EP3505253B1 - Verfahren zur extraktion von nukleinsäure und extraktionskassette dafür - Google Patents
Verfahren zur extraktion von nukleinsäure und extraktionskassette dafür Download PDFInfo
- Publication number
- EP3505253B1 EP3505253B1 EP18215536.6A EP18215536A EP3505253B1 EP 3505253 B1 EP3505253 B1 EP 3505253B1 EP 18215536 A EP18215536 A EP 18215536A EP 3505253 B1 EP3505253 B1 EP 3505253B1
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- EP
- European Patent Office
- Prior art keywords
- compartment
- liquid
- waste
- path
- reaction
- Prior art date
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- 238000000605 extraction Methods 0.000 title claims description 108
- 102000039446 nucleic acids Human genes 0.000 title claims description 32
- 108020004707 nucleic acids Proteins 0.000 title claims description 32
- 150000007523 nucleic acids Chemical class 0.000 title claims description 32
- 238000000034 method Methods 0.000 title claims description 15
- 239000007788 liquid Substances 0.000 claims description 221
- 239000003599 detergent Substances 0.000 claims description 36
- 239000003480 eluent Substances 0.000 claims description 20
- 239000011358 absorbing material Substances 0.000 claims description 12
- 125000006850 spacer group Chemical group 0.000 claims description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 7
- 230000000284 resting effect Effects 0.000 claims description 4
- 239000012530 fluid Substances 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 238000001514 detection method Methods 0.000 description 2
- 238000007886 magnetic bead extraction Methods 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 238000005070 sampling Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000002032 lab-on-a-chip Methods 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 230000002123 temporal effect Effects 0.000 description 1
Images
Classifications
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- 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
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/02—Adapting objects or devices to another
- B01L2200/028—Modular arrangements
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/06—Fluid handling related problems
- B01L2200/0647—Handling flowable solids, e.g. microscopic beads, cells, particles
- B01L2200/0668—Trapping microscopic beads
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/14—Process control and prevention of errors
- B01L2200/141—Preventing contamination, tampering
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/16—Reagents, handling or storing thereof
-
- 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
- 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
-
- 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
- B01L2400/0487—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure fluid pressure, pneumatics
Definitions
- the present invention relates to an extraction cassette, and in particular to an extraction cassette with an extraction module.
- the conventional extraction module is only for extracting nucleic acid, which cannot receive waste-liquid. Since the waste-liquid may pollute the filter inside the reaction compartment, the conventional waste-liquid compartment is far away from the collection compartment.
- the waste-liquid compartment and the reaction compartment are disposed on different modules, and the size and cost of the conventional extraction cassette are increased.
- an all-in-one extraction module which extracts nucleic acid by the magnetic bead extraction technology.
- the efficiency and purity of the magnetic bead extraction technology are unqualified.
- GB 2 516 666 A discloses an extraction cassette for extracting a target nucleic acid as a sample from a mixed liquid including the target nucleic acid.
- the extraction cassette comprises a extraction module body comprising a fluidic portion (lab-on-a-chip) through which the sample flows and in which nucleic acid amplification and detection takes place, e.g. using PCR; a pneumatic portion which controls flow through the fluidic portion, using pneumatically-controlled valves; and at least two electrodes which provide a potential difference for the detection of an amplified nucleic acid of interest.
- the extraction cassette does not comprise an extraction module body comprising a collection compartment, a first waste-liquid compartment and a second waste-liquid compartment each provided in the extraction module body.
- US 2008/153078 A1 discloses an automated system for purification of a substance of interest.
- the system generally comprises an instrument for moving fluids through the system, a reagent pack for storing fluids, and a purification cartridge.
- the cartridge comprises two filtration units for binding substances based on different physical properties.
- the cartridge also comprises rotary valves for control of movement of fluids on the cartridge.
- the present invention provides an extraction cassette for extracting a sample from a mixed liquid of sample and alcohol, comprising a liquid receiving module and an extraction module, the extraction module communicating with the liquid receiving module and comprising an extraction module body, which comprises an expansion compartment, a reaction compartment and a filter.
