Accessing data storage provided using double-stranded nucleic acid molecules

1. A method for accessing data storage provided using double-stranded nucleic acid molecules provided on a thermal control device comprising a plurality of sites and temperature control circuitry to independently control a temperature of each of the plurality of sites;

the method comprising:

controlling temperatures of the plurality of sites using the temperature control circuitry, to provide a different temperature at a target site compared to other sites of the plurality of sites; and

performing a read operation to read data from one or more selected double-stranded nucleic acid molecules at the target site or a write operation to form one or more new double-stranded nucleic acid molecules encoded with data at the target site, where the different temperatures at the target site and the other sites provide a greater probability of the read or write operation acting on the target site compared to the other sites.

2. The method of claim 1 , in which the plurality of sites are at respective portions of a shared fluid well, without a physical barrier blocking fluid from passing between adjacent sites.

3. The method of any of claim 1 , in which the read operation or the write operation comprises flowing fluid across at least two of the plurality of sites including the target site.

4. The method of claim 1 , in which:

each double-stranded nucleic acid molecule includes at least a data portion and an address portion;

double-stranded nucleic acid molecules with different data portions but the same address portion are provided at different sites of the thermal control device; and

at a given site of the thermal control device the double-stranded nucleic acid molecules located at the given site which have different data portions also have different address portions.

5. The method of claim 1 , in which when a read operation is performed, said controlling temperatures comprises setting the target site to a higher temperature than the other sites during at least part of the read operation, to provide a greater probability of the double-stranded nucleic acid molecules separating into single-stranded nucleic acid molecules at the target site than at the other sites.

6. The method of claim 5 , in which the read operation comprises restoring the double-stranded nucleic acid molecules which were separated into single-stranded nucleic acid molecules.

7. The method of claim 6 , in which each double-stranded nucleic acid molecule comprises a bound strand which is bound to a surface at one of the plurality of sites, and a further strand which is bound to the bound strand; and

the restoring comprises applying a restoration mixture comprising a restoration primer for annealing with at least part of a tag portion at one end of the bound strand of each separated double-stranded nucleic acid molecule.

8. The method of claim 7 , in which the tag portion includes an address-independent part which is the same for double-stranded nucleic acid molecules having different address portions at a given site, and the restoration primer is complementary to the address-independent part.

9. The method of claim 6 , in which during the restoring, the target site is maintained at a lower temperature than other sites.

10. The method of claim 1 , in which each double-stranded nucleic acid molecule includes at least a data portion and an address portion, and the read operation comprises:

exposing separated single-stranded nucleic acid molecules to an amplification mixture comprising at least one primer for selectively amplifying a single-stranded nucleic acid molecule separated from a double-stranded nucleic acid molecule having an address portion at least partially matching a target address portion; and

sequencing amplified nucleic acid molecules amplified by the amplification mixture to identify at least the data portion of the amplified nucleic acid molecules.

11. The method of claim 6 , in which each double-stranded nucleic acid molecule comprises first and second tag portions at opposite ends of the double-stranded nucleic acid molecule; and

at least one of the first and second tag portions is an address-specific tag portion which includes at least part of the address portion of the double-stranded nucleic acid molecule.

12. The method of claim 7 , in which the amplification mixture comprises:

a first primer complementary to the first tag portion of a first strand of a double-stranded nucleic acid molecule having a target address portion; and

a second primer complementary to the second tag portion of a second strand of the double-stranded nucleic acid molecule having the target address portion.

13. The method of claim 11 , in which one of the first and second tag portions is an address-independent tag portion which is the same for double-stranded nucleic acid molecules having different address portions at the same site.

14. The method of claim 11 , in which both the first tag portion and the second tag portion are address-specific tag portions.

15. The method of claim 11 , in which at least one of the first tag portion and the second tag portion is an address-specific tag portion comprising:

an address-dependent part comprising at least part of said address portion; and

an address-independent part which is the same for double-stranded nucleic acid molecules having different address portions at the same site.

16. The method of claim 10 , in which the amplification mixture is applied to the plurality of sites to amplify the released single-stranded nucleic acid molecules locally on the thermal control device.

17. The method of claim 16 , in which the amplification is performed by one of:

PCR, where said controlling temperatures comprises thermal cycling of the target site through repeated cycles of heating and cooling, while maintaining other sites at a temperature lower than a maximum temperature used in said thermal cycling; and

an isothermal enzyme-based amplification method, where said controlling temperatures comprises setting the temperature of the target site to a temperature greater than or equal to an activation temperature of at least one amplification-dependent enzyme.

18. The method of claim 10 , in which the amplification mixture is applied to the separated single-stranded nucleic acid molecules after removal of the separated single-stranded nucleic acid molecules from the thermal control device.

19. The method of claim 1 , in which when a write operation is performed, the target site is maintained at a lower temperature than other sites, to provide a greater probability of the new double-stranded nucleic acid molecules forming at the target site compared to other sites.

20. The method of claim 1 , in which the write operation comprises:

providing tag fragments of single-stranded nucleic acid bound to a surface at the target site; and

supplying a write set of single-stranded nucleic acid molecules corresponding to the new double-stranded nucleic acid molecules, each of the write set of single-stranded nucleic acid molecules including a tag portion complementary to the tag fragments, said different temperature at the target site providing a greater probability of the write set of single-stranded nucleic acid molecules annealing to the tag fragments at the target site compared to other sites.

21. The method of claim 20 , in which the write operation also comprises applying an extension mixture to extend each tag fragment with bases complementary to a remaining portion of the single-stranded nucleic acid molecule that annealed to that tag fragment, to form a corresponding double-stranded nucleic acid molecule.

22. The method of claim 20 , in which the write set of single-stranded nucleic acid molecules is exposed to at least two sites of the thermal control device including the target site.

23. The method of claim 1 , in which the thermal control device comprises a substrate, and the plurality of sites are disposed at respective locations on the substrate;

each site comprises at least one attachment surface for attaching single or double-stranded nucleic acid molecules; and

a total surface area of said at least one attachment surface at a given site is greater than an area of a projection of the given site onto the plane of the substrate.

24. The method of claim 1 , in which the thermal control device comprises:

a plurality of active thermal regions disposed at respective locations on a substrate, each active thermal region comprising a heating element configured to apply a variable amount of heat to a corresponding one of the plurality of sites, and a thermal insulation layer disposed between the heating element and the substrate; and

one or more passive thermal regions disposed between the plurality of active thermal regions on the substrate, each passive thermal region comprising a thermal conduction layer configured to conduct heat to the substrate;

in which the thermal conduction layer of said one or more passive thermal regions has a lower thermal resistance in a direction perpendicular to a plane of the substrate than the thermal insulation layer of said plurality of active thermal regions.

25. A non-transitory computer-readable program or data structure comprising instructions or control data for controlling an apparatus to perform the method of claim 1 .