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WO2001046465A2 - Dispositif de microanalyse - Google Patents

Dispositif de microanalyse Download PDF

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Publication number
WO2001046465A2
WO2001046465A2 PCT/EP2000/013145 EP0013145W WO0146465A2 WO 2001046465 A2 WO2001046465 A2 WO 2001046465A2 EP 0013145 W EP0013145 W EP 0013145W WO 0146465 A2 WO0146465 A2 WO 0146465A2
Authority
WO
WIPO (PCT)
Prior art keywords
chamber
fluid
disc
arm
microstructure
Prior art date
Application number
PCT/EP2000/013145
Other languages
English (en)
Other versions
WO2001046465A3 (fr
Inventor
Per Andersson
Arvi Aksberg
Gunnar Ekstrand
Björn BERG
Original Assignee
Gyros Ab
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
Priority claimed from PCT/EP1999/010347 external-priority patent/WO2000040750A1/fr
Application filed by Gyros Ab filed Critical Gyros Ab
Priority to JP2001546961A priority Critical patent/JP4612262B2/ja
Priority to DE60035611T priority patent/DE60035611T2/de
Priority to AU44105/01A priority patent/AU4410501A/en
Priority to EP00992452A priority patent/EP1239962B1/fr
Priority to US10/169,056 priority patent/US7261859B2/en
Priority to CA002395159A priority patent/CA2395159A1/fr
Publication of WO2001046465A2 publication Critical patent/WO2001046465A2/fr
Publication of WO2001046465A3 publication Critical patent/WO2001046465A3/fr

Links

Classifications

    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027Containers 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
    • B01L3/502761Containers 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 specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads, for physically stretching molecules
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027Containers 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
    • B01L3/502746Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the means for controlling flow resistance, e.g. flow controllers, baffles
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/06Fluid handling related problems
    • B01L2200/0605Metering of fluids
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/06Fluid handling related problems
    • B01L2200/0647Handling flowable solids, e.g. microscopic beads, cells, particles
    • B01L2200/0668Trapping microscopic beads
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/18Means for temperature control
    • B01L2300/1861Means for temperature control using radiation
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00Moving or stopping fluids
    • B01L2400/04Moving fluids with specific forces or mechanical means
    • B01L2400/0403Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0409Moving fluids with specific forces or mechanical means specific forces centrifugal forces
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00Moving or stopping fluids
    • B01L2400/06Valves, specific forms thereof
    • B01L2400/0688Valves, specific forms thereof surface tension valves, capillary stop, capillary break

