# US 10,370,650 B2 · System and method for collecting a sample of nucleic acid

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- Number: US 10,370,650 B2
- Document ID: US10370650B2
- Status: Granted
- Kind: B2
- Application number: 14/892,709
- Filed: 2014-05-23
- Published: 2016-04-07
- Granted: 2019-08-06
- Earliest claimed: 2013-05-24
- Assignees: Occam Biolabs, Inc.
- Applicants: Occam Biolabs, Inc.
- Inventors: Mingwei Qian
- Web page: https://patentgrep.com/patent/US10370650B2

## CPC

- C12N 15/1017: {by filtration, e.g. using filters, frits, membranes}
- B01L 3/502: {with fluid transport, e.g. in multi-compartment structures}
- B01L 3/508: {Rigid containers without fluid transport within}
- B65B 7/28: by applying separate preformed closures, e.g. lids, covers
- C12Q 1/6806: Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay (C12Q1/6804 takes precedence)
- B01L 2200/023: adapted for different sizes of tubes, tips or container
- B01L 2200/025: Align devices or objects to ensure defined positions relative to each other
- B01L 2200/0684: Venting, avoiding backpressure, avoid gas bubbles
- B01L 2200/0689: Sealing
- B01L 2200/185: Long distance transport, e.g. mailing
- B01L 2300/042: Caps; Plugs
- B01L 2300/046: Function or devices integrated in the closure
- B01L 2300/048: enabling gas exchange, e.g. vents
- B01L 2300/0681: Filter
- B01L 2300/0854: Double walls
- B01L 2300/105: using desiccants
- B01L 2400/0409: centrifugal forces
- B01L 2400/049: vacuum
- B01L 2400/0605: check valves
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- B01L: CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B65B: MACHINES, APPARATUS OR DEVICES FOR, OR METHODS OF, PACKAGING ARTICLES OR MATERIALS; UNPACKING (bundling and pressing devices for cigars A24C1/44; devices for tensioning and securing binders adapted to be supported by the article or articles to be bound B25B25/00; applying closure members to bottles, jars or similar containers B67B1/00-B67B6/00; concurrent cleaning, filling and closing of bottles B67C7/00; emptying bottles, jars, cans, casks, barrels or similar containers B67C9/00)
- 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

## Abstract

A system for collecting and shipping a sample of nucleic acid, the system comprising a receptacle, a removable cap for the receptacle having a breather port and sample connection port, and a filter column removably attached to the inside of the receptacle cap in fluid communication with the sample connection port and containing a substrate for collecting the nucleic acid. A sample collection container interlocks to the sample collection port. A shipping container, closeable by a lid, is configured to detach the filter column from the receptacle cap and contain the column for shipping. Methods for collecting samples using the system preferably include a dehydrating wash step, such as with ethanol, and placement of a dessicant in the shipping container, so that nucleic acid samples can be transported under ambient, non-climate-controlled conditions, with stability for at least up to 4 weeks, ideal for collecting samples from undeveloped regions.

## Claims

### Claim 1

A system for collecting a sample of nucleic acid, the system comprising:
a receptacle defining an internal volume;
a removable cap for the receptacle, the cap having an internal side facing the internal volume of the receptacle and an external side facing away from the internal volume, the cap comprising a breather port communicating between the internal side and the external side and a sample connection port communicating between the internal side and the external side, the sample connection port comprising a first interlocking component for releasably locking the sample connection port to a cooperating second interlocking component, the internal side of the cap comprising a connection interface in fluid communication with the sample connection port;
a filter column adapted to be removably attached to the connection interface of the receptacle cap, the filter column having an open first end, an open second end, and an internal passage therebetween containing a substrate for collecting the nucleic acid;
a sample collection container comprising the second interlocking component adapted to connect to the first interlocking component of the sample collection port in the receptacle cap;
a shipping container having an open end and defining a volume adapted to contain the filter column, the shipping container adapted to releasably engage the filter column for detaching it from the connection interface of the receptacle cap, the shipping container further comprising a removable lid for temporarily sealing the filter column within the shipping container.

### Claim 2 (depends on 1)

The collection system of claim 1, wherein the filter column substrate comprises a filter, a frit upstream of the filter, and a retaining ring downstream of the filter.

### Claim 3 (depends on 1)

The collection system of claim 1, wherein the sample connection port protrudes from the external side of the cap.

### Claim 4 (depends on 3)

The collection system of claim 3, wherein the sample connection port first interlocking component comprises one end of a Luer lock fitting.

### Claim 5 (depends on 1)

The collection system of claim 1, wherein the breather port protrudes from the external side of the cap.

### Claim 6 (depends on 1)

The collection system of claim 1 further comprising a vacuum chamber, the vacuum chamber having an internal portion adapted to be connected to a source of vacuum, an external portion having one or more wells, each well adapted to receive one of the receptacles, and one or more vacuum connection ports in communication with the internal portion of the chamber and adapted to be connected to the breather port of the receptacle via a flexible conduit.

### Claim 7 (depends on 1)

The collection system of claim 1, further comprising a desiccant in the shipping container.

### Claim 8 (depends on 1)

The collection system of claim 1, wherein the filter column comprises a first component of a threaded interface and the receptacle cap comprises a second component of the threaded interface.

### Claim 9 (depends on 8)

The collection system of claim 8 wherein the filter column further comprises a first member disposed on an external surface thereof adapted to be releasably engaged by a cooperating second member disposed on an internal surface of the shipping container, the second member adapted to transmit force to the first member when a torsional force is applied to the filter column in a direction for unscrewing the filter column from its threaded connection with the receptacle cap.

