WO2008128534A1 - Cuvette pour l'analyse optique de petits volumes - Google Patents

Cuvette pour l'analyse optique de petits volumes Download PDF

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Publication number
WO2008128534A1
WO2008128534A1 PCT/DE2008/000716 DE2008000716W WO2008128534A1 WO 2008128534 A1 WO2008128534 A1 WO 2008128534A1 DE 2008000716 W DE2008000716 W DE 2008000716W WO 2008128534 A1 WO2008128534 A1 WO 2008128534A1
Authority
WO
WIPO (PCT)
Prior art keywords
cuvette
channel
carrier substrate
structured carrier
optical analysis
Prior art date
Application number
PCT/DE2008/000716
Other languages
German (de)
English (en)
Inventor
Claudia Gärtner
Jens Aurich
Original Assignee
Analytik Jena Ag
Microfluidic Chipshop Gmbh
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 Analytik Jena Ag, Microfluidic Chipshop Gmbh filed Critical Analytik Jena Ag
Publication of WO2008128534A1 publication Critical patent/WO2008128534A1/fr

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Classifications

    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502715Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
    • 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
    • G01N21/01Arrangements or apparatus for facilitating the optical investigation
    • G01N21/03Cuvette constructions
    • 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
    • G01N21/25Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
    • G01N21/251Colorimeters; Construction thereof
    • G01N21/253Colorimeters; Construction thereof for batch operation, i.e. multisample apparatus
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/12Specific details about manufacturing devices
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/06Auxiliary integrated devices, integrated components
    • B01L2300/0627Sensor or part of a sensor is integrated
    • B01L2300/0654Lenses; Optical fibres
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/08Geometry, shape and general structure
    • B01L2300/0887Laminated structure
    • 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
    • G01N21/01Arrangements or apparatus for facilitating the optical investigation
    • G01N21/03Cuvette constructions
    • G01N2021/0325Cells for testing reactions, e.g. containing reagents
    • 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
    • G01N21/01Arrangements or apparatus for facilitating the optical investigation
    • G01N21/03Cuvette constructions
    • G01N2021/0346Capillary cells; Microcells
    • 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
    • G01N21/01Arrangements or apparatus for facilitating the optical investigation
    • G01N21/03Cuvette constructions
    • G01N21/05Flow-through cuvettes
    • G01N2021/054Bubble trap; Debubbling
    • 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
    • G01N21/01Arrangements or apparatus for facilitating the optical investigation
    • G01N21/03Cuvette constructions
    • G01N21/05Flow-through cuvettes
    • G01N2021/058Flat flow cell
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N2035/00178Special arrangements of analysers
    • G01N2035/00237Handling microquantities of analyte, e.g. microvalves, capillary networks

