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11. 发明授权

US11964244B2 Methods of releasing and analyzing cellular components 有权
公开(公告)号：US11964244B2
公开(公告)日：2024-04-23
申请号：US17197177
申请日：2021-03-10
申请人： STOKES BIO LIMITED
发明人： Mark Davies , Tara Dalton
IPC分类号： B01L3/00 , B01F25/10 , B01F33/30 , B01F33/302 , B01L7/00 , G01N33/50 , G01N35/08 , G01N35/00 , G01N35/10
CPC分类号： B01F25/10 , B01F33/30 , B01F33/3021 , B01L3/502784 , B01L7/525 , G01N33/5008 , G01N35/08 , B01L2200/0636 , B01L2200/0673 , B01L2300/0816 , B01L2300/0861 , B01L2300/087 , B01L2300/185 , B01L2400/0409 , B01L2400/0487 , G01N2035/00514 , G01N35/1095
摘要： A system for analyzing a biological sample may include at least one sample acquisition stage comprising a sample acquisition device for acquiring the biological sample from a sample source; a droplet generator device for forming a droplet wrapped in an immiscible carrier fluid, wherein the wrapped droplet comprises at least the biological sample and a reagent, the droplet generator configured to receive the biological sample transferred from the sample acquisition device; a collection vessel for collecting the wrapped sample droplet from the droplet generator, the vessel configured to contain a carrier fluid for receiving and protecting the sample droplet; and an analysis system for analyzing the wrapped sample droplet and detecting products of a polymerase chain reaction.

12. 发明公开

US20230356227A1 LIQUID BRIDGE AND SYSTEM 审中-公开
公开(公告)号：US20230356227A1
公开(公告)日：2023-11-09
申请号：US18312209
申请日：2023-05-04
申请人： STOKES BIO LIMITED
发明人： Mark Davies , Tara Dalton , Kieran Curran
IPC分类号： B01L3/00 , C12Q1/686 , F17D1/08 , B01F35/71 , B01F33/302 , B01F101/23 , B01L7/00
CPC分类号： B01L3/502784 , C12Q1/686 , B01L3/502746 , F17D1/08 , B01F35/7172 , B01F33/3021 , B01L3/502715 , B01F2101/23 , B01L3/5025 , B01L2400/0478 , Y10T436/2575 , Y10T137/87676 , B01L2200/0673 , Y10T436/118339 , B01L2300/0838 , B01F35/71 , B01L2400/0633 , B01L2300/0829 , Y10T436/117497 , B01L2400/082 , B01L2400/0487 , B01L7/525
摘要： A system for processing a biological sample can include a droplet generation assembly comprising a plurality of first reservoirs configured to contain an aqueous sample and a plurality of second reservoirs configured to contain a carrier fluid immiscible with the aqueous sample. The plurality of first reservoirs and the plurality of second reservoirs can be arranged to be in respective flow communication in pairs of reservoirs comprising a first reservoir of the plurality of first reservoirs and a second reservoir of the plurality of second reservoirs constituting a plurality of pairs of reservoirs. The droplet generation assembly can further include a flow control system configured to control a pressure in the plurality of pairs of reservoirs so as to generate a flow of a series of volumes of the aqueous sample separated by the carrier fluid. The system can further include a thermocycling system.

13. 发明授权

US10676786B2 Microfluidic analysis system 有权
公开(公告)号：US10676786B2
公开(公告)日：2020-06-09
申请号：US15278894
申请日：2016-09-28
申请人： STOKES BIO LIMITED
发明人： Mark Davies , Tara Dalton
IPC分类号： C12Q1/686 , B01L3/00 , B01L7/00 , G01N35/08 , B01F5/00 , B01F13/00 , G01N35/10 , G01N35/00
摘要： 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.

