Abstract
Cellular circulating biomarkers from the primary tumor such as circulating tumor cells (CTCs) and circulating hybrid cells (CHCs) have been described to harbor tumor-like phenotype and genotype. CHCs are present in higher numbers than CTCs supporting their translational potential. Methods for isolation of CHCs do not exist and are restricted to low-throughput, time consuming, and biased methodologies. We report the development of a label-free dielectrophoretic microfluidic platform facilitating enrichment of CHCs in a high-throughput and rapid fashion by depleting healthy peripheral blood mononuclear cells (PBMCs). We demonstrated up to 96.5% depletion of PBMCs resulting in 18.6-fold enrichment of cancer cells. In PBMCs from pancreatic adenocarcinoma patients, the platform enriched neoplastic cells identified by their KRAS mutant status using droplet digital PCR with one hour of processing. Enrichment was achieved in 75% of the clinical samples analyzed, establishing this approach as a promising way to non-invasively analyze tumor cells from patients.
Highlights
Cellular circulating biomarkers from the primary tumor such as circulating tumor cells (CTCs) and circulating hybrid cells (CHCs) have been described to harbor tumor-like phenotype and genotype
In the past 5 years, other promising types of unconventional circulating neoplastic cells have been described such as tumor hybrid cells (THC) and circulating hybrid cells (CHCs)[11,12], CHCs are described as having hybrid phenotypes of a neoplastic cell and a leukocyte with dual expression of CD45 and tumor markers such as epithelial cell adhesion molecule (EpCAM) or CK11–15
To find the optimal frequency and voltage parameters to enrich for CHCs, we evaluated the enrichment of B16Mφ-RFP cells from peripheral blood mononuclear cells (PBMCs)
Summary
Cellular circulating biomarkers from the primary tumor such as circulating tumor cells (CTCs) and circulating hybrid cells (CHCs) have been described to harbor tumor-like phenotype and genotype. Advances in medical technologies have led to significant progress in both treatment and diagnosis, yet clinicians rely on invasive and often risky biopsies for cancer detection To address these limitations, the field of liquid biopsy has rapidly emerged as a non-invasive method to obtain tumor-derived biomarkers for diagnosis, staging, treatment, and prognosis[2,3]. Many groups have focused on using microfluidic sorting, density-based devices, size exclusion filtration, or marker specific isolation methods[8,9,10] These technologies rely on either a single physical property (size, density) or on specific protein expression (EpCAM, ECAD, CK) to differentiate CTCs from peripheral blood mononuclear cells (PBMCs). While CHCs are more abundant, their physical and phenotypic similarity to PBMCs makes their isolation and analysis a challenge[14]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
