NUMBER CODING FOR IDENTIFICATION OF SUBTYPES OF CODED TYPES OF SOLID PHASE CARRIERS

• US 20110184655A1
• Filed: 03/24/2011
• Published: 07/28/2011
• Est. Priority Date: 09/18/2003
• Status: Active Grant

• Current Assignee: BioArray Solutions Limited (Werfen SA)
• Original Assignee: BioArray Solutions Limited (Werfen SA)
• Inventors: Seul, Michael, Chau, Chiu, Tan, Enqing
• Granted Patent: US 8,615,367 B2
• Time in Patent Office: Days
• US Class Current: 702/19
• CPC Class Codes: G01N 33/543 with an insoluble carrier for immobilising immunochemicals
• CPC Class Codes: G01N 33/54313 the carrier being characterised by its particulate form
• CPC Class Codes: G01N 33/564 for pre-existing immune complex or autoimmune disease , i.e. systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, rheumatoid factors or complement components C1-C9
• CPC Class Codes: G01N 33/6845 Methods of identifying protein-protein interactions in protein mixtures

Abstract

Disclosed is number coding of pairs (“doublets”) or small sets (“multiplets”) of solid phase carriers which provides distinguishable subtypes of a given type of such carriers, where each carrier type is distinguishable on the bases of a different code. Such number coding is useful for augmenting a coding system, such as a color code, and thereby effectively multiplying the number of “colors” (distinguishable sub-types). It can be applied, for example, to determine whether a sample is homozygous or heterozygous at a number of different sites for one of two different alleles, where the same color code is applied for each of the two alleles, and the alleles with the same color code are distinguished by knowing how many carriers are associated with molecules which detect each different allele.

Claims

1. A method of expanding the set of distinguishable codes for encoding particles in a bioassay of a sample, where analytes are distinguished using encoded particles displaying different ligands, where ligands which bind to different analytes can be distinguished through the codes, comprising:

forming groups, each group made up of different numbers of particles having the same code, where members of each group display up to four different ligands, and wherein the number of particles in each group displaying the same ligand has a unique decomposition into one or more summands, such that no partial sum of one or more summands can be obtained in any other way of combining summands, and no summand is itself the sum of two or more of the other summands;

reacting the sample with the particles;

determining for each group of particles, the number of particles generating a positive assay signal;

comparing for each group of particles, said number with the number of particles displaying each said different ligand; and

determining for each group of particles, which analytes which bind to the ligands attached to the particles in a group, are present in the sample.

2. The method of claim 1 used to analyze the polymorphic form of a nucleic acid analyte present in a genomic sample, wherein each group of encoded particles is functionalized with one of four oligonucleotide probes, each probe differing by having one of the nucleotides A, C, G or T in the 3′

terminal position.

3. The method of claim 2 wherein a positive assay signal is generated by an elongation reaction.

4. A method of expanding the distinguishable set of codes for coding particles displaying different ligands, each ligand being a peptide or an antibody, where the particles are used in a bioassay of a sample, and where ligands which bind to different analytes can be distinguished through the codes, comprising:

forming groups of different numbers of particles having the same code, where members of each group display up to four different ligands, and wherein the number of particles in each group displaying the same ligand has a unique decomposition into one or more summands, such that no partial sum of one or more summands can be obtained in any other way of combining summands, and no summand is itself the sum of two or more of the other summands;

reacting the sample with the particles;

determining for each group of particles, the number of particles generating a positive assay signal;

comparing for each group of particles, said number with the number of particles displaying each said different ligand; and

determining for each group of particles, which analytes which bind to the ligands attached to the particles in a group, are present in the sample.

5. The method of claim 4 wherein the ligands are peptides used to detect specific epitopes of auto-antibodies in a sample.

6. The method of claim 4 wherein determining the binding between peptides and antibodies is by a secondary detection antibody which binds to the auto-antibodies bound to the peptides.

7. The method of claim 4 wherein the solid phase carriers are beads encoded by different colors, and different colors correspond to different groups of peptide ligands, each such group of peptides corresponding to epitopes of a specific autoantibody.

8. The method of claim 4 wherein two or more different types of peptides are attached to beads of the same color.