EP1419818B1 - Dispositif pour le transport de liquide avec des forces capillaires - Google Patents

Dispositif pour le transport de liquide avec des forces capillaires Download PDF

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Publication number
EP1419818B1
EP1419818B1 EP03025615.0A EP03025615A EP1419818B1 EP 1419818 B1 EP1419818 B1 EP 1419818B1 EP 03025615 A EP03025615 A EP 03025615A EP 1419818 B1 EP1419818 B1 EP 1419818B1
Authority
EP
European Patent Office
Prior art keywords
channel
liquid
vent
capillary
cover element
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 - Lifetime
Application number
EP03025615.0A
Other languages
German (de)
English (en)
Other versions
EP1419818A1 (fr
Inventor
Gert Blankenstein
Ralf-Peter Peters
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.)
Boehringer Ingelheim Microparts GmbH
Original Assignee
Boehringer Ingelheim Microparts GmbH
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
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Publication of EP1419818A1 publication Critical patent/EP1419818A1/fr
Application granted granted Critical
Publication of EP1419818B1 publication Critical patent/EP1419818B1/fr
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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
    • B01L3/502738Containers 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 integrated valves
    • 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
    • B01L3/50273Containers 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 or forces applied to move the 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
    • B01L2200/0621Control of the sequence of chambers filled or emptied
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/04Closures and closing means
    • B01L2300/041Connecting closures to device or container
    • B01L2300/044Connecting closures to device or container pierceable, e.g. films, membranes
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/08Geometry, shape and general structure
    • B01L2300/0861Configuration of multiple channels and/or chambers in a single devices
    • B01L2300/0864Configuration of multiple channels and/or chambers in a single devices comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/08Geometry, shape and general structure
    • B01L2300/0861Configuration of multiple channels and/or chambers in a single devices
    • B01L2300/087Multiple sequential chambers
    • 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
    • B01L2400/0406Moving fluids with specific forces or mechanical means specific forces capillary 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
    • B01L2400/0677Valves, specific forms thereof phase change valves; Meltable, freezing, dissolvable plugs; Destructible barriers
    • 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
    • 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
    • B01L2400/0694Valves, specific forms thereof vents used to stop and induce flow, backpressure valves

