WO2009007888A1 - Agencement opto-mécanique pour fournir un accès optique à une chambre d'échantillon - Google Patents

Agencement opto-mécanique pour fournir un accès optique à une chambre d'échantillon Download PDF

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Publication number
WO2009007888A1
WO2009007888A1 PCT/IB2008/052689 IB2008052689W WO2009007888A1 WO 2009007888 A1 WO2009007888 A1 WO 2009007888A1 IB 2008052689 W IB2008052689 W IB 2008052689W WO 2009007888 A1 WO2009007888 A1 WO 2009007888A1
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WO
WIPO (PCT)
Prior art keywords
light
opto
carrier
mechanical arrangement
light beam
Prior art date
Application number
PCT/IB2008/052689
Other languages
English (en)
Inventor
Coen A. Verschuren
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 WO2009007888A1 publication Critical patent/WO2009007888A1/fr

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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
    • 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
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/55—Specular reflectivity
    • G01N21/552—Attenuated total reflection
    • G01N21/553—Attenuated total reflection and using surface plasmons
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62—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
    • G01N21/65—Raman scattering
    • 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
    • G01N21/75—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated
    • G01N21/76—Chemiluminescence; Bioluminescence
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2201/00—Features of devices classified in G01N21/00
    • G01N2201/06—Illumination; Optics
    • G01N2201/064—Stray light conditioning
    • G01N2201/0642—Light traps; baffles

