HK1159684B - Matrices and media for storage and stabilization of biomolecules - Google Patents
Matrices and media for storage and stabilization of biomolecules Download PDFInfo
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Abstract
The present invention provides compositions useful for biomolecule storage comprising a water soluble inorganic compound, a stabilizer, or a combination thereof. The present invention also provides methods of using the compositions of the invention to store biomolecules in the dry state and in solution, as well as sample carriers and kits comprising compositions of the invention.
Description
This invention claims priority from U.S. provisional application 61/096,747 filed on 12.9.2008, the contents of which are expressly incorporated herein by reference.
Background
In many applications, such as pharmaceutical and medical research, law enforcement, and military identification, it is often desirable to store and have access to large quantities of biological samples. Conventional biological preservation facilities or other sample storage facilities utilize liquid or cryogenic systems for sample storage. Both these liquid and cryogenic systems are expensive to produce and maintain, and current technology often places the system operator in complex and burdensome maintenance and management responsibilities. In addition, these systems do not address the workflow issues that arise when processing large numbers of samples simultaneously. Under these conditions, the sample may be exposed to ambient temperatures for extended periods of time, resulting in degradation of the sample.
With respect to workflow issues, it is becoming increasingly important to ship samples collected on-site or elsewhere so that the samples can be analyzed and/or stored remotely. However, shipping samples on dry ice is expensive and dangerous, and standard shipping practices, like those employed by carriers such as FedEx, can subject the samples to large temperature fluctuations, including high temperatures that can denature or degrade biomolecules present in the biological sample. For example, FedEx warns that in the summer of southern climates, temperatures in a closed, parked transport vehicle may reach 140 ° f (60 ℃). Also, for worldwide transportation applications, the united states military envisioned the worst scenario, where samples were exposed to temperatures as high as 160 ° f (71 ℃).
There is a need in the art to develop additional biomolecule storage materials and systems.
Disclosure of Invention
The present invention is based in part on the following findings: certain compounds, particularly water-soluble inorganic compounds and compounds that act as singlet oxygen quenchers, may be used for stabilization and/or storage of biomolecules in the dry state, including at elevated temperatures. The present invention is also based in part on the following findings: certain combinations of compounds can stabilize biomolecules, including RNA, in aqueous solution. Accordingly, the present invention provides compositions, devices and methods for stabilizing and storing biomolecules.
In one aspect, the present invention provides compositions useful for storing and/or stabilizing biomolecules. In certain embodiments, the composition is a matrix (e.g., a solid state matrix) comprising a water-soluble inorganic compound, a stabilizer (e.g., a small molecule stabilizer), or a combination thereof. In other embodiments, the composition is a medium (e.g., an aqueous medium) comprising a water-soluble inorganic compound, a stabilizer (e.g., a small molecule stabilizer), or a combination thereof. In still other embodiments, the composition is a matrix (e.g., a solid matrix) or a medium (e.g., an aqueous medium) comprising at least three ingredients selected from the group consisting of inorganic compounds, singlet oxygen quenchers, hydroxyl radical scavengers, hydroperoxide scavengers, reducing agents, metal chelators, detergents, and plasticizers. In certain embodiments, the matrix or medium further comprises a plasticizer. In certain embodiments, the matrix or medium further comprises an RNase inhibitor. In certain embodiments, the matrix or medium further comprises a biomolecule (e.g., a nucleic acid, such as DNA or RNA). For example, the matrix or medium may comprise a sample containing biomolecules, such as a biological sample.
In another aspect, the present invention provides a sample carrier (samplecarrier) that can be used to store biomolecules. In certain embodiments, the sample carrier comprises a container and a sample node (sample node), wherein the sample node is a composition disclosed herein (e.g., a matrix or medium disclosed herein). The container may, for example, support a sample node. In certain embodiments, the sample carrier comprises a plurality of containers and a plurality of discrete sample nodes. For example, each of the plurality of sample nodes may be supported by a respective one of the containers. In certain embodiments, the sample carrier further comprises a biomolecule. For example, the sample carrier may comprise one or more samples containing biomolecules, such as biological samples. The biomolecules may, for example, be stored in the sample node (e.g., mixed with a matrix or medium as disclosed herein). In certain embodiments, the sample carrier comprises an identifying label. In certain embodiments, the container or sample node comprises an identifying label.
In another aspect, the invention provides a kit comprising a composition disclosed herein (e.g., a matrix or medium disclosed herein) and instructions for using the composition to store and/or stabilize (e.g., store in a dry state or stabilize in an aqueous medium) a biomolecule. In certain embodiments, the kit comprises a container containing the composition. In certain embodiments, a kit comprises a sample carrier disclosed herein.
In another aspect, the present invention provides a method of storing and/or stabilizing a biomolecule. In certain embodiments, the method comprises mixing a sample comprising a biomolecule, such as a biological sample, with a composition disclosed herein (e.g., a matrix or medium disclosed herein) to form a mixture, and drying the mixture. In certain embodiments, the sample is a liquid sample, such as a bodily fluid, a cell lysate, or a tissue homogenate. In certain embodiments, the sample is carried by a solid support such as a cotton swab, filter paper, or sponge. In certain related embodiments, mixing comprises rinsing the sample-carrying solid support with the medium disclosed herein.
Other aspects and details of the invention will be apparent from the detailed description below.
Drawings
Fig. 1 is an image of a sample carrier having a plurality of containers and a plurality of discrete sample nodes. In this embodiment, the container is a well of a multi-well plate. Each container is shown supporting a discrete sample node. Each discrete sample node consists of a solid storage matrix formed by evaporation of a storage medium containing boric acid and DNA.
FIG. 2(a) shows a photograph of a gel after storage of about 100ng of DNA recovered from a 1. mu.g DNA sample in a matrix containing boric acid in a dried state at Room Temperature (RT), 37 ℃ and 56 ℃. FIG. 2(b) is a photograph showing a gel of about 100ng of DNA recovered from a 1. mu.g DNA sample after storage in a medium containing boric acid and histidine in a dried state at room temperature, 37 ℃, 56 ℃ and 76 ℃. Before storage in the dry state, the DNA sample is stored in a solution of water or TE buffer.
FIG. 3(a) shows the results of real-time PCR of DNA recovered from a 250ng DNA sample after storage in a medium containing boric acid in a dry state at room temperature, 37 ℃ and 56 ℃. FIG. 3(b) shows the results of real-time PCR of DNA recovered from a 250ng DNA sample after storage in a medium containing boric acid and histidine in a dry state at room temperature, 37 ℃, 56 ℃ and 76 ℃.
FIG. 4 shows microarray data of DNA recovered from a 1. mu.g DNA sample after storage in a matrix comprising boric acid or boric acid and histidine in a room temperature dry state.
FIG. 5 is a set of graphs showing Agilent Bioanalyzer data after storage of 1 microgram of purified total RNA in a matrix consisting of borate, citrate, EDTA, pyruvate and dextran in a dried state at either (A)25 ℃ or (B)76 ℃ for 7 days. The two peaks that appear at about 41 seconds and about 48 seconds correspond to ribosomal RNA.
FIG. 6 is a set of graphs showing Agilent Bioanalyzer data after storage of 1 microgram of purified total RNA in a matrix consisting of tris, borate, mannitol and EDTA for 7 days in either (A)25 ℃ or (B)76 ℃ dry state. The two peaks that appear at about 41 seconds and about 48 seconds correspond to ribosomal RNA.
FIG. 7 is a set of graphs showing Agilent Bioanalyzer data after storage of 1 microgram of purified total RNA in a matrix consisting of borate, citrate, mannitol and dextran for 7 days in a dry state at (A)25 ℃ or (B)76 ℃. The two peaks that appear at about 41 seconds and about 48 seconds correspond to ribosomal RNA.
FIG. 8 is a set of graphs showing Agilent Bioanalyzer data after storage of 1 microgram of purified total RNA in a matrix consisting of borate, citrate, mannitol, and pyruvate in a dry state at (A)25 ℃ or (B)76 ℃ for 7 days. The two peaks that appear at about 41 seconds and about 48 seconds correspond to ribosomal RNA.
FIG. 9 is a set of graphs showing Agilent Bioanalyzer data after storage of 1 microgram of purified total RNA in a matrix consisting of borate, citrate, pyruvate and dextran for 7 days in a dry state at either (A)25 ℃ or (B)76 ℃. The two peaks that appear at about 41 seconds and about 48 seconds correspond to ribosomal RNA.
FIG. 10 is a set of photographs showing Agilent Bioanalyzer data after storage of 1 microgram of purified total RNA in a matrix consisting of borate, citrate, EDTA and dextran for 7 days in a dry state at either (A)25 ℃ or (B)76 ℃. The two peaks that appear at about 41 seconds and about 48 seconds correspond to ribosomal RNA.
FIG. 11 is a set of graphs showing Agilent Bioanalyzer data after storage of 1 microgram of purified total RNA in a matrix consisting of borate, EDTA and pyruvate in a dry state at (A)25 ℃ or (B)76 ℃ for 7 days. The two peaks that appear at about 41 seconds and about 48 seconds correspond to ribosomal RNA.
FIG. 12 is a set of graphs showing Agilent Bioanalyzer data after storage of 1 microgram of purified total RNA in a matrix consisting of borate, citrate and pyruvate in a dry state at either (A)25 ℃ or (B)76 ℃ for 7 days. The two peaks that appear at about 41 seconds and about 48 seconds correspond to ribosomal RNA.
FIG. 13 is a set of graphs showing Agilent Bioanalyzer data after storage of 1 microgram of purified total RNA in a matrix consisting of borate, citrate and mannitol for 7 days in a dry state at (A)25 ℃ or (B)76 ℃. The two peaks that appear at about 41 seconds and about 48 seconds correspond to ribosomal RNA.
FIG. 14 is a set of graphs showing Agilent Bioanalyzer data after storage of 1 microgram of purified total RNA in a matrix consisting of borate, citrate and EDTA for 7 days in a dry state at either (A)25 ℃ or (B)76 ℃. The two peaks that appear at about 41 seconds and about 48 seconds correspond to ribosomal RNA.
FIG. 15 is a set of graphs showing Agilent Bioanalyzer data after storage of 1 microgram of purified total RNA in the absence of matrix for 7 days in the dry state at (A)25 ℃ or (B)76 ℃. The two peaks that appear at about 41 seconds and about 48 seconds correspond to ribosomal RNA.
Detailed Description
The following terms used herein have the following meanings.
The term "biomolecule" is specifically intended to include short and long biopolymers, including but not limited to polymeric molecules such as DNA, RNA, proteins, immunoglobulins, and carbohydrates, whether naturally occurring or synthetic, with or without modifications such as modified amino acids or nucleotides. Thus, for example, the term includes short oligomeric nucleic acid molecules (e.g., less than 50 bases in length), long nucleic acid molecules (e.g., greater than 50kB in length), and any length in between. The term also includes short peptide sequences (e.g., less than 10 amino acids), long polypeptide sequences (e.g., greater than 1000 amino acids in length), and any length in between. In addition, the term "biomolecule" is specifically intended to include small molecules found in biological samples, such as lipids, coenzymes, metabolites and agents and metabolites thereof.
The term "protein" as used herein is used interchangeably with the term "polypeptide".
The terms "nucleic acid", "oligonucleotide" and "polynucleotide" are used interchangeably and include DNA, RNA, cDNA, whether single-stranded or double-stranded, and chemically modified and artificial nucleic acids (e.g., PNA, LNA, etc.).
Composition comprising a metal oxide and a metal oxide
The present invention is based in part on the following findings: certain compounds, particularly water-soluble inorganic compounds and compounds that act as singlet oxygen quenchers, may be used for stabilization and/or storage of biomolecules in the dry state, including at elevated temperatures. The present invention is also based in part on the following findings: certain combinations of compounds can stabilize biomolecules, including RNA, in aqueous solution.
Thus, in one aspect, the present invention provides compositions useful for storing and/or stabilizing biomolecules. In certain embodiments, the composition comprises an inorganic compound, wherein the inorganic compound is water soluble.
As used herein, an "inorganic compound" is a compound whose formula does not contain carbon. In certain embodiments, the inorganic compound is an acid (i.e., a compound that, when dissolved in water, produces a solution having a pH of less than 7.0). In certain embodiments, the inorganic compound is a base (i.e., a compound that, when dissolved in water, produces a solution having a pH greater than 7.0). In other embodiments, the inorganic compound is not a base (e.g., the inorganic compound is not a lewis base). In still other embodiments, the inorganic compound is a salt.
In certain embodiments, the inorganic compound is a metal chelator. As used herein, a "metal chelator" is a compound that forms two or more bonds with one metal ion. In certain embodiments, the inorganic compound chelates at least one type of metal ion selected from the group consisting of magnesium ion, chromium ion, manganese ion, iron ion, cobalt ion, nickel ion, copper ion, zinc ion, lead ion, or any combination thereof. In certain embodiments, the inorganic compound chelates at least one type of metal ion and inhibits metal-dependent reactions between these ions and biomolecules present in the composition. In certain embodiments, the inorganic compound chelates at least one type of metal ion and prevents these ions from degrading biomolecules present in the composition. In a preferred embodiment, the inorganic compound chelates magnesium and/or manganese ions and inhibits metal-dependent reactions between these ions and biomolecules present in the composition. In other preferred embodiments, the inorganic compound chelates magnesium and/or manganese ions and prevents these ions from degrading biomolecules present in the composition.
In certain embodiments, the inorganic compound is a microbicide (microcidalagent). As used herein, a "microbicide" is any compound that slows or stops the growth of microorganisms. In certain embodiments, the inorganic compound kills one or more microorganisms, such as bacteria, protists, and/or fungi. In certain embodiments, the inorganic compound inhibits the growth of one or more microorganisms, such as bacteria, protists, and/or fungi.
In certain embodiments, the inorganic compound is capable of absorbing or sequestering water molecules, thereby preventing hydrolysis of the biomolecule. In certain embodiments, the inorganic compound is hydrated to about 70%, 60%, 50%, 45%, 40%, 38%, 36%, 35%, 34%, 33%, 32%, 31%, 30% or less by mass when equilibrated with 50% atmospheric humidity.
In certain embodiments, the inorganic compound concentrates and forms a crystalline or paracrystalline structure upon drying. In certain embodiments, the inorganic compound does not form a glass structure upon drying. The term "glass structure" as used herein refers to a solid state structure in which the molecules comprising the glass structure exhibit only short range order, rather than long range crystalline order, with respect to each other. In certain embodiments, the inorganic compound is capable of co-localization with a biomolecule. For example, in certain embodiments, the inorganic compound concentrates upon drying and forms a crystalline or paracrystalline state in direct contact with the biomolecule.
In certain embodiments, the inorganic compound is inert to one or more types of biomolecules. As used herein, "inert" means that the inorganic compound either does not bind to one or more types of biomolecules or binds reversibly such that the biomolecules are not degraded by such binding. In a preferred embodiment, the inorganic compound is inert towards nucleic acids, proteins, carbohydrates, lipids, coenzymes, metabolites, pharmaceutical agents, metabolites of pharmaceutical agents, or any combination thereof.
In certain embodiments, the inorganic compound is inert to one or more downstream methods that may be used to analyze biomolecules that have been stored in and/or stabilized by the compositions of the present invention. The term "inert" as used in the present context means that the presence of inorganic compounds in the sample cannot reduce the rate of the process by more than 50% and significantly reduce the fidelity of the process. In certain embodiments, the inorganic compound is inert to a method selected from the group consisting of nucleic acid transcription and/or amplification (e.g., reverse transcription, PCR, real-time PCR, etc.), endonuclease digestion (e.g., reactions involving type II endonucleases such as EcoRI, BamHI, HindIII, NotI, SmaI, BglII, etc.), cloning techniques (e.g., ligation), protein digestion (e.g., reactions involving proteases such as proteinase K, trypsin, chymotrypsin, savinase, etc.), microarray analysis (e.g., microarray analysis of nucleic acids or proteins), immunoassay (e.g., immunoprecipitation, ELISA, etc.), mass spectrometry, or any combination thereof. In certain embodiments, the inorganic compound is inert upon dilution (e.g., 2, 3, 4, 5, 6,7, 8, 9, 10, 15, 20-fold or more dilution). In other embodiments, the inorganic compound is inert in undiluted form. In certain embodiments, the inorganic compound is inert to one or more such methods when present in the reaction at a concentration of 0.075mg/ml, 0.1mg/ml, 0.2mg/ml, 0.3mg/ml, 0.4mg/ml, 0.5mg/ml, 0.6mg/ml, 0.7mg/ml, 0.8mg/ml, 0.9mg/ml, 1.0mg/ml, 2.0mg/ml, 5.0mg/ml, 10.0mg/ml or more.
As used herein, "water-soluble" means that the inorganic compound has a solubility in water of 1.0mg/ml or more at 25 ℃. In certain embodiments, the inorganic compound has a solubility in water at 25 ℃ of at least 1.5mg/ml, 2.0mg/ml, 3.0mg/ml, 4.0mg/ml, 5.0mg/ml, 7.5mg/ml, 10mg/ml, 15mg/ml, 20mg/ml, 25mg/ml, 30mg/ml, 35mg/ml, 40mg/ml, 50mg/ml, 60mg/ml, 70mg/ml, 80mg/ml, 90mg/ml, 100mg/ml, 125mg/ml, 150mg/ml, 200mg/ml or more. In certain embodiments, the inorganic compound is readily soluble in water. For example, in certain embodiments, the inorganic compound may be soluble in water at 25 ℃ in 75, 60, 50, 40, 30, 25, 20, 15, 10, 9, 8, 7, 6, 5, 4, 3, 2 minutes or less. In other embodiments, the inorganic compound may be soluble in water at 25 ℃ in 7, 6, 5, 4, 3, 2, 1.5 hours, or less. In certain embodiments, the inorganic compound is soluble in water at 25 ℃ with or without agitation (e.g., pipetting, shaking, or vortexing).
