title: 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 "stimulus channel", which diffuses through the membrane into the lower "cell 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 actin-disrupting agent (Cytochalasin-D). Furthermore, as proof of principle of the device application, the effect of an anti-inflammatory 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.
authors.affiliation: Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, Netherlands.
authors.forename: Agnese
authors.initials: A
authors.lastname: Ravetto
authors.affiliation: Deparment of Experimental Cardiology, University Medical Center Utrecht, Utrecht, Netherlands.
authors.forename: Imo E
authors.initials: IE
authors.lastname: Hoefer
authors.affiliation: Department of Mechanical Engineering, Eindhoven University of Technology, Eindhoven, Netherlands. J.M.J.d.Toonder@tue.nl.|Institute for Complex Molecular Systems, Eindhoven University of Technology, Eindhoven, Netherlands. J.M.J.d.Toonder@tue.nl.
authors.forename: Jaap M J
authors.initials: JM
authors.lastname: den Toonder
authors.affiliation: Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, Netherlands. C.V.C.Bouten@tue.nl.|Institute for Complex Molecular Systems, Eindhoven University of Technology, Eindhoven, Netherlands. C.V.C.Bouten@tue.nl.
authors.forename: Carlijn V C
authors.initials: CV
authors.lastname: Bouten
mesh_terms: D001696:Biomechanical Phenomena / Q000187:drug effects; D015638:Cytochalasin D / Q000494:pharmacology; D003584:Cytological Techniques / Q000295:instrumentation*; D004058:Diffusion; D005240:Feasibility Studies; D018922:HL-60 Cells; D006801:Humans; D056656:Lab-On-A-Chip Devices; D055595:Mechanical Phenomena; D008567:Membranes, Artificial; D009000:Monocytes / Q000166:cytology / Q000187:drug effects; D016062:Porosity
chemical_list: D008567:Membranes, Artificial; D015638:Cytochalasin D
keywords: Mechanical deformation; chemical stimulation; circulating cell mechanics; integrated membrane