Definitions

  • the present invention relates to microanalysis devices and methods for moving fluids in such devices.
  • micro-analysis systems that are based on microchannels formed in a rotatable, usually plastic, disc, often called a "centrifugal rotor" or "lab on a chip".
  • Such discs can be used to perform analysis and separation on small quantities of fluids.
  • the discs should be not restricted to use with just one type of reagent or fluid but should be able to work with a variety of fluids.
  • the disc permits the user to dispense accurate volumes of any desired combination of fluids or samples without modifying the disc.
  • any air bubbles present between two samples of fluids in the microchannels can act as separation barriers or can block the microchannel and thereby can prevent a fluid from entering a microchannel that it is supposed to enter.
  • US patent no. 5 591 643 teaches the use of a centrifugal rotor which has microchannels that have cross sectional areas which are sufficiently large that unwanted air can be vented out of the microchannel at the same time as the fluid enters the microchannel.
  • An object of the present invention is to provide a structure for a centrifugal rotor and a method for using such a centrifugal rotor, which structure and which method permits the reliable transport of fluids in the centrifugal rotor.
  • a further object of the present invention is to provide a structure for a centrifugal rotor and a method for using such a centrifugal rotor, which structure and which method permits the accurate metering of fluids in the centrifugal rotor.
  • the present invention achieves the objects of the invention by means of a structure having the features of claim 1.
  • a method for using such a structure to achieve the objects of the invention has the features of claim 5.
  • Figure 1 a shows the peripheral part of a centrifugal rotor having five radially extending microchannel structures K7-K12 in accordance with the present invention
  • Figure lb shows an enlarged view of one microchannel structure from figure la in accordance with the present invention
  • Figure lc shows an enlarged view of a sample volume-defining structure in the microchannel structure of figure lb;
  • Figure Id shows an enlarged view of the chamber area plus chambers for the disposal of waste fluids, wherein variations in depth are shown by cross-hatching;
  • Figures 2a and 2b show the structure of figure lb with the chamber containing a first fluid
  • Figures 3a and 3b shows the addition of a second fluid to a volume-defining chamber
  • Figures 4a and 4b show the replacement of the first fluid in the chamber by said second fluid
  • Figure 5 shows a second embodiment of a microchannel structure in accordance with the present invention
  • Figure 6 shows a third embodiment of a microchannel structure in accordance with the present invention.
  • Figure 7 shows a fourth embodiment of a microchannel structure in accordance with the present invention.
  • Figure 8 shows a fifth embodiment of a microchannel structure in accordance with the present invention.
  • microchannel structures (K7-K12) in accordance with the present invention are shown in figures la-d arranged radially on a microfluidic disc (D).
  • the microfluidic disc is of a one- or two-piece moulded construction and is formed of an optionally transparent plastic or polymeric material by means of separate mouldings which are assembled together (e.g. by heating) to provide a closed structure with openings at defined positions to allow loading of the device with fluids and removal of fluid samples.
  • Suitable plastic of polymeric materials may be selected to have hydrophobic properties.
  • Preferred plastics or polymeric materials are selected from polystyrene and polycarbonate.
  • the surface of the microchannels may be additionally selectively modified by chemical or physical means to alter the surface properties so as to produce localised regions of hydrophobicity or hydrophilicity within the microchannels to confer a desired property.
  • Preferred plastics are selected from polymers with a charged surface, suitably chemically or ion-plasma treated polystyrene, polycarbonate or other rigid transparent polymers.
  • the microchannels may be formed by micro-machining methods in which the micro-channels are micro-machined into the surface of the disc, and a cover plate, for example, a plastic film is adhered to the surface so as to enclose the channels.
  • the microfluidic disc (D) has a thickness which is much less than its diameter and is intended to be rotated around a central hole so that centrifugal force causes fluid arranged in the microchannels in the disc to flow towards the outer periphery of the disc.
  • the microchannels start from a common, annular inner application channel (1) and end in common, annular outer waste channel (2), substantially concentric with channel (1).
  • Each inlet opening (3) of the microchannel structures (K7-K12) may be used as an application area for reagents and samples.
  • Each microchannel structure (K7-K12) is provided with a waste chamber (4) that opens into the outer waste channel (2).
  • Each microchannel (K7-K12) forms a U-shaped volume-defining structure (7) and a U-shaped chamber (10) between its inlet opening (3) and the waste chamber (4).
  • the normal desired flow direction is from the inlet opening (3) to the waste chamber (4) via the U-shaped volume-defining structure (7) and the U-shaped chamber (10).
  • Flow can be driven by capillary action, pressure and centrifugal force, i.e.
  • fluid can flow from the inlet opening (3) via an entrance port (6) into a volume-defining structure (7) and from there into a first arm of a U-shaped chamber (10).
  • the volume- defining structure (7) is connected to a waste outlet for removing excess fluid, for example, radially extending waste channel (8) which waste channel (8) is preferably connected to the annular outer waste channel (2).
  • the waste channel (8) preferably has a vent (9) that opens into open air via the top surface of the disk. Vent (9) is situated at the part of the waste channel (8) that is closest to the centre of the disc and prevents fluid in the waste channel (8) from being sucked back into the volume-defining structure (7).
