Organic transistor platform with integrated microfluidics for in-line multi-parametric in vitro cell monitoring

被引:71
作者
Curto, Vincenzo F. [1 ]
Marchiori, Bastien [1 ,2 ]
Hama, Adel [1 ]
Pappa, Anna-Maria [1 ]
Ferro, Magali P. [1 ]
Braendlein, Marcel [1 ]
Rivnay, Jonathan [1 ,3 ]
Fiocchi, Michel [1 ]
Malliaras, George G. [1 ]
Ramuz, Marc [2 ]
Owens, Roisin M. [1 ]
机构
[1] Ecole Natl Super Mines, Dept Bioelect, CMP EMSE, MOC, 880 Ave Mimet, F-13541 Gardanne, France
[2] Ecole Natl Super Mines, Flexible Elect Dept, CMP EMSE, MOC, 880 Ave Mimet, F-13541 Gardanne, France
[3] Northwestern Univ, Dept Biomed Engn, Evanston, IL 60208 USA
来源
MICROSYSTEMS & NANOENGINEERING | 2017年 / 3卷
关键词
bioelectronics; in-line sensors; in vitro; microfluidics; ON-A-CHIP; PROXIMAL TUBULE; ELECTROCHEMICAL TRANSISTOR; MODEL; CULTURE; COCULTURE; IMPEDANCE; BIOLOGY; LIVER; SKIN;
D O I
10.1038/micronano.2017.28
中图分类号
TB3 [工程材料学];
学科分类号
0805 ; 080502 ;
摘要
Future drug discovery and toxicology testing could benefit significantly from more predictive and multi-parametric readouts from in vitro models. Despite the recent advances in the field of microfluidics, and more recently organ-on-a-chip technology, there is still a high demand for real-time monitoring systems that can be readily embedded with microfluidics. In addition, multi-parametric monitoring is essential to improve the predictive quality of the data used to inform clinical studies that follow. Here we present a microfluidic platform integrated with in-line electronic sensors based on the organic electrochemical transistor. Our goals are twofold, first to generate a platform to host cells in a more physiologically relevant environment (using physiologically relevant fluid shear stress (FSS)) and second to show efficient integration of multiple different methods for assessing cell morphology, differentiation, and integrity. These include optical imaging, impedance monitoring, metabolite sensing, and a wound-healing assay. We illustrate the versatility of this multi-parametric monitoring in giving us increased confidence to validate the improved differentiation of cells toward a physiological profile under FSS, thus yielding more accurate data when used to assess the effect of drugs or toxins. Overall, this platform will enable high-content screening for in vitro drug discovery and toxicology testing and bridges the existing gap in the integration of in-line sensors in microfluidic devices.
引用
收藏
页数:12
相关论文
共 63 条
  • [1] Pumpless microfluidic platform for drug testing on human skin equivalents
    Abaci, Hasan Erbil
    Gledhill, Karl
    Guo, Zongyou
    Christiano, Angela M.
    Shuler, Michael L.
    [J]. LAB ON A CHIP, 2015, 15 (03) : 882 - 888
  • [2] Pluripotent stem cells in disease modelling and drug discovery
    Avior, Yishai
    Sagi, Ido
    Benvenisty, Nissim
    [J]. NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2016, 17 (03) : 170 - 182
  • [3] Impedance-based cell monitoring: Barrier properties and beyond
    Benson K.
    Cramer S.
    Galla H.-J.
    [J]. Fluids and Barriers of the CNS, 10 (1)
  • [4] Microfluidic organs-on-chips
    Bhatia, Sangeeta N.
    Ingber, Donald E.
    [J]. NATURE BIOTECHNOLOGY, 2014, 32 (08) : 760 - 772
  • [5] Characterization of a microfluidic in vitro model of the blood-brain barrier (μBBB)
    Booth, Ross
    Kim, Hanseup
    [J]. LAB ON A CHIP, 2012, 12 (10) : 1784 - 1792
  • [6] Lactate Detection in Tumor Cell Cultures Using Organic Transistor Circuits
    Braendlein, Marcel
    Pappa, Anna-Maria
    Ferro, Marc
    Lopresti, Alexia
    Acquaviva, Claire
    Mamessier, Emilie
    Malliaras, George G.
    Owens, Roisin M.
    [J]. ADVANCED MATERIALS, 2017, 29 (13)
  • [7] Three-dimensional cell culture: the missing link in drug discovery
    Breslin, Susan
    O'Driscoll, Lorraine
    [J]. DRUG DISCOVERY TODAY, 2013, 18 (5-6) : 240 - 249
  • [8] Molecular Model of the Microvillar Cytoskeleton and Organization of the Brush Border
    Brown, Jeffrey W.
    McKnight, C. James
    [J]. PLOS ONE, 2010, 5 (02):
  • [9] CYTOCHALASIN-D INHIBITS ACTIN POLYMERIZATION AND INDUCES DEPOLYMERIZATION OF ACTIN-FILAMENTS FORMED DURING PLATELET SHAPE CHANGE
    CASELLA, JF
    FLANAGAN, MD
    LIN, S
    [J]. NATURE, 1981, 293 (5830) : 302 - 305
  • [10] Real-time sweat pH monitoring based on a wearable chemical barcode micro-fluidic platform incorporating ionic liquids
    Curto, Vincenzo F.
    Fay, Cormac
    Coyle, Shirley
    Byrne, Robert
    O'Toole, Corinne
    Barry, Caroline
    Hughes, Sarah
    Moyna, Niall
    Diamond, Dermot
    Benito-Lopez, Fernando
    [J]. SENSORS AND ACTUATORS B-CHEMICAL, 2012, 171 : 1327 - 1334