CN1331575C - Implementation of microfluidic components in a microfluidic system - Google Patents

Implementation of microfluidic components in a microfluidic system Download PDF

Info

Publication number
CN1331575C
CN1331575C CNB038249804A CN03824980A CN1331575C CN 1331575 C CN1331575 C CN 1331575C CN B038249804 A CNB038249804 A CN B038249804A CN 03824980 A CN03824980 A CN 03824980A CN 1331575 C CN1331575 C CN 1331575C
Authority
CN
China
Prior art keywords
substrate
chamber
flow path
microchannel
capping module
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.)
Expired - Fee Related
Application number
CNB038249804A
Other languages
Chinese (zh)
Other versions
CN1694756A (en
Inventor
J·R·吉尔伯特
M·德什潘德
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.)
Cytonome Inc
Original Assignee
Cytonome Inc
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 Cytonome Inc filed Critical Cytonome Inc
Publication of CN1694756A publication Critical patent/CN1694756A/en
Application granted granted Critical
Publication of CN1331575C publication Critical patent/CN1331575C/en
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

Links

Images

Landscapes

  • Automatic Analysis And Handling Materials Therefor (AREA)
  • Physical Or Chemical Processes And Apparatus (AREA)
  • Separation Using Semi-Permeable Membranes (AREA)

Abstract

A system and method for integrating microfluidic components in a microfluidic system enables the microfluidic system to perform a selected microfluidic function. A capping module includes a microfluidic element for performing a microfluidic function. The capping module is stacked on a microfluidic substrate having microfluidic plumbing to incorporate the microfluidic function into the system.

