Fluidic system for reagent delivery to a flow cell

• US 9,410,977 B2
• Filed: 08/07/2014
• Issued: 08/09/2016
• Est. Priority Date: 08/08/2013
• Status: Active Grant

• Current Assignee: Illumina Incorporated
• Original Assignee: Illumina Incorporated
• Inventors: Stone, Michael, Verkade, Drew
• Primary Examiner(s): Wecker, Jennifer
• Application Number:
  US14/453,868
• Publication Number:
  US 20150045234A1
• Time in Patent Office: 733 Days
• US Class Current: 1/1
• CPC Class Codes: B01L 2200/025 Align devices or objects to ensure defined positions relative to each other
• CPC Class Codes: B01L 2200/026 Fluid interfacing between devices or objects, e.g. connectors, inlet details
• CPC Class Codes: B01L 2200/0621 Control of the sequence of chambers filled or emptied
• CPC Class Codes: B01L 2200/16 Reagents, handling or storing thereof
• CPC Class Codes: B01L 2300/0654 Lenses; Optical fibres
• CPC Class Codes: B01L 2300/0867 Multiple inlets and one sample wells, e.g. mixing, dilution
• CPC Class Codes: B01L 2300/0877 Flow chambers
• CPC Class Codes: B01L 2300/0883 Serpentine channels
• CPC Class Codes: B01L 2300/0887 Laminated structure
• CPC Class Codes: B01L 2300/168 Specific optical properties, e.g. reflective coatings
• CPC Class Codes: B01L 2400/02 Drop detachment mechanisms of single droplets from nozzles or pins
• CPC Class Codes: B01L 2400/0622 distribution valves, valves having multiple inlets and/or outlets, e.g. metering valves, multi-way valves
• CPC Class Codes: B01L 2400/086 using baffles or other fixed flow obstructions
• CPC Class Codes: B01L 3/021 Pipettes, i.e. with only one conduit for withdrawing and redistributing liquids
• CPC Class Codes: B01L 3/0268 using pulse dispensing or spraying, eg. inkjet type, piezo actuated ejection of droplets from capillaries
• CPC Class Codes: B01L 3/0275 Interchangeable or disposable dispensing tips
• CPC Class Codes: B01L 3/502715 characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• CPC Class Codes: B01L 3/502738 characterised by integrated valves microvalves F16K99/0001
• CPC Class Codes: B01L 3/527 for a plurality of reagents
• CPC Class Codes: C12Q 1/6874 involving nucleic acid arrays, e.g. sequencing by hybridisation
• CPC Class Codes: G01N 2035/00237 : Handling microquantities of analyte, e.g. microvalves, capillary networks
• CPC Class Codes: G01N 21/6428 : Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" in vivo A61B5/00; immunoassay G01N33/53
• CPC Class Codes: G01N 21/6456 : Spatial resolved fluorescence measurements; Imaging
• CPC Class Codes: G01N 35/1002 : Reagent dispensers
• CPC Class Codes: G01N 35/1016 : Control of the volume dispensed or introduced
• CPC Class Codes: G01N 35/1065 : Multiple transfer devices
• CPC Class Codes: G01N 35/1095 : for supplying the samples to flow-through analysers for a specific analyser see relevant groups, e.g. under G01N15/00, G01N21/00, G01N27/00, G01N30/00, H01J49/00
• CPC Class Codes: G01N 35/1097 : characterised by the valves valves in general F16K
• CPC Class Codes: Y10T 436/2575 : Volumetric liquid transfer

Abstract

A fluidic system that includes a reagent manifold comprising a plurality of channels configured for fluid communication between a reagent cartridge and an inlet of a flow cell; a plurality of reagent sippers extending downward from ports in the manifold, each of the reagent sippers configured to be placed into a reagent reservoir in a reagent cartridge so that liquid reagent can be drawn from the reagent reservoir into the sipper; at least one valve configured to mediate fluid communication between the reservoirs and the inlet of the flow cell. The reagent manifold can also include cache reservoirs for reagent re-use.

