Integrated Microfluidics for Parallel Screening of an In Situ Click Chemistry Library

摘要

There is growing interest in performing chemical reactions in microfluidic devices[1]-[3] because they offer a variety of advantages over macroscopic reactors, such as reduced consumption of reagents, high surface-area-to-volume ratios, and improved control over mass and heat transfer. Organic reactions[4], [5] that involve highly reactive intermediates often exhibit greater selectivities and specificities in microreactors compared to conventional macroscopic synthesis. Many challenges remain, however, in the development of microreactors for 1) multistep syntheses in which the individual steps require a change in solvents, reagents, and conditions, as well as 2) parallel screening in which similar types of reactions are performed using different combinations of reagents. Significant efforts have been devoted to develop functioning modules to improve the performance of microreactors. For example, various valves[6], [7] have been demonstrated to isolate distinct regions and prevent cross-contamination from different reactions in a microchip. Elsewhere, different mixing modules[8], [9] have been utilized to overcome diffusion-limited mixing in the turbulence-free microfluidic environment. Also, functioning pumps[7], [10] that are capable of delivering and metering fluidic components have been successfully integrated with microchannels. With these functioning modules, it becomes feasible to handle complicated chemical and biological processes in microreactors in an automated fashion. In fact, integrated microreactors have been utilized for sequential syntheses of molecular imaging probes,[9] polymerase chain reaction,[11] protein crystallization,[12] and cell culture.