EP-4739434-A1 - SELECTIVE REACTIONS IN MICROREACTOR ARRAYS

Abstract

A microreactor array is provided that includes a plurality of microreactors in a substrate. The plurality of microreactors is in fluid communication with a common fluid delivery channel. Each of the microreactors includes an electrode configured to generate one or more gaseous bubbles that can block reagent access to selected microreactors. A method for selective reactions in a microreactor array is also provided. The method includes flooding the array of microreactors with a first fluid selected to release a gas during electrolysis, applying a bias to the electrode associated with one or more selected microreactors in the array, thereby forming one or more gaseous bubbles at or near the electrode. The next step involves flushing the array with a second fluid, and carrying out a reaction in the microreactors that are not blocked by the bubble.

Inventors

• BOYANOV, BOYAN
• MUSA, Rean Silke
• FLANNERY, ANTHONY
• PEISAJOVICH, SERGIO

Assignees

• Illumina, Inc.

Dates

Publication Date

20260513

Application Date

20240701

Claims (20)

1. WHAT IS CLAIMED IS: 1. A method for selective reactions in a microreactor array comprising: providing an array of microreactors in fluid communication with a common fluid delivery channel, wherein each of the microreactors is associated with a first electrode; flooding the array of microreactors with a first fluid, wherein the first fluid is selected to release a gas upon electrolytic decomposition at the first electrode; applying a bias to the first electrode associated with one or more selected microreactors in the array, thereby forming one or more gaseous bubbles at or near the first electrode; flushing the array of microreactors with a second fluid, wherein the one or more gaseous bubbles blocks the second fluid from accessing the one or more selected microreactors in the array; and carrying out a reaction in the microreactors that are not blocked by the one or more gaseous bubbles.
2. 2. The method of Claim 1, wherein the first fluid comprises an electrolyte.
3. 3. The method of Claim 1 or 2, wherein the second fluid comprises a reagent.
4. 4. The method of any one of Claims 1-3, further comprising flushing the array of microreactors with a third fluid selected to dissolve the one or more gaseous bubbles blocking the one or more selected microreactors in the array.
5. 5. The method of Claim 4, wherein the third fluid comprises a deblocking agent.
6. 6. The method of any one of Claims 1-3, further comprising turning off the bias to the first electrode associated with the one or more selected microreactors, thereby allowing the one or more gaseous bubbles to shrink or dissolve in the second fluid.
7. 7. The method of any one of Claims 1-6, wherein each of the microreactors in the array comprises a well.
8. 8. The method of Claim 7, wherein the one or more gaseous bubbles reside in the well of the one or more selected microreactors in the array.
9. 9. The method of Claim 7, wherein the array of microreactors further comprises one or more reaction zones, and each reaction zone comprises a plurality of wells.
10. 10. The method of Claim 9, wherein the one or more gaseous bubbles reside in a selected reaction zone.
11. 11. The method of any one of Claims 1-10, wherein each of the microreactors in the array is connected to a common fluid delivery channel via an access channel.
12. 12. The method of Claim 11, wherein the first electrode is disposed in the access channel.
13. 13. The method of Claim 11 or 12, wherein the one or more gaseous bubbles are formed in the access channel.
14. 14. A method for selective reactions in a microreactor array comprising: providing a microreactor array comprising: two or more reaction zones, wherein each reaction zone comprises a plurality of microreactors; a common fluid delivery channel in fluid communication with the two or more reaction zones and the plurality of microreactors; and wherein each of the reaction zones is associated with a second electrode, and optionally each of the microreactors is associated with a first electrode; flooding the microreactor array with a first fluid, wherein the first fluid is selected to release a gas upon electrolytic decomposition at the first electrode or at the second electrode; applying a bias to the second electrode associated with one or more selected reaction zones or the first electrode associated with one of more of the plurality of microreactors in the one or more selected reaction zones, thereby forming one or more gaseous bubbles in the one or more selected reaction zones; flushing the microreactor array with a second fluid, wherein the one or more gaseous bubbles blocks the second fluid from accessing the plurality of microreactors in the one or more selected reaction zones; and carrying out a reaction in the microreactors that are not blocked by the one or more gaseous bubbles.
15. 15. The method of Claim 14, wherein the first fluid comprises an electrolyte.
16. 16. The method of Claim 14 or 15, wherein the second fluid comprises a reagent.
17. 17. The method of any one of Claims 14-16, further comprising flushing the microreactor array with a third fluid selected to dissolve the one or more gaseous bubbles in the one or more selected reaction zones.
18. 18. The method of Claim 17, wherein the third fluid comprises a deblocking agent.
19. 19. The method of any one of Claims 14-18, further comprising turning off the bias to the first electrode and the second electrode, thereby allowing the one or more gaseous bubbles to shrink or dissolve in the second fluid.
20. 20. A microreactor array comprising: a plurality of microreactors in a substrate, wherein the plurality of microreactors are in fluid communication with a common fluid delivery channel; a first electrode associated with each of the plurality of microreactors; and wherein the first electrode is configured to generate one or more gaseous bubbles via electrolytic decomposition of a first fluid.

