公开(公告)号：US11084039B2

公开(公告)日：2021-08-10

申请号：US15429765

申请日：2017-02-10

Applicant: STOKES BIO LIMITED

Inventor： Mark Davies ,  Tara Dalton

IPC: B01L7/00 ,  B01L3/00 ,  G01N21/64 ,  C12Q1/686

Abstract: A biological sample analysis system including a sample preparation system forming droplets of segmented sample separated by a carrier fluid immiscible with the sample. The droplets include reaction mixtures for amplification of at least one target nucleic acid. A thermal cycling device having a sample block having a plurality of controlled thermal zones, and a containment structure in thermal communication with the plurality of controlled thermal zones. The containment structure receives and contains the droplets of segmented sample separated by the immiscible carrier fluid from the sample preparation system. A controller for controlling a temperature in each thermal zone of the sample block. A detection system detects electromagnetic radiation emitted from each of the droplets individually from the queue of droplets as they flow past the detection system. A positioning system to facilitate moving a queue of the droplets in the thermal cycling device relative to the detection system.

公开(公告)号：US10967338B2

公开(公告)日：2021-04-06

申请号：US16155411

申请日：2018-10-09

Applicant: STOKES BIO LIMITED

Inventor： Mark Davies ,  Tara Dalton

IPC: G01N33/50 ,  B01F5/00 ,  B01F13/00 ,  B01L3/00 ,  B01L7/00 ,  G01N35/08 ,  G01N35/10 ,  G01N35/00

Abstract: 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.

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

IPC: B01L3/00 ,  B01F13/00 ,  B01F15/02 ,  C12Q1/68 ,  F17D1/08 ,  C12Q1/686 ,  B01L7/00

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.

公开(公告)号：US20160281135A1

公开(公告)日：2016-09-29

申请号：US15055311

申请日：2016-02-26

Applicant: STOKES BIO LIMITED

Inventor： Mauro Aguanno ,  Brian T. Chawke ,  Kieran Curran ,  Tara Dalton ,  Mark Davies ,  Xiaona Hou ,  David Kinahan ,  Mark Korenke ,  David McGuire ,  Michael Sayers ,  Noel Sirr ,  Ryan J. Talbot ,  Brian Barrett ,  Damian Curtin ,  Damien King ,  Conor McCarthy

IPC: C12Q1/68 ,  G01N21/64 ,  G01N35/00 ,  B01L7/00 ,  B01L3/00

CPC classification number: C12Q1/686 ,  B01F13/0005 ,  B01F13/0071 ,  B01F15/00214 ,  B01L3/502715 ,  B01L3/502784 ,  B01L7/52 ,  B01L7/525 ,  B01L2200/143 ,  B01L2300/06 ,  B01L2300/0654 ,  B01L2300/0867 ,  G01N21/6428 ,  G01N35/00623 ,  G01N2021/6439 ,  G01N2021/6441 ,  G01N2035/00465 ,  G01N2201/062

Abstract: Provided herein is a biological detection system and method of use wherein the biological detection system comprises at least one mixer or liquid bridge for combining at least two liquid droplets and an error correction system for detecting whether or not proper mixing or combining of the two component droplets have occurred.

Abstract translation: 本文提供了一种生物检测系统和使用方法，其中生物检测系统包括用于组合至少两个液滴的至少一个混合器或液体桥，以及用于检测是否适当混合或组合两个组分液滴的误差校正系统 已经发生

公开(公告)号：US20160123513A1

公开(公告)日：2016-05-05

申请号：US14930487

申请日：2015-11-02

Applicant: STOKES BIO LIMITED

Inventor： Mark Davies ,  Tara Dalton

IPC: F16L41/18

CPC classification number: F16L41/18 ,  B01L3/5027 ,  B01L3/5635 ,  B01L3/565 ,  B01L2200/027 ,  F16L39/00 ,  Y10T137/0318

Abstract: A microfluidic connector (1) comprises and 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）包括壳体（6,7），流体入口端口（2）和流体出口端口（3），其中入口端口和出口端口（2,3）可移动 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）。