14. 发明授权

US09108177B2 Microfluidic droplet queuing network 有权
标题翻译：微流控液滴排队网络
公开(公告)号：US09108177B2
公开(公告)日：2015-08-18
申请号：US14057301
申请日：2013-10-18
申请人： STOKES BIO LIMITED
发明人： Mark Davies , Tara Dalton , Julie Garvey , Kieran Curran , Damian Curtin
IPC分类号： C12M1/34 , B01J19/00 , B01F13/00 , B01F15/02 , B01L3/00
CPC分类号： B01J19/0046 , B01F13/0071 , B01F15/0201 , B01F15/0232 , B01J2219/00313 , B01J2219/00353 , B01J2219/00479 , B01J2219/00587 , B01J2219/00608 , B01L3/5025 , B01L3/502784 , B01L2200/0673 , B01L2300/0829 , B01L2400/0487 , Y10T436/25
摘要： A multi-port liquid bridge (1) adds aqueous phase droplets (10) in an enveloping oil phase carrier liquid (11) to a draft channel (4, 6). A chamber (3) links four ports, and it is permanently full of oil (11) when in use. Oil phase is fed in a draft flow from an inlet port (4) and exits through a draft exit port (6) and a compensating flow port (7). The oil carrier and the sample droplets (3) (“aqueous phase”) flow through the inlet port (5) with an equivalent fluid flow subtracted through the compensating port (7). The ports of the bridge (1) are formed by the ends of capillaries held in position in plastics housings. The phases are density matched to create an environment where gravitational forces are negligible. This results in droplets (10) adopting spherical forms when suspended from capillary tube tips. Furthermore, the equality of mass flow is equal to the equality of volume flow. The phase of the inlet flow (from the droplet inlet port (5) and the draft inlet port (4) is used to determine the outlet port (6) flow phase.
摘要翻译：多端口液体桥（1）将包含油相载体液体（11）中的水相液滴（10）加入到通风道（4,6）。室（3）连接四个端口，在使用时永久充满油（11）。油相在进气口（4）的进料流中进料，并通过排气口（6）和补偿流通口（7）排出。油载体和样品液滴（“水相”）以相当的流体流通过入口端口（5）流过补偿口（7）。桥梁（1）的端口由保持在塑料壳体中的位置的毛细管的端部形成。这些阶段是密度匹配的，以创造引力几乎可忽略的环境。这导致当从毛细管尖端悬浮时，液滴（10）采用球形。此外，质量流量的相等性等于体积流量的相等。入口流（从液滴入口端口5和进气口4）的相位用于确定出口（6）的流动相位。

15. 发明申请

US20140038196A1 Forming Sample Combinations Using Liquid Bridge Systems 有权
标题翻译：使用液桥系统形成样品组合
公开(公告)号：US20140038196A1
公开(公告)日：2014-02-06
申请号：US13960720
申请日：2013-08-06
申请人： Stokes Bio Limited
发明人： Mark Davies , Tara Dalton
IPC分类号： B01L3/00
CPC分类号： B01L3/5025 , B01F13/0071 , B01J2219/00599 , B01J2219/00722 , B01J2219/00889 , B01L3/502715 , B01L3/502784 , B01L7/52 , B01L7/525 , B01L2200/027 , B01L2200/0605 , B01L2200/0673 , B01L2300/0819 , B01L2300/0838 , B01L2300/0867 , B01L2300/1805 , B01L2400/0406 , B01L2400/0487 , B01L2400/0688 , C40B50/08 , C40B60/14 , G01N2035/00544
摘要： The present invention generally relates to methods of constructing liquid bridges and methods of forming predetermined combinations of samples using liquid bridges.
摘要翻译：本发明一般涉及构造液体桥的方法以及使用液体桥形成样品的预定组合的方法。

16. 发明授权

US09322511B2 Liquid bridge and system 有权
标题翻译：液桥和系统
公开(公告)号：US09322511B2
公开(公告)日：2016-04-26
申请号：US13627593
申请日：2012-09-26
申请人： Stokes BIO Limited
发明人： Mark Davies , Tara Dalton , Kieran Curran
IPC分类号： G01N1/10 , F17D1/08 , B01F13/00 , B01F15/02 , B01L3/00 , B01L7/00
CPC分类号： B01L3/502784 , B01F13/0071 , B01F15/0201 , B01F15/0232 , B01F2215/0037 , B01L3/5025 , B01L3/502715 , B01L3/502746 , B01L7/525 , B01L2200/0673 , B01L2300/0829 , B01L2300/0838 , B01L2400/0478 , B01L2400/0487 , B01L2400/0633 , B01L2400/082 , C12Q1/686 , F17D1/08 , Y10T137/87676 , Y10T436/117497 , Y10T436/118339 , Y10T436/2575
摘要： A bridge comprises a first inlet port, a second inlet port, an outlet port, and a chamber for silicone oil. The oil is density-matched with the reactor droplets such that a neutrally buoyant environment is created within the chamber. 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. 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 causes the formation of an unstable funicular bridge that quickly ruptures from the, finer, second inlet port, and the droplets combine at the liquid bridge. In another embodiment, a droplet segments into smaller droplets which bridge the gap between the inlet and outlet ports.
摘要翻译：桥梁包括第一入口端口，第二入口端口，出口端口和用于硅油的室。油与反应器液滴密度匹配，使得在室内产生中性浮力的环境。室内的油通过分离反应器液滴的油不断补充。这使得液滴在进入室时呈现稳定的毛细管悬浮球形。球形增长直到足够大以跨越端口之间的间隙，形成轴对称液桥。从第二入口引入第二液滴导致不稳定的索道桥的形成，其从较细的第二入口快速破裂，并且液滴在液桥处结合。在另一个实施例中，液滴分段成较小的液滴，桥接入口和出口之间的间隙。

