US2014065627A1PendingUtilityA1
Compositions and methods for biological sample storage
Est. expiryMay 11, 2029(~2.8 yrs left)· nominal 20-yr term from priority
A01N 1/128A01N 1/00C12Q 1/6806
59
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Claims
Abstract
Compositions and methods are disclosed for substantially dry storage at ambient or elevated temperatures of biological samples such as nucleic acids, proteins and cells in a form from which the samples can be substantially recovered, using a dissolvable or dissociable dry storage matrix comprising a borate composition and a stabilizer as disclosed, such as any of a number of zwitterionic stabilizers.
Claims
exact text as granted — not AI-modifiedWhat is claimed is:
1 . A matrix for substantially dry storage of a biological sample, comprising:
(a) a borate composition; and (b) at least one stabilizer that is selected from the group consisting of:
(i) a compound of formula I:
wherein R 1 , R 2 , R 3 are independently selected from aryl, arylalkyl, —H, —CH 3 and —CH 2 —CH 3 , wherein when R 1 and R 2 are CH 3 or CH 2 —CH 3 , R 3 is either H or absent, wherein X is selected from —CH 2 —, —CH 2 CH 2 —, —CH 2 CH 2 CH 2 —, —CH 2 CH 2 CH 2 CH 2 —,
and wherein Y is selected from COO − and SO 3 − ;
(ii) a compound of formula II:
wherein R 1 is selected from CH 3 and CH 2 CH 3 , and wherein when X is CH, Y is selected from H and OH, and when X is CH 2 —CH, Y is H;
(iii) a compound of formula III:
wherein R 1 and R 2 are independently selected from —H, —CH 3 , and —CH 2 CH 3 , and wherein X is selected from H, OH and SH;
(iv) a compound of formula IV:
wherein R 1 is selected from aryl, arylaklyl, —H, —CH 3 —CH 2 —CH 3 , —CH 2 CH 2 OH, CH 2 CHOHCH 3 , CH 2 CHOHCH 2 OH, and CH 2 CH 2 CH 2 OH,
wherein X is selected from —CH 2 —, —CH 2 CH 2 —, —CH 2 CHOH, —CH 2 CH 2 CH 2 —, CH 2 CH 2 CH 2 CH 2 , CH 2 CHOHCH 2 and —CH 2 CHOHCHOHCH 2 —,
wherein Y is selected from COO − and SO 3 − ,
and wherein Z is selected from —CH 2 —, —CHOH—, O and S;
(v) a compound of formula V:
wherein R 1 and R 2 are each independently selected from aryl, arylaklyl, —H, —CH 3 —CH 2 —CH 3 , —CH 2 CH 2 OH, CH 2 CHOHCH 3 , CH 2 CHOHCH 2 OH; and CH 2 CH 2 CH 2 OH,
(vi) a compound of formula VI:
wherein R 1 and R 2 are each independently selected from aryl, arylakyl, —H, —CH 3 —CH 2 —CH 3 , —CH 2 CH 2 OH, CH 2 CHOHCH 3 , CH 2 CHOHCH 2 OH, and CH 2 CH 2 CH 2 OH;
(vii) a compound of formula VII:
wherein R 1 is selected from aryl, arylalkyl, —H, —CH 3 —CH 2 —CH 3 , —CH 2 CH 2 OH, CH 2 CHOHCH 3 , CH 2 CHOHCH 2 OH, and CH 2 CH 2 CH 2 OH,
wherein X is selected from —CH 2 —, —CH 2 CH 2 —, —CH 2 CHOH, —CH 2 CH 2 CH 2 —, —CH 2 CH 2 CH 2 CH 2 —, —CH 2 CHOHCH 2 —, and —CH 2 CHOHCHOHCH 2 —,
wherein Y is selected from CO 2 − and SO 3 − ,
and wherein Z is selected from CH 2 , CHOH, O and S; and
(viii) an osmoprotectant compound that is selected from the group consisting of trimethylammonium acetate, glycerol phosphate, diglycerol phosphate, N-(2-hydroxy-1,1-bis(hydroxymethyl)ethyl)glycine (tricine), 3-(N-morpholino)-2-hydroxypropanesulfonic acid (MOPSO), pentaerythritol, glyceric acid, malic acid, tartaric acid, lactic acid, glycolic acid, 2-hydroxybutyric acid, 3-hydroxybutyric acid, 4-amino-3-hydroxybutyric acid, 3-(1-azoniabicyclo[2.2.2]oct-1-yl)propane-1-sulfonate, and 1-(2-carboxylatoethyl)-1-azabicyclo[2.2.2]octan-1-ium,
wherein the borate composition and the stabilizer are present at a molar ratio that is selected from a molar ratio of from about 10:1 to about 1:10, a molar ratio of from about 5:1 to about 1:5, and a molar ratio of from about 20:1 to about 1:20,
and wherein the matrix is capable of preventing degradation of an isolated DNA fragment of at least 10 kilobases during substantially dry storage of the DNA fragment in the matrix at 85° C. for a time period of at least two weeks.
