Extracorporeal microchannel device to capture and eliminate circulating tumor cells from cancer patient’s blood.

Abstract

e14522 Background: Metastatic progression accounts for nearly 90% of cancer-related deaths and has been directly correlated with the presence of circulating tumor cells (CTCs) in numerous carcinomas including breast, lung, ovarian, colorectal, and head and neck cancers. The removal of CTCs from cancer patient’s blood is directly implicated with reduction of extravasation and disease invasiveness to secondary organs. Methods: We designed and printed 3 Dimensional (3D) microchannel devices using biocompatible polymer and packed it with anti-EpCAM (EpCAM) mediated glass-based (G) compositions (G-EpCAM). The computational fluid dynamic (CFD) analysis simulation was explored to optimize the hemodynamic effect of the G-EpCAM device for measuring the pressure and velocity difference for blood along the spiral flow microchannels. Red blood cell (RBC) hemolysis was estimated using G-EpCAM compositions packed in a device to determine optimal biocompatibility. We assessed cancer cell lines (breast cancer MCF7, lung cancer A549) interactions and capture with varying incubation time points, effect of anti-EpCAM concentrations, number of G-EpCAMs, and series of devices. We evaluated G-EpCAM-on-device’s CTC capture capability and biocompatibility using head and neck, colorectal, lung, and ductal breast cancer patient’s blood samples. All G-EpCAM captured CTCs were immuno-stained for cytokeratin 18 (CK18) expression and the optimal fluorescence acquisition intensity was quantified. Results: Extracorporeal G-EpCAM microchannel device was 3D printed and consisted of interlocking top lid and bottom base with inlet and outlet channels. The path length of the spiral device consisted of 20 microchannels with 6.0-feet length. Device accommodated 28 gm of non-hemolytic G-EpCAM compositions. CFD analysis showed 3.8 mm as the ideal channel diameter and 2mm as the superlative G-EpCAM diameter for maximal cells and CTC capture with minimal blood hemolysis (less than 1%) as compared to control. Series 1 and 2 device indicated 90% and 85% cell capture efficiency, respectively using G-EpCAM devices indicating highest interactions and efficiency with cells. Conversely, the first device in series captured the highest cells. In addition, the efficiency improved as the number of G-EpCAM compositions was increased. We accounted device to capture CTCs with specificity having G-EpCAM composition and observed no hemolysis and non-specific interactions with other blood cells like RBCs or leukocytes. Conclusions: Continuous CTC removal from cancer patient’s blood circulation using such device offers promising therapeutic utility in stemming aggressive metastatic invasion and progression for improving the overall survival of epithelial origin cancer patients. Clinical trial information: CTRI U1111/1192-3951.