A three dimensional thermoplastic microfluidic chip for robust cell capture and high
resolution imaging |
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| Authors: | Guillaume Mottet Karla Perez-Toralla Ezgi Tulukcuoglu Francois-Clement Bidard Jean-Yves Pierga Irena Draskovic Arturo Londono-Vallejo Stephanie Descroix Laurent Malaquin Jean Louis Viovy |
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| Institution: | 1.Institut Curie, UMR 168, 11 rue Pierre et Marie Curie, 75005 Paris, France;2.Department of Medical Oncology, Institut
Curie, Paris, France;3.Université Paris Descartes, Paris, France;4.Telomeres and Cancer Laboratory, Institut Curie, UPMC
Univ. Paris 06, Equipe Labellisé « Ligue », Paris, France |
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| Abstract: | We present a low cost microfluidic chip integrating 3D micro-chambers for the capture and the
analysis of cells. This device has a simple design and a small footprint. It allows the
implementation of standard biological protocols in a chip format with low volume consumption. The
manufacturing process relies on hot-embossing of cyclo olefin copolymer, allowing the development of
a low cost and robust device. A 3D design of microchannels was used to induce high flow velocity
contrasts in the device and provide a selective immobilization. In narrow distribution channels, the
liquid velocity induces a shear stress that overcomes adhesion forces and prevents cell
immobilization or clogging. In large 3D chambers, the liquid velocity drops down below the threshold
for cell attachment. The devices can be operated in a large range of input pressures and can even be
handled manually using simple syringe or micropipette. Even at high flow injection rates, the 3D
structures protect the captured cell from shear stress. To validate the performances of our device,
we implemented immuno-fluorescence labeling and Fluorescence in Situ Hybridization
(FISH) analysis on cancer cell lines and on a patient pleural effusion sample. FISH is a Food and
Drug Administration approved cancer diagnostic technique that provides quantitative information
about gene and chromosome aberration at the single cell level. It is usually considered as a long
and fastidious test in medical diagnosis. This process can be easily implanted in our platform, and
high resolution fluorescence imaging can be performed with reduced time and computer intensiveness.
These results demonstrate the potential of this chip as a low cost, robust, and versatile tool
adapted to complex and demanding protocols for medical diagnosis. |
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