EP0594259B1 - Flow control in a containment device - Google Patents
Flow control in a containment device Download PDFInfo
- Publication number
- EP0594259B1 EP0594259B1 EP19930202961 EP93202961A EP0594259B1 EP 0594259 B1 EP0594259 B1 EP 0594259B1 EP 19930202961 EP19930202961 EP 19930202961 EP 93202961 A EP93202961 A EP 93202961A EP 0594259 B1 EP0594259 B1 EP 0594259B1
- Authority
- EP
- European Patent Office
- Prior art keywords
- compartment
- passageway
- configuration
- opposing walls
- wall
- 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
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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
-
- 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
- B01L2400/0475—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
- B01L2400/0481—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure squeezing of channels or chambers
Definitions
- This invention relates to containment devices used to process a liquid under contained conditions, including detection of analyte and collection of waste liquids.
- a containment device for amplifying and detecting nucleic acid material comprising:-
- the invention provides the advantageous feature of a containment device with a dead-end waste compartment which minimizes the build-up of back pressures as the waste compartment fills up without leaking the contents of the device to the atmosphere.
- the invention is hereinafter described in connection with certain preferred embodiments, in which a particular flexible device is processed by a certain processor for amplification and detection of DNA.
- the invention is useful regardless of the peculiar construction of the device and/or processor, and regardless whether the device is processed horizontally or while inclined, as long as there is a waste compartment which receives liquid from a detection site, with the risk of the build-up of back pressure in such compartment.
- this invention does not concern or require any particular chemistry or reaction, so long as the reaction is contained in a closed device.
- the invention is independent of the particular liquid reaction occurring at the detection chamber and is not limited just to detection of nucleic acid materials.
- reaction cuvettes 10 useful with the present invention comprise those having an inlet port 22 for patient injection of sample liquid, which connects via a passageway 21 to a PCR reaction compartment 26.
- a seal 46 temporarily blocks flow out of compartment 26.
- liquid feeds via a passageway 44 to a detection chamber 40 having sites 41 comprising, preferably, beads anchored in place which will complex with any targeted analyte passing them from compartment 26, and then with reagents coming from the other reagent compartments.
- Those other compartments are compartments 30, 32, 34 and optionally additional compartments 36, each feeding via passageways 48, 50, and 52, to chamber 40.
- Each of those passageways is temporarily sealed at 56, and contains an appropriate reagent liquid (and possibly, residual air).
- compartments 26, 30, 32, and 34 preferably comprise: Compartment 26, in addition to the patient liquid later added by the user, can include all the conventional reagents needed for PCR amplification, kept in place by temporary seal 25. This includes primers which are bound to one member of a binding pair, the other member of which appears in compartment 30 described below.
- a useful example of the binding member attached to a primer is biotin. (Seal 25 is burst by injecting sample.) Alternatively, the reagents can be injected with the sample, so that seal 25 is eliminated.
- Compartment 30 comprises, preferably, an enzyme bound to a complexing agent, such as avidin, which is a member of a binding pair, the other member of that pair being bound to a targeted analyte in the reaction compartment 26 as described above.
- a useful reagent in compartment 30 is strep-avidin horseradish peroxidase (hereinafter, strep-avidin HRP).
- Compartment 32 preferably comprises a wash solution as the reagent.
- Compartment 34 preferably comprises a signal precursor, and any dye stabilizing agent which may be useful.
- a useful reagent solution in compartment 34 is a solution of a leuco dye which is a conventional substrate for the enzyme of compartment 30.
- compartments 36 are preferably eliminated, along with their passageways, but can be optionally added. Hence, if a second wash is desired prior to adding the leuco dye of compartment 34, then such wash is provided by compartment 34 and the leuco dye is moved to compartment 36, and so forth.
- Compartment 40 feeds to compartment 42 via passageway 58.
- Compartment 42 is the waste-collecting compartment to which the invention is particularly applicable, as described hereinafter.
- Roller 60 exemplifies the exterior pressure means used to burst sequentially each of the compartments to advance the contents of the respective compartment to detection chamber 40 sequentially. Roller 60 advances along path 62 having width "A".
- Distances P1, P2, and so forth, between the exit locations for each burstable compartment are preferably equal.
