1. Diamagnetic trapping of cells above micro-magnets
P. Kauffmann1,2, N. M. Dempsey3, D. O’Brien3, S. Combe2, B. Schaack2, V. Haguet2, G. Reyne1
1 G2Elab, Grenoble-INP/UJF/CNRS; 2 Biopuces, iRTSV, CEA; 3 Institut Néel, CNRS/UJF Grenoble, France
Introduction
Cell arraying greatly facilitates quantitative analysis of cell behavior submitted to input signals, e.g. soluble factors, cell-substrate interaction, cell-cell interaction or electromechanical stress [1]. Here, we propose a contactless and biocompatible technique which exploits diamagnetic trapping of cells above micro-magnet arrays. By accurately designing the magnetic wells where cells are captured, this technique may provide information about non adhesive cell-cell interactions.
Principle of diamagnetic trapping
NdFeB µ-magnet thick films [4]
Design  optimization of B
High quality NdFeB µmagnets fabrication  Br~1T, μ0Hc>1T
Submitted to an inhomogeneous magnetic field, a cell experiences the following magnetic force [2,3]:
Lithography
<0
Si wafer
Top view
Magnetic hole ≠0
DRIE 90 µm
100nm Ta deposition Ta
Honeycomb array
Square shape array
cell < medium  repulsive force
Diamagnetic trapping: F=Weight, F<0
F=Weight: B &   Biocompatible trapping
NdFeB
30µm NdFeB deposition
Cross sectional view
100nm Ta deposition
~30µm thick
Micro-fabrication steps
SEM images of the µ-magnets
Fluorescent Jurkat cell trapping in very low χ paramagnetic media
Trapping troubles
Convection flow
Marangoni effect
[CGd-HP-DO3A] = 10mM =4 10-6
hole
magnet
Peltier device
Microscope objective Br
µfluidic chamber (Al)
[CGd-HP-DO3A] = 10mM =4 10-6
… between square shaped magnetic holes (CGd =10mM)
After 30 min, cells may sediment on magnets
Peltier device
Cell array…
Cell rank …
Iso-energy in the levitating plane
Sometimes trapping ceases.
Assumptions :
Contrast Agent (CA) internalization (endocytosis)?
CA adsorption on the cell membrane? Br
(hlev=12.5µm)
hole
magnet
[CGd-HP-DO3A] = 1.5mM =
… between square shaped magnets (CGd =0.8mM)
… between magnetic honeycomb (CGd =10mM)
Proliferation of Jurkat cells in paramagnetic media
Conclusion and outlook
Diamagnetic trapping
Time (h)
Cell concentration (ml-3)
Proliferation – GdBOPTA
Cell concentration (ml-3)
Proliferation – GdHP-DO3A
Time (h)
Cell arraying
above NdFeB µmagnets
in very low paramagnetic buffer < SI
using biocompatible CA: GdHPDO3A
Towards cell sorting
according to the cell sizes (e.g. White B.C./Red B.C.)
according to cell (e.g. deoxy RBC/OxyRBC)
For [GdBOPTA] < 50mM, cells proliferate
For any tested [GdHPDO3A], cells proliferate
Perfect recovery after 3 hours of GdHPDO3A exposition
References
D. Di Carlo et al., “Dynamic single cell analysis for quantitative biology”, Anal. Chem., 78, , 2006.
H. Chetouani et al., “Diamagnetic levitation of beads and cells above permanent magnets”, Proc. Transducers & Eurosensors, vol. 1, pp , Lyon, France, June 10-14, 2007.
A. Winkleman et al. “A magnetic trap for living cells suspended in a paramagnetic buffer”, Appl. Phys. Lett., 85, , 2004.
A. Walther et al., “Micro-patterning of NdFeB and SmCo magnet films for integration into micro-electro-mechanical-systems”, J. Magn. Magn. Mat., 321, 590–594, 2009, and D. O’Brien et al., in preparation.