Neural Interface Device

Abstract

In variations, the neural interface system (e.g., retinal implant, neural implant, etc.) may include a display, a controller, a power source, and / or any other suitable components. The system may be used with an external device that includes a communication element, a display-brain interface (e.g., cells), and / or any other suitable components.

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of U.S. Provisional Patent Application No. 63 / 359,100, filed July 7, 2022, U.S. Provisional Patent Application No. 63 / 433,130, filed December 16, 2022, and U.S. Provisional Patent Application No. 63 / 438,947, filed January 13, 2023, each of which is incorporated by reference herein in its entirety.

[0002] The present invention relates generally to the field of neural interfaces, and more particularly to new and useful systems and methods in the field of neural interfaces. [Brief explanation of the drawings]

[0003] [Figure 1] FIG. 1 is a schematic representation of one variant of the system. [Figure 2] FIG. 2 is a schematic representation of an exemplary embodiment of data transfer between components of the system. [Figure 3] Figures 3A, 3B, and 3C show an example of a system in which the display-brain interface comprises in situ genetically modified native cells. Figures 3D, 3E, and 3F show an exemplary embodiment of a system in which the display-brain interface comprises in situ genetically modified native cells. [Figure 4] Figures 4A, 4B, and 4C show an example of a system in which the display-brain interface comprises genetically modified cells seeded within a cell support. Figures 4D, 4E, and 4F show an exemplary example of a system in which the display-brain interface comprises genetically modified cells seeded within a cell support. [Figure 5] Figure 5A shows an example of a system in which the display-brain interface comprises native, non-recombinant cells. Figure 5B shows an exemplary example of a system in which the display-brain interface comprises native, non-recombinant cells. [Figure 6] FIG. 6 is a schematic representation of one embodiment of the system. [Figure 7] 7A, 7B, and 7C show examples of display units. [Figure 8] 8A and 8B show an example of a set of display units. [Figure 9] FIG. 9 shows an exemplary embodiment of a display "superpixel." [Figure 10] FIG. 10 is a diagram illustrating an embodiment of a system including a driver. [Figure 11] FIG. 11 is a schematic representation of an exemplary embodiment of the system. [Figure 12] FIG. 12 illustrates an exemplary embodiment of a display and a display-brain interface. [Figure 13] Figure 13A shows an exemplary embodiment of a system that does not include a cell support, and Figure 13B shows an exemplary embodiment of a system that includes a cell support. [Figure 14] FIG. 14 shows an exemplary embodiment of a display aligned with a cell matrix. [Figure 15] FIG. 15 illustrates an exemplary embodiment of an embedded display. [Figure 16] FIG. 16 illustrates a first exemplary embodiment of the system. [Figure 17] FIG. 17 illustrates a second exemplary embodiment of the system. [Figure 18] FIG. 18 illustrates a third exemplary embodiment of the system. [Figure 19] FIG. 19 illustrates an embodiment of an embedded display and controller. [Figure 20] 20A and 20B are diagrams illustrating an exemplary embodiment of an external device, respectively, and an exploded view of the exemplary embodiment of the external device. [Figure 21] 21A and 21B illustrate an example of manufacturing a system component. [Figure 22]FIG. 22 shows an example of a tack hole. [Figure 23] 23A and 23B show examples of optical components. [Figure 24] Figures 24A and 24B are example images of a system with a "hinge" display-controller connector configuration, and Figure 24C is an example image of a system with a "u-turn" display-controller connector configuration. [Figure 25] FIG. 25 is an image of the thin film layers of a system with a "u-turn" display-controller connector configuration prior to bonding to the controller component. [Figure 26] Figure 26 is a scanning electron microscope image of the display. [Figure 27] FIG. 27 shows the emission spectra of an exemplary display at 1 μA and 10 μA. [Figure 28] FIG. 28 is an image of a system implantation procedure in which the system (eg, retinal implant) is attached to a surgical carrier device. [Figure 29] FIG. 29 is an image of the implantation procedure after the surgical carrier device has been removed. [Figure 30] Figure 30 shows an exemplary spectrogram showing output as a function of frequency over time following presentation of optogenetic stimulation via an exemplary retinal implant system, measured using an implantable electrocorticography grid. [Figure 31] FIG. 31 illustrates an example of raw local field potentials (LFPs) versus time and normalized gamma power versus time resulting from stimulus presentation from an exemplary retinal implant system, measured using an implantable electrocorticography grid. [Figure 32]Figure 32 shows an exemplary series of heat maps measured using an implantable electrocorticography grid showing the relationship between peak gamma power (20-80 Hz, mV2) as a function of time from stimulus onset (top, green bar) and position on the grid (ML: central, lateral; AP: anterior, posterior). [Figure 33] Figure 33 shows an exemplary histogram showing the number of significantly responding electrocorticography channels (implantable electrocorticography grid; up to 32 response channels) for each trial of optogenetic stimulation using an exemplary retinal implant system compared to extraocular optogenetic stimulation and high-contrast 10-degree visual stimulation. DETAILED DESCRIPTION OF THE INVENTION

[0004] The following description of embodiments of the invention is not intended to limit the invention to these embodiments, but rather to enable any person skilled in the art to make and use the invention.

[0005] 1. Overview 1, the system may include a display 100, a controller 300, and a power supply 500. The system may be used with an external device 400, a display-brain interface 200, and / or other components. However, additionally or alternatively, the system may include any other suitable components.

[0006] In a variation, the system may function to transmit information to the user's brain. In a first example, the system (e.g., a retinal implant) may function as a visual prosthesis to restore vision for a user who has lost the function of all or part of their photoreceptors (e.g., degenerated and / or damaged photoreceptors), ganglia, and / or other sensory cells. In a second example, the system (e.g., a neural implant) may function to provide stimulation to the brain to restore and / or enhance one or more senses the user.

[0007] 2. Working Example In one example, a display is implanted in situ (e.g., in the eye, brain, ear, brainstem, muscle, arm, etc.). The display emits an excitation signal (e.g., one or more wavelengths of light), and receptor cells generate a biochemical signal in response to detecting the excitation signal. The biochemical signal can be interpreted (e.g., by the brain) as data. The data presented by the display (via the excitation signal) can be determined based on input (e.g., an image sampled by a camera, a virtual reality engine, etc.) sent to a controller, which is connected to the display. Preferably, the receptor cells are genetically engineered to express a transgenic protein that is sensitive to the excitation signal emitted by the display (e.g., sensitive to a wavelength of light), and the engineered cells stimulate neurons in the brain in response to light activation. The brain can then interpret the stimulation, allowing the user to "see" the content. Alternatively, the cells can be non-modified or genetically engineered. The receptor cells can be ocular cells (e.g., retinal ganglion cells, etc.), neurons, somatic cells, and / or any other cell type.

[0008] 3.Technical advantages Variations in the technology provide one or more advantages over the prior art.

[0009] First, variations of the technology may restore and / or enhance one or more senses in a user (e.g., restoring vision to a blind user). In some diseases, such as retinitis pigmentosa and macular degeneration, photoreceptors are damaged, but cells in the optic nerve, retinal ganglion cells (RGCs), remain functional. Variations of the technology may directly stimulate ganglion cells, which may restore visual input to the brain without replacing photoreceptors. In certain examples, the system includes an optogenetic visual prosthesis that stimulates genetically engineered cells transfected with genes for light-sensitive proteins (e.g., opsins).

[0010] Second, conventional methods of interfacing with neurons require large capacitive electrode systems with cumbersome hermetic feedthroughs (to seal the implanted electrodes). In variations, this technology may provide content to the brain (e.g., via RGCs, neurons, etc.) using display implants with higher resolution (e.g., 1:1 mapping of cells to the light-emitting system on the display), a larger number of signal elements, and / or smaller form factors with fewer or no hermetic feedthroughs. In one example, variations of the technology may be scalable (e.g., to thousands of pixels, hundreds of thousands of pixels, etc.), enabling implantable visual prostheses that can generate vision by stimulating RGCs at or near cellular resolution.

[0011] Third, variations of the technique may include fabricating an implantable neural interface device (e.g., including a display, a display-controller connector, and a controller) that may better conform to the eye and reduce mechanical stress during and after implantation. In a first example, the neural interface device may be fabricated using monolithic integration on a multilayer thin film, which may increase flexibility. In a second example, the neural interface device may be fabricated in a three-dimensional (3D) geometry. In a particular example, the device is fabricated using a multilayer film with a sacrificial layer that dissolves to reveal a 3D geometry that includes a first flap (housing the controller) that may be implanted on the exterior of the eye and a second flap (housing the display) that may be implanted inside the retina of the eye. In a third example, the flap may not be necessary, and the device flexes into the eye.

[0012] Fourth, the diversity of coding schemes present in distinct RGC subtypes can pose problems for visual prostheses. Multiple classes of RGCs may exist within the retina, each carrying distinct information, such as ON and OFF RGCs, which increase firing rates at increased or decreased luminance, respectively. Each RGC type may contribute to the reconstruction of visual stimuli, and neighboring RGCs may encode different aspects of the visual stimulus. Variations in technology may offer the advantage of addressing RGCs at or near cellular resolution using advanced visual prostheses for photoreceptor degeneration. In certain embodiments, approaches to visual restoration may include optogenetic stimulation of RGCs using implantable thin-film μLED displays with pixels approximately the size of the RGC soma, thereby allowing the display (e.g., functioning as an implantable optogenetic therapy) to operate at or near cellular resolution.

