EP1860060A1 - Procédé et appareil pour mélanger des micro-gouttelettes - Google Patents

Procédé et appareil pour mélanger des micro-gouttelettes Download PDF

Info

Publication number: EP1860060A1
Authority: EP; European Patent Office
Prior art keywords: hydrophilic surface; carrier; carriers; hydrophilic; microdroplets
Prior art date: 2006-05-22
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.): Granted

Application number

EP06010516A

Other languages

German (de)

English (en)

Other versions

EP1860060B1 (fr

Inventor

Ulrich Dr. Rer. Nat. Sieben

Dr. Klapproth Holger

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.)

TDK Micronas GmbH

Original Assignee

TDK Micronas 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.)

2006-05-22

Filing date

2006-05-22

Publication date

2007-11-28

2006-05-22 Application filed by TDK Micronas GmbH filed Critical TDK Micronas GmbH

2006-05-22 Priority to DE502006007372T priority Critical patent/DE502006007372D1/de

2006-05-22 Priority to EP06010516A priority patent/EP1860060B1/fr

2007-05-22 Priority to US11/805,242 priority patent/US20090017505A1/en

2007-11-28 Publication of EP1860060A1 publication Critical patent/EP1860060A1/fr

2010-07-07 Application granted granted Critical

2010-07-07 Publication of EP1860060B1 publication Critical patent/EP1860060B1/fr

Status Not-in-force legal-status Critical Current

2026-05-22 Anticipated expiration legal-status Critical

Images

Classifications

- 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
- B01L3/02—Burettes; Pipettes
- B01L3/0241—Drop counters; Drop formers
- B01L3/0262—Drop counters; Drop formers using touch-off at substrate or container
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
- B01F33/00—Other mixers; Mixing plants; Combinations of mixers
- B01F33/30—Micromixers
- B01F33/302—Micromixers the materials to be mixed flowing in the form of droplets
- B01F33/3021—Micromixers the materials to be mixed flowing in the form of droplets the components to be mixed being combined in a single independent droplet, e.g. these droplets being divided by a non-miscible fluid or consisting of independent droplets
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
- B01F33/00—Other mixers; Mixing plants; Combinations of mixers
- B01F33/30—Micromixers
- B01F33/3035—Micromixers using surface tension to mix, move or hold the fluids
- B01F33/30351—Micromixers using surface tension to mix, move or hold the fluids using hydrophilic/hydrophobic surfaces
- 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
- B01L3/508—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above
- B01L3/5085—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above for multiple samples, e.g. microtitration plates
- 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
- B01L3/508—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above
- B01L3/5088—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above confining liquids at a location by surface tension, e.g. virtual wells on plates, wires
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
- B01F35/00—Accessories for mixers; Auxiliary operations or auxiliary devices; Parts or details of general application
- B01F35/90—Heating or cooling systems
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/02—Adapting objects or devices to another
- B01L2200/025—Align devices or objects to ensure defined positions relative to each other
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/14—Process control and prevention of errors
- B01L2200/143—Quality control, feedback systems
- 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
- B01L2300/18—Means for temperature control
- B01L2300/1805—Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks
- B01L2300/1822—Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks using Peltier elements
- 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
- B01L3/56—Labware specially adapted for transferring fluids
- B01L3/563—Joints or fittings ; Separable fluid transfer means to transfer fluids between at least two containers, e.g. connectors

