Multiplexed Scleral Lens Sensors for Monitoring Ocular Physiology

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.

This research program aims to develop a contact lens sensing platform to monitor ocular physiology in point-of-care settings. We expect to demonstrate a multiplexed scleral lens sensor capable of providing diagnostic information of the tear fluid, which can be quantitatively analysed using a smartphone. The implementation of this project will provide crucial know-how expertise of creating wearable sensor devices in the UK. This will have a profound academic, industrial and societal impact.

Knowledge
Academic beneficiaries will be able to use the output from this research program to develop optical sensors for the diagnosis and monitoring of ocular eye disorders. In the short term, the knowledge will be transferred through project partners including Prof. Dunn, Prof. Wolffsohn, Prof. Cordeiro and NIHR London IVD Co-operative. The project collaborators will be able to build on the continual scleral sensing platform and exploit broader applications in wearable point-of-care diagnostics. This research will underpin future studies into the non- or minimally-invasive continual tear monitoring. The knowledge and academic impact will extend beyond the field of ocular diagnostics to any polymeric wearable device that features biomarker sensors.


People
The proposed project will expand the know-how expertise within the UK and globally. The PDRA will benefit from the training in multiplexed biosensor development and wearable device design, while gaining in depth-knowledge in the diagnosis of ocular disorders through tear film analysis. The PhD students in the PI's group as well as the students in the Institute for Molecular Sciences will benefit from the expertise developed in chelator synthesis and sensor fabrication. Furthermore, the PI is the co-director of Clinician Engineer Hub, a non-profit organisation, which provides training to engineers and clinicians in medical device development. The PI will utilise this educational platform will create outreach events to the general public.

Economy
The knowledge and academic impact will translate into industrial, economic and strategic impact. This project will lead to the development of continual point-of-care diagnostic devices, which will provide a competitive edge to the UK biotechnology companies (GlaxoSmithKline and AstraZeneca) involved in ophthalmic drug development. UK-based eye drops manufacturers including Reckitt Benckiser (Optrex), Medicom Healthcare and Entod Research Cell will benefit from the findings of this project to develop personalised eye drops. The ability to create wearable devices for companion diagnostics is a route to significant industrial and economic impact. Additionally, contact lens manufacturers within the UK (Bausch + Lomb UK Ltd., UltraVision CLP Ltd. and Contamac Ltd. will also benefit from the findings of this study. The project's protocols and expertise developed will be available through NIHR London In Vitro Diagnostics Co-operative. The PI will partner with Imperial Innovations to increase the commercialisation impact as well as knowledge transfer to startup companies. This will ultimately extent the list of beneficiaries to a broad audience, creating a pioneering pathway for the development of ophthalmic sensors.

Society
The industrial and economic impact will result in a considerable societal impact. This project aims to support the on-going activities of NHS Ophthalmology services in personalised medicine by developing continual biomarker monitoring devices. The capability to acquire continual patient data in point-of-care settings through contact lens sensing platform will improve the quality of life of patients by personalised treatments. Such point-of-care technologies aim to shift the burden from centralised hospitals to home settings to reduce the burden on NHS public health services. Furthermore, the PI will continue to work with government agencies to create regulatory legislations regarding digital health in the UK.