System and apparatus for sequential processing of analytes

• US 6,969,488 B2
• Filed: 07/17/2001
• Issued: 11/29/2005
• Est. Priority Date: 05/22/1998
• Status: Expired due to Term

• Current Assignee: Solexa Incorporated (Illumina Incorporated)
• Original Assignee: Solexa Incorporated (Illumina Incorporated)
• Inventors: Corcoran, Kevin, Bridgham, John, Brenner, Sydney, Golda, George, Pallas, Michael C.
• Primary Examiner(s): Alexander, Lyle A.
• Application Number:
  US09/908,131
• Publication Number:
  US 20020061529A1
• Time in Patent Office: 1,596 Days
• Field of Search: 422/99, 422101-104, 422/82.05, 422/61, 422/58, 435/287.2, 435/287.9, 435/288.4, 435/288.5, 435/288.7, 435/810
• US Class Current: 422/430
• CPC Class Codes: B01J 2219/00274 Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
• CPC Class Codes: B01L 2200/0647 Handling flowable solids, e.g. microscopic beads, cells, particles
• CPC Class Codes: B01L 2200/10 Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
• CPC Class Codes: B01L 2300/0877 Flow chambers
• CPC Class Codes: B01L 2400/0403 specific forces
• CPC Class Codes: B01L 2400/0475 specific mechanical means and fluid pressure
• 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 2400/0644 rotary valves
• CPC Class Codes: B01L 3/5027 by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip B01L3/5023 takes precedence; micromixers B01F33/30; microreactors for synthesis B01J19/0093; microcapillary devices in general B81B1/00
• CPC Class Codes: B01L 3/502715 characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• CPC Class Codes: B01L 3/502761 specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads, for physically stretching molecules investigating characteristics of particles G01N15/00
• CPC Class Codes: G01N 2015/144 Imaging characterised by its optical setup
• CPC Class Codes: G01N 2015/1452 Adjustment of focus; Alignment
• CPC Class Codes: G01N 2035/00158 Elements containing microarrays, i.e. "biochip"
• CPC Class Codes: G01N 21/253 for batch operation, i.e. multisample apparatus analytical automats G01N35/00
• CPC Class Codes: Y10S 435/81 Packaged device or kit
• CPC Class Codes: Y10T 436/13 Tracers or tags
• CPC Class Codes: Y10T 436/143333 Saccharide [e.g., DNA, etc.]

Abstract

An apparatus and system are provided for simultaneously analyzing a plurality of analytes anchored to microparticles. Microparticles each having a uniform population of a single kind of analyte attached are disposed as a substantially immobilized planar array inside of a flow chamber where steps of an analytical process are carried out by delivering a sequence of processing reagents to the microparticles by a fluidic system under microprocessor control. In response to such process steps, an optical signal is generated at the surface of each microparticle which is characteristic of the interaction between the analyte carried by the microparticle and the delivered processing reagent. The plurality of analytes are simultaneously analyzed by collecting and recording images of the optical signals generated by all the microparticles in the planar array. A key feature of the invention is the correlation of the sequence of optical signals generated by each microparticle in the planar array during the analytical process.

Claims

1. A flow chamber, comprising:

an inlet at one end of said flow chamber;

an outlet at another end of said flow chamber; and

a planar cavity in fluid communication with each of said inlet and outlet,

wherein said planar cavity comprises a floor having a plurality of parallel ridges disposed parallel to a longitudinal axis of the flow chamber, and holds a monolayer of microparticles in a substantially immobilized planar array, such that said microparticles form rows between the parallel ridges, and such that processing reagents can access each microparticle during a sequence of processing steps,

wherein the number of microparticles per unit area in the planar array is at least eighty percent of the number of microparticles in a hexagonal array of equal area, or the average distance between centers of adjacent microparticles in the planar array is less than two microparticle diameters;

each of a plurality of the microparticles having an analyte anchored thereto.

2. The flow chamber of claim 1, wherein the planar cavity further comprises an optically transmissive ceiling substantially parallel to said floor.

3. The flow chamber of claim 1, wherein each said microparticle has a diameter between about 0.1 and 100μ

, which diameter is approximately the same for each microparticle, and said optically transmissive ceiling and said floor are separated by a distance of between about 120 to 150 percent of said diameter.

4. The flow chamber of claim 1, further comprising a dam adjacent to the outlet, wherein the dam is effective to prevent the passage of the microparticles through said outlet when fluid passes through said flow chamber from said inlet to said outlet.