title: Biomimetic postcapillary expansions for enhancing rare blood cell separation on a microfluidic chip.
abstract: Blood cells naturally auto-segregate in postcapillary venules, with the erythrocytes (red blood cells, RBCs) aggregating near the axis of flow and the nucleated cells (NCs)--which include leukocytes, progenitor cells and, in cancer patients, circulating tumor cells--marginating toward the vessel wall. We have used this principle to design a microfluidic device that extracts nucleated cells (NCs) from whole blood. Fabricated using polydimethylsiloxane (PDMS) soft lithography, the biomimetic cell extraction device consists of rectangular microchannels that are 20-400 μm wide, 11 μm deep and up to 2 cm long. The key design feature is the use of repeated expansions/contractions of triangular geometry mimicking postcapillary venules, which enhance margination and optimize the extraction. The device operates on unprocessed whole blood and is able to extract 94 ± 4.5% of NCs with 45.75 ± 2.5-fold enrichment in concentration at a rate of 5 nl s(-1). The device eliminates the need to preprocess blood via centrifugation or RBC lysis, and is ready to be implemented as the initial stage of lab-on-a-chip devices that require enriched nucleated cells. The potential downstream applications are numerous, encompassing all preclinical and clinical assays that operate on enriched NC populations and include on-chip flow cytometry (A. Y. Fu et al., Anal. Chem., 2002, 74, 2451-2457; A. Y. Fu et al., Nat. Biotechnol., 1999, 17, 1109-1111), genetic analyses (M. M. Wang et al., Nat. Biotechnol., 2005, 23, 83-87; L. C. Waters et al., Anal. Chem., 1998, 70, 5172-5176) and circulating tumor cell extraction (S. Nagrath et al., Nature, 2007, 450, 1235-1241; S. L. Stott et al., Proc. Natl. Acad. Sci. U. S. A., 2010, 18392-18397; H. K. Lin et al., Clin. Cancer Res., 2010, 16, 5011-5018).
authors.affiliation: Department of Biomedical Engineering, Boston University, 44 Cummington Street, Boston, MA 02119, USA. ajain@steele.mgh.harvard.edu
authors.forename: Abhishek
authors.initials: A
authors.lastname: Jain
authors.forename: Lance L
authors.initials: LL
authors.lastname: Munn
mesh_terms: D040761:Biomimetic Materials / Q000737:chemistry*; D001773:Blood Cells / Q000166:cytology*; D002469:Cell Separation / Q000379:methods*; D004129:Dimethylpolysiloxanes / Q000737:chemistry; D004912:Erythrocytes / Q000166:cytology; D006801:Humans; D056656:Lab-On-A-Chip Devices; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation* / Q000379:methods
chemical_list: D004129:Dimethylpolysiloxanes; C013830:baysilon