Microfluidic Research Tool to
regulate mechanical forces and properties in Branching Morphogenesis
Princeton Docket #
13-2864-1
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