Ординатура / Офтальмология / Английские материалы / Artificial Sight Basic Research, Biomedical Engineering, and Clinical Advances_Humayun, Weiland, Chader_2007

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Figure 8.8. Fabrication process of stacked bump electrodes (a) and SEM of the stacked bump electrode (b).

chip, enabling close contact with retinal cells. In order to construct this jutting Pt electrode, we have formed the stacked bump in two steps, in which a gold bump is initially formed, on top of which the Pt bump is formed. The gold bump acts as a cushion for the hard Pt bump. Direct formation of the Pt bump sometimes breaks the LSI I/O pad; I/O pad is usually formed on an Si substrate and insulators such as silicon dioxide and silicon nitride films are sandwiched in between.

After the fabrication of the stacked Pt/Au bump, the entire LSI chip, including bonding wires, is covered with a biocompatible epoxy resin. Finally, the resin on top of the electrodes is completely removed using a high-power Ar ion laser, and thus the entire LSI chip except for the top of the Pt electrodes is covered with resin. Parylene coating can be additionally applied to the resin to ensure durability in the biological environment and can be removed by Ar ion laser.

Figure 8.8b shows a scanning electron micrograph (SEM) of the stacked Pt/Au bump electrode. The diameter of the structure is approximately 100 m and can be controlled by changing the Au and Pt wire diameter. Note that

other biocompatible and efficient materials such as TiN and IrOx can be deposited on top of the Pt electrode.

In Vitro Electrophysiological Experiment Using

the PFM Photosensor

In order to verify the operation of the PFM photosensor chip, we have conducted in vitro experiments using detached bullfrog retinas. The chip acts as a stimulator that is controlled by input light intensity as is the case in photoreceptor cells. A current source and pulse shape circuits are integrated onto the chip. The details have been reported in [11]. The Pt/Au stacked bump electrode and chip molding processes were performed as described in the previous section. Before molding, the chip was bonded onto a printed circuit board for handling. A reservoir of Ringer solution was placed surrounding the chip.

A piece of the bullfrog retina was placed, with the retinal ganglion cell (RGC) side face up, on the surface of the packaged chip. Figure 8.9 shows the experimental setup. Electrical stimulation was performed using the chip at a selected single pixel. A tungsten counter electrode with a tip diameter of 5 m was placed on the retina, producing a transretinal current between the counter electrode and the chip electrode. A cathodic-first biphasic current pulse was used as the stimulation [20]. The pulse parameter is described in the inset of Figure 8.10a. Note that near-infrared (NIR) light does not excite the retinal cells, but does excite the PFM photosensor cells. A typical response curve is shown in Figure 8.10a. The arrow indicates the response from a RGC. Figure 8.10b demonstrates the experimental results of evoking retinal cells with the PFM photosensor, which is illuminated by input NIR light. We have confirmed that the firing rate increases in proportion to the input NIR light intensity. This demonstrates that the PFM photosensor activates the retinal cells through the input of NIR light, and suggests that it can be applied to human retinal prostheses. Details of the experimental setup are given in [11].

Figure 8.9. Experimental setup for in vitro stimulation of detached frog retina with the PFM photosensor. Reprinted from Ref. [11] with permission from Elsevier.

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Figure 8.10. Experimental results of evoking retinal cells with the PFM photosensor. Response data (a) and firing rate as a function of input light intensity (b). Reprinted from Ref. [11] with permission from Elsevier.

Implantation of LSI-based Retinal Prosthesis Devices

In the previous sections, we have demonstrated the possibility of application of the PFM photosensor in subretinal stimulation. In this section, we focus on the implantation of the LSI-based device into the eye. Using the packaging and electrode technologies described in the previous sections, a thin Si dummy chip with bump electrodes was implanted on the suprachoroid+ of a rabbit. A 3-mm- wide and 4-mm-long chip was mounted on a polyimide substrate. Although the chip was successfully implanted, such a thin LSI chip must be handled very carefully. Another issue is how bending affects the device characteristics [5].

In order to overcome the issue of mechanical rigidity and realize a feasible LSI-based device, we have proposed a device architecture consisting of small microchips that work under a single set of control signals [8–10]. Figure 8.11 shows the concept of the proposed smart distributed stimulator. The array consists of a number of LSI-based microchips, each of which is approximately 500- m square in size. Each microchip has several Pt-/Au-stacked bump electrodes and is covered by the process described in a previous section. The detailed fabrication process is described in [10].