2 . The matrix of claim 1 wherein the time period is selected from at least four weeks, at least eight weeks, at least 12 weeks, at least 16 weeks, at least 20 weeks, at least 24 weeks, at least 30 weeks, at least 36 weeks, at least 40 weeks, at least 48 weeks, and at least one year.
3 . The matrix of claim 1 wherein the borate composition comprises at least one compound selected from the group consisting of boric acid, dihydrogen borate, hydrogen borate, diborate, triborate, tetraborate, metaborate, hydroxoborate (borax), borate salt, boric acid-glycerol, boric anhydride (B 2 O 3 ) and boric-acid-1,3 propanediol.
4 . The matrix of claim 1 wherein the stabilizer is selected from the group consisting of hydroxyectoine, ectoine, homoectoine, betaine, L-carnitine, sarcosine, N,N-dimethylglycine, triethylammonium acetate, glycerol phosphate, N-(2-Hydroxy-1,1-bis(hydroxymethyl)ethyl)glycine (tricine), 3-(N-Morpholino)-2-hydroxypropanesulfonic acid (MOPSO), pentaerythritol, N-ethyl-N,N-bis-(2-hydroxyethyl)ammonium-N-4-butyl sulfonate, glycolic acid, lactic acid, malic acid, tartaric acid, 2-hydroxybutyric acid, 3-hydroxybutyric acid, 4-amino-3-hydroxybutyric acid, pyridine 2,5-dicarboxylic acid, 3-(1-azoniabicyclo[2.2.2]oct-1-yl)propane-1-sulfonate, 1-(2-carboxylatoethyl)-1-azabicyclo[2.2.2]octan-1-ium, and 4-[benzyl(2-hydroxyethyl)methylazaniumyl]butane-1-sulfonate.
5 . The matrix of claim 1 , further comprising a chelator.
6 . The matrix of claim 5 wherein the chelator is selected from the group consisting of ethylenediaminetetraacetic acid (EDTA), ethylene glycol tetraacetic acid (EGTA), diethylenetriaminepentaacetic acid (DTPA), trans-1,2-diaminocyclohexane-N,N,N′,N′-tetraacetic acid (CDTA), 1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid (BAPTA), 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), N-(2-hydroxyethyl)ethylenediamine-N,N′,N′-triacetic acid, and nitrilotriacetic acid (NTA).
7 . The matrix of claim 1 which dissolves or dissociates in a biocompatible solvent.
8 . The matrix of claim 7 which dissolves in a biocompatible solvent.
9 . The matrix of claim 7 wherein the biocompatible solvent comprises water.
10 . The matrix of claim 9 wherein the biocompatible solvent comprises a pH buffer.
11 . The matrix of claim 10 wherein the pH buffer is selected from the group consisting of Tris, citrate, acetate, phosphate, borate, CAPS, CAPSO, HEPES, MES, MOPS, MOPSO, PIPES, carbonate and bicarbonate.
12 . The matrix of any one of claims 1 and 3 - 5 , further comprising a biological inhibitor or a biochemical inhibitor.
13 . A matrix for substantially dry storage of a biological sample, comprising:
(a) a borate composition which comprises at least one compound selected from the group consisting of boric acid, boric anhydride, dihydrogen borate, hydrogen borate, diborate, triborate, tetraborate, metaborate, hydroxoborate (borax), borate salt, boric acid-glycerol and boric-acid-1,3 propanediol; (b) at least one stabilizer that is selected from the group consisting of:
(i)
wherein R 1 , R 2 , R 3 are independently selected from aryl, arylalkyl, —H, —CH 3 or —CH 2 —CH 3 , wherein when R 1 and R 2 are CH 3 or CH 2 —CH 3 , R 3 may be absent or H, wherein X is selected from —CH 2 —, —CH 2 CH 2 —, —CH 2 CH 2 CH 2 —,
and wherein Y is selected from COO − and SO 3 − ;
(ii)
wherein R 1 is CH 3 or CH 2 CH 3 , and wherein when X is CH, Y is H or OH, and when X is CH 2 —CH, Y is H;
(iii)
wherein R 1 and R 2 are independently selected from —H, —CH 3 , and —CH 2 CH 3 , and wherein X is H, OH, or SH;
