing portions 126 are present on the sensor chip 250. In Figure 5E, four such sensing portions 126 are shown as an example. Each sensing portion 126 may carry a different CIMP for detecting a different respiratory pathogen. Alternatively, two or more of the sensing portions 126 may carry the same CIMP for detecting the same respiratory pathogen. The sensor chip 250 shown in Figure 5E has multiple first electrodes 510a that are electrically connected to one side of a sensing portion 126 and second electrodes that are electrically connected to the opposite side of each sensing portion 126. Conductors 511 are couped to respective ones of the first and second electrodes in order to electrically couple to the processor 124, either directly or via another chip, such as a multiplexer, amplifier, etc. [0102] Figure 6 is a schematic illustration of a process in which a CIMP can be attached to a base for binding with an antigen, such as a respiratory pathogen. Firstly, a suitable carrier structure, such as sensor chip 250 as shown in Figures 5B and 5D, is provided. The carrier structure has a ZnO or other suitable metal oxide deposited on an upper surface thereof. For example, the sensor chip 250 may be fabricated on rigid (Si02/Si) and flexible plastic (polyimide foil) substrates by depositing a 100 nm thick thin film of a metal oxide, such as zinc oxide (ZnO), to act as a sensing or conductive element in the sensing portions 126, 128. The structure of the sensing portion 126 may be formed by reactive sputtering to produce an oxygen deficient metal oxide film with a conductance in the range of 0.08-2 Siemens/m ² , more preferably in the range of 0.08- 0.6 Siemens/m ² . For conductance measurements to determine conductance of the sensing area between the electrodes, two terminal in-plane electrodes 352a, 352b are patterned with a sensing area of as much as 16x10^’ m ² . The change in conductance corresponding to the presence of a respiratory pathogen bound to a CIMP targeted to that pathogen can then be detected by the processor 124. Such conductance change may be measured, for testing purposes, using a commercial current source meter (B2901A precision source/measure unit from Keysight Technologies).

[0103] In an initial step 610, the carrier matrix for the CIMPs is disposed on the upper surface 522. This may be done by silanisation with GPS, for example. In other examples, other silanes may be employed in forming the carrier matrix. Silanisation of oxygen-deficient metal oxide sensor surfaces using GPS has been reported before, albeit for invasive sensors. For preparation of a sensor chip 250 as described herein, the silanisation of ZnO was conducted with few modifications to the reported silanisation procedure. In brief, freshly prepared ZnO devices were exposed to 02 plasma for 10 minutes (Plasma Cleaner PDC-002, Harrick Plasma) to activate the hydroxyl groups on the ZnO surface. Then, 20 pL of freshly prepared GPS solution was drop-casted onto an A1 foil, which was placed inside a vacuum desiccator, allowing GPS vapour to build up inside the desiccator. Then, the 02 plasma cleaned-ZnO sensors were exposed to this GPS vapour for 30-45 min. The exposure of the plasma cleaned ZnO sensors to the GPS vapour was conducted inside an LC 200 Glovebox System. Upon completion of the exposure to GPS vapour, the ZnO sensors were rinsed thoroughly with Milli-Q water for 2 minutes to remove any unbound silane groups from the surface of the ZnO sensors. Then, the washed ZnO sensors were heated at 150C for 10 minutes to strengthen the bonding of the silane groups to the ZnO surface. Such GPS-silanised sensors are then ready for the immobilisation of CIMPs, which may emulate binding properties of target antibodies.

[0104] In a subsequent step 620, the CIMPs are immobilised on and/or in the carrier matrix. A CIMP modified with amine groups bound to the opposite side of the CIMP to the active virus binding region is used to bind the silanised zinc oxide sensors. The CIMP is drop casted on each sensing portion 126, 128 and incubated for a period of around 30 min or more. The sensing portions 126, 128 with CIMPs immobilised thereon are washed with PBS (pH 7.4) to remove unabsorbed CIMPs and are then dried under N2 gas. In an example immobilisation process performed for targeting the SARS-CoV-2 virus, the CIMP prepared to target SARS-CoV-2 (provided by MTP Diagnostics Limited, in Bedfordshire, UK) was prepared with amine groups for binding silanised zinc oxide sensors and drop casted (IOmI) on each sensing portion of a sensor device and incubated for 30 min. The CIMP-immobilised sensor devices were washed extensively with PBS (pH 7.4) to remove unabsorbed CIMPs and dried under N2 gas.

[0105] Figure 7 is a schematic illustration of how an antigen, such as a respiratory pathogen, can interact with CIMPs 622 immobilised on a sensing portion 126 of the sensing chip 250 in order to allow sensing of the presence of the antigen on the sensing chip 250. State 720 illustrates a non- interacted state of the sensor chip 250 formed by the process shown and describe in relation to Figure 6, with CIMPs 622 immobilised on the sensing portion 126 of the sensing chip 250. Once the sensing portion 126 of the sensor chip comes into fluid contact with one or more target respiratory pathogens and such pathogens bind with the CIMPs 622, then the sensor is in an activated state 730. The unbound CIMPs 622 then become bound CIMPs 632 that, by their presence ion sensing portion 126, cause the sensing portion 126 to exhibit different resistance/conductance properties from the unbound CIMPs 622. [0106] Figure 8A is an example electrical schematic diagram of the sensor device 120 interacting with a sensor reader 119. Figure 8B shows the electrical circuitry provided by the conductor layer 220 of the sensor device 120, corresponding to the electrical schematic of Figure 8A. In embodiments of the sensing device 120 illustrated by Figures 8A and 9B, the sensing device employs an NFC chip as the processor 124. The NFC chip is in electrical communication with the antenna 122 that can be used to communicate with an external device, such as sensor reader 119, having a suitable interfacing antenna 822. The antenna 122 and the antenna 822 of the sensor reader 119 may communicate in frequencies of around 13.56mhz, for example, or at other suitable frequencies. The sensor reader 119 includes matching and modulation circuitry 824 in communication with antenna 822, in order to condition the signal output received from sensor device 120 via antenna 822. The sensor reader 119 may form part of computing device 110 or another system, for example.

[0107] The circuitry of sensor device 120 includes a low dropout (LDO) regulator 127 help avoid overcharging the processor 124 from excitation of the coil 123. The circuitry of sensor device 120 further includes an amplifier 125 a to amplify analog output signals from the sensing portions 126, 128 of the sensor chip 250.

[0108] Figure 17 is a flowchart of a method 1700 of operation of the processor 124 of sensor device 120. The flowchart illustrates an example process 1700 executed by the processor 124 to determine whether a respiratory pathogen appears to be present or absent on pathogen sensing portion 126 or 128. The steps of process 1700 are performed by the processor 124. The processor 124 may be a programmable 16 bit MSP430™ microcontroller, for example. In-built ROM firmware of the microcontroller may be used to execute all the described steps of process 1700.

