Microfabricated PDMS Vessel Mimetics for Cancer Cell Culture

Studies evaluating potential chemotherapeutics and multi-drug resistance (MDR) in cancer cells have been established using in vitro two-dimensional (2D) culture and in vivo animal models. However, neither method accurately recapitulates human tissue or the course of tumorigenesis. Three-dimensional (3D) cell culture better simulates the in vivo environment for tumor growth, but is currently limited by insufficient mass transport of oxygen due to a lack of vasculature.

An interdisciplinary team from several NIH laboratories has recently developed microfabricated synthetic mimetics of vasculature to provide oxygen to 3D cultured tumors and other tissues. A second generation prototype with a six-well plate format has been recently developed, undergone preliminary characterization, and tested under a limited number of cell culture conditions. The bioreactor setup allows for multiple 6-well plates increasing experimental throughput – in particular, to enable multiple parallel culture conditions under controlled hypoxia – to expand the potential application of the system to a variety of problems, including drug screening studies.

A summer project will likely center on exploring the ability of the bioreactor to support 3D growth of various cell lines or clinical samples in 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, assisting with further characterization of the oxygen distribution and consumption in the system, 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 a 3D chemotaxis model and a microfluidic device for controlled surface functionalization.