WO2009027896A1 - Dispositif à capteur microélectronique à détection d'humidité - Google Patents

Dispositif à capteur microélectronique à détection d'humidité Download PDF

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Publication number
WO2009027896A1
WO2009027896A1 PCT/IB2008/053308 IB2008053308W WO2009027896A1 WO 2009027896 A1 WO2009027896 A1 WO 2009027896A1 IB 2008053308 W IB2008053308 W IB 2008053308W WO 2009027896 A1 WO2009027896 A1 WO 2009027896A1
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WIPO (PCT)
Prior art keywords
contact surface
light beam
detector
sensor device
medium
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Application number
PCT/IB2008/053308
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English (en)
Inventor
Coen A. Verschuren
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Koninklijke Philips Electronics N. V.
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Publication date
Application filed by Koninklijke Philips Electronics N. V. filed Critical Koninklijke Philips Electronics N. V.
Publication of WO2009027896A1 publication Critical patent/WO2009027896A1/fr

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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G01N33/54366—Apparatus specially adapted for solid-phase testing
    • G01N33/54373—Apparatus specially adapted for solid-phase testing involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings
    • 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
    • G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
    • G01N27/72—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating magnetic variables
    • G01N27/74—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating magnetic variables of fluids
    • G01N27/745—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating magnetic variables of fluids for detecting magnetic beads used in biochemical assays

