EP2183573A1 - Sensor array for spr-based detection. - Google Patents

Sensor array for spr-based detection.

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Publication number
EP2183573A1
EP2183573A1 EP08789471A EP08789471A EP2183573A1 EP 2183573 A1 EP2183573 A1 EP 2183573A1 EP 08789471 A EP08789471 A EP 08789471A EP 08789471 A EP08789471 A EP 08789471A EP 2183573 A1 EP2183573 A1 EP 2183573A1
Authority
EP
European Patent Office
Prior art keywords
sensor array
nano
sized particles
carrier substrate
radiation
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP08789471A
Other languages
German (de)
French (fr)
Inventor
Otto L. Muskens
Jaime Gomez Rivas
Erik M. H. P. Van Dijk
Derk J.W. Klunder
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Stichting Imec Nederland
Original Assignee
Koninklijke Philips Electronics NV
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Koninklijke Philips Electronics NV filed Critical Koninklijke Philips Electronics NV
Priority to EP08789471A priority Critical patent/EP2183573A1/en
Publication of EP2183573A1 publication Critical patent/EP2183573A1/en
Withdrawn legal-status Critical Current

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Classifications

    • 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
    • G01N21/554—Attenuated total reflection and using surface plasmons detecting the surface plasmon resonance of nanostructured metals, e.g. localised surface plasmon resonance
    • 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
    • G01N2021/258—Surface plasmon spectroscopy, e.g. micro- or nanoparticles in suspension

Definitions

  • the invention relates to a sensor array for detecting the presence of a target, and in particular to a sensor array where a target is detected based on a detection of a surface plasmon resonance (SPR). Moreover, the invention relates to an optical detection system comprising a sensor array, and to a method for detecting the presence of a target on a sensor array.
  • SPR surface plasmon resonance
  • Bio-molecules Detection methods for particular biological molecules (bio-molecules) are manifold and several different approaches are presently available to the skilled person.
  • low concentrations of a bio-molecule (the target) in a liquid analyte mixture are detected by means of detection of Surface Plasmon Resonances (SPR).
  • SPR Surface Plasmon Resonances
  • incident light is coupled into a sensor surface.
  • a specific wavelength or angle may be needed before absorption from surface plasmons occurs, resulting in an attenuation of the scattered light.
  • no or fewer requirement may be present in order to excite surface plasmons.
  • single clear resonances are typically observed.
  • Metal nano-sized particles exhibit characteristic scattering and absorption peaks in the optical spectrum from surface plasmon absorption. Recently it has been found that single nano-sized particles may detect the presence of only a few hundred molecules. Sensor surfaces incorporating nanoparticulate metal may therefore be used as sensitive bio- sensors.
  • the sensor chip comprises a layer-shaped base body, which has a plurality of fine holes formed in a surface, and fine metal particles, each of which is loaded in one of the fine holes of the base body.
  • the sensor chip constitutes a sensor utilizing localized plasmon resonance for detecting a specific substance with a high sensitivity.
  • it is described to shine white light onto the sensor chip and spectrophotometrically detect the shift of the resonance peak wavelength.
  • the use of broadband sources and spectroscopic detection are complicated and expensive.
  • it is disclosed to shine monochromatic light onto the sensor chip a change in light intensity accompanying a change in scattering and absorption of the measuring light is thereby detected.
  • only an indirect measurement of the shift of the resonance peak wavelength is thereby made.
  • the present invention seeks to provide an improved sensor array.
  • the invention alleviates, mitigates or eliminates one or more of the above, or other, disadvantages singly or in any combination.
  • a sensor array for detecting the presence of a target comprising:
  • the surface plasmon resonance (SPR) for each of the nano-sized particles is correlated to a structural parameter of the nano-sized particles or group of nano-sized particles; wherein for the plurality of nano-sized particles, the structural parameter and thereby the surface plasmon resonance is varied in a pre-defined way in at least a first area of the carrier substrate, so that the target is detected based on detecting intensity variations in radiation resulting from the sensor array, the intensity variations being correlated to the pre-defined variation in the structural parameter.
  • the target may be a molecular species, such as bio-molecules.
  • the target may be any target capable of changing the local refractive index or by other means shift the SPR peak of the nano-sized particles.
  • the target may be any binding complex where a binding to the nano-particles results in an SPR shift, e.g. due to a change in the local refractive index.
  • the target may be detected from a concentration change of a gas or liquid, or other change, such that the local refractive index changes.
  • the target in a situation of use of the sensor array, is detected by irradiating the sensor array with a beam of radiation and subsequently detecting the resulting scattered radiation.
  • the radiation is typically electromagnetic radiation in the optical range, however the radiation may also be in the infrared or ultraviolet range.
  • the invention is particularly, but not exclusively advantageous in that a SPR sensor array is provided which enables the detection of SPR peaks by use of monochromatic light and single-wavelength detection. Thus expensive broadband radiation sources and spectroscopic detection is avoided.
  • the invention is based on the insight that in an array of structurally varying supported nano-sized particles, the position of each resonance peak is shifted in accordance with the structural variation of the nano-sized particles. For supported nano-sized particles, the spectral shifts that are associated with a structural variation are relative large.
  • an array in accordance with the present invention is illuminated with a single wavelength, the scattering intensity from the different particles varies in dependence upon how well the incident wavelength matches the plasmon resonance of the nano-sized particles.
  • spectroscopic information can nevertheless be provided.
  • the spectroscopic information is however extracted by analysis of the geometrical variations in the intensity of the scattering radiation from the sensor array, not by analysis of the spectroscopic properties of the scattered radiation.
  • the nano-sized particles are metal particles. It is advantageous to use metal particles, since metal nano-sized particles often possess clear and distinct SPR peaks. Moreover, metal particles are suitable for binding of receptor molecules thereby enabling functionalization of the nano-sized particles.
  • the nano-sized particles are functionalized by chemical receptors. It is an advantage to functionalize the particles since a selective bio sensor may thereby be provided. Moreover, upon binding of the target the SPR of the particles will shift resulting in changes in the relative scattering intensity, thereby enabling to read-out when a target molecule is captured by a receptor.
  • the structural parameter may be selected as any structural parameter which can be correlated to a shift in the SPR peak position.
