Nanoparticle‐Mediated Binning and Profiling of Heterogeneous Circulating Tumor Cell Subpopulations

Abstract

The analysis of circulating tumor cells (CTCs) is an important capability that may lead to new approaches for cancer management. CTC capture devices developed to date isolate a bulk population of CTCs and do not differentiate subpopulations that may have varying phenotypes with different levels of clinical relevance. Here, we present a new device for CTC spatial sorting and profiling that sequesters blood-borne tumor cells with different phenotypes into discrete spatial bins. Validation data are presented showing that cancer cell lines with varying surface expression generate different binning profiles within the device. Working with patient blood samples, we obtain profiles that elucidate the heterogeneity of CTC populations present in cancer patients and also report on the status of CTCs within the epithelial-to-mesenchymal transition (EMT).

Circulating Tumor Cells as a Biomarker in Pancreatic Ductal Adenocarcinoma

“…Few studies to date have reported a close relationship between aneuploidy and tumor metastasis. CTCs identified based on the EpCAM staining detection method were closely related to epithelial-mesenchymal transition (EMT) [28] and served as an independent prognostic factor for tumor metastasis [29]. The relationship between CTCs and tumor metastasis should be assessed based on the detection method.…”

Optofluidic device for the quantification of circulating tumor cells in breast cancer

“…Currently, most of liquid biopsy approaches for CTCs are based on the use of the epithelial cell adhesion molecule (EpCAM) antibodies to capture the CTCs and their subsequent characterization with immunostaining or retro-transcription polymerase chain reaction 10–13 . Some methods employ the intrinsic differences in shape, size and/or density of the tumor cells as compared with the normal circulating cells to collect and later recount CTCs by using filters 14–16 , micro-obstacles and gravity 17 , activated surfaces 18–20 or particles 15, 20–22 . Several CTC detection systems are commercially available and most of them rely on immunomagnetic separation strategies.…”

Materials and microfluidics: enabling the efficient isolation and analysis of circulating tumour cells

“…Velocity valley and magnetic ranking microfluidic technologies 114–119 (Fig. 3D) isolate magnetic affinity-labelled CTCs in different zones of the device depending on antigen (e.g., EpCAM 114–119 HER2, 114,117 EGFR, 117 , MUC1, 114 N-Cadherin 118 ) expression level, thus correlating disease progression with CTC phenotype, 114,118 similar to CTC immunophenotyping 29 and RNA-ISH analysis.…”

“…Whole blood, 114–118 RBC lysed blood, 117,118 or RBC lysed and WBC-depleted blood 117,119 was spiked with Ab-coated 114–116,118 or aptamer-coated 117,119 (discussed below) magnetic nanoparticles. The sample was infused through a series of microfluidic chambers, and an external magnetic field pulled both free magnetic nanoparticles and labelled CTCs onto the device surface.…”