Real time in vivo imaging and measurement of serine protease activity in the mouse hippocampus using a dedicated complementary metal-oxide semiconductor imaging device.
The aim of the present study is to demonstrate the application of complementary metal-oxide semiconductor (CMOS) imaging technology for studying the mouse brain. By using a dedicated CMOS image sensor, we have successfully imaged and measured brain serine protease activity in vivo, in real-time, and for an extended period of time. We have developed a biofluorescence imaging device by packaging the CMOS image sensor which enabled on-chip imaging configuration. In this configuration, no optics are required whereby an excitation filter is applied onto the sensor to replace the filter cube block found in conventional fluorescence microscopes. The fully packaged device measures 350 microm thick x 2.7 mm wide, consists of an array of 176 x 144 pixels, and is small enough for measurement inside a single hemisphere of the mouse brain, while still providing sufficient imaging resolution. In the experiment, intraperitoneally injected kainic acid induced upregulation of serine protease activity in the brain. These events were captured in real time by imaging and measuring the fluorescence from a fluorogenic substrate that detected this activity. The entire device, which weighs less than 1% of the body weight of the mouse, holds promise for studying freely moving animals.
Graduate School of Materials Science, Nara Institute of Science and Technology, 8916-5 Takayama, Ikoma, Nara 630-0192, Japan.
David C
DC
Ng
Hideki
H
Tamura
Takashi
T
Tokuda
Akio
A
Yamamoto
Masamichi
M
Matsuo
Masahiro
M
Nunoshita
Yasuyuki
Y
Ishikawa
Sadao
S
Shiosaka
Jun
J
Ohta
D000818:Animals; D003952:Diagnostic Imaging / Q000295:instrumentation*; D004790:Enzyme Induction / Q000187:drug effects; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005453:Fluorescence; D006624:Hippocampus / Q000201:enzymology*; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D051379:Mice; D008856:Microscopy, Fluorescence; D009473:Neuronal Plasticity / Q000502:physiology; D012666:Semiconductors; D012697:Serine Endopeptidases / Q000096:biosynthesis / Q000378:metabolism*
D018690:Excitatory Amino Acid Agonists; D012697:Serine Endopeptidases; D007608:Kainic Acid