- the reaction compartment comprises a reaction compartment inlet, a reaction compartment outlet and a reaction compartment notch, wherein the expansion compartment is connected to the reaction compartment notch and the reaction compartment notch is located between the reaction compartment inlet and the reaction compartment outlet.
- the filter is disposed in the reaction compartment and is disposed corresponding to the reaction compartment outlet.
- the extraction module body further comprises a collection compartment, a first waste-liquid compartment and a second waste-liquid compartment, wherein the collection compartment communicates with the reaction compartment outlet, the first waste-liquid compartment communicates with the reaction compartment outlet, and the second waste-liquid compartment communicates with the reaction compartment outlet, wherein the extraction module further comprises a first path and a second path, the first path connects the reaction compartment outlet to the first waste-liquid compartment and the second waste-liquid compartment, and the second path connects the reaction compartment outlet to the collection compartment; and wherein the collection department, the first waste-liquid compartment, second waste-liquid compartment and expansion compartment each comprises a pressure hole adapted to be connected to an external pressure supply.
- the reaction compartment includes a cone-shaped portion, the filter is disposed on the cone-shaped portion, and the reaction compartment outlet is formed on one end of the cone-shaped portion.
- the first path intersects the second path at the reaction compartment outlet, a stopper wall is formed in the second path, and the stopper wall is formed on one end of the second path and is adjacent to the reaction compartment outlet.
- the extraction module further includes a third path and a fourth path, the third path connects the first path to the first waste-liquid compartment, and the fourth path connects the first path to the second waste-liquid compartment.
- the first waste-liquid compartment includes a first waste-liquid compartment connection hole
- the second waste-liquid compartment includes a second waste-liquid compartment connection hole
- the third path connects the first path to the first waste-liquid compartment connection hole
- the fourth path connects the first path to the second waste-liquid compartment connection hole
- at least one portion of the second waste-liquid compartment is located between the first waste-liquid compartment connection hole and the second waste-liquid compartment connection hole.
- At least one portion of the fourth path extends in a first direction, and the first direction is away from the first waste-liquid compartment.
- the second waste-liquid compartment includes a second waste-liquid compartment pressure hole, and at least one portion of the waste-liquid compartment is located between the first waste-liquid compartment and the second waste-liquid compartment pressure hole.
- At least one portion of the second path extends in the first direction.
- the collection compartment includes a collection compartment pressure hole, and at least one portion of the collection compartment is located between the first waste-liquid compartment and the collection compartment pressure hole.
- the extraction module further includes an absorbing material, the absorbing material is disposed in the first waste-liquid compartment, the first waste-liquid compartment includes a first waste-liquid compartment pressure hole, and at least one portion of the absorbing material is located in a space of the first waste-liquid compartment between the first waste-liquid compartment pressure hole and the first waste-liquid compartment connection hole.
- the first waste-liquid compartment pressure hole, the second waste-liquid compartment pressure hole and the collection compartment pressure hole are on the same plane.
- the expansion compartment further includes an expansion compartment inlet, an expansion compartment pressure hole and an expansion compartment spacer, the expansion compartment spacer is located between the expansion compartment inlet and the expansion compartment pressure hole, and the expansion compartment spacer is bent toward the expansion compartment pressure hole.
- a method for extracting nucleic acid includes the following steps. First, an extraction cassette as outlined above is provided, wherein the extraction cassette includes a liquid receiving module and an extraction module, the extraction module communicates with the liquid receiving module, the extraction module includes a reaction compartment, a filter, a collection compartment, a first waste-liquid compartment and a second waste-liquid compartment. Next, a mixed liquid of sample and alcohol is moved from the liquid receiving module to the extraction module, and the filter captures nucleic acid from the mixed liquid. Then, the mixed liquid is moved to the first waste-liquid compartment. Next, a first detergent is moved from the liquid receiving module to the extraction module, wherein the first detergent passes through the reaction compartment and the filter. Then, the first detergent is moved to the first waste-liquid compartment. In this method wherein the extraction cassette is adapted to be connected to an external pressure supply to provide pressure toward the extraction cassette, and liquid movement inside the extraction cassette is controlled by the pressure.