Definitions

  • the invention relates to a wetting detector and a method for detecting which one of a first and a second medium is present at a contact surface of a carrier. Moreover, it relates to a microelectronic sensor device comprising such a wetting detector and its use.
  • a magnetic sensor device is known from the WO 2005/010543 Al and
  • WO 2005/010542 A2 (which are incorporated into the present application by reference) which may for example be used in a micro fluidic biosensor for the detection of molecules, e.g. biological molecules, labeled with magnetic beads.
  • the magnetic sensor device is provided with an array of sensor units comprising wires for the generation of a magnetic field and Giant Magneto Resistances (GMR) for the detection of stray fields generated by magnetized beads.
  • GMR Giant Magneto Resistances
  • the signal of the GMRs is then indicative of the number of the beads near the sensor unit.
  • a problem of this and similar sensor devices is that they require a sufficient contact of the sample to the contact surface where sensing takes place. Disturbances of this contact, for example by gas bubbles, can therefore severely deteriorate the measurements.
  • the invention relates to a wetting detector for detecting which one of a first and a second medium is present at a contact surface of a carrier.
  • the wetting detector comprises the following components: a) A light source for emitting a light beam, called “primary light beam” in the following for purposes of reference, onto a test region of the contact surface at an angle of incidence that has a value between the critical angles of total internal reflection (TIR) prevailing at the contact surface with respect to the first medium and the second medium, respectively.
  • 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 primary light beam.
  • a light detector for detecting a light beam called “secondary light beam” in the following for purposes of reference, that originates from a reflection or a refraction of the primary light beam at the contact surface.
  • the 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.
  • the "carrier” that is mentioned in connection with the wetting detector may be a component of this wetting detector or not. It is often made from a transparent material, for example glass or polystyrene, to allow the propagation of light of a given (particularly visible, UV, and/or IR) spectrum. Moreover, the carrier will typically be a disposable component (synonymously called “cartridge").
  • contact surface is chosen primarily as a unique reference to a particular part of the surface of the carrier, and though a sample will in many applications actually contact said surface, this does not necessarily need to be the case.
  • the first and the second medium may be arbitrary materials, provided that they have different refractive indices (and therefore different critical angles of TIR at the contact surface with respect to the carrier material).
  • the refractive indices of the first and second medium may be smaller or larger than the refractive index of the carrier (including the case that one of them is smaller and the other is larger).
  • the refractive indices of both the first and the second medium are smaller than the refractive index of the carrier; a (primary) light beam impinging onto the contact surface from the side of the carrier can then experience total internal reflection provided that its angle of incidence is sufficiently large.
  • the described wetting detector has the advantage that it provides a simple but reliable means for detecting if a first or a second medium is present at the contact surface of a carrier.
  • a further advantage is that the detection is achieved with optical means and does not require a physical contact or the application of electricity to the carrier.
  • the invention further relates to a microelectronic sensor device for examining a sample, wherein the examination shall comprise any kind of manipulation and/or interaction with the sample.
  • the examination 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 following components: a) A carrier with a sample chamber in which a sample to be examined can be provided and with a transparent light channel comprising the path of a light beam that propagates from an entrance window of the carrier to a test region at a contact surface of the sample chamber and that is reflected there, for example towards an exit window of the carrier or towards some region where it is absorbed.
  • sample chamber is typically an empty cavity or a cavity filled with some substance like a gel that may absorb a sample substance; it may be an open cavity, a closed cavity, or a cavity connected to other cavities by fluid connection channels.
  • a wetting detector of the kind described above for emitting a primary light beam through the entrance window onto the test region at an angle of incidence between the critical angles of total internal reflection with respect to a first and second medium, respectively, and for detecting a secondary light beam that originates from a reflection or a refraction of the primary light beam at the contact surface.
  • the microelectronic sensor device comprises as a principal component a wetting detector of the kind described above.
  • a wetting detector of the kind described above.
  • the microelectronic sensor device preferably comprises a sensor element that is suited for sensing a parameter of interest from a sample and/or from target particles in a sample, for example an optical, magnetic, mechanical, acoustic, thermal and/or electrical sensor element.
  • a magnetic sensor element may particularly comprise a coil, Hall sensor, planar Hall sensor, flux gate sensor, SQUID (Superconducting Quantum Interference Device), magnetic resonance sensor, magneto -restrictive sensor, or magneto -resistive sensor of the kind described in the WO 2005/010543 Al or
  • WO 2005/010542 A2 especially a GMR (Giant Magneto Resistance), a TMR (Tunnel Magneto Resistance), or an AMR (Anisotropic Magneto Resistance).
  • An optical sensor element may particularly be adapted to detect variations in an output light beam that arise from a frustrated total internal reflection due to target particles at a sensing surface.
  • Other optical, mechanical, acoustic, and thermal sensor concepts are described in the WO 93/22678, which is incorporated into the present text by reference.
  • the sensor element may (exclusively or in addition) be used as light detector of the wetting detector, i.e. for sensing the secondary light beam.
  • the microelectronic sensor device may comprise a fluid-mo vement-device for inducing a flow of a sample fluid within the sample chamber.
  • a sample to be examined can for example be transported into the reach of sensor elements, or a sample can be mixed to establish homogeneous conditions.
  • the fluid-movement-device may optionally comprise microfluidic pumping elements, valves and the like.
