System and apparatus for sequential processing of analytes

• US 7,282,370 B2
• Filed: 08/18/2005
• Issued: 10/16/2007
• Est. Priority Date: 05/23/1997
• Status: Expired due to Fees

• 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): Gakh; Yelena G.
• Application Number:
  US11/207,443
• Publication Number:
  US 20060051876A1
• Time in Patent Office: 789 Days
• Field of Search: None
• US Class Current: 436/172
• 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 method for tracking and analysis of multiple analytes through a series of processing steps, wherein said analytes are anchored to a plurality of microparticles, the method comprising:

providing a population of microparticles, held in a planar array within a flow chamber, of which said plurality of microparticles have said multiple analytes anchored thereto;

for each of a series of processing steps;

(i) delivering processing reagents having optically detectable labels to the flow chamber, such that said multiple analytes are contacted with the processing reagents,

(ii) exposing said plurality of microparticles to radiation, thereby producing optical signals from products of interaction between said optically labeled reagents and said analytes on the microparticles, and

(iii) detecting and recording said optical signals from each microparticle of the plurality,

to produce a sequence of optical signals for each microparticle of the plurality;

tracking the positions of said plurality of microparticles within the array during said processing steps, by collecting images derived from scattered or focused light from said microparticles, thereby determining the approximate center of each microparticle; and

correlating said sequences of optical signals with said positions.

2. The method of claim 1, wherein said detecting and recording comprises focusing said optical signals onto a solid state imaging device which is capable of generating a digital image of the microparticle array with sufficient resolution for individual microparticles to be distinguished.

3. The method of claim 1, wherein said collected images comprise focused back light from back lighted microparticles or the scatter centers of top-lighted microparticles.

4. The method of claim 1, wherein said analytes are oligonucleotides or nucleic acid molecules.