In certain embodiments, the formula of the inorganic compound contains an element from group 1 (e.g., IA), group 3 (e.g., IIIA or IIIB), group 5 (e.g., VA or VB), group 6 (e.g., VIA), or group 7 (e.g., VIIA) of the periodic table of elements, or a combination thereof. For example, in certain embodiments, the inorganic compound has a formula comprising hydrogen, sodium, potassium, boron, aluminum, phosphorus, vanadium, oxygen, sulfur, chlorine, or combinations thereof. In certain embodiments, the formula of the inorganic compound contains at least an element from group 3 (e.g., IIIA or IIIB) or group 5 (e.g., VA or VB) of the periodic table of elements. In certain embodiments, the inorganic compound has a formula comprising boron, aluminum, phosphorus, or vanadium. In other embodiments, the inorganic compound has a formula that is free of elements selected from boron, aluminum, phosphorus, vanadium, or combinations thereof.
In certain embodiments, the inorganic compound is boric acid or a corresponding salt of boric acid (e.g., borax). In certain embodiments, the inorganic compound is phosphoric acid or a corresponding salt of phosphoric acid (e.g., Na)3PO4、Na2HPO4、NaH2PO4、K3PO4、K2HPO4、KH2PO4). In certain embodiments, the inorganic compound is a vanadate (e.g., Na)3VO4、K3VO4). In certain embodiments, the inorganic compound is an aluminum salt (e.g., alum, such as potassium alum (KAl (SO)4)2·12H2O), sodium alum (Na)2SO4Al2(SO4)3·24H2O) or ammonium alum (NH)4Al(SO4)2·12H2O)). In certain embodiments, the inorganic compound is sodium chloride or potassium chloride. In certain embodiments, the inorganic compound is selected from boric acid, a corresponding salt of boric acid (e.g., borax), phosphoric acid, a corresponding salt of phosphoric acid (e.g., Na)3PO4、Na2HPO4、NaH2PO4、K3PO4、K2HPO4、KH2PO4) Vanadate (e.g. Na)3VO4、K3VO4) Aluminum salts (e.g., alum, such as potassium alum (KAl (SO))4)2·12H2O), sodium alum (Na)2SO4Al2(SO4)3·24H2O) or ammonium alum (NH)4Al(SO4)2·12H2O)), a combination of sodium chloride and potassium chloride.
In certain embodiments, the inorganic compound is neither boric acid nor the corresponding salt of boric acid (e.g., borax). In certain embodiments, the inorganic compound is neither phosphoric acid nor the corresponding salt of phosphoric acid (e.g., Na)3PO4、Na2HPO4、NaH2PO4、K3PO4、K2HPO4、KH2PO4). In certain embodiments, the inorganic compound is not a vanadate (e.g., Na)3VO4、K3VO4). In certain embodiments, the inorganic compound is not an aluminum salt (e.g., alum, such as potassium alum (i.e., KAl (SO)4)2·12H2O), sodium alum (i.e., Na)2SO4Al2(SO4)3·24H2O) or ammonium alum (i.e. NH)4Al(SO4)2·12H2O)). In certain embodiments, the inorganic compound is not sodium chloride. In certain embodiments, noneThe organic compound is not potassium chloride.
In certain embodiments, the inorganic compound is not an inorganic mineral. As used herein, an "inorganic mineral" is an inorganic compound that is insoluble in water at 25 ℃. Examples of the inorganic minerals include hydroxyapatite (hydroxyapatite), Ca10(PO4)6(OH)2And various clays, such as kaolin (i.e., Al)2O3·2SiO2·2H2O) and montmorillonite (i.e., Na)0.2Ca0.1Al2Si4O10(OH)2(H2O)10)。
In certain embodiments, the formula of the inorganic compound does not include magnesium, chromium, manganese, iron, cobalt, nickel, copper, zinc, or lead.
In certain embodiments, an inorganic compound (or mixture of inorganic compounds) is the major component of the composition. As used herein, the "major constituent" of a composition is the one chemical compound (or a particular group of compounds) that is most abundant in the composition by importance. In certain embodiments, the inorganic compound (or mixture of inorganic compounds) comprises at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50% or more of the composition. In other embodiments, the inorganic compound (or mixture of inorganic compounds) is the primary non-aqueous component of the composition. In certain embodiments, the inorganic compound (or mixture of inorganic compounds) comprises at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50% or more of the nonaqueous portion of the composition.
In certain embodiments, the inorganic compound (or mixture of inorganic compounds) is part of the aqueous medium of the present invention and is present in a concentration of from about 0.5mg/ml to about 200mg/ml, from about 1.0mg/ml to about 150.0mg/ml, from about 1.5mg/ml to about 100.0mg/ml, from about 2.0mg/ml to about 50.0mg/ml, from about 2.5mg/ml to about 25.0mg/ml, or from about 3.0mg/ml to about 10.0 mg/ml. In certain embodiments, the inorganic compound (or mixture of inorganic compounds) is part of an aqueous solution of the present invention and is at a concentration of about 0.1mg/ml to about 10mg/ml, about 0.2mg/ml to about 8mg/ml, about 0.3mg/ml to about 6mg/ml, about 0.4mg/ml to about 4mg/ml, about 0.5mg/ml to about 2mg/ml, or about 0.6mg/ml to about 1 mg/ml. In certain embodiments, the inorganic compound (or mixture of inorganic compounds) is part of an aqueous solution of the present invention and is at a concentration of from about 5.0mg/ml to about 150.0mg/ml, from about 10.0mg/ml to about 125.0mg/ml, from about 20.0mg/ml to about 100.0mg/ml, or from about 25.0mg/ml to about 75.0 mg/ml.
In certain embodiments, the inorganic compound is part of the aqueous medium of the present invention and is at a concentration of about 5mM to about 500mM, about 6mM to about 450mM, about 7mM to about 400mM, about 8mM to about 350mM, about 9mM to about 300mM, about 10mM to about 250mM, about 10mM to about 200mM, about 10mM to about 150mM, about 15mM to about 140mM, about 20mM to about 130mM, about 25mM to about 120mM, about 30mM to about 110mM, about 35mM to about 105mM, or about 40mM to about 100 mM. In certain embodiments, the inorganic compound is part of the aqueous medium of the present invention and is at a concentration of about 1mM to about 100mM, about 2mM to about 80mM, about 3mM to about 60mM, about 4mM to about 40mM, about 5mM to about 30mM, about 6mM to about 25mM, about 7mM to about 20mM, or about 8mM to about 15 mM.
In certain embodiments, the compositions of the present invention further comprise a stabilizer. For example, in certain embodiments, the composition comprises an inorganic compound and a stabilizer. The inorganic compound may be as described above. As used herein, a "stabilizer" is any agent capable of protecting at least one type of biomolecule from damage during storage. In certain embodiments, the at least one type of biomolecule protected by the stabilizing agent is DNA, protein, carbohydrate, lipid, pharmaceutical agent, or a metabolite thereof, or any combination thereof. In certain embodiments, the stabilizing agent is capable of inhibiting undesirable contact of the biomolecule with various contaminants or potential degradation sources, including but not limited to oxygen (e.g., reactive oxygen species such as singlet oxygen, hydroxyl radicals, superoxide anions, etc.), free water, enzymes, metal ions, or other reactive chemicals.
In certain embodiments, the stabilizer concentrates upon drying and forms a crystalline or paracrystalline structure. In certain embodiments, the stabilizing agent does not form a glass structure upon drying. In certain embodiments, the stabilizing agent is capable of co-localization with the biomolecule. For example, in certain embodiments, the stabilizing agent concentrates upon drying and forms a crystalline or paracrystalline state in direct contact with the biomolecule. Co-localization of the stabilizing agent and the biomolecule may provide additional stabilization of the biomolecule.
In certain embodiments, the stabilizer is a small molecule stabilizer. In certain embodiments, the stabilizing agent is selected from the group consisting of singlet oxygen quenchers, hydroxyl radical scavengers, hydroperoxide scavengers, reducing agents, metal chelators, detergents, chaotropes, and combinations thereof. Examples of singlet oxygen quenchers include, but are not limited to, alkylimidazoles (e.g., histidine, L-carnosine, histamine, imidazole 4-acetic acid), indoles (e.g., tryptophan and derivatives thereof, such as N-acetyl-5-methoxytryptamine, N-acetyl serotonin, 6-methoxy-1, 2, 3, 4-tetrahydro- β -carboline), sulfur-containing amino acids (e.g., methionine, ethionine, muchine, lanthionine, N-formylmethionine, felinine, S-allylcysteine, S-aminoethyl-L-cysteine), phenolic compounds (e.g., tyrosine and derivatives thereof), aromatic acids (e.g., ascorbic acid, salicylic acid, and derivatives thereof), azides (e.g., sodium azide), tocopherols and related vitamin E derivatives, and carotenes and related vitamin a derivatives. Examples of hydroxyl radical scavengers include, but are not limited to, azide, dimethyl sulfoxide, histidine, mannitol, sucrose, glucose, salicylate, and L-cysteine. Examples of hydroperoxide scavengers include, but are not limited to, catalase, pyruvate, glutathione, and glutathione peroxidase enzymes. Examples of reducing agents include, but are not limited to, cysteine and mercaptoethylene. Examples of metal chelators include, but are not limited to, EDTA, EGTA, phenanthroline, and citrate. Examples of detergents include, but are not limited to, SDS and sarcosyl. Examples of chaotropic agents include, but are not limited to, guanidine hydrochloride, isothiocyanates, urea, and formamide.
In certain embodiments, the stabilizing agent comprises a singlet oxygen quencher (e.g., an alkyl imidazole, an indole, or a sulfur-containing amino acid). In certain embodiments, the stabilizing agent comprises two or more singlet oxygen quenchers (e.g., selected from alkyl imidazoles, indoles, and sulfur-containing amino acids). In certain embodiments, the stabilizing agent comprises a singlet oxygen quencher and a hydroxyl radical scavenger, a hydroperoxide scavenger, a metal chelator, or any combination thereof. In certain embodiments, the stabilizing agent comprises a hydroxyl radical scavenger. In certain embodiments, the stabilizing agent comprises a hydroperoxide scavenger. In certain embodiments, the stabilizing agent comprises a metal chelator. In certain embodiments, the stabilizing agent comprises two or more metal chelating agents. In certain embodiments, the stabilizing agent comprises a hydroxyl radical scavenger, a hydroperoxide scavenger, a metal chelator, or any combination thereof (e.g., hydroxyl radical scavenger and hydroperoxide scavenger; hydroxyl radical scavenger and metal chelator; hydroperoxide scavenger and metal chelator; hydroxyl radical scavenger, hydroperoxide scavenger, and metal chelator).
In certain embodiments, the stabilizing agent does not include EDTA, EGTA, or a combination of EDTA and EGTA. In certain embodiments, the stabilizing agent does not include SDS. In certain embodiments, the stabilizing agent does not include cysteine, mercaptoethylene, or a combination of cysteine and mercaptoethylene.
In certain embodiments, the ratio of inorganic compound to stabilizer in the composition is from about 20: 1 to about 1: 2, from about 15: 1 to about 1: 1.5, from about 12: 1 to about 1: 1, from about 10: 1 to about 1.5: 1, from about 8: 1 to about 2: 1, or from about 5: 1 to about 2.5: 1, by weight. In still other embodiments, the ratio of inorganic compound to stabilizer is from about 5: 1 to about 1: 5, from about 4: 1 to about 1: 4, from about 3: 1 to about 1: 3, from about 2: 1 to about 1: 2, or about 1: 1. In other embodiments, the ratio of inorganic compound to stabilizer is from about 20: 1 to about 5: 1, from about 18: 1 to about 10: 1, or from about 16: 1 to about 12: 1.
In certain embodiments, the stabilizer (or mixture of stabilizers) is part of the aqueous medium of the present invention and is present in a concentration of from about 0.05mg/ml to about 100.0mg/ml, from about 0.1mg/ml to about 80.0mg/ml, from about 0.2mg/ml to about 60.0mg/ml, from about 0.3mg/ml to about 40.0mg/ml, from about 0.4mg/ml to about 20.0mg/ml, from about 0.5mg/ml to about 15.0mg/ml, from about 1.0mg/ml to about 10.0mg/ml, or from about 1.5mg/ml to about 5.0 mg/ml. In certain embodiments, the stabilizer (or mixture of stabilizers) is part of the aqueous medium of the present invention and is present in a concentration of from about 0.05mg/ml to about 10.0mg/ml, from about 0.1mg/ml to about 8.0mg/ml, from about 0.2mg/ml to about 6.0mg/ml, from about 0.3mg/ml to about 5.0mg/ml, from about 0.4mg/ml to about 4.0mg/ml, from about 0.5mg/ml to about 3.0mg/ml, from about 0.6mg/ml to about 2.5mg/ml, or from about 0.7mg/ml to about 2.0 mg/ml.
In certain embodiments, the stabilizing agent is part of the aqueous medium of the present invention and is at a concentration of about 5mM to about 500mM, about 6mM to about 400mM, about 7mM to about 300mM, about 8mM to about 250mM, about 9mM to about 200mM, about 10mM to about 150mM, about 15mM to about 100mM, or about 20mM to about 50 mM. In certain embodiments, the stabilizing agent is part of the aqueous medium of the present invention and is at a concentration of about 0.1mM to about 100mM, about 0.2mM to about 80mM, about 0.3mM to about 60mM, about 0.4mM to about 40mM, about 0.5mM to about 30mM, about 0.6mM to about 25mM, about 0.7mM to about 20mM, about 0.8 to about 15mM, about 0.9mM to about 12.5mM, or about 1.0mM to about 10 mM.
In certain embodiments, the compositions of the present invention further comprise a plasticizer. For example, in certain embodiments, the composition comprises an inorganic compound and a plasticizer. As used herein, a "plasticizer" is any agent capable of promoting or improving the storage function of a substrate in the dry state. Thus, in certain embodiments, the plasticizer improves the mechanical properties (e.g., flexibility) of the substrate in the dry state. In certain embodiments, the plasticizer improves the durability (e.g., resistance to vibration damage) of the matrix in the dry state. In certain embodiments, the plasticizer promotes reversible dissociation between the inorganic compound and the biomolecule upon rehydration of the matrix in the dry state. In other embodiments, the plasticizer promotes reversible dissociation between the stabilizer and the biomolecule upon rehydration of the matrix in the dry state.
In certain embodiments, the plasticizer does not significantly interfere with the properties of the biomolecules stored in the dry state matrix of the present invention (e.g., does not interfere with the chemical or physical stability of the stored biomolecules). In other embodiments, the plasticizer inhibits microbial growth (e.g., bacterial or fungal growth) during storage of the dry state substrate of the present invention.
In certain embodiments, the plasticizer is a polyol. As used herein, a "polyol" is an organic compound having two or more hydroxyl groups. In certain embodiments, the plasticizer is a long chain polyol (e.g., polyvinyl alcohol or polyserine). In certain embodiments, the plasticizer is a sugar (e.g., a monosaccharide, a disaccharide, or a complex sugar). Monosaccharides include, but are not limited to, hexoses, pentoses, tetroses, sedoheptulose, glucose, mannose, galactose, allose, altrose, gulose, idose, talose, fructose, sorbose, psicose, tagatose, fucose, fucosyl, rhamnose, ribose, arabinose, xylose, lyxose, ribulose, xylulose, deoxyribose, erythrulose, erythrose, threose, dihydroxyacetone, and glycerol. Disaccharides include, but are not limited to, sucrose, lactose, trehalose, and maltose. Complex carbohydrates include, but are not limited to, trisaccharides, tetrasaccharides, polysaccharides, glycosaminoglycans, aminoglycosides, raffinose, melezitose, maltotriose, acarbose, stachyose, fructooligosaccharides, galactooligosaccharides, oligomannans, glycogen, starch, amylose, amylopectin, cellulose, chitin, inulin, dextrin, dextran (e.g., beta-dextran, dextran), heparin, chondroitin sulfate, hyaluronic acid, heparin sulfate, dermatan sulfate, keratan sulfate, kanamycin, streptomycin, tobramycin, neomycin, paromomycin, apramycin, gentamicin, netilmicin, and amikacin.
In certain embodiments, the plasticizer is a short chain polyol (e.g., a linear or branched short chain polyol). As used herein, a "short chain" polyol is a polyol having a backbone of 6 or less carbon atoms. In certain embodiments, the short chain polyol comprises 12 or fewer carbon atoms. In certain embodiments, the short chain polyol is linear and has the formula Cn(OH)mH2n+2-mWherein n is 2 to 6 and m is 2 to n. In certain embodiments, the short chain polyol is linear and has the formula Cn(OH)mH2n+2-mWherein n is 2 to 12 and m is 2 to n. In certain embodiments, the short chain polyol is branched and has the formula Cn(OH)mH2n+2-mWherein n is 4 to 6 and m is 2 to n. In certain embodiments, the short chain polyol is branched and has the formula Cn(OH)mH2n+2-mWherein n is 4 to 12 and m is 2 to n. Short chain polyols of the present invention include, but are not limited to, ethylene glycol, 1-3 propylene glycol, glycerol, butanetriol (e.g., n-butanetriol or iso-butanetriol), erythritol, pentanetriol (e.g., n-pentanetriol or iso-butanetriol), pentanetetraol (e.g., n-pentanetetraol, iso-pentanetetraol), pentaerythritol, xylitol, sorbitol, and mannitol.
