Apparatus for high density information storage in molecular chains

Patent metadata

Field	Value
Publication number	US-11995558-B2
Application number	US-201916415666-A
Country	US
Kind code	B2
Filing date	May 17, 2019
Priority date	May 17, 2018
Publication date	May 28, 2024
Grant date	May 28, 2024

Abstract

A parallelized chain-synthesizing technique includes capillary tubes, where each tube provides multiple locations or addresses where a specific arbitrary sequence for polymeric chains can be synthesized. An optical addressing system selectively delivers light to the locations to mediate or control reactions in the tubes.

First claim

What is claimed is:

1. A polymeric chain-synthesizing method, comprising:
providing a manifold system including an input manifold and an output manifold;
forming internal channels in the input manifold and the output manifold;
holding several tubes extending parallel to each other between the input manifold and the output manifold and coupled to the internal channels;
immobilizing seed molecules in the tubes; and
selectively delivering light to different locations of the tubes to mediate or control chemical reactions for synthesis of sequences from the seed molecules to thereby synthesize polymeric chains to encode digital data into the polymeric chains by the selective delivery of the light while the tubes are held between the input manifold and the output manifold; and
introducing different reagents required for synthesis of the polymeric chains by flowing the different reagents through the tubes via the manifold system;
wherein different seed molecules are used to enable random access of the different chains.

2. A method as claimed in claim 1 , wherein the polymeric chains include DNA.

3. A method as claimed in claim 1 , wherein the seed molecules are immobilized using click chemistry, biotin-streptavidin interactions, or a photo-cleavable or enzymatically-cleavable group.

4. A method as claimed in claim 1 , wherein the seed molecules are immobilized using click chemistry, biotin-streptavidin interactions, or a photo-cleavable or enzymatically-cleavable group, where synthesis occurs on a complementary DNA strand that is hybridized to the surface immobilized DNA molecule and leaves a 3′ overhang.

5. A method as claimed in claim 1 , further comprising sequentially introducing adenine (A), cytosine (C), guanine (G), thymine (T) for synthesis of DNA polymeric chains.

6. A method as claimed in claim 1 , further comprising using microfluidics for controlled introductions of the reagents required for synthesis into the tubes.

7. A method as claimed in claim 1 , further comprising storing the polymeric chains in the tubes.

8. A method as claimed in claim 1 , further comprising sequencing the polymeric chains in the tubes.

9. A method as claimed in claim 1 , further comprising eluting the polymeric chains from the tubes and then sequencing the polymeric chains.

10. A method as in claim 9 , where the elution is performed by heating the tubes to dehybridize the synthesized chains.

11. A method as claimed in claim 1 , further comprising robotically retrieving the tubes from a store to access information encoded in the polymeric chains in the tubes.

12. A method as claimed in claim 1 , further comprising in situ sequencing of the chains using sequencing by synthesis, through the sequential microfluidic introduction of fluorescently labeled nucleotides and DNA polymerase and detection of fluorescence.

13. A method as claimed in claim 1 , further comprising magnetically securing and fluidically sealing an interface to the tubes.

14. A method as claimed in claim 1 , wherein the different locations are distributed along a longitudinal length of the tubes.

15. A method as claimed in claim 1 , wherein a spatial light modulator selectively delivers the light to the different locations.

16. A method as claimed in claim 15 , wherein the spatial light modulator is a micromirror device.

17. A method as claimed in claim 15 , wherein the spatial light modulator is a liquid crystal on a silicon device.

18. A method as claimed in claim 15 , wherein the spatial light modulator projects a hologram into the volumetric region.

19. A method as claimed in claim 15 , further comprising illuminating the tubes to excite fluorescently labeled nucleotides and capturing fluorescence for in situ sequencing with an image sensor.

20. A polymeric chain-synthesizing method, comprising:
providing a manifold system including an input manifold and an output manifold;
forming internal channels in the input manifold and the output manifold;
holding several tubes extending parallel to each other between the input manifold and the output manifold and coupled to the internal channels;
immobilizing different types of seed molecules in the tubes;
selectively delivering light to different locations of the tubes to mediate or control chemical reactions for synthesis of sequences from the seed molecules to thereby synthesize polymeric chains to encode digital data into the polymeric chains by the selective delivery of the light while the tubes are held between the input manifold and the output manifold;
introducing different reagents required for synthesis of the polymeric chains by flowing the different reagents through internal channels of the input manifold and then into the tubes; and
performing multiple readout cycles using the different types of seed molecules to enable random access of the different chains.

21. A method as claimed in claim 20 , further comprising fabricating the input manifold and the output manifold from respective polymer blocks.

22. A method as claimed in claim 20 , wherein a pitch between the tubes between 120 and 200 micrometers.

23. A method as claimed in claim 20 , further comprising adding and immobilizing the different types of seed molecules sequentially.

24. A method as claimed in claim 23 , further comprising attaching the different types of seed molecules at different locations in the tubes.

Assignees

• Charles Stark Draper Laboratory Inc

Inventors

• Mcfarland Kirsty A
• Magyar Andrew P
• Frank Ian Ward
• Kotz Kenneth T
• Markovic Stacey
• Huang Haiyao
• Byrnes Steven J
• Favalora Gregg E
• Sprachman Melissa M
• Dubay Ryan A
• Vargo Emma
• Cavanagh Peter
• Rosenberger Erin

Classifications

• G06N3/123 Primary

  DNA computing · CPC title

• B01L3/5027

  by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip · CPC title

• B01L3/502761

  specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads or physically stretching molecules · CPC title

• B01L3/50851

  specially adapted for heating or cooling samples · CPC title

• B01L3/527

  for a plurality of reagents · CPC title