Photolithographic Synthesis of High-Density DNA and
RNA Arrays on Flexible, Transparent, and Easily Subdivided Plastic
Substrates
- Publication date
- Publisher
Abstract
The photolithographic fabrication
of high-density DNA and RNA arrays
on flexible and transparent plastic substrates is reported. The substrates
are thin sheets of poly(ethylene terephthalate) (PET) coated with
cross-linked polymer multilayers that present hydroxyl groups suitable
for conventional phosphoramidite-based nucleic acid synthesis. We
demonstrate that by modifying array synthesis procedures to accommodate
the physical and chemical properties of these materials, it is possible
to synthesize plastic-backed oligonucleotide arrays with feature sizes
as small as 14 μm × 14 μm and feature densities in
excess of 125 000/cm<sup>2</sup>, similar to specifications attainable
using rigid substrates such as glass or glassy carbon. These plastic-backed
arrays are tolerant to a wide range of hybridization temperatures,
and improved synthetic procedures are described that enable the fabrication
of arrays with sequences up to 50 nucleotides in length. These arrays
hybridize with S/N ratios comparable to those fabricated on otherwise
identical arrays prepared on glass or glassy carbon. This platform
supports the enzymatic synthesis of RNA arrays and proof-of-concept
experiments are presented showing that the arrays can be readily subdivided
into smaller arrays (or “millichips”) using common laboratory-scale
laser cutting tools. These results expand the utility of oligonucleotide
arrays fabricated on plastic substrates and open the door to new applications
for these important bioanalytical tools