- waste compartment 42 is intended to receive all excess liquids flowing past the detection sites in compartment 40, without creating back-pressure due to the absence of an outlet. This is achieved by forming waste compartment 42 comprising opposing side walls 70, 72, Figure 2, which provide the major interior surface area of the compartment (in contrast to side walls 80), that is, at least 51% of the total surface area. At least wall 72 has therein sufficient fold lines 74 to provide wall 72 with a bi-stable configuration. The fold lines are formed in at least one of the opposing walls of the pair 70, 72, as to project a bead out of the plane of that opposing wall.
- the fold lines and the bead can either be a continuous, closed loop, or a majority fraction of a closed loop, for example, at least 50% of the loop which would be formed if the fold lines and bead extended all the way around. Further, the fold lines and bead can either be at the perimeter of the waste compartment, or just inside that perimeter.
- fold lines 74 form a closed loop, which most preferably traces a pattern, Figure 1, which is congruent with the overall shape and inside the perimeter of compartment 42 as determined by the side walls 80.
- Walls 80 connect walls 70 and 72, Figure 2, to form the sealed enclosure of the compartment except for incoming passageway 58. As shown, that shape is roughly a rectangle. Other shapes will be readily apparent.
- wall 72 is collapsed as shown in the solid lines, so it is proximal to wall 70.
- wall 72 snaps outwardly along fold line 74, to occupy the phantom position, thus relieving any back-pressure which is created.
- back-pressure first builds up to a point sufficient to snap wall 72 outwardly, at which point the pressure in compartment 42 becomes negative until more liquid comes in.
- more than one fold line can be present (not shown), to provide, for example, concentric shapes which in turn allow for greater expansion of the wall; for example, there could be included another fold line inside that of line 74, tracing a concentric rectangle.
- an expansion pad 90 is included, which when wetted tends to expand, further aiding in the process of pushing wall 72 to its outward position where it is distal to wall 70.
- Such pad can be any conventional sponge, such as a commercially available cellulose sponge dried to a compressed state.
- both walls of the waste compartment can have the fold lines so that both walls have a bi-stable configuration. Parts similar to those previously shown bear the same reference numeral, to which the distinguishing suffix "A" is appended.
- waste compartment 42A is constructed as in the embodiment of Figure 2, except that wall 70A has a fold line 74A' which is similar to fold line 74A of wall 72A.
- the solid line positions are of course the collapsed configuration where the two opposing walls are proximal, whereas the phantom positions are the expanded configurations in which the walls are distal to each other. Greater expansion is possible when both walls are so provided.
- optional pad 90A can be present, preferably adhered to one or the other of walls 70A or 72A if present.
- passageways 44, 48, 50 and 52 need not be as shown, nor need they extend so far away from path 62 of roller 60. Instead, the passageways can be disposed so that the majority of their path length (at least one-half) is within path 62 of the roller, Figure 4. Parts similar to those previously described bear the same reference numeral, to which the distinguishing suffix "B" is applied.
- cuvette 10B has inlet port 22B and all the compartments 26B, 30B, 32B, 34B, 36B, 40B and 42B as described with reference to the previous embodiments with passageways 44B, 48B, 50B and 52B, respectively, providing flow means connecting the upstream compartments with compartments 40B and 42B.
- Waste compartment 42B has the fold line 74B to allow at least wall 72B to snap outward to relieve back-pressure.
- passageways 48B and 50B have a majority of their paths extending parallel and closely adjacent to the path of passageway 44B providing the flow means from compartment 26B, so that application of the roller pressure along path 62B having a width "A", will cause the roller to at some point compress each of the noted passageways along at least half of their length.
- Such coverage by the roller allows for better positive control of the emptying of each respective passageway. That is, as long as the roller is pinching off each passageway, including passageway 44B, which occurs up to point "X,” there can be no "back-flow" into that passageway such as might disturb proper sequential delivery of reagents to the detection sites.
- each of the compartments 30B, 32B, 34B and 36B can be provided with a side-fill port 100, such that the filling proceeds by filling each compartment out to line 102, eliminating any air, and thereafter heat-sealing the opposing walls together at 104 through the liquid, as is conventional. This ensures that no air bubbles will be pushed by the external roller into compartment 40B where they might interfere with the liquid-phase reactions which occur.
