Arrays and Bead-based Technologies for Clinical Applications
CGH arrays, marketed by PerkinElmer (www.perkinelmer.com), function as a result of the comparative genomic hybridization technique. These arrays provide coverage of the entire human genome or specific chromosomal regions. Whole-genome arrays or targeted arrays can be used to look at chromosome structure, copy number, and chromosomal abnormalities that represent disease conditions or inherited disorders.
“Currently neonatal and prenatal screening is based on protein or metabolite markers. CGH arrays have the potential to serve as a molecular diagnostic tool to fill the gap in genetic screenings in these areas. CGH arrays are a complement to the existing fluorescent in situ hybridization (FISH) technology. CGH arrays are more powerful as they can assess a few hundred markers at one time compared to FISH, which can assess only 5–6 markers at one time. Hence, CGH arrays have applications in cytogenetics and post-natal diagnosis,” explains Howard Grey, Ph.D., director of molecular diagnostics.
Illumina (www.illumina.com) plans to enter the clinical diagnostics market by the year-end with its VeraCode™ technology. VeraCode utilizes digitally inscribed cylindrical glass microbeads that are 240 µm in length x 28 µm in diameter. The beads are inscribed with holographic elements that diffract light when excited by a laser beam, creating a unique code image. The BeadXpress™ reader, a high-throughput, two-color laser detection system performs bead analysis and detection. The reader scans the beads for their code and fluorescence intensity signals. Data analysis is done with Illumina’s BeadStudio data-analysis software.
“Since the beads are inscribed, it is a stable technology. This technology can be used in discovery stage to validate markers and track samples or in diagnostic assays to screen for markers. Researchers can custom-tailor their bead arrays in a solution-based format. The multiplexing capability offered by this system makes it suitable for a variety of applications, such as biomarker discovery, SNP genotyping, development of molecular diagnostic assays, gene expression, and protein-based assays,” says Mickie Henshall, product marketing manager for molecular diagnostics at Illumina.
Invitrogen (www.invitrogen.com) is taking a two-pronged provider and developer approach to enhance its position in the molecular diagnostics arena. The company is an OEM supplier of products that support nucleic acid testing, antibody, flow cytometry, and immunohistochemistry applications of pharmaceutical, in vitro diagnostics firms, and specialty and reference laboratories.
Some key products marketed by Invitrogen are TAQ polymerases, microarray kits for molecular phenotyping, oligonucleotides, primers, and magnetic beads for the development of nucleic acid and immunoassay formats. The company is now also focusing on developing analyte-specific reagents (ASRs) using a molecular technique known as chromogenic in situ hybridization (CISH).
“The CISH technology is an alternative to the existing fluorescent in situ hybridization technology, or FISH. CISH, we believe, represents a significant opportunity for us within the anatomic pathology segment of the market,” says Todd R. Nelson, Ph.D., vp of corporate development. “CISH is a flexible molecular technology that allows for the detection of a broad array of gene amplifications and deletions, as well as morphological interpretation using a standard bright field light microscope.
“Signal stability is longer with CISH technology; the results are 100% concordant with FISH results and can be used effectively in diagnostic tests. We market 30 CISH probes under the SpoT-Light CISH product line and intend to take several of them into the market following regulatory approval. We recently filed our first PMA with the FDA for HER-2 CISH for use as a companion diagnostic for Herceptin therapy.”
Another interesting product line based on ASR is the LUX™ (Light upon eXtension) reagents for infectious disease screening.
Invitrogen is also targeting the HLA genotyping market with HLA diagnostics tools, enabled by its recent acquisition of Dynal HLA Diagnostics (www.dynalbiotech.com). These find use in genotyping assays for bone marrow and organ transplantations. Invitrogen sells its RELI, UNITRAY, and SeCore products directly to leading transplant centers worldwide.