In order to implant the device smoothly, the thickness of the device must be as thin as possible. The proposed device has a thickness of approximately 200 m, which is acceptable. A microchip-based stimulator is fabricated in order to demonstrate proof-of-concept. The microchips are dummy Si chips with Pt/Au bumps. The entire image of the stimulator with Pt wires covered with silicone tubing is shown in Figure 8.12a. The width of the stimulator is approximately 3 mm.

The device was implanted into a pocket that was made in the sclera of a rabbit eye to stimulate retinal cells by the STS method. Figure 8.12b shows the

Figure 8.11. The concept and structure of the distributed microchip-based stimulator. Reprinted from Ref. [10] with permission from Elsevier.

extracted rabbit eye into which the device was implanted in 2 weeks. The device is bent along the eye curvature. The short-time stimulation experiment, in which only the small change of electrically evoked potentials (EEPs) was observed between the first and last stages of the implantation, demonstrate that the device can work properly during the implantation.

In the next step, we develop an advanced architecture of the distributed microchip-based stimulator device. In this device, the microchips are connected to each other via two wires, not including the power supply lines, and are placed on a flexible polyimide substrate. The features of the device are as follows. First, the device is thin and flexible so that it can contact neural cells more closely when implanted, and thus is suitable for simulating neural cells. Second, the introduction of LSI to the microchip makes it possible to introduce, for example, a PFM photosensor. This provides the device with high performance and versatility. In addition, the LSI reduces the number of input/output pads needed in the device. Apart from the power supply lines, only two signal lines of stimulation/record and control are required. The control line operates the entire set of microchips. Each microchip includes enough circuitry to decode the control signal. Third, the device can be connected to another device. Such a daisy chain could combine a large number of electrodes, e.g. over 1000 electrodes.

four I/O pads for addressing (ADDRESS) and stimulation/record (STIM/REC) and four pads for power supply (VDD and GND), as shown in Figure 8.13a. Note that each microchip relays ADDRESS and STIM/REC lines in the vertical direction and VDD and GND lines in the horizontal direction, as shown in Figure 8.13. This wiring architecture reduces the wiring area on the substrate.

We use a broadcast topology to assign one electrode to be activated. This consumes only a small area of circuitry, sufficiently small for the size of the microchip. An external controller broadcasts a control signal to all of the microchips. Each microchip has its own identification (ID). The microchip has an 8-bit asynchronous counter as an address buffer. The addressing counter counts the digital pulses applied to the ADDRESS line, and the microchip interprets the value in the counter as the address of the selected electrode. The upper 4 bits and the lower 4 bits represent the addresses of the selected chip and the selected electrode, respectively. Only the selected electrode on the selected chip is connected to the STIM/REC line. Once selected, the neural stimulation/recording can be activated at the selected electrode via the STIM/REC line. Figure 8.14

Figure 8.14. Experimental result of the distributed microchip-based stimulator device under the saline environment (a) testing board, (b) experimental results.

to effectively apply the PFM photosensor to the stimulation of retinal cells, we modified the original PFM photosensor. The output was converted into biphasic current pulse and the photosensitivity was variable. These features can be easily introduced thanks to the nature of the PFM photosensor, which is compatible with logic circuits. The PFM photosensor has been applied to the stimulation of detached retinas from a frog eye. In vitro electrophysiological experiments demonstrated that the PFM photosensor evokes retinal cells under the illumination of IR light. Finally, we proposed a distributed microchip-based stimulator device that can be bent easily and can realize a large number of electrodes. The short-time implantation via the STS method was performed using the proposed implantation device and showed that the device can stimulate retinal cells. Further development is required for applying the device to clinical implantation.

Acknowledgments. The authors would like to thank Professor Tetsuya Yagi for valuable advices on the electrophysiological experiments, and Dr. Shigeru Nishimura and Naoko Tsunematsu for their continuous encouragement and valuable discussion. The authors also would like to thank Dr. Uehara of Nidek and Dr. Furumiya of NAIST for the experimental data used here. This work was supported by the New Energy Development Organization (NEDO) of Japan “Artificial Vision System” Project and Health and Labor Sciences Research Grants, Japan.

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