Definitions

  • the invention relates to an opto -mechanical arrangement for providing optical access to a sample chamber in which a sample can be provided. Moreover, it relates to a microelectronic sensor device comprising such an arrangement.
  • the US 2005/0048599 Al discloses a method for the investigation of microorganisms that are tagged with particles such that a (e.g. magnetic) force can be exerted on them.
  • a light beam is directed through a transparent material to a surface where it is totally internally reflected.
  • Light of this beam that leaves the transparent material as an evanescent wave is scattered by microorganisms and/or other components at the surface and then detected by a photodetector or used to illuminate the microorganisms for visual observation.
  • a problem of this and similar setups is that they are prone to disturbances by e.g. light scattering.
  • quantitative measurements require a precise knowledge of the amount of light that reaches the surface of total internal reflection.
  • the opto -mechanical arrangement shall provide optical access to a sample chamber, i.e. to some space in which a sample to be manipulated or investigated can be provided.
  • the opto -mechanical arrangement comprises two principal components: a) A carrier that may optionally be constructed as a one-piece element from a homogeneous material, for example from glass or from transparent plastics.
  • the carrier comprises: - A "contact surface” with an "investigation region” that is or that can be disposed adjacent to the sample chamber.
  • the term "contact surface” is chosen here primarily as a unique reference to a particular part of the surface of the carrier, and though target components of a sample will in many applications actually contact and bind to said surface, this does not necessarily need to be the case.
  • the "investigation region” may be a sub-region of the contact surface or comprise the complete contact surface; it will typically have the shape of a substantially circular spot.
  • At least one optical window through which a light beam can pass, i.e. enter or leave the carrier.
  • a transparent light path optically connecting the aforementioned optical window and the investigation region; a light beam can therefore propagate within the carrier from the optical window to the investigation region or vice versa along said light path.
  • the light path will be realized by a straight channel between the optical window and the investigation region that is made from a transparent material with homogeneous refractive index.
  • At least one blocking element for blocking light that deviates from a predetermined light corridor which comprises the aforementioned transparent light path between the optical window and the investigation region.
  • Said predetermined light corridor usually corresponds to the path a light beam would take under idealized conditions, i.e. if all optical components, surfaces etc. would be perfectly aligned and free from contaminations or damages such that no scattering of light could occur.
  • the blocking element is therefore to be understood in the following as “at least one of the possibly several blocking elements”.
  • the described opto -mechanical arrangement can limit the disturbances that may be caused by deviations from ideal conditions, for example due to scattered light generated at contaminations on the optical window(s).
  • the opto -mechanical arrangement thus allows for more accurate measurements and helps to increase the robustness of the setup it is used in.
  • the blocking element comprises an opaque material with at least one transparent opening that encloses the predetermined light corridor. Light that deviates from the predetermined light corridor, i.e. that does not pass through the transparent opening, impinges onto the opaque material and will thus be prevented from further propagation.
  • an opaque blocking element can readily be produced, for example by staining or coating transparent parts of the carrier and/or by punching holes into a non-transparent sheet material.
  • the size of the transparent opening(s) may optionally be adjustable. This can for example be realized by diaphragm-mechanisms as they are known from photography.
  • the blocking element with a transparent opening may further optionally be adapted to absorb and/or divert light that does not pass through the opening. This can for example be achieved by light absorbing materials or by the arrangement of reflective wedges around the opening. Absorption or diversion of the off-opening light prevents that this light will find another way (e.g. by diffraction or multiple reflections) through or around the blocking element.
  • the blocking element may completely or at least partially be integrated into the carrier, for example embedded in a transparent plastic carrier material, or the blocking element may be attached (e.g. glued) to the optical window of the carrier.
  • the blocking element can be precisely aligned during fabrication of the carrier. Moreover, it is guaranteed that the exact alignment will remain throughout the application of the opto -mechanical arrangement.
  • the blocking element is arranged a distance away from the carrier, i.e. it is a component distinct from and unconnected to the carrier. This may be advantageous as deviations of a light beam can be corrected at their origin and/or right before they have negative effects on e.g. a detection process.
  • the predetermined beam corridor may in general have an arbitrary shape and dimension.
  • the predetermined beam corridor corresponds to the ideal path of a parallel light beam, i.e. of a bundle of parallel (light or geometrical) rays. This corresponds to the typical situation that a light source and a light detector are located a distance away from the carrier and that a parallel light beam is sent from the light source into the carrier, from which it returns to the detector after some interactions, wherein diversion of said light beam shall be avoided to allow for a geometrically compact design.
  • the op to -mechanical arrangement comprises indeed two, preferably three blocking elements disposed at different positions along the predetermined beam corridor. As there is always a (small) probability that unwanted light can pass a single blocking element, the risk of having unwanted light at the destination of the light beam can significantly be reduced if several blocking elements are used.
  • the invention further relates to a microelectronic sensor device for examinations in a sample chamber, wherein the term “examination” is to be understood in a broad sense, comprising any kind of manipulation and/or interaction of light with some entity in the sample chamber.
  • the examinations may preferably comprise the qualitative or quantitative detection of target components comprising label particles, wherein the target components may for example be biological substances like biomolecules, complexes, cell fractions or cells.
  • the microelectronic sensor device comprises:
  • the light source may for example be a laser or a light emitting diode (LED), optionally provided with some optics for shaping and directing the input light beam.
  • the input light beam that is directed towards the contact surface may be used for many different purposes, for example to initiate chemical reactions, to stimulate fluorescence, or just to illuminate some region for visual inspection.
  • the input light beam is reflected at the contact surface as a beam that will be called “output light beam” in the following.
  • this reflection takes place as a “total internal reflection” (TIR), which requires that the refractive index of the carrier is larger than the refractive index of the material adjacent to the contact surface.
