[논문]Viable and high-throughput isolation of heterogeneous circulating tumor cells using tapered-slit filters

Shim, Jae-Eul; Bu, Jiyoon; Lee, Mi-Kyung; Cho, Young-Ho; Kim, Tae-Ha; Bu, Jong-Uk; Han, Sae-Won

doi:10.1016/j.snb.2020.128369

[해외논문] Viable and high-throughput isolation of heterogeneous circulating tumor cells using tapered-slit filters

Sensors and actuators. B, Chemical, v.321, 2020년, pp.128369 -

Shim, Jae-Eul (Cell Bench Research Center, Korea Advanced Institute of Science and Technology (KAIST)) , Bu, Jiyoon (Cell Bench Research Center, Korea Advanced Institute of Science and Technology (KAIST)) , Lee, Mi-Kyung (Cell Bench Research Center, Korea Advanced Institute of Science and Technology (KAIST)) , Cho, Young-Ho (Cell Bench Research Center, Korea Advanced Institute of Science and Technology (KAIST)) , Kim, Tae-Ha (SenPlus, Ltd.) , Bu, Jong-Uk (SenPlus, Ltd.) , Han, Sae-Won (Seoul National University Hospital)

Abstract ▼ AI-Helper

Abstract Circulating tumor cells (CTCs) have received a great amount of attention, as they are known to promote metastatic spread of cancer. Despite a wide variety of techniques developed to utilize CTCs as a diagnostic and prognostic tumor biomarker, clinical trials based on CTC analysis have shown inconsistent benefits due to difficulties in isolating these heterogeneous rare cells with high sensitivity, as well as maintaining their viability. Here, we developed a tapered slit filter (TSF) for high throughput isolation of viable heterogeneous CTCs. TSF prototypes were fabricated using a single-mask photolithography of SU-8 dry films, which were achieved by precisely adjusting UV exposure condition. The numerical analysis and in vitro cell capture assay revealed that the optimal TSF prototype was capable to reduce the stress applied on cells by 10 % compared to straight-walled slit filters (SSFs), which in turns enabled high throughput (25 mL/h), viable (87–94 %), and highly sensitive (83–100 %) capture of cancer cells, regardless of their epithelial/mesenchymal features. As a result, TSF outperformed conventional CTC isolation devices (or methods), as an EpCAM-targeting approach demonstrated low capture efficiency for mesenchymal-like SW620 cells (∼10 %), while sharp edges of the SSFs significantly reduced the cell viability (∼70 %). The clinical study using blood samples obtained from colorectal cancer patients further demonstrated that TSF was capable to isolate heterogeneous CTC subtypes, which expressed epithelial, mesenchymal, or hybrid of epithelial/mesenchymal markers. The results presented in this study support that the new device has potential to provide in-depth information on pathological status of the patients. Highlights A tapered slit filter (TSF) for high throughput isolation of viable and heterogeneous CTCs was developed. TSF reduced stress applied on the cells at the edges of slits, enabling high throughput and viable capture of cancer cells. TSF captured cancer cells highly sensitive (83-100%), regardless of their epithelial/mesenchymal features. TSF’s clinical studies demonstrated the detection of heterogeneous CTCs and clusters.

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