- the method for extracting nucleic acid further includes the following steps. First, a second detergent is moved from the liquid receiving module to the extraction module, wherein the second detergent passes through the reaction compartment and the filter. Then, the second detergent is moved to the second waste-liquid compartment. Next, an eluent is moved from the liquid receiving module to the extraction module, wherein the eluent is resting in the reaction compartment. Then, a positive pressure is provided via a second waste-liquid compartment pressure hole of the second waste-liquid compartment, and a negative pressure is provided via a collection compartment pressure hole of the collection compartment, wherein the eluent with the nucleic acid is moved to the collection compartment.
- the reaction compartment and the waste-liquid compartments are incorporated in one single extraction module, and the size and cost of the extraction cassette are reduced.
- the waste-liquid can be controlled to be moved to the first waste-liquid compartment and the second waste-liquid compartment, and the eluent with the nucleic acid is controlled to be moved to the collection compartment.
- the waste-liquid is prevented from polluting the reaction compartment and the collection compartment.
- Fig. 1A is an assembled view of an extraction cassette C of an embodiment of the present invention.
- Fig. 1B is an exploded view of the extraction cassette C of the embodiment of the present invention.
- the extraction cassette C includes an extraction module 1, a liquid receiving module 2, a sampling module 3 and a connection module 4.
- the extraction cassette C is adapted to be disposed into an analyzer.
- the analyzer includes a first pressure supplying module, an analyzing module and a second pressure supplying module.
- the first pressure supplying module and the second pressure supplying module provide pressure toward the extraction cassette C to control the liquid movement inside the extraction cassette C.
- the analyzing module heats and cools the extraction cassette C, and analyzes the sample inside extraction cassette C.
- the liquid receiving module 2 communicates with the extraction module 1 via the connection module 4.
- Fig. 2 shows the details of the extraction module 1.
- the extraction module 1 includes an extraction module body 19, an expansion compartment 18, a reaction compartment 11, a filter 111, a collection compartment 12, a first waste-liquid compartment 13 and a second waste-liquid compartment 14.
- the expansion compartment 18 is formed on the extraction module body 19.
- the reaction compartment 11 is formed on the extraction module body 19.
- the reaction compartment 11 includes a reaction compartment inlet 114, a reaction compartment outlet 112 and a reaction compartment notch 115.
- the expansion compartment 18 is connected to the reaction compartment notch 115.
- the reaction compartment notch 115 is located between the reaction compartment inlet 114 and the reaction compartment outlet 112.
- the filter 111 is disposed in the reaction compartment 11 and corresponding to the reaction compartment outlet 112.
- the collection compartment 12 is formed on the extraction module body 19 and communicates with the reaction compartment outlet 112.
- the first waste-liquid compartment 13 is formed on the extraction module body 19.
- the first waste-liquid compartment 13 communicates with the reaction compartment outlet 112.
- the second waste-liquid compartment 14 is formed on the extraction module body 19, wherein the second waste-liquid compartment 14 communicates with the reaction compartment outlet 112.
- the expansion compartment 18 further includes an expansion compartment inlet 181, an expansion compartment pressure hole 182 and an expansion compartment spacer 183.
- the expansion compartment spacer 183 is located between the expansion compartment inlet 181 and the expansion compartment pressure hole 182.
- the expansion compartment spacer 183 is bent toward the expansion compartment pressure hole 182.
- the expansion compartment spacer 183 prevents the liquid entering the expansion compartment 18 via the expansion compartment inlet 181 from polluting the expansion compartment pressure hole 182.
- the reaction compartment 11 includes a cone-shaped portion 113.
- the filter 111 is disposed on the cone-shaped portion 113.
- the reaction compartment outlet 112 is formed on one end of the cone-shaped portion 113.
- the extraction module 1 further includes a first path 15 and a second path 16.
- the first path 15 connects the reaction compartment outlet 112 to the first waste-liquid compartment 13 and the second waste-liquid compartment 14.
- the second path 16 connects the reaction compartment outlet 112 to the collection compartment 12.
- the first path 15 intersects the second path 16 at the reaction compartment outlet 112.
