Methods for Retrievable Information Storage Using Nucleic Acids

• US 20170017436A1
• Filed: 07/13/2016
• Published: 01/19/2017
• Est. Priority Date: 07/13/2015
• Status: Active Grant

• Current Assignee: President and Fellows of Harvard College (Harvard Corporation)
• Original Assignee: President and Fellows of Harvard College (Harvard Corporation)
• Inventors: Church, George M.
• Granted Patent: US 9,928,869 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: B01J 19/0046 Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays synthesis methods per se C40B50/00
• CPC Class Codes: B01J 2219/00529 DNA chips
• CPC Class Codes: B01J 2219/00547 Bar codes
• CPC Class Codes: B01J 2219/00572 Chemical means
• CPC Class Codes: B01J 2219/00596 Solid-phase processes
• CPC Class Codes: B01J 2219/00608 DNA chips
• CPC Class Codes: B01J 2219/00675 In-situ synthesis on the substrate
• CPC Class Codes: B01J 2219/00711 Light-directed synthesis
• CPC Class Codes: B01J 2219/00713 Electrochemical synthesis
• CPC Class Codes: B01J 2219/00722 Nucleotides
• CPC Class Codes: C12Q 1/68 involving nucleic acids
• CPC Class Codes: C12Q 1/6874 involving nucleic acid arrays, e.g. sequencing by hybridisation
• CPC Class Codes: C12Q 2563/179 the label being a nucleic acid
• CPC Class Codes: C12Q 2563/185 Nucleic acid dedicated to use as a hidden marker/bar code, e.g. inclusion of nucleic acids to mark art objects or animals
• CPC Class Codes: G06F 5/08 having a sequence of storage locations, the intermediate ones not being accessible for either enqueue or dequeue operations, e.g. using a shift register G06F5/065 takes precedence; shift registers per se G11C19/00
• CPC Class Codes: G11B 7/241 characterised by the selection of the material
• CPC Class Codes: G11B 7/245 containing a polymeric component
• CPC Class Codes: G11C 13/0016 comprising polymers
• CPC Class Codes: G11C 13/0019 comprising bio-molecules
• CPC Class Codes: G11C 7/00 Arrangements for writing information into, or reading information out from, a digital store G11C5/00 takes precedence; auxiliary circuits for stores using semiconductor devices G11C11/4063, G11C11/413
• CPC Class Codes: G16B 20/00 : ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
• CPC Class Codes: G16B 50/00 : ICT programming tools or database systems specially adapted for bioinformatics
• CPC Class Codes: G16H 20/00 : ICT specially adapted for therapies or health-improving plans, e.g. for handling prescriptions, for steering therapy or for monitoring patient compliance
• CPC Class Codes: G16Z 99/00 : Subject matter not provided for in other main groups of this subclass

Abstract

A method of storing information using monomers such as nucleotides is provided including converting a format of information into a plurality of bit sequences of a bit stream with each having a corresponding bit barcode, converting the plurality of bit sequences to a plurality of corresponding oligonucleotide sequences using one bit per base encoding, synthesizing the plurality of corresponding oligonucleotide sequences on a substrate having a plurality of reaction locations, and storing the synthesized plurality of corresponding oligonucleotide sequences.

Claims

1. A method of creating a binary encoded polymer comprising

repeatedly extending a growing polymer chain with an extension product of

(i) one or more than one of either a first monomer or a second monomer of a first monomer pair, or

(ii) one or more than one of either a first monomer or a second monomer of a second monomer pair, and

wherein the extension product represents a binary information bit corresponding to a bit stream translated from text or an image or a video or an audio format and

wherein the first monomer and the second monomer of the first monomer pair each is representative of a first binary information bit, and

wherein the first monomer and the second monomer of the second monomer pair each is representative of a second binary information bit, and

alternating between the first monomer and second monomer of a given monomer pair when the extension products are representative of the same binary information bit and occur directly in series,

wherein the extension product includes at least one homopolymer of either the first monomer or the second monomer of the first monomer pair or at least one homopolymer of either the first monomer or the second monomer of the second monomer pair, and

wherein the binary encoded polymer encodes the text or image or video or audio format.

2. The method of claim 1 wherein the polymer is a nucleic acid.

3. The method of claim 1 wherein the first monomer or the second monomer of the first monomer pair is a nucleotide.

4. The method of claim 1 wherein the first monomer or the second monomer of the second monomer pair is a nucleotide.

5. The method of claim 1 wherein the first monomer pair includes adenine (A) and thymine (T) or uracil (U).

6. The method of claim 1 wherein the second monomer pair includes cytosine (C) and guanine (G).

7. The method of claim 1 wherein the extension products are formed using an enzyme and a selected monomer under conditions to catalyze addition of the selected monomer.

