Quantitative Magnetic Separation of Particles and Cells Using Gradient Magnetic Ratcheting

Coleman Murray, Edward Pao, Peter Tseng, Shayan Aftab, Rajan Kulkarni, Matthew Rettig, Dino Di Carlo

Research output: Contribution to journalArticlepeer-review

43 Scopus citations

Abstract

Extraction of rare target cells from biosamples is enabling for life science research. Traditional rare cell separation techniques, such as magnetic activated cell sorting, are robust but perform coarse, qualitative separations based on surface antigen expression. A quantitative magnetic separation technology is reported using high-force magnetic ratcheting over arrays of magnetically soft micropillars with gradient spacing, and the system is used to separate and concentrate magnetic beads based on iron oxide content (IOC) and cells based on surface expression. The system consists of a microchip of permalloy micropillar arrays with increasing lateral pitch and a mechatronic device to generate a cycling magnetic field. Particles with higher IOC separate and equilibrate along the miropillar array at larger pitches. A semi-analytical model is developed that predicts behavior for particles and cells. Using the system, LNCaP cells are separated based on the bound quantity of 1 μm anti-epithelial cell adhesion molecule (EpCAM) particles as a metric for expression. The ratcheting cytometry system is able to resolve a ±13 bound particle differential, successfully distinguishing LNCaP from PC3 populations based on EpCAM expression, correlating with flow cytometry analysis. As a proof-of-concept, EpCAM-labeled cells from patient blood are isolated with 74% purity, demonstrating potential toward a quantitative magnetic separation instrument.

Original languageEnglish (US)
Pages (from-to)1891-1899
Number of pages9
JournalSmall
Volume12
Issue number14
DOIs
StatePublished - Apr 13 2016
Externally publishedYes

Keywords

  • cell manipulation
  • circulating tumor cells
  • equilibrium separation
  • magnetic separation

ASJC Scopus subject areas

  • Biotechnology
  • Biomaterials
  • General Chemistry
  • General Materials Science

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