The microfluidic PicoArray reactor is made from silicon using standard microelectronic fabrication procedures. The reactor contains three topographical features: pico-reaction chambers, fluid microchannels, and inlet/outlet through holes. The fluid microchannels are of a tapered shape that was derived from a fluid mechanical model to produce a uniform flow rate across all reaction chambers. This technology enables a high density of uniform spots.
Digital Photolithographic Device
A major advancement in making photolithography a practical method for combinatorial chemical synthesis is the introduction of the digital optical device for light patterning projection onto a reaction surface. This technology allows parallel synthesis of a large number of different molecules on the same reaction surface without the need for the expensive, inconvenient microfabricated photomasks previously used. Custom microarray synthesis via digital optical device is completely programmable. The entire process is controlled by automation.
Photo Generated Acid (PGA) Deprotection
A PGA precursor is fed into the microfluidic chamber prior to the light irradiation step to create the acid which removes the acid labile DMT protecting group (for oligo synthesis) or t-Boc protecting group (for peptide synthesis). This process is simple in that it does not require an electrochemical surface or specialty monomers with photolabile protecting groups (PLPG).
Electrochemical deprotection methods require a complex circuitry of electrodes that can withstand contact with the strong organic reagents through multiple synthesis cycles. Another limitation of deprotection with electrodes is that side reactions can occur on the electrode surface. The need for specialty PLPG monomers means no flexibility for creating content variations in the sequences. Studies show the reaction efficiency is much lower than standard monomers and they have been known to give rise to randomized misincorporation or insertion errors lowering sequence fidelity.
PGA deprotection allows parallel synthesis with conventional chemicals and supplies, following well established synthesis processes. The quality of the synthesis reaction is comparable to that of conventional synthesis and this approach is very flexible because any customer requested sequences can be synthesized and virtually any modified monomer can be used creating a wide array of non-regular oligonucleotides and peptides.