WO2009104123A1 - Source de lumière pour biocapteur de spectroscopie infrarouge à transformée de fourier (ftir) - Google Patents

Source de lumière pour biocapteur de spectroscopie infrarouge à transformée de fourier (ftir) Download PDF

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Publication number
WO2009104123A1
WO2009104123A1 PCT/IB2009/050617 IB2009050617W WO2009104123A1 WO 2009104123 A1 WO2009104123 A1 WO 2009104123A1 IB 2009050617 W IB2009050617 W IB 2009050617W WO 2009104123 A1 WO2009104123 A1 WO 2009104123A1
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WO
WIPO (PCT)
Prior art keywords
light source
light
led
holes
biosensor
Prior art date
Application number
PCT/IB2009/050617
Other languages
English (en)
Inventor
Dominique M. Bruls
Johannes J. H. B. Schleipen
Original Assignee
Koninklijke Philips Electronics N.V.
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 N.V. filed Critical Koninklijke Philips Electronics N.V.
Publication of WO2009104123A1 publication Critical patent/WO2009104123A1/fr

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Classifications

    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/55Specular reflectivity
    • G01N21/552Attenuated total reflection
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2201/00Features of devices classified in G01N21/00
    • G01N2201/06Illumination; Optics
    • G01N2201/062LED's
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2201/00Features of devices classified in G01N21/00
    • G01N2201/06Illumination; Optics
    • G01N2201/064Stray light conditioning
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2201/00Features of devices classified in G01N21/00
    • G01N2201/08Optical fibres; light guides
    • G01N2201/0813Arrangement of collimator tubes, glass or empty