  • the structural parameter is a parameter selected from the group of: size, geometric dimension, orientation, shape, aspect ratio or arrangement. It is an advantage that a large number of structural parameters can be applied, since it gives rise to a large number of parameters that can be used when designing a sensor array for a given purpose. In general may a single structural parameter, one or more parameters, or a combination of multiple parameters be varied.
  • the plurality of nano-sized particles is defined by a lithographic technique.
  • Lithographic techniques can be provided which enables both serial fabrication if small batch sizes are desired and parallel fabrication if large batch sizes are desired.
  • At least part of the combined system of carrier substrate and plurality of nano-sized particles is covered by a cover layer.
  • a cover layer By providing a cover layer on at least a part of the sensor array, a sensor array with an integrated reference array may be provided. A shift of the resonance position which is not related to an interaction with a target, e.g. which relates to a thermally induced shift, may thereby be calibrated by the reference array.
  • the sensor array comprises a plurality of areas, wherein each area comprises a plurality of nano-sized particles with a pre-defined variation of the structural parameter.
  • an optical detection system for detecting a target is provided.
  • the optical detection system is provided so that a target may be detected on a sensor array in accordance with the present invention.
  • a method for detecting the presence of a target on a sensor array in accordance with the present invention comprising:
  • the excitation radiation being capable of inducing a surface plasmon resonance (SPR) on the sensor array; - detecting the resulting radiation with a radiation detector after interaction with the sensor array; wherein the target is detected based on detecting intensity variations in the resulting radiation, the intensity variations being correlated to the predefined variation in the structural parameter.
  • SPR surface plasmon resonance
  • FIG.l schematically illustrates a general overview of an optical detection system in accordance with embodiments of the present invention
  • FIG.2 is a schematic illustration of intensity variation arising from shining light onto nanoparticles of different sizes
  • FIGS.3 A to 3E illustrate an embodiment of a sensor array as well as examples of nanoparticles
  • FIGS.4A to 4C show scattering images obtained from 'clean' particles and particles covered with a layer of sol-gel silica;
  • FIG.5 illustrates calculated optical extinction spectra for a nanorod particle;
  • FIG.6 illustrates an embodiment of the sensor array applied as a bio-sensor;
  • FIG.7 illustrates a sensor array having an area covered by a cover layer;
  • FIG.8 schematically illustrates a sensor array comprising a plurality of areas;
  • FIG.9 illustrates an embodiment of an optical detection system for detecting a target;
  • FIG.10 illustrates steps of an embodiment of a method in accordance with the present invention.
  • FIG.l schematically illustrates a general overview of an optical detection system in accordance with embodiments of the present invention.
  • a radiation source 1 emits excitation radiation 2 onto a sensor surface 3.
  • the excitation radiation excites surface plasmon on the sensor, and the scattered radiation 4 is detected by a radiation detector 5 in order to analyse the interaction between the excitation radiation and the sensor.
  • nano-sized particles hereafter nanoparticles
  • nanoparticles supported on a carrier substrate possess a high cross-section for surface plasmon excitation, in general resulting in large distinct SPR resonance peaks.
  • FIG.2 schematically illustrates the intensity, I, of three SPR peaks 21 as a function of the wavelength ⁇ for nanoparticles 20 of three different sizes.
  • the position of the SPR peak also shifts.
  • the intensity of the scattered light from plasmon excitation decreases, I 0 , I 1 , h, since the surface plasmon excitation cross-sections decrease at the wavelength ⁇ o.
  • FIG.3A schematically illustrate a sensor array 30.
  • the sensor array comprising a carrier substrate 31, and a plurality of nanoparticles (nano-sized particles) 32 disposed on the carrier substrate.
  • a structural parameter of the nanoparticles, or a group of nanoparticles is correlated to an associated surface plasmon resonance (SPR).
  • SPR surface plasmon resonance
  • the structural parameter and thereby the surface plasmon resonance is varied in a pre-defined way in at least a first area of the carrier substrate.
  • the variation of the structural parameter is schematically illustrated on FIG.3A by a variation in the length 34 of the nanoparticles along the vertical direction 33.
  • the variation of the structural parameter in a pre-defined way include, but are not limited to, a structural variation along a predefined direction, for example, along the vertical direction 33 or any other direction 35 in the surface plane of the carrier substrate.
  • FIGS.3B to 3E show examples of nanoparticles and groups of nanoparticles.
  • the Figures are scanning electron microscopy (SEM) images of gold nanoparticles supported on silica.
  • the nanoparticles have been fabricated using e-beam lithography.
  • FIGS.3B and 3C illustrate nanorods with a length (L), a height (H) and a thickness (out of the plane).
  • L length
  • H height
  • a thickness out of the plane.
  • Each of the length, height and thickness may be used as the structural parameter and varied in a pre-defined way.
  • the length may range between 10 nm and 1000 nm
  • the height may range between 10 nm and 1000 nm
  • the thickness may range between 10 nm and 1000 nm.
  • FIG.3D illustrates a group of substantially identical nanoparticles.
  • the arrangement of the group of nanoparticles may be used as the structural parameter and varied in a pre-defined way.
  • a pre-defined spacing, or inter-particle gaps, e.g. Sl or S2 between the nanoparticles may be varied in a predefined way.
  • FIG.3E illustrates a group of substantially identical nanoparticles, in the form of a dimer of opposing triangles (a 'bow tie').
  • a spacing, e.g. the inter-particle gap S3, between the nanoparticles may be varied in a predefined way.
  • the inter-particle gap may be varied in the range between 5 nm and 150 nm.
  • a single structural parameter or a combination of multiple parameters may be varied to shift the plasmon resonance.
  • the structural parameter may be a parameter selected from the group of: size, geometric dimension, orientation, shape, aspect ratio or arrangement.
  • Other structural parameter may also be envisioned and used by the skilled person.
  • the size of the nanoparticles may be in the range of 10 nm to 1000 nm in a plane parallel to the plane of the carrier substrate. That is the height or length for a rectangular particle, the diameter for a particle with circular cross-section, major and minor axes for a particle with elliptic cross-section, the base of a triangle, etc.
  • the size of the nanoparticles may in a plane perpendicular to the plane of the carrier substrate be in the range of 10 nm to 1000 nm, for example the thickness at the thickest area of the particle.
  • the geometric dimension may relate to a gradual variation from a substantial 2D particle to a 3D particle.