Claims

1. A fluidic system for delivering reagents from a reagent cartridge to a flow cell comprising:

a reagent manifold comprising a manifold body comprising a solid material through which a plurality of channels pass, wherein the plurality of channels is configured to fluidly connect a reagent cartridge to an inlet of a flow cell, wherein one or more of the channels in the manifold comprises a cache reservoir;

a plurality of reagent sippers attached to the manifold body and extending downward from ports in the manifold, each of the reagent sippers configured to be placed into a reagent reservoir in a reagent cartridge so that liquid reagents can be drawn from a plurality of the reagent reservoirs into the sippers;

at least one valve configured to mediate fluid communication through the plurality of reagent sippers, then through the channels and then through the inlet of the flow cell; and

a detection apparatus configured to detect nucleic acid features in the flow cell.

2. The fluidic system of claim 1, further comprising a flow cell comprising a flow cell channel that is fluidly connected to a channel of the reagent manifold.

3. The fluidic system of claim 2, wherein one or more of the cache reservoirs has a volume that is at least 30% of the volume of the flow cell channel.

4. The fluidic system of claim 3, wherein the cache reservoir comprises sufficient volume to allow a quantity of liquid reagent in one or more flow cell channels to flow to the cache reservoir such that the liquid reagent from the flow cell is not directed back to the reagent reservoir after contacting the flow cell.

5. The fluidic system of claim 4, wherein the quantity of liquid reagent comprises at least 30% of the liquid reagent in one or more flow cell channels.

6. The fluidic system of claim 1, wherein one or more of the cache reservoirs is in fluid communication with a pump configured to move liquid reagent from the cache reservoir to the flow cell and from the flow cell back to the cache reservoir, wherein ingress of reagent to the flow cell and egress of reagent from the flow cell occur through the same port of the flow cell.

7. The fluidic system of claim 6, wherein at least one valve is configured to differentially direct liquid reagent from the flow cell back to the cache reservoir or from the flow cell to a waste reservoir.

8. The fluidic system of claim 1, wherein said cache reservoir is configured to reduce mixing of fluid within the cache reservoir, thereby maintaining a gradient of liquid reagent along the length of the reservoir from the end proximal to the flow cell to the end distal to the flow cell.

9. The fluidic system of claim 1, wherein said cache reservoir comprises a plurality of mixing elements configured to promote mixing of fluid within the cache reservoir.

10. The fluidic system of claim 9, wherein the mixing elements comprise static features in the cache reservoir or on an interior surface of the cache reservoir.

11. The fluidic system of claim 9, wherein the mixing elements comprise baffle elements.

12. The fluidic system of claim 1, wherein said cache reservoir comprises a serpentine channel.

13. The fluidic system of claim 1, wherein said cache reservoir comprises a channel of non-cylindrical shape.

14. The fluidic system of claim 1, wherein the manifold is configured to deliver reagent from a first reagent reservoir to a first valve via a first channel and from the first reagent reservoir to a second valve via a second channel.

15. The fluidic system of claim 14, wherein the manifold comprises a plurality of layers, and wherein each of the first and second channels resides in a separate layer of the plurality of layers.

16. The fluidic system of claim 15, wherein the two separate channels converge to form a T-junction at the port.

17. The fluidic system of claim 1, wherein at least one of the reagent sippers comprises a compliant tip configured to flex when the tip impinges upon the bottom of a reagent well in a reagent cartridge.

18. The fluidic system of claim 1, wherein the detection apparatus comprises a plurality of microfluorometers, wherein each of the microfluorometers comprises an objective configured for image detection in an image plane in x and y dimension.

19. The fluidic system of claim 1, wherein the manifold comprises between 10 and 20 ports, each port configured to couple a reagent sipper to a channel in fluid communication with the at least one valve.

20. The fluidic system of claim 1, further comprising one or more alignment pins which extend downward from the manifold in an axis parallel to the reagent sippers, the alignment pins being longer than the reagent sippers and configured to engage with corresponding interface slots on a reagent cartridge.

21. The fluidic system of claim 1, the at least one valve having a plurality of inlet ports and one or more outlet ports, each of the inlet ports in fluid communication with a reagent sipper and each outlet port in fluid communication with an inlet of a flowcell or a waste receptacle.

22. The fluidic system of claim 1, wherein the system comprises a first valve and a second valve configured to independently deliver separate reagents across a first channel and a second channel of a flow cell.

23. The fluidic system of claim 1, further comprising a sensor for detecting air bubbles in a fluid flowing from the plurality of reagent sippers to the inlet of the flow cell.