17. 发明申请

US20150352513A1 Microfluidic Droplet Queuing Network 审中-公开
标题翻译：微流控液滴排队网络
公开(公告)号：US20150352513A1
公开(公告)日：2015-12-10
申请号：US14828336
申请日：2015-08-17
申请人： STOKES BIO LIMITED
发明人： Mark Davies , Tara Dalton , Julie Garvey , Kieran Curran , Damian Curtin
IPC分类号： B01J19/00
CPC分类号： B01J19/0046 , B01F13/0071 , B01F15/0201 , B01F15/0232 , B01J2219/00313 , B01J2219/00353 , B01J2219/00479 , B01J2219/00587 , B01J2219/00608 , B01L3/5025 , B01L3/502784 , B01L2200/0673 , B01L2300/0829 , B01L2400/0487 , Y10T436/25
摘要： A multi-port liquid bridge (1) adds aqueous phase droplets (10) in an enveloping oil phase carrier liquid (11) to a draft channel (4, 6). A chamber (3) links four ports, and it is permanently full of oil (11) when in use. Oil phase is fed in a draft flow from an inlet port (4) and exits through a draft exit port (6) and a compensating flow port (7). The oil carrier and the sample droplets (3) (“aqueous phase”) flow through the inlet port (5) with an equivalent fluid flow subtracted through the compensating port (7). The ports of the bridge (1) are formed by the ends of capillaries help in position in plastics housings. The phases are density matched to create an environment where gravitational forces are negligible. This results in droplets (10) adopting spherical forms when suspended from capillary tube tips. Furthermore, the equality of mass flow is equal to the equality of volume flow. The phase of the inlet flow from the droplet inlet port (5) and the draft inlet port (4) is used to determine the outlet port (6) flow phase.
摘要翻译：多端口液体桥（1）将包含油相载体液体（11）中的水相液滴（10）加入到通风道（4,6）。室（3）连接四个端口，在使用时永久充满油（11）。油相在进气口（4）的进料流中进料，并通过排气口（6）和补偿流通口（7）排出。油载体和样品液滴（“水相”）以相当的流体流通过入口端口（5）流过补偿口（7）。桥（1）的端口由毛细管的端部形成在塑料外壳中的位置。这些阶段是密度匹配的，以创造引力几乎可忽略的环境。这导致当从毛细管尖端悬浮时，液滴（10）采用球形。此外，质量流量的相等性等于体积流量的相等。来自液滴入口（5）和进气口（4）的入口流的相位用于确定出口（6）流动相。

