Microfluidic Platform for the Dynamic Regulation of Mechanical Forces on Embryonic Organs

Researchers at Princeton University, Department of Chemical & Biological Engineering, have developed a microfluidic research tool to solve previously unanswered questions in the study of branching morphogenesis.

Development of tubular branched organs such as the lung and kidney is dynamic, highly regulated, and dependent on mechanical forces, leading to an architecture that is critical for survival. Dysregulation during development of these organs leads to several clinical pathologies that give rise to an under-branched or hypoplastic state producing significant fetal mortality.  To date, the ability to interface with and dynamically control the mechanical forces on developing embryonic organs in small animals has not been attainable.

To address this challenge, a microfluidic device to culture and apply dynamically-controlled transmural pressures across mouse whole lung explants has been developed. The microdevice consists of two fluidic chambers, one in which the organ is cultured (pleural chamber) and a second chamber to access the airways of the lung (lumenal chamber). Lumenal and pleural pressures are dynamically regulated, enabling the culture and real-time imaging of branching morphogenesis over 60 hours. 

This microdevice platform has several key applications that can span a range of embryonic organs and animal species (common animal models, e.g. mice, rats, rabbits, etc.).   The microdevice can be used for in vitro culture of embryonic whole organ explants (e.g. lung, kidney, etc) under defined and dynamically-controlled static or dynamic pressures.  Additionally, this device also has the ability to act as a mechanical test platform to measure the mechanical properties (e.g. compliance) over gestation or over culture of the developing embryonic organ explants.  The final novelty lies in the fact that this system works with embryonic mouse organs ¿ the main experimental mammalian model ¿ thus leveraging the ability to understand mechanics in a system with well-established molecular and genetic tools available.  Using this microdevice to understand how mechanical variables influence branching morphogenesis in tubular fluid-filled organs will suggest potential therapeutic targets for the treatment of fetal pediatric pathologies, as well as elucidate microenvironmental cues needed to engineer these organs. Additionally this approach to control the mechanical environment can complement existing molecular and genetic tools to elucidate how the mechanical microenviroment feeds back to regulate lung development.

Publications:

J.P. Gleghorn, V.D. Varner, H.A. Stone, and C.M. Nelson, Lung Development on a Chip: Lumenal Fluid Flows Regulate Airway Architecture, Abstract, Biomedical Engineering Society Annual Meeting, October 24-17, 2012

The Inventors

Celeste M. Nelson is an Associate Professor in the departments of Chemical & Biological Engineering and Molecular Biology at Princeton University. Dr. Nelson¿s group works at the interface of cell biology, developmental biology, and engineering, developing tools to engineer organotypic culture models that mimic tissue development, enabling rigorous quantitative analysis and computational predictions of the dynamics of morphogenesis. Dr. Nelson's contributions to the fields of tissue mechanics and morphogenesis have been recognized by a number of awards, including a Burroughs Wellcome Fund Career Award at the Scientific Interface, a Packard Fellowship, a Sloan Fellowship, the MIT TR35, the Allan P. Colburn Award from the AIChE, and a Dreyfus Teacher-Scholar Award.

Jason Gleghorn is a Postdoctoral Associate in Dr. Nelson's group.

Intellectual Property & Development status

Patent protection is pending and a working prototype has been developed

Princeton is currently seeking commercial partners for the further development and commercialization of this opportunity.

Contact:

Laurie Tzodikov
Princeton University Office of Technology Licensing

(609) 258-7256 tzodikov@princeton.edu

Wenting Luo

Princeton University Office of Technology Licensing

(609) 258-5579 wluo@princeton.edu