Description

The realization of the microfluidic components in the microfluidic systems
The priority of U.S. Provisional Patent Application No.60/409489 that the application requires to enjoy in the U.S. Patent application No.10/329018 that submitted on December 23rd, 2002, submitted on September 9th, 2002 and the U.S. Provisional Patent Application No.60/410685 that submits on September 13rd, 2002, the content of these applications is incorporated herein by reference.
Technical field
The present invention relates to a kind of microfluidic systems that is used under the microjet level, handling fluid sample.More particularly, the present invention relates to a kind of system and method that is used for realizing microfluidic function in microfluidic systems.
Background technology
Microfluidic device and system provide chemistry, biochemistry and biological analysis and the synthetic improved method carried out.Microfluidic device and system allow to carry out rapid, the eurypalynous chemical operation of multistep in the little chemical analysis system of chip base.Chip base microfluidic systems generally includes traditional " microjet " element, and it especially can processing and analytical chemistry and biological sample.As a rule, the term in this area " microjet " is meant the system or the device of the network with processing node, chamber and storage tank of linking to each other by passage, wherein the typical section size of these passages be in about 1.0 microns in about 500 microns scope.In the art, the passage with these sectional dimensions is called " microchannel ".
In chemistry, biomedical, bioscience and pharmaceutical industry, carrying out in the mode of highly-parallel that a large amount of chemical operation become as reaction, separation and subsequent detection step is to press for.Synthesizing, screen and analyzing of the high yield of (biology) compound makes it possible to find economically new medicine and drug candidate, and can realize complicated medical diagnostic equipment.For the improvement of chemical operation required in using at these, importantly improve speed, strengthen reproducibility, reduce the consumption of expensive samples and reagent, and reduce the waste of material.
In the field of biotechnology especially cytology and medicine screening, need the particulate filter of high yield.Need the example of the particle of filtration that various types of cells is arranged, for example blood platelet, white blood cell, tumour cell and blastocyte etc.These particles gain a special interest in cytological field.Other particle has (greatly) molecular species, for example protein, enzyme and polynucleotide.In the field of the drug screening during new drug development, this class particle gains a special interest.
Summary of the invention
The invention provides a kind of being used for is integrated into microfluidic systems so that make microfluidic systems can carry out the system and method for selected microfluidic function with microfluidic components.The present invention has used the capping module that includes the microfluidic element that can carry out microfluidic function.This capping module stack is on the microfluidic substrate with microjet pipeline, so that microfluidic function is integrated in the system.
According to a first aspect of the invention, provide a kind of microfluidic systems, having comprised: be formed at first microchannel in the substrate; First communications ports that first microchannel is linked to each other with substrate surface; Be formed at second microchannel in the substrate; Be formed at the 3rd microchannel in the substrate; And capping module, it has the groove that is formed at wherein, and covered groove so as to form the chamber be used for repel to come the semi-permeable membrane of separate substance by size, this film has formed the wall in described chamber, the capping module comprises the outlet that is formed at the inlet that leads to the chamber wherein and leads to the chamber, wherein capping module can be stacked on the substrate, make the inlet in chamber be arranged to be communicated with first microchannel, the outlet in chamber is arranged to be communicated with second microchannel, and film is arranged to be communicated with the 3rd microchannel, like this, the filtrate of process film enters into the 3rd microchannel, thereby the microjet filtering function is incorporated in the microfluidic systems.
According to a second aspect of the invention, provide a kind of capping module that is used for microfluidic systems, having comprised: substrate, it has the groove that is formed in the substrate surface; Be located at being used on the substrate and repel the semi-permeable membrane that carries out the material filtration by size, this film has covered groove so that form the chamber; Be formed at the inlet that leads to described chamber in the substrate; Be formed at the outlet that comes from described chamber in the substrate; Wherein, the capping module can be stacked on the microfluidic systems that wherein is formed with the microchannel, makes described chamber be arranged to be communicated with the microchannel via inlet, thereby filtering function is incorporated in the microfluidic systems.
According to a third aspect of the invention we, provide a kind of microfluidic systems, having comprised: have a plurality of substrates that are formed at microchannel wherein, wherein each microchannel comprises one or more communications ports that the microchannel is linked to each other with substrate surface of being used for; A plurality of microjet capping modules, each module have and are arranged on the groove so that form the semi-permeable membrane that is used to carry out the microjet filtering function in chamber, the outlet of leading to the inlet in described chamber and leading to described chamber in corresponding capping module; Wherein, in the microjet capping module first is stacked on the substrate, and one of make by the communications ports that is associated with one or more microchannels in the entrance and exit of first microjet capping module and described one or more microchannels fluidic communication, thereby the first microjet filtering function is attached in the system, second in the microjet capping module is stacked on the described substrate, and one of make by the communications ports that is associated with another one or a plurality of microchannel in the entrance and exit of second microjet capping module and described another one or a plurality of microchannels fluidic communication, thereby the second microjet filtering function is attached in the system.