Definitions

  • the invention relates to a device for the stepwise transport of liquid through a plurality of fluidically arranged in series reaction chambers taking advantage of capillary forces, wherein it is preferably to be examined sample liquids in the liquids.
  • sample liquids it is necessary to examine sample liquids in a wide variety of analytical and diagnostic applications.
  • the assays used sometimes require that the sample liquid be sequentially contacted with different reagents. With regard to the automation of such assays, it is advantageous to be able to gradually transport the sample liquid to be examined.
  • US-A-3,799,742 describes a fluid system in which, by utilizing gravity and selective venting of individual chambers connected in series and in parallel, a liquid flow from a reservoir into the individual chambers is produced.
  • a liquid channel extends from a reservoir.
  • branch channels which terminate in two chambers connected in series.
  • the branch channels in the chambers branch off from these vent lines, the are all closed and can be opened selectively.
  • the channel system described above allows a liquid transport exclusively by utilizing gravity. As long as all vents are closed, liquid transport from the reservoir is prevented by retaining the liquid by the gas back pressure.
  • a fluid system in which two fluids flowing through different conduits enter a common chamber.
  • the transport of each liquid through each line and both liquids in the common chamber is carried out selectively, namely by opening vent holes, on the one hand upstream of the common chamber and in fluid communication with the lines and on the other hand downstream of the common chamber and in fluid communication therewith are.
  • opening vent holes On the one hand upstream of the common chamber and in fluid communication with the lines and on the other hand downstream of the common chamber and in fluid communication therewith are.
  • various sections of the fluid system can be selectively vented, which allows selective transport of the fluids. Liquid that flows through a portion of the fluid system after opening a vent hole flows through the port in question to a line adjacent to the port.
  • An object of the invention is to provide a device for the stepwise transport of liquid, in particular to be examined sample liquid, which has a fairly simple structure and is convenient and easy to handle and reliable.
  • the invention proposes a device for the stepwise transport of liquid, in particular sample liquid to be examined, by means of a plurality of fluidically arranged reaction chambers in series utilizing capillary forces, which is provided with the features of claim 1.
  • capillary forces are utilized for the stepwise transport of liquids.
  • the channel of the device is to be transported through the liquid, designed accordingly. This applies with regard to the cross-sectional areas, cross-sectional area configurations and surface characteristics of the channel.
  • the channel is in fluid communication with at least two vents which are closed in their initial state.
  • the fluid connection of the vents to the channel is made at spaced along the channel connecting points.
  • the venting channels are designed for liquid transport by means of capillary forces.
  • the transport of liquid through the channel is prevented as long as the channel (at its end) and the vents are closed. If now the first vent opening in the flow direction of the channel, so liquid reaches up to the open vent hole in fluid communication Connection point of the channel and thereby filling the upstream of this junction chamber; the further transport of the liquid through the channel beyond this connection point is not possible because the adjoining part of the channel is closed to the outside. Only when the vent opening which is next in the direction of flow is opened does the channel section fill between the aforementioned connection point and the connection point associated with the next vent opening, and the liquid chamber arranged in this channel section fills.
  • the chambers may be empty or equipped with substances, inserts (porous bodies or the like) or capillary-generating devices, such as surface textures.
  • a (re) closure of the vents, after the liquid front has passed through the associated joints of the channel, is not mandatory, but can certainly be made.
  • An advantage of the invention is that the liquid does not matter the vent can escape. This is inventively achieved with mechanisms that exploit capillary forces to transport the liquid. The transport through a venting channel leading from a connection point to the vent opening also takes place by utilizing capillary forces. The vent is preceded by a capillary stop. This is designed as a hydrophobic part surface of the vent channel.
  • reagents are arranged within the chambers located in the individual channel sections. Contact with the liquid causes the reagents to mobilize and react with the liquid.