In certain embodiments, the plasticizer is a short chain polyol selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, and erythritol. In other embodiments, the plasticizer is glucose. In other embodiments, the plasticizer is sucrose, trehalose, or mannose. In other embodiments, the plasticizer is ficol or dextran (e.g., short chain dextran with a molecular weight less than 10 kD). In still other embodiments, the plasticizer is polyvinyl alcohol or polyserine. Thus, for example, the addition of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, ficol, dextran, polyvinyl alcohol, or polyserine to the dry state composition of the present invention makes the composition (e.g., substrate) more resistant to vibration damage and promotes reversible dissociation upon rehydration of the air dried substrate.
In certain embodiments, the plasticizer is a polyol, wherein the polyol is not a monosaccharide. In certain embodiments, the plasticizer is a polyol, wherein the polyol is not a hexose. In certain embodiments, the plasticizer is a polyol, wherein the polyol is not a pentose sugar. In certain embodiments, the plasticizer is a polyol, wherein the polyol is not a tetrose. In certain embodiments, the plasticizer is a polyol, wherein the polyol is not one or more monosaccharides selected from sedoheptulose, glucose, mannose, galactose, allose, altrose, gulose, idose, talose, fructose, sorbose, psicose, tagatose, fucose, fucosyl, rhamnose, ribose, arabinose, xylose, lyxose, ribulose, xylulose, deoxyribose, erythrulose, erythrose, threose, dihydroxyacetone, and glycerol.
In certain embodiments, the plasticizer is a polyol, wherein the polyol is not a disaccharide. In certain embodiments, the plasticizer is not one or more disaccharides selected from the group consisting of sucrose, lactose, trehalose, and maltose.
In certain embodiments, the plasticizer is a polyol, wherein the polyol is not a complex sugar. In certain embodiments, the plasticizer is a polyol, wherein the polyol is not a trisaccharide. In certain embodiments, the plasticizer is a polyol, wherein the polyol is not a tetrasaccharide. In certain embodiments, the plasticizer is a polyol, wherein the polyol is not a polysaccharide. In certain embodiments, the plasticizer is a polyol, wherein the polyol is not a glycosaminoglycan. In certain embodiments, the plasticizer is a polyol, wherein the polyol is not an aminoglycoside. In certain embodiments, the plasticizer is a polyol, wherein the polyol is not one or more complex sugars selected from the group consisting of raffinose, melezitose, maltotriose, acarbose, stachyose, fructooligosaccharides, galactooligosaccharides, oligomannans, glycogen, starch, amylose, amylopectin, cellulose, chitin, inulin, dextrin, dextran (e.g., β -dextran, dextran), heparin, chondroitin sulfate, hyaluronic acid, heparin sulfate, dermatan sulfate, keratan sulfate, kanamycin, streptomycin, tobramycin, neomycin, paromomycin, apramycin, gentamicin, netilmicin, and amikacin.
In certain embodiments, the compositions of the present invention comprise an inorganic compound, a stabilizer, and a plasticizer. In certain embodiments, the composition comprises an inorganic compound, two or more stabilizers, and a plasticizer. The inorganic compound and stabilizer can be any of those described herein.
In certain embodiments, the ratio of inorganic compound to plasticizer in the composition is from about 20: 1 to about 1: 2, from about 15: 1 to about 1: 1.5, from 12: 1 to about 1: 1, from about 10: 1 to about 1.5: 1, from about 8: 1 to about 2: 1, by weight. In still other embodiments, the ratio of inorganic compound to plasticizer is from about 500: 1 to about 50: 1, from about 480: 1 to about 100: 1, from about 460: 1 to about 150: 1, from about 440: 1 to about 200: 1, from about 420: 1 to about 250: 1, or from about 400: 1 to about 300: 1.
In certain embodiments, the plasticizer is part of the aqueous medium of the present invention and is present at a concentration of from about 0.01% to about 10%, from about 0.02% to about 8%, from about 0.03% to about 5%, from about 0.04% to about 2%, from about 0.05% to about 1%, or from about 0.06% to about 0.5%.
In certain embodiments, the compositions of the invention further comprise one or more RNase inhibitors. For example, in certain embodiments, the composition comprises an inorganic compound and an RNase inhibitor. RNase inhibitors include, but are not limited to, 2 ' -cytidine monophosphate free acid (2 ' -CMP), aluminum reagent (aluminum), adenosine 5 ' -pyrophosphate, 5 ' -diphosphonidine adenosine 3 ' -phosphate (ppA-3 ' -P), 5 ' -diphosphonidine adenosine 2 ' -phosphate (ppA-2 ' -P), leucine, poly-L-aspartic acid, tyrosine-glutamic acid polymers, oligovinylsulfonic acid, P ' → 5 ' -ester of 5 ' -phospho-2 ' -deoxyuridine 3 ' -pyrophosphate with adenosine 3 ' -phosphate (pdUppAp). In certain embodiments, the composition comprises two or more RNase inhibitors.
In certain embodiments, the composition comprises 2' -CMP. In certain embodiments, the composition further comprises 2' -CMP and an aluminum reagent. In certain embodiments, the composition further comprises 2 '-CMP and ppA-3' -p. In certain embodiments, the composition further comprises 2' -CMP and leucine. In certain embodiments, the composition further comprises 2' -CMP and poly-L-aspartic acid. In certain embodiments, the composition further comprises 2' -CMP and a tyrosine glutamic acid polymer. In certain embodiments, the composition further comprises 2' -CMP and an oligovinyl sulfonic acid. In certain embodiments, the composition further comprises 2' -CMP and pdUppAp. In certain embodiments, the composition further comprises an aluminum reagent. In certain embodiments, the composition further comprises an aluminum reagent and ppA-3' -p. In certain embodiments, the composition further comprises an aluminum agent and leucine. In certain embodiments, the composition further comprises an aluminum agent and poly-L-aspartic acid. In certain embodiments, the composition further comprises an aluminum reagent and a tyrosine glutamic acid polymer. In certain embodiments, the composition further comprises an aluminum reagent and an oligovinyl sulfonic acid. In certain embodiments, the composition further comprises an aluminum reagent and pdUppAp. In certain embodiments, the composition further comprises ppA-3' -p. In certain embodiments, the composition further comprises ppA-3' -p and leucine. In certain embodiments, the composition further comprises ppA-3' -p and poly-L-aspartic acid. In certain embodiments, the composition further comprises ppA-3' -p and a tyrosine glutamic acid polymer. In certain embodiments, the composition further comprises ppA-3' -p and oligovinyl sulfonic acid. In certain embodiments, the composition further comprises ppA-3' -p and pdUppAp. In certain embodiments, the composition further comprises leucine. In certain embodiments, the composition further comprises leucine and poly-L-aspartic acid. In certain embodiments, the composition further comprises leucine and tyrosine glutamate polymers. In certain embodiments, the composition further comprises leucine and oligovinyl sulfonic acid. In certain embodiments, the composition further comprises leucine and pdUppAp. In certain embodiments, the composition further comprises poly-L-aspartic acid. In certain embodiments, the composition further comprises poly-L-aspartic acid and tyrosine glutamic acid polymers. In certain embodiments, the composition further comprises poly-L-aspartic acid and an oligovinyl sulfonic acid. In certain embodiments, the composition further comprises poly-L-aspartic acid and pdUppAp. In certain embodiments, the composition further comprises a tyrosine glutamate polymer. In certain embodiments, the composition further comprises a tyrosine glutamate polymer and an oligovinyl sulfonic acid. In certain embodiments, the composition further comprises a tyrosine glutamate polymer and pdUppAp. In certain embodiments, the composition further comprises an oligovinyl sulfonic acid. In certain embodiments, the composition further comprises oligomeric vinyl sulfonic acid and pdUppAp.
In certain embodiments, the RNase inhibitor is part of the aqueous medium of the present invention and is in a concentration of about 1mM to about 250mM, about 1mM to about 200mM, about 1mM to about 150mM, about 1mM to about 100mM, about 2mM to about 50mM, about 3mM to about 40mM, about 4mM to about 30mM, about 5mM to about 20mM, about 6mM to about 15mM or about 10 mM. In certain embodiments, the RNase inhibitor is part of the aqueous medium of the present invention and is at a concentration of about 1. mu.M to about 500. mu.M, about 1. mu.M to about 400. mu.M, about 1. mu.M to about 300. mu.M, about 1. mu.M to about 200. mu.M, about 1. mu.M to about 100. mu.M, about 1. mu.M to about 50. mu.M, about 2. mu.M to about 40. mu.M, about 3. mu.M to about 30. mu.M, about 4. mu.M to about 20. mu.M, about 5. mu.M to about 15. mu.M or about 10. mu.M.
In certain embodiments, the composition comprises an inorganic compound, a stabilizer, and an RNase inhibitor. In certain embodiments, the composition comprises an inorganic compound, a stabilizer, a plasticizer, and an RNase inhibitor. In certain embodiments, the composition comprises an inorganic compound, a metal chelator, and an RNase inhibitor. In certain embodiments, the composition comprises an inorganic compound, a metal chelator, a plasticizer, and an RNase inhibitor. In certain embodiments, the compositions comprise an inorganic compound, at least two stabilizers (including at least one metal chelator), and an RNase inhibitor. In certain embodiments, the compositions comprise an inorganic compound, at least two stabilizers (including metal chelators), a plasticizer, and an RNase inhibitor.
In certain embodiments, the compositions of the present invention further comprise a biomolecule. Thus, for example, any of the compositions described herein can further comprise a biomolecule. In certain embodiments, the composition comprises a biological sample containing a biomolecule, such as a bodily fluid (e.g., blood, serum, cerebrospinal fluid, urine, sputum, semen, etc.), a tissue sample (e.g., a piece of solid tissue, such as a biopsy, a homogenate, a hair sample, etc.), a cell lysate (e.g., a blood cell lysate, a skin cell lysate, etc.), or a fraction thereof. In some further embodiments, the composition comprises a purified or synthetic biomolecule sample (e.g., a purified or synthetic nucleic acid or protein sample). In certain embodiments, the depot composition comprises a small molecule isolated from a biological sample (i.e., a small molecule that is neither synthetic nor industrially produced). In certain embodiments, the depot composition comprises one or more types of small molecules selected from the group consisting of lipids, coenzymes, metabolites, agents and metabolites of agents, wherein the small molecules are isolated from a biological sample.
In certain embodiments, the composition comprises genomic DNA. In certain embodiments, the composition comprises DNA greater than about 0.1kB, 0.2kB, 0.3kB, 0.5kB, 0.75kB, 1kB, 5kB, 10kB, 15kB, 20kB, 25kB, 30kB, 35kB, 40kB, 45kB, 50kB or longer in length. In certain embodiments, the composition safely stores genomic DNA such that fragments of genomic DNA greater than about 0.1kB, 0.2kB, 0.3kB, 0.5kB, 0.75kB, 1kB, 5kB, 10kB, 15kB, 20kB, 25kB, 30kB, 35kB, 40kB, 45kB, 50kB, or longer in length can be recovered.
In certain embodiments, the composition comprises RNA. In certain embodiments, the RNA is present in a crude lysate of the sample, a partially purified sample, or an RNA fraction purified from the sample. In certain embodiments, the RNA is mRNA. In other embodiments, the RNA is rRNA or tRNA. In other embodiments, the RNA is siRNA. In still other embodiments, the RNA is total RNA.
In certain embodiments, the ratio of inorganic compound to biomolecule in the composition is from about 20000: 1 to about 2: 1 by weight. In still other embodiments, the ratio of inorganic compound to biomolecule in the composition is from about 10000: 1 to about 1000: 1 by weight. In still other embodiments, the ratio of inorganic compound to biomolecule is from about 1000: 1 to about 100: 1 by weight. In still other embodiments, the ratio of inorganic compound to biomolecule is from about 100: 1 to about 10: 1 by weight. In other embodiments, the ratio of inorganic compound to biomolecule is from about 10: 1 to about 1: 1. In other embodiments, the ratio of inorganic compound to biomolecule is from about 5: 1 to about 1: 5. In still other embodiments, the ratio of inorganic compound to biomolecule in the composition is from about 5000: 1 to about 50: 1, from about 1000: 1 to about 10: 1, from about 500: 1 to about 5: 1, from about 100: 1 to about 2: 1, or from about 50: 1 to about 1: 2, by weight. In still other embodiments, the ratio of inorganic compound to biomolecule is about 50: 1, about 40: 1, about 30: 1, about 20: 1, about 10: 1, or about 1: 1 by weight.
In certain embodiments, the compositions comprise a water-soluble inorganic compound (e.g., a boron-, phosphorus-, vanadium-, or aluminum-containing compound), a singlet oxygen quencher (e.g., an alkyl imidazole, an indole, and/or a sulfur-containing amino acid), and optionally a biomolecule. In some further embodiments, the composition comprises a water-soluble inorganic compound (e.g., a boron-, phosphorus-, vanadium-, or aluminum-containing compound), a singlet oxygen quencher (e.g., an alkyl imidazole, an indole, and/or a sulfur-containing amino acid), a plasticizer (e.g., glycerol, polyvinyl alcohol, trehalose, and/or dextran), and optionally a biomolecule. In some further embodiments, the composition comprises a water-soluble inorganic compound (e.g., a boron-, phosphorus-, vanadium-, or aluminum-containing compound), a singlet oxygen quencher (e.g., an alkyl imidazole, indole, and/or sulfur-containing amino acid), a plasticizer (e.g., glycerol, polyvinyl alcohol, trehalose, and/or dextran), a metal chelator (e.g., EDTA), and optionally a biomolecule.
In certain embodiments, the composition comprises a water-soluble inorganic compound (e.g., a boron, phosphorus, vanadium, or aluminum-containing compound), a hydroxyl radical scavenger, and optionally a biomolecule. In still other embodiments, the composition comprises a water-soluble inorganic compound (e.g., a boron, phosphorus, vanadium, or aluminum-containing compound), a hydroxyl radical scavenger, a plasticizer (e.g., glycerol, polyvinyl alcohol, trehalose, and/or dextran), and optionally a biomolecule. In still other embodiments, the composition comprises a water-soluble inorganic compound (e.g., a boron, phosphorus, vanadium, or aluminum-containing compound), a hydroxyl radical scavenger, a plasticizer (e.g., glycerol, polyvinyl alcohol, trehalose, and/or dextran), a metal chelator (e.g., EDTA), and optionally a biomolecule.
In certain embodiments, the compositions comprise a water-soluble inorganic compound (e.g., a boron-, phosphorus-, vanadium-, or aluminum-containing compound), a hydroperoxide scavenger, and optionally a biomolecule. In other embodiments, the composition comprises a water-soluble inorganic compound (e.g., a boron-, phosphorus-, vanadium-, or aluminum-containing compound), a hydroperoxide scavenger, a plasticizer (e.g., glycerol, polyvinyl alcohol, trehalose, and/or dextran), and optionally a biomolecule. In still other embodiments, the composition comprises a water-soluble inorganic compound (e.g., a boron, phosphorus, vanadium, or aluminum-containing compound), a hydroperoxide scavenger, a plasticizer (e.g., glycerol, polyvinyl alcohol, trehalose, and/or dextran), a metal chelator (e.g., EDTA), and optionally a biomolecule.
In certain embodiments, the composition comprises a water-soluble inorganic compound (e.g., a boron, phosphorus, vanadium, or aluminum-containing compound), a hydroxyl radical scavenger, a hydroperoxide scavenger, and optionally a biomolecule. In still other embodiments, the composition comprises a water-soluble inorganic compound (e.g., a boron, phosphorus, vanadium, or aluminum-containing compound), a hydroxyl radical scavenger, a hydroperoxide scavenger, a plasticizer (e.g., glycerol, polyvinyl alcohol, trehalose, and/or dextran), and optionally a biomolecule. In still other embodiments, the composition comprises a water-soluble inorganic compound (e.g., a boron, phosphorus, vanadium, or aluminum-containing compound), a hydroxyl radical scavenger, a hydroperoxide scavenger, a plasticizer (e.g., glycerol, polyvinyl alcohol, trehalose, and/or dextran), a metal chelator (e.g., EDTA), and optionally a biomolecule.
In certain embodiments, the composition comprises boric acid, histidine and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol and polyserine. In certain embodiments, the composition comprises boric acid, histidine, methionine and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol and polyserine. In certain embodiments, the composition comprises boric acid, histidine, tryptophan, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises boric acid, tryptophan, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises boric acid, tryptophan, methionine, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises boric acid, methionine, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises boric acid, tyrosine, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises boric acid, an ascorbate salt, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises boric acid, an azide (e.g., sodium azide), and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises boric acid, tocopherol, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises boric acid, carotene, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises boric acid, phenanthroline, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises boric acid, sodium lauryl sarcosinate, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises boric acid, guanidine hydrochloride, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. Each embodiment in this paragraph can further comprise one or more RNase inhibitors (e.g., any of the RNase inhibitors described or suggested herein or a combination thereof) and/or biomolecules (e.g., any sample comprising biomolecules, such as biological samples).
In certain embodiments, the composition comprises borate, histidine, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises borate, histidine, methionine and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol and polyserine. In certain embodiments, the composition comprises borate, histidine, tryptophan, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises borate, tryptophan, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises borate, tryptophan, methionine, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises borate, methionine, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises borate, tyrosine, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises borate, ascorbate, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises a borate salt, an azide (e.g., sodium azide), and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises borate, tocopherol, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises borate, carotene, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises borate, phenanthroline, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises borate, sodium lauryl sarcosinate, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises borate, guanidine hydrochloride, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. Each embodiment in this paragraph can further comprise one or more RNase inhibitors (e.g., any of the RNase inhibitors described or suggested herein or a combination thereof) and/or biomolecules (e.g., any sample comprising biomolecules, such as biological samples).