[0109] At step 1705 of process 1700, the processor 124 is initialised as part of factory setup. Following initialisation, the processor 124 enters a (passive) low power mode (LPM), in which it performs few or no processing functions and waits until it receives current from excitation of the antenna coil 122 by a nearby excitation field. [0110] At step 1715, the processor 124 receives a RF packet from a reader device, such as sensor reader 119. The RF packet may be from an ISO/IEC 15693 enabled reader, for example. In this case, the reader is NFC enabled mobile phone. Once the sensor device 120 comes close (e.g. less than 10 cm) to the reader, the antenna and coil 122 harvests sufficient energy from the excitation field of the sensor reader 119 to initialize the processor 124 for a short sampling period. If a battery or other active power source is used in place of antenna and coil 122, the processor 124 can always stay on LPM until a RF packet is received, while drawing only a small leakage current.

[0111] At step 1720, the processor 124 processes the RF packet. The RF packet may contain commands to write and read to or from specific memory blocks in processor 124 for setting different memory registers of the processor 124. The memory registers are used to execute the required functions of processor 124 in interacting with the sensor portion 250, such as enabling/disabling the ADCs, setting sampling rate, processing sample data, etc. The higher the sampling frequency, the better accuracy of sample data is achieved for detecting the presence or absence of pathogens on the sensing portions 126, 128.

[0112] Through a control status block (register) in the memory of processor 124, the processor 124 controls the sensor settings and determines whether to read sensing portions 126, 128. At step 1725, processor 124 determines whether to write to the control status block according to the received RF packet. If the RF packet does not indicate that a sensing portion is to be read (sampled), then the processor 124 returns to low power mode (LPM). Based on the sensor control register settings that control various sensors, polling of each sensing portion 126. 128 of sensor portion 250 may be enabled or disabled. Disabled sensing portions are not sampled and skipped in the sampling process.

[0113] At step 1730, the processor 124 executes any commands written to the control status (CS) block as part of step 1720. At step 1735, if a start command is set in the CS block, processor 124 proceeds with sampling of selected ones of the sensor portions 126, 128 as specified in the CS block in the next step. Otherwise, processor 124 returns to LPM after an initial delay.

[0114] At step 1740, processor 124 starts the sampling (sensor polling) process. The processor 124 has a specific module with a multi-channel sigma-delta analog to digital converter (ADC) (SD 14) with up to 14 bits of resolution. The processor 124 has a frequency modulator which can a create a sampling period as low as 32 ms. Two types of filters may be used to execute the sampling operation in step 1740. A first filter may be or include a cascaded integrator-comb (CIC) filter. The CIC filter can allow a sampling rate change between 32 and 2048 ms, as required by settings of the processor 124. The second filter may be a moving average filter with a programmable number of samples. The first filter allows the processor 124 to sample as needed, while the second filter allows noise reduction by applying an averaging function.

[0115] At step 1745, the output from the sensing portions 126, 128 is prepared for conversion by the ADCs and is fed into an 8 channel multiplexer which is controlled by a program of processor 124 for channel selection. The multiplexer can be provided by functionality of the processor 124 or as a separate multiplexing chip. If more sensing portions 126, 128 are present on the sensing chip 250 than can be accommodated by the native multiplexing capability of the processor 124, then a separate multiplexer circuit can be employed for the multiplexing.

[0116] At step 1750, the one or more ADCs are configured by processor 124 for conversion of the analog signals from the sensing portions 126, 128 and conversion is started. A sigma-delta analog-to-digital converter (ADC) SD 14 consists of two parts: the analog part (called the modulator) and the digital part (called the decimation filter). The modulator of the SD14 provides a bit stream of zeros and ones to the digital decimation filter. The digital decimation filter averages the bitstream from the modulator over a given number of bits (specified by the oversampling rate) and provides samples at a reduced rate for further processing to the processor 124. [0117] At step 1755, the processor 124 waits until analog to digital conversion is performed in low power mode if the battery is used. Under the RF field powered operation of sensor device 120, step 1755 is not necessary as processor 124 operates only at the presence of a RF excitation field.

[0118] At step 1760, the digitised output data from sensing portions 126, 128 is stored into memory of the processor 124, such as random access memory (RAM, optionally ferroelectric RAM) in the order it is sampled. After initiating and concluding a sampling process, the logged data can be read from the memory through a read command from the reading device. The read command may be received from sensor reader 119, for example in response to a command automatically generated by the sensor data processing module 193 or responsive to input received via the user interface module 192.

[0119] At step 1765, the processor 124 repeats the conversion from analog to digital (steps 1745 to 1760) in cyclic order as long as the analog signal provides input to the pins of the chip.

[0120] Figures 9A and 9B are front and back views, respectively, of embodiments of an object carrying the sensor device 120, shown in the example form of a card 900. The card 900 may be a semi-rigid plastic card of the kind that is commonly used to identify a person or authorise access by the person to a particular area, as is known in the art. As shown in Figure 9 A, the card 900 has a front face 910 on one side of a card body 905. The sensor device 120 is disposed on the front face 910, with the sensing portion 250 being disposed so that air or other fluids carrying respiratory pathogens can come in contact with the sensor portion 250, for example via aperture 235 (as shown in Figure 3). Card 900 has a rear face of the card body 905, as shown in Figure 9B, although the sensing portion 250 is not accessible to fluids from the rear face 912.

[0121] The sensor device 120 may be carried by the card body 905 by attachment of the sensor device 120 thereto, for example by adhesion of an adhesive backing layer of the sensor device 120 onto a surface of the front face 910. In other embodiments, the sensor device 120 may be integrally formed with the body 905 of card 900. For example, the antenna 122 and/or coil 123 may be enlarged and embedded within the card body 905 in order to provide increased excitation and data transmission capabilities. Although Figure 9 A shows the sensor device 120 being positioned in a middle of the front side 910 of the card 900, the sensor device 120 may be positioned elsewhere within a generally non-peripheral area on the front side 910, as desired.

[0122] Figure 10 shows a carrier 1000 to carry the access object (i.e. card 900) of Figure 9A. The carrier 1000 includes an object receptacle 1010 sized and configured to receive and the carry the access object. The object receptacle 1010 may be or include a sleeve or pocket, for example, sized and configured to receive the card 900. The receptacle 1010 is arranged to leave at least a part of the access object exposed in order to allow fluid to come into contact with the sensor device 120 carried by the access object. For example, the receptacle 1010 may have an opening or aperture 1015 in a side wall, positioned to coincide with a position of the sensor device 120 on the access object (card 900). The carrier 1000 may have a connector 1020 to allow the receptacle 1010 to be connected to another object or carried by a person. For example, the connector 1020 may couple the receptacle 1010 to a lanyard or a clip so that the access object carrying the sensor device 120 can be carried in a manner that exposes the sensor device 120 to fluid in the ambient environment that may carry respiratory pathogens, while also allowing the access object to be readily brought close to a reader device for interaction therewith as described previously.

[0123] Figures 11 A, 1 IB and 12 illustrate a further object to which the sensor device 120 can be usefully applied. In this instance, the object shown in Figures 11 A, 11B and 12 is a face mask 1100 that can be readily worn by a human. The face mask may have multiple layers of porous material and loops 1140 for placement around the ears, as is known in the art.