  • the vents can be arranged in the simplest case directly in the wall of the channel. The joints then coincide with the vents. Alternatively, it is also possible that branch off from the connection points venting channels that end in the vents.
  • the opening of the vents is advantageously carried out selectively by means of individual cover elements or a common cover element with which the vents can be selectively exposed according to their arrangement along the channel.
  • the lid member is an adhesive tape which is glued over one or more vents.
  • the cover element may be removable or puncturable, for example.
  • the lid member is melted or dissolved by the initiation of a reaction or permeable to air.
  • it is the lid member to an adhesive strip over the Vents of a substrate or the like.
  • Carrier is laid in which the channel system according to the invention is formed.
  • the cover elements it is for example advantageous if these cover elements are thermally coupled with one or more heating elements. By controlling the heating elements thus selectively cover elements are melted and thus vent openings exposed.
  • the initiation of a reaction that dissolves a cover element can take place by contacting the cover element with a reaction agent from the outside. It should be formed only for the sample liquid inert reaction mixtures.
  • a hydrophilic material e.g., gel such as agarose, sucrose or the like, polysaccharides
  • the sample liquid reaches into the next channel section.
  • the cover elements are therefore arranged in this case in the flow direction immediately behind a vent opening or a connection point, so that a released from a dissolved cover element channel section can be vented via this associated vent opening.
  • the device according to the invention can be used, for example, for a blood test, in which the blood to be examined reacts in a first reaction chamber with a first antibody or a conjugate and subsequently bind second antibodies in a second chamber to the bound first antibodies.
  • Task for the blood to be examined then passes this after exposure of the first vent the up to the associated junction extending channel portion of the channel in which the first reaction chamber is arranged with the first antibody or the conjugate.
  • the blood sample to be examined with the partially bound antibodies is then transferred by exposing the next venting vent in the direction of flow into a second channel section in which the second reaction chamber with the second antibodies is arranged. Subsequently, by exposing a further vent opening or by exposing the end of the channel, the sample liquid in this further transported or transported out of this.
  • the device according to the invention can advantageously also have several of the previously described (sample liquid transport) channels with ventilation openings. All of these channels are fluidically parallel to each other, extending from a sample receiving arrangement with a common sample receiving chamber or a plurality of individual, the channels respectively associated sample receiving chambers and preferably have mutually equal length channel sections between the individual connection points.
  • the connection points respectively associated ventilation openings are arranged directly adjacent to each other and can be advantageously exposed with one and the same lid member. This allows a parallel stepwise transport of liquid through the individual channels.
  • Fig. 1 13 shows the basic structure of a capillary channel system 10.
  • the capillary channel system 10 is formed in a substrate 12 (plastic body or the like) and has a channel 14 which includes an inlet port 16 (in fluid communication with a reservoir, not shown) and an outlet port 18 , Liquid located in the channel 14 is transported in the channel by utilizing capillary forces.
  • the channel 14 has a plurality of (four in the embodiment) connection points 20,22,24 and 26, from which branch off vent lines 28,30,32,34, which end in vents 36,38,40,42.
  • the channel 14 is divided by the connection points 20,22,24,26 into individual channel sections 44,46,48; in each channel section 44, 46, 48 there is a reaction chamber 50, 52, 54.
  • capillary channel system 10 can be selectively filled with liquid as follows.
  • vents 36,38,40,42 and the outlet 18 of the channel 14 are closed. If now the first vent opening 36 is opened in the flow direction 56 (see arrow), then sample liquid, which is present at the inlet 16 of the channel 14, to the junction 20 and into the vent channel 28 to the vent opening 36. By shortening the vent channels 28, the dead volume of the capillary channel system 10 are minimized.
  • the vent openings 36 may also be formed directly in the wall of the channel 14. After the opening 36 exposed has been, the liquid front within the channel 14 thus migrates to the junction 20; In any case, (still) no liquid enters the channel section 44.
  • next vent opening 40 is opened, then the procedure described above for the further channel section 46 is repeated, so that finally the situation according to Fig. 3 established.
  • the next channel section 48 is filled with liquid, which in Fig. 4 is shown.