In certain embodiments, the composition comprises phosphoric acid, histidine and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol and polyserine. In certain embodiments, the composition comprises phosphoric acid, histidine, methionine and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol and polyserine. In certain embodiments, the composition comprises phosphoric acid, histidine, tryptophan, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises phosphoric acid, tryptophan, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises phosphoric acid, tryptophan, methionine, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises phosphoric acid, methionine, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises phosphoric acid, tyrosine, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises phosphoric acid, an ascorbate salt, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises phosphoric acid, an azide (e.g., sodium azide), and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises phosphoric acid, tocopherol, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises phosphoric acid, carotene, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises phosphoric acid, phenanthroline, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises phosphoric acid, sodium lauryl sarcosinate, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises phosphoric acid, guanidine hydrochloride, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. Each embodiment in this paragraph can further comprise one or more RNase inhibitors (e.g., any of the RNase inhibitors described or suggested herein or a combination thereof) and/or biomolecules (e.g., any sample comprising biomolecules, such as biological samples).
In certain embodiments, the composition comprises a salt of phosphoric acid, histidine, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises a salt of phosphoric acid, histidine, methionine, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises a salt of phosphoric acid, histidine, tryptophan, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises a salt of phosphoric acid, tryptophan, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises a salt of phosphoric acid, tryptophan, methionine, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises a salt of phosphoric acid, methionine, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises a salt of phosphoric acid, tyrosine, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises a salt of phosphoric acid, an ascorbate salt, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises a salt of phosphoric acid, an azide (e.g., sodium azide), and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises a salt of phosphoric acid, tocopherol, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises a salt of phosphoric acid, carotene, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises a salt of phosphoric acid, phenanthroline, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises a salt of phosphoric acid, sodium lauryl sarcosinate, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises a salt of phosphoric acid, guanidine hydrochloride, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. Each embodiment in this paragraph can further comprise one or more RNase inhibitors (e.g., any of the RNase inhibitors described or suggested herein or a combination thereof) and/or biomolecules (e.g., any sample comprising biomolecules, such as biological samples).
In certain embodiments, the composition comprises vanadate, histidine, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises vanadate, histidine, methionine and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol and polyserine. In certain embodiments, the composition comprises vanadate, histidine, tryptophan, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises vanadate, tryptophan, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises vanadate, tryptophan, methionine and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol and polyserine. In certain embodiments, the composition comprises vanadate, methionine, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises vanadate, tyrosine, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises a vanadate, an ascorbate, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises a vanadate, an azide (e.g., sodium azide), and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises a vanadate, a tocopherol, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises vanadate, carotene, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises a vanadate, phenanthroline, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises vanadate, sodium lauryl sarcosinate, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises vanadate, guanidine hydrochloride, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. Each embodiment in this paragraph can further comprise one or more RNase inhibitors (e.g., any of the RNase inhibitors described or suggested herein or a combination thereof) and/or biomolecules (e.g., any sample comprising biomolecules, such as biological samples).
In certain embodiments, the composition comprises potassium alum, histidine, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises potassium alum, histidine, methionine, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises potassium alum, histidine, tryptophan, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises potassium alum, tryptophan, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises potassium alum, tryptophan, methionine, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises potassium alum, methionine, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises potassium alum, tyrosine, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises potassium alum, ascorbate, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises potassium alum, an azide (e.g., sodium azide), and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises potassium alum, tocopherol, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises potassium alum, carotene, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises potash alum, phenanthroline, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises potassium alum, sodium lauryl sarcosinate, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises potassium alum, guanidine hydrochloride, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. Each embodiment in this paragraph can further comprise one or more RNase inhibitors (e.g., any of the RNase inhibitors described or suggested herein or a combination thereof) and/or biomolecules (e.g., any sample comprising biomolecules, such as biological samples).
In certain embodiments, the composition comprises sodalum, histidine, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises sodalum, histidine, methionine, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises sodalum, histidine, tryptophan, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises sodalum, tryptophan, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises sodalum, tryptophan, methionine, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises sodalum, methionine, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises sodalum, tyrosine, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises sodalum, ascorbate, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises sodiumsulvin, an azide (e.g., sodium azide), and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises sodalum, tocopherol, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises sodalum, carotene, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises sodalum, phenanthroline, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises sodiumsulvin, sodium lauryl sarcosinate, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises sodalum, guanidine hydrochloride, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. Each embodiment in this paragraph can further comprise one or more RNase inhibitors (e.g., any of the RNase inhibitors described or suggested herein or a combination thereof) and/or biomolecules (e.g., any sample comprising biomolecules, such as biological samples).
In certain embodiments, the composition comprises ammonium alum, histidine, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises ammonium alum, histidine, methionine, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises ammonium alum, histidine, tryptophan, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises ammonium alum, tryptophan, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises ammonium alum, tryptophan, methionine, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises ammonium alum, methionine, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises ammonium alum, tyrosine, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises ammonium alum, ascorbate, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises ammonium alum, an azide (e.g., sodium azide), and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises ammonium alum, tocopherol, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises ammonium alum, carotene, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises ammonium alum, phenanthroline, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises ammonium alum, sodium lauryl sarcosinate, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises ammonium alum, guanidine hydrochloride, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. Each embodiment in this paragraph can further comprise one or more RNase inhibitors (e.g., any of the RNase inhibitors described or suggested herein or a combination thereof) and/or biomolecules (e.g., any sample comprising biomolecules, such as biological samples).
In certain embodiments, the inorganic compounds of the above compositions (e.g., boric acid, borates, phosphoric acid, salts of phosphoric acid, vanadates, potash alum, sodalum, and ammonium alum) are in an aqueous medium (e.g., before or after mixing with a sample) and at a concentration of about 5mM to about 500mM, about 6mM to about 400mM, about 7mM to about 300mM, about 8mM to about 250mM, about 9mM to about 200mM, about 10mM to about 150mM, about 20mM to about 140mM, about 30mM to about 130mM, about 40mM to about 120mM, about 50mM to about 110mM, about 60mM to about 100mM, about 70mM to about 90mM, or about 80 mM. In certain embodiments, the stabilizing agent (e.g., histidine, tryptophan, methionine, tyrosine, ascorbate, sodium azide, tocopherol, carotene, phenanthroline, sarcosyl, and guanidine hydrochloride) of the above-described compositions is in an aqueous medium (e.g., before or after mixing with a sample) and at a concentration of about 1mM to about 250mM, about 2mM to about 200mM, about 3mM to about 150mM, about 4mM to about 100mM, about 5mM to about 75mM, about 10mM to about 50mM, about 15mM to about 45mM, about 20mM to about 40mM, about 25mM to about 35mM, or about 30 mM. In certain embodiments, the plasticizers (e.g., ethylene glycol, 1, 3-propylene glycol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine) of the above-described compositions are in an aqueous medium (e.g., before or after mixing with a sample) and at a concentration of about 0.01% to about 8.0%, about 0.02% to about 5.0%, about 0.03% to about 2.0%, about 0.04% to about 1.5%, about 0.05% to about 1%, or about 0.06% to about 0.5%.
In certain embodiments, the composition comprises boric acid and dimethyl sulfoxide. In certain embodiments, the composition comprises boric acid, dimethyl sulfoxide, and catalase. In certain embodiments, the composition comprises boric acid, dimethyl sulfoxide, and pyruvate. In certain embodiments, the composition comprises boric acid, dimethyl sulfoxide, and glutathione. In certain embodiments, the composition comprises boric acid, dimethyl sulfoxide, and glutathione peroxidase. In certain embodiments, the composition comprises boric acid and histidine. In certain embodiments, the composition comprises boric acid, histidine, and catalase. In certain embodiments, the composition comprises boric acid, histidine, and pyruvate. In certain embodiments, the composition comprises boric acid, histidine, and glutathione. In certain embodiments, the composition comprises boric acid, histidine, and glutathione peroxidase. In certain embodiments, the composition comprises boric acid and mannitol. In certain embodiments, the composition comprises boric acid, mannitol, and catalase. In certain embodiments, the composition comprises boric acid, mannitol, and pyruvate. In certain embodiments, the composition comprises boric acid, mannitol, and glutathione. In certain embodiments, the composition comprises boric acid, mannitol, and glutathione peroxidase. In certain embodiments, the composition comprises boric acid and sucrose. In certain embodiments, the composition comprises boric acid, sucrose, and catalase. In certain embodiments, the composition comprises boric acid, sucrose and pyruvate. In certain embodiments, the composition comprises boric acid, sucrose, and glutathione. In certain embodiments, the composition comprises boric acid, sucrose, and glutathione peroxidase. In certain embodiments, the composition comprises boric acid and glucose. In certain embodiments, the composition comprises boric acid, glucose, and catalase. In certain embodiments, the composition comprises boric acid, glucose, and pyruvate. In certain embodiments, the composition comprises boric acid, glucose, and glutathione. In certain embodiments, the composition comprises boric acid, glucose, and glutathione peroxidase. Each embodiment in this paragraph can further comprise one or more RNase inhibitors (e.g., any of the RNase inhibitors described or suggested herein or a combination thereof) and/or biomolecules (e.g., any sample comprising biomolecules, such as biological samples).
In certain embodiments, the composition of the previous paragraph further comprises EDTA. In certain embodiments, the composition of the previous paragraph further comprises EDTA and glycerol. In certain embodiments, the composition of the previous paragraph further comprises EDTA and trehalose. In certain embodiments, the composition of the previous paragraph further comprises EDTA and dextran. In certain embodiments, the composition of the previous paragraph further comprises EDTA and polyvinyl alcohol. In certain embodiments, the composition of the previous paragraph further comprises EGTA. In certain embodiments, the composition of the previous paragraph further comprises EGTA and glycerol. In certain embodiments, the composition of the previous paragraph further comprises EGTA and trehalose. In certain embodiments, the composition of the previous paragraph further comprises EGTA and dextran. In certain embodiments, the composition of the previous paragraph further comprises EGTA and polyvinyl alcohol. In certain embodiments, the composition of the previous paragraph further comprises a phenanthroline. In certain embodiments, the composition of the previous paragraph further comprises phenanthroline and glycerol. In certain embodiments, the composition of the previous paragraph further comprises phenanthroline and trehalose. In certain embodiments, the composition of the previous paragraph further comprises phenanthroline and a dextran. In certain embodiments, the composition of the previous paragraph further comprises phenanthroline and polyvinyl alcohol. In certain embodiments, the composition of the previous paragraph further comprises EDTA and citrate. In certain embodiments, the composition of the previous paragraph further comprises EDTA, citrate, and glycerol. In certain embodiments, the composition of the previous paragraph further comprises EDTA, citrate, and trehalose. In certain embodiments, the composition of the previous paragraph further comprises EDTA, citrate, and dextran. In certain embodiments, the composition of the previous paragraph further comprises EDTA, citrate, and polyvinyl alcohol. In certain embodiments, the composition of the previous paragraph further comprises EGTA and citrate. In certain embodiments, the composition of the previous paragraph further comprises EGTA, citrate, and glycerol. In certain embodiments, the composition of the previous paragraph further comprises EGTA, citrate, and trehalose. In certain embodiments, the composition of the previous paragraph further comprises EGTA, citrate, and dextran. In certain embodiments, the composition of the previous paragraph further comprises EGTA, citrate, and polyvinyl alcohol. In certain embodiments, the composition of the previous paragraph further comprises phenanthroline and a citrate salt. In certain embodiments, the composition of the previous paragraph further comprises phenanthroline, citrate, and glycerol. In certain embodiments, the composition of the previous paragraph further comprises phenanthroline, citrate, and trehalose. In certain embodiments, the composition of the previous paragraph further comprises phenanthroline, citrate, and dextran. In certain embodiments, the composition of the previous paragraph further comprises phenanthroline, citrate, and polyvinyl alcohol.
In certain embodiments, the composition comprises borate and dimethyl sulfoxide. In certain embodiments, the composition comprises borate, dimethyl sulfoxide, and catalase. In certain embodiments, the composition comprises borate, dimethyl sulfoxide, and pyruvate. In certain embodiments, the composition comprises borate, dimethyl sulfoxide, and glutathione. In certain embodiments, the composition comprises borate, dimethyl sulfoxide, and glutathione peroxidase. In certain embodiments, the composition comprises borate and histidine. In certain embodiments, the composition comprises borate, histidine, and catalase. In certain embodiments, the composition comprises borate, histidine, and pyruvate. In certain embodiments, the composition comprises borate, histidine, and glutathione. In certain embodiments, the composition comprises borate, histidine, and glutathione peroxidase. In certain embodiments, the composition comprises borate and mannitol. In certain embodiments, the composition comprises borate, mannitol, and catalase. In certain embodiments, the composition comprises borate, mannitol, and pyruvate. In certain embodiments, the composition comprises borate, mannitol, and glutathione. In certain embodiments, the composition comprises borate, mannitol, and glutathione peroxidase. In certain embodiments, the composition comprises borate and sucrose. In certain embodiments, the composition comprises borate, sucrose, and catalase. In certain embodiments, the composition comprises borate, sucrose and pyruvate. In certain embodiments, the composition comprises borate, sucrose, and glutathione. In certain embodiments, the composition comprises borate, sucrose, and glutathione peroxidase. In certain embodiments, the composition comprises borate and glucose. In certain embodiments, the composition comprises borate, glucose, and catalase. In certain embodiments, the composition comprises borate, glucose, and pyruvate. In certain embodiments, the composition comprises borate, glucose, and glutathione. In certain embodiments, the composition comprises borate, glucose, and glutathione peroxidase. Each embodiment in this paragraph can further comprise one or more RNase inhibitors (e.g., any of the RNase inhibitors described or suggested herein or a combination thereof) and/or biomolecules (e.g., any sample comprising biomolecules, such as biological samples).
In certain embodiments, the composition of the previous paragraph further comprises EDTA. In certain embodiments, the composition of the previous paragraph further comprises EDTA and glycerol. In certain embodiments, the composition of the previous paragraph further comprises EDTA and trehalose. In certain embodiments, the composition of the previous paragraph further comprises EDTA and dextran. In certain embodiments, the composition of the previous paragraph further comprises EDTA and polyvinyl alcohol. In certain embodiments, the composition of the previous paragraph further comprises EGTA. In certain embodiments, the composition of the previous paragraph further comprises EGTA and glycerol. In certain embodiments, the composition of the previous paragraph further comprises EGTA and trehalose. In certain embodiments, the composition of the previous paragraph further comprises EGTA and dextran. In certain embodiments, the composition of the previous paragraph further comprises EGTA and polyvinyl alcohol. In certain embodiments, the composition of the previous paragraph further comprises a phenanthroline. In certain embodiments, the composition of the previous paragraph further comprises phenanthroline and glycerol. In certain embodiments, the composition of the previous paragraph further comprises phenanthroline and trehalose. In certain embodiments, the composition of the previous paragraph further comprises phenanthroline and a dextran. In certain embodiments, the composition of the previous paragraph further comprises phenanthroline and polyvinyl alcohol. In certain embodiments, the composition of the previous paragraph further comprises EDTA and citrate. In certain embodiments, the composition of the previous paragraph further comprises EDTA, citrate, and glycerol. In certain embodiments, the composition of the previous paragraph further comprises EDTA, citrate, and trehalose. In certain embodiments, the composition of the previous paragraph further comprises EDTA, citrate, and dextran. In certain embodiments, the composition of the previous paragraph further comprises EDTA, citrate, and polyvinyl alcohol. In certain embodiments, the composition of the previous paragraph further comprises EGTA and citrate. In certain embodiments, the composition of the previous paragraph further comprises EGTA, citrate, and glycerol. In certain embodiments, the composition of the previous paragraph further comprises EGTA, citrate, and trehalose. In certain embodiments, the composition of the previous paragraph further comprises EGTA, citrate, and dextran. In certain embodiments, the composition of the previous paragraph further comprises EGTA, citrate, and polyvinyl alcohol. In certain embodiments, the composition of the previous paragraph further comprises phenanthroline and a citrate salt. In certain embodiments, the composition of the previous paragraph further comprises phenanthroline, citrate, and glycerol. In certain embodiments, the composition of the previous paragraph further comprises phenanthroline, citrate, and trehalose. In certain embodiments, the composition of the previous paragraph further comprises phenanthroline, citrate, and dextran. In certain embodiments, the composition of the previous paragraph further comprises phenanthroline, citrate, and polyvinyl alcohol.