  • total internal reflection shall include the case called “frustrated total internal reflection” (FTIR), where some of the incident light is lost (absorbed, scattered etc.) during the reflection process.
  • FTIR frustrated total internal reflection
  • the microelectronic sensor device comprises a light detector for detecting a characteristic parameter of the output light beam.
  • the characteristic parameter may particularly be related to the amount of light in the output light beam, expressed for example as the intensity of this beam in its cross section.
  • the light detector may comprise any suitable sensor or plurality of sensors by which light of a given spectrum can be detected, for example photodiodes, photo resistors, photocells, a CCD chip, or a photo multiplier tube.
  • at least one of the blocking elements is preferably arranged in the path of the input light beam and/or in the path of the output light beam. Blocking elements at different positions can provide different functions:
  • the output light beam In the path of the output light beam, they can suppress light scattered at structures of the carrier and/or light that originates from other sources than the input light beam (e.g. ambient light or fluorescence).
  • the input light beam e.g. ambient light or fluorescence
  • the invention further relates to the use of the microelectronic device described above for molecular diagnostics, biological sample analysis, or chemical sample analysis, food analysis, and/or forensic analysis.
  • Molecular diagnostics may for example be accomplished with the help of magnetic beads or fluorescent particles that are directly or indirectly attached to target molecules.
  • Figure 1 schematically shows the general setup of a microelectronic sensor device with various possible sources of light deviations
  • Figures 2 to 9 show various possible positions for blocking elements of an opto -mechanical arrangement according to the present invention.
  • Figure 1 shows a general setup with a microelectronic sensor device according to the present invention.
  • a central component of this setup is the carrier 11 that may for example be made from glass or transparent plastic like poly-styrene.
  • the carrier 11 is located next to a sample chamber 2 in which a sample fluid with target components to be detected (e.g. drugs, antibodies, DNA, etc.) can be provided.
  • the sample further comprises magnetic particles, for example superparamagnetic beads, wherein these particles are usually bound as labels to the aforementioned target components.
  • target particle 1 For simplicity only the combination of target components and magnetic particles is shown in the Figure and will be called “target particle 1 " in the following. It should be noted that instead of magnetic particles other label particles, for example electrically charged or fluorescent particles, could be used as well.
  • the interface between the carrier 11 and the sample chamber 2 is formed by a surface called “contact surface” 12. This contact surface 12 is coated with capture elements, e.g. antibodies, which can specifically bind the target particles.
  • the sensor device comprises a magnetic field generator 41, for example an electromagnet with a coil and a core, for controllably generating a magnetic field at the contact surface 12 and in the adjacent space of the sample chamber 2.
  • a magnetic field generator 41 for example an electromagnet with a coil and a core, for controllably generating a magnetic field at the contact surface 12 and in the adjacent space of the sample chamber 2.
  • the target particles 1 can be manipulated, i.e. be magnetized and particularly be moved (if magnetic fields with gradients are used).
  • the sensor device further comprises a light source 21 that generates an input light beam Ll (solid line) which is transmitted into the carrier 11 through an "entrance window" 14.
  • a collimator lens may be used inside the light source 21 to make the input light beam Ll parallel, and a pinhole of e.g. 0.5 mm may be used to reduce the beam diameter.
  • the input light beam Ll arrives at the contact surface 12 at an angle larger than the critical angle ⁇ c of total internal reflection (TIR) and is therefore totally internally reflected in an "output light beam” L2 (solid line).
  • the output light beam L2 leaves the carrier 11 through another surface ("exit window” 15) and is detected by a light detector 31.
  • the light detector 31 determines the amount of light of the output light beam L2 (e.g. expressed by the light intensity of this light beam in the whole spectrum or a certain part of the spectrum).
  • the measured sensor signals are evaluated and optionally monitored over an observation period by an evaluation and recording module (not shown) that is coupled to the detector 31. It is possible to use the detector 31 also for the sampling of fluorescence light emitted by fluorescent particles 1 which were stimulated by the input light beam Ll, wherein this fluorescence may for example spectrally be discriminated from reflected light L2.
  • the described microelectronic sensor device applies optical means for the detection of target particles 1.
  • the detection technique should be surface-specific. As indicated above, this is achieved by using the principle of frustrated total internal reflection (FTIR). This principle is based on the fact that an evanescent wave penetrates (exponentially dropping) into the sample 2 when the incident light beam Ll is totally internally reflected.
  • FTIR frustrated total internal reflection
  • this evanescent wave then interacts with another medium like the bound target particles 1, part of the input light will be coupled into the sample fluid (this is called "frustrated total internal reflection"), and the reflected intensity will be reduced (while the reflected intensity will be 100% for a clean interface and no interaction).
  • the amount of disturbance i.e. the amount of target particles on or very near (within about 200 nm) to the TIR surface (not in the rest of the sample chamber 2)
  • the reflected intensity will drop accordingly. This intensity drop is a direct measure for the amount of bonded target particles 1, and therefore for the concentration of target particles in the sample.
  • the described procedure is independent of applied magnetic fields. This allows real-time optical monitoring of preparation, measurement and washing steps.
  • the monitored signals can also be used to control the measurement or the individual process steps.
  • medium A of the carrier 11 can be glass and/or some transparent plastic with a typical refractive index of 1.52.
  • the carrier 11 can consist of a relatively simple, injection-molded piece of polymer material.
  • the contact surface 12 in a disposable cartridge can be optically scanned over a large area.
  • large-area imaging is possible allowing a large detection array.
  • Such an array located on an optical transparent surface
  • the method also enables high-throughput testing in well-plates by using multiple beams and multiple detectors and multiple actuation magnets (either mechanically moved or electro-magnetically actuated).
  • Actuation and sensing are orthogonal: Magnetic actuation of the target particles (by large magnetic fields and magnetic field gradients) does not influence the sensing process.
  • the optical method therefore allows a continuous monitoring of the signal during actuation. This provides a lot of insights into the assay process and it allows easy kinetic detection methods based on signal slopes.
  • the system is really surface sensitive due to the exponentially decreasing evanescent field.