According to a forth aspect of the invention, provide the filtration system of the little manufacturing in a kind of microfluidic systems, having comprised: the capping module, it comprises the film that is used for separating substances is become first and second components; Be used to transmit first flow path of material by microfluidic systems, wherein when the capping module stack was on substrate, the capping module and first flow path intersected; First storage tank, it is formed in the capping module and is on the film, has the inlet that is communicated with first flow path that is used to accept described material, and the outlet that is communicated with first flow path that is used for first component is sent out from first storage tank; Second storage tank, it is formed in the substrate and is used to accept second component of described material; Be used to accept second component and the second flow path second storage tank fluidic communication of described material; And be used for the first-class body source that is communicated with first flow path that evocating substance flows, wherein capping module stack is on substrate, the storage tank of winning is communicated with second storage tank, and separate by the film and second storage tank, the material that transmits along first flow path is divided into first component and second component, wherein first component flows path flow through first storage tank along first, and second component is along second flow path film of flowing through.
According to a fifth aspect of the invention, provide the filtration system of the little manufacturing in a kind of microfluidic systems, having comprised: substrate; Be arranged in first flow path that is used to transmit material of substrate; Being formed at being used in the substrate accepts and transmits second flow path of component after the filter of material; Be formed in the substrate and the groove that is communicated with second flow path; Define the lid in retention chamber, this lid is stacked on the substrate, makes the retention chamber be arranged to be communicated with first flow path; Be fixed on the lid to have covered the film in retention chamber, wherein the size of this film is made for and described separating substances can be become filter back component and retained fraction, and when being stacked on the substrate, lid is arranged on the groove, thereby define the filter chamber that is in film below, so just can second flow path is arranged near the of first flow path and separate with it by film; Be formed in the substrate and the 3rd flow path that is communicated with the retention chamber, be used for accepting and send retained fraction from the described material in retention chamber.
According to an aspect, the invention provides the microfiltration system in a kind of microfluidic chip, it is used for the material such as the compound separation of the closed channel system of process capillary dimensions are become different components.Filtration system of the present invention provides filtering module, and it can assemble by lower one-tenth originally, can provide time per unit to filter the accurate means of relatively large compound simultaneously.Microfiltration system is integrated into traditional membrane filtration technology in the microfluidic systems that is formed by glass, plastics or other suitable material.The filtration system of little manufacturing can comprise in the microfluidic systems that is designed for the standard of being inserted into so that the subsystem that filters on the sheet to be provided.An exemplary filtration system comprises that film has been isolated the material of first flow path of flowing through by size discrimination by separated two flow paths of film.Be formed with the storage tank that communicates with flow path in the both sides of film.On film, connect the lid of little manufacturing, thereby defined the storage tank of film top.
According on the other hand, can adopt the closure construction that wherein is formed with electromagnetic valve components that magnetic valve is integrated in the microfluidic systems.Electromagnetic valve components comprises the film that flows that is used for optionally stopping through one or more communications ports of substrate, and the actuating assembly that is used to control film position.
Description of drawings
Fig. 1 has shown microfluidic systems, and it includes the closure construction that is used for microfluidic function is integrated into microfluidic systems.
Fig. 2 has shown and has been applicable to the diagnostic microfluidic chip that includes microfiltration system according to an illustrative embodiment of the invention.
Fig. 3 is the perspective cross-sectional view of the microfiltration system in according to an illustrative embodiment of the invention the chip shown in Figure 2.
Fig. 4 is the detailed view of the film on the microfiltration system shown in Figure 3.
Fig. 5 has shown the lid of little manufacturing of microfiltration system shown in Figure 3.
Fig. 6 is the top view of microfiltration system shown in Figure 3.
Fig. 7 is the top view of the diagnosing chip shown in Figure 2 before the assembling microfiltration system.
Fig. 8 is the top view of the diagnosing chip shown in Figure 2 after the assembling microfiltration system.
Fig. 9 a is the top view of the direct microfiltration system of two-port formula of the alternative according to the present invention.
Fig. 9 b is the perspective cross-sectional view of microfiltration system shown in Fig. 9 a.
Figure 10 a is the top view of the direct microfiltration system of three port type of the alternative according to the present invention.
Figure 10 b is the perspective cross-sectional view of microfiltration system shown in Figure 10 a, and wherein the lid of little manufacturing is removed.
Figure 11 has shown the magnetic valve that is attached to according to an embodiment of the invention in the microfluidic systems.
The specific embodiment
The invention provides a kind of filtration system that is used to allow sample is carried out little manufacturing of filtration on the sheet, purification or separation.The filtration system of little manufacturing can be used in many kinds application, and include but not limited to blood separation and filtration, micro-dialysis, need little chemical analysis of filtration or dialysis subsystem and synthesize application, and other microfluidic application.To the present invention be described at an exemplary embodiment hereinafter.Those skilled in the art will appreciate that the present invention can implement in multiple different application and embodiment, and its application can not be limited in the specific embodiment as herein described particularly.
The employed term of this paper " microjet " refers to a kind ofly to be used to load and unload, handles, the system that includes at least one passage with microscale dimensions or the device of ejection and/or analysing fluid samples.
The employed term of this paper " passage " and " flow channel " refer to a kind of form or in medium and allow the path of fluid such as liquids and gases motion.Passage in the microfluidic systems preferably has and is in about 1.0 microns sectional dimensions in about 500 micrometer ranges, its more desirably be in about 25 microns in about 250 microns scope, preferably be in about 50 microns in about 150 microns scope.Those of ordinary skill in the art possesses the suitable volumes of definite flow channel and the ability of length.These scopes comprise that above-mentioned value is as the upper limit or lower limit.Flow channel can have any selected shape or setting, and their example comprises linear or nonlinear structure, and the U-shaped structure.
