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

Abstract

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) innerfilling 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.

Why ammonium detection is particularly challenging but insightful with ionophore-based potentiometric sensors – an overview of the progress in the last 20 years

“…For ionophores with log P octanol/water < 6, leaching is generally expected after 2-3 days from the prepared membrane under common storage conditions (e.g., millimolar concentrations of the primary ion). 73 In the case of nonactin, log P octanol/water = 5.8, 74 thereby representing a limitation on the lifetime of nonactin-based ISEs.…”

Real-time particle-by-particle detection of erythrocyte-camouflaged microsensor with extended circulation time in the bloodstream

“…This type of sensor has been used previously, and no apparent toxicity was noted (73). However, it is conceivable that there may be specific organ toxicity that would arise from a systemic injection and subsequent collection in the liver.…”

Solid-Contact Ion-Selective Electrodes: Response Mechanisms, Transducer Materials and Wearable Sensors

“…Development of new ISM membrane or making transducer with ion selectivity are plausible. (4) The biocompatibility of SC transducer and the ISM should be focused upon [101,102]. The ISM component, like the valinomycin for K + ionophore, is a neurotoxin.…”