[0013] Fifth, variations of the technology may use active drivers for the display (e.g., including thin-film transistor backplanes), which may improve frame rates when taken with a minimal amount of time to reliably elicit optogenetically induced action potentials at one or more light levels (e.g., light levels below a safety threshold). In embodiments, the driver electronics may be located inside the eye (e.g., for active displays with more pixels). This may allow for a significant reduction in the number of wires routed through the sclera, thereby allowing for more flexible placement of the device. This may also reduce the power consumed and / or transmitted through the eye between the controller 300 and the display 100, since the controller only needs to signal state changes rather than constantly drive the display. Additional embodiments include thin-film transistors directly on each pixel and / or integration of CMOS devices with microLEDs directly bonded to them.

[0014] Sixth, increasing coverage on the retina may provide access to a greater field of view. In embodiments, a larger display may be unfolded inside the eye during surgery (e.g., to compensate for surgical constraints on sclerotomy size).

[0015] Seventh, a variation of the system could achieve optogenetic control of the peripheral retina using a display with stimulation pixels whose size and pitch roughly match the density of RGCs. Achieving single-cell resolution with one-photon optogenetic excitation in vivo without complex optics can be extremely difficult due to significant axial light propagation. This axial resolution issue can be eliminated in the peripheral retina, where RGCs can be arranged in a single layer. In the perifoveal region, where RGCs can be stacked in layers up to 10 cells deep, axial light propagation can reduce resolution, but sparse viral transfection can limit the number of off-target RGC activations.

[0016] Eighth, in a variant, an implantable retinal display has several advantages over optical stimulation from outside the eye. Stimulation from the goggles can contend with both macroscopic and microscopic movements of the goggles relative to the eye, rapid changes in eye position, and variable pupil diameters that affect the system's numerical aperture. Stimulating RGCs from outside the eye with single-cell or near-single-cell accuracy and millisecond resolution can require extremely low-latency closed-loop tracking and calculations, which can be difficult to implement. On the other hand, an implantable display can feature a fixed mapping between a given pixel and a specific RGC or set of RGCs. In a variant, the display can move with the eye, eliminating the need to dynamically correct the stimulation pattern. For example, eye tracking can be used to render a scene on the implant, but the stimulation pattern does not need to dynamically track a moving target.

[0017] Ninth, in a variant, implantable displays may be more efficient in terms of pixel usage: Because the eye can saccade to any part of the visual scene, an augmented reality display can render the visual scene in high detail across the entire field of view. On the other hand, the resolution of an implantable display may decrease concentrically away from the fovea to match the density of RGCs. This difference can be used when designing implants that utilize retinal coding principles: a display that renders the entire visual scene may not know which RGCs to address before saccades, thus limiting the encoding potential of the prosthesis. Finally, the stable mapping of pixels to cells using an implantable display may aid plasticity even in cases of poor encoding, as downstream structures may receive consistently patterned input.

[0018] However, other advantages may be provided by the systems and methods disclosed herein.

[0019] 4. System 1, the system may include a display 100, a controller 300, and a power supply 500. Optionally, the system may include a display-controller connector, a display-brain interface 200, and / or any other suitable components. The system may be used with an external device 400. One example is shown in FIG.

[0020] Preferably, one or more components of the system (e.g., one or more components of display 100) are partially or fully transparent, but may alternatively be translucent, opaque, or have any other suitable optical properties. One or more components of the system are biocompatible and / or encapsulated within a biocompatible material, but may alternatively be non-biocompatible and / or otherwise configured.

[0021] Preferably, the system is an implant, but may additionally or alternatively include non-implantable devices and / or be otherwise configured. In examples, one or more components of the system are implanted in or on the eye (e.g., retina, sclera, etc.), brain, brainstem, spinal cord, ear, muscle, skin, on or near nerves, and / or any other body region of a user. The user may be a human, an animal (e.g., a rabbit), and / or any other living organism. When the system is an implant, one or more components of the system may be held in place by tissue adhesive, via protrusions (e.g., "spikes") that act as anchors, tacks (e.g., through tack holes in the device), sutures, by inducing fibrous growth around or through the component (e.g., fenestrations in the component may allow fibrous growth to secure the component), and / or any other method.

[0022] The display 100 (e.g., photonic interconnects) functions to emit excitation signals that are received by cells (e.g., cells within the display-brain interface 200), and the signals may encode content (e.g., visual data, sensory data, other external information, artificial data, any other data, etc.). Additionally or alternatively, the display 100 may function to measure cellular states. The cells may be genetically modified cells (e.g., cells with optogenetic actuators and / or optogenetic sensors, hypoimmune cells, etc.) and / or non-genetically modified cells.

[0023] Display 100 may be implanted at an implantation location. Examples of implantation locations include the retina (e.g., over the macula, peripheral retina, all or part of both the macula and peripheral retina, etc.; on the internal limiting membrane on the surface of the retina), the optic nerve (e.g., aligned with the optic nerve), the brain (e.g., visual cortex, motor cortex, etc.; within the brain, on the brain surface, combinations thereof, etc.), the brainstem, spinal cord, ear (e.g., ear canal), muscle, skin, nerve, or nearby, and / or any other location associated with a user. In certain embodiments, display 100 (and optionally a display-controller connector) may be an intraocular component of a system. One embodiment is shown in FIG. 15.

[0024] Display 100 may be connected to a display-controller connector, controller 300 (e.g., wirelessly connected and connected via the display-controller connector), and / or any other system components. Display 100 may include one or more excitation signal emission systems (e.g., light emission systems) including circuits and / or components configured to emit a signal (e.g., light) based on control received from controller 300 (e.g., via the display-controller connector). The control instructions (e.g., display instructions) may include emission parameters and / or any other display instructions. Optionally, display 100 may include one or more signal sensor systems configured to measure cellular conditions, which may optionally be transmitted to controller 300 (e.g., via the display-controller connector). In certain examples, the signal sensor systems include sensors for measuring signals emitted by cells (e.g., protein fluorescence spatiotemporal parameters, intensity, ions, voltage, current, etc.). Optionally, the display may include one or more integrated circuits, optical components, and / or any other suitable components.

[0025] The display 100 may include a set of display units. The display units may be pixels (e.g., having one signal element), superpixels (e.g., having multiple signal elements), and / or configured in other ways. Examples are shown in FIGS. 7A, 7B, 7C, and 9. The signal elements may be excitation signal emission systems, signal sensor systems, and / or any other signal components. The mapping between display units and cells may be 1:1 (e.g., one display unit for each cell with an optogenetic actuator; one display unit for one cell with both an optogenetic actuator and an optogenetic sensor, etc.; the example shown in FIG. 14), 1:2 (e.g., one display unit for two cells: one cell with an optogenetic actuator and one cell with an optogenetic sensor), randomly determined and unconstrained across the display, variable mapping (e.g., the ratio between display units and cells increases away from the fovea), and / or any other mapping. In certain examples, display 100 may operate at or near cellular resolution (e.g., one display unit and / or its signaling elements may excite fewer than 20 cells, fewer than 10 cells, fewer than 5 cells, fewer than 2 cells, 1 cell, etc.). The display units within a set of display units may be identical to one another or different. In a first example, the display units are substantially identical (e.g., identical size each having identical signaling elements or sets of signaling elements), an example being shown in FIG. 8A. In a second example, the set of display units may include a first subset of display units that are different (e.g., each having only an excitation signal emission system) from a second subset of display units (e.g., each having a signal sensor system; each having a signal sensor system and an excitation signal emission system, etc.), and the number of display units in the first subset may be greater than, less than, or the same as the number of display units in the second subset. An example being shown in FIG. 8B.

[0026] The number of display units can be between 100 and 50,000, or any range or value therebetween (e.g., at least 1,000, at least 2,000, at least 5,000, at least 10,000, 2,048, 4,096, 8,192, 16,000, etc.), but alternatively can be less than 100 or more than 50,000. All or some of the display units can be functional (e.g., connected to the controller via a display-controller connector). In one example, only a portion of the display units are connected to the controller to reduce the number of connections at the display-controller connector. The percentage of functional display units among the set of display units can be between 20% and 100%, or any range or value therebetween (40% to 90%, 50%, less than 90%, less than 80%, less than 70%, etc.), but alternatively can be less than 20%. In a first exemplary example, 8,192 display units out of a total of 16,000 display units are functional. In a second exemplary embodiment, 2,048 display units are functional out of a total of 4,096 display units. The resolution of the set of display units is between 100 and 5,000 display units / mm. 2 or any range or value therebetween (500 display units / mm 2 Over 1000 display units / mm 2 Over 2000 display units / mm 2 (exceeding 100 display units / mm) 2 Less than or equal to 5,000 display units / mm 2The resolution of the display units may be the same across the display or may vary across the display (e.g., increasing resolution of the display units or functional display units towards the fovea of the retina). The diameter of the display units and / or their signal elements may be between 1 μm and 10 cm, or any other range or value therebetween (e.g., less than 500 μm, less than 100 μm, less than 50 μm, less than 20 μm, less than 10 μm, less than 5 μm, 5 μm to 100 μm, 10 μm to 20 μm, 15 μm, etc.), but may alternatively be less than 1 μm or greater than 10 cm. An example is shown in FIG. 26. An example is shown in FIG. 26. The emitting area of each excitation signal emitting element may be between 10 μm and 10 cm. 2 ~10,000μm 2 or any other range or value therebetween (e.g., 1000 μm 2 Less than 500 μm 2 Less than 100 μm 2 Less than 50 μm 2 ~100μm 2 , 66 μm 2 , 285 μm 2 ~680μm 2 ), but alternatively 10 μm 2 Less than or equal to 10,000 μm 2 The display unit pitch (e.g., the center-to-center distance between display units) can be between 5 μm and 10 cm, or any range or value therebetween (e.g., less than 500 μm, less than 100 μm, less than 50 μm, 5 μm to 100 μm, 20 μm, 42 μm, etc.), but can alternatively be less than 5 μm or greater than 10 cm.

