# US 10,767,226 B2 · Honeycomb tube

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- Number: US 10,767,226 B2
- Document ID: US10767226B2
- Status: Granted
- Kind: B2
- Application number: 16/230,458
- Filed: 2018-12-21
- Published: 2019-07-11
- Granted: 2020-09-08
- Earliest claimed: 2012-09-26
- Assignees: Cepheid
- Applicants: Cepheid
- Inventors: Yuh-Min Chiang; Douglas B Dority; Dustin Dickens; Jennifer Glass; Reuel Van Atta
- Web page: https://patentgrep.com/patent/US10767226B2

## 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.

## Claims

### Claim 1

A reaction tube comprising:
a planar frame defining a fluidic path between a first planar substrate that encloses a first side of the planar frame and a second planar substrate that encloses a second side of the planar frame;
a fluidic interface disposed at one end of the planar frame, the fluidic interface comprising a fluidic inlet of the fluidic path and fluidic outlet of the fluidic path;
wherein the fluidic path further includes a well chamber including a well-substrate configured with a plurality of wells, the well chamber being arranged in the planar frame between the first substrate and a well-substrate on or within the second substrate, the well chamber being in fluidic communication between the fluidic inlet and the fluidic outlet and in fluid communication with the fluidic inlet and the fluidic outlet;
wherein the well-substrate is planar and configured with a plurality of wells that open on one-side of the well-substrate into the well chamber;
wherein the fluidic path includes an inlet passage extending from the fluidic inlet and in fluid communication with the well chamber and an outlet passage in fluid communication with the well chamber and extending to the fluidic outlet; and
wherein fluidic path further includes an intermediate channel between the inlet passage and the well chamber, wherein the intermediate channel includes a plurality of elongated channel portions connected in a serpentine manner.

### Claim 2 (depends on 1)

The reaction tube of claim 1, wherein the fluidic path includes a pre-amplification chamber arranged in the planar frame between the first and second planar substrates, wherein the pre-amplification chamber is an enlarged portion of the fluidic path between the fluidic inlet and the well-chamber that is sized such that a fluid sample introduced through the fluidic inlet, when the first and second planar substrates are vertically oriented with the fluidic outlet above the fluidic inlet, is maintained within the pre-amplification chamber to allow pre-amplification of the fluid sample before the fluid sample fills the well-chamber.

### Claim 3 (depends on 2)

The reaction tube of claim 2, wherein the pre-amplification chamber includes a pre-amplification chamber exit that exits the pre-amplification chamber and is in fluidic communication with a well chamber entrance that enters the well chamber.

### Claim 4 (depends on 3)

The reaction tube of claim 3, further comprising:
an intermediate passage of the fluidic path extending between the pre-amplification chamber exit and the well chamber entrance, wherein the pre-amplification chamber exit is separated from the well chamber entrance by the intermediate passage.

### Claim 5 (depends on 4)

The reaction tube of claim 4, wherein the pre-amplification chamber exit positioned at an upper-most portion of the pre-amplification chamber when the first and second planar substrates are vertically orientated with the fluidic outlet disposed directly above the fluidic inlet.

### Claim 6 (depends on 5)

The reaction tube of claim 5, wherein the well chamber entrance is positioned at a lower-most portion of the well chamber when the first and second planar substrates are vertically oriented with the fluidic outlet above the fluidic inlet.

### Claim 7 (depends on 6)

The reaction tube of claim 6, wherein the well chamber entrance is positioned beneath the pre-amplification chamber when the first and second planar substrates are vertically oriented with the fluidic outlet above the fluidic inlet.

### Claim 8 (depends on 7)

The reaction tube of claim 7, wherein the passage slopes downward from the pre-amplification chamber exit to the well chamber entrance when the first and second planar substrates are vertically oriented with the fluidic outlet above the fluidic inlet.

### Claim 9 (depends on 1)

The reaction tube of claim 1, wherein the fluidic path comprises a serpentine channel.

### Claim 10 (depends on 1)

The reaction tube of claim 1, wherein the fluidic path is valveless.

### Claim 11 (depends on 1)

The reaction tube of claim 1, wherein the well-substrate comprises 100-1000 nanowells.

### Claim 12 (depends on 1)

The reaction tube of claim 1, wherein the well-substrate comprises a plurality of wells having a depth of about 100 to about 500 μm.

### Claim 13 (depends on 1)

The reaction tube of claim 1, wherein the well-substrate comprises a plurality of wells having a diameter of about 50 to about 500 μm.

### Claim 14 (depends on 1)

The reaction tube of claim 1, wherein the well-substrate comprises a plurality of 0.8 nl capacity wells.

### Claim 15 (depends on 1)

The reaction tube of claim 1, wherein a portion of the planar frame defines an oil chamber disposed along the flowpath and configured for holding a hydrophobic substance, wherein the oil chamber is separate from the well chamber.

### Claim 16 (depends on 15)

The reaction tube of claim 15, wherein the oil chamber is in fluidic communication with the well chamber.

### Claim 17 (depends on 1)

The reaction tube of claim 1, wherein the planar frame comprises a scaffold extending from a base portion, the base portion comprising the fluidic interface.

### Claim 18 (depends on 17)

The reaction tube of claim 17, wherein the first and second planar substrates comprise first and second films that fluidically seal the scaffold and the well chamber having the well-substrate disposed therein.

### Claim 19 (depends on 1)

The reaction tube of claim 1, wherein the fluidic interface is configured to fluidically and mechanically couple with a sample container so as to cantilever a majority of the planar frame when mechanically coupled with the sample container.

### Claim 20 (depends on 1)

The reaction tube of claim 1, wherein the well-substrate comprises a nickel material.

### Claim 21 (depends on 1)

The reaction tube of claim 1, wherein the fluidic interface is integrally formed with the planar frame.

### Claim 22 (depends on 1)

The reaction tube of claim 1, wherein the second substrate is integrally formed with the planar frame.

### Claim 23 (depends on 22)

The reaction tube of claim 22, wherein the well-substrate is an integral portion of the second substrate.

### Claim 24 (depends on 1)

The reaction tube of claim 1, wherein the well-substrate is a separate component attached to the second substrate.

### Claim 25 (depends on 1)

The reaction tube of claim 1, wherein the plurality of elongated channel portions includes between two and ten elongated channels extending at least partly in opposing directions from each other.

### Claim 26 (depends on 1)

The reaction tube of claim 1, wherein the flowpath is without any enlarged chamber for pre-amplification between the fluidic inlet and the well chamber.