Patent Description:
The transmission of the SARS-CoV-<NUM> (COVID-<NUM>) virus or other diseases through respiratory droplets poses a significant challenge to society. Reducing the spread of respiratory diseases requires the ability to quickly detect the presence of those diseases in a rapid and noninvasive manner. However, current tests for the SARS-CoV-<NUM> virus often rely on directly sampling bodily fluids (such as nasopharyngeal aspirate or saliva) from patients and sending those samples to laboratories, where the samples are then processed and finally tested. Unfortunately, this can be an extremely slow process, and these tests are often performed on symptomatic individuals and miss cases of diseases spread through asymptomatic or pre-symptomatic individuals. As a result, this creates a significant burden on the public health infrastructure and is highly insufficient in reducing the spread of the respiratory diseases.

<NPL> describes a series of experiments on vapor phase surface acoustic wave (SAW) sensors using a layer of antibodies as the chemically sensitive film.

<NPL> relates to real-time vapor phase detection of cocaine molecules using immunosensors based on Surface Acoustic Wave (SAW) resonators.

<NPL> relates to on-the-spot detection of low vapor pressure plastic explosives containing nitro groups such as RDX, TNT, and their analogous substances.

<CIT> relates to methods and compositions for analyzing test samples containing target analytes including proteins and nucleic acids using a surface acoustic wave sensor in combination with a hydrogel to obtain an ultra sensitive non-fluorescent detection system.

This disclosure provides for surface acoustic wave (SAW)-based hydrogel testing for detecting viruses.

In a first embodiment, an apparatus includes a SAW sensor. The SAW sensor includes a piezoelectric substrate. The SAW sensor also includes first and second interdigitating transistors over the piezoelectric substrate. The first interdigitating transistor is configured to convert an input electrical signal into an acoustic wave. The second interdigitating transistor is configured to convert the acoustic wave into an output electrical signal. The piezoelectric substrate is configured to transport the acoustic wave. The SAW sensor further includes a detection layer over the piezoelectric substrate and positioned at least partially between the first and second interdigitating transistors. The detection layer includes (i) antibodies configured to bind to one or more biological analytes and (ii) a hydrogel layer over the antibodies, wherein: the antibodies are configured to bind to one or more viruses; and the hydrogel layer is configured to permit the one or more viruses to diffuse through the hydrogel layer and contact the antibodies, wherein the hydrogel layer comprises an agarose hydrogel, a polyacrylamide hydrogel, or a guar gum hydrogel.

In a second embodiment, a system includes multiple SAW sensors. Each SAW sensor includes a piezoelectric substrate. Each SAW sensor also includes first and second interdigitating transistors over the piezoelectric substrate. The first interdigitating transistor is configured to convert an input electrical signal into an acoustic wave. The second interdigitating transistor is configured to convert the acoustic wave into an output electrical signal. The piezoelectric substrate is configured to transport the acoustic wave. Each SAW sensor further includes a detection layer over the piezoelectric substrate and positioned at least partially between the first and second interdigitating transistors. The detection layer includes (i) antibodies and (ii) a hydrogel layer over the antibodies. The antibodies of at least one of the SAW sensors are configured to bind to one or more biological analytes, wherein, in the at least one of the SAW sensors: the antibodies are configured to bind to one or more viruses; and the hydrogel layer is configured to permit the one or more viruses to diffuse through the hydrogel layer and contact the antibodies, wherein the hydrogel layer comprises an agarose hydrogel, a polyacrylamide hydrogel, or a guar gum hydrogel.

In a third embodiment, a method includes providing a flow of air to one or more SAW sensors and detecting one or more biological analytes in the flow of air using the one or more SAW sensors. At least one of the SAW sensors includes a piezoelectric substrate, first and second interdigitating transistors over the piezoelectric substrate, and a detection layer over the piezoelectric substrate and positioned at least partially between the first and second interdigitating transistors. The first interdigitating transistor is configured to convert an input electrical signal into an acoustic wave. The second interdigitating transistor is configured to convert the acoustic wave into an output electrical signal. The piezoelectric substrate is configured to transport the acoustic wave. The detection layer includes (i) antibodies configured to bind to the one or more biological analytes and (ii) a hydrogel layer over the antibodies, wherein: the antibodies are configured to bind to one or more viruses; and the hydrogel layer is configured to permit the one or more viruses to diffuse through the hydrogel layer and contact the antibodies, wherein the hydrogel layer comprises an agarose hydrogel, a polyacrylamide hydrogel, or a guar gum hydrogel.