[0124] The sensor device 120 may be positioned on an inner layer 1120 of the face mask 1100, in order to protect the sensor device 120 from inadvertent physical contact, for example as a person touches their face. The sensor device 120 may alternatively be positioned on an inner layer 1130 or an outer layer 1110 of the face mask 1100. In embodiments of the face mask 1100 that have only a single layer, the sensor device 120 may be positioned on an inside of the single layer in order to maximise the prospect of detecting respiratory pathogens exhaled from a person while wearing the mask 1100. In embodiments of the face mask 1100 that have two layers, the sensor device 120 may be positioned in between the two layers and attached, for example via adhesion, to the innermost layer. Face mask embodiments described herein contemplate that the material of the layers of the face mask 1100 are relatively porous and readily allow fluid transmission of exhaled respiratory pathogens to the sensing portion 250 of the sensor device 120 carried thereon. The sensor device 120 may be positioned on the face mask 1100 so as to face the sensing portion 250 toward an inner side of the face mask 1100. This may maximise the prospect of respiratory pathogens in exhaled breath coming into contact with the sensing portion 250. For this reason, the sensor device 120 can be positioned generally centrally on the mask 1100 within an area that will be reasonably proximate and in front of the nostrils and/or mouth of a wearer. In this regard, parts of the face mask 1100 that are configured to overlie the cheeks, chin and bridge of the nose of the wearer are not desirable for carrying the sensor device 120 thereon. Flowever, as shown in Figure 11, the sensor device 120 need not be directly in front of the nose or mouth.

[0125] Figures 13 and 14 illustrate an access system 1300 according to some embodiments. The access system includes a reader device 1310 configured for wireless excitation of the coil 123 of the sensor device 120 and communication with processor 124 via antenna 122, for example via NFC protocols as described above. Figure 13 shows an access object, such as a card 900, carried in a carrier 1000 and placed in sufficient proximity to the reader device 1310 to provide an excitation field to the coil 123 of the sensor device 120 carried on the access object.

[0126] The reader device 1310 may have a housing 1320 to house components of the reader device 1310, such as an antenna 822 and a modulation circuit 824 in communication with a reader processor (not shown). The access system 1300 further includes an access actuator in communication with the reader device 1310 and a portal 1350 responsive to the access actuator 1340 to allow access to an area beyond the portal 1350. The portal 1350 may remain closed and/or locked. The portal 1350 may be a door, a gate, a turnstile or other barrier, for example. The reader device 1310 and the access actuator 1340 may receive power from a local power source, such as a local battery, a local DC power supply or mains power supply.

[0127] The components of reader device 1310 are configured to wirelessly interrogate the sensor device 120 and wirelessly receive back from the sensor device 120 a data packet including data indicative of the presence or absence of a respiratory pathogen for which the sensor device 120 is targeted. The data indicative of the presence or absence of a respiratory pathogen may include resistivity or conductivity measurement data of each sensing portion 126, 128 carried on the sensor device 120. Alternatively, or in addition, the data indicative of the presence or absence of a respiratory pathogen may include a positive detection output (indicating detection of the presence of the respiratory pathogen) or a negative detection output (indicating no detection of the respiratory pathogen) for each sensing portion 126, 128 carried on the sensor device 120.

[0128] Upon receiving the data indicative of the presence or absence of a respiratory pathogen from the sensor device 120, the reader device 1310 is configured to transmit an access signal to the access actuator 1340 via a communication cable 1350 (and/or a wireless communication medium, not shown). The access signal indicates that access through a portal 1350 is either authorised or not authorised. The reader device 1310 is configured to generate an “authorised” access signal when the data indicative of the presence or absence of a respiratory pathogen indicates that no respiratory pathogen has been detected. The reader device 1310 is configured to generate a “not authorised” access signal when the data indicative of the presence or absence of a respiratory pathogen indicates that a respiratory pathogen has been detected. When the access actuator 1340 receives an access signal indicating that access is authorised, the access actuator 1340 opens and/or unlocks the portal 1350. When the access actuator 1340 receives an access signal indicating that access is not authorised, the access actuator 1340 retains the portal 1350 in a locked and closed state. In alternative embodiments, the reader device 1310 only sends an access signal to the access actuator 1340 when the data indicative of the presence or absence of a respiratory pathogen on the sensor device 120 indicates that no respiratory pathogen has been detected, and the portal 1350 otherwise remains closed.

[0129] Figures 15A and 15B illustrate a pathogen detection system 1500 according to some embodiments. The pathogen detection system 1500 includes a sensor housing 1510 mounted on a wall 1560. The wall 1560 combines with other nearby walls, a floor, a ceiling and at least one portal to define an enclosed or mostly enclosed space. The enclosed space may be an elevator (as illustrated in Figure 15B), lavatory, office or other kind of room or area through which people may pass or spend time, for example.

[0130] Sensor housing 1510 houses at least one sensor device 120 and defines a generally enclosed housing volume but for an inlet aperture 1525 and at least one outlet aperture or vent 1535. A fan 1530 or other device is disposed inside the housing 1510 for drawing air into the housing 1510 via inlet aperture 1525. The aperture 1530 and the vent 1535 face different directions. The air is drawn into the housing 1510 from a first direction 1531 that generally faces a main area of the enclosed space. Air drawn into the sensor housing 1510 is directed to pass onto the sensor device 120 positioned inside the space of the sensor housing 1510, so that pathogens carried in the air in the enclosed space can bind with CIMPs on a sensing portion 126, 128 for detection by the sensor device 120. The air drawn into the housing 1510 is vented through vent 1535 in a second direction 1532 that is a different direction from the first direction 1531. The second direction 1532 maybe along the wall 1560, for example.

[0131] The sensor housing 1510, fan 1530 may be powered by a local power source, such as a local battery, a local DC power supply or mains power supply. Optionally the sensor device 120 is also powered by the local power source, since the sensor device 120 does not need to be portable and, being mounted inside the sensor housing 1510 on a wall, can have ready access to the local power source. [0132] The pathogen detection system 1500 in some embodiments is configured to allow a sensor reader 119 carried by a computing device 110 to interact with the sensor device 120 to identify whether the sensor device 120 has detected the presence of a respiratory pathogen. Alternatively or in addition, the pathogen detection system 1500 may include a communication cable or wireless communication subsystem (not shown) to allow periodic sampling of the air in the enclosed space by the sensor housing 1510 and to generate automatic alerts to a separate monitoring system or a computing device, such as computing device 110. The sensor housing 1510 may be normally locked but readily opened (e.g. by a key or other access device) for withdrawal and replacement of the sensor device 120 after a positive respiratory pathogen detection result has been recorded.

[0133] Figure 16 illustrates a further example use of the sensor device 120 as described herein within a portable respiratory pathogen detector 1600. Figure 16 illustrates the portable respiratory pathogen detector 1600 schematically as a handheld device with an exhalation capture part 1630, and a detector housing (or housing body) 1610 within which is disposed at least one sensor device 120. The respiratory pathogen detector 1600 may also have a display 1620. The exhalation capture part 1630 may have the form of a nozzle, for example, for receiving an exhaled breath of a person 1605 or other animal. The exhalation capture part 1630 communicates with an internal space of the housing body 1610. The housing body 1610 may also have a vent (not shown) for venting captured breath. The respiratory pathogen detector 1600 is of a size to be easily held with or in an adult human hand and may generally resemble a breath analysis device, commonly known as a “breathalyser.”

