GENOMIC-SCALED NUCLEIC ACID SYNTHESIS, AND OTHER COMBINATORIAL SYNTHESES

摘要

Provided is a method of synthesis comprising: (I) providing separate reaction sequences to TABs; (II) utilizing reaction vessels configured to react a separate combinatorial building block with a moiety on a surface of a TAB; and (III) operating one or more TAB sorters comprising a TAB reader, a sorting tree comprising valves or switches and sorting nodes, and a monitor configured to detect TAB location, wherein the operating comprises serially conducting: (a) reacting distinct combinatorial building blocks in the reaction chambers with surfaces of TABs distributed in the reaction chambers; (b) operating a controller to operate the TAB sorters to segregate the TABs to allocations appropriate for the next assigned reaction, the operating including recycling TABs with ambiguous identity back through the sorter; and (c) repeating steps (a) and (b) as needed to complete 30% or more of the assigned sequences.

主权项

1. A combinatorial synthesizer comprising:
four or more reaction vessels configured to react a separate combinatorial building block with a moiety on a surface of a TAB; one or more TAB sorters comprising a TAB reader, a sorting tree comprising valves or switches and sorting nodes, wherein the TAB sorter sorts to outlets that number more than the number of reaction vessels, and a monitor configured to detect TAB location, wherein the TAB reader is configured to read TABs in the TAB sorter, wherein the TAB sorter has outlets at least matching the number of reaction chambers plus one; one or more RCY sorting chambers for ambiguously ID'd TABs, such chambers configured to receive such TABs from one or more outlets of the TAB sorter, with a given RCY sorting chamber configured to direct ambiguously ID'd TABs back to an inlet of a said TAB sorter; and a controller (i) programmable to track an assigned separate reaction sequences for 104 or more TABs, (ii) operatively connected to receive ID data from the TAB reader, (iii) operatively connected to the valves or switches to sort the TAB consistent with the TAB's ID, (iv) operatively connected to receive TAB location data from the monitor, (v) configured to identify TAB's with ambiguous IDs, (vi) configured to operate the valves or switches of the TAB sorter to direct such ambiguously ID'd TABs to a said aRCY sorting chamber, and (vii) configured to operate the valves or switches of the TAB sorter to direct an ID'd TAB to a TAB sorter outlet appropriate for its assigned reaction sequence, wherein the combinatorial synthesizer is configured to direct via the outlets the TABs to the reaction chamber appropriate for the next reaction in the TAB's assigned reaction sequence.