For a more complete understanding of this disclosure, reference is made to the following description, taken in conjunction with the accompanying drawings, in which:.

<FIG>, described below, and the various embodiments used to describe the principles of the present disclosure are by way of illustration only and should not be construed in any way to limit the scope of the disclosure. Those skilled in the art will understand that the principles of the present disclosure may be implemented in any type of suitably arranged device or system.

As noted above, the transmission of the SARS-CoV-<NUM> (COVID-<NUM>) virus or other diseases through respiratory droplets poses a significant challenge to society. Reducing the spread of respiratory diseases requires the ability to quickly detect the presence of those diseases in a rapid and noninvasive manner. However, current tests for the SARS-CoV-<NUM> virus often rely on directly sampling bodily fluids (such as nasopharyngeal aspirate or saliva) from patients and sending those samples to laboratories, where the samples are then processed and finally tested. Unfortunately, this can be an extremely slow process, and these tests are often performed on symptomatic individuals and miss cases of diseases spread through asymptomatic or pre-symptomatic individuals. As a result, this creates a significant burden on the public health infrastructure and is highly insufficient in reducing the spread of the respiratory diseases.

This disclosure provides platforms that support immunosensor designs configured to rapidly detect the presence of one or more aerosol viruses. Each platform uses at least one surface acoustic wave (SAW)-based sensor that is functionalized with antibodies specific for one or more antigens, such as the SARS-CoV-<NUM> antigen (like its viral spike protein). A hydrogel scaffold supports the antibodies for use in a non-aqueous environment. As aerosol particles (such as respiratory droplets) come into contact with the hydrogel, the contents of the particles diffuse through and interact with the antibodies. Due to the highly specific nature of antibodies, only a specific antigen will interact with the corresponding antibody, and this interaction occurs immediately upon the antigen meeting the antibody. This interaction also changes the oscillation frequency of the SAW-based sensor, which enables detection of the oscillation frequency change and therefore detection of the specific antigen.

In this way, these platforms can quickly detect the presence of individuals shedding viruses like SARS-CoV-<NUM>, including asymptomatic and pre-symptomatic individuals, in a non-contact manner. This helps to reduce or eliminate the need to rely on slow contact-based testing and lagging or inconsistent reports from healthcare providers. Also, this approach can be used to create highly-specific sensors that are able to detect particular diseases with limited or no direct interactions with users. Further, this approach can provide rapid results (such as within seconds) and can be compatible with any suitable viral collection technique (such as from breathalyzer masks to wide-area environmental sampling). In addition, this approach does not depend on complex computation or modeling, and this approach supports the use of an extensible platform that only requires a new antibody in order to support the detection of an additional biological threat.

<FIG> illustrate an example SAW-based hydrogel sensor <NUM> for use in detecting viruses in accordance with this disclosure. As shown in <FIG>, the sensor <NUM> includes a piezoelectric substrate <NUM>, which generally represents a structure in or on which other components of the sensor <NUM> are carried. The piezoelectric substrate <NUM> may be formed from any suitable piezoelectric material(s), such as quartz. As a particular example, the piezoelectric substrate <NUM> may be formed using Y-rotated, X-propagating (ST-X) quartz. The piezoelectric substrate <NUM> may also be formed in any suitable manner, such as by cutting and polishing the piezoelectric material. The piezoelectric substrate <NUM> may have any suitable size, shape, and dimensions.

Two interdigitating transistors (IDTs) 104a-104b are positioned over the piezoelectric substrate <NUM>. Each interdigitating transistor 104a-104b includes two bases <NUM> and two sets of conductive fingers <NUM>. The bases <NUM> are positioned opposite each other, and each conductive finger <NUM> is electrically coupled to one of the bases <NUM><NUM> and extends towards the other of the bases <NUM>. The conductive fingers <NUM> are also interleaved or interdigitated such that the conductive fingers <NUM> are electrically coupled to the bases <NUM> in an alternating manner. Each interdigitating transistor 104a-104b may be formed from any suitable material(s), such as one or more metals like aluminum. Each interdigitating transistor 104a-104b may also be formed in any suitable manner, such as by depositing and etching metal or other material(s). Each base <NUM> and each conductive finger <NUM> of the interdigitating transistors 104a-104b may have any suitable size, shape, and dimensions. Each interdigitating transistor 104a-104b may include any suitable number of conductive fingers <NUM> and any suitable spacing between its conductive fingers <NUM>.

