Abstract A10: Biomarker independant microfluidic Labyrinth for the high throughput enrichment and characterization of circulating tumor cells in pancreatic cancer

Abstract

Abstract Introduction and Objective: Pancreatic cancer is a devastating disease with a 5-year survival rate of less than 6%. By the time of diagnosis, less than 15% of patients have surgically resectable tumors, which is one reason why it has the highest mortality rate among all cancer types. Emerging evidence has pointed the importance of circulating tumor cells (CTCs) in the spread of cancers and metastasis. CTCs are believed to be the most promising cancer biomarkers available in blood. Recent reports also show that these cells could be a good surrogate biomarker for not only prognosis, but also for cancer detection and development of personalized treatment. We have developed an inertial microfluidic-based separation technique for high throughput and label-free isolation of CTCs. Methods: To investigate the isolation efficiency of our technology before running cancer patients’ samples, PANC-1 cells labeled with cell tracker dye were spiked into 1 mL of whole blood. Using this optimized platform we isolate CTCs from pancreatic cancer patients, followed by downstream analysis . CTCs are characterized using immunocytochemistry for heterogeneity studies among CTC population. Results: Our microfluidic device consists of a size based separation platform in which CTCs are separated from other blood components. This high throughput label free separation device was designed and developed by our lab. After more than 20 generations of device revision, an optimized flow rate of 2.5 ml/min for PANC-1 pancreatic cancer cell line has yielded a 95% recovery of these cells from whole blood, with cancer cells traveling to the second outlet and 80% of the White Blood Cells (WBC) to the first outlet. We have successfully isolated CTCs from over 100 pancreatic cancer patients. Among several patients we were able to characterize different subpopulations using the epithelial marker CK-19 and EpCAM, and the EMT-like marker ZEB1. Conclusion: The implementation of our engineering technology to the study of pancreatic cancer can present novel ways to confront major hurdles in cancer research, such as early detection and the lack of effective therapeutics. The isolation and expansion of CTCs, the heterogeneous population of cells that promote metastasis, can provide meaningful information to elucidate the process of pancreatic tumorigenesis to preempt its fatal result. Citation Format: Lianette Rivera-Baez, Eric Lin, Meghna Waghray, Shamileh Fouladdel, Ebrahim Azizi, Max Wicha, Vaibhav Sahai, Diane Simeone, Sunitha Nagrath.{Authors}. Biomarker independant microfluidic Labyrinth for the high throughput enrichment and characterization of circulating tumor cells in pancreatic cancer. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2016 May 12-15; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(24 Suppl):Abstract nr A10.