(iv) a compound of formula IV:
wherein R 1 is selected from aryl, arylaklyl, —H, —CH 3 —CH 2 —CH 3 , —CH 2 CH 2 OH, CH 2 CHOHCH 3 , CH 2 CHOHCH 2 OH, and CH 2 CH 2 CH 2 OH,
wherein X is selected from —CH 2 —, —CH 2 CH 2 —, —CH 2 CHOH, —CH 2 CH 2 CH 2 —, CH 2 CH 2 CH 2 CH 2 , CH 2 CHOHCH 2 and —CH 2 CHOHCHOHCH 2 —,
wherein Y is selected from COO − and SO 3 − ,
and wherein Z is selected from —CH 2 —, —CHOH—, O and S;
(v) a compound of formula V:
wherein R 1 and R 2 are each independently selected from aryl, arylaklyl, —H, —CH 3 —CH 2 —CH 3 , —CH 2 CH 2 OH, CH 2 CHOHCH 3 , CH 2 CHOHCH 2 OH; and CH 2 CH 2 CH 2 OH,
(vi) a compound of formula VI:
wherein R 1 and R 2 are each independently selected from aryl, arylakyl, —H, —CH 3 —CH 2 —CH 3 , —CH 2 CH 2 OH, CH 2 CHOHCH 3 , CH 2 CHOHCH 2 OH, and CH 2 CH 2 CH 2 OH;
(vii) a compound of formula VII:
wherein R 1 is selected from aryl, arylalkyl, —H, —CH 3 —CH 2 —CH 3 , —CH 2 CH 2 OH, CH 2 CHOHCH 3 , CH 2 CHOHCH 2 OH, and CH 2 CH 2 CH 2 OH,
wherein X is selected from —CH 2 —, —CH 2 CH 2 —, —CH 2 CHOH, —CH 2 CH 2 CH 2 —, —CH 2 CH 2 CH 2 CH 2 —, —CH 2 CHOHCH 2 —, and —CH 2 CHOHCHOHCH 2 —,
wherein Y is selected from CO 2 − and SO 3 − ,
and wherein Z is selected from CH 2 , CHOH, O and S; and
(viii) an osmoprotectant compound that is selected from the group consisting of trimethylammonium acetate, glycerol phosphate, diglycerol phosphate, N-(2-hydroxy-1,1-bis(hydroxymethyl)ethyl)glycine (tricine), 3-(N-morpholino)-2-hydroxypropanesulfonic acid (MOPSO), pentaerythritol, glyceric acid, malic acid, tartaric acid, lactic acid, glycolic acid, 2-hydroxybutyric acid, 3-hydroxybutyric acid, 4-amino-3-hydroxybutyric acid, 3-(1-azoniabicyclo[2.2.2]oct-1-yl)propane-1-sulfonate, and 1-(2-carboxylatoethyl)-1-azabicyclo[2.2.2]octan-1-ium,
wherein the borate composition and the stabilizer are present at a molar ratio that is selected from a molar ratio of from about 10:1 to about 1:10, a molar ratio of from about 5:1 to about 1:5, and a molar ratio of from about 20:1 to about 1:20,
and wherein the matrix is capable of preventing degradation of an isolated DNA fragment of at least 10 kilobases during substantially dry storage of the DNA fragment in the matrix at 85° C. for a time period of at least two weeks.
14 . The matrix of either claim 1 or claim 13 wherein the biological sample comprises at least one of
(i) an isolated biomolecule that is selected from the group consisting of a nucleic acid, a protein, a polypeptide, a lipid, a glyconconjugate, an oligosaccharide, and a polysaccharide, and
(ii) a biological material that is selected from the group consisting of a mammalian cell, a bacterium, a yeast cell, a virus, a vaccine, blood, urine, a biological fluid, and a buccal swab.
15 . The matrix of either claim 1 or claim 13 wherein the biological sample comprises at least one isolated nucleic acid that is selected from DNA and RNA.
16 . The matrix of claim 12 wherein the biological inhibitor or biochemical inhibitor is selected from the group consisting of a reducing agent, an alkylating agent, an antifungal agent and an antimicrobial agent.
17 . The matrix of either claim 1 or claim 13 which comprises at least one detectable indicator.
18 . The matrix of claim 17 wherein the detectable indicator comprises a dye or a colorimetric indicator.
19 . The matrix of claim 17 wherein the detectable indicator is selected from the group consisting of phenol red, ethidium bromide, a DNA polymerase, a restriction endonuclease, cobalt chloride, Reichardt's dye and a fluorogenic protease substrate.
