EP2322276B1 - Dispositif d'exécution de tests, notamment de tests biomoléculaires - Google Patents

Dispositif d'exécution de tests, notamment de tests biomoléculaires Download PDF

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Publication number
EP2322276B1
EP2322276B1 EP10185269.7A EP10185269A EP2322276B1 EP 2322276 B1 EP2322276 B1 EP 2322276B1 EP 10185269 A EP10185269 A EP 10185269A EP 2322276 B1 EP2322276 B1 EP 2322276B1
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EP
European Patent Office
Prior art keywords
area
flow element
reaction chamber
flow
solution
Prior art date
Legal status (The legal status 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 status listed.)
Active
Application number
EP10185269.7A
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German (de)
English (en)
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EP2322276A1 (fr
Inventor
Jochen Rupp
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Robert Bosch GmbH
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Robert Bosch GmbH
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Publication date
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Publication of EP2322276A1 publication Critical patent/EP2322276A1/fr
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Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L7/00—Heating or cooling apparatus; Heat insulating devices
    • B01L7/52—Heating or cooling apparatus; Heat insulating devices with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples
    • B01L7/525—Heating or cooling apparatus; Heat insulating devices with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples with physical movement of samples between temperature zones
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers 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
    • B01L3/502715—Containers 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
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers 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
    • B01L3/502746—Containers 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 the means for controlling flow resistance, e.g. flow controllers, baffles
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0809—Geometry, shape and general structure rectangular shaped
    • B01L2300/0819—Microarrays; Biochips
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0809—Geometry, shape and general structure rectangular shaped
    • B01L2300/0822—Slides
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
    • B01L2300/087—Multiple sequential chambers
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
    • B01L2300/088—Channel loops
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/18—Means for temperature control
    • B01L2300/1805—Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks
    • B01L2300/1827—Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks using resistive heater
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/08—Regulating or influencing the flow resistance
    • B01L2400/084—Passive control of flow resistance
    • B01L2400/086—Passive control of flow resistance using baffles or other fixed flow obstructions