Definitions

the invention relates to a method and apparatus for mixing microdroplets.
a first liquid is stored in a reservoir of a first nanopipette.
a nozzle of the nanopipette connected via a channel to the reservoir is positioned on a substrate for ejecting a microdroplet of the liquid onto the substrate by means of an actuator.
a second nanopipette is positioned on the substrate to correspondingly form a second microdroplet of a second liquid to apply to the substrate, for example, to start a chemical reaction between the liquids.
the microdroplets because of the small size of the microdroplets, it is difficult to apply the second microdroplet to the substrate at exactly the same location as the first microdroplet. This is particularly problematic for liquids with low viscosity, since in these liquids, the microdroplets can easily split after exiting the nozzle. If several microdroplets are successively applied to the substrate, there is also a risk that the microdroplets evaporate before they come into contact with each other. In addition, the liquids are dispensed depending on their surface energy. Thus, e.g. Liquids with high surface energy larger microdroplets than liquids with low surface energy.
At least two carriers are provided whose surfaces are each patterned such that at least one hydrophilic surface area of at least A hydrophobic surface region is bounded by disposing a first microdroplet on a hydrophilic surface region of a first carrier and a second microdroplet on a hydrophilic surface region of a second carrier, and positioning the carriers with the first and second surfaces facing each other by moving toward each other in such close proximity in that the microdroplets come into contact with each other.
microdroplets can be applied to the carrier with great positioning accuracy and precision. By positioning the carriers in the correct position, the microdroplets are brought into contact with one another and mixed.
the surface of a first carrier is provided with a preferably matrix-shaped surface structure having a plurality of hydrophilic surface regions separated from each other by the at least one hydrophobic surface region such that the surface of a second carrier having a surface texture of the first carrier suitable surface structure is provided, that on the individual individual hydrophilic surface areas in each case a microdroplet is applied, and that the carrier with the surface structures facing each other by moving towards each other are positioned together so that the microdroplets of each corresponding hydrophilic surface areas in each case come into contact with each other.
a plurality of pairwise associated microdroplets may be mixed together as the carriers are positioned one another.
the abovementioned object is also achieved with regard to the method in that at least two carriers are provided such that the surface of a first carrier is structured so that closely adjacent hydrophilic surface regions are separated from each other by at least one hydrophobic surface region, that the hydrophilic surface regions each with be brought into contact with a microdroplet, and that one second support is positioned relative to the hydrophilic surface areas such that the microdroplets are in contact with the second support and each other.
the hydrophobic surface area of the first carrier located between the adjacent hydrophilic surface areas is bridged by the second carrier so that the microdroplets come into contact with each other and mix, for example because the microdroplets are displaced laterally when positioning the carrier and / or in the diffuse each other microdroplets.
the surface of the second support is preferably hydrophilic. The method is particularly simple and inexpensive to carry out, since only one of the two carriers must be structured.
At least two carriers are provided such that the surface of a first carrier is structured such that closely adjacent first hydrophilic surface regions are separated from each other by at least one first hydrophobic surface region second support is patterned such that at least a second hydrophilic surface region is bounded by at least a second hydrophobic surface region, the first hydrophilic surface regions and the at least one second hydrophilic surface region are each contacted with a microdroplet, and the supports are bonded to the first hydrophilic surface regions Surface areas and the at least one second hydrophilic surface area facing each other by moving towards each other are positioned so close to each other that the second hydrophilic O.
the surface region covers a region of the first hydrophobic surface region situated between the first hydrophilic surface regions and the at least three microdroplets come into contact with one another.
At least one of the carriers for applying the microdroplet (s) to the hydrophilic surface area (s) is immersed in a liquid and then preferably at a speed in the range of 0.1 to 10 mm / s the liquid is withdrawn.
the at least one hydrophilic surface region can thereby be easily loaded with the microdroplet.
the carrier As the carrier is withdrawn from the liquid, it will bead from the hydrophobic surface areas while adhering to the hydrophilic surface areas in the form of the microdroplet.
a first microdroplet contains an enzyme and a second microdroplet at least one DNA molecule, primer and nucleoside triphosphate in a sufficient for a polymerase chain reaction concentration.
a first microdroplet of hydrogen peroxide and a second microdroplet of luminol may then be used for the optical detection of receptor-ligand complexes which are directly or indirectly labeled with an enzyme which, when present, decomposes the luminol upon contact with the hydrogen peroxide with the emission of chemiluminescent radiation.
the method can be used in particular in the ELISA or sandwich ELISA method.
At least one support is provided as a metal oxide or semimetal oxide substrate, and if the substrate is coated with a polymer having at least one reactive group at the locations where the hydrophilic surface regions are to be.
the substrate can then be patterned with great precision using methods known per se for semiconductor production become.
