Sharp Life Science (Eu) Limited

Sharp Kabushiki Kaisha Corporation

Oxford Nanopore Technologies Limited

Sharp Life Science Corporation

Sally Anderson

Benjamin James Hadwen

Christopher James Brown

Pamela Ann Dothie

Philip Mark Shryane Roberts

Adam Christopher Wilson

Campbell Donald Brown

Andrew John Heron

James White

James Anthony Clarke

Peter Neil Taylor

Jason Robert Hyde

Gregory Gay

Matthew Holden

Andrew James Hudson

Michael Stuart Weaver

Yoshimasa Fujita

Craig Tombling

Harald Reinhart Bock

Laura Huang

Judy Megan Rorison

Simon M Bryant

Leslie Anne Parry-Jones

Stan Kwang

Michael A Reeve

A method of operating an EWOD device to employs a magnetic field to separate magnetically responsive particles from a polar liquid droplet. The method includes the steps of dispensing a liquid droplet onto an element array of the EWOD device, wherein the liquid droplet includes magnetically responsive particles; performing an electrowetting operation to move the liquid droplet along the element array to a location relative to a magnet element in proximity to that location of the EWOD device; operating the magnet element to apply a magnetic field to the liquid droplet, wherein at least a portion of the magnetically responsive particles aggregate within the liquid droplet in response to the magnetic field; and separating the aggregated magnetically responsive particles from the liquid droplet with the magnetic field, wherein the aggregated magnetically responsive particles move in response to the magnetic field to a location on the element array in proximity to the magnet element. Embodiments of the methods of the present application may be performed by an EWOD control system executing program code stored on a non-transitory computer readable medium.

Magnetic particle extraction in an EWOD instrument

Droplet interfaces are formed between droplets in an electro-wetting device comprising an array of actuation electrodes. Actuation signals are applied to selected actuation electrodes to place the droplets into an energised state in which the shape of the droplets is modified compared to a shape of the droplets in a lower energy state and to bring the two droplets into proximity. The actuation signals are then changed to lower the energy of the droplets into the lower energy state so that the droplets relax into the gap and the two droplets contact each other thereby forming a droplet interface. The use of sensing electrodes in the device permit electrical current measurements across the droplet interface. The sensing electrodes can be used for either (i) applying a reference signal during droplet actuation or (ii) recording electrical current measurements.

Droplet interfaces in electro-wetting devices

A microfluidic system and related methods of operating an electrowetting on dielectric (EWOD) device operate to concentrate particles within a liquid droplet dispensed onto an element array of the EWOD device. The method includes the steps of providing a non-polar liquid onto the element array of the EWOD device; providing a polar liquid droplet onto the element array of the EWOD device within the non-polar liquid, wherein the polar liquid droplet includes particles; and applying an actuation cycle comprising a plurality of actuation patterns, wherein at least one of the actuation patterns includes actuating one or more array element electrodes within a perimeter of the polar liquid droplet, and the particles migrate within the polar liquid droplet to become concentrated within a portion of the liquid droplet at one or more array element electrodes corresponding to one of the plurality of actuation patterns.

Method of concentrating particles in a liquid droplet using an EWOD device with sensing apparatus

A method of operating an electrowetting on dielectric (EWOD) device performs microfluidic diffusion separation. The method includes the steps of: inputting a sample droplet into the EWOD device, wherein the sample droplet includes a mixture of particles including first particles and second particles that are different from each other; inputting a collection droplet into the EWOD device; performing an electrowetting operation to bring the sample droplet into contact with the collection droplet; at an initial time, initiating a process of particle separation by which a portion of the sample droplet is introduced into the collection droplet, wherein the first particles move through the collection droplet at a rate different from the second particles; and after a time interval from the initial time, performing an electrowetting operation to segment a leaving droplet from the collection droplet, wherein the leaving droplet has a higher concentration of the first particles relative to the second particles as compared to a concentration of the first particles relative to the second particles in the sample droplet at the initial time. The method may be performed by an AM-EWOD control system executing program code stored on a non-transitory computer readable medium.

