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2017 ; 17
(8
): 1452-1461
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Biophysical isolation and identification of circulating tumor cells
#MMPMID28352869
Che J
; Yu V
; Garon EB
; Goldman JW
; Di Carlo D
Lab Chip
2017[Apr]; 17
(8
): 1452-1461
PMID28352869
show ga
Isolation and enumeration of circulating tumor cells (CTCs) from blood is
important for determining patient prognosis and monitoring treatment. Methods
based on affinity to cell surface markers have been applied to both purify (via
immunoseparation) and identify (via immunofluorescence) CTCs. However,
variability of cell biomarker expression associated with tumor heterogeneity and
evolution and cross-reactivity of antibody probes have long complicated CTC
enrichment and immunostaining. Here, we report a truly label-free high-throughput
microfluidic approach to isolate, enumerate, and characterize the biophysical
properties of CTCs using an integrated microfluidic device. Vortex-mediated
deformability cytometry (VDC) consists of an initial vortex region which enriches
large CTCs, followed by release into a downstream hydrodynamic stretching region
which deforms the cells. Visualization and quantification of cell deformation
with a high-speed camera revealed populations of large (>15 ?m diameter) and
deformable (aspect ratio >1.2) CTCs from 16 stage IV lung cancer samples, that
are clearly distinguished by increased deformability compared to contaminating
blood cells and rare large cells isolated from healthy patients. The VDC
technology demonstrated a comparable positive detection rate of putative CTCs
above healthy baseline (93.8%) with respect to standard immunofluorescence
(71.4%). Automation allows full enumeration of CTCs from a 10 mL vial of blood
within <1 h after sample acquisition, compared with 4+ hours with standard
approaches. Moreover, cells are released into any collection vessel for further
downstream analysis. VDC shows potential for accurate CTC enumeration without
labels and confirms the unique highly deformable biophysical properties of large
CTCs circulating in blood.