Systems and methods for rapid generation of droplet libraries

Patent metadata

Field	Value
Publication number	US-11754579-B2
Application number	US-201816620127-A
Country	US
Kind code	B2
Filing date	Jun 6, 2018
Priority date	Jun 6, 2017
Publication date	Sep 12, 2023
Grant date	Sep 12, 2023

Abstract

Arrays of droplet-on-demand dispensers are controlled by a row-column addressing scheme that can reduce the number of on-chip address lines, thereby making it feasible to construct large dispenser arrays. Decoders are used to further reduce the number of control lines that select a specific address line. A microfluidic logic controller includes row-select lines, each coupled to dispensers disposed on the same row, and column-select lines, each coupled to dispensers disposed on the same column such that each dispenser is associated with a unique row-column address. A logic circuit can actuate a dispenser only if the logic circuit receives signals from both of the row-select line and the column-select line corresponding to the row-column address of the selected dispenser. Reagents can be dispensed from the dispenser array, thereby allowing for rapid formatting of a reagent library into microfluidic droplets.

First claim

What is claimed is:

1. A system ( 100 ) for generating a reagent droplet, said system comprising:
a. an “N” number of droplet dispensers ( 110 ) arranged in an array of rows ( 102 ) and columns ( 104 ), wherein each droplet dispenser ( 110 ) comprises a well ( 120 ) fluidly coupled to a dispensing valve ( 115 ), wherein the well ( 120 ) stores a reagent, wherein the dispensing valve ( 115 ) is normally closed;
b. a microfluidic logic controller ( 300 ) comprising:
i. an “A” number of row-select lines ( 314 ), wherein for each row ( 102 ) of the array, one row-select line ( 314 ) is operatively coupled to the droplet dispensers ( 110 ) disposed on said row ( 102 );
ii. a “B” number of column-select lines ( 324 ), wherein for each column ( 104 ) of the array, one column-select line ( 324 ) is operatively coupled to the droplet dispensers ( 110 ) disposed on said column ( 104 ); and
iii. an “N” number of logic circuits ( 350 ), each logic circuit ( 350 ) operatively coupled to one dispensing valve ( 115 ) such that said logic circuit ( 350 ) is configured to actuate the dispensing valve ( 115 ), wherein “N”≥1, “A”≥1, and “B”≥1, wherein A×B=N; and

c. a microfluidic channel network ( 150 ) configured to have a continuous phase fluid flowing therein, wherein the microfluidic channel network ( 150 ) is fluidly coupled to each of the droplet dispensers, wherein the microfluidic channel network ( 150 ) is adapted to receive reagent droplets dispensed from the wells ( 120 );
wherein each droplet dispenser ( 110 ) is associated with a unique row-column address defined by its row-select line ( 314 ) and column-select line ( 324 ), wherein each droplet dispenser ( 110 ) is operatively coupled to its row-select line ( 314 ) and its column-select line ( 324 ) via the logic circuit ( 350 ) that actuates the dispensing valve ( 115 ) only if said logic circuit receives signals from both of the row-select line ( 314 ) and the column-select line ( 324 ) corresponding to the row-column address of said selected droplet dispenser ( 110 ), wherein actuation of the dispensing valve allows for dispensing of a reagent droplet from the well ( 120 ) and into the microfluidic channel network ( 150 ).

2. The system ( 100 ) of claim 1 , wherein the microfluidic channel network ( 150 ) comprises a single continuous phase channel that comprises a serpentine portion that winds from row-to-row or column-to-column so as to serially couple the droplet dispensers.

3. The system ( 100 ) of claim 1 , wherein the microfluidic channel network ( 150 ) comprises a plurality of continuous phase channels, wherein each channel is disposed in along a single row such that rows of droplet dispensers are coupled to the continuous phase channels in parallel.

Assignees

• Univ California

Inventors

• Hui Elliot En-Yu
• Werner Erik Morgan

Classifications

• G01N35/1002 Primary

  Reagent dispensers · CPC title

• C40B60/00

  Apparatus specially adapted for use in combinatorial chemistry or with libraries · CPC title

• G01N2035/1034

  Transferring microquantities of liquid · CPC title

• B01L3/0265

  using valves to interrupt or meter fluid flow, e.g. using solenoids or metering valves · CPC title

• B01L3/502738

  characterised by integrated valves (throttle valves in microfluidic sample containers B01L3/502746) · CPC title