The employed term of this paper " microfluidic element " refers to be used for carry out the parts of the microfluidic systems of microfluidic function, it includes but not limited to: passive check valve, aggressive valve, pressure sensor, interface channel, membrane filtration unit, the thread plug that is used for external connecting pipe, compression chamber, pump, and other known parts of those of ordinary skill in the art.
The employed term of this paper " film " or " filter " refer to can be used to by size exclusion or other measure separates or the material of any proper composition of medium and size.
The employed term of this paper " substrate " refers to wherein be formed with the supporting construction of the passage that is used for transmitting fluid.
The employed term of this paper " lid " or " capping module " refer to a kind ofly have identical size with substrate or smaller slightly size, have any selected size of being formed by any selected material or shape and have the structure of microfluidic element.The capping module structure becomes to be stacked on the substrate or can communicate by letter with it, thereby completely or partially finishes fluid path.
The employed term of this paper " material " refers to be used in any material in the microjet technology, includes but not limited to compound, molecule, virus, cell, particle, bead, buffer, and perhaps any other can be used on material in the microjet technology.
The employed term of this paper " microfluidic function " refers to include but not limited to any operation, function or technology that the fluid in the microfluidic systems or sample are carried out or applied: filtration, dialysis, pumping, fluid flow adjustment, control fluid flow etc.
The employed term of this paper " port " refers to provide the structure of fluid connection between two elements.
The employed term of this paper " pump " refers to be used to suck and discharge the device of fluid, and it can be of different sizes, and comprises microscale dimensions, is called " Micropump " here.
The present invention allows to adopt the capping module with the microfluidic element that can carry out microfluidic function that different microfluidic function is implemented in the microfluidic chip.As shown in Figure 1, be suitable for realizing that the microfluidic chip 10 of one embodiment of the invention comprises substrate 11, it has one or more flow channels that are shown as the microchannel 3 located therein.Flow channel can transmit fluid through microfluidic systems 10, so that any other suitable operation is handled, loads and unloads and/or carried out to fluid samples.Microfluidic systems 10 can comprise the flow channel 3 that is used for transmitting fluid process microfluidic systems 10 of any right quantity.
As shown in Figure 1, flow channel 3 is formed in the substrate 11, and can be via one or more communications ports 13a, and 13b links to each other with substrate surface.Be provided with capping module 15 to form the fluid path of sealing on substrate 11, this capping module comprises the microfluidic element 18 that is used to carry out microfluidic function, for example filter, one or more valve, pressure sensor or other parts.According to an alternative, the capping module can comprise and is used for guiding once more the flow through interface channel of microchannel of another structure periphery of fluid.This illustrative substrate 11 comprises two communications ports 13a, 13b, each port is with the part 3a that do not link to each other of flow channel 3, and 3b links to each other with substrate surface, yet those skilled in the art will recognize that and to make amendment in size, quantity and the configuration aspects of communications ports and flow channel.
This exemplary capping module 15 can comprise the connectivity port that has a common boundary with the communications ports of substrate, and/or is used for providing between first connectivity port and second connectivity port chamber 12 or the passage of fluidic paths.Those skilled in the art will recognize that the capping module can have other structure, is not limited to embodiment shown in Figure 1.
Adopt capping module 15 just microfluidic function such as for example filtration, dialysis, pumping, the control of flowing can be integrated in the microfluidic systems 10, do not need substrate 11 is improved significantly.Include any amount or setting be used for transmit the conduit of fluid or the substrate of passage 3 can be transformed into functional fluidic circuits, this is that one or more to have the capping module 15 of functional microfluidic element 18 and it is arranged on substrate be to realize on the chip by selecting.According to an exemplary embodiment, can adopt and " pick up and put (pick and place) " surperficial erection unit technology with the identical automation that is used for making integrated circuit and utilize various closure constructions to come to form fluidic circuits having on the substrate of microchannel.The suitable equipment of putting that picks up for example can be by Manncorp, and (Huntingdon Valley PA) makes Inc..
In order to make fluidic circuits, the passage 3 in the substrate 11 can be made by chip microfabrication.Passage or pipeline can be made like this, promptly etch hemichannel in first substrate, and bonding then and/or lamination second substrate to be sealing these hemichannels, thereby form the microchannel.More complicated if desired fluidic networks, substrate can be formed by one or more layers that contains etched channels.Can in substrate, make communications ports then, so that the microchannel is linked to each other with the outer surface of substrate.The proper technology that is used to make communications ports comprises boring, laser-induced thermal etching, powder explosion or other technology as known in the art.After having made substrate and communications ports, the capping module that will have desired function is adhered on the substrate, forms the microfluidic components in the big microjet loop.
The capping module of varying number and size can be adhered on the substrate, form microfluidic systems so that apply various microfluidic function.The capping module can be removed and change, so that can reuse substrate.
According to an exemplary embodiment, the capping module has the sectional dimension that is between about 1 millimeter to about 5 centimetres, yet those skilled in the art will recognize that the present invention is not limited to this scope.The capping module can be formed by any suitable material, includes but not limited to plastics, glass, silicon and other material known in the art.