the reactive group may, for example, have an OH, SH and / or NH 2 group.
the polymer may be a gel and in particular contain a polysaccharide and / or poly (2-hydroxyethyl) methacrylate (pHEMA).
the above object is achieved with respect to the device of the type mentioned above in that it has at least two carriers whose surfaces are each structured such that at least one hydrophilic surface area is bounded by at least one hydrophobic surface area, that the device has a positioning device by means of the carriers with the structured surfaces facing one another are positionable in such close proximity to one another that microdroplets which can be applied to the hydrophilic surface areas come into contact with one another.
the carrier surfaces By structuring the carrier surfaces into hydrophilic and hydrophobic regions, an independent adjustment of microdroplets on the hydrophilic regions is made possible upon contact of the carrier surface with an aqueous liquid. Thereafter, the carriers can be easily positioned together with the hydrophilic surface regions by means of the positioning device in such a way that the microdroplets come into contact with each other and mix.
the above-mentioned object is also achieved with respect to the device of the type mentioned above in that the device has at least two carriers such that the surface of a first carrier is structured so that closely adjacent hydrophilic surface regions are separated from one another by at least one hydrophobic surface region, and the device has a positioning device by means of which the carriers can be positioned so close to one another that microdroplets which can be applied to the hydrophilic surface regions of the first carrier come into contact with the second carrier and with one another.
the self-alignment of the microdroplets is made possible by structuring the carrier surfaces into hydrophilic and hydrophobic regions. Since only one of the two carriers must have a surface structuring, the device can be produced inexpensively.
the device has at least two carriers such that the surface of a first carrier is structured so that closely adjacent first hydrophilic surface regions are separated from each other by at least one first hydrophobic surface region, in that the surface of a second carrier is structured in such a way that at least one second hydrophilic surface region is bounded by at least one second hydrophobic surface region, and in that the device has a positioning device by means of which the carriers with the structured surfaces can be positioned so close to each other that they are so close together the second hydrophilic surface region covers a first hydrophobic surface region located between the first hydrophilic surface regions and the first hydrophilic surface In this case, microdroplets which can be applied can be brought into contact with microdroplets which can be applied to the second hydrophilic surface regions.
the device has at least three of the carrier, and if these carriers by means of the positioning optionally or alternately positioned to each other. This makes it possible, in particular, to mix a plurality of microdroplets in succession, for example to mix first two microdroplets A and B into a microdroplet AB and then this with a microdroplet C to form a microdroplet ABC.
At least one carrier has a metal oxide or semimetal oxide substrate which is coated on the hydrophilic surface regions with a polymer having at least one reactive group.
the substrate can then be mass produced with high precision by methods of semiconductor manufacturing.
the positioning device cooperates with one another on the carriers to be positioned against each other Centering on, in particular centering bevels.
the carriers can then be easily positioned with their surface structuring in a predetermined position relative to each other.
a centering can be provided on one carrier a projection and on the other carrier a matching recess.
the centering elements can also be optical markings, such as crosshairs, which are brought to coincide when the carriers are positioned one against the other.
At least one carrier preferably has a moisture and / or conductivity sensor on a hydrophilic surface area. With the sensor can be easily controlled whether the microdroplets are in contact with each other, for example, if the fluids of the microdroplets have different electrical conductivities.
At least one carrier has a cooling and / or heating element, in particular a Peltier element.
the device can then be used to perform a polymerase chain reaction (PCR).
PCR polymerase chain reaction
a device 1 for mixing microdroplets 2a, 2b, shown in FIGS. 1 to 3, has two approximately plate-shaped carriers 3a, 3b whose surfaces 4a, 4b are each structured such that a plurality of hydrophilic surface regions 5a, 5b are defined by a hydrophobic surface region 6a bordering them , 6b are laterally spaced from each other.
the hydrophilic surface regions 5a, 5b are arranged in a matrix-like manner in a plurality of rows and columns.
the matrices of the two carriers 3a, 3b are configured in such a way that the hydrophobic surface regions 6a, 6b of a first carrier 3a can be used with those of a second carrier 3b to cover when the carriers 3a, 3b with their hydrophilic surface regions 5a, 5b face each other be positioned together.
Fig. 1 it can be seen that the carrier has formed as crosshairs optical position marks, which are arranged in a predetermined position relative to the hydrophilic surface regions 5a, 5b.
the supports 3a, 3b each consist of a semiconductor material, e.g. Silicon, which has on its surface a not shown in the drawing fluoropolymer layer which forms the hydrophobic surface region 6a, 6b.
a polymer hydrogel is applied, which may have reactive groups.
First microdroplets 2a are applied to the hydrophilic surface regions 5a of the first carrier 3a.
the carrier 3a may be immersed in, for example, a liquid and then withdrawn therefrom at a rate chosen to adhere the liquid only to the hydrophilic surface regions 5a.
the microdroplets 2a can also be applied in any other way to the hydrophilic surface regions 5a, e.g. with the help of a needle, a pipette or by printing, in particular by means of a jet printer.