  • the detected drop in the intensity of the reflected light beam L2 should accurately correspond to the amount of light which is scattered and/or absorbed at the contact surface 12.
  • source light Ll being scattered from contamination or damage of the optical windows 14, 15 (in particular the entrance window 14) can reach the detector 31 without being reflected in the investigation region ("biospot") of the contact surface where the bound target particles 1 are. This part of the light therefore gives a constant, but a-priori unknown offset to the detector signal, affecting the accuracy of the measurement.
  • a predetermined beam corridor i.e. particularly scattered light.
  • This can be achieved by spatial filtering, e.g. by arranging aligned beam blocks such as a pinhole in the source light path (around the input light beam Ll) and/or in the detector light path (around output light beam L2). The latter will also minimize unwanted scattering from the contact surface 12.
  • FIGS 2 to 9 schematically illustrate different embodiments of optomechanical arrangements that comprise the aforementioned blocking means.
  • the drawings of these Figures only show the main components of the microelectronic sensor device, i.e. the transparent carrier 11 with its two optical windows, the light source, the light detector, and, in different positions, blocking elements 51 to 55, realized e.g. as pinholes in an opaque material.
  • Dotted lines in the Figures indicate various light beams originating for example from scattering of the input light beam or light that is derived therefrom.
  • Figure 2 shows a first blocking element 51 that is integrated into the carrier close to the investigation region. This blocking element 51 effectively blocks light that was scattered at the optical entrance window.
  • Figure 3 shows a blocking element 52 located on the exit window 15 that blocks light scattered at the entrance window and/or at the contact surface 12.
  • Figure 4 shows a blocking element 53 located immediately in front of the detector 31 which is able to block scattered light from various origins.
  • the blocking elements 51, 52, 53 shown in Figures 2 to 4 have a similar effect in case of a parallel input light beam and if the entrance window is the only scattering surface.
  • a non-parallel (divergent or convergent) incoming beam has however a range of directions, usually around the desired direction. After reflection, part of this light may erroneously end up at the detector 31.
  • a beam divergence in the input light beam can (only) be treated in a similar way as shown in Figures 2 to 4 in the absence of scattering surfaces.
  • analysis shows that the main problem areas are diverging (or converging) beams, a scattering at the entrance window, and a scattering at the contact surface (the exit window is usually not critical).
  • the isolated problems can be suppressed using a single beam block. In practice, however, the three problem areas can occur simultaneously. In that case, a single pinhole or the like is no longer sufficient, and at least two well-chosen beam blocks are required. Such designs are shown in Figures 5 to 9.
  • Figure 5 shows a combination of the blocking elements 52 and 53 on the exit window and in front of the light detector, respectively.
  • These two aligned beam blocks in the detector path are a simple configuration with several beam blocks, but alignment will be critical, especially for the beam block 53 closest to the detector.
  • Figure 6 illustrates the combination of one blocking element 51 in front of the investigation region and one blocking element 52 in the detector path, close to (or on) the exit window (to avoid light mixing due to possible exit window scattering). As shown, this configuration works for blocking scattered light from the entrance window and the investigation region. However, when beam divergence (or convergence) is also present, erroneous light can still end up at the detector.
  • minimizing beam divergence in the input light beam can be achieved by at least one blocking element 55 close to or even on the entrance window, but preferably by two or more aligned beam blocks, e.g. with an additional blocking element 54 immediately behind the light source.
  • FIGS 8 and 9 Additional beam blocks may be added to improve performance or relax tolerances.
  • the embodiment of Figure 8 is similar to that of Figure 5 but uses an additional beam block 55 near or at the entrance window to suppress beam divergence.
  • the embodiment of Figure 9 uses a further internal beam block 51 close to and in front of the investigation region. This helps in preventing erroneous illumination of the investigation region, leading to more relaxed tolerances for the beam block closest to the detector. Best results are achieved for a highly parallel light beam with a small diameter (best light efficiency) entering the entrance window 14, and preferably two (or more) aligned beam blocks with an opening diameter equal to or smaller than the original beam in the detector light path.
  • the problems described above are even more critical.
  • the beam blocks in the illumination part either only transmit the main beam (single aperture per beam block), or only transmit each separate beam (e.g. array of apertures corresponding to each beam).
  • the beam blocks in the detection part either only transmit the main beam (single aperture per beam block), or only transmit each separate beam (e.g. array of apertures corresponding to each beam).
  • beam blocks should only transmit the main beam with negligible edge diffraction.
  • absorbing or wedge shaped blocks e.g. absorbing or wedge shaped blocks
  • the sensor can comprise any suitable sensor to detect the presence of magnetic particles on or near to a sensor surface, based on any property of the particles, e.g. it can detect via magnetic methods, optical methods
  • moieties can be detected with sensor devices according to the invention, e.g. cells, viruses, or fractions of cells or viruses, tissue extract, etc.
  • the detection can occur with or without scanning of the sensor element with respect to the sensor surface.
  • - Measurement data can be derived as an end-point measurement, as well as by recording signals kinetically or intermittently.
  • the particles serving as labels can be detected directly by the sensing method.
  • the particles can be further processed prior to detection.
  • An example of further processing is that materials are added or that the (bio)chemical or physical properties of the label are modified to facilitate detection.
  • the device and method can be used with several biochemical assay types, e.g. binding/unbinding assay, sandwich assay, competition assay, displacement assay, enzymatic assay, etc. It is especially suitable for DNA detection because large scale multiplexing is easily possible and different oligos can be spotted via ink-jet printing on the optical substrate.
  • biochemical assay types e.g. binding/unbinding assay, sandwich assay, competition assay, displacement assay, enzymatic assay, etc.
  • the device and method are suited for sensor multiplexing (i.e. the parallel use of different sensors and sensor surfaces), label multiplexing (i.e. the parallel use of different types of labels) and chamber multiplexing (i.e. the parallel use of different reaction chambers).
  • the device and method can be used as rapid, robust, and easy to use point-of-care biosensors for small sample volumes.
  • the reaction chamber can be a disposable item to be used with a compact reader, containing the one or more field generating means and one or more detection means.
  • the device, methods and systems of the present invention can be used in automated high- throughput testing.
  • the reaction chamber is e.g. a well-plate or cuvette, fitting into an automated instrument.

