# US 8,784,745 B2 · Methods for manipulating liquid substances in multi-chambered receptacles

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 8,784,745 B2
- Document ID: US8784745B2
- Status: Granted
- Kind: B2
- Application number: 13/925,047
- Filed: 2013-06-24
- Published: 2014-01-02
- Granted: 2014-07-22
- Earliest claimed: 2007-06-21
- Assignees: Gen-Probe Incorporated
- Applicants: Gen-Probe Incorporated
- Inventors: Norman C. Nelson; Gianluca Roma
- Web page: https://patentgrep.com/patent/US8784745B2

## CPC

- B01F 31/00: Mixers with shaking, oscillating, or vibrating mechanisms
- B01F 23/59: {Mixing systems, i.e. flow charts or diagrams}
- B01F 31/31: using receptacles with deformable parts, e.g. membranes, to which a motion is imparted
- B01F 31/65: the materials to be mixed being directly submitted to a pulsating movement, e.g. by means of an oscillating piston or air column
- B01F 33/30: Micromixers
- B01F 35/2131: {Colour or luminescence}
- B01L 3/502: {with fluid transport, e.g. in multi-compartment structures}
- B01L 3/502715: {characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces}
- B01L 3/502761: {specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads or physically stretching molecules}
- B01L 7/52: {with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples}
- B01L 7/525: {with physical movement of samples between temperature zones}
- C12N 15/1006: {by means of a solid support carrier, e.g. particles, polymers}
- C12Q 1/6806: Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay (C12Q1/6804 takes precedence)
- C12Q 1/6844: Nucleic acid amplification reactions
- G01N 1/44: Sample treatment involving radiation, e.g. heat
- G01N 21/01: Arrangements or apparatus for facilitating the optical investigation
- G01N 21/6428: {Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" (in vivo A61B5/00; immunoassay G01N33/53)}
- G01N 21/645: {Specially adapted constructive features of fluorimeters}
- G01N 35/0098: {involving analyte bound to insoluble magnetic carrier, e.g. using magnetic separation (magnetic particles used in immunoassays G01N33/54326; magnetic separation in general B03C)}
- B01F 2101/23: Mixing of laboratory samples e.g. in preparation of analysing or testing properties of materials
- B01F 2101/33: Mixing compost ingredients or organic waste
- B01L 3/50273: {characterised by the means or forces applied to move the fluids}
- B01L 3/505: {Flexible containers without fluid transport within}
- B01L 2200/0621: Control of the sequence of chambers filled or emptied
- B01L 2200/0647: Handling flowable solids, e.g. microscopic beads, cells, particles
- B01L 2200/0673: Handling of plugs of fluid surrounded by immiscible fluid
- B01L 2200/0689: Sealing
- B01L 2200/10: Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
- B01L 2200/14: Process control and prevention of errors
- B01L 2200/16: Reagents, handling or storing thereof
- B01L 2300/0816: Cards, e.g. flat sample carriers usually with flow in two horizontal directions
- B01L 2300/087: Multiple sequential chambers
- B01L 2300/0887: Laminated structure
- B01L 2300/123: Flexible; Elastomeric
- B01L 2300/1805: Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks
- B01L 2300/1822: using Peltier elements
- B01L 2300/1883: using thermal insulation
- B01L 2400/0457: passive flow or gravitation
- B01L 2400/0478: pistons
- B01L 2400/0481: squeezing of channels or chambers
- B01L 2400/0655: pinch valves
- B01L 2400/0677: phase change valves; Meltable, freezing, dissolvable plugs; Destructible barriers
- G01N 2021/6419: {Excitation at two or more wavelengths}
- G01N 2021/6421: {Measuring at two or more wavelengths}
- G01N 2021/6432: {Quenching}
- G01N 2021/6439: {with indicators, stains, dyes, tags, labels, marks}
- G01N 2021/6463: {Optics}
- G01N 2035/00544: {using fluid flow}
- G01N 2201/0627: Use of several LED's for spectral resolution
- Y10T 137/0391: Affecting flow by the addition of material or energy
- Y10T 436/143333: Saccharide [e.g., DNA, etc.]
- Y10T 436/25: including sample preparation
- Y10T 436/255: including use of a solid sorbent, semipermeable membrane, or liquid extraction
- B01F: MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING (mixing paints B44D3/06)
- B01L: CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- 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
- 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 receptacle having a plurality of interconnected chambers arranged to permit multiple process steps or processes to be performed independently or simultaneously. The receptacles are manufactured to separate liquid from dried reagents and to maintain the stability of the dried reagents. An immiscible liquid, such as an oil, is included to control loading of process materials, facilitate mixing and reconstitution of dried reagents, limit evaporation, control heating of reaction materials, concentrate solid support materials to prevent clogging of fluid connections, provide minimum volumes for fluid transfers, and to prevent process materials from sticking to chamber surfaces. The receptacles can be adapted for use in systems having a processing instrument that includes an actuator system for selectively moving fluid substances between chambers and a detector. The actuator system can be arranged to concentrate an analyte. The detector can be used to detect an optical signal emitted by contents of the receptacle.

