HIGH VISUAL ACUITY, HIGH SENSITIVITY LIGHT SWITCHABLE NEURAL STIMULATOR ARRAY FOR IMPLANTABLE RETINAL PROSTHESIS
20220387786 · 2022-12-08
Inventors
- Yu-Hsin Liu (San Diego, CA, US)
- Yu-Hwa Lo (San Diego, CA)
- Hiren D. Thacker (San Diego, CA, US)
- Nicholas Oesch (Del Mar, CA, US)
Cpc classification
International classification
Abstract
Retinal prostheses are described with visual acuity better than 20/150, and higher sensitivity, dynamic range, and FOV than the state-of-the-art. At least two different techniques are presented, the first being an optically-switched vertical single-transistor amplifier for ultrahigh photocurrent amplification, and the second being nanopatterned pillar electrodes.
Claims
1. A retinal prosthesis, comprising: an array of pixels, each pixel containing a photoconductor, a vertical MOSFET amplifier, and a stimulation electrode; and a local return electrode in communication with each pixel to form a local current flow loop between the pixel, a proximal bipolar cell, and the return electrode.
2. The retinal prosthesis in claim 1, wherein the stimulation electrode has a high CIC.
3. The retinal prosthesis in claim 1, wherein the stimulation electrode comprises IrO.
4. The retinal prosthesis in claim 1, wherein the photoconductor is partially blocked.
5. The retinal prosthesis in claim 4, wherein the photoconductor is annular.
6. The retinal prosthesis in claim 5, wherein the photoconductor is amorphous.
7. The retinal prosthesis in claim 6, wherein the photoconductor comprises Si/Ge.
8. The retinal prosthesis in claim 1, wherein the MOSFET amplifier has an effective channel length of 0.2 um.
9. The retinal prosthesis in claim 8, wherein the MOSFET amplifier has an effective channel width of 50 um.
10. The retinal prosthesis in claim 1, wherein the retinal prosthesis is adapted such that 100 pW of light over the pixel is converted into a current of 1-10 μA, giving rise to an effective responsivity of 10.sup.4-10.sup.5 A/W.
11. A retinal prosthesis, comprising: an array of pixels, each pixel containing a partially blocked Si/Ge photoconductor, a vertical MOSFET amplifier, and a high CIC IrO stimulation electrode; and a local return electrode in communication with each pixel to form a local current flow loop between the pixel, a proximal bipolar cell, and the return electrode.
12. The retinal prosthesis in claim 11, wherein the photoconductor is annular.
13. The retinal prosthesis in claim 12, wherein the photoconductor is amorphous.
14. The retinal prosthesis in claim 11, wherein the MOSFET amplifier has an effective channel length of 0.2 um.
15. The retinal prosthesis in claim 14, wherein the MOSFET amplifier has an effective channel width of 50 um.
16. A retinal prosthesis, comprising: an array of pixels including pillar structure electrodes with nanopatterned stimulation surfaces; and a local return electrode in communication with each pixel to limit electric field spreading and minimize crosstalk.
17. The retinal prosthesis in claim 16, wherein the pillar structure has a diameter of 12-18 um.
18. The retinal prosthesis in claim 17, wherein the pillar structure has a height of 30-70 um.
19. The retinal prosthesis in claim 16, wherein the pillar structure is cylindrical or tapered.
20. The retinal prosthesis in claim 16, wherein the pillar structure has a tip with a nanopatterned corrugated pattern or convoluted pattern.
Description
BRIEF DESCRIPTION OF THE DRAWINGS
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DETAILED DESCRIPTION OF THE SUBJECT DISCLOSURE
[0028] The present subject disclosure overcomes many of the drawbacks of conventional systems as described above. To develop a retinal prosthesis with visual acuity better than 20/150, and higher sensitivity, dynamic range, and FOV than the state-of-the-art, Applicants propose the following exemplary but non-limiting innovations.
[0029] (1) An optically-switched vertical single-transistor amplifier for ultrahigh photocurrent amplification: This design can yield both high sensitivity and packing density. The high sensitivity greatly reduces the required corneal irradiance level so the device could operate with standard intensity AR/VR goggles well within the long-term retinal and corneal safety limits or even under natural light (in bright sunlight), and with a large FOV. The high packing density is enabled by the unique design of the single-transistor vertical amplifier, which (a) reduces the area needed for photodetection due to high responsivity, (b) eliminates area needed for complex amplifier circuitry, and (c) shares the footprint of the stimulating electrode.