Definitions

  • the invention relates to a cuvette for the optical analysis of small volumes.
  • the disadvantage of this system is that it is a glass cuvette that has to be produced in a costly manner by glass structuring and joining of glass elements.
  • the measuring range of the known cuvettes is almost exclusively limited to one layer thickness except for the cuvette of Eppendorf called "UVette", which realizes two thicknesses.Therefore dilutions outside the cuvette and a new measurement are necessary for the acquisition of further measuring ranges.
  • Another disadvantage is that when measuring several samples, the cuvette must be replaced or cleaned.
  • none of the cuvettes is suitable for a simple, space-saving storage.
  • DE 197 07 044 A1 discloses a micromechanical transmission cell for determining an optical absorption of a sample fluid or as a reactor for exporting an optically detectable chemical reaction.
  • the micromechanical transmission cell has a container for holding the sample fluid, a Licht barnlassöffhung for introducing the light into the container and a reflector device which directs the light with respect to the container, that a large part of the light passes through the container without multiple reflections on one of the container walls.
  • a microfluidic module for chemical analysis in which a rapid sample change and thus inexpensive investigations of fast-running processes time-resolved and with small time constants is made possible and optionally at the same time allows the possibility of performing a scanning calorimetry, wherein the microfluidic module of a first chip, in which an outstretched channel region with a Y-shaped branched input region, to which two input channels connect, is introduced and the first chip is connected to a second chip covering, which is provided on the channel side with at least one thermosensitive thin-film element consists.
  • the disclosed systems are not an easy-to-use measuring device, such as a cuvette. Furthermore, the systems are not suitable for measuring different volumes of liquid or in different layer thicknesses.
  • the object of the present invention is to provide a cuvette for small volumes, which has the disadvantages of the prior art prevents, in particular directly in a system, only by supplying additional samples, measurements allows.
  • the present invention is a chip cuvette for small volume optical analysis.
  • the chip cuvette has a flat, planar shape, which is characterized in that it has a minimum layer of cuvette material when used as intended in a measuring channel at the measuring points.
  • the influence of the cuvette material itself is minimized to the measurement.
  • This thin cuvette material which is preferably in the form of films, overcomes the disadvantages of conventional cuvettes known hitherto and enables measurements even in the VUV range, even in the case where the cuvette material is a plastic polymer.
  • the chip cuvette according to the invention is characterized in that it is made up of at least two, preferably three layers, wherein at least one layer is optically transparent. All embodiments have in common that they consist of a structured layer (carrier substrate) with channels or through-holes, which is closed at least from one side, but particularly advantageously both sides with a thin, optically transparent film.
  • a structured layer carrier substrate
  • channels or through-holes which is closed at least from one side, but particularly advantageously both sides with a thin, optically transparent film.
  • the structured layer (carrier substrate) and the one film side may be formed in one piece.
  • the channel system in the structured layer serves to supply the sample to the actual, in the structured layer (Carrier substrate) located measuring cell, as a reservoir and as a reaction vessel, where it structurally passes into the measuring cell.
  • the carrier substrate may also have through holes connected to channels extending in the one outer layer and the two outer layers, respectively.
  • connection of the channel structures to the outside is realized by at least two fluidic interfaces and is used for filling with sample or for taking sample.
  • connections are designed in one embodiment of the chip cuvette according to the invention as a simple or conical through holes.
  • the chip cuvette is thereby unproblematic to handle since different pipettes can be used to fill the channel structures via the connections.
  • the automatic filling of the channel structures via the connections for example, with pipetting robots is possible.
  • the terminals of the channel structures can be used in a differently shaped fluid connection form, such as, for example, in the form of olives, lures or miniaturized Luer-like connections.
  • any evaporation problems that occur can be avoided according to the invention simply by covering or masking the Einfullöffhungen the structured layer (carrier substrate), for example. With a film.
  • the materials used for the chip cuvette according to the invention are a wide variety of plastic polymers, preferably transparent ones Polymers with low optical interferences such as COC, COP, PMMA, PC, etc., but also glass, quartz glass or other crystalline or amorphous materials in combination with thin glass, quartz or other transparent crystalline disks as a lid for use. That is, the chip cuvette may consist exclusively of a plastic, of different plastics or of one of the abovementioned non-plastic materials, which may also be combined with one another, or hybrid constructions of plastics and non-plastics (for example a combination of glass-plastic, Glass - plastic - glass, glass - plastic - glass plus additional connecting layer etc.).