[0027] The surface area of the display 100 (e.g., the active area of the display including the entire display and / or set of display units) is less than 0.5 mm 2 ~50cm 2 or any range or value therebetween (e.g., 2 mm 2 ~10mm 2 , 5mm 2 ~10mm2 , 7.29mm 2 , 6.55mm 2 ) but alternatively 0.5 mm 2 Less than or 50cm 2 The thickness of display 100 (e.g., including optional encapsulant, backing, and / or any other secondary materials) can be between 2 μm and 150 μm, or any range or value therebetween (e.g., 20 μm to 60 μm, 10 μm to 30 μm, 20 μm, 22 μm, 30 μm, 40 μm, 50 μm, 60 μm, etc.), but can alternatively be less than 2 μm or greater than 150 μm. The display surface geometry can be square, rectangular, circular, oval, and / or any other shape. Preferably, display 100 is flexible, but can alternatively be rigid and / or have both flexible and rigid components.

[0028] The excitation signal emission system may be a light-emitting system, an electrical emission system (e.g., emitting a current signal and / or a voltage signal), and / or any other signaling system. Preferably, the light-emitting system includes μLEDs, but may additionally or alternatively include laser diodes (e.g., vertical-cavity surface-emitting lasers, laser cavities, etc.), phosphors, and / or any other light-emitting system. In particular examples, phosphors may enable wavelength-shifting and / or emission lifetime-shifting of the light-emitting system (e.g., to better match the time constants of cells in display-brain interface 200). In one example, the light-emitting system may include μLEDs (e.g., a display includes an array of μLEDs), and drivers for the μLEDs may be located with the μLEDs on display 100 (e.g., within corresponding display units, adjacent to corresponding display units, adjacent to a set of display units, etc.), adjacent to the display, in the display-controller connector, in controller 300, and / or otherwise. One example is shown in FIG. 10 . In a first particular example, the driver may be a passive driver. In a second particular example, the driver may be an active driver (e.g., including integrated circuits, transistors, other logic components, etc.), allowing the display 100 to include an active array of display units (e.g., an active array of μLEDs). The μLED material may include indium gallium nitride, gallium nitride (e.g., biocompatible gallium nitride), indium gallium phosphide, organic light emitters, and / or any other light emitting material. The μLEDs may be fabricated directly with the display (e.g., on the same traces, on the same wafer, etc.), assembled on the display backing and / or encapsulant after circuit fabrication, and / or otherwise manufactured.

[0029] The light emitting system may emit one or more wavelengths of light at one or more luminous flux levels. Preferably, the luminous flux is at or above the photoactivation threshold of the optogenetic actuators (e.g., opsins) associated with the cells in the display-brain interface 200, but may alternatively be below the photoactivation threshold of the optogenetic actuators and / or have any other value. In an embodiment, the luminous flux (and / or irradiance experienced by the cells in the display-brain interface 200) is 0.01 mW / cm 2 ~100mW / cm 2 or any range or value therebetween (e.g., 0.1 to 20 mW / cm 2 , 5mW / cm 2 Ultra, 10mW / cm 2 Ultra, 20mW / cm 2 Ultra, 30mW / cm 2 Ultra, 50mW / cm 2 Ultra, 70mW / cm 2 less than 0.01mW / cm 2 Less than or equal to 100mW / cm 2The wavelength may be greater than 400 nm. Preferably, the wavelength corresponds to the excitation wavelength of an optogenetic actuator (e.g., opsin) associated with cells in the display-brain interface 200, but alternatively may not be associated with an optogenetic actuator (e.g., when the display 100 emits light to normal photoreceptors). The wavelength (e.g., spectral peak) may be between 400 nm and 800 nm, or any range or value therebetween (e.g., 510 nm and 550 nm, 530 nm and 540 nm, 530 nm, 540 nm, 545 nm, 550 nm, 560 nm, 450 nm and 485 nm, 500 nm and 570 nm, 625 nm and 750 nm, etc.), but alternatively may be less than 400 nm or greater than 800 nm. In a first example, the wavelength value corresponds only to red light (e.g., between 625 nm and 750 nm). In a second example, the wavelength value corresponds only to blue light (e.g., between 450 nm and 485 nm). In a third example, the wavelength values correspond to green light (e.g., between 500 nm and 570 nm). In a fourth example, the wavelength values correspond to red, blue, and / or green light (e.g., an RGB light display). In certain examples, the wavelengths may not include red light (e.g., blue and / or green wavelengths are used) to reduce photochemical hazards in display 100. The full width at half maximum value of the light-emitting system may be between 5 nm and 50 nm, or any range or value therebetween (e.g., 20 nm), but may alternatively be less than 5 nm or greater than 50 nm. However, the display may emit light having any other wavelength, frequency, photon energy, brightness, luminous flux, amplitude, and / or other parameters. An example is shown in FIG. 27. Additionally or alternatively, the display may emit non-optical signals (e.g., tactile signals, acoustic signals, electrical signals, etc.).

[0030] The excitation signal emission systems may operate according to emission parameters (e.g., emission commands) received from the controller 300, where the emission parameters encode content. The emission parameters may include spatial parameters (e.g., which display units to operate), temporal parameters (e.g., when to start signal emission, the length of signal emission, etc.), intensity and / or amplitude parameters (e.g., light brightness and / or amplitude), light wavelength, and / or any other parameters defining the signal emitted by the excitation signal emission systems. For example, the emission parameters may define a time series of light array patterns (e.g., including wavelength, brightness, spatial information, etc. for each excitation signal emission system), where each light array pattern encodes a frame of content. The frame rate of the time series may be between 50 FPS and 500 FPS (e.g., greater than 50 FPS, greater than 80 FPS, 90 FPS, etc.), but may alternatively be less than 50 FPS or greater than 500 FPS. The pulse duration of the excitation signal (e.g., defining the frame rate when the display includes a passive array of μLEDs) can be between 0.1 ms and 100 ms (e.g., 1 ms and 5 ms), but can alternatively be less than 0.1 ms or greater than 100 ms. In particular examples (e.g., when the display 100 includes an array of μLEDs driven by an active driver of the display 100), the emission parameters can include state change instructions for the excitation signal emission system. In variations, one or more emission parameters can be fixed (e.g., fixed wavelength, fixed brightness, etc.) or variable.

[0031] Control instructions ("controls") for implant control (e.g., including radiation parameters) may be determined and / or adjusted by the external device 400, the controller 300, the display 100, a combination thereof, and / or any other system component. In a first example, the controls may be determined in a processing system of the external device 400 based on content (e.g., received from the sensor 450), cell status information (e.g., measured by the display 100 and transmitted to the external device 400 via the communication elements of the controller 300), display information (e.g., current μLED state), controller status information (e.g., measured by the controller sensors), and / or any other information. In a second example, the controls may be determined in a processing system of the controller 300 based on content (e.g., raw content and / or processed content received from the external device 400), cell status information (e.g., measured by the display 100 and transmitted to the controller 300 via the display-controller connector), display information, controller status information, and / or any other information. In a third example, control may be determined by a processing system of the external device 400 and a processing system of the controller 300 (eg, regulated by the controller 300).

[0032] Preferably, the emission parameters are determined based on content (e.g., visual data, sensory data, other external information, artificial data, any other data, etc.), but may additionally or alternatively be determined based on cellular state, display information (e.g., the current state of each excitation signal emission system, where the emission parameters include state changes for all or a portion of the excitation signal emission systems), controller state information, calibration information, and / or any other information. For example, the emission parameters may be determined so that the resulting excitation signals collectively encode content (e.g., the emission parameters define a time sequence of light array patterns, where each light array pattern encodes a frame of content). In particular examples, the emission parameters may be determined and / or adjusted so that the display 100 emits signals corresponding to an image (e.g., so that signals relayed to the brain based on the excitation signals can be interpreted by the brain as an image); in this example, the content may be video and the image may be a frame of the video. In an exemplary example, the brightness of the light emitted by each display unit may be controlled so that the displays collectively project a grayscale (e.g., single-channel) or color (e.g., multi-channel) version of the image.

[0033] Optionally, the radiation parameters may be adjusted based on a retinal coding scheme (e.g., mapping of retinal ganglion cell type classifications within the retina), radiance calibration, manual feedback, and / or other calibration information. In a first embodiment, the radiation parameters may be adjusted based on cellular conditions (e.g., measured by one or more signal sensor systems). In a first example, signal strength is reduced when a protein (e.g., a cellular receptor) is deemed saturated. In a second example, signal strength is increased when a protein is not activated in response to signal radiation. In a third example, the display 100 may include a signal sensor system (e.g., optical and / or electrical sensors) that may be used to determine a retinal coding scheme (e.g., based on in vivo mapping of cellular responses) that may be used to calibrate the radiation parameters. In a second embodiment, the radiation parameters may be adjusted manually. For example, feedback from a user (e.g., a patient report of perceptual results of a stimulus) may be used to determine the retinal coding scheme used to adjust the radiation parameters. In an exemplary embodiment, because the cone hits a single small ganglion cell and humans can detect single cone simulation, the user can consciously perceive a single retinal ganglion cell (RGC) stimulation and report on the location and effect of the sensation.

[0034] However, the radiation parameters can be determined in other ways.