  • the orientation may relate to a gradual rotation around a symmetry axis.
  • the shape may relate to a gradual shape change.
  • the aspect ratio may relate to a gradual change in the height-to-width ratio, and the arrangement may relate to a gradual change of the arrangement of a group of nanoparticles, e.g. an increasing inter-particle distance between particles.
  • a range would be selected to match an expected or known wavelength, or vice versa.
  • a lower limit or a higher limit may be selected at any value within the range, such as at 25 nm, 50 nm, 75 nm, 100 nm, 150 nm, 200 nm, 250 nm, 300 nm, 400 nm, 500 nm, 600 nm, 700 nm, 800 nm, 900 nm, or other values within a range, in accordance with a desired pre-defined variation.
  • FIG.4 illustrates embodiments of sensor arrays.
  • FIGS.4A and 4B are dark field scattering microscopy images of gold particles supported on a silica carrier obtained at a single wavelength of 730 nm.
  • the shape of the individual nanoparticles is schematically illustrated by the insert denoted by 43.
  • the individual nanoparticles are dimers of nanorods where the length, Ll, varies along the vertical direction 41 and the inter- particle gap, Gl, varies along the horizontal direction 42.
  • the length of the nanoparticles are varied from 70 nm to 150 nm, and the inter-particle gaps are varied from 20 to 150 nm.
  • FIG.4A shows a scattering image obtained from a sensor array 46 comprising 'clean' particles
  • FIG.4B is obtained from a sensor array 47 with the nanoparticles of FIG.4A, but are covered with a 10 nm layer of sol-gel silica.
  • the intensity varies at varying particle size, i.e. decreases as the position of the SPR for a nanoparticle of a given size moves away from the excitation wavelength.
  • the SPR peak shifts upon interaction with a target along the direction 41 extending from the top to the middle, corresponding to a shift of more than 100 nm.
  • a clear effect arising from the horizontal variation of the inter-particle gap is not seen in the images, even though some intensity variation can be observed.
  • FIG.4C illustrates a line scan obtained along the vertical direction as indicated by the reference numeral 44.
  • the vertical axis represents intensity measured in counts (from 0 to 1200 counts).
  • the horizontal is the position, ranging from 0 to 20 ⁇ m.
  • reference numeral 45 a peak in the intensity is observed.
  • the shift of the surface plasmon can be measured at a single wavelength by the relative change of the scattered intensity between particles with a varied structural parameter. From image analysis, e.g. by means of software, not only the resonance shift can be found, but the entire resonance spectra as well as difference spectra can be extracted.
  • optical extinction spectra have been calculated for different particle sizes and for different local refractive indices.
  • FIG.5 illustrates calculated optical extinction spectra for a nanorod particle of dimension 140x70x20 nm 3 for local refractive indices in the range of 1.35 to 1.5. As can be seen the position of the SPR also shift for various values of the local refractive index.
  • the carrier substrate may be any substrate suitable for supporting nanoparticles.
  • the carrier substrate may be a substrate suitable for use with a given lithographic techniques.
  • the carrier substrate may be, but is not limited to, a substrate of silicon, silica or polymer.
  • the nature of the carrier substrate may influence the position of the resonance peaks, and the substrate may be selected in accordance with this aspect.
  • the nanoparticles may be of any type of nanoparticle where the surface plasmon resonance (SPR) can be correlated to a structural parameter. Examples include, but are not limited, to silicon-based substrates and metal nanoparticles, such as a nanoparticle selected from the group of Au, Ag, Pt, Pd, Al, Cr, Ti, Cu, Ru, Rh, or any combination or alloying of such or other metals. Additionally, vertical layered nanoparticles, such as multilayer structures of the metal-insulator-metal type may be applied.
  • the sensor array may be fabricated by using a lithographic technique, including but not limited to e-beam lithography, optical lithography, focused ion-beam lithography and nano-imprint lithography.
  • a lithographic technique including but not limited to e-beam lithography, optical lithography, focused ion-beam lithography and nano-imprint lithography.
  • improved techniques including techniques based on self-assembly or other bottom-up techniques as well as next-generation lithography, for example high-index immersion lithography, extreme ultraviolet lithography (EUV-lithography), X-ray lithography can be applied as they become available.
  • a serial lithography technique such as e-beam lithography, may advantageously be applied for small-scale production since specific nanoparticle shapes can be produced.
  • a parallel lithography technique, such as nano-imprint lithography may advantageously be applied for large-scale production, since it requires the production of a stamp.
  • FIG.6 illustrates an embodiment of the sensor array applied as a bio-sensor.
  • a sensor array in accordance with the broadest aspect of the present invention may be applied as a bio-sensor.
  • Noble metals, and especially gold bind many bio-molecules, and the binding the bio-molecules would induce a shift in the SPR that could be detected.
  • the nano-sized particles are functionalized by chemical receptors, or receptor molecules.
  • Receptor molecules as known in the art, are capable of selectively binding specific molecules, such as macro-molecules, bio- molecules, DNA, RNA, antigens, nucleic acids, amino acids, proteins, cells, bacteria, virus, fungus, micro tubili, various drug molecules, etc.
  • FIG.6 illustrates aspects relating to detection of bio-molecules in accordance with application of the present invention.
  • the plurality of nanoparticles here illustrated as a cross-section of a single nanoparticle 60, are supported on a carrier substrate 61.
  • the nanoparticles are functionalized by receptor molecules 62, here illustrated as a layer of separate receptor species, this is for illustrative purposes only.
  • the receptor molecules may be any type of receptors within the scope of the invention.
  • the receptor molecules may be exposed to a molecular species 63 which they bind, resulting in modified molecular binding complexes 64 which bind to the nanoparticles.
  • the resulting images 67, 68 on sensor arrays in accordance with embodiment of the present invention are schematically illustrated by a shift from a first position 69 to a second position 600.
  • Thermal drift may induce refractive index changes, which can influence the position of the SPR. This can be accounted for by covering part of an array with a cover layer or spacer to prevent influence of molecules.
  • the refractive index of the cover layer may be adapted to match the refractive index of a medium on top of the nanoparticles.
  • FIG.7 illustrates a sensor array 70 having a free area 71 to be exposed to a molecular species for detection and a covered area 72 for calibration.