In certain embodiments, the composition comprises phosphoric acid or a salt thereof and dimethyl sulfoxide. In certain embodiments, the composition comprises phosphoric acid or a salt thereof, dimethyl sulfoxide, and catalase. In certain embodiments, the composition comprises phosphoric acid or a salt thereof, dimethyl sulfoxide, and pyruvate. In certain embodiments, the composition comprises phosphoric acid or a salt thereof, dimethyl sulfoxide, and glutathione. In certain embodiments, the composition comprises phosphoric acid or a salt thereof, dimethyl sulfoxide, and glutathione peroxidase. In certain embodiments, the composition comprises phosphoric acid or a salt thereof and histidine. In certain embodiments, the composition comprises phosphoric acid or a salt thereof, histidine, and catalase. In certain embodiments, the composition comprises phosphoric acid or a salt thereof, histidine, and pyruvate. In certain embodiments, the composition comprises phosphoric acid or a salt thereof, histidine, and glutathione. In certain embodiments, the composition comprises phosphoric acid or a salt thereof, histidine, and glutathione peroxidase. In certain embodiments, the composition comprises phosphoric acid or a salt thereof and mannitol. In certain embodiments, the composition comprises phosphoric acid or a salt thereof, mannitol, and catalase. In certain embodiments, the composition comprises phosphoric acid or a salt thereof, mannitol, and pyruvate. In certain embodiments, the composition comprises phosphoric acid or a salt thereof, mannitol, and glutathione. In certain embodiments, the composition comprises phosphoric acid or a salt thereof, mannitol, and glutathione peroxidase. In certain embodiments, the composition comprises phosphoric acid or a salt thereof and sucrose. In certain embodiments, the composition comprises phosphoric acid or a salt thereof, sucrose, and catalase. In certain embodiments, the composition comprises phosphoric acid or a salt thereof, sucrose, and pyruvate. In certain embodiments, the composition comprises phosphoric acid or a salt thereof, sucrose, and glutathione. In certain embodiments, the composition comprises phosphoric acid or a salt thereof, sucrose, and glutathione peroxidase. In certain embodiments, the composition comprises phosphoric acid or a salt thereof and glucose. In certain embodiments, the composition comprises phosphoric acid or a salt thereof, glucose, and catalase. In certain embodiments, the composition comprises phosphoric acid or a salt thereof, glucose, and pyruvate. In certain embodiments, the composition comprises phosphoric acid or a salt thereof, glucose, and glutathione. In certain embodiments, the composition comprises phosphoric acid or a salt thereof, glucose, and glutathione peroxidase. Each embodiment in this paragraph can further comprise one or more RNase inhibitors (e.g., any of the RNase inhibitors described or suggested herein or a combination thereof) and/or biomolecules (e.g., any sample comprising biomolecules, such as biological samples).
In certain embodiments, the composition of the previous paragraph further comprises EDTA. In certain embodiments, the composition of the previous paragraph further comprises EDTA and glycerol. In certain embodiments, the composition of the previous paragraph further comprises EDTA and trehalose. In certain embodiments, the composition of the previous paragraph further comprises EDTA and dextran. In certain embodiments, the composition of the previous paragraph further comprises EDTA and polyvinyl alcohol. In certain embodiments, the composition of the previous paragraph further comprises EGTA. In certain embodiments, the composition of the previous paragraph further comprises EGTA and glycerol. In certain embodiments, the composition of the previous paragraph further comprises EGTA and trehalose. In certain embodiments, the composition of the previous paragraph further comprises EGTA and dextran. In certain embodiments, the composition of the previous paragraph further comprises EGTA and polyvinyl alcohol. In certain embodiments, the composition of the previous paragraph further comprises a phenanthroline. In certain embodiments, the composition of the previous paragraph further comprises phenanthroline and glycerol. In certain embodiments, the composition of the previous paragraph further comprises phenanthroline and trehalose. In certain embodiments, the composition of the previous paragraph further comprises phenanthroline and a dextran. In certain embodiments, the composition of the previous paragraph further comprises phenanthroline and polyvinyl alcohol. In certain embodiments, the composition of the previous paragraph further comprises EDTA and citrate. In certain embodiments, the composition of the previous paragraph further comprises EDTA, citrate, and glycerol. In certain embodiments, the composition of the previous paragraph further comprises EDTA, citrate, and trehalose. In certain embodiments, the composition of the previous paragraph further comprises EDTA, citrate, and dextran. In certain embodiments, the composition of the previous paragraph further comprises EDTA, citrate, and polyvinyl alcohol. In certain embodiments, the composition of the previous paragraph further comprises EGTA and citrate. In certain embodiments, the composition of the previous paragraph further comprises EGTA, citrate, and glycerol. In certain embodiments, the composition of the previous paragraph further comprises EGTA, citrate, and trehalose. In certain embodiments, the composition of the previous paragraph further comprises EGTA, citrate, and dextran. In certain embodiments, the composition of the previous paragraph further comprises EGTA, citrate, and polyvinyl alcohol. In certain embodiments, the composition of the previous paragraph further comprises phenanthroline and a citrate salt. In certain embodiments, the composition of the previous paragraph further comprises phenanthroline, citrate, and glycerol. In certain embodiments, the composition of the previous paragraph further comprises phenanthroline, citrate, and trehalose. In certain embodiments, the composition of the previous paragraph further comprises phenanthroline, citrate, and dextran. In certain embodiments, the composition of the previous paragraph further comprises phenanthroline, citrate, and polyvinyl alcohol.
In certain embodiments, the composition comprises vanadate and dimethyl sulfoxide. In certain embodiments, the composition comprises a vanadate, dimethyl sulfoxide, and catalase. In certain embodiments, the composition comprises a vanadate, dimethyl sulfoxide, and a pyruvate. In certain embodiments, the composition comprises vanadate, dimethyl sulfoxide, and glutathione. In certain embodiments, the composition comprises vanadate, dimethyl sulfoxide, and glutathione peroxidase. In certain embodiments, the composition comprises vanadate and histidine. In certain embodiments, the composition comprises vanadate, histidine, and catalase. In certain embodiments, the composition comprises vanadate, histidine, and pyruvate. In certain embodiments, the composition comprises vanadate, histidine, and glutathione. In certain embodiments, the composition comprises vanadate, histidine and glutathione peroxidase. In certain embodiments, the composition comprises vanadate and mannitol. In certain embodiments, the composition comprises vanadate, mannitol, and catalase. In certain embodiments, the composition comprises vanadate, mannitol, and pyruvate. In certain embodiments, the composition comprises vanadate, mannitol, and glutathione. In certain embodiments, the composition comprises vanadate, mannitol, and glutathione peroxidase. In certain embodiments, the composition comprises vanadate and sucrose. In certain embodiments, the composition comprises vanadate, sucrose, and catalase. In certain embodiments, the composition comprises vanadate, sucrose and pyruvate. In certain embodiments, the composition comprises vanadate, sucrose, and glutathione. In certain embodiments, the composition comprises vanadate, sucrose and glutathione peroxidase. In certain embodiments, the composition comprises vanadate and glucose. In certain embodiments, the composition comprises vanadate, glucose, and catalase. In certain embodiments, the composition comprises vanadate, glucose, and pyruvate. In certain embodiments, the composition comprises vanadate, glucose, and glutathione. In certain embodiments, the composition comprises vanadate, glucose, and glutathione peroxidase. Each embodiment in this paragraph can further comprise one or more RNase inhibitors (e.g., any of the RNase inhibitors described or suggested herein or a combination thereof) and/or biomolecules (e.g., any sample comprising biomolecules, such as biological samples).
In certain embodiments, the composition of the previous paragraph further comprises EDTA. In certain embodiments, the composition of the previous paragraph further comprises EDTA and glycerol. In certain embodiments, the composition of the previous paragraph further comprises EDTA and trehalose. In certain embodiments, the composition of the previous paragraph further comprises EDTA and dextran. In certain embodiments, the composition of the previous paragraph further comprises EDTA and polyvinyl alcohol. In certain embodiments, the composition of the previous paragraph further comprises EGTA. In certain embodiments, the composition of the previous paragraph further comprises EGTA and glycerol. In certain embodiments, the composition of the previous paragraph further comprises EGTA and trehalose. In certain embodiments, the composition of the previous paragraph further comprises EGTA and dextran. In certain embodiments, the composition of the previous paragraph further comprises EGTA and polyvinyl alcohol. In certain embodiments, the composition of the previous paragraph further comprises a phenanthroline. In certain embodiments, the composition of the previous paragraph further comprises phenanthroline and glycerol. In certain embodiments, the composition of the previous paragraph further comprises phenanthroline and trehalose. In certain embodiments, the composition of the previous paragraph further comprises phenanthroline and a dextran. In certain embodiments, the composition of the previous paragraph further comprises phenanthroline and polyvinyl alcohol. In certain embodiments, the composition of the previous paragraph further comprises EDTA and citrate. In certain embodiments, the composition of the previous paragraph further comprises EDTA, citrate, and glycerol. In certain embodiments, the composition of the previous paragraph further comprises EDTA, citrate, and trehalose. In certain embodiments, the composition of the previous paragraph further comprises EDTA, citrate, and dextran. In certain embodiments, the composition of the previous paragraph further comprises EDTA, citrate, and polyvinyl alcohol. In certain embodiments, the composition of the previous paragraph further comprises EGTA and citrate. In certain embodiments, the composition of the previous paragraph further comprises EGTA, citrate, and glycerol. In certain embodiments, the composition of the previous paragraph further comprises EGTA, citrate, and trehalose. In certain embodiments, the composition of the previous paragraph further comprises EGTA, citrate, and dextran. In certain embodiments, the composition of the previous paragraph further comprises EGTA, citrate, and polyvinyl alcohol. In certain embodiments, the composition of the previous paragraph further comprises phenanthroline and a citrate salt. In certain embodiments, the composition of the previous paragraph further comprises phenanthroline, citrate, and glycerol. In certain embodiments, the composition of the previous paragraph further comprises phenanthroline, citrate, and trehalose. In certain embodiments, the composition of the previous paragraph further comprises phenanthroline, citrate, and dextran. In certain embodiments, the composition of the previous paragraph further comprises phenanthroline, citrate, and polyvinyl alcohol.
In certain embodiments, the composition comprises alum (e.g., potassium alum, sodium alum, or ammonium alum) and dimethyl sulfoxide. In certain embodiments, the composition comprises alum, dimethyl sulfoxide, and catalase. In certain embodiments, the composition comprises alum, dimethyl sulfoxide, and pyruvate. In certain embodiments, the composition comprises alum, dimethyl sulfoxide, and glutathione. In certain embodiments, the composition comprises alum, dimethyl sulfoxide, and glutathione peroxidase. In certain embodiments, the composition comprises alum (e.g., potassium alum, sodium alum, or ammonium alum) and histidine. In certain embodiments, the composition comprises alum, histidine, and catalase. In certain embodiments, the composition comprises alum, histidine, and pyruvate. In certain embodiments, the composition comprises alum, histidine, and glutathione. In certain embodiments, the composition comprises alum, histidine, and glutathione peroxidase. In certain embodiments, the composition comprises alum (e.g., potassium alum, sodium alum, or ammonium alum) and mannitol. In certain embodiments, the composition comprises alum, mannitol, and catalase. In certain embodiments, the composition comprises alum, mannitol, and pyruvate. In certain embodiments, the composition comprises alum, mannitol, and glutathione. In certain embodiments, the composition comprises alum, mannitol, and glutathione peroxidase. In certain embodiments, the composition comprises alum (e.g., potassium alum, sodium alum, or ammonium alum) and sucrose. In certain embodiments, the composition comprises alum, sucrose, and catalase. In certain embodiments, the composition comprises alum, sucrose and pyruvate. In certain embodiments, the composition comprises alum, sucrose, and glutathione. In certain embodiments, the composition comprises alum, sucrose, and glutathione peroxidase. In certain embodiments, the composition comprises alum (e.g., potassium alum, sodium alum, or ammonium alum) and glucose. In certain embodiments, the composition comprises alum, glucose, and catalase. In certain embodiments, the composition comprises alum, glucose, and pyruvate. In certain embodiments, the composition comprises alum, glucose, and glutathione. In certain embodiments, the composition comprises alum, glucose, and glutathione peroxidase. Each embodiment in this paragraph can further comprise one or more RNase inhibitors (e.g., any of the RNase inhibitors described or suggested herein or a combination thereof) and/or biomolecules (e.g., any sample comprising biomolecules, such as biological samples).
In certain embodiments, the composition of the previous paragraph further comprises EDTA. In certain embodiments, the composition of the previous paragraph further comprises EDTA and glycerol. In certain embodiments, the composition of the previous paragraph further comprises EDTA and trehalose. In certain embodiments, the composition of the previous paragraph further comprises EDTA and dextran. In certain embodiments, the composition of the previous paragraph further comprises EDTA and polyvinyl alcohol. In certain embodiments, the composition of the previous paragraph further comprises EGTA. In certain embodiments, the composition of the previous paragraph further comprises EGTA and glycerol. In certain embodiments, the composition of the previous paragraph further comprises EGTA and trehalose. In certain embodiments, the composition of the previous paragraph further comprises EGTA and dextran. In certain embodiments, the composition of the previous paragraph further comprises EGTA and polyvinyl alcohol. In certain embodiments, the composition of the previous paragraph further comprises a phenanthroline. In certain embodiments, the composition of the previous paragraph further comprises phenanthroline and glycerol. In certain embodiments, the composition of the previous paragraph further comprises phenanthroline and trehalose. In certain embodiments, the composition of the previous paragraph further comprises phenanthroline and a dextran. In certain embodiments, the composition of the previous paragraph further comprises phenanthroline and polyvinyl alcohol. In certain embodiments, the composition of the previous paragraph further comprises EDTA and citrate. In certain embodiments, the composition of the previous paragraph further comprises EDTA, citrate, and glycerol. In certain embodiments, the composition of the previous paragraph further comprises EDTA, citrate, and trehalose. In certain embodiments, the composition of the previous paragraph further comprises EDTA, citrate, and dextran. In certain embodiments, the composition of the previous paragraph further comprises EDTA, citrate, and polyvinyl alcohol. In certain embodiments, the composition of the previous paragraph further comprises EGTA and citrate. In certain embodiments, the composition of the previous paragraph further comprises EGTA, citrate, and glycerol. In certain embodiments, the composition of the previous paragraph further comprises EGTA, citrate, and trehalose. In certain embodiments, the composition of the previous paragraph further comprises EGTA, citrate, and dextran. In certain embodiments, the composition of the previous paragraph further comprises EGTA, citrate, and polyvinyl alcohol. In certain embodiments, the composition of the previous paragraph further comprises phenanthroline and a citrate salt. In certain embodiments, the composition of the previous paragraph further comprises phenanthroline, citrate, and glycerol. In certain embodiments, the composition of the previous paragraph further comprises phenanthroline, citrate, and trehalose. In certain embodiments, the composition of the previous paragraph further comprises phenanthroline, citrate, and dextran. In certain embodiments, the composition of the previous paragraph further comprises phenanthroline, citrate, and polyvinyl alcohol.
In certain embodiments, the inorganic compound (e.g., boric acid, borate, phosphoric acid or salt thereof, vanadate, alum) of the above-described compositions is in an aqueous medium (e.g., before or after mixing with a sample) and at a concentration of about 5mM to about 500mM, about 5.5mM to about 400mM, about 6mM to about 300mM, about 6.5mM to about 250mM, about 7mM to about 200mM, about 7.5mM to about 150mM, about 8mM to about 140mM, about 8.5mM to about 130mM, about 9mM to about 120mM, about 9.5mM to about 110mM, about 10mM to about 100mM, about 10.1mM to about 90mM, about 10.2mM to about 80mM, about 10.3mM to about 70mM, about 10.4mM to about 60mM, about 10.5mM to about 50mM, about 10.6mM to about 40mM, about 10.7mM to about 30mM, about 10.8mM to about 25mM, About 10.9mM to about 20mM, about 11mM to about 15mM, or about 12.5 mM. In certain embodiments, the stabilizing agent (e.g., dimethyl sulfoxide, histidine, mannitol, catalase, pyruvate, glutathione, and glutathione peroxidases) of the foregoing compositions is in an aqueous medium (e.g., before or after mixing with a sample) and at a concentration of about 1.0mM to about 250mM, about 1.5mM to about 200mM, about 2.0mM to about 150mM, about 2.5mM to about 100mM, about 3.0mM to about 75mM, about 3.5mM to about 50mM, about 4.0mM to about 40mM, about 4.5mM to about 30mM, about 5.0mM to about 20mM, about 5.5mM to about 10mM, about 6.0mM to about 7.5mM, or about 6.25 mM.
In certain embodiments, the metal chelator (e.g., EDTA, EGTA) of the compositions described above is in an aqueous medium (e.g., before or after mixing with the sample) and at a concentration of about 0.01mM to about 50mM, about 0.02mM to about 45mM, about 0.03mM to about 40mM, about 0.04mM to about 35mM, about 0.05mM to about 30mM, about 0.06mM to about 25mM, about 0.07mM to about 20mM, about 0.08 mM to about 15mM, about 0.09mM to about 10mM, about 0.1mM to about 5mM, or about 0.1 mM. In certain embodiments, the metal chelator (e.g., citrate) of the compositions described above is in an aqueous medium (e.g., before or after mixing with the sample) and at a concentration of about 0.01mM to about 200mM, about 0.02mM to about 180mM, about 0.03mM to about 160mM, about 0.04mM to about 140mM, about 0.05mM to about 120mM, about 0.06mM to about 100mM, about 0.07mM to about 80mM, about 0.08 mM to about 60mM, about 0.09mM to about 40mM, about 0.1mM to about 20mM, about 0.1mM to about 15mM, about 0.1mM to about 10mM, about 0.2mM to about 9mM, about 0.3mM to about 8mM, about 0.4mM to about 7mM, about 0.5mM to about 6mM, about 0.6mM to about 5mM, about 0.7mM to about 4mM, about 0.8mM to about 3mM, about 0.9mM to about 2mM, about 1.0mM to about 1.5mM, or about 1.25 mM. In certain embodiments, the plasticizers (e.g., glycerol, trehalose, dextran, and polyvinyl alcohol) of the above-described compositions are in an aqueous medium (e.g., before or after mixing with a sample) and at a concentration of about 0.01% to about 8.0%, about 0.02% to about 5.0%, about 0.03% to about 2.0%, about 0.04% to about 1.5%, about 0.05% to about 1%, or about 0.06% to about 0.5%.