Fig. 2 has shown the architecture of an illustrative microfluidic diagnostic chip of can content according to the present invention making.Diagnosing chip 20 can comprise one or more microfluidic components, and it can be individually or is constructed to be permeable to promote the processing of sample with combining.For example as shown in the figure, diagnosing chip 20 comprises microfiltration system 100, and the material in its separable solution is for example isolated selected particle or other particle from cell or suspension.Diagnosing chip 20 also can comprise and one or morely is used to store and supply the storage tank 90 that sample, reagent or other compound are given system, and one or more waste liquid storage tank 91 that is used to assemble the sample waste liquid.Diagnosing chip also can comprise one or more mensuration consumptions, mixing and cultivation parts, sample dilution system on the sheet for example, and it is used to handle sample, for example carries out the mixing of specific amount of sample and reagent.For example this example system comprises hydrid component 60 and cultivates zone 61.Chip also can comprise the detector 70 that is used for analyzing from thing after the filter of microfiltration system 100.Detector 70 can utilize any suitable detection means, includes but not limited to fluorescence, electrochemical analysis, dielectrophoresis, surface plasma resonance (SPR), radio frequency, heat analysis and combination thereof.Chip 10 can adopt and be used for Selective Control through the valve of the fluid flow of passage, and one or morely is arranged on the chip or chip is outer is used for the driver element of Fluid Motion Driven By Moving through the passage 3 on the chip.Those skilled in the art will recognize that microfluidic systems is not limited to diagnosing chip shown in Figure 2,, can make amendment structure, position, quantity and the combination of various microfluidic components according to the present invention.
Microfiltration system 100 of the present invention utilizes the capping module that traditional membrane filtration technology is integrated in the microfluidic chip.Filtration system can be inserted in the existing microfluidic chip, so that the particle in the suspension, cell or other material are filtered, does not need chip structure is carried out significant or the expensive improvement of cost.
Fig. 3,4 and 6 has shown and has been applicable to the filter subsystem 100 that is implemented in the little manufacturing in the microfluidic systems shown in Figure 2 according to an embodiment of the invention.Fig. 5 has shown and has been used for making the capping module 15 of filtration system 100 according to an embodiment of the invention.Filter subsystem is used for for example including the sample of the mixture of particle and fluid by film 110 separate substances, and collects the component that is separated afterwards.According to an exemplary embodiment, adopt filter subsystem to come washed corpuscles from blood plasma, yet those skilled in the art will recognize that the present invention also includes other application.According to other application, can adopt this filtration system to come isolated viral from cell, bead isolation from cell, and the material that separates of separating compound, molecule or other available film.As shown in the figure, filter subsystem 100 is formed directly on the microfluidic chip, thereby for chip has increased strainability, and do not require and carry out significant or the expensive improvement of cost.
Filter subsystem 100 utilizes traditional membrane filter 110 to isolate two flow paths in substrate 11, so that the small volume controlled filter of sampling.This illustrative filtration system is four port type transversal filters, it comprises and is used for providing to filtration system the first fluid flow path 120 of the mixture of material, for example particle and fluid, and second fluid flow path 130 that is used for accepting and send thing (being filtrate) after the filter of inherent filtration system.First fluid flow path 120 comprises first communications ports, and it is shown as at the first inlet 121a place and the first crossing access road 121 of filtration system.First fluid flow path 120 comprises second communications ports, and it is shown as first exit passageway 122, and it comprises the outlet 122a that comes from filter chamber, is used for accepting and sending the reservation material of inherent filtration system.Second fluid flow path is included in the access road 131 that the filter chamber of second porch and film 110 belows intersects, and second exit passageway 132 that is used for sending thing after the filter of inherent filtration system.Second fluid flow path 130 can comprise the carrier fluid that is used for transmitting filter back thing.The source drives mixture filtration system of flowing through is separated through the component of film realizing.Fluid source can comprise the peristaltic pump of the syringe pump of chip exterior, little manufacturing, the syringe of little manufacturing, any suitable fluid source perhaps known in the art, for example be entitled as those fluid sources described in the U.S. Provisional Patent Application No.60/391868 (attorney docket CVZ-019-2) of " microfluidic systems and parts ", the content of this application is incorporated herein by reference.
The filtration system 100 of this exemplary little manufacturing has less floor space (less than about 1 square millimeter), has caused compact structure, lower cost simply to be made with relative.This particle separator also provides the relatively low deformation rate that has seldom or do not stop up.If necessary, the Fluid Volume that is kept can be very big, and in addition if necessary, this design can be at extra analytical procedure bi-directional scaling and repetition.
Filter subsystem of the present invention can form by the microfluidic chip that the intersection 101 that includes two flow channels 120,130 is provided.The parts that assembly technology is only made for integrated batch, it is simple relatively, and can realize low-cost under big capacity.According to an exemplary embodiment, chip is formed with the groove 140 that communicates with second flow path 130 at intersection 101 places.First flow path 120 is initial separated or separately by groove 140.Adopt suitable adhesive or other suitable bindiny mechanism with suitable film 110 attached on the microfluidic chip, so that the covering groove is used for holding filter back thing and transmits the storage tank of filter back thing through second flow path 130 thereby formed below film.This film can comprise any suitable filtration membrane known in the art.