  • the liquid passes out of the channel 14 in a (not shown) collecting container or a collecting chamber.
  • the capillary channel system 10 described above may still have so-called capillary stops, which are overcome only after impressing a pressure pulse on the liquid, wherein subsequently the further transport of the liquid is again induced by capillary forces.
  • capillary stops could for example be formed or arranged at the outlets of the reaction chambers 50, 52, 54.
  • the selective transport of the liquid through the Kapillarkanalsystem 10 is carried out in such a case so alternately by exposing vents and impressing a pressure pulse.
  • FIGS. 5 to 7 A second embodiment of a capillary channel system 10 'is shown.
  • the basic structure of the capillary channel system 10 'of FIGS. 5 to 7 is identical to the one according to the FIGS. 1 to 4 , One difference is the way in which the vents are exposed. These were in the embodiment according to the FIGS. 1 to 4 for example, exposed by individual cover elements 58, while in the embodiment according to the FIGS. 5 to 7 a continuous cover strip 60 is provided as a cover member which is more or less withdrawn and thus gradually exposing the vents 36,38,40,42.
  • the cover strip 60 may be formed as an adhesive strip having individual sections 64, 66, 68 connected by perforation lines or other types of predetermined breaking lines 62.
  • the predetermined breaking lines 62 are located between each two adjacent vent openings 38,40 and 40,42 and preferably approximately in the middle between these openings. At least on the side of a predetermined breaking line 62 facing the downstream vent opening, the adhesive side of the cover strip is free of adhesive in a region 70 adjacent to the predetermined breaking line 62. After detachment of the first section 64, which has at its free end a non-adhesive region 72, which serves as a handle, this section 64 can be torn off at the predetermined breaking line 62. The area 70 of the next section 66 then again serves as a grasping to facilitate the detachment of the portion 66 for the purpose of exposing the next vent opening 40th
  • FIG. 8 Finally, another embodiment of a capillary channel system 10 ", which has a plurality of (in this embodiment, two) channels 14, each of which, as described in connection with the preceding embodiments, procured and configured, that is several (in this embodiment, two) fluidically has reaction chambers 50, 52 connected in series from each channel 14 So branch off a plurality of vent lines 28,30,32 with vents 36,38,40 at their ends.
  • the first vent openings 36 of all the channels 14 in the flow direction are closed in groups or all by a plurality or a common cover element 74.
  • the same constellation results for the next in the flow direction vents 38,40, which are closed by a cover member 76 and 78, respectively.
  • This system of common cover elements 74, 76, 78 is the same across the entire capillary channel system 10.
  • the channels 14 branch off from a reservoir 80 which is filled with the liquid to be passed into and through the reaction chambers 50, 52 is or is.
  • first flow reaction chamber 50 upstream vent openings 36 of the channels 14 becomes clear considering that the channels 14 may be of different lengths in their sections between the reservoir 80 and the first reaction chambers 50 (for example, by design).
  • the connection points 20 of the channels 14, at which the vent lines 28 branch off, are arranged at the same distance along the channel 14 of the first reaction chambers 50. After exposure of the first vent openings 36 is then in each channel 14, the liquid front equidistant from the first reaction chamber 50 at. Thus, the simultaneous filling of the first reaction chambers 50 after exposing the second vent openings 38 is ensured.
  • venting channels 28, 30, 32 branching off from the sample liquid transport channels 14 are arranged in groups (the first group comprises the first venting channels 28, the second group in the flow direction second venting channels 30, etc.) in a common vent opening 36,38,40 end.
  • the capillary channel systems 10 'and 10 "of the FIGS. 5 to 8 additionally be provided with capillary stops, which, as also mentioned above, for example, at the outlet end of the reaction chambers 50,52 considered with respect to the flow direction are arranged.
  • the capillary channel system according to the invention is characterized by a precise timing and triggering of the further transport of the liquid. Furthermore, extremely simple opening mechanisms for the vents are described.
  • the system is expediently designed for single use and designed as a disposable item. It requires a minimum of test fluid and no filter / membrane components used. Further, the system allows the completely closed formation on a substrate or the like. Carrier, which is why the risk of contamination is minimized. For triggering the reactions and in particular the transport of the liquid are no centrifugal forces or the like. required.
  • the system according to the invention operates independently of position, since capillary forces are utilized for liquid transport.