An input port <NUM> is coupled to the interdigitating transistor 104a, and an output port <NUM> is coupled to the interdigitating transistor 104b. During operation, a radio frequency (RF) signal or other electrical signal can be applied to the input port <NUM>, and the interdigitating transistor 104a converts the electrical signal into an acoustic wave. The acoustic wave travels across the substrate <NUM> to the interdigitating transistor 104b, which converts the acoustic wave into an RF signal or other electrical signal that is provided via the output port <NUM>.

Two sets of reflectors 114a-114b are positioned over the piezoelectric substrate <NUM> such that the interdigitating transistors 104a-104b are located between the reflectors 114a-114b. The reflectors 114a-114b operate to reflect parts of the acoustic wave that is directed towards the edges of the substrate <NUM> back towards an interior of the substrate <NUM>, thereby forming a resonant acoustic cavity. The interdigitating transistors 104a-104b and the reflectors 114a-114b cooperate to generate an acoustic standing wave within the resonant acoustic cavity when an input signal is applied to the input port <NUM>. Each reflector 114a-114b may be formed from any suitable material(s), such as one or more metals. Each reflector 114a-114b may also be formed in any suitable manner, such as by depositing and etching metal or other material(s). Each reflector 114a-114b may have any suitable size, shape, and dimensions. Each set of reflectors 114a-114b may include any suitable number of reflectors and any suitable spacing between its reflectors.

In order to support the sensing of one or more viruses, the sensor <NUM> includes a detection layer <NUM>, which is positioned over the piezoelectric substrate <NUM> and within and between the interdigitating transistors 104a-104b. The detection layer <NUM> is configured to detect the presence of one or more viruses as described below. Note that the detection layer <NUM> is shown in <FIG> as extending across the collections of conductive fingers <NUM> of the interdigitating transistors 104a-104b This helps to reduce or minimize the amount of bare substrate material in the cavity region of the sensor <NUM>. This also helps achieve a more uniform distribution of biomolecules in the SAW resonator's most sensitive region.

As shown in <FIG>, the input port <NUM> and output port <NUM> are coupled to an oscillator circuit <NUM>, which is shown generically here as an amplifier. Note that the reflectors 114a-114b are omitted here and that the interdigitating transistors 104a-104b are shown in simplified form here for ease of illustration. The oscillator circuit <NUM> generally represents a free-running oscillator that causes the sensor <NUM> to produce an acoustic wave, and the interdigitating transistor 104b feeds its output back into the oscillator circuit <NUM>. The result is that the acoustic wave has a specified frequency, and the frequency can then become lower as viruses bind to the detection layer <NUM>. An output <NUM> of the oscillator circuit <NUM> represents the output of the SAW-based sensor <NUM> and can be provided to a controller <NUM> for processing. The oscillator circuit <NUM> includes any suitable structure configured to cause a SAW-based sensor <NUM> to generate an output at a specified frequency. For instance, the oscillator circuit <NUM> may include a first matching circuit, a phase shifter, an amplifier, an attenuator, and a second matching circuit coupled in series from the output port <NUM> to the input port <NUM>. Note, however, that this disclosure is not limited to any particular implementation of the oscillator circuit <NUM>.

The use of the detection layer <NUM> in the SAW-based sensor <NUM> allows an immediate translation of a biological detection event into an electrical signal. That is, the detection layer <NUM> includes antibodies for at least one virus to be detected. Without any antigens present, the output <NUM> of the SAW-based sensor <NUM> may have a specified frequency. As antibodies in the detection layer <NUM> bind to antigens, the frequency of the acoustic wave produced in the SAW-based sensor <NUM> decreases, which decreases the oscillator frequency and changes the output <NUM> of the SAW-based sensor <NUM>. When at least one specific virus binds to the antibodies of the detection layer <NUM> in a suitable quantity to change the frequency of the output <NUM> by at least some threshold amount, this can be sensed by the controller <NUM> and used as an indicator that the at least one specific virus or other antigen is present.

