Microfabricated PDMS Vessel Mimetics for Cancer Cell Culture
Studies evaluating potential chemotherapeutics and multi-drug resistance (MDR) in cancer cells have been limited by the inability of in vitro two-dimensional (2D) culture to accurately recapitulate human tissue or the course of tumorigenesis. Three-dimensional (3D) cell culture better simulates the in vivo environment for tumor growth, but mass transport of oxygen in systems without vasculature limits tissues to dimensions of a few hundred microns. For many 3D systems, this spatial limit effectively limits the duration of culture, as oxygenated cells on the tissue periphery proliferate and starve the cells on the interior.
An interdisciplinary team from several NIH laboratories has developed a bioreactor system that uses microfabricated synthetic mimetics of vasculature to deliver oxygen to 3D cultured tumors and other tissues. The bioreactor setup allows for multiple multiwell plates, enabling multiple parallel culture conditions under controlled normoxia or hypoxia with minimal instrumentation.
A summer project will likely center on exploring the role of hypoxia in drug resistance using the multiwell plate format. This evaluation will involve cell culture laboratory processes, as well as gene expression analyses and various imaging techniques, including confocal microscopy. Beyond this focus, the project can be expanded according to the student’s interests. Some possibilities include designing and micro-fabricating vasculature array patterns with different geometries to study the effects on cell growth, developing and characterizing biomolecular and imaging readouts, or refining the engineering design and operation of the bioreactor system.
The BESIP student working on this project should have a background and interest in cell culture and working with prototype bioinstrumentation. Working closely with the interdisciplinary team, the intern will gain valuable hands-on experience with multiple procedures and technologies including cancer cell and tissue culture, microfabrication, sensors, process automation, data acquisition, laser-cutting, and 3D-printing for rapid prototyping.
Gottesman lab: Ongoing projects in the laboratory are dedicated to ascertaining the clinical relevance of in vitro studies of drug resistance and elucidating other mechanisms of multidrug resistance in cancer cells. The lab has extensive experience in gene expression analysis, tissue culture, and in vitro drug screening.
Pohida group: Provides electrical, electronic, electro-optical, mechanical, computer, and software engineering expertise to NIH projects that require in-house technology development. Collaborations involve advanced signal transduction and data acquisition; real-time signal and image processing; control and monitoring systems (e.g., robotics and process automation); and rapid prototype development. Collaborations result in the design of first-of-a-kind biomedical/clinical research systems, instrumentation, and methodologies.
Morgan group: Expertise in and facilities for microfabrication and characterization of bioreactor components and finite element modeling of oxygen transport in bioreactor. Other collaborations include a number of devices aimed at controlling cellular environments in culture, including an in vitro fibrosis model and a project investigating the effects of vessel geometry on endothelial cell organization.
Intern Name: Aasim Hawa
Institution: Organoid Culture in Bioreactor With Three-Dimensional Spatial Control of Oxygen Delivery
Project Title: University of Rochester