Chemical and physical processes for integrated temperature control in microfluidic devices Rosanne M. Guijt†, ab Arash Dodge†, a Gijs W. K. van Dedem, b Nico F. de Rooij a and Elisabeth Verpoorte* a a SAMLAB, Institute of Microtechnology, University of Neuchâtel, Switzerland b Kluyver Institute for Biotechnology, Delft University of Technology, the Netherlands Received 29th October 2002, Accepted 2nd December 2002 First published as an Advance Article on the web 16th December 2002 Microfluidic devices are a promising new tool for studying and optimizing (bio)chemical reactions and analyses. Many (bio)chemical reactions require accurate temperature con- trol, such as for example thermocycling for PCR. Here, a new integrated temperature control system for microfluidic devices is presented, using chemical and physical processes to locally regulate temperature. In demonstration experi- ments, the evaporation of acetone was used as an endo- thermic process to cool a microchannel. Additionally, heating of a microchannel was achieved by dissolution of concentrated sulfuric acid in water as an exothermic process. Localization of the contact area of two flows in a micro- fluidic channel allows control of the position and the magnitude of the thermal effect. Introduction Since the introduction of the miniaturized total chemical analysis system (mTAS) concept in 1990, 1 the development of so-called ‘lab-on-chip’ devices has been an area of exponential growth. Miniaturization of chemical systems allows faster chemical reactions, due to reduced diffusion-driven transport times, and faster and more efficient separations. Working on a small scale reduces the risks involved in manipulation of explosive and unstable mixtures required for chemical reac- tions. Additionally, working with a microchip format dramat- ically reduces the consumption of sample and reagents, and allows the performance of multiple analyses in parallel, thereby lowering the price per analysis. Large surface-to-volume ratios also allow better thermal control. Heating and cooling of small liquid volumes can be accomplished in much shorter periods of time. The small thermal mass of the chips themselves also contributes to increased heating and cooling rates. Enhanced heat transfer introduces the potential for improved control of chemical process conditions in microreactors. Certainly, the excessive heat build-up which often leads to runaway reactions in conventional reactors can be avoided. 2 Precise temperature control is also required in certain (bio- )chemical reactions, such as DNA amplification using the polymerase chain reaction (PCR), 3 and the investigation of reaction kinetics. PCR is a biochemical reaction requiring rapid and precise thermocycling of reagents at three different temperatures between 50 °C and 100 °C. The potential of faster temperature ramping and more precise temperature control has been the impetus for the integration of PCR into micro- fabricated devices. The earliest examples of this development were presented by Northrup et al. in 1993 4 and Wilding et al. in 1994. 5 More recently, efforts in a number of groups have resulted in several examples of PCR on chip. In the devices described in references 5–9 external thermal control was used, whereas in references 2, 4 and 10 heating elements were incorporated in the device through integration of resistive layers heated by the Joule effect. Control of exothermic reactions in micromachined chemical reactors has also been presented using integrated heaters in microreaction chambers. 2 Until now, cooling of microfluidic devices has only been done with external components or by convection. It has been achieved by clamping 5 or gluing the microfluidic device to an external Peltier element, 9 or by contacting the microdevice with a copper block, passively cooled by contact with cooling fins. 6 The convection technique primarily consists of using the heat exchange between the device and ambient air, an effect which may be enhanced by blowing compressed air or nitrogen gas over the microdevice. 7,8,10 Only two integrated cooling tech- niques have been presented, neither of them for microfluidic devices but for micro-electronics. In one case, an integrated cooling system utilizing a microchannel in a printed circuit board (PCB) was described. Either water or methoxynona- fluorobutane were used as coolants and pumped through the microchannel, removing heat from the electronics. 11 The heat was dissipated in a heat exchanger, positioned elsewhere on the PCB. A comparable system using microfluidics in combination with a heat exchanger for cooling electronics has been described elsewhere. 12 In the second case, integrated cooling of micro- electronic devices took the form of the ‘fridge-on-a-chip’. 13 Here, microPeltier elements were integrated during the micro- fabrication process on the back of microelectronic devices. Most of the cooling systems described above require external and often bulky components, thereby limiting the possibilities of integration in a microfluidic device. Even the microfluidic cooling system integrated on the PCB 11 required a heat exchanger elsewhere on the device, complicating the micro- fabrication process and increasing the footprint of the device and fabrication costs. Similarly, heating small volumes on-chip involves the use of external elements, or additional fabrication steps for integration of heating elements. The approach for chip- based temperature modification presented here is quite differ- ent, as it is based on the exploitation of endothermic or exothermic processes in microchannels to respectively cool or heat solutions in an adjacent microchannel. The temperature control channels (TCCs) are directly integrated in the chip at the same time that the microfluidics are fabricated by simple single- level microfabrication. Localization of the cooling or heating effect is controlled by positioning the endothermic or exo- thermic processes at the reactant flow interface. Experimental Under the usual operating conditions for microfluidic devices, fluid flows are laminar. That is, the velocity at any one point in a channel is predictable and unchanging, and streamlines are well defined. When two fluids coming from two different reactant channels (RC) are merged together into a single microfluidic channel (Fig. 1A), they generally follow laminar streamlines and flow side-by-side. The stream from RC 2 flows along the side of the TCC closest to the central channel (Fig. 1B). The relative widths of the fluid flows are determined by the flow rate ratio. At the interface, chemical or physical processes † Both authors contributed equally to this research. This journal is © The Royal Society of Chemistry 2003 Communication DOI: 10.1039/b210629a Lab Chip, 2003, 3, 1–4 1