The capping module 15 of the exemplary little manufacturing of shown in Figure 5 this is fixed on the top of film 110, thereby has formed a filter chamber 161 that communicates with first flow path 120.Lid 15 can adopt suitable adhesive or other suitable bindiny mechanism to connect.This exemplary capping module 15 comprises inlet 162 and the outlet 163 that is communicated with filter chamber, so that first flow path 120 is linked to each other with filter chamber 161, and realizes composition to be filtered flowing via the filter chamber above the film.Perhaps, film 110 directly is fixed on the capping module 15, and the capping module is connected on the substrate, thereby filtration system is integrated on the substrate.Those skilled in the art will recognize that the capping module is not limited to this exemplary embodiment, can content according to the present invention change.
Fig. 7 has shown microfluidic systems 10, and it is included in assembling and has the passage 3 that just is formed at before the capping module 15 of film 110 wherein.Fig. 8 is the decline top view of fluidic system 10 of the capping that possesses strainability.
Composition to be filtered is incorporated into the filter subsystem from access road, and enters on the filter chamber neutralized film 110.The component of material is separated by film 110, and less component such as plasma flow enter into groove 140 through film, and second flow path 130 of flowing through.Remainder such as haemocyte are flowed through filter chamber and are arrived the outlet of first flow path 120.
According to this exemplary embodiment, the substrate of microfluidic chip can be formed by glass, plastics, silicon, quartz, pottery or any other suitable material.In the microfluidic chip of being made by glass, chip can comprise two-layer, i.e. chip and being fixed on the chip to form the lid of filter subsystem.In the microfluidic chip that is formed by plastics, these parts can be pressed in the plastic supporting base.
Shown in Fig. 9 a and 9b, according to an alternative, the microfiltration subsystem can comprise the direct filter 180 of double port type, and it comprises the film 110 that is inserted in the fluid flow path 181.As shown in the figure, the direct filter of double port type comprises the fluid flow path 181 that is formed in the microfluidic substrate, and it is divided into two part 181a, 181b.Second portion 181b has formed groove 186, and film 110 sticks on the groove, has formed the filter chamber that is used to accept to filter the back thing.The lid 15 that comprises little manufacturing of the groove 186 that has formed filter chamber is being connected on the substrate above the film, so that link to each other with flow path 181.Material to be filtered is sent in the filter chamber via fluid flow path 181, and the film 110 of flowing through.Film 110 comes separate substance by capturing bigger molecule, and thing and flows out microfiltration system for further analysis, processing and collection etc. along flow through film and enter into groove 182 of fluid flow path 181 after the filter that is made of the residue molecule.
Shown in Figure 10 a and 10b, according to another embodiment, microfiltration system can comprise the direct filter 190 of three port type.The direct filter 190 of this three port type comprises and is used for two kinds of samples are input in the filter chamber 195 two inlet flow channels 191,192, and is used for filter back thing is sent out an exit passageway 193 of filter 190.The direct filter of this three port type comprises the lid 15 of the little manufacturing that defines filter chamber, and the film 110 that filter chamber and exit passageway 193 are separated.In operation, provide two kinds of samples via access road 191,192.Sample mixes in filter chamber 195, and sample mixture is through membrane filtration, the component of the separable sample mixture of this film.Flowing through, thing is transmitted through exit passageway after the filter of film, to be used for further processing, analysis and collection etc.
The technical staff of film separation field can recognize, filtration system described here can be used to realize separate on all types of sheets that comprise film, it comprises by size and comes isolated molecule, perhaps from molecule, isolate bead, perhaps from macroparticle, isolate small-particle, perhaps from cell, isolate virus, perhaps be used for realizing other separation known to those of skill in the art.
According to another embodiment of the present invention, can adopt capping module 15 that magnetic valve is attached in the microfluidic systems.In Figure 11, shown and be used for the example that is contained in the magnetic valve in the closure construction that content according to the present invention realizes in microfluidic systems.As shown in the figure, electromagnetic module 150 comprises lid 15, and it has formed inner chamber 151, has been used for optionally stopping up the film 154 that flows via one or two communications ports in the substrate, and the actuating assembly 160 that is used to make film 154 deflections.According to this exemplary embodiment, actuating assembly comprises coil 162 and magnet 164.Those skilled in the art will recognize that and to use other can make the appropriate device of film deflection, comprise piezo actuator.
Electromagnetism capping module 110 can be stacked on the substrate 11, makes film can block communications ports 13a when deflection, one or more among the 13b.Therefore, electromagnetism capping module 110 is integrated is used for optionally blocking through the valve that flows of passage 3 to the microjet flow path.As mentioned above, electromagnetism capping module can be placed on the substrate by " pick up and put " equipment or any appropriate device known in the art of using automation.
Those skilled in the art will recognize that the capping module is not limited to this exemplary embodiment, can adopt other element to increase other microfluidic function, as filtering and flow-control additional or alternative.
Microfiltration system of the present invention can be advantageously in conjunction with in the microfluidic systems that possesses little manufacturing/micro-structural the function and the scope of conventional films technology of intrinsic small size dynamic flow control.The invention provides any suitable thin polymer film and worthwhile the mixing of the cost efficiency of microjet network.It is simple and lower-cost that this microfiltration system is added on the microfluidic systems, and this is relatively low for the cost of microfluidic systems itself because of the extra cost that microfiltration system is assembled in the microfluidic chip.
Can include one or more above-mentioned parts in combination individually or with other parts according to microfluidic systems of the present invention.
The present invention has been described hereinbefore at an exemplary embodiment.Owing to can carry out certain change to said structure without departing from the scope of the invention, therefore comprise in the foregoing description or be shown in all foregoings in the accompanying drawing and all should be interpreted as exemplaryly, do not possess restrictive, sense.
Should be appreciated that following claim covered all of invention described here general with concrete feature, all of the scope of the invention are set out on the language and all belong to wherein.

