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WO2022002992A1 - Appareil de résonance plasmonique de surface d'imagerie - Google Patents

Appareil de résonance plasmonique de surface d'imagerie Download PDF

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Publication number
WO2022002992A1
WO2022002992A1 PCT/EP2021/067934 EP2021067934W WO2022002992A1 WO 2022002992 A1 WO2022002992 A1 WO 2022002992A1 EP 2021067934 W EP2021067934 W EP 2021067934W WO 2022002992 A1 WO2022002992 A1 WO 2022002992A1
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Prior art keywords
electromagnetic radiation
beams
plasmon resonance
prism
surface plasmon
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English (en)
Inventor
Remco VERDOOLD
Erik Jan Lous
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Ams International AG
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Ams International AG
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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/55—Specular reflectivity
    • G01N21/552—Attenuated total reflection
    • G01N21/553—Attenuated total reflection and using surface plasmons
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
    • G01N21/251—Colorimeters; Construction thereof
    • G01N21/253—Colorimeters; Construction thereof for batch operation, i.e. multisample apparatus
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2201/00—Features of devices classified in G01N21/00
    • G01N2201/06—Illumination; Optics
    • G01N2201/063—Illuminating optical parts
    • G01N2201/0633—Directed, collimated illumination
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2201/00—Features of devices classified in G01N21/00
    • G01N2201/06—Illumination; Optics
    • G01N2201/063—Illuminating optical parts
    • G01N2201/0634—Diffuse illumination
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2201/00—Features of devices classified in G01N21/00
    • G01N2201/06—Illumination; Optics
    • G01N2201/063—Illuminating optical parts
    • G01N2201/0638—Refractive parts
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2201/00—Features of devices classified in G01N21/00
    • G01N2201/08—Optical fibres; light guides
    • G01N2201/0826—Fibre array at source, distributing

Definitions

  • the imaging surface plasmon resonance apparatus may have application, for example, in an assay (also sometimes referred to as a molecular interaction assay), which is arranged to measure the presence or concentration of a specific target molecule.
  • an assay also sometimes referred to as a molecular interaction assay
  • a molecular interaction assay which is arranged to measure the presence or concentration of a specific target molecule (which may be referred to as an analyte).
  • a molecular interaction assay typically uses a bio-receptor which can bind to the analyte. Such interactions are extremely specific with the bio-receptor and analyte binding in a similar way to a key and a lock. Typically, only the correct analyte is able to bind to the bio receptor.
  • reporter molecule is operable to bind to the analyte, typically only once the analyte has bound to the bio receptor.
  • the reporter molecule can report the presence of the analyte target molecule in some way.
  • the reporter molecule may use: an enzyme, as in an enzyme linked immunosorbent assay (ELISA); radioactivity, as in a radio immunosorbent assay (RIA); or, more commonly, a fluorophore, as in a fluorescent immunosorbent assay (FIA).
  • label-free detection assay methods As an alternative to the usage of reporter molecules, label-free detection assay methods have been developed and are gaining popularity.
  • One known label-free detection method is surface plasmon resonance (SPR).
  • SPR surface plasmon resonance
  • the present disclosure relates to such a label-free detection assay method, in particular to an imaging surface plasmon resonance apparatus.
  • One arrangement for using surface plasmon resonance as a label-free detection method (which may be referred to as a surface plasmon resonance apparatus) comprises a prism which is provided with a relatively thin layer of metal (for example gold) on one face thereof. Electromagnetic radiation is coupled into the prism and is incident on the interface between the prism and the metal such that total internal reflection occurs. 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 a direction perpendicular to the interface between the prism and the metal.
  • a surface plasmon resonance apparatus comprises a prism which is provided with a relatively thin layer of metal (for example gold) on one face thereof. Electromagnetic radiation is coupled into the prism and is incident on the interface between the prism and the metal such that total internal reflection occurs. This generates an evanescent wave in the metal layer which propagates parallel to the interface between the prism and the metal (and in the
  • surface plasmon polaritons are a type of coupled oscillation of electrons (plasmons) within the metal layer and an electromagnetic oscillation (polaritons) in the dielectric medium.
  • surface plasmons are collective conduction electron oscillations at the interface of two layers, one layer being a metal (usually a noble metal) and the second layer being a dielectric. If the thickness of the metal layer is sufficiently thin (with respect to a penetration depth of the evanescent wave) and a resonance condition is met, an evanescent wave can excite surface plasmon polaritons on an opposite side of the metal layer to the prism. This uses some of the energy from the incident electromagnetic radiation and therefore reduces the intensity of the electromagnetic radiation reflected from the interface between the prism and the metal layer.
  • Reflected electromagnetic radiation is coupled out of the prism and is incident on a detector, which is arranged to determine an intensity of the reflected electromagnetic radiation (which, in turn, is dependent on whether or surface plasmon polaritons have been excited).
  • the resonance condition is dependent on the wavelength and angle of incidence of the incident electromagnetic radiation.
  • the resonance condition is also dependent on optical properties of both the metal and the adjacent (dielectric) medium. If the metal is provided with a bio-receptor on its surface then these optical properties (and therefore the resonance condition) may vary in dependence on the presence or absence of a specific target molecule (or analyte) being bound to the bio-receptor. Therefore, by measuring information related to the resonance condition, it is possible to determine information about the presence and/or quantity of the specific target molecule adjacent the metal layer.
  • a plurality of different bio-receptors are provided on the metal layer; each one is irradiated with electromagnetic radiation and the electromagnetic radiation reflected from each is detected by a separate detector. Such an arrangement is known as imaging SPR (iSPR).
  • one of the main design challenges in the above-described imaging surface plasmon resonance apparatus is the optical system.
  • many lenses are required to project light properly onto the prism and to observe the reflected light on the imaging sensor.
  • Each lens has a specific aligned optical path and focal distance to achieve the best illumination and image quality.
  • the optics which illuminate the metal layer may be required to do so with a precision of the order of 0.1° in order to operate correctly.
  • the measurement may involve scanning through different angles of incidence in order to identify the resonance condition (as a local minimum in the intensity of the reflected electromagnetic radiation), which further complicates the optical system.
  • this disclosure proposes to overcome the problems in existing arrangements by providing an imaging surface plasmon resonance apparatus using a radiation source operable to produce a two dimensional array of generally parallel beams of electromagnetic radiation.
  • This arrangement is advantageous since it provides an apparatus with a very high degree of multiplexing and which is very compact.
  • an imaging surface plasmon resonance apparatus comprising: a prism; a radiation source operable to produce a two dimensional array of beams of electromagnetic radiation and arranged such that each one of said two dimensional array of beams of electromagnetic radiation is coupled into the prism and is incident on a different one of a plurality of regions on a surface of the prism at substantially the same angle of incidence; a layer of metal disposed on or adjacent to the surface of the prism in the vicinity of each of the plurality of regions on the surface of the prism; and a detector arranged to receive a portion of each of the two dimensional array of beams of electromagnetic radiation which is reflected from the interface between the prism and the layer of metal and operable to determine an intensity of said portion of each of the plurality of beams of electromagnetic radiation.
