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公开(公告)号:US10676786B2
公开(公告)日:2020-06-09
申请号:US15278894
申请日:2016-09-28
Applicant: STOKES BIO LIMITED
Inventor: Mark Davies , Tara Dalton
Abstract: A microfluidic analysis system (1) performs polymerase chain reaction (PCR) analysis on a bio sample. In a centrifuge (6) the sample is separated into DNA and RNA constituents. The vortex is created by opposing flow of a silicon oil primary carrier fluid effecting circulation by viscous drag. The bio sample exits the centrifuge enveloped in the primary carrier fluid. This is pumped by a flow controller (7) to a thermal stage (9). The thermal stage (9) has a number of microfluidic devices (70) each having thermal zones (71, 72, 73) in which the bio sample is heated or cooled by heat conduction to/from a thermal carrier fluid and the primary carrier fluid. Thus, the carrier fluids envelope the sample, control its flowrate, and control its temperature without need for moving parts at the micro scale.
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公开(公告)号:US20210023561A1
公开(公告)日:2021-01-28
申请号:US16922265
申请日:2020-07-07
Applicant: STOKES BIO LTD.
Inventor: Mark DAVIES , Tara DALTON , Kieran CURRAN
Abstract: A bridge (30) comprises a first inlet port (31) at the end of a capillary, a narrower second inlet port (32) which is an end of a capillary, an outlet port (33) which is an end of a capillary, and a chamber (34) for silicone oil. The oil is density-matched with the reactor droplets such that a neutrally buoyant environment is created within the chamber (34). The oil within the chamber is continuously replenished by the oil separating the reactor droplets. This causes the droplets to assume a stable capillary-suspended spherical form upon entering the chamber (34). The spherical shape grows until large enough to span the gap between the ports, forming an axisym metric liquid bridge. The introduction of a second droplet from the second inlet port (32) causes the formation of an unstable funicular bridge that quickly ruptures from the, finer, second inlet port (32), and the droplets combine at the liquid bridge (30). In another embodiment, a droplet (55) segments into smaller droplets which bridge the gap between the inlet and outlet ports.
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公开(公告)号:US10730051B2
公开(公告)日:2020-08-04
申请号:US15131546
申请日:2016-04-18
Applicant: STOKES BIO LIMITED
Inventor: Mark Davies , Tara Dalton , Kieran Curran
Abstract: A bridge (30) comprises a first inlet port (31) at the end of a capillary, a narrower second inlet port (32) which is an end of a capillary, an outlet port (33) which is an end of a capillary, and a chamber (34) for silicone oil. The oil is density-matched with the reactor droplets such that a neutrally buoyant environment is created within the chamber (34). The oil within the chamber is continuously replenished by the oil separating the reactor droplets. This causes the droplets to assume a stable capillary-suspended spherical form upon entering the chamber (34). The spherical shape grows until large enough to span the gap between the ports, forming an axisymmetric liquid bridge. The introduction of a second droplet from the second inlet port (32) causes the formation of an unstable funicular bridge that quickly ruptures from the, finer, second inlet port (32), and the droplets combine at the liquid bridge (30). In another embodiment, a droplet (55) segments into smaller droplets which bridge the gap between the inlet and outlet ports.
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公开(公告)号:US09631230B2
公开(公告)日:2017-04-25
申请号:US12539343
申请日:2009-08-11
Applicant: Mark Davies , Tara Dalton
Inventor: Mark Davies , Tara Dalton
CPC classification number: C12Q1/6851 , B01L3/502784 , B01L7/525 , B01L2300/0838 , B01L2300/0867 , B01L2400/0487 , C12Q2561/101 , C12Q2563/159 , C12Q2565/629
Abstract: The invention provides methods of conducting a nucleic acid reaction, including methods for performing digital PCR using a “droplet-in-oil” technology. In the methods, the starting sampled is segmented at least partially into a set of sample droplets each containing on average about one or fewer copies of a target nucleic acid. The droplets are passed in a continuous flow of immiscible carrier fluid through a channel that passes through a thermal cycler, whereby the target is amplified. In one implementation, the droplets are about 350 nl each and the number of positively amplified droplets is counted at the near-saturation point.