Definitions

  • the invention relates to a device for carrying out tests, in particular of molecular biological tests, according to the preamble of claim 1.
  • hybridization is an important process for molecular genetic techniques in which a single strand of a DNA or an RNA more or less completely complementary DNA or RNA single strand attached by hydrogen bonds formed between the respective complementary Nukleinbasen become.
  • the hybridization technique serves to detect the structural relationship of nucleic acids as well as to isolate specific nucleic acid sequences from a mixture.
  • the hybridization technique is gaining in importance in connection with other molecular genetic techniques in neurobiological research, the diagnosis of pathogens, inter alia, as an in situ method.
  • a standard slide is wetted with the reagent to be examined, capped and then allowed to rest in a temperature chamber at a temperature range of 30 ° C to 70 ° C. This process sometimes takes days to arrive at a desired reaction or result.
  • the DE 10 2006 024355 A1 discloses a microfluidic device for detecting molecules contained in a sample.
  • the microfluidic arrangement has, within a measuring channel, barrier elements which are arranged such that the flow of a sample flowing through the measuring channel is changed.
  • the US 2003/0162283 A1 discloses a microfluidic device with channels, which influences a flow-through sample liquid in its flow behavior by barrier elements.
  • the US 2003/0178641 A1 also describes the use of flow elements disposed in or in front of a reaction chamber so as to alter the flow of a sample through the reaction chamber.
  • This object is achieved in a device for carrying out tests, in particular of molecular biological tests, with the features of claim 1.
  • the invention is based on the idea of deflecting or influencing the flow by means of a flow element arranged between the inlet region of the reaction chamber and the area with the reference patterns in such a way that compared to a reaction chamber without flow element, a greater width is considered within the flow direction Reaction chamber flows and thus also arranged in the edge regions of the area with the reference patterns reference pattern are better or flowed over with a higher probability.
  • the inlet region of the reaction chamber is flared funnel-shaped, that viewed in the flow direction of the solution, the flow element directly adjoins the funnel-shaped expansion, the flow element with the expansion centered is aligned and that the flow element viewed transversely to the flow direction has a greater extent than the expansion in the region of the beginning of the expansion.
  • the flow element has a height which corresponds at least to the height of the reference pattern on the slide. This makes it possible to achieve a complete deflection of the flow of the solution in the region of the reference pattern.
  • the slide is covered by a cover, which is part of the reaction chamber and that the flow element on the Abdeckele-element is arranged on the side facing the slide.
  • a cover which is part of the reaction chamber and that the flow element on the Abdeckele-element is arranged on the side facing the slide.
  • the flow element extends over the entire height of the reaction chamber between the slide and the cover.
  • the flow element is designed as a separate component. As a result, it is not necessary to form special slides or cover elements with flow elements, but depending on the requirement, different flow elements can be used for the device in a simple manner.
  • the flow element is integrally formed on the slide or on the cover. This will always be advantageous if one always provides an identical area with the reference patterns so that a flow element can be optimally adapted to an existing area.
  • An advantageous manufacturing method for forming a formed on the slide or the cover element flow element provides that the flow element is formed by a structuring of the surface of the slide or the cover.
  • a structuring may, for example, consist of a grinding process, an etching process or the like.
  • the flow element is arranged near the inlet area. Furthermore, this achieves the advantage that the entire flow flowing into the reaction chamber via the inlet region is detected by the flow element, without the flow element having to be made particularly large for this purpose.
  • a device 10 for performing tests, in particular of molecular biological tests shown in a schematic representation.
  • the device 10 has a reaction chamber 11, which in plan view in is formed approximately rectangular or block-shaped.
  • the reaction chamber 11 has a funnel-shaped inlet region 12 and, on the opposite side, a funnel-shaped outlet region 13.
  • the outlet region 13 is adjoined by a first line 14, which merges into a branch 15.
  • an outlet 16 is arranged, via which a solution flowing in the reaction chamber 11 or the device 10 can be discharged from the device 10.
  • the other end of the branch 15 opens into a pumping device 17, which always circulates the addressed solution within the device 10 or the reaction chamber 11.
  • a second line 19 connects, which via a further branch 20 on the one hand with an inlet 21, via which the solution can be introduced into the device 10 and on the other hand connected to the inlet portion 12 of the reaction chamber 11.
  • the reaction chamber 11 has a heater 23 which includes an upper heating element 24 and a lower heating element 25.
  • the two, in particular electrically operated heating elements 24 and 25 in this case cover the surface of the reaction chamber 11 at least almost completely.
  • the reaction chamber 11 in turn consists of a slide 26, which consists in particular of glass, and a cover 28, which cooperates with the slide 26.
  • the cover element 28 consists of a base material such as plastic or glass, the slide 26 facing side 29 is structured. Depending on the type of material used, the structuring may be effected, for example, by means of an etching or a grinding process.
  • the cover element 28 may have a peripheral edge 30 in the region of the end faces of the reaction chamber 11 which has a lower height in the region of the inlet region 12 and the outlet region 13 than in the remaining regions, so that the solution through the reaction chamber 11 in the direction of the arrow 32 can flow from the inlet region 12 in the direction of the outlet region 13.
  • a reaction chamber 33 (with the exception of the inlet region 12 and the outlet region 13) is formed in the interior of the reaction chamber 11.
  • the slide 26 On the slide 26 is located on the outlet region 13 side facing an area 35 on which a plurality of reference patterns 36, consisting of molecular biological materials or molecular biological reference patterns 36, are applied in a point-like arrangement stationary.
  • the reference patterns 36 are each preferably different reference patterns 36, which are arranged next to one another in the form of "spots.”
  • the height of the individual spots or reference patterns 36 is only a few nanometers
  • the object carrier has a typical length and width of approximately 20 mm, and the area 35 in the exemplary embodiment is typically approximately 10 mm to 15 mm wide and long.
  • a flow element 38 is arranged within the reaction chamber 11 or the reaction space 33.
  • the flow element 38 is integrally formed on the cover 28 and formed due to the structuring of the cover 28 and projects over the entire height of the reaction space 33.
  • the flow element 38 is round or cylindrical and arranged near the inlet region 12.
  • the diameter d of the flow element 38 is about 5mm and the distance to the area 35 is also about 5mm.
  • the flow element 38 connects approximately in the plane in which the funnel-shaped inlet portion 12 ends.
  • the Diameter d of the flow element 38 is greater than the width w in the region of the inlet or in the region of the inlet region 12, which is smaller in its flow cross-section.
  • each of the reference patterns 36 viewed across the flow cross-section of the solution or over the entire width b of the area 35, has the same probability of reacting with a counter-reference in the solution.
  • the device 10 described so far can be modified or modified in a variety of ways.
  • an adaptation of the flow body 38 to the respectively existing geometric arrangements of the reference pattern 36 and to the size of the reaction chamber 11 is required.
  • a cross-sectionally round flow element 38 differently shaped flow elements 38, for example lenticular or angular flow elements 38, are conceivable.
  • the flow of the solution in the reaction chamber 11 is influenced by means of the flow element 38 so that it has a greater width transversely to the flow direction through the reaction chamber 11 or a larger flow cross section compared to a reaction chamber 11 without flow element 38 that the area 35 in its transverse to the flow direction edge regions of the solution with the counter-references is overflowed.
  • the solution flows uniformly over the entire width b of the area 35.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Health & Medical Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Dispersion Chemistry (AREA)
  • Hematology (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)