  • Expansion stages of this platform include the integration of mixers in front of the measuring channels as well as the integration of distribution systems (channel systems) on the chip, in order to carry a sample to different measuring points in which, if necessary, reactions to be tracked can also take place due to the reagents provided.
  • Integrated mixers for creating dilution series are another option for enabling very different measuring ranges, even for the simultaneous acquisition of multiple analytes.
  • the input and output of light can be optimally designed, the scattered light significantly reduced and thus also sensitive fluorescence measurements are possible.
  • the chip cuvette in its design as a flat cuvette with several channel systems accommodates different samples or sample series and thus offers the possibility of a very simple and space-saving later storage. Possibly.
  • the chip cuvettes can also be frozen and thus made accessible to later analyzes. For archiving, labeling is possible via permanent markers as well as barcodes or RFID tags.
  • the channels of the chip cuvette according to the invention can, for example, be designed such that, with the same measuring arrangement, measurements can be carried out simultaneously or successively in different measuring ranges.
  • An embodiment of the chip cuvette according to the invention may, for example, be designed in such a way that a small channel is arranged on one side and a larger channel on the other side of the carrier substrate and the ends of which are connected by a hole or collide at the ends by their depths and so already make a breakthrough.
  • the chip cuvette may be provided with a depression above the channel to minimize the material thickness between sample and excitation light source as well as detector.
  • the chip cuvette can have a three-layer structure in which the connection of the small measuring volume with the large measuring volume is realized by a small through-channel or a small through-hole in the chip.
  • the inputs and outputs of the respective measuring elements can have different fluidic interfaces, for example bores with different diameters, in order to realize different possibilities of fluid supply (eg in order to inject or remove samples with different sized pipette tips.
  • interfaces can be designed in the form of conical inlet and outlet nozzles, which can be designed differently in order to be able to use the widest possible spectrum of different pipette tips with the chip cuvette.
  • the conical inlet nozzle according to the invention ensure a good seal against pipette tips and at the same time prevent closing of the channel by the pipette tip.
  • the fluidic interfaces may be provided with sealing rings to allow a good seal, for example. With respect to a fluidic equipment connection.
  • these directly integrated seals a liquid and / or gas-tight termination of the chip cell to other components, such as. A control gear, can be realized.
  • numerous, preferably parallel, channels can be provided for the measurement of different samples, which can be assigned to a measuring unit. Through different channel widths different measurement volumes can be realized.
  • the chip cuvette may have the format of a slide, possibly with a smaller or larger thickness, wherein the fluidic interfaces are arranged such that they can be filled with common pipetting robots, i. have the well spacing of microtiter plates (18 mm, 9 mm, 4.5 mm, 2.25 mm ).
  • the chip cuvette may also have the format of a titer plate, wherein the fluidic interfaces are arranged such that they are common Pipetting robots can be filled, ie the well spacing of microtiter plates (18 mm, 9 mm, 4.5 mm, 2.25 mm ...) have.
  • the chip cuvette according to the invention can be provided with integrated optical elements for the use of total reflection, in order to obtain the longest possible optical path through the channel or to enable coupling and / or decoupling of the light.
  • the chip cuvette according to the invention can be designed with different measuring elements, for example different volumes, channel geometries, etc., in order to be able to measure various analytical tasks with a sample on the chip.
  • the carrier substrate can be sealed after infestation with a foil (for example self-adhesive, self-adhesive or tight-fitting foil or aluminum foil) or a plane-lying or geometrically adapted cover, in order, for example, to be able to carry out long-term measurements without evaporation effects.
  • a foil for example self-adhesive, self-adhesive or tight-fitting foil or aluminum foil
  • a plane-lying or geometrically adapted cover in order, for example, to be able to carry out long-term measurements without evaporation effects.
  • the chip cuvette according to the invention may, for example, be widened by a mixer which is integrated in the channel within the carrier substrate in order to mix certain substances before the measurement or to dilute certain substances on the chip cuvette either simultaneously or in one or more dilution stages offset to be able to measure.
  • the chip cuvettes according to the invention may also have a distribution system (channel system) in order to guide the sample to different measuring points in which, if appropriate, reactions can be carried out and monitored by reagents presented.
  • a distribution system channel system
