WO2010032157A1 - Détecteur à grille caractérisé par une hauteur de volume de détection réglable en continu - Google Patents

Détecteur à grille caractérisé par une hauteur de volume de détection réglable en continu Download PDF

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Publication number
WO2010032157A1
WO2010032157A1 PCT/IB2009/053915 IB2009053915W WO2010032157A1 WO 2010032157 A1 WO2010032157 A1 WO 2010032157A1 IB 2009053915 W IB2009053915 W IB 2009053915W WO 2010032157 A1 WO2010032157 A1 WO 2010032157A1
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WIPO (PCT)
Prior art keywords
wire
grid
excitation radiation
substrate
height
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PCT/IB2009/053915
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English (en)
Inventor
Derk J. W. Klunder
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Koninklijke Philips Electronics N.V.
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Publication of WO2010032157A1 publication Critical patent/WO2010032157A1/fr

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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
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64—Fluorescence; Phosphorescence
    • G01N21/645—Specially adapted constructive features of fluorimeters
    • G01N21/648—Specially adapted constructive features of fluorimeters using evanescent coupling or surface plasmon coupling for the excitation of fluorescence

Definitions

  • the present invention relates to a wire-grid sensor assembly for detecting e.g. particles, beads, or molecules. More specifically to an assembly and a method for the adjustment of the height of the evanescent detection volume.
  • Wire-grid sensors are often applied in relation to luminescent biosensing for detecting labeled target compounds, or in testing the binding affinity of target compounds.
  • wire- grid sensors can be used in setups applying other means of sensing.
  • capture molecules are deposited in a pattern on a surface (hereafter the sample side of the surface).
  • a solution containing target analytes is flown over the pattern and the target analytes attach to the capture molecules if there is a match.
  • the matched sites are either designed to become luminescent, or are made so by introducing luminescently labeled compounds (luminophores such as fluorophores) that bind to matched sites with a high degree of specificity or by labeling the target molecules with luminescent compounds.
  • excitation light is directed to the surface in a way so that it generates an evanescent field at the sample side of the surface. This evanescent field will be (partially) absorbed by the matched sites and generate luminescent light.
  • the luminescent signal is filtered to remove the excitation wavelengths and is monitored by a CCD imaging system. Detection of multiple target analytes is achieved by spatial multiplexing, where spots with different capture molecules are deposited on the sample side of the surface.
  • the reason for using the evanescent field for excitation is to ensure that the field excites only luminophores bound to biomolecules on or at the vicinity of the surface. Free luminophores in the solution are only excited to a very limited degree, and will therefore essentially not contribute to the background noise.
  • the evanescent field used for excitation typically results from total internal reflection (TIR) of light incident at the surface at angles larger than the critical angle. Thereby, no light is transmitted, only the evanescent field penetrates into sample side of the surface.
  • TIR total internal reflection
  • the surface is typically a waveguide or a microscope slide as is the case for a total internal reflection fluorescence microscope (TIRFM).
  • a special class of luminescence sensors is wire-grid sensors where sub-diffraction-limited metal wire-grids are formed on substrate surfaces, typically by photolithography, and are used as binding surface for biomolecules.
  • the wire-grid is illuminated with polarized light which is reflected by the sub-diffraction- limited metal wire-grid, and a rapidly decaying evanescent field is generated in the volume between the wires. Little or no excitation light is therefore transmitted by the wire grid.
  • By patterning the wire grid with spots of capture molecules that bind at the sample side of the surface of the carrier on which the wires are deposited.
  • the target molecules can bind with the capture molecules resulting in matched sides on the sample side of the surface.
  • the matched sites are either designed to become luminescent, or are made so by introducing luminescently labeled compounds (luminophores such as fluorophores) that bind to matched sites with a high degree of specificity or by labeling the target molecules with luminescent compounds.
  • the luminophores inside the slits can be excited by the evanescent field generated by the incident excitation light. This leads to luminescence light signals emitted from a small volume at the bottom, that is close to the sample side of the surface of the carrier, of the slits, and this luminescent light will typically be visible from both sides of the wire-grid.