Claims (8)

  1. Dispositif (10) pour effectuer des tests biomoléculaires, comprenant un support d'objet (26) sur lequel, dans une zone (35) délimitée localement par une largeur (b) et une longueur, sont disposés localement une pluralité de modèles de référence (36) qui sont potentiellement appropriés pour coopérer avec des références conjuguées se trouvant dans une solution, la solution étant amenée en continu au moyen d'un système de pompe (17) sur la zone (35) en vue d'accélérer une réaction entre les modèles de référence (36) et les références conjuguées, le support d'objet (26) faisant partie d'une chambre de réaction (11) avec une région d'entrée (12) espacée de la zone (35) et une région de sortie (13) espacée de la zone (35), et la solution circulant à travers la chambre de réaction (11) depuis la direction de la région d'entrée (12) dans la direction de la région de sortie (13),
    caractérisé en ce
    qu'entre la région d'entrée (12) de la chambre de réaction (11) et la zone (35) munie des modèles de référence (36), est disposé un élément d'écoulement (38) pour dévier la solution affluant par le biais de la zone d'entrée (12) dans la région de la chambre de réaction (11) et pour augmenter la section transversale d'écoulement, en ce qu'au moins la région d'entrée (12) de la chambre de réaction (11) est réalisée de manière élargie en forme d'entonnoir, en ce que l'élément d'écoulement (38), considéré dans la direction d'écoulement (32) de la solution, se raccorde directement à l'élargissement en forme d'entonnoir, l'élément d'écoulement (38) étant orienté centralement avec l'élargissement, en ce que l'élément d'écoulement (38), considéré transversalement à la direction d'écoulement (32), présente une plus grande étendue (w) que l'élargissement dans la région du début de l'élargissement, en ce que l'élément d'écoulement (38) présente une surface en section transversale circulaire et est réalisé sous forme cylindrique et en ce que la distance entre l'élément d'écoulement (38) et la zone (35) d'une part et l'élément d'écoulement (38) et la région d'entrée (12) d'autre part sont approximativement égales.
  2. Dispositif selon la revendication 1,
    caractérisé en ce que
    l'élément d'écoulement (38) présente une hauteur qui correspond au moins à la hauteur du modèle de référence (36) sur le support d'objet (26).
  3. Dispositif selon la revendication 1 ou 2,
    caractérisé en ce que
    le support d'objet (26) est recouvert par un élément de recouvrement (28) qui fait partie de la chambre de réaction (11) et en ce que l'élément d'écoulement (38) est disposé sur l'élément de recouvrement (28) sur le côté tourné vers le support d'objet (26).
  4. Dispositif selon la revendication 3,
    caractérisé en ce que
    l'élément d'écoulement (38) s'étend sur toute la hauteur de la chambre de réaction (11) entre le support d'objet (26) et l'élément de recouvrement (28).
  5. Dispositif selon l'une quelconque des revendications 1 à 4,
    caractérisé en ce que
    l'élément d'écoulement (38) est réalisé sous forme de composant séparé.
  6. Dispositif selon la revendication 3 ou 4,
    caractérisé en ce que
    l'élément d'écoulement (38) est façonné d'une seule pièce sur le support d'objet (26) ou sur l'élément de recouvrement (28).
  7. Dispositif selon la revendication 6,
    caractérisé en ce que
    l'élément d'écoulement (38) est réalisé par une structuration de la surface du support d'objet (26) ou de l'élément de recouvrement (28).
  8. Dispositif selon l'une quelconque des revendications 1 à 7,
    caractérisé en ce que
    le support d'objet (26) présente, au moins dans la région de la zone (35), une forme approximativement rectangulaire, en ce que la zone (35) présente une surface de base approximativement rectangulaire, dont la largeur et la longueur correspondent à chaque fois approximativement à la moitié de la largeur du support d'objet (26) dans la région de la zone (35), des distances approximativement égales aux bords latéraux du support d'objet (26) étant de préférence réalisées.
EP10185269.7A 2009-11-11 2010-10-01 Dispositif d'exécution de tests, notamment de tests biomoléculaires Active EP2322276B1 (fr)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
DE102009046598.7A DE102009046598B4 (de) 2009-11-11 2009-11-11 Vorrichtung zur Durchführung von Tests, insbesondere von molekularbiologischen Tests

