Abstract

Abstract Introduction and Objective: Circulating tumor cells (CTCs) have been identified in the art in peripheral blood from cancer patients and are likely the origin of metastatic disease. Isolation and capture of CTCs represent a potential alternative to invasive biopsies during diagnosis of disease. In the recent past, vVarious microfluidic- based CTC isolation technologieschips have been developed to capture, indentify, sort, and enumerate CTCs. but, they need to be more sensitive, reliable, and specific for CTC detection in early stage cancer patients. Here we present a microfluidic CTC-chip with functionalized nanomaterials to capture and culture CTCs. Methods: Micro-sized structuresposts functionalized with anti-epithelial-adhesion-molecule antibodies (Anti-EpCAM) are is the common approachstructures to capture CTCs. Here we present a microfluidic device with functionalized planar structure to capture CTCs. The CTC-chipmicrofluidic device has a PDMS chamber and patterned gold postatterns . functionalized with graphene oxides as nanomaterial and anti-epithelial-cell-adhesion-molecule antibodies (Anti-EpCAM). To investigate the capture efficiency before running cancer patients’ samples, a low number of cells were spiked into 1 mL of whole blood. We stained the captured cells with cytokeratin, CD45, and DAPI to identify CTCs. For clinical studies, we searched for CTCs in 10 pancreatic cancer patients, 6 breast cancer patients, 4 early lung cancer patients, and 5 healthy donors. Results: It is much easier to scan, count and grow captured cells in comparison with previous micro-sized post-based structure. CTCs were isolated by assembling Graphene oxide on the planar structures for enhanced sensitivity. is easy to functionalize the surface and sensitive to detect biomaterial. The functionalized graphene oxide has been used to selectively capture MCF-7 breast cancer cells with a capture rate higher than 8790 %. This new CTC-chip identified CTCs in the peripheral blood of patients with pancreatic, breast, and lung cancer in 20 of 20 samples (100%). Conclusion: We present a sensitive CTC-chip using graphene oxides as nanomaterial to isolate, capture, identify, and characterize extremely rare CTCs. This CTC-chipIt is much easier to scan, count, and grow captured cells in comparison with previous micro-sized post-based structure. We believe this CTC-chip offers great potential for clinical research on cancer. Citation Format: Hyeun Joong Yoon, Tae Hyun Kim, Zhuo Zhang, Nithya Ramnath, Max S. Wicha, Daniel F. Hayes, Diane M. Simeone, Sunitha Nagrath. Integrated micro nanotechnology for the sensitive isolation of circulating tumor cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5109. doi:10.1158/1538-7445.AM2013-5109

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