- each passageway in the embodiment of Figure 4 has a substantial length from its respective burstable compartment, to the location where it joins the other passageways just upstream of compartment 40B. This is the feeder portion of each passageway. It is not necessary that this be so. Rather, the feeder portion length of the passageway from its compartment to the junction location with other passageways can be minimized to the extent that the length is less than the maximum diameter of the burstable compartment from which it extends, Figure 5. Parts similar to those previously described bear the same reference numeral, to which the distinguishing suffix "C" is applied.
- cuvette 10C has inlet port 22C and all the compartments 26C, 30C, 32C, 34C, 40C and 42C as described with reference to the previous embodiments, with passageways 44C, 48C, and 50C, respectively, providing the flow means connecting the upstream compartments with compartments 40C and 42C.
- Waste compartment 42C has the fold line 74C to allow at least wall 72C to snap outward to relieve back-pressure.
- each passageway 48C and 50C has a junction with passageway 44C such that the length L of the passageway from its respective burstable storage compartment, to the junction, is less than the maximum dimension D of its storage compartments. (As shown, that dimension is measured from the future exit aperture of the compartment to an opposite point closest to the next upstream compartment, due to the tear-drop shape of the compartments.)
- most preferably L is less than one-half of D for a respective compartment.
- Such an arrangement further minimizes back-flow of reagent from an upstream compartment into the passageway length L, prior to expulsion of the contents of the storage compartment through length L. This in turn minimizes undesired side-reactions which might occur between reagents in path length L rather than in compartment 40C where they are desired.
- roller path 62C covers the majority of the path lengths of the passageways.
- an air vent path 200 can be provided from reaction compartment 26C back into a sealed portion of the pouch, for example, to dead storage area 202 of the pouch, to minimize build-up of back-pressure such as might inhibit ingestion of sample from port 22C along passageway 21C.
- path 200 is also sealed from leakage to the atmosphere to provide positive containment against leakage of amplified nucleic acid material which could cause carry-over contamination.
- cuvette 10D, Figure 6 is constructed as described in the previous embodiments, except that waste compartment 42D has a fold line 74D, Figure 6, in opposing wall 72D, Figure 7A, forming a crease or bead which does not join itself to form a closed loop, and it is at the periphery of the compartment, rather than spaced inside.
- fold line 74D is formed into parts 174 and 176 which are a majority fraction of the periphery, or a majority of what would be a closed loop if it did extend to join both parts 174 and 176 together.
- Majority as applied to fold line 74D means, at least 50%, since amounts less than this are unlikely to allow wall 72D, Figure 7A, to move far enough out when liquid L enters, Figure 7B.
- wall 72D When liquid enters compartment 42D, wall 72D eventually pops out from its collapsed configuration or position, Figure 7A, to its expanded, second configuration or position, Figure 7B, due to its bi-stable construction. Only the portion 178 of wall 72D which is pinch-sealed to opposing wall 70D, Figure 8, remains un-expanded.
- Side wall 80D is unaffected by the in-flowing liquid. That is, as in the previously described embodiment, it does not expand sideways from its original position shown in Figure 7B, as indeed it cannot since it is sealed at 180 to opposing wall 70D.
- cuvette 10E features a waste compartment 42E having fold lines 74E in one of its paired opposite walls 72E which forms the major interior surface area of the compartment.
- the fold lines form a beaded crease generally in the shape of an "H”, comprising a cross-member 190 and legs 192 and 194.
- the linear extent of the crease defined as (L 1 + 4 x L 2 ) , is such as to comprise at least 50% of what would exist if lines 74E formed a closed loop around the periphery.
- the expansion of wall 72E outward will, of course, peak along cross-member 190, when liquid enters compartment 42E.