Description

ILLINC.578WO PATENT SELECTIVE REACTIONS IN MICROREACTOR ARRAYS RELATED APPLICATIONS [0001] This PCT application claims priority to U.S. Provisional Application 63/512237, filed July 6, 2023, the entirety of which is incorporated herein for any and all purposes. BACKGROUND OF THE INVENTION Field [0002] The present technology relates generally to an microreactor array or a method for carrying chemical reactions selectively and in parallel, and more specifically to an microreactor array or a method for providing selective reagent access into a micro-reactor array. Description of the Related Art [0003] Many applications in biology benefit from the parallelization of sequential chemical reactions in micro-reactor arrays. For example, DNA synthesis is often performed in 96-well plates where a liquid handling robot delivers the next base to be added to the target. Alternatively, inkjet printers have also been configured to deposit micro-droplets of nucleotides at designated locations. Barcoding DNA samples and/or attaching specific adapters, indices, or other landmarks to sets of DNA inserts during library preparation is another example of an application that uses a similar approach. There is a need for parallelization when using DNA as a medium for storing digital data, particularly during the writing stage when DNA synthesis is employed to mirror “bits-to-bases.” [0004] However, current methods suffer from a common limitation – the reagent delivery is sequential, and thus their plexicities are limited. At low plexicities, sequential reagent delivery using these methods is not a serious limitation, but, as parallelization is increased, the limitations from the overhead of sequential delivery can become substantial. For example, if 100,000 parallel reactions are carried out and the delivery of reagents to each reactor zone takes 0.1s, then the time overhead for each cycle of the reaction would be 2.7 hrs. A significant delay of time is a limitation associated with massive parallelization with sequential reagent delivery technologies. [0005] Therefore, there is a long-felt need for microreactor arrays and methods that reduce the overhead time of sequential chemical reactions while achieving high plexicities in microreactor arrays, such as an array, microarray, or flow cell. SUMMARY [0006] The systems, fluidic devices, and methods disclosed herein each have several aspects, no single one of which is solely responsible for their desirable attributes. Without limiting the scope of the claims, some prominent features will now be discussed briefly. Numerous other embodiments are also contemplated, including embodiments that have fewer, additional, and/or different components, steps, features, objects, benefits, and advantages. The components, aspects, and steps may also be arranged and ordered differently. After considering this discussion, and particularly after reading the section entitled “Detailed Description”, one will understand how the features of the devices and methods disclosed herein provide advantages over other known devices and methods. [0007] The following are examples of certain devices and methods for providing selective reagent access with increased parallelization of sequential chemical reaction in microreactor arrays. [0008] Described herein includes a method for selective reactions in a microreactor array. The method comprises providing an array of microreactors in fluid communication with a common fluid delivery channel, wherein each of the microreactors is associated with a first electrode, followed by flooding the array of microreactors with a first fluid, wherein the first fluid is selected to release a gas upon electrolytic decomposition at the first electrode, then applying a bias to the first electrode associated with one or more selected microreactors in the array, thereby forming one or more gaseous bubbles at or near the first electrode. The method further includes flushing the array of microreactors with a second fluid, wherein the one or more gaseous bubbles blocks the second fluid from accessing the one or more selected microreactors in the array, and carrying out a reaction in the microreactors that are not blocked by the one or more gaseous bubbles. [0009] In some embodiments, the first fluid comprises an electrolyte. In some embodiments, the second fluid comprises a reagent. [0010] In some embodiments, the method further comprising flushing the array of microreactors with a third fluid selected to dissolve the one or more gaseous bubbles blocking the one or more selected microreactors in the array. In some embodiment, the third fluid comprises a deblocking agent. [0011] In some embodiments, the method further comprises turning off the bias to the first electrode associated with the one or more selected microreactors, thereby allowing the one or more gaseous bubbles to shrink or dissolve in the second fluid. [0012] In some embodiments, each of the microreactors in the array compr