Unravelling respiratory microflows in silico and in vitro: novel paths for targeted pulmonary delivery in infants and young children
About the project
Fundamental research on respiratory transport phenomena, quantifying momentum and mass transfer in the lung depths, is overwhelmingly focused on adults. Yet, children are not just miniature adults; their distinct lung structures and heterogeneous ventilation patterns set them aside from their parents. In RespMicroFlows, we will break this cycle and unravel the complex microflows characterizing alveolar airflows in the developing pulmonary acini. Our discoveries will foster ground-breaking transport strategies to tackle two urgent clinical needs that burden infants and young children. The first challenge relates to radically enhancing the delivery and deposition of therapeutics using inhalation aerosols; the second involves targeting liquid bolus installations in deep airways for surfactant replacement therapy. By developing advanced in silico numerical simulations together with microfluidic in vitro platforms mimicking the pulmonary acinar environment, our efforts will not only deliver a gateway to reliably assess the outcomes of inhaling aerosols and predict deposition patterns in young populations, we will furthermore unravel the fundamentals of liquid bolus transport to achieve optimal surfactant delivery strategies in premature neonates. By recreating cellular alveolar environments that capture underlying physiological functions, our advanced acinus-on-chips will deliver both at true scale and in real time the first robust and reliable in vitro screening platforms of exogenous therapeutic materials in the context of inhaled aerosols and surfactant-laden installations. Combining advanced engineering-driven flow visualization solutions with strong foundations in transport phenomena, fluid dynamics and respiratory physiology, RespMicroFlows will pave the way to a new and unprecedented level in our understanding and quantitative mapping of respiratory flow phenomena and act as catalyst for novel targeted pulmonary drug delivery strategies in young children.
The ERC team
Prof. Josué Sznitman
Dr. Arbel Artzy-Schnirman
Mrs. Osnat Nixon
Former ERC team members
Dr. Prashant Das
Dr. Alessandro De-Rosis
Dr. Rami Fishler
Dr. Hagit Stauber
Dr. Alexander Shapiro
Ostrovski Y, Dorfman S, Mezhericher M, Kassinos SC, and Sznitman J. Targeted drug delivery to upper airways using a pulsed aerosol bolus and inhaled volume tracking method. Flow, Turbulence and Combustion, in press, 2018.
Bauer K, Nof E and Sznitman J. Revisiting high-frequency oscillatory ventilation in vitro and in silico in neonatal conductive airways. Clinical Biomechanics, in press.
Das P, Nof E, Amirav I, Kassinos SC, and Sznitman J. Targeting inhaled aerosol delivery to upper airways in children: insight from computational fluid dynamics. PLoS One 13: e0207711, 2018.
Tenenbaum-Katan J, Artzy-Schnirman A, Fishler R, Korin N, and Sznitman J. Biomimetics of the pulmonary environment in vitro: A microfluidics perspective. Biomicrofluidics 12: 042208, 2018.
Hofemeier P, Koshiyama K, Wada S and Sznitman J. One (sub-)acinus for all: Fate of inhaled aerosols in heterogeneous pulmonary acinar structures. European Journal of Pharmaceutical Sciences 113: 53-63, 2018.
Fishler R, Verhoeven F, de Kruijf W and Sznitman J. Particle sizing of pharmaceutical aerosols via direct imaging of particle settling velocities. European Journal of Pharmaceutical Sciences, 113: 152-158, 2018.
Shachar-Berman L, Ostrovski Y, Kassinos SC and Sznitman J. Transport of ellipsoid fibers in oscillatory shear flows: implications for aerosol deposition in deep airways. European Journal of Pharmaceutical Sciences, 113: 145-151, 2018.
Stauber H, Waisman D, Korin N and Sznitman J. Red blood cell (RBC) suspensions in confined microflows: Pressure-flow relationship. Medical Engineering & Physics 48: 49-54, 2017.
Fishler R, Sznitman J. Novel aerodynamic sizing method using image-based analysis of settling velocities. Inhalation 11: 21-25, 2017.
Stauber H, Waisman D, Korin N and Sznitman J. Red blood cell dynamics in microfluidic networks of pulmonary alveolar capillaries, Biomicrofluidics 11: 014103, 2017.
Fishler R, Ostrovski Y, Lu C-Y, and Sznitman J. Streamline crossing: an essential mechanism for aerosol dispersion in the pulmonary acinus, Journal of Biomechanics, 50: 222-227, 2017 .
Hofemeier P and Sznitman J. The role of anisotropic expansion for pulmonary acinar deposition. Journal of Biomechanics 49: 3543-3548, 2016.
Ostrovski Y, Hofemeier P and Sznitman J. Augmenting Regional and Targeted Delivery in the Pulmonary Acinus using Magnetic Particles, International Journal of Nanomedicine 11: 3385-3395, 2016.
Fishler R, Sznitman J. Acini-on-Chip: Novel In Vitro Assessment of Particle Dynamics and Deposition in the Deep Lungs. RDD Europe 2017. Volume 1: 119-128, 2017.
