Atmospheric Pressure Mass Spectrometry of Single Viruses and Nanoparticles by Nanoelectromechanical Systems

Mass spectrometry of intact nanoparticles and viruses can serve as a potent characterization tool for material science and biophysics. Inaccessible by widespread commercial techniques, the mass of single nanoparticles and viruses (>10MDa) can be readily measured by NEMS (Nanoelectromechanical Systems) based Mass Spectrometry, where charged and isolated analyte particles are generated by Electrospray Ionization (ESI) in air and transported onto the NEMS resonator for capture and detection. However, the applicability of NEMS as a practical solution is hindered by their miniscule surface area, which results in poor limit-of-detection and low capture efficiency values. Another hindrance is the necessity to house the NEMS inside complex vacuum systems, which is required in part to focus analytes towards the miniscule detection surface of the NEMS. Here, we overcome both limitations by integrating an ion lens onto the NEMS chip. The ion lens is composed of a polymer layer, which charges up by receiving part of the ions incoming from the ESI tip and consequently starts to focus the analytes towards an open window aligned with the active area of the NEMS electrostatically. With this integrated system, we have detected the mass of gold and polystyrene nanoparticles under ambient conditions and with two orders-of-magnitude improvement in capture efficiency compared to the state-of-the-art. We then applied this technology to obtain the mass spectrum of SARS-CoV-2 and BoHV-1 virions. With the increase in analytical throughput, the simplicity of the overall setup and the operation capability under ambient conditions, the technique demonstrates that NEMS Mass Spectrometry can be deployed for mass detection of engineered nanoparticles and biological samples efficiently.Comment: 38 pages, 6 figure

Efficient sensing of single viruses and nanoparticles by nanomechanical sensors integrated with ion lenses

Nanoelectromechanical Systems (NEMS) resonators can be used to detect, weigh and identify single nanoparticles and viruses. Given their small footprint, however, NEMS are plagued by low analyte detection rate since the active sensing cross-sections to capture analyte particles is very small. Here we report on the development of an on-chip focusing lens operating in air and integrated with the NEMS sensor. The integrated system increases the capture efficiency by orders of magnitude, and allows for operation under ambient conditions to measure the mass of nanoparticles and virions. With this system, mass spectrum of nanoparticle samples and mammalian viruses at biologically relevant concentrations can be characterized within less than 30 minutes

Atmospheric pressure mass spectrometry of single viruses and nanoparticles by nanoelectromechanical systems

Mass spectrometry of intact nanoparticles and viruses can serve as a potent characterization tool for material science and biophysics. Inaccessible by widespread commercial techniques, the mass of single nanoparticles and viruses (>10MDa) can be readily measured by nanoelectromechanical systems (NEMS)-based mass spectrometry, where charged and isolated analyte particles are generated by electrospray ionization (ESI) in air and transported onto the NEMS resonator for capture and detection. However, the applicability of NEMS as a practical solution is hindered by their miniscule surface area, which results in poor limit-of-detection and low capture efficiency values. Another hindrance is the necessity to house the NEMS inside complex vacuum systems, which is required in part to focus analytes toward the miniscule detection surface of the NEMS. Here, we overcome both limitations by integrating an ion lens onto the NEMS chip. The ion lens is composed of a polymer layer, which charges up by receiving part of the ions incoming from the ESI tip and consequently starts to focus the analytes toward an open window aligned with the active area of the NEMS electrostatically. With this integrated system, we have detected the mass of gold and polystyrene nanoparticles under ambient conditions and with two orders-of-magnitude improvement in capture efficiency compared to the state-of-the-art. We then applied this technology to obtain the mass spectrum of SARS-CoV-2 and BoHV-1 virions. With the increase in analytical throughput, the simplicity of the overall setup, and the operation capability under ambient conditions, the technique demonstrates that NEMS mass spectrometry can be deployed for mass detection of engineered nanoparticles and biological samples efficiently

Dielectric Detection of Single Nanoparticles Using a Microwave Resonator Integrated with a Nanopore

The characterization of individual nanoparticles in a liquid constitutes a critical challenge for the environmental, material, and biological sciences. To detect nanoparticles, electronic approaches are especially desirable owing to their compactness and lower costs. While electronic detection in the form of resistive-pulse sensing has enabled the acquisition of geometric properties of various analytes, impedimetric measurements to obtain dielectric signatures of nanoparticles have scarcely been reported. To explore this orthogonal sensing modality, we developed an impedimetric sensor based on a microwave resonator with a nanoscale sensing gap surrounding a nanopore built on a 220 nm silicon nitride membrane. The microwave resonator has a coplanar waveguide configuration with a resonance frequency of approximately 6.6 GHz. The approach of single nanoparticles near the sensing region and their translocation through the nanopores induced sudden changes in the impedance of the structure. The impedance changes, in turn, were picked up by the phase response of the microwave resonator. We worked with 100 and 50 nm polystyrene nanoparticles to observe single-particle events. Our current implementation was limited by the nonuniform electric field at the sensing region. This work provides a complementary sensing modality for nanoparticle characterization, where the dielectric response, rather than ionic current, determines the signal