# US 8,465,707 B2 · Composite liquid cells

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- Number: US 8,465,707 B2
- Document ID: US8465707B2
- Status: Granted
- Kind: B2
- Application number: 13/147,679
- Filed: 2011-07-22
- Published: 2012-02-23
- Granted: 2013-06-18
- Earliest claimed: 2010-07-22
- Assignees: Gencell Biosystems Ltd.
- Applicants: Kieran Curran; Paul Fleming; Séamus Gillhooley; Micheál Keane; Inga Rosca; Patrick Tuohy
- Inventors: Kieran Curran; Paul Fleming; Séamus Gillhooley; Micheál Keane; Inga Rosca; Patrick Tuohy
- Web page: https://patentgrep.com/patent/US8465707B2

## CPC

- C12Q 1/6806: Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay (C12Q1/6804 takes precedence)
- B01F 23/41: Emulsifying
- B01F 33/3021: {the components to be mixed being combined in a single independent droplet, e.g. these droplets being divided by a non-miscible fluid or consisting of independent droplets}
- B01L 3/0293: {for liquids}
- B01L 3/502784: {specially adapted for droplet or plug flow, e.g. digital microfluidics}
- C12Q 1/686: Polymerase chain reaction [PCR]
- G01N 1/28: Preparing specimens for investigation {including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q}(mounting specimens on microscopic slides G02B21/34; means for supporting the objects or the materials to be analysed in electron microscopes H01J37/20 {; laboratory gas handling apparatus B01L5/00})
- G01N 1/36: Embedding or analogous mounting of samples
- B01F 2101/23: Mixing of laboratory samples e.g. in preparation of analysing or testing properties of materials
- B01L 3/0241: {Drop counters; Drop formers}
- B01L 7/525: {with physical movement of samples between temperature zones}
- B01L 2200/027: for microfluidic devices
- B01L 2200/0647: Handling flowable solids, e.g. microscopic beads, cells, particles
- B01L 2200/0668: Trapping microscopic beads
- B01L 2200/0673: Handling of plugs of fluid surrounded by immiscible fluid
- B01L 2300/0816: Cards, e.g. flat sample carriers usually with flow in two horizontal directions
- B01L 2300/0819: Microarrays; Biochips
- B01L 2300/0864: comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
- B01L 2300/0867: Multiple inlets and one sample wells, e.g. mixing, dilution
- B01L 2300/089: Virtual walls for guiding liquids
- B01L 2400/0406: capillary forces
- B01L 2400/0409: centrifugal forces
- B01L 2400/0415: electrical forces, e.g. electrokinetic
- B01L 2400/0475: specific mechanical means and fluid pressure
- B01L 2400/0487: fluid pressure, pneumatics
- B01L 2400/0633: with moving parts
- B01L 2400/086: using baffles or other fixed flow obstructions
- Y10T 436/11: Automated chemical analysis
- Y10T 436/119163: with aspirator of claimed structure
- Y10T 436/25: including sample preparation
- Y10T 436/2525: Stabilizing or preserving
- Y10T 436/25625: Dilution
- Y10T 436/2575: Volumetric liquid transfer
- C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- B01F: MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING (mixing paints B44D3/06)
- B01L: CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)
- Y10T: TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION

## 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.

## Claims

### Claim 1

A sample handling system comprising:
a sample-liquid input;
an encapsulating-liquid input;
a carrier-liquid conduit comprising a stabilisation feature;
a liquid-handling system; and
a controller operably connected to the liquid-handling system;
wherein the controller is programmed to cause the liquid-handling system to:
(1) draw an encapsulating liquid from the encapsulating-liquid input;
(2) discharge the drawn encapsulating liquid (a) onto a free surface of a carrier liquid in the carrier-liquid conduit 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;
(3) draw a sample liquid from the sample-liquid input; and
(4) discharge 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.

### Claim 2 (depends on 1)

The system of claim 1, wherein the liquid-handling system comprises a control tube and a driver, and the controller is programmed to actuate the driver to cause the control tube to carry out steps (1) and (3) before carrying out steps (2) and (4).