[0134] Exhaled breath received through exhalation capture part 1630 is directed by internal conduits, passages or baffles of the housing body 1610 to pass across the sensing surface of sensing portion 126, 128 of sensor device 120. This allows any respiratory pathogens present in the breath to bind with CIMPs (that are targeted to those pathogens) on sensing portion 126, 128 for detection by processor 124 as described herein. A detector processor 1625 of the respiratory pathogen detector 1600 may be configured to communicate with the processor 124 of the sensor device 120 to determine whether it has detected the presence of the target respiratory pathogen. A detection result of the detection determination by detector processor 1625 may be caused by the detector processor to be displayed on the display 1620, for example. Alternatively or in addition, the detector processor 1625 may transmit the detection result (via an antenna 1635 in detector housing 1610) to an external device, such as a computing device like computing device 110. Alternatively or in addition, the sensor device 120 may be removed from housing body 1610 or scanned in place by a sensor reader 119 of a computing device 110.

Examples

[0135] In a study performed, a MIPs-incorporated conductometric micro-biosensor (referred to hereinafter as “biosensor”), an example embodiment of the sensor device 120 as described in relation to Figure 1, 2A, and 2B, for example, was investigated for sensitive, selective, and rapid detection of SARS-CoV-2 proteins and its variants in artificial saliva and phosphate buffered saline (PBS). The example conductometric micro-biosensor was formed as a two-terminal electrode biosensor photolithographically fabricated on an intrinsic silicon wafer. The performed study reveals that careful selection of intrinsic silicon wafers with suitable resistivity is useful in SARS-CoV-2 proteins detection. In the study, RBD of spike (5) glycoprotein (RBDS) and FHA (forkhead- associated) protein were primarily used as the model target SARS-CoV-2 proteins along with several other commercially available SARS- CoV-2 RBDS protein variants (Alpha, Beta, Gamma, and Delta strains).

[0136] Electrical signals, or resistances, were obtained before the SARS-CoV-2 protein addition and after SARS-CoV-2 protein addition. The underlying mechanism for the change in the resistance values upon addition of SARS-CoV-2 proteins was determined to be via the changes in the surface charge transfer occurring due to the intermolecular interactions of incoming proteins with the binding sites of MIPs. Flighly selective and sensitive detection of RBDS and FHA proteins was observed in real-time monitoring. Capability of sensitive and selective detection of these two types of SARS- CoV-2 proteins ensures that the results from the biosensors are accurate. The tests resulted in no false negative/positive outcomes in COVID-19 diagnosing. The biosensor was also capable of rapid identification of different SARS-CoV-2 RBDS protein variants used in this study in both PBS and artificial saliva. Another key finding as a result of this study is that the biosensors, as described herein, can be reused for the detection of RBDS proteins for at least one reuse cycle by treatment with pure isopropyl alcohol (IP A).

[0137] A mobile computing device app (i.e. software application) was also developed, as an example of sensor application 190, where the results from the biosensor can be wirelessly transferred to a smartphone, as an example of computing device 110, via near field transmission (NFC) in less than 10s. Due to the simple sensor geometry and relatively straight-forward detection technique employed, the biosensor is compatible and easily integrated with conventional portable electronics and wearable devices. It is important to note that the usage of this sensor platform is not only limited to SARS- CoV-2 protein detection. By careful selection of biomaterials to functionalise the device surface, this platform can be further extended to detect an array of biomolecules including DNA, antigens, and other viral sub-types. Figure 21 is a schematic diagram illustrating an example use case of the face mask 1100 in combination with the sensor application 190 and the computing device 110. As previously described in relation to Figures 8B, 11 A, 11B, and 11C, the sensor device 120 may, after detection of a pathogen, wirelessly communicate with a computing device 110, such as a smartphone, for example via NFC, to provide and optionally display the results from the sensor device 120 using a mobile computing device app, such as sensor application 190.

[0138] The sensor chip 250 in this example primarily consists of photolithographically fabricated Ti/Au two-terminal electrodes on a high resistivity silicon wafer (>5000 D.cm). Freshly fabricated sensor surfaces are associated with dangling hydroxyl groups which are used in the following steps of silanisation, further explained in relation to step 610 of Figure 6. Figure 4 demonstrates the geometry of the two-electrodes to be patterned on the highly resistive silicon wafer. The following described geometry was selected to facilitate the placement of the resistance measuring probes. A series of resistance measurements were obtained at different electrode gaps to determine an optimal electrode gap. Considering the packing density of the nano- MIPs and the optimised baseline resistance values, the electrode gap (Figure 4 ref. 355) was selected to be 40 pm for the biosensor. Furthermore, optimisation of the channel lengths was conducted by changing the length of the electrodes (2, 3, and 4 mm lengths). The resistance values for all three types of lengths did not show any significant changes. Therefore the sensing areas were considered in determining the optimum channel length. At 2 mm channel length, nano-MIP packing does not provide for a high signal response due to the lower sensing area. At 4 mm channel length, the nano-MIP packing is increased, but there could be a drop of electrical signal due to the long charge transfer pathway. This hypothesis was tested based on the RBDS detection at different channel lengths. The highest resistance change for as-received RBDS protein was obtained for the electrodes with 3 mm long channel lengths. Based on these results, a 3 mm channel length was selected as a suitable length of the electrodes.

[0139] Proceeding determination of the electrode channel length and electrode gap, the sensor surface was functionalised with GPS silane, as previously described in relation to Figure 6. The silicon device surface was functionalised with GPS silane for ordered binding of COVID-19 nano-MIPs to the device. GPS silanisation was confirmed based on water contact angle measurements and Fourier transform infrared (FTIR) spectroscopy. The water contact angle of the freshly fabricated silicon sensor surface was 80.2+5.1°. Prior to the GPS silanisation, the sensor surface was O2 plasma cleaned to remove any organic contaminants and to activate the hydroxyl groups on the surface to facilitate the GPS binding. After O2 plasma cleaning, the surface became extremely hydrophilic with a water contact angle of 4.2+1.4°, with similar results being observed in previous studies. After the sensor surfaces were GPS silanised, the water contact angle increased to 76.1+3.2° indicating a modification to the system after GPS vapour exposure. The sensor surface became extremely hydrophobic after GPS silanisation with respect to the O2 plasma cleaned surface due to the long carbon chain in GPS molecule.

[0140] FTIR spectral features of a freshly fabricated silicon device were clearly seen to have been modified after exposing the devices to GPS silane, suggesting that GPS bound to the silicon device. The broad peak found at -3500 cm ¹ and multiple peaks found between the 1000-1500 cm ¹ region for the silicon device are attributed to the OH stretching vibration band of adsorbed water molecules and Si-0 stretching vibration modes of oxygen impurities, respectively. Once the silicon device was exposed to oxygen plasma followed by being GPS silanised, a FTIR spectrum with a much smoother baseline was observed, indicating the oxygen plasma had cleaned the silicon surface successfully. The peaks found at -1000 cm ¹ and 788 cm ¹ in the FTIR spectra of GPS silanised silicon devices are assigned to Si-O-Si asymmetrical stretching and Si-0 stretching vibrational bands of GPS on silicon device, respectively.

