Inertia based microfluidic capture and characterisation of circulating tumour cells for the diagnosis of lung cancer

Abstract

Background: Routine clinical application of circulating tumour cells (CTCs) for blood based diagnostics is yet to be established. Despite growing evidence of their clinical utility for diagnosis, prognosis and treatment monitoring, the efficacy of a robust platform and universally accepted diagnostic criteria remain uncertain. We evaluate the diagnostic performance of a microfluidic CTC isolation platform using cytomorphologic criteria in patients undergoing lung cancer surgery.Methods: Blood was processed from 51 patients undergoing surgery for known or suspected lung cancer using the ClearBridge ClearCell FX system TM (ClearBridge Biomedics, Singapore). Captured cells were stained on slides with haematoxylin and eosin (H&E) and independently assessed by two pathologist teams. Diagnostic performance was evaluated against the pathologists reported diagnosis of cancer from surgically obtained specimens.Results: Cancer was diagnosed in 43.1% and 54.9% of all cases. In early stage primary lung cancer, between the two reporting teams, a positive diagnosis of CTCs was made for 50% and 66.7% of patients. The agreement between the reporting teams was 80.4%, corresponding to a kappa-statistic of 0.61±0.11 (P<0.001), indicating substantial agreement. Sensitivity levels for the two teams were calculated as 59% (95% CI, 41-76%) and 41% (95% CI, 24-59%), with a specificity of 53% for both. Conclusions:The performance of the tested microfluidic antibody independent device to capture CTCs using standard cytomorphological criteria provides the potential of a diagnostic blood test for lung cancer.

Detection of CTCs in portal vein was associated with intrahepatic metastases and prognosis in patients with advanced pancreatic cancer

“…Peripheral blood was then collected in parallel and processed identically. The blood sample was processed using the ClearBridge ClearCell FX system TM (ClearBridge Biomedics, Singapore) 29 . Samples were further negatively sorted to remove the CD45 positive monocytes using EasySep™ Human CD45 Depletion Kit (18259RF, StemCell, USA).…”

The Diagnostic and Prognostic Value of a Liquid Biopsy for Esophageal Cancer: A Systematic Review and Meta-Analysis

“…Ohnaga reported that the CTC chip was able to isolate EC cell lines spiked in whole blood, and that its recovery rate was over 70% [ 33 ]. Following the CTC chip, many kinds of microfluidic platforms have been developed, such as ClearCell FX, based on size, deformability, and inertia separation [ 34 ]; CTC-iChip, based on positive and negative enrichment with size-based separation [ 35 ]; IsoFlux, based on automated continuous flow with EpCAM beads [ 19 ]; magnetic sifter, based on vertical flow configuration [ 36 ]; and vortex, based on inertial microfluidics and laminar microscale vortices without a red blood cells (RBC) lysis buffer [ 31 ].…”

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“…Over the past years, the concept of liquid biopsies has been introduced as an alternative to conventional tissue biopsy. Circulating tumour cells (CTCs) are cells that invade into the bloodstream from the primary tumours in the abdominal cavity ( 41 , 42 ). These cells are different to normal circulating blood cells and express tumour-specific characteristics.…”