(101b) New Strategies for Preconcentration, CE Injection, and Ionization for Mass Spectrometry-Coupled Microfluidic Bioanalyses

Mass spectrometry (MS) provides information-rich, label-free identification of biomolecules for comprehensive and high throughput biological analyses. Coupling microfluidics with MS enables new applications, novel workflows, and a reduction in required sample sizes. In particular, active microfluidic devices with integrated microvalves allow automated, multistep biochemical analyses to be performed using subnanoliter volumes of sample and reagents. We will show that integrated computer-controlled pneumatic microvalves enable bias-free and volume-tunable hydrodynamic injections for microchip electrophoresis. Applying a potential across a closed microvalve can also serve to rapidly enrich analytes prior to injection by the mechanism of concentration polarization. Enrichment factors of ~450 have been achieved using this approach. Integrated electrospray interface designs will also be described that enable the facile coupling of both segmented and continuous flow microfluidics with MS. These have achieved the lowest flow rates to date for integrated microchip emitters, enabling subattomole detection limits. Finally, we will describe progress in implementing the above described technologies to enable multidimensional separations, online reaction monitoring and single cell analyses.