[0141] Further evidence supporting successful GPS silanisation was provided by the resistance measurements obtained for the silicon device before and after GPS silanisation. The resistance value for the freshly fabricated silicon device had dropped -70% from -10.6MW to -2.8MW after GPS silanisation, suggesting the silicon surface interacted with the GPS silane.

[0142] Stepwise development of the SARS-CoV-2 biosensor is depicted in Figure 6. The freshly prepared silicon device surface is rich in dangling hydroxyl groups. O2 plasma cleaning for the freshly fabricated device activates the hydroxyl groups on the device surface. Once the device is exposed to GPS silane, the hydroxyl groups on the device surface interact with the GPS silane and form Si-0 bonds. The epoxy ring of the GPS silane is then reacted with the incoming COVID-19 nano-MIPs to facilitate ordered binding of the nano-MIPs. The COVID-19 nano-MIP binding to GPS silanised devices was characterised via two methods, FTIR spectra and resistance measurements. The significant change in the FTIR spectral features of the GPS silanised devices in the presence of nano-MIPs suggests that the GPS had interacted with the COVID-19 nano- MIPs. Such a drastic change in FTIR spectral features of GPS silanised devices was not observed when treating with PBS which was utilised as a negative control.

[0143] Upon addition of COVID-19 nano-MIPs to the GPS silanised devices, the resistance dropped by an average of 25%, whereas for the PBS control, the resistance dropped by an average of 78%. Such a drastic drop in resistance in the presence of PBS is likely due to the high ionic composition of the system, which can be physically adsorbed to the GPS, causing an increase in conductivity across the electrodes after PBS addition. Such a large change in ionic composition is not expected for nano-MIPs and the drop in resistance indicates that COVID-19 nano-MIPs act as electron donors upon GPS interaction, thus contributing electrons to the system causing a reduction in resistance. In the final step 630, the COVID-19 nano-MIP immobilised-biosensor binds with the incoming SARS-CoV-2 proteins. The binding sites of the COVID-19 nano- MIPs can selectively bind with the incoming proteins. The changes observed in FTIR spectral features of the pristine protein samples after interacting with the COVID-19 nano-MIPs confirms protein interaction occurred with the COVID-19 nano-MIPs.

[0144] The as-received COVID-19 nano-MIPs were used for the experiment without any dilution. Considering the COVID-19 nano-MIP particle size (range -70-150 nm), the amount of undiluted COVID-19 nano-MIP solution (10 pL of 0.339 mg/mL nano- MIPs)) was sufficient to completely occupy the GPS molecules in the sensing area of the device with no exposed GPS molecules being available to directly interact with the incoming SARS-CoV-2 proteins. The sensor surface was washed thoroughly with PBS solution after COVID-19 nano-MIP immobilisation, only the COVID-19 nano-MIPs chemically adsorbed onto the GPS molecules were retained on the surface whereas loosely bound COVID-19 nano-MIPs were removed during the wash step of device preparation.

[0145] Both RBDS and FHA proteins displayed a linear correlation for the change in resistance as a function of protein concentration, as evident from data obtained via test results. The responsivity (i.e. the slope of the graph) for RBDS and FHA proteins are 8.8 and 7.8 %/mg/mL, respectively. This suggests that the biosensor is more sensitive in detecting RBDS protein than FHA protein. To evaluate the contribution from the matrix in the protein solution in resistance change, control experiments were conducted for PBS solution. The average resistance change for PBS was -12%, which is in a reversed polarity to the change in resistance observed for both SARS-CoV-2 proteins, suggesting that there is no significant contribution from PBS to the resistance changes in both SARS-CoV-2 proteins. Therefore, the resistance change in the SARS-CoV-2 protein conditions were attributed to the binding of the protein to the biosensors, without interference from the matrix.

[0146] The detection limit for both RBDS and FHA proteins was determined to be 7pg/mL, as this was the concentration in which a positive change in resistance following protein addition was no longer observed. This value is much lower than the reported clinically relevant SARS-CoV-2 protein concentration of 1 ng/mL. This signifies that the biosensor device, as described herein, is a suitable tool for detecting SARS-CoV-2 proteins. As in this study, both RBDS and FHA SARS-CoV-2 surface proteins can be detected at low concentrations, the biosensor device is useful in producing accurate (no false positive/negative outcomes) and sensitive results when determining whether the user has been exposed to SARS-CoV-2 virus.

[0147] The same experimental methodology was followed using devices fabricated on a relatively lower resistivity silicon wafer (1000-2000 W-cm) to compare the results with the devices fabricated with a high resistivity silicon wafer. The devices fabricated on the lower resistivity silicon wafers also demonstrated a linear relationship in resistance change as a function of both RBDS and FHA proteins with the same detection limit (7pg/mL). However, the responsivity for RBDS and FHA proteins were determined to be 8.0 and 6.8 %/mg/mL, respectively. These responsivity values are lower for both proteins compared to the corresponding responsivities of the devices fabricated on high resistivity silicon wafers. This suggests that a high resistivity silicon wafer is better suited when fabricating the biosensor device for increased sensitivity in biomolecule detection.

[0148] The plausible explanation for the resistance changes observed when binding the proteins with the COVID-19 nano-MIPs is the intermolecular charge transfer supported by the intrinsic silicon wafer. Though the high resistivity intrinsic silicon wafer contains a relatively lower amount of charge carriers compared to the lower resistivity counterpart, these charge carriers are sufficient for electron transportation across the electrodes. The protein detection results from low resistive silicon wafers suggests that excessive charge carriers in a silicon wafer do not necessarily improve the device sensitivity/detection limit/efficacy.

[0149] The COVID-19 nano-MIPs-immobilised biosensor can selectively detect both RBDS and FHA proteins in the presence of a mixture of other proteins (Figure 22).

This conclusion was drawn based on the experiment conducted for a mixture of proteins in the presence of both RBDS and FF1A proteins. Since both RBDS and FFIA proteins are available in SARS-CoV-2 virus particles, the resistance change for the RBDS and FFIA protein combined solution was first determined. The resistance change for the combined solution was calculated to be -24%, which was approximately the same as of the additive resistance changes for the individual RBDS (-16%) and FFIA (-6%) protein samples. In contrast, other protein samples used for the selectivity study (i.e. interleukin-6 (IL-6), C-reactive protein (CRP), cardiac Troponin I (cTnl), and brain natriuretic peptide (BNP)) displayed negative resistance changes on the COVID- 19 nano-MIPs. The molecular sizes of these proteins (IL-6 (-21 kDa), CRP (-25 kDa), cTnl (-24 kDa), and BNP (-3 kDa)) are relatively lower than that of RBDS (-30 kDa) and FHA (-170-180 kDa) proteins. The resistance change observed for the mixture of all these proteins (RBDS, FHA, IL-6, CRP, cTnl, and BNP) was -26%, which is close to the additive resistance changes of the individual RBDS and FHA proteins. This suggests that even the smaller proteins cannot directly bind to the COVID-19 nano- MIPs, highlighting the extreme selectivity of COVID-19 nano-MIP binding sites for RBDS and FHA protein binding.

