# US 11,078,521 B2 · Stabilization of nucleic acids on paper

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- Number: US 11,078,521 B2
- Document ID: US11078521B2
- Status: Granted
- Kind: B2
- Application number: 16/343,886
- Filed: 2017-10-24
- Published: 2019-08-29
- Granted: 2021-08-03
- Earliest claimed: 2016-10-24
- Assignees: Biomatrica, Inc.
- Applicants: Biomatrica, Inc.
- Inventors: Joel Desharnais; Daniela Roth; Vasco Liberal
- Web page: https://patentgrep.com/patent/US11078521B2

## CPC

- C12Q 1/6806: Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay (C12Q1/6804 takes precedence)
- C12M 1/00: Apparatus for enzymology or microbiology
- C12M 1/26: Inoculator or sampler
- C12M 1/34: Measuring or testing with condition measuring or sensing means, e.g. colony counters
- C12Q 1/68: involving nucleic acids
- C12Q 1/6809: Methods for determination or identification of nucleic acids involving differential detection
- B01L 3/5023: {with a sample being transported to, and subsequently stored in an absorbent for analysis}
- 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
- C12M: APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; {APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS}
- B01L: CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE

## Abstract

The present invention and embodiments thereof relates to compositions and methods for storage, stabilization and preservation of biological samples and/or nucleic acids on a solid matrix. Methods for extracting, collecting, and recovering the biological samples and/or nucleic acids from the solid matrix are also described.

## Claims

### Claim 1

A solid matrix for storing a biological sample, comprising:
a matrix material that is a non-dissolvable dry solid material;
a buffer impregnated in the matrix material in a substantially dry state or a dry state; and
at least one reducing agent and at least one antioxidant, but no denaturant or chelator;
wherein the biological sample comprises one or more nucleic acids.

### Claim 2 (depends on 1)

The solid matrix of claim 1, wherein the at least one reducing agent is impregnated in the matrix material in a substantially dry state.

### Claim 3 (depends on 2)

The solid matrix of claim 2, wherein the at least one reducing agent is dithiothreitol (DTT), 2-mercaptoethanol (2-ME), 2-mercaptoethylamine, or cysteine.

### Claim 4 (depends on 1)

The solid matrix of claim 1, wherein the at least one antioxidant is impregnated in the matrix material in a substantially dry state.

### Claim 5 (depends on 4)

The solid matrix of claim 4, wherein the at least one antioxidant is hydroquinone monomethyl ether (MEHQ), hydroquinone (HQ), or toluhydroquinone (THQ).

### Claim 6 (depends on 1)

The solid matrix of claim 1, wherein the non-dissolvable dry solid material is a cellulosic paper.

### Claim 7 (depends on 1)

The solid matrix of claim 1, wherein the buffer is selected from citric acid, tris(2-carboxyethyl)phosphine hydrochloride (TCEP-HCl), oxidized form of tris(2-carboxyethyl)phosphine hydrochloride (TCEPO-HCl), 2-amino-2-hydroxymethyl-propane-1,3-diol (Tris), 2-(N-morpholino)ethanesulfonic acid (MES), 3-(N-morpholino)propanesulfonic acid (MOPS), 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES), phosphate buffers, acetic acid, ascorbic acid, sulfosalicylic acid, formic acid, glycine, glycine-glycine, malic acid, and succinic acid.

### Claim 8 (depends on 1)

The solid matrix of claim 1, wherein the buffer has a pH of 2.0 to 8.0.

### Claim 9 (depends on 1)

The solid matrix of claim 1, wherein the biological sample is blood, serum, plasma, tissue, saliva, cells, synovial fluids, urine, or semen.

### Claim 10 (depends on 1)

A method for storing one or more biological samples, the method comprising:
contacting the solid matrix of claim 1 with a biological sample, wherein the biological sample comprises one or more nucleic acids;
drying the solid matrix containing the biological sample; and
storing the biological sample on the solid matrix in a substantially dry state or a dry state.

### Claim 11 (depends on 10)

The method of claim 10, further comprising recovering the biological sample from the solid matrix.

### Claim 12 (depends on 11)

The method of claim 11, further comprising extracting the nucleic acids from the biological sample.

### Claim 13 (depends on 10)

The method of claim 10, wherein the nucleic acids are extracted from the biological sample and stored on the solid matrix in a substantially dry state or a dry state.

### Claim 14 (depends on 13)

The method of claim 13, further comprising recovering the nucleic acids from the solid matrix.

### Claim 15 (depends on 10)

The method of claim 10, wherein the non-dissolvable dry solid material is a cellulosic paper.

### Claim 16 (depends on 10)

The method of claim 10, wherein the buffer is selected from citric acid, tris(2-carboxyethyl)phosphine hydrochloride (TCEP-HCl), oxidized form of tris(2-carboxyethyl)phosphine hydrochloride (TCEPO-HCl), 2-amino-2-hydroxymethyl-propane-1,3-diol (Tris), 2-(N-morpholino)ethanesulfonic acid (MES), 3-(N-morpholino)propanesulfonic acid (MOPS), 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES), phosphate buffers, acetic acid, ascorbic acid, sulfosalicylic acid, formic acid, glycine, glycine-glycine, malic acid, and succinic acid.

### Claim 17 (depends on 10)

The method of claim 10, wherein the buffer has a pH of 2.0 to 8.0.

### Claim 18 (depends on 10)

The method of claim 10, wherein the biological sample is blood, serum, plasma, tissue, saliva, cells, synovial fluids, urine, or semen.

### Claim 19 (depends on 10)

The method of claim 10, wherein the nucleic acids are RNA.

### Claim 20 (depends on 10)

The method of claim 10, wherein the nucleic acids are virus RNA.