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Analytical Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Hematology (AREA)
- Clinical Laboratory Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Apparatus Associated With Microorganisms And Enzymes (AREA)
- Devices For Use In Laboratory Experiments (AREA)
Applications Claiming Priority (6)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US96568392A | 1992-10-23 | 1992-10-23 | |
US965683 | 1992-11-20 | ||
US07/979,569 US5422271A (en) | 1992-11-20 | 1992-11-20 | Nucleic acid material amplification and detection without washing |
US979569 | 1992-11-20 | ||
US42361 | 1993-04-02 | ||
US08/042,361 US5288463A (en) | 1992-10-23 | 1993-04-02 | Positive flow control in an unvented container |
Publications (2)
Publication Number | Publication Date |
---|---|
EP0594259A1 EP0594259A1 (en) | 1994-04-27 |
EP0594259B1 true EP0594259B1 (en) | 1996-09-25 |
Family
ID=27366113
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP19930202961 Expired - Lifetime EP0594259B1 (en) | 1992-10-23 | 1993-10-21 | Flow control in a containment device |
Country Status (5)
Country | Link |
---|---|
EP (1) | EP0594259B1 (fi) |
JP (1) | JP3594979B2 (fi) |
DE (1) | DE69305046T2 (fi) |
DK (1) | DK0594259T3 (fi) |
FI (1) | FI934670A (fi) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US11192108B2 (en) | 2014-12-08 | 2021-12-07 | Berkeley Lights, Inc. | Actuated microfluidic structures for directed flow in a microfluidic device and methods of use thereof |
Families Citing this family (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5639428A (en) * | 1994-07-19 | 1997-06-17 | Becton Dickinson And Company | Method and apparatus for fully automated nucleic acid amplification, nucleic acid assay and immunoassay |
FR2744803B1 (fr) * | 1996-02-12 | 1998-03-13 | Bio Merieux | Procede et dispositif de traitement d'une carte d'analyse |
FR2760838B1 (fr) * | 1997-03-13 | 1999-05-21 | Corning Inc | Circuit fluidique integre d'execution d'un processus de preparation ou d'analyse d'un echantillon de matiere fluide, son procede de fabrication et appareil d'exploitation de ce circuit |
DE10006214A1 (de) | 2000-02-11 | 2001-08-16 | Roche Diagnostics Gmbh | System zur einfachen Nukleinsäureanalytik |
JP4244534B2 (ja) | 2001-06-12 | 2009-03-25 | 横河電機株式会社 | バイオチップ |
JP4106977B2 (ja) | 2002-06-21 | 2008-06-25 | 株式会社日立製作所 | 分析チップ及び分析装置 |
US7854897B2 (en) | 2003-05-12 | 2010-12-21 | Yokogawa Electric Corporation | Chemical reaction cartridge, its fabrication method, and a chemical reaction cartridge drive system |
US8961900B2 (en) * | 2004-04-28 | 2015-02-24 | Yokogawa Electric Corporation | Chemical reaction cartridge, method of producing chemical reaction cartridge, and mechanism for driving chemical reaction cartridge |
DE102009015395B4 (de) | 2009-03-23 | 2022-11-24 | Thinxxs Microtechnology Gmbh | Flusszelle zur Behandlung und/oder Untersuchung eines Fluids |
JP5146399B2 (ja) * | 2009-04-27 | 2013-02-20 | 横河電機株式会社 | 化学反応用カートリッジおよびその駆動機構 |
DE102009050175A1 (de) * | 2009-10-21 | 2011-04-28 | Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. | Biochip, zugehöriges Untersuchungsgerät und entsprechendes Betriebsverfahren |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4873100A (en) * | 1987-04-15 | 1989-10-10 | The Procter & Gamble Company | Bistable expandable bottle |
CA1338505C (en) * | 1989-02-03 | 1996-08-06 | John Bruce Findlay | Containment cuvette for pcr and method of use |
-
1993
- 1993-10-21 JP JP26321593A patent/JP3594979B2/ja not_active Expired - Lifetime
- 1993-10-21 EP EP19930202961 patent/EP0594259B1/en not_active Expired - Lifetime
- 1993-10-21 DK DK93202961T patent/DK0594259T3/da active
- 1993-10-21 DE DE1993605046 patent/DE69305046T2/de not_active Expired - Lifetime
- 1993-10-22 FI FI934670A patent/FI934670A/fi not_active Application Discontinuation
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US11192108B2 (en) | 2014-12-08 | 2021-12-07 | Berkeley Lights, Inc. | Actuated microfluidic structures for directed flow in a microfluidic device and methods of use thereof |
Also Published As
Publication number | Publication date |
---|---|
FI934670A0 (fi) | 1993-10-22 |
JP3594979B2 (ja) | 2004-12-02 |
DK0594259T3 (da) | 1996-11-18 |
FI934670A (fi) | 1994-04-24 |
DE69305046D1 (de) | 1996-10-31 |
DE69305046T2 (de) | 1997-04-03 |
EP0594259A1 (en) | 1994-04-27 |
JPH06197751A (ja) | 1994-07-19 |
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