### Claim 10 (depends on 9)

The collection system of claim 9, wherein the first and second members each comprises tabs.

### Claim 11 (depends on 1)

The collection system of claim 1, further comprising a three-way port having a first port adapted to be disposed to the receptacle cap sample connection port, a second port adapted to be connected to the collection container, and a third port adapted to be connected to a fluid source containing a fluid for treating the sample after it has been collected.

### Claim 12 (depends on 11)

The collection system of claim 11, further comprising one or more containers of fluid adapted to be connected to the third port.

### Claim 13 (depends on 11)

The collection system of claim 11, wherein the collection container comprises a syringe and the three way port comprises a check valve adapted to exclusively permit flow from the collection container into the receptacle when a positive relative pressure exists between the sample collection container and the receptacle, and to exclusively permit flow from the fluid source into the collection container when a negative relative pressure exists between the sample collection container and the fluid source.

### Claim 14 (depends on 12)

The collection system of claim 12, wherein the fluid comprises a fluid for washing the sample.

### Claim 15 (depends on 14)

The collection system of claim 14, wherein the fluid comprises ethanol.

### Claim 16 (depends on 1)

The collection system of claim 1 further comprising a sample holder for receiving a plurality of filter columns and adapted to fit in a centrifuge for centrifuging the plurality of filter columns.

### Claim 17

A method for collecting a sample of nucleic acid, the method comprising the steps of:
(a) providing a collection system comprising
i) receptacle defining an internal volume;
ii) a removable cap for the receptacle, the cap having an internal side facing the internal volume of the receptacle and an external side facing away from the internal volume, the cap comprising a breather port communicating between the internal side and the external side and a sample connection port communicating between the internal side and the external side, the sample connection port comprising first means for releasably locking the sample connection port to cooperating second means, the internal side of the cap comprising a connection interface in fluid communication with the sample connection port;
iii) a filter column removably attached to the connection interface of the receptacle cap, the filter column having an open first end, an open second end, and an internal passage therebetween containing a substrate for collecting the nucleic acid;
iv) a sample collection container comprising the second means adapted to connect to the first means of the sample collection port receptacle cap;
v) a shipping container having an open end and defining a volume adapted to contain the filter column, the shipping container adapted to releasably engage the filter column for detaching it from the connection interface of the receptacle cap, the shipping container further comprising a removable lid for temporarily sealing the filter column within the shipping container;
(b) collecting a volume of sample-containing fluid in the sample collection container;
(c) connecting the sample collection container to the receptacle via the sample collection port;
(d) passing the volume of sample-containing fluid from the sample collection container through the filter column, thereby collecting the sample on the substrate and collecting a reminder in the receptacle;
(e) placing the shipping container open end over the filter column, engaging the filter column with the shipping container, and detaching the filter column from the receptacle cap;
(f) temporarily sealing the shipping container with the removable lid.

### Claim 18 (depends on 17)

The method claim 17, wherein the sample-containing fluid comprises a lysate comprising an extract of bodily fluid collected from a patient.

### Claim 19 (depends on 17)

The method of claim 17, wherein the sample collection container comprises a syringe and the method of passing the volume through the filter column comprises manually applying pressure to a plunger of the syringe.

### Claim 20 (depends on 17)

The method of claim 17, wherein the sample collection container comprises a syringe, and the method of passing the volume through the filter column comprises attaching the breather port of the receptacle cap to a source of vacuum, and then applying a negative pressure across the filter column using the vacuum source.

### Claim 21 (depends on 17)

The method of claim 17, further comprising treating the collected sample on the substrate after step (d) by passing one or more volumes of fluid through the filter column before performing step (e).

### Claim 22 (depends on 21)

The method of claim 21, wherein the treatment fluid comprises a washing fluid.

### Claim 23 (depends on 22)

The method of claim 22, wherein the washing fluid comprises 100% ethanol or 100% acetone.

### Claim 24 (depends on 23)

The method of claim 23, wherein the washing fluid comprises 1-10 ml of 100% ethanol.

### Claim 25 (depends on 24)

The method of claim 24, wherein the washing fluid comprises at least 2 ml of 100% ethanol.

### Claim 26 (depends on 25)

The method of claim 25, wherein the washing fluid comprises 2-6 ml of 100% ethanol.

### Claim 27 (depends on 23)

The method of claim 23, further comprising placing a desiccant in the shipping container.

### Claim 28 (depends on 27)

The method of claim 27, further comprising transporting the shipping container under ambient, non-climate-controlled conditions.

### Claim 29 (depends on 28)

The method of claim 28, further comprising further processing the nucleic acid after a period of time up to 4 weeks after completion of step (f).

### Claim 30 (depends on 29)

The method of claim 29, wherein the further processing comprises processing of the nucleic acid for detection of a disease.

### Claim 31 (depends on 30)

The method of claim 30, wherein the disease is tuberculosis.

### Claim 32 (depends on 31)

The method of claim 31, wherein the processing is for detection of latent tuberculosis.

### Claim 33 (depends on 17)

The method of claim 17, wherein the sample-containing fluid comprises plasma or serum.

### Claim 34 (depends on 33)

The method of claim 33, wherein the volume of sample-containing fluid collected is in a range of 1-20 ml.

### Claim 35 (depends on 34)

The method of claim 34, wherein the volume of sample-containing fluid collected is at least 2 ml.

### Claim 36 (depends on 35)

The method of claim 35, wherein the volume of sample-containing fluid collected is in a range of 2-10 ml.

### Claim 37 (depends on 36)

The method of claim 36, wherein the volume of sample-containing fluid collected is in a range of 2-5 ml.