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Development of a minimally invasive optical biosensor to improve hyperphosphatemia management

开发微创光学生物传感器以改善高磷血症管理

基本信息

批准号：
10742278
负责人：
Daniel Alge
金额：
$ 42.44万
依托单位：
TEXAS ENGINEERING EXPERIMENT STATION
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-01 至 2025-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10742278
关键词：
Address Animal Model Biocompatible Materials Biomedical Engineering Biosensing Techniques Biosensor Blood Calcium Calibration Cardiovascular system Childhood Chronic Kidney Failure Clinical Data Set Detection Development Diagnostic tests Diffusion Disease Disease model Encapsulated End stage renal failure Engineering Exhibits Foundations Goals Histologic Home Homeostasis Hydrogels Immune response Immune system Implant In Vitro Ingestion Intake Intercellular Fluid Intervention Kidney Diseases Knockout Mice Measurement Measures Medicine Metabolism Metalloporphyrins Monitor Morbidity - disease rate Non-Invasive Detection Optical Methods Optics Oxygen Patients Performance Pharmaceutical Preparations Phosphorus Physicians Physiological Population Porosity Porphyrins Pyruvate Pyruvate Oxidase Research Scientist Serum Signal Transduction Skin Technology Testing Texas Thick Titrations Universities absorption acetyl phosphate biomaterial compatibility clinical translation college crosslink density design dietary dietary restriction empowerment ethylene glycol implant material improved improved outcome in vitro testing in vivo in vivo evaluation inorganic phosphate mid-career faculty minimally invasive mortality mouse model new technology non-invasive monitor particle phosphorescence professor sensor standard of care tool

项目摘要

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.

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。由此可见，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.