  • FIG.8 schematically illustrates a sensor array comprising a plurality of areas 80-83.
  • all areas are identical, in that these areas comprise the same number of nanoparticles and have the same variation of the structural parameter.
  • a sensor array comprising a number of different areas may be provided.
  • a sensor array comprising a plurality of areas may e.g. be used as a bio-array or micro-array.
  • different area may be functionalized with different chemical receptors, alternatively the entire sensor array may be functionalized with the same chemical receptors, and different areas may be exposed to different target molecules.
  • the different array on the sensor array may e.g. be functionalized, or exposed to a target solution, by application of drop deposition from pulsejets, or by other suitable means.
  • a sensor array comprising a plurality of areas may be applied in connection with a bio- assay.
  • the number of spots on a bio-array may vary from around 1 to 1000 pr. mm , and even higher, e.g. up to 10 6 spots pr. mm 2 .
  • FIG.9 illustrates an embodiment of an optical detection system for detecting a target.
  • the optical system comprises a sensor array 90 in accordance with embodiments of the present invention.
  • a radiation source 91 is present, typically in the form of a monochromatic laser source, and a detector 92 for detecting the scattered light after interaction with the sensor array.
  • the optical system may comprise optical elements 93, 94, such as filters, polarizers, beam splitters, etc., placed in the beam path before 93 the sensor array and/or after 94 the sensor array.
  • a sample handling system 95 such as a liquid flow cell or other means for exposing a gaseous or liquid solution to the sensor surface, may be present.
  • the detection system may comprise or be connected to a computer system 96, for control of the detection system and for processing and possible displaying the obtained detection results.
  • the radiation source 91 may be a tuneable laser source for emitting monochromatic radiation at a number of selectable wavelengths. The light may illuminate the whole array or may be focus sed onto a spot that can be scanned through the sensor array.
  • the detector may be a photodetector, such as a spatially resolved detector e.g. a CDD-based detector. A non-spatially resolved detector, such as a photo- diode, may also be applied.
  • the optical detection system may also comprise or be connected to additional sample handling units, such as a unit for contacting the substrate with a target. The optical detection system may be automated or semi- automated.
  • the angle of incidence may in general range from perpendicularly incident from the top to perpendicularly incident from the bottom, as long as it is possible to excite surface plasmons of the supported nanoparticles.
  • the radiation may be polarized, and especially may be a variation between an angle of polarization and an orientation or arrangement of the nanoparticles be applied in order to detect intensity variations.
  • a large number of different types of measurements may be made by a sensor array in accordance with embodiments of the present invention.
  • a measurement may comprise, but are not limited to steps as illustrated in FIG.10.
  • the sensor array is exposed to the target; 101: the sensor array is exposed to excitation radiation capable of inducing a surface plasmon resonance (SPR) on the sensor array; 102: the resulting radiation is detected with a radiation detector after interaction with the sensor array;
  • SPR surface plasmon resonance
  • 103 detecting intensity variations in the resulting radiation, and correlating the intensity variation to the pre-defined variation in the structural parameter in order to detect the presence of the target.
  • parameters as particle size, predefined structural parameter, excitation wavelength, etc. are disclosed in connection with description of different embodiment. It is to be understood a large number of variations with in the scope of the invention is possible for the skilled person. Moreover, in a measurement, a number of parameters may need to be correlated. For example, a sensor array with a specific type of structural variation may be selected in accordance with a desired target to be detected. The excitation wavelength may be correlated with nanoparticles, or vice versa, in order to be able to detect an SPR shift. Also a specific carrier substrate may be selected, etc.

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Abstract

The invention relates to a sensor array for detecting the presence of a target, where a target is detected based on a detection of a surface plasmon resonance (SPR). The sensor array (30) comprises a carrier substrate (31), and a plurality of nano-sized particles (32) disposed on the carrier substrate. The surface plasmon resonance (SPR) for each of the nano-sized particles is correlated to a structural parameter of the nano-sized particles or group of nano-sized particles. The structural parameter and thereby the surface plasmon resonance is varied in a pre-defined way in at least a first area of the carrier substrate. The target is detected based on detecting intensity variations in the radiation resulting from the sensor array, the intensity variations being correlated to the pre-defined variation in the structural parameter. In embodiments, the sensor array may be a bio-sensor for the detection of bio-molecules.

Description

SENSOR ARRAY FOR SPR-BASED DETECTION
FIELD OF THE INVENTION
The invention relates to a sensor array for detecting the presence of a target, and in particular to a sensor array where a target is detected based on a detection of a surface plasmon resonance (SPR). Moreover, the invention relates to an optical detection system comprising a sensor array, and to a method for detecting the presence of a target on a sensor array.
BACKGROUND OF THE INVENTION
Detection methods for particular biological molecules (bio-molecules) are manifold and several different approaches are presently available to the skilled person. In one method low concentrations of a bio-molecule (the target) in a liquid analyte mixture are detected by means of detection of Surface Plasmon Resonances (SPR).
In an SPR method, incident light is coupled into a sensor surface. For metal surfaces, a specific wavelength or angle may be needed before absorption from surface plasmons occurs, resulting in an attenuation of the scattered light. However, for nanoparticulate systems, no or fewer requirement may be present in order to excite surface plasmons. Moreover, for nanoparticulate systems, single clear resonances are typically observed.
Metal nano-sized particles exhibit characteristic scattering and absorption peaks in the optical spectrum from surface plasmon absorption. Recently it has been found that single nano-sized particles may detect the presence of only a few hundred molecules. Sensor surfaces incorporating nanoparticulate metal may therefore be used as sensitive bio- sensors.
In the published US patent application US 2004/0183176 a sensor chip is disclosed. The sensor chip comprises a layer-shaped base body, which has a plurality of fine holes formed in a surface, and fine metal particles, each of which is loaded in one of the fine holes of the base body. The sensor chip constitutes a sensor utilizing localized plasmon resonance for detecting a specific substance with a high sensitivity. In the disclosure, it is described to shine white light onto the sensor chip and spectrophotometrically detect the shift of the resonance peak wavelength. However, the use of broadband sources and spectroscopic detection are complicated and expensive. Alternatively, it is disclosed to shine monochromatic light onto the sensor chip, a change in light intensity accompanying a change in scattering and absorption of the measuring light is thereby detected. However, only an indirect measurement of the shift of the resonance peak wavelength is thereby made.