- a stopper wall 161 is formed in the second path 16, and the stopper wall 161 is formed on one end of the second path 16 and is adjacent to the reaction compartment outlet 112.
- the extraction module 1 further includes a third path 151 and a fourth path 152.
- the third path 151 connects the first path 15 to the first waste-liquid compartment 13.
- the fourth path 152 connects the first path 15 to the second waste-liquid compartment 14.
- the first waste-liquid compartment 13 includes a first waste-liquid compartment connection hole 131.
- the second waste-liquid compartment 14 includes a second waste-liquid compartment connection hole 141.
- the third path 151 connects the first path 15 to the first waste-liquid compartment connection hole 131.
- the fourth path 152 connects the first path 15 to the second waste-liquid compartment connection hole 141. At least one portion of the second waste-liquid compartment 14 is located between the first waste-liquid compartment connection hole 131 and the second waste-liquid compartment connection hole 141. In one embodiment, at least one portion of the fourth path 152 extends in a first direction Z, and the first direction Z is away from the first waste-liquid compartment 13. The disclosure is not meant to restrict the present invention.
- the second waste-liquid compartment 14 includes a second waste-liquid compartment pressure hole 142. At least one portion of the waste-liquid compartment 14 is located between the first waste-liquid compartment 13 and the second waste-liquid compartment pressure hole 142. In one embodiment, at least one portion of the second path 16 extends in the first direction Z. The disclosure is not meant to restrict the present invention.
- the collection compartment 12 includes a collection compartment pressure hole 121. At least one portion of the collection compartment 12 is located between the first waste-liquid compartment 13 and the collection compartment pressure hole 121.
- the extraction module 1 further includes an absorbing material 17.
- the absorbing material 17 is disposed in the first waste-liquid compartment 13.
- the first waste-liquid compartment 13 includes a first waste-liquid compartment pressure hole 132. At least one portion of the absorbing material 17 is located in a space of the first waste-liquid compartment 13 between the first waste-liquid compartment pressure hole 132 and the first waste-liquid compartment connection hole 131.
- the absorbing material 17 can be sponge.
- the first waste-liquid compartment pressure hole 132, the second waste-liquid compartment pressure hole 142 and the collection compartment pressure hole 121 are on the same plane.
- Figs. 3A ⁇ 3J show the operation of the extraction module 1 of the embodiment of the present invention.
- a mixed liquid 286 of sample and alcohol is moved from the liquid receiving module 2 to the expansion compartment 18 and the reaction compartment 11 via the expansion compartment inlet 181, and the filter 111 captures the nucleic acid from the mixed liquid 286.
- the mixed liquid 286 is moved to the first waste-liquid compartment 13 by a negative pressure ( ⁇ -10kpa) provided via the first waste-liquid compartment pressure hole 132.
- a negative pressure ⁇ -10kpa
- a first detergent 282 is progressively moved from the liquid receiving module 2 to the filter 111 via the expansion compartment inlet 181, expansion compartment 18 and the reaction compartment 11, and the salts concentration and the PH value on the filter 111 is adjusted.
- the first detergent 282 is moved to the first waste-liquid compartment 13 by the negative pressure ( ⁇ -10kpa) provided via the first waste-liquid compartment pressure hole 132.
- a portion of second detergent 283 is moved from the liquid receiving module 2 to the filter 111 via the expansion compartment inlet 181, expansion compartment 18 and the reaction compartment 11, and the salts concentration and the PH value on the filter 111 is adjusted.
- Fig. 3C a first detergent 282 is progressively moved from the liquid receiving module 2 to the filter 111 via the expansion compartment inlet 181, expansion compartment 18 and the reaction compartment 11, and the salts concentration and the PH value on the filter 111 is adjusted.