20 . A method of storing a biological sample, comprising:
contacting a biological sample with a matrix for substantially dry storage of a biological sample, the matrix comprising (a) a borate composition; and (b) at least one stabilizer that is selected from the group consisting of:
(i)
wherein R 1 , R 2 , R 3 are independently selected from aryl, arylalkyl, —H, —CH 3 or —CH 2 —CH 3 , wherein when R 1 and R 2 are CH 3 or CH 2 —CH 3 , R 3 may be absent or H, wherein X is selected from —CH 2 —, —CH 2 CH 2 —, —CH 2 CH 2 CH 2 —,
and wherein Y is selected from COO − and SO 3 − ;
(ii)
wherein R 1 is CH 3 or CH 2 CH 3 , and wherein when X is CH, Y is H or OH, and when X is CH 2 —CH, Y is H;
(iii)
wherein R 1 and R 2 are independently selected from —H, —CH 3 , and —CH 2 CH 3 , and wherein X is H, OH, or SH;
(iv) a compound of formula IV:
wherein R 1 is selected from aryl, arylaklyl, —H, —CH 3 —CH 2 —CH 3 , —CH 2 CH 2 OH, CH 2 CHOHCH 3 , CH 2 CHOHCH 2 OH, and CH 2 CH 2 CH 2 OH,
wherein X is selected from —CH 2 —, —CH 2 CH 2 —, —CH 2 CHOH, —CH 2 CH 2 CH 2 —, CH 2 CH 2 CH 2 CH 2 , CH 2 CHOHCH 2 and —CH 2 CHOHCHOHCH 2 —,
wherein Y is selected from COO − and SO 3 − ,
and wherein Z is selected from —CH 2 —, —CHOH—, O and S;
(v) a compound of formula V:
wherein R 1 and R 2 are each independently selected from aryl, arylaklyl, —H, —CH 3 —CH 2 —CH 3 , —CH 2 CH 2 OH, CH 2 CHOHCH 3 , CH 2 CHOHCH 2 OH; and CH 2 CH 2 CH 2 OH,
(vi) a compound of formula VI:
wherein R 1 and R 2 are each independently selected from aryl, arylakyl, —H, —CH 3 —CH 2 —CH 3 , —CH 2 CH 2 OH, CH 2 CHOHCH 3 , CH 2 CHOHCH 2 OH, and CH 2 CH 2 CH 2 OH;
(vii) a compound of formula VII:
wherein R 1 is selected from aryl, arylalkyl, —H, —CH 3 —CH 2 —CH 3 , —CH 2 CH 2 OH, CH 2 CHOHCH 3 , CH 2 CHOHCH 2 OH, and CH 2 CH 2 CH 2 OH,
wherein X is selected from —CH 2 —, —CH 2 CH 2 —, —CH 2 CHOH, —CH 2 CH 2 CH 2 —, —CH 2 CH 2 CH 2 CH 2 —, —CH 2 CHOHCH 2 —, and —CH 2 CHOHCHOHCH 2 —,
wherein Y is selected from CO 2 − and SO 3 − ,
and wherein Z is selected from CH 2 , CHOH, O and S; and
(viii) an osmoprotectant compound that is selected from the group consisting of trimethylammonium acetate, glycerol phosphate, diglycerol phosphate, N-(2-hydroxy-1,1-bis(hydroxymethyl)ethyl)glycine (tricine), 3-(N-morpholino)-2-hydroxypropanesulfonic acid (MOPSO), pentaerythritol, glyceric acid, malic acid, tartaric acid, lactic acid, glycolic acid, 2-hydroxybutyric acid, 3-hydroxybutyric acid, 4-amino-3-hydroxybutyric acid, 3-(1-azoniabicyclo[2.2.2]oct-1-yl)propane-1-sulfonate, and 1-(2-carboxylatoethyl)-1-azabicyclo[2.2.2]octan-1-ium,
wherein the borate composition and the stabilizer are present at a molar ratio that is selected from a molar ratio of from about 10:1 to about 1:10, a molar ratio of from about 5:1 to about 1:5, and a molar ratio of from about 20:1 to about 1:20,
and wherein the matrix is capable of preventing degradation of an isolated DNA fragment of at least 10 kilobases during substantially dry storage of the DNA fragment in the matrix at 85° C. for a time period of at least two weeks.
21 . The method of claim 20 , comprising maintaining the matrix without refrigeration subsequent to the step of contacting.
22 . The method of claim 20 , further comprising substantially drying the matrix, and thereby storing said biological sample.
23 . The method of claim 22 , comprising maintaining the matrix without refrigeration subsequent to the steps of contacting and drying.
24 . The method of claim 20 wherein the time period is selected from at least four weeks, at least eight weeks, at least 12 weeks, at least 16 weeks, at least 20 weeks, at least 24 weeks, at least 30 weeks, at least 36 weeks, at least 40 weeks, at least 48 weeks, and at least one year.
25 . The method of claim 20 wherein the borate composition comprises at least one compound selected from the group consisting of boric acid, dihydrogen borate, hydrogen borate, diborate, triborate, tetraborate, metaborate, hydroxoborate (borax), borate salt, boric acid-glycerol, boric anhydride (B 2 O 3 ) and boric-acid-1,3 propanediol.
26 . The method of claim 20 wherein the stabilizer is selected from the group consisting of hydroxyectoine, ectoine, homoectoine, betaine, L-carnitine, sarcosine, N,N-dimethylglycine, triethylammonium acetate, glycerol phosphate, N-(2-Hydroxy-1,1-bis(hydroxymethyl)ethyl)glycine (tricine), 3-(N-Morpholino)-2-hydroxypropanesulfonic acid (MOPSO), pentaerythritol, N-ethyl-N,N-bis-(2-hydroxyethyl)ammonium-N-4-butyl sulfonate, glycolic acid, lactic acid, malic acid, tartaric acid, 2-hydroxybutyric acid, 3-hydroxybutyric acid, 4-amino-3-hydroxybutyric acid, pyridine 2,5-dicarboxylic acid, 3-(1-azoniabicyclo[2.2.2]oct-1-yl)propane-1-sulfonate, 1-(2-carboxylatoethyl)-1-azabicyclo[2.2.2]octan-1-ium, and 4-[benzyl(2-hydroxyethyl)methylazaniumyl]butane-1-sulfonate.