[0030] (2) Nanopatterned pillar electrodes: In recognition of the high (˜1 mA/mm.sup.2) neural stimulation threshold in diseased eyes and the CIC (charge injection capacity) limits of stimulation electrode materials (e.g., IrO), pillar electrodes are proposed here with nanopatterned stimulation surfaces. This will not only increase electrode surface area without increasing footprint, but also bring electrodes closer to the target neurons, minimizing both electrode crosstalk and stimulation threshold. The proposed pixel design also includes local (pixel-wise) return electrodes to limit electric field spreading and further minimize crosstalk.
[0031] The innovations in (1) and (2) above significantly advance the field of retinal prostheses by producing a device containing as many as 23,000 pixels at a 35 μm pitch to achieve a VA of 20/150 for a sensor FOV better than 20 degrees and a wide dynamic range. Applicants estimate this optoelectronic hardware would allow the optical power requirement from the goggles to be reduced by at least 2-orders of magnitude compared to current systems. The anticipated performance is a great leap from the state-of-the-art.
[0032] Pixel Design
[0033]
[0034] The retinal prosthesis contains a dense array of pixels each comprising a high CIC IrO stimulation electrode atop a vertical single transistor amplifier and a partially-blocked annular amorphous semiconductor photoconductor as a highly photosensitive voltage provider (see
[0035] The output current from the vertical transistor flows through an IrO electrode that sits atop the vertical transistor area and occupies the same footprint, in a configuration that produces the most efficient use of the chip real estate. The drain current in the IrO electrode flows into the ionic buffer between the electrode and the retinal bipolar cell as Faradaic current (plus some displacement current as biphasic bias is applied to assure charge balance for each cycle of neural stimulation).
[0036] Overall, the high responsivity reduces the required light illumination level by 4 orders of magnitude compared to the cascaded photovoltaic design [12]. Importantly, the single transistor design consumes 1 uW/pixel to achieve neural stimulation, which is more power efficient than CMOS pixels [29]. These features and the efficient use of chip real estate favor high acuity, large FOV (≥20°) retinal prosthesis.
[0037] Optically-Controlled, Vertical Single-Transistor Amplifier
[0038]
[0039] A vertical MOSFET follows the typical field-effect-transistor relation in the saturation regime as a planar device:
I.sub.D=(w/2L)μnC.sub.i(V.sub.gs−V.sub.th).sup.2
where I.sub.D: drain current, W: channel width (the circumference of the device mesa), L: channel length, μ.sub.n; electron mobility (assuming n-channel FET), C.sub.i: gate capacitance. The gate voltage is controlled by an optically controlled photoconductive switch made of an amorphous Si/Ge thin film with one part of the film exposed to light and another part covered. The resistance of the exposed section and the covered section are modeled by R1 and R2 (
[0040] Next to the vertical MOSFET, an a-SiGe or a-Si thin film photoconductor, sensitive to 850 nm wavelength, is deposited on the isolation layer. An a-Si film about 1 μm thick has been previously reported that can vary its own resistance by 3 orders of magnitude from dark to 50 μW/mm.sup.2 with visible light [30] owing to its high sensitivity. a-Si and a-SiGe alloys may be used to obtain the photoconductor device with the best sensitivity and controllability of the gate voltage on the vertical MOSFET. The a-Si film has strong sensitivity to green/blue light and its response drops rapidly at red and NIR wavelength. Amorphous SiGe alloys have a much stronger response at red and NIR light and would be particularly suitable for illumination from an NIR goggle. However, high Ge content in the a-SiGe alloy increases the dark current, thus reducing the sensitivity. For the present application, high responsivity to NIR light enhances photosensitivity, and a large photoconductivity change relative to the dark state gives rise to a high voltage swing, thus a high magnitude of transistor switching current. The optimal design for the Ge composition, film thickness, and photoconductor geometry for the exposed and covered sections may be deduced from experimentation.
[0041] Penetrating Pillar Electrode and Localized Return Electrode
[0042]
[0043] In the subretinal prosthesis approach, a 30-70 μm thick layer of degenerated photoreceptors separates the implanted electrode array from bipolar cells in the INL of the retina [22,23]. According to one study [35], stimulation current threshold increases roughly proportionally to the square of the separation between the electrode and the targeted cell. Furthermore, the electric field generated by the stimulation spreads through this tissue and may stimulate multiple neurons causing pixel crosstalk and reducing VA. Thus, there are significant advantages to minimizing the distance between stimulating electrode and target neurons. Prior work [22,36] has also shown that when animal retina is placed on surfaces with topology, cells gradually migrate to fill up spaces between positive features. Even when 128 μm tall polymer structures were implanted in Yucatan minipigs, there was no significant gliosis observed or damage to the retina during implantation [22]. Therefore, an optimally designed 3D electrode, that penetrates the retina to deliver stimulation directly to the bipolar cells, and intelligently placed return electrodes to confine the electric field to individual neurons, will complement device-level advances to drive meaningful improvements to VA.
