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This paper describes the development of a complementary metal-oxide-semiconductor (CMOS) image sensor for in vitro and in vivo imaging of the hippocampus. The 176 Â 144 pixel array image sensor is designed based on a modified three-transistor active pixel sensor circuit. Flexibility in readout for real-time imaging and wide dynamic range measurement is implemented using analog and digital output. A minimum light intensity detection level of 50 nW/cm 2 has been measured using the image sensor. A novel packaging method is developed to enable both in vitro and in vivo imaging. In this method, a color filter is applied onto the image sensor that selectively blocks excitation light transmittance to below À44 dB. The packaged device thickness measuring 350 mm, limits tissue damage during invasive imaging. Using the device, static images of the mouse brain slice and real time imaging of the hippocampus of a mouse are successfully demonstrated for the first time.

We have designed and fabricated a 176×144-pixels (QCIF) CMOS image sensor for on-chip bio-fluorescence imaging of the mouse brain. In our approach, a single CMOS image sensor chip without additional optics is used. This enables imaging at arbitrary depths into the brain; a clear advantage compared to existing optical microscopy methods. Packaging of the chip represents a challenge for in vivo imaging. We developed a novel packaging process whereby an excitation filter is applied onto the sensor. This eliminates the use of a filter cube found in conventional fluorescence microscopes. The fully packaged chip is about 350 µm thick. Using the device, we demonstrated in vitro on-chip fluorescence imaging of a 400 µm thick mouse brain slice detailing the hippocampus. The image obtained compares favorably to the image captured by conventional microscopes in terms of image resolution. In order to study imaging in vivo, we also developed a phantom media. In situ fluorophore measurement shows that detection through the turbid medium of up to 1 mm thickness is possible. We have successfully demonstrated imaging deep into the hippocampal region of the mouse brain where quantitative fluorometric measurements was made. This work is expected to lead to a promising new tool for imaging the brain in vivo.

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