  • the radiation source of the imaging surface plasmon resonance apparatus provides an apparatus with a very high degree of multiplexing and which is very compact, as now discussed.
  • Prior art imaging surface plasmon resonance apparatuses which comprise a prism (upon which the metal layer is disposed) typically have illumination optics to couple radiation into the prism that this bulky and which must be accurately aligned.
  • One known arrangement uses a single light source (for example a diode laser) with a single pinhole and a collimating lens to ensure that the (divergent) electromagnetic radiation from the pinhole is collimated and is incident on the metal layer at a suitable angle to observe the resonance.
  • the light source or pinhole
  • the desired dimension of the collimated beam will be of the order of the dimensions of the prism.
  • the focal length of the lens will typically scale with the size of the lens.
  • the present imaging surface plasmon resonance apparatus disclosed here has the following advantages. First, by providing a plurality of beams of electromagnetic radiation it may be that no collimating illumination optics is required. Even if such optics are provided, since there is a plurality of smaller electromagnetic radiation beams, such optics can be smaller and, in particular, can have a significantly smaller focal length.
  • this allows for a particularly compact apparatus. For example, the optical volume may be reduced by at least a factor of 10.
  • Some prior art imaging surface plasmon resonance apparatuses are arranged to illuminate a metal layer with electromagnetic radiation at a plurality of different angles and the amount of reflected radiation from each is determined by a separate detector so as to determine a resonance spectrum. It will be appreciated that these prior art arrangements are incompatible with an arrangement that has a radiation source operable to produce a two dimensional array of generally mutually parallel beams of electromagnetic radiation that have substantially the same angle of incidence at the interface between the prism and the layer of metal.
  • the present imaging surface plasmon resonance apparatus disclosed here has the advantage that it allows for a two dimensional array of beams of electromagnetic radiation that are generally mutually parallel and therefore incident on the surface of the prism at substantially the same angle. This therefore allows for a two dimensional array of different receptors to be simultaneously monitored whilst all of these remain within a dynamic range of a detector for determining the presence and/or concentration of a target molecule being bound to those receptors.
  • this significantly increases the number of receptors that can be monitored simultaneously (i.e. it allows a significant increase in the amount of multiplexing).
  • the beams of electromagnetic radiation in the two dimensional array of beams of electromagnetic radiation may be considered to be generally mutually parallel if the directions of all of the beams of electromagnetic radiation vary by less than 1 °.
  • the directions of all of the beams of electromagnetic radiation may vary by less than 0.5°.
  • the directions of all of the beams of electromagnetic radiation may vary by less than 0.1°.
  • the direction of each beam of electromagnetic radiation may be the direction of a chief ray of that beam.
  • beams of electromagnetic radiation may be considered to be have the same angle of incidence at the surface of the prism if their angles of incidence vary by less than 1°.
  • the angles of incidence of all of the beams of electromagnetic radiation may vary by less than 0.5°.
  • the angles of incidence of all of the beams of electromagnetic radiation may vary by less than 0.1°.
  • the radiation source may be operable to produce other beams of electromagnetic radiation which are not parallel to the two dimensional array of generally mutually parallel beams of electromagnetic radiation.
  • the radiation source may be operable to produce a plurality two dimensional arrays of generally mutually parallel beams of electromagnetic radiation, the beams from each array being generally mutually parallel and the beams from different arrays being not parallel.
  • an imaging surface plasmon resonance apparatus comprising: a prism; a radiation source operable to produce a two dimensional array of beams of electromagnetic radiation and arranged such that each one of said two dimensional array of beams of electromagnetic radiation is coupled into the prism and is incident on a different one of a plurality of regions on a surface of the prism; a layer of metal disposed on or adjacent to the surface of the prism in the vicinity of each of the plurality of regions on the surface of the prism and comprising a two dimensional array of receptor sites for supporting a receptor, each receptor site disposed on a surface of the layer of metal that is distal to the prism and adjacent one of the plurality of regions on the surface of the prism; and a detector arranged to receive a portion of each of the two dimensional array of beams of electromagnetic radiation which is reflected from the interface between the prism and the layer of metal and operable to determine an intensity of said portion of each of the plurality of beams of electromagnetic radiation.
  • the combination of: a two-dimensional array of receptor sites disposed on the surface of the layer of metal that is distal to the prism; and a source operable to produce a two-dimensional array of beams of electromagnetic radiation provides an apparatus with a very high degree of multiplexing and which is very compact.
  • the beams of electromagnetic radiation in the two dimensional array of beams of electromagnetic radiation may be generally mutually parallel.
  • a receptor is intended to mean anything (for example a molecule) which can receive and bind to something else.
  • Receptors can comprise any one of a number of biological molecules such as, for example, proteins, viruses and the like.
  • the imaging surface plasmon resonance apparatus may further comprise a plurality of receptors, each disposed on a surface of the layer of metal that is distal to the prism.
  • the receptors may be disposed at the receptor sites.
  • the two-dimensional array of receptors (which are disposed on a surface of the layer of metal that is distal to the prism) are on an opposite surface of the layer of metal to that which the electromagnetic radiation is incident on.
  • a beam of electromagnetic radiation being incident on an interface between the prism and the layer of metal in the vicinity of one of the receptors from the two-dimensional array of receptors means that that beam is incident on a position on one surface that generally corresponds to the position on the opposite surface where the receptor is (for example merely translated in a direction of the thickness of the layer of metal, which may be generally perpendicular to the two opposed surfaces).
  • the radiation source may comprise a radiation emitting apparatus operable to emit electromagnetic radiation and an optical system arranged to receive the electromagnetic radiation output by the radiation emitting apparatus, split this electromagnetic radiation and output the two dimensional array of beams of electromagnetic radiation.
  • the radiation emitting apparatus may comprise a vertical-cavity surface-emitting laser (VC SEL), a light emitting diode (LED) or an edge emitting laser diode.
  • VC SEL vertical-cavity surface-emitting laser
  • LED light emitting diode
  • edge emitting laser diode an edge emitting laser diode
  • the optical system may comprise integrated optics.
  • integrated optics may be referred to as on-chip technology or on-chip optics.
  • the radiation emitting apparatus may comprises more than one radiation emitter (for example for embodiments wherein multiple wavelengths are produced, one radiation emitter may be provided for each distinct wavelength.
  • the optical system may comprise an integrated optics plate arranged to receive the electromagnetic radiation output by the radiation emitting apparatus at an input surface and to spread out the electromagnetic radiation over an output surface.
  • the integrated optics plate may comprise a diffusor plate.
  • the integrated optics plate may comprise a plurality of beam splitters or optical waveguide splitters arranged to spread the radiation over the output surface.
  • the integrated optics plate may comprise one or more grating structures arranged to produce an interference pattern and spread the radiation over the output surface.
  • the integrated optics plate may comprise one or more Fresnel lens.
