N.L. Wagner, D. Sylva, H. Sylva, K. Dixit, J.A. Greco
LambdaVision,
United States
Keywords: biomanufacturing, artificial retina, layer-by-layer, protein-based technologies, bacteriorhodopsin, low-earth orbit, thin films, protein layering
Summary:
LambdaVision has developed a protein-based artificial retina to restore vision to the millions of people blinded by retinal degenerative diseases, including retinitis pigmentosa and age-related macular degeneration. The artificial retina thin films are manufactured using a layer-by-layer (LBL) assembly technique, in which alternating layers of the light-activated protein, bacteriorhodopsin (BR), and a polycation binder are deposited onto an ion-permeable film. The resulting artificial retina thin films contain hundreds of oriented layers of BR, and upon the absorption of light, the thin films generate a unidirectional ion gradient that can stimulate the remaining neuronal network of the retina for patients suffering from advanced retinal degeneration. Despite early proof of concept work that demonstrated implant activity and effectiveness of stimulating retinal ganglion cells of degenerated retinal tissue, LBL production of the artificial retina thin films requires optimization to ensure consistency in thickness, homogeneity, and protein orientation. A microgravity environment is known to improve the three-dimensional assembly of thin films due to the elimination of buoyancy-driven convective turbulence and Stokes sedimentation effects. To date, LambdaVision, along with implementation partner, Space Tango, have completed a series of nine microgravity experiments on the International Space Station (ISS) that have established the hardware and software required for producing artificial retinas using a LEO platform. These experiments demonstrated the fluidics, operational controls, and in-process quality measurements were validated through the assembly of multiple artificial retina thin films in microgravity. These missions have demonstrated reproducible hardware performance in both a terrestrial and microgravity environment, and the CubeLabs have a proven tech stack with good control and automation. We have consistently met the goal of assembling 200-layer thin films in microgravity, and have also strengthened thin film quality assessment techniques using confocal microscopy, thus enabling the direct comparison of terrestrial- and microgravity-assembled artificial retinas films. Specifically, confocal microscopy was used to examine the thickness of the multilayered films, the extent of uniformity across the film, and the degree of aggregate deposition. Despite some midline shearing, the LBL assembly of the thin films was successful and validated the hardware and software required for production in the closed-loop CubeLab architecture. These advancements place LambdaVision and Space Tango in a favorable position for further microgravity tests, scaling up the production capabilities, and implementing GMP procedures for preclinical and clinical efforts.