  • the chamber (10) has a first, inlet arm (10a) connected at its lower end to a base (10c) which is also connected to the lower end of a second, outlet arm (10b).
  • the chamber (10) may have sections I, II, III, IV which have different depths, for example each section could be shallower than the preceding section in the direction towards the outlet end, or alternatively sections I and III could be shallower than sections II and IV, or vice versa.
  • a restricted waste outlet (11), i.e. a narrow waste channel, is provided between the chamber (10) and the waste chamber (4). This makes the resistance to fluid flow through the chamber (10) greater than the resistance to fluid flow through the path that goes through volume-defining structure (7) and waste channel (8).
  • the top and bottom surfaces of the waste chamber (4) are preferably separated by one or more supports (12) to ensure that the top and bottom surfaces of the microfluidic device do not bend inwards towards the waste chamber (4) and thereby change its volume.
  • the volume-defining structure (7) is U-shaped with the entrance port (6) opening into the upper end (i.e. the end nearest to the centre of the disc) of one of the arms (7a) of the U and the waste channel (8) connected to the upper end of the other arm (7b) of the U.
  • the vent (9) is also placed at the top of this other arm (7b).
  • the base (7c) of the U-formed volume-defining structure (7) is connected to the upper end of a first arm (10a) of the chamber (10).
  • an additional application area (13) that opens out into the top surface of the disc and is connected to the entrance port (6).
  • This additional application area (13) can be used when it is desired to add different reagents or samples to each of the different microstructures (K7-K12).
  • a hydrophobic break is preferably provided at the connection (16) of the chamber (10) to the volume-defining structure (7) in order to guide fluid into arm (7b)
  • the outer annular waste channel (2) may be sectioned so as to collect waste from a selected number of closely located microchannel structures.
  • Hydrophobic breaks can be introduced into the microchannel structures (K7-K12), for example by marking with an over-head pen (permanent ink) (Snowman pen, Japan), and suitable places for such breaks (shown by crosshatching in the figures) include: (a) between microchannel structure inlets (3) in the inner annular application channel (1), (b) each opening (15) into the outer annular waste channel (i.e. the openings of the waste chambers) and, (c) if present, also the radial waste channels (5) which connect the inner annular application channel (1) and the outer annular waste channel (2), and also the waste channel (8) which guides away excess fluid from the volume-defining structure (7).
  • the purpose of the hydrophobic breaks is to prevent capillary action from drawing the fluid into undesired directions. Hydrophobic breaks can be overcome by centrifugal force i.e. by spinning the disc at high speed.
  • the sample to be analysed is in the form or cells or sedimenting material or particles then it can be held in the lower U-channel by a particle filter (21) (shown by a dotted line in figure lb and Id) or the flow through the chamber (10) can be controlled such that particles are retained in the chamber while fluids flow through it - as will be described later.
  • a particle filter (21) shown by a dotted line in figure lb and Id
  • the flow through the chamber (10) can be controlled such that particles are retained in the chamber while fluids flow through it - as will be described later.
  • a first reagent or sample fluid X can be introduced into the chamber (10) by connecting a source (not shown) of the fluid X to the common annular inner application channel (1) from where it flows by capillary action and/or, if the disc is spun, centrifugal force to the lower U- bend. If the volume of fluid X which is introduced into common annular inner application channel (1) is in excess (i.e. is greater than the volume of the chamber (10) up to the level of the restricted channel (11) (distance L4 in figure Id)) then some of it flows to waste via the radial waste channel (5) while the rest flows to waste chamber (4) via the chamber (10) though the restricted channel (11) as shown in figure 2.
  • fluid Y When it is time to add a new reagent or sample fluid Y, then fluid Y is added by the common annular inner application channel (1) (or, alternatively, as shown in figure 3a) by the additional application area (13)).
  • the fluid Y travels by capillary action through the volume- defining structure (7) and down the waste channel (5) as shown in figure 3a). It cannot flow into chamber (10) as the air cushion (19) contained between the base of the volume defining structure and the top of the fluid in arm (7a) of the chamber acts as a barrier to prevent the fluid flowing into chamber 10.
  • an air cushion (19) can be left between the first fluid X and the second fluid Y by making the distance L4 from the base of the U-bend in the chamber (10) to the restricted channel (11) less than the distance L3 from the base of the U-bend in the chamber (10) to the base of the U-bend of the volume-defining structure (7).
  • This can prevent the second fluid Y from flowing by capillary action into the chamber (10) and can also prevent mixing of the fluids X and Y.
  • the vent (9) which is open to atmospheric pressure, makes it easier for the second fluid Y to flow towards the waste channel (5).
  • Gentle, i.e. low speed, spinning of the disc (D) empties the excess fluid Y from waste channel (5), leaving the volume-defining structure (7) full of fluid Y, as shown in figure 3b).
  • All of the first fluid X in the chamber (10) can be displaced by the second fluid Y by spinning the disc if the volume of the second fluid in the volume-defining structure (7) and any air between the first and second fluids is equal to or greater than the volume of the first fluid X in the chamber (10).
  • This can be achieved by ensuring that the volume of the volume- defining structure (7) is greater than the volume of the chamber (10).
  • Figure 4a shows an intermediate situation where the disc is being spun and centrifugal force causes fluid Y to flow from the volume-defining structure (7) into chamber (10), thereby displacing first fluid X which flows to waste via restricted channel (11). Any excess second fluid Y flows out of the chamber (10) through the restricted channel (11) into waste chamber (4).
