Pancreatic cancer is the fourth most common cause of cancer related death in the United States, with a five year survival rate of only 4%. We have recently shown that circulating pancreatic cells (CPCs) can be detected in the blood at the onset of the disease cycle in both mice and humans. These findings present an opportunity to develop a non-invasive diagnostic for pancreatic cancer that has enormous potential to improve patient outcomes. The current gold-standard for circulating tumor cell (CTC) detection fails to measure the extremely sparse and heterogeneous CPCs. Even next generation microfluidic technologies, which do not rely on epithelial markers, have limited utility due to the inherently low-throughput of microfluidics and the large sample volumes of blood (V > 10 mL) necessary for ultra-rare cell detection. To address these challenges, we are developing a new approach to rare cell detection, using magnetic micropores, which combines the benefits of micro-scale sorting with extremely fast flow rates (100x faster than typical microfluidic approaches2,5-7). In addition to its improved throughput, our technique is robust against unprocessed clinical samples, allowing rare CPCs and CPC clusters to be isolated directly from whole blood. Moreover, we are integrating this approach with ultra-rapid on-chip RNA fluorescence in-situ hybridization (RNA FISH), enabling single molecule, multiplexed RNA analysis in individual rare cells. Our device, which combines the above features into a self-contained, automated format, is designed to extract the RNA expression of single CPCs in clinical settings.
Cells are known to shed from the pancreas into the blood stream, carrying with them the molecular signatures of pancreatic cancer. We propose an innovative, clinically practical approach to probe the RNA contained within these rare cells to better understand the disease's development and spread. Our rapid and easily multiplexed platform has great potential for non-invasive monitoring of both disease progression and drug efficacy, and offers tremendous benefits for patients.
|Ko, Jina; Bhagwat, Neha; Yee, Stephanie S et al. (2017) A magnetic micropore chip for rapid (<1 hour) unbiased circulating tumor cell isolation and in situ RNA analysis. Lab Chip 17:3086-3096|
|Ko, Jina; Yelleswarapu, Venkata; Singh, Anup et al. (2016) Magnetic Nickel iron Electroformed Trap (MagNET): a master/replica fabrication strategy for ultra-high throughput (>100 mL h(-1)) immunomagnetic sorting. Lab Chip 16:3049-57|