A membrane-based microfluidic device for mechano-chemical cell manipulation

Abstract

We introduce a microfluidic device for chemical manipulation and mechanical investigation of circulating cells. The device consists of two crossing microfluidic channels separated by a porous membrane. A chemical compound is flown through the upper Bstimulus channel^, which diffuses through the membrane into the lower Bcell analysis channel^, in which cells are mechanically deformed in two sequential narrow constrictions, one before and one after crossing the stimulus channel. Thus, this system permits to measure cell deformability before and after chemical cues are delivered to the cells within one single chip. The validity of the device was tested with monocytic cells stimulated with an actindisrupting agent (Cytochalasin-D). Furthermore, as proof of principle of the device application, the effect of an antiinflammatory drug (Pentoxifylline) was tested on monocytic cells activated with Lipopolysaccharides and on monocytes from patients affected by atherosclerosis. The results show that the system can detect differences in cell mechanical deformation after chemical cues are delivered to the cells through the porous membrane. Diffusion of Cytochalasin-D resulted in a considerable decrease in entry time in the narrow constriction and an evident increase in the velocity within the constriction. Pentoxifylline showed to decrease the entry time but not to affect the transit time within the constriction for monocytic cells. Monocytes from patients affected by atherosclerosis were difficult to test in the device due to increased adhesion to the walls of the microfluidic channel. Overall, this analysis shows that the device has potential applications as a cellular assay for analyzing cell-drug interaction.

Review of membranes in microfluidics

“…Zhang et al carried out the high throughput cell‐free extraction of plasma by an integrated microfluidic device combining inertial microfluidics and membrane . Ravetto et al presented a membrane‐based microfluidic device for mechano‐chemical cell manipulation . Fan et al presented a microfluidic chip integrated with a high‐density PDMS‐based microfiltration membrane for rapid isolation and detection of circulating tumor cells .…”

“…60 Ravetto et al presented a membrane-based microfluidic device for mechano-chemical cell manipulation. 61 Fan et al presented a microfluidic chip integrated with a high-density PDMS-based microfiltration membrane for rapid isolation and detection of circulating tumor cells. 62 Zhao et al studied simultaneous characterization of instantaneous Young's modulus and specific membrane capacitance of single cells using a microfluidic system.…”

Design of Microfluidic Device and Measurements of MPWM for Single Cell /Particle Manipulation

“…Microfluidics is increasingly being used in many areas of biotechnology and chemistry [1][2][3][4][5] to achieve reduced consumption of reagents /analytes, improved performance, low costs of fabrications and decrease time of analyses, and also, among other advantages, to obtain miniaturization and integration of fluidic components, developed as well known concept of "lab on a chip" [3,4,5].…”

“…The device design and selection of materials are important steps for fabrication of microfluidic device for biomedical, chemistry or biochemisry applications [1][2][3][5][6][7][8][9][10][11].…”

Convection–diffusion molecular transport in a microfluidic bilayer device with a porous membrane

“…A microfluidic device was proposed to rapidly generate various concentration gradients in a controllable manner for chemotaxis study of motile bacterial cells (Kim et al 2014). Another microfluidic device was introduced to monitor cell mechanical deformation after chemical cues are delivered to the cells via diffusion through a porous membrane (Ravetto et al 2016).…”