WO2000055618A2 - Collecteur - Google Patents

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Publication number
WO2000055618A2
WO2000055618A2 PCT/DE2000/000768 DE0000768W WO0055618A2 WO 2000055618 A2 WO2000055618 A2 WO 2000055618A2 DE 0000768 W DE0000768 W DE 0000768W WO 0055618 A2 WO0055618 A2 WO 0055618A2
Authority
WO
WIPO (PCT)
Prior art keywords
manifold
manifold according
working chamber
fluid
circuit
Prior art date
Application number
PCT/DE2000/000768
Other languages
German (de)
English (en)
Other versions
WO2000055618A3 (fr
Inventor
Steffen Howitz
Mario Bürger
Lars Rebenklau
Original Assignee
GeSIM Gesellschaft für Silizium-Mikrosysteme mbH
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 GeSIM Gesellschaft für Silizium-Mikrosysteme mbH filed Critical GeSIM Gesellschaft für Silizium-Mikrosysteme mbH
Priority to DE10080648T priority Critical patent/DE10080648D2/de
Priority to AU40993/00A priority patent/AU4099300A/en
Publication of WO2000055618A2 publication Critical patent/WO2000055618A2/fr
Publication of WO2000055618A3 publication Critical patent/WO2000055618A3/fr

Links

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
    • B01L3/50—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
    • 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
    • B01L2200/026—Fluid interfacing between devices or objects, e.g. connectors, inlet details
    • B01L2200/027—Fluid interfacing between devices or objects, e.g. connectors, inlet details for microfluidic devices
    • 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
    • B01L2200/12—Specific details about manufacturing devices
    • 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
    • B01L2300/06—Auxiliary integrated devices, integrated components
    • B01L2300/0627—Sensor or part of a sensor is integrated
    • B01L2300/0645—Electrodes
    • 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
    • B01L2300/0816—Cards, e.g. flat sample carriers usually with flow in two horizontal directions
    • 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
    • B01L2300/0887—Laminated structure
    • 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
    • B01L2300/12—Specific details about materials
    • 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
    • B01L2300/1838—Means for temperature control using fluid heat transfer medium
    • B01L2300/185—Means for temperature control using fluid heat transfer medium using a liquid as fluid
    • 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
    • B01L2400/06—Valves, specific forms thereof
    • B01L2400/0633—Valves, specific forms thereof with moving parts
    • B01L2400/0655—Valves, specific forms thereof with moving parts pinch valves
    • 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
    • B01L2400/06—Valves, specific forms thereof
    • B01L2400/0677—Valves, specific forms thereof phase change valves; Meltable, freezing, dissolvable plugs; Destructible barriers
    • 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

