EP1611955A1 - Mikrofluidische Vorrichtung mit Filterkanal - Google Patents

Mikrofluidische Vorrichtung mit Filterkanal Download PDF

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Publication number
EP1611955A1
EP1611955A1 EP04103111A EP04103111A EP1611955A1 EP 1611955 A1 EP1611955 A1 EP 1611955A1 EP 04103111 A EP04103111 A EP 04103111A EP 04103111 A EP04103111 A EP 04103111A EP 1611955 A1 EP1611955 A1 EP 1611955A1
Authority
EP
European Patent Office
Prior art keywords
channel
cross sectional
sectional shape
particles
chip
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.)
Withdrawn
Application number
EP04103111A
Other languages
English (en)
French (fr)
Inventor
Konstantin Choikhet
Stefan Falk-Jordan
Andreas Ruefer
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.)
Agilent Technologies Inc
Original Assignee
Agilent Technologies 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 Agilent Technologies Inc filed Critical Agilent Technologies Inc
Priority to EP04103111A priority Critical patent/EP1611955A1/de
Publication of EP1611955A1 publication Critical patent/EP1611955A1/de
Withdrawn legal-status Critical Current

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Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • 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
    • B01L3/502753—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 bulk separation arrangements on lab-on-a-chip devices, e.g. for filtration or centrifugation
    • 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
    • B01L2300/00—Additional constructional details
    • B01L2300/06—Auxiliary integrated devices, integrated components
    • B01L2300/0681—Filter
    • 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
    • B01L2300/0825—Test strips
    • 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
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0406—Moving fluids with specific forces or mechanical means specific forces capillary forces
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/08—Regulating or influencing the flow resistance
    • B01L2400/084—Passive control of flow resistance