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Dispersion Chemistry (AREA)
  • Analytical Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Hematology (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)
  • Sampling And Sample Adjustment (AREA)
  • Devices For Use In Laboratory Experiments (AREA)

Claims (7)

  1. Dispositif pour le transport pas à pas de liquide, en particulier d'échantillon liquide à examiner, à travers plusieurs chambres de réaction disposées fluidiquement en série, en utilisant des forces capillaires, comprenant
    - un canal (14) à travers lequel un liquide peut être transporté sous l'action de forces capillaires, et
    - au moins deux orifices d'évent (38, 40, 42) fermés, qui sont en liaison fluidique avec le canal (14) au niveau de points de raccordement (22, 24, 26) espacés les uns des autres le long du canal (14) et peuvent être ouverts individuellement,
    - les points de raccordement (22, 24, 26) divisant le canal (14) en plusieurs parties de canal (44, 46, 48),
    - la liaison fluidique entre une partie de canal (44, 46, 48) respective et l'orifice d'évent fermé (38, 40, 42) associé à celle-ci pouvant être traversée par le liquide par ouverture individuelle dudit orifice d'évent,
    - au moins une chambre (50, 52, 54) étant disposée dans les parties de canal (44, 46, 48) respectivement en amont - tel que vu dans le sens d'écoulement - des points de raccordement (22, 24, 26),
    - des canaux de purge d'air capillaires (30, 32, 34) qui débouchent dans les orifices d'évent (38, 40, 42) partant du canal (14) au niveau de ses points de raccordement (22, 24, 26),
    - une butée capillaire disposée à l'intérieur du canal de purge d'air (30, 32, 34) respectif étant située en amont de chaque orifice d'évent (38, 40, 42), et
    - les butées capillaires étant conçues chacune sous forme d'une surface partielle hydrophobe du canal de purge d'air (30, 32, 34) respectif.
  2. Dispositif selon la revendication 1, caractérisé en ce qu'une substance réactive est disposée dans au moins une chambre (50, 52, 54).
  3. Dispositif selon la revendication 2, caractérisé en ce que la substance réactive est immobilisée et est mobilisable lors du contact avec le liquide.
  4. Dispositif selon l'une des revendications 1 à 3, caractérisé en ce que chaque orifice d'évent (38, 40, 42) est fermé par un élément de recouvrement (60, 74, 76, 78) pouvant être détaché, percé, ôté par fusion et/ou dissous en initiant une réaction ou perméable à l'air.
  5. Dispositif selon la revendication 4, caractérisé en ce que tous les orifices d'évent (38, 40, 42) sont recouverts d'un élément de recouvrement (60, 74, 76, 78) commun, l'élément de recouvrement (60, 74, 76, 78) pouvant, de manière sélective, être détaché, percé, ôté par fusion et/ou dissous par initiation d'une réaction ou perméable à l'air.
  6. Dispositif selon la revendication 4 ou 5, caractérisé en ce que sont prévus pour la fusion de l'élément de recouvrement (60, 74, 76, 78) un ou plusieurs éléments chauffants couplés thermiquement à l'élément de recouvrement (60, 74, 76, 78).
  7. Dispositif selon l'une des revendications 1 à 6, caractérisé en ce que sont prévus plusieurs canaux (14) dont les premier, second orifices d'évent et suivants (38, 40, 42) se succédant dans la direction d'écoulement peuvent être dégagés ensemble par groupes respectifs.
EP03025615.0A 2002-11-14 2003-11-06 Dispositif pour le transport de liquide avec des forces capillaires Expired - Lifetime EP1419818B1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE10254874 2002-11-14
DE10254874 2002-11-14

Publications (2)

Publication Number Publication Date
EP1419818A1 EP1419818A1 (fr) 2004-05-19
EP1419818B1 true EP1419818B1 (fr) 2013-10-30

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US (1) US7316802B2 (fr)
EP (1) EP1419818B1 (fr)
JP (1) JP2004170408A (fr)
CN (1) CN100571871C (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105676389A (zh) * 2016-04-14 2016-06-15 杭州富通通信技术股份有限公司 一种光缆