Definitions

  • Manifold with at least one microscope chamber in particular for biological or genetic engineering studies, with devices for supplying and discharging fluids.
  • the manifold forms the system basis with which fluidic components are networked together to form the microsystem.
  • the manifold has the task of keeping individual components mechanically defined, fluidly connecting them to one another and, if necessary, electrically coupling them.
  • Such microsystems are created by combining sensors, actuators and electronic components on the manifold, with devices for supplying and discharging fluids being integrated at the same time.
  • Such a manifold usually consists of a composite of different materials, for example a silicon-glass composite, the fluid channels in the manifold, possibly chemical microsensors and other functional units, being structured in silicon before the glass-silicon composite is joined. If new microsystems are to be designed, then one assumes fixed geometric conditions of the components to be integrated and fits them
  • Manifold accordingly is therefore changeable and fixed components are integrated.
  • Customized manifolds for microfluidics in silicon-glass construction are currently customary on the market.
  • the joining of the different materials into a composite is carried out with the aid of the known technology of anodic bonding.
  • the choice of material is determined by the application and the technological know-how. Different material combinations are practically feasible.
  • a manifold can be produced from a silicon-glass composite by anodic bonding, which enables extremely short iteration times with a module concept that is easy to implement.
  • the actual channel system is created by anodic bonding, which is extremely reliable and robust and can also be easily linked using conventional techniques.
  • the advantages of a silicon-glass composite are high reagent compatibility and the possibility of realizing structure sizes down to the sub- ⁇ m range.
  • the actual duct system is created by anodic bonding, which is extremely reliable and robust and can also be easily linked with conventional techniques.
  • Another possibility for realizing a manifold is to implement a silicon-silicon composite. Extremely short iteration cycles are achieved here with a module concept that is easy to implement.
  • the advantages of a silicon-silicon composite are high reagent compatibility and the possibility of realizing structure sizes down to the sub- ⁇ m range.
  • a manifold can also be produced from a polymethyl methacrylate (PMMA) or polydimethylsiloxane (PDMS).
  • PMMA polymethyl methacrylate
  • PDMS polydimethylsiloxane
  • LTCC Low Temperature Cofiring Technology
  • This technology is characterized by the use of individual layers of green ceramic. These layers are mechanically structured separately and provided with vias and electrical functional layers. After the lamination of the individual layers, that is to say the actual layer structure, this takes place in a subsequent technological step Burning out and sintering to a stable ceramic wiring carrier with several control levels.
  • the wiring carriers created in this way are used as ceramic multi-chip modules (MCM-C), especially in high-frequency technology, although the three-dimensional shape and the integration of non-electrical functions are also increasingly being added. Another focus is the use of photo-structurable thick-film pastes.
  • the invention is based on the object of creating a manifold with at least one microscope chamber, in particular for biological or genetic engineering investigations, which can be structured in a completely universal and cost-effective manner and which permits the combination of any desired fluidic, electrical and mechanical components.
  • the object on which the invention is based is achieved in a manifold of the type mentioned at the outset in that the working chamber extends through a sandwich-like multilayer arrangement which consists of a combination of layers produced in thick-film and thin-film technology, in that the working chamber is fixed or reversible by means of a glass cover is closed that the devices for supplying and discharging fluids are designed as buried structures in at least one of the levels of the sandwich-like multilayer arrangement and that the devices for supplying and discharging fluids are designed in the form of several mutually independent fluid circuits.
  • the multilayer arrangement can consist of a stack of alternating glass and silicon layers, or of a stack of a large number of ceramic layers (multilayer ceramic).
  • the ceramic layers are produced from an LTCC ceramic, particularly cost-effective production is made possible.
  • the devices for supplying and discharging the fluids are designed as three-dimensionally intersecting fluid channels and can additionally be equipped with control valves, the membrane of the control valve should be made of silicon.
  • control valves If the passage cross section of the control valves is designed to be switchable or controllable, simple metering of the fluids passed through the valves can be achieved.
  • the control valves can be actuated pneumatically, fluidically or electrically, or also by changing the pressure in the fluid circuit.
  • each control valve is designed as a thermoelectric valve with a heating element, wherein it is also possible to arrange the heating element spatially separated from the control valve.
  • the heating element can be implemented particularly easily if it is designed as a printed interconnect.
  • each control valve is equipped with a silicon membrane over the valve chamber, which is firmly connected at the edge to the LTCC ceramic.
  • the working chamber is provided with electrodes for generating an electrical field.
  • electrodes can advantageously be realized in that the microscope camera is provided with an internal metalization, which is electrically connected to the electrical connections of the manifold.
  • a further development of the invention is characterized in that a fluid connection strip is provided in which all fluid channels and hydraulic fluid channels and the fluid channels of the cooling circuit open.
  • This fluid connection strip is advantageously arranged on an outer edge of the manifold.
  • an electrical connection strip is provided, in which all electrical functional connections are combined.
  • This electrical connection strip should advantageously also be arranged on an outer edge of the manifold, it being particularly favorable for the user of the manifold if the electrical connection strip is arranged on the outer edge of the manifest, which is opposite the fluid connection strip.
  • the invention enables complex, planar microfluidic manifolds to be implemented using the LTCC technology and the hybrid technology for integrating microfluidic components that have been produced with other than the LTCC technology.
  • Such manifolds can be used for the purposes of cell therapy or pharmaceutical development / testing in biological test systems.