  • the chip cuvette is a robust and inexpensive measuring means. Designed as a disposable component, the chip cuvette according to the invention, as well as commercially available disposable plastic cuvettes, has no contamination problems.
  • FIG. 1 is a schematic representation of a first embodiment of the cuvette according to the invention
  • Fig. Ia is a longitudinal section through the cuvette of FIG. 1,
  • FIG. 2 is a schematic representation of a second embodiment of the cuvette according to the invention.
  • FIG. 3 is a schematic representation of a third embodiment of the cuvette according to the invention.
  • 3a shows a longitudinal section through the cuvette of FIG. 3,
  • FIG. 3b shows a cross section through the deep measuring chamber of the chip cuvette according to FIG. 3 with representation of the measuring light geometry
  • FIG. 3c shows a cross section through the flat measuring chamber of the chip cuvette according to FIG. 3 with representation of the measuring light geometry.
  • FIGS. 1 to 3 consist of a series of channels which are introduced at a spacing of 4.5 mm corresponding to the grid dimension of a 384er titer plate into a flat carrier substrate (1), which has a cover film (2, 3) along the open channel course ) are closed.
  • this version can accommodate a maximum of 14 - 16 channels.
  • the channels are numbered with numbers.
  • larger chip board formats with multi-row arrangement of the channels are possible.
  • Glass, quartz or polymers are used as carrier and film material, which have good transparency with regard to their spectroscopic properties for the UV-VIS range.
  • the polymers are at present special TOPAS ® COC types show a high transparency up to the UV-range, the drawn films exhibit compared to the granule again shifted in the UV region absorption edge and are therefore preferably selected.
  • This polymer material also shows good chemical resistance to a number of frequently used in the analysis of solvents such as dilute mineral acids but also organic solvents such as ethanol, acetonitrile or dimethyl sulfoxide.
  • the channel sections (10) located in front of and between the two measuring chambers are likewise very shallow and serve as an evaporation barrier.
  • the channel sections (10) have the same depth as the flat measuring chamber, which results on the one hand from the selected thickness of the chip carrier and on the other hand manufacturing advantage.
  • the maximum layer thickness is selected 1 mm and for the small layer thickness a measuring channel height of 0.1, which corresponds to exactly one order of magnitude. This is advantageous for the user because of the easy conversion (factor 10) and, in terms of the small layer thickness, is within a good tolerance range in terms of production.
  • the channel shape is trapezoidal in the beam direction both along (Fig. 1a, 2a, 3a) and transversely (Fig. 3b, c) and thus adapted to the opening angle of the measuring beam (17).
  • the ratio of measuring chamber length to width is generally common elongated (rectangular) input gap of the spectral optical system adapted.
  • a channel width of 600 ⁇ m is determined as the optimum. This results in a necessary sample volume of 0.3 .mu.l for a filling from the side of the small measuring chamber and a necessary sample volume of 2 .mu.l for a filling from the side of the large measuring chamber.
  • the capacity with complete filling of the entire channel up to the channel openings is approx. 4 ⁇ l.
  • each channel is led upwards via cones (4, 5), which can be used as fluidic interfaces for commercial pipettes.
  • the tips used on the market for volumes of 0.1-200 ⁇ l can be divided into two size groups according to their suction conical shape, for each of which an optimized conical shape could be found.
  • the smaller cone is located on the side of the smaller measuring chamber and the larger one on the side of the large measuring chamber.
  • the chip design shown in FIG. 2 is provided. It consists of raised edge areas (11) at the ends of the channel where the cones (4, 5) are located. These serve to accommodate the funnel-shaped attachments (12) which adjoin the cones (4, 5) and compensate for the tolerances in the position of the tips of the multipipettes to each other when inserted into the sealing Koni (4, 5).
  • the channel design according to the invention shown in FIGS. 1 to 3 allows both a good filling and on the other hand has no air bubble formation during filling, since the air bubbles are reliably outside the measuring window.
  • the resulting very low surface roughness in the channels reliably prevents the formation of air bubbles at the Meßhuntstellen.
  • the material thickness is minimized by introducing a depression in the form of an optically polished measuring window (8).
  • a control gear notches are selected which are arranged on both longitudinal sides in each case centrally to the channel.
  • the design variant shown in FIG. 2 is designed for automated handling in an operating device with XY positioning device and orientation and orientation of the chip as well as the determination of the position by an automatic calibration.
  • a groove with a total reflection surface (13) is introduced next to each measuring chamber, as shown in FIGS. 3, 3a-c. This allows emission through a fiber light guide for the emission excitation light (14), lateral, 90 ° to the fiber optic of the transmission and emission detection system excitation of the emission, allowing a significant reduction of the excitation scattered light compared to a frontal excitation.
  • the optically flat surfaces of the depression (8) and of the film (3) likewise act as total reflection surfaces.

