This NSF award by the Chemical and Biological Separations program supports work by Professor Wei Shen to develop a novel platform to efficiently detach affinity-captured cells with minimal biochemical and biophysical perturbation. Cell separation is essential in many clinical practices and biomedical studies, ranging from disease diagnosis and prognosis to cell-based therapy and fundamental investigations of stem cell biology. Cell separation mediated by the affinity between a cell surface biomarker and a complementary ligand immobilized on a material is label-free and highly specific, and therefore is particularly attractive. However, this method has been limited by the difficulty in efficiently detaching captured cells in a viable and unperturbed state due to the multivalent nature of cell-material interactions. Although this limitation is not an issue for diagnostic and prognostic applications, it is a major challenge when rare, sensitive cells need to be isolated and recovered for use in an unperturbed and functional state, such as stem-cell-based therapy. To fully unleash the potential of label-free, affinity-based cell separation, new cell detachment methods must be developed. In this project, we will harness self-assembly of biopolymers to bring polyethylene glycol (PEG) to the material surface after cell capture, so that multivalent cell-substrate interactions can be disrupted for efficient release of affinity-captured cells due to the conformational energy of extended PEG chains. Successful completion of this project will lead to a novel cell detachment method that, together with label-free and highly specific affinity capture, will allow cell separation to be performed with unprecedented collective quality in terms of high specificity, high yield, and minimal perturbation on cells. This cell detachment platform can be readily adapted for affinity cell separation based on various cell surface biomarkers. The method is compatible with various formats of cell separation: either small-scale operation in microfluidic devices or large-scale affinity chromatography; either flat affinity substrates or bead-based affinity matrices.
This project will provide interdisciplinary training opportunities for graduate and undergraduate students. Such training opportunities are important for preparing a qualified workforce in the field of biomedical engineering, which is one of the major driving forces for the health care industries. Through this project, the PI will promote the research activities of undergraduate students, in particular underrepresented minority and women students, in her laboratory through various programs. The PI will participate in K-12 outreach activities to stimulate interest in biomolecular engineering, biomaterials engineering, and regenerative medicine among young students and inspire more students to pursue careers in these fields.