公开(公告)号：US20150140645A1

公开(公告)日：2015-05-21

申请号：US14486987

申请日：2014-09-15

Applicant: STOKES BIO LIMITED

Inventor： Mark Davies ,  Tara Dalton

IPC: B01L7/00

CPC classification number: B01L7/525 ,  B01L3/5027 ,  B01L3/502715 ,  B01L3/502784 ,  B01L2200/0673 ,  B01L2300/0627 ,  B01L2300/0654 ,  B01L2300/0838 ,  B01L2300/0867 ,  B01L2300/18 ,  B01L2300/1822 ,  B01L2300/185 ,  B01L2400/0487 ,  C12Q1/686 ,  G01N21/6428 ,  G01N2201/0826 ,  G01N2201/0833

Abstract: A thermal cycling device (3) device a number of fixed thermal zones (11, 12, 13) and a fixed conduit (10) passing through the thermal zones. A controller maintains each thermal zone including its section of conduit (10) at a constant temperature. A series of droplets flows through the conduit (10) so that each droplet is thermally cycled, and a detection system detects fluorescence from droplets at all of the thermal cycles. The conduit is in a single plane, and so a number of thermal cycling devices may be arranged together to achieve parallelism. The flow conduit comprises a channel (17) and a capillary tube (10) inserted into the channel. The detection system may perform scans along a direction to detect radiation from a plurality of cycles in a pass.

Abstract translation: 热循环装置（3）装置设有多个固定热区（11,12,13）和通过热区的固定导管（10）。 控制器将每个热区域保持在其恒定温度下的导管（10）部分。 一系列液滴流过导管（10），使得每个液滴热循环，并且检测系统在所有热循环中检测来自液滴的荧光。 导管处于单个平面中，因此可以将多个热循环装置布置在一起以实现平行。 流动管道包括插入通道中的通道（17）和毛细管（10）。 检测系统可以沿着一个方向执行扫描，以检测通过中多个周期的辐射。

公开(公告)号：US20140051604A1

公开(公告)日：2014-02-20

申请号：US14057301

申请日：2013-10-18

Applicant: STOKES BIO LIMITED

Inventor： Mark Davies ,  Tara Dalton ,  Julie Garvey ,  Kieran Curran ,  Damian Curtin

IPC: B01J19/00

CPC classification number: 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

Abstract: 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.

Abstract translation: 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。

公开(公告)号：US20170081705A1

公开(公告)日：2017-03-23

申请号：US15278894

申请日：2016-09-28

Applicant: STOKES BIO LIMITED

Inventor： Mark Davies ,  Tara Dalton

IPC: C12Q1/68 ,  B01L3/00 ,  B01L7/00

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.

公开(公告)号：US20160339435A1

公开(公告)日：2016-11-24

申请号：US15131546

申请日：2016-04-18

Applicant: STOKES BIO LIMITED

Inventor： Mark Davies ,  Tara Dalton ,  Kieran Curran

IPC: B01L3/00 ,  B01F15/02 ,  C12Q1/68 ,  B01F13/00

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.

Abstract translation: 桥（30）包括在毛细管端部的第一入口（31），作为毛细管端部的较窄的第二入口（32），作为毛细管的端部的出口（33） 和用于硅油的室（34）。 油与反应器液滴密度匹配，使得在室（34）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（34）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。 从第二入口端口（32）引入第二液滴导致形成不稳定的索道桥，其从较细的第二入口（32）快速破裂，并且液滴在液体桥（30）处结合。 在另一个实施例中，液滴（55）分段成较小的液滴，桥接入口和出口之间的间隙。

公开(公告)号：US09387472B2

公开(公告)日：2016-07-12

申请号：US14295223

申请日：2014-06-03

Applicant: STOKES BIO LIMITED

Inventor： Mark Davies ,  Tara Dalton ,  Michael Sayers ,  Brian T. Chawke

IPC: B01L3/02 ,  B01L7/00

CPC classification number: B01L3/021 ,  B01L3/0293 ,  B01L7/52 ,  B01L2200/0642 ,  B01L2200/0673 ,  Y10T436/25 ,  Y10T436/25625

Abstract: 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.

Abstract translation: 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。