Fluidic system for reagent delivery to a flow cell

{
  "publication_number": "US9410977B2",
  "country": "US",
  "kind": "B2",
  "title": "Fluidic system for reagent delivery to a flow cell",
  "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."
  ],
  "description_excerpt": "Embodiments of the present disclosure relate generally to apparatus and methods for fluidic manipulation and optical detection of samples, for example, in nucleic acid sequencing procedures.\n\nOur genome provides a blue print for predicting many of our inherent predispositions such as our preferences, talents, susceptibility to disease and responsiveness to therapeutic drugs. An individual human genome contains a sequence of over 3 billion nucleotides. Differences in just a fraction of those nucleotides impart many of our unique characteristics. The research community is making impressive strides in unraveling the features that make up the blue print and with that a more complete understanding of how the information in each blue print relates to human health. However, our understanding is far from complete and this is hindering movement of the information from research labs to the clinic where the hope is that one day each of us will have a copy of our own personal genome so that we can sit down with our doctor to determine appropriate choices for a healthy lifestyle or a proper course of treatment.\n\nThe current bottleneck is a matter of throughput and scale. A fundamental component of unraveling the blue print for any given individual is to determine the exact sequence of the 3 billion nucleotides in their genome. Techniques are available to do this, but those techniques typically take many days and thousands upon thousands of dollars to perform. Furthermore, clinical relevance of any individual's genomic sequence is a matter of comparing unique features of their genomic sequence (i.e.",
  "cpc": [
    "G01N 35/1097",
    "B01L 2200/025",
    "B01L 2200/026",
    "B01L 2200/0621",
    "B01L 2200/16",
    "B01L 2300/0654",
    "B01L 2300/0867",
    "B01L 2300/0877",
    "B01L 2300/0883",
    "B01L 2300/0887",
    "B01L 2300/168",
    "B01L 2400/02",
    "B01L 2400/0622",
    "B01L 2400/086",
    "B01L 3/021",
    "B01L 3/0268",
    "B01L 3/0275",
    "B01L 3/502715",
    "B01L 3/502738",
    "B01L 3/527",
    "C12Q 1/6874",
    "G01N 2035/00237",
    "G01N 21/6428",
    "G01N 21/6456",
    "G01N 35/1002",
    "G01N 35/1016",
    "G01N 35/1065",
    "G01N 35/1095",
    "Y10T 436/2575"
  ],
  "ipc": [
    "B01L 3/00",
    "C12Q 1/68",
    "G01N 35/10"
  ],
  "assignees": [
    "Illumina Inc"
  ],
  "inventors": [
    "Michael Stone",
    "Drew Verkade"
  ],
  "filing_date": "2014-08-07",
  "publication_date": "2016-08-09",
  "grant_date": "2016-08-09",
  "priority_date": "2013-08-08",
  "application_number": "US-201414453868-A",
  "family_id": "52107647",
  "cited_by_count": 41,
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}