Definitions

  • the invention relates to an improved light source for biosensors and a biosensor including said light source.
  • biosensors allow for the detection of a given specific molecule within an analyte, wherein the amount of said molecule is typically small. Therefore, label particles, for example magnetic actuated beads, are used which bind to a specific binding site or spot only, if the molecule to be detected is present within the analyte.
  • label particles for example magnetic actuated beads
  • One known technique to detect these label particles bound to the binding spots is FTIR. Therein, light is coupled into the sample at an angle of total internal reflection. If no particles are present close to the sample surface, the light is completely reflected.
  • the condition of total internal reflection is violated, a portion of the light is scattered or absorbed by the beads present at the surface and thus the amount of light reflected by the surface is decreased.
  • a geometry may be used which is shown in Figure 1.
  • a laser diode or a light emitting diode (LED) 10 is used as a light source to generate a collimated monochromatic beam of light through an entrance window 15 of a biosensor cartridge 16.
  • Magnetic actuated beads 14 are detected using a total internal reflection principle sampling the surface area 11 of the biosensor cartridge 16 at the position where the light beam emitted by laser diode 10 hits the surface area 11, the light being reflected from the surface 11 is measured using a photo-detector 12.
  • By binding or non-binding of these magnetic beads 14 to the surface in a biological assay the presence of various substances, e.g., drugs-of abuse, can be detected in the assay, for example in saliva.
  • a magnet 13 is used to actuate the magnetic beads 14.
  • a laser as light source has the advantage that a narrow collimated beam can be generated to illuminate a small surface on which the bio-assay takes place, thereby illuminating the surface at one distinct angle.
  • the laser further emits light of only one wavelength, which exactly determines the angle at which total internal reflection occurs in the biosensor cartridge. Both the parallelness and monochromaticity of the laser beam result in a better defined evanescent field intensity distribution at the surface.
  • a laser as light source and using a single or split photo-diode only one or at most a few (typically 2-4) substances can be tested at the same time. However, in many applications, it is desirable to test more different substances at the same time.
  • Imaging the surface of the printed spots may be done by using a CCD.
  • a CCD which contains pixels arranged in lines and columns, i.e., in a periodic structure
  • the temporally and spatially coherent light beam emitted by the laser causes picture artefacts, rendering the obtained images useless. Further distortions of the image may arise due to diffraction and optical interference effects caused by edges and pinholes that are present in the optical setup. Also laser speckle distorts the image.
  • the cartridge which generally is made of plastic, small defects may be present, such as small air bubbles or small enclosures of foreign material, giving rise to diffraction effects.
  • Figure 2(a) shows an image of the surface of a biosensor illuminated using a laser beam in combination with a CCD as photo-detector.
  • Many diffraction effects and optical interference effects are visible at all the edges.
  • a large defect due to an imperfection in the plastic of the cartridge is visible.
  • the coherence of the laser may be destroyed, for example by adding diffusing or moving (e.g. rotating and/or vibrating) optics inside the optical setup.
  • diffusing or moving e.g. rotating and/or vibrating
  • modulating the laser diode at RF frequencies typically a few hundred MHz, may be used to partially destroy the coherence of the laser.
  • experiments show that this is not enough in order to overcome the problems mentioned above.
  • Another solution may be to replace the laser by a LED.
  • a LED is quasi- monochromatic and therefore well suited for the application in an FTIR biosensor.
  • the light source for a biosensor comprises a
  • the corrector means may be a piece of material that is placed in front of the LED, wherein one or a plurality of holes having a large aspect ratio, that is, having a diameter that is made small with respect to the depth of the hole, is arranged in the piece of material. In this way, the piece of material acts substantially as an angle selector which filters out the unwanted angles.
  • the inside of the holes should be opaque, i.e., non- reflecting and light-absorbing. In this way, unwanted reflections of light inside the holes is avoided and a proper angular selection is guaranteed.
  • one or several "point-like sources" can be obtained using an LED which provides an almost monochromatic and substantially incoherent light beam.
  • the light emerging from the holes of the corrector means may further be collimated by using e.g. a collimator lens.
  • the holes act as quasi-point sources. This is done in such a way that a clear image of the holes can be generated at a certain distance from the corrector means.
  • the total length of the light path in the biosensor device i.e. from light source to detector plane, is typically only a fraction of the distance at which an image of the holes is generated, i.e. typically more than 1 meter
  • a quasi-collimated light beam is generated with an almost uniform intensity distribution, a part of which is being used for illuminating the sensor area.
  • a LED which already has a light profile that is favorable, i.e. emitting a light beam with a forward propagating intensity distribution as uniform as possible. For example, by using a LED with a so-called bat- wing or Lambertian profile in combination with the corrector means, a homogeneous light distribution can be obtained.
  • the invention further provides a biosensor device including the light source according to the invention in combination with a CCD for detecting the light reflected from the surface of the biosensor.
  • a biosensor device which may be similar to the one shown in Figure 1 , it is preferred to place an additional diaphragm as close as possible to the entrance window 15 of the biosensor cartridge 16.
  • the size of the diaphragm should be matched to the area which is to be illuminated, in order to suppress the generation of unwanted stray light inside the cartridge 16 and enhance the angular selection of the incoming light beam even further.
  • Fig. 1 schematically shows a FTIR biosensor device
  • Fig. 2 shows images taken by a CCD in a biosensor device using (a) laser illumination and (b) LED illumination;
  • Fig. 3 schematically shows a light source according to an embodiment of the present invention
  • Fig. 4 shows an image similar to the images of Fig. 2, taken using a light source according to an embodiment of the invention.
  • Fig. 5 shows illumination profiles of a light source according to an embodiment of the invention (a) without and (b) with an optimization.
  • Fig. 3 schematically shows a light source comprising an LED 1 and a corrector means 2 according to an embodiment of the present invention.
  • a top view on the corrector means 2 is shown.
  • the lower portion of Fig. 3 shows a side view on the light source.
  • the corrector means 2 includes three holes 3 in the form of elongate pinholes 3 which have a length through the corrector means 2 which is substantially longer than the diameter of the holes 3.
  • the ratio of the depth and the diameter should be at least 10 which results in an angular spread which is reduced to a few degrees only.
  • the inside of the holes should be absorbing and non-reflecting since otherwise, light at extreme angles may still "bounce" through the holes arranged in the corrector means. Furthermore, the diameter of the holes should not be too small since otherwise, almost no light would reach the detector means unless the LED is driven at vary high powers which should be avoided considering power consumption and heat generation. Further reasons why the holes should not have an extremely small diameter is that otherwise large diffraction effects will occur at the edges of the holes, introducing an extra unwanted angular distribution. On the other hand, the diameter of the holes should also not be too large since otherwise, the holes will not act as a quasi-point source anymore and it may happen that the structure of the LED chip is imaged upon the FTIR image leading to image artifacts, shadowing effects etc.
  • the diameter of the holes preferably is around 0.3mm. This diameter yields an extra angle due to diffraction at the holes of about +0.15°, which is acceptable.
  • the choice of the diameter of the holes also depends on the total length of the light path, and the available optical power, as this introduces losses.
  • the maximum allowable size for the diameter of the holes is lmm, considering LEDs with a light emitting surface of around lxlmm. In a preferred embodiment of the light source, similar to what is shown in
  • Fig. 3 three holes are provided having a diameter of 0.3mm with a spacing of 0.6mm.
  • This arrangement is optimized for illumination of a surface having a size of 1.5x2mm in a FTIR biosensor.
  • the above solution results in a very compact light source which may be made into a very compact illumination module.
  • the maximum required length of the total illumination unit can be made smaller than 20mm which is to be compared to solutions using a light source like an LED or a laser in combination with collimating optics which typically have a total length of more than 30mm. Reduction of the size of the illumination unit is especially important when integrating the illumination unit in a handheld, compact reader design.
  • FIG. 4 An image of a biosensor surface, similar to the images shown in Fig. 2, but taken using a light source according to the above embodiment of the invention, is shown in Fig. 4.
  • the number and size of the holes may be varied in order to optimize the illumination profile of the light source.
  • the illumination profile is influenced by using multiple holes but also depends on the spacing between the holes and the diameter of the holes.
  • An example of different illumination profiles achieved and optimized in this way is shown in Fig. 5(a) wherein no optimization has been performed.
  • Fig. 5(b) brightness of the illuminated surface is presented by the height of the plot.
  • an additional collimator lens can be used collecting the light emitted by the holes array and making an image of the holes array at large distance, thereby obtaining a quasi-collimated light beam at the position of the sensor area.
  • the collection NA of this lens is governed by the geometry of the holes. If each hole has length L and diameter D, the NAc 011 of the collimator lens should be typically equal to ⁇ D/L in order to collect as much light as possible from each single hole.
  • the focal length of the collimator lens is governed by the outer diameter of the complete holes array.
  • the invention is described with regard to FTIR for optical detection, other optical detection technologies are applicable.

