Patents Assigned to Stokes Bio Ltd.
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Patent number: 11807902Abstract: 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.Type: GrantFiled: June 4, 2020Date of Patent: November 7, 2023Assignee: STOKES BIO LTD.Inventors: Mark Davies, Tara Dalton
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Patent number: 11772096Abstract: 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.Type: GrantFiled: July 7, 2020Date of Patent: October 3, 2023Assignee: STOKES BIO LTD.Inventors: Mark Davies, Tara Dalton, Kieran Curran
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Publication number: 20230295703Abstract: 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.Type: ApplicationFiled: February 3, 2023Publication date: September 21, 2023Applicant: STOKES BIO LTD.Inventors: Mark B. DAVIES, Tara DALTON
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Patent number: 11084039Abstract: 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.Type: GrantFiled: February 10, 2017Date of Patent: August 10, 2021Assignee: STOKES BIO LTD.Inventors: Mark Davies, Tara Dalton
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Patent number: 10967338Abstract: 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.Type: GrantFiled: October 9, 2018Date of Patent: April 6, 2021Assignee: STOKES BIO LTD.Inventors: Mark Davies, Tara Dalton
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Publication number: 20210023561Abstract: 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).Type: ApplicationFiled: July 7, 2020Publication date: January 28, 2021Applicant: STOKES BIO LTD.Inventors: Mark DAVIES, Tara DALTON, Kieran CURRAN
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Publication number: 20200354772Abstract: 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.Type: ApplicationFiled: June 4, 2020Publication date: November 12, 2020Applicant: STOKES BIO LTD.Inventors: Mark DAVIES, Tara DALTON
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Publication number: 20200283837Abstract: 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.Type: ApplicationFiled: March 9, 2020Publication date: September 10, 2020Applicant: STOKES BIO LTD.Inventors: Mark B. DAVIES, Tara DALTON
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Patent number: 10730051Abstract: 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).Type: GrantFiled: April 18, 2016Date of Patent: August 4, 2020Assignee: STOKES BIO LTD.Inventors: Mark Davies, Tara Dalton, Kieran Curran
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Patent number: 10676786Abstract: 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.Type: GrantFiled: September 28, 2016Date of Patent: June 9, 2020Assignee: STOKES BIO LTD.Inventors: Mark Davies, Tara Dalton
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Patent number: 9631230Abstract: 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.Type: GrantFiled: August 11, 2009Date of Patent: April 25, 2017Assignee: STOKES BIO LTDInventors: Mark Davies, Tara Dalton
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Patent number: 8550503Abstract: 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.Type: GrantFiled: September 27, 2007Date of Patent: October 8, 2013Assignee: Stokes Bio Ltd.Inventors: Mark Davies, Tara Dalton
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Publication number: 20100294048Abstract: 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: a sampling member for acquiring or dispensing a sample; and a supply of a fluid that is immiscible with the sample; in which the device is configured to provide a continuous flow of immiscible fluid enveloping the sampling member.Type: ApplicationFiled: May 19, 2009Publication date: November 25, 2010Applicant: Stokes Bio Ltd.Inventors: David McGuire, Kieran Curran, Julie Garvey, Damian Curtain
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Publication number: 20100216128Abstract: 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.Type: ApplicationFiled: May 20, 2009Publication date: August 26, 2010Applicant: STOKES BIO LTD.Inventors: Mark Davies, Tara Dalton
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Publication number: 20100029512Abstract: The present invention generally relates to methods of constructing liquid bridges and methods of forming predetermined combinations of samples using liquid bridges.Type: ApplicationFiled: May 20, 2009Publication date: February 4, 2010Applicant: Stokes Bio Ltd.Inventors: Mark Davies, Tara Dalton