Multiplexed Scleral Lens Sensors for Monitoring Ocular Physiology

由于泪腺疾病、睑板腺功能障碍、激光辅助原位角膜磨镶术（LASIK）和屈光性眼科手术导致的慢性眼部疾病和创伤导致泪液分泌减少和/或泪液蒸发增加。这种眼部生理的不平衡改变了泪膜中电解质的浓度。相关的干眼综合征（干燥性角膜结膜炎）损害了英国530万患者和全球6000万人的日常活动。早期有效治疗此类眼部疾病对于预防导致视力受损和失明的角膜瘢痕形成至关重要。尽管存在有效的眼科仪器来在临床环境中测试眼部生理学，但是在护理点环境中没有便携式伴随诊断可用于调整滴眼剂和药物剂量。尽管低渗人工泪液制剂通常用于治疗眼部生理学的不平衡，但效果有限，但人工泪液中的个体化电解质组合物和受控药物剂量已显示在重建眼部稳态方面显著更有效。因此，持续监测眼部生理的能力可以实现个性化配方和滴眼液的受控给药。该项目旨在创建多路复用巩膜透镜传感器，该传感器以比色方式显示泪液电解质的浓度，用于在护理点设置中持续监测眼部生理。巩膜透镜代表了一种聚合物平台，用于构建用于泪液电解质的微创连续测量的生物传感器。该项目将涉及开发可穿戴的多路复用巩膜透镜传感器，以采样和分析泪液电解质成分。该项目的成功完成将产生一个配套的诊断平台，可以实现个性化的眼科治疗。在第一个目标中，将合成丙烯酰化离子选择性螯合剂以可逆地结合到电解质。第二个目的是使用全息激光干涉光刻在巩膜透镜的螯合剂官能化的感测区域中形成比色传感器。泪液将被收集在物理分离的传感区域中，以基于颜色变化显示电解质的浓度。第三个目标是开发一种便携式光谱仪，其使用智能手机相机应用程序将巩膜透镜传感器的比色图像转换为定量浓度值。第四个目的是在离体前猪眼疾病模型中测试巩膜透镜传感器。将通过模拟离体眼模型中的电解质浓度不平衡来评价巩膜透镜传感器的选择性和灵敏度，以监测眼部生理学病症。在最后一个目的中，将从患有干眼综合征的志愿者患者和健康患者中获得人泪液样品。巩膜透镜传感器在监测人类泪液电解质方面的选择性、灵敏度和响应时间将与离子选择性电极（金标准）进行比较，以验证体外设备性能。该项目将产生一个智能手机辅助的伴随诊断平台，为个性化医疗提供泪液生物标志物的定量测量。利用巩膜透镜传感器连续监测泪液生物标志物的能力将使得能够制定个性化的眼部药物并调整眼部疾病中的药物剂量。这种眼科传感平台的更广泛应用是在护理点环境中诊断慢性眼部疾病和代谢缺陷。该项目的结果将用于创建巩膜透镜传感器的对照临床试验的基础。微创伴随诊断的部署将减少NHS眼科服务的工作量并降低住院费用。

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.