27 . The method of claim 20 wherein the matrix further comprises a chelator.
28 . The method of claim 27 wherein the chelator is selected from the group consisting of ethylenediaminetetraacetic acid (EDTA), ethylene glycol tetraacetic acid (EGTA), diethylenetriaminepentaacetic acid (DTPA), trans-1,2-diaminocyclohexane-N,N,N′,N′-tetraacetic acid (CDTA), 1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid (BAPTA), 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), N-(2-hydroxyethyl)ethylenediamine-N,N′,N′-triacetic acid, and nitrilotriacetic acid (NTA).
29 . The method of claim 20 wherein the matrix dissolves or dissociates in a biocompatible solvent.
30 . The method of claim 20 wherein the matrix dissolves in a biocompatible solvent.
31 . The method of claim 29 wherein the biocompatible solvent comprises water.
32 . The matrix of claim 31 wherein the biocompatible solvent comprises a pH buffer.
33 . The method of claim 32 wherein the pH buffer is selected from the group consisting of Tris, citrate, acetate, phosphate, borate, CAPS, CAPSO, HEPES, MES, MOPS, MOPSO, PIPES, carbonate and bicarbonate.
34 . The method of any one of claims 20 and 25 - 27 wherein the matrix further comprises a biological inhibitor or a biochemical inhibitor.
35 . The method of claim 20 wherein the matrix comprises:
(a) a borate composition which comprises at least one compound selected from the group consisting of boric acid, boric anhydride, dihydrogen borate, hydrogen borate, diborate, triborate, tetraborate, metaborate, hydroxoborate (borax), borate salt, boric acid-glycerol and boric-acid-1,3 propanediol;
(b) at least one stabilizer that is selected from the group consisting of:
(i)
wherein R 1 , R 2 , R 3 are independently selected from aryl, arylalkyl, —H, —CH 3 or —CH 2 —CH 3 , wherein when R 1 and R 2 are CH 3 or CH 2 —CH 3 , R 3 may be absent or H, wherein X is selected from —CH 2 —, —CH 2 CH 2 —, —CH 2 CH 2 CH 2 —,
and wherein Y is selected from COO − and SO 3 − ;
(ii)
wherein R 1 is CH 3 or CH 2 CH 3 , and wherein when X is CH, Y is H or OH, and when X is CH 2 —CH, Y is H;
(iii)
wherein R 1 and R 2 are independently selected from —H, —CH 3 , and —CH 2 CH 3 , and wherein X is H, OH, or SH;
(iv) a compound of formula IV:
wherein R 1 is selected from aryl, arylaklyl, —H, —CH 3 —CH 2 —CH 3 , —CH 2 CH 2 OH, CH 2 CHOHCH 3 , CH 2 CHOHCH 2 OH, and CH 2 CH 2 CH 2 OH,
wherein X is selected from —CH 2 —, —CH 2 CH 2 —, —CH 2 CHOH, —CH 2 CH 2 CH 2 —, CH 2 CH 2 CH 2 CH 2 , CH 2 CHOHCH 2 and —CH 2 CHOHCHOHCH 2 —,
wherein Y is selected from COO − and SO 3 − ,
and wherein Z is selected from —CH 2 —, —CHOH—, O and S;
(v) a compound of formula V:
wherein R 1 and R 2 are each independently selected from aryl, arylaklyl, —H, —CH 3 —CH 2 —CH 3 , —CH 2 CH 2 OH, CH 2 CHOHCH 3 , CH 2 CHOHCH 2 OH; and CH 2 CH 2 CH 2 OH,
(vi) a compound of formula VI:
wherein R 1 and R 2 are each independently selected from aryl, arylakyl, —H, —CH 3 —CH 2 —CH 3 , —CH 2 CH 2 OH, CH 2 CHOHCH 3 , CH 2 CHOHCH 2 OH, and CH 2 CH 2 CH 2 OH;
(vii) a compound of formula VII:
wherein R1 is selected from aryl, arylalkyl, —H, —CH3-CH2-CH3, —CH2CH2OH, CH 2 CHOHCH 3 , CH 2 CHOHCH 2 OH, and CH 2 CH 2 CH 2 OH,
wherein X is selected from —CH 2 —, —CH 2 CH 2 —, —CH 2 CHOH, —CH 2 CH 2 CH 2 —, —CH 2 CH 2 CH 2 CH 2 —, —CH 2 CHOHCH 2 —, and —CH 2 CHOHCHOHCH 2 —,
wherein Y is selected from CO 2 − and SO 3 − ,
and wherein Z is selected from CH 2 , CHOH, O and S; and
(viii) an osmoprotectant compound that is selected from the group consisting of trimethylammonium acetate, glycerol phosphate, diglycerol phosphate, N-(2-hydroxy-1,1-bis(hydroxymethyl)ethyl)glycine (tricine), 3-(N-morpholino)-2-hydroxypropanesulfonic acid (MOPSO), pentaerythritol, glyceric acid, malic acid, tartaric acid, lactic acid, glycolic acid, 2-hydroxybutyric acid, 3-hydroxybutyric acid, 4-amino-3-hydroxybutyric acid, 3-(1-azoniabicyclo[2.2.2]oct-1-yl)propane-1-sulfonate, and 1-(2-carboxylatoethyl)-1-azabicyclo[2.2.2]octan-1-ium,
wherein the borate composition and the stabilizer are present at a molar ratio that is selected from a molar ratio of from about 10:1 to about 1:10, a molar ratio of from about 5:1 to about 1:5, and a molar ratio of from about 20:1 to about 1:20,
and wherein the matrix is capable of preventing degradation of an isolated DNA fragment of at least 10 kilobases during substantially dry storage of the DNA fragment in the matrix at 85° C. for a time period of at least two weeks.