- the second detergent 283 is moved to the first waste-liquid compartment 13 by the negative pressure ( ⁇ -10kpa) provided via the first waste-liquid compartment pressure hole 132. Then, with reference to Fig. 3G , the other portion of second detergent 283 is moved from the liquid receiving module 2 to the filter 111 via the expansion compartment inlet 181, expansion compartment 18 and the reaction compartment 11, and the salts concentration and the PH value on the filter 111 is adjusted. Next, with reference to Fig. 3H , the second detergent 283 is moved to the second waste-liquid compartment 14 by the negative pressure ( ⁇ -10kpa) provided via the second waste-liquid compartment pressure hole 142. Then, with reference to Fig.
- an eluent 284 is moved from the liquid receiving module 2 to the reaction compartment 11 via the reaction compartment inlet 114, wherein the eluent 284 is resting in the reaction compartment 11 for three minutes, and the nucleic acid is released from the filter 111 to the eluent 284.
- a big positive pressure 45kpa
- a little positive pressure is provided via the second waste-liquid compartment pressure hole 142 to prevent the eluent 284 with the nucleic acid from entering the first path 15.
- the big positive pressure (45kpa) is provided via the liquid receiving module 2 through the reaction compartment inlet 114.
- the first detergent 282 can be progressively moved from the liquid receiving module 2 to the filter 111, or totally moved from the liquid receiving module 2 to the filter 111 in single one movement, so does the second detergent 283.
- the disclosure is not meant to restrict the present invention.
- the first detergent 282 can neutralize PH value
- the second detergent 283 can remove protein and organic impurities.
- the expansion compartment 18 prevents the mixed liquid 286, the first detergent 282 and the second detergent 283 from contacting the reaction compartment inlet 114 to prevent the reaction compartment inlet 114 from being polluted.
- the stopper wall 161 prevents the mixed liquid 286, the first detergent 282 and the second detergent 283 from entering the collection compartment 12.
- the second path 16 has a bent portion 162.
- the bent portion 162 makes the eluent 284 with the nucleic acid to sufficiently enter the collection compartment 12.
- the collection compartment 12 further includes a collection compartment inclined surface 122 and a collection compartment outlet 123.
- the collection compartment inclined surface 122 connects the collection compartment outlet 123.
- the collection compartment inclined surface 122 makes the eluent 284 with the nucleic acid to totally leave the collection compartment 12 via the collection compartment outlet 123 (to the sampling module 3, with reference to Fig. 1B ).
- the bent portion 162 is bent toward the collection compartment inclined surface 122.
- the second detergent 283 finally entering the second waste-liquid compartment 14 is the cleanest waste-liquid.
- the little positive pressure is provided via the second waste-liquid compartment pressure hole 142 to prevent the eluent 284 with the nucleic acid from entering the first path 15. Because the second detergent 283 in the second waste-liquid compartment 14 is the cleanest waste-liquid, the pollution caused by the air inside the second waste-liquid compartment 14 to the eluent 284 can be reduced.
- the waste-liquid in the first waste-liquid compartment 13 contacts the absorbing material 17.
- the absorbing material 17 removes the bubbles of the waste-liquid, and the waste-liquid is prevented from overflowing out of the first waste-liquid compartment pressure hole 132.
- the filter 111 can be silicon filter or other filters.
- the extraction module can be integrally formed.
- a method for extracting nucleic acid includes the following steps. First, an extraction cassette is provided, wherein the extraction cassette includes a liquid receiving module and an extraction module, the extraction module communicates with the liquid receiving module, the extraction module includes a reaction compartment, a filter, a collection compartment, a first waste-liquid compartment and a second waste-liquid compartment (S11). Next, a mixed liquid of sample and alcohol is moved from the liquid receiving module to the extraction module, and the filter captures nucleic acid from the mixed liquid (S12). Then, the mixed liquid is moved to the first waste-liquid compartment (S13).
- a first detergent is moved from the liquid receiving module to the extraction module, wherein the first detergent passes through the reaction compartment and the filter (S14). Then, the first detergent is moved to the first waste-liquid compartment (S15).
- a second detergent is moved from the liquid receiving module to the extraction module, wherein the second detergent passes through the reaction compartment and the filter (S16). Then, the second detergent is moved to the second waste-liquid compartment (S17).
- an eluent is moved from the liquid receiving module to the extraction module, wherein the eluent is resting in the reaction compartment (S18).