The controller <NUM> processes the output of the SAW-based sensor <NUM> in order to detect when an adequate number of viruses have bound to the antibodies of the detection layer <NUM> in order to change the oscillating frequency of the sensor <NUM>. For example, the controller <NUM> may determine if the frequency of the output of the SAW-based sensor <NUM> has dropped by at least a specified threshold amount. Note that the specific threshold used here can vary based on various factors, such as the desired amount of viruses to bind to the detection layer <NUM>. In some cases, for instance, it might take about one thousand virus particles to bind to the detection layer <NUM> in order to change the frequency of the sensor <NUM> by about <NUM> Hertz (Hz). Since a person may have a much higher number of virus particles in his or her breathe, a larger frequency change may be used as an indicator of the presence of the viruses. Also note that each virus might actually be able to bind to multiple antibodies in the detection layer <NUM>, such as when different instances of spike proteins of the SARS-CoV-<NUM> virus can bind to different instances of an antibody in the detection layer <NUM>. This may allow a larger change in the frequency of the SAW-based sensor <NUM> to be detected based on fewer antigens. Upon the detection of the presence of a specific antigen, the controller <NUM> may take any suitable action(s), such as triggering an audible or visual alert. The controller <NUM> may also provide a graphical or other output identifying the change in the frequency of the sensor <NUM> over time.

The controller <NUM> includes any suitable structure configured to receive and use outputs of a SAW-based sensor <NUM>. For example, the controller <NUM> may include processing or other circuitry configured to sense when the frequency output by the SAW-based sensor <NUM> changes by at least a threshold amount or falls below a threshold value. In some embodiments, the SAW-based sensor <NUM> may be placed on a first circuit board, and the controller <NUM> may be placed on a second circuit board that can be coupled to the first circuit board via a Universal Serial Bus (USB) connector or other connector. Note that the controller <NUM> may be used with one SAW-based sensor <NUM> or with multiple SAW-based sensors <NUM>.

Some SAW-based designs have been proposed to detect small molecules, such as trace molecules of cocaine or explosives like trinitrotoluene (TNT). These molecules can have molecular weights of <NUM> daltons (Da) to <NUM> kilo-daltons (kDa). However, viruses typically have much larger molecular weights, such as when viral particles can reach the mega-dalton (MDa) range. As a particular example, the SARS-CoV-<NUM> virus can have a mass of about <NUM>,<NUM> MDa and a diameter of about <NUM> nanometers (nm). Moreover, the SAW-based sensor <NUM> may be deployed to operate by receiving an air flow and not a liquid flow. As a result, the detection layer <NUM> can allow for rapid diffusion of particles with large molecular weights while still sufficiently supporting and hydrating antibodies used to detect antigens.

As shown in <FIG>, the detection layer <NUM> includes a layer of antibodies <NUM>. Each of the antibodies <NUM> can be used to bind to a specific antigen. The specific antibodies <NUM> used in the sensor <NUM> can vary as needed or desired. For example, in some embodiments, a single type of antibody <NUM> may be used to sense a single type of antigen in each sensor <NUM>, and multiple sensors <NUM> may be used to sense the same antigen or different antigens. Any suitable antibodies <NUM> may be used in the sensor <NUM> to identify any desired antigen(s). As particular examples, the antibodies <NUM> may be used to detect SARS-CoV (which is associated with severe acute respiratory syndrome coronavirus), SARS-CoV-<NUM> (which is associated with COVID-<NUM>), MERS-CoV (which is associated with Middle East Respiratory Syndrome), or hemagluttinin or neuraminidase (which are associated with influenza).

The antibodies <NUM> are immobilized on the piezoelectric substrate <NUM> using a layer of cross-linkers <NUM>. The cross-linkers <NUM> help to hold the antibodies <NUM> on the surface of the piezoelectric substrate <NUM>. Any suitable cross-linkers <NUM> can be used here, and the specific cross-linkers <NUM> used can vary depending on the material(s) forming the substrate <NUM> and the antibodies <NUM> to be immobilized. In some embodiments, for example, the cross-linkers <NUM> represent a layer of "protein A", which is a protein originally discovered in the cell walls of the bacteria Staphylococcus aureus (commonly found in the upper respiratory tract and on the skin).

A thin hydrogel layer <NUM> (also called a hydrogel scaffold) is placed over the antibodies <NUM>. The hydrogel layer <NUM> supports the use of the antibodies <NUM> in a non-aqueous environment. The hydrogel layer <NUM> includes a collection of polymer chains linked in a three-dimensional network. The hydrophilic nature of the polymers allows the hydrogel layer <NUM> to contain a high concentration of water without dissolving or falling apart and to retain the water over a prolonged period of time. This high concentration of water supports and hydrates the antibodies <NUM>, allowing them to maintain their specificity for an antigen of interest. Here, one or more antigens of interest can diffuse through the hydrogel layer <NUM> in order to interact with and bind to the antibodies. The hydrogel layer <NUM> may support the use of antibodies <NUM> for any suitable length of time. In some embodiments, for example, the hydrogel layer <NUM> may last for up to a week or more at <NUM>% relative humidity (RH).

