Oligonucleotide microarray synthesis with a micromirror array.

摘要

Genome sequencing projects and the development of DNA chips, or high-density microarrays, allow researchers to obtain genome-wide expression patterns for organisms in different developmental states, environmental conditions, or disease states. Expression profiles can be obtained for organisms with gene knockouts and compared with wild type organisms to identify pathway components and compensatory mechanisms. Currently, two types of microarrays predominate: oligonucleotide microarrays (OMAs) on which the DNA probes are synthesized in situ using photolithography and light-directed chemistry, and cDNA spotted microarrays on which pre-made DNA probes are mechanically spotted onto the substrate with robots. Both types of arrays have advantages and drawbacks. OMAs have greater specificity (allowing discrimination between closely related gene family members) and better controls, while the cDNA arrays have greater sensitivity and up until now, have been the most accessible array format. One of the major drawbacks to the OMAs is the expense of the photolithography process used in their manufacture. A large number of expensive masks must be fabricated to pattern the OMAs, resulting in high setup costs for new OMA designs. A new technology is reported that allows facile and economical synthesis of OMAs. This technology involves the creation of virtual masks with a microarray of mirrors controlled by a computer. Patterns of light created by the micromirror array replace the expensive photolithography masks and greatly reduce the time required to synthesize a custom OMA. This allows nimble production of arrays based on new sequence information and eliminates high setup costs, allowing economical production of custom designs. The technology is also applicable to the fabrication of many types of biopolymer microarrays such as peptides, hormones, antibodies, drugs, or pesticides.