A microfluidic gradient maker for toxicity testing of bupivacaine and lidocaine

被引:43
作者
Tirella, Annalisa [1 ]
Marano, Mauro [1 ]
Vozzi, Federico [2 ]
Ahluwalia, Arti [1 ]
机构
[1] Univ Pisa, Ctr Interdipartimentale Ric E Piaggio, I-56126 Pisa, Italy
[2] CNR, Inst Clin Physiol, I-56100 Pisa, Italy
关键词
Microfluidics; Bupivacaine; Lidocaine; Concentration gradient; C2C12; myoblasts;
D O I
10.1016/j.tiv.2008.09.016
中图分类号
R99 [毒物学(毒理学)];
学科分类号
100405 ;
摘要
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.
引用
收藏
页码:1957 / 1964
页数:8
相关论文
共 29 条
  • [1] Differential susceptibility of C2C12 myoblasts and myotubes to group II phospholipase A2 myotoxins from crotalid snake venoms
    Angulo, Y
    Lomonte, B
    [J]. CELL BIOCHEMISTRY AND FUNCTION, 2005, 23 (05) : 307 - 313
  • [2] Diffusive transport properties of some local anesthetics applicable for iontophoretic formulation of the drugs
    Brounéus, F
    Karami, K
    Beronius, P
    Sundelöf, LO
    [J]. INTERNATIONAL JOURNAL OF PHARMACEUTICS, 2001, 218 (1-2) : 57 - 62
  • [3] Human neural stem cell growth and differentiation in a gradient-generating microfluidic device
    Chung, BG
    Flanagan, LA
    Rhee, SW
    Schwartz, PH
    Lee, AP
    Monuki, ES
    Jeon, NL
    [J]. LAB ON A CHIP, 2005, 5 (04) : 401 - 406
  • [4] Generation of gradients having complex shapes using microfluidic networks
    Dertinger, SKW
    Chiu, DT
    Jeon, NL
    Whitesides, GM
    [J]. ANALYTICAL CHEMISTRY, 2001, 73 (06) : 1240 - 1246
  • [5] Gradients of substrate-bound laminin orient axonal specification of neurons
    Dertinger, SKW
    Jiang, XY
    Li, ZY
    Murthy, VN
    Whitesides, GM
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (20) : 12542 - 12547
  • [6] Cell migration and polarity on microfabricated gradients of extracellular matrix proteins
    Gunawan, RC
    Silvestre, J
    Gaskins, HR
    Kenis, PJA
    Leckband, DE
    [J]. LANGMUIR, 2006, 22 (09) : 4250 - 4258
  • [7] Universal microfluidic gradient generator
    Irimia, Daniel
    Geba, Dan A.
    Toner, Mehmet
    [J]. ANALYTICAL CHEMISTRY, 2006, 78 (10) : 3472 - 3477
  • [8] Bupivacaine myotoxicity is mediated by mitochondria
    Irwin, W
    Fontaine, E
    Agnolucci, L
    Penzo, D
    Betto, R
    Bortolotto, S
    Reggiani, C
    Salviati, G
    Bernardi, P
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (14) : 12221 - 12227
  • [9] Neutrophil chemotaxis in linear and complex gradients of interleukin-8 formed in a microfabricated device
    Jeon, NL
    Baskaran, H
    Dertinger, SKW
    Whitesides, GM
    Van de Water, L
    Toner, M
    [J]. NATURE BIOTECHNOLOGY, 2002, 20 (08) : 826 - 830
  • [10] Biomolecular gradients in cell culture systems
    Keenan, Thomas M.
    Folch, Albert
    [J]. LAB ON A CHIP, 2008, 8 (01) : 34 - 57