title: Microfluidic platform for negative enrichment of circulating tumor cells.
abstract: Negative enrichment is the preferred approach for tumor cell isolation as it does not rely on biomarker expression. However, size-based negative enrichment methods suffer from well-known recovery/purity trade-off. Non-size based methods have a number of processing steps that lead to compounded cell loss due to extensive sample processing and handling which result in a low recovery efficiency. We present a method that performs negative enrichment in two steps from 2 ml of whole blood in a total assay processing time of 60 min. This negative enrichment method employs upstream immunomagnetic depletion to deplete CD45-positive WBCs followed by a microfabricated filter membrane to perform chemical-free RBC depletion and target cells isolation. Experiments of spiking two cell lines, MCF-7 and NCI-H1975, in the whole blood show an average of >90 % cell recovery over a range of spiked cell numbers. We also successfully recovered circulating tumor cells from 15 cancer patient samples.
authors.affiliation: BioElectronics Programme, Institute of Microelectronics, A*STAR (Agency for Science, Technology and Research), 1 Science Park Road, Singapore, 117528, Singapore.
authors.forename: Bhuvanendran Nair Gourikutty
authors.initials: BN
authors.lastname: Sajay
authors.forename: Chia-Pin
authors.initials: CP
authors.lastname: Chang
authors.forename: Hamizah
authors.initials: H
authors.lastname: Ahmad
authors.forename: Puttachat
authors.initials: P
authors.lastname: Khuntontong
authors.forename: Chee Chung
authors.initials: CC
authors.lastname: Wong
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Wang
authors.forename: Poenar Daniel
authors.initials: PD
authors.lastname: Puiu
authors.forename: Ross
authors.initials: R
authors.lastname: Soo
authors.forename: Abdur Rub Abdur
authors.initials: AR
authors.lastname: Rahman
mesh_terms: D002452:Cell Count; D045744:Cell Line, Tumor; D002469:Cell Separation / Q000379:methods; D005260:Female; D005374:Filtration / Q000379:methods; D064368:Healthy Volunteers; D006801:Humans; D007962:Leukocytes / Q000166:cytology / Q000378:metabolism; D061986:MCF-7 Cells; D008297:Male; D046210:Microfluidic Analytical Techniques / Q000379:methods; D044085:Microfluidics / Q000295:instrumentation / Q000379:methods*; D055616:Microtechnology / Q000295:instrumentation; D009360:Neoplastic Cells, Circulating / Q000473:pathology*