Events
Tuesday, May 20, 2008
Department of Biomedical Engineering Final Oral Examination
MICROENVIRONMENTAL CONTROL IN MICROFLUIDIC BIOREACTORS FOR LONG TERM CULTURE OF BONE MARROW CELLS
Geeta Mehta
Co-Chairs: Shuichi Takayama and Jennifer Linderman
Tuesday, May 20, 2008,
9:30 AM - 11:30 AM
1180 Duderstadt Center Conference
The goal of this research is to create in vitro microenvironments for long term culture of hematopoeitic stem cell (HSC) in microfluidic bioreactors. In vivo, HSCs reside in the bone marrow osteoblastic and vascular niches in adult mammals. Some of the defining features of their in vivo niche are: small number of HSCs, heterogeneous population of bone marrow cells that support HSCs, and low oxygen tension. In vivo studies with HSCs are often tedious and time consuming, while the conventional in vitro cultures do not capture the microenvironments found in vivo. We are using microfluidic tools to study and re-create the microenvironmental HSC niches in vitro. We engineer niche elements in microfluidic bioreactors by: modulation of oxygen tension in the microbioreactors, optimal attachment and growth of HSC supporting bone marrow stromal cells, and also by culturing small numbers of HSCs in their physiologically relevant ratios between HSCs and supporting cells.
By using a combination of a mathematical model and quantitative experiments, we have created a design tool to manipulate and control oxygen tension for cell culture inside the poly(dimethyl siloxane) (PDMS) microbioreactors. Dissolved oxygen concentrations in the microbioreactor are quantified in real time using fluorescence lifetime imaging of an oxygen sensitive dye. Experimental results are consistent with the mathematical model1 and give insight into the conditions under which the devices must be operated to get desired oxygen tension in cell culture regions of the microbioreactor.
We also have used microfluidic perfusion systems to develop nanocoatings made from electrostatic self assembly of PDDA (poly(diallyldimethyl ammonium chloride)), clay, type IV collagen and fibronectin to optimize attachment of primary murine bone marrow cells (support cells for HSCs) onto PDMS bioreactors. Assays for cell attachment, spreading, proliferation and cell viability were performed at regular intervals during fifteen days of culture. PDDA topped coatings were found to be cytotoxic, while coatings with two or more bilayers of proteins collagen and fibronectin were found to have highest spreading, proliferation, and viability compared to other surfaces.
Additionally, 3-D co-culture of hematopoeitic cells with supporting cells in PDMS bioreactors were undertaken to create on-chip model for erythropoiesis, to optimize the ratio of support cells to HSCs for maximum number of colony formation and also to test efficacy of our in vitro artificial HSC niches. Thus, by the combination of hypoxia (which simulates in vivo bone marrow oxygen tension), biofunctional surfaces, and 3-D co-cultures, we are moving towards a microfluidic HSC niche, in which hypothesis-driven studies about crosstalk between HSCs and stromal cells can be carried out.
Sunday, June 15, 2008
Satellite event to the 2008 Neural Interfaces Conference
Summit Meeting on Chronic Microscale Neural Interfaces: Towards Standards and Benchmarks for an R&D Roadmap
Organizers: Daryl Kipke (dkipke@umich.edu), Director & William Shain (shain@wadsworth.org), Assoc. Director , Center for Neural Communication Technology
Sunday, June 15, 2008,
12:30 – 5:00pm
Cleveland InterContinental Hotel and Conference Center
The 2008 CNCT Summit Meeting will center on broad-based, directed discussions of the design and analysis of chronic microscale neural interface technologies for recording and stimulation and neurochemical sensing and delivery. The goals of this meeting are to (1) build an organizational framework for the formation of an open-source, collaborative knowledge-base of neural interface technologies and (2) begin directed discussions of developing design and performance guidelines of various types of microscale devices. Relevant technical areas include microelectrode technologies, materials, surgical techniques, embedded electronics and related components and subsystems. This meeting is part of the kick off an emerging “Neural Interface Technologies Initiative” organized by the CNCT that will provide an ongoing, international collaborative community forum for neural interface design, analysis, and advancement.
Engineers, neuroscientists, and physicians are invited. Early stage researchers, post-docs, and students are expressly encouraged to participate. This will be an excellent opportunity to network and get engaged in the neural interface community.
Please register here by June 1, 2008. Registration is free.
For more and updated information, please go here.