Definitions

  • the present invention relates to a microfluidic chip assembly.
  • Fluidic microchip technologies are increasingly utilized in order to carry out chemical or biological laboratory functions such as experiments, analyses or preparation. These miniaturized instruments allow the performance of traditional and new developed processes under a perfectly controllable setting of parameters. Furthermore, the development of instruments permitting to conduct experiments with very small volumes of e.g. substances that are hard to prepare or very expensive has enabled scientists to proceed in research remarkably.
  • micro-fabricated devices were demonstrated integrating sample filtration. Filtering of the sample was accomplished at the sample inlet with an array of channels.
  • Embodiments of the present invention address the aforementioned needs in the art and provide a microfluidic chip assembly in which the chan nel or capillary system has a filtering function.
  • Chemical or biological fluids which are subjected to processes in microfluidic chips and which contain particles from the very beginning when they are introduced into the microfluidic chip system, or which form particles due to chemical, physical or biological reactions during their residence time in the system have to be filtered in order to avoid blockage of the fluid flow and to guarantee the reliability of results obtained by using these chips. Thus it is desirable to retain particles.
  • the present invention provides a microfluidic chip assembly wherein the channel comprises a kind of filter or frit.
  • the central improvement of the present invention is to use the channel or capillary, which opens into the well, itself as a filtering instrument at the channel/well interface or during the course of the channel(s). This is achieved substantially by deformation of the channel in order to create different cross sectional shapes.
  • only one channel is shown, having substantially two different cross sectional shapes, one of which being sized rather circular or of any other form with an aspect ratio close to 1, thus providing depth being big enough to guarantee the foreseen hydraulic flow of the fluid and allowing particles to pass, the other one being sized so flat and wide, creating a very shallow channel, that particles are retained but the hydraulic flow of the fluid is maintained.
  • one main channel is split into several side channels forming a "river delta", each of which side channels opening into the well by which the fluid is introduced into the channel system.
  • the cross sectional shapes are designed in a way not to allow particles to pass.
  • one main channel is split into two side channels shaping a "Y", each of which side channels opening into the well by which the fluid is introduced into the channel system, again realizing the filtering effect by designing shallow channels causing the retaining of particles by maintenance of the desired flow through.
  • one "main" channel is shown, being deformed not at the well/channel interface but during its course, in order to retain particles, which have been formed in the channel system during the process.
  • a method is shown according to which a chemical or biological fluid is introduced into a well of a microfluidic chip, being filtered at the channel/well interface or in the course of the channel, the filtering effect being achieved by deformation of the channels at the corresponding portions.
  • microfluidic chip assemblies with filtering effects By the use of microfluidic chip assemblies with filtering effects according to the present invention the lifetime of the microfluidic chip can be prolonged since particles having been retained within the well can be removed by performing a cleaning step. Furthermore, the reliability of experimental results can be optimized by maintaining the initial setting of the microfluidic chip assembly including the maintenance of a homogeneous fluid flow.
  • FIG. 1a a cross sectional side view of a part of a chip composed of two components, comprising one well and a conventional channel,
  • FIG. 1b a plan view of FIG. 1a
  • FIG. 1c a detail of FIG. 1 b: the cross sectional shape of the channel
  • FIG. 2a a cross sectional side view of a part of a chip composed of two layers, comprising one well and channel with substantially two differing cross sectional shapes
  • FIG. 2b a plan view of FIG. 2a
  • FIG. 2c detail of FIG. 2b: the cross sectional shape of the channel at the channel/well interface
  • FIG. 2d a detail of FIG. 2b: the cross sectional shape of the channel during its course
  • FIG. 3a a plan view of another embodiment of the present invention comprising well and channel as in FIG. 1a, but with another design of the channel and channel/well interface, the "river- delta" design,
  • FIG. 3b an enlarged detail of FIG. 3a: the cross sectional shape of the channel at the channel/well interface
  • FIG. 3c a detail of FIG. 3a: the cross sectional shape of the channel in its course
  • FIG. 4a a plan view of another embodiment of the present invention comprising well and channel as in FIG. 1a, but with another design of the channel and channel/well interface, the "Y" design
  • FIG. 4b an enlarged detail of FIG. 4a: the cross sectional shape of the channel at the channel/well interface
  • FIG. 4c a detail of FIG. 4a: the cross sectional shape of the channel along its course
  • FIG. 5a a plan view of another embodiment of the present invention comprising well and channel as in FIG. 1a, the channel having different cross sectional shapes in its course,
  • FIG. 5b a detail of FIG. 5a: the cross sectional shape of the channel in a first portion of the channel
  • FIG. 5c a detail of FIG. 5a: the cross sectional shape of the channel in a second portion of the channel,
  • FIG. 5c a detail of FIG. 5a: the cross sectional shape of the channel in a third portion of the channel.
  • substantially two different cross sectional shapes means herein, that the transition portion between two different cross sectional shapes is not considered.
  • a “channel” comprises as well channels that are micro- or nano sized, thus being capillaries.
  • a "well” is a cavity in a microfluidic chip serving as reservoir for fluids.
  • a "caddy” is the cowl being mounted on the cavity in order to help carrying fluids.
  • the present invention depicts an assembly of a microfluidic chip, which is provided for subjecting chemical or biological fluids to analysis or preparation steps.
  • a plurality of wells is comprised in the chip, serving as reservoir for fluidic chemical and biological substances.
  • channels are generated within the chip.
  • the chip body substantially comprises a system of microfluidic channels in a solid body or housing, which is preferably planar and is made of quartz, glass, polymer material or the like.
  • the channels can be e.g. etched in one of the planar plates, opening into the wells, thus linking the wells with the corresponding device.
  • the etched structures are usually closed to form channels by bonding another planar plate on the etched side of the first plate.
  • the chips can also be of multilayer structure, non-planar and so on.
  • the channel interfaces to the wells are of the same width and depth as the further course of the channel, furthermore it is possible that the channel narrows in its downstream sections.
  • the fluid which is processed in those microfluidic chips may occasionally contain particles such as dust particles from the very beginning when it is introduced into the well or particles may be formed due to chemical, physical or biological processes during the residence time of the fluid in the channel system.
  • the fluid is moved through the channel by means of moving forces, providing a desired and preset flow through. Since the fluid moves, defined hydrodynamic and electrical conditions exist within the channel. According to the present invention, blocking or partial obstruction of the channel, or the channel cross section, respectively, is avoided. Thus a significant change of hydrodynamic and electrical conditions within the channel, which would otherwise lead to unreliable results, is prevented.
  • a microfluidic chip which is an assembly composed of two parts, one of which being a caddy 10 with well walls and the other one being a chip plate 17 with one well 1 is shown.