  • the integrated optics plate may comprise a two dimensional array of collimating tubes, each arranged to receive and at least partially collimate one of the two dimensional array of beams of electromagnetic radiation.
  • the integrated optics plate may comprise a fiber optics plate.
  • the input surface of the integrated optics plate may be opposite the output surface of the integrated optics plate.
  • the input surface of the integrated optics plate may be an edge surface of the integrated optics plate.
  • the optical system may further comprise a microlens array.
  • the optical system may further comprise a pinhole array.
  • Each one of the beams of electromagnetic radiation in the two dimensional array of beams of electromagnetic radiation may be formed by a pinhole from a pinhole array and a microlens from a microlens array.
  • the beams of electromagnetic radiation in the two dimensional array of beams of electromagnetic radiation may each have a divergence of 1° or less.
  • the beams of electromagnetic radiation in the two dimensional array of beams of electromagnetic radiation each have a divergence of 0.5° or less.
  • the beams of electromagnetic radiation in the two dimensional array of beams of electromagnetic radiation each have a divergence of the order of 0.3° or less.
  • the radiation source may be operable to produce a plurality of two dimensional arrays of beams of electromagnetic radiation, wherein the beams of electromagnetic radiation in each two dimensional array of beams of electromagnetic radiation are generally mutually parallel and beams of electromagnetic radiation from different two dimensional arrays of beams of electromagnetic radiation are not parallel.
  • the range of angles of incidence for all of the plurality of two dimensional arrays of beams of electromagnetic radiation may be less than 1°.
  • the radiation source may be operable to produce a plurality of two dimensional arrays of beams of electromagnetic radiation, wherein the beams of electromagnetic radiation in each two dimensional array of beams of electromagnetic radiation have substantially the same wavelength and beams of electromagnetic radiation from different two dimensional arrays of beams of electromagnetic radiation have different wavelengths.
  • the radiation source may be operable to produce electromagnetic radiation having a wavelength from a range of different selectable wavelengths.
  • the imaging surface plasmon resonance apparatus may further comprise a processor operable to determine a concentration of a target molecule from the intensity of the portion of each of the plurality of beams of electromagnetic radiation determined by the detector.
  • the detector may comprise any suitable electromagnetic radiation setector.
  • Suitable detectors include, for example, a single-photon avalanche detectors (SPAD), photodiodes, complementary metal-oxide-semiconductor (CMOS) diode arrays and/or charge-coupled device (CCD) arrays.
  • SPAD single-photon avalanche detectors
  • CMOS complementary metal-oxide-semiconductor
  • CCD charge-coupled device
  • the prism may be a right prism.
  • the prism may be a 5x5x5 mm 90-degrees prism.
  • the layer of metal may comprise any type of metal.
  • the layer of metal may comprise a noble metal.
  • noble metals are less prone to oxidization.
  • the layer of metal may comprise gold.
  • the layer of metal may have a thickness of the order of 50 nm.
  • the layer of metal may comprise a substantially continuous layer of metal disposed on or adjacent to the surface of the prism in the vicinity of all of the plurality of regions on the surface of the prism.
  • the layer of metal may comprise a plurality of discrete patches of metal disposed on or adjacent to the surface of the prism.
  • the layer of metal may comprise a plurality of discrete patches of metal, each discrete patch of metal being disposed in the vicinity of a different one of the plurality of regions on the surface of the prism.
  • the imaging surface plasmon resonance apparatus may further comprise a polarizer arranged to polarize the two dimensional array of beams of electromagnetic radiation such that the electric field of each of the beams of electromagnetic radiation is parallel to the plane of incidence at the surface of the prism.
  • the imaging surface plasmon resonance apparatus may further comprise one or more sensors operable to determine one or more ambient conditions.
  • the apparatus may comprise sensors operable to determine one or more of: a relative humidity, temperature and/or pressure adjacent the layer of metal.
  • the imaging surface plasmon resonance apparatus may further comprise a printed circuit board to which the radiation source and the detector are mounted.
  • the imaging surface plasmon resonance apparatus may further comprise a user interface for providing signals to the radiation source and/or receiving signals from the detector.
  • the printed circuit board may be provided with a USB port, which mat form part of the user interface.
  • Figure 1 shows a schematic illustration of an imaging surface plasmon resonance apparatus according to the present disclosure
  • Figure 2 shows a plan view of the imaging surface plasmon resonance apparatus shown in Figure 1 , showing a layer of metal;
  • Figure 3 shows an example resonance curve for the intensity of the reflected radiation of one of a two dimensional array of beams of electromagnetic radiation within the imaging surface plasmon resonance apparatus shown in Figure 1 as a function of the angle of incidence of that beam of electromagnetic radiation;
  • Figure 4 shows a schematic illustration of a known imaging surface plasmon resonance apparatus
  • Figure 5 shows a schematic illustration of another imaging surface plasmon resonance apparatus according to the present disclosure
  • Figure 6 shows a schematic illustration of another imaging surface plasmon resonance apparatus according to the present disclosure
  • Figure 7 shows the same example resonance curve for the intensity of the reflected radiation of one of a two dimensional array of beams of electromagnetic radiation as a function of the angle of incidence that beam of electromagnetic radiation as is shown in Figure 3;
  • Figure 8 shows a schematic illustration of another imaging surface plasmon resonance apparatus according to the present disclosure.
  • Figure 9 shows some example resonance curves for the intensity of the reflected radiation of one of a two dimensional array of beams of electromagnetic radiation as a function of the angle of incidence that beam of electromagnetic radiation for four different wavelengths.
  • the disclosure provides an imaging surface plasmon resonance apparatus that uses a radiation source operable to produce a two dimensional array of beams of electromagnetic radiation.
  • a radiation source operable to produce a two dimensional array of beams of electromagnetic radiation.
  • each beam of electromagnetic radiation in the two dimensional array of beams of electromagnetic radiation is incident on a metal layer proximate to a different one of a plurality of receptor patches at substantially the same angle of incidence.
  • FIG 1 is a schematic illustration of an imaging surface plasmon resonance apparatus 100 according to the present disclosure.
  • the imaging surface plasmon resonance apparatus 100 comprises a prism 102, a radiation source 104; a layer of metal 106 disposed on or adjacent to a surface of the prism 102; and a detector 108.
  • the prism 102 is a right prism.
  • the prism 102 is in the form of a right triangular prism having three rectangular surfaces 110, 112, 114 (out of the plane of Figure 1) and two triangular surfaces (parallel to the plane of Figure 1).
  • the triangular cross section of the prism 102 (see Figure 1) is an isosceles right triangle. That is, the triangle has two mutually perpendicular shorter sides (shorter surfaces 110, 112) that are equal in length and one longer side (longer surface 114) that is disposed at 45° to each of the shorter sides 110, 112.
  • the shape of the prism 102 is defined by two parallel, congruent triangular surfaces one being a copy of the other but translated in a direction perpendicular to the other triangular surface (out of the plane of Figure 1), with one rectangular surface extending between each pair of corresponding sides of the two triangular surfaces.
