Ординатура / Офтальмология / Английские материалы / Artificial Sight Basic Research, Biomedical Engineering, and Clinical Advances_Humayun, Weiland, Chader_2007
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Figure 9.10. Serial to parallel converter.
Figure 9.11. (a) DACC with bridge to generate biphasic current. (b) Regulated cascade current sink.
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data conversion technique. We are to generate 600 A current at 10 K load from 8-bit pixel. It is very important that the output current is linear with the pixel value to produce the linear gray level in the retina and at the same time the supply voltage requirement does not go up. Unlike some other designs [1, 5, 6], our DACC is capable of delivering 600 A current at 10 K load linearly for the full range of the pixel. We designed our DACC using regulated cascade current sink (RCCS) (Figure 9.11b). RCCS uses negative feedback to stabilize the output current and increases the output impedance. We checked our design for different voltages and found that it is capable of delivering our required current linearly at 7 V power supply (Figure 9.13). The loading affect on output current is shown in Figure 9.12 for 5 V power supply. From the plot, we see that if we limit supply voltage to 5 V then our DACC is able to supply 600 A at 7 5 K instead of 10 K . It is possible to reduce the load resistance from 10 K by bringing the reference electrode closer to the stimulating electrode. The resolution of the DACC is 2 5 A. To generate biphasic waveform, usually one requires midpoint of power supply and use of PMOSs and NMOSs together. Our DACC uses only NMOSs, and we do not need midpoint of supply voltage. A bridge circuit consisting of four transmission gates is incorporated with anodic control voltage P and
cathodic control voltage |
N . By controlling voltages P and N the anodic |
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and cathodic pulses are |
generated. The linearity problem that arises with |
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the use of |
PMOS and NMOS together is eliminated by using only NMOS |
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transistors, |
which is essential for biphasic charge-balance current stimulation |
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(Figure 9.3).
Figure 9.12. Output current generated by 8-bit pixel.
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Figure 9.13. Loading effect on current.
Biphasic Current Controller (BCC)
As mentioned earlier, the width and interphase delay of biphasic current waveform depend on the degree of a patient’s retinal damage. This will be ascertained by the doctor through clinical experiments on each patient. To generate biphasic current waveform of variable width and interphase delay, we have designed BCC (Figure 9.14). It is designed to control the widths of anodic and cathodic pulses and interphase delay independently. The first block of BCC controls P, the second ensures interphase delay, and the third controls N . Each block is composed of three T Flip-Flops (TFF) connected as threestage synchronous binary counter with three parallel inputs P0, P1, and P2. By programming 9 bits of the three blocks, the variable widths and interface delay are generated. When RST is asserted low, each block is loaded with P0, P1, and P2. Binary counter can count up to 7 from 0 or any number programmed by P0, P1, and P2. On reaching count 7, RC becomes high, which is fed back to the input of a1 after inversion blocking the toggle of TFFs and locking the counter state. On reset P is set high and N low. After the set time of anodic width, P is reset triggering interphase delay. On expiry of interphase delay, N is set high enabling cathodic pulse, which is reset after the set period of time of cathodic width. The beauty of the circuit is that we can generate only anodic or cathodic pulse by setting the other to zero or biphasic pulse without delay by setting interphase delay to zero. For longer width or delay the counter should be set to lower value. This is because the width or delay is the difference between the set value and 7.
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Figure 9.14. (a) Biphasic current control circuit, (b) T Flip-Flop.
Retinal Stimulator
The design of a 32 × 32 array RS is shown in Figure 9.15a. P11-P3232 is the probe matrix and DFF1-DFF64 is the decoder. It has six I/Os (SIG, BDY, PCK, SYN, VDD, and VSS). Figure 9.15b shows the structure of a probe. When the chip is fabricated, the entire top layer (metal-3) is covered with glass. But for creating contact with the neurons, we left an opening of 7 8 m × 7 8 m on the metal-3 layer for each probe. Microelectrodes are grown on this opening to reduce the contact resistance with the neurons. Each probe is controlled by two NPN transistors connected in series. These two transistors are again controlled by the decoder. Control of these two transistors helped us reduce the number of DFFs required for decoder significantly. To turn any particular probe on, we are to apply control voltages to both the transistors. At any particular time, only one probe is turned on. Inputs of all the probes are connected together and
Figure 9.15. (a) Design of 32 × 32 array RS, (b) structure of a probe.