- a positive pressure is provided via a second waste-liquid compartment pressure hole of the second waste-liquid compartment, and a negative pressure is provided via a collection compartment pressure hole of the collection compartment, wherein the eluent with the nucleic acid is moved to the collection compartment (S19).
- the reaction compartment and the waste-liquid compartments are incorporated in one single extraction module, and the size and cost of the extraction cassette are reduced.
- the waste-liquid can be controlled to be moved to the first waste-liquid compartment and the second waste-liquid compartment, and the eluent with the nucleic acid is controlled to be moved to the collection compartment.
- the waste-liquid is prevented from polluting the reaction compartment and the collection compartment.
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- 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)
- Apparatus Associated With Microorganisms And Enzymes (AREA)
Claims (15)
- Extraktionskassette (C) zum Extrahieren einer Probe aus einer gemischten Flüssigkeit (286) aus einer Probe und Alkohol, umfassend:ein Flüssigkeitsaufnahmemodul (2) zur Aufnahme der gemischten Flüssigkeit (286); undein Extraktionsmodul (1), das mit dem Flüssigkeitsaufnahmemodul (2) in Verbindung steht und einen Extraktionsmodulkörper (19) umfasst, wobei der Extraktionsmodulkörper (19) umfasst:einen Expansionsraum (18);einen Reaktionsraum (11), wobei der Reaktionsraum einen Reaktionsraum-Einlass (114), einen Reaktionsraum-Auslass (112) und eine Reaktionsraum-Aussparung (115) umfasst, der Expansionsraum (11) mit der Reaktionsraum-Aussparung (115) verbunden ist und die Reaktionsraum-Aussparung (115) zwischen dem Reaktionsraum-Einlass (114) und dem Reaktionsraum-Auslass (112) angeordnet ist; undeinen Filter (111), der in dem Reaktionsraum (11) angeordnet ist und entsprechend dem Reaktionsraum-Auslass (112) angeordnet ist;dadurch gekennzeichnet, dass der Extraktionsmodulkörper (19) weiterhin umfasst:einen Sammelraum (12), der mit dem Reaktionsraum-Auslass (112) in Verbindung steht;einen ersten Reststoff-Flüssigkeitsraum (13), der mit dem Reaktionsraum-Auslass (112) in Verbindung steht; undeinen zweiten Reststoff-Flüssigkeitsraum (14), der mit dem Reaktionsraum-Auslass (112) in Verbindung steht; wobeidas Extraktionsmodul (1) weiterhin einen ersten Pfad (15) und einen zweiten Pfad (16) umfasst, wobei der erste Pfad den Reaktionsraum-Auslass (112) mit dem ersten Reststoff-Flüssigkeitsraum (13) und dem zweiten Reststoff-Flüssigkeitsraum (14) verbindet, und der zweite Pfad (16) den Reaktionsraum-Auslass (112) mit dem Sammelraum (12) verbindet; und wobeider Sammelraum (12), der erste Reststoff-Flüssigkeitsraum (13), der zweite Reststoff-Flüssigkeitsraum (14) und der Expansions-Raum (18) jeweils ein Druckloch (121, 132, 142, 181, 182) aufweisen, das dazu geeignet ist, mit einer externen Druckversorgung verbunden zu werden.
- Extraktionskassette nach Anspruch 1, wobei der Reaktionsraum (11) einen kegelförmigen Abschnitt (113) aufweist, der Filter (111) an dem kegelförmigen Abschnitt (113) angeordnet ist, der Reaktionsraum-Auslass (112) an einem Ende des kegelförmigen Abschnitts (113) ausgebildet ist und der Filter (111) entsprechend dem Reaktionsraum-Auslass (112) angeordnet ist.
- Extraktionskassette nach einem der vorhergehenden Ansprüche, wobei der erste Pfad (15) den zweiten Pfad (16) am Reaktionsraum-Auslass (112) schneidet, eine Stopfenwand (161) im zweiten Pfad (16) ausgebildet ist und die Stopfenwand (161) an einem Ende des zweiten Pfades (16) ausgebildet ist und dem Reaktionsraum-Auslass (112) benachbart ist.