Families Citing this family (61)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6571651B1 (en) * 2000-03-27 2003-06-03 Lifescan, Inc. Method of preventing short sampling of a capillary or wicking fill device
US7148257B2 (en) * 2002-03-04 2006-12-12 Merck Hdac Research, Llc Methods of treating mesothelioma with suberoylanilide hydroxamic acid
CN1650173B (zh) * 2002-04-30 2012-06-06 爱科来株式会社 分析用具、使用分析用具的试样分析方法及分析装置、和分析用具的开口形成方法
US20070014694A1 (en) * 2003-09-19 2007-01-18 Beard Nigel P High density plate filler
US20050220675A1 (en) * 2003-09-19 2005-10-06 Reed Mark T High density plate filler
US20060233673A1 (en) * 2003-09-19 2006-10-19 Beard Nigel P High density plate filler
US20050232821A1 (en) * 2003-09-19 2005-10-20 Carrillo Albert L High density plate filler
US7695688B2 (en) * 2003-09-19 2010-04-13 Applied Biosystems, Llc High density plate filler
US7407630B2 (en) * 2003-09-19 2008-08-05 Applera Corporation High density plate filler
US20050226782A1 (en) * 2003-09-19 2005-10-13 Reed Mark T High density plate filler
US8277760B2 (en) * 2003-09-19 2012-10-02 Applied Biosystems, Llc High density plate filler
US9492820B2 (en) 2003-09-19 2016-11-15 Applied Biosystems, Llc High density plate filler
US20060233671A1 (en) * 2003-09-19 2006-10-19 Beard Nigel P High density plate filler
US7998435B2 (en) * 2003-09-19 2011-08-16 Life Technologies Corporation High density plate filler
US20060272738A1 (en) * 2003-09-19 2006-12-07 Gary Lim High density plate filler
EP1824600B1 (fr) * 2004-10-18 2016-12-28 Life Technologies Corporation Dispositif de traitement de fluide comprenant une barriere a changement de taille
DE102004054551B4 (de) * 2004-11-11 2021-07-22 Orgentec Diagnostika Gmbh Vorrichtung zur vollautomatischen Durchführung eines Einzelimmunoassays
ES2361169T3 (es) 2005-01-27 2011-06-14 Boehringer Ingelheim Microparts Gmbh Uso de un dispositivo para el análisis de muestras de líquido.
WO2006099042A2 (fr) * 2005-03-09 2006-09-21 The Regents Of The University Of California Soupape microfluidique pour liquides
DE102005042601A1 (de) * 2005-04-09 2006-10-12 Boehringer Ingelheim Microparts Gmbh Vorrichtung und Verfahren zur Untersuchung einer Probenflüssigkeit
JP4837725B2 (ja) * 2005-04-09 2011-12-14 ベーリンガー インゲルハイム マイクロパーツ ゲゼルシャフト ミット ベシュレンクテル ハフツング サンプル液の検査装置及び方法
DE102005016509A1 (de) * 2005-04-09 2006-10-12 Boehringer Ingelheim Microparts Gmbh Vorrichtung und Verfahren zur Untersuchung einer Probenflüssigkeit
DE102005016508A1 (de) * 2005-04-09 2006-10-12 Boehringer Ingelheim Microparts Gmbh Vorrichtung und Verfahren zur Untersuchung einer Probenflüssigkeit
DE102005017653A1 (de) 2005-04-15 2006-10-19 Boehringer Ingelheim Microparts Gmbh Vorrichtung und Verfahren zur Manipulation einer Flüssigkeit
US7935318B2 (en) * 2005-06-13 2011-05-03 Hewlett-Packard Development Company, L.P. Microfluidic centrifugation systems
US7723120B2 (en) * 2005-10-26 2010-05-25 General Electric Company Optical sensor array system and method for parallel processing of chemical and biochemical information
US8905073B2 (en) * 2006-03-09 2014-12-09 Sekisui Chemical Co. Ltd. Micro fluid device and trace liquid diluting method
TWI310835B (en) * 2006-06-23 2009-06-11 Ind Tech Res Inst Gravity-driven fraction separator and method thereof
US8986449B2 (en) 2006-06-28 2015-03-24 Microlytic North America Inc. Device and a method for promoting crystallisation
EP1878498A1 (fr) 2006-07-14 2008-01-16 Roche Diagnostics GmbH Kit pour analyser un échantillon liquide par amplification d'acides nucléiques
WO2008108481A1 (fr) * 2007-03-05 2008-09-12 Nec Corporation Mécanisme de commande d'écoulement pour micropuce