Abstract

L'objectif de l'invention est de fournir une cuvette pour petits volumes évitant les inconvénients de la technique actuelle, qui permet, en particulier, d'effectuer des mesures directement dans un système, seulement par introduction d'autres échantillons. A cet effet, la cuvette pour l'analyse optique de petits volumes comporte une couche structurée (substrat support) au moins pourvue d'un canal, au moins la face inférieure de la couche structurée étant obturée par une couche mince transparente et le canal présentant au moins deux interfaces fluidiques, en communication fluidique avec ledit canal.
PCT/DE2008/000716 2007-04-24 2008-04-22 Cuvette pour l'analyse optique de petits volumes WO2008128534A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE102007019695.6 2007-04-24
DE200710019695 DE102007019695B4 (de) 2007-04-24 2007-04-24 Küvette für die optische Analyse kleiner Volumina

Publications (1)

Publication Number Publication Date
WO2008128534A1 true WO2008128534A1 (fr) 2008-10-30

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Application Number Title Priority Date Filing Date
PCT/DE2008/000716 WO2008128534A1 (fr) 2007-04-24 2008-04-22 Cuvette pour l'analyse optique de petits volumes

Country Status (2)

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DE (1) DE102007019695B4 (fr)
WO (1) WO2008128534A1 (fr)

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WO2009034563A2 (fr) * 2007-09-14 2009-03-19 Nanocomms Patents Limited Système d'analyse
DE102013215210B3 (de) * 2013-08-02 2014-10-16 Analytik Jena Ag Reaktionsgefäß, Reaktionsgefäßanordnung und Verfahren zur Analyseeiner Substanz
US9199232B2 (en) 2010-04-07 2015-12-01 Biosensia Patents Limited Flow control device for assays
DE102014113163B3 (de) * 2014-09-12 2015-12-17 Analytik Jena Ag Reaktionsgefäß, Reaktionsgefäßanordnung und Verfahren zur Analyse einer Substanz

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DE102015013026B4 (de) 2015-10-09 2021-07-01 Rheinische Friedrich-Wilhelms-Universität Bonn Polarisationserhaltende Vakuum-Zelle zur Anwendung oder Messung elektromagnetischer Wellen im Vakuum, Verfahren zu deren Herstellung sowie deren Verwendung
EP3184989B1 (fr) 2015-12-23 2018-07-25 Analytik Jena AG Cuvette
DE202015009231U1 (de) 2015-12-23 2016-12-21 Analytik Jena Ag Küvette
DE102017211431B4 (de) * 2017-07-05 2024-04-25 Robert Bosch Gmbh Küvette zum Aufnehmen eines Fluids, Vorrichtung zum Analysieren des Fluids sowie Herstellungsverfahren
DE102020101415A1 (de) 2020-01-22 2021-07-22 Gbn Systems Gmbh Analysevorrichtung

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DE10222478A1 (de) * 2002-05-22 2003-12-04 Bartels Mikrotechnik Gmbh Verteilelement für Flüssigkeiten und Gase, Lab-on-a-Cip, Lab-on-a-Card
EP1533035A1 (fr) * 2003-11-21 2005-05-25 Boehringer Ingelheim microParts GmbH Porte-échantillon

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009034563A2 (fr) * 2007-09-14 2009-03-19 Nanocomms Patents Limited Système d'analyse
WO2009034563A3 (fr) * 2007-09-14 2009-04-30 Nanocomms Patents Ltd Système d'analyse
US8835184B2 (en) 2007-09-14 2014-09-16 Biosensia Patents Limited Analysis system
US9199232B2 (en) 2010-04-07 2015-12-01 Biosensia Patents Limited Flow control device for assays
DE102013215210B3 (de) * 2013-08-02 2014-10-16 Analytik Jena Ag Reaktionsgefäß, Reaktionsgefäßanordnung und Verfahren zur Analyseeiner Substanz
DE102014113163B3 (de) * 2014-09-12 2015-12-17 Analytik Jena Ag Reaktionsgefäß, Reaktionsgefäßanordnung und Verfahren zur Analyse einer Substanz

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