title: An integrated on-chip platform for negative enrichment of tumour cells.
abstract: The study of cancer cells in blood, popularly called circulating tumour cells (CTCs), has exceptional prospects for cancer risk assessment and analysis. Separation and enrichment of CTCs by size-based methods suffer from a well-known recovery/purity trade-off while methods targeting certain specific surface proteins can lead to risk of losing CTCs due to Epithelial to Mesenchymal Transition (EMT) and thus adversely affect the separation efficiency. A negative selection approach is thus preferred for tumour cell isolation as it does not depend on biomarker expression or defines their physical property as the separation criteria. In this work, we developed a microfluidic chip to isolate CTCs from whole blood samples without targeting any tumour specific antigen. This chip employs a two-stage cell separation: firstly, magnetophoresis depletes the white blood cells (WBCs) from a whole blood sample and is then followed by a micro-slit membrane that enables depleting the red blood cells (RBCs) and retaining only the tumour cells. By creating strong magnetic field gradients along with customized antibody complexes to target WBCs, we are able to remove >99.9% of WBCs from 1:1 diluted blood at a sample processing rate of 500μL/min. This approach achieves an average of >80% recovery of spiked tumour cells from 2mL of whole blood in a total assay processing time of 50min without multiple processing steps.
authors.affiliation: BioElectronics Programme, Institute of Microelectronics, A*STAR (Agency for Science, Technology and Research), 2 Fusionopolis Way, #08-02, Innovis, 117528, Singapore; NOVITAS-Centre for Micro-/Nano-electronics, School of Electrical and Electronics Engineering, Nanyang Technological University, 50 Nanyang Avenue, 639798, Singapore. Electronic address: sajaygouri@gmail.com.
authors.forename: Sajay
authors.initials: S
authors.lastname: Bhuvanendran Nair Gourikutty
authors.affiliation: BioElectronics Programme, Institute of Microelectronics, A*STAR (Agency for Science, Technology and Research), 2 Fusionopolis Way, #08-02, Innovis, 117528, Singapore.
authors.forename: Chia-Pin
authors.initials: CP
authors.lastname: Chang
authors.affiliation: NOVITAS-Centre for Micro-/Nano-electronics, School of Electrical and Electronics Engineering, Nanyang Technological University, 50 Nanyang Avenue, 639798, Singapore.
authors.forename: Daniel Puiu
authors.initials: DP
authors.lastname: Poenar
mesh_terms: D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition; D004867:Equipment Design; D006801:Humans; D018189:Immunomagnetic Separation / Q000295:instrumentation*; D056656:Lab-On-A-Chip Devices; D047589:Leukocyte Reduction Procedures / Q000295:instrumentation; D007962:Leukocytes / Q000166:cytology; D008567:Membranes, Artificial; D009369:Neoplasms / Q000097:blood / Q000473:pathology; D009360:Neoplastic Cells, Circulating / Q000473:pathology*
chemical_list: D008567:Membranes, Artificial
keywords: Cell separation; Circulating tumour cells (CTCs); Magnetic separation; Negative enrichment; White blood cell (WBC) depletion