  • one of the first and the second medium is preferably a liquid and the other a gas. In this case it is possible to detect if the wetting of the contact surface with the liquid medium has taken place or not, which is a crucial precondition for the proper function of many biosensors that shall measure properties of a liquid sample (e.g. blood or saliva).
  • a liquid sample e.g. blood or saliva
  • the wetting detector and/or the microelectronic sensor device may preferably comprise an evaluation unit for evaluating a detection signal that is provided by the light detector, wherein this evaluation takes place with respect to the presence of the first or the second medium at the contact surface.
  • the evaluation unit may for example be realized by dedicated electronic hardware, digital data processing hardware with appropriate software, or a mixture of both.
  • the detection signal provided by the light detector may particularly represent the amount of light that was detected in the secondary light beam coming from the contact surface, and the evaluation unit may be adapted to infer from this amount of light if the first or the second medium is present in the test region.
  • the presence of one of these media will be accompanied by the occurrence of total internal reflection while the presence of the other medium will not. Accordingly, the light of the primary light beam will completely be converted into a (totally internally) reflected beam or it will be subdivided between a reflected and a refracted beam.
  • the presence or absence of total internal reflection i.e. the presence of the first or the second medium at the contact surface, will therefore change the amount of light in the secondary light beam, a fact that can be exploited by the evaluation unit.
  • the amount of light in the secondary light beam is evaluated, the amount of light in the primary light beam is preferably taken into account, for example in a normalization process, to make the result robust with respect to variations of the power of the light source.
  • the wetting detector may for example comprise a second light source for emitting a further primary light beam onto the second test region of the contact surface at an angle between the critical angles of total internal reflection with respect to the first and the second medium, respectively, and a second light detector for detecting a further secondary light beam that originates from a reflection or a refraction of the further primary light beam at the second test region.
  • scanning may be applied to direct a single primary light beam from a single light source in succession to the first and the second test region and/or to direct secondary light beams coming from the first and the second test region, respectively, in succession onto a single light detector.
  • the provision of two or more test regions at the contact surface allows to check for the presence of the first or second medium at more than one location, thus increasing the reliability of the detection result with respect to a generalization for the whole contact surface.
  • the previously mentioned evaluation unit is adapted to infer which one of the first and the second medium is present at the contact surface in a zone between the two different test regions.
  • the evaluation unit may for instance control which media have entered and left the zone between the test regions, which allows to infer which medium is currently in that zone.
  • the presence of a gas bubble in a sensor zone between the test regions may thus be detected even if no gas bubble is present in the test regions themselves.
  • the evaluation unit is adapted to detect a misalignment of the carrier with respect to the wetting detector.
  • a detection may for example be based on the observation that no secondary light beam at all or only an extraordinarily small secondary light beam is observed, which indicates that the light path from the light source to the light detector is corrupted.
  • the invention further relates to a method for detecting which one of a first and a second medium is present at a contact surface of a carrier, the method comprising the following steps: a) Emitting a primary light beam onto a test region of the contact surface at an angle of incidence between the critical angles of total internal reflection with respect to the first and the second medium, respectively. b) Detecting a secondary light beam that originates from a reflection or a refraction of the primary light beam at the contact surface.
  • the method comprises in general form the steps that can be executed with a wetting detector of the kind described above. Therefore, reference is made to the preceding description for more information on the details, advantages and improvements of that method.
  • 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 shows schematically a microelectronic sensor device with a wetting detector according to the present invention, wherein the drawing corresponds to a section along line I-I indicated in Figure 2;
  • Figure 2 shows a top view of the microelectronic sensor device;
  • Figure 3 corresponds to a section through the microelectronic sensor device along line III-III of Figure 2.
  • Figure 1 illustrates a microelectronic magnetic sensor device according to the present invention in the particular application as a biosensor for the detection of magnetically interactive particles 1, e.g. biomolecules labeled with super-paramagnetic beads, in a sample chamber 202.
  • Magneto-resistive biochips or biosensors have promising properties for bio-molecular diagnostics, in terms of sensitivity, specificity, integration, ease of use, and costs. Examples of such biochips are described in the WO 2003/054566, WO 2003/054523, WO 2005/010542 A2, WO 2005/010543 Al, and WO 2005/038911 Al, which are incorporated into the present application by reference.
  • the microelectronic sensor device may for example be intended for roadside drugs of abuse testing in saliva. Drugs of abuse are generally small molecules that only possess one epitope and for this reason cannot be detected by a sandwich assay.
  • a competitive or inhibition assay is the method to detect these molecules.
  • a competitive assay setup can be realized by coupling the target molecules of interest onto a sensing surface 212' above a sensor element 220, and link antibodies to a detection tag (e.g. an enzyme, fluorophore, or, as assumed in Figure 1, a magnetic bead), yielding the target particles 1 of Figure 1. This system is used to perform a competitive assay between the target molecules from the sample and the target molecules on the surface, using the tagged antibodies.
  • a detection tag e.g. an enzyme, fluorophore, or, as assumed in Figure 1, a magnetic bead
  • the assay should be fast ( ⁇ 1 min) and robust.
  • the superparamagnetic beads can be used in the magnetic biosensors both for detection as well as for actuation (attraction of the magnetic particles to the sensing surface 212' speeds up the binding process, and magnetic washing removes the unbound beads).
