Apparatus for determining the presence or concentration of a target molecule

Abstract

An apparatus for determining the presence or concentration of a target molecule, comprising: a radiation source; a surface; a waveguide; a detector; and a spectral filter. The radiation source is operable to generate electromagnetic radiation. The surface defines a two-dimensional array of acceptor sites. The waveguide is arranged to receive electromagnetic radiation generated by the radiation source, divide the electromagnetic radiation, and direct a portion of the electromagnetic radiation to each of the two-dimensional array of acceptor sites. The detector comprises a two-dimensional array of sensing elements, each sensing element arranged to receive electromagnetic radiation from a different one of the two-dimensional array of acceptor sites. The spectral filter is disposed between the surface and the detector.

Description

Technical Field

[0001] This disclosure relates to an apparatus for determining the presence or concentration of a target molecule. The apparatus can be applied, for example, to an assay (sometimes also called a molecular interaction assay) arranged to measure the presence or concentration of a specific target molecule. Background Technology

[0002] There are known techniques capable of reporting or visualizing specific interactions between biomolecules. Such techniques or assays, often called molecular interaction assays, are arranged to measure the presence or concentration of a specific target molecule (which may be called an analyte). Molecular interaction assays typically utilize biological receptors that can bind to the analyte. This interaction is highly specific to the binding of the biological receptor and the analyte, much like a key and a lock. Generally, only the correct analyte will bind to the biological receptor.

[0003] Many such assays also require the use of reporter molecules. Typically, a reporter molecule is only operable to bind to the analyte once the analyte has already bound to a biological receptor. A reporter molecule can report the presence of the analyte target molecule in some way. For example, reporter molecules can be: enzymes, as in enzyme-linked immunosorbent assays (ELISA); radioactivity, as in radioimmunosorbent assays (RIA); or more commonly, fluorophores, as in fluorescent immunosorbent assays (FIA).

[0004] As an alternative to using reporter molecules, label-free detection methods have been developed and are becoming increasingly popular. One known label-free detection method is surface plasmon resonance (SPR).

[0005] An arrangement using surface plasmon resonance (SPR) as a label-free detection method (which may be called a SPR device) includes a prism with a relatively thin layer of metal (e.g., gold) disposed on one of its faces. Electromagnetic radiation is coupled into the prism and incident on the interface between the prism and the metal, resulting in total internal reflection. This generates an evanescent wave in the metal layer, which propagates parallel to the interface between the prism and the metal (and in the plane of incidence) and has an amplitude that decays exponentially in the direction perpendicular to the interface between the prism and the metal.

[0006] Surface plasmon polaritons can be generated at the interface between a metal layer and an adjacent (dielectric) medium. Surface plasmon polaritons are coupled oscillations of electrons (plasma) within the metal layer and electromagnetic oscillations (polarons) in the dielectric. Specifically, surface plasmons are collective conduction electron oscillations at the interface of two layers: one is a metal (usually a noble metal), and the other is a dielectric. If the metal layer is thin enough (relative to the penetration depth of the evanescent wave) and the resonance condition is met, an evanescent wave can excite surface plasmon polaritons on the side of the metal layer opposite the prism. This utilizes some energy from the incident electromagnetic radiation, thus reducing the intensity of the electromagnetic radiation reflected from the interface between the prism and the metal layer.

[0007] The reflected electromagnetic radiation is coupled out of the prism and incident on a detector that is arranged to determine the intensity of the reflected electromagnetic radiation (which in turn depends on whether surface plasmons are excited).

[0008] Resonance conditions depend on the wavelength and angle of incidence of the incident electromagnetic radiation. They also depend on the optical properties of the metal and the adjacent (dielectric) medium. If the metal has biological receptors on its surface, these optical properties (and therefore the resonance conditions) can vary depending on the presence or absence of a specific target molecule (or analyte) bound to the biological receptor. Therefore, by measuring information related to the resonance conditions, information related to the presence and / or quantity of a specific target molecule adjacent to the metal layer can be determined.

[0009] In some systems, multiple different biological receptors are provided on a metal layer; each is irradiated with electromagnetic radiation, and the electromagnetic radiation reflected from each is detected by a separate detector. This arrangement is called imaging SPR (iSPR).

[0010] One challenge of the aforementioned imaging surface plasmon resonance (SPR) device is the very narrow resonance condition, making precise control over the wavelength and angle of incidence of the incident electromagnetic radiation crucial. Specifically, one of the main design challenges in such an SPR device is the optical system. Typically, numerous lenses are required to properly project light onto the prism and observe the reflected light on the imaging sensor. Each lens has a specific alignment path and focal length to achieve optimal illumination and image quality. Specifically, proper operation may require optics illuminating the metal layer with an accuracy on the order of 0.1°.

[0011] The purpose of this disclosure is to provide an apparatus for determining the presence or concentration of a target molecule that solves one or more problems associated with prior art methods, whether or not they are identified above. Summary of the Invention

[0012] In summary, this disclosure proposes to overcome the problems of existing arrangements by providing a device that, in use, excites localized surface plasmon resonance (LSPR) in metallic nanoparticles and uses a spectral filter to sample the spectral resonance curve of the LSPR. Multiplexing of multiple signals is provided by providing multiple acceptor sites, each acceptor site having a corresponding detector, and waveguides are arranged to receive electromagnetic radiation generated by a radiation source, divide the electromagnetic radiation, and guide a portion of the electromagnetic radiation to each of the acceptor sites in a two-dimensional array. This arrangement is advantageous because it provides a device with very high multiplexing and a very compact design.

[0013] According to a first aspect of this disclosure, an apparatus for determining the presence or concentration of a target molecule is provided, the apparatus comprising: a surface defining acceptor sites of a two-dimensional array; a waveguide arranged to receive at least a portion of incident electromagnetic radiation, dividing the electromagnetic radiation and directing a portion of the electromagnetic radiation to each of the acceptor sites of the two-dimensional array; a detector including sensing elements of the two-dimensional array, each sensing element arranged to receive electromagnetic radiation from a different acceptor site of the two-dimensional array; and a spectral filter disposed between the surface and the detector.

[0014] Advantageously, as now discussed, the device according to the first aspect of this disclosure provides a device with very high reusability and very compact design.

[0015] One existing device for determining the presence or concentration of a target molecule is an imaging surface plasmon resonance (SPR) device. One type of SPR device includes a prism with a metal layer disposed thereon to form multiple acceptor sites. This type of arrangement is configured to generate excited surface plasmons on the outer surface of the metal layer. When a specific molecule binds to the acceptor, the optical properties of the medium adjacent to the outer surface of the metal layer are altered. However, this arrangement involves a prism and optics arranged to couple radiation into and out of the prism. Therefore, this arrangement is quite large and has multiple optical components that must be precisely aligned. In fact, for the device to function, the alignment of the optics is critical, ensuring that radiation enters the prism at a specific angle with a tolerance on the order of 0.1°.