  • the prism 102 is formed from a light-transmitting material (for example glass).
  • the prism 102 is formed from a material that is transmits radiation emitted by the radiation source 104.
  • the prism 102 may have dimensions of 5x5x5 mm. That is, the dimensions of each of the shorter surfaces 110, 112 are 5 mm (in the plane of Figure 1) and 5 mm (perpendicular to the plane of Figure 1).
  • the radiation source 104 is operable to produce a two dimensional array of beams of electromagnetic radiation. These are illustrated very schematically in Figure 1 by three dotted lines with arrows. It will be appreciated that there will also be beams of electromagnetic radiation not in the plane of Figure 1 but in parallel planes. It will be further appreciated that in each direction of the two dimensional array of beams of electromagnetic radiation there may be fewer than or more than three beams of electromagnetic radiation. In general, the two dimensional array of beams of electromagnetic radiation can be an n x m array of parallel beams of electromagnetic radiation.
  • the radiation source 104 is arranged such that each one of said two dimensional array of beams of electromagnetic radiation is coupled into the prism 102.
  • the radiation source 104 is disposed adjacent a first one of the shorter surfaces 110 of the prism 102.
  • the radiation source 104 is orientated such that the two dimensional array of beams of electromagnetic radiation produced thereby is coupled into the prism 102 through the first shorter surface 110 and is incident on the longer surface 114 of the prism 102.
  • the imaging surface plasmon resonance apparatus 100 further comprises a polarizer 116.
  • the polarizer 116 is a plane polarizer, also referred to as a linear polarizer.
  • the polarizer 116 is arranged to polarize the two dimensional array of beams of electromagnetic radiation output by the radiation source 104.
  • the radiation is polarized such that the electric field of each of the beams of electromagnetic radiation is parallel to the plane of incidence at the longer surface 114 of the prism 102 (i.e. parallel to the plane of Figure 1).
  • This polarization state may be referred to as p-polarization.
  • the beams of electromagnetic radiation output by the radiation source 104 are generally parallel. Therefore, each of the beams of electromagnetic radiation output by the radiation source 104 is incident on a different region on the longer surface 114 of the prism 102 at generally the same angle of incidence.
  • the longer surface 114 of the prism 102 may be considered to comprise a plurality of regions (each region, for example, defined by a position of each beam spot from the two dimensional array of beams of electromagnetic radiation).
  • the layer of metal 106 is disposed on the longer surface 114 of the prism 102 in the vicinity of each of the plurality of regions on the surface of the prism 102 (each region being defined by a position of each beam spot from the two dimensional array of beams of electromagnetic radiation on the longer surface).
  • the layer of metal 106 is disposed on the longer surface 114 of the prism 102, in alternative embodiments it may be disposed adjacent to said longer surface 114.
  • the layer of metal 106 comprises a layer of gold having a thickness of the order of 50 nm. However, it will be appreciated that in alternative embodiments other metals and thicknesses may be used. In general, the layer of metal may comprise a noble metal. At least a portion of each of the two dimensional array of beams of electromagnetic radiation is reflected from the interface between the prism 102 and the layer of metal 106. These reflected portions are illustrated very schematically in Figure 1 by three dotted lines with arrows.
  • the detector 108 is arranged to receive a portion of each of the two dimensional array of beams of electromagnetic radiation which is reflected from the interface between the prism 102 and the layer of metal 106.
  • the detector 108 is operable to determine an intensity of said portion of each of the plurality of beams of electromagnetic radiation.
  • the detector 108 may comprise any suitable electromagnetic radiation sensor. Suitable detectors include, for example, a single-photon avalanche detectors (SPAD), photodiodes, complementary metal-oxide-semiconductor (CMOS) diode arrays and/or charge-coupled device (CCD) arrays.
  • SPAD single-photon avalanche detectors
  • CMOS complementary metal-oxide-semiconductor
  • CCD charge-coupled device
  • Figure 2 shows a plan (top) view of the layer of metal 106 in one embodiment. It will be appreciated that Figure 2 shows a surface of the layer of metal 106 that is distal to the prism 102 and which may be referred to herein as a distal surface of the layer of metal 106. The distal surface is opposite the surface the layer of metal 106 which is disposed on the prism 106, which may be referred to as a proximal surface of the layer of metal 106. It is the proximal surface which forms part of the interface from which the electromagnetic radiation is at least partially reflected.
  • the positions of the beam spots of the two dimensional array of beams of electromagnetic radiation at the interface between the prism 102 and the layer of metal 106 are coincident with the plurality of regions on the longer surface 114 of the prism 102 defined by a position of each beam spot from the two dimensional array of beams of electromagnetic radiation. Also shown in Figure 2 (in dotted lines) are the positions 200 on the distal surface that correspond to (i.e. are opposite to) the positions of the beam spots from the two dimensional array of beams of electromagnetic radiation at the interface between the prism 102 and the layer of metal 106.
  • a receptor for example a bio-receptor
  • a receptor may be disposed on each of the positions 200 on the distal surface of the layer of metal 106 that correspond to the positions of the beam spots from the two dimensional array of beams of electromagnetic radiation at the interface between the prism 102 and the layer of metal 106.
  • each of the positions 200 on the distal surface of the layer of metal 106 that corresponds to the position of the beam spot of one of the beams of electromagnetic radiation may be provided with a different type of bio-receptor such that the imaging surface plasmon resonance apparatus 100 can be used to identify the presence and/or concentration of a plurality of different target molecules or analytes.
  • Each of the positions 200 on the distal surface of the layer of metal 106 that corresponds to the positions of a beam spot from the two dimensional array of beams of electromagnetic radiation at the interface between the prism 102 and the layer of metal 106 may be referred to as a receptor site 200. Therefore, the layer of metal 106 disposed on the longer surface 114 of the prism 102 may be considered to comprise a two dimensional array of receptor sites for supporting a receptor. Each such receptor site 200 being disposed on a surface of the layer of metal 106 that is distal to the prism 102 and adjacent one of the plurality of regions on the surface of the prism 102 defined by the beam spots.
  • the imaging surface plasmon resonance apparatus 100 may have application in an assay (also sometimes referred to as an assay or a molecular interaction assay), which is arranged to measure the presence or concentration of a specific target molecule, as now discussed.
  • an assay also sometimes referred to as an assay or a molecular interaction assay
  • a plurality of receptors are provided, each on a different one of the receptor sites 200.
  • the distal surface of the layer of metal 106 is disposed in a sample fluid (for example a gas or a liquid) to be analysed. If certain target molecules are present in the sample fluid they can bind to the receptors. It will be appreciated that these interactions are extremely specific with the receptor and target molecule (analyte) binding in a similar way to a key and a lock. Typically, only the correct analyte is able to bind to the receptor.
  • the receptor sites 200 may have dimensions of the order of 100-200 pm. A lower limit of the dimensions of the receptor sites 200 may be imposed by the smallest size of a patch of receptor that can be deposited on the layer of metal 106.
