2, Università di Bologna, Bologna, , Italy
In recent years three dimensional cell culture systems have witnessed rapid expansion in the fields of tissue engineering and drug testing due to their ability to reproduce with more accuracy in-vivo cell microenvironments1. Among the available models, the use of scaffold-free techniques for the formation of 3D cell constructs like spheroids or organoids has greatly advanced. Thanks to the ability of cells to secrete their own extracellular matrix and to self-organize into stable structure, organoids are now widely used to mimic several tissues such as cardiac, liver and neural tissue. Despite the push towards the use of spheroids for high-throughput toxicology and drug discovery assays, there is a definite gap in terms of available technologies for on-line monitoring of spheroids. Here we show the development of a sensing platform for the dynamic impedance monitoring of micro-tissue spheroids. Progressing from previous work where we coupled an organic electrochemical transistor (OECT) with spheroids trapped in a microcapillary2, this couples the transistor with a PDMS microfluidic trap in order to assess spheroid integrity over-time. We propose a new fabrication strategy for both the OECT and the circular-shape microtrap to achieve the optimal performance for our organic impedance sensor. We have tested the validity of our device by sensing both mono- and co-culture spheroids, demonstrating the ability of the platform to discriminate spheroids based on the difference in cell number and cell type. Dynamic toxicological assays were also performed using the porogenic agent Triton X-100. Among techniques used for spheroids characterization the impedance-based system present the advantage to dynamically detect morphological changes in a label-free and minimally invasive manner.
1. Edmondson, R., Broglie, J. J., Adcock, A. F. & Yang, L. Three-Dimensional Cell Culture Systems and Their Applications in Drug Discovery and Cell-Based Biosensors. ASSAY Drug Dev. Technol. 12, 207–218 (2014).
2. Huerta, M., Rivnay, J., Ramuz, M., Hama, A. & Owens, R. M. Research Update: Electrical monitoring of cysts using organic electrochemical transistors a. APL Mater. 3, 030701 (2015).