A glass microfluidic chip for continuous blood cell sorting by a magnetic gradient without labeling

AbstractThis paper presents a microfluidic chip for highly efficient separation of red blood cells (RBCs) from whole blood on the basis of their native magnetic properties. The glass chip was fabricated by photolithography and thermal bonding. It consisted of one inlet and three outlets, and a nickel wire of 69-μm diameter was positioned in the center of a separation channel with 149-μm top width and 73-μm depth by two parallel ridges (about 10 μm high). The two ridges were formed simultaneously during the wet etching of the channels. The nickel wire for generating the magnetic gradient inside the separation channel was introduced from the side of the chip through a guide channel. The external magnetic field was applied by a permanent magnet of 0.3 T placed by the side of the chip and parallel to the main separation channel. The RBCs were separated continuously from the 1:40 (v/v) diluted blood sample at a flow rate in the range 0.12–0.92 μL/min (9–74 mm/min) with the chip, and up to 93.7% of the RBCs were collected in the middle outlet under a flow rate of 0.23 μL/min. The cell sedimentation was alleviated by adjusting the specific density of the supporting media with bovine serum albumin. Quantum dot labeling was introduced for visual fluorescence tracking of the separation process. The uneven distribution phenomenon of the blood cells around the nickel wire was reported and discussed. FigureGlass chip with single Ni wire aligned in the microchannel for continuous magnetic separation of blood cells

[1]  M. Stelzle,et al.  Microdevices for manipulation and accumulation of micro‐ and nanoparticles by dielectrophoresis , 2003, Electrophoresis.

[2]  A. B. Frazier,et al.  Paramagnetic capture mode magnetophoretic microseparator for high efficiency blood cell separations. , 2006, Lab on a chip.

[3]  Wei-Hua Huang,et al.  A micropillar‐integrated smart microfluidic device for specific capture and sorting of cells , 2007, Electrophoresis.

[4]  G. Shi,et al.  A water-soluble cationic oligopyrene derivative : Spectroscopic studies and sensing applications , 2009 .

[5]  Mengsu Yang,et al.  Cell docking and on-chip monitoring of cellular reactions with a controlled concentration gradient on a microfluidic device. , 2002, Analytical chemistry.

[6]  Electrodeless Dielectrophoretic Trapping and Separation of Cells , 2002 .

[7]  D. Pang,et al.  CdSe/ZnS-labeled carboxymethyl chitosan as a bioprobe for live cell imaging. , 2005, Chemical communications.

[8]  Maciej Zborowski,et al.  Red blood cell magnetophoresis. , 2003, Biophysical journal.

[9]  J. Jaiswal,et al.  Potentials and pitfalls of fluorescent quantum dots for biological imaging. , 2004, Trends in cell biology.

[10]  Shukun Xu,et al.  Synthesis of glutathione-capped CdS quantum dots and preliminary studies on protein detection and cell fluorescence image. , 2007, Luminescence : the journal of biological and chemical luminescence.

[11]  C. Owen.  High gradient magnetic separation of erythrocytes. , 1978, Biophysical journal.

[12]  B. Bakshi,et al.  Toward Bayesian chemometrics--a tutorial on some recent advances. , 2007, Analytica chimica acta.

[13]  Mattias Goksör,et al.  Optical tweezers applied to a microfluidic system. , 2004, Lab on a chip.

[14]  P. Yager,et al.  A planar microfabricated fluid filter , 1996 .

[15]  M. Heller,et al.  Dielectrophoretic cell separation and gene expression profiling on microelectronic chip arrays. , 2002, Analytical chemistry.

[16]  T. Crowley,et al.  Isolation of plasma from whole blood using planar microfilters for lab-on-a-chip applications. , 2005, Lab on a chip.

[17]  Dai-Wen Pang,et al.  Biofunctionalization of fluorescent-magnetic-bifunctional nanospheres and their applications. , 2005, Chemical communications.

[18]  Itamar Willner,et al.  Probing biocatalytic transformations with CdSe-ZnS QDs. , 2006, Journal of the American Chemical Society.

[19]  Mengsu Yang,et al.  Microfluidics technology for manipulation and analysis of biological cells , 2006 .

[20]  Ming C. Wu,et al.  Massively parallel manipulation of single cells and microparticles using optical images , 2005, Nature.

[21]  D. Pang,et al.  Quantum-dot-labeled DNA probes for fluorescence in situ hybridization (FISH) in the microorganism Escherichia coli. , 2006, Chemphyschem : a European journal of chemical physics and physical chemistry.

[22]  HGMS studies of blood cell behavior in plasma , 1982 .

[23]  Maciej Zborowski,et al.  Magnetic cell separation: characterization of magnetophoretic mobility. , 2003, Analytical chemistry.

[24]  P. Grodzinski,et al.  A Modular Microfluidic System for Cell Pre-concentration and Genetic Sample Preparation , 2003 .

[25]  Robert H. Austin,et al.  Continuous microfluidic immunomagnetic cell separation , 2004 .

[26]  B. A. Wills,et al.  Mineral processing technology , 1979 .

[27]  J. Liesveld,et al.  Investigating the Feasibility of Stem Cell Enrichment Mediated by Immobilized Selectins , 2007, Biotechnology progress.

[28]  Haruko Takeyama,et al.  Magnetic cell separation using antibody binding with protein a expressed on bacterial magnetic particles. , 2004, Analytical chemistry.

[29]  D. J. Harrison,et al.  Immunomagnetic T cell capture from blood for PCR analysis using microfluidic systems. , 2004, Lab on a chip.

[30]  Xiujun Li,et al.  Microfluidic selection and retention of a single cardiac myocyte, on-chip dye loading, cell contraction by chemical stimulation, and quantitative fluorescent analysis of intracellular calcium. , 2005, Analytical chemistry.

[31]  D. Pang,et al.  Cell-targeting multifunctional nanospheres with both fluorescence and magnetism. , 2005, Small.

[32]  Xing Chen,et al.  Microfluidic chip for blood cell separation and collection based on crossflow filtration , 2008 .

[33]  A. Bruno Frazier,et al.  Continuous magnetophoretic separation of blood cells in microdevice format , 2004 .

[34]  William H. Green,et al.  High‐gradient magnetic separation of coated magnetic nanoparticles , 2004 .

[35]  D. Melville,et al.  Direct magnetic separation of red cells from whole blood , 1975, Nature.