  • Controlled fluid management means the serial or parallel execution of functions. These functions concern the controlled heating and cooling of a working chamber as well as the exact temperature measurement by integrated temperature sensors. They concern a freely selectable number of microfluidic inflows and outflows in this working chamber. The rate of the liquids in these inlets and outlets can be regulated with the aid of microvalves or can be switched off completely or completely. The flow rate of the fluids in these channel systems can be measured online by means of integrated high-resolution flow sensors.
  • Electrochemical eg: pH electrodes
  • micromechanical sensors eg: pressure sensors
  • the working chamber is reversibly or irreversibly closed by substrates mounted on the top and bottom.
  • These substrates preferably consist of the materials glass, silicon or a biocompatible polymer, it being possible for these substrates themselves to be carriers of electrically active microelectrodes (for example: micro-T sensor, micro heater).
  • the manifolds can be combined in combination with all microscopes (e.g. high-resolution fluorescence microscopes, light-optical microscopes, inverse microscopes, microscopes with optical or dielectric cell tweezers).
  • Figure 1 is a plan view of an inventive manifold of a microscope chamber.
  • FIG. 2 shows a plan view of a middle buried layer of the manifold with electrical functional assemblies and electrical external connections
  • Fig. 3 shows a first fluid level for supplying the fluid for Chamber of Labor
  • Fig. 5 shows a third fluid level with a cooling circuit for the manifold.
  • the manifold here consists of a ceramic base body in LTCC technology, the microscopy chamber K, which is formed by a glass cover (not shown) in a central hole in the ceramic body, and the hybrid-integrated microsensors and microactuators, the electrical and fluidic connection elements.
  • a fluid connection strip FL is provided for the fluid connection for all required functions, which is connected to the fluid channels FK and the hydraulic channels HF of the manifold.
  • the flui connection strip FL is arranged along an edge of the manifold.
  • the opposite edge of the manifold is connected to an electrical connection strip EL for connecting the electrical components of the manifold. This significantly improves the handling of the manifold.
  • the ceramic base body BK consists of individual ceramic layers with a thickness of 150 to 200 ⁇ m and contains three fluid circuits (FIGS. 3 to 5) which have different functions.
  • the first fluid circuit is the working chamber circuit, which combines all the fluidic channels that lead into or out of the working chamber.
  • the second circuit is the valve circuit (FIG. 4) which summarizes all the channels that are required for filling and operating the thermoelectric silicon microvalves.
  • the third fluid circuit is the cooling circuit KK (FIG. 5), with the aid of which the temperature in the working chamber can be kept constant even in the event of any electrical heat loss. Conversely, the cooling circuit KK prevents the flow of heat from a possibly high microscope chamber K or working chamber A to the thermoelectric microvalves V.
  • each ceramic layer is mechanically structured separately in the unsintered state and provided with vias and electrical functional layers by means of screen printing. After the lamination of the individual layers, in a subsequent technological step, the burnout and sintering takes place to form a stable ceramic multilayer structure. In addition to mechanical and electrical functions, this structure also fulfills microfluidic functions.
  • the manifold shown in FIGS. 1 to 5 consists of 16 ceramic individual layers with a microscope chamber K, the fluidic working chamber circuit has 3 fluid inlet channels and a fluid outlet channel, as well as two valve circuits and a cooling channel that encompasses the working chamber A. All fluidic circuits are arranged on an area of 45x45 mm 2 , crossing three-dimensionally.
  • Two of the fluid inlet channels in the working chamber circuit have an integrated silicon-based microvalve V, which allows the setting of a defined closing rate in the range from 0 to a few 100 microliters per minute.
  • This microvalve V is designed as a thermoelectric valve, in which the actuator of the thermoelectric valve is geometrically separated from its place of action of the Si membrane.
  • the LTCC allows the construction of a microfluidic hydraulic circuit, which separates the heater and the microchannel to be switched. The advantage is that the channel fluid is not heated when valve V is switched. The switching process itself takes place by heating an actuator fluid circuit (valve circuit), the expansion of which deforms the Si membrane at valve V and the valve seat is closed or opened.
  • the heater of the valve can also benefit from the KK cooling circuit through the integration in the manifold, which makes valve V faster in its switching dynamics. If, for example, a normally open valve is used to activate the actuator fluid has to cool down in order to release the valve seat, you only have to wait until the actuator fluid is cool enough again, which can be accelerated by the cooling circuit.
  • a flow sensor is integrated in each of the microchannels FK, which can be designed, for example, as a miniaturized electrocaloric flow sensor F.
  • the cooling duct comprises the working chamber A and, in another position, overlapping three dimensions, has a thick-film heater comprising the working chamber.
  • a cooling fluid for active cooling can be pumped through the manifold.
  • the thick film heater allows the fluid in the working chamber A to be heated in the temperature range from room temperature to 100 ° C with settling times of approx. 1 minute.
  • the cooling fluid circulating in the cooling circuit KK prevents, on the one hand, the heating of the manifold when heating is required in the working chamber A.
  • the cooling duct also thermally decouples the micro heater and the working chamber. This is important because the silicon microvalves used in the exemplary embodiment each have a thermoelectric actuator which must be heated to approximately 42 to 45 ° C. during operation.
  • the fluidically usable working chamber A is created by covering the central hole on both sides, which extends through all the ceramic individual layers, with a glass substrate.
  • one of the glass substrates is irreversible and one is reversibly connected to the manifold.
  • the irreversible glass substrate consists of a 500 ⁇ m thick Pyrex glass plate. This also has a temperature sensor T that extends into the working chamber A. As a result, the temperature of the fluid in the working chamber A can be determined continuously at any time.
  • the reversibly mounted glass substrate can be placed on the manifold in a thickness from 150 ⁇ m, which can also be used to perform confocal microscopy on biological objects in the working chamber.
  • the working chamber is provided with an inner hole metallization.
  • This inner hole metallization can be designed as electrodes that extend over the entire bore depth of the working chamber. With these electrodes, an electric field acting on biological cells to be examined can be generated.