[0035] Optionally, the display 100 may include one or more signal sensor systems (e.g., an optical sensor system including an imaging sensor with recording electrodes and detector circuits, a voltage sensor, a current sensor, etc.). The signal sensor system functions to detect cell state information. The signal sensor system may measure the presence and / or concentration of one or more cellular molecules (e.g., calcium ions), a protein (e.g., a cell receptor) response to an excitation signal (e.g., fluorescence spatial distribution, intensity, attenuation, etc.), a protein response to a secondary signal (e.g., light of a different wavelength, a signal from another cell, etc.), a protein mechanical response, and / or any other cell state metric. In a first variant, the signal sensor system may be associated with an excitation signal emission system. For example, the excitation signal emission system emits a first signal (e.g., light of a first wavelength emitted from the display 100 and received by the cell) that stimulates an optogenetic sensor in the cell to emit a second signal (e.g., light of a second wavelength emitted by the cell and received by the display 100), and the second signal is detected by the signal sensor system. In certain embodiments, the intensity of the second signal indicates the intensity of a cellular event (e.g., an activation potential firing from the cell), the cellular event being caused by the optogenetic actuator receiving the initial signal emitted by the excitation signal emission system. In embodiments, the optogenetic sensor may be a protein different from the optogenetic actuator, and a single cell may include both an optogenetic sensor and an optogenetic actuator, or only one of the above. In a second variant, the signal sensor system may receive an electrical signal (e.g., a biopotential, current, changes therein, etc.). The electrical signal may be emitted by the same cell associated with the excitation signal emission system, by a different cell, and / or by any other biological and / or electrical component. For example, a feedthrough may be used to connect an electrical sensor (e.g., a voltage and / or current sensor) in the signal sensor system to the cell.In exemplary embodiments, electrical sensors are inserted (e.g., via prongs, spikes, other projections, etc.) into the retinal surface (e.g., 10 μm to 200 μm, 50 μm, 100 μm, any range or value therebetween, less than 10 μm, more than 200 μm, etc.). In certain embodiments, recording electrical signals directly from cells may reduce crosstalk (e.g., optical signals from an excitation signal emission system minimally excite electrical sensors in a signal sensor system), which may be particularly important in low signal-to-noise ratio conditions such as neural recording.

[0036] In a first example, the signal sensor system may be used for calibration. In certain examples, the signal sensor system may ensure that the brightness of light emitted by the light emitting system is calibrated to be above an activation threshold (e.g., an activation threshold of a cellular protein) and / or below a saturation threshold. In a second example, the signal sensor system may be used to determine cellular activity, and optionally, stimulation by the excitation signal emission system may be adjusted based on the cellular activity. In certain examples, when the display 100 is used directly in the brain and cells in the display-brain interface 200 are receiving additional signals from neurons, the emission parameters may depend on the cellular activity. Optionally, the display 100 may transmit cellular state information to the controller 300 (e.g., to calibrate the emission parameters), the display processing circuitry (e.g., to directly calibrate the light emitting system), the external device 400, and / or any other system.

[0037] In an exemplary embodiment, one display unit includes a first signaling element having a light-emitting system that emits light at a first wavelength configured to stimulate a first cell having an optogenetic actuator (e.g., by activating the optogenetic actuator of the first cell for neuronal signaling), a second signaling element having a light-emitting system that emits light at a second wavelength configured to stimulate a second cell having an optogenetic sensor (e.g., the light at the second wavelength stimulates the optogenetic sensor to emit light at a third wavelength based on the cell state), and a third signaling element having a light-sensing system that detects light at the third wavelength from the second cell. In this embodiment, the first cell can be the second cell (e.g., a single cell has the optogenetic actuator and the optogenetic sensor), or the first cell can be separate from the second cell (e.g., the first cell is associated with the first signaling element, and the second cell is associated with the second and third signaling elements).

[0038] Optionally, display 100 may include and / or be coupled (e.g., glued, mounted, etc.) to one or more optical components (e.g., micro-optical components). The optical components may serve to collimate light, homogenize light, focus light (e.g., onto fewer cells), reduce light that reflects back through eye lenses, and / or otherwise modify light emitting into or emitting from display 100. The optical components may be positioned in front of display 100 (facing display-brain interface 200) and / or behind display 100. One example is shown in FIG. 23A . In a first variation, the optical components include lenses (e.g., microlenses, diffractive lenses, metalens, etc.). In particular examples, lenses may be positioned in front of each μLED (e.g., on the emitting side) to collimate light from the μLED toward one or more cells in display-brain interface 200. In a second variant, the optical component includes a back reflector (e.g., disposed on the back surface of the display 100, behind each μLED, etc.). In an embodiment, the back reflector can be a metal (e.g., aluminum, silver, etc.), a Bragg reflector, and / or any other reflector. In a third variant, the optical component can include a designed μLED, where the designed μLED is the μLED of the pump signal emission system. An embodiment is shown in FIG. 23B. In a first embodiment, the designed μLED has a smaller emitter that can have an improved emission profile (e.g., including collimated light). In a first particular embodiment, the entire μLED can be designed to be smaller. In a second particular embodiment, the pumping area of the quantum well of the μLED can be designed to be smaller. In a second embodiment, the μLED can have a modified shape. In a particular embodiment, the μLED can have a parabolic shape on the back side of the μLED (e.g., creating a parabolic back reflector). In a third example, an optical component can be bonded to the μLED (on the emitting side and / or front side). In a fourth example, the μLED can include a buffer layer (e.g., gallium nitride) on the emitting side that can be patterned to function as an optical component.In a fourth variant, the optical components may be a combination of the first, second, and / or third variants. The mapping between the optical components and the light emitting system may be 1:1 (e.g., one optical component for each μLED), 2:1, one optical component for the entire set of display units (e.g., a back reflector across display 100), and / or any ratio between optical components and signal elements.

[0039] However, the display 100 may be configured in other ways.

[0040] Optionally, the system may include a display-controller connector, which may function to connect the display 100 to the controller 300. Preferably, the display-controller connector includes an electronic connection (e.g., wire, metal line, trace, etc.) that physically connects the display 100 to the controller 300, but may alternatively include a wireless connection (e.g., Bluetooth, BLE, NFC, IR, RF, etc.). The number of connections on the display-controller connector may be between 1 and 10,000, or any range or value therebetween (e.g., 5 to 1000, 5 to 20, 100 to 1000, 10 to 500, more than 100, more than 200, more than 500, more than 1000, etc.), or alternatively, more than 10,000. Each connection may be between 0.5 μm and 100 μm, or any range or value therebetween (e.g., 2 μm to 10 μm, 5 μm, etc.), but alternatively, may be less than 0.5 μm or more than 100 μm. The display-controller connector may include a single row of connections, multiple rows of connections (e.g., stacked), and / or any other configuration of one or more connections. The connections may be adhered to a backing, encapsulated in an encapsulant, and / or otherwise supported. The thickness of the display-controller connector may be between 5 and 150 μm, or any range or value therebetween (e.g., 10 μm to 30 μm, less than 30 μm, less than 20 μm, etc.), but alternatively may be less than 5 μm or greater than 150 μm. The width of the display-controller connector may be between 0.5 mm and 100 mm, or any range or value therebetween (e.g., 1 mm to 5 mm, 2 mm, less than 50 mm, less than 20 mm, less than 10 mm, less than 5 mm, etc.), but alternatively may be less than 0.5 mm or greater than 100 mm. The length of the display-controller connector (e.g., the length of each connection) may be between 1 mm and 1 cm, or any range or value therebetween (e.g., 5 mm to 100 mm, 10 mm to 40 mm, etc.), but may alternatively be less than 1 mm or greater than 1 cm.The display 100 and the display-controller connector may be fabricated on the same wafer, assembled together after display 100 fabrication, and / or otherwise manufactured.

[0041] In a first example, display 100 includes an active driver (e.g., along with logic components disposed on display 100). In this example, optionally, the display-controller connector includes fewer wires than the number of pixels. In a second example, display 100 includes a passive driver. In this example, the display-controller connector may include multiple wires (e.g., one for each pixel or set thereof, one for each pixel-color channel combination, etc.); alternatively, the display-controller connector may include fewer wires (e.g., a smaller density relative to the display unit).

[0042] However, the display-controller connection can be configured in other ways.

[0043] Optionally, the system includes a display-brain interface 200, which functions to convert excitation signals from the display 100 into neural signals that can be interpreted by the brain.

[0044] Preferably, display-brain interface 200 includes a set of cells connected (e.g., directly or indirectly) to the brain, but may be configured in other ways. Preferably, display-brain interface 200 is located within a signaling pathway between display 100 and the nervous system (e.g., the brain), but may be located in other ways. In particular examples, the cells, when activated by an excitation signal from display 100, may induce activity in the visual cortex (e.g., induce a focal visual evoked potential in the visual cortex). Examples are shown in FIGS. 30 and 31. In an exemplary example, display 100, which corresponds to ∼10 degrees of human visual space (e.g., has an active area of 2.56 × 2.56 mm), may stimulate a pattern of evoked activity similar to the visual evoked potential elicited by high-contrast 10-degree stimulation, much higher than that from full-field optogenetic stimulation from outside the eye (e.g., the examples shown in FIGS. 32 and 33).

[0045] In a first variation, the display-brain interface 200 includes native, non-recombinant cells. For example, the display-brain interface 200 may include photoreceptors (e.g., the display 100 emits light that is detected by photoreceptors), plexiform layer cells, retinal ganglion cells, neurons, and / or any other cells that directly or indirectly interface with the nervous system.

