Design, Fabrication and Testing of a Multi-electrode Electroretinogram System for Mouse Eyes

Neurodegenerative retinal diseases are the leading cause of blindness nowadays, and they are becoming increasingly common. In many cases, retinal diseases begin in the peripheral areas of the retina, where common clinical tests are less effective, making early diagnosis difficult. The Electroretinogram (ERG) is a diagnostic test that is able to record, at the level of the cornea, the electrical response of the cells that make up the retina as they are stimulated by light stimuli. It is therefore an effective way to study the function of the retina itself, identifying possible abnormalities and dysfunction, often caused by diseases such as Glaucoma, Macular Degeneration or Diabetic Retinopathy. Conventional ERG makes use of a single measuring electrode, which then shows a response that is an average of all potentials present on the cornea. Lacking spatial accuracy, what is more recently used is what is called Multi Electrode Electroretinogram (meERG), which proposes the use of several measurement channels to improve the spatial resolution of the recorded signals. To record the meERG signals, contact lens electrode arrays, so-called CLEAr lenses, were introduced, capable of performing a meERG on both the human and rat eye. Because of the small size of the mice, which are an extremely useful model for studying the course and treatment (with innovative Gene Therapy techniques) of retinal diseases, it had not yet been possible to scale this technology to the size of their corneas. This project, therefore, aims to design, fabricate, and test an innovative prototype CLEAr lens capable of performing a meERG on the eye of a mouse, with the ultimate goal of providing a viable shoulder in the field of early detection of retinal diseases to work alongside human and rat studies. The experimental research for this thesis project has been carried out at the University of Illinois at Chicago’s Neural Engineering Vision Laboratory (NEVL). The starting idea was taken from a previous research group that had begun a rough study of a possible prototype. This consisted of a backbone containing everything necessary to obtain a working device: PCB, LED, measurement electrodes, and a contact lens. Starting from this draft, a detailed study of each component began in an attempt to optimize the final prototype and make it fully functional and suitable for the purpose for which it was conceived. Using CAD design software, the study of the design of the device was carried out, managing to improve the distribution of space inside and outside the device itself, bringing the LED and PCB into contact, and making a contact lens of right dimensions. Next came the fabrication of the device, using innovative techniques such as 3D printing and milling, resulting in a prototype that featured a silicone lens on which were as many as five measurement electrodes, perfectly symmetrical with respect to the center of the cornea and connected to an external circuit for data conditioning, recording and eventual analysis. The internal presence of the LED (appropriately positioned so as to maximize the light coming out of the device) was a further step forward and a reason for great innovation, as it allows the device both to generate the light stimulus and to record retinal potentials. Finally, a preliminary test of the prototype’s functionality was carried out through some electrical and bioelectric signal recordings to evaluate its optimization. The first chapter presents a brief description of the eye, with a special focus on the retina and its main diseases. It also introduces the problem of spatial resolution present in the conventional Electroretinogram and how it progressively led to meERG on mice as a possible innovation in the field of studying retinal diseases combined with Gene therapy. The second chapter lists the specific aims of this thesis project. The third chapter describes the entire design phase of the new innovative prototype CLEAr lens design using Fusion360 software. The fourth chapter discusses the fabrication process that from CAD models led to the realization of a ’physical’ contact lens device, and the realization of the external front-end circuits, signal acquisition and LED driving. The fifth chapter presents the analysis of the prototype from the point of view of both geometry and emitted light, verifying compliance with the requirements placed in the design phase, and finally shows the results of the first signal recording tests (sine wave, EKG and ECG). Finally, the last chapter focuses on drawing conclusions on the thesis work, as well as including limitations of the current device and the future developments.