Development of a minimally invasive optical biosensor to improve hyperphosphatemia management

项目摘要 晚期慢性肾脏病患者体内钙磷平衡显著紊乱 (CKD)和晚期肾病血清磷酸盐浓度升高-一种已知的情况 如高磷酸盐血症-是心血管疾病发病率和死亡率的重要原因， 人口因此，医生对这些患者进行磷摄入的饮食限制， 抑制磷吸收的药物。护理标准是滴定这些 对患者的血清磷酸盐浓度进行干预，但该水平仅在每月检查一次 间隔，其仅提供患者的动态状况的不频繁的快照。因此，新 需要磷酸盐监测技术，使医生和患者能够更好地管理 高磷血症该项目的目标是通过开发 一种可用于非侵入性测量血清磷酸盐浓度的光学生物传感器。 目标1是生物传感器的开发，将通过设计水凝胶来实现 包封含有金属卟啉的生物传感器颗粒的复合材料 磷酸盐浓度与可以通过皮肤检测到的光学信号相关联。体外测试 在模拟生理条件下进行，以优化范围和灵敏度的 生物传感器目的2包括生物传感器的体内测试。测试将在 Col 4a 3敲除小鼠CKD模型，其表现出钙和磷酸盐失调 代谢和高磷酸盐血症。生物传感器性能将通过与 血液和组织液中磷酸盐的测量。如果成功，该项目将提供一个 为后续在大型CKD动物模型中进行测试奠定了基础， 翻译.

PROJECT SUMMARY Calcium and phosphate homeostasis is significantly disrupted in advanced chronic kidney disease (CKD) and end-stage kidney disease. Elevated serum phosphate concentration – a condition known as hyperphosphatemia – is a significant cause of cardiovascular morbidity and mortality in this population. Thus, physicians treat these patients with dietary restriction of phosphorus intake and medications that inhibit the absorption of ingested phosphorus. The standard of care is to titrate these interventions to a patient’s serum phosphate concentration, but this level is checked only at monthly intervals, which provides only an infrequent snapshot of a patient’s dynamic condition. Thus, new technology for phosphate monitoring is needed to empower physicians and patients to better manage hyperphosphatemia. The objective of this project is to address this need through the development of an optical biosensor that can be used to non-invasively measure serum phosphate concentration. Aim 1 is focused on biosensor development, which will be approached by designing hydrogel composites encapsulating metalloporphyrin-containing biosensor particles that will transduce phosphate concentration to an optical signal that can be detected through the skin. In vitro testing under simulated physiologic conditions will be performed to optimize the range and sensitivity of the biosensor. Aim 2 encompasses in vivo testing of the biosensor. Testing will be performed in the Col4a3 knockout mouse model of CKD, which exhibits dysregulated calcium and phosphate metabolism and hyperphosphatemia. Biosensor performance will be evaluated by comparison to blood and interstitial fluid measurements of phosphate. If successful, this project will provide a foundation for subsequent testing in a large animal model of CKD and efforts toward clinical translation.