Abstract

L'invention porte sur un agencement opto-mécanique pour fournir un accès optique à une chambre d'échantillon (2), comprenant un support (11) avec une surface de contact (12) vers ladite chambre d'échantillon (2) et avec au moins une fenêtre optique. De plus, l'agencement comprend au moins un élément de blocage (51-55) pour bloquer la lumière qui dévie d'un couloir de faisceau prédéterminé.
PCT/IB2008/052689 2007-07-09 2008-07-04 Agencement opto-mécanique pour fournir un accès optique à une chambre d'échantillon WO2009007888A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP07112058.8 2007-07-09
EP07112058 2007-07-09

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Publication Number Publication Date
WO2009007888A1 true WO2009007888A1 (fr) 2009-01-15

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9075052B2 (en) 2009-09-28 2015-07-07 Koninklijke Philips N.V. Biosensor system for single particle detection
EP3180601A4 (fr) * 2014-08-12 2018-05-02 Ecolab USA Inc. Fluorimètre à main
EP3683571A4 (fr) * 2017-10-19 2020-11-25 Konica Minolta, Inc. Fente d'élimination de lumière diffractée et système de détection d'échantillon optique utilisant cette dernière

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Publication number Priority date Publication date Assignee Title
US6570657B1 (en) * 1998-04-02 2003-05-27 Institut Fuer Physikalische Hochtechnolgolie E.V. Arrangement for surface plasmon resonance spectroscopy
US20030206291A1 (en) * 2002-05-06 2003-11-06 Leica Microsystems Inc. Optical configuration and method for differential refractive index measurements
US20050012932A1 (en) * 2003-05-27 2005-01-20 Aisin Seiki Kabushiki Kaisha Surface plasmon resonance measuring device

Patent Citations (3)

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Publication number Priority date Publication date Assignee Title
US6570657B1 (en) * 1998-04-02 2003-05-27 Institut Fuer Physikalische Hochtechnolgolie E.V. Arrangement for surface plasmon resonance spectroscopy
US20030206291A1 (en) * 2002-05-06 2003-11-06 Leica Microsystems Inc. Optical configuration and method for differential refractive index measurements
US20050012932A1 (en) * 2003-05-27 2005-01-20 Aisin Seiki Kabushiki Kaisha Surface plasmon resonance measuring device

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9075052B2 (en) 2009-09-28 2015-07-07 Koninklijke Philips N.V. Biosensor system for single particle detection
US9261501B2 (en) 2009-09-28 2016-02-16 Koninklijke Philips N.V. Biosensor system for single particle detection
EP3180601A4 (fr) * 2014-08-12 2018-05-02 Ecolab USA Inc. Fluorimètre à main
US10254224B2 (en) 2014-08-12 2019-04-09 Ecolab Usa Inc. Handheld fluorometer
EP3719480A1 (fr) * 2014-08-12 2020-10-07 Ecolab USA Inc. Un fluoromètre pour mesurer la fluorescence d'un échantillon
EP3683571A4 (fr) * 2017-10-19 2020-11-25 Konica Minolta, Inc. Fente d'élimination de lumière diffractée et système de détection d'échantillon optique utilisant cette dernière
US11169090B2 (en) 2017-10-19 2021-11-09 Konica Minolta, Inc. Diffracted light removal slit and optical sample detection system using same

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