A Novel Automatic Device for Circulating Tumor Cell Isolation and Characterization

摘要

Analysis of circulating tumor cells (CTCs) in the peripheral blood could be used for tumor recurrence and metastasis prediction, therapy response evaluation, clinical staging and prognostics. Due to CTCs' extreme rarity, the capture efficiency and enrichment ratio are the most important factors to evaluate the performance of the device. It has been shown that the diameters of most types of CTCs are in the range of 15um-30um, we use polymer membrane filters to isolate and enrich CTCs from blood cells. The diameter of the pore is about 8um, the diameter of membrane is about 13mm, and there are about 200 thousand pores in the membrane. Based on this novel membrane filter, we have developed an automatic device named CTC-Biopsy. With CTC-Biopsy, circulating tumor cells can be isolated and stained automatically, which improves the uniformity and reproducibility. Spiking experiment was carried out with the CTC-Biopsy. The result is as following: 1) CTC-Biopsy has high throughput and takes about 14 minutes for each sample process. 2) CTC-Biopsy can process 10 samples as a group. 3) When using SKBR-3 cells to do the spiking experiment, the capture efficiency reaches 85%(R2=0.9923 , CV=10%) and enrichment ratio is about 1000. The capture efficiency is about 66.7% when the CTCs concentration is very low (about one SKBR-3 cell in 1mL sample). When clinic samples were examined, CTCs (CTCs>5) were detected in 76% of the patients with different tumor stage and CTM (CTM>=1) were detected in 10% of the patients. On the other hand, for 30 healthy volunteers, CTCs were not detected nearly (CTCs=0, 94%), the other 6% only has 1-2 CTCs. Our data proved that CTC-Biopsy is a potential device for clinic testing circulating tumor cells.