  • a lower limit of the dimensions of the receptor sites 200 may be imposed by the smallest size of a patch of receptor that can be deposited on the layer of metal 106.
  • this generates an evanescent wave in the layer of metal 106 which propagates parallel to the interface between the prism 102 and the layer of metal 106 (and in the plane of incidence) and has an amplitude that decays exponentially in a direction perpendicular to the interface between the prism 102 and the layer of metal 106.
  • surface plasmon polaritons are a type of coupled oscillation of electrons (plasmons) within the layer of metal 106 and an electromagnetic oscillation (polaritons) in the dielectric medium.
  • surface plasmons are collective conduction electron oscillations at the interface of two layers, one layer being a metal (usually a noble metal) and the second layer being a dielectric.
  • the thickness of the layer of metal 106 is sufficiently thin (with respect to a penetration depth of the evanescent wave) and a resonance condition is met, it can excite surface plasmon polaritons on an opposite side of the layer of metal 106 to the prism 102 (i.e. on the distal surface of the layer of metal 106).
  • This uses some of the energy from the incident electromagnetic radiation and therefore reduces the intensity of the electromagnetic radiation that is reflected from the interface between the prism 102 and the layer of metal 106. In turn, this reduces the intensity of the reflected portion of each of the two dimensional array of beams of electromagnetic radiation determined by the detector 108.
  • the resonance condition is dependent on the wavelength and angle of incidence of the incident electromagnetic radiation (generated by the radiation source 104).
  • the resonance condition is also dependent on optical properties of both the layer of metal 106 and the adjacent (dielectric) medium, i.e. the receptors at the receptor sites 200.
  • the optical properties of the dielectric vary in dependence on the presence or absence of the specific target molecule (or analyte) that can bind to the receptor.
  • the optical properties of the dielectric vary in dependence on the concentration of the specific target molecule (or analyte) that is bound to the receptor.
  • Figure 3 shows an example resonance curve 300 for the intensity of the reflected radiation of one of the two dimensional array of beams of electromagnetic radiation as a function of the angle of incidence of that beam of electromagnetic radiation.
  • concentration of the specific target molecule (or analyte) that is bound to the receptor at the receptor site corresponding to a particular beam of electromagnetic radiation varies, resonance curve 300 will also vary.
  • the resonance curve 300 may move to the left or right such that the angle at which the minimum 302 of the resonance curve 300 occurs varies.
  • apparatus scan through a range of different angles of incidence in order to identify the position of a minimum 302 of the resonance curve 300.
  • this can result in a bulky and complicated optical system and/or a reduction in the level of multiplexing that is possible.
  • the imaging surface plasmon resonance apparatus 100 uses an individual beam of radiation (from the radiation source 104) for each receptor site 200 that has a fixed angle of incidence.
  • the beams of electromagnetic radiation in the two dimensional array of beams of electromagnetic radiation may typically each have a divergence of 0.5° or less (for example, less than 0.3°). Therefore, the detector 108 samples the resonance curve 300 at a fixed angle. Since this fixed angle is on the resonance trough, as the resonance curve 300 moves to the left or right the sampled value will increase or decrease.
  • the dynamic range of a typical detector 108 is illustrated in Figure 3 as a rectangle 304.
  • the rectangle 304 has a non-zero width in the direction of the axis for the angle of incidence for a number of reasons. For example the electromagnetic radiation will have some non-zero bandwidth, some non-zero divergence and/or the detector 108 subtends a non-zero range of angles at which it can receive the reflected radiation.
  • the rectangle 304 has a finite height which corresponds to the dynamic range of intensities over which the detector 108 can operate.
  • the imaging surface plasmon resonance apparatus 100 can no longer operate (since the resonance curve 300 no longer overlaps the rectangle 304 representing the dynamic range). This is one reason that miniaturization of the imaging surface plasmon resonance apparatus 100 and having fewer components in the imaging surface plasmon resonance apparatus 100 result in a more robust system for measurement. Increasing the range of angles of incidence (for example by increasing the divergence of the beams of electromagnetic radiation) or the bandwidth of the radiation will effectively broaden the thickness of the line in of the resonance curve 300, which reduces the resolution of the imaging surface plasmon resonance apparatus 100.
  • the radiation source 104 of the imaging surface plasmon resonance apparatus 100 provides an apparatus with a very high degree of multiplexing and which is very compact, as now discussed.
  • Prior art imaging surface plasmon resonance apparatuses which comprise a prism (upon which the metal layer is disposed) typically have illumination optics to couple radiation into the prism that this bulky and which must be accurately aligned.
  • One such known apparatus 400 is shown in Figure 4.
  • the known apparatus 400 shown in Figure 4 shares some features in common with the imaging surface plasmon resonance apparatus 100 according to the present disclosure.
  • the known apparatus comprises: a prism 402, having two mutually perpendicular shorter surfaces 410, 412 and one longer surface 414; a layer of metal 406 disposed on the longer surface 414 of the prism 102; a detector 408 adjacent one of the shorter surfaces 412; and a polarizer 416.
  • the known apparatus 400 uses a different illumination system, as now discussed.
  • the known apparatus 400 uses a single light source 418 (for example a diode laser) which illuminates a single pinhole 420 in a screen 422.
  • the single pinhole 420 acts as a point source and illuminates a collimating lens 424 to ensure that the (divergent) electromagnetic radiation from the pinhole 420 is collimated and is incident on the metal layer 406 at a suitable angle to observe the resonance.
  • the pinhole 420 should be disposed at a focal point of the collimating lens 424.
  • the desired dimension of the collimated beam will be of the order of the dimensions of the prism 402.
  • the focal length of the lens will typically scale with the size of the lens 424. Therefore, with such an arrangement 400 the illumination system is at least the same size as the prism 402 or larger.
  • the present imaging surface plasmon resonance apparatus 100 has the following advantages.
  • a radiation source 104 operable to produce a two dimensional array of beams of electromagnetic radiation no collimating illumination optics is required.
  • this allows for a particularly compact apparatus.
  • the optical volume may be reduced by at least a factor of 10.
  • Some prior art imaging surface plasmon resonance apparatuses are arranged to illuminate a metal layer with electromagnetic radiation at a plurality of different angles and the amount of reflected radiation from each is determined by a separate detector so as to determine a resonance spectrum. It will be appreciated that these prior art arrangements are incompatible with an arrangement that has a radiation source operable to produce a two dimensional array of beams of electromagnetic radiation that are generally mutually parallel and are incident on the interface between the prism 102 and the layer of metal 106 at substantially the same angle of incidence (since a range of angles of incidence is required).
  • the present imaging surface plasmon resonance apparatus 100 disclosed here has the advantage that it allows for a two dimensional array of beams of electromagnetic radiation that are generally mutually parallel and therefore incident on the surface 114 of the prism 402 at substantially the same angle. This therefore allows for a two dimensional array of different receptors to be simultaneously monitored whilst all of these remain within a dynamic range of a detector for determining the presence and/or concentration of a target molecule being bound to those receptors.