[0044] Pillar structures with diameters 12-18 μm and height ranging from 30-70 μm are fabricated on glass or silicon substrates for experimental evaluation in ex vivo animal models. The proposed 3D electrode structures are fabricated using electroplated gold and SIROF.
[0045] Experimental Results
[0046] Bias Controlled FET Current
[0047] The center amplifier is a vertical FET, which can be configured in either a N-P-N or P-N-P configuration for a n-channel or p-channel FET. A dielectric film is deposited on the sidewall of the silicon mesa for passivation and to induce a weak inversion layer along the vertical edge of the middle layer, forming a vertical channel along the mesa sidewall. Silicon dioxide (SiO.sub.2) or aluminum oxide (Al2O3) can be used to control the threshold voltage of the sidewall FET.
[0048] A layer of metal covers the dielectric layer as the gate terminal to control the channel. The relationship between the current output and the gate voltage can be found in a typical FET equation,
wherein the drain current I.sub.D is related to the device height L and the width W of the FET (circumference of the device mesa). V.sub.TH is determined by the Si epitaxial layer design and the passivation dielectric layer. I.sub.D links with the V.sub.GS, the gate voltage that interconnected with the surrounding photoconductor.
[0049] In order to adjust the amplification, the FET can also incorporate a third (gate) electrode overlying the thin passivation layer (e.g., SiO2 or Al2O3). The third electrode can be applied as a metal layer overlying the dielectric passivation shown in
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[0051] Optically Controlled Photoconductive Switch
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[0053] An amorphous structure is implanted around the amplifier to provide the light sensitive voltage output to the gate of the FET. The principle of the voltage generation from an amorphous structure is demonstrated by the device shown in
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[0055] Another structure as
[0056] This application incorporates by reference herein in their entirety into this disclosure all of the following cited references, which disclose various findings as discussed in the present disclosure: [0057] 1. American Academy of Ophthalmology. https://www.aao.org/eye-disease-statistics [0058] 2. Bright Focus Foundation. https://www.brightfocus.org/ [0059] 3. Foundation Fighting Blindness. https://www.fightingblindness.org/ [0060] 4. J. W. Y. Yau et al., “Global prevalence and major risk factors of diabetic retinopathy,” Diabetes Care, 35, 556-564, 2012. [0061] 5. M. S. Humayun et al., “Interim results from the international trial of Second Sight's visual prosthesis,” Ophthalmology, 119, 779-788, 2012. [0062] 6. M. S. Humayun et al., “Preliminary 6 month results from the Argus II epiretinal prosthesis feasibility study,” in Conf. Proc. IEEE Eng. Med. Biol. Soc., 2009, 4566-4568. [0063] 7. J. D. Dorn et al., “The detection of motion by blind subjects with the epiretinal 60-electrode (Argus II) retinal prosthesis,” JAMA Ophthalmol., 131(2), 183-189, 2013. [0064] 8. A. K. Ahuja et al., “Blind subjects implanted with the Argus II retinal prosthesis are able to improve performance in a spatial-motor task,” Br. J. Ophthalmol., 95(4), 539-543, 2011. [0065] 9. A. C. Ho et al, “Long term results from an epiretinal prosthesis to restore sight to the blind,” Ophthalmology, 122(8), 1547-1554, 2015. [0066] 10. Y. Mandel et al., “Cortical responses elicited by photovoltaic subretinal prostheses exhibit similarities to visually evoked potentials,” Nat. Commun., 4:1980, 2013. [0067] 11. D. Boinagrov et al., “Photovoltaic pixels for neural stimulation: circuit models and performance,” IEEE Trans. Biomed. Circ. and Sys., 10(1), 2016. [0068] 12. D. Palanker et al., “Photovoltaic restoration of central vision in atrophic age-related macular degeneration,” Ophthalmology, 127(8), 1097-1204, 2020. [0069] 13. L. Wang et al., “Photovoltaic retinal prosthesis: implant fabrication and performance,” J. Neural Eng., 9(4), 2012. [0070] 14. S. Ha et al., “Towards high-resolution retinal prostheses with direct optical addressing and inductive telemetry,” J. Neural Eng., 13, 2016. [0071] 15. B. Bosse et al., “In vivo photovoltaic performance of a silicon nanowire photodiode-based retinal prosthesis,” Invest. Ophthalmol. Vis. Sci., 59(15), 5885-5892, 2018. [0072] 16. FDA HUD designation: http://www.fda.gov/ForIndustry/DevelopingProductsforRareDiseases Conditions/Designating HumanitarianUseDevices HUDS/default.htm) [0073] 17. S. Shim et al., “Retinal prosthetic approaches to enhance visual perception for blind