the different surface regions 5a, 6a cause the microdroplets 2a to align themselves in such a way that they are arranged only on the hydrophilic surface regions 5a.
Second microdroplets 2b are applied in a corresponding manner to the hydrophilic surface regions 5a, 5b of the second carrier 3b. Then, the carriers 3a, 3b are positioned with their extension planes parallel to each other such that the hydrophilic surface regions 5a of the first carrier 3a are mirror images of the hydrophilic surface regions 5b of the second carrier 3b. For the correct alignment of the carriers 3a, 3b, the position marks 7 of the one carrier 3a are brought into coincidence with the position marks 7 of the other carrier 3b.
the carriers 3a, 3b are initially spaced so far apart that the microdroplets 2a, 2b do not touch each other.
the microdroplets 2a of the upper side of the first carrier 3a and the microdroplets 2b are arranged on the underside of the second carrier 3b.
the last-mentioned microdroplets adhere to the hydrophilic surface regions 5b against the force of gravity.
the plate assembly formed from the carriers 3a, 3b in a positioned elsewhere in the room, for example, rotated by 90 ° about an axis normal to the plane in Fig. 2 and 3 extending axis.
the carriers 3a, 3b are moved by means of a positioning device not shown in detail in the drawing, e.g. a robot, as long as normal moves to their extension planes until the located on the surface of the first carrier 3a microdroplets 2a each touch a corresponding thereto microdroplet 2b of the second carrier 3b and mix each with this, for example, a chemical reaction between the different Liquids of the microdroplets 2a, 2b and / or substances dissolved therein to start.
a positioning device not shown in detail in the drawing, e.g. a robot
the carriers 3a, 3b after the mixing of the microdroplets 2a, 2b to a new microdroplet 2 by a narrow gap are spaced apart from each other such that the microdroplets 2 by the hydrophobic surface regions 6a, 6b are spaced from each other.
the positioning device has a first housing part 8a connected to the first support 3a and a second housing part 8b connected to the second support 3b.
the first housing part 8a has a receiving recess and the second housing part 8b has a matching one Head Start.
inclined surfaces 9 are arranged, which act together in inserted into the first housing part 8a second housing part, that the housing parts 8a, 8b are centered in a predetermined position relative to each other.
the housing parts 8a, 8b are preferably made of an inert plastic, with which the carrier parts 3a, 3b are partially encapsulated.
hydrophilic surface regions 5 a are provided only on the surface of the first carrier part 3 a, which are separated from one another by a hydrophobic surface region 6 a.
the hydrophilic surface regions 5a are arranged in a matrix-like manner in a plurality of rows and columns.
FIG. 5 it can be clearly seen that in each case two surface regions 5a are associated in pairs with one another and have a smaller distance from one another than to the remaining hydrophilic surface regions 5a.
the surface of the second, serving as a stamp carrier part 3b is completely hydrophilic.
a first microdroplet 2a and a second microdroplet 2b on the other surface area 5b are used up on a respective surface area 5a of the paired surface regions 5a.
the application of the microdroplets 2a, 2b can be effected for example by printing.
the carriers 3a, 3b are arranged with their extension planes parallel to one another, wherein the carriers 3a, 3b are initially spaced from one another so far that the second carrier 3b does not comprise the microdroplets 2a, 2b located on the first carrier 3a touched. Then the carriers are moved towards each other approximately normal to their planes of extent until the second carrier 3b touches the pairwise associated microdroplets 2a, 2b and these come into contact with each other.
Fig. 8 it can be seen that the carriers 3a, 3b after mixing the microdroplets 2a, 2b to a new microdroplet 2 by a narrow gap are spaced apart from each other such that the microdroplets 2 are spaced apart by the hydrophobic surface portion 6a. Thus, only the pairwise associated microdroplets 2a, 2b are mixed together.
the arrangement of the surface portions 5a, 6a corresponds to that in Fig. 5.
second hydrophilic surface portions 5b are provided on the second support, which are spaced apart from each other by a second hydrophobic surface portion 6b.
the first hydrophilic surface regions 5a are coated with first and second microdroplets 2a, 2b as in the embodiment in FIG.
Third microdroplets 2c are applied to the second hydrophilic surface regions 5b.
the carriers 3a, 3b are arranged with their extension planes parallel to one another such that the second hydrophilic surface regions 5b each have one between the first hydrophilic surface regions 5a overlap region of the first hydrophobic surface region 6a.
the third microdroplet 2 c is arranged in the plan view of the extension planes of the carriers 3 a, 3 b between a first microdroplet 5 a assigned to it and a second microdroplet 5 b.
the carriers 3a, 3b are initially spaced apart from one another such that the microdroplets 2a, 2b, 2c do not touch each other. Then, the carriers are moved toward each other approximately normal to their planes of extent until the third microdroplets 2c touch and mix with the first and second microdroplets 2a, 2b.
Fig. 10 it can be seen that the carriers 3a, 3b after the mixing of the microdroplets 2a, 2b, 2c to a new microdroplet 2 by a narrow gap are spaced apart such that the microdroplets 2 by the hydrophobic surface region 6a, 6b spaced from each other are. Thus, only three mutually associated microdroplets 2a, 2b, 2c are mixed together.
the first microdroplet 2a may contain hydrogen peroxide, the second microdroplet 2b luminol, and the third microdroplet a serum to be assayed, in which ligands are reacted with an enzymatic marker, e.g. Horseradish peroxidase (HRP) are labeled.
an enzymatic marker e.g. Horseradish peroxidase (HRP) are labeled.

