A review on microscale polymerase chain reaction based methods in molecular diagnosis, and future prospects for the fabrication of fully integrated portable biomedical devices

Abstract

Since the advent of microfabrication technology and soft lithography, the lab-on-a-chip concept has emerged as a state-of-the-art miniaturized tool for conducting the multiple functions associated with micro total analyses of nucleic acids, in series, in a seamless manner with a miniscule volume of sample. The enhanced surface-to-volume ratio inside a microchannel enables fast reactions owing to increased heat dissipation, allowing rapid amplification. For this reason, PCR has been one of the first applications to be miniaturized in a portable format. However, the nature of the basic working principle for microscale PCR, such as the complicated temperature controls and use of a thermal cycler, has hindered its total integration with other components into a micro total analyses systems (mu TAS). This review (with 179 references) surveys the diverse forms of PCR microdevices constructed on the basis of different working principles and evaluates their performances. The first two main sections cover the state-of-the-art in chamber-type PCR microdevices and in continuous-flow PCR microdevices. Methods are then discussed that lead to microdevices with upstream sample purification and downstream detection schemes, with a particular focus on rapid on-site detection of foodborne pathogens. Next, the potential for miniaturizing and automating heaters and pumps is examined. The review concludes with sections on aspects of complete functional integration in conjunction with nanomaterial based sensing, a discussion on future prospects, and with conclusions.