Reagent channel mixing system and method

Patent metadata

Field	Value
Publication number	US-11192105-B2
Application number	US-202016827391-A
Country	US
Kind code	B2
Filing date	Mar 23, 2020
Priority date	Jan 5, 2017
Publication date	Dec 7, 2021
Grant date	Dec 7, 2021

Abstract

An analysis system may perform operations on an analyte that may be combined with multiple regents prior to being introduced into a flow cell. The instrument may include a volume into which the reagents to be combined with the analyte are aspirated one-by-one. The volume may be formed as a serpentine channel in a valve manifold associated with sippers for aspirating the reagents. The reagents may then be mixed by cycling a pump to move the reagents within the mixing volume or channel. For this, the reagents may be aspirated from a recipient into the volume or channel, ejected back into the recipient, and this process may be performed repeatedly to enhance mixing.

First claim

What is claimed is:

1. A method comprising:
a) performing a reagent pre-mixing operation for two or more reagents including:
commanding a selector valve to select a first reagent;
actuating a pump to aspirate a portion of the first reagent from a first recipient into a mixing volume;
commanding the selector valve to select a second reagent; and
actuating the pump to aspirate a portion of the second reagent from a second recipient into the mixing volume;

b) actuating the pump to cyclically move the aspirated reagents into and out of the mixing volume to mix the reagents; and
c) actuating the pump to eject the mixed reagents into a destination recipient.

2. The method of claim 1 , wherein the mixing volume comprises a serpentine channel.

3. The method of claim 1 , wherein the destination recipient contains DNA to be sequenced.

4. The method of claim 1 , wherein (a) further comprises commanding the selector valve to select a third reagent and actuating the pump to aspirate a portion of the third reagent from a third recipient into the mixing volume.

5. The method of claim 4 , wherein (a) further includes selecting and aspirating at least one of the reagents more than once prior to performing (b).

6. The method of claim 5 , further comprising repeating (a) one or more times prior to performing (b).

7. The method of claim 1 , comprising aspirating air into the mixing volume prior to aspirating the first reagent.

8. A method comprising:
actuating a pump to aspirate a gas into a mixing volume;
controlling a selector valve to select, one-by-one, a plurality of liquid reagents for an analysis operation;
for each selected reagent, actuating a pump to aspirate the selected reagent from a respective recipient containing the selected reagent into a serpentine mixing volume;
controlling the selector valve to fluidically connect the serpentine mixing volume with a destination recipient;
cycling the pump to move the reagents back and forth between the serpentine mixing volume and a destination recipient to mix the reagents, wherein the destination recipient contains an analyte of interest to be analyzed in the analysis operation; and
actuating the pump to eject the mixed reagents into the destination recipient.

9. The method of claim 8 , comprising selecting and aspirating each reagent more than once prior to cycling the pump to move the reagents.

10. The method of claim 8 , wherein the pump cyclically moves the reagents with a volume of air between the pump and the reagents.

11. The method of claim 8 , wherein the reagents comprise at least three reagents of different specific gravities.

12. A method comprising:
loading a mixing volume with a first reagent sequence formed by a first amount of a first reagent followed by a second amount of a second reagent, wherein loading the mixing volume with the first reagent sequence comprises:
controlling a selector valve to select the first reagent;
actuating a pump to aspirate the first amount of the selected first reagent from a first recipient containing the selected first reagent and into the mixing volume;
controlling the selector valve to select the second reagent; and
actuating the pump to aspirate the second amount of the selected second reagent from a second recipient containing the selected second reagent and into the mixing volume; and

actuating the pump to eject the aspirated reagents from the mixing volume and into a destination recipient.

13. The method of claim 12 , wherein the first reagent sequence further includes a third amount of a third reagent that follows the second amount of the second reagent and wherein loading the mixing volume with the first reagent sequence further comprises:
controlling the selector valve to select the third reagent; and
actuating the pump to aspirate the third amount of the selected third reagent from a third recipient containing the selected third reagent into the mixing volume.

14. The method of claim 12 , wherein loading the mixing volume further comprises:
loading the mixing volume with a second reagent sequence formed by a third amount of the first reagent followed by a fourth amount of the second reagent, wherein the second reagent sequence follows the first reagent sequence.

15. The method of claim 12 , wherein the destination recipient contains an analyte of interest to be analyzed.

16. The method of claim 12 , wherein the destination recipient contains DNA to be sequenced.

17. The method of claim 12 , further comprising actuating the pump to cyclically move the aspirated reagents into and out of the mixing volume to mix the aspirated reagents.

18. The method of claim 12 further comprising cycling the pump to move the aspirated reagents back and forth between the mixing volume and the destination recipient to mix the aspirated reagents.

19. The method of claim 12 further comprising actuating the pump to aspirate a gas into the mixing volume, the gas being fluidically interposed between the pump and the aspirated reagents.

20. The method of claim 12 , wherein loading the mixing volume comprises loading the mixing volume with a plurality of repetitions of the first reagent sequence.

Assignees

• Illumina Inc

Inventors

• Drews Bradley Kent
• Wang Michael Dai
• Ulmanella Umberto
• Clark Stephen Wayne
• Whitacre Johanna Lynn
• Phelps Steven Scott
• Alvarez Michelle L
• Niziolek Michael Adalbert
• Bryan Debra Sue
• Darland Joshua Augustin

Classifications

• B01F35/7544

  using pumps · CPC title

• B01F35/7176

  using pumps · CPC title

• B01F25/4331

  Mixers with bended, curved, coiled, wounded mixing tubes or comprising elements for bending the flow · CPC title

• B01F25/103

  with additional mixing means other than vortex mixers, e.g. the vortex chamber being positioned in another mixing chamber · CPC title

• B01F23/49

  Mixing systems, i.e. flow charts or diagrams · CPC title