Molecular separation by diffusion using an EWOD device

An EWOD device and a related method of performing a digital biological assay are described that employs two volume measurements for enhanced assay determination. The method includes partitioning a sample reservoir and measuring the volume of each partition; initiating a biological assay wherein the biological assay includes measuring a partition property and a volume of each partition in real time as part of determining a concentration of the product substance in each partition based on the measured partition property and volume; and categorizing the partitions by a number of biological entities contained in each partition from which the number of biological entities may be calculated, which in turn may be used to calculate the total number of biological entities or concentration in the sample reservoir. The method further may include an enhanced partitioning process that minimizes variation in the volume of the partitions.

Microfluidic device and methods for digital assays in biological analyses

A method of digital quantification of a species in an EWOD device includes inputting a sample volume and a diluent volume into the EWOD device; performing an electrowetting operation to generate a first sample droplet from the sample volume; performing an amplification process on the first sample droplet and measuring a turn-on value for the sample droplet; comparing the measured turn-on value to a target turn-on value for digital quantification; calculating a dilution factor based on the comparison of the measured and target turn-on values; performing an electrowetting operation to extract a second sample droplet from the sample volume; performing an electrowetting operation to dilute the second sample droplet with the diluent volume by the dilution factor to form a diluted second sample droplet; and performing a digital quantification on the diluted second sample droplet to quantify an initial concentration of the species in the sample volume.

EWOD system and methods to increase dynamic range for digital nucleic acid amplification

An electrowetting on dielectric (EWOD) device includes an EWOD device array that applies electrowetting forces and contains a non-polar fluid. A barrier droplet configuration is formed using electrowetting forces to obstruct migration of a species from a first area of the EWOD device array to a protected area of the EWOD device array. A method of operating the EWOD device includes the steps of: dispensing a source droplet into a first area of the EWOD device array, the source droplet containing a migrating species, wherein the EWOD device array includes a second area to be protected from the migrating species; and forming a barrier droplet configuration positioned between the first area and the second area of the EWOD device array that obstructs a migration pathway of the migrating species between the first area and the second area. The barrier droplet configuration includes at least one aqueous or polar barrier droplet, and the migrating species exhibits a preference for either the polar or aqueous environment of the barrier or the non-polar environment of the oil to obstruct migration.

Barrier droplet configurations against migration between droplets on AM-EWOD devices

A microfluidic system is configured for enhanced temperature control by combining spatial and temporal temperature control. The microfluidic system includes an electro-wetting on dielectric (EWOD) device comprising an element array configured to receive one or more liquid droplets, the element array comprising a plurality of individual array elements; a control system configured to control actuation voltages applied to the element array to perform manipulation operations of the liquid droplets; and a plurality of thermal control elements located at different spatial locations along the EWOD device, at least one of the thermal control elements being variable in temperature with respect to time. The control system includes a thermal control unit configured to control temperatures of the thermal control elements to generate a plurality of thermal zones located at different spatial locations along the EWOD device, at least one of the thermal zones being variable in temperature with respect to time.

Microfluidic device with multiple temperature zones and enhanced temperature control

A pixel circuit acts as a sensing element in a sensing device. The pixel circuit includes a sensing electrode, a first gate electrically connected to the sensing electrode, a second gate in electrical communication with the first gate, and a readout device that is electrically connected to the second gate. An input voltage applied to the sensing electrode is amplified between the first gate and the second gate, the amplification being measured as an output signal from the readout device to perform a sensing operation. For example, the output signal may be relatable to pH, analyte measurements, or other properties of sample liquids analyzed by the sensing device. A sensing device may include multiple pixels disposed on a substrate, each pixel including said pixel circuit. Driver circuits controlled by control electronics are configured to generate signals that selectively address the pixels and to read out voltages at the sensing electrodes.

Bio-sensor pixel circuit with amplification

A charge-transport structure, e g an opto-electronic structure such an electroluminescent device is manufactured by forming a uniform first charge-transport (eg electron-transport) polymer layer on a substrate. Low molar mass dyes in a solvent are ink-jet printed onto the exposed surface of the first layer to form a multicolor pattern, and the dyes are allowed to diffuse into the layer to form charge-recombination/emitter regions within the layer. Excess dyes are washed away from the surface and then a uniform second charge-transport (eg hole-transport) polymer layer is formed on the resultant smooth surface of the first layer over the tops of the regions. Finally, electrodes are deposited on the top of the second layer in registration with the regions. Photovoltaic structures and organic transistors are also disclosed.

Charge-transport structures

Triazine compounds and their use

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Oxford, United Kingdom

Sally Anderson