8. The method of claim 1 wherein the extension products are formed using a polymerase and a selected monomer under conditions to catalyze addition of the selected monomer.

9. The method of claim 1 wherein the extension products are formed using a template independent polymerase and a selected monomer under conditions to catalyze addition of the selected monomer.

10. The method of claim 1 wherein the growing polymer chain is attached to a substrate.

11. The method of claim 1 including a plurality of growing polymer chains formed from steps (i) and (ii).

12. The method of claim 1 including a plurality of growing polymer chains formed from steps (i) and (ii) and wherein the plurality of growing polymer chains is attached to a substrate.

13. The method of claim 1 wherein the first monomer or the second monomer of the first monomer pair is a natural nucleotide.

14. The method of claim 1 wherein the first monomer or the second monomer of the second monomer pair is a natural nucleotide.

15. The method of claim 1 wherein the first and second monomer pairs include natural nucleotides and the extension product is made by catalyzing the addition of a natural nucleotide under conditions sufficient to add a single nucleotide or more than one nucleotide.

16. The method of claim 1 wherein the first and second monomer pairs include natural nucleotides and the extension product is made by alternating at one or more locations on the substrate administration of a polymerase and a selected nucleotide with a nucleotide deficient buffer to catalyzing the addition of a natural nucleotide under conditions sufficient to add the nucleotide.

17-30. -30. (canceled)

31. A method of encoding information using nucleotides comprising converting a format of information into a plurality of bit sequences of a bit stream with each having a corresponding bit barcode, converting the plurality of bit sequences to a plurality of corresponding oligonucleotide sequences using one bit per base encoding, synthesizing the plurality of corresponding oligonucleotide sequences by pulsing and synchronizing, nucleotides, reagents and washes across the surface of a substrate having a plurality of reaction locations, and storing the synthesized plurality of corresponding oligonucleotide sequences,

wherein the oligonucleotide sequences are produced by limiting reaction time of the nucleotide by adding nucleotide depleted buffer to remove the nucleotide thereby limiting its reaction time or where pulse rate of flow of the nucleotide across the surface of the substrate limits its reaction time at a particular desired location.

32. The method of claim 31 wherein the oligonucleotide sequences include one or more or all of a data block sequence, an address sequence specifying the location of the data block in the bit stream, or flanking common sequences at each end of the oligonucleotide for amplification and sequencing.

43. The method of claim 31 wherein the oligonucleotide sequences are formed using a template independent polymerase and a selected monomer under conditions to catalyze addition of the selected monomer.

44. The method of claim 31 wherein the oligonucleotide sequences are attached to the substrate.

33. A method of retrieving a format of information from a plurality of synthesized oligonucleotide sequences encoding bit sequences of the format of information comprising amplifying the plurality of oligonucleotide sequences, sequencing the amplified oligonucleotide sequences, converting the oligonucleotide sequences to bit sequences by interpreting homopolymer runs as a single nucleotide, and converting the bit sequences to the format of information.

34. The method of claim 33 wherein the oligonucleotide sequences include one or more or all of a data block sequence, an address sequence specifying the location of the data block in the bit stream, or flanking common sequences at each end of the oligonucleotide for amplification and sequencing.

35. The method of claim 33 further comprising outputting the format of information.

36. The method of claim 35 wherein the oligonucleotide sequences include one or more or all of a data block sequence, an address sequence specifying the location of the data block in the bit stream, or flanking common sequences at each end of the oligonucleotide for amplification and sequencing.

41. The method of claim 33 wherein the oligonucleotide sequences are formed using a template independent polymerase and a selected monomer under conditions to catalyze addition of the selected monomer.

42. The method of claim 33 wherein the oligonucleotide sequences are attached to the substrate.

37. A method of encoding and decoding information using nucleotides comprising converting a format of information to a bit stream, encoding bit sequences into corresponding oligonucleotide sequences, synthesizing the oligonucleotide sequences by pulsing and synchronizing, nucleotides, reagents and washes across the surface of a substrate having a plurality of reaction locations, sequencing the oligonucleotide sequences, decoding the oligonucleotide sequences into bit sequences by interpreting homopolymer runs as a single nucleotide, assembling the bit sequences into a bit stream and converting the bit stream into the format of information.

38. The method of claim 37 wherein the oligonucleotide sequences include one or more or all of a data block sequence, an address sequence specifying the location of the data block in the bit stream, or flanking common sequences at each end of the oligonucleotide for amplification and sequencing.

45. The method of claim 37 wherein the oligonucleotide sequences are formed using a template independent polymerase and a selected monomer under conditions to catalyze addition of the selected monomer.

46. The method of claim 37 wherein the oligonucleotide sequences are attached to the substrate.

39-40. -40. (canceled)