[0016] Compared to such known systems, the imaging surface plasmon resonance device disclosed herein has the following advantages. First, by providing a spectral filter between the surface and the detector, each sensing element of the detector receives electromagnetic radiation with a single wavelength (or at least a narrow range of wavelengths) from a single receptor site. This allows the device to use localized surface plasmon resonance devices, as discussed now. In use, metallic nanoparticles are provided on the surface at each receptor site. Receptors are coated onto the nanoparticles. For example, the nanoparticles at each different receptor site can be coated with different receptors.

[0017] Localized surface plasmon resonance (LSPR) occurs at the interface between the surface of a metal nanoparticle, nanoshell, or nanostructure and a dielectric. When radiation is incident on a metal nanoparticle, conduction electrons in the metal layer can be excited, causing them to oscillate coherently with high amplitude. The excitation of LSPR depends on the wavelength of the radiation. If broadband radiation (e.g., white light or full-spectrum visible light) is incident on the metal nanoparticle, the scattering efficiency has a maximum resonance frequency. The absorption spectrum of the metal nanoparticle (e.g., the maximum resonance frequency) depends on the optical properties of the (dielectric) medium adjacent to the metal nanoparticle. Subsequently, the optical properties of the (dielectric) medium adjacent to the metal nanoparticle depend on the presence and concentration of a specific target molecule that binds to the acceptor coated on the metal nanoparticle. Therefore, by determining the information associated with the LSPR absorption spectrum of the metal nanoparticle, the presence and concentration of the specific target molecule bound to the acceptor coated on the metal nanoparticle can be determined.

[0018] As the concentration of a specific target molecule (or analyte) bound to the receptor at the receptor site changes, the LSPR resonance profile will also change. For example, when a specific molecule is bound, the scattering wavelength of the nanoparticles may shift towards the red end of the spectrum. A spectral filter positioned between the surface and the detector effectively samples the resonance spectrum at a fixed wavelength. As the LSPR resonance profile shifts along the wavelength, the sampled values ​​will increase or decrease.

[0019] As used herein, it should be understood that a receptor is intended to represent any substance (e.g., a molecule) capable of receiving and binding other substances. Receptors can include any of many biomolecules, such as proteins, viruses, etc.

[0020] The device may also include a radiation source operable to generate electromagnetic radiation, and the incident electromagnetic radiation received by the waveguide may include at least a portion of the electromagnetic radiation.

[0021] The device may also include a radiation source operable to generate electromagnetic radiation, and waveguides may be arranged to receive at least a portion of the electromagnetic radiation generated by the radiation source, divide the electromagnetic radiation, and guide a portion of the electromagnetic radiation to each of the receiver sites in the two-dimensional array.

[0022] In some embodiments, the device may include a plurality of radiation sources operable to generate electromagnetic radiation, and a waveguide may be arranged to receive at least a portion of the electromagnetic radiation generated by each of the plurality of radiation sources.

[0023] Radiation sources can include broadband radiation sources.

[0024] For example, the spectrum of the radiation source can have a bandwidth of at least 100 nm. In some embodiments, the radiation source can be operated to produce white light, i.e., radiation that spans the visible spectrum.

[0025] The radiation source may include a white light-emitting diode.

[0026] The device may also include metallic nanostructures disposed on each of the receptor sites in a two-dimensional array on the surface.

[0027] For example, a metal microstructure may include multiple nanoparticles.

[0028] Nanoparticles can have any desired shape. Possible shapes for nanoparticles include, for example, spherical, cubic, dendritic or star-shaped, rod-shaped, and / or bipyramidal. The refractive index unit (RIU) of the LSPR can be defined as the offset (in nanometers) of the LSPR resonance curve per unit refractive index of the surrounding (dielectric) medium. The LSPR RIU depends on the shape of the nanoparticle. Generally, the higher the asymmetry of the nanoparticle, the higher the RIU. Generally, shapes with a higher aspect ratio (e.g., rod-shaped or bipyramidal) result in a higher RIU.

[0029] Generally, it is desirable for nanoparticles to have a relatively large RIU (Ratio of Intraceability). In general, it may be desirable for nanoparticles to have a shape that can be manufactured with well-controlled dimensions and consistent aspect ratios.

[0030] Metal nanostructures can include any type of metal. They can include noble metals. Advantageously, noble metals are not easily oxidized. For example, metal nanostructures can include gold nanoparticles.

[0031] The device may also include receptors disposed on each metal microstructure.

[0032] The device may also include a printed circuit board, and the detector may be mounted on the printed circuit board.

[0033] In embodiments that include a radiation source, both the radiation source and the detector can be mounted on a printed circuit board.

[0034] For example, radiation sources and detectors can be placed next to each other on a printed circuit board.

[0035] The waveguide can be positioned between the detector and the surface of the receptor site that defines the two-dimensional array.

[0036] The waveguide may include a generally planar body. The surface defining the receptor site of the two-dimensional array may be the surface of the body.

[0037] The body may be formed of glass. The waveguide may include a generally planar body. The body may include a plurality of channels formed therein, each channel being arranged to receive a portion of electromagnetic radiation generated by a radiation source and to guide that portion of the electromagnetic radiation to one of the receiver sites of the two-dimensional array. The channels may, for example, be formed of a material with a refractive index greater than that of the portion surrounding the body.

[0038] Waveguides can include integrated optical devices. Such integrated optical devices can be referred to as on-chip technology or on-chip optics.

[0039] The waveguide may include an integrated optical plate arranged to receive electromagnetic radiation output from a radiation source at the input and to distribute the electromagnetic radiation on a surface defining a receiver location of a two-dimensional array.

[0040] Waveguides may include one or more diffusers, collimators, pinholes and / or molded lenses.

[0041] Waveguides may include multiple beam splitters or optical waveguide splitters arranged to scatter incident radiation on the surface of a receiver site that defines a two-dimensional array.

[0042] Waveguides may include one or more grating structures arranged to generate interference patterns and to scatter radiation onto a surface at a receiver location that defines a two-dimensional array.

[0043] The device may also include a processor operable to determine the concentration of the target molecule based on the intensity of electromagnetic radiation received from a corresponding receptor site in the two-dimensional array.

[0044] The detector can include any suitable electromagnetic radiation detector. Suitable detectors include, for example, single-photon avalanche detectors (SPADs), photodiodes, complementary metal-oxide-semiconductor (CMOS) diode arrays, and / or charge-coupled device (CCD) arrays.

