title: Size and deformability based separation of circulating tumor cells from castrate resistant prostate cancer patients using resettable cell traps.
abstract: The enumeration and capture of circulating tumor cells (CTCs) are potentially of great clinical value as they offer a non-invasive means to access tumor materials to diagnose disease and monitor treatment efficacy. Conventional immunoenrichment of CTCs may fail to capture cells with low surface antigen expression. Micropore filtration presents a compelling label-free alternative that enriches CTCs using their biophysical rather than biochemical characteristics. However, this strategy is prone to clogging of the filter microstructure, which dramatically reduces the selectivity after processing large numbers of cells. Here, we use the resettable cell trap (RCT) mechanism to separate cells based on their size and deformability using an adjustable aperture that can be periodically cleared to prevent clogging. After separation, the output sample is stained and analyzed using multi-spectral analysis, which provides a more sensitive and unambiguous method to identify CTC biomarkers than traditional immunofluorescence. We tested the RCT device using blood samples obtained from 22 patients with metastatic castrate-resistant prostate cancer while comparing the results with the established CellSearch® system. The RCT mechanism was able to capture ≥5 CTCs in 18/22 (82%) patients with a mean count of 257 in 7.5 ml of whole blood, while the CellSearch system found ≥5 CTCs in 9/22 (41%) patients with a mean count of 25. The ~10× improvement in the CTC capture rate provides significantly more materials for subsequent analysis of these cells such as immunofluorescence, propagation by tissue culture, and genetic profiling.
authors: Department of Mechanical Engineering, University of British Columbia, 2054-6250 Applied Science Lane, Vancouver, BC V6T 1Z4, Canada. hongma@mech.ubc.ca.
authors: Xi
authors: X
authors: Qin
authors: Sunyoung
authors: S
authors: Park
authors: Simon P
authors: SP
authors: Duffy
authors: Kerryn
authors: K
authors: Matthews
authors: Richard R
authors: RR
authors: Ang
authors: Tilman
authors: T
authors: Todenhöfer
authors: Hamid
authors: H
authors: Abdi
authors: Arun
authors: A
authors: Azad
authors: Jenny
authors: J
authors: Bazov
authors: Kim N
authors: KN
authors: Chi
authors: Peter C
authors: PC
authors: Black
authors: Hongshen
authors: H
authors: Ma
mesh_terms: D002469:Cell Separation / Q000295:instrumentation / Q000379:methods; D048429:Cell Size; D006801:Humans; D056656:Lab-On-A-Chip Devices; D008297:Male; D009360:Neoplastic Cells, Circulating / Q000378:metabolism / Q000473:pathology; D064129:Prostatic Neoplasms, Castration-Resistant / Q000378:metabolism / Q000473:pathology