Landscapes

Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Clinical Laboratory Science (AREA)
Analytical Chemistry (AREA)
General Health & Medical Sciences (AREA)
Hematology (AREA)
Apparatus Associated With Microorganisms And Enzymes (AREA)
Immobilizing And Processing Of Enzymes And Microorganisms (AREA)

EP06010516A 2006-05-22 2006-05-22 Appareil pour mélanger des micro-gouttelettes Not-in-force EP1860060B1 (fr)

Priority Applications (3)

Application Number	Priority Date	Filing Date	Title
DE502006007372T DE502006007372D1 (de)	2006-05-22	2006-05-22	Vorrichtung zum Mischen von Mikrotröpfchen
EP06010516A EP1860060B1 (fr)	2006-05-22	2006-05-22	Appareil pour mélanger des micro-gouttelettes
US11/805,242 US20090017505A1 (en)	2006-05-22	2007-05-22	Process and device for mixing microdroplets

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
EP06010516A EP1860060B1 (fr)	2006-05-22	2006-05-22	Appareil pour mélanger des micro-gouttelettes

Publications (2)

Publication Number	Publication Date
EP1860060A1 true EP1860060A1 (fr)	2007-11-28
EP1860060B1 EP1860060B1 (fr)	2010-07-07

Family

ID=37116094

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
EP06010516A Not-in-force EP1860060B1 (fr)	2006-05-22	2006-05-22	Appareil pour mélanger des micro-gouttelettes

Country Status (3)

Country	Link
US (1)	US20090017505A1 (fr)
EP (1)	EP1860060B1 (fr)
DE (1)	DE502006007372D1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
EP2228132A1 (fr) *	2009-03-10	2010-09-15	Qiagen GmbH	Dispositif isotherme PCR
CN104114280A (zh) *	2011-09-30	2014-10-22	生命科技公司	用于生物分析的系统和方法

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US20070047388A1 (en) *	2005-08-25	2007-03-01	Rockwell Scientific Licensing, Llc	Fluidic mixing structure, method for fabricating same, and mixing method
ATE494061T1 (de) *	2007-07-10	2011-01-15	Hoffmann La Roche	Mikrofluidische vorrichtung, mischverfahren und verwendung der vorrichtung
CN105749995B (zh) *	2016-04-28	2017-10-31	宁波大学	一种生物芯片杂交装置
CN113713868B (zh) *	2021-09-13	2023-05-12	北京京东方技术开发有限公司	一种微流控制芯片及其制作方法

Citations (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
EP0075605A1 (fr)	1981-09-25	1983-04-06	Winfried Dr. med. Stöcker	Dispositif pour analyses photométriques
US20040018615A1 (en)	2000-08-02	2004-01-29	Garyantes Tina K.	Virtual wells for use in high throughput screening assays
US20050019224A1 (en)	2003-06-16	2005-01-27	Schering Corporation	Virtual well plate system