[0045] In some embodiments, the device may include one or more polarizers arranged as part of polarized radiation. In other embodiments, such polarizers may be omitted.

[0046] The device may also include one or more sensors operable to determine one or more environmental conditions.

[0047] For example, the device may include a sensor operable to determine one or more of the relative humidity, temperature, and / or pressure near the metal layer.

[0048] The device may also include a user interface for receiving signals from the detector.

[0049] For example, a printed circuit board may be provided with a USB port, which can form part of the user interface. In embodiments that include a radiation source, the user interface may also be adapted to provide signals to the radiation source.

[0050] Spectral filters can have a full width at half maximum (FWHM) bandwidth of 10 nm or less.

[0051] For example, a spectral filter can have a full width at half maximum (FWHM) bandwidth of 5 nm or less.

[0052] The spectral filter may include individual spectral filters of a two-dimensional array, each of which is configured to be adjacent to a different one of the sensing elements in the two-dimensional array.

[0053] A waveguide may include multiple waveguide channels formed in a waveguide body, each waveguide channel being arranged to guide radiation to a different one of multiple discrete locations within the body, each such discrete location being adjacent to a different one of the sensing elements in a two-dimensional array.

[0054] Each waveguide channel can be formed from a core material surrounded by a cladding material. The cladding material can confine radiation to the core material, thereby guiding the radiation.

[0055] A waveguide may include multiple waveguide channels and waveguide splitters.

[0056] Each waveguide splitter can be arranged to receive a portion of the radiation from a radiation source, divide the electromagnetic radiation, and direct a portion of the electromagnetic radiation to each of two waveguide channels. The waveguide channels and waveguide splitters can be arranged consecutively such that radiation in each of the two waveguide channels that receives radiation from one of the waveguide splitters can then be received by the other of the waveguide splitters.

[0057] The waveguide may include a two-dimensional array of coupling optics, each of which is arranged to couple radiation out of the waveguide and toward a different receiver location in the two-dimensional array.

[0058] Each coupling optic may include a patterned portion at the end of the waveguide channel within the body of the waveguide.

[0059] The patterned portion at the end of the waveguide channel may include multiple grooves formed on the cladding material of the waveguide channel.

[0060] The patterned portion can be formed, for example, on the surface of the cladding material of the waveguide channel, away from an adjacent sensing element of the two-dimensional array and close to one of the receptor sites of the two-dimensional array. The grooves of the patterned portion can have any desired cross-sectional shape. For example, the grooves of the patterned portion can be square or circular (e.g., round) grooves.

[0061] Alternatively, different types of patterned portions can be formed on the surface of the cladding material of the waveguide channel. Examples of different patterned portions used to couple radiation out of the waveguide channel include: holes in the cladding material; thinner portions of the cladding material; cladding materials with different refractive indices (reflected relative to the other sides of the cladding material); or other grooved or patterned structures.

[0062] Alternatively, each coupling optic may include a mirror or a prism.

[0063] Each coupling optics may include a microlens array arranged to receive radiation coupled out of the waveguide channel and to direct the radiation as an illumination beam to one of the receiver locations of the two-dimensional array. Attached Figure Description

[0064] Some embodiments of this disclosure will now be described by way of example only and with reference to the accompanying drawings, in which:

[0065] Figure 1 This is a schematic diagram of the device according to the present invention;

[0066] Figure 2 An example local surface plasmon resonance absorption spectrum of gold nanorods is shown;

[0067] Figure 3 The local surface plasmon resonance absorption spectra of five different sizes of nanoparticles are shown;

[0068] Figure 4 It shows including Figure 1 The apparatus shown is a device;

[0069] Figure 5 It shows that it can be used Figure 1 A schematic plan view (top view) of the waveguide channels formed within the waveguide of the device shown.

[0070] Figure 6 Is with Figure 1 A schematic top view of the waveguide portion adjacent to a single sensing element of the detector in the device shown.

[0071] Figure 7 yes Figure 6 The schematic representation shown is a cross-sectional view along line AA; and

[0072] Figure 8 yes Figure 6 The schematic representation shown is a cross-sectional view along line BB. Detailed Implementation

[0073] In summary, this disclosure proposes a device that excites localized surface plasmon resonance (LSPR) in metal nanoparticles during use and uses a spectral filter to sample the spectral resonance profile of the LSPR. The spectral filter can be incorporated into the detector sensing element. Multiplexing of multiple signals is provided by offering multiple acceptor sites, each acceptor site having a corresponding detector, and optical waveguides are arranged to receive electromagnetic radiation generated by a radiation source, divide the electromagnetic radiation, and guide a portion of the electromagnetic radiation to each of the acceptor sites in a two-dimensional array. This arrangement is advantageous because it provides a device with very high multiplexing and a very compact design, as discussed herein.

[0074] As discussed now, some examples of such devices are shown in the accompanying drawings.

[0075] Figure 1 This is a schematic diagram of the apparatus 100 according to the present disclosure. The apparatus 100 is adapted to determine the presence or concentration of a target molecule. The apparatus 100 includes: a radiation source 102, a waveguide 104, a detector 106, and a spectral filter 108.

[0076] Radiation source 102 is operable to generate electromagnetic radiation 110. Typically, radiation source 102 is a broadband radiation source. For example, the spectrum of radiation source 102 may have a bandwidth of at least 100 nm. In some embodiments, the radiation source may be used to generate white light, i.e., radiation spanning the visible spectrum. In one embodiment, radiation source 102 includes a white light-emitting diode.

[0077] Detector 106 includes a two-dimensional array of sensing elements 112. In Figure 1 In the illustrated embodiment, detector 106 includes sensing elements 112 in an 8×8 two-dimensional array. It should be understood that, in Figure 1 Only one row of eight sensing elements 112 is shown in the plane, but in the plane parallel to Figure 1 There are another 7 rows of 8 sensing elements 112 in the plane. It should be understood that in other embodiments, there may be fewer or more than 64 sensing elements 112.

[0078] Detector 106 may include any suitable type of electromagnetic radiation detector. Suitable detectors include, for example, single-photon avalanche detectors (SPADs), photodiodes, complementary metal-oxide-semiconductor (CMOS) diode arrays, and / or charge-coupled device (CCD) arrays. In one embodiment, detector 106 is an array of photodiodes 112. Alternatively, detector 106 may include an image sensor.

[0079] Detector 106 can have any desired resolution. In one embodiment, detector 106 includes a 16-bit analog-to-digital converter. However, it should be understood that in other embodiments, 106 may include an analog-to-digital converter with a different resolution.