Landscapes

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

Abstract

Cette invention concerne un collecteur présentant au moins une chambre de microscope, notamment pour des recherches en biologie ou en génie génétique, ainsi que des dispositifs pour conduire et évacuer des fluides. L'objectif de l'invention est de réaliser un collecteur présentant au moins une chambre de microscope, notamment pour des recherches en biologie ou en génie génétique, dont la structure est parfaitement universelle et économique, et qui comprend une combinaison de composants quelconques fluidiques, électriques et mécaniques. L'objectif est atteint par le fait que la chambre de travail (A) s'étend à travers un agencement multicouche en sandwich, constitué d'une combinaison de couches épaisses et de couches minces, par le fait que la chambre de travail (A) est fermée par un couvercle de verre, de façon définitive ou réversible, par le fait que les dispositifs pour conduire et évacuer des fluides sont insérés dans au moins une des couches de l'agencement multicouche en sandwich, et par le fait que les dispositifs pour conduire et évacuer des fluides sont sous forme de plusieurs circuits fluidiques indépendants les uns des autres.
PCT/DE2000/000768 1999-03-15 2000-03-14 Collecteur WO2000055618A2 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
DE10080648T DE10080648D2 (de) 1999-03-15 2000-03-14 Manifold
AU40993/00A AU4099300A (en) 1999-03-15 2000-03-14 Manifold

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE19911345.9 1999-03-15
DE19911345 1999-03-15

Publications (2)

Publication Number Publication Date
WO2000055618A2 true WO2000055618A2 (fr) 2000-09-21
WO2000055618A3 WO2000055618A3 (fr) 2000-12-28

Family

ID=7900940

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/DE2000/000768 WO2000055618A2 (fr) 1999-03-15 2000-03-14 Collecteur

Country Status (3)

Country Link
AU (1) AU4099300A (fr)
DE (1) DE10080648D2 (fr)
WO (1) WO2000055618A2 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1489404A1 (fr) * 2003-06-16 2004-12-22 GeSIM Gesellschaft für Silizium-Mikrosysteme mbH Méthode de production d'une cellule d'écoulement 3-D pour microscope

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996028664A1 (fr) * 1995-03-14 1996-09-19 Baxter International Inc. Module electrofluidique normalise et ensemble de cartes a circuits imprimes personnalisees
WO1996035971A2 (fr) * 1995-05-10 1996-11-14 Epigem Limited Element a microrelief et sa fabrication

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996028664A1 (fr) * 1995-03-14 1996-09-19 Baxter International Inc. Module electrofluidique normalise et ensemble de cartes a circuits imprimes personnalisees
WO1996035971A2 (fr) * 1995-05-10 1996-11-14 Epigem Limited Element a microrelief et sa fabrication

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1489404A1 (fr) * 2003-06-16 2004-12-22 GeSIM Gesellschaft für Silizium-Mikrosysteme mbH Méthode de production d'une cellule d'écoulement 3-D pour microscope

Also Published As

Publication number Publication date
DE10080648D2 (de) 2002-02-28
WO2000055618A3 (fr) 2000-12-28
AU4099300A (en) 2000-10-04

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