  • the caddy 10 has a drilling hole 14 that forms the sidewalls of the well 1, the bottom of which is formed by the chip plate 17.
  • the well serves as reservoir for fluidic chemical and/or biological materials, which may contain particles 7 from the very moment when the fluid is filled into the well or which can form particles 7 during the subsequent process.
  • Each well 1 has an outlet being an orifice 3 which permits that the fluid flows from the well into a channel 4.
  • FIGS 1b and 1c point out that the channel 4, which opens into the well 1 has a homogeneous cross sectional shape A, which is designed to permit the fluid to pass the channel with a desired flow through rate. In case of the presence of particles having a size that prevents the particles to pass, blockage occurs partially or completely.
  • FIG. 2a shows a first embodiment of the present invention wherein the microfluidic chip is substantially built like the conventional microfluidic chip a section of which is shown in FIGS. 1a, 1b, 1c, but instead of the channel 4, a channel 4', 4 with substantially two different cross sectional shapes A and B is comprised.
  • the orifice 3 is the entry into a channel 4', having a cross sectional shape B which is being sized and wide, providing a shallow channel entry in order to retain particles 7 in the well; the width being that large that despite of the filtering function, which is subsequently followed by partial obstruction of this first portion 9 of the channel, the flow cross section is large enough to remain partially open, thus maintaining a desired flow through rate of the fluid from the well through the entire channel.
  • the first portion 9 of the channel 4 transits at the transition portion 15 into a second portion of the channel 4, having cross sectional shape A which is shaped rather circular or semi-circular providing depth in order to lead to optimal flow properties.
  • FIG. 2b shows a plan view of the device depicted in FIG 2a, in connection with FIGS. 2c and 2d it is pointed out how the cross sectional shape B of the first portion 9 of the channel 4 at the orifice 3 differs from the cross sectional shape A which is provided during the course of the channel 4.
  • FIG. 3a it is shown a plan view of another embodiment of the present invention depicting a "main" channel 4, which splits at the junctions 12 into “side” channels 4', thus forming a “river delta” design.
  • five orifices 3 can be counted, each having a smaller cross sectional shape A than that of the "main" channel 4, but having in total a larger cross sectional shape than the main channel has.
  • FIGS. 3b and 3c show the shapes of the cross sections at the orifices 3, channel 4' respectively, and during the course of the channel 4.
  • FIG. 4a shows again a plan view of an additional embodiment of the device of the present invention.
  • the "main” channel 4 which splits only into two “side” channels 4', forms a "Y".
  • FIG.4b which gives a detail of FIG 4a
  • the "side” channel 4 widens and flattens where the channel 4' opens into the well 1.
  • FIG. 4c indicates the cross sectional shape A of the "main” channel 4 during its course. Again, the total of the two cross sectional shapes B is larger than that of the "main” channel 4.
  • a junction 12 within a channel 4 links two channels 4' with the channel 4, thus forming a "Y", or it links more than two channels 4' at once, which is not shown in a Figure, resulting in a "river delta” design. That means in reverse, the "main" channel 4 can split into two or more channels at once. Another possibility is, that one junction 12 links only two channels 4' at once, but two - or more - junctions 12 are located one after the other, leading to five (FIG.3) or more "side" channels 4', interfacing the well in parallel.
  • FIG. 5a a further embodiment is pointed out, showing the microfluidic device of the present invention with a design, which is preferably used when the particles 7 form due to chemical, physical or biological processes during the passage of the device.
  • the plan view depicts an embodiment comparable to that one of FIG. 1, but with the decisive difference, that the channel 4 has three different cross sectional shapes A, B, B' in its course, what can be seen clearly in the details shown in FIG. 5b, 5c and 5d. Only one channel 4 opens into the well 1, being subdivided into three portions. Each of which portions has a different cross sectional shape. The first portion begins at the orifice 3, the cross section has a flattened shape.
  • the second portion is wider and more flat than the forgoing first portion, its cross sectional shape B doesn't permit particles to pass and, thus, bears the filter-function.
  • the third and last portion has a rather circular cross sectional shape, thus providing a deep channel, and permits the filtered fluid to flow with an optimal flow velocity.
  • the circumferences of the cross sections are nearly equal in this Figure, but it can be preferable to choose larger circumferences for the cross sectional shapes B or B' in order.
  • the circumferences of a cross sectional shape A and a cross sectional shape B, B' can be unequal but at least two different cross sectional shapes must be comprised.
  • FIG.5 Another possibility to obtain the filter effect as pointed out in FIG.5 is to choose identical cross sectional shapes, except of circular or nearly circular shapes, and to arrange two or more adjacent portions 9,9',9" in a way that an appropriate displacement is created, resulting in a filtering effect.
  • this channel design can be used for "main" channel 4 as well as for "side” channels 4'. Furthermore it may be reasonable to locate a first portion of a channel 4,4' having a cross sectional shape A downstream to a first portion 9,9' having a cross sectional shape B, B', but when the filtering effect is desired during the course of the channel system since, for example, the formation of particles takes place at a definite portion of the channel due to environmental circumstances, it can be reasonable to locate a portion of a channel 4,4' having a cross sectional shape B, B' downstream to a portion having a cross sectional shape A.
  • composition of the microfluidic chip as described above, bonding an upper and a bottom layer together could also be a chip composed of more than two layers or plates.
  • the channel discussed in the above embodiments is etched in the bottom plate, but it can also be etched in the upper plate, as far as the fluid can be moved from the well into the channel. Other methods than etching are also possible in order to create the channels.
  • the method for retaining particles 7 from fluidic chemical and biological materials, which undergo processing in a microfluidic chip can be performed by means of a microfluidic device according to the present invention. It comprises introducing the fluidic chemical and biological materials into a well 1 and moving it then via an orifice 3 through a channel 4, 4'.
  • the fluidic chemical and biological substance flows through two or more portions of the channel 4,4', at least two of which having different cross sectional shapes A, B, B'. Particles 7 carried by the fluid are retained when the flow cross-section, which has to be passed, is smaller than the size of the particle 7, thus filtering is performed and the fluid maintains the flow velocity that is desired.
  • cross-section area of the junction bearing the filtering function or the total cross-section area of the orifices within one such junction is larger than the cross-section of the subsequent channel which is to be protected from entering particles, so that the amount of particles, which otherwise would significantly block the channel can only block an insignificant part of the cross-section of the filtering orifice, thus the behavior in the channel is not disturbed.
  • the above method which is performed by a microfluidic device according to the present invention prevents changes of the fluid flow due to blockage or partial obstruction of the channels, thus hydrodynamic and electrical conditions within the channel are maintained, and the reliability of the results is optimized.
EP04103111A 2004-07-01 2004-07-01 Mikrofluidische Vorrichtung mit Filterkanal Withdrawn EP1611955A1 (de)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP04103111A EP1611955A1 (de) 2004-07-01 2004-07-01 Mikrofluidische Vorrichtung mit Filterkanal