[0080] The device 100 also includes a common printed circuit board 126. Both the radiation source 102 and the detector 108 are mounted on the printed circuit board 126. Specifically, the radiation source 102 and the detector 106 are arranged adjacent to each other on the printed circuit board 126. A waveguide 104 is disposed above the radiation source 102 and the detector 106. That is, the radiation source 102 and the detector 106 are disposed between the printed circuit board 126 and the waveguide 104.

[0081] Waveguide 104 comprises a generally planar body. For example... Figure 1 As shown schematically, waveguide 104 may include two generally planar main body portions: an adjacent main body portion 114 disposed adjacent to detector 106 and a distal main body portion 116 disposed away from detector 106. The adjacent and distal main body portions 114, 116 are separated by a central waveguide portion 118.

[0082] As now discussed, the surface 120 of the distal body portion 116 defines receiver sites 122 of the two-dimensional array. Each receiver site 122 includes a portion of the surface 120 of the distal body portion 116, which is opposite to one or more sensing elements 112 of the detector 106. More specifically, each receiver site 122 includes a portion of the surface 120 of the distal body portion 116 that can emit radiation that can be received by a corresponding sensing element 112 of the detector 106. Thus, each sensing element 112 of the detector 106 can be considered to be arranged to receive electromagnetic radiation from a different one of the receiver sites 122 of the two-dimensional array.

[0083] Waveguide 104 is disposed between detector 106 and surface 120, which defines the receptor site 122 of the two-dimensional array.

[0084] A spectral filter 108 is disposed between the surface 120 of the waveguide 104 and the detector 106. In this embodiment, the spectral filter 108 includes a plurality of individual spectral filters 124, each of which is disposed adjacent to a different one of the sensing elements 112 of the detector 106.

[0085] Each of the spectral filter 108 and / or the plurality of individual spectral filters 124 may include any desired type of filter. Suitable filters include bandpass filters with relatively narrow bandwidths, such as those with a full width at half maximum (FWHM) of 5 to 10 nm. Suitable filters also include interference filters and / or dichroic filters. Typically, each of the spectral filter 108 and / or the plurality of individual spectral filters 124 may have a relatively narrow bandwidth, such as a full WHM of 5 to 10 nm.

[0086] In this embodiment, the spectral filter 108 includes a plurality of individual spectral filters 124. The plurality of individual spectral filters 124 may sample at different wavelengths or at substantially the same wavelength. Although in this embodiment the spectral filter 108 includes a plurality of individual spectral filters 124, in an alternative embodiment a single filter may be provided on all sensing elements 112 of the detector 106.

[0087] In addition to the spectral filter 106, each sensing element 112 of the detector 106 may be provided with an angle filter to limit the numerical aperture of each sensing element 112. This can help ensure that each sensing element receives only radiation scattered from its corresponding receptor site 122.

[0088] like Figure 1 As schematically shown, the distal body portion 116 of the waveguide extends over both the radiation source 102 and the detector 106, while the adjacent body portion 114 of the waveguide 104 extends only over the detector 104. That is, the adjacent body portion 114 of the waveguide 104 does not extend over the radiation source 102. Therefore, the radiation 110 emitted by the radiation source can be coupled into the central waveguide portion 118. Thus, the waveguide 104 is arranged to receive at least a portion of the electromagnetic radiation 110 generated by the radiation source 102.

[0089] A barrier 128 is provided between the radiation source 102 and the detector 106. This barrier prevents any radiation 110 emitted by the radiation source 102 from being directly received by the detector 106.

[0090] Waveguide 104 is also arranged to divide the electromagnetic radiation 110 it receives from the radiation source and to guide a portion of that electromagnetic radiation 110 to each of the receiver sites 122 in the two-dimensional array. Those skilled in the art will understand that there are many optical arrangements that allow the waveguide to operate in this manner, some of which will now be discussed.

[0091] The main body of waveguide 104 can be formed of glass. For example, adjacent and distal main body portions 114 and 116 can be formed of glass. Similarly, the central waveguide portion 118 can be formed of glass.

[0092] In some embodiments, the central waveguide portion 118 may include a plurality of channels formed in the body of the waveguide 104. Each channel may be arranged to receive a portion of the electromagnetic radiation 110 generated by the radiation source 102 and to guide that portion of the electromagnetic radiation 110 to one of the receiver sites 122 of the two-dimensional array. The channels may be formed, for example, of a material with a refractive index greater than that of the surrounding portion of the body of the waveguide 104.

[0093] Waveguide 104 may include integrated optics. Such integrated optics may be referred to as on-chip technology or on-chip optics.

[0094] In some embodiments, waveguide 104 may include an integrated optical plate arranged to receive electromagnetic radiation 110 output by radiation source 102 at an input and to distribute the electromagnetic radiation on a surface 120 of a receiver site 122 defining a two-dimensional array.

[0095] Waveguide 104 may include one or more diffusers, collimators, pinholes and / or molded lenses.

[0096] In some embodiments, waveguide 104 may include a plurality of beam splitters or optical waveguide splitters arranged to scatter radiation on surface 120 of receiver site 122 defining a two-dimensional array.

[0097] In some embodiments, waveguide 104 may include one or more grating structures arranged to generate an interference pattern and to scatter radiation on a surface 120 of a receiver site 122 that defines a two-dimensional array.

[0098] Waveguide 104 is an asymmetric optical leakage waveguide. Specifically, radiation 110 within waveguide 104 leaks through the distal body portion 116 (as shown by the dashed line). However, radiation 110 within waveguide 104 does not leak through adjacent body portions 114. Radiation 110 within waveguide 104 leaks through the distal body portion 116 at multiple discrete locations, each such discrete location being adjacent to one of the receiver locations 122. Because radiation 110 leaks through, or couples out from, the distal body portion 116 of the waveguide at these discrete locations, it can illuminate the receiver location 122 from the waveguide.

[0099] It should be understood that electromagnetic radiation can be coupled out of each adjacent waveguide 104 in a variety of different ways. For example, using mirrors, prisms, and / or patterns in the cladding material of waveguide 104, radiation 110 within waveguide 104 can be coupled out at each of multiple discrete locations via the distal body portion 116. For example, patterns in the cladding material of waveguide 104 can be provided on the side of waveguide 104 closest to the receiver location 122: holes or thinner portions of the cladding material, materials with different refractive indices (relative to the refractive index of the other sides of the waveguide), or groove structures.

[0100] As discussed further below, in use, receptor-functionalized nanoparticles are provided at receptor site 122. Waveguide 104 allows these receptor-functionalized nanoparticles to be irradiated from the side, which can excite local surface plasmon resonances. This results in the scattering of radiation, which can be measured by detector 106. Since the radiation 110 within waveguide 104 does not leak through the adjacent body portion 114, the radiation 110 emitted by the radiation source cannot directly irradiate detector 106. This is advantageous because such direct irradiation of detector 106 by radiation source 102 will provide background for LSPR measurements.

