Sessile Droplet Microfluidic Platforms for Improvements in Mass Spectrometry Sample Preparation

Abstract

Sessile droplet microfluidic devices (SDMF) allow for small, uniform liquid volumes to be arrayed, addressed, and manipulated independently. SDMF platforms diverge from typical flow-based lab-on-a-chip (LOC) devices while maintaining their advantages (low sample consumption, high throughput, and easy automation and portability). Previous work by Bachus et al. has shown that SDMF arrays can be made rapidly and reproducibly by applying a hydrophobic coating to a glass surface, then milling surface energy traps (SETs) into the surface using picosecond laser micromachining. Resulting SETs serve as anchor points to hold liquid droplets and can be filled spontaneously by discontinuous dewetting (DDW). By modifying the SET shape, evaporation dynamics of droplets can be controlled so that solute particles inside droplets are confined to a certain location, thus achieving droplet preconcentration with no further steps. The means to preconcentrate sessile droplets on open surfaces serves as an attractive option to improve the sample preparation and detection sensitivity for various mass spectrometry-based analytical techniques. Preliminary results show a significant increase (18-fold) in colourimetric detection sensitivity of cadmium-dye complexed droplets on SETs. SET designs were then modified to improve suitability of the platform for analysis in matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS). Microscopy and MALDI imaging mass spectrometry (IMS) were used to assess analyte localization and matrix application methods. MALDI sample spot reduction using evaporative preconcentration was shown to increase detection sensitivities two-fold. Finally, arrays of miniaturized SETs (“microspots”) were explored as an open surface platform for single cell isolation and analysis. Using silica particle suspensions, microspot fabrication was optimized for single particle occupancy and average particles per microspot.