Multianalyte molecular analysis using application-specific random particle arrays

• US 9,709,559 B2
• Filed: 12/28/2001
• Issued: 07/18/2017
• Est. Priority Date: 06/21/2000
• Status: Expired due to Term

• Current Assignee: BioArray Solutions Limited (Werfen SA)
• Original Assignee: BioArray Solutions Limited (Werfen SA)
• Inventors: Banerjee, Sukanta, Seul, Michael
• Primary Examiner(s): Shibuya, Mark
• Assistant Examiner(s): Hollinden, Gary E
• Application Number:
  US10/032,657
• Publication Number:
  US 20060240416A1
• Time in Patent Office: 5,681 Days
• Field of Search: 436526, 436546, 436 2, 436800
• CPC Class Codes: B01J 19/0046 Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays synthesis methods per se C40B50/00
• CPC Class Codes: B01J 2219/005 Beads
• CPC Class Codes: B01J 2219/00545 Colours
• CPC Class Codes: B01J 2219/00576 fluorophore
• CPC Class Codes: B82Y 15/00 Nanotechnology for interacting, sensing or actuating, e.g. quantum dots as markers in protein assays or molecular motors
• CPC Class Codes: C12Q 1/6837 using probe arrays or probe chips C12Q1/6874 takes precedence
• CPC Class Codes: C12Q 1/6876 Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
• CPC Class Codes: G01N 27/745 for detecting magnetic beads used in biochemical assays concerning the assays G01N33/54326; sensors therefor G01R33/1269; automatic analysers therefor G01N35/0098
• CPC Class Codes: G01N 33/54326 Magnetic particles
• CPC Class Codes: G01N 33/54333 Modification of conditions of immunological binding reaction, e.g. use of more than one type of particle, use of chemical agents to improve binding, choice of incubation time or application of magnetic field during binding reaction
• CPC Class Codes: G01N 33/5434 using magnetic particle immunoreagent carriers which constitute new materials per se
• CPC Class Codes: G01N 33/54346 Nanoparticles
• CPC Class Codes: G01N 33/587 Nanoparticles
• CPC Class Codes: G01N 33/588 with semiconductor nanocrystal label, e.g. quantum dots

Abstract

The present invention provides a method for the generation of novel libraries of encoded magnetic particles from sub-libraries of by the generation of novel sub-libraries of magnetic nanoparticles and encoded particles. The sub-libraries are functionalized on demand are useful in the formation of arrays. The present invention is especially useful for performing multiplexed (parallel) assays for qualitative and/or quantitative analysis of binding interactions of a number of analyte molecules in a sample.

Claims

1. A method of multiplex analysis of analytes in a solution, comprising:

providing a plurality of magnetically polarizable microparticles of two or more types wherein different types bear an optically distinguishable signature, and the different types display different capture moieties on their surfaces capable of binding to different analytes;

suspending the microparticles in a first solution containing, or suspected to contain, analytes of interest, under conditions permitting the capture of analytes by the capture moieties, and wherein an optical signal is generated following such capture;

using a magnetic field to assemble the microparticles in a planar array on a designated section of a substrate, where said magnetic field is generated by coils or magnets, and is uniformly distributed over the surface of the substrate, and wherein the spacing between particles within the array is varied by varying the strength of the magnetic field; and

imaging the optically distinguishable signatures associated with the microparticles and the optical signals, and correlating the optical signals with microparticles having particular optically distinguishable signatures to determine which analytes are bound by which capture moieties.

2. The method of claim 1 wherein the optical signals arise as a result of the binding of an analyte by a capture moiety.

3. The method of claim 2 wherein the optical signal indicates the transformation of the capture moiety mediated by the binding of the analyte.

4. The method of claim 1 wherein the first solution is removed and replaced with a second solution prior to imaging the optically distinguishable signatures associated with the microparticles and the optical signals.

5. The method of claim 1 wherein array assembly is initiated at a preselected time by actuating a magnetic field.