EP2282190B1 (fr) 2008-05-29 2017-07-12 Nippon Telegraph and Telephone Corporation Cuve à circulation et procédé de distribution de liquide
JP5155800B2 (ja) * 2008-09-29 2013-03-06 富士フイルム株式会社 反応方法及び反応装置
WO2011066361A1 (fr) 2009-11-24 2011-06-03 Claros Diagnostics, Inc. Mélange et distribution de fluides dans des systèmes microfluidiques
US20110312732A1 (en) * 2010-06-17 2011-12-22 Geneasys Pty Ltd Test module using lanthanide metal-ligand complex, electrochemiluminescent luminophores
WO2012062646A1 (fr) * 2010-11-10 2012-05-18 Boehringer Ingelheim Microparts Gmbh Procédé de remplissage d'un emballage à blister avec un liquide et emballage à blister muni d'une cavité à remplir avec un liquide
WO2012123750A1 (fr) * 2011-03-15 2012-09-20 Carclo Technical Plastics Limited Préparation de surface
WO2012178187A1 (fr) 2011-06-23 2012-12-27 Paul Yager Modélisation de réactif dans des analyseurs de capillarité, et systèmes et procédés associés
WO2013011652A1 (fr) * 2011-07-20 2013-01-24 株式会社エンプラス Dispositif de manipulation de fluide, procédé de manipulation de fluide et système de manipulation de fluide
EP2559488A1 (fr) * 2011-08-18 2013-02-20 Koninklijke Philips Electronics N.V. Contrôle de l'écoulement d'un fluide dans un système microfluidique
EP2751021A4 (fr) 2011-08-30 2015-09-30 Univ Mcgill Procédé et système destinés à des circuits microfluidiques autonomes préprogrammés
GB201202519D0 (en) 2012-02-13 2012-03-28 Oxford Nanopore Tech Ltd Apparatus for supporting an array of layers of amphiphilic molecules and method of forming an array of layers of amphiphilic molecules
GB201216454D0 (en) * 2012-09-14 2012-10-31 Carclo Technical Plastics Ltd Sample metering device
CN104870092A (zh) * 2012-11-29 2015-08-26 皇家飞利浦有限公司 用于样本的摄取和处理的盒
EP2948249A1 (fr) 2013-01-22 2015-12-02 University of Washington through its Center for Commercialization Délivrance séquentielle de volumes de fluide et dispositifs, systèmes et procédés associés
FR3003033B1 (fr) * 2013-03-07 2015-04-17 Commissariat Energie Atomique Dispositif de prelevement d'un echantillon de liquide par capillarite et procede d'analyse associe
JP6290261B2 (ja) * 2013-12-26 2018-03-07 京セラ株式会社 検体液センサ、検体液センサユニット及び検体液検査方法
RU2685660C2 (ru) * 2014-06-16 2019-04-22 Конинклейке Филипс Н.В. Картридж для быстрого отбора пробы
WO2016092333A2 (fr) * 2014-12-12 2016-06-16 Bio Amd Holdings Limited Appareil d'analyse
WO2017056748A1 (fr) * 2015-09-28 2017-04-06 パナソニックヘルスケアホールディングス株式会社 Capteur d'analyse d'analyte, dispositif de mesure, et procédé d'analyse d'analyte
CN105964315B (zh) * 2016-05-23 2017-12-22 杭州霆科生物科技有限公司 一种多级自控的微流控芯片
GB201611770D0 (en) 2016-07-06 2016-08-17 Oxford Nanopore Tech Microfluidic device
JP6799308B2 (ja) * 2016-09-30 2020-12-16 株式会社アイビー 液体試料搬送方法および試薬チップ
EP3978134A1 (fr) * 2017-07-05 2022-04-06 miDiagnostics NV Dispositif pour dissoudre un réactif dans un fluide dans un système microfluidique à commande capillaire
GB2568895B (en) * 2017-11-29 2021-10-27 Oxford Nanopore Tech Ltd Microfluidic device
US11154864B2 (en) 2018-01-17 2021-10-26 Qiagen Sciences, Llc Microfluidic device with vented microchambers
CN109738632B (zh) * 2019-01-09 2022-04-29 南京岚煜生物科技有限公司 多指标微流控芯片及其使用方法
AU2020239385A1 (en) 2019-03-12 2021-08-26 Oxford Nanopore Technologies Plc Nanopore sensing device and methods of operation and of forming it
GB202105032D0 (en) * 2021-04-08 2021-05-26 Kromek Ltd Microfludic system and method
DE102021211545A1 (de) * 2021-10-13 2023-04-27 Robert Bosch Gesellschaft mit beschränkter Haftung Klebefolie für eine mikrofluidische Vorrichtung, mikrofluidische Vorrichtung mit Klebefolie und Verwendung einer Klebefolie zum Verschließen einer Öffnung einer mikrofluidischen Vorrichtung
CN218298031U (zh) * 2022-09-07 2023-01-13 上海睿钰生物科技有限公司 一种样品分析设备及样品分析系统

