Complementary Metal Oxide Semiconductor Based Multimodal Sensor for In vivo Brain Function Imaging with a Function for Simultaneous Cell Stimulation

Abstract

We have developed a multimodal complementary metal oxide semiconductor (CMOS) sensor device embedded with Au electrodes for fluorescent imaging and cell stimulation in the deep brain of mice. The Au electrodes were placed on the pixel array of the image sensor. Windows over the photodiodes were opened in the electrode area for simultaneous fluorescent imaging and cell stimulation in the same area of the brain tissue. The sensor chip was shaped like a shank and was packaged by two packaging methods for high strength or minimal invasion. The experimental results showed that the 90 Â 90 mm 2 Au electrodes with windows were capable of injecting theta burst stimulation (TBS)-like current pulses at 0.2 -1 mA in a saline solution. We successfully demonstrated that fluorescent imaging and TBS-like current injection can be simultaneously performed in the electrode area of a brain phantom. #

Intravital fluorescence imaging of mouse brain using implantable semiconductor devices and epi-illumination of biological tissue

“…Complementary metal-oxide semiconductor (CMOS) technology enables simple and compact imaging devices for intravital imaging [16][17][18][19]. Imaging devices based on CMOS technology have the following important advantages: (1) Simple device design without optical elements, such as objective lens and relay lens, is mass-producible and feasible for disposable use.…”

“…(2) A compact size of several hundred micrometers means low invasiveness to animals and feasibility for long-term imaging even under freely moving conditions. (3) CMOS technology enables the integration of image data acquisition, compression, logging, analysis, electrical measurement [18], and stimulation [19] on a single chip, and the large-scale integration based on CMOS technology is highly attractive for in situ monitoring and diagnostics of brain diseases as medical applications (e.g. wireless communication, deep brain stimulation, and the brain machine-interface).…”

An all-digital, time-gated 128X128 spad array for on-chip, filter-less fluorescence detection

“…The conventional approach is to use an on-chip optical filter to separate the excitation light from the faint fluorescence signal [2]. However, the limit of detection (LOD) of such on-chip fluorescence detection systems is determined by the nature of the filtering material, such as photoresist-based color filters.…”

Implantable Distributed Biomedical Photonic Devices

“…(4,5) By solving these problems, we have developed a biomedical photonic device that can be implanted in the mouse deep brain and can measure brain activities through the fl uorescence of specifi c neural activities at a spatiotemporal resolution of less than 100 ms and less than 100 µm. (6)(7)(8)(9)(10) The basic confi guration of the device is shown in Fig. 1, in which the device is implanted into the deep brain of a mouse.…”

“…The proposed device is based on a complementary metal-oxide-semiconductor (CMOS) image sensor with a multimodal sensing function, which includes the measurement of neural potentials and the simulation of neuron cells. (9,10) Since CMOS image sensors can be integrated into functional circuits on the chip, such multimodal sensing can be realized. We have successfully demonstrated LTP activities in the mouse hippocampus using a biomedical photonic device.…”