[0150] The COVID-19 biosensor can detect SARS-CoV-2 protein variants in both PBS and artificial saliva media (Figures 23A and 23B). Given the evolvement of the SARS-CoV-2 virus to different variants, it is important to develop methods to rapidly detect these variants as the severity of the COVID-19 infection depends on the type of COVID-19 variant. The biosensor can detect all four model SARS-CoV-2 protein variants used in the study (Alpha, Beta, Gamma, and Delta variants). To compare the SARS-CoV-2 protein variant responses with respect to the RBDS reference strain response, commercially available RBDS protein with a relatively similar amino acid sequence to the COVID-19 variants was chosen for the study. The change in resistance for a given variant is increased with the variant concentration in both PBS and artificial saliva media. The lowest variant concentration tested was lOpg/mL which is the detection limit for RBDS protein for the biosensor.

[0151] The resistance change for the SARS-CoV-2 protein variants are in the order of RBDS reference<Alpha<Beta<Gamma<Delta in both PBS and artificial saliva. The resistance changes for all SARS-CoV-2 protein variants for a given concentration is higher in PBS than in artificial saliva. The ionic strength of artificial saliva is much higher than PBS due to the high proportion of ionic components present in it. This is reflected in the resistance change observed for the control samples where artificial saliva had an average -50% resistance change compared to the average -12% resistance change in PBS. This strong ionic composition might have affected the charge transfer effect of SARS-CoV-2 protein variants upon interacting with COVID-19 nano-MIPs, thus causing a lower resistance change compared to that of PBS for the same sample. Low resistivity silicon devices also displayed successful detection of COVID-19 variants. However, unlike the high resistivity silicon wafer, the low resistivity silicon wafer did not show a clear trend in detecting the SARS-CoV-2 protein variants as a function of protein concentration in PBS. This indicates that high resistivity silicon devices are much better performers in detecting SARS-CoV-2 protein variants than the low resistivity silicon devices.

[0152] The test results as shown in Figures 20A and 20B show that SARS-CoV-2- targetting CIMP immobilised sensing portions according to embodiments described herein can be used for at least two cycles of RBD protein detection. Figure 20A plots results of treatment of the sensor utilising pure isopropyl alcohol (IP A). Figure 20B plots results of treatment of the sensor utilising acetic acid. The graphs of Figure 20A and 20B illustrate the efficiency of the removal of SARS-CoV-2 proteins from the CIMPs, removing the CIMPs from the sensing portion 126, and if relevant additional sensing portion 128. This is indicated by the “Control” labels and the “After IPA Addition” or “After Acetic Acid Addition” labels of Figures 20A and 20B, respectively. The graphs of Figures 20A and 20B further illustrate the efficiency of re binding the SARS-CoV-2 proteins onto the treated sensor portion 126, and if relevant additional sensing portion 128. This is indicated by the “RBD 1 ^st Addition” and “RBD 2 ^nd Addition” labels of Figures 20 A and 20B, respectively.

[0153] In relation to treatment of the sensor utilising IPA, Figure 20A illustrates that the resistance change in the control and the resistance change in the system post treatment (“After IPA Addition”) are in the same polarity and are of comparable magnitude. In some embodiments, this indicates that treatment utilising IPA can completely, or at least partially, remove RBD proteins from the sensor. Further, Figure 20 A illustrates that an appreciable amount of RBD protein binding to the sensor was observed in the “RBD 2 ^nd Addition”, indicating successful binding of RBD proteins to the retained CIMPs on the sensor portion 126, and if relevant the additional sensor portion 128. In some embodiments, a variation in the change in resistance between the “RBD 1 ^st Addition” and the “RBD 2 ^nd Addition” may suggest that the treatment compromised the structural integrity of the sensor. Figure 20A shows a similar change in resistance between the “RBD 1 ^st Addition” and the “RBD 2 ^nd Addition” suggesting no loss of structural integrity of the sensor.

[0154] Similarly, in relation to treatment of the sensor utilising acetic acid, Figure 20B illustrates that acetic acid may partially remove RBD proteins from the sensor, according to some embodiments. Further, Figure 20B illustrates that acetic acid may allow for successful binding of RBD proteins to the retained CIMPs on the sensor portion 126, and if relevant the additional sensor portion 128, after treatment. Figure 20B also shows a similar change in resistance between the “RBD 1 ^st Addition” and the “RBD 2 ^nd Addition”, suggesting no loss of structural integrity of the sensor. In some embodiments, treatment with either IPA or acetic acid may allow the sensor device 120 to be used at least two times in order to detect respiratory pathogens. That is, after a first detection of a respiratory pathogen, the sensor device 120 may be treated using either IPA or acetic acid to then be enabled to perform a second detection of a respiratory pathogen.

[0155] To wirelessly transmit an instant (or at least near-instant, when compared to previous sensing techniques) sensing response to a cloud connected interface, a battery- free near field communication (NFC) system was employed, as an example of sensor device 120. The wireless electronic measurement device (e.g. sensor device 120) was powered through a magnetically coupled primary coil of an NFC supported smartphone and a secondary loop coil incorporated on the device resonating at 13.56 MFlz. The induced voltage in the secondary loop coil was fed into the half-wave bridge rectifier followed by a low-dropout voltage regulator (1.8 V) to enable a constant and uninterrupted DC power supply to the circuit. Figure 8A illustrates the basic operational principle of the entire circuit. The analog front-end is comprised of a Wheatstone bridge with resistances R1 and R2, and sensor chip 250 to detect any resistance change of the sensor due to incoming covid variants and a differential amplifier 125a configured to distinguish and amplify the voltage difference that can occur because of resistance changes of the sensor. The analog-to-digital converter (ADCO) of the NFC System on Chip (SoC) digitalised the incoming signal from the amplifier 125a output pin and then transmitted the digitalised data over air using ISO/IEC 15693 protocol for contactless data reading by a smartphone (as an example of computing device 110). An android app, as an example of sensor application 190, can be configured to receive and plot the data from the NFC SoC.

[0156 j The performances of the secondary loop coil antenna and the energy harvesting by the antenna to power the active and passive components allows for reliable wireless data transmission. To achieve the resonant frequency of 13.56 MFlz, a capacitor of 10 pF was utilised between pins 1 and 2 of the NFC SoC. A resonance peak position (fr) at 13.56 MFlz of the loop coil antenna was measured by a precision spectrum analyser. The narrow bandwidth {Ϊ2 -fi) of full width at half maximum (FWHM) demonstrated a higher Q-factor (fr/(f2-fi)), indicating a low rate of energy loss of the loop coil antenna.

[0157] To evaluate the efficacy of the SARS-CoV-2 biosensor in detecting the SARS- CoV-2 proteins to the end-user using the fabricated device, an aerosolised protein experiment was conducted to mimic the saliva and mucosa droplets that are released during sneezing. A commercial spray bottle was used in the experiment to spray the proteins onto the nano-MIP-immobilised sensors. Similar to the observation in the drop casted method (Figures 23A and 23B), the aerosolised/spray SARS-CoV-2 protein on the sensor attached to the wireless device displayed a positive change in resistance in the same order of Delta>Gamma>Beta>Alpha>RBDS reference. The control of solvent artificial saliva produced a negative contribution to the resistance change. The resistance change, AR(%), of the sensor chip 250 was calculated within the smart computing device app, as well as determining the corresponding COVID variants which were then displayed to the user. Figure 24 illustrates the detection of covid variants which is comparable to the drop casted detection of COVID variants as demonstrated in Figures 23 A and 23 B.