  • Figure 4b) shows that the second fluid Y has replaced the first fluid X. This process can be repeated using different fluids as often as is desired.
  • the chamber (10) In the event that the fluids contain particles and it is desired to hold them in the chamber it is possible to provide the chamber (10) with a particle filter (21) with suitable sized orifices. In the event that it is necessary to only temporarily hold the particles in the chamber (10) then the sections I, II, III, IV of the chamber (10) which have different depths can be used to temporarily trap the particles. This is done by increasing the speed of rotation of the disc so that the particles collect at the boundary wall between two sections while the fluid flows over the wall.
  • particles can be selectively held in, or flushed out of a chamber (10'), which does not have a particle trap or sections having different depths as shown in figure 5.
  • Particles that have been sedimented, or otherwise collected, in the bottom of the chamber (10') can be drawn out of the chamber (10') by the meniscus of a fluid which flows out of the chamber (10').
  • air cushion (19') between the volume-defining structure and the chamber (10') and this is driven through the chamber, then as the meniscus between the fluid in the chamber and the air cushion passes the particles they are entrained by the meniscus and flow out of the chamber.
  • the arm (7b') of the volume- defining structure (7') is not connected to a waste channel (8), but is instead enlarged at its end nearest the centre of the disk in order to form a reservoir (61 ) for fluid to prevent fluid overflowing out of a vent (9').
  • This vent and/or sample inlet (9') vents this reservoir (61) to atmosphere and can also permit samples to be introduced into the structure.
  • the reservoir (61) preferably has a length which makes the length of the volume defining structure i.e. reservoir (61) and arm (7b') equal to or greater than the length of arm (7a').
  • vent (9') is made so small that the surface tension of the fluid prevents it from flowing out of the vent when the volume-defining structure (7') is being charged by spinning, then the amount of fluid which can enter the volume-defining structure (7') is minimised and no fluid is wasted.
  • the volume of the volume defining structure must be greater than the volume of the chamber (10). If the arm (10a) of the chamber is made to widen from its upper end to its lower end then it is possible to push the air barrier (19) out of the chamber when adding a second fluid without the two fluids mixing.
  • All the chambers of the present invention can be provided with heating means in the form of a coating as shown crosshatched in figure 7.
  • This coating (71) which can be painted or printed or applied in some other way to one or both sides of the disk in the vicinity of the chamber, can absorb energy from electromagnetic radiation which is directed onto it and thereby heat up the chamber.
  • the incident radiation can be infra red light, laser light, visible light, ultraviolet light, microwaves or any other suitable type of radiation.
  • the heating up of the chamber can be used to initiate or accelerate reactions in the chamber. If the disk is stationary while the chamber is being heated then if the fluid boils it will produce bubbles of vapour which will travel up the arms of the chamber and may even pass out into the waste channel (8) and waste chamber (4). This is not always desirable as it is often preferred that substantially all the fluid should remain in the chamber after the heating has been finished.
  • the radiation sources (not shown) can be focused onto areas that the coating passes through as the disc spins.
  • the coating can be dimensioned such that heat is only applied to only the smallest amount of the base consistent with adequate heating of the reagents. In this way the arms of the U are keep cool and provide condensation surfaces for the fluid vapour to condense on. The centrifugal force exerted on the condensed vapour causes it to flow back into the base of the chamber.
  • each further chamber may have a plurality of inlets and a plurality of outlets so that samples and reagents may be combined in a chamber.
  • the subsequent results of any process, which has taken place in a chamber, can be dispensed to one or more additional chambers for further processing or sent to the waste channel.
  • An example of this is shown in figure 8.
  • Figure 8 shows a microstructure, of a design similar to that shown in figure 6, in which the base (110c) of U-shaped chamber (110) is connected by a base outlet channel (134) to a second chamber (136), which second chamber (136) is positioned further away from the centre of the disk than second chamber (110).
  • Second chamber (136) is vented to atmosphere by a vent (138) that opens out on the top surface of the disc.
  • Second chamber (136) is also provided with an inlet/outlet connection (140) that also opens out on the top surface of the disk.
  • Inlet/outlet (140) can be used to supply substances to second chamber (136) e.g. by injecting them into connection (140) and/or to extract substances from second chamber (136) e.g.
  • hydrophobic break (132) is dimensioned so that when the disc is spun at a certain number of revolutions per second then any fluid in chamber (1 10) leaves the chamber via chamber outlet arm (110b), and when the disc is spun at a higher number of revolutions per minutes then the centrifugal force acting on the fluid is sufficient to overcome the hydrophobic effect of hydrophobic break (132) and the fluid flows into second chamber (136).
  • the outlet arm (1 10b) of chamber (110) is almost as long as inlet arm (110a).
  • the level of fluid in inlet arm (110b) will be very close to the base (107c') of the volume-defining structure (107').
  • a second fluid is supplied to the volume-defining structure (107'), e.g. via inlet (109') in the reservoir (161), it will come into direct contact with the first fluid in the chamber (110) and no air bubble will form between the two fluids.
  • This arrangement can be used to facilitate mixing of two fluids.

