Micro air bubble formation and its control during polymerase chain reaction (PCR) in polydimethylsiloxane (PDMS) microreactors

Air bubble formation during polymerase chain reaction (PCR) thermocycling in microreactors has been reported as one of the major causes for PCR failure. In this paper we investigate the locations, mechanisms and other characteristics of the micro bubble formation inside a PCR microreactor array chip made by polydimethylsiloxane (PDMS) bonded with glass. The bubble formation is found to be strongly related to the micro features inside the microreactors and inside the chip bonding interface, especially near the inner corners of the microreactors, which are dependent on the micro-fabrication methods used. Gas permeability of PDMS and the wetting property of PCR sample also have influence on the air bubble formation. After investigation of various methods to control the bubble formation, we present the two most viable ones through micro bubble absorption and chip bonding interface modification. Finally, a bubble-free PCR in PDMS microreactors is demonstrated, in which the micro bubbles are suppressed with a bonding interface cladding technique.