- Extraktionskassette nach einem der vorhergehenden Ansprüche, wobei das Extraktionsmodul (1) weiterhin einen dritten Pfad (151) und einen vierten Pfad (152) aufweist, wobei der dritte Pfad den ersten Pfad (15) mit dem ersten Reststoff-Flüssigkeitsraum (13) verbindet, und der vierte Pfad (152) den ersten Pfad (15) mit dem zweiten Reststoff-Flüssigkeitsraum (14) verbindet.
- Extraktionskassette nach Anspruch 4, wobei der erste Reststoff-Flüssigkeitsraum (13) eine erste Reststoff-Flüssigkeitsraum-Verbindungsöffnung (13) aufweist, der zweite Reststoff-Flüssigkeitsraum (14) eine zweite Reststoff-Flüssigkeitsraum-Verbindungsöffnung (141) aufweist, der dritte Pfad (151) den ersten Pfad (15) mit der ersten Reststoff-Flüssigkeitsraum-Verbindungsöffnung (131) verbindet, der vierte Pfad (152) den ersten Pfad (15) mit der zweiten Reststoff-Flüssigkeitsraum-Verbindungsöffnung (141) verbindet, und mindestens ein Abschnitt des zweiten Reststoff-Flüssigkeitsraums (14) zwischen der ersten Reststoff-Flüssigkeitsraum-Verbindungsöffnung (131) und der zweiten Reststoff-Flüssigkeitsraum-Verbindungsöffnung (141) angeordnet ist.
- Extraktionskassette nach Anspruch 5, wobei sich mindestens ein Abschnitt des vierten Pfads (152) in einer ersten Richtung (Z) erstreckt und die erste Richtung von dem ersten Reststoff-Flüssigkeitsraum (13) weg zeigt.
- Extraktionskassette nach Anspruch 5 oder 6, wobei der zweite Reststoff-Flüssigkeitsraum (14) eine zweite Reststoff-Flüssigkeitsraum-Drucköffnung (142) aufweist und mindestens ein Teil des Reststoff-Flüssigkeitsraums (14) zwischen dem ersten Reststoff-Flüssigkeitsraum (13) und der zweiten Reststoff-Flüssigkeitsraum-Drucköffnung (142) angeordnet ist.
- Extraktionskassette nach Anspruch 7, wobei sich mindestens ein Abschnitt des zweiten Pfades (16) in einer ersten Richtung (Z) erstreckt.
- Extraktionskassette nach Anspruch 7 oder 8, wobei der Sammelraum eine Sammelraum-Drucköffnung aufweist und mindestens ein Teil des Sammelraums zwischen dem ersten Reststoff-Flüssigkeitsraum und der Sammelraum-Drucköffnung angeordnet ist.
- Extraktionskassette nach einem der vorhergehenden Ansprüche, wobei das Extraktionsmodul (1) weiterhin ein absorbierendes Material (17) aufweist, das absorbierende Material in dem ersten Reststoff-Flüssigkeitsraum (13) angeordnet ist, der erste Reststoff-Flüssigkeitsraum eine erste Reststoff-Flüssigkeitsraum-Drucköffnung (132) aufweist und mindestens ein Teil des absorbierenden Materials (17) in einem Raum des ersten Reststoff-Flüssigkeitsraums zwischen der ersten Reststoff-Flüssigkeitsraum-Drucköffnung (132) und der ersten Reststoff-Flüssigkeitsraum-Verbindungsöffnung (131) angeordnet ist.
- Extraktionskassette nach Anspruch 10, wobei das erste Reststoff-Flüssigkeitsraum-Druckloch (132), das zweite Reststoff-Flüssigkeitsraum-Druckloch (142) und das Sammelraum-Druckloch (1221) auf derselben Ebene liegen.
- Extraktionskassette nach einem der vorhergehenden Ansprüche, wobei der Expansionsraum (18) weiterhin einen Expansionsraum-Einlass (181), ein Expansionsraum-Druckloch (182) und ein Expansionsraum-Abstandselement (183) umfasst, wobei das Expansionsraum-Abstandselement (183) zwischen dem Expansionsraum-Einlass (181) und dem Expansionsraum-Druckloch (182) angeordnet ist und das Expansionsraum-Abstandselement (183) zum Expansionsraum-Druckloch (182) hin gekrümmt ist.