[0158] In conclusion, a highly selective and sensitive conductometric biosensor for the rapid detection of SARS-CoV-2 proteins and its variants was developed. The sensor platform consisted of a commercially available high resistivity silicon wafer and photolithographically developed two-terminal electrode. After surface functionalisation utilising GPS silanisation, COVID- 19 nano-MIPs were immobilised for selective binding of SARS-CoV-2 surface proteins. Both model SARS-CoV-2 proteins, RBDS and FF1A, displayed a linear relationship in change in resistance with the protein concentration with both displaying a detection limit of 7 pg/mL. The sample immobilisation time was as low as 10 min and the readings were obtained in <1 min. The biosensor was extremely selective to the detection of model SARS-CoV-2 proteins even in the presence of other types of proteins with similar molecular sizes used in the study. In addition, the biosensor could detect different variants of SARS-CoV-2 proteins in the order of resistance changes at Delta>Gamma>Beta>Alpha>RBDS reference. Another important finding in this study was that pure IPA and acetic acid can be used for the complete or partial removal of SARS-CoV-2 proteins from the sensor surface without detrimental damage to the nano-MIPs or sensor integrity. Furthermore, the sensor can be used for at least two cycles of RBDS protein detection when regenerated with these treatments. By using a NFC circuit, the SARS-CoV-2 protein detection results were successfully transferred to a mobile app. This example demonstrates the suitability of using a high resistivity silicon wafer-based conductometric sensor platform for respiratory pathogen detection, for example as part of an economically viable, sensitive, and reusable next- generation point-of-care medical device.

[0159] Device Fabrication: silicon wafers (resistivities: >5000 W-cm and 1000- 2000 W-cm) for biosensor fabrication were purchased from D&X Co. Ltd. (Japan). As- received Si wafers were rinsed sequentially in acetone, IPA, and deionised (DI) water followed by drying under compressed N2 gas. Then, these Si wafers were dehydrated at 120 °C for 2 min. AZ 5214E photoresist was spin coated on the dehydrated Si wafers using a SPIN150 spin coater for 30 s at a spinning speed of 3000 rpm. The Si wafers were then soft baked at 95 °C for 1 min. The electrode patterns with desired electrode gaps and lengths were designed on the Si substrate using a MLA150 Maskless Aligner (Heidelberg Instruments). The electrode patterns were then hard baked at 120 °C for 2 min followed by flood exposure for UV radiation for 15 s. Finally, the substrate was developed in a 400 K developer for 20 s followed by 30 s of rinsing in DI water. The electrodes were then tested under a light microscope to ensure there were no remaining photoresists between the electrode gaps. The electron beam deposition (PVD75 E-beam Evaporator, Kurt J. Lesker) was used to deposit a 30 nm titanium adhesion layer and a 300 nm gold layer atop of the electrodes. At the end of the photolithography process, the electrode patterns were realised by a lift-off process.

[0160] GPS Silanisation: GPS silane was purchased from Sigma- Aldrich (Castle Hill, New South Wales, Australia) and used as-received. GPS silanisation was conducted by same procedure followed according to our recent publication. ⁴⁷ In brief, freshly prepared Si devices were exposed to O2 plasma for 10 min (Plasma Cleaner PDC-002, Harrick Plasma). These devices were then exposed to GPS vapour for 1-2 h in a vacuum desiccator placed inside a fume hood. Then, the devices were rinsed thoroughly with DI water for 2 min followed by heating at 150 °C for 10 min.

[0161] Surface Characterisations: FTIR spectra of the samples were acquired using a Spotlight 400 FT-IR Imaging System equipped with Perkin Elmer Spectrum and Spectrum IMAGE Viewer software. The size of the scanned area was 100 pm x 100 pm and an average of 516 scans were taken for a given scanned spot. Three spots were scanned for a given sample and the average spectra of the sample were reported in the manuscript. Water contact angle measurements were obtained using a Dataphysics OCA 15 plus Contact Angle instniment equipped with SCA 20 software.

[0162] In some embodiments, the SARS CoV-2 S2Pi ₂ os-FHA protein used in tests and to acquire data as described herein, was provided by the Burnet Institute, Melbourne, Australia. This protein comprised the S glycoprotein ectodomain sequence (residues 16-1208) from the Wuhan Hu-1 isolate (Genbank accession number: YP_009724390.1). Three key modifications were included: (i) K986P/V987P mutations (the “2P” mutation to maintain prefusion conformation), (ii) R628ARR- >G628SAS mutation (to remove the furin cleavage site; thus the S glycoprotein was not cleaved into SI and S2 subunit), and (iii) addition of GlySerGlySer-Fibritin-GSGS- His8-GSGS-Avitag (FHA) sequence to the C-terminus: GSGS- YIPEAPRDGQAYVRKDGEWVLLSTFL-GSGS-HHHHHHHH-GSGS- GLNDIFEAQKIEWHE (SEQ ID NO: 1).

[0163] SARS CoV-2 S2Pi ₂ os-FHA amino acid sequence:

VNLTTRQLPPAYTNSFTRGVYYPDKVFRSSVLHSTQDLFLPFFSNVTWFHAIHV

SGTNGTKRFDNPVFPFNDGVYFASTEKSNIIRGWIFGTTFDSKTQSFFIVNNATN

VVIKVCEFQFCNDPFFGVYYHKNNKSWMESEFRVYSSANNCTFEYVSQPFFM

DFEGKQGNFKNFREFVFKNIDGYFKIYSKHTPINFVRDFPQGFSAFEPFVDFPIG

INITRFQTFFAFHRSYFTPGDSSSGWTAGAAAYYVGYFQPRTFFFKYNENGTIT

DAVDCAFDPFSETKCTFKSFTVEKGIYQTSNFRVQPTESIVRFPNITNFCPFGEV

FNATRFASVYAWNRKRISNCVADYSVFYNSASFSTFKCYGVSPTKFNDFCFTN

VYADSFVIRGDEVRQIAPGQTGKIADYNYKFPDDFTGCVIAWNSNNFDSKVGG

NYNYFYRFFRKSNFKPFERDISTEIY QAGSTPCNGVEGFNCYFPFQS YGFQPTN

GVGYQPYRVVVFSFEFFHAPATVCGPKKSTNFVKNKCVNFNFNGFTGTGVFT

ESNKKFFPFQQFGRDIADTTDAVRDPQTFEIFDITPCSFGGVSVITPGTNTSNQV

AVLYQDVNCTEVPVAIHADQLTPTWRVYSTGSNVFQTRAGCLIGAEHVNNSY

ECDIPIGAGICASYOTOTNSPGSASSVASOSIIAYTMSFGAENSVAYSNNSIAIPT

NFTISVTTEIEPVSMTKTSVDCTMYICGDSTECSNEEEQYGSFCTQENRAETGIA

VEQDKNTQEVFAQVKQIYKTPPIKDFGGFNFSQIEPDPSKPSKRSFIEDEEFNKV TLADAGFIKQYGDCLGDIAARDLICAQKFNGLTVLPPLLTDEMIAQYTSALLAG

TITSGWTFGAGAALQIPFAMQMAYRFNGIGVTQNVLYENQKLIANQFNSAIGKI

QDSLSSTASALGKLQDVVNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDPPE

AE VQIDRLITGRLQS LQT Y VT QQLIR A AEIRA S ANLA ATKMS EC VLGQS KR VDF

CGKGYHLMSFPQSAPHGVVFLHVTYVPAQEKNFTTAPAICHDGKAHFPREGVF

VSNGTHWFVTQRNFYEPQIITTDNTFVSGNCDVVIGIVNNTVYDPLQPELDSFK

EELDKYFKNHTSPDVDLGDISGINASVVNIQKEIDRLNEVAKNLNESLIDLQELG

KYEOGSGSYIPEAPRDGOAYVRKDGEWVLLSTFLGSGSHHHHHHHHGSGSGL

NDIFEAOKIEWHE (SEQ ID NO: 2)