[0046] In a second variation, the display-brain interface 200 includes, produces, and / or utilizes genetically engineered cells. The genetically engineered cells may include photo-engineered cells having a light-sensitive biochemical signaling pathway (e.g., whereby the cells generate a biochemical signal in response to detecting a certain wavelength of light), hypoimmune cells genetically engineered to contain a small molecule kill switch (e.g., transfected with a kill switch gene) (e.g., genetically engineered to reduce an immune response due to implantation of the display 100), combinations thereof, and / or other genetically engineered cells. Examples of cells that may be genetically engineered may include organoids (e.g., having multiple retinal cell types), selected cells (e.g., specific cell types) from organoids, retinal ganglion cells, plexiform layer cells (e.g., plexiform layer cells may signal to native retinal ganglion cells), photoreceptors, any cells used in vision, neurons, stem cells (e.g., stem cells genetically engineered prior to differentiation), any animal cells (e.g., human cells), and / or any other cells. In certain examples, the cells may include neurons, retinal ganglion cells, and / or other cells derived from pluripotent stem cells. The cells may be native to the implantation site of display 100 (e.g., modified in situ) and / or may originate outside the implantation site (e.g., modified and / or grown ex vivo; extracted and optionally differentiated user stem cells, etc.).

[0047] In variations utilizing recombinant cells, cells can be genetically engineered by transfecting the cells (e.g., using a virus with a plasmid and capsid) with light-sensitive proteins that act as optogenetic actuators (e.g., optogenetic effectors) and / or optogenetic sensors. The optogenetic actuator generates a biochemical signal (e.g., an action potential) in response to receiving light of a particular wavelength, and the optogenetic sensor generates light of a particular wavelength based on (e.g., proportional to) the state of the cell (e.g., the concentration of a given molecule). However, optogenetic actuators and sensors can be defined in other ways. In variations, the optogenetic sensor can be coupled to the optogenetic actuator within the cell (e.g., a fusion construct), such that when the optogenetic actuator receives light of a first wavelength, the optogenetic sensor is activated to emit light of a second wavelength based on the cellular state.

[0048] In embodiments, cells (e.g., native retinal ganglion cells) can be transfected using intravitreal injection, periretinal injection, subinternal limiting membrane injection (e.g., guided by optical coherence tomography), post-vitreous surgery and post-internal limiting membrane peeling injection, injection through a hole in the internal limiting membrane created using a Nd:YAG laser, and / or any other transfection method. Cells can be transfected in situ (e.g., in the eye), ex situ (e.g., outside the eye and then implanted in the eye), and / or any other suitable location. Optionally, the virus used to transfect the cells can target a specific cell type (e.g., general somatic cells, neurons, retinal ganglion cells, a type of retinal ganglion cell, stem cells, etc.). The capsid can be an adeno-associated virus capsid (e.g., AAV2.7M8) and / or any other suitable capsid. The plasmid can be an opsin, a fluorescent biosensor protein, and / or any other suitable plasmid. Examples of opsins may include CheRiff, ChroMD, ChroME, ChroME2S, ChRmine (e.g., ChRmine-mScarlet), ChrimsonR (e.g., including red-shifted mutations), ReachR, and / or any other opsin. In an exemplary embodiment, cells may be transfected using AAV2.7m8 hSyn1-ChRmine-Kv2.1-WPRE. Examples of fluorescent biosensor proteins include GCaMP8s, GCaMP8m, jRGeco1a, YCaMP, iGECI, and / or any other suitable protein. Opsins may be activated by blue light, green light, red light, and / or any other wavelength. Optionally, different plasmids (e.g., having different wavelength sensitivities) may be used for content transfer (e.g., input), sensing (e.g., cell monitoring), and / or sensing activation. Optionally, different plasmids may be used for different types of content (eg, different communication modalities).Optionally, different plasmids can be used for different types of cells (e.g., different types of ganglion cells), with the wavelength of light emitted by the excitation signal emission system tailored to the cell type, although any optogenetic method can be implemented.

[0049] In a variant, the number of opsin-expressing cells can be reduced. In a first example, cell-type-specific expression can be encoded via the promoter. In a first particular example, the promoter can be a CAG promoter, which can represent opsin in most infected cells. In a second particular example, the promoter can be a human synapsin promoter, which can confine opsin expression to neurons. In a second example, the virus can be spatially restricted (e.g., spatially restricted within the retina). In an exemplary example, the virus can be embedded on the display surface (e.g., with a silk fibroin hydrogel), thereby significantly reducing the number of opsin-expressing cells in the eye without altering the device's functionality.

[0050] Preferably, the cells (e.g., non-recombinant or recombinant cells) are positioned such that they can send and / or receive signals to and / or from the display signaling elements, but may additionally or alternatively be positioned separately from the display signaling elements. In variations, the recombinant cells may be sparse (e.g., separated by a minimal distance such as 1 μm, 5 μm, 10 μm or more), dense (e.g., separated by a threshold distance or less), and / or otherwise positioned.

[0051] In a first variant, cells are disposed within a cell support that is connected (e.g., adhered) to and / or part of the display 100 (e.g., the cells can be genetically modified before and / or after being seeded within the cell support). One example is shown in FIG. 13B. In an example, the cell support can be adhered to the display 100 using adhesives (e.g., epoxy), polymerization, and / or any other suitable method. Preferably, the cell support is adhered to the display 100 with a gap between the cell support and the display 100 (e.g., to improve optics), but alternatively, it can be directly adhered to the display 100. The gap can be 10 nm to 20 μm, or any range or value therebetween, but alternatively, it can be less than 10 nm or greater than 20 μm. Preferably, the cell body is trapped by the cell support, but the cells project axons and / or dendrites from the cell support to interface with native cells. Alternatively, the cells may be completely trapped (e.g., without axonal or dendritic protrusions) or may not be trapped (e.g., the cell body may migrate outside the cell support). Examples of methods for trapping cells include expanding a hydrogel, a capping layer attached to the cell support after seeding (e.g., closing the cell support microwells), chemical functionalization of the surface of the cell support (e.g., via surface treatment) that may promote cell growth and / or inhibit cell growth, and / or any other trapping method.

[0052] In a first example, the cell support is a matrix (e.g., microwells; examples shown in Figures 12 and 14) defining a set of cell-retention units configured to retain one or more cells. The cell-retention units may be open, closed, and / or have any other geometric shape. The matrix material may be a soft polymer, a substantially rigid material, and / or any other suitable material. Preferably, the cell-retention unit pattern and / or cell pattern (e.g., cell-to-cell separation, cell frequency, etc.) is identical to or based on the display unit pattern (e.g., each signal element corresponds to a cell), but may alternatively be any other pattern. In an exemplary example, each display unit and / or its signal element (e.g., each μLED) corresponds to a single cell-retention unit, and the single cell-retention unit is configured to retain a single cell. Examples are shown in Figures 4A, 4B, 4C, 4D, 4E, and 4F. In a second example, the cell support is a gel (e.g., a hydrogel). However, any other suitable cell support may be used.

[0053] In a first embodiment, the cells in the cell support function as photoreceptors (e.g., the cells interface with retinal ganglion cells and, optionally, replace non-functional photoreceptors). In a second embodiment, the cells function as retinal ganglion cells (e.g., the cells interface with neurons in the brain). In a third embodiment, the cells function as neurons (e.g., located in the brain and directly interfacing with neurons). However, the cells may function to interface with the nervous system in other ways.

[0054] In a second variation, the cells are placed in their native location (e.g., retinal ganglion cells, neurons in the visual cortex, cells in the brainstem, etc.). In a first example, native cells are genetically modified in situ (e.g., converting native non-modified cells into genetically modified cells), examples of which are shown in Figures 3A, 3B, 3C, 3D, 3E, and 3F. In a second example, the native cells remain non-modified, examples of which are shown in Figures 5A and 5B. However, cells may be placed in any location and / or multiple locations.

[0055] However, the display-brain interface 200 can be configured in other ways.

[0056] The controller 300 functions to communicate with the external device 400 and to control system operation (e.g., display 100 operation) based on the communication (e.g., based on radiation parameters determined based on the communication and / or received via the communication). Optionally, the controller 300 may function to power the display 100, and the controller 300 itself may be powered by an external power source or an on-board power source (e.g., a battery). Preferably, the controller 300 is not physically connected to the external device 400, but alternatively may be physically connected. Preferably, the controller 300 is physically connected to the display 100 (e.g., via physical wires in a display-controller connector), but alternatively may not be physically connected to the display 100 (e.g., radiation parameters are transmitted wirelessly to the display 100). Optionally, the controller may be coupled to multiple displays (e.g., to increase the total display surface area without increasing the implantation incision). Optionally, power supply 500 and / or its components may be within controller 300, coupled to controller 300 (eg, outside the controller volume), and / or otherwise connected to the controller.

[0057] Preferably, the controller 300 is flexible, but may alternatively be rigid and / or have both flexible and rigid components. The controller thickness may be between 0.1 mm and 20 mm, or any range or value therebetween (e.g., 0.5 mm to 2 mm, less than 10 mm, less than 5 mm, less than 2 mm, etc.), but alternatively may be less than 0.1 mm or greater than 20 mm. The controller 300 volume may be between 50 μL and 500 μL, or any range or value therebetween (e.g., 100 μL to 200 μL, 130 μL to 150 μL, etc.), but alternatively may be less than 50 μL or greater than 500 μL. Preferably, the controller 300 is designed to fit within the footprint of a glaucoma tube shunt device (e.g., 50 mm 2 ~500mm 2 ) but may alternatively be larger or smaller than the footprint of a glaucoma tube shunt device (e.g., a conventional glaucoma drainage implant). In certain examples, the controller may have a form factor of a glaucoma tube shunt device. One example is shown in FIG. 18.