In another aspect, the present invention provides a composition comprising a stabilizer. The stabilizer may be any stabilizer disclosed or suggested herein (e.g., singlet oxygen quencher, hydroxyl radical scavenger, hydroperoxide scavenger, reducing agent, metal chelator, detergent, chaotrope, or any combination thereof). In certain embodiments, the stabilizing agent is a singlet oxygen quencher. The singlet oxygen quencher may be any singlet oxygen quencher described or suggested herein. In other embodiments, the stabilizing agent is a hydroxyl radical scavenger. The hydroxyl radical scavenger may be any of the hydroxyl radical scavengers described or suggested herein. In still other embodiments, the stabilizing agent may be a hydroperoxide scavenger. The hydroperoxide scavenger can be any hydroperoxide scavenger described or suggested herein.
In certain embodiments, the composition further comprises an inorganic salt, a plasticizer, or a combination thereof. The inorganic salt may be any inorganic salt disclosed or suggested herein. Thus, in certain embodiments, the composition comprises a stabilizer and an inorganic salt. In certain embodiments, the inorganic salt comprises an element from group 1 (e.g., group IA) of the periodic table of elements. In certain embodiments, the inorganic salt is sodium chloride. In other embodiments, the inorganic salt is potassium chloride. In certain embodiments, the ratio of stabilizer (e.g., singlet oxygen quencher, hydroxyl radical scavenger, hydroperoxide scavenger) to inorganic salt is from about 20: 1 to about 1: 20, from about 15: 1 to about 1: 15, from about 10: 1 to about 1: 10, from about 7: 1 to about 1: 7, from about 5: 1 to about 1: 5, from about 4: 1 to about 1: 4, from about 3: 1 to about 1: 3, from about 2: 1 to about 1: 2, or about 1: 1.
In certain embodiments, the composition comprises a stabilizer and a plasticizer. The plasticizer may be any plasticizer described or suggested herein (e.g., a monosaccharide, a disaccharide, a complex sugar, a long chain polyol, or a short chain polyol). In certain embodiments, the plasticizer is a linear or branched short chain polyol (e.g., glycerol). In certain embodiments, the plasticizer is glycerin. In certain embodiments, the plasticizer is a monosaccharide (e.g., glucose). In other embodiments, the plasticizer is a disaccharide (e.g., sucrose, trehalose, or mannose). In other embodiments, the plasticizer is a complex sugar (e.g., ficol or dextran (e.g., short chain dextran with a molecular weight less than 10 kD)). In certain embodiments, the ratio of stabilizer to plasticizer is from about 20: 1 to about 1: 20, from about 15: 1 to about 1: 15, from about 10: 1 to about 1: 10, from about 7: 1 to about 1: 7, from about 5: 1 to about 1: 5, from about 4: 1 to about 1: 4, from about 3: 1 to about 1: 3, from about 2: 1 to about 1: 2.
In certain embodiments, the composition further comprises one or more RNase inhibitors. Thus, in certain embodiments, the compositions comprise a stabilizer, or an inorganic salt or plasticizer (or combinations thereof) and one or more RNase inhibitors. The RNase inhibitor may be any RNase inhibitor disclosed or suggested herein.
In certain embodiments, the composition further comprises a biomolecule. The biomolecule may be any biomolecule described or suggested herein. In certain embodiments, the ratio of stabilizing agent (e.g., singlet oxygen quencher, hydroxyl radical scavenger, hydroperoxide scavenger) to biomolecule in the composition is from about 20000: 1 to about 2: 1, from about 10000: 1 to about 1000: 1, from about 1000: 1 to about 100: 1, from about 100: 1 to about 10: 1, or from about 10: 1 to about 1: 1. In still other embodiments, the ratio of stabilizing agent (e.g., singlet oxygen quencher, hydroxyl radical scavenger, hydroperoxide scavenger) to biomolecule in the composition is from about 5000: 1 to about 50: 1, from about 1000: 1 to about 10: 1, from about 500: 1 to about 5: 1, from about 100: 1 to about 2: 1, from about 50: 1 to about 1: 2. In still other embodiments, the ratio of inorganic compound to biomolecule is about 50: 1, about 40: 1, about 30: 1, about 20: 1, about 10: 1, or about 1: 1, by weight.
In certain embodiments, the compositions comprise a singlet oxygen quencher (e.g., an alkyl imidazole) in combination with an inorganic salt, a plasticizer, or a combination thereof. The inorganic salt and plasticizer may be any of those disclosed or suggested herein. In certain embodiments, the composition further comprises an additional stabilizer. For example, in certain embodiments, the additional stabilizer is a second singlet oxygen quencher (e.g., an indole or a sulfur-containing amino acid). In other embodiments, the additional stabilizer is a stabilizer other than a singlet oxygen quencher (e.g., a hydroxyl radical scavenger, a hydroperoxide scavenger, a metal chelator, or any combination thereof). The additional stabilizer may be any of the stabilizers disclosed herein. In certain embodiments, the composition further comprises one or more RNase inhibitors, biomolecules, or combinations thereof. The RNase inhibitor and biomolecule may be any of the RNase inhibitors and biomolecules disclosed herein.
In certain embodiments, the composition comprises a hydroxyl radical scavenger in combination with an inorganic salt, a plasticizer, or a combination thereof. The inorganic salt and plasticizer may be any of those disclosed or suggested herein. In certain embodiments, the composition further comprises an additional stabilizer. For example, in certain embodiments, the additional stabilizing agent is a second hydroxyl radical scavenger. In other embodiments, the additional stabilizer is a stabilizer other than a hydroxyl radical scavenger (e.g., a singlet oxygen quencher, a hydroperoxide scavenger, a metal chelator, or any combination thereof). The additional stabilizer may be any of the stabilizers disclosed herein. In certain embodiments, the composition further comprises one or more RNase inhibitors, biomolecules, or combinations thereof. The RNase inhibitor and biomolecule may be any of the RNase inhibitors and biomolecules disclosed herein.
In certain embodiments, the composition comprises a hydroperoxide scavenger in combination with an inorganic salt, a plasticizer, or a combination thereof. The inorganic salt and plasticizer may be any of those disclosed or suggested herein. In certain embodiments, the composition further comprises an additional stabilizer. For example, in certain embodiments, the additional stabilizing agent is a second hydroperoxide scavenger. In other embodiments, the additional stabilizing agent is a stabilizing agent other than a hydroperoxide scavenger (e.g., a singlet oxygen quencher, a hydroxyl radical scavenger, a metal chelator, or any combination thereof). The additional stabilizer may be any of the stabilizers disclosed herein. In certain embodiments, the composition further comprises one or more RNase inhibitors, biomolecules, or combinations thereof. The RNase inhibitor and biomolecule may be any of the RNase inhibitors and biomolecules disclosed herein.
In certain embodiments, the composition comprises histidine and a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises histidine, sodium chloride, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises histidine, potassium chloride, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. Each embodiment in this paragraph may further comprise one or more metal chelators (e.g., EDTA, EGTA, phenanthroline, and/or citrate), one or more RNase inhibitors (e.g., any of the RNase inhibitors described or suggested herein, or combinations thereof), biomolecules (e.g., any biomolecule-containing sample, such as a biological sample), or any combination thereof.
In certain embodiments, the composition comprises tryptophan and a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises tryptophan, sodium chloride, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises tryptophan, potassium chloride, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. Each embodiment in this paragraph may further comprise one or more metal chelators (e.g., EDTA, EGTA, phenanthroline, and/or citrate), one or more RNase inhibitors (e.g., any of the RNase inhibitors described or suggested herein, or combinations thereof), biomolecules (e.g., any biomolecule-containing sample, such as a biological sample), or any combination thereof.
In certain embodiments, the composition comprises methionine and a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises methionine, sodium chloride, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises methionine, potassium chloride, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. Each embodiment in this paragraph may further comprise one or more metal chelators (e.g., EDTA, EGTA, phenanthroline, and/or citrate), one or more RNase inhibitors (e.g., any of the RNase inhibitors described or suggested herein, or combinations thereof), biomolecules (e.g., any biomolecule-containing sample, such as a biological sample), or any combination thereof.
In certain embodiments, the composition comprises tyrosine and a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises tyrosine, sodium chloride, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises tyrosine, potassium chloride, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. Each embodiment in this paragraph may further comprise one or more metal chelators (e.g., EDTA, EGTA, phenanthroline, and/or citrate), one or more RNase inhibitors (e.g., any of the RNase inhibitors described or suggested herein, or combinations thereof), biomolecules (e.g., any biomolecule-containing sample, such as a biological sample), or any combination thereof.
In certain embodiments, the composition comprises ascorbate and a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises ascorbate, sodium chloride, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises ascorbate, potassium chloride, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. Each embodiment in this paragraph may further comprise one or more metal chelators (e.g., EDTA, EGTA, phenanthroline, and/or citrate), one or more RNase inhibitors (e.g., any of the RNase inhibitors described or suggested herein, or combinations thereof), biomolecules (e.g., any biomolecule-containing sample, such as a biological sample), or any combination thereof.
In certain embodiments, the composition comprises an azide and a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises an azide, sodium chloride, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises an azide, potassium chloride, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. Each embodiment in this paragraph may further comprise one or more metal chelators (e.g., EDTA, EGTA, phenanthroline, and/or citrate), one or more RNase inhibitors (e.g., any of the RNase inhibitors described or suggested herein, or combinations thereof), biomolecules (e.g., any biomolecule-containing sample, such as a biological sample), or any combination thereof.
In certain embodiments, the composition comprises tocopherol and a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises tocopherol, sodium chloride, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises tocopherol, potassium chloride, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. Each embodiment in this paragraph may further comprise one or more metal chelators (e.g., EDTA, EGTA, phenanthroline, and/or citrate), one or more RNase inhibitors (e.g., any of the RNase inhibitors described or suggested herein, or combinations thereof), biomolecules (e.g., any biomolecule-containing sample, such as a biological sample), or any combination thereof.
In certain embodiments, the composition comprises carotene and a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises carotene, sodium chloride, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises carotene, potassium chloride, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. Each embodiment in this paragraph may further comprise one or more metal chelators (e.g., EDTA, EGTA, phenanthroline, and/or citrate), one or more RNase inhibitors (e.g., any of the RNase inhibitors described or suggested herein, or combinations thereof), biomolecules (e.g., any biomolecule-containing sample, such as a biological sample), or any combination thereof.
In certain embodiments, the composition comprises DMSO and a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises DMSO, sodium chloride, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises DMSO, potassium chloride, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. Each of the embodiments of this paragraph can further comprise one or more metal chelators (e.g., EDTA, EGTA, phenanthroline, and/or citrate), one or more RNase inhibitors (e.g., any of the RNase inhibitors described or suggested herein, or combinations thereof), biomolecules (e.g., any biomolecule-containing sample, such as a biological sample), or any combination thereof.
In certain embodiments, the composition comprises mannitol and a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises mannitol, sodium chloride, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises mannitol, potassium chloride, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. Each embodiment in this paragraph may further comprise one or more metal chelators (e.g., EDTA, EGTA, phenanthroline, and/or citrate), one or more RNase inhibitors (e.g., any of the RNase inhibitors described or suggested herein, or combinations thereof), biomolecules (e.g., any biomolecule-containing sample, such as a biological sample), or any combination thereof.
In certain embodiments, the composition comprises catalase and a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises catalase, sodium chloride, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises catalase, potassium chloride, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. Each embodiment in this paragraph may further comprise one or more metal chelators (e.g., EDTA, EGTA, phenanthroline, and/or citrate), one or more RNase inhibitors (e.g., any of the RNase inhibitors described or suggested herein, or combinations thereof), biomolecules (e.g., any biomolecule-containing sample, such as a biological sample), or any combination thereof.
In certain embodiments, the composition comprises pyruvate and a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises pyruvate, sodium chloride, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises pyruvate, potassium chloride, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. Each embodiment in this paragraph may further comprise one or more metal chelators (e.g., EDTA, EGTA, phenanthroline, and/or citrate), one or more RNase inhibitors (e.g., any of the RNase inhibitors described or suggested herein, or combinations thereof), biomolecules (e.g., any biomolecule-containing sample, such as a biological sample), or any combination thereof.
In certain embodiments, the composition comprises glutathione and a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises glutathione, sodium chloride, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. In certain embodiments, the composition comprises glutathione, potassium chloride, and optionally a plasticizer selected from the group consisting of ethylene glycol, 1, 3-propanediol, glycerol, erythritol, glucose, sucrose, trehalose, mannose, dextran, polyvinyl alcohol, and polyserine. Each embodiment in this paragraph may further comprise one or more metal chelators (e.g., EDTA, EGTA, phenanthroline, and/or citrate), one or more RNase inhibitors (e.g., any of the RNase inhibitors described or suggested herein, or combinations thereof), biomolecules (e.g., any biomolecule-containing sample, such as a biological sample), or any combination thereof.
In certain embodiments, a stabilizer (e.g., singlet oxygen quencher, hydroxyl radical scavenger, hydroperoxide scavenger) is a major component of the composition. In certain embodiments, the stabilizing agent comprises at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45% or more of the composition. In other embodiments, stabilizers (e.g., singlet oxygen quenchers, hydroxyl radical scavengers, hydroperoxide scavengers) are the primary non-aqueous component of the composition. In certain embodiments, the stabilizing agent comprises at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45% or more of the non-aqueous portion of the composition.
In certain embodiments, a stabilizer (e.g., singlet oxygen quencher, hydroxyl radical scavenger, hydroperoxide scavenger) is part of the aqueous medium of the present invention (e.g., before or after mixing with the sample) and is present at a concentration of from about 0.05mg/ml to about 100.0mg/ml, from about 0.1mg/ml to about 75.0mg/ml, from about 0.2mg/ml to about 50.0mg/ml, from about 0.3mg/ml to about 25.0mg/ml, from about 0.4mg/ml to about 15.0mg/ml, or from about 0.5mg/ml to about 10.0 mg/ml. In certain embodiments, a stabilizing agent (e.g., singlet oxygen quencher, hydroxyl radical scavenger, hydroperoxide scavenger) is part of the aqueous medium of the invention (e.g., before or after mixing with the sample) and is at a concentration of about 1.0mM to about 500mM, about 2.0mM to about 400mM, about 3.0mM to about 300mM, about 4.0mM to about 200mM, about 5.0mM to about 100mM, about 6.0mM to about 95mM, about 7.0mM to about 90mM, about 8.0mM to about 85mM, about 9.0mM to about 80mM, about 10mM to about 75mM, about 11mM to about 70mM, about 12mM to about 65mM, about 13mM to about 60mM, about 14mM to about 55mM, about 15mM to about 50mM, about 20mM to about 40mM, or about 30 mM. In certain embodiments, a stabilizing agent (e.g., singlet oxygen quencher, hydroxyl radical scavenger, hydroperoxide scavenger) is part of the aqueous medium of the invention (e.g., before or after mixing with the sample) and is at a concentration of about 1.0mM to about 50mM, about 2.0mM to about 40mM, about 3.0mM to about 30mM, about 4.0mM to about 20mM, about 5.0mM to about 10mM, or about 6.25 mM.
In certain embodiments, the inorganic salt (e.g., sodium chloride or potassium chloride) is part of the aqueous medium of the present invention (e.g., before or after mixing with the sample) and is at a concentration of about 0.05mg/ml to about 100.0mg/ml, about 0.1mg/ml to about 75.0mg/ml, about 0.2mg/ml to about 50.0mg/ml, about 0.3mg/ml to about 25.0mg/ml, about 0.4mg/ml to about 15.0mg/ml, or about 0.5mg/ml to about 10.0 mg/ml. In certain embodiments, an inorganic salt (e.g., sodium chloride or potassium chloride) is part of the aqueous medium of the present invention (e.g., before or after mixing with a sample) and is at a concentration of about 1.0mM to about 500mM, about 2.0mM to about 450mM, about 3.0mM to about 400mM, about 4.0mM to about 350mM, about 5.0mM to about 300mM, about 6.0mM to about 250mM, about 7.0mM to about 200mM, about 8.0mM to about 150mM, about 9.0mM to about 125mM, about 10mM to about 100mM, about 11mM to about 90mM, about 12mM to about 80mM, about 13mM to about 70mM, about 14mM to about 60mM, about 15mM to about 50mM, about 20mM to about 40mM, or about 30 mM. In certain embodiments, an inorganic salt (e.g., sodium chloride or potassium chloride) is part of the aqueous medium of the present invention (e.g., before or after mixing with the sample) and is at a concentration of about 1.0mM to about 50mM, about 2.0mM to about 40mM, about 3.0mM to about 30mM, about 4.0mM to about 20mM, about 5.0mM to about 10mM, or about 6.25 mM.
In certain embodiments, the plasticizer is the major component of the composition. In certain embodiments, the plasticizer comprises at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45% or more of the composition. In other embodiments, the plasticizer is the primary non-aqueous component of the composition. In certain embodiments, the plasticizer comprises at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45% or more of the non-aqueous portion of the composition.
In certain embodiments, the plasticizers (e.g., glycerol, trehalose, dextran, and polyvinyl alcohol) of the above-described compositions are in an aqueous medium (e.g., before or after mixing with a sample) and at a concentration of about 0.01% to about 8.0%, about 0.02% to about 5.0%, about 0.03% to about 2.0%, about 0.04% to about 1.5%, about 0.05% to about 1%, or about 0.06% to about 0.5%.
In another aspect, the present invention provides a composition comprising at least three ingredients selected from the group consisting of an inorganic compound, a singlet oxygen quencher, a hydroxyl radical scavenger, a hydroperoxide scavenger, a reducing agent, a metal chelator, a detergent, and a plasticizer. The inorganic compound, singlet oxygen quencher, hydroxyl radical scavenger, hydroperoxide scavenger, reducing agent, metal chelator, detergent and plasticizer may be any of the inorganic compounds, singlet oxygen quenchers, hydroxyl radical scavengers, hydroperoxide scavengers, reducing agents, metal chelators, detergents and plasticizers described or suggested herein. In certain embodiments, the composition comprises at least three ingredients selected from the group consisting of inorganic compounds, singlet oxygen quenchers, hydroxyl radical scavengers, hydroperoxide scavengers, and metal chelators.
