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.

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.

Abstract: 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.

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.

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.

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.

Abstract: The present invention provides an improved capacitive bead sensor for detection and/or quantification of target analytes in a sample, with a detection limit down to single-beads, which is re-usable for multiple bead tests, or for a continuous flow of beads, and which is easily manufacturable and automatable. It enables sensitivity down to single molecule detection without the need for enzymatic amplification such as PCR, by use of various structural advantages and electronic signal amplification techniques that further allow for multiplex target detection not only across various nucleic acid targets but across entire target classes allowing for simultaneous detection of viral nucleic acids and host antibodies to that virus for example.

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.

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.

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.

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.

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).

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.

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.

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).

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.

Abstract: Methods of conducting a nucleic acid reaction, including methods for performing digital PCR using a “droplet-in-oil” technology, may include at least partially segmenting a starting sampled 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.

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: 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.

Abstract: Methods of conducting a nucleic acid reaction, including methods for performing digital PCR using a “droplet-in-oil” technology, may include at least partially segmenting a starting sampled 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.