Multimodal Complementary Metal–Oxide–Semiconductor Sensor Device for Imaging of Fluorescence and Electrical Potential in Deep Brain of Mouse

Abstract

We have developed a multimodal complementary metal-oxide-semiconductor (CMOS) sensor device for observing neural activities in the deep brain of a mouse. The CMOS sensor includes an image sensor, electrodes, and a light-emitting diode (LED). The image sensor was designed to be operated using only four inputs/outputs (I/Os) to reduce the number of connecting wires. The electrodes were placed on the pixel array of the sensor. Windows were opened in the electrode over the photodiodes to enable the fluorescence to be imaged using the pixels under the electrodes. An LED was mounted on the chip. The sensor chip was shaped like a shank to facilitate smooth insertion into the brain tissue. The entire device was coated with a parylene layer to make it biocompatible. The experimental results showed that the green fluorescent beads on the pixel array were successfully imaged using the LED on the chip as a light source. In a brain phantom, the change in the electrical potential was successfully sensed by the electrode, and green fluorescent beads were simultaneously imaged using the pixels under the electrode. We also demonstrated that the CMOS sensor device could successfully operate in the hippocampal area of an anesthetized mouse.

Implantable CMOS Imaging Devices

“…To overcome this difficulty, three types of imaging devices have been developed: a fiber endoscope [25][26][27][28][29], a head-mountable device [28][29][30], and a brain-implantable device [31][32][33][34][35][36], as shown in Figure 10.20. In the following sections, these devices are introduced, and the brain-implantable device is described in detail.…”

“…In order to address this issue, an implantable CMOS imaging device has been proposed and demonstrated. This device has a submillimeter/sub-second spatiotemporal resolution and has successfully been used to monitor the time course of serine protease activity inside a mouse hippocampus [31][32][33][34][35][36]. In the next section, the brain-implantable CMOS imaging device is discussed.…”

CMOS Imaging Devices for Biomedical Applications

“…We have developed a CMOS-based bmp-LSI imaging device with a sub-millimeter/sub-second spatiotemporal resolution and have successfully demonstrated monitoring of the time course of serine protease activities inside the mouse hippocampus [10]- [13].…”

“…The pixel structure is a three-transistor type active pixel sensor (APS) with a parasitic photodiode composed of n-wells and p-substrate junctions. The number of input/outputs is limited to four in order to minimize the constraint of the implanted animals by the external wires [13]. The pixel size was designed to be 7.5 × 7.5 µm 2 , which is sufficient to image neural cells with sizes of approximately 10 to 50 µm, because spatial resolution is directly related to pixel size.…”

Development of a local light stimulation device integrated with micro electrode array

“…Fabrication method for tiny electrodes and electrode pads is also developed (Green, 2010;Yand, 2005;Gao, 2013). A probe-formed MEMS device is also integrated with LED or light guide for stimulating inside of the brain (Tagawa, 2010;Wu, 2013). However, this kind of devices stimulates multitude neurons because of light disperse.…”