Periodic Reporting for period 1 - VIR-Quantify (Nanowire device for single virus delivery and sensing in vacuum)
Okres sprawozdawczy: 2024-07-01 do 2025-12-31
Airborne viruses causing respiratory diseases represent a mayor global health threat, being viruses with RNA-genomes from animal reservoirs highly likely to cause public health emergencies in the future. VIR-Quantify aimed to provide proof of concept for a technology capable of highly sensitive, fast and untargeted airborne virus detection with infectivity assessment, providing a comparative advantage in the competitive landscape. VIR-Quantify builds upon an unprecedented application of NMS sensors to the field of airborne viral particles detection. VIR-Quantify proposes the use of ionic liquids to preserve the virus structure, together nanowire sensors that allow mass and stiffness measurements for identification and infectivity studies of the pathogens. The innovative solution lies in two fronts: 1) an unprecedented capability to measure with high throughput (30 particles/minute) the stiffness of intact viruses to infer their infectivity potential, not at reach to other techniques; 2) the capability to count and characterize all the viral particles present in the liquid sample without loss of bioanalytes during the measurements.
VIR-Quantify aimed to exploit this novel technology for on-site identification and quantification of airborne viral particles and validate the innovation potential of such technological tool for commercialization by developing a market entry strategy built upon IPR consolidation and spin-off set-up plans. This will lead to high-gain, disruptive outcomes in the form of unprecedented mechanistic understanding for detecting the quick spread of airborne viral particles with great socioeconomic benefits visible at three levels: (1) fueling industrial innovation and economic growth in a game-changing sector (preventive medicine); (2) reducing healthcare costs worldwide, thus enabling more resilient and efficient health systems; (3) improving human welfare.
VIR-Quantify aimed to exploit this novel technology for on-site identification and quantification of airborne viral particles and validate the innovation potential of such technological tool for commercialization by developing a market entry strategy built upon IPR consolidation and spin-off set-up plans. This will lead to high-gain, disruptive outcomes in the form of unprecedented mechanistic understanding for detecting the quick spread of airborne viral particles with great socioeconomic benefits visible at three levels: (1) fueling industrial innovation and economic growth in a game-changing sector (preventive medicine); (2) reducing healthcare costs worldwide, thus enabling more resilient and efficient health systems; (3) improving human welfare.
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.
The mass of nanoparticles has a critical influence on their phenomenology and functional performance, driving the need for measurement tools that combine high-throughput with high-resolution single-particle analysis. Mass characterization of large nanoparticle populations under such demands remains a persistent challenge, particularly for nanoparticles of higher mass, where state-of-the-art mass spectrometry encounters intrinsic constraints. We have developed a dip-in nanomechanical sensing approach for weighing nanoparticles in liquid suspensions.
Advancements beyond the state of the art of the developed technology include:
- Nanoparticle is transfered to nanowire resonator probes via iterative immersion in the suspension, requiring minimal suspension volume and resulting in negligible sample loss.
- Ionic liquids are introduced as suspension media; these liquids have negligible vapour pressure, enabling vacuum operation for optimizing mass resolution through single-mode resonance frequency tracking of the probes.
- Acoustofluidic actuation is implemented on the suspension to regulate nanoparticle adsorption/desorption on the probes, significantly enhancing the sensing rate.
- Measurements of 30 nm gold nanoparticles demonstrate accurate characterization of their mass distribution with a sensor resolution of 0.1 attogram, a sampling rate of 38 nanoparticles/minute, and a sample volume of a few nanoliters.
The concurrent advances in all these performance characteristics demonstrate the potential of dip-in nanomechanical probes for precise and fast characterization of individual nanoparticles over a wide mass range.
Advancements beyond the state of the art of the developed technology include:
- Nanoparticle is transfered to nanowire resonator probes via iterative immersion in the suspension, requiring minimal suspension volume and resulting in negligible sample loss.
- Ionic liquids are introduced as suspension media; these liquids have negligible vapour pressure, enabling vacuum operation for optimizing mass resolution through single-mode resonance frequency tracking of the probes.
- Acoustofluidic actuation is implemented on the suspension to regulate nanoparticle adsorption/desorption on the probes, significantly enhancing the sensing rate.
- Measurements of 30 nm gold nanoparticles demonstrate accurate characterization of their mass distribution with a sensor resolution of 0.1 attogram, a sampling rate of 38 nanoparticles/minute, and a sample volume of a few nanoliters.
The concurrent advances in all these performance characteristics demonstrate the potential of dip-in nanomechanical probes for precise and fast characterization of individual nanoparticles over a wide mass range.