In some embodiments, a formulation of the hydrogel layer <NUM> for use with a specific type of antibody can be determined as follows. Note, however, that the following details are examples only, and a hydrogel formulation can be determined in any other suitable manner. In order to determine an appropriate hydrogel formulation and concentration over a specified range of particle sizes, commercially-available biotin-labeled microspheres of diameters from <NUM> to <NUM> micrometers (µm) can be functionalized with a streptavidin conjugated fluorophore, such as fluorescein or rhodamine <NUM> (R6G). A surface of the SAW-based sensor <NUM> can be functionalized with an antibody specific to the fluorophore using protein A. After functionalization, the surface of the SAW-based sensor <NUM> can be covered in a thin layer <NUM> of hydrogel, where different formulations of the hydrogel can be created as described below. Testing can be performed by liquid injection using a known concentration of functionalized microspheres and/or by nebulizing a known concentration of microspheres, such as by using a Collison nebulizer in a calm air chamber. A determination can then be made which formulation(s) of the hydrogel adequately bind to the microspheres. The testing here can be used to identify a viable formulation for the hydrogel layer <NUM>.

Some formulations can involve the use of agarose hydrogels with concentrations ranging from <NUM>% agarose to <NUM>% agarose weight by volume. Hydrogels can be created by dissolving an appropriate amount of powdered agarose into ultrapure water (pH <NUM>) or phosphate buffered saline (PBS, pH <NUM>), boiling the solution, and allowing it to cool to slightly above the gel point before pipetting onto the surface of the SAW-based sensor <NUM>.

Other formulations can involve the use of polyacrylamide hydrogels at concentrations ranging from <NUM>% to <NUM>% polyacrylamide. Both Bis-Tris and Tris-Glycine acrylamide solutions can be formulated and tested. Hydrogels can be formulated by diluting a commercial <NUM>% stock solution into a Tris buffer to achieve a final pH of <NUM>. Other common buffers such as <NUM>-(N-morpholino)propanesulfonic acid (MOPS), <NUM>-(<NUM>-hydroxyethyl)-<NUM>-piperazineethanesulfonic acid (HEPES), and <NUM>-(N-morpholino)ethanesulfonic acid (MES) may also be formulated and tested at neutral pH. After diluting the polyacrylamide to a desired solution and degassing, a gel can be crosslinked using tetramethylethylenediamine (TEMED) and ammonium persulfate (APS). Before crosslinking is completed, a thin layer of the gel can be used to coat the surface of the SAW-based sensor <NUM>.

Still other formulations can involve the use of guar gum hydrogels with concentrations ranging from <NUM>% guar gum to <NUM>% guar gum weight by volume. A desired amount of guar gum can be dissolved in <NUM>% glutaraldehyde and used to coat the surface of the SAW-based sensor <NUM> before completely gelling.

Although <FIG> illustrate one example of a SAW-based hydrogel sensor <NUM> for use in detecting viruses, various changes may be made to <FIG>. For example, the sizes, shapes, and dimensions of the sensor <NUM> and its various components may vary as needed or desired. Also, the layout and arrangement of components may vary as needed or desired.

<FIG> illustrates an example device <NUM> having multiple SAW-based hydrogel sensors <NUM> for use in detecting viruses in accordance with this disclosure. In particular, <FIG> illustrates an example device <NUM> in which four sensors <NUM> are mounted on a common carrier <NUM>, such as a printed circuit board. As discussed above, these sensors <NUM> may be coupled to a controller <NUM>, such as via a USB or other connector. Of course, the controller <NUM> may also be mounted on the carrier <NUM> itself.

The ability to have multiple sensors <NUM> positioned very close to one another enables different sensors <NUM> to be used in different ways. For example, different sensors <NUM> may be functionalized with different antibodies <NUM> in order to detect different viruses. As another example, different sensors <NUM> may be functionalized with different antibodies <NUM> in order to detect different mutations of the same virus. In some cases, one of the sensors <NUM> may be used as a reference and include inactivated antibodies <NUM>. This reference sensor <NUM> may be used as a control, such as to determine when all sensors <NUM> need to be replaced due to water loss from their hydrogel layers <NUM>.