Family Cites Families (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3799742A (en) * 1971-12-20 1974-03-26 C Coleman Miniaturized integrated analytical test container
US4426451A (en) * 1981-01-28 1984-01-17 Eastman Kodak Company Multi-zoned reaction vessel having pressure-actuatable control means between zones
USRE33858E (en) * 1985-01-25 1992-03-24 Mallinckrodt Sensor Systems Inc. Apparatus for measuring a chemical entity in a liquid
US4806316A (en) * 1987-03-17 1989-02-21 Becton, Dickinson And Company Disposable device for use in chemical, immunochemical and microorganism analysis
US4849340A (en) * 1987-04-03 1989-07-18 Cardiovascular Diagnostics, Inc. Reaction system element and method for performing prothrombin time assay
US4946795A (en) * 1987-08-27 1990-08-07 Biotrack, Inc. Apparatus and method for dilution and mixing of liquid samples
US5242606A (en) * 1990-06-04 1993-09-07 Abaxis, Incorporated Sample metering port for analytical rotor having overflow chamber
US5230866A (en) * 1991-03-01 1993-07-27 Biotrack, Inc. Capillary stop-flow junction having improved stability against accidental fluid flow
US5478751A (en) * 1993-12-29 1995-12-26 Abbott Laboratories Self-venting immunodiagnositic devices and methods of performing assays
US6130098A (en) * 1995-09-15 2000-10-10 The Regents Of The University Of Michigan Moving microdroplets
US6117396A (en) * 1998-02-18 2000-09-12 Orchid Biocomputer, Inc. Device for delivering defined volumes
WO1999046045A1 (fr) * 1998-03-11 1999-09-16 MICROPARTS GESELLSCHAFT FüR MIKROSTRUKTURTECHNIK MBH Porte-echantillon
DE60144142D1 (de) * 2000-03-02 2011-04-14 Microchips Inc Mikromechanische geräte und verfahren zur speicherung und zur selektiven exposition von chemikalien
ATE287291T1 (de) * 2000-03-07 2005-02-15 Symyx Technologies Inc Prozessoptimierungsreaktor mit parallelem durchfluss
US6627159B1 (en) * 2000-06-28 2003-09-30 3M Innovative Properties Company Centrifugal filling of sample processing devices
SE0004350D0 (sv) * 2000-11-27 2000-11-27 Patrick Griss System och metod för tillförlitliga passiva ventiler och gas volym dosering
US7010391B2 (en) * 2001-03-28 2006-03-07 Handylab, Inc. Methods and systems for control of microfluidic devices
US6883957B2 (en) * 2002-05-08 2005-04-26 Cytonome, Inc. On chip dilution system
JP4081721B2 (ja) * 2004-02-20 2008-04-30 富士フイルム株式会社 科学現象の評価装置、及びその製造方法
US20050249641A1 (en) * 2004-04-08 2005-11-10 Boehringer Ingelheim Microparts Gmbh Microstructured platform and method for manipulating a liquid

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105676389A (zh) * 2016-04-14 2016-06-15 杭州富通通信技术股份有限公司 一种光缆
CN105676389B (zh) * 2016-04-14 2018-08-07 杭州富通通信技术股份有限公司 一种光缆

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US7316802B2 (en) 2008-01-08
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JP2004170408A (ja) 2004-06-17
CN1500555A (zh) 2004-06-02

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