  • the penetration depth of the evanescent field from the sample side of the surface and into the (typically liquid) sample also referred to as the height of the detection volume generated by the evanescent field, determines how far away from the sample side of the surface luminophores are excited.
  • US 7,193,711 describes a TIR based luminescence sensors where the height and intensity of the evanescent field is controlled by controlling optical properties of a control layer, e.g. thickness, refractive index, and reflectivity characteristic.
  • the means of controlling the penetration depth of the evanescent field of the prior art requires controlling either the angle of incidence or optical properties of the materials of the sensor, since such means are difficult to vary during the course of a measurement or require a high-end set-up to provide the necessary accurate control of e.g., the angle of incidence. It is therefore a problem of prior art sensing concepts that these require accurate control of the angle of incidence to adjust the penetration depth.
  • the height of the detection volume, H can be controlled by controlling the distribution of evanescent field from TE and TM components of polarized excitation light.
  • the contributions to the evanescent field from TE and TM components vary with at least the angle of incidence as well as the polarization state of the excitation light.
  • the invention provides a wire-grid sensor assembly with a continuously controllable height of detection volume, the wire-grid sensor assembly comprising: - a source of excitation radiation having wavelength ⁇ for illuminating a wire-grid; a wire-grid formed by a material that is substantially non-transmissive for the excitation radiation on a surface part of a transparent substrate and defining a plurality of parallel slits with a width W along a short axis being smaller than a diffraction limit of the excitation radiation and a length L along a long axis, perpendicular to the short axis, being larger than the diffraction limit of the excitation radiation; an adjustable polarizer for adjusting a linear polarization state, ⁇ , of the excitation radiation; the wire-grid sensor assembly being arranged so that the excitation radiation illuminates the wire- grid at an angle of incidence on the substrate surface part holding the wire-grid which is larger than a critical angle etc of the interface between the substrate
  • the invention provides a method for controlling a height of the detection volume of a wire-grid sensor, comprising: irradiating a wire-grid formed on a substrate surface part with excitation radiation at an angle of incidence, ⁇ , on said substrate surface part,
  • the wire-grid is formed by a material that is substantially non-transmissive for the excitation radiation and that define a plurality of parallel slits with a width W along a short axis being smaller than a diffraction limit of the excitation radiation and a length L along a long axis, perpendicular to the short axis, being larger than the diffraction limit of the excitation radiation;
  • the wire-grid sensor assembly may be applied in e.g. biosensors or chemical sensors. Even though the described examples relates to detecting the presence of luminescently labeled particles, the invention is not limited to luminescent sensing but can rely on other detection mechanisms.
  • the particles to be detected may be organic or inorganic particles, beads, molecules (including macro molecules), micro organisms, etc.
  • the wire-grid is a grating formed by a material that is substantially non-transmissive for the excitation radiation with wavelength ⁇ , preferably an electrically conductive material (i.e. the complex refractive index has a non-zero imaginary component).
  • the wire-grid is formed on a surface of optically transparent solid dielectric substrate.
  • the wire-grid is a metal film lattice formed on a glass or plastic substrate (e.g., Polystyrene) substrates by photolithographic processes. The substrate with the wire-grid is also referred to as the substrate wire-grid.
  • the wire-grid is to be illuminated by excitation light through the substrate.
  • the substrate surface part holding the wire-grid is preferably planar so that the wire-grid is defined in a plane sheet.
  • the medium filling the slits is typically a liquid such as water-based solutions.
  • the wire-grid and substrate are back-lit, i.e. illuminated through the substrate from the backside of the substrate (at the substrate surface opposite the wire-grid).
  • the wire grid is illuminated by waveguiding where the excitation light is coupled in via a side facet of the substrate and the excitation light is transported towards the wire grid by means of multiple total internal reflections.
  • the medium (which is typically air) on the backside of the substrate has a refractive index that is in general smaller than the refractive index of medium that fills the space between the wires (which is typically water), it is not possible to couple light that is total internally reflected at the substrate side holding the wire-grid ( ⁇ > etc) into the substrate.