  • an optical, contactless wetting detection in a carrier or cartridge 200 (such as a disposable cartridge used for a biosensor) is proposed here that exploits the difference in refractive index between different media, particularly between air (empty cartridge) and the liquid to be tested (the latter being larger than 1 , typically 1.33).
  • the principle used in this approach is to detect the amount of light that is reflected from the cartridge interface with the fluidics channel.
  • Figure 1 illustrates a corresponding "wetting detector” 100 that is added to the biosensor and that comprises the following components: a) A light source 110, e.g. a laser, for emitting a "primary light beam” LO via an entrance window 215 onto a test region 213 at the contact surface 212 of the cover 214 of the carrier 200. b) A light detector 120 behind a pinhole 121 (or a similar structure to shield light from other directions) for detecting a "secondary light beam” LR that originates from a reflection of the primary light beam LO at the contact surface 212.
  • the cover 214 of the cartridge should be transparent for the light of the light source 110 at least in a light channel along the paths of the light beams LO, LR.
  • An evaluation module 130 e.g. a digital data processor with associated software, receiving the detection signals that encode the detection results of the light detector 120 and optionally also receiving an information from the light source 110 about the intensity of the primary light beam LO.
  • An evaluation module 130 e.g. a digital data processor with associated software, receiving the detection signals that encode the detection results of the light detector 120 and optionally also receiving an information from the light source 110 about the intensity of the primary light beam LO.
  • the intensity of the secondary light beam LR is sensed by the light detector 120, resulting in a high signal when the light source 120 is on and there is no liquid in the test region 213 and in a low signal if liquid is present (indicating good wetting). Even when the injected liquid is highly dispersive and/or absorbing, the intensity at the detector will still drop due to the presence of the liquid. In this way, wetting is still correctly detected.
  • the differences in the intensity of the secondary light beam LR that are sensed by the light detector 120 are evaluated by the evaluation module 130 with respect to the presence of gas or liquid in the test region 213. As only (part of) the fluidics part of the cartridge 200 needs to be transparent, the method can easily be used in combination with a GMR-based biosensor platform as shown in the Figures.
  • a prism- like structure like that shown in Figure 1 can be used.
  • Other possibilities may contain spherical or cylindrical surfaces, and even grating structures.
  • the refracted light beam LT instead of LR
  • This light beam LT could for instance be measured by an optical particle- sensor element 220 or by some optical sensor (e.g. a photodiode) added to a (non- optical, e.g. GMR-based) particle-sensor element 220.
  • Figure 2 shows a top view onto the microelectronic sensor device with the line I-I indicating the section shown in Figure 1.
  • the sample chamber 202 is (part of) a fluidics channel through which sample fluid is pumped with a fluid-movement-device (not shown) in the direction indicated by the arrow.
  • the lower part 211 of the cartridge 200 is non-transparent and contains a GMR chip 220 for sensing. A structure for optical detection might be used as well.
  • Figure 3 shows in a section through the microelectronic sensor device (along line HI-III of Figure 2) two electromagnets 231, 232 directly above and below the bio-detection area above the sensor element 220.
  • the magnet diameter is large compared to the cartridge height, wetting detection directly at this area, i.e. in the test region 213 above the GMR sensor 220, is not easy. It is therefore proposed to do detection in test regions 213a, 213b outside the bio-detection area.
  • continuous wetting detection in a first test region 213a directly in front (left in Figure 2) of the bio- detection area allows reliable detection. To improve reliability, this can especially be combined with wetting detection in a second test region 213b behind the bio-detection area.
  • a drop in signal in the first test region 213a indicates the successful injection of fluid, and a drop in signal in the second test region 213b indicates the arrival of fluid at the end of the channel 202.
  • a drop in signal in the second test region 213b indicates the arrival of fluid at the end of the channel 202.
  • the bio-detection area is also filled with liquid.
  • an air bubble may have entered the channel 202 and gets stuck in the bio-detection area.
  • This situation can be detected by monitoring the signal of the first test region 213a: after injection, it should stay low until at least a short time after the fluid has reached the second test region 213b (end of channel, fluid stopped moving). If this is the case, no air bubble has passed the first test region 213a. In case an air bubble does pass, the signal from the first test region 213a will (briefly) go up again after the first detection.
  • a cartridge 200 provided with transparent windows 215, 216 coinciding with the light beams' nominal entrance and exit areas and being non-transparent outside these areas has the additional advantage that it can also be used to check and confirm correct insertion of the cartridge 200 into the reader: The reader expects to find an empty cartridge 200, which should give a "high” signal (secondary light beam LR hits detector 120 through pinhole). Misalignment of the cartridge 200 will however lead to a "low” signal, since the primary light beam can no longer reach the detector (blocked by one or both windows 215, 216).
  • the sensor element can be any suitable sensor to detect the presence of 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 (e.g. imaging, fluorescence, chemiluminescence, absorption, scattering, surface plasmon resonance, Raman, etc.), sonic detection (e.g. surface acoustic wave, bulk acoustic wave, cantilever, quartz crystal etc), electrical detection (e.g. conduction, impedance, amperometric, redox cycling), etc.
  • optical methods e.g. imaging, fluorescence, chemiluminescence, absorption, scattering, surface plasmon resonance, Raman, etc.
  • sonic detection e.g. surface acoustic wave, bulk acoustic wave, cantilever, quartz crystal etc
  • electrical detection e.g. conduction, impedance, amperometric, redox cycling
  • a magnetic sensor can be any suitable sensor based on the detection of the magnetic properties of the particle on or near to a sensor surface, e.g. a coil, magneto -resistive sensor, magneto -restrictive sensor, Hall sensor, planar Hall sensor, flux gate sensor, SQUID, magnetic resonance sensor, etc.
  • a sensor surface e.g. a coil, magneto -resistive sensor, magneto -restrictive sensor, Hall sensor, planar Hall sensor, flux gate sensor, SQUID, magnetic resonance sensor, etc.
  • 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.
  • 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.

