Toward Functional Biointerfaces with Origami‐on‐a‐Chip

Studying the behavior of electroactive cells, such as firing dynamics and chemical secretion, is crucial for developing human disease models and therapeutics. Following the recent advances in cell culture technology, traditional monolayers are optimized to resemble more 3D, organ‐like structures. The biological and electrochemical complexity of these structures requires devices with adaptive shapes and novel features, such as precise electrophysiological mapping and stimulation in the case of brain‐ and heart‐derived tissues. However, conventional organ‐on‐chip platforms often fall short, as they do not recreate the native environment of the cells and lack the functional interfaces necessary for long‐term monitoring. Origami‐on‐a‐chip platforms offer a solution for this problem, as they can flexibly adapt to the structure of the desired biological sample and can be integrated with functional components enabled by chosen materials. In this review, the evolution of origami‐on‐a‐chip biointerfaces is discussed, emphasizing folding stimuli, materials, and critical findings. In the prospects, microfluidic integration, functional tissue engineering scaffolds, and multi‐organoid networks are included, allowing patient‐specific diagnoses and therapies through computational and in vitro disease modeling. In this review, advances are highlighted in origami‐on‐a‐chip platforms based on functional thin films. Unlike conventional 2D cell culturing substrates, these shape‐changing platforms provide 3D microenvironments for multi‐scale biological samples, including neurites, single cells, and organoids. Combined with advances in biocomputing, this helps bring single cell analysis and organoid technology closer to replicating human development and diseases in vitro.