# US 10,870,884 B2 · Honeycomb tube

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- Number: US 10,870,884 B2
- Document ID: US10870884B2
- Status: Granted
- Kind: B2
- Application number: 15/890,154
- Filed: 2018-02-06
- Published: 2018-08-30
- Granted: 2020-12-22
- Earliest claimed: 2012-09-26
- Assignees: Cepheid
- Applicants: Cepheid
- Inventors: Yuh-Min Chiang; Doug Dority; Dustin Dickens; Jennifer Glass; Reuel Van Atta
- Web page: https://patentgrep.com/patent/US10870884B2

## CPC

- C12Q 1/6876: Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
- B01L 3/502: {with fluid transport, e.g. in multi-compartment structures}
- B01L 3/5027: {by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip}
- B01L 3/50851: {specially adapted for heating or cooling samples}
- B01L 7/52: {with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples}
- B01L 2200/0642: Filling fluids into wells by specific techniques
- B01L 2200/0673: Handling of plugs of fluid surrounded by immiscible fluid
- B01L 2300/0636: Integrated biosensor, microarrays
- B01L 2300/0819: Microarrays; Biochips
- B01L 2400/0406: capillary forces
- B01L 2400/0487: fluid pressure, pneumatics
- 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
- B01L: CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE

## Abstract

A honeycomb tube with a planar frame defining a fluidic path between a first planar surface and a second planar surface. A fluidic interface is located at one end of the planar frame. The fluidic interface has a fluidic inlet and fluidic outlet. The fluidic path further includes a well chamber having an well-substrate with a plurality of wells. The well chamber is arranged in the planar frame between the first or second surface and the well-substrate. The well chamber is in fluidic communication between the pre-amplification chamber and the fluidic outlet.

## Claims

### Claim 1

A method comprising:
providing a reaction tube, wherein the reaction tube comprises a frame, a first substrate, and a second substrate, wherein a fluidic path is defined between the first substrate and the second substrate by the frame, and wherein the fluidic path comprises a pre-amplification chamber and a well chamber having a plurality of wells;
providing a liquid sample to a fluidic interface of the fluidic path;
advancing the liquid sample through the fluidic path from the fluidic interface to the pre-amplification chamber and amplifying the liquid sample in the pre-amplification chamber;
advancing the amplified liquid sample through the fluidic path from the pre-amplification chamber to the well chamber such that at least a first portion of the amplified liquid sample occupies the plurality of wells of the well chamber; and
evacuating at least a second portion of the amplified liquid sample, distinct from the first portion of the liquid sample, from the well chamber such that the plurality of wells remain occupied with at least the first portion of the amplified liquid sample.

### Claim 2 (depends on 1)

The method of claim 1, wherein the frame extends between a first end and a second end opposite the first end,
wherein the fluidic interface is disposed along the first end of the reaction tube,
wherein the fluidic interface comprises a fluidic inlet and a fluidic outlet of the fluidic path,
wherein the pre-amplification chamber includes an upper-most exit of the pre-amplification chamber when the first substrate and the second substrate are vertically oriented and with the fluidic outlet positioned above the fluidic inlet while advancing the liquid sample to the well chamber, and
wherein the pre-amplification chamber is filled at a level below the pre-amplification exit with the fluidic outlet positioned above the fluidic inlet.

### Claim 3 (depends on 2)

The method of claim 2, wherein the pre-amplification chamber exit is fluidly connected to a well chamber entrance via a downward leading passage.

### Claim 4 (depends on 3)

The method of claim 3, wherein the fluidic path is valveless.

### Claim 5 (depends on 1)

The method of claim 1, further comprising filling the evacuated well chamber with a hydrophobic substance after evacuating the at least a second portion of the amplified liquid sample from the well chamber.

### Claim 6 (depends on 5)

The method of claim 5, wherein the hydrophobic substance is supplied from an oil chamber of the frame.

### Claim 7 (depends on 1)

The method of claim 1, further comprising applying heating and cooling cycles to the first substrate and the second substrate after evacuating the at least a second portion of the amplified liquid sample from the well chamber.

### Claim 8

A method comprising:
providing a reaction tube, wherein the reaction tube comprises a planar frame defining a fluidic path between a first planar substrate and a second planar substrate, wherein the planar frame extends lengthwise between a first end and a second end opposite the first end, a fluidic interface disposed along the first end of the reaction tube, the fluidic interface comprising a fluidic inlet and a fluidic outlet of the fluidic path;
introducing a liquid sample through the fluidic inlet of the fluidic interface of the reaction tube, while the reaction tube oriented vertically with the fluidic outlet disposed above the fluidic inlet, and advancing the liquid sample along the fluidic path via application of pressure to the fluidic inlet or the fluidic outlet of the fluidic interface;
filling a well chamber along the fluidic path with the liquid sample by further advancing the liquid sample along the fluidic path, with the reaction tube oriented vertically with the fluidic outlet disposed above the fluidic inlet, thereby depositing the liquid sample within a plurality of wells of the well chamber; and
evacuating at least a portion of the liquid sample from the well chamber outside of the plurality of wells via application of pressure to the fluidic inlet or the fluidic outlet of the fluidic interface, with the reaction tube oriented vertically with the fluidic outlet disposed above the fluidic inlet, such that at least some of the liquid sample remains deposited within the plurality of wells.

### Claim 9 (depends on 8)

The method of claim 8, wherein the fluidic path is valveless.

### Claim 10 (depends on 8)

The method of claim 8, further comprising:
filling the well chamber with a hydrophobic fluid substance after the evacuating the at least a portion of the liquid sample from the well chamber outside of the plurality of wells.

### Claim 11 (depends on 10)

The method of claim 10, wherein the hydrophobic fluid substance is supplied from an oil chamber of the planar frame that is in fluid communication with the well chamber, wherein the hydrophobic fluid substance comprises an oil.

### Claim 12 (depends on 9)

The method of claim 9, wherein application of pressure comprises applying a positive or negative pressure via the fluidic inlet or the fluidic outlet of the fluidic interface.

### Claim 13 (depends on 9)

The method of claim 9, wherein the well chamber is disposed along the second end of the reaction tube.

### Claim 14 (depends on 9)

The method of claim 9, wherein the fluidic path further includes a pre-amplification chamber comprising an enlarged portion of the fluidic path, the method further comprising:
advancing the liquid sample through the fluidic path from the fluidic interface to the pre-amplification chamber, while the reaction tube is oriented vertically with the fluidic outlet above the fluidic inlet, and amplifying the liquid sample in the pre-amplification chamber; and
advancing the amplified liquid sample through the fluidic path from the pre-amplification chamber to the well chamber, while the reaction tube is oriented vertically with the fluidic outlet above the fluidic inlet, such that at least a first portion of the amplified liquid sample occupies a plurality of wells of the well chamber.

### Claim 15 (depends on 14)

The method of claim 14, wherein the pre-amplification chamber includes an upper-most exit of the pre-amplification chamber when the reaction tube is vertically oriented with the fluidic outlet positioned above the fluidic inlet while advancing the liquid sample to the well chamber.

### Claim 16 (depends on 15)

The method of claim 15, wherein the pre-amplification chamber is filled at a level below the pre-amplification exit when the reaction tube is oriented vertically with the fluidic outlet positioned above the fluidic inlet.

### Claim 17 (depends on 15)

The method of claim 15, wherein the pre-amplification chamber exit is fluidly connected to a well chamber entrance via a downward leading passage.