  • this significantly increases the number of receptors that can be monitored simultaneously (i.e. it allows a significant increase in the amount of multiplexing).
  • the beams of electromagnetic radiation in the two dimensional array of beams of electromagnetic radiation may be considered to be generally mutually parallel if the directions of all of the beams of electromagnetic radiation vary by less than 1 °.
  • the directions of all of the beams of electromagnetic radiation may vary by less than 0.5°.
  • the directions of all of the beams of electromagnetic radiation may vary by less than 0.1°.
  • the direction of each beam of electromagnetic radiation may be the direction of a chief ray of that beam.
  • beams of electromagnetic radiation may be considered to be have the same angle of incidence if their angles of incidence vary by less than 1°.
  • the angles of incidence of all of the beams of electromagnetic radiation may vary by less than 0.5°.
  • the angles of incidence of all of the beams of electromagnetic radiation may vary by less than 0.1°.
  • the layer of metal 106 may comprise a substantially continuous layer of metal disposed on, or adjacent to, the surface 114 of the prism 102 in the vicinity of all of the plurality of regions on the surface of the prism 102 corresponding to one of the beam spots. That is, all of the receptor sites 200 shown in Figure 2 are provided on a single layer of metal 106.
  • the layer of metal 106 may comprise a plurality of discrete patches of metal disposed on or adjacent to the surface 114 of the prism 102.
  • the layer of metal 106 may comprise a plurality of discrete patches of metal, each discrete patch of metal being disposed in the vicinity of a different one of the plurality of regions on the surface of the prism 102 corresponding to one of the beam spots. That is, each of the receptor sites 200 shown in Figure 2 may be provided on a different patch of metal 106.
  • the radiation source 104 comprises: a radiation emitting apparatus operable to emit electromagnetic radiation; and an optical system arranged to receive the electromagnetic radiation output by the radiation emitting apparatus, split this electromagnetic radiation and output the two dimensional array of beams of electromagnetic radiation. Example embodiments of such systems are now described with reference to Figure 5.
  • FIG 5 is a schematic illustration of an imaging surface plasmon resonance apparatus 500 according to the present disclosure.
  • the imaging surface plasmon resonance apparatus 500 shown in Figure 5 is of the form of, and shares many features in common with, the imaging surface plasmon resonance apparatus 100 shown in Figure 1. Such features share common reference numerals and will not be described further here unless a feature of the imaging surface plasmon resonance apparatus 500 shown in Figure 5 differs from the corresponding feature of the imaging surface plasmon resonance apparatus 100 shown in Figure 1.
  • the imaging surface plasmon resonance apparatus 500 shown in Figure 5 gives an example structure for the radiation source 104.
  • the radiation source 104 comprises a radiation emitting apparatus 502 operable to emit electromagnetic radiation and an optical system 504 arranged to receive the electromagnetic radiation output by the radiation emitting apparatus 502, split this electromagnetic radiation and output the two dimensional array of beams of electromagnetic radiation.
  • the radiation emitting apparatus 502 may comprise a vertical-cavity surface-emitting laser (VC SEL), a light emitting diode (LED) or an edge emitting laser diode.
  • VC SEL vertical-cavity surface-emitting laser
  • LED light emitting diode
  • edge emitting laser diode As will be described further below, the radiation source 104 may comprise more than one radiation emitting apparatus 502 (for example for embodiments wherein multiple wavelengths are produced, one radiation emitting apparatus 502 may be provided for each distinct wavelength).
  • the optical system 504 may comprise integrated optics. Such integrated optics may be referred to as on-chip technology or on-chip optics. There are various different arrangements of integrated optics that may be operable to receive the electromagnetic radiation output by the radiation emitting apparatus 502, split this electromagnetic radiation and output the two dimensional array of beams of electromagnetic radiation, as now discussed.
  • the optical system 504 comprises an integrated optics plate arranged to receive the electromagnetic radiation output by the radiation emitting apparatus at an input surface 506 and to spread out the electromagnetic radiation over an output surface 508.
  • the integrated optics plate 504 comprises a diffusor plate, a pinhole array and a microlens array.
  • the diffusor plate may be arranged to spread out the radiation received from the radiation emitting apparatus 502 so as to illuminate all of the pinholes in the pinhole array.
  • Each such pinhole may act as a point source and may be collimated and directed by a lens in the microlens array.
  • the integrated optics plate 504 may comprise a plurality of beam splitters or optical waveguide splitters arranged to spread the radiation over the output surface 508 in a desired pattern.
  • such embodiments may further comprise a pinhole array and/or a microlens array.
  • Each such pinhole in the pinhole array may act to at least partially define one of the two dimensional array of beams of electromagnetic radiation.
  • Each microlens in the microlens array may be arranged to collimate and/or direct radiation so as to at least partially define one of the two dimensional array of beams of electromagnetic radiation.
  • the integrated optics plate 504 may comprise one or more grating structures arranged to produce an interference pattern and spread the radiation over the output surface 508 in a desired pattern.
  • such embodiments may further comprise a pinhole array and/or a microlens array.
  • Each such pinhole in the pinhole array may act to at least partially define one of the two dimensional array of beams of electromagnetic radiation.
  • Each microlens in the microlens array may be arranged to collimate and/or direct radiation so as to at least partially define one of the two dimensional array of beams of electromagnetic radiation.
  • the integrated optics plate 504 may comprise one or more Fresnel lens arranged to spread the radiation over the output surface 508 in a desired pattern.
  • such embodiments may further comprise a pinhole array and/or a microlens array.
  • Each such pinhole in the pinhole array may act to at least partially define one of the two dimensional array of beams of electromagnetic radiation.
  • Each microlens in the microlens array may be arranged to collimate and/or direct radiation so as to at least partially define one of the two dimensional array of beams of electromagnetic radiation.
  • the integrated optics plate 504 may comprise a two dimensional array of collimating tubes.
  • Each collimating tube may be arranged to collimate one of the two dimensional array of beams of electromagnetic radiation.
  • the collimating tubes may be mutually parallel and may be arranged to ensure that each of the two dimensional array of beams of electromagnetic radiation has a narrow angle directionality (i.e. low divergence) at the interface between the prism 102 and the layer of metal 106.
  • the collimating tubes may be hollow and may act as light pipes. Alternatively collimating tubes may be provided by a fiber optics plate.
  • the integrated optics plate 504 may comprise a combination of above methods described.
  • the imaging surface plasmon resonance apparatus 500 shown in Figure 5 comprises some additional, optional features, not present in the imaging surface plasmon resonance apparatus 100 shown in Figure 1, as now discussed.
  • the imaging surface plasmon resonance apparatus 500 further comprises a printed circuit board 510.
  • the radiation source 104 is mounted on the printed circuit board 510 via a support 512 and a contact 514 (for example one or more soldered contacts).
  • the radiation emitting apparatus 502 is mounted on the printed circuit board 510 via a support 512 and a contact 514.
