Fast, Reusable, Cell Uniformly Distributed Membrane Filtration Device for Separation of Circulating Tumor Cells

Abstract

Isolation of circulating tumor cells (CTCs) is of great significance for the diagnosis, prognosis, and treatment of metastatic cancer. Among CTC capture methods independent of antibodies, membrane filtration-based methods have the advantages of simplicity, rapidity, and high throughput but usually have problems such as clogging, high pressure drop, and impaired cell viability. In this study, we designed and tested a reusable device that used horizontal rotor and fluid-assisted separation to capture CTCs by centrifugal membrane filtration, achieving simple, fast, highly efficient, and viable cell capture on traditional centrifuge. The average capture efficiency was 95.8% for different types of cancer cells with >90% survival, and the removal of white blood cells can reach 99.72% under four times cleaning of the membrane after filtration. A further clinic demo was performed using the device to detect residual leukemic cells in patients; the results showed a 10-fold enrichment of the leukemic cells in peripheral blood samples. Taken together, the simple, robust, and efficient CTC capture device may have the potential for clinic routine detection and analysis of circulating tumor cells.

Novel Isolating Approaches to Circulating Tumor Cell Enrichment Based on Microfluidics: A Review

“…However, microfilters that isolate cells based on their size tend to cause cell clogging, reducing cell recovery and purity. To solve this problem, Han et al designed a membrane filtration device with a horizontal rotor for even cell distribution, improving cells isolation in centrifuges, as shown in Figure 6 A [ 101 ]. Li et al designed a windmill-like uniform touch (SU-8 film) pore array, as shown in Figure 6 B.…”

“…15, x FOR PEERREVIEW 12 of 32 shown in Figure 6A[101]. Li et al designed a windmill-like uniform touch (SU-8 film) pore array, as shown in Figure6B.…”

Recent advances of liquid biopsy: Interdisciplinary strategies toward clinical decision‐making

“…However, challenges such as low CTC recovery and clogging of the porous filter arise due to high filtration pressure and elevated hematocrit levels. 60 It is worth noting that the future of sizebased isolation can serve as an accessible and preliminary method for CTC isolation. By sidestepping complex channel designs, they may enable rapid CTC isolation and enumeration within 10 min, while maintaining clinically acceptable sensitivity and specificity.…”

“…The physical strategies for CTC isolation can be categorized into two main approaches: active isolation and passive isolation. Passive isolation techniques rely on specialized channel designs to separate CTCs based on their intrinsic properties, such as size, 60 deformability, 62 hydrodynamic features, 64 and viscoelastic migration 65 . On the other hand, active isolation involves the use of external fields to manipulate cancer cells, such as light, 67 dielectric fields, 69 acoustic fields, 71 and magnetic force 73 .…”

“… 61 These strategies offer simple fabrication processes and easy operation procedures, accelerating their clinical implementation. However, challenges such as low CTC recovery and clogging of the porous filter arise due to high filtration pressure and elevated hematocrit levels 60 . It is worth noting that the future of size‐based isolation can serve as an accessible and preliminary method for CTC isolation.…”