[0101] Advantageously, the device 100 allows the surface and the receptor site 122 to be irradiated while keeping the radiation source 102 and the detector 106 on the same PCB layer.

[0102] Generally, in use, device 100 excites localized surface plasmon resonance (LSPR) in metal nanoparticles and uses a spectral filter 108 in conjunction with a detector 106 to sample the spectral resonance curve of the LSPR. Multiplexing of multiple signals is provided by offering multiple acceptor sites 122, each acceptor site 122 having a corresponding sensing element 112. This arrangement is advantageous because it provides a device with very high multiplexing and a very compact design, as now discussed.

[0103] In use, the metal nanostructure is disposed on each of the acceptor sites 122 of a two-dimensional array on the surface 120 of the waveguide. For example, the metal microstructure may include multiple nanoparticles.

[0104] Nanoparticles can have any desired shape. Possible shapes for nanoparticles include, for example, spherical, cubic, dendritic or star-shaped, rod-shaped, and / or bipyramidal. The refractive index unit (RIU) of the LSPR can be defined as the offset (in nanometers) of the LSPR resonance curve per unit refractive index of the surrounding (dielectric) medium. The LSPR RIU depends on the shape of the nanoparticle. Generally, the higher the asymmetry of the nanoparticle, the higher the RIU. Generally, shapes with a higher aspect ratio (e.g., rod-shaped or bipyramidal) result in a higher RIU.

[0105] Generally, it is desirable for nanoparticles to have a relatively large RIU (Ratio of Intraceability). In general, it may be desirable for nanoparticles to have a shape that can be manufactured with well-controlled dimensions and consistent aspect ratios.

[0106] As an alternative to depositing nanoparticles on surface 120, in other embodiments, nanolithography can be used to form nanostructures, for example, formed of gold, on surface 120.

[0107] Metal nanostructures can include noble metals. For example, metal nanostructures can include gold nanoparticles.

[0108] Each metal nanostructure is coated with a receptor. For example, nanoparticles at different receptor sites 122 can be coated with different receptors.

[0109] Localized surface plasmon resonance (LSPR) occurs at the interface between the surface of a metal nanoparticle, nanoshell, or nanostructure and a dielectric. When radiation is incident on a metal nanoparticle, conduction electrons in the metal layer can be excited, causing them to oscillate coherently with high amplitude. The excitation of LSPR depends on the wavelength of the radiation. If broadband radiation (e.g., white light or full-spectrum visible light) is incident on the metal nanoparticle, the scattering efficiency has a maximum resonance frequency. The absorption spectrum of the metal nanoparticle (e.g., the maximum resonance frequency) depends on the optical properties of the (dielectric) medium adjacent to the metal nanoparticle. Subsequently, the optical properties of the (dielectric) medium adjacent to the metal nanoparticle depend on the presence and concentration of a specific target molecule that binds to the acceptor coated with the metal nanoparticle. Therefore, by determining the information associated with the LSPR absorption spectrum of the metal nanoparticle, the presence and concentration of the specific target molecule bound to the acceptor coated with the metal nanoparticle can be determined.

[0110] The LSPR resonance profile changes as the concentration of a specific target molecule (or analyte) bound to the receptor at the receptor site varies. Generally, the LSPR resonance profile depends on the net refractive index directly around the nanoparticle. The refractive index of air is typically 1, while that of odor molecules is typically around 1.45. The nanoparticles are functionalized with receptors, thus selectively allowing the binding / interaction of odor molecules. Therefore, when a specific molecule is bound, the scattering wavelength of the nanoparticle may, for example, shift towards the red end of the spectrum. A spectral filter 108 positioned between surface 120 and detector 106 effectively samples the resonance spectrum at a fixed wavelength. As the LSPR resonance profile shifts along the wavelength, the sampled values ​​will increase or decrease.

[0111] Figure 2An example LSPR absorption spectrum 200 of a gold nanorod is shown, with a maximum resonance wavelength of 775 nm. Line 202 represents an 840 nm spectral filter with a full width at half maximum (FWHM) of 5 nm. If the absorption spectrum 200 is measured using such a spectral filter 108 (e.g., using one of the sensing elements 112 of detector 106), the observed scattering efficiency will be approximately 0.5 of the peak value.

[0112] Figure 2 An example LSPR absorption spectrum 204 of gold nanorods functionalized with receptors is also shown. Once functionalized with receptors, the extinction peak shifts to 783.6 nm. An increase in scattering intensity is observed when sampled by a filter. Figure 2 An example LSPR absorption spectrum 206 of a gold nanorod functionalized with an acceptor and bound to a target molecule is also shown. The extinction peak of spectrum 206 is further shifted to 789.2 nm, a total shift of 5.6 nm. The observed scattering intensity also further increases to 0.65. If the detector 106 has a resolution of 16 bits, the observable precision for intensity changes is 1.5 × 10⁻⁶ per intensity level. 5 (When represented by 0 to 1).

[0113] Importantly, detector 106 only receives responses from nanoparticles that bind to or interact with, for example, odor molecules. To this end, a spectral filter 108 (specifically a separate spectral filter 124) is provided above detector 106.

[0114] Advantageously, the device 100 according to the first aspect of this disclosure provides a device with very high reusability and very compactness, which has many advantages over existing devices, as now discussed.

[0115] One existing device for determining the presence or concentration of a target molecule is an imaging surface plasmon resonance (SPR) device. One type of SPR device includes a prism with a metal layer disposed thereon to form multiple acceptor sites. This type of arrangement is configured to generate excited surface plasmons on the outer surface of the metal layer. When a specific molecule binds to the acceptor, the optical properties of the medium adjacent to the outer surface of the metal layer are altered. However, this arrangement involves a prism and optics arranged to couple radiation into and out of the prism. Therefore, this arrangement is quite large and has multiple optical components that must be precisely aligned. In fact, for the device to function, the alignment of the optics is critical, ensuring that radiation enters the prism at a specific angle with very small tolerances on the order of 0.1°. A major problem with this prism-based SPR system is the angular alignment of the prism, as well as the illumination and detection systems. Due to these stringent tolerances, large-scale manufacturing is either problematic or extremely expensive.

[0116] Advantageously, the present device 100, which uses scattering nanoparticles, eliminates this problem.

[0117] Compared to such known systems, the imaging surface plasmon resonance device disclosed herein has the following advantages.