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公开(公告)号:US11807902B2
公开(公告)日:2023-11-07
申请号:US16892488
申请日:2020-06-04
Applicant: STOKES BIO LTD.
Inventor: Mark Davies , Tara Dalton
CPC classification number: C12Q1/686 , B01F25/10 , B01F33/30 , B01L3/50273 , B01L3/502776 , B01L3/502784 , B01L7/525 , G01N35/08 , B01L2200/0636 , B01L2200/0673 , B01L2200/141 , B01L2300/087 , B01L2300/0816 , B01L2300/0861 , B01L2300/185 , B01L2400/0409 , B01L2400/0487 , G01N35/1095 , G01N2035/00514
Abstract: A microfluidic analysis system (1) performs polymerase chain reaction (PCR) analysis on a bio sample. In a centrifuge (6) the sample is separated into DNA and RNA constituents. The vortex is created by opposing flow of a silicon oil primary carrier fluid effecting circulation by viscous drag. The bio sample exits the centrifuge enveloped in the primary carrier fluid. This is pumped by a flow controller (7) to a thermal stage (9). The thermal stage (9) has a number of microfluidic devices (70) each having thermal zones (71, 72, 73) in which the bio sample is heated or cooled by heat conduction to/from a thermal carrier fluid and the primary carrier fluid. Thus, the carrier fluids envelope the sample, control its flowrate, and control its temperature without need for moving parts at the micro scale.
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公开(公告)号:US11772096B2
公开(公告)日:2023-10-03
申请号:US16922265
申请日:2020-07-07
Applicant: STOKES BIO LTD.
Inventor: Mark Davies , Tara Dalton , Kieran Curran
IPC: B01L3/00 , B01F13/00 , B01F15/02 , F17D1/08 , C12Q1/686 , B01F35/71 , B01F33/302 , B01F101/23 , B01L7/00
CPC classification number: B01L3/502784 , B01F33/3021 , B01F35/7172 , B01L3/502715 , B01L3/502746 , C12Q1/686 , F17D1/08 , B01F35/71 , B01F2101/23 , B01L3/5025 , B01L7/525 , B01L2200/0673 , B01L2300/0829 , B01L2300/0838 , B01L2400/0478 , B01L2400/0487 , B01L2400/0633 , B01L2400/082 , Y10T137/87676 , Y10T436/117497 , Y10T436/118339 , Y10T436/2575
Abstract: A system for processing a biological sample includes a substrate comprising a plurality of wells and a plurality of flow channels. The system further includes a flow control system comprising a manifold having a plurality of ports configured to fluidically couple to the plurality of wells, and one or more containment structures configured to contain carrier fluid and fluidically couple to the ports. The flow control system further includes a cradle configured to removably receive the substrate. The flow control system is configured to transmit pressure differential, via the manifold, to the plurality of wells so as to cause a plurality of sample volumes held by at least some wells of the plurality of wells to flow through respective flow channels and cause the carrier fluid to flow through the flow channels and form a plurality of droplets of the plurality of sample volumes separated by the carrier fluid.
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公开(公告)号:US20200283837A1
公开(公告)日:2020-09-10
申请号:US16812987
申请日:2020-03-09
Applicant: STOKES BIO LTD.
Inventor: Mark B. DAVIES , Tara DALTON
IPC: C12Q1/6851 , B01L3/00 , B01L7/00
Abstract: A method comprises flowing a plurality of sample droplets in a continuous flow of a carrier fluid, immiscible with the sample droplets, such that the droplets are separated from each other by the carrier fluid, wherein an average number of copies of target nucleic acid contained in each droplet the plurality of sample droplets is one or fewer. The method may further comprise subjecting the droplets to thermal cycling sufficient to allow amplification of the target nucleic acid, and detecting one or more of the presence or absence of amplified target nucleic acid in the droplets.