  • a prism is preferred over a diffraction grating, as the amount of light that can be coupled into the substrate is typically larger than for a diffraction grating.
  • the prism can either be integrated with the substrate or can be an external prism attached to the backside of the substrate. It is preferred to comprise a prism on a surface part of the substrate opposite the surface part holding the wire-grid for coupling exciting radiation into the substrate.
  • the components of the wire-grid sensor assembly are then preferably arranged so that the excitation radiation is incident on a facet of the prism at an angle of incidence smaller than the critical angle of the interface between the prism and the surrounding medium, even more preferably at normal angle at incidence.
  • the volume between the wires of the wire-grid are slits with sub-diffraction limit dimensions in only one transverse dimension.
  • the ratio between the width of the space between the wires (size of slit along the short axis) and the pitch between the wires (width of space between the wires + wire width) is referred to as duty cycle.
  • the invention may also be utilized with wire-grids where the volume between the wires define holes with sub-diffraction limit dimensions in all transverse dimensions, where the width in a first transverse direction is different than in the second transverse direction .
  • the holes support two modes, a first mode with an electric field in said first transverse direction and a second mode with an electric field in said second transverse direction, where the two modes have different heights of the evanescent detection volume.
  • Advantage of this embodiment is that it is more or less independent of the angle of incidence, and does not require an angle of incidence that would is total internally reflected at the interface between the substrate and the medium that fills the space between the wires; one could also use normal incident light. Disadvantage is that the control of the height of the detection volume by the angle of incidence is limited.
  • the evanescent intensity in the z-direction into the sample side of the surface may be described as
  • Io the evanescent intensity at the substrate surface part holding the wire-grid
  • H the evanescent decay length.
  • the height of the evanescent detection volume follows from integration of this intensity along the z-direction and equals the evanescent decay length H for a wire grid with a height (H wg ) of the wires substantially larger than the evanescent decay length. .
  • the polarization states are defined as:
  • TE polarized light is incident radiation where the projection of electric field on the substrate surface part holding the wire-grid is parallel to the long axis of the slits. If the wire-grid is formed in a conducting material, TE polarized light results in a rapidly decaying evanescent wave in the space between the wires, with a decay length that does not depend on the angle of incidence, i.e. also for angles of incidence smaller than the critical angle.
  • TM polarized light is incident radiation where the projection of electric field on the substrate surface part holding the wire-grid is perpendicular to the long axis of the slits.
  • TM polarized light can be transmitted for angles of incidence smaller than the critical angle and and results in an evanescent field with a decay length given by equation (2) for angles of incidence larger than the critical angle.
  • a decaying evanescent field is generated in the volume between the wires, and the height of the detection volume generated by the evanescent field from TE polarized light, H TE , is determined by the dimensions of the wire-grid.
  • TM polarized light For TM polarized light, a decaying evanescent field is generated in the slits, and the height of the detection volume generated by the evanescent field from TM polarized light, H TM , is determined by the angle of incidence ⁇ : where ⁇ is the wavelength, and n su b str ate and n me dmm are the refractive indices on the substrate holding the wire-grid and the medium filling the slits, respectively.
  • the height of the detection volume as a function of the polarization state of the excitation light and for fixed angle of incidence is:
  • X TE and X TM are the efficiencies with which TE and TM polarized light are coupled into the wire-grid.
  • the coupling of the incident light into the wire-grid depends on the angle of incidence.
  • the coupling efficiency into the TE polarized light X TE is approximately equal to the duty cycle of the wire-grid, so that for a typical wire-grid with a duty cycle of 50% is X TE ⁇ 0.5.
  • TM polarized light the coupling efficiency is typically larger than for TE polarized light, for the example of a wire-grid with aluminum wires and a duty cycle of 50%, X TM ⁇ 0,8.
  • X TE and X TM may be determined by numerical simulation.
  • the control of the height of the detection volume H( ⁇ ) by adjustment of the polarization state of light incident on an exemplary wire-grid is illustrated in Figure 1.
  • the exemplary wire-grid is formed on a glass substrate and illuminated under an angle of incidence larger than the critical angle.
