Poly(ethylene glycol)-Modified Tapered-Slit Membrane Filter for Efficient Release of Captured Viable Circulating Tumor Cells

Abstract

The grafting of poly(ethylene glycol) (PEG) onto an SU8 microfilter has been demonstrated for efficient capture and release of circulating tumor cells (CTCs). Previous CTC filters showed low cell release efficiency due to hydrophobic surfaces, even though their capture efficiency was considerable. PEG, a hydrophilic polymeric compound mainly used to form nonfouling thin films on silicon surfaces, induces repulsive force so that the nonspecific adsorption of the surface is incomparably reduced in comparison with unmodified filter surfaces. The effectiveness of PEG-modified CTC filters was verified through lung (H358) and colorectal (SW620) cancer cells spiked, respectively, in phosphate-buffered saline (PBS) and unprocessed whole blood. The modified SU8 filters achieved approximately 37.7% and 22.8% improvement in release efficiency without significant changes in cell viability and capture efficiency. In order to verify the filter's potential for clinical applications, we extended our experiments using cancer patient blood samples. Six blood samples from colorectal and lung cancer patients were processed, and captured CTCs were efficiently released. From these experiments, the present PEG-modified filter captures and releases on average 14 +/- 7.4 CTCs/mL, including EpCAM-negative CTCs, which could not be captured by previous single antibody-based methods. The antibody free isolation with enhanced release efficiency facilitates viable cell retrieval, which is significant to CTC culture and comprehensive molecular study for verifying the mechanism of metastasis and cancer