Flow cell device and use thereof

Patent metadata

Field	Value
Publication number	US-11426732-B2
Application number	US-202017082445-A
Country	US
Kind code	B2
Filing date	Oct 28, 2020
Priority date	Dec 7, 2018
Publication date	Aug 30, 2022
Grant date	Aug 30, 2022

Abstract

Flow cell devices, cartridges, and systems are described that provide reduced manufacturing complexity, lowered consumable costs, and flexible system throughput for nucleic acid sequencing and other chemical or biological analysis applications. The flow cell device can include a capillary flow cell device or a microfluidic flow cell device.

First claim

What is claimed is:

1. A flow cell device comprising:
a) a capillary comprising an interior surface of a lumen of the capillary wherein the interior surface is configured to immobilize a biological molecule;
b) a first fluidic adapter disposed at a distal end of the capillary and a second fluidic adapter disposed at a proximal end of the capillary, wherein the first fluidic adapter and the second fluidic adapter are each formed of a polymeric material, and wherein the first fluidic adapter and the second fluidic adapter are fluidically connected to the capillary, a sample input port of the flow cell, or a reagent reservoir; and
c) a cartridge comprising the capillary, the first fluidic adapter and the second fluidic adapter, wherein the first fluidic adapter and the second fluidic adapter are compressible, and wherein the capillary is mounted in the cartridge upon mating with the first adapter and the second adapter.

2. The flow cell device of claim 1 , wherein the capillary is optically transparent.

3. The flow cell device of claim 1 , wherein the capillary is fabricated from glass, fused-silica, acrylic, polycarbonate, cyclic olefin copolymer (COC), cyclic olefin polymer (COP), or any combination thereof.

4. The flow cell device of claim 1 , wherein the interior surface of a lumen of the capillary comprises a hydrophilic coating having nucleic acid primers covalently tethered thereto.

5. The flow cell device of claim 4 , wherein the nucleic acid primers are tethered at a surface density of at least 1000 molecules per μm 2 .

6. The flow cell device of claim 4 , wherein the hydrophilic coating comprises a hydrophilic polymer.

7. The flow cell device of claim 4 , further comprising two or more of the capillary.

8. The flow cell device of claim 7 , wherein each of the two or more capillaries comprises the interior surface of the lumen comprising the hydrophilic-coating.

9. The flow cell device of claim 4 , wherein the hydrophilic coating comprises one or more layers of a hydrophilic polymer and has a water contact angle of less than 50 degrees.

10. The flow cell device of claim 4 , wherein at least one discrete region of the interior surface of the lumen of the capillary comprises a plurality of clonally-amplified, sample nucleic acid molecules annealed to the nucleic acid primers.

11. The flow cell device of claim 10 , wherein the plurality of clonally-amplified, sample nucleic acid molecules comprises a concatemer sequence.

12. The flow cell device of claim 10 , wherein the plurality of clonally-amplified, sample nucleic acid molecules is obtained from a eukaryotic genome, a prokaryotic genome, or a transcriptome.

13. The flow cell device of claim 10 , wherein the plurality of clonally-amplified, sample nucleic acid molecules, or complementary sequences thereof, are labeled with a fluorophore such that a fluorescence image of the interior surface exhibits a contrast-to-noise ratio (CNR) of at least 20 when the fluorescence image is acquired using an inverted fluorescence microscope equipped with a 20× objective, a 532 nm light source, a bandpass and dichroic mirror filter set optimized for 532 nm long-pass excitation light, an emission bandpass filter optimized for emission of the fluorophore, and a sCMOS camera, under non-signal saturating conditions while the interior surface is immersed in 25 mM N-(2-Acetamido)-2-aminoethanesulfonic acid (ACES), pH 7.4 buffer.

14. The flow cell device of claim 1 , further comprising:
a) a first reservoir configured to house a first reagent solution;
b) a second reservoir configured to house a second reagent solution; and
c) at least one reagent valve;
wherein a first outlet of the first reservoir and a second outlet of the second reservoir are fluidically-coupled to an inlet of the capillary through the at least one reagent valve such that a volume of the first reagent solution flowing from the first outlet of the first reservoir to the inlet of the capillary is less than a volume of the second reagent solution flowing from the second outlet of the second reservoir to the inlet of the capillary.

15. The flow cell device of claim 14 , wherein the at least one reagent valve is a diaphragm valve.

16. The flow cell device of claim 14 , further comprising a first valve and a second valve of the at least one reagent valve, wherein the first outlet of the first reservoir is fluidically-coupled to the inlet of the capillary through the first valve, and the second outlet of the second reservoir is fluidically-coupled to the inlet of the capillary through the second valve.

17. The flow cell device of claim 1 , further comprising: at least one valve mechanically coupled to the first fluidic adapter or the second fluidic adapter, wherein the at least one valve is in fluidic communication with an outlet of a reservoir of a fluid control system and the first fluidic adapter or the second fluidic adapter.

18. The flow cell device of claim 14 , wherein the outlet of the first reservoir is positioned closer to the inlet of the capillary than is the outlet of the second reservoir.

19. The flow cell device of claim 1 , further comprising:
a) a reservoir configured to house a first solution; and
b) at least one valve mechanically coupled to the first fluidic adapter or the second fluidic adapter, wherein the at least one valve is in fluidic communication with an outlet of the reservoir and an inlet of the capillary housed in the cartridge.

20. The flow cell device of claim 16 , wherein the first reagent solution comprises a reaction-specific reagent, and wherein the second reagent solution comprises at least one reagent common to a plurality of reactions occurring in the capillary.

21. The flow cell device of claim 16 , wherein the second reagent solution comprises at least one reagent selected from the group consisting of a solvent, a polymerase, and a dNTP.

22. The flow cell device of claim 1 , wherein the cartridge comprises a temperature control component that is thermally coupled to the capillary.

23. The flow cell device of claim 22 , wherein the temperature control component comprises a heat block, a course for air flow, or a fan.

24. The flow cell device of claim 1 , wherein the cartridge comprises a chassis having a screw, clip, clamp, or fastener mechanically coupled thereto configured to open the cartridge to access the capillary.

25. The flow cell device of claim 1 , wherein the polymeric material comprises glass, fused-silica, ceramic, metal, polydimethylsiloxane, polystyrene (PS), macroporous polystyrene (MPPS), polymethylmethacrylate (PMMA), polycarbonate (PC), polypropylene (PP), polyethylene (PE), high density polyethylene (HDPE), cyclic olefin polymers (COP), cyclic olefin copolymers (COC), or polyethylene terephthalate, or any combination thereof.

26. The flow cell device of claim 1 , wherein the cartridge comprises a substrate fabricated with a material comprising glass, fused-silica, acrylic, polycarbonate, cyclic olefin copolymer (COC), cyclic olefin polymer (COP), or any combination thereof.

27. The flow cell device of claim 1 , wherein the first fluidic adapter and the second fluidic adapter comprise a fluorelastomer.

28. The flow cell device of claim 1 , wherein the first fluidic adapter and the second fluidic adapter comprise silicone.

Assignees

• Element Biosciences Inc

Inventors

• Guo Minghao
• Zhang Leon Zilun
• Zhou Chunhong
• Kellinger Matthew
• Previte Michael

Classifications

• B01L2300/1844

  using fans · CPC title

• B01L2300/1805

  Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks · CPC title

• B01L2400/0638

  membrane valves, flap valves · CPC title

• B01L7/52

  with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples · CPC title

• B01L3/50

  Containers for the purpose of retaining a material to be analysed, e.g. test tubes (devices for taking samples of blood A61B5/15) · CPC title