4.8 Article

Microfluidic Magnetic Bead Assay for Cell Detection

Journal

ANALYTICAL CHEMISTRY
Volume 88, Issue 1, Pages 711-717

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/acs.analchem.5b02716

Keywords

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Funding

  1. National Science Foundation [DBI-IDBR-1353720]
  2. Direct For Biological Sciences
  3. Div Of Biological Infrastructure [1353720] Funding Source: National Science Foundation
  4. Directorate For Engineering
  5. Div Of Electrical, Commun & Cyber Sys [1200032] Funding Source: National Science Foundation

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We present a novel cell detection device based on a magnetic bead cell assay and microfluidic Coulter counting technology. The device cannot only accurately measure cells size distribution and concentration but also detect specific target cells. The device consists of two identical micro Coulter counters separated by a fluid chamber where an external magnetic field is applied. Antibody-functionalized magnetic beads were bound to specific antigens expressed on the target cells. A high-gradient magnetic field was applied to the chamber closer to the second counter via an external cylindrical magnet. Because of the magnetic interaction between the magnetic beads and the magnetic field, target cells were retarded by the magnetic field; transit time of a target cell (bound with magnetic beads) passing through the second counter was longer than that through the first counter. In comparison, transit times of a nontarget cell remained nearly the same when it passed through both counters. Thus, from the transit time delay we can identify target cells and quantify their concentration in a cell suspension. The transit time and the size of each cell were accurately measured in terms of the width and amplitude of the resistive pulses generated from the two Coulter counters. Experiments demonstrated that for mixed cells with various target cell ratios, the transit time delay increased approximately linearly with the increasing target cell ratio. The limit of detection (LOD) of the assay was estimated to be 5.6% in terms of target cell ratio. Cell viability tests further demonstrated that most cells were viable after the detection. With the simple device configuration and easy sample preparation, this rapid and reliable method is expected to accurately detect target cells and could be applied to facilitate stem cell isolation and characterization.

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