patients,” Micromachines, 11, 535-560, 2020. [0074] 18. J. D. Weiland et al., “Retinal prosthesis,” Annu. Rev. Biomed. Eng., 7, 361-401, 2005. [0075] 19. E. Bloch et al., “Advances in retinal prosthesis systems,” Ther. Adv. Ophthalmol., 11, 1-16, 2019. [0076] 20. S. Damle et al., “Vertically integrated photo junction-field-effect transistor pixels for retinal prosthesis,” Biomed. Opt. Expr., 11, 55-67, 2020. [0077] 21. N. Oesch, “Influence of iridium oxide electrode size on stimulation thresholds and dynamic range,” presented at The Eye and The Chip, 2019. [0078] 22. J. Chen et al., “Implantation and extraction of penetrating electrode arrays in minipig retinas,” Transl. Vis. Sci. Technol., 9(5), 2020. [0079] 23. J. D. Loudin et al., “Optoelectronic retinal prosthesis: system design and performance,” J. Neural Eng., 4(1), 2007. [0080] 24. T. L. Edwards et al., “Assessment of the electronic retinal implant Alpha AMS in restoring vision to blind patients with end-stage retinitis pigmentosa,” Ophthalmology, 125(3), 432-443, 2018. [0081] 25. K. Stingl et al., “Interim results of a multicenter trial with the new electronic subretinal implant Alpha AMS in 15 patients blind from inherited retinal degenerations,” Front. Neurosci., 11, 2017. [0082] 26. K. Stingl et al., “Artificial vision with wirelessly powered subretinal electronic implant Alpha-IMS,” Proc. Biol. Soc., 280(1757), 2013. [0083] 27. R. Daschner et al., “Laboratory and clinical reliability of conformally coated subretinal implants”, Biomed. Microdevices, 19(7), 2017. [0084] 28. F. Yang et al., “Flexible, high-density microphotodiode array with integrated sputtered iridium oxide electrodes for retinal stimulation,” Journ. Micro/Nanolith., MEMS and MOEMS, 15(1), 2016. [0085] 29. C. L. Lee et al., “A 0.8-V 4096-pixel CMOS sense-and-stimulus imager for retinal prosthesis,” IEEE Trans. Electron Devices, 60, 1162-1168, 2013. [0086] 30. F. Dong et al., “Thin film amorphous silicon nanoscale photodetectors,” Procedia Chemistry, 1, 433-436, 2009. [0087] 31. X. Zhang et al., “Characterization of a light switchable microelectrode array for retinal prosthesis,” Appl. Phys. Lett., 99, 253702, 2011. [0088] 32. A. Coma et al., “Electrode-size dependent thresholds in subretinal neuroprosthetic stimulation,” J. Neural Eng., 15, 2018. [0089] 33. H. Lorach et al., “Retinal safety of near infrared radiation in photovoltaic restoration of sight,” Biomed. Opt. Expr., 7(1), 2016. [0090] 34. S. F. Cogan, “Neural stimulation and recording electrodes,” Annu. Rev. Biomed. Eng., 10, 275-309, 2008. [0091] 35. D. Palanker et al., “Design of a high-resolution optoelectronic retinal prosthesis,” J. Neural Eng., 2, 105-120, 2005. [0092] 36. E. Ho et al., “Characteristics of prosthetic vision in rats with subretinal flat and pillar electrode arrays,” J. Neural Eng., 16, 2019.
[0093] The foregoing disclosure of the exemplary embodiments of the present subject disclosure has been presented for purposes of illustration and description. It is not intended to be exhaustive or to limit the subject disclosure to the precise forms disclosed. Many variations and modifications of the embodiments described herein will be apparent to one of ordinary skill in the art in light of the above disclosure. For example, the example measurements and values presented in the disclosure are not limiting of the subject matter, but merely show an example that has been used. It would be apparent to one having ordinary skill in the art that some variation and range is possible and expected with each of the variables presented, and which would result in the desired outcome. The scope of the subject disclosure is to be defined only by the claims appended hereto, and by their equivalents.
[0094] Further, in describing representative embodiments of the present subject disclosure, the specification may have presented the method and/or process of the present subject disclosure as a particular sequence of steps. However, to the extent that the method or process does not rely on the particular order of steps set forth herein, the method or process should not be limited to the particular sequence of steps described. As one of ordinary skill in the art would appreciate, other sequences of steps may be possible. Therefore, the particular order of the steps set forth in the specification should not be construed as limitations on the claims. In addition, the claims directed to the method and/or process of the present subject disclosure should not be limited to the performance of their steps in the order written, and one skilled in the art can readily appreciate that the sequences may be varied and still remain within the spirit and scope of the present subject disclosure.