Microfluidic high-throughput encapsulation and hydrodynamic self-sorting of single cells

doi:10.1073/pnas.0708321105

Microfluidic high-throughput encapsulation and hydrodynamic self-sorting of single cells

Max Chabert*,^† and
Jean-Louis Viovy*,^†,^‡

*Institut Curie, Section de Recherche, 26, rue d'Ulm, 75005 Paris, France; and
^†Centre National de la Recherche Scientifique, Unité Mixte de Recherche 168, 75005 Paris, France

Edited by Howard Brenner, Massachusetts Institute of Technology, Cambridge, MA, and approved December 28, 2007 (received for review September 3, 2007)

Abstract

We present a purely hydrodynamic method for the high-throughput encapsulation of single cells into picoliter droplets, and spontaneous self-sorting of these droplets. Encapsulation uses a cell-triggered Rayleigh–Plateau instability in a flow-focusing geometry, and self-sorting puts to work two extra hydrodynamic mechanisms: lateral drift of deformable objects in a shear flow, and sterically driven dispersion in a compressional flow. Encapsulation and sorting are achieved on-flight in continuous flow at a rate up to 160 cells per second. The whole process is robust and cost-effective, involving no optical or electrical discrimination, active sorting, flow switching, or moving parts. Successful encapsulation and sorting of 70–80% of the injected cell population into drops containing one and only one cell, with <1% contamination by empty droplets, is demonstrated. The system is also applied to the direct encapsulation and sorting of cancerous lymphocytes from a whole blood mixture, yielding individually encapsulated cancer cells with a >10,000-fold enrichment as compared with the initial mix. The method can be implemented in simple “soft lithography” chips, allowing for easy downstream coupling with microfluidic cell biology or molecular biology protocols.

Footnotes

^‡To whom correspondence should be addressed. E-mail: jean-louis.viovy{at}curie.fr
Author contributions: M.C. and J.-L.V. designed research; M.C. performed research; M.C. and J.-L.V. analyzed data; and M.C. and J.-L.V. wrote the paper.
Conflict of interest statement: The authors have a pending patent on the technology presented in this manuscript.
This article is a PNAS Direct Submission.
This article contains supporting information online at www.pnas.org/cgi/content/full/0708321105/DC1.