[0118] First, a bulky optical system with prisms and lenses is unnecessary. In contrast, the waveguide 104 of this device 100 is flat and compact. In fact, the complete imaging system of device 100 can be reduced to a volume of less than 1 cubic centimeter, or even to a size similar to that of current camera modules in mobile phones. The radiation source 102 and detector 106 are arranged on the same plane (e.g., mounted adjacent to each other on a common PCB, or even in the same package).

[0119] Second, the device does not require applying a gold layer to the optics, for example, using physical vapor deposition (PVD). This is advantageous because gold PVD is incompatible with complementary metal-oxide-semiconductor (CMOS) technology, which would require the CMOS array and gold PVD to be fabricated in separate locations.

[0120] Third, there are no strict alignment requirements or associated risks of prism misalignment. Therefore, the system can be constructed more precisely and reliably, with fewer components, resulting in significantly lower costs.

[0121] Typically, LSPR absorption spectra depend on the size and shape of the nanoparticles or nanostructures. Therefore, if, for example, nanorods are used, variations in the length and / or aspect ratio of the nanorods will affect the LSPR absorption spectra. However, due to the LSPR absorption spectra (see, for example, [link to relevant documentation]), the LSPR absorption spectra are generally stable. Figure 2 The large front of the LSPR absorption spectrum (200) suggests that potential changes in the size or shape of nanoparticles will not have a significant impact on the system, as is currently referenced. Figure 3 The subject of discussion.

[0122] Generally, as long as the wavelength of the LSPR absorption spectrum sampled (e.g., through spectral filter 108) remains on one side of the LSPR absorption spectrum (preferably in a region where the LSPR absorption spectrum is relatively linear) for substantially the entire position range of the LSPR absorption spectrum, it is possible to measure the selective binding of the target molecule to the nanoparticle.

[0123] Figure 3 The LSPR absorption spectra of five different sized nanoparticles (300, 302, 304, 306, and 308) are shown. All nanorods have a width (diameter) of 20 nm. Figure 3The following are shown: LSPR absorption spectra 300 for nanorods with a resonance wavelength of 700 nm; LSPR absorption spectra 302 for nanorods with a resonance wavelength of 750 nm; LSPR absorption spectra 304 for nanorods with a resonance wavelength of 780 nm; LSPR absorption spectra 306 for nanorods with a resonance wavelength of 808 nm; and LSPR absorption spectra 308 for nanorods with a resonance wavelength of 850 nm. As shown in line 310, the intensity is measured at wavelengths up to 850 nm (i.e., the wavelength at which the spectral filter samples these LSPR absorption spectra 300, 302, 304, 306, and 308). The device 100 will be able to measure the selective binding of the target molecule to the nanorods of the particles with resonance wavelengths of 750 nm, 780 nm, and 808 nm, because in each case, the curves (see LSPR absorption spectra 302, 304, and 306) can be shifted to the right, resulting in an observed increase in intensity. It is also possible to measure the selective binding of target molecules to nanorods with a resonance wavelength of 700 nm, although the sampling at line 310 is performed on a portion of the LSPR absorption spectrum 300, which is not very linear, making it more difficult to accurately determine the response. Because the wavelength at which the intensity is measured (~850 nm) coincides with the peak of the LSPR absorption spectrum 308, it is impossible to measure the selective binding of target molecules to nanorods with a resonance wavelength of 850 nm.

[0124] It has been found that the method employed by device 100 is robust to size variations that cause resonant wavelength shifts exceeding 50 nm. This translates to a length variation of ~20 nm for a 20 nm wide gold nanorod. Consequently, this corresponds to a robustness of ~24% to 33% for nanoparticle size variations.

[0125] To obtain a fingerprint, it may be necessary to measure multiple receptors simultaneously. Detector 106 is capable of measuring 64 points almost simultaneously (e.g., using a 16-bit analog-to-digital converter). With such a device 100, most of the sensing elements 112 (e.g., 60 sensing elements 112) can be used for different receptors, and the remaining sensing elements (e.g., 4 sensing elements 112) can be used for background purposes. This can be described as multiplexing.

[0126] Because device 100 will wear and age due to the receptors it uses, resulting in a loss of sensitivity, it is desirable that device 100 be easy to replace. Now refer to... Figure 4 Describe an arrangement that provides this functionality. Figure 4 Device 400 is shown, which includes Figure 1The device 100 shown and described above. Device 100, together with functionalized nanostructures provided on acceptor site 122, is mounted on a removable daughter card 402. The removable daughter card 402 may resemble a (miniature) Secure Digital (SD) card. The advantage of the SD card's size form factor is the number of pins available for performing communication and powering device 100.

[0127] Sub-board 402 provides a user interface for device 100 for providing signals to radiation source 102 and / or receiving signals from detector 106.

[0128] The advantage is that Figure 4 The illustrated device 400 offers a particularly cost-effective design. Advantageously, the microcard form factor allows it to be fitted into wearable devices. Advantageously, the microcard is very easy to replace (e.g., compared to optics such as prisms).

[0129] The device 400 also includes a housing 404, which is provided with a port 406 for releasably engaging with a daughterboard 402. The housing 404 (in...) Figure 4 The portion shown is partially cut out and has a hole 408 to provide a flow channel, allowing fluid (e.g., gas) to flow 410 through the housing 404 (and through the device 100 provided on the sub-board 402).

[0130] The device 400 may also include a processor 412 operable to determine the concentration of the target molecule based on the intensity of electromagnetic radiation received from a corresponding one of the receptor sites 122 in the two-dimensional array.

[0131] The device 400 also includes one or more sensors 414 operable to determine one or more environmental conditions. For example, the device 400 may include sensors operable to determine one or more of relative humidity, temperature, and / or pressure near the metal layer. For gas-phase applications, knowing the relative humidity, temperature, and pressure of the environment can be useful, as all these variables affect the interaction of odor molecules on the surface of the nanoparticles. The sensor 414 may be positioned in a flow channel or air duct of the device 400 to obtain accurate information about bonding.

[0132] An air sample containing odor molecules can be forced into the flow channel using a pump. Alternatively, the fluid flow 410 through housing 404 can be provided by air diffusion. The embodiment using diffusion will produce a slower response, but advantageously, eliminating the need for active components such as pumps reduces the complexity and cost of device 400.

[0133] Figure 5 It shows that it can be used Figure 1A schematic plan view (top view) of the waveguide channel formed within the waveguide 104 of the device 100 shown. Figure 5 The detector 106 is shown schematically as a sensing element 112 comprising an 8×8 two-dimensional array.