- Verfahren zur Extraktion von Nukleinsäure, umfassend die folgenden Schritte
Bereitstellen einer Extraktionskassette (C) nach einem der Ansprüche 1 bis 12, wobei die Extraktionskassette (C) ein Flüssigkeitsaufnahmemodul (2) zur Aufnahme einer gemischten Flüssigkeit (286) aus einer Probe und Alkohol und ein Extraktionsmodul (1) umfasst, das mit dem Flüssigkeitsaufnahmemodul (2) in Verbindung steht und einen Extraktionsmodulkörper (19) umfasst, wobei der Extraktionsmodulkörper (19) einen Expansionsraum (18), einen Reaktionsraum (11), einen Filter (111), einen Sammelraum (12), einen ersten Reststoff-Flüssigkeitsraum (13) und einen zweiten Reststoff-Flüssigkeitsraum (14) umfasst;
Bewegen der gemischten Flüssigkeit (286) aus der Probe und Alkohol von dem Flüssigkeitsaufnahmemodul (2) zu dem Extraktionsmodul (1), so dass der Filter (11) Nukleinsäure aus der gemischten Flüssigkeit (286) auffängt;
Bewegen der gemischten Flüssigkeit (286) in den ersten Reststoff-Flüssigkeitsraum (13);
Bewegen eines ersten Detergens bzw. Reinigungsmittels (282) von dem Flüssigkeitsaufnahmemodul (1) zu dem Extraktionsmodul (1), wobei das erste Detergens bzw. Reinigungsmittel (282) durch den Reaktionsraum (11) und den Filter (111) läuft; und
Bewegen des ersten Detergens bzw. Reinigungsmittels (282) in den ersten Reststoff-Flüssigkeitsraum (13); wobei
die Extraktionskassette (C) dazu ausgelegt ist, mit einer externen Druckversorgung verbunden zu werden, um einen Druck in Richtung der Extraktionskassette (C) bereitzustellen, und
die Flüssigkeitsbewegung innerhalb der Extraktionskassette (C) durch den Druck gesteuert wird. - Verfahren nach Anspruch 13, das weiterhin die folgenden Schritte umfasst:Bewegen eines zweiten Detergens bzw. Reinigungsmittels (283) von dem Flüssigkeitsaufnahmemodul (2) zu dem Extraktionsmodul (1), wobei das zweite Detergens bzw. Reinigungsmittel (283) durch den Reaktionsraum (11) und den Filter (111) läuft;Bewegen des zweiten Detergens bzw. Reinigungsmittels (283) zu dem zweiten Reststoff-Flüssigkeitsraum (14);Bewegen eines Eluenten bzw. Extraktionsmittels (284) von dem Flüssigkeitsaufnahmemodul (2) zu dem Extraktionsmodul (1), wobei der Eluent bzw. das Extraktionsmittel in dem Reaktionsraum (11) ruht; undBereitstellen eines Überdrucks über ein zweites Reststoff-Flüssigkeitsraum-Druckloch (142) des zweiten Reststoff-Flüssigkeitsraums (14) und Bereitstellen eines Unterdrucks über ein Sammelraum-Druckloch (121) des Sammelraums (12), wobei der Eluent bzw. das Extraktionsmittel (284) mit der Nukleinsäure zu dem Sammelraum (12) bewegt wird.
- Verfahren nach Anspruch 14, wobei die gemischte Flüssigkeit (286) und das erste Detergens bzw. Reinigungsmittel (282) durch Unterdruck in den ersten Reststoff-Flüssigkeitsraum (13) bewegt werden, das zweite Detergens bzw. Reinigungsmittel (283) durch Unterdruck in den zweiten Reststoff-Flüssigkeitsraum (14) bewegt wird, um eine Verschmutzung des Reaktionsraums (11) und des Sammelraums (12) durch eine Reststoffflüssigkeit zu verhindern.
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