Claims (7)

1. microfluidic systems comprises:
Be formed at first microchannel in the substrate;
First communications ports that described first microchannel is linked to each other with the surface of described substrate;
Be formed at second microchannel in the described substrate;
Be formed at the 3rd microchannel in the described substrate; With
The capping module, it has the groove that is formed at wherein, and covered described groove so as to form the chamber be used for repel to come the semi-permeable membrane of separate substance by size, described film has formed the wall in described chamber, described capping module comprises the outlet that is formed at the inlet that leads to described chamber wherein and leads to described chamber, wherein said capping module can be stacked on the described substrate, make the inlet in described chamber be arranged to be communicated with described first microchannel, the outlet in described chamber is arranged to be communicated with described second microchannel, and described film is arranged to be communicated with described the 3rd microchannel, like this, filtrate through described film enters into described the 3rd microchannel, thereby the microjet filtering function is incorporated in the described microfluidic systems.
2. system according to claim 1 is characterized in that, described system also comprises second communications ports that described second microchannel is linked to each other with the surface of described substrate.
3. capping module that is used for microfluidic systems comprises:
Substrate, it has the groove that is formed in the described substrate surface;
Be located at being used on the described substrate and repel the semi-permeable membrane that carries out the material filtration by size, described semi-permeable membrane has covered described groove so that form the chamber;
Be formed at the inlet that leads to described chamber in the described substrate;
Be formed at the outlet that comes from described chamber in the described substrate;
Wherein, described capping module can be stacked on the microfluidic systems that wherein is formed with the microchannel, makes described chamber be arranged to be communicated with described microchannel via described inlet, thereby filtering function is incorporated in the described microfluidic systems.
4. capping module according to claim 3 is characterized in that, when described capping module stack was on described microfluidic systems, described chamber was provided with by the second microchannel fluidic communication in film and the described substrate, and separates with it.
5. microfluidic systems comprises:
Have a plurality of substrates that are formed at microchannel wherein, wherein each microchannel comprises one or more communications ports that described microchannel is linked to each other with the surface of described substrate of being used for; With
A plurality of microjet capping modules, each module have the semi-permeable membrane that is used to carry out the microjet filtering function that is arranged on the groove so that forms the chamber in corresponding capping module, lead to the inlet in described chamber and lead to described chamber outlet and
In the described microjet capping module first is stacked on the described substrate, and one of make by the communications ports that is associated with one or more microchannels in the entrance and exit of first microjet capping module and described one or more microchannels fluidic communication, thereby the first microjet filtering function is attached in the described system, second in the described microjet capping module is stacked on the described substrate, and one of make by the communications ports that is associated with another one or a plurality of microchannel in the entrance and exit of second microjet capping module and described another one or a plurality of microchannels fluidic communication, thereby the second microjet filtering function is attached in the described system.
6. the filtration system of the little manufacturing in the microfluidic systems comprises:
The capping module, it comprises the film that is used for separating substances is become first and second components;
Be used to transmit first flow path of material by described microfluidic systems, wherein when described capping module stack was on described substrate, described capping module and described first flow path intersected;
First storage tank, it is formed in the described capping module and is on the described film, have the inlet that is communicated with described first flow path that is used to accept described material, and the outlet that is communicated with described first flow path that is used for described first component is sent out from described first storage tank;
Second storage tank, it is formed in the described substrate and is used to accept second component of described material;
Be used to accept second component and the second flow path described second storage tank fluidic communication of described material; With
Be used to bring out the first-class body source that is communicated with described first flow path of described flow of matter, wherein said capping module stack is on described substrate, make described first storage tank be communicated with described second storage tank, and separate by described film and described second storage tank, the material that transmits along described first flow path is divided into first component and second component, wherein said first component flows path flow through described first storage tank along described first, and described second component is along the described second flow path described film of flowing through.
7. the filtration system of the little manufacturing in the microfluidic systems comprises:
Substrate;
Be arranged in first flow path that is used to transmit material of described substrate;
Being formed at being used in the described substrate accepts and transmits second flow path of component after the filter of described material;
Be formed in the described substrate and the groove that is communicated with described second flow path;
Define the lid in retention chamber, described lid is stacked on the described substrate, makes described retention chamber be arranged to be communicated with described first flow path;
Be fixed on the described lid to have covered the film in described retention chamber, the size of wherein said film is made for and described separating substances can be become filter back component and retained fraction, and when being stacked on the described substrate, described lid is arranged on the described groove, thereby define the filter chamber that is in described film below, so just can described second flow path is arranged near the of described first flow path and separate with it by described film;
Be formed in the described substrate and the 3rd flow path that is communicated with described retention chamber, be used for accepting and send retained fraction from the described material in described retention chamber.
CNB038249804A 2002-09-09 2003-09-09 Implementation of microfluidic components in a microfluidic system Expired - Fee Related CN1331575C (en)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US40948902P 2002-09-09 2002-09-09
US60/409,489 2002-09-09
US60/410,685 2002-09-13
US10/329,018 2002-12-23