[0134] The device 500 includes a plurality of waveguide channels 502 and waveguide splitters 504. Each waveguide splitter 504 is arranged to receive a portion of the radiation from the radiation source 102, divide the electromagnetic radiation, and direct a portion of the electromagnetic radiation to each of two waveguide channels 502. The waveguide channels 502 and waveguide splitters 504 are arranged sequentially such that radiation in each of the two waveguide channels 502 that receives radiation from one of the waveguide splitters 504 can then be received by the other of the waveguide splitters 504.

[0135] Thus, in Figure 5 In the example arrangement 500 shown, the radiation received by the first waveguide splitter 504 is divided between each of the two waveguide channels 502. The radiation in these two waveguide channels 502 is then divided by two waveguide splitters 504 between four waveguide channels 502. The radiation in these four waveguide channels 502 is then divided by four waveguide splitters 504 between eight waveguide channels 502. The radiation in these eight waveguide channels 502 is then divided by eight waveguide splitters 504 between sixteen waveguide channels 502. Finally, the radiation in these sixteen waveguide channels 502 is divided by sixteen waveguide splitters 504 between thirty-two waveguide channels 502.

[0136] These thirty-two waveguide channels 502 may be referred to as end waveguides 506. Each such end waveguide 506 is arranged to guide radiation to a different one of a plurality of discrete locations 508, each such discrete location 508 being adjacent to a different one of the sensing elements 112 of the detector 106. In this way, radiation is guided to a plurality of discrete locations 508 adjacent to half of the sensing elements 112 of the detector 106.

[0137] Although not shown, in Figure 5 In the arrangement shown, another waveguide can be provided to direct light around detector 106 to the edge of detector 106 opposite to radiation source 102. On this opposite side of detector 106, another arrangement 500 similar to the one described above can be used to direct radiation to a plurality of discrete locations 508 adjacent to the other half of sensing element 112 of detector 106.

[0138] It should be understood that, in alternative embodiments, a similar arrangement of waveguide channels 502 and waveguide splitters 504 can be used to divide radiation between discrete locations 508 of different numbers or arrangements adjacent to the sensing elements of detector 106.

[0139] It should be understood that each waveguide channel 502 can be formed of a core material surrounded by a cladding material. The cladding material confines the radiation to the core material, thereby guiding the radiation.

[0140] Apart from Figure 5 In addition to the device 500 of the type shown and described above, waveguide 104 may have multiple coupling optics at each of a plurality of discrete locations 508, which are configured to couple radiation out of end waveguide 506, as now referred to Figure 6 , Figure 7 and Figure 8 The subject of discussion.

[0141] Figure 6 The schematic top view of 600 is a portion of waveguide 602 adjacent to the single sensing element 112 of detector 106 (and the associated separate spectral filter 124). Figure 7 yes Figure 6 The schematic representation shown is a cross-sectional view along line AA at 600. Figure 8 yes Figure 6 The schematic representation shown is a cross-sectional view along line BB at 600.

[0142] like Figure 6 and Figure 7 As schematically illustrated, waveguide 602 is arranged to receive radiation from radiation source 102 and guide it to one of a plurality of discrete locations 604 adjacent to one of the sensing elements 112 of detector 106 (and an associated separate spectral filter 124). For example, waveguide 602 could be... Figure 5 One of the end waveguides 506 shown and described above. Similarly, discrete positions 604 can correspond to Figure 5 One of the multiple discrete positions 508 shown and described above.

[0143] like Figure 7 and 8 As shown, waveguide 602 includes a core material 606 surrounded by a cladding material 608. The cladding material 608 confines radiation to the core material 606, thereby guiding radiation along waveguide 602. It should be understood (see, for example, see...) Figure 5 The device 500 shown), waveguide 602 can be in ( Figure 1 One of the multiple waveguides formed in the main body 610 of waveguide 104 shown above.

[0144] Waveguide 602 extends from radiation source 102 to discrete location 604. Opaque walls are provided at the ends of waveguide 602 to prevent radiation from propagating out of waveguide 602 and into body 610.

[0145] Near discrete location 604, a patterned portion 614 is provided on the surface of the cladding material 608 of the waveguide 602, away from the sensing element 112 of the detector 106. The patterned portion 614 includes a plurality of grooves in the surface of the cladding material 608 of the waveguide 602, away from the sensing element 112 of the detector 106. For ease of understanding, in Figure 7 and Figure 8 These grooves of the patterned portion 614 are schematically shown in the cross-sectional view. The grooves of the patterned portion 614 can have any desired cross-sectional shape. For example, the grooves of the patterned portion 614 can be square or circular (e.g., round) grooves.

[0146] like Figure 8 As schematically shown, the patterned portion 614 couples radiation out of the waveguide within an angular range. A microlens array 616 is disposed adjacent to the patterned portion 614. The microlens array 616 may include a molded condenser lens array. The microlens array 616 is arranged to collimate the radiation coupled out of the waveguide 602 via the patterned portion 614 and direct it as an illumination beam 620 at a desired incident angle to a receiver location 122 adjacent to the sensing element 112.

[0147] As described above, the receptor site 122 may be provided with a metal nanostructure 622 (e.g., gold nanoparticles), which can be functionalized with the receptor.

[0148] Irradiation beam 620 excites local surface plasmon resonance (LSPR) in metal nanostructure 622, which in turn emits scattered radiation 624. At least a portion of the scattered radiation 624 is incident on sensing element 112 of detector 106 (via body 610 and separate spectral filter 124).

[0149] It should be understood that Figure 6 , Figure 7 and Figure 8 The schematic shown and described above, representing 600, is merely an example of an arrangement for coupling radiation out of waveguide 602 and directing it to receiver location 122.

[0150] It should be understood that electromagnetic radiation can be coupled out of each adjacent waveguide 104 of receiver site 122 in various different ways. For example, radiation 110 within waveguide 104 can be coupled out at each of a plurality of discrete locations 604 using mirrors, prisms and / or patterns in the cladding material of waveguide 104.

[0151] Alternatively, different forms of patterned portions 614 may be formed on the surface of the cladding material 608 of the waveguide 602, away from the sensing element 112 of the detector 106, and the patterned portions 614 may be provided thereon. Examples of different patterned portions used to couple radiation out of the waveguide include: holes in the cladding material 608; thinner portions of the cladding material 608; cladding materials with different refractive indices (refractive indices relative to the other sides of the cladding material); or other grooved structures.

[0152] List of reference numerals in the attached diagram:

[0153] 100 devices

[0154] 102 radiation source

[0155] 104 waveguide

[0156] 106 detectors

[0157] 108 spectral filter

[0158] 110 Electromagnetic Radiation

[0159] 112 sensing element

[0160] 114 Adjacent main body parts

[0161] 116 Remote Main Body

[0162] 118 Central Waveguide Section

[0163] 120 surface

[0164] 122 receptor sites

[0165] 124 individual spectral filters

[0166] 126 Printed Circuit Board

[0167] 128 Barrier

[0168] Absorption spectrum of 200 gold nanorods

[0169] 202 Spectral Filter

[0170] The absorption spectrum of 204 gold nanorods functionalized with receptors has been obtained.