Publications (2)

Publication Number Publication Date
EP2322276A1 EP2322276A1 (fr) 2011-05-18
EP2322276B1 true EP2322276B1 (fr) 2013-12-25

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EP10185269.7A Active EP2322276B1 (fr) 2009-11-11 2010-10-01 Dispositif d'exécution de tests, notamment de tests biomoléculaires

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DE (1) DE102009046598B4 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8797527B2 (en) 2011-08-24 2014-08-05 Abbott Point Of Care, Inc. Biologic fluid sample analysis cartridge

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108132170A (zh) * 2017-12-22 2018-06-08 杭州依美洛克医学科技有限公司 用于生物反应的密封盖
DE102022209419A1 (de) 2022-09-09 2024-03-14 Robert Bosch Gesellschaft mit beschränkter Haftung Mikrofluidische Vorrichtung und Verfahren zu ihrem Betrieb

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20030178641A1 (en) 2002-01-23 2003-09-25 Blair Steven M. Microfluidic platforms for use with specific binding assays, specific binding assays that employ microfluidics, and methods
US20030162283A1 (en) 2002-02-22 2003-08-28 Hitachi, Ltd. Circulating type biochemical reaction apparatus
DE102006024355B4 (de) 2006-05-19 2008-04-03 Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. Mikrofluidische Anordnung zur Detektion von in Proben enthaltenen chemischen, biochemischen Molekülen und/oder Partikeln

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
MICHAEL SCHLÜTER: "Mikrofluidische Strukturenfür biochemische Analysen", 28 May 2004 (2004-05-28), Retrieved from the Internet <URL:http://sylvester.bth.rwth-aachen.de/dissertationen/2004/156/04_156.pdf> [retrieved on 20111208] *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8797527B2 (en) 2011-08-24 2014-08-05 Abbott Point Of Care, Inc. Biologic fluid sample analysis cartridge

Also Published As

Publication number Publication date
DE102009046598B4 (de) 2024-06-13
EP2322276A1 (fr) 2011-05-18
DE102009046598A1 (de) 2011-05-12

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