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  • Physics & Mathematics (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Investigating Or Analysing Materials By Optical Means (AREA)

Abstract

L'invention porte sur une source de lumière pour un biocapteur. La source de lumière comprend une diode électroluminescente (DEL) et un moyen de correction. Le moyen de correction sert à corriger la lumière émise par la DEL en supprimant par filtrage la plupart des angles non voulus émis par la DEL. Le moyen de correction comprend un ou plusieurs trous ayant un rapport de forme important, c'est-à-dire ayant une profondeur qui est supérieure au diamètre. L'intérieur du trou est non réfléchissant et absorbe la lumière de façon à éviter des réflexions de lumière indésirables à l'intérieur du trou. L'invention porte en outre sur un dispositif de biocapteur comprenant la source de lumière décrite.
PCT/IB2009/050617 2008-02-22 2009-02-16 Source de lumière pour biocapteur de spectroscopie infrarouge à transformée de fourier (ftir) WO2009104123A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP08101861.6 2008-02-22
EP08101861 2008-02-22

Publications (1)

Publication Number Publication Date
WO2009104123A1 true WO2009104123A1 (fr) 2009-08-27

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2499480A4 (fr) * 2009-11-12 2017-11-08 General Electric Company Système de capteur optique basé sur une réflexion totale atténuée et procédé de détection
US11333821B2 (en) * 2018-09-28 2022-05-17 Lumileds Llc Flexible low Z-height LED arrays with controllable light beams

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4420687A (en) * 1982-10-28 1983-12-13 Teledyne Ind Non-dispersive infrared gas analyzer
WO1991012515A1 (fr) * 1990-02-16 1991-08-22 Eqm Research, Inc. Dispositif multisource d'analyse photometrique et chromogenes associes
US5402240A (en) * 1994-02-17 1995-03-28 Dupree, Inc. Sperm densimeter
US6212154B1 (en) * 1997-10-08 2001-04-03 Samsung Electronics Co., Ltd. Optical pickup for optical disk and light source for optical pickup
WO2002086468A1 (fr) * 2001-04-19 2002-10-31 Maven Technologies Llc. Appareil et procede d'imagerie
US6574425B1 (en) * 1997-10-31 2003-06-03 Jack L. Aronowitz Reflectometer

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4420687A (en) * 1982-10-28 1983-12-13 Teledyne Ind Non-dispersive infrared gas analyzer
WO1991012515A1 (fr) * 1990-02-16 1991-08-22 Eqm Research, Inc. Dispositif multisource d'analyse photometrique et chromogenes associes
US5402240A (en) * 1994-02-17 1995-03-28 Dupree, Inc. Sperm densimeter
US6212154B1 (en) * 1997-10-08 2001-04-03 Samsung Electronics Co., Ltd. Optical pickup for optical disk and light source for optical pickup
US6574425B1 (en) * 1997-10-31 2003-06-03 Jack L. Aronowitz Reflectometer
WO2002086468A1 (fr) * 2001-04-19 2002-10-31 Maven Technologies Llc. Appareil et procede d'imagerie

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
CHAPMAN G H ET AL: "Angular domain imaging of objects within highly scattering media using silicon micromachined collimating arrays", IEEE JOURNAL OF SELECTED TOPICS IN QUANTUM ELECTRONICS, IEEE SERVICE CENTER, PISCATAWAY, NJ, US, vol. 9, no. 2, 1 March 2003 (2003-03-01), pages 257 - 266, XP011102892, ISSN: 1077-260X *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2499480A4 (fr) * 2009-11-12 2017-11-08 General Electric Company Système de capteur optique basé sur une réflexion totale atténuée et procédé de détection
US11333821B2 (en) * 2018-09-28 2022-05-17 Lumileds Llc Flexible low Z-height LED arrays with controllable light beams

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