Biosensor-based approaches: Exploring hapten-protein interactions for the prediction of skin sensitisation

Assays to predict the skin sensitisation potential of substances commonly address the molecular initiating event (MIE) of the adverse outcome pathway (AOP), which is the covalent binding of chemicals to proteins. This represents the first key event in the pathway. In chemico approaches have emerged as validated alternatives to conventional animal testing methods to determine this process. This review explores the integration of biosensor-based approaches to supplement other in chemico methods, for use as alternatives to the 'gold standard' Local Lymph Node Assay (LLNA) in skin sensitisation testing. While surface plasmon resonance-based biosensors have shown promise, they exhibit limitations such as poor sensitivity. To overcome such limitations, this review highlights the use of impedance-based biosensors in the study of hapten-skin protein interactions, which are associated with the MIE in skin sensitisation. Impedance-based biosensors have exhibited impressive performance, with a specificity of 97%, a sensitivity of 83% and an accuracy of 92% being obtained in one study (N = 49 substances). The advantages of impedance-based biosensors include label-free methodologies, high sensitivity, low cost and operational simplicity. This review also covers recent advancements in the use of biosensors in cosmetic studies and skin research, as well as comparisons of the limitations of the various in chemico methods and future perspectives for skin sensitisation assessment. The use of impedance-based biosensors as part of integrated testing approaches alongside other in chemico testing methods, can represent a reliable approach for skin sensitisation assessment, while supporting the reduction and replacement of animal use in toxicity testing.