In certain embodiments, the composition comprises an inorganic compound, a hydroxyl radical scavenger, and a hydroperoxide scavenger. In other embodiments, the composition comprises an inorganic compound, a singlet oxygen quencher, and a hydroxyl radical scavenger. In other embodiments, the composition comprises an inorganic compound, a singlet oxygen quencher, and a hydroperoxide scavenger. In some further embodiments, the composition comprises a singlet oxygen quencher, a hydroxyl radical scavenger, and a hydroperoxide scavenger. In certain related embodiments, the composition further comprises a metal chelator, a plasticizer, one or more RNase inhibitors, or any combination thereof.
In certain embodiments, the composition further comprises a biomolecule (e.g., a sample comprising a biomolecule, such as a biological sample).
The compositions of the present invention may be provided in any form suitable for storage of biomolecules. In one embodiment, the composition of the present invention is provided as a solid matrix. As used herein, "solid" means that the matrix is provided in a solid or dry form, which can be converted to a liquid form by suspending in water, rehydrating, or dissolving the matrix in water. In certain embodiments, the solid substrate is obtained by air drying (e.g., in a chemical fume hood). In other embodiments, the solid storage matrix is obtained by vacuum drying (e.g., in a vacuum centrifuge). In certain embodiments, the solid state matrix has a crystalline or paracrystalline structure. In certain embodiments, the solid state matrix does not have a glass structure. In certain embodiments, the solid substrate has been equilibrated with atmospheric relative humidity and has a moisture content of 70%, 60%, 55%, 50%, 48%, 46%, 44%, 42%, 40%, 38%, 36%, 35%, 34%, 33%, 32%, 31%, 30% or less by weight.
In other embodiments, the compositions of the present invention are provided as an aqueous medium. As used herein, "aqueous" refers to a solution in which water is the primary solvent. The aqueous medium may be in the form of the composition prior to mixing with the sample. Alternatively, the aqueous medium may be the result of mixing the matrix in a dry state with the liquid sample. In a preferred embodiment, the aqueous medium of the invention may be dried (e.g. by air drying or vacuum drying) to obtain the solid matrix of the invention. In certain embodiments, the aqueous medium forms a solid matrix having a crystalline or paracrystalline structure upon drying. In certain embodiments, the aqueous medium does not form a glass structure upon drying. In other embodiments, the solid matrix of the invention may be dissolved in water or a liquid biological sample (e.g., a body fluid, a tissue homogenate, a cell lysate, a purified or synthetic biomolecule sample), diluted, or otherwise, to produce an aqueous medium of the invention.
In certain embodiments, the compositions of the invention do not comprise Tris base, EDTA, EGTA, or a combination thereof.
In certain embodiments, the composition is substantially free of magnesium, chromium, manganese, iron, cobalt, nickel, copper, zinc, or lead. In this context, the term "substantially free" means that the composition contains less than 0.5% by weight of magnesium, chromium, manganese, iron, cobalt, nickel, copper, zinc, or lead, wherein the percentage is determined by dividing (1) the weight of magnesium, chromium, manganese, iron, cobalt, nickel, copper, zinc, or lead in the composition by (2) the weight of all non-hydrates in the composition, and multiplying the result by 100. In preferred embodiments, the composition contains less than 0.1%, 0.05%, 0.01%, 0.005% or less of magnesium, chromium, manganese, iron, cobalt, nickel, copper, zinc or lead.
In certain embodiments, the composition is substantially free of one or more water-soluble organic polymers, such as polyvinyl alcohol, dextran sulfate, and cellulose. In this context, "substantially free" means that the composition contains less than 0.5% by weight of the particular water-soluble organic polymer, where the percentage is determined by dividing (1) the weight of the water-soluble organic polymer in the composition by (2) the weight of all non-hydrate compounds in the composition, and then multiplying the result by 100. In certain embodiments, the composition contains less than 0.1%, 0.05%, 0.01%, 0.005% of a particular water-soluble organic polymer.
In certain embodiments, the composition is inert to one or more downstream methods that can be used to analyze biomolecules that have been stored in and/or stabilized by the composition. The term "inert" as used in this context means that the presence of a composition in the sample does not reduce the rate of the process by more than 50% and significantly reduces the fidelity of the process. In certain embodiments, the composition is inert to methods selected from the group consisting of nucleic acid transcription and/or amplification (e.g., reverse transcription, PCR, real-time PCR, etc.), endonuclease digestion (e.g., reactions involving type II endonucleases such as EcoRI, BamHI, HindIII, NotI, SmaI, BglII, etc.), cloning techniques (e.g., ligation), protein digestion (e.g., reactions involving proteases such as proteinase K, trypsin, chymotrypsin, savinase, etc.), microarray analysis (e.g., microarray analysis of nucleic acids or proteins), immunoassays (e.g., immunoprecipitation, ELISA, etc.), mass spectrometry, or any combination thereof. In certain embodiments, the composition is inert upon dilution (e.g., 2, 3, 4, 5, 6,7, 8, 9, 10, 15, 20-fold or more dilution). In other embodiments, the composition is inert in undiluted form. Sample carrier
In another aspect, the present invention provides a sample carrier comprising a composition of the present invention. In certain embodiments, a sample carrier comprises a container and a sample node, wherein the sample node comprises or consists of a composition disclosed herein (e.g., a solid matrix or an aqueous medium disclosed herein). In certain embodiments, the sample node is reversibly attached to the container. In certain embodiments, the container houses and/or supports a sample node. The container can be of any size and shape suitable for holding or supporting such compositions and/or performing the methods of the invention. For example, in certain embodiments, the container is a tube (e.g., a test tube having a volume of about 0.1ml to about 2.0ml, a sample tube, etc.) or a well (e.g., a well in a plate such as a standard multiwell plate).
In certain embodiments, the volume of the container is from about 10. mu.l to about 2ml, from about 25. mu.l to about 1.5ml, from about 50. mu.l to about 1000. mu.l, from about 75. mu.l to about 800. mu.l, from about 100. mu.l to about 700. mu.l, from about 125. mu.l to about 600. mu.l, or from about 150. mu.l to about 500. mu.l.
In certain embodiments, the sample carrier comprises an identification marker, such as an optical barcode (optical barcode). In certain embodiments, the container comprises an identifying indicia. For example, in certain embodiments, the container comprises an optical barcode or a bio-barcode. For example, bio-barcodes have been described in U.S. patent applications 2004/0219533 and 2005/0026181. In certain embodiments, the sample node comprises an identifying label, such as a bio-barcode.
In certain embodiments, the sample node comprises from about 10 μ g to about 1000 μ g, from about 15 μ g to about 900 μ g, from about 20 μ g to about 800 μ g, from about 25 μ g to about 700 μ g, from about 30 μ g to about 600 μ g, from about 35 μ g to about 500 μ g, from about 40 μ g to about 400 μ g, from about 45 μ g to about 300 μ g, from about 50 μ g to about 200 μ g, from about 55 μ g to about 150 μ g, from about 60 μ g to about 125 μ g, from about 65 μ g to about 100 μ g, or from about 70 μ g to about 80 μ g of the solid matrix disclosed herein. In still other embodiments, the sample node comprises from about 1.0mg to about 100mg, from about 2.0mg to about 90mg, from about 3.0mg to about 80mg, from about 4.0mg to about 70mg, from about 5.0mg to about 60mg, from about 6.0mg to about 50mg, from about 7.0mg to about 40mg, from about 8.0mg to about 30mg, from about 9.0mg to about 20mg, or about 10mg of the solid matrix disclosed herein. In still other embodiments, the sample node comprises from about 10 μ l to about 1000 μ l, from about 15 μ l to about 900 μ l, from about 20 μ l to about 800 μ l, from about 25 μ l to about 700 μ l, from about 30 μ l to about 600 μ l, from about 35 μ l to about 500 μ l, from about 40 μ l to about 400 μ l, from about 45 μ l to about 300 μ l, from about 50 μ l to about 200 μ l, from about 55 μ l to about 150 μ l, from about 60 μ l to about 125 μ l, from about 65 μ l to about 100 μ l, or from about 70 μ l to about 90 μ l of the aqueous medium disclosed herein.
In certain embodiments, the sample carrier comprises a plurality of containers and a plurality of discrete sample nodes. "discrete" as used in this context means that the sample node is physically separated from other sample nodes of the sample carrier and can be evaluated and manipulated separately. Thus, for example, each of a plurality of sample nodes may be individually housed or supported by a container. In certain embodiments, the plurality of containers is a plurality of tubes (e.g., an 8x12 array of spiral cap tubes having SBS microtitre footprints). In certain embodiments, the plurality of containers are a plurality of wells in a multiwell plate (e.g., a microtiter plate having a SBS microtitre footprint). Typically, such multi-compartment containers are compatible with automation and robotic handling.
In certain embodiments, each of the plurality of containers comprises an identifying indicia. For example, in certain embodiments, each of the plurality of containers comprises an optical barcode or a bio-barcode. In other embodiments, each of the plurality of containers may be identified by its position within the sample carrier (e.g., the coordinates of a well within a multi-well plate).
In certain embodiments, the sample carrier further comprises a biomolecule. Thus, in certain embodiments, the sample carrier comprises one or more samples containing biomolecules, such as biological samples. The sample may be any biological sample disclosed herein, such as a bodily fluid, a tissue homogenate, a cell lysate, a fraction thereof, a purified sample, or a synthetic sample.
Reagent kit
In another aspect, the invention provides a kit comprising a composition disclosed herein and instructions for using the composition to store a biomolecule. In certain embodiments, the composition is a solid matrix as disclosed herein. In other embodiments, the composition is an aqueous medium as disclosed herein. In certain embodiments, the instructions describe methods of dry storage of the biomolecules disclosed herein. In other embodiments, the instructions describe methods of stabilizing biomolecules (e.g., in a dry state or in a liquid medium). In still other embodiments, the instructions describe methods of transporting the biomolecules described herein (e.g., in a dry state).
In certain embodiments, the kit comprises a container containing the composition. The container can be of any size or shape suitable for holding the composition. In certain embodiments, the container is a bottle. In certain embodiments, the container contains a sufficient amount of a composition disclosed herein (e.g., an aqueous medium or a matrix in a dry state) to provide storage and/or stability for a plurality of samples (e.g., 10, 20, 30, 40, 50, 75, 100, 150, 200 or more samples). In certain embodiments, the container contains 100. mu.l, 200. mu.l, 300. mu.l, 400. mu.l, 500nl, 750. mu.l, 1.0ml, 1.5ml, 2.0ml, 2.5ml, 5.0ml, 7.5ml, 10.0ml, 15.0ml, 20.0ml or more of the aqueous medium of the present invention. In still other embodiments, the container contains 500 μ g, 1mg, 1.5mg, 2.0mg, 2.5mg, 5.0mg, 7.5mg, 10.0mg, 15.0mg, 20.0mg, 50.0mg, 100mg, 250mg, 500mg, 1g or more of the dry-state matrix of the invention.
In other embodiments, the kit comprises a sample carrier disclosed herein. For example, in certain embodiments, a kit comprises a sample carrier comprising a plurality of containers (e.g., multi-well plates), wherein each of the plurality of wells contains a storage composition disclosed herein.
Method of producing a composite material
In another aspect, the invention provides a method of storing a biomolecule. In certain embodiments, the method comprises mixing a biomolecule-containing sample, such as a biological sample, with a composition described herein (e.g., a solid matrix or an aqueous medium described herein) to form a mixture, and drying the mixture to form a matrix comprising the biomolecule in a dried state. The sample may be any type of sample described herein.
In certain embodiments, the sample is a liquid sample, such as a bodily fluid (e.g., blood, serum, sputum, urine, cerebrospinal fluid, etc.), cell lysate, or tissue homogenate. In certain embodiments, the sample is a liquid sample and is mixed with the matrix of the invention in a dry state. In other embodiments, the sample is a liquid sample and is mixed with the aqueous medium of the present invention. In other embodiments, the sample is carried by a solid support such as a cotton swab, filter paper, or sponge. For example, in certain embodiments, the sample is a liquid sample and the mixing comprises washing the solid support with the aqueous medium of the present invention. In still other embodiments, the sample is a solid sample, such as a piece of tissue (e.g., biopsy). For example, in certain embodiments, the sample is a solid sample and is stored in an aqueous medium for storage (e.g., overnight, or for 1, 2, 3, 4, 5, 6,7 days, or longer). In certain embodiments, the solid sample is placed in a mixture of the aqueous medium of the present invention and another liquid known to stabilize biomolecules present in solid tissue samples, such as biopsies. For example, in certain embodiments, a sample is placed in an aqueous medium of the invention with RNAlaterTM(Ambion) or AllProtectTM(Qiagen).
In certain embodiments, mixing the sample with the composition of the invention comprises stirring (e.g., by pipetting, shaking, or vortexing repeatedly) the sample in combination with the composition. In still other embodiments, mixing the sample with the composition of the invention comprises incubating the combination of the sample and the composition at a temperature above room temperature (e.g., a temperature of 30 ℃, 37 ℃, 40 ℃, 42 ℃, 45 ℃, 50 ℃, 55 ℃, 60 ℃ or more). In certain embodiments, mixing the sample with the composition of the invention comprises incubating the combination of the sample and the composition at a temperature of less than 70 ℃, 65 ℃, 60 ℃, 55 ℃, 50 ℃, 45 ℃, 40 ℃ or less. In certain embodiments, mixing the sample with the composition of the invention comprises stirring the combination of the sample and the composition, and incubating the combination at a temperature between room temperature and 60 ℃. As used herein, "room temperature" is the temperature of a typical laboratory. Thus, room temperature is typically from about 20 ℃ to about 28 ℃, or from about 22 ℃ to about 26 ℃.
In certain embodiments, drying the storage solution comprises air drying (e.g., overnight drying in a chemical fume hood). In other embodiments, drying the stock solution comprises vacuum drying (e.g., in a vacuum centrifuge for one hour or more). After drying, the matrix in the dry state can be stored, for example, in a sample archive (archive). Suitable documents have been described in e.g. us patent 7,142,987 and us patent application 2003/0129755.
In certain embodiments, storage is short-term (e.g., the time it takes to transport the biomolecule to a remote location for further processing). Thus, for example, in certain embodiments, storage lasts 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24 hours or more, or 1, 2, 3, 4, 5, 6,7 days or more. In certain embodiments, storage is for a moderate length of time (e.g., 1, 2, 3, 4, 5, 6,7, 8, 9, 10 weeks or more, or 1, 2, 3, 4, 5, 6,7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18 months or more). In still other embodiments, storage is long-term (e.g., for archiving). Thus, for example, in certain embodiments, storage lasts 1, 2, 3, 4, 5, 6,7, 8, 9, 10, 11, 12, 15, 20 years or more.
In general, the compositions of the present invention can be used to store any biomolecule. Typical biomolecules include, but are not limited to, DNA, RNA, nucleic acids, polynucleotides, oligonucleotides, amino acids, peptides, polypeptides. Such biomolecules may be in any form, for example in a biological sample, an extract, any other intermediate or semi-processed biological sample, a purified sample or a synthetic sample. Typical biological samples include, but are not limited to, blood, plasma, urine, saliva, cerebrospinal fluid or any biological fluid, skin cells, cell or tissue samples, cell lysates, nuclear extracts, nucleic acid extracts, protein extracts, cytoplasmic extracts, and the like.
In a related aspect, the invention provides a method of transporting a biomolecule. In certain embodiments, the method comprises storing the biomolecule in the substrate of the invention in a dry state (e.g., according to the methods for storing the biomolecule described herein). Thus, for example, in certain embodiments, the method comprises mixing a biomolecule-containing sample, such as a biological sample, with a composition described herein (e.g., a solid matrix or an aqueous medium described herein) to form a mixture, drying the mixture to form a matrix comprising the biomolecules in a dried state, and transporting the matrix comprising the biomolecules in a dried state. The sample may be any type of sample described herein.
In certain embodiments, the matrix comprising the biomolecule in a dry state is transported to a location (e.g., an archive) where the biomolecule can be stored for later use. In other embodiments, the substrate comprising the biomolecule in a dried state is transported to a location (e.g., a laboratory) where the biomolecule can be analyzed. In certain embodiments, the matrix comprising the biomolecule in a dry state is transported at a temperature above 25 ℃. In other embodiments, the matrix comprising the biomolecule in a dry state is transported at a temperature above 37 ℃. In still other embodiments, the matrix comprising the biomolecule in a dry state is transported at a temperature above 50 ℃. Thus, for example, in certain embodiments, the matrix comprising the biomolecule in a dry state is exposed to an ambient temperature of about 25 ℃ to about 80 ℃, about 37 ℃ to about 75 ℃, or about 50 ℃ to about 70 ℃ during the transporting step.
In certain embodiments, the substrate comprising the biomolecule in a dry state is exposed to an elevated temperature for 1 or more hours (e.g., 1, 2, 3, 4, 5, 6,7, 8, 9, 10, 12, 14, 16, 18, 20, 22, or 24 hours or more) during the transport. "elevated temperature" as used in this context means a temperature above 25 ℃. Thus, for example, in certain embodiments, a substrate comprising biomolecules in a dry state is exposed to a temperature of greater than 25 ℃, greater than 37 ℃, greater than 50 ℃ and/or greater than 70 ℃ for 1 or more hours (e.g., 1, 2, 3, 4, 5, 6,7, 8, 9, 10, 12, 14, 16, 18, 20, 22 or 24 hours or more.