Related Child Applications (1)

Application Number Title Priority Date Filing Date
CNA200710128025XA Division CN101199917A (en) 2002-09-09 2003-09-09 Implementation of microfluidic components in a microfluidic system

Publications (2)

Publication Number Publication Date
CN1694756A CN1694756A (en) 2005-11-09
CN1331575C true CN1331575C (en) 2007-08-15

Family

ID=35353397

Family Applications (2)

Application Number Title Priority Date Filing Date
CNA200710128025XA Pending CN101199917A (en) 2002-09-09 2003-09-09 Implementation of microfluidic components in a microfluidic system
CNB038249804A Expired - Fee Related CN1331575C (en) 2002-09-09 2003-09-09 Implementation of microfluidic components in a microfluidic system

Family Applications Before (1)

Application Number Title Priority Date Filing Date
CNA200710128025XA Pending CN101199917A (en) 2002-09-09 2003-09-09 Implementation of microfluidic components in a microfluidic system

Country Status (2)

Country Link
CN (2) CN101199917A (en)
ZA (1) ZA200502324B (en)

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE102008002336A1 (en) * 2008-06-10 2009-12-24 Robert Bosch Gmbh Pinch valve and method for its production
EP2992327B1 (en) * 2013-04-30 2018-11-21 Hewlett-Packard Development Company, L.P. Microfluidic sensing device and system
CN106542495A (en) * 2016-12-12 2017-03-29 墨宝股份有限公司 A kind of preparation method of micro-electrical-mechanical system vibration jet actuator
CN108745012B (en) * 2018-06-14 2021-04-20 四川大学 But miniature venturi type bubble generating device of modularization combination
CN113101985B (en) * 2019-06-26 2022-07-22 京东方科技集团股份有限公司 Detection chip and detection system

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5922210A (en) * 1995-06-16 1999-07-13 University Of Washington Tangential flow planar microfabricated fluid filter and method of using thereof
US5962081A (en) * 1995-06-21 1999-10-05 Pharmacia Biotech Ab Method for the manufacture of a membrane-containing microstructure
US6440725B1 (en) * 1997-12-24 2002-08-27 Cepheid Integrated fluid manipulation cartridge

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5922210A (en) * 1995-06-16 1999-07-13 University Of Washington Tangential flow planar microfabricated fluid filter and method of using thereof
US5962081A (en) * 1995-06-21 1999-10-05 Pharmacia Biotech Ab Method for the manufacture of a membrane-containing microstructure
US6440725B1 (en) * 1997-12-24 2002-08-27 Cepheid Integrated fluid manipulation cartridge

Also Published As

Publication number Publication date
CN101199917A (en) 2008-06-18
ZA200502324B (en) 2006-05-31
CN1694756A (en) 2005-11-09

Similar Documents

Publication Publication Date Title
US6878271B2 (en) Implementation of microfluidic components in a microfluidic system
US7870964B2 (en) Implementation of microfluidic components in a microfluidic system
US7416892B2 (en) Method and system for microfluidic manipulation, amplification and analysis of fluids, for example, bacteria assays and antiglobulin testing
US8323887B2 (en) Miniaturized fluid delivery and analysis system
US7186383B2 (en) Miniaturized fluid delivery and analysis system
US6742661B1 (en) Well-plate microfluidics
US20050150765A1 (en) Integrated microchip design
EP3361263B1 (en) Specimen treatment chip
US20240027487A1 (en) System, device and methods of sample processing using semiconductor detection chips
CN1331575C (en) Implementation of microfluidic components in a microfluidic system
CN114292734A (en) Full-process integrated droplet digital PCR chip, preparation method and application
JP2006284451A (en) Micro total analysis system for analyzing target material in specimen
WO2005031163A1 (en) Implementation of microfluidic components in a microfluidic system

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
C14 Grant of patent or utility model
GR01 Patent grant
C17 Cessation of patent right
CF01 Termination of patent right due to non-payment of annual fee

Granted publication date: 20070815

Termination date: 20090909