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Application Number Priority Date Filing Date Title
EP04103111A EP1611955A1 (de) 2004-07-01 2004-07-01 Mikrofluidische Vorrichtung mit Filterkanal

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EP1611955A1 true EP1611955A1 (de) 2006-01-04

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009112982A1 (en) * 2008-03-11 2009-09-17 Koninklijke Philips Electronics N.V. Filtering apparatus for filtering a fluid
WO2010115454A1 (en) * 2009-04-06 2010-10-14 Trinean Nv Sample storage in microfluidics devices
CN110187117A (zh) * 2019-06-18 2019-08-30 清华大学深圳研究生院 β-内酰胺抗生素的检测试剂盒及其应用

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5296375A (en) * 1992-05-01 1994-03-22 Trustees Of The University Of Pennsylvania Mesoscale sperm handling devices
EP1201304A2 (de) * 2000-10-25 2002-05-02 MICROPARTS GESELLSCHAFT FÜR MIKROSTRUKTURTECHNIK mbH Mikrostrukturierte Plattform für die Untersuchung einer Flüssigkeit
US20020179447A1 (en) * 1997-06-06 2002-12-05 Caliper Technologies Corp. Microfabricated structures for facilitating fluid introduction into microfluidic devices
US6632655B1 (en) * 1999-02-23 2003-10-14 Caliper Technologies Corp. Manipulation of microparticles in microfluidic systems
US6637463B1 (en) * 1998-10-13 2003-10-28 Biomicro Systems, Inc. Multi-channel microfluidic system design with balanced fluid flow distribution

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5296375A (en) * 1992-05-01 1994-03-22 Trustees Of The University Of Pennsylvania Mesoscale sperm handling devices
US20020179447A1 (en) * 1997-06-06 2002-12-05 Caliper Technologies Corp. Microfabricated structures for facilitating fluid introduction into microfluidic devices
US6637463B1 (en) * 1998-10-13 2003-10-28 Biomicro Systems, Inc. Multi-channel microfluidic system design with balanced fluid flow distribution
US6632655B1 (en) * 1999-02-23 2003-10-14 Caliper Technologies Corp. Manipulation of microparticles in microfluidic systems
EP1201304A2 (de) * 2000-10-25 2002-05-02 MICROPARTS GESELLSCHAFT FÜR MIKROSTRUKTURTECHNIK mbH Mikrostrukturierte Plattform für die Untersuchung einer Flüssigkeit

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009112982A1 (en) * 2008-03-11 2009-09-17 Koninklijke Philips Electronics N.V. Filtering apparatus for filtering a fluid
US8475734B2 (en) 2008-03-11 2013-07-02 Koninklijke Philips Electronics N.V. Filtering apparatus for filtering a fluid
CN101965225B (zh) * 2008-03-11 2014-04-30 皇家飞利浦电子股份有限公司 用于过滤流体的过滤装置
WO2010115454A1 (en) * 2009-04-06 2010-10-14 Trinean Nv Sample storage in microfluidics devices
WO2010115907A1 (en) * 2009-04-06 2010-10-14 Trinean Nv Sample storage in microfluidics devices
CN110187117A (zh) * 2019-06-18 2019-08-30 清华大学深圳研究生院 β-内酰胺抗生素的检测试剂盒及其应用

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