Harvesting and concentrating epithelial cells from body fluids is a challenging (expensive and time-consuming) but important task required for translational advances in the early-detection and treatment of cancer, since many cancer types involve epithelial cells. As an example, a highly promising and accurate risk detection method for breast cancer, based on changes in the DNA of breast epithelial cells found in human milk, requires purification and concentration of these cells, and exclusion of lymphocytes, fats, and proteins that are prevalent in milk. Because the necessary immediate epithelial enrichment process is costly in terms of labor, instrumentation, and lab supplies (antibody-coated beads), alternate methods of epithelial cell collection and concentration are needed. The proposed program will develop surfaces capable of selectively adhering epithelial cells from milk and rejecting the undesired cell fractions and molecules. The potential impact of this separation scheme comes from the innovative features of the surfaces themselves: robust and economical nano-scale adhesive elements such as polymer coils and immobilized nanoparticles are employed instead of expensive and fragile biomolecular fragments and antibodies. These sophisticated surfaces could be deployed in highly sensitive microfluidic devices or on beads, which could be used in the field by individuals who lack highly specialized training. The screening methods made possible by these innovative surfaces are expected to have wide accessibility and therefore broad positive impact for early detection of breast cancer. At the same time the surface design strategies developed in this program could, with minor modification, be applied to the creation of additional surfaces targeting cancer and pre-cancerous cell changes in other epithelial tissues, collected from urine, saliva, and mucus.
This proposal will develop novel surfaces that selectively adhere epithelial cells from suspensions and human breast milk, to enable their subsequent analysis for molecular indicators of breast cancer or cancer risk. The surfaces are innovative because they will achieve selective binding of targeted cells using immobilized nano-scale adhesive elements rather than biomolecular fragments or antibodies. The surfaces developed in this proposal can be refined for other body fluids besides milk, and form the foundation for scaled-up portable cell enrichment technologies that increase the accessibility of early risk assessment to a broader population of women.
| Kalasin, S; Browne, E P; Arcaro, K F et al. (2017) Selective Adhesive Cell Capture without Molecular Specificity: New Surfaces Exploiting Nanoscopic Polycationic Features as Discrete Adhesive Units. RSC Adv 7:13416-13425 |
| Fang, Bing; Jiang, Ying; Nüsslein, Klaus et al. (2015) Antimicrobial surfaces containing cationic nanoparticles: how immobilized, clustered, and protruding cationic charge presentation affects killing activity and kinetics. Colloids Surf B Biointerfaces 125:255-63 |
| Gon, S; Kumar, Kushi-Nidhi; Nusslein, Klaus et al. (2012) How Bacteria Adhere to Brushy PEG Surfaces: Clinging to Flaws and Compressing the Brush. Macromolecules 45:8373-8381 |