36 . The method of claim 35 wherein the biological sample comprises at least one of
(i) an isolated biomolecule that is selected from the group consisting of a nucleic acid, a protein, a polypeptide, a lipid, a glyconconjugate, an oligosaccharide, and a polysaccharide, and
(ii) a biological material that is selected from the group consisting of a mammalian cell, a bacterium, a yeast cell, a virus, a vaccine, blood, urine, a biological fluid, and a buccal swab.
37 . The method of claim 35 wherein the biological sample comprises at least one isolated nuclei.
38 . The method of claim 34 wherein the biological inhibitor or biochemical inhibitor is selected from the group consisting of a reducing agent, an alkylating agent, an antifungal agent and an antimicrobial agent.
39 . The method of claim 35 wherein the matrix further comprises at least one detectable indicator.
40 . The method of claim 39 wherein the detectable indicator comprises a dye or a colorimetric indicator.
41 . The method of claim 39 wherein the detectable indicator is selected from the group consisting of phenol red, ethidium bromide, a DNA polymerase, a restriction endonuclease, cobalt chloride, Reichardt's dye and a fluorogenic protease substrate.
42 . The method of claim 23 wherein biological activity of the sample subsequent to the step of maintaining is substantially the same as biological activity of the sample prior to the step of contacting.
43 . The method of claim 23 wherein degradation of the biological sample is decreased relative to degradation of a control biological sample maintained without refrigeration in the absence of the matrix material.
44 . The method of claim 22 which is selected from (i) the method wherein the step of contacting comprises simultaneously dissolving or dissociating the matrix material in a solvent, (ii) the method wherein the step of contacting is preceded by dissolving or dissociating the matrix material in a solvent, and (iii) the method wherein the step of contacting is followed by dissolving or dissociating the matrix material in a solvent.
45 . A method of preparing a biological sample storage device for one or a plurality of biological samples, comprising:
(a) administering a matrix to one or a plurality of sample wells of a biological sample storage device, wherein (1) said biological sample storage device comprises a sample plate comprising one or a plurality of sample wells that are capable of containing a biological sample, and wherein (2) the matrix comprises (a) a borate composition; and (b) at least one stabilizer that is selected from the group consisting of:
(i)
wherein R 1 , R 2 , R 3 are independently selected from aryl, arylalkyl, —H, —CH 3 or —CH 2 —CH 3 , wherein when R 1 and R 2 are CH 3 or CH 2 —CH 3 , R 3 may be absent or H, wherein X is selected from —CH 2 —, —CH 2 CH 2 —, —CH 2 CH 2 CH 2 —,
and wherein Y is selected from COO − and SO 3 − ;
(ii)
wherein R 1 is CH 3 or CH 2 CH 3 , and wherein when X is CH, Y is H or OH, and when X is CH 2 —CH, Y is H;
(iii)
wherein R 1 and R 2 are independently selected from —H, —CH 3 , and —CH 2 CH 3 , and wherein X is H, OH, or SH;
(iv) a compound of formula IV:
wherein R 1 is selected from aryl, arylaklyl, —H, —CH 3 —CH 2 —CH 3 , —CH 2 CH 2 OH, CH 2 CHOHCH 3 , CH 2 CHOHCH 2 OH, and CH 2 CH 2 CH 2 OH,
wherein X is selected from —CH 2 —, —CH 2 CH 2 —, —CH 2 CHOH, —CH 2 CH 2 CH 2 —, CH 2 CH 2 CH 2 CH 2 , CH 2 CHOHCH 2 and —CH 2 CHOHCHOHCH 2 —,
wherein Y is selected from COO − and SO 3 − ,
and wherein Z is selected from —CH 2 —, —CHOH—, O and S;
(v) a compound of formula V:
wherein R 1 and R 2 are each independently selected from aryl, arylaklyl, —H, —CH 3 —CH 2 —CH 3 , —CH 2 CH 2 OH, CH 2 CHOHCH 3 , CH 2 CHOHCH 2 OH; and CH 2 CH 2 CH 2 OH,
(vi) a compound of formula VI:
wherein R 1 and R 2 are each independently selected from aryl, arylakyl, —H, —CH 3 —CH 2 —CH 3 , —CH 2 CH 2 OH, CH 2 CHOHCH 3 , CH 2 CHOHCH 2 OH, and CH 2 CH 2 CH 2 OH;
(vii) a compound of formula VII:
wherein R 1 is selected from aryl, arylalkyl, —H, —CH 3 —CH 2 —CH 3 , —CH 2 CH 2 OH, CH 2 CHOHCH 3 , CH 2 CHOHCH 2 OH, and CH 2 CH 2 CH 2 OH,
wherein X is selected from —CH 2 —, —CH 2 CH 2 —, —CH 2 CHOH, —CH 2 CH 2 CH 2 —, —CH 2 CH 2 CH 2 CH 2 —, —CH 2 CHOHCH 2 —, and —CH 2 CHOHCHOHCH 2 —,
wherein Y is selected from CO 2 − and SO 3 − ,
and wherein Z is selected from CH 2 , CHOH, O and S; and
(viii) an osmoprotectant compound that is selected from the group consisting of trimethylammonium acetate, glycerol phosphate, diglycerol phosphate, N-(2-hydroxy-1,1-bis(hydroxymethyl)ethyl)glycine (tricine), 3-(N-morpholino)-2-hydroxypropanesulfonic acid (MOPSO), pentaerythritol, glyceric acid, malic acid, tartaric acid, lactic acid, glycolic acid, 2-hydroxybutyric acid, 3-hydroxybutyric acid, 4-amino-3-hydroxybutyric acid, 3-(1-azoniabicyclo[2.2.2]oct-1-yl)propane-1-sulfonate, and 1-(2-carboxylatoethyl)-1-azabicyclo[2.2.2]octan-1-ium,
wherein the borate composition and the stabilizer are present at a molar ratio that is selected from a molar ratio of from about 10:1 to about 1:10, a molar ratio of from about 5:1 to about 1:5, and a molar ratio of from about 20:1 to about 1:20,
and wherein the matrix is capable of preventing degradation of an isolated DNA fragment of at least 10 kilobases during substantially dry storage of the DNA fragment in the matrix at 85° C. for a time period of at least two weeks; and
(b) substantially drying one or more of the sample wells, and thereby preparing the biological sample storage device.
46 . The method of claim 45 wherein the step of administering comprises administering a liquid solution or a liquid suspension that contains the matrix and a solvent.
47 . The method of claim 45 wherein at least one well comprises at least one detectable indicator.
48 . The method of claim 47 wherein the detectable indicator comprises a dye or colorimetric indicator.
49 . The method of claim 47 wherein the detectable indicator is selected from the group consisting of phenol red, a food dye, ethidium bromide, a dye compatible with qPCR, a DNA polymerase, a restriction endonuclease, cobalt chloride, Reichardt's dye and a fluorogenic protease substrate.
50 . A method of recovering a stored biological sample, comprising:
(a) contacting, simultaneously or sequentially and in either order in a biological sample storage device, one or a plurality of biological samples with a matrix for substantially dry storage of a biological sample, wherein (1) said biological sample storage device comprises a sample plate comprising one or a plurality of sample wells that are capable of containing the biological sample, wherein one or more of said wells comprises the matrix, and wherein (2) the matrix comprises (a) a borate composition; and (b) at least one stabilizer that is selected from the group consisting of:
(i)
wherein R 1 , R 2 , R 3 are independently selected from aryl, arylalkyl, —H, —CH 3 or —CH 2 —CH 3 , wherein when R 1 and R 2 are CH 3 or CH 2 —CH 3 , R 3 may be absent or H, wherein X is selected from —CH 2 —, —CH 2 CH 2 —, —CH 2 CH 2 CH 2 —,
and wherein Y is selected from COO − and SO 3 − ;
(ii)
wherein R 1 is CH 3 or CH 2 CH 3 , and wherein when X is CH, Y is H or OH, and when X is CH 2 —CH, Y is H;
(iii)
wherein R 1 and R 2 are independently selected from —H, —CH 3 , and —CH 2 CH 3 , and wherein X is H, OH, or SH;
(iv) a compound of formula IV:
wherein R 1 is selected from aryl, arylaklyl, —H, —CH 3 —CH 2 —CH 3 , —CH 2 CH 2 OH, CH 2 CHOHCH 3 , CH 2 CHOHCH 2 OH, and CH 2 CH 2 CH 2 OH,
wherein X is selected from —CH 2 —, —CH 2 CH 2 —, —CH 2 CHOH, —CH 2 CH 2 CH 2 —, CH 2 CH 2 CH 2 CH 2 , CH 2 CHOHCH 2 and —CH 2 CHOHCHOHCH 2 —,
wherein Y is selected from COO − and SO 3 − ,
