Interfacing Digital Microfluidics with Ambient Mass Spectrometry Using SU-8 as Dielectric Layer

This work describes the interfacing of electrowetting-on-dielectric based digital microfluidic (DMF) sample preparation devices with ambient mass spectrometry (MS) via desorption atmospheric pressure photoionization (DAPPI). The DMF droplet manipulation technique was adopted to facilitate drug distribution and metabolism assays in droplet scale, while ambient mass spectrometry (MS) was exploited for the analysis of dried samples directly on the surface of the DMF device. Although ambient MS is well-established for bio- and forensic analyses directly on surfaces, its interfacing with DMF is scarce and requires careful optimization of the surface-sensitive processes, such as sample precipitation and the subsequent desorption/ionization. These technical challenges were addressed and resolved in this study by making use of the high mechanical, thermal, and chemical stability of SU-8. In our assay design, SU-8 served as the dielectric layer for DMF as well as the substrate material for DAPPI-MS. The feasibility of SU-8 based DMF devices for DAPPI-MS was demonstrated in the analysis of selected pharmaceuticals following on-chip liquid-liquid extraction or an enzymatic dealkylation reaction. The lower limits of detection were in the range of 1⁻10 pmol per droplet (0.25⁻1.0 µg/mL) for all pharmaceuticals tested.