The inventors of the present invention have appreciated that an improved way of performing SPR measurements is of benefit, and has in consequence devised the present invention.
SUMMARY OF THE INVENTION
The present invention seeks to provide an improved sensor array. Preferably, the invention alleviates, mitigates or eliminates one or more of the above, or other, disadvantages singly or in any combination.
According to a first aspect of the present invention there is provided, a sensor array for detecting the presence of a target, the sensor array comprising:
- a carrier substrate;
- a plurality of nano-sized particles disposed on the carrier substrate, where the surface plasmon resonance (SPR) for each of the nano-sized particles is correlated to a structural parameter of the nano-sized particles or group of nano-sized particles; wherein for the plurality of nano-sized particles, the structural parameter and thereby the surface plasmon resonance is varied in a pre-defined way in at least a first area of the carrier substrate, so that the target is detected based on detecting intensity variations in radiation resulting from the sensor array, the intensity variations being correlated to the pre-defined variation in the structural parameter. The target may be a molecular species, such as bio-molecules. In general, however, the target may be any target capable of changing the local refractive index or by other means shift the SPR peak of the nano-sized particles. For example, the target may be any binding complex where a binding to the nano-particles results in an SPR shift, e.g. due to a change in the local refractive index. In a general example, the target may be detected from a concentration change of a gas or liquid, or other change, such that the local refractive index changes.
In embodiments, in a situation of use of the sensor array, the target is detected by irradiating the sensor array with a beam of radiation and subsequently detecting the resulting scattered radiation. The radiation is typically electromagnetic radiation in the optical range, however the radiation may also be in the infrared or ultraviolet range.
The invention is particularly, but not exclusively advantageous in that a SPR sensor array is provided which enables the detection of SPR peaks by use of monochromatic light and single-wavelength detection. Thus expensive broadband radiation sources and spectroscopic detection is avoided. The invention is based on the insight that in an array of structurally varying supported nano-sized particles, the position of each resonance peak is shifted in accordance with the structural variation of the nano-sized particles. For supported nano-sized particles, the spectral shifts that are associated with a structural variation are relative large. When an array in accordance with the present invention is illuminated with a single wavelength, the scattering intensity from the different particles varies in dependence upon how well the incident wavelength matches the plasmon resonance of the nano-sized particles. As an advantageous result, even though single-wavelength detection is applied, spectroscopic information can nevertheless be provided. The spectroscopic information is however extracted by analysis of the geometrical variations in the intensity of the scattering radiation from the sensor array, not by analysis of the spectroscopic properties of the scattered radiation.
In an advantageous embodiment, the nano-sized particles are metal particles. It is advantageous to use metal particles, since metal nano-sized particles often possess clear and distinct SPR peaks. Moreover, metal particles are suitable for binding of receptor molecules thereby enabling functionalization of the nano-sized particles.
In an advantageous embodiment, the nano-sized particles are functionalized by chemical receptors. It is an advantage to functionalize the particles since a selective bio sensor may thereby be provided. Moreover, upon binding of the target the SPR of the particles will shift resulting in changes in the relative scattering intensity, thereby enabling to read-out when a target molecule is captured by a receptor.
The structural parameter may be selected as any structural parameter which can be correlated to a shift in the SPR peak position. In advantageous embodiments, the structural parameter is a parameter selected from the group of: size, geometric dimension, orientation, shape, aspect ratio or arrangement. It is an advantage that a large number of structural parameters can be applied, since it gives rise to a large number of parameters that can be used when designing a sensor array for a given purpose. In general may a single structural parameter, one or more parameters, or a combination of multiple parameters be varied.
In an advantageous embodiment, the plurality of nano-sized particles is defined by a lithographic technique. Lithographic techniques can be provided which enables both serial fabrication if small batch sizes are desired and parallel fabrication if large batch sizes are desired.
In an advantageous embodiment, at least part of the combined system of carrier substrate and plurality of nano-sized particles is covered by a cover layer. By providing a cover layer on at least a part of the sensor array, a sensor array with an integrated reference array may be provided. A shift of the resonance position which is not related to an interaction with a target, e.g. which relates to a thermally induced shift, may thereby be calibrated by the reference array.
In an advantageous embodiment, the sensor array comprises a plurality of areas, wherein each area comprises a plurality of nano-sized particles with a pre-defined variation of the structural parameter. By providing a plurality of areas, either with same or different pre-defined variation, a micro-array suitable for use in a bio-assay may be provided.
In a second aspect of the present invention, an optical detection system for detecting a target is provided. The optical detection system is provided so that a target may be detected on a sensor array in accordance with the present invention.
In a third aspect of the present invention, a method for detecting the presence of a target on a sensor array in accordance with the present invention is provided, the method comprising:
- exposing the sensor array to the target;
- exposing the sensor array to excitation radiation, the excitation radiation being capable of inducing a surface plasmon resonance (SPR) on the sensor array; - detecting the resulting radiation with a radiation detector after interaction with the sensor array; wherein the target is detected based on detecting intensity variations in the resulting radiation, the intensity variations being correlated to the predefined variation in the structural parameter.
In general the various aspects of the invention may be combined and coupled in any way possible within the scope of the invention. These and other aspects, features and/or advantages of the invention will be apparent from and elucidated with reference to the embodiments described hereinafter.
BRIEF DESCRIPTION OF THE DRAWINGS
Embodiments of the invention will be described, by way of example only, with reference to the drawings, in which
FIG.l schematically illustrates a general overview of an optical detection system in accordance with embodiments of the present invention;
FIG.2 is a schematic illustration of intensity variation arising from shining light onto nanoparticles of different sizes; FIGS.3 A to 3E illustrate an embodiment of a sensor array as well as examples of nanoparticles;
FIGS.4A to 4C show scattering images obtained from 'clean' particles and particles covered with a layer of sol-gel silica; FIG.5 illustrates calculated optical extinction spectra for a nanorod particle; FIG.6 illustrates an embodiment of the sensor array applied as a bio-sensor; FIG.7 illustrates a sensor array having an area covered by a cover layer; FIG.8 schematically illustrates a sensor array comprising a plurality of areas; FIG.9 illustrates an embodiment of an optical detection system for detecting a target; FIG.10 illustrates steps of an embodiment of a method in accordance with the present invention.
