6 February 2006 In vitro and in vivo on-chip biofluorescence imaging using a CMOS image sensor
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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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David C. Ng, David C. Ng, Masamichi Matsuo, Masamichi Matsuo, Takashi Tokuda, Takashi Tokuda, Keiichiro Kagawa, Keiichiro Kagawa, Masahiro Nunoshita, Masahiro Nunoshita, Jun Ohta, Jun Ohta, } "In vitro and in vivo on-chip biofluorescence imaging using a CMOS image sensor", Proc. SPIE 6068, Sensors, Cameras, and Systems for Scientific/Industrial Applications VII, 606801 (6 February 2006); doi: 10.1117/12.642591; https://doi.org/10.1117/12.642591

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