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公开(公告)号:US08550503B2
公开(公告)日:2013-10-08
申请号:US12443303
申请日:2007-09-27
Applicant: Mark Davies , Tara Dalton
Inventor: Mark Davies , Tara Dalton
IPC: F16L39/04
CPC classification number: F16L41/18 , B01L3/5027 , B01L3/5635 , B01L3/565 , B01L2200/027 , F16L39/00 , Y10T137/0318
Abstract: A microfluidic connector (1) comprises an enclosure (6, 7), a fluidic inlet port (2) and a fluidic outlet port (3), in the enclosure, in which the inlet and outlet ports (2, 3) are movable with respect to each other, for example, mutual spacing between the inlet and outlet ports (2, 3) is variable. A port (2) is in a fixed part (6) of the enclosure, and another port (3) is in a part (7) of the enclosure which slides with respect to the fixed part. There may be multiple inlet ports (22, 23) and/or multiple outlet ports (24, 25). Also, there may be an auxiliary port (45) for introduction of fluid into the enclosure (47, 48) or removal of fluid from the enclosure.
Abstract translation: 微流体连接器(1)包括外壳中的外壳(6,7),流体入口端口(2)和流体出口端口(3),入口端口和出口端口(2,3)可通过外壳 彼此相对,例如,入口端口(3)之间的相互间隔是可变的。 端口(2)位于外壳的固定部分(6)中,另一个端口(3)位于外壳的相对于固定部分滑动的部分(7)中。 可以有多个入口端口(22,23)和/或多个出口端口(24,25)。 而且,可以存在用于将流体引入外壳(47,48)或从外壳移除流体的辅助端口(45)。
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公开(公告)号:US20100216128A1
公开(公告)日:2010-08-26
申请号:US12469339
申请日:2009-05-20
Applicant: Mark Davies , Tara Dalton
Inventor: Mark Davies , Tara Dalton
IPC: C12Q1/68 , C12Q1/02 , G01N33/566 , G01N33/92 , G01N33/00
CPC classification number: G01N1/38 , B01F13/0071 , B01F15/0201 , B01F15/0232 , B01L3/502784 , B01L3/5088 , B01L2200/10 , B01L2300/0816 , B01L2300/0864 , B01L2300/165 , G01N33/5308 , G01N2035/00237
Abstract: The present invention generally relates methods for analyzing agricultural and/or environmental samples using liquid bridges. In certain embodiments, the invention provides a method for analyzing an agricultural sample for a desired trait including obtaining a gene or gene product from an agricultural sample, in which the gene or gene product is in a first fluid; providing a liquid bridge for mixing the gene or gene product with at least one reagent to form a mixed droplet that is wrapped in an immiscible second fluid; and analyzing the mixed droplet to detect a desired trait of the agricultural sample.
Abstract translation: 本发明一般涉及使用液体桥分析农业和/或环境样品的方法。 在某些实施方案中,本发明提供了一种用于分析所需性状的农业样品的方法,包括从农业样品获得基因或基因产物,其中所述基因或基因产物处于第一种流体中; 提供用于将基因或基因产物与至少一种试剂混合以形成被包裹在不混溶的第二流体中的混合液滴的液体桥; 并分析混合液滴以检测农业样品的期望性状。
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公开(公告)号:US20230295703A1
公开(公告)日:2023-09-21
申请号:US18164453
申请日:2023-02-03
Applicant: STOKES BIO LTD.
Inventor: Mark B. DAVIES , Tara DALTON
IPC: C12Q1/6851 , B01L3/00 , B01L7/00
CPC classification number: C12Q1/6851 , B01L3/502784 , B01L7/525 , B01L2300/0838 , B01L2300/0867 , B01L2400/0487
Abstract: A method comprises flowing a plurality of sample droplets in a continuous flow of a carrier fluid, immiscible with the sample droplets, such that the droplets are separated from each other by the carrier fluid, wherein an average number of copies of target nucleic acid contained in each droplet the plurality of sample droplets is one or fewer. The method may further comprise subjecting the droplets to thermal cycling sufficient to allow amplification of the target nucleic acid, and detecting one or more of the presence or absence of amplified target nucleic acid in the droplets.
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