18. 发明申请

US20150165440A1 QPCR Analysis Apparatus 审中-公开
标题翻译： QPCR分析仪
公开(公告)号：US20150165440A1
公开(公告)日：2015-06-18
申请号：US14539822
申请日：2014-11-12
申请人： STOKES BIO LIMITED
发明人： Mark Davies , John Daly , Tara Dalton
IPC分类号： B01L7/00 , G01N21/64
CPC分类号： B01L7/525 , B01L3/508 , B01L7/54 , B01L2300/0654 , B01L2300/0809 , B01L2300/1827 , B01L2400/0442 , B01L2400/0445 , G01N21/6428 , G01N2021/6439 , G01N2201/062
摘要： An apparatus (1) is for DNA amplification with quantitative measurements. A biological sample is held in a cell (2) for the amplification, the cell (2) defining a single space within which the sample rotates. On one side a copper heater (3) is located to supply heat to the cell (2), and on the other side there is a cooling copper block (4) withdrawing heat from the cell. The locations of the heater (3) and the cooling block (4) generate a natural convection loop internally within the cell (2) without need for active cooling—the block (4) passively cooling by withdrawing heat from the direction of the heater (3). A detector (9, 27) captures readings in real time and a processor (10) generates an S-curve for change of sample emission with time. The S-curve (FIGS. 4 and 5) also includes a thermal cycle number corresponding to the time parameter, so that the S-curve is given in the traditional qPCR intensity vs. cycle number.
摘要翻译：装置（1）用于通过定量测量进行DNA扩增。将生物样品保持在用于扩增的细胞（2）中，细胞（2）限定样品旋转的单个空间。在一侧，铜加热器（3）被定位成向电池（2）供热，另一侧有一个冷却铜块（4）从电池中取出热量。加热器（3）和冷却块（4）的位置在电池（2）内部产生自然对流回路，而不需要主动冷却 - 通过从加热器的方向抽出热量来阻止块（4）的被动冷却（ 3）。检测器（9,27）实时捕获读数，并且处理器（10）产生用于随时间改变样品发射的S曲线。 S曲线（图4和图5）还包括对应于时间参数的热循环数，使得S曲线以传统的qPCR强度对周期数给出。

19. 发明申请

US20140349387A1 Sampling Device 审中-公开
标题翻译：取样装置
公开(公告)号：US20140349387A1
公开(公告)日：2014-11-27
申请号：US14295223
申请日：2014-06-03
申请人： STOKES BIO LIMITED
发明人： Mark Davies , Tara Dalton , Michael Sayers , Brian T. Chawke
IPC分类号： B01L3/02
CPC分类号： B01L3/021 , B01L3/0293 , B01L7/52 , B01L2200/0642 , B01L2200/0673 , Y10T436/25 , Y10T436/25625
摘要： The present invention generally relates to devices, systems, and methods for acquiring and/or dispensing a sample without introducing a gas into a microfluidic system, such as a liquid bridge system. An exemplary embodiment provides a sampling device including an outer sheath; a plurality of tubes within the sheath, in which at least one of the tubes acquires a sample, and at least one of the tubes expels a fluid that is immiscible with the sample, in which the at least one tube that acquires the sample is extendable beyond a distal end of the sheath and retractable to within the sheath; and a valve connected to a distal portion of the sheath, in which the valve opens when the tube extends beyond the distal end and closes when the tube retracts to within the sheath.
摘要翻译：本发明一般涉及用于获取和/或分配样品而不将气体引入诸如液体桥系统的微流体系统中的装置，系统和方法。示例性实施例提供了一种包括外护套的取样装置; 鞘内的多个管，其中至少一个管获取样品，并且至少一个管排出与样品不混溶的流体，其中获取样品的至少一个管可扩展超出护套的远端并伸缩到护套内; 以及连接到所述护套的远端部分的阀，当所述管延伸超过所述远端时所述阀打开，并且当所述管缩回到所述护套内时所述阀闭合。

20. 发明申请

US20140096833A1 Microfluidic Connector 审中-公开
标题翻译：微流体连接器
公开(公告)号：US20140096833A1
公开(公告)日：2014-04-10
申请号：US14039759
申请日：2013-09-27
申请人： STOKES BIO LIMITED
发明人： Mark Davies , Tara Dalton
IPC分类号： F16L41/18
CPC分类号： F16L41/18 , B01L3/5027 , B01L3/5635 , B01L3/565 , B01L2200/027 , F16L39/00 , Y10T137/0318
摘要： A microfluidic connector comprises an enclosure, a fluidic inlet port and a fluidic outlet port, in the enclosure, in which the inlet and outlet ports are movable with respect to each other, for example, mutual spacing between the inlet and outlet ports is variable. A port is in a fixed part of the enclosure, and another port is in a part of the enclosure which slides with respect to the fixed part. There may be multiple inlet ports and/or multiple outlet ports. Also, there may be an auxiliary port for introduction of fluid into the enclosure or removal of fluid from the enclosure.
摘要翻译：微流体连接器包括外壳中的外壳，流体入口端口和流体出口端口，其中入口端口和出口端口可相对于彼此移动，例如，入口端口和出口端口之间的相互间隔是可变的。一个端口位于外壳的固定部分中，另一端口位于相对于固定部件滑动的外壳的一部分中。可能有多个入口端口和/或多个出口端口。此外，可能存在用于将流体引入外壳或从外壳移除流体的辅助端口。

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