Integrated Micro-Optical System Revolutionizes Tissue Monitoring

Microphysiological systems and organ-on-chip technologies are increasingly used to model human tissues outside the body, offering alternatives to animal experiments and traditional cell cultures. However, monitoring biological activity within these systems remains challenging. Conventional fluorescence imaging typically relies on large microscopes positioned far from the tissue, limiting continuous observation, scalability, and long-term measurements. In addition, repeated handling and transfers can disrupt physiological conditions and introduce variability. Although fluorescence is a powerful and widely used sensing method, its integration into compact, on-chip platforms has been constrained by the size of optical components and limited system integration. Based on these challenges, there is a clear need to develop deeply integrated, miniaturized fluorescence monitoring systems for continuous in situ measurements.

Researchers from KTH Royal Institute of Technology and Karolinska Institutet reported (DOI: 10.1038/s41378-025-01073-4) on November 12, 2025, in Microsystems & Nanoengineering the development of a fully integrated microoptical system designed for continuous fluorescence monitoring of living microtissues. The study demonstrates how the chip-scale platform can be combined with microphysiological systems to track functional activity in three-dimensional tissues over hours. By validating the system using pancreatic islet models, the team shows that complex cellular dynamics can be monitored in real time without relying on bulky external optical instruments.

The newly developed system integrates all essential optical components-including a micro light-emitting diode, a photodetector, optical filters, and a custom-designed light guide-into a compact structure measuring approximately 1 mm². A microcage physically stabilizes the tissue while maintaining a physiologically relevant environment, allowing light to excite fluorescent signals and collect emissions in close proximity. This design minimizes signal loss and enables stable, long-term measurements directly on chip.

To demonstrate performance, the researchers monitored pancreatic islets engineered to express a calcium-sensitive fluorescent indicator. Calcium oscillations within these islets reflect functional activity related to insulin secretion. The system successfully recorded rhythmic calcium signals for over two hours, capturing both slow oscillations and rapid responses to chemical stimulation. Importantly, the platform achieved clear signal separation between excitation and emission wavelengths, reducing background noise and phototoxicity.

Compared with traditional fluorescence microscopy, the integrated system offers comparable functional readouts while eliminating the need for bulky optics and manual alignment. Its small footprint also allows multiple sensors to be deployed in parallel, opening the door to scalable, high-throughput experiments and multi-organ monitoring within interconnected chip platforms.

"This work shows that advanced biological monitoring no longer needs to rely on large external instruments," said the study's senior researchers. "By bringing fluorescence excitation and detection directly next to the tissue, we can observe living systems continuously and with minimal disturbance. This approach makes long-term functional studies more practical and reproducible, particularly for complex microtissues. It also creates new opportunities for integrating sensing technologies into organ-on-chip models that better reflect real physiological conditions."

The integrated microoptical system offers broad potential for biomedical research and drug development. Continuous, in situ monitoring of tissue function could improve studies of chronic diseases, drug toxicity, and treatment efficacy by capturing slow or subtle biological changes that are often missed in snapshot experiments. Beyond pancreatic islets, the platform could be adapted for cardiac, neural, or other organoid models, supporting multi-organ interaction studies. Its compact and modular design also makes it suitable for high-throughput screening and automated analysis. Ultimately, this technology advances organ-on-chip platforms toward more precise, scalable, and physiologically relevant tools for studying human health and disease.