Matrices and media for storage and stabilization of biomolecules

Inventors

Hogan, Michael • Saghbini, Michael • Shi, Chunnian • Wong, David

Assignees

GENTEGRA LLC

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Publication Number

US-8283165-B2

Patent

Publication Date

2012-10-09

Expiration Date


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.

Core Innovation

The invention relates to biomolecule-storage compositions and systems that stabilize biomolecules using water-soluble inorganic compounds, including boric acid or a corresponding salt of boric acid. The compositions include a poly-alcohol plasticizer, an RNase inhibitor, and a hydroxyl radical scavenger to address degradation mechanisms during storage in solid or liquid form.

In one aspect, the invention provides a dry-state matrix in a solid or dry form that is converted to a liquid form by suspending, re-hydrating, or solubilizing the matrix in water. The dry-state matrix is formulated to stabilize biomolecules during dry storage and to return to a liquid form suitable for downstream handling. In further aspects, the invention provides an aqueous medium in a liquid state comprising boric acid or a corresponding salt, a poly-alcohol plasticizer, a hydroxyl radical scavenger, and an RNase inhibitor.

The invention also describes storage systems that include sample carriers and kits, where the matrix or aqueous medium is associated with a discrete sample node. The described formulations additionally include stabilizing components selected from singlet oxygen quenchers, hydroxyl radical scavengers, hydroperoxide removing agents, reducing agents, metal chelators, and detergents, with optional chaotropes and poly-alcohol plasticizers. Documented examples report DNA recovery after dry storage and RNA stabilization during elevated-temperature storage compared to absence of the described matrix.

Claims Coverage

The partial claim set includes two independent claims: one directed to a dry-state matrix and one directed to an aqueous liquid medium. Each independent claim contains four core inventive ingredients and specifies the physical state, dry matrix convertible to liquid versus liquid medium.

Dry-state matrix with boric acid, poly-alcohol plasticizer, hydroxyl radical scavenger, and RNase inhibitor

A dry-state matrix comprising boric acid or a corresponding salt of boric acid, a poly-alcohol plasticizer, a hydroxyl radical scavenger, and an RNase inhibitor, wherein the matrix is in a solid or dry form which can be converted to a liquid form by suspending, re-hydrating, or solubilizing the matrix in water.

Aqueous medium with boric acid, poly-alcohol plasticizer, hydroxyl radical scavenger, and RNase inhibitor

An aqueous medium comprising boric acid or a corresponding salt of boric acid, a poly-alcohol plasticizer, a hydroxyl radical scavenger, and an RNase inhibitor, wherein said aqueous medium is in a liquid state.

Across the independent claims, the inventive coverage centers on using boric acid or a corresponding salt together with a poly-alcohol plasticizer, a hydroxyl radical scavenger, and an RNase inhibitor, with the distinguishing feature being dry-state matrix convertibility to liquid versus an aqueous medium already in liquid form.

Stated Advantages

Enables conversion of a solid or dry matrix to a liquid form by suspending, re-hydrating, or solubilizing in water.

Stabilizes biomolecules in aqueous solution.

Shows DNA recovery after dry storage at elevated temperatures.

Provides RNA stabilization for 7 days at 76°C versus degradation without matrix.

Documented Applications

Storing and recovering biomolecules, including DNA and RNA, after dry-state storage and elevated-temperature conditions, including comparison to conditions without the matrix.

Using the disclosed aqueous medium for stabilizing biomolecules in aqueous solution by mixing a sample comprising biomolecules with the aqueous medium.

Inertness with respect to downstream methods including nucleic acid amplification, nucleic acid digestion, and/or protein digestion.

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