An integrated optofluidic device for single-cell sorting driven by mechanical properties

Abstract

We present a novel optofluidic device for real-time sorting on the basis of cell mechanical properties, measured by optical stretching. The whole mechanism, based on optical forces, does not hamper the viability of the tested cells, which can be used for further analysis. The device effectiveness is demonstrated by extracting a sample population enriched with highly metastatic cells from a heterogeneous cell mixture.

Investigation of temperature effect on cell mechanics by optofluidic microchips

“…Besides, it was also demonstrated that cell's mechanical properties can be used as an intrinsic and reliable marker to distinguish between different cell types [6,7]. Cells' cytoskeleton, the fundamental support and basic structure for cell mechanics, has a complex and dynamic framework mainly composed of actin filaments, microtubules and intermediate filaments, which continuously assemble and disassemble according to cell status.…”

Hydrodynamic lift for single cell manipulation in a femtosecond laser fabricated optofluidic chip

“…The design is based on an X-shaped channel, similarly to what already presented in [9,21]: two input channels merge in a central section, where optical investigation and sorting can be performed, which then separates into two output channels for sample collection and waste. Here we rotated the two input channels by 90°, so as to exploit the bottom channel as a buffer to lift the upper stream containing the sample.…”

“…The sample is mounted on a translation stage FIBERglide 3D from Areotech and it is translated with respect to the laser beam to obtain the 3D irradiation pattern that will define both the microchannel shape and the optical waveguides. As already described in [9] the microchannels have been written parallely to the writing beam direction, to obtain low channel roughness and to optimize the image quality. The details of the fabrication process are described in the following.…”

“…Many different techniques have been proposed to assess cellular mechanical properties [6]; among these, the methods based on microfluidics usually allows for high throughput, as recently demonstrated in the real-time deformability cytometer [7]. However if cells need to be sorted and recollected for further analysis different devices should be used [8,9]. The microfluidic *Corresponding Author: Francesca Bragheri: Istituto di Fotonica e Nanotecnologie (IFN)-CNR, Piazza Leonardo da Vinci 32, 20133 Milano, Italy, E-mail: francesca.bragheri@ifn.cnr.it Roberto Osellame: Istituto di Fotonica e Nanotecnologie (IFN)-CNR, Piazza Leonardo da Vinci 32, 20133 Milano, Italy, E-mail: roberto.osellame@polimi.it optical stretcher allows measuring single-cell deformability and sorting in a dual-beam laser trap, without affecting cells' viability [10].…”

Femtosecond laser fabrication of optofluidic devices for single cell manipulation

“…Here we present two recently developed integrated optofluidic microchips fabricated by 3D femtosecond laser micromachining to analyze cell mechanics. In the first chip (an optical stretcher and sorter, OS in the following) optical forces are used both to induce cell deformation and to sort the cells, whereas in the second one (a constriction-chip, CC in the following) mechanical properties are tested in terms of cells' ability to passively squeeze through a small constriction [7,8].…”