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We have developed two CMOS devices to demonstrate the use of CMOS technology for neural imaging and interfacing with the aim of studying the functions of the brain at the molecular level. In this work, we discuss the design, packaging, and implementation of a compact, single device imaging system for imaging inside the mouse brain. We show that the device is capable of imaging and measuring fluorophore concentrations down to 1 mum . The packaged device was tested for in vivo fluorescence imaging by imaging the activity of serine protease in the mouse hippocampus. The result shows imaging of neural activity with spatial resolution close to the pixel size of 7.5 mum and less than 300 ms temporal resolution. A second device was developed to image neuronal network activity and to provide a means for electrical interfacing with neurons. Characterization tests show that the device has comparable performance to current tools used in electrophysiological experiments of the brain. This work paves the way for simultaneous imaging and electrophysiological experiments using a single compact and minimally invasive device in the future.