and wherein Z is selected from —CH 2 —, —CHOH—, O and S;
(v) a compound of formula V:
wherein R 1 and R 2 are each independently selected from aryl, arylaklyl, —H, —CH 3 —CH 2 —CH 3 , —CH 2 CH 2 OH, CH 2 CHOHCH 3 , CH 2 CHOHCH 2 OH; and CH 2 CH 2 CH 2 OH,
(vi) a compound of formula VI:
wherein R 1 and R 2 are each independently selected from aryl, arylakyl, —H, —CH 3 —CH 2 —CH 3 , —CH 2 CH 2 OH, CH 2 CHOHCH 3 , CH 2 CHOHCH 2 OH, and CH 2 CH 2 CH 2 OH;
(vii) a compound of formula VII:
wherein R 1 is selected from aryl, arylalkyl, —H, —CH 3 —CH 2 —CH 3 , —CH 2 CH 2 OH, CH 2 CHOHCH 3 , CH 2 CHOHCH 2 OH, and CH 2 CH 2 CH 2 OH,
wherein X is selected from —CH 2 —, —CH 2 CH 2 —, —CH 2 CHOH, —CH 2 CH 2 CH 2 —, —CH 2 CH 2 CH 2 CH 2 —, —CH 2 CHOHCH 2 —, and —CH 2 CHOHCHOHCH 2 —,
wherein Y is selected from CO 2 − and SO 3 − ,
and wherein Z is selected from CH 2 , CHOH, O and S; and
(viii) an osmoprotectant compound that is selected from the group consisting of trimethylammonium acetate, glycerol phosphate, diglycerol phosphate, N-(2-hydroxy-1,1-bis(hydroxymethyl)ethyl)glycine (tricine), 3-(N-morpholino)-2-hydroxypropanesulfonic acid (MOPSO), pentaerythritol, glyceric acid, malic acid, tartaric acid, lactic acid, glycolic acid, 2-hydroxybutyric acid, 3-hydroxybutyric acid, 4-amino-3-hydroxybutyric acid, 3-(1-azoniabicyclo[2.2.2]oct-1-yl)propane-1-sulfonate, and 1-(2-carboxylatoethyl)-1-azabicyclo[2.2.2]octan-1-ium,
wherein the borate composition and the stabilizer are present at a molar ratio that is selected from a molar ratio of from about 10:1 to about 1:10, a molar ratio of from about 5:1 to about 1:5, and a molar ratio of from about 20:1 to about 1:20,
and wherein the matrix is capable of preventing degradation of an isolated DNA fragment of at least 10 kilobases during substantially dry storage of the DNA fragment in the matrix at 85° C. for a time period of at least two weeks;
(b) substantially drying one or more of the sample wells;
(c) maintaining the biological sample storage device without refrigeration subsequent to the steps of contacting and drying; and
(d) resuspending or redissolving the biological sample in a biocompatible solvent, and therefrom recovering the stored biological sample.
51 . The method of claim 50 wherein biological activity of the sample subsequent to the step of maintaining is substantially the same as biological activity of the sample prior to the step of contacting.
52 . A matrix for substantially dry storage of a biological sample, comprising:
(a) a borate composition which comprises at least one compound selected from the group consisting of boric acid, dihydrogen borate, hydrogen borate, diborate, triborate, tetraborate, metaborate, hydroxoborate (borax), borate salt, boric acid-glycerol, boric anhydride (B2O 3 ) and boric-acid-1,3 propanediol; (b) at least one stabilizer selected from the group consisting of hydroxyectoine, ectoine, homoectoine, betaine, L-carnitine, sarcosine, N,N-dimethylglycine, triethylammonium acetate, glycerol phosphate, tricine, MOPSO, pentaerythritol and N-ethyl-N,N-bis-(2-hydroxyethyl)ammonium-N-4-butyl sulfonate, glycolic acid, lactic acid, malic acid and tartaric acid; and (c) a sample treatment composition, wherein the borate composition and the stabilizer are present at a molar ratio of from about 10:1 to about 1:10, and wherein the matrix is capable of preventing degradation of an isolated DNA fragment of at least 10 kilobases during substantially dry storage of the DNA fragment in the matrix at 85° C. for a time period of at least two weeks.
53 . The matrix of claim 52 wherein the sample treatment composition comprises a composition that is selected from the group consisting of an activity buffer, a cell lysis buffer, a free radical trapping agent, a sample denaturant and a pathogen-neutralizing agent.Cited by (0)
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