New bioimaging avenues for organs‐on‐chips by integration of bioluminescence

The unmet demand for the development of advanced in vitro models that emulate key features of human (patho‐)physiology and organ or tissue functionality led to the emergence of organ‐on‐a‐chip screening platforms. This biomimetic microtechnology enables accurate prediction of human responses, even at the multitissue or organ interaction level. With these advances, the necessity of incorporating biosensing within these platform becomes increasingly evident, to ultimately allow in situ, noninvasive, monitoring of cells, tissues and organs’ behavior. Seamlessly integrated biosensors on‐chip also offer the prospect of uninterrupted and fully automated analysis. The continuous search for biosensors that not only avoid disruptive analyses, but are also highly sensitive and permit instant in situ evaluation, steered further developments of optical biosensors including bioluminescence (BL). BL is particularly suitable to interrogate biological systems at the multiparameter level and it is well matched to address the intrinsic biological systems’ heterogeneity due to its inherent high signal to background ratio, to which the demand of simple measurement equipment can be added. Moreover, BL can be effortlessly integrated into any available organ‐on‐a‐chip platform and provides unique groundbreaking means for online monitoring, at the cellular level, and/or detection of cell secreted/excreted compounds. This review depicts recent advances in biosensors, with particular focus on BL. We highlight current challenges and future directions, aimed at stimulating the application of BL to interface organ‐on‐a‐chip systems, leading to the exponential advancement of both fields.