Flow cell with integrated manifold

Patent metadata

Field	Value
Publication number	US-11951477-B2
Application number	US-202217809604-A
Country	US
Kind code	B2
Filing date	Jun 29, 2022
Priority date	May 4, 2018
Publication date	Apr 9, 2024
Grant date	Apr 9, 2024

Abstract

An example method includes connecting a flow cell to an instrument. The flow cell includes a flow channel including a manifold section having a manifold section swept volume and a detection section having a detection section swept volume. A ratio of the detection section swept volume to manifold section swept volume is at least 10 to 1. A first reagent is pumped through the flow channel. A first chemical reaction is performed between the first reagent and analytes positioned in the detection section. A subsequent reagent is pumped through the flow channel to flush out the remaining reagent. A concentration of at least 99.95 percent of reagent positioned in the detection section is the subsequent reagent, after pumping a total volume of the subsequent reagent through the flow channel that is equal to or less than 2.5 times a total swept volume of the manifold section plus the detection section.

First claim

What is claimed is:

1. A method comprising:
connecting a flow cell to an instrument, the flow cell comprising a plurality of inlet ports, an outlet port and a flow channel in fluid communication therebetween, the flow channel comprising a manifold section having a manifold section swept volume and a detection section having a detection section swept volume, wherein a ratio of the detection section swept volume to manifold section swept volume is at least about 10 to 1;
operating a first valve of a plurality of valves of the instrument to select a first reagent of a plurality of reagents, each reagent positioned in a reagent well of one of a cartridge or the instrument;
pumping the first reagent through a first inlet port of the plurality of inlet ports and through the flow channel of the flow cell;
performing a first chemical reaction between the first reagent and analytes positioned in the detection section of the flow channel, wherein at least some of the first reagent remains in the flow channel as a remaining reagent after completion of the first chemical reaction;
operating a subsequent valve of the plurality of valves to select a subsequent reagent of the plurality of reagents; and
pumping the subsequent reagent through a subsequent inlet port of the plurality of inlet ports and through the flow channel to flush out the remaining reagent from the flow channel, wherein, due at least in part to the ratio of the detection section swept volume to the manifold section swept volume being at least about 10 to 1, a concentration of at least about 99.95 percent of reagent positioned in the detection section is the subsequent reagent, after pumping a total volume of the subsequent reagent through the flow channel that is equal to or less than about 2.5 times a total swept volume of the manifold section plus the detection section.

2. The method of claim 1 , comprising:
performing a subsequent chemical reaction between the subsequent reagent and the analytes positioned in the detection section after the concentration of at least about 99.95 percent of the subsequent reagent positioned in the detection section has been achieved, wherein at least some of the second reagent remains in the flow channel as the remaining reagent after completion of the subsequent chemical reaction.

3. The method of claim 2 , comprising repeating the operating a subsequent valve, the pumping the subsequent reagent and the performing a subsequent chemical reaction one or more times.

4. The method of claim 1 , comprising:
configuring the manifold section with a plurality of manifold branches in fluid communication with a common line, the manifold section having a swept volume comprising a swept volume of the plurality of manifold branches and the common line, each manifold branch of the plurality of manifold branches connected to a corresponding inlet port of the plurality of inlet ports; and
configuring the detection section such that it is in fluid communication with the common line and the outlet port.

5. The method of claim 4 , comprising:
configuring the plurality of manifold branches to be in fluid communication with the common line through a plurality of forked junctions, each of the plurality of forked junctions directing a corresponding flow of reagent through the common line and into the detection section, wherein the forked junctions form only acute angles between the manifold branches.

6. The method of claim 1 , comprising:
configuring the manifold section and the detection section of the flow channel to be substantially planar.

7. The method of claim 1 , comprising:
providing a top layer defining a top surface of the flow channel;
providing a bottom layer defining a bottom surface of the flow channel; and
providing an intermediate layer defining a geometry of the flow channel.

8. The method of claim 7 , comprising:
providing a gap height, wherein the gap height is defined by a distance between the bottom surface of the flow channel and the top surface of the flow channel, wherein the gap height is substantially constant throughout the flow channel and is within a range of about 60 to 100 microns.

9. The method of claim 1 , comprising:
pumping the subsequent reagent through a subsequent inlet port of the plurality of inlet ports and through the flow channel to flush out the remaining reagent from the flow channel, wherein, due at least in part to the ratio of the detection section swept volume to the manifold section swept volume being at least about 10 to 1, a concentration of at least about 99 percent of reagent positioned in the detection section is the subsequent reagent, after pumping a total volume of the subsequent reagent through the flow channel that is equal to or less than about 2.0 times a total swept volume of the manifold section plus the detection section.

10. The method of claim 1 , comprising:
positioning each valve of the plurality of valves between a corresponding reagent well of the plurality of respective reagent wells and a corresponding inlet port of the plurality of inlet ports such that each valve controls a flow of reagent from the corresponding reagent well of the plurality of respective reagent wells.

11. The method of claim 1 , comprising:
configuring the swept volumes of the detection section and the manifold section such that the ratio of the detection section swept volume to manifold section swept volume is at least about 20 to 1.

12. The method of claim 1 , comprising:
configuring the swept volumes of the detection section and the manifold section such that the ratio of the detection section swept volume to manifold section swept volume is at least about 50 to 1.

13. The method of claim 1 , comprising:
configuring the swept volumes of the detection section and the manifold section such that the ratio of the detection section swept volume to manifold section swept volume is at least about 100 to 1.

Assignees

• Illumina Inc

Inventors

• Lin Sz-Chin
• Taylor Jay
• Rhee Minsoung
• Foley Jennifer
• Cox-Muranami Wesley
• Delattre Cyril
• Khurana Tarun
• Crivelli Paul

Classifications

• G01N33/00 Primary

  Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00 · CPC title

• B01L2400/08

  Regulating or influencing the flow resistance · CPC title

• B01L2400/0487

  fluid pressure, pneumatics · CPC title

• B01L2200/026

  Fluid interfacing between devices or objects, e.g. connectors, inlet details · CPC title

• B01L3/502738

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