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US6893877B2 (en) *	1998-01-12	2005-05-17	Massachusetts Institute Of Technology	Methods for screening substances in a microwell array
WO1999039829A1 (fr) *	1998-02-04	1999-08-12	Merck & Co., Inc.	Puits virtuels destines a etre utilises dans des criblages a haut rendement
DE19859623A1 (de) *	1998-12-23	2000-08-24	Basf Drucksysteme Gmbh	Photopolymerisierbare Druckformen mit Oberschicht zur Herstellung von Reliefdruckformen
US20020151040A1 (en) *	2000-02-18	2002-10-17	Matthew O' Keefe	Apparatus and methods for parallel processing of microvolume liquid reactions
US20020197733A1 (en) *	2001-06-20	2002-12-26	Coventor, Inc.	Microfluidic system including a virtual wall fluid interface port for interfacing fluids with the microfluidic system

2006
- 2006-05-22 EP EP06010516A patent/EP1860060B1/fr not_active Not-in-force
- 2006-05-22 DE DE502006007372T patent/DE502006007372D1/de active Active
2007
- 2007-05-22 US US11/805,242 patent/US20090017505A1/en not_active Abandoned

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
EP0075605A1 (fr)	1981-09-25	1983-04-06	Winfried Dr. med. Stöcker	Dispositif pour analyses photométriques
US20040018615A1 (en)	2000-08-02	2004-01-29	Garyantes Tina K.	Virtual wells for use in high throughput screening assays
US20050019224A1 (en)	2003-06-16	2005-01-27	Schering Corporation	Virtual well plate system

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
EP2228132A1 (fr) *	2009-03-10	2010-09-15	Qiagen GmbH	Dispositif isotherme PCR
CN104114280A (zh) *	2011-09-30	2014-10-22	生命科技公司	用于生物分析的系统和方法
US10385383B2 (en)	2011-09-30	2019-08-20	Life Technologies Corporation	Systems and methods for biological analysis

Also Published As

Publication number	Publication date
EP1860060B1 (fr)	2010-07-07
US20090017505A1 (en)	2009-01-15
DE502006007372D1 (de)	2010-08-19

Publication	Publication Date	Title
DE69824586T2 (de)	2005-06-23	Probenträger hoher dichte für die analyse biologischer proben
DE60312220T2 (de)	2007-11-15	Vorrichtung zum abgeben einer probe in elektrospray-massenspektrometern
DE60000539T2 (de)	2003-03-06	Vorrichtung und verfahren zur übertragung von kleinen substanzvolumen
DE60307552T2 (de)	2007-08-09	Vorrichtung zum Austragen kleiner Volumen Flüssigkeit einer Mikrokettenlinie entlang
EP1508808B1 (fr)	2009-10-21	Procédé de distribution microscopique a commande électrique
DE69015511T2 (de)	1995-05-24	Verfahren und Vorrichtung zum Verbinden von Halbleitersubstraten.
DE19952764C2 (de)	2003-02-27	Mikroanalysevorrichtung
DE10309583A1 (de)	2003-12-11	Mikroplatte mit einem integrierten mikrofluidischen System zum parallelen Verarbeiten winziger Fluidvolumen
DE10328730B4 (de)	2006-08-17	Verfahren zum Herstellen eines Microarrays und Vorrichtung zum Versehen eines Trägers für ein Microarray mit Beschichtungsstoffen
EP1212133B1 (fr)	2003-09-10	Dispositif et procede pour deposer une pluralite de microgouttelettes sur un substrat
DE69913721T2 (de)	2004-10-28	Testträger zur chemischen und/oder biochemischen analyse
DE60201257T2 (de)	2005-09-29	Verfahren und vorrichtung zur kontinuerlichen durchführung einer biologischen, chemischen oder biochemischen reaktion
DE10041536A1 (de)	2002-03-07	Vorrichtung und Verfahren zum berührungslosen Aufbringen von Mikrotröpfchen auf ein Substrat
WO2004071660A1 (fr)	2004-08-26	Procede et dispositif pour etablir un contact avec une structure microfluidique
EP1427521A1 (fr)	2004-06-16	Microcomposant
EP1860060A1 (fr)	2007-11-28	Procédé et appareil pour mélanger des micro-gouttelettes
DE60107953T2 (de)	2006-01-19	Thermischer injektions- und dosierkopf, verfahren zu seiner herstellung sowie funktionalisierungs- oder adressierungssystem mit einem solchem kopf
DE60213645T2 (de)	2007-08-09	Verfahren zum befüllen von löchern in substraten
DE602004010542T2 (de)	2008-12-04	Verfahren zur verteilung von tropfen einer betreffenden flüssigkeit auf einer fläche
DE60315375T2 (de)	2008-05-08	Spotting pin
DE10329983A1 (de)	2005-03-31	Mikroreaktorsystem mit einer Reaktionsräume aufweisenden Trägerplatte und Verfahren zum Betrieb desselben
EP1537402A1 (fr)	2005-06-08	Procede et dispositif pour pratiquer des techniques de marquage immunologique sur des coupes tissulaires
DE69910613T2 (de)	2004-06-17	Verfahren zum dosierten auftrag einer flüssigkeit auf eine oberfläche
EP1203398A1 (fr)	2002-05-08	Substrat et porte-piece destine a recevoir le substrat
EP1404447B1 (fr)	2008-09-17	Dispositif d'analyse