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marked as SIG. This common bus carries the time-multiplexed signals of all the probes. PCK is the clock for DFF1 to DFF32 connected in a ring, while Q of DFF32 is the clock for DFF33 to DFF64 connected in another ring. DFF1 and DFF33 are designed with set input, while the rest with reset input. When SYN is made low, DFF1 and DFF33 are set and the rest of the DFFs are cleared selecting probe P0101 and initiating the stimulation process beginning with P0101. With the rising edge of next clock cycle P0102 is selected, and so on till the 32nd clock cycle. At the rising edge of 33rd clock cycle, Q of DFF32 switches from low to high clocking row decoder. With that, 2nd row is selected and stimulation proceeds with P0201, P0202, etc. This pattern goes on till the end of 32nd row and 32nd column. So we see the stimulation progresses from left to right and from top to bottom of the array and it progresses with the rising edge of the clock. Each probe is sequentially selected at each rising edge of clock resetting the previous one. After the 32 × 32nd clock cycle, SYN is made low again to force the decoder to point to the beginning of the array for synchronization. For retinal stimulation, data is sent in multiplexed fashion. Upon sending the SYN pulse, the first data corresponding to P0101 is sent, followed by P0102, in sequence from left to right and from top to bottom of the array. For retinal response monitoring, the multiplexed signal is decoded. Upon sending the SYN pulse, the first decoded data corresponds to P0101, followed by P0102, etc. in the same sequence as in stimulation.
Experimental Results
Figure 9.16 shows the microscopic view of 32 × 32 array RS fabricated using 0.5 m CMOS technology. For testing, RS is fabricated without package, and tested by microtest probes under microscope. We have also fabricated it in package specially designed for testing. Typical 10 K neural impedance is used as load. Test result of RS as a stimulator is presented in Figure 9.17a. We have presented here the output of probes P0201, P0202, and P0203 only. These three probes are consecutive probes. We have excited them by biphasic waveforms. Their stimulations are one cycle apart. The result shows that each probe was excited for the duration of one clock cycle by the biphasic waveform. We have tested it for other experimental waveforms and found that it stimulates the neurons as expected. This means that RS is capable of stimulating the neurons sequentially by any kind of analog waveforms.
The RS has also been tested as reader (Figure 9.17b). In this test, we have applied 0.5 V AC signals of different frequencies to the probes simultaneously and monitored the output on output signal (SIG) line. Here we have presented the result for probes P0201 and P0202. P0201 was excited by 1 KHz sinusoidal signal and P0202 by 4 KHz sinusoidal signal. The SIG came out multiplexed. This signal can be sent out through reverse telemetry.
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Figure 9.16. Microscopic view of 32 × 32 array RS.
Figure 9.17. (a) Test result of RS as stimulator (b) test result of RS as reader.
Conclusion
We have presented the design, fabrication, and testing of a CMOS stimulator microarray for retinal prosthesis. The retinal prosthesis is designed for bidirectional data communication. A multiplexing technique is utilized allowing the use of only one SPC and one DACC. The design eliminates direct
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wiring requirements and uses only six interface wires for power and control. Furthermore, the prosthesis does not require direct addressing of any probe for active stimulation. Rather, a sequential stimulation by the clock timing eliminates need for wireless address transmission overhead. The system is also capable of stimulating the retina by programming large variety of experimental waveforms.
References
1.W. Liu, K. Vichienchom, M. Clements, S. C. DeMarco, C. Huges, E. McGucken,
M.S. Humayun, E. DeJuan, J. D. Weiland, and R. Greenberg, “A Neuro-stimulus Chip with Telemetry Unit for Retinal Prosthetic Device,” IEEE Journal of Solid-State Circuits, vol. 35, no. 10, Oct 2000, pp. 1487–1497.
2.E. Zrenner, K. D. Miliczek, V. P. Gabel, H. G. Graf, E. Guenther, H. Haemmerle,
B.Hoefflinger, K. Kohler, W. Nisch, M. Schubert, A. Stett, and S. Weiss, “The development of sub-retinal microphotodiodes for replacement of degenerated photoreceptors.” Opthalmic Research, 1997, 29, 269–280.
3.G. Peyman, A. Y. Chow, C. Liang, V. Y. Chow, J. I. Perlman, and N. S. Peachey, “Subretinal semiconductor microphotodiode array,” Ophthalmic Surg. Lasers, vol. 29, pp. 234–241, 1998.
4.H.K. Trieu, L. Ewe, W. Mokwa, M. Schwarz, and B. J. Hostica, “Flexible Silicon Structures For A Retina Implant”, IEEE Transaction, 1998, vol. 10, pp. 515–519 VI.
5.Y. Yao, M. N. Gulari, J. F. Hetke, and K. D. Wise, “A self-testing multiplexed CMOS stimulating probe for a 1024-site neural prosthesis”, The 12th International Conference on Solid State Sensors, Actuators and Microsystems, Boston, June 8–12, 2003, Transducer ’03, pp. 1213–1216.
6.Shuenn-Yuh Lee, Shyh-Chyang Lee, and Jia-Jin Jason Chen, “VLSI Implementation of Implantable Wireless Power and Data Transmission Micro-Stimulator for Neuromuscular Stimulation”, IEICE Transactions on Electronics, vol. E87-C, no.6, June 2004, pp. 1062–1067.