[0164] The glycoprotein was expressed in 293F cells and purified from the supernatant via Co ²⁺ TALON affinity chromatography followed by Superose 6 size exclusion chromatography (SEC). The purified glycoprotein appeared as a single symmetrical peak in SEC and a single band (170-180 kDa) in an SDS-PAGE. Binding of S2Pi ₂₀₈ -FHA protein to human ACE2-Fc was confirmed in biolayer interferometry. The sample had been filter-sterilised and contained 200 mg S2Pi ₂₀₈ -FHA (290 pL @

0.7 mg/mL) in PBS. The concentration was inferred from the absorbance at 280 nm (extinction coefficient = 1.019).

[0165] SARS CoV-2 RBD of spike glycoprotein was provided by the Burnet Institute, Melbourne, Australia. This protein comprised the RBD ectodomain sequence (amino acids 332-532) from the Wuhan Hu-1 isolate (Genbank accession number: YP_009724390.1). Four key modifications were included: (i) A serine at the first position for optimised leader sequence cleavage, (ii) GGSGS (SEQ ID NO: 3) flexible linker after final ⁵³² N, (iii) HHHHHHHH (SEQ ID NO: 4) poly His tag for purification and detection with anti-HIS antibodies, and (iv) GLNDIFEAQKIEWHE (SEQ ID NO: 5) Avi tag for site-specific biotinylation.

[0166] RBD sequence:

S ³³² ITNLCPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGV

SPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCVIA

WNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNGVEGFNC YFPLOSYGFOPTNGVGYOPYRVVVLSFELLHAPATVCGPKKST ⁵³² NGGSGSHH

HHHHHHGSGSGLNDIFEAQKIEWHE (SEQ ID NO: 6)

[0167] The glycoprotein was expressed in 293 expi cells and purified from the supernatant via Co ²⁺ TALON affinity chromatography followed by Superdex200 16/600 size exclusion chromatography (SEC). The purified glycoprotein appeared as a single symmetrical peak in SEC and a single band (30 kDa) in an SDS-PAGE. Binding of the RBD to human ACE2-Fc was confirmed in biolayer interferometry. The sample had been filter- sterilised and contained 100 pg of protein at 2.14 mg/mL. The concentration was inferred from the absorbance at 280 nm (extinction coefficient 1.48. OD280 of 1:10 = 0.317).

[0168] Details of Commercial SARS CoV-2 Protein Variants: SARS CoV-2 spike protein (S-RBD) (aa 330-524), His tag recombinant protein (Catalogue No. RP87674) was purchased from Thermo Fisher Scientific (Scoresby, Australia). All SARS-CoV-2 protein variants (Alpha strain: SARS-CoV-2 (2019-nCoV) Spike RBD (N501Y)-His Recombinant Protein [Catalogue No. 40592 -V08H82], >95% purity; Beta strain: SARS-CoV-2 (2019-nCoV) Spike RBD (K417N, E484K, N501Y)-His Recombinant Protein [Catalogue No. 40592- V08H85], >90% purity; Gamma strain: SARS-CoV-2 (2019-nCoV) Spike RBD (K417T, E484K, N501Y) Protein (His Tag) [Catalogue No. 40592-V08H86], >95% purity; and Delta strain: SARS-CoV-2 Spike RBD (T478K) Protein (His Tag) [Catalogue No. 40592-V08H91]) were purchased from Sino Biological Inc. (China).

[0169] SARS CoV-2 nano-MIPs, Antigen Solutions, and Other Chemicals: SARS- CoV-2 nano-MIPs solution (with 0.05% v/v ProClin 300 preservative, concentration of as-received nano-MIPs was 0.339 mg/mL, particle size range from -70-150 nm) was provided by MIP Diagnostics Ltd. (UK). IL-6, CRP, and IX PBS (pH 7.4) solutions were purchased from Sigma- Aldrich (Castle Hill, New South Wales, Australia). Human cTnl antigen was purchased from HyTest Ltd. (Turku, Finland). Human BNP antigen was purchased from Bachem (Bubendorf, Switzerland). Artificial saliva was purchased from Pickering Laboratories Inc. (Mountain View, California, USA). IPA (purity >99.5%) was purchased from Merck KGaA (Germany). Urea (purity >99%) was purchased from Chem Supply (Australia) and was dissolved in PBS to produce a 10 M solution. Acetic acid (purity >99%) was purchased from Sigma- Aldrich (Castle Hill, New South Wales, Australia). Instrumax® Pink (Whiteley®) disinfectant was purchased from Total Cleaning (Melbourne, Australia). All materials were used as- received.

[0170] Immobilisation of SARS-CoV-2 nano-MIPs: SARS-CoV-2 nanoMIP solution (10 pL) was drop casted onto freshly prepared GPS-silanised Si devices and incubated for 0.5-1 h, allowing maximal binding of the nano-MIPs onto the devices. Then, the devices were rinsed extensively with PBS solution to remove any unbound nano-MIPs followed by drying with compressed N2 gas (>99.9% purity). The resistance across the nano-MIP-immobilised electrodes (Ro) was measured using a LTS120 Linkam Stage and a B2901A Precision Source/Measure Unit (Keysight Technologies). Keysight Quick I-V Measurement software was used in acquiring resistance data.

[0171] Immobilisation of SARS-CoV-2 Proteins: All the as-received SARS-CoV-2 protein solutions were diluted to the predetermined concentrations in either PBS or artificial saliva (depending on the experiment of interest). SARS-CoV-2 protein solution (10 pL) was drop casted onto the nano-MIP-immobilised Si devices and incubated for 10 min. After 10 min, the remaining SARS-CoV-2 protein solution was pipetted out and the devices were dried under compressed N2 gas (>99.9% purity). The resistance across the electrodes (R) was measured using a LTS120 Linkam Stage and a B2901A Precision Source/Measure Unit (Keysight Technologies). Keysight Quick I-V Measurement software was used in acquiring resistance data. In each experiment, 3-5 devices were used, and the average values were utilised in the change in resistance calculations.

[0172] It will be appreciated by persons skilled in the art that numerous variations and/or modifications may be made to the above-described embodiments, without departing from the broad general scope of the present disclosure. The present embodiments are, therefore, to be considered in all respects as illustrative and not restrictive.