## Claims

### Claim 1

A method of altering the temperature of a liquid substance contained in a chamber of a receptacle, the method comprising the steps of:
(a) forming a volume in a first chamber of a receptacle so that a flexible portion of a first chamber wall expands to contact a stationary thermal element positioned adjacent to the first chamber, wherein the volume comprises a liquid substance and a corresponding immiscible liquid, and wherein the immiscible liquid causes the flexible portion of the first chamber wall to expand to contact the thermal element to a greater extent than if the immiscible liquid was absent from the first chamber; and
(b) altering the temperature of the liquid substance in the first chamber by transmitting thermal energy between the thermal element and the volume.

### Claim 2 (depends on 1)

The method of claim 1, further comprising the step of closing the first chamber between steps (a) and (b), the first chamber remaining closed until a predetermined temperature of the volume is reached during step (b).

### Claim 3 (depends on 1)

The method of claim 1, wherein the liquid substance comprises a reagent for performing an assay in the receptacle.

### Claim 4 (depends on 3)

The method of claim 3, wherein the immiscible liquid is not reactive with any component of the assay.

### Claim 5 (depends on 1)

The method of claim 1, wherein the immiscible liquid is an oil.

### Claim 6 (depends on 5)

The method of claim 5, wherein the oil is a mineral oil.

### Claim 7 (depends on 1)

The method of claim 1, wherein the ratio of the immiscible liquid to the remainder of the volume in the chamber is up to about 10:1.

### Claim 8 (depends on 1)

The method of claim 1, wherein the receptacle comprises opposed members configured to define the first chamber and a second chamber.

### Claim 9 (depends on 8)

The method of claim 8, wherein at least one of the opposed members comprises a flexible sheet, such that the flexible sheet comprises the first chamber wall.

### Claim 10 (depends on 8)

The method of claim 8, wherein the receptacle comprises a second chamber wall, the first and second chamber walls having opposed flexible portions.

### Claim 11 (depends on 10)

The method of claim 10, wherein each of the opposed members comprises a flexible sheet, the flexible sheets comprising the first and second chamber walls.

### Claim 12 (depends on 10)

The method of claim 10, wherein the first chamber is defined by seals formed between the opposed members.

### Claim 13 (depends on 10)

The method of claim 10, further comprising, after step (b), the step of moving at least a portion of the volume from the first chamber to the second chamber of the receptacle.

### Claim 14 (depends on 13)

The method of claim 13, wherein one or more compressive forces are applied to the flexible portion of the second chamber wall to move the portion of the volume to the second chamber.

### Claim 15 (depends on 14)

The method of claim 14, wherein the compressive forces comprise one or more actuators having compression pads arranged to generally conform to the shape of the flexible portion of the second chamber wall.

### Claim 16 (depends on 15)

The method of claim 15, wherein the actuators are pneumatic actuators.

### Claim 17 (depends on 13)

The method of claim 13, wherein the portion of the volume is moved from the first chamber to the second chamber through an openable connection.

### Claim 18 (depends on 17)

The method of claim 17, wherein the openable connection is altered from a closed state to an open state prior to moving the portion of the volume into the second chamber.

### Claim 19 (depends on 18)

The method of claim 18, wherein the first and second chambers are adjacent to each other, and wherein the openable connection is an opening blocked by a burstable seal that is altered from the closed state to the open state when the substance-moving force is applied to the flexible portion of the first chamber.

### Claim 20 (depends on 19)

The method of claim 19, wherein the burstable seal is a heat seal.

### Claim 21 (depends on 15)

The method of claim 15, wherein the thermal element and the compression pads cooperate to adjust the temperature of the volume during step (b).

### Claim 22 (depends on 1)

The method of claim 1, wherein the thermal element comprises a heat transfer element formed from a thermally conductive material.

### Claim 23 (depends on 22)

The method of claim 22, wherein the thermally conductive material is formed from aluminum.

### Claim 24 (depends on 22)

The method of claim 22, wherein the thermal element further comprises a thermoelectric device in thermal contact with the heat transfer element.

### Claim 25 (depends on 24)

The method of claim 24, wherein the thermoelectric device is a Peltier device.

### Claim 26 (depends on 1)

The method of claim 1, wherein the temperature of the volume is elevated during step (b).