  • the integrated optics plate 504 is mounted to the radiation emitting apparatus 502 such that radiation from the radiation emitting apparatus 502 is received by the input surface 506.
  • the detector 108 is also mounted on the printed circuit board 510 via a support 516 and a contact 518 (for example one or more soldered contacts).
  • the supports 512, 516 may comprise printed circuit boards.
  • the imaging surface plasmon resonance apparatus 500 further comprises one or more sensors operable to determine one or more ambient conditions.
  • the imaging surface plasmon resonance apparatus 500 further comprises a support 520 which is provided with one or more sensors operable to determine one or more ambient conditions.
  • the support 520 may comprise, for example, sensors operable to determine one or more of: a relative humidity, temperature and/or pressure adjacent the layer of metal 106.
  • the support 520 is connected to the support 516 of the detector 108 via a contact 522 (for example one or more soldered contacts).
  • the support 522 may comprise a printed circuit board.
  • the imaging surface plasmon resonance apparatus 500 further comprises a universal serial bus (USB) port 524.
  • the USB port 524 provides a user interface for providing signals to the radiation source 104, in particular to the radiation emitting apparatus 502.
  • the USB port 524 provides a user interface for receiving signals from the detector 108.
  • the USB port 524 provides a user interface for receiving signals from the one or more sensors provided on the support 520.
  • the imaging surface plasmon resonance apparatus 500 may further comprise a processor 526 operable to determine a concentration of a target molecule from the intensity of the portion of each of the plurality of beams of electromagnetic radiation determined by the detector 108.
  • the processor 526 may be operable to implement the methods described above with reference to Figure 3 (or any of the methods described below with reference to Figures 7 to 9).
  • signals from the detector 108 may be processed by a separate processor connected to the detector 108 via the USB port 524.
  • the input surface 506 of the integrated optics plate 504 is opposite the output surface 506 of the integrated optics plate 504.
  • different geometries may be provided. For example, one such alternative is now described with reference to Figure 6.
  • FIG. 6 is a schematic illustration of another imaging surface plasmon resonance apparatus 600 according to the present disclosure.
  • the imaging surface plasmon resonance apparatus 600 shown in Figure 6 shares many features in common with the imaging surface plasmon resonance apparatus 500 shown in Figure 5. Such features share common reference numerals and will not be described further here unless a feature of the imaging surface plasmon resonance apparatus 500 shown in Figure 5 differs from the corresponding feature of the imaging surface plasmon resonance apparatus 100 shown in Figure 1.
  • the differences between the imaging surface plasmon resonance apparatus 600 shown in Figure 6 and the imaging surface plasmon resonance apparatus 500 shown in Figure 5 are described.
  • the imaging surface plasmon resonance apparatus 600 shown in Figure 6 gives a different example structure for the radiation source 104.
  • the radiation source 104 also comprises a radiation emitting apparatus 602 operable to emit electromagnetic radiation and an optical system 604 arranged to receive the electromagnetic radiation output by the radiation emitting apparatus 602, split this electromagnetic radiation and output the two dimensional array of beams of electromagnetic radiation.
  • the radiation emitting apparatus 602 may comprise a vertical-cavity surface-emitting laser (VC SEL), a light emitting diode (LED) or an edge emiiting laser diode.
  • VC SEL vertical-cavity surface-emitting laser
  • LED light emitting diode
  • edge emiiting laser diode an edge emiiting laser diode.
  • the radiation source 104 may comprise more than one radiation emitting apparatus 602 (for example for embodiments wherein multiple wavelengths are produced, one radiation emitting apparatus 602 may be provided for each distinct wavelength).
  • the optical system 604 may comprise integrated optics. Such integrated optics may be referred to as on-chip technology or on-chip optics.
  • the optical system 604 also comprises an integrated optics plate arranged to receive the electromagnetic radiation output by the radiation emitting apparatus 602 at an input surface 606 and to spread out the electromagnetic radiation over an output surface 608.
  • the input surface 606 of the integrated optics plate 604 is an edge surface or side surface of the integrated optics plate 604.
  • the radiation emitting apparatus 602 is operable to emit radiation into the integrated optics plate 604 from one side 606 thereof and the integrated optics plate 604 is operable to direct the radiation to a plurality of locations on a perpendicular surface 608 of the plate (as a two dimensional array of beams of electromagnetic radiation).
  • integrated optics plate 505 of the imaging surface plasmon resonance apparatus 500 shown in Figure 5 there are various different arrangements of integrated optics that may be operable to receive the electromagnetic radiation output by the radiation emitting apparatus 602, split this electromagnetic radiation and output the two dimensional array of beams of electromagnetic radiation, as now discussed.
  • the integrated optics plate 604 may comprise any combination of diffusors, beam splitters or optical waveguide splitters, grating structures and/or Fresnel lenses and/or collimating tubes and/or fiber optics plates that may be arranged to spread the radiation over the output surface 608 in a desired pattern.
  • such embodiments may further comprise a pinhole array and/or a microlens array.
  • Each such pinhole in the pinhole array may act to at least partially define one of the two dimensional array of beams of electromagnetic radiation.
  • Each microlens in the microlens array may be arranged to collimate and/or direct radiation so as to at least partially define one of the two dimensional array of beams of electromagnetic radiation.
  • the imaging surface plasmon resonance apparatus 600 shown in Figure 6 also differs from the imaging surface plasmon resonance apparatus 500 shown in Figure 5 in that both the radiation emitting apparatus 602 and the detector 108 are mounted directly onto a common printed circuit board 610.
  • the radiation emitting apparatus 502 is mounted on a common printed circuit board 510 via a support 512 (for example another PCB) and a contact 514 the radiation emitting apparatus 602 of the imaging surface plasmon resonance apparatus 600 shown in Figure 6 is mounted directly on the common printed circuit board 610.
  • a support 512 for example another PCB
  • the detector 108 is mounted on a common printed circuit board 510 via a support 516 (for example another PCB) and a contact 518 the detector 108 of the imaging surface plasmon resonance apparatus 600 shown in Figure 6 is mounted directly on the common printed circuit board 610.
  • a support 516 for example another PCB
  • the support 520 which is provided with one or more sensors operable to determine one or more ambient conditions is generally as described above with reference to Figure 5 although it is connected directly to the common printed circuit board 610 via the contact 522 (for example one or more soldered contacts).
  • this arrangement may therefore reduce the complexity, assembly time and cost of the imaging surface plasmon resonance apparatus 600 shown in Figure 6 (for example relative to the imaging surface plasmon resonance apparatus 500 shown in Figure 5).
  • the imaging surface plasmon resonance apparatus 100 shown in Figure 1 has a limited dynamic range within which it can determine a concentration of target molecules.
  • the radiation source 104 is operable to produce a plurality of two dimensional arrays of beams of electromagnetic radiation.
  • the beams of electromagnetic radiation in each two dimensional array of beams of electromagnetic radiation are generally mutually parallel and beams of electromagnetic radiation from different two dimensional arrays of beams of electromagnetic radiation are not parallel.