  • the adjustable polarizer can vary the polarization continuously between a TE polarization state and a TM polarization state. This will allow the height, H, of the detection volume in the slits to be continuously controlled between a minimum value, H min , and a maximum value, H max . It is further preferred to vary the height, H, of the detection volume in the slits between a minimum value, H min , and a maximum value, H max , without changing the angle of incidence.
  • the endpoints of the range in which the height of the detection volume can be adjusted can be controlled by proper selecting of wire-grid parameters, that control H min , and angle of incidence, that controls H max .
  • H TM extremum value
  • H TE extremum value
  • Typical material parameters may be the complex index of refraction of the wires
  • typical dimensional parameters may be the width (W) along the short axis, i.e. the space between the wires and the duty cycle.
  • angles and orientations are determined by the terms 'parallel', 'perpendicular', or 'normal to' . It is to be understood, as will also be recognized by the person skilled in the art, that angles and orientations that are not exactly parallel or normal to (i.e. 0 ° or 90°) will result in the same effect, albeit possibly with a lower efficiency.
  • the invention can therefore be embodied, implemented and applied using small deviations from exactly parallel or normal for the relevant angles and orientations, and it is stressed that the claims are intended to cover also such small deviations.
  • the term 'parallel' means an angle of 0 ° ⁇ 3 ° such as 0 o ⁇ 5 ° or 0 o ⁇ 10°.
  • the terms 'perpendicular' , or 'normal to' mean an angle of 90 ° ⁇ 3 ° such as 90 ° ⁇ 5 ° or 90 ° ⁇ 10 °.
  • the wire-grid sensor assembly may comprise means for correlating a chosen polarization state with a height of the evanescent detection volume in the wire-grid.
  • Such means for correlating may be in digital or analogue form, and may be embodied by storage holding e.g. a look-up table, a curve, a formula, a program, or an algorithm from which H can be determined from ⁇ .
  • the means for correlating may be determined using theoretic calculations, numeric simulations or by measurements of corresponding ⁇ and H for a given wire-grid sensor assembly.
  • the evanescent penetration depth and thus the height of the detection volume in the wire-grid can be adjusted by illuminating the wire- grid at angles above the critical angle and controlling the mixture of TE and TM polarized light.
  • Figure 1 is a graph showing the control of the height of the detection volume H( ⁇ ) by adjusting the polarization state of light incident on a wire-grid.
  • Figure 2 is a side-view of an illustration of a substrate wire-grid to be used in a wire-grid sensor assembly in accordance with an embodiment of the invention.
  • Figure 3 is a top-view of an illustration of a substrate wire-grid to be used in a wire-grid sensor assembly in accordance with an embodiment of the invention.
  • Figure 4 illustrates a wire-grid sensor assembly according to an embodiment of the invention.
  • Figure 5 is a graph with a curve describing H TE from a numerical simulation for a wire-grid sensor assembly in accordance with an embodiment of the invention.
  • Figure 6 is a graph with curves X TE ( ⁇ ) and X TM ( ⁇ ) from numerical simulations for a wire- grid sensor assembly in accordance with an embodiment of the invention.
  • Figure 1 shows the dependence of the height of the detection volume H( ⁇ ) on the polarization state ⁇ for an exemplary wire-grid.
  • Figure 2 illustrates a side-view of a substrate wire-grid 1 to be used in a wire-grid sensor assembly in accordance with an embodiment of the invention.
  • a substrate 2 holds a wire-grid 3 with wires 4 of height H wg defining slits 5 having a short axis (SA) of width W and a long axis (LA) (not shown).
  • the substrate has a front surface part 6 holding the wire-grid and an opposite back surface part 7 where the excitation radiation is coupled in.
  • the substrate is formed in a dielectric material that is substantially transmissive for the excitation radiation, e.g. glass (silica), or plastic (polycarbonate, polystyrene).
  • the wires 4 are formed in a material that is substantially non-transmissive (preferably has an imaginary part of the refractive index larger than 1 ; even more preferably larger than 3) for the excitation radiation, e.g. metal such as Aluminum, Gold, Silver, or Copper.
  • Exemplary sizes for the width W of the slits along the short axis should be below the diffraction limit.
  • the values for a wire grid with water in the space between the wires and a wavelength in vacuum of 633 nm preferably smaller than ⁇ /2 (119 nm); more preferably between 0.15 * ⁇ and ⁇ /4 (71-119 nm); most preferably between 0.1* ⁇ and 0.2* ⁇ (48-95 nm).
  • the figure shows the exciting radiation 8 illuminating the front surface part 6 at an angle of incidence ⁇ .
  • Figure 3 is a top view of the substrate wire-grid 1 of Figure 2.
  • the TE and the TM polarization states of the incident exciting radiation 8 are shown in relation to the wire-grid 3.