DESCRIPTION OF EMBODIMENTS
FIG.l schematically illustrates a general overview of an optical detection system in accordance with embodiments of the present invention.
A radiation source 1 emits excitation radiation 2 onto a sensor surface 3. The excitation radiation excites surface plasmon on the sensor, and the scattered radiation 4 is detected by a radiation detector 5 in order to analyse the interaction between the excitation radiation and the sensor. It is known that nano-sized particles (hereafter nanoparticles) supported on a carrier substrate possess a high cross-section for surface plasmon excitation, in general resulting in large distinct SPR resonance peaks.
FIG.2 schematically illustrates the intensity, I, of three SPR peaks 21 as a function of the wavelength λ for nanoparticles 20 of three different sizes. As the size of the nanoparticles changes, the position of the SPR peak also shifts. For excitation light of a given wavelength, λo, and in the particular example, the distance between the excitation wavelength, λo, and the resonance wavelength increases for increasing particle size. As a consequence, the intensity of the scattered light from plasmon excitation decreases, I0, I1, h, since the surface plasmon excitation cross-sections decrease at the wavelength λo.
Embodiments of a sensor array as well as examples of nanoparticles are illustrated in connection with FIG.3. FIG.3A schematically illustrate a sensor array 30. The sensor array comprising a carrier substrate 31, and a plurality of nanoparticles (nano-sized particles) 32 disposed on the carrier substrate. For each of the nanoparticles a structural parameter of the nanoparticles, or a group of nanoparticles, is correlated to an associated surface plasmon resonance (SPR). Moreover, for the plurality of nanoparticles, the structural parameter and thereby the surface plasmon resonance is varied in a pre-defined way in at least a first area of the carrier substrate. The variation of the structural parameter is schematically illustrated on FIG.3A by a variation in the length 34 of the nanoparticles along the vertical direction 33. The variation of the structural parameter in a pre-defined way, include, but are not limited to, a structural variation along a predefined direction, for example, along the vertical direction 33 or any other direction 35 in the surface plane of the carrier substrate.
The FIGS.3B to 3E show examples of nanoparticles and groups of nanoparticles. The Figures are scanning electron microscopy (SEM) images of gold nanoparticles supported on silica. The nanoparticles have been fabricated using e-beam lithography. FIGS.3B and 3C illustrate nanorods with a length (L), a height (H) and a thickness (out of the plane). Each of the length, height and thickness may be used as the structural parameter and varied in a pre-defined way. The length may range between 10 nm and 1000 nm, the height may range between 10 nm and 1000 nm, and the thickness may range between 10 nm and 1000 nm. FIG.3D illustrates a group of substantially identical nanoparticles. The arrangement of the group of nanoparticles may be used as the structural parameter and varied in a pre-defined way. For example a pre-defined spacing, or inter-particle gaps, e.g. Sl or S2, between the nanoparticles may be varied in a predefined way. FIG.3E illustrates a group of substantially identical nanoparticles, in the form of a dimer of opposing triangles (a 'bow tie'). A spacing, e.g. the inter-particle gap S3, between the nanoparticles may be varied in a predefined way. For example, the inter-particle gap may be varied in the range between 5 nm and 150 nm. In general a single structural parameter or a combination of multiple parameters may be varied to shift the plasmon resonance. In general the structural parameter may be a parameter selected from the group of: size, geometric dimension, orientation, shape, aspect ratio or arrangement. Other structural parameter may also be envisioned and used by the skilled person. The size of the nanoparticles may be in the range of 10 nm to 1000 nm in a plane parallel to the plane of the carrier substrate. That is the height or length for a rectangular particle, the diameter for a particle with circular cross-section, major and minor axes for a particle with elliptic cross-section, the base of a triangle, etc. The size of the nanoparticles may in a plane perpendicular to the plane of the carrier substrate be in the range of 10 nm to 1000 nm, for example the thickness at the thickest area of the particle. The geometric dimension may relate to a gradual variation from a substantial 2D particle to a 3D particle. The orientation may relate to a gradual rotation around a symmetry axis. The shape may relate to a gradual shape change. The aspect ratio may relate to a gradual change in the height-to-width ratio, and the arrangement may relate to a gradual change of the arrangement of a group of nanoparticles, e.g. an increasing inter-particle distance between particles.
The ranges mentioned above are provided as examples of lower and upper limits for the mentioned ranges. In a specific embodiment, a range would be selected to match an expected or known wavelength, or vice versa. In general a lower limit or a higher limit may be selected at any value within the range, such as at 25 nm, 50 nm, 75 nm, 100 nm, 150 nm, 200 nm, 250 nm, 300 nm, 400 nm, 500 nm, 600 nm, 700 nm, 800 nm, 900 nm, or other values within a range, in accordance with a desired pre-defined variation.
FIG.4 illustrates embodiments of sensor arrays. FIGS.4A and 4B are dark field scattering microscopy images of gold particles supported on a silica carrier obtained at a single wavelength of 730 nm. The shape of the individual nanoparticles is schematically illustrated by the insert denoted by 43. The individual nanoparticles are dimers of nanorods where the length, Ll, varies along the vertical direction 41 and the inter- particle gap, Gl, varies along the horizontal direction 42. In FIGS.4A and 4B the length of the nanoparticles are varied from 70 nm to 150 nm, and the inter-particle gaps are varied from 20 to 150 nm. The gold nanoparticles are defined by e-beam lithography, the size of the images are 25 x 25 μm2. FIG.4A shows a scattering image obtained from a sensor array 46 comprising 'clean' particles, and FIG.4B is obtained from a sensor array 47 with the nanoparticles of FIG.4A, but are covered with a 10 nm layer of sol-gel silica. At least two effects can directly be seen on the Figures. Firstly, as schematically illustrated on FIG.2, the intensity varies at varying particle size, i.e. decreases as the position of the SPR for a nanoparticle of a given size moves away from the excitation wavelength. Secondly, as indicated by the bar denoted with reference numeral 40, the SPR peak shifts upon interaction with a target along the direction 41 extending from the top to the middle, corresponding to a shift of more than 100 nm. A clear effect arising from the horizontal variation of the inter-particle gap is not seen in the images, even though some intensity variation can be observed.
