We have developed a new analytical method and associated instrumentation, protected by two registered patents, that combines nanomechanical resonators with a novel dip-in approach to measure the physical properties of nanoparticles directly in liquid suspensions without significant sample loss. By applying controlled acoustic vibrations (acoustofluidics), we regulated how individual nanoparticles attach and detach from the resonator surface, allowing us to track tiny shifts in vibration frequency that reveal particle mass with exceptional precision. In proof-of-concept experiments, we have demonstrated that gold nanoparticles in nanoliter volume suspensions can be characterized at a rate of ~38 particles per minute and with a resolution down to 0.1 attograms (one hundred billionth of a nanogram), without any significant loss of analytes. This result shows that our dip-in approach uniquely combines the high resolution of nanomechanical sensors with high throughput and minimal waste, overcoming a major limitation of existing methods. We have showed for the first time that it is possible to analyse single viral sized particles one by one, with the precision of a laboratory instrument but at the speed and efficiency required for real world applications. We have also designed and fabricated early prototypes of the open fluidic and nanomechanical sensing system, and successfully demonstrated that single gold nanoparticles in the same mass range as viral vectors can be detected and characterized. We have advanced the technology from TRL2 to TRL4 as the prototype has been tested with actual viral particles and obtained positive results. We have identified the most critical bottlenecks to further advance the technology to be able to address real samples, beyond controlled laboratory samples. We have tested several ionic liquids and identified challenges in the preservation of virus infectivity in these samples, concluding that ILs designed specifically to preserve the original infectivity of the viral particles are needed and we have already stablished the necessary collaborations to reach this goal. Furthermore, we have identified new applications in the field of medicine and drug development that we had not originally envisioned. Through interviews and meetings with relevant stakeholders in advanced therapies, we conclude that application of the technology for quality control of viral vectors used in gene therapies has also large potential impact. We have started the route for the exploitation of the results towards this identified niche application.
