Interfacing Microfluidics and Laser Desorption/Ionization Mass Spectrometry by Continuous Deposition for Application in Single Cell Analysis

We present a simple method for continuous deposition of effluent originating from a microfluidic device on a flat metal surface for subsequent analysis by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS). The sample is delivered using a microscale fused silica capillary and passed onto the surface of a stainless steel plate coated with a layer of a standard matrix. The key parameters optimized in order to obtain high quality and reproducible sample traces are: i) sample flow rate, ii) speed of the XY-stage movement, and iii) distance of the capillary tip from the plate. Tapering the capillary end as well as surface functionalization to induce hydrophobicity were shown to further enhance the deposition process. The described continuous deposition method is compared with a previously published mass spectrometric method utilizing a piezoelectric microdispenser for microspotting onto the MALDI plates which enabled detection of primary metabolites at the single cell level. Research is underway to adapt the continuous deposition as an interface for single cell metabolite detection and enhancement of quantitative abilities of the MALDI methodology. We envisage that the presented continuous deposition method may also be suitable for sensitive detection of analytes using other surface analysis tools.