[0058] Optionally, controller 300 may include one or more of a communication element, power source 500 and / or its components (e.g., power receiver components, power rectification and / or conditioning components, etc.), a processing system (e.g., a processor, memory, data processing circuitry, etc.), filters, controller sensors, memory (e.g., flash memory for storing instructions), analog-to-digital converters, additional safety features, and / or any other system components. In one example, the processing system includes an integrated circuit (e.g., a field programmable gate array (FPGA), a microcontroller, a system-on-chip, etc.). One example is shown in FIG. 11.

[0059] The controller sensors may function to measure controller states and may additionally or alternatively determine implant states (including, for example, controller states, display states, etc.). Optionally, the controller 300, the external device 400, and / or the display 100 may be controlled based on the controller states. In a first example, power to one or more components may be shut off in response to the detection or occurrence of a predetermined controller state (e.g., indicating water intrusion, a temperature above a threshold, etc.). In a second example, content and / or radiation parameters from the content may be adjusted based on the controller state (e.g., processing the content based on the attitude and / or movement of the controller). The controller states may include temperature, humidity, movement, attitude (e.g., including position and / or orientation), electrical shorts (of the controller 300, the display 100 connected to the controller 300, etc.), and / or any other information related to the controller, and the controller may include one or more sensors measuring the respective parameters. In a first example, the controller 300 may include a motion sensor (e.g., an inertial measurement unit, a retroreflector, other optical components, etc.) that functions to track the position, orientation, and / or movement of the eye (e.g., eye gaze) and / or one or more components of the system. Preferably, the motion sensor tracks movement between 3 DoF and 6 DoF, or any range or value therebetween, but may alternatively track movement less than 3 DoF or more than 6 DoF. In a second example, the controller 300 may include a temperature sensor that functions to detect overheating. In a third example, the controller 300 may include a moisture sensor (e.g., a humidity sensor) that functions to detect water intrusion into the controller 300. In a fourth example, the controller 300 may include a current measurement sensor that functions to detect a short circuit (e.g., in the display 100).

[0060] The communication element of the controller 300 may include a receiver, a transmitter, a wired connection, and / or any other component. Controller communication with the display 100 may be via a display-controller connector and / or any other connection. Controller communication with an external device may be via wireless communication (e.g., radio frequency (RF), infrared (IR), Bluetooth, BLE, NFC, another transmission frequency, the same or a different wavelength as used to stimulate the display-brain interface 200, etc.), wired communication, and / or any other connection. In particular examples, the controller includes an IR diode and associated integrated circuit. Information received by the communication element of the controller 300 may include content (e.g., the controller calculates radiation parameters based on the received content), radiation parameters (e.g., calculated by the external device 400), cellular measurements (e.g., cellular conditions measured by the display 100), and / or any other information. Information transmitted by the communication elements of the controller 300 may include emission parameters (e.g., transmitted to the display 100), controller measurements (e.g., controller states measured by controller sensors), controller attitude signals (e.g., emitted light received by tracking sensors of the external device 400), and / or any other information. Information transferred between the external device 400 and the controller 300, between the controller 300 and the display 100, and / or between any other system components may be transferred in real time (e.g., in response to a request, in response to the sensor 450 sampling a measurement, etc.), repeatedly, asynchronously, periodically, and / or at any other suitable time. An exemplary example of information transfer is shown in FIG. 2.

[0061] Controller 300 may be implanted, co-located with display 100, located ex situ, and / or otherwise located. In examples, controller 300 may be located on the eye, inside the eye, in the orbit, on or near the brain (e.g., on the brain surface, brainstem, etc.), on or near the spinal column (e.g., spinal cord), in any subcutaneous location, on or near the ear (e.g., ear canal), and / or in any other location. In a first embodiment, controller 300 is an extraocular component of the system located on the eyeball (e.g., having a form factor and / or location similar to a glaucoma tube shunt device). In this embodiment, controller 300 is preferably located episclerally, subconjunctivally of the eye (e.g., no percutaneous wires are used) so that the implantable system components (e.g., display 100 and controller 300) do not breach the immune barrier. In a second embodiment, the controller 300 is located on or near the brainstem (e.g., so that the controller 300 can be physically connected to a display 100 implanted on the brainstem without the use of percutaneous wires), however, the controller 300 can be located elsewhere.

[0062] Optionally, controller 300 includes an ocular attachment mechanism, which functions to attach controller 300 to the external surface of the eye (e.g., under the conjunctiva of the eye). In certain examples, the ocular attachment mechanism includes one or more suture attachments (e.g., suture holes, tabs, etc.). Optionally, the ocular attachment mechanism may include a mechanism used in glaucoma tube shunt implantation. Optionally, controller 300 includes a carrier attachment mechanism, which functions to interface with a surgical carrier device used to facilitate implantation. The carrier attachment mechanism may include holes in controller 300, ridges on controller 300 (e.g., for interfacing with clips), suture attachments, and / or any other fixation mechanism. Optionally, the carrier attachment mechanism may include all or a subset of the ocular attachment mechanisms (e.g., a subset of ocular attachment suture holes). One example is shown in FIG. 17 .

[0063] However, the controller 300 may be configured in other ways.

[0064] The display 100, display-controller connector, controller 300, and / or any other embedded system components may be fabricated using a membrane (e.g., a thin film) and optionally a secondary material (e.g., a backing and / or encapsulant), but may alternatively be fabricated by other methods. The membrane material may include titanium, platinum, gold, palladium, silicon, and / or any other metal. The thin film thickness may be between 50 nm and 50 μm, or any range or value therebetween (e.g., 100 nm to 5 μm), but may alternatively be less than 50 nm or greater than 50 μm.

[0065] In a first variation, fabricating the embedded system components includes integrated fabrication of a monolithic thin film including the array of excitation signal emission systems (e.g., an array of μLEDs) and the display-controller connector (e.g., wiring). Additionally or alternatively, the monolithic thin film includes one or more electronic components of the controller 300 and / or connections therefor. In one example, the array of excitation signal emission systems and the display-controller connector may be fabricated using the same wafer. In an example, integrated fabrication may enable reduced interfaces, improved component alignment, reduced thickness, increased component density (including, e.g., wiring between μLEDs), reduced tolerances, and / or other advantages.

[0066] In certain examples, embedded system components can be monolithically fabricated on epitaxially grown GaN-on-sapphire substrates using polyimide and / or any other backing material as a flexible backbone for multiple layers (e.g., 4-6 layers) and through-via routing of traces (e.g., gold traces). Optionally, electronic components can be assembled directly on the polyimide-metal structure before substrate peeling. Optionally, individual μLEDs can be embedded within monolithic polyimide packages (e.g., rather than transferred onto existing routing layers). In a variation, this can take advantage of high-resolution alignment on an inherently flexible substrate by building flexible components on the μLEDs and then later peeling them off. Additionally or alternatively, this can take advantage of denser routing and more tightly integrated packaging layers.

[0067] In a first example, the display 100 is fabricated using a monolithic multilayer film (e.g., bonded to a substrate). In an exemplary embodiment, this multilayer film may appear as a single laminate film. In a first particular example, the display-controller connector may include connections routed in a generally straight configuration (e.g., the μLED array is fabricated with its emitting side below the layer containing the display-controller connections, and the controller components are assembled on top of the layer), an example of which is shown in FIG. 21A. In this example, the display-controller connector may be flexible, such that the display-controller connector may bend when embedded (e.g., bend greater than 60°, greater than 90°, greater than 120°, or greater than 150°), an example of which is shown in FIG. 16. In a second particular example, the display-controller connector may include connections routed in a “u-turn” configuration (e.g., the μLED array is fabricated with its emitting side above the layer containing the display-controller connections, and the controller components are assembled on top of the layer), an example of which is shown in FIGS. 24C and 25. In a second example, display 100 is fabricated using a multilayer film (e.g., bonded to a substrate) that includes a sacrificial layer (e.g., a partial or full layer) that dissolves after tracing and / or other manufacturing processes are complete; one example is shown in FIG. 21B. The sacrificial layer may allow for the creation of a 3D geometry using two-dimensional manufacturing techniques, which may better fit the eye. The 3D geometry (e.g., a "hinge" configuration) may include a first flap that may be embedded in the exterior of the eye (supporting controller 300) and a second flap that may be embedded in the retina inside the eye (supporting display 100). Examples are shown in FIGS. 17, 24A, and 24B.

[0068] In a second variation, manufacturing the display 100 includes separately fabricating (e.g., on a thin film) the array of excitation signal emission systems and the display-controller connector. Optionally, the array of excitation signal emission systems may be assembled adjacent to additional electronic components (e.g., fabricated separately and then assembled on the film supporting the excitation signal emission system array using an interconnect layer). The additional electronic components may include drivers, transistors, and / or other logic components, filters, signal sensor system wiring between display components, and / or any other electronic circuitry. In an example, locating the additional electronic components adjacent to the excitation signal emission system may reduce the number of wires (channel count) in the display-controller connector (e.g., less than 20, less than 10, etc.), increase the flexibility of the display-controller connector, increase wire diameter, increase data bandwidth, reduce current losses, increase efficiency, and / or provide other advantages.

