01872nas a2200181   4500008004100000022001400041245008400055210006900139300001400208490000700222520133400229653001901563100001501582700001401597700001301611700001801624856004801642       2008                        eng d  a0887-233300aA microfluidic gradient maker for toxicity testing of bupivacaine and lidocaine0 amicrofluidic gradient maker for toxicity testing of bupivacaine   a1957–640 v223 a<p>A great deal of effort is being dedicated to the development of new devices able to conduct effective in vitro toxicology analyses. This paper describes the use of a microfluidic gradient maker for the toxicological analysis of two conventional local anesthetics, bupivacaine and lidocaine on cell cultures. The microfluidic device was designed and simulated using COMSOL Multiphysics and the concentration gradient in the microfluidic network was analysed through a fluidodynamic and diffusive study. Subsequently the device was fabricated with soft lithography, casting PDMS in a master to obtain channels about 250 microm deep. Both drugs were tested on C2C12 myoblasts and an analysis was performed using propidium iodide staining followed by an imaging processing routine to obtain quantitative dose-response profiles in the gradient maker. The system was critically compared with microwell-based toxicity testing. The results show that the GM is a more sensitive method for detection of cell toxicity, and compared with testing of drug toxicity using microwells with individual cell cultures, allows one shot testing with a single cell culture exposed to a large number of concentrations. However, the flow rates required to obtain a suitable concentration range across the device may damage shear sensitive cells.</p>
10aBioengineering1 aTirella, A1 aMarano, M1 aVozzi, F1 aAhluwalia, A.  uhttp://www.ncbi.nlm.nih.gov/pubmed/18940244