Although <FIG> illustrates one example of a device <NUM> having multiple SAW-based hydrogel sensors for use in detecting viruses, various changes may be made to <FIG>. For example, the device <NUM> may include less than four or more than four sensors <NUM>. Also, the sensors <NUM> may be arranged in the device <NUM> in any suitable manner and may or may not be placed laterally or side-by-side on a common carrier <NUM>.

<FIG> illustrate specific example devices having one or more SAW-based hydrogel sensors <NUM> for use in detecting viruses in accordance with this disclosure. In particular, <FIG> illustrate specific example types of devices in which one or more SAW-based sensors <NUM> may be used. Note, however, that the SAW-based sensors <NUM> may be used in any other suitable types of devices.

In <FIG>, one or more SAW-based sensors <NUM> can be positioned within a handheld breathalyzer <NUM> or similar type of device. The breathalyzer <NUM> includes an input tube into which a person can blow. One or more SAW-based sensors <NUM> within the breathalyzer <NUM> can then sense whether the person's breathe includes adequate viruses to change the frequency of the SAW-based sensor(s) <NUM> as described above. This type of device may be useful in various scenarios, such as when there is a need to tightly control access to a facility and prevent potentially ill personnel from entering the facility.

In <FIG>, one or more SAW-based sensors <NUM> can be positioned within a wide-area monitor <NUM> or similar type of device. The monitor <NUM> can receive air within a space that might be occupied by a large number of people. One or more SAW-based sensors <NUM> within the monitor <NUM> can then sense whether the air includes adequate viruses to change the frequency of the SAW-based sensor(s) <NUM> as described above. This type of device may be useful in various scenarios, such as determining whether certain locations are contaminated hot spots in which people are likely to be exposed to a virus. Note that while this embodiment may not operate as quickly as the breathalyzer <NUM> to detect an infected individual (since there is not direct airflow from an individual into the monitor <NUM>), the monitor <NUM> enables collective monitoring of a much larger area and a greater number of people.

Although <FIG> illustrate specific examples of devices having one or more SAW-based hydrogel sensors <NUM> for use in detecting viruses, various changes may be made to <FIG>. For example, the form factors of the devices shown here are for illustration only.

Note that while often described above as being used to detect viruses affecting people, the approaches described above can be used to sense any viruses. Thus, for example, sensors <NUM> may be used to detect viruses that can affect livestock or other animals. One specific example use of the sensors <NUM> may be in detecting swine flu or other diseases that affect animals.

It may be advantageous to set forth definitions of certain words and phrases used throughout this patent document. The phrase "associated with," as well as derivatives thereof, may mean to include, be included within, interconnect with, contain, be contained within, connect to or with, couple to or with, be communicable with, cooperate with, interleave, juxtapose, be proximate to, be bound to or with, have, have a property of, have a relationship to or with, or the like.

The description in the present application should not be read as implying that any particular element, step, or function is an essential or critical element that must be included in the claim scope. The scope of patented subject matter is defined only by the allowed claims.

Claim 1:
An apparatus comprising:
a surface acoustic wave 'SAW' sensor (<NUM>) comprising:
a piezoelectric substrate (<NUM>);
first and second interdigitating transistors (104a, 104b) over the piezoelectric substrate (<NUM>), the first interdigitating transistor (104a) configured to convert an input electrical signal into an acoustic wave, the second interdigitating transistor (104b) configured to convert the acoustic wave into an output electrical signal, the piezoelectric substrate (<NUM>) configured to transport the acoustic wave; and
a detection layer (<NUM>) over the piezoelectric substrate (<NUM>) and positioned at least partially between the first and second interdigitating transistors (104a, 104b), the detection layer (<NUM>) comprising (i) antibodies (<NUM>) configured to bind to one or more biological analytes and (ii) a hydrogel layer (<NUM>) over the antibodies (<NUM>), wherein:
the hydrogel layer (<NUM>) is configured to permit the one or more biological analytes to diffuse through the hydrogel layer (<NUM>) and contact the antibodies (<NUM>),
characterized in that the antibodies (<NUM>) are configured to bind to one or more viruses; and
the hydrogel layer (<NUM>) comprises an agarose hydrogel, a polyacrylamide hydrogel, or a guar gum hydrogel.