Legal Events

Date	Code	Title	Description
2007-10-26	PUAI	Public reference made under article 153(3) epc to a published international application that has entered the european phase	Free format text: ORIGINAL CODE: 0009012
2007-11-28	AK	Designated contracting states	Kind code of ref document: A1 Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IS IT LI LT LU LV MC NL PL PT RO SE SI SK TR
2007-11-28	AX	Request for extension of the european patent	Extension state: AL BA HR MK YU
2008-05-14	17P	Request for examination filed	Effective date: 20080326
2008-06-11	17Q	First examination report despatched	Effective date: 20080514
2008-08-06	AKX	Designation fees paid	Designated state(s): CH DE FR GB IT LI NL
2009-05-27	RTI1	Title (correction)	Free format text: APPARATUS FOR MIXING MICRODROPLETS
2009-12-11	GRAP	Despatch of communication of intention to grant a patent	Free format text: ORIGINAL CODE: EPIDOSNIGR1
2010-03-23	GRAS	Grant fee paid	Free format text: ORIGINAL CODE: EPIDOSNIGR3
2010-06-04	GRAA	(expected) grant	Free format text: ORIGINAL CODE: 0009210
2010-06-16	RAP1	Party data changed (applicant data changed or rights of an application transferred)	Owner name: MICRONAS GMBH
2010-07-07	AK	Designated contracting states	Kind code of ref document: B1 Designated state(s): CH DE FR GB IT LI NL
2010-07-07	REG	Reference to a national code	Ref country code: GB Ref legal event code: FG4D Free format text: NOT ENGLISH
2010-07-15	REG	Reference to a national code	Ref country code: CH Ref legal event code: EP
2010-08-19	REF	Corresponds to:	Ref document number: 502006007372 Country of ref document: DE Date of ref document: 20100819 Kind code of ref document: P
2010-08-25	REG	Reference to a national code	Ref country code: NL Ref legal event code: T3
2011-05-13	PLBE	No opposition filed within time limit	Free format text: ORIGINAL CODE: 0009261
2011-05-13	STAA	Information on the status of an ep patent application or granted ep patent	Free format text: STATUS: NO OPPOSITION FILED WITHIN TIME LIMIT
2011-06-15	26N	No opposition filed	Effective date: 20110408
2011-07-14	REG	Reference to a national code	Ref country code: DE Ref legal event code: R097 Ref document number: 502006007372 Country of ref document: DE Effective date: 20110408
2011-12-14	REG	Reference to a national code	Ref country code: NL Ref legal event code: V1 Effective date: 20111201
2011-12-30	REG	Reference to a national code	Ref country code: CH Ref legal event code: PL
2012-01-25	GBPC	Gb: european patent ceased through non-payment of renewal fee	Effective date: 20110522
2012-01-31	PG25	Lapsed in a contracting state [announced via postgrant information from national office to epo]	Ref country code: NL Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20111201 Ref country code: LI Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20110531 Ref country code: CH Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20110531
2012-02-17	REG	Reference to a national code	Ref country code: FR Ref legal event code: ST Effective date: 20120131
2012-02-29	PG25	Lapsed in a contracting state [announced via postgrant information from national office to epo]	Ref country code: IT Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20110522
2012-03-15	REG	Reference to a national code	Ref country code: DE Ref legal event code: R119 Ref document number: 502006007372 Country of ref document: DE Effective date: 20111201
2012-04-30	PG25	Lapsed in a contracting state [announced via postgrant information from national office to epo]	Ref country code: FR Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20110531
2012-06-29	PG25	Lapsed in a contracting state [announced via postgrant information from national office to epo]	Ref country code: GB Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20110522
2013-06-28	PG25	Lapsed in a contracting state [announced via postgrant information from national office to epo]	Ref country code: DE Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20111201