[0069] Optionally, the display 100, the display-controller connector, the controller 300, and / or any other system components may be attached to a backing (e.g., placed on and glued to the backing, etc.) and / or encapsulated in an encapsulant (e.g., all embedded components encapsulated in the encapsulant; the controller 300 encapsulated in the encapsulant while the display 100 and display-controller connector are glued to the backing; the μLEDs are left unencapsulated while the driver and / or other system components are encapsulated, etc.). In a first example, the backing and / or encapsulant is rigid (e.g., sapphire). In a second example, the backing and / or encapsulant is flexible (e.g., a flexible polymer). Examples of backing and / or encapsulant materials include polyimide, liquid crystal polymer, parylene, elastomeric polyurethane, and / or any other suitable material. The backing and / or encapsulant material may be biocompatible, flexible (e.g., at a reasonable thickness), water-resistant, robust to surgical procedures, have high adhesive strength for adhering to other displays and / or backing and / or encapsulant materials, and / or have any other properties. Preferably, the backing and / or encapsulant is transparent or translucent (e.g., so that the display 100 does not block any remaining photoreceptor function when the display 100 is implanted on the retina), but may alternatively be opaque (e.g., when the display 100 is implanted in the brain). Optionally, the backing and / or encapsulant may include an insulating material. For example, the insulating material may include a ceramic insulating material (e.g., silicon carbide, alumina, hafnia, etc.). Optionally, the backing and / or encapsulant may include a secondary buffer material (e.g., epoxy underfill), examples of which are shown in FIGS. 13A and 13B. For example, when the backing and / or encapsulant comprises a hard material, a soft polymer may be used to interface with the implantation location (e.g., the retina). Optionally, a cushioning material may facilitate adhesion of the display 100 to the implantation location.Optionally, the backing and / or sealant may include tabs that the surgeon may use to position the display 100 at or near the implantation location (eg, by holding the tabs with forceps).

[0070] Optionally, fabricating optical components (e.g., microlenses, back reflectors, etc.) on display 100 may include simultaneously fabricating the optical components during fabrication of the array of excitation signal emission systems (e.g., designed μLEDs are constructed with parabolic geometries that function as optical components), bonding the optical components and / or arrays of optical components (e.g., arrays of microlenses) to display 100, a backing, and / or an encapsulant, fabricating the optical components on a (shared) substrate (e.g., a wafer) together with the excitation signal emission systems (e.g., the optical components may be fabricated on the substrate before or after the μLEDs are fabricated on the substrate), and / or any other fabrication technique.

[0071] In variations, the backing and / or encapsulant may be manufactured with a designed tension to facilitate implantation. For example, manufacturing the backing and / or encapsulant may include forming the backing and / or encapsulant material in a 3D geometry, so that when implanted, the backing and / or encapsulant material exerts a spring force (e.g., biased radially outward) to press the display 100 against the implantation location (e.g., the retina). In particular examples, manufacturing the encapsulant may include encapsulating the display 100, the display-controller connector, and / or any other system components within the encapsulant material, with the system components positioned in a specified 3D geometry. However, the backing and / or encapsulant may be manufactured in other ways.

[0072] However, the display 100, the display-controller connector, the controller 300, and / or other system components may be manufactured in other ways.

[0073] The display 100, the display-brain interface 200, and / or the display-controller connector may be anchored (e.g., glued, fixed, etc.) at the implantation location. Anchoring methods may include tissue adhesives, protrusions (e.g., “spikes” of material) on the backing and / or sealant that act as anchors, packing, pressing the device against the implantation location (e.g., replacing fluid in the eye due to pressurized gas), tacks and / or pins inserted through tack holes in the backing and / or sealant, inducing fibrous growth around the device (e.g., via a laser), cell growth into or out of the display-brain interface, pressing the device against other tissue (e.g., connective tissue forming the eyeball), combinations thereof, and / or any other methods. For example, the number of tacks may be between 1 and 5, or any range or value therebetween (e.g., 2 to 4), but may alternatively be greater than 5. In certain examples, tack holes may be disposed on the display-controller connector (e.g., connections routed around the tack holes; an example is shown in FIG. 22 ). In an exemplary embodiment, implanting display 100 and controller 300 involves making an incision in the eye (e.g., a sclerotomy), inserting display 100 and a display-controller connector into the eye through the incision (e.g., using a surgical carrier device), anchoring display 100 to the retina, and anchoring controller 300 to the exterior of the eye. Examples are shown in FIGS. 19, 28, and 29.

[0074] The system may be used with one or more external devices that may function to receive cellular measurements (e.g., from the system), determine control (e.g., emission parameters) for display 100, determine the attitude of one or more implantable system components, and / or perform any other set of functions. Examples of external devices that may be used include eyeglasses, contact lenses, hats, personal computing devices (e.g., smartphones, laptops, etc.), televisions, combinations thereof, and / or any other suitable external devices. Examples are shown in Figures 20A and 20B.

[0075] Optionally, the external device 400 includes a communication element 420 configured to communicate with the system (e.g., to communicate with a communication element of the controller 300), a processing system (e.g., a processor, memory, etc.), a sensor 450, a power source 500 and / or components thereof, a tracking sensor, and / or any other set of components.

[0076] Preferably, the communication element 420 of the external device is complementary to the communication element of the controller (e.g., communicating using the same wavelength, such as IR, RF, etc.), but may be configured in other ways. The communication element 420 may include a transmitter, a receiver, a wired connection, and / or any other set of components. Preferably, the communication element 420 is not embedded within the user, but may alternatively be embedded within the user. The communication element 420 may be statically positioned relative to the controller 300 (e.g., the communication element 420 moves with the controller 300) or may move relative to the controller 300 (e.g., using beam steering and / or other methods to transmit data from a transmitter to the controller 300, the controller moves as the eyes move, and the communication element 420 remains stationary, etc.). The information transmitted by the communication element 420 may include content (e.g., processed or unprocessed content), radiation parameters (e.g., calculated based on the content), and / or any other information. The information received by the communication element 420 may include cell measurements (e.g., cell states measured by the display 100), controller measurements (e.g., controller states measured by a controller sensor), controller attitude signals, display attitude signals, and / or any other information.

[0077] The optional tracking sensor may function to determine the pose of one or more components of the system (e.g., controller 300, display 100, etc.) and / or the eye (e.g., eye gaze). In a first variant, the tracking sensor includes a camera that functions to track the eye (e.g., pupil, intrinsic eye feature, transfected cells, etc.) and / or a system component (e.g., display 100 and / or controller 300 seen through the eye, light backscattered by display 100, etc.). In a second variant, the tracking sensor includes a receiver configured to receive light emitted and / or reflected from one or more system components, a controller attitude signal (e.g., a tracking signal or attitude estimate emitted via a controller communication element), a display attitude signal (e.g., emitted via one or more excitation signal emission systems), and / or any other signal. In one example, the receiver includes a set of photodiodes (e.g., at least two photodiodes, at least three photodiodes, etc.), and the set of photodiodes may track the light intensity of the signal. Optionally, the external device 400 may use a light propagation model (e.g., that models light passing from a system component through the pupil) to localize the system component and / or the eye (e.g., the pupil) based on tracking sensor measurements.

[0078] Optionally, the external device 400 may determine the content to be displayed. Preferably, the content is visual content, but alternatively may be any other content (e.g., content about other senses such as temperature, other information unrelated to senses, etc.). Examples of content include measurements of a real-world scene (e.g., adjacent to the user, in front of the user or external device 400, in the direction of eye gaze, etc.), an artificial reality (AR) overlay (e.g., AR overlay only), AR, virtual reality (VR) overlaid on measurements of an adjacent real-world scene, and / or any other information.

[0079] In a first variant, the content is measured using a sensor 450. Examples of the sensor 450 include a camera (or any optical sensor), a temperature sensor, a motion sensor, a pressure or force sensor, and / or any other sensor. Preferably, the sensor 450 is statically positioned relative to the external device 400 and / or its components (e.g., statically held within a shared external device housing), but may alternatively move relative to the external device 400 (e.g., separate from or movable relative to the external device 400). In a first example, the sensor 450 is attached to the user (e.g., via glasses, contact lenses, a hat, etc.), and optionally, the sensor moves with the user's eye movements. In a second example, the sensor 450 is attached separately from the user (e.g., to a drone, a second user, a stationary camera at a secondary location, etc.). In a second variant, the content is generated using an AR engine, a VR engine, and / or any other content simulation method. In a third variation, the content is generated in other ways (eg, from a database, content retrieved from another device, etc.).

[0080] Optionally, the content may be processed by the external device 400 (e.g., as part of generating emission parameters based on the content). For example, the content may be processed (e.g., temporally, spatially, brightness-adjusted, etc.) so that the resulting signal received by the user from the display 100 is more natural (e.g., mapping an image to a display excitation signal emission so that the brain can better interpret the signal in response to the emission). The content processing may depend on the display 100 implantation location (e.g., processing an image for retinal display may differ from processing an image for direct neural stimulation), cell state, and / or other parameters. In a first embodiment, processing the content includes adjusting the resolution. In a first particular example, the image may be compressed (e.g., downsampled) based on the number of cells in the display-brain interface 200 (e.g., optionally simulating natural compression between photoreceptors and retinal ganglion cells). In a second particular example, the content may be adjusted for variable resolution within the display 100 (e.g., lower resolution at locations on the display 100 located away from the fovea). In a second embodiment, content may be processed based on eye and / or eyelid movement. In a first example, content may be based on an image sampled by a first sensor and gaze tracking determined using a second sensor (e.g., a motion sensor on the controller 300, a tracking sensor on the external device 400, a combination thereof, etc.), and content may be associated with the field of view of the eye based on the orientation of the eye. In a second example, content may be stopped or otherwise adjusted when the user's eyelids close. In a third embodiment, content may be processed to reflect image depth (e.g., to enable the brain to process 2D images as 3D images). In a third embodiment, content may be adjusted based on cell state (e.g., brightness may be increased when less than a threshold number of cells are stimulated, and brightness may be decreased when more than a threshold number of cells are saturated).