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Dispersion Chemistry (AREA)
  • Analytical Chemistry (AREA)
  • Hematology (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Fluid Mechanics (AREA)
  • Physics & Mathematics (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)
  • Physical Or Chemical Processes And Apparatus (AREA)
  • Centrifugal Separators (AREA)

Abstract

L'invention concerne une microstructure, laquelle est destinée à des fluides, est montée dans un disque rotatif (D) et possède une structure (7) définissant un volume en forme de U et reliée à sa base à un segment d'entrée d'une chambre également en forme de U (10).
PCT/EP2000/013145 1998-12-30 2000-12-22 Dispositif de microanalyse WO2001046465A2 (fr)

Priority Applications (6)

Application Number Priority Date Filing Date Title
JP2001546961A JP4612262B2 (ja) 1999-12-23 2000-12-22 ミクロ分析装置
DE60035611T DE60035611T2 (de) 1999-12-23 2000-12-22 Mikrofluid-analysevorrichtung
AU44105/01A AU4410501A (en) 1999-12-23 2000-12-22 Microanalysis device
EP00992452A EP1239962B1 (fr) 1999-12-23 2000-12-22 Dispositif de microanalyse
US10/169,056 US7261859B2 (en) 1998-12-30 2000-12-22 Microanalysis device
CA002395159A CA2395159A1 (fr) 1999-12-23 2000-12-22 Dispositif de microanalyse

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
EPPCT/EP99/10347 1999-12-23
PCT/EP1999/010347 WO2000040750A1 (fr) 1998-12-30 1999-12-23 Procede de sequençage d'adn a l'aide d'un dispositif microfluidique
SE0001779-8 2000-05-12
SE0001779A SE0001779D0 (sv) 2000-05-12 2000-05-12 Microanalysis device

Publications (2)

Publication Number Publication Date
WO2001046465A2 true WO2001046465A2 (fr) 2001-06-28
WO2001046465A3 WO2001046465A3 (fr) 2001-12-27

