Miniaturized PCR chips for nucleic acid amplification and analysis: latest advances and future trends

Zhang, Chunsun; Xing, Da

In this format of PCR chip, the PCR solution is kept stationary and the temperature of the reaction chamber is cycled between different temperatures. The first PCR chip developed by Northrup et al. in 1993 was based on such a stationary chamber (84) . Since then, this format has been widely replicated and improved (2) (3) (4) . During the past two years, the miniaturization of such PCR devices has been of growing interest. In general, they can be classified as single chamber stationary PCR chip ( Figure 1A ) (10, (12) (13) (14) (15) (16) 18, 21, 22, 24, 26, 27, 29, 32, 37, 39, 40, 43, 45, 46, 48, (51) (52) (53) 57, 62, 63, (68) (69) (70) and multi chamber stationary PCR chip ( Figure 1B) (11, 17, 19, 20, 25, 28, 31, (33) (34) (35) (36) 38, 47, 49, 54, 78) . The former can perform very well in terms of fluidic and thermal controls and offer beneficial properties such as reduced thermal and fluidic crosstalk between chambers. However, they cannot realize highthroughput and cannot readily be used for special purposes such as single cell gene expression analysis. To circumvent these issues, great efforts have been made to develop multi-chamber stationary PCR. This type of PCR chip allows generation of standard curves, use of multiple primer sets and optimization of microfluidic PCR. However, special care must be taken to achieve the thermal optimization of chamber array in order to obtain homogeneous temperature fields between chambers.