Composite liquid cells
Inventors
Curran, Kieran • Fleming, Paul • Gilhooley, Seamus • Keane, Micheál • Rosca, Inga • Tuohy, Patrick
Assignees
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Publication Number
US-10125389-B2
Publication Date
2018-11-13
Expiration Date
Abstract
A sample handling method may include drawing an encapsulating liquid from an encapsulating-liquid input; discharging the drawn encapsulating liquid (a) onto a free surface of a carrier liquid in a carrier-liquid conduit comprising a stabilisation feature and (b) proximate to the stabilisation feature, the encapsulating liquid being immiscible with the carrier liquid, so that the discharged encapsulating liquid does not mix with the carrier liquid, floats on top of the carrier liquid, and is immobilised by the stabilisation feature; drawing a sample liquid from a sample-liquid input; and discharging the drawn sample liquid, the sample liquid being immiscible with the encapsulating liquid and with the carrier liquid, so that the sample liquid does not mix with the encapsulating liquid or with the carrier liquid.
Core Innovation
The invention relates to producing an encapsulated aqueous sample on a surface of a carrier liquid by combining an encapsulating liquid and an aqueous sample liquid. The encapsulating liquid, the aqueous sample liquid, and the carrier liquid are mutually immiscible, such that the aqueous sample is encapsulated on the carrier-liquid surface.
The described composite liquid cells are formed by encapsulating a biological sample in an immiscible buffer or fluid cell on a free surface of a mutually immiscible carrier liquid. Stabilisation features support immobilization and handling of the composite liquid cells on the carrier liquid, including electrostatics, hydrophobic control surfaces, capillary tension, directional control tube or air jet control, and control tube deposition.
The composite cell system includes a network of stabilisation regions for staged merging and processing, including merging and separation of composite liquid cells, formation of multi-sample composite liquid cells, and formation of internal sample arrays. The encapsulated aqueous sample concept supports nucleic-acid processing workflows, including PCR/dPCR, isothermal amplification, nucleic acid ligation, bead coating and sequencing, and fluorescence-based SNP detection with no carryover contamination, including use of a no template control.
Claims Coverage
The provided independent claim covers forming an encapsulated aqueous sample on a surface of a carrier liquid by combining an encapsulating liquid volume with an aqueous sample liquid volume, where all three liquids are mutually immiscible. The independent claim and dependent refinements identify 6 inventive features.
Encapsulated aqueous sample on a carrier liquid surface via mutual immiscibility
Providing a volume of encapsulating liquid and a volume of aqueous sample liquid; combining the volumes into an encapsulated aqueous sample liquid on a surface of a carrier liquid, wherein the aqueous sample liquid, the encapsulating liquid and the carrier liquid are mutually immiscible.
Spatial arrangement of liquid volumes before combining
Positioning the volumes of encapsulating liquid and aqueous sample liquid at different locations on a surface of the carrier liquid and then combining them to produce an encapsulated aqueous sample liquid.
Differing densities for encapsulating, aqueous sample, and carrier liquids
Specifying that the encapsulating liquid, aqueous sample liquid, and carrier liquid each have different densities.
Density ordering where the aqueous sample density is between the other two
Specifying that the aqueous sample liquid density lies between the density of the carrier liquid and the density of the encapsulating liquid.
Biological sample in the aqueous sample liquid
Specifying that the aqueous sample liquid contains a biological sample.
Encapsulating and carrier liquids as immiscible oils
Specifying that the encapsulating liquid and the carrier liquid are immiscible oils.
Coverage centers on forming an encapsulated aqueous sample on a carrier-liquid surface through combining mutually immiscible encapsulating and aqueous sample liquids, with refinements addressing spatial placement and density relationships, and optionally defining the sample as biological and the encapsulating and carrier liquids as immiscible oils.
Stated Advantages
Reduced cross-contamination, supported by fluorescence-based SNP detection in composite liquid cells with no carryover contamination.
Minimized dead volume.
100% volume retrieval.
Documented Applications
PCR/dPCR for nucleic-acid processing using composite liquid cells.
Isothermal nucleic acid amplification using composite liquid cells.
Nucleic acid ligation using composite liquid cells.
Bead coating and sequencing using composite liquid cells.
Fluorescence-based SNP detection in composite liquid cells with no carryover contamination, including use of a no template control.
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