Vibrating Sharp-edge Spray Ionization (VSSI) for voltage-free direct analysis of samples using mass spectrometry.

Rationale: The development of miniaturized and field portable mass spectrometers could not succeed without a simple, compact, and robust ionization source. Here we present a voltage-free ionization method, Vibrating Sharp-edge Spray Ionization (VSSI), which can generate a spray of liquid samples using only one standard microscope glass slide to which a piezoelectric transducer is attached. Compared with existing ambient ionization methods, VSSI eliminates the need for a high electric field (~5000 V·cm ) for spray generation, while sharing a similar level of simplicity and flexibility with the simplest direct ionization techniques currently available such as paper spray ionization (PSI) and other solid substrate-based electrospray ionization methods.

Methods: The VSSI device was fabricated by attaching a piezoelectric transducer onto a standard glass microscope slide using epoxy glue. Liquid sample was aerosolized by either placing a droplet onto the vibrating edge of the glass slide or touching a wet surface with the glass edge. Mass spectrometric detection was achieved by placing the VSSI device 0.5-1 cm from the inlet of the mass spectrometer (Q-Exactive, ThermoScientific).

Results: VSSI is demonstrated to ionize a diverse array of chemical species, including small organic molecules, carbohydrates, peptides, proteins, and nucleic acids. Preliminary sensitivity experiments show that high-quality mass spectra of acetaminophen can be obtained by consuming 100 femtomoles of the target. The dual spray of VSSI was also demonstrated by performing in-droplet denaturation of ubiquitin. Finally, due to the voltage-free nature and the direct-contact working mode of VSSI, it has been successfully applied for the detection of chemicals directly from human fingertips.

Conclusions: Overall, we report a compact ionization method based on vibrating sharp-edges. The simplicity and voltage-free nature of VSSI make it an attractive option for field portable applications or analyzing biological samples that are sensitive to high voltage or difficult to access by conventional ionization methods.