Device and method for microdroplet detection of cells
Inventors
Isaac, Tom • Frayling, Cameron
Assignees
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Publication Number
US-12157123-B2
Publication Date
2024-12-03
Expiration Date
Abstract
Devices, systems, and associated methods are provided for manipulating and/or determining one or more characteristics of cells contained within a biological sample. In particular a device and methods of use thereof are provided, the device comprising a sorting component configured to separate cell-containing microdroplets from empty ones into a population of cell-containing first microdroplets; a microdroplet manipulation component configured to manipulate the first microdroplets using real or virtual electrowetting electrodes, and an optical detection system configured to detect an optical signal from the microdroplets via the one or more detection windows.
Core Innovation
The invention provides a device for manipulating and/or determining one or more characteristics of cells contained within a biological sample by working with cell-containing microdroplets. The device includes a sorting component configured to separate cell-containing microdroplets from empty ones into a population of cell-containing first microdroplets, and a microdroplet manipulation component configured to manipulate the first microdroplets using real or virtual electrowetting electrodes.
The microdroplet manipulation component includes a first zone configured to arrange the first microdroplets into an array for optical inspection and, optionally, to introduce a reporter system into each first microdroplet by means of microdroplet merging. A second zone located within or adjacent the first zone is configured to detect merged microdroplets in one or more detection windows, and optionally a third zone is provided in which microdroplets can be sub-divided and isolated for later recovery from the instrument.
An optical detection system detects an optical signal from the microdroplets via the one or more detection windows. For merged microdroplets, the signal arises from an interaction between the reporter system and the cells or an expressed product thereof, enabling rapid, parallel cell characterization in a microfluidic workflow using opto-addressing when virtual electrowetting electrodes are used.
Claims Coverage
The partial content provided contains one explicitly independent claim, defining the core device architecture and the optical detection mechanism tied to reporter-cell interactions in detection windows. Inventive features are specified across the independent claim’s components and are further narrowed in dependent claims identified in the partial content.
Sorting cell-containing from empty microdroplets into first microdroplets
A sorting component configured to separate cell-containing microdroplets from empty ones into a population of cell-containing first microdroplets.
Real or virtual electrowetting electrode manipulation for microdroplets
A microdroplet manipulation component configured to manipulate the first microdroplets using real or virtual electrowetting electrodes.
Arranging microdroplets into an array for optical inspection and optionally merging with reporter microdroplets
A first zone configured to arrange the first microdroplets into an array for optical inspection and, optionally, to introduce a reporter system into each first microdroplet by means of microdroplet merging.
Detection windows for merged microdroplets
A second zone located within or adjacent the first zone and configured to detect merged microdroplets in one or more detection windows.
Optional microdroplet sub-division and isolation for later recovery
Optionally a third zone in which microdroplets can be sub-divided and isolated for later recovery from the instrument.
Optical signal arising from reporter-cell interaction or expressed product
An optical detection system configured to detect an optical signal from the microdroplets via the one or more detection windows, wherein, for merged microdroplets, the signal arises from an interaction between the reporter system and the cells or an expressed product thereof.
Selecting an optical detection modality for the optical detection system
The optical detection system is selected from brightfield microscopy, darkfield microscopy, chemiluminescence detection, Förster resonance energy transfer detection, or fluorescence detection.
Merging reporter microdroplets with first microdroplets via a holding-site reservoir array
A first zone includes a reservoir of first microdroplet-holding sites and a port that introduces second microdroplets containing a reporter system, and the device drives the second microdroplets across the sites to merge the first and second microdroplets.
Overall claim coverage centers on a microfluidic device that sorts cell-containing microdroplets from empty ones, arranges them into an array using real or virtual electrowetting, optionally merges reporter-containing microdroplets, and performs optical detection in detection windows where the signal is attributed to reporter-cell interaction or expressed products. Dependent features further narrow optical detection to specific microscopy or assay modalities and specify a reservoir/port-driven reporter microdroplet merging arrangement.
Stated Advantages
Enables rapid, parallel cell characterization using a microfluidic workflow.
Provides multiplexed opto-addressing in relation to virtual OEWOD implementations.
Allows detection signals to arise from interactions between a reporter system and cells or expressed products.
Documented Applications
Cell line development.
Immune functionality screening (B/T/dendritic cells).
Drug functionality/efficacy screening.
Stem cell differentiation.
Organoid formation.
CRISPR-Cas9 gRNA-pair screening.
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