Multiplexed Scleral Lens Sensors for Monitoring Ocular Physiology

由于泪腺疾病、眉板腺功能障碍、准分子激光原位角膜磨镶术(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。这种眼生理失衡会改变泪膜中电解质的浓度。相关的干眼综合征(干燥性角结膜炎)损害了英国530万患者和全球6000万人的日常活动。早期有效地治疗此类眼病是防止角膜瘢痕形成导致视力受损和失明的关键。虽然在临床环境中存在有效的眼科仪器来测试眼生理，但在护理地点环境中没有便携式伴随诊断可用来调整眼药水和药物剂量。虽然低渗人工泪液制剂通常用于治疗眼生理失衡，但效果有限，但个性化的电解质成分和人工泪液中受控的药物剂量已被证明在重建眼内稳态方面明显更有效。因此，持续监测眼部生理的能力可以实现个性化的滴眼液配方和受控给药。该项目旨在创造多路复用的巩膜晶状体传感器，以色度计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。巩膜镜片是一种聚合物平台，可以构建用于泪液电解质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式巩膜透镜传感器，以采样和分析泪液电解质成分。该项目的成功完成将带来一个配套的诊断平台，使个性化的眼睛治疗成为可能。在第一个目标中，将合成丙烯酰化的离子选择性螯合剂以可逆地结合到电解液上。第二个目标是使用全息激光干涉光刻在巩膜晶状体的螯合剂功能化传感区域形成比色换能器。泪液将被收集在物理上分离的感应区，以根据颜色变化显示电解液的浓度。第三个目标是开发一种便携式光谱仪，使用智能手机相机应用程序将巩膜晶状体传感器的色度图像转换为定量浓度值。第四个目标是在体外猪眼前部疾病模型中测试巩膜晶状体传感器。巩膜晶状体传感器的选择性和灵敏度将通过模拟眼球体外模型中的电解质浓度失衡来评估，以监测眼生理疾病。在最后一个目标中，人类泪液样本将从患有干眼综合征的志愿者患者和健康患者身上获得。在监测人类泪液电解质方面，巩膜晶状体传感器的选择性、灵敏度和响应时间将与离子选择电极(金标准)的选择性、灵敏度和响应时间进行比较，以验证体外设备的性能。该项目将导致一个由智能手机辅助的配套诊断平台，以提供个性化医学中泪液生物标记物的定量测量。用巩膜晶状体传感器连续监测泪液生物标志物的能力将使制定个性化的眼部药物和调整眼部疾病的药物剂量成为可能。该眼科传感平台在诊断慢性眼部疾病和护理场所的代谢缺陷方面有更广泛的应用。该项目的结果将被用于为巩膜晶状体传感器的受控临床试验奠定基础。部署微创辅助诊断将减少NHS眼科服务的工作量和住院成本。

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.