Cytotoxicity Study of Ionophore-Based Membranes: Toward On- Body and in Vivo Ion Sensing

We present the most complete study to date comprising in vitro
cytotoxicity tests of ion-selective membranes (ISMs) in terms of cell viability,
proliferation, and adhesion assays with human dermal fibroblasts. ISMs were prepared
with different types of plasticizers and ionophores to be tested in combination with
assays that focus on the medium-term and long-term leaching of compounds.
Furthermore, the ISMs were prepared in different configurations considering (i) inner-
filling solution-type electrodes, (ii) all-solid-state electrodes based on a conventional
drop-cast of the membrane, (iii) peeling after the preparation of a wearable sensor, and
(iv) detachment from a microneedle-based sensor, thus covering a wide range of
membrane shapes. One of the aims of this study, other than the demonstration of the
biocompatibility of various ISMs and materials tested herein, is to create an awareness
in the scientific community surrounding the need to perform biocompatibility assays
during the very first steps of any sensor development with an intended biomedical
application. This will foster meeting the requirements for subsequent on-body application of the sensor and avoiding further problems during massive validations toward the final in vivo use and commercialization of such devices.