Fishler R, and Sznitman J. Computer Vision-based Aerodynamic Particle Sizing: A Rapid Method for Real-time Characterization of Inhaled Aerosols. RDD Europe 2017. Volume 2: 305-308, 2017.
Invited Talks (PI)
Sznitman J. Biomimetic in vitro airway platforms for drug delivery assays and precision medicine. Keystone Symposia on Delivering Therapeutics across Biological Barriers, Dublin, Ireland, May 2019.
Sznitman J. Bioengineering strategies for targeted drug delivery in the lungs. Drug Delivery to the Lungs 2018, Edinburgh, UK, December 2018. Award Keynote
Sznitman J. Biomimetic lung-on-chips for physiological screening assays. Biobarriers 2018, Saarbruecken Germany, August 2018.
Sznitman J. Point targeting in the lungs using inhaled magnetic aerosols. 3rd Annual Inhalation & Respiratory Drug Delivery Congress, London UK, May 2018.
Sznitman J. Systemic drug delivery via the lungs: Can we do better? International Drug Discovery Science & Technology. Osaka, Japan, July 2017.
Sznitman J. Acini-on-Chip: Novel in vitro assessments of particle dynamics and deposition in the deep lungs. Respiratory Drug Delivery Europe 2017. Nice, France, April 2017 (Podium Presentation).
Sznitman J. Paradigms of targeted aerosol delivery in the deep lungs: lessons from in vitro and in silico studies. RMIT Enabling Capability Platforms Workshop on Inhaled Therapeutics for Treating Lung & Neurodegenerative Diseases. Melbourne, Australia, November 2016.
Sznitman J. Unraveling the fate of inhaled aerosols in the pulmonary depths in silico and in vitro. Workshop on Pulmonary Drug Delivery (COST Action 1404 “SimInhale”). Prague, Czech Republic, October 2016.
Das P, Eliram N, Amirav I, and Sznitman J. Evolution of respiratory flow phenomena with age and implications for inhalation aerosol targeting. World Congress of Biomechanics, Dublin, Ireland, July 2018
Belenkovich M, Alison B, Gutierrez M, Korin N, Eniola-Adefeso L, and Sznitman J. In vitro biomimetic blood microcirculatory assays for cardiovascular targeted drug carrier design. World Congress of Biomechanics, Dublin, Ireland, July 2018
Ostrovski Y and Sznitman J. Targeted delivery in upper airways using inhaled magnetic particles. European Aerosol Conference, Zurich, Switzerland, August 2017.
Shachar-Berman L, Ostrovski Y, De Rosis A, Koshiyama K, Wada S and Sznitman J. Exploring the fate of inhales non-spherical aerosol for systemic drug delivery. International Drug Discovery Science & Technology. Osaka, Japan, July 2017.
Ostrovski Y and Sznitman J. Point targeting in the lungs using inhaled magnetic aerosols. International Drug Discovery Science & Technology. Osaka, Japan, July 2017.
Fishler R and Sznitman J. Computer vision-based aerodynamic particle sizing: A rapid method for real-time characterization of inhaled aerosols. Respiratory Drug Delivery Europe 2017. Nice, France, April 2017 (Poster).
Bauer K and Sznitman J. Evolution from childhood to adulthood of respiratory flow behavior in bronchial airways. 14th International Symposium on Computer Methods in Biomechanics and Biomedical Engineering, 20-22 September 2016, Tel Aviv, Israel.
Ostrovski Y and Sznitman J. Targeted delivery in upper airways using inhaled magnetic particles, 14th International Symposium on Computer Methods in Biomechanics and Biomedical Engineering, 20-22 September 2016, Tel Aviv, Israel.
Shachar-Berman L, Ostrovski Y, Hofemeier P and Sznitman J. Transport and deposition of non-spherical aerosols in pulmonary acinar airways. 14th International Symposium on Computer Methods in Biomechanics and Biomedical Engineering, 20-22 September 2016, Tel Aviv, Israel.
Hofemeier P, Koshiyama K, Wada S and Sznitman J. Fate of inhaled aerosols in heterogeneous pulmonary acini, 14th International Symposium on Computer Methods in Biomechanics and Biomedical Engineering, 20-22 September 2016, Tel Aviv, Israel.
Stauber H, Waisman D, and Sznitman J. Characteristics of red blood cell perfusion in microfluidic models of pulmonary capillary networks. 5th International Conference on Micro and Nano Flows, Milano, Italy, 11-14 September 2016.
Fishler R and Sznitman J. Flow mixing and dispersion phenomena in lung-inspired microfluidics structures. 5th International Conference on Micro and Nano Flows, Milano, Italy, 11-14 September 2016.
Ostrovski Y and Sznitman J. Foam for pulmonary drug delivery. PCT/IL2017/051208. November 2017.
Ostrovski Y and Sznitman J. Targeted delivery of aerosols of magnetized active agents. PCT/IL2017/050472. April 2017.