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

Zhang, Chunsun; Xing, Da

For chamber-based stationary PCR chips, thermal cycling can be performed either with contact heating methods or noncontact heating methods. The former is defined as having heaters fabricated within the chip or in thermal contact with the outside of the chip, where the thermal mass of the microchip is in contact with the heating element. The latter uses a heating method that is not in physical contact with the PCR chamber (3). Among the contact heating methods, the MEMSbased film heating elements have smaller thermal mass, faster thermal response and higher heating rates (e.g. 4108C/s) (11, 14, 31, 32, 35, 38, 40, 45, 47, 48, 51, 77, 79, 80, 89 ) (see Table 1 ). To date, the fastest heating rate (1758C/s) and cooling rate (1258C/s) have been obtained (65) using this method (80) . However, since these heating elements are usually fabricated in a complicated process, the costs are considerably higher than other designs. To reduce costs, the temperature control chip can be physically separated from the PCR reaction chip and reused after initial temperature calibration (20, 46, 48, 79, 80) . To develop a cost-effective heating element, interest was focused on the commercially available flexible thin film heaters with a heating rate of 6.58C/s or higher (54, 59, 60, 67, 70) . Alternatively, contact heating is also often realized by a Peltier device (17, 37, 43, 53, 62, 63) . Although its high thermal mass weakens the thermal response of the entire PCR chip, 58C/s heating rates can be acquired and thus the system performances are better than most of Peltier effect or metal block-based PCR machines. A disadvantage associated with the contact heating is that a certain amount of thermal mass is added in the PCR chip assembly, which inevitably hinders fast thermal transitions. Moreover, when PCR and analytical function (e.g. CE) are integrated on a single chip, it is very difficult to confine the contact heating to the PCR chip itself and not analysis part of the chip. In order to overcome these issues, interest in noncontact heating continues to grow (4) . Recently, Landers's group successfully realized the integration of noncontact infrared (IR)-mediated PCR with CE separation (26) or with SPE and CE separation (27) on a single glass chip. Hu et al. proposed a new method to control PCR thermal cycling using an alternating-electric-current induced buffer Joule heating effect without an external heater component (39) . Although this approach obtained a low heating rate of 38C/s and cooling rate of 28C/s, there is still much room to improve the thermal response of Joule heating if the total thermal mass of the chip can be reduced.