DNA Microarrays

In the late 1990s and 2000s, DNA array technology progressed rapidly from long DNA sequences to oligo arrays, thanks to the increasing quantity of publicly available DNA sequence information. The use of oligos increased in specificity. Nowadays, microarrays are widely used to measure the relative concentration of DNA or RNA in solution as they allow the analysis of many—tens of thousands—different sequences on a small surface (often referred to as “chips”). The main applications include gene expression analysis, transcription factor binding analysis and genotyping.

To prepare a microarray assay, unknown nucleic acid molecules are cut into fragments and fluorescent markers are attached to those fragments. Then, the nucleic acid fragments bind to their complementary sequence of the pre-loaded sequences on a chip. The remaining fragments are washed away. The target nucleic acid pieces can be identified by their fluorescence emission after illumination with an appropriate laser light source. With a computer, the fluorescent emission pattern is recorded and then sequences can be identified.

While this technology is extremely useful, microarrays have a number of limitations. First, arrays provide an indirect measure of relative concentration. At high concentrations, the array may become saturated, and at low concentrations the equilibrium favors no binding. Second, it is difficult to design probes that will not bind to different related sequences, particularly problematic in gene families. Finally, an array can only detect sequences that it was design to detect. This can be a problem when working with variable bacterial genomes, for example, where probes are designed using the reference genome.

The largest markets for microarrays are hospital and clinics, academia and CROs. The technology is transitioning from research-use only in the past to a more active role in the diagnostic space, informing physicians about patients’ conditions. Some of the main applications of this technology include agrigenomics, cytogenetics and biobank genotyping studies.

Illumina, the leading vendor of the market, manufactures the HiScan, iScan and HiScan HQ scanners and a range of microarray chips including the Infinium Global Screening Arrary for human genotyping. The company benefits from the strong synergy of NGS sequencing and microarray technology, which are both part of its portfolio. Affymetrix, which pioneered the high-density microarray market and accounts for a quarter of the market, was acquired by Thermo Fisher Scientific in 2016 (see IBO 1/15/16) Thermo Fisher offers the flagship Affymetrix GeneChip instrument system and the GeneAtlas microarray system, as well as microarrays such as the CytoScan HD Array. Agilent Technologies also participates in the market, offering two systems, the SureScan microarray scanner and the SurePrint G3 for gene expression, as well as microarray chips, including the Agilent Human Genome CGH Microarray.

In 2016, the total microarray market was about $870 million. Although threatened by NGS and PCR technologies, microarrays will continue to grow at low single digits for the next five years due mostly to their relative ease of use.

 

Microarrays at a Glance:

Leading Suppliers:

  • Illumina
  • Thermo Fisher Scientific
  • Agilent Technologies

Largest Markets:

  • Hospital and Clinical
  • Academia
  • CROs

Scanner Cost:

  • $75,000–$150,000
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