  • each of the plurality of two dimensional arrays of beams of electromagnetic radiation can be an n x m array of parallel beams of electromagnetic radiation.
  • the radiation source 104 is operable to produce three two dimensional arrays of beams of electromagnetic radiation. It will be appreciated that the different two dimensional arrays of beams of electromagnetic radiation may be spatially separate or overlapping.
  • each different receptor is applied to three different receptor sites. Therefore, for a fixed number of receptor sites 200 the number of different receptors that can be multiplexed by the imaging surface plasmon resonance apparatus is reduced by a factor of 3.
  • each different receptor site receives a beam of electromagnetic radiation from a different one of the three two-dimensional arrays of beams of electromagnetic radiation. In turn, the reflection of each of these three beams of electromagnetic radiation is received by a different sensing element of the detector 108.
  • Figure 7 shows the same example resonance curve 300 for the intensity of the reflected radiation of one of the two dimensional array of beams of electromagnetic radiation as a function of the angle of incidence that beam of electromagnetic radiation as is shown in Figure 3.
  • concentration of the specific target molecule (or analyte) that is bound to the receptor at the receptor site 200 corresponding to a particular beam of electromagnetic radiation varies, resonance curve 300 will also vary.
  • the resonance curve 300 may move to the left or right such that the angle at which the minimum 302 of the resonance curve 300 occurs varies.
  • embodiments of the imaging surface plasmon resonance apparatus 100, 500, 600 wherein the radiation source 104 is operable to produce three two dimensional arrays of beams of electromagnetic radiation use an individual beam of radiation (from the radiation source 104) for each receptor site 200 that has a fixed angle of incidence.
  • each type of receptor is probed using three different (discrete) angles of incidence.
  • the dynamic range of the typical detector 108 for such an embodiment is illustrated in Figure 7 as three rectangles 304, 700 702.
  • Each of the three rectangles 304, 700 702 has a non-zero width in the direction of the axis for the angle of incidence for a number of reasons, as discussed with reference to Figure 3.
  • the three rectangles 304, 700 702 are centered at different angles of incidence, each one corresponding to an angle of incidence of a different one of the three two dimensional arrays of beams of electromagnetic radiation.
  • the different angles of incidence of a different one of the three two dimensional arrays of beams of electromagnetic radiation may be selected, bearing in mind the non-zero width in the direction of the axis for the angle of incidence of each of the three rectangles 304, 700702 such that the three rectangles 304, 700702 overlap.
  • the resonance curve 300 can now move by of the order of 0.5° and still be within the dynamic range of one of the three detectors that is monitoring any given type of receptor. Even for embodiments wherein the radiation source 104 is operable to produce a plurality of two dimensional arrays of beams of electromagnetic radiation a range of angles of incidence for all of the plurality of two dimensional arrays of beams of electromagnetic radiation may be less than 1°.
  • the radiation source 104 of the imaging surface plasmon resonance apparatus may be provided with a microlens array, the microlenses arranged to direct each different two dimensional array of beams of electromagnetic radiation into the prism 102 at slightly different angles. For example, this can be done by slightly displacing each micro-lens with respect to the centre of each beam of electromagnetic radiation.
  • FIG 8 is a schematic illustration of another imaging surface plasmon resonance apparatus 800 according to the present disclosure.
  • the imaging surface plasmon resonance apparatus 800 shown in Figure 8 shares many features in common with the imaging surface plasmon resonance apparatus 500 shown in Figure 5. Such features share common reference numerals and will not be described further here unless a feature of the imaging surface plasmon resonance apparatus 800 shown in Figure 8 differs from the corresponding feature of the imaging surface plasmon resonance apparatus 500 shown in Figure 5.
  • imaging surface plasmon resonance apparatus 800 shown in Figure 8 The only differences between the imaging surface plasmon resonance apparatus 800 shown in Figure 8 and the imaging surface plasmon resonance apparatus 500 shown in Figure 5 is that the radiation source 104 is provided with an array of microlenses 802, as discussed above.
  • the surface plasmon resonance condition is dependent on the wavelength of the incident electromagnetic radiation (generated by the radiation source 104).
  • Figure 9 shows some example resonance curves 900, 902, 904, 906 for the intensity of the reflected radiation of one of the two dimensional array of beams of electromagnetic radiation as a function of the angle of incidence that beam of electromagnetic radiation for four different wavelengths.
  • Figure 9 shows: an example resonance curve 900 for a wavelength of 532 nm; an example resonance curve 902 for a wavelength of 632 nm; an example resonance curve 904 for a wavelength of 850 nm; and an example resonance curve 906 for a wavelength of 845 nm.
  • the radiation source 104 is operable to produce a plurality of two dimensional arrays of beams of electromagnetic radiation, wherein the beams of electromagnetic radiation in each two dimensional array of beams of electromagnetic radiation have substantially the same wavelength and beams of electromagnetic radiation from different two dimensional arrays of beams of electromagnetic radiation have different wavelengths.
  • a radiation source 104 may have a plurality of different radiation emitting apparatus 502 (for example one for each different wavelength).
  • the radiation source 104 may have a tunable wavelength.
  • the radiation source 104 may be operable to produce electromagnetic radiation having a wavelength from a range of different selectable wavelengths.
  • Embodiments of the present disclosure can be employed in many different applications including any optical system or imaging system, for example, in the cellular telephone (mobile telephone) and other industries.
  • USB universal serial bus

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Abstract

Appareil de résonance plasmonique de surface d'imagerie comprenant : un prisme ; une source de rayonnement ; une couche de métal ; et un détecteur. La source de rayonnement peut servir à produire un réseau bidimensionnel de faisceaux de rayonnement électromagnétique, et est conçue de telle sorte que chacun dudit réseau bidimensionnel de faisceaux de rayonnement électromagnétique est couplé dans le prisme et est incident sur une région différente parmi une pluralité de régions sur une surface du prisme. Les faisceaux de rayonnement électromagnétique dans le réseau bidimensionnel de faisceaux de rayonnement électromagnétique peuvent être généralement parallèles entre eux. La couche de métal est disposée sur ou de manière adjacente à la surface du prisme à proximité de chacune de la pluralité de régions sur la surface du prisme. La couche de métal peut comprendre un réseau bidimensionnel de sites récepteurs permettant de supporter un récepteur, chaque site récepteur étant disposé sur une surface de la couche de métal qui est distale par rapport au prisme et adjacente à l'une de la pluralité de régions sur la surface du prisme. Le détecteur est conçu pour recevoir une partie de chacun de la pluralité de faisceaux de rayonnement électromagnétique qui est réfléchie par l'interface entre le prisme et la couche de métal, et peut servir à déterminer une intensité de ladite partie de chacun de la pluralité de faisceaux de rayonnement électromagnétique.
PCT/EP2021/067934 2020-06-30 2021-06-30 Appareil de résonance plasmonique de surface d'imagerie Ceased WO2022002992A1 (fr)

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