FIG.4C illustrates a line scan obtained along the vertical direction as indicated by the reference numeral 44. The vertical axis represents intensity measured in counts (from 0 to 1200 counts). The horizontal is the position, ranging from 0 to 20 μm. As denoted by reference numeral 45, a peak in the intensity is observed.
As shown in FIG.4, the shift of the surface plasmon can be measured at a single wavelength by the relative change of the scattered intensity between particles with a varied structural parameter. From image analysis, e.g. by means of software, not only the resonance shift can be found, but the entire resonance spectra as well as difference spectra can be extracted.
To further illustrate the SPR shifts with a structural parameter, optical extinction spectra have been calculated for different particle sizes and for different local refractive indices.
Table 1 presents calculated SPR wavelengths for a local refractive index of n=1.3 and resulting figure of merits for nanorods with three different lengths. It is found that the figure of merit increases with increasing particle length, associated with a strong red shift of the resonance. Table 1:
From Table 1 it can be seen that the SPR wavelength varies over a large range from visual to near infrared. It is therefore possible to design sensor arrays with a resonance wavelength in water (n=1.3) that is compatible with standard lasers used in DVD (λ^660 nm) or even in telecom (λ^l.5 μm).
FIG.5 illustrates calculated optical extinction spectra for a nanorod particle of dimension 140x70x20 nm3 for local refractive indices in the range of 1.35 to 1.5. As can be seen the position of the SPR also shift for various values of the local refractive index.
The carrier substrate may be any substrate suitable for supporting nanoparticles. The carrier substrate may be a substrate suitable for use with a given lithographic techniques. The carrier substrate may be, but is not limited to, a substrate of silicon, silica or polymer. The nature of the carrier substrate may influence the position of the resonance peaks, and the substrate may be selected in accordance with this aspect. The nanoparticles may be of any type of nanoparticle where the surface plasmon resonance (SPR) can be correlated to a structural parameter. Examples include, but are not limited, to silicon-based substrates and metal nanoparticles, such as a nanoparticle selected from the group of Au, Ag, Pt, Pd, Al, Cr, Ti, Cu, Ru, Rh, or any combination or alloying of such or other metals. Additionally, vertical layered nanoparticles, such as multilayer structures of the metal-insulator-metal type may be applied.
The sensor array may be fabricated by using a lithographic technique, including but not limited to e-beam lithography, optical lithography, focused ion-beam lithography and nano-imprint lithography. Moreover, it is envisioned by the inventors that improved techniques including techniques based on self-assembly or other bottom-up techniques as well as next-generation lithography, for example high-index immersion lithography, extreme ultraviolet lithography (EUV-lithography), X-ray lithography can be applied as they become available. A serial lithography technique, such as e-beam lithography, may advantageously be applied for small-scale production since specific nanoparticle shapes can be produced. A parallel lithography technique, such as nano-imprint lithography, may advantageously be applied for large-scale production, since it requires the production of a stamp.
FIG.6 illustrates an embodiment of the sensor array applied as a bio-sensor. In general a sensor array in accordance with the broadest aspect of the present invention may be applied as a bio-sensor. Noble metals, and especially gold bind many bio-molecules, and the binding the bio-molecules would induce a shift in the SPR that could be detected. In another type of bio-senor, the nano-sized particles are functionalized by chemical receptors, or receptor molecules. Receptor molecules, as known in the art, are capable of selectively binding specific molecules, such as macro-molecules, bio- molecules, DNA, RNA, antigens, nucleic acids, amino acids, proteins, cells, bacteria, virus, fungus, micro tubili, various drug molecules, etc.
FIG.6 illustrates aspects relating to detection of bio-molecules in accordance with application of the present invention. The plurality of nanoparticles, here illustrated as a cross-section of a single nanoparticle 60, are supported on a carrier substrate 61. The nanoparticles are functionalized by receptor molecules 62, here illustrated as a layer of separate receptor species, this is for illustrative purposes only. The receptor molecules may be any type of receptors within the scope of the invention. The receptor molecules may be exposed to a molecular species 63 which they bind, resulting in modified molecular binding complexes 64 which bind to the nanoparticles. As a result the SPR peaks shift from a first position 65 associated with the nanoparticle -receptor system to a second position 66 associated with the nanoparticle-binding complex system. The resulting images 67, 68 on sensor arrays in accordance with embodiment of the present invention are schematically illustrated by a shift from a first position 69 to a second position 600. Thermal drift may induce refractive index changes, which can influence the position of the SPR. This can be accounted for by covering part of an array with a cover layer or spacer to prevent influence of molecules. The refractive index of the cover layer may be adapted to match the refractive index of a medium on top of the nanoparticles. For water as a medium on top of the particle, Teflon has a refractive index close to water, and may therefore be applied. Shifts of the SPR position of the sensor array can then be calibrated to the shift of this reference array. FIG.7 illustrates a sensor array 70 having a free area 71 to be exposed to a molecular species for detection and a covered area 72 for calibration.
FIG.8 schematically illustrates a sensor array comprising a plurality of areas 80-83. Here all areas are identical, in that these areas comprise the same number of nanoparticles and have the same variation of the structural parameter. However, a sensor array comprising a number of different areas may be provided. A sensor array comprising a plurality of areas may e.g. be used as a bio-array or micro-array. For example, different area may be functionalized with different chemical receptors, alternatively the entire sensor array may be functionalized with the same chemical receptors, and different areas may be exposed to different target molecules. The different array on the sensor array may e.g. be functionalized, or exposed to a target solution, by application of drop deposition from pulsejets, or by other suitable means. A sensor array comprising a plurality of areas may be applied in connection with a bio- assay. The number of spots on a bio-array may vary from around 1 to 1000 pr. mm , and even higher, e.g. up to 106 spots pr. mm2.