In certain embodiments, the transfer is by air (e.g., on an airplane). In certain embodiments, the transfer is performed by ground means (e.g., in a transportation vehicle).
In another aspect, the present invention provides a method of stabilizing a biomolecule. In certain embodiments, the method comprises mixing a sample comprising a biomolecule with a composition described herein (e.g., a matrix or an aqueous medium in a dry state as described herein) to form a mixture, wherein the presence of the composition stabilizes at least one biomolecule in the mixture. As used herein, a biomolecule is "stabilized" by a composition when the likelihood of degradation over time in the presence of the composition is low compared to when the composition is absent. In certain embodiments, stabilization occurs in solution. Thus, for example, the present invention provides a method of stabilizing biomolecules in solution, the method comprising mixing a sample containing biomolecules with an aqueous medium as described herein, wherein at least one biomolecule is stabilized by the aqueous medium. In other embodiments, the method comprises mixing a liquid sample comprising biomolecules with a matrix described herein in a dry state, and resuspending the matrix in the dry state in the liquid sample to form a mixture, wherein at least one biomolecule in the mixture is stabilized by the resuspended matrix.
In certain embodiments, the mixture is maintained at a temperature above 0 ℃. The term "maintain" as used in this context simply means to place the mixture at a particular location characterized by a particular ambient temperature. Thus, for example, if the resulting mixture is placed (e.g., while other samples are placed) after a sample is mixed with a composition of the invention, the sample is maintained at ambient temperature in the chamber in which the mixture is located. In certain embodiments, the mixture is maintained at a temperature greater than 4 ℃, 10 ℃, 15 ℃, 20 ℃, 25 ℃, 30 ℃, 35 ℃, 37 ℃ or more. In certain embodiments, the biomolecule is maintained at a particular temperature (e.g., 25 ℃ or greater) for 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 75, 90, 105, 120 minutes or more. In certain embodiments, the biomolecule is maintained at a particular temperature (e.g., 25 ℃ or higher) for 1, 2, 3, 4, 5, 6,7, 8, 9, 10, 12, 18, 24, 30, 36, 42, 48 hours or more. In certain embodiments, the biomolecule is maintained at a particular temperature (e.g., 25 ℃ or higher) for 1, 2, 3, 4, 5, 6,7, 8, 9, 10, 11, 12, 13, 14 or more days.
In certain embodiments, the stable biomolecule is a nucleic acid (e.g., DNA and/or RNA). In other embodiments, the stabilized biomolecule is a protein or peptide. In other embodiments, the stable biomolecule is a carbohydrate. In other embodiments, the stable biomolecule is a lipid. In still other embodiments, the stabilized molecule is a small molecule, such as a steroid, a drug, and a metabolite thereof.
In another aspect, the invention provides a method of recovering a biomolecule. In certain embodiments, the method comprises adding a resuspension liquid to a dry-state matrix of the invention comprising a biomolecule, and resuspending the matrix. In certain embodiments, the volume of resuspension liquid added to the storage matrix is greater than the volume of storage solution that is dried to form the storage matrix. For example, in certain embodiments, the volume of resuspension liquid added to the storage matrix is 1.25, 1.5, 1.75, 2.0 times or more the volume of the storage solution. In other embodiments, the volume of resuspension liquid added to the storage matrix is less than the volume of storage solution that is dried to form the storage matrix. For example, in certain embodiments, the volume of resuspension liquid added to the storage matrix is 1.25, 1.5, 1.75, 2.0 times or more less than the volume of the storage solution. In a preferred embodiment, the volume of resuspension liquid added to the storage matrix is about the same volume of storage solution that is dried to form the storage matrix.
In certain embodiments, the resuspension liquid is water. In other embodiments, the resuspension liquid is a buffer. For example, in certain embodiments, the resuspension liquid is a Tris base-containing buffer (e.g., 10mM Tris or TE). In certain embodiments, the pH of the resuspension liquid is about 7.0. For example, in certain embodiments, the pH of the resuspension liquid is from about 5.5 to about 8.5 or from about 6.0 to about 8.0 or from about 6.5 to about 7.5 or about 7.0.
Biomolecules recovered from the dried state matrix of the present invention can be analyzed and manipulated using standard molecular and biochemical techniques. For example, recovered nucleic acid molecules can be amplified (e.g., using standard PCR or real-time PCR) and/or analyzed (e.g., using restriction endonucleases and other nucleic acid modifying enzymes, and by hybridization, e.g., to a microarray or blot). In a preferred embodiment, the recovered biomolecules do not require any purification prior to such manipulation and/or analysis.
Examples
The following examples are intended to illustrate, but not to limit, the invention, either explicitly or implicitly, in any way, shape or form. Although they are typical of the protocols that may be used, other procedures, methods, or techniques known to those skilled in the art may also be used.
Example 1: boric acid dry state matrix
Matrices containing water-soluble inorganic compounds were prepared in conical-bottom, polypropylene, 96-well microtiter plates. To each well was added a 20. mu.L aliquot of medium consisting of 4.0mg/ml aqueous boric acid. The media was then air dried at room temperature onto the bottom surface of each well to form discrete, solid inorganic matrices (i.e., discrete sample nodes). The drying process typically takes 2 hours in a vacuum centrifuge or overnight in a fume hood. Figure 1 shows a representative substrate formed according to this method.
Example 2: boric acid + histidine in dry state matrix
Matrices containing water-soluble inorganic compounds (boric acid) and small molecule stabilizers (histidine) were prepared in conical-bottom, polypropylene, 96-well microtiter plates. To each well was added 20. mu.L aliquots of a medium consisting of an aqueous solution of boric acid (4.0mg/ml) and histidine (from 0.5mg/ml to 2.5 mg/ml). The media was then air dried at room temperature onto the bottom surface of each well to form discrete, solid inorganic matrices (i.e., discrete sample nodes). The drying process typically takes 2 hours in a vacuum centrifuge or overnight in a fume hood.
Example 3: boric acid + glycerol dry state matrix
Matrices containing water-soluble inorganic compounds (boric acid) and plasticizers (glycerol) were prepared in conical-bottom, polypropylene, 96-well microtiter plates. To each well was added 20. mu.L aliquots of a medium consisting of boric acid (4.0mg/ml) and an aqueous solution of glycerol (from 0.5mg/ml to 4.0 mg/ml). The media was then air dried at room temperature onto the bottom surface of each well to form discrete, solid inorganic matrices (i.e., discrete sample nodes). The drying process typically takes 2 hours in a vacuum centrifuge or overnight in a fume hood.
Example 4: storage in a matrix comprising boric acid, with or without histidine, in dry form
DNA
To each well of the matrix described in example 1-2 was added 20. mu.L aliquots of human DNA in TE buffer (supplied by Roche). The solid matrix in each well was resuspended and dissolved in the DNA solution by repeated pipetting. The resulting solution is then air dried to form a solid matrix comprising the biomolecules. The amount of DNA added to each well is about 100ng to about 5000 ng. After the DNA-containing matrix is formed, the plate is stored at room temperature (i.e., about 25 ℃), 37 ℃, 55 ℃ or 76 ℃.
Example 5: DNA recovery from a dried matrix by addition of water
To recover DNA from the dry storage of example 4, 20. mu.L of water was added to each well and the plates were incubated at room temperature for about 15 minutes. The solution containing the DNA is recovered by pipetting and then used "as is" or diluted with water as needed for further analysis.
Example 6: gel electrophoresis of DNA recovered from a matrix in a dry state
The DNA stored according to example 4 and recovered according to example 5 was analyzed by gel electrophoresis. A volume of DNA-containing solution corresponding to 100ng of recovered DNA (assuming 100% recovery) was electrophoresed on a 0.8% agarose gel at 250 volts for 1 hour and stained with ethidium bromide. The results are shown in fig. 2.
Example 7: real-time PCR analysis of human DNA recovered from a substrate in a dried state
Real-time PCR was used to compare and evaluate DNA recovery from the dried state matrix of example 4. The DNA was recovered as described in example 5. PCR analysis was based on the nuclear chromosome-encoding gene, β -actin, provided by ABI (Cat # 401846).
The PCR reaction was performed in a volume of 25. mu.L. The reaction contained 1 × ABI TaqMan buffer A, 3.5mM MgCl20.3. mu.M primer-probe, 0.2mM dNTPs and 0.125. mu.L 5U/. mu.L Amplitaq Gold. The conditions for these PCR tests are as follows: (1) 10 minutes at 95 ℃; (2) 40 cycles of 95 ℃ for 15 seconds and 60 ℃ for 1 minute; and (3) holding at 4 ℃. Approximately 80. mu.g of DNA recovered from storage in the dry state (assuming 100% recovery) was used as a template for each reaction. For the control, 80. mu.g of frozen DNA was used as template. All PCR results were evaluated by real-time PCR using ABI 7700. The results are shown in FIG. 3.
Example 8: microarray analysis of DNA recovered from a substrate in a dried state
Microarray analysis was performed on the DNA recovered from the substrate in a dried state of example 6. The DNA was recovered as described in example 8. Affymetrix 6.0 and Illumina 1M microarray SNP Analysis was performed by Expression Analysis, Inc. (Durham, NC) according to the manufacturer's recommendations. The analysis results are shown in FIG. 4.
Example 9: buccal swab or blood swab lysate in dry state containing borax
Storage in the middle of the body
Whole blood or buccal cell samples were collected on cotton swabs and air dried. The cotton swab was then rehydrated by the addition of 100mM aqueous borax solution, followed by heating to 95 ℃ for 10 minutes. Swab extracts were collected from the cotton swab by centrifugation or manually squeezing the liquid from the swab. The resulting solution is then aliquoted into one or more wells of a 96-well microtiter plate in a volume of no more than about 200 μ L per well. The plate is allowed to dry at room temperature, thereby forming a dried state matrix comprising the biomolecules.
The biomolecules in the resulting dried state matrix are recovered from the pre-selected wells by adding a volume of water equal to the original liquid volume before drying (i.e. up to 200 μ L/well). The recovered nucleic acid molecules are ready for use in applying genetic analysis or in preparing nucleic acid biochemistry.
Example 10: oral cavitySwab or blood swab lysate in a dry product comprising borax and histidine
Storage in a dry matrix
Whole blood or buccal cell samples were collected on cotton swabs and air dried. The cotton swab was then rehydrated by the addition of an aqueous solution of 100mM borax and 2mM-100mM histidine, followed by heating to 95 ℃ for 10 minutes. Swab extracts were collected from the cotton swab by centrifugation or manually squeezing the liquid from the swab. The resulting solution is then aliquoted into one or more wells of a 96-well microtiter plate in a volume of no more than about 200 μ L per well. The plate was allowed to dry at room temperature to form an inorganic storage matrix.
The biomolecules in the resulting dried state matrix are recovered from the pre-selected wells by adding a volume of water equal to the original liquid volume before drying (i.e. up to 200 μ L/well). The recovered nucleic acid molecules are ready for use in applying genetic analysis or in preparing nucleic acid biochemistry.
Example 11: stability of RNA during storage in dry state at elevated temperature
One microgram of purified total RNA sample was mixed with various compositions of the present invention (described below) and then stored in a dry state at (A)25 ℃ or (B)76 ℃ for 7 days. At this point, the samples were resuspended and analyzed with an Agilent Bioanalyzer. The matrix in the dry state was as follows:
1) borate, citrate, EDTA, pyruvate and dextran (results are shown in figure 5);
2) tris, borate, mannitol and EDTA (results are shown in fig. 6);
3) borate, citrate, mannitol, and dextran (results are shown in fig. 7);
4) borate, citrate, mannitol, and pyruvate (results are shown in fig. 8);
5) borate, citrate, pyruvate and dextran (results are shown in figure 9);
6) borate, citrate, EDTA and dextran (results are shown in figure 10);
7) borate, EDTA and pyruvate (results are shown in fig. 11);
8) borate, citrate and pyruvate (results are shown in figure 12);
9) borate, citrate and mannitol (results are shown in fig. 13);
10) borate, citrate and EDTA (results are shown in fig. 14);
11) control without matrix (results are shown in figure 15).
In the Agilent bioanalyzer trace of total RNA, if the RNA is intact, the ribosomal RNA complements of the total RNA appear as a pair of sharp bands (sharp bands) that migrate at approximately 41 and 48 seconds. When the RNA is degraded, the ribosomal RNA tip is broadened and finally undetectable due to strand breakage caused by RNA backbone cleavage, as shown in fig. 15 (B).
In summary, the data of FIGS. 5-14 show that all 10 of the above compositions resulted in high levels of DNA stabilization at 76 ℃ as assessed by using ribosomal RNA as a surrogate. This high temperature exceeded the highest possible ambient transport temperature predicted by FEDEX and department of defense, thus indicating that the above 10 formulations (and other similar matrices) allow RNA to be stored and transported in a dry state under extreme conditions. By comparison, RNA stored dry in the absence of these compositions was moderately degraded when stored at 25 deg.C (FIG. 15(A)), and was highly degraded when stored dry at 76 deg.C (FIG. 15 (B)).
Additional compositions suitable for storage, transport and/or stabilization of RNA in a dry state include: borate, citrate, mannitol, and dextran; borate, mannitol, pyruvate and dextran; borate, EDTA, mannitol, pyruvate, and dextran; and borates, citrates, EDTA, mannitol, pyruvate and dextran. For water stabilization of RNA, one or more RNase inhibitors (as described herein) may be added to the compositions of this example.
All patents and publications, including all sequences disclosed in such patents and publications, are specifically incorporated by reference herein.
While the invention has been described with reference to the presently preferred embodiments and the foregoing non-limiting examples, it is to be understood that various changes and modifications as will be apparent to those skilled in the art may be made without departing from the spirit of the invention. Accordingly, the invention is limited only by the following claims.
Claims (17)
1. A substrate in a dry state comprising:
an inorganic compound;
a plasticizer; and
a hydroxyl radical scavenger;
wherein the inorganic compound is water-soluble and comprises an element selected from the group consisting of boron, phosphorus, vanadium, and aluminum; and is
Wherein the matrix in the dry state is in a solid state and can be converted to a liquid form by suspending, rehydrating or dissolving the matrix in water.
2. The matrix of claim 1, wherein the inorganic compound is a metal chelator or a microbicide, or is inert with respect to biomolecules.
3. The matrix of claim 1, wherein the inorganic compound comprises an element from group IIIA, group VA or group VB of the periodic table of elements.
4. The matrix of claim 1, wherein the inorganic compound comprises boric acid, a corresponding salt of boric acid, phosphoric acid, a corresponding salt of phosphoric acid, a salt comprising vanadate, potassium alum, sodium alum, ammonium alum, or any combination thereof.
5. The matrix of claim 1, further comprising a singlet oxygen quencher, a hydroperoxide scavenger, a reducing agent, a metal chelator, a detergent, a chaotrope, or any combination thereof.
6. The matrix of claim 5, wherein the singlet oxygen quencher is selected from the group consisting of an alkyl imidazole, an indole, a sulfur-containing amino acid, a phenolic compound, an aromatic acid, an azide, a tocopherol, a vitamin E derivative, a carotene, a vitamin A derivative, and any combination thereof.
7. The matrix of claim 5, wherein the metal chelator is selected from the group consisting of EDTA, EGTA, phenanthroline, citrate, and any combination thereof.
8. The substrate of claim 1, wherein the hydroxyl radical scavenger is selected from the group consisting of azide, dimethyl sulfoxide, histidine, mannitol, sucrose, glucose, salicylate, L-cysteine, and any combination thereof.
9. The substrate of claim 5, wherein said hydroperoxide scavenger is selected from the group consisting of catalase, pyruvate, glutathione peroxidase enzymes, and any combination thereof.
10. The matrix of claim 1, wherein the plasticizer is selected from the group consisting of monosaccharides, disaccharides, complex sugars, long chain polyols, and linear or branched short chain polyols.
11. The substrate of claim 1, wherein the substrate is inert to methods of nucleic acid amplification, nucleic acid transcription, nucleic acid cloning, nucleic acid digestion, protein digestion, microarray analysis, immunoassay, mass spectrometry, or any combination thereof.
12. The matrix of claim 1, further comprising a sample comprising a biomolecule.
13. The matrix of claim 1, further comprising an RNase inhibitor.
14. The matrix of claim 13, wherein said RNase inhibitor is selected from the group consisting of 2 ' -cytidine monophosphate free acid (2 ' -CMP), aluminum reagent (aluminum), adenosine 5 ' -pyrophosphate, 5 ' -diphosphoni 3 ' -phosphate (ppA-3 ' -P), 5 ' -diphosphoni 2 ' -phosphate (ppA-2 ' -P), leucine, poly-L-aspartic acid, tyrosine-glutamic acid polymers, oligovinyl sulfonic acid, P ' → 5 ' -ester of 5 ' -phospho-2 ' -deoxyuridine 3 ' -pyrophosphate and adenosine 3 ' -phosphate (pdUppAp), and any combination thereof.
15. The matrix of claim 4, wherein the inorganic compound comprises boric acid or a corresponding salt of boric acid.
16. The matrix of claim 1, contained in a container.
17. The matrix of claim 16, wherein the container is a cuvette or well.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US9674708P | 2008-09-12 | 2008-09-12 | |
| US61/096,747 | 2008-09-12 | ||
| PCT/US2009/056869 WO2010031007A2 (en) | 2008-09-12 | 2009-09-14 | Matrices and media for storage and stabilization of biomolecules |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| HK1159684A1 HK1159684A1 (en) | 2012-08-03 |
| HK1159684B true HK1159684B (en) | 2014-04-17 |
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