Anticlogging Hemofiltration Device for Mass Collection of Circulating Tumor Cells by Ligand-Free Size Selection

Abstract

A new hemofiltration system was developed to continuously capture circulating tumor cells (CTCs) from a large volume of whole blood using a column that was packed with antifouling zwitterionized silica microspheres. The silica microspheres were modified with sulfobetaine silane (SBSi) to inhibit fouling, resist clogging, and give a high surface wettability and prolonged operation time. Packed microspheres with different diameters formed size-controllable interstitial pores that effectively captured CTCs by ligand-free size selection. For optimized performance of the hemofiltration system, operational factors, including the size of microspheres, flow rate, and cross-sectional area of the column, were considered with respect to the removal rate for colorectal cancer cells and the retention rate for white blood cells and red blood cells. The captured CTCs were collected from the column by density sedimentation. A large quantity of colorectal cancer cells was spiked into sheep blood, and the sample was circulated for 5 h with a total operational volume of 2 L followed by collection and culture in vitro. The results showed that the proposed hemofiltration device selectively removed abundant CTCs from in vitro circulatory blood. The viable cells were harvested for amplification and potential applications for precision medicine.

Targeted inhibition of tumor-derived exosomes as a novel therapeutic option for cancer

“…It is worth noting that PVA also presented promising biosafety, making it suitable for hemoperfusion in future translational medicine. Wu et al also applied silica microspheres with a hemofiltration device to achieve the selective capture and removal of abundant circulating tumor cells as well as TDEs, providing potential choices for tumor therapy 114 . Recently, the rapid development of microfluid chips has paved the way for TDE filtration.…”

3-Aminopropylsilatrane and Its Derivatives: A Variety of Applications

“…A simple and convenient silatrane ( 41 )-based filtering system for hemofiltration and collection of circulating tumor cells (CTCs) with fouling resistance and high hemocompatibility and selectivity was developed [ 86 ]. It was shown that the proposed device selectively removed the human colorectal carcinoma cell line (HCT116) from circulatory blood.…”

Liposome-tethered supported lipid bilayer platform for capture and release of heterogeneous populations of circulating tumor cells

“…[16][17][18][19] On the other hand, the techniques based on cellular physical properties ideally allow the isolation of the full heterogeneous population of CTCs from any type of cancer. Nevertheless, the inevitable high leukocyte contamination rates, 20,21 low survival rates, and clogging events 22 can lead to low selectivity, recovery, and short operation time. To address these technical challenges, methods for the detection of the heterogeneous population of CTCs were proposed by combing different antibodies specific for surface proteins, 18 integrating a microfluidic system with flow cytometry, 21 and proceeding with tedious sample handling and depletion of blood cells.…”