[0081] However, the external device 400 may be configured in other ways.

[0082] The power source 500 functions to power one or more implanted system components (e.g., the controller 300 and / or the display 100). In a first variation, the power source 500 (or components of the power source 500) are remote from the implanted system components. The power source 500 may include a power transmitter component remote from the implanted system components (e.g., coupled to the external device 400, a separate device, etc.) as well as a power receiver component connected to one or more implanted system components (e.g., coupled to the controller 300). For example, the power receiver component may be coupled to the controller 300 via a flexible connection wire (e.g., allowing for flexible placement). In particular examples, the power receiver component may include a magnetic coil, a magnetoresistive film, and / or other receiver component that can interface with an external inductive power source. The power source 500 may supply power to the implanted system components via inductive, IR, RF, and / or any other remote power method. Power source 500 and / or its components may be located in the same or a different external device as communications element 420 (e.g., power source 500 is located on a pair of eyeglasses that includes communications element 420). Preferably, the implanted system components do not have substantial power storage components (e.g., when power source 500 is located on a pair of eyeglasses, power is turned off to (implanted) controller 300 and / or display 100 when the eyeglasses are removed from the user), such that the implanted system components are not fully operational without power from power source 500, but may alternatively have a power storage mechanism. In a second variation, power source 500 is implanted along with the system components (e.g., a battery implant).

[0083] The power consumption of the embedded system components may be between 10 mW and 100 mW, or any range or value therebetween (e.g., 30 mW to 35 mW, less than 50 mW, etc.), but may alternatively be greater than 10 mW or less than 100 mW.

[0084] However, power supply 500 may be configured in other ways.

[0085] In a variant, the system may use the systems and methods disclosed in "A thin-film optogenetic visual prosthesis" (Knudsen EB, Zappitelli K, Brown J, Reeder J, Smith KS, Rostov M, Choi J, Rochford A, Slager N, Miura SK, Rodgers K, Reed A, Israeli YRL, Shiraga S, Seo KJ, Wolin C, Dawson P, Eltaeb M, Dasgupta A, Chong P, Charles S, Stewart JM, Silva RA, Kim T, Kong Y, Mardinly AR, Hodak M. 2023. bioRxiv doi:10.1101 / 2023.01.31.526482), which is incorporated by reference in its entirety.

[0086] Illustrative Examples In a first exemplary embodiment, the system may function as a visual prosthesis for a user who has lost photoreceptor function but still has functional retinal ganglion cells. An external device 400 transmits images (e.g., sampled by a camera) and / or emission parameters determined based on the images to a controller 300, which controls the display 100 based on the received information. A light-emitting system within the display 100 emits light based on the emission parameters and / or other control information. The light is received by the user's native retinal ganglion cells (display-brain interface 200), which are genetically engineered to express a transgenic protein sensitive to the emission wavelength. In response to the received light, the retinal ganglion cells stimulate neurons in the brain, which may interpret the stimulation (e.g., allowing the user to "see" an image).

[0087] In a second exemplary embodiment, the system may function as a visual prosthesis for a user who has lost photoreceptor and / or retinal ganglion cell function. The controller 300 provides the display 100 with emission parameters determined based on the received image, and a light-emitting system within the display 100 emits light based on the emission parameters. The light is received by genetically modified cells (e.g., genetically modified to express a transgenic protein sensitive to the emission wavelength) seeded within a cell support connected to the display 100. The genetically modified cells interface with native cells (e.g., using axons and / or dendrites) and provide signals to the native cells, which ultimately provide signals to the brain. In a particular embodiment, the genetically modified cells within the cell support stimulate native retinal ganglion cells (e.g., the native retinal ganglion cells are functional). In a second particular embodiment, the genetically modified cells within the cell support function as retinal ganglion cells and directly stimulate the brain.

[0088] In a third illustrative example, the system may function as a retinal display (e.g., for a virtual reality system) for a user with functional photoreceptors and retinal ganglion cells. A controller 300 provides emission parameters determined based on the generated image to the display 100, and an emission system within the display 100 emits light based on the emission parameters. The emission includes multiple wavelengths of light (e.g., RGB wavelengths) and is received by the user's native retinal ganglion cells (display-brain interface 200), which are not genetically modified. The retinal ganglion cells stimulate neurons in the brain in response to receiving the light, and the brain may interpret the stimulation.

[0089] In a fourth illustrative example, the system may function to directly stimulate neurons, allowing the brain to receive and interpret any type of content (e.g., visual and / or non-visual content, simulated and / or measured information, etc.). The controller 300 provides emission parameters determined based on the received content to the display 100 (implanted in the brain, brainstem, spinal cord, or other nervous system component), and a light-emitting system within the display 100 emits light based on the emission parameters. The light is received by genetically modified cells (e.g., genetically modified to express a transgenic protein sensitive to the emission wavelength) seeded within a cell support connected to the display 100. The genetically modified cells interface with native neurons (e.g., using axons and / or dendrites) to provide signals directly to the brain.

[0090] The various subsystems and / or modules discussed above may be operated and controlled by the same or different entities. In the latter variation, the different subsystems may communicate via APIs, requests, and / or other communication channels (e.g., using API requests and responses, API keys, etc.).

[0091] Alternative embodiments implement the above-described methods and / or processing modules in a non-transitory computer-readable medium storing computer-readable instructions that, when executed by a processing system, cause the processing system to perform the methods discussed herein. The instructions may be executed by computer-executable components integrated with the computer-readable medium and / or the processing system. The computer-readable medium may include any suitable computer-readable medium, such as RAM, ROM, flash memory, EEPROM, optical devices (CD or DVD), hard drives, floppy drives, non-transitory computer-readable media, or any suitable device. The computer-executable components may include a computing system and / or processing system (e.g., including one or more co-located or distributed, remote or local processors) connected to the non-transitory computer-readable medium, such as a CPU, GPU, TPUS, microprocessor, ASIC, etc., although alternatively or additionally, the instructions may be executed by any suitable dedicated hardware device.

[0092] Embodiments of the systems and / or methods may include any combinations and permutations of the various system components and various method processes, and one or more example methods and / or processes described herein may be performed asynchronously (e.g., sequentially), simultaneously (e.g., concurrently, in parallel, etc.), or in any other suitable order by and / or using one or more example systems, elements, and / or entities described herein. The following system and / or method components and / or processes may be used with, in addition to, instead of, or otherwise integrated with all or a portion of the systems and / or methods disclosed in the aforementioned applications, each of which is incorporated by reference in its entirety.

[0093] Those skilled in the art will appreciate from the foregoing detailed description, drawings and claims that modifications and variations can be made to the preferred embodiments of the invention without departing from the scope of the invention as defined in the following claims.

Claims

1. a controller configured to couple to an external surface of a user's eye, a receiver configured to receive content from an external device; a processor configured to determine display instructions based on said content; a controller comprising: a connector comprising a plurality of electrical connections configured to transmit the display instructions from the controller to a display; a display configured to couple to the user's retina, an array of μLEDs configured to emit light signals in accordance with the display instructions, the light signals being received by genetically modified cells within the retina; a display comprising: A system comprising:

2. 10. The system of claim 1, wherein the genetically modified cells are transfected with a gene for a light-sensitive protein, and the genetically modified cells produce a biochemical signal in response to receiving the light signal.

3. The system of claim 2 , wherein the genetically modified cells comprise retinal ganglion cells.

4. 2. The system of claim 1, wherein the display instructions include a time sequence of light array patterns, each light array pattern including a light intensity parameter, each light array pattern encoding a frame of the content.

5. 10. The system of claim 1, wherein the display further comprises a logic component, and the display instructions include μLED state change instructions.

6. The system of claim 1 , fabricated using monolithic integration on thin films.

7. 10. The system of claim 1, wherein the array of μLEDs is configured to emit optical signals at a fixed wavelength.

8. The system of claim 7 , wherein the fixed wavelength is between 510 nm and 550 nm.

9. The system of claim 1 , wherein the display further comprises a micro-optical component configured to collimate the optical signal.

10. 10. The system of claim 9, wherein the micro-optical component comprises at least one of a microlens, a metalens, or a back-reflector.

11. 10. The system of claim 1, wherein the array of μLEDs is configured to emit optical signals at near cellular resolution.

12. The system of claim 1 , wherein the content includes an image, and the external device comprises a pair of glasses and a camera configured to sample the image.

13. a cell support comprising a set of microwells configured to hold a set of cells transfected with a gene for a light-sensitive protein; a μLED array coupled to the cell support, the μLED array configured to emit light signals based on a display command, the light signals being received by the set of cells; and a receiver configured to receive content from an external device; a processor configured to determine the display instructions based on the content; A system comprising:

14. 14. The system of claim 13, wherein the set of cells comprises neurons derived from pluripotent stem cells, and the cell support is configured to be attached to a user's brain.

15. 14. The system of claim 13, wherein the μLED array comprises at least 1000 μLEDs.

16. 14. The system of claim 13, wherein the set of cells comprises hypoimmune cells, and the set of cells is further transfected with a kill switch gene.

17. 14. The system of claim 13, wherein each μLED in the μLED array corresponds to a single microwell in the set of microwells, and wherein the single microwell is configured to hold a single cell in the set of cells.

18. The system of claim 13 , further comprising a sensor configured to be implanted within a user, wherein the display instructions are adjusted based on measurements from the sensor.

19. The system of claim 18 , wherein the sensor includes at least one of a temperature sensor or a humidity sensor.

20. 20. The system of claim 18, wherein the sensor is configured to measure a cellular state of the user's native cells, the cellular state including at least one of current or voltage, and the display instructions are adjusted based on the cellular state.

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