FIG.9 illustrates an embodiment of an optical detection system for detecting a target. The optical system comprises a sensor array 90 in accordance with embodiments of the present invention. Moreover a radiation source 91 is present, typically in the form of a monochromatic laser source, and a detector 92 for detecting the scattered light after interaction with the sensor array. In addition to these elements, the optical system may comprise optical elements 93, 94, such as filters, polarizers, beam splitters, etc., placed in the beam path before 93 the sensor array and/or after 94 the sensor array. Also a sample handling system 95, such as a liquid flow cell or other means for exposing a gaseous or liquid solution to the sensor surface, may be present. Moreover, the detection system may comprise or be connected to a computer system 96, for control of the detection system and for processing and possible displaying the obtained detection results. The radiation source 91 may be a tuneable laser source for emitting monochromatic radiation at a number of selectable wavelengths. The light may illuminate the whole array or may be focus sed onto a spot that can be scanned through the sensor array. The detector may be a photodetector, such as a spatially resolved detector e.g. a CDD-based detector. A non-spatially resolved detector, such as a photo- diode, may also be applied. The optical detection system, may also comprise or be connected to additional sample handling units, such as a unit for contacting the substrate with a target. The optical detection system may be automated or semi- automated.
In FIG.9 a specific optical setup is illustrated. It is however to be understood that the invention is not limited to this setup. The angle of incidence may in general range from perpendicularly incident from the top to perpendicularly incident from the bottom, as long as it is possible to excite surface plasmons of the supported nanoparticles. Moreover, the radiation may be polarized, and especially may be a variation between an angle of polarization and an orientation or arrangement of the nanoparticles be applied in order to detect intensity variations.
A large number of different types of measurements may be made by a sensor array in accordance with embodiments of the present invention. A measurement may comprise, but are not limited to steps as illustrated in FIG.10.
In steps prior to the steps of FIG.10, a sensor array has been prepared. Followed by the steps:
100: the sensor array is exposed to the target; 101: the sensor array is exposed to excitation radiation capable of inducing a surface plasmon resonance (SPR) on the sensor array; 102: the resulting radiation is detected with a radiation detector after interaction with the sensor array;
103: detecting intensity variations in the resulting radiation, and correlating the intensity variation to the pre-defined variation in the structural parameter in order to detect the presence of the target.
In the present disclosure, such parameters as particle size, predefined structural parameter, excitation wavelength, etc. are disclosed in connection with description of different embodiment. It is to be understood a large number of variations with in the scope of the invention is possible for the skilled person. Moreover, in a measurement, a number of parameters may need to be correlated. For example, a sensor array with a specific type of structural variation may be selected in accordance with a desired target to be detected. The excitation wavelength may be correlated with nanoparticles, or vice versa, in order to be able to detect an SPR shift. Also a specific carrier substrate may be selected, etc.
Although the present invention has been described in connection with the specified embodiments, it is not intended to be limited to the specific form set forth herein. Rather, the scope of the present invention is limited only by the accompanying claims. In the claims, the term "comprising" does not exclude the presence of other elements or steps. Additionally, although individual features may be included in different claims, these may possibly be advantageously combined, and the inclusion in different claims does not imply that a combination of features is not feasible and/or advantageous. In addition, singular references do not exclude a plurality. Thus, references to "a", "an", "first", "second" etc. do not preclude a plurality. Furthermore, reference signs in the claims shall not be construed as limiting the scope.

Claims

1. A sensor array (3, 30 46, 47, 90) for detecting the presence of a target, the sensor array comprising
- a carrier substrate (31, 61);
- a plurality of nano-sized particles (32, 60) disposed on the carrier substrate, where the surface plasmon resonance (SPR) for each of the nano-sized particles is correlated to a structural parameter of the nano-sized particles or group of nano-sized particles; wherein for the plurality of nano-sized particles, the structural parameter and thereby the surface plasmon resonance is varied in a pre-defined way in at least a first area of the carrier substrate, so that the target is detected based on detecting intensity variations in radiation resulting from the sensor array, the intensity variations being correlated to the pre-defined variation in the structural parameter.
2. The sensor array according to claim 1, wherein the nano-sized particles (32, 60) are metal particles.
3. The sensor array according to claim 1, wherein the nano-sized particles (32, 60) are functionalized by chemical receptors (62).
4. The sensor array according to claim 1, wherein the structural parameter is a parameter from the group of: size, geometric dimension, orientation, shape, aspect ratio or arrangement.
5. The sensor array according to claim 1, wherein the nano-sized particles are layered particles.
6. The sensor array according to claim 1, wherein the plurality of nano- sized particles is defined by a lithographic technique.
7. The sensor array according to claim 1, wherein at least part of the combined system of carrier substrate and plurality of nano- sized particles are covered by a cover layer
(72).
8. The sensor array according to claim 1, wherein the size of the nano- sized particles in a plane parallel to the plane of the carrier substrate is in the range of 10 nm to 1000 nm.
9. The sensor array according to claim 1, wherein the size of the nano- sized particles in a plane perpendicular to the plane of the carrier substrate is in the range of 10 nm to 1000 nm.
10. The sensor array according to claim 1, wherein the sensor array comprises a plurality of areas (80-83), wherein each area comprises a plurality of nano-sized particles with a pre-defined variation of the structural parameter.
11. An optical array detection system for detecting a target, the detection system comprising:
- a sensor array (3, 30 46, 47, 90) in accordance with claim 1;
- a radiation source (1, 91) for emitting excitation light onto the sensor array; and
- a detector (5, 92) for detecting the scattered radiation after interaction with the sensor array;
12. A method for detecting the presence of a target on a sensor array, the sensor array (3, 30, 46, 47, 90) comprising a carrier substrate (31, 61) and a plurality of nano-sized particles disposed on the carrier substrate, where the surface plasmon resonance (SPR) for each of the nano-sized particles is correlated to a structural parameter of the nano- sized particles or group of nano-sized particles; wherein for the plurality of nano-sized particles, the structural parameter and thereby the surface plasmon resonance is varied in a pre-defined way in at least a first area of the carrier substrate; the method comprising:
- exposing (100) the sensor array to the target;
- exposing (101) the sensor array to excitation radiation, the excitation radiation being capable of inducing a surface plasmon resonance (SPR) on the sensor array; - detecting (102) the resulting radiation with a radiation detector after interaction with the sensor array; wherein the target is detected based on detecting intensity variations in the resulting radiation, the intensity variation being correlated to the predefined variation in the structural parameter.
13. The method according to claim 10, wherein the excitation radiation is substantial monochromatic.
14. The method according to claim 10, wherein the radiation detection is a single wavelength detector.
EP08789471A 2007-08-10 2008-07-29 Sensor array for spr-based detection. Withdrawn EP2183573A1 (en)

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