10
Visual Prosthesis Based on Optic Nerve Stimulation with Penetrating Electrode Array
Qiushi Ren1 2, Xinyu Chai1 2, Kaijie Wu1 2, Chuanqing Zhou1 2
and C-Sight Group2
1Institute for Laser Medicine and Bio-Photonics, College of Life Science and Technology, Shanghai Jiao-Tong University
2C-Sight Group: C-Sight Group is a Research Consortium on Visual Prosthesis Funded by the Chinese Ministry of Science and Technology Under National Key Basic Research Program (973 Program, 2005CB724300). The principal investigators of the C-Sight Group include:
1.Qiushi Ren, Ph.D. (Program Chief Scientist), Department of Biomedical Engineering, Shanghai Jiao-Tong University
2.Li, Xiao-Xin, M.D., Department of Ophthalmology, Beijing University School of Medicine
3.Liang, Pei-Ji, Ph.D., Department of Biomedical Engineering, Shanghai Jiao-Tong University
4.Zhu, Yi-Sheng, Ph.D., Department of Biomedical Engineering, Shanghai Jiao-Tong University
5.Zhuang, Song-Lin, Ph.D., Shanghai University of Science and Technology
6.Zhao Jian-Long, Ph.D., Shanghai Inst. For Micro-System Fabrication Research
of CAS
7. Wang, Jin-Ye, Ph.D., Department of Biomedical Engineering, Shanghai Jiao-Tong
University
Introduction
The successful development and application of cochlear implants in the deaf has encouraged several research groups to start projects on visual prosthesis for the blind. The C-Sight (Chinese Project for Sight) is the first multidisciplinary research project on visual prosthesis in China funded by the Chinese Ministry of Science and Technology under the National Key Basic Research Program (973 Program, 2005CB724300) and by the Science and Technology Commission of Shanghai Municipality (STCSM). The goal of the C-Sight Project is to develop an implantable microelectronic medical device that will restore useful vision to blind patients.
The attempts involved electrical stimulation of primary visual cortex [1–3] and retina [4–6] have proved that phosphene can be artificially elicited in blind
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individuals since the sixties of last century. The optic nerve serves as a compact conduit for all of the information in the visual scene. Because it can be accessed via a minimally invasive procedure and is relatively spared by the most prevalent degenerative eye diseases, it can be chosen as a site for a neural interface or as a stimulating site in the visual prosthesis design. The main challenge is to evaluate the possibility of visual prosthesis based on optic nerve stimulation. In 1998, C. Veraart et al. proved that electrical stimulation of the optic nerve in a 59-year-old volunteer with retinitis pigmentosa can also elicit phosphenes [7–9]. The contact spiral cuff electrode was used in their experiment. However, the spatial resolution of recovered vision was limited because surface stimulating electrodes were used.
With the development of technology, the electrode can be made more and more elaborately. Therefore, the damage of electrode to the optic nerve can be minimized and the spatial resolution can also be greatly enhanced.
In our approach, we proposed the penetrating multi-electrode arrays with specific configurations into the optic nerve as a neural interface to couple the encoded electrical stimuli into the axons of the ganglion cells for vision recovery. Figure 10.1 shows the schematic presentation of our experimental approach. Another important feature of our approach is that the function of photoreceptors of retina is replaced by a self-contained implantable micro-camera.
The full structure of our proposed visual prosthesis is shown in Figure 10.2. The images are captured by a CMOS micro-camera which can be implanted into the lens of the blind eye. Then, the key features of the image can be extracted from the actual scenes with some advanced image-processing algorithm. After
Figure 10.1. Schematic drawing of electrical stimulation at optic nerve bundle with penetrating electrode array.
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Image |
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Visual information/ |
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Encoder/ |
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acquistion |
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image processing |
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Transmitter |
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Receiver/ |
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Figure 10.2. The structure of visual prosthesis based on penetrating optic nerve electrical stimulation.
that the “retinal encoder” encodes the processed visual information as trains of electrical impulses with a specific spatiotemporal stimulation pattern. Finally, the electrical stimulation pattern is delivered by the penetrating multi-electrode array directly into the optic nerve where action potentials are generated and conducted to the visual cortex.
Animal Experiment
Optic Nerve Electrical Stimulation
In order to evaluate the feasibility of our approach, we carried out a series of animal experiments. Firstly, we chose three different anatomical positions of optic nerve for placing the stimulating electrode. To determine whether the electrodes implanted into the three different places can all elicit cortical potentials, stimulations were applied to the three stimulating positions, respectively. Furthermore, several different electrical stimulus patterns were applied to the optic nerve at one certain position with the purpose of investigating whether different pattern stimulations could elicit different cortical responses.
Materials and Methods
Animal model
Albino rabbits weighting about 2.8 kg (7 8 months old) were used. They were maintained in a 12-hour light and 12-hour dark diurnal cycle, supplied with water and food. Experimental procedures on rabbits conformed to the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research issued by the National Institutes of Health.
Exposition of optic nerve
The rabbits were anesthetized generally with intraperitoneal injection of pentobarbital sodium (30 mg/kg), and the eyeballs were locally anaesthetized with a few drips of procaine. At the upper site of the right eye’s outer canthus, several