  • the substrate wire-grid 1 is arranged so that the excitation radiation 8 illuminates the wire-grid 3 from a direction which, when projected onto the substrate surface part holding the wire-grid, is perpendicular to the long axis LA of the slits, which is a preferred arrangement.
  • the projection of electric field E on the substrate surface part holding the wire-grid is parallel to the long axis LA of the slits.
  • the projection of electric field E on the substrate surface part holding the wire-grid is perpendicular to the long axis LA of the slits.
  • Figure 4 illustrates a wire-grid sensor assembly 10 according to an embodiment of the invention, and is used to embodying a method for controlling the height of the detection volume according to another embodiment of the invention.
  • the substrate wire-grid 1 of Figure 2 is shown with a source of excitation radiation 11 , which is preferably a laser as the light generated by a laser can easily be collimated, for illuminating a wire-grid and an adjustable polarizer 12, which is preferably a polarizer on a rotation stage, for adjusting a linear polarization state, ⁇ , of the excitation radiation.
  • a source of excitation radiation 11 which is preferably a laser as the light generated by a laser can easily be collimated, for illuminating a wire-grid
  • an adjustable polarizer 12 which is preferably a polarizer on a rotation stage, for adjusting a linear polarization state, ⁇ , of the excitation radiation.
  • the wire-grid 3 is irradiated with excitation radiation 8 through the substrate 2 at an angle of incidence ⁇ that is larger than a critical angle etc of the interface between the substrate 2 and a medium that fills the slits 5.
  • ⁇ a linear polarization state
  • H a height of the detection volume (not shown) in the slits 5 can be controlled according to Equation 3 described previously.
  • Figure 4 also shows a prism 13 for coupling the excitation radiation into the substrate under an angle smaller than the critical angle of the air-prism interface.
  • the prism is arranged with a facet 14 where the excitation radiation is incident with a substantially normal angle of incidence.
  • the prism should preferably be formed in the same material as the substrate and secured with an index-matched paste.
  • the prism can be formed as part of the substrate, e.g. by injection molding.
  • the wire-grid sensor assembly can be used in a sensor setup.
  • setup can include a signal detector 15, e.g. a luminescence detector for detecting luminescent radiation 17 from labeled particles that are excited by the evanescent field in the slits of the wire-grid 3.
  • a signal detector 15 e.g. a luminescence detector for detecting luminescent radiation 17 from labeled particles that are excited by the evanescent field in the slits of the wire-grid 3.
  • a wavelength filter 16 may be used.
  • the sensor and filter are placed on the backside of the substrate, to detect the luminescent radiation 17 through the substrate. In this case, a filter should be used to block scattered excitation radiation.
  • This set-up may be advantageous when transmission of luminescent radiation 17 on the sample side is blocked by e.g. fluid handling infrastructure as described next.
  • the wire-grid sensor can comprise a fluid handling infrastructure (not shown), e.g. a cover with flow channels, canals or compartments, for adapting the substrate surface part holding the wire-grid to receive a sample solution containing particles to be detected in the slits.
  • a fluid handling infrastructure e.g. a cover with flow channels, canals or compartments, for adapting the substrate surface part holding the wire-grid to receive a sample solution containing particles to be detected in the slits.
  • H TE The detection volume generated by the evanescent field from TE polarized light, H TE , is set by the dimensions of the wire-grid, and the variation and/or specific values of H TE , can be determined by empirical measurement on a given wire-grid sensor assembly. Alternatively, H TE , can be determined by numerical simulations for a given wire-grid geometry and excitation radiation wavelength.
  • Figure 5 shows a calculated curve of H TE and H TM (for angles of incidence below the critical angle) as a function of the width between the space of the wires for a wire grid with aluminum wires and a wavelength in vacuum of 630 nm, which clearly shows that the decay length for TE polarized light is substantially smaller than for TM polarized light. .
  • X TE and X TM are the efficiencies with which TE and TM polarized light are coupled into the wire-grid, and these are dependent on the angle of incidence.
  • X TE is approximately equal to the duty cycle of the wire-grid
  • X TM is in the range XTE ⁇ XTM ⁇ 1 •
  • the variation and/or specific values of XTE and XTM can be determined by empirical measurement on a given wire-grid sensor assembly under the variance of ⁇ .
  • X TE and X TM can also be determined by numerical simulations for a given wire-grid geometry and excitation radiation wavelength.
  • Figure 6 shows curves X TE (ct) and X TM (ct) from such numerical simulations for the same wire grid used in the calculations in Fig. 5.
  • Figure 6 clearly shows that the excitation efficiency for TE polarized light is indeed lower than for TM polarized light.