### Claim 3 (depends on 2)

The system of claim 2, wherein the controller is programmed to actuate the driver to cause the control tube to carry out step (1), then step (3), then to (5) draw additional encapsulating liquid, then to (6) discharge the encapsulating liquid, then to carry out step (4), then step (2), so that the encapsulating liquid, the sample liquid, and the additional encapsulating liquid are discharged as a unit from the control tube and onto the free surface of the carrier liquid in the carrier-liquid conduit, the encapsulating liquid and the additional encapsulating liquid thereby merging and surrounding the sample liquid to form a composite liquid cell.

### Claim 4 (depends on 3)

The system of claim 3, wherein the controller is further programmed to actuate the driver to cause the control tube, after step (5) and before step (6), to (7) draw a separator.

### Claim 5 (depends on 4)

The system of claim 4, wherein the separator comprises air.

### Claim 6 (depends on 4)

The system of claim 4, wherein the controller is further programmed to actuate the driver to cause the control tube, after step (7) and before step (6), to (1a) draw an encapsulating liquid from an encapsulating-liquid input, then (3a) draw a sample liquid from a sample-liquid input, then (5a) draw additional encapsulating liquid, then (6a) discharge the encapsulating liquid of steps (1a) and (5a) with the sample liquid of step (3a) as a second unit from the control tube and onto the free surface of the carrier liquid in the carrier-liquid conduit, the second unit thereby forming a second composite liquid cell.

### Claim 7 (depends on 3)

The system of claim 3, wherein the controller is further programmed to actuate the driver to cause the control tube, after step (5) and before step (6), to (8) draw a second sample liquid from a second sample-liquid input, the second sample liquid being immiscible with the carrier liquid and the encapsulating liquid, then (9) draw additional encapsulating liquid, then (10) discharge the additional encapsulating liquid of step (9) and the second sample liquid into the unit, so that the composite liquid cell thereby formed comprises a droplet of the sample liquid and a droplet of the second sample liquid.

### Claim 8 (depends on 1)

The system of claim 1, wherein the liquid-handling system comprises a control tube and a driver, and the controller is programmed to actuate the driver to cause the control tube to carry out steps (1) through (4) in the order recited.

### Claim 9 (depends on 8)

The system of claim 8, wherein the controller is programmed to perform step (1), then repeat step (2) for a plurality of stabilization features, then perform step (3), then repeat step (4) for the plurality of stabilization features, thereby forming a plurality of composite liquid cells distributed among the stabilization features.

### Claim 10 (depends on 8)

The system of claim 8, wherein the controller is further programmed to actuate the driver to cause the control tube to (11) draw a reagent that is miscible with the sample liquid, and (12) discharge the reagent proximate to the discharged sample liquid.

### Claim 11 (depends on 1)

The system of claim 1, wherein (a) the carrier-liquid conduit comprises a bath sized to receive a disc rotatable therewithin upon a bath of carrier liquid; (b) the stabilisation feature is formed in the disc; (c) the system further comprises (1) a rotation driver operably coupled to the disc to cause it to rotate in the bath, and (2) a motion system that translates at least a discharging portion of the liquid-handling system vertically relative to the carrier-liquid conduit; and (d) the controller is operably connected to the rotation driver and to the motion system and is programmed to cause the rotation system to rotate the disc and to cause the motion system to translate the discharging portion of the liquid-handling system vertically relative to the disc.

### Claim 12 (depends on 11)

The system of claim 11, wherein the controller is further programmed to actuate the motion system to cause the control tube to move a composite liquid cell formed on the free surface of the carrier liquid relative to the carrier liquid conduit.

### Claim 13 (depends on 1)

The system of claim 1, wherein the controller is further programmed to cause the liquid-handling system to discharge sufficient encapsulating liquid between two composite liquid cells, formed on the free surface of the carrier liquid and separated by a gap, liquid to bridge the gap, thereby causing the two composite liquid cells to merge with one another.

### Claim 14 (depends on 1)

The system of claim 1, wherein the controller is programmed to cause the liquid-handling system to discharge the sample liquid of step (4) proximate to the discharged encapsulating liquid.

### Claim 15

A sample handling method, comprising:
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.