Sharp Life Science (eu) Limited

Sharp Kabushiki Kaisha Corporation

Oxford Nanopore Technologies Limited

Sharp Microfluidic Solutions Limited

Associates of Cape Cod, Incorporated

Sharp Life Science Corporation

Benjamin James Hadwen

Christopher James Brown

Adrian Marc Simon Jacobs

Jason Roderick Hector

Sally Anderson

Oliver James Beard

Hiromi Katoh

Michael James Brownlow

Patrick Zebedee

Gregory Gay

Adam Christopher Wilson

Andrew John Heron

Masahiro Adachi

James White

James Anthony Clarke

Peter Neil Taylor

Pamela Ann Dothie

Jason Robert Hyde

Masakazu Satoh

Michael Paul Coulson

Philip Mark Shryane Roberts

Matthew Holden

Laura Huang

Sunay Shah

Campbell Donald Brown

Alison Mary Skinner

Mark Childs

Jonathan Buse

Hiroyuki Ogawa

Hajime Washio

David James Montgomery

Takeshi Hara

Emma Jayne Walton

Jonathan Heffernan

Tomoko Teranishi

Lesley Anne Parry-Jones

Tomohiro Kosaka

Gareth John

Rakesh Roshan

Phillip Mark Shryane Roberts

Simon M Bryant

Michael Robert Prior-Jones

Leslie Anne Parry-Jones

Julie Karen Deacon

Robert Julian Amos

Adam Robinson

Sinéad Matthews

Chris Clarke

Peter Matthew Forrest

Stan Kwang

Patrick Adrian Zebedee

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

An electro-wetting on dielectric (EWOD) device, comprises first and second substrates defining a fluid chamber therebetween, a plurality of electro-wetting electrodes on the first substrate, and at least one first electrode and at least two second electrodes on the second substrate. The device further includes a current sensor for sensing a difference between (1) a first current flowing between the first electrode and one of the second electrodes via a first fluid package in the fluid chamber of the EWOD device and (2) a second current flowing between the first electrode and another of the second electrodes via a second fluid package in the fluid chamber of the EWOD device.

EWOD device with sensing apparatus

A microfluidic device performs a method of partitioning droplets from a fluid reservoir containing particles that provides a non-Poissonian distribution of dispensed droplets containing a desired number of particles. Using an electrowetting on dielectric (EWOD) device, droplets are dispensed having a Poissonian distribution of dispensed droplets containing a desired number of particles, and the droplets are interrogated to determine whether each dispensed droplet has a desired number of particles. Droplets that contain the desired number of particles are moved by EWOD operation to a reaction area on the EWOD device, and droplets that do not contain the desired number of particles are rejected and moved by EWOD operation to a holding area on the EWOD device that is different and spaced apart from the reaction area. The result is that droplets in the reaction area have a non-Poissonian distribution of droplets containing the desired number of particles.

Non-poissonian droplet partitioning using feedback

A method of determining the result of an assay in a microfluidic device includes the steps of: dispensing a sample droplet onto a first portion of an electrode array of the microfluidic device; dispensing a reagent droplet onto a second portion of the electrode array of the microfluidic device; controlling actuation voltages applied to the electrode array to mix the sample droplet and the reagent droplet into a product droplet; sensing a dynamic property of the product droplet; and determining an assay of the sample droplet based on the sensed dynamic property. The dynamic property is a physical property of the product droplet that influences a transport property of the product droplet on the electrode array. Example dynamic properties of the product droplet include the moveable state, split-able state, and viscosity based on droplet properties. The method may be used to perform an amoebocyte lysate (LAL) assay.

Droplet microfluidic device and methods of sensing the result of an assay therein

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 control method and related apparatus are disclosed for controlling actuation voltages applied to array elements of an element array on an electrowetting on dielectric (EWOD) device, wherein test metrics are determined and employed for optimizing subsequent droplet manipulation operations. The control method includes the steps of: receiving a liquid droplet onto the element array; applying an electrowetting actuation pattern of actuation voltages to actuate the droplet to modify a footprint of the droplet from a first state having an initial footprint to a second state having a modified footprint; sensing the modified footprint with a sensor; determining a test metric from sensing the modified footprint indicative of one or more droplet properties based on a droplet response of the liquid droplet to the electrowetting actuation pattern; and controlling actuation voltages applied to the array elements based on the test metric. The test metrics may include a transition rate and/or conformance to an actuation pattern.

