Fluorinated liquid-enabled protein handling and surfactant-aided crystallization for fully in situ digital microfluidic MALDI-MS analysis

Digital microfluidics refers to a method for manipulating discrete droplets of very small amounts of liquid through the localized application of electric fields. Because droplet movement is driven entirely by electric fields, digital microfluidics can be completely automated, allowing complex or tedious liquid handling protocols to be performed with minimal manual effort. For this reason, digital microfluidics has been shown to be effective at enhancing various chemical and biological assays. In this work, we developed a digital microfluidic technique for automated sample preparation of proteins for analysis by matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS). While the use of mass spectrometry to study proteins is common throughout the biochemical sciences, the manual sample handling protocols for performing such analyses can be time consuming and tedious. By using fluorinated liquids and surfactants to facilitate the movement and crystallization of protein solutions on digital microfluidic devices, we show that this platform can be used to perform all the sample handling steps necessary to obtain high quality protein mass spectra in a completely automated manner, requiring minimal manual input. Ultimately, such automated microfluidic tools could be used to increase the throughput and reduce the cost of protein-based diagnostic or drug discovery research.