Liquid chromatography (LC) is a powerful analytical tool for molecular separation. Temperature variation can be an important parameter in liquid chromatography (see e.g. T. Greibrokk, T. Andersen, Journal of Separation Science, 24, 899-909, 2001; T. Greibrokk, Analytical Chemistry, 74(13), 374A-378A, 2002). Temperature can affect several physical parameters in LC such as retention factor, analyte solubility, diffusivity, and mobile phase viscosity. However, temperature control can be slow and difficult to implement due to radial temperature gradients associated with the large sizes of traditional chromatography columns.
The recent trend toward miniaturization of chromatography columns has stimulated research into temperature control (V. R. Meyer, “Practical High-Performance Liquid Chromatography”, John Wiley & Sons, 1999, 310-311). For example, temperature controlled separation columns were microfabricated for gas chromatography (U.S. Pat. No. 6,666,907 to Manginell et. al. issued Dec. 23, 2003, U.S. Pat. No. 6,663,697 to Kottenstette et. al. issued Dec. 16, 2003, and U.S. Pat. No. 6,838,640 to Wise et. al. issued Jan. 4, 2005). Yet, it is highly desirable to develop an on-chip, temperature controlled system for liquid chromatography. LC provides greater engineering challenges in view of the high pressures. Moreover, it is a challenge to generate and control temperature gradients on chips, particularly in view of the high thermal conductivity of silicon, and a need exists for better thermal management systems including better heating and cooling systems. Also, a need exists for better integrated systems, wherein device components are fabricated on a common substrate using sequential processing steps.