A Complementary Metal–Oxide–Semiconductor Image Sensor for On-Chip in Vitro and in Vivo Imaging of the Mouse Hippocampus

Abstract

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.

Real time in vivo imaging and measurement of serine protease activity in the mouse hippocampus using a dedicated complementary metal-oxide semiconductor imaging device

“…It was used to image internally inside the mouse brain (Ng et al, 2006b). Also, using a model reaction inside a brain tissue phantom, we have demonstrated the possibility of biofluorescence measurement in vivo (Ng et al, 2006a).…”

Implantable optogenetic device with CMOS IC technology for simultaneous optical measurement and stimulation

“…[7][8][9] This method is based on CMOS IC technology. [10][11][12][13][14] In this study, we have developed an implantable optogenetic device based on a previously described device for cell culture experiments. 15) The device is integrated with a CMOS image sensor for brain functional imaging and a multi-LED array for optical stimulation in a miniaturized flexible sub-strate.…”

Intrinsic signal imaging of brain function using a small implantable CMOS imaging device

“…To alleviate these problems, we developed a small implantable CMOS imaging device in our previous work. [13][14][15][16][17][18][19][20] For this device, we designed a dedicated image sensor in the 0.35 µm CMOS technology. This device can be fully implanted by introducing contact imaging, which needs no bulky optics such as an objective lens.…”