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  • Health & Medical Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Physics & Mathematics (AREA)
  • Life Sciences & Earth Sciences (AREA)
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Abstract

La présente invention concerne un ensemble biodétecteur à grille permettant de détecter par exemple des particules, des billes ou des molécules, la hauteur du volume de détection dans la grille pouvant être ajustée en éclairant la grille selon des angles supérieurs à l'angle limite, ainsi qu'en régulant le mélange de la lumière polarisée TE et TM. La grille est située sur un substrat et comporte des fentes présentant un axe court inférieur à la limite de diffraction du rayonnement appliqué et un axe long supérieur à ladite limite de diffraction. La grille est exposée à un rayonnement excitateur traversant le substrat selon un angle d'incidence supérieur à l'angle limite de l'interface entre le substrat et un milieu remplissant les fentes. En modulant un état de polarisation linéaire, θ, du rayonnement excitateur au moyen d'un polariseur, on peut contrôler la hauteur du volume de détection dans les fentes ou, de même, la profondeur de pénétration du champ évanescent.
PCT/IB2009/053915 2008-09-17 2009-09-08 Détecteur à grille caractérisé par une hauteur de volume de détection réglable en continu WO2010032157A1 (fr)

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EP08305560.8 2008-09-17

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR3102573A1 (fr) * 2019-10-28 2021-04-30 Centre National De La Recherche Scientifique Elément optique diffractif comprenant une métasurface pour la microscopie TIRF

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE19923563A1 (de) * 1999-05-21 2000-12-07 Stiftung Fuer Lasertechnologie Vorrichtung zur tiefenauflösenden Totalreflexionsfluorometrie mikroskopischer Proben
WO2006135782A2 (fr) * 2005-06-10 2006-12-21 Applera Corporation Procede et systeme d'analyse genetique multiplexe
US20070206187A1 (en) * 2006-02-13 2007-09-06 Pacific Biosciences Of California, Inc. Methods and systems for simultaneous real-time monitoring of optical signals from multiple sources

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE19923563A1 (de) * 1999-05-21 2000-12-07 Stiftung Fuer Lasertechnologie Vorrichtung zur tiefenauflösenden Totalreflexionsfluorometrie mikroskopischer Proben
WO2006135782A2 (fr) * 2005-06-10 2006-12-21 Applera Corporation Procede et systeme d'analyse genetique multiplexe
US20070206187A1 (en) * 2006-02-13 2007-09-06 Pacific Biosciences Of California, Inc. Methods and systems for simultaneous real-time monitoring of optical signals from multiple sources

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
EREMINA E ET AL: "Analysis of light scattering in the evanescent waves area by a cylindrical nanohole in a noble-metal film", OPTICS COMMUNICATIONS, NORTH-HOLLAND PUBLISHING CO. AMSTERDAM, NL, vol. 281, no. 13, 1 July 2008 (2008-07-01), pages 3581 - 3586, XP022670273, ISSN: 0030-4018, [retrieved on 20080411] *
KLUNDER D J W ET AL: "A novel nano-photonics biosensor concept for rapid molecular diagnostics", PROGRESS IN BIOMEDICAL OPTICS AND IMAGING, SPIE, BELLINGHAM, WA, US, vol. 6991, 2 May 2008 (2008-05-02), pages 69910P - 1, XP002507453, ISSN: 1605-7422 *
WENGER J ET AL: "Single molecule fluorescence in rectangular nano-apertures", OPTICS EXPRESS, OSA (OPTICAL SOCIETY OF AMERICA), WASHINGTON DC, (US), vol. 13, no. 17, 1 August 2005 (2005-08-01), pages 7035 - 7044, XP002481400, ISSN: 1094-4087 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR3102573A1 (fr) * 2019-10-28 2021-04-30 Centre National De La Recherche Scientifique Elément optique diffractif comprenant une métasurface pour la microscopie TIRF
WO2021083787A1 (fr) * 2019-10-28 2021-05-06 Centre National De La Recherche Scientifique Element optique diffractif comprenant une metasurface pour la microscopie tirf

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