title: A novel microfluidic platform for size and deformability based separation and the subsequent molecular characterization of viable circulating tumor cells.
abstract: Circulating tumor cells (CTCs) were introduced as biomarkers more than 10 years ago, but capture of viable CTCs at high purity from peripheral blood of cancer patients is still a major technical challenge. Here, we report a novel microfluidic platform designed for marker independent capture of CTCs. The Parsortix™ cell separation system provides size and deformability-based enrichment with automated staining for cell identification, and subsequent recovery (harvesting) of cells from the device. Using the Parsortix™ system, average cell capture inside the device ranged between 42% and 70%. Subsequent harvest of cells from the device ranged between 54% and 69% of cells captured. Most importantly, 99% of the isolated tumor cells were viable after processing in spiking experiments as well as after harvesting from patient samples and still functional for downstream molecular analysis as demonstrated by mRNA characterization and array-based comparative genomic hybridization. Analyzing clinical blood samples from metastatic (n = 20) and nonmetastatic (n = 6) cancer patients in parallel with CellSearch(®) system, we found that there was no statistically significant difference between the quantitative behavior of the two systems in this set of twenty six paired separations. In conclusion, the epitope independent Parsortix™ system enables the isolation of viable CTCs at a very high purity. Using this system, viable tumor cells are easily accessible and ready for molecular and functional analysis. The system's ability for enumeration and molecular characterization of EpCAM-negative CTCs will help to broaden research into the mechanisms of cancer as well as facilitating the use of CTCs as "liquid biopsies."
authors.affiliation: ANGLE North America Inc, Philadelphia, PA.
authors.forename: G E
authors.initials: GE
authors.lastname: Hvichia
authors.affiliation: ANGLE North America Inc, Philadelphia, PA.
authors.forename: Z
authors.initials: Z
authors.lastname: Parveen
authors.affiliation: ANGLE North America Inc, Philadelphia, PA.
authors.forename: C
authors.initials: C
authors.lastname: Wagner
authors.affiliation: Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.|Department of Hematology/Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.|Bone Marrow Transplantation with Section Pneumology, Hubertus Wald Tumorzentrum, University Comprehensive Cancer Center Hamburg, Hamburg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Janning
authors.affiliation: Department of Hematology/Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.|Bone Marrow Transplantation with Section Pneumology, Hubertus Wald Tumorzentrum, University Comprehensive Cancer Center Hamburg, Hamburg, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Quidde
authors.affiliation: Department of Hematology/Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.|Bone Marrow Transplantation with Section Pneumology, Hubertus Wald Tumorzentrum, University Comprehensive Cancer Center Hamburg, Hamburg, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Stein
authors.affiliation: Gynecology Department and Clinic, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: V
authors.initials: V
authors.lastname: Müller
authors.affiliation: Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.|Department of Hematology/Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.|Bone Marrow Transplantation with Section Pneumology, Hubertus Wald Tumorzentrum, University Comprehensive Cancer Center Hamburg, Hamburg, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Loges
authors.affiliation: Department of General, Visceral and Pediatric Surgery, University Hospital and Medical Faculty of the Heinrich-Heine University Düsseldorf, Düsseldorf, Germany.
authors.forename: R P L
authors.initials: RP
authors.lastname: Neves
authors.affiliation: Department of General, Visceral and Pediatric Surgery, University Hospital and Medical Faculty of the Heinrich-Heine University Düsseldorf, Düsseldorf, Germany.
authors.forename: N H
authors.initials: NH
authors.lastname: Stoecklein
authors.affiliation: Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Wikman
authors.affiliation: Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Riethdorf
authors.affiliation: Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Pantel
authors.affiliation: Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: T M
authors.initials: TM
authors.lastname: Gorges
mesh_terms: D045744:Cell Line, Tumor; D002469:Cell Separation / Q000295:instrumentation; D048430:Cell Shape; D048429:Cell Size; D002470:Cell Survival; D006801:Humans; D056656:Lab-On-A-Chip Devices; D009360:Neoplastic Cells, Circulating
keywords: circulating tumor cell; deformability; epithelial-mesenchymal transition; liquid biopsy