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Abstract

L'invention concerne un détecteur d'humidité (100) permettant de détecter la présence de l'un ou l'autre de deux milieux présents à une surface de contact (212) d'un support (200). En mode de réalisation préféré, ce détecteur (100) comprend une source lumineuse (110) émettant un faisceau de lumière primaire (L0) vers une zone test (213) à la surface de contact (212), à partir de laquelle un faisceau de lumière secondaire (LR) est réfléchi et ensuite détecté par un détecteur lumineux (120). L'angle (ϑ) d'incidence du faisceau primaire (L0) est choisi de manière à se situer entre les angles critiques (ϑc,a, ϑc,f) de réflexion interne totale des deux milieux cités. La présence ou l'absence de réflexion interne totale, que l'on peut détecter dans la quantité de lumière dans le faisceau secondaire (LR) permet alors d'établir si l'on est en présence du premier milieu ou du second milieu à la surface de contact (212). Ce détecteur peut être utilisé en particulier dans un dispositif à capteur microélectronique pour déterminer si la surface de contact (212) est humidifiée par un échantillon liquide ou si par exemple des bulles de gaz (3) sont présentes.
PCT/IB2008/053308 2007-08-24 2008-08-18 Dispositif à capteur microélectronique à détection d'humidité WO2009027896A1 (fr)

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EP07114946 2007-08-24

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Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012164438A1 (fr) 2011-06-01 2012-12-06 Koninklijke Philips Electronics N.V. Détermination d'une caractéristique d'écoulement d'un objet mobile dans un élément
WO2013013966A1 (fr) * 2011-07-25 2013-01-31 Nestec S.A. Système de détecteur de bulles d'air réfléchissant les infrarouges
WO2013071910A1 (fr) * 2011-11-17 2013-05-23 Forschungszentrum Jülich GmbH Détecteur de particules magnétiques contenues dans un liquide
JP2014521060A (ja) * 2011-06-28 2014-08-25 コーニンクレッカ フィリップス エヌ ヴェ 体液の検査用手段
WO2014138179A1 (fr) * 2013-03-08 2014-09-12 Magellan Diagnostics, Inc. Appareil et procédé pour analyser des échantillons multiples
JP2015099166A (ja) * 2015-03-02 2015-05-28 コニカミノルタ株式会社 計測装置及び計測方法
CN103826674B (zh) * 2011-07-25 2016-11-30 雀巢产品技术援助有限公司 红外线反射管线中空气传感器系统
CN107991266A (zh) * 2017-11-22 2018-05-04 合肥泰禾光电科技股份有限公司 一种黄曲霉素的在线检测装置
WO2019070486A1 (fr) * 2017-10-04 2019-04-11 Eli Lilly And Company Tubulure ayant des marqueurs visuels pour la visualisation d'un fluide à l'intérieur de celle-ci
CN111634436A (zh) * 2020-06-03 2020-09-08 北京星网宇达科技股份有限公司 靶机发射控制方法、装置、靶机飞控计算机及存储介质

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EP0289833A2 (fr) * 1987-05-07 1988-11-09 Becton, Dickinson and Company Procédé et capteur de détection de présence de bulles d'air dans un liquide
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US20070166195A1 (en) * 2004-05-14 2007-07-19 Honeywell International Inc. Analyzer system

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Publication number Priority date Publication date Assignee Title
EP0289833A2 (fr) * 1987-05-07 1988-11-09 Becton, Dickinson and Company Procédé et capteur de détection de présence de bulles d'air dans un liquide
US5072595A (en) * 1990-09-19 1991-12-17 Barbier William J Apparatus for detecting small bubbles in a pressurized fluid stream
US20070166195A1 (en) * 2004-05-14 2007-07-19 Honeywell International Inc. Analyzer system
US20070031283A1 (en) * 2005-06-23 2007-02-08 Davis Charles Q Assay cartridges and methods for point of care instruments

Cited By (17)

* Cited by examiner, † Cited by third party
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WO2012164438A1 (fr) 2011-06-01 2012-12-06 Koninklijke Philips Electronics N.V. Détermination d'une caractéristique d'écoulement d'un objet mobile dans un élément
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