Development of a Fully Integrated Complementary Metal–Oxide–Semiconductor Image Sensor-Based Device for Real-Time In vivo Fluorescence Imaging inside the Mouse Hippocampus

In our previous work, we demonstrated the potential of a complementary metal-ox i de-semi conductor (CMOS) imaging device for use in imaging of the mouse brain. We showed that the device is capable of detecting fluorescence signal inside the mouse brain and successfully imaged real-time protease activity inside the hippocampus. In this work, we have improved the imaging device by integrating an excitation light source in the form of an ultraviolet light-emitting diode chip and an injection needle onto the sensor chip. This results in a compact single device imaging system for minimal invasive imaging inside the mouse brain. Also experimental repeatability is improved which enabled us to successful perform calibration of fluorophore concentration using the device. Fluorescence imaging experiments inside the brain phantom as well as in the mouse brain show that the device is capable of real time fluorescence detection. Using the device, we found that diffusion rate of chemical injected into the brain is smaller than 10 pmol/min. This work is expected to lead to the successful use of a CMOS imaging device for the study of the functions of the brain.