Portable filter-based microdevice for detection and characterization of circulating tumor cells.
OBJECTIVE
Sensitive detection and characterization of circulating tumor cells (CTC) could revolutionize the approach to patients with early-stage and metastatic cancer. The current methodologies have significant limitations, including limited capture efficiency and ability to characterize captured cells. Here, we report the development of a novel parylene membrane filter-based portable microdevice for size-based isolation with high recovery rate and direct on-chip characterization of captured CTC from human peripheral blood.


METHODS
We evaluated the sensitivity and efficiency of CTC capture in a model system using blood samples from healthy donors spiked with tumor cell lines. Fifty-nine model system samples were tested to determine the recovery rate of the microdevice. Moreover, 10 model system samples and 57 blood samples from cancer patients were subjected to both membrane microfilter device and CellSearch platform enumeration for direct comparison.


RESULTS
Using the model system, the microdevice achieved >90% recovery with probability of 95% recovering at least one cell when five are seeded in 7.5 mL of blood. CTCs were identified in 51 of 57 patients using the microdevice, compared with only 26 patients with the CellSearch method. When CTCs were detected by both methods, greater numbers were recovered by the microfilter device in all but five patients.


CONCLUSIONS
This filter-based microdevice is both a capture and analysis platform, capable of multiplexed imaging and genetic analysis. The microdevice presented here has the potential to enable routine CTC analysis in the clinical setting for the effective management of cancer patients.
Lin
Henry K
HK
Biosciences Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee, USA.
Zheng
Siyang
S
Williams
Anthony J
AJ
Balic
Marija
M
Groshen
Susan
S
Scher
Howard I
HI
Fleisher
Martin
M
Stadler
Walter
W
Datar
Ram H
RH
Tai
Yu-Chong
YC
Cote
Richard J
RJ
D045744:Cell Line, Tumor; D004129:Dimethylpolysiloxanes; D006440:Hemofiltration / Q000295:instrumentation*; D006801:Humans; D008567:Membranes, Artificial; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation*; D009369:Neoplasms / Q000097:blood* / Q000473:pathology; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D011108:Polymers; D014992:Xylenes
D004129:Dimethylpolysiloxanes; D008567:Membranes, Artificial; D011108:Polymers; D014992:Xylenes; C011055:parylene; C013830:baysilon