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 (R) 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 mu m 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. (C) 2008 Elsevier Ltd. All rights reserved.
机构:Univ Costa Rica, Fac Microbiol, Inst Clodomiro Picado, San Jose, Costa Rica
Angulo, Y
Lomonte, B
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Univ Costa Rica, Fac Microbiol, Inst Clodomiro Picado, San Jose, Costa RicaUniv Costa Rica, Fac Microbiol, Inst Clodomiro Picado, San Jose, Costa Rica
机构:Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med & Surg Serv, Boston, MA 02114 USA
Jeon, NL
Baskaran, H
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机构:Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med & Surg Serv, Boston, MA 02114 USA
Baskaran, H
Dertinger, SKW
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机构:Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med & Surg Serv, Boston, MA 02114 USA
Dertinger, SKW
Whitesides, GM
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机构:Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med & Surg Serv, Boston, MA 02114 USA
Whitesides, GM
Van de Water, L
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机构:Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med & Surg Serv, Boston, MA 02114 USA
Van de Water, L
Toner, M
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Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med & Surg Serv, Boston, MA 02114 USAHarvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med & Surg Serv, Boston, MA 02114 USA
机构:Univ Costa Rica, Fac Microbiol, Inst Clodomiro Picado, San Jose, Costa Rica
Angulo, Y
Lomonte, B
论文数: 0引用数: 0
h-index: 0
机构:
Univ Costa Rica, Fac Microbiol, Inst Clodomiro Picado, San Jose, Costa RicaUniv Costa Rica, Fac Microbiol, Inst Clodomiro Picado, San Jose, Costa Rica
机构:Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med & Surg Serv, Boston, MA 02114 USA
Jeon, NL
Baskaran, H
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h-index: 0
机构:Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med & Surg Serv, Boston, MA 02114 USA
Baskaran, H
Dertinger, SKW
论文数: 0引用数: 0
h-index: 0
机构:Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med & Surg Serv, Boston, MA 02114 USA
Dertinger, SKW
Whitesides, GM
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机构:Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med & Surg Serv, Boston, MA 02114 USA
Whitesides, GM
Van de Water, L
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h-index: 0
机构:Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med & Surg Serv, Boston, MA 02114 USA
Van de Water, L
Toner, M
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h-index: 0
机构:
Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med & Surg Serv, Boston, MA 02114 USAHarvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med & Surg Serv, Boston, MA 02114 USA