This NSF award by the Chemical and Biological Separations program supports work by Professor Shashi Murthy to understand molecular-level phenomena at the surfaces of cells during separation processes in microfluidic devices. Microfluidic cell separation is one of many microscale approaches being investigated for the manipulation of cells for scientific, diagnostic, or therapeutic applications. The general principle behind the design of microfluidic cell separation systems is to selectively isolate one or more cell types from a heterogeneous suspension of several cell types. The development of microfluidic cell manipulation systems has, to date, followed an application- and technology-driven approach where knowledge of molecular-level phenomena is lacking. This proposal aims to address the existing need to understand molecular-level phenomena within the framework of an integrated research and education program. To accomplish this objective, experiments will be carried out to determine of receptor expression is increased or decreased under controlled conditions of cell flow through ligand-coated microchannels of progressively increasing geometric complexity. Based on the observed receptor response, a "fingerprint" of selected cell-ligand will be created and utilized to identify unknown cell types in heterogeneous suspensions. The Intellectual Merit of this project lies in providing a new method of identifying cells that does not rely on a priori knowledge of cell type, surface receptor type, or fluorescence staining. This method will be valuable in identifying as-yet unknown and rare stem and progenitor cell populations that are resident in certain types of tissue, such as cardiac, skin, gastrointestinal or hepatic tissue. Such identification will have significant implications in stem cell-based tissue engineering, where the ability of stem and progenitor cells to differentiate into functional cells is crucial. The Broader Impacts of this project emerge from an educational component that will utilize the PI's existing relationships with two predominantly-minority high schools to promote bioengineering by giving presentations at the schools and taking students on field trips to laboratories at Northeastern University, Massachusetts General Hospital, and Massachusetts Eye and Ear Infirmary; engages high school teachers and students, as well as undergraduates, in experimental research.
Cells are currently used to produce vaccines as well as complex proteins that are the active ingredient of many pharmaceutical drugs. Increasingly cells are also starting to play a direct role in the treatment of diseases via transplantation. Bone marrow transplantation, for instance, is a well-known treatment procedure for cancer and other diseases. Therapies based on transplantation of stem cells and other cell types are being developed and are expected to play a broader role in the near future. These advances bring with them the need for robust methods of purifying cells, and, in turn, methods of characterizing the impact of purification methods on the cell types of interest. This project examined how fluidic shear forces, which are involved in every kind of cell purification process, impact cells. The intellectual merit of this project lies in the finding that even short levels of shear exposure can cause detactable changes within and on the surfaces of multiple cell types. The broader impact of this project comprises the generation of two doctoral theses, participation of 8 undergraduate students, and outreach activities that introduced science and engineering to 121 ninth graders. A substantial proportion of these individuals were women and members of underrepresented minorities.