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2000/013145 WO2001046465A2 (fr) 1998-12-30 2000-12-22 Dispositif de microanalyse

Country Status (7)

Country Link
JP (1) JP4612262B2 (fr)
AT (1) ATE367204T1 (fr)
AU (1) AU4410501A (fr)
CA (1) CA2395159A1 (fr)
DE (1) DE60035611T2 (fr)
SE (1) SE0001779D0 (fr)
WO (1) WO2001046465A2 (fr)

Cited By (31)

* Cited by examiner, † Cited by third party
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WO2002075312A1 (fr) 2001-03-19 2002-09-26 Gyros Ab Caracterisation de variables de reaction
WO2003018198A1 (fr) 2001-08-28 2003-03-06 Gyros Ab Microcavite microfluidique de retention microfluidique et autres structures microfluidiques
WO2003024598A1 (fr) * 2001-09-17 2003-03-27 Gyros Ab Unite fonctionnelle de gestion des flux d'un dispositif de microfluidique
WO2004036204A2 (fr) 2002-10-13 2004-04-29 Picosep A/S Systeme microfluidique de separation de biomolecules
WO2005001766A1 (fr) 2003-06-30 2005-01-06 Gyros Patent Ab Determination du degre de confiance
EP1500937A1 (fr) * 2002-04-30 2005-01-26 Arkray, Inc. Instrument d'analyse, procede d'analyse d'echantillon et dispositif d'analyse utilisant un tel instrument, procede de formation d'ouverture dans l'instrument
US6919058B2 (en) 2001-08-28 2005-07-19 Gyros Ab Retaining microfluidic microcavity and other microfluidic structures
WO2005065827A1 (fr) * 2004-01-06 2005-07-21 Gyros Patent Ab Systeme de chauffage par contact
JP2005523728A (ja) * 2002-04-30 2005-08-11 ユィロス・アクチボラグ 集中マイクロ流体デバイス(ea)
US6985672B2 (en) 2000-11-23 2006-01-10 Gyros Ab Device and method for the controlled heating in micro channel systems
US6990290B2 (en) 2000-11-23 2006-01-24 Gyros Ab Device for thermal cycling
US6992278B2 (en) 2002-04-08 2006-01-31 Gyros Ab Homing process
EP1628137A1 (fr) * 2003-08-05 2006-02-22 Taiyo Yuden Co., Ltd. Dispositif d'analyse d'echantillon et support d'analyse d'echantillon en forme de disque
US7005265B1 (en) 2002-06-20 2006-02-28 Wenhong Fan Nonenzymatic catalytic signal amplification for nucleic acid hybridization assays
US7026131B2 (en) 2000-11-17 2006-04-11 Nagaoka & Co., Ltd. Methods and apparatus for blood typing with optical bio-discs
US7054258B2 (en) 2000-12-08 2006-05-30 Nagaoka & Co., Ltd. Optical disc assemblies for performing assays
US7079468B2 (en) 2000-12-08 2006-07-18 Burstein Technologies, Inc. Optical discs for measuring analytes
US7087203B2 (en) 2000-11-17 2006-08-08 Nagaoka & Co., Ltd. Methods and apparatus for blood typing with optical bio-disc
US7091034B2 (en) 2000-12-15 2006-08-15 Burstein Technologies, Inc. Detection system for disk-based laboratory and improved optical bio-disc including same
WO2006110095A1 (fr) 2005-04-14 2006-10-19 Gyros Patent Ab Dispositif microfluidique comprenant des valves digitiformes
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US7429354B2 (en) 2001-03-19 2008-09-30 Gyros Patent Ab Structural units that define fluidic functions
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SE0001779D0 (sv) 2000-05-12
DE60035611T2 (de) 2008-05-21
ATE367204T1 (de) 2007-08-15
AU4410501A (en) 2001-07-03
CA2395159A1 (fr) 2001-06-28
DE60035611D1 (de) 2007-08-30
JP2003518250A (ja) 2003-06-03
WO2001046465A3 (fr) 2001-12-27
JP4612262B2 (ja) 2011-01-12

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