Adpative droplet operations in an AM-EWOD device based on test measurement of droplet properties

A method of partitioning droplets from a fluid reservoir containing particles provides a non-Poissonian distribution of dispensed droplets containing a desired number of particles. The method constitutes a method of operating an electrowetting on dielectric (EWOD) device including the steps of: inputting a fluid reservoir containing particles into the EWOD device; performing an electrowetting operation to dispense a plurality of dispensed droplets from the fluid reservoir; interrogating each droplet with a detector and determining whether each dispensed droplet has a desired number of particles; selecting dispensed droplets that contain the desired number of particles and performing an electrowetting operation to move the selected dispensed droplets to a reaction area on the EWOD device; and rejecting dispensed droplets that do not contain the desired number of particles and performing an electrowetting operation to move the rejected dispensed droplets to a holding area on the EWOD device that is different and spaced apart from the reaction area. The selected droplets may be combined, including with or without a portion of the rejected droplets and/or additional reagent, into a larger reaction droplet that may be used in subsequent reaction protocols.

Droplet microfluidic device and methods of sensing the results of an assay therein

An AM-EWOD device includes a plurality of array elements arranged in an array of rows and columns, each of the array elements including array element circuitry, an element electrode, and a reference electrode. The array element circuitry includes actuation circuitry configured to apply actuation voltages to the element and/or reference electrodes for actuating the array element, and impedance sensor circuitry configured to sense impedance at the array element electrode to determine a droplet or device property at the array element, the impedance sensor circuitry comprising a sensor capacitor and a sensor readout transistor that outputs an output current for sensing. The sensor capacitor is electrically connected to a gate of the sensor readout transistor such that during a sensing phase a voltage perturbation is coupled through the sensor capacitor (and possibly other circuit elements) to the gate of the sensor readout transistor. The impedance sensor circuitry further comprises a pre-charging element that operates to turn on the sensor readout transistor during the sensing phase in combination with coupling of the voltage perturbation, thereby increasing the effect of the voltage perturbation on the output current.

AM-EWOD array element circuitry with high sensitivity for small capacitance

A method of operating an active matrix electro-wetting on dielectric (AM-EWOD) device provides for enhanced mutual capacitance sensing using integrated impedance sensing circuitry. Array element circuitry of each array element includes actuation circuitry configured to apply actuation voltages to the array element electrode for actuating the array element, and impedance sensor circuitry integrated into the array element circuitry and configured to sense impedance at the array element electrode. The method of operating includes the steps of: perturbing a voltage applied to the array element electrode of a first array element; coupling the voltage perturbation to the array element electrode of a second array element different from the first array element; and measuring the output current from the sensor readout transistor of the second array element for sensing in response to the voltage perturbation. The method may be performed by an AM-EWOD control system executing program code stored on a non-transitory computer readable medium.

AM-EWOD array element circuitry with integrated sensing and method of sensing droplet merging

An AM-EWOD device includes a plurality of array elements arranged in an array of rows and columns; each column including a column addressing line that applies control signals to a corresponding column of array elements, and each row including a row addressing line that applies control signals to a corresponding row of array elements; each array element including an element electrode for receiving an actuation voltage and a switch transistor, wherein the switch transistor is electrically connected between the column addressing line and the element electrode and is switched by the row addressing line; and a column detection circuit comprising an addressing circuit that applies an electrical perturbation during a sensing operation to the column addressing line of an array element being sensed, and a measuring circuit that measures an output signal from one of the column addressing lines, wherein the output signal varies based upon a capacitance present at the element electrode.

AM-EWOD circuit configuration with sensing column detection circuit

A microfluidic system includes: an electro-wetting on dielectric (EWOD) cartridge having an element array configured to receive liquid droplets, the element array including individual array elements each including array element circuity comprising sensing circuitry that is integrated into the array element circuitry; a microfluidic instrument that is configured to receive the EWOD cartridge and having an electrically conductive locator that is external to the EWOD cartridge; and a control system configured perform electrowetting operations by controlling actuation voltages applied to the element array to perform manipulation operations as to liquid droplets present on the element array. The control system further is configured to read an output from the sensing circuitry, determine a position of the locator relative to the element array based on the output, and determine a misalignment of the EWOD cartridge relative to the microfluidic instrument based on the position of the locator. The control system may adjust a droplet manipulation operation to compensate for the determined misalignment.

EWOD cartridge position sensing when docked in EWOD instrument

An active matrix electro-wetting on dielectric (AM-EWOD) device has an optically black array element structure to enhance optical detection of constituents within a liquid droplet. The AM-EWOD device includes a thin film transistor (TFT) substrate assembly having a hydrophobic layer; thin film electronics having a plurality of array elements arranged in an array of rows and columns, each of the array elements including an array element electrode and a TFT device; and an optically black material disposed between a plane of the TFT device and the hydrophobic layer. The TFT substrate assembly further includes a planarization structure that includes a component having the optically black material. The planarization structure has a planarization component disposed between the TFT device and the array element electrode, and an ionic barrier disposed between the array element electrode and the hydrophobic coating. The planarization component or the ionic barrier includes the optically black material.

Optically black AM-EWOD array element structure

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Oxford, United Kingdom

Benjamin James Hadwen