[0171] The absorption spectrum of gold nanorods that have been functionalized with receptors and have bound to the target molecule.

[0172] Absorption spectrum of nanorods with a resonance wavelength of 700 nm at 300 nm

[0173] Absorption spectrum of nanorods with a resonance wavelength of 750 nm (302).

[0174] Absorption spectrum of 304 nanorods with a resonance wavelength of 780 nm

[0175] Absorption spectrum of nanorods with a resonance wavelength of 808 nm (306).

[0176] Absorption spectrum of nanorods with a resonance wavelength of 850 nm (308)

[0177] 310 spectral filter

[0178] 400 device

[0179] 402 sub-board

[0180] 404 casing

[0181] Port 406

[0182] 408 holes

[0183] 410 fluid flow

[0184] 412 processor

[0185] 414 sensor

[0186] Arrangement of 500 waveguide channels

[0187] 502 waveguide channel

[0188] 504 waveguide splitter

[0189] 506 End Waveguide

[0190] 508 Discrete Positions

[0191] Schematic representation of device 600

[0192] 602 waveguide

[0193] 604 Discrete Positions

[0194] 606 core material

[0195] 608 cladding material

[0196] 610 main body

[0197] 614 patterned part

[0198] 616 microlens array

[0199] 620 irradiation beam

[0200] 622 Metal Nanostructure

[0201] 624 Scattered Radiation

[0202] Those skilled in the art will understand that in the foregoing description and appended claims, positional terms such as “above,” “along,” and “side” are used with reference to conceptual illustrations (such as those shown in the accompanying drawings). These terms are used for ease of reference and are not intended to be restrictive. Therefore, these terms should be understood to refer to objects positioned as shown in the accompanying drawings.

[0203] Although this disclosure has been described with reference to preferred embodiments as described above, it should be understood that these embodiments are merely illustrative and the claims are not limited to these embodiments. In view of the disclosure, those skilled in the art will be able to make modifications and substitutions, which are considered to fall within the scope of the appended claims. Each feature disclosed or shown in this specification may be incorporated into any embodiment, either alone or in any suitable combination with any other feature disclosed or shown herein.

Claims

1. An apparatus for determining the presence or concentration of a target molecule, the apparatus comprising: The surface, which defines the receptor sites of the two-dimensional array; A waveguide, which is arranged to receive at least a portion of incident electromagnetic radiation, divides the electromagnetic radiation and guides a portion of the electromagnetic radiation to each of the receiver sites in the two-dimensional array. The detector includes a two-dimensional array of sensing elements, each of which is arranged to receive electromagnetic radiation from a different receiver location in the two-dimensional array. A spectral filter is disposed between the surface and the detector; Metal nanostructures disposed on each of the receptor sites in the two-dimensional array on the surface; as well as Receptors are disposed on each metal nanostructure, wherein the receptors are coated on the nanostructure. The waveguide is disposed between the detector and the surface defining the receptor site of the two-dimensional array. The waveguide comprises a generally flat body, and the surface defining the receptor site of the two-dimensional array is the surface of the body. The waveguide includes a plurality of waveguide channels formed in the waveguide body, each waveguide channel being arranged to guide radiation to a different one of a plurality of discrete locations within the body, each such discrete location being adjacent to a different sensing element of the two-dimensional array. The waveguide includes a two-dimensional array of coupling optics, each of which is arranged to couple radiation out of the waveguide toward a different receiver location in the two-dimensional array.

2. The apparatus of claim 1, further comprising a radiation source operable to generate electromagnetic radiation, wherein the waveguide is arranged to receive at least a portion of the electromagnetic radiation generated by the radiation source, divide the electromagnetic radiation, and direct a portion of the electromagnetic radiation to each of the receiver sites of the two-dimensional array.

3. The apparatus according to claim 2, wherein the radiation source is a broadband radiation source.

4. The apparatus according to claim 2 or claim 3, wherein the radiation source comprises a white light-emitting diode.

5. The apparatus according to any one of claims 1 to 3, further comprising a printed circuit board, wherein the detector is mounted on the printed circuit board.

6. The apparatus of claim 2 further includes a printed circuit board, wherein both the radiation source and the detector are mounted on the printed circuit board.

7. The apparatus according to any one of claims 1 to 3, wherein the waveguide comprises an integrated optical plate arranged to receive the electromagnetic radiation output from a radiation source at an input and to distribute the electromagnetic radiation onto the surface defining the receiver location of the two-dimensional array.

8. The apparatus according to any one of claims 1 to 3, wherein the waveguide comprises a plurality of beam splitters or optical waveguide splitters arranged to scatter incident radiation onto the surface defining the receiver location of the two-dimensional array.

9. The apparatus according to any one of claims 1 to 3, wherein the waveguide comprises one or more grating structures arranged to generate an interference pattern and to scatter the radiation onto the surface defining the receiver location of the two-dimensional array.

10. The apparatus according to any one of claims 1 to 3, further comprising a processor operable to determine the concentration of the target molecule based on the intensity of the electromagnetic radiation received from a corresponding receptor site in the two-dimensional array.

11. The apparatus according to any one of claims 1 to 3, further comprising one or more sensors operable to determine one or more environmental conditions.

12. The apparatus according to any one of claims 1 to 3, further comprising a user interface for receiving signals from the detector.

13. The apparatus according to any one of claims 1 to 3, wherein the spectral filter has a full width at half maximum (FWHM) bandwidth of 10 nm or less.

14. The apparatus according to any one of claims 1 to 3, wherein the spectral filter comprises individual spectral filters of a two-dimensional array, each individual spectral filter being configured to be adjacent to a different one of the sensing elements of the two-dimensional array.

15. The apparatus according to any one of claims 1 to 3, wherein the waveguide comprises a plurality of waveguide channels and a waveguide splitter.

16. The apparatus of claim 1, wherein each coupling optic includes a patterned portion at the end of a waveguide channel within the body of the waveguide.

17. The apparatus of claim 16, wherein the patterned portion at the end of the waveguide channel comprises a plurality of grooves formed in the cladding material of the waveguide channel.

18. The apparatus of claim 1, wherein each coupling optic comprises a mirror or a prism.

19. The apparatus according to any one of claims 16 to 18, wherein each coupling optics comprises a microlens array arranged to receive radiation coupled from a waveguide channel and to direct the radiation as an illumination beam to one of the receiver locations of the two-dimensional array.

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