The genomic revolution is fundamentally changing today's medical practice. Disease biomarkers have been identified for multiple human diseases, and this opened up the filed of molecular diagnostics. Genomics based biomarkers are being used for diagnosing a number of conditions, as well as directing the proper therapeutics regimen for others. Some of these genomics biomarkers are gene expression signatures, while others are genotype/haplotype based signatures, including single nucleotide polymorphisms. New signatures are rapidly been identified for more diseases and conditions.
High throughput DNA analysis such as DNA microarrays based assays play an important role in biomarker discovery as well as diagnostics and disease monitoring. It has and will continue to make substantial contributions to the medical field, enabling the transition of medical practice from the current late disease model to an early health model, in that disease prevention plays an ever increasingly important role in the new era of personalized healthcare.
Oligonucleotide based microarray platform is rapidly becoming a preferred platform for biomarker discovery and molecular diagnostics. Recently, Roche AMPLICHIP™ Cytochrome P450 Genotyping test and Affymetrix GENECHIP™ Microarray Instrumentation System was cleared to enter the US and European market, for use to help a clinician determine if a patient has mutations in their CYP450 2D6 gene that may affect their ability to metabolize certain drugs. It is anticipated that additional, similar platforms will enter the market.
Increasingly, it is found that a small number of genes/signatures are enough for diagnosis of a certain disease or condition. In these instances, it is possible to use a bead based platform, for the discovery and diagnostics. Platform such as the XMAP™ technology from Luminex Corporation is one such example. XMAP™ uses color-codes tiny beads, called microspheres, and up to 100 distinct assay reactions can be multiplexed in a single volume.
Quality assurance for nucleic acid fragments used in these assays, especially oligonucleotides, is a key to the success of the system. U.S. Pat. No. 6,714,299 describes the use of light scattering particles in the quality control of microscale devices including microarrays. U.S. patent application Ser. No. 10/802,249, published as US2004-0235022, discloses a quality control method for the on-chip synthesis of biopolymer arrays, with the use of detectable protecting groups. However, there is currently no effective method for the quality control/assurance for oligonucleotides deposited on a microarray or bead, especially for arrays or beads produced in a high volume.