Periodic Reporting for period 4 - BuBble Gun (Penetrating microjets in soft substrates: towards controlled needle-free injections)
Periodo di rendicontazione: 2024-07-01 al 2025-06-30
The needle-free delivery of liquid jets into soft and heterogeneous substrates, e.g. human tissue, is hindered by the need to reach specific penetration depths with energy efficient means, the break-up of jets that impedes control over liquid splash-back after impacting the substrate that cause cross-contamination between injections, and the dose delivery. These issues are faced by many applications, particularly the delivery of drugs or cosmetic products.
The main objective of this project was to achieve a fundamental understanding of liquid jets injection on soft substrates. We have generated new knowledge in the fields of microfluidics, physics, and bioengineering. These, combined, have started to open new ways to improve injection phenomena, e.g. in the delivery of drugs, dermatologic applications and other industries. This project has studied the energy partition between the input laser energy, creation of bubbles, the formation of liquid jets, and the penetration of these jets into soft substrates. We have found new ways to control cavitation within microfluidic confinement, tune the rheology of jets emerging from confined cavitation. As a result, we have unveiled new relationships between fluid dynamics and material properties governing jet injection into soft substrates. The original ambition to probe the rheological properties of jets made of biocompatible additives has been more difficult to materialize. However, the results are promising and have helped to clarify the path forward.
To conclude, this project has been a success in several aspects, covering the fundamental research, application of findings to solve societal relevant problems, and in the training of young researchers. Currently, FlowBeams, a spin-off company from the University of Twente is taking further steps in developing a portable energy-efficient injection platform that could help quantifying injections with experimental resolutions below the microsecond and micrometer scales.
The main objective of this project was to achieve a fundamental understanding of liquid jets injection on soft substrates. We have generated new knowledge in the fields of microfluidics, physics, and bioengineering. These, combined, have started to open new ways to improve injection phenomena, e.g. in the delivery of drugs, dermatologic applications and other industries. This project has studied the energy partition between the input laser energy, creation of bubbles, the formation of liquid jets, and the penetration of these jets into soft substrates. We have found new ways to control cavitation within microfluidic confinement, tune the rheology of jets emerging from confined cavitation. As a result, we have unveiled new relationships between fluid dynamics and material properties governing jet injection into soft substrates. The original ambition to probe the rheological properties of jets made of biocompatible additives has been more difficult to materialize. However, the results are promising and have helped to clarify the path forward.
To conclude, this project has been a success in several aspects, covering the fundamental research, application of findings to solve societal relevant problems, and in the training of young researchers. Currently, FlowBeams, a spin-off company from the University of Twente is taking further steps in developing a portable energy-efficient injection platform that could help quantifying injections with experimental resolutions below the microsecond and micrometer scales.
The three work packages (WP) were led by the PI, and by motivated and independent researchers with complimentary experiences and skills. In WP1 we have characterized different laser (light sources) equipment to understand the differences of using additives for improved energy absorption that lead to bubble formation (cavitation, boiling). In WP2 the focus was on understanding how to predict the break-up or fragmentation of fast traveling liquid jets generated by the bubble growing inside the microfluidic channels studied in WP1. Finally, WP3 has covered the impact and penetration of the liquid jets onto different materials with increased complexity level: droplets of liquids with known physicochemical properties, gelatins (translucent and fair reproducibility of preparation), ex vivo skin samples (animal and human). All combined, the team has published 16 peer-reviewed publications (including a highly cited review, a series of original articles, and a book used in education), 5 Conference proceedings and several Outreach activities including interviews and articles in global news outlets. At least 4 manuscripts are being prepared for publication. We have also applied for Intellectual Property protection (patent) on three ideas. Besides a Dutch Research Council (NWO) Vidi grant, the PI has secured three Proof of Concepts and a succesful EIC Transition grant for the academic startup/spin-off company FlowBeams.
As evidenced in our several publications we opened a new area at the intersection of engineering, physics, chemistry, and biomedical applications. The ultrafast generation of droplets with accurate control is a feat. With the modeling and characterization experiments , we can convincingly say that we have advanced the state-of-the-art in microfluidics generation of fast liquid jets for needle-free injections. There has been scientific breakthrough mostly in utilizing laser-induced cavitation to explore novel mass transfer phenomena, bringing ‘inertial’ phenomena at the microscale, which is notoriously difficult. The advancement of biomedical engineering field has just begun. I expect the impact will only increase after the work published (and in preparation) is picked up by the scientific community. Moreover, industrial partners will be able to incorporate our findings in their own processes.