Optofluidic integrated cell sorter fabricated by femtosecond lasers.

The main trend in optofluidics is currently towards full integration of the devices, thus improving automation, compactness and portability. In this respect femtosecond laser microfabrication is a very powerful technology given its capability of producing both optical waveguides and microfluidic channels. The current challenge in biology is the possibility to perform bioassays at the single cell level to unravel the hidden complexity in nominally homogeneous populations. Here we report on a new device implementing a fully integrated fluorescence-activated cell sorter. This non-invasive device is specifically designed to operate with a limited amount of cells but with a very high selectivity in the sorting process. Characterization of the device with beads and validation with human cells are presented.

[1]  Nicole Rusk,et al.  Functional genomic resources , 2011, Nature Methods.

[2]  Ming C. Wu,et al.  Massively parallel manipulation of single cells and microparticles using optical images , 2005, Nature.

[3]  R. Osellame,et al.  Optofluidic chip for single cell trapping and stretching fabricated by a femtosecond laser , 2010, Journal of biophotonics.

[4]  J. Settleman,et al.  Dissecting cancer heterogeneity , 2011, Nature Biotechnology.

[5]  R. Osellame,et al.  Shape control of microchannels fabricated in fused silica by femtosecond laser irradiation and chemical etching. , 2009, Optics express.

[6]  Roberta Ramponi,et al.  Three-dimensional Mach-Zehnder interferometer in a microfluidic chip for spatially-resolved label-free detection. , 2010, Lab on a chip.

[7]  K. Jensen,et al.  Cells on chips , 2006, Nature.

[8]  E. Mazur,et al.  Femtosecond laser micromachining in transparent materials , 2008 .

[9]  Stefan Schinkinger,et al.  Reconfigurable microfluidic integration of a dual-beam laser trap with biomedical applications , 2007, Biomedical microdevices.

[10]  E. Elson,et al.  Mechanical properties of HL60 cells: role of stimulation and differentiation in retention in capillary-sized pores. , 1991, American journal of respiratory cell and molecular biology.

[11]  Dong Sun,et al.  Enhanced cell sorting and manipulation with combined optical tweezer and microfluidic chip technologies. , 2011, Lab on a chip.

[12]  Andrew A. Bettiol,et al.  Microfluidic sorting system based on optical force switching , 2009 .

[13]  Jan Vijg,et al.  Increased cell-to-cell variation in gene expression in ageing mouse heart , 2006, Nature.

[14]  A. Ben-Ze'ev,et al.  The cytoskeleton in cancer cells. , 1985, Biochimica et biophysica acta.

[15]  Eric P. Y. Chiou,et al.  EWOD-driven droplet microfluidic device integrated with optoelectronic tweezers as an automated platform for cellular isolation and analysis. , 2009, Lab on a chip.

[16]  Elinore M Mercer,et al.  Microfluidic sorting of mammalian cells by optical force switching , 2005, Nature Biotechnology.

[17]  Che-Hsin Lin,et al.  Microfluidic cell counter/sorter utilizing multiple particle tracing technique and optically switching approach , 2008, Biomedical microdevices.

[18]  Debaditya Choudhury,et al.  A 3D mammalian cell separator biochip. , 2012, Lab on a chip.

[19]  J. Sturm,et al.  Deterministic hydrodynamics: Taking blood apart , 2006, Proceedings of the National Academy of Sciences.

[20]  Francesco De Angelis,et al.  Miniaturized all-fibre probe for three-dimensional optical trapping and manipulation , 2007 .

[21]  A. Ashkin Acceleration and trapping of particles by radiation pressure , 1970 .

[22]  Alan P. Morrison,et al.  Development of a microfluidic device for fluorescence activated cell sorting , 2002 .

[23]  Gwo-Bin Lee,et al.  Electrokinetically driven micro flow cytometers with integrated fiber optics for on-line cell/particle detection , 2004 .

[24]  R. Osellame,et al.  Femtosecond laser fabricated monolithic chip for optical trapping and stretching of single cells. , 2010, Optics express.

[25]  X. Xie,et al.  Probing Gene Expression in Live Cells, One Protein Molecule at a Time , 2006, Science.

[26]  R. Osellame,et al.  Femtosecond laser microstructuring: an enabling tool for optofluidic lab‐on‐chips , 2011 .

[27]  Francesco Favero,et al.  Reduced Expression of the ROCK Inhibitor Rnd3 Is Associated with Increased Invasiveness and Metastatic Potential in Mesenchymal Tumor Cells , 2010, PloS one.

[28]  Alan Arai,et al.  Waveguide writing in fused silica with a femtosecond fiber laser at 522 nm and 1 MHz repetition rate. , 2005, Optics express.

[29]  C. Grigoropoulos,et al.  Single cell detection using a glass-based optofluidic device fabricated by femtosecond laser pulses. , 2009, Lab on a chip.

[30]  M. Yamada,et al.  Pinched flow fractionation: continuous size separation of particles utilizing a laminar flow profile in a pinched microchannel. , 2004, Analytical chemistry.

[31]  J. Käs,et al.  The optical stretcher: a novel laser tool to micromanipulate cells. , 2001, Biophysical journal.

[32]  Samuel P Forry,et al.  Microfluidic magnetophoretic separations of immunomagnetically labeled rare mammalian cells. , 2012, Lab on a chip.

[33]  H. H. van den Vlekkert,et al.  Integration of femtosecond laser written optical waveguides in a lab-on-chip. , 2009, Lab on a chip.