Acoustic-based methods have demonstrated broad range of applications for bioanalytical applications, including cell/extra cellular vesicle separation, cell patterning, sample enrichment, and fluid mixing/pumping. In recent years, our group explored the phenomenon induced by the interaction of vibrating sharp-edges with fluids, and developed unique techniques for mass spectrometry and digital biosensing applications. First, we developed a unique ionization method, Vibrating Sharp-edge Spray Ionization (VSSI), which consists only of a microscope glass slide and a piezoelectric transducer. The simplicity, versatility, and high efficiency make the VSSI technique easily adaptable for various mass spectrometry applications, including direct surface analysis, negative ion mode native mass spectrometry, LC-MS, and CE-MS. Second, we developed a high performance and portable monodisperse droplet generator based on a vibrating sharp-tip capillary, which enables a high dynamic range digital PCR assay. The system is readily portable and can be driven by a battery powered low-cost signal generator. On top of the small system footprint and portability is the superior droplet generation performance. In a single experiment run, droplet with a wide size range (6.77-661 μm, 163 fL-151 nL) can be generated with a throughput up to 5000 droplets/s and good monodispersity. The utility of the present system was demonstrated by performing multi-volume digital PCR, which achieved absolute nucleic acid quantification with a dynamic range spanning ~6 orders of magnitude.

Developing vibrating sharp-edge techniques for mass spectrometry and digital biosensing

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