Multiplexed Scleral Lens Sensors for Monitoring Ocular Physiology

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Chronic eye diseases and trauma due to lacrimal gland disease, meibomian gland dysfunction, laser-assisted in situ keratomileusis (LASIK) and refractive eye surgeries result in a decrease in tear secretion and/or an increase in tear evaporation. This imbalance of ocular physiology alters the concentrations of electrolytes in the tear film. The associated dry eye syndrome (keratoconjunctivitis sicca) impairs the daily activities of 5.3 million patients in the UK and 60 million people globally. Early-stage and effective treatment of such ocular disorders is paramount to prevent corneal scarring that lead to impaired vision and blindness. Although efficacious ophthalmic instruments exist to test ocular physiology in clinical settings, no portable companion diagnostic is available in point-of-care settings to adjust eye drops and medication dose. Although hypotonic artificial tear formulations are commonly used to treat imbalances in ocular physiology with limited effectiveness, individualised electrolyte compositions and controlled drug dosing in artificial tears have been shown to be significantly more efficacious in re-establishing ocular homeostasis. Hence, the ability to monitor continually ocular physiology can enable personalised formulation and controlled administration of eye drops.This project aims to create multiplexed scleral lens sensors that colorimetrically display the concentrations of tear electrolytes for continually monitoring ocular physiology in point-of-care settings. Scleral lenses represent a polymeric platform to build biosensors for minimally-invasive continual measurements of tear electrolytes. This project will involve developing wearable multiplexed scleral lens sensors to sample and analyse tear electrolyte composition. The successful completion of this project will result in a companion diagnostic platform that will enable personalised eye treatments. In the first objective, acryloylated ion-selective chelators will be synthesised to bind to electrolytes reversibly. The second objective is to form a colorimetric transducer in the chelator-functionalised sensing regions of a scleral lens using holographic laser interference lithography. The tear fluid will be collected in physically-separated sensing regions to display the concentration of electrolytes based on colour changes. The third objective is to develop a portable spectrometer using a smartphone camera application to convert the colorimetric images of the scleral lens sensors into quantitative concentration values. The fourth objective is to test the scleral lens sensors in an ex vivo anterior porcine eye disease model. The selectivity and sensitivity of the scleral lens sensors will be evaluated by simulating the electrolyte concentrations imbalances in the ex vivo eye model to monitor ocular physiology disorders. In the last objective, human tear samples will be obtained from volunteer patients with dry eye syndrome and healthy patients. Selectivity, sensitivity and response time of the scleral lens sensors in monitoring human tear electrolytes will be compared to those of ion-selective electrodes (gold standard) to validate in vitro device performance.This project will result in a companion diagnostic platform assisted by smartphones to provide quantitative measurements of tear biomarkers in personalised medicine. The ability to monitor continually tears biomarkers with scleral lens sensors will enable the formulation of individualised eye medications and adjusting drug dosing in eye disorders. Broader applications of this ophthalmic sensing platform are in the diagnoses of chronic ocular diseases and metabolic deficiencies in point-of-care settings. The results of this project will be used to create a basis for a controlled clinical trial of the scleral lens sensors. The deployment of minimally-invasive companion diagnostics will decrease the work load and reduce hospitalisation costs in the NHS ophthalmology services.