Novel Point-of-Care Device for Urinary Hepcidin to Detect Iron Deficiency in Children and Adolescents

摘要/摘要 缺铁(ID)是世界范围内贫血的主要原因，影响超过17 仅在美国就有数百万儿童。然而，它现在被认为是即使没有贫血，ID 对认知发展、内分泌功能以及身体和行为产生不利影响 儿童的成长和发展。而在美国，贫血在3.4%的儿童中普遍存在 年龄在0.5-4岁之间，非贫血型糖尿病的患病率要大得多，估计为15.1% 12-23个月的儿童占16.5%，2-5岁的占16.5%。理想情况下，一个非侵入性的护理点 (POC)设备自信地诊断ID将引起儿科医生的极大兴趣。海普西丁-25 已被证明是全身性铁稳态的主要调节者。测量 血清海普西丁是评估铁状态的可靠标记物，并可被证明是有价值的 成人和儿童生理ID的指示器。尿海普西丁与 血清海普西丁可作为诊断儿童ID的良好标志物 使用我们计划商业化的非侵入性PoC设备的青少年。 内在生命科学(ILS)正在请求直接向第二阶段提供资金以继续 多重POC侧向流动分析(LFA)法定量尿海普西汀的商业化 归一化为尿肌酐。我们已经成功地完成了原理论证研究 从而形成了LFA的工作原型。为了达到这个里程碑，ILS与一家 圣地亚哥当地公司NanoComposx(NCX)利用他们的超亮金纳米壳 显著提高诊断灵敏度的技术。读者的选择将是下一步的关键 参与该设备的商业开发。最终用户的设计输入将帮助选择 适当的条带阅读器，然后优化横向流动条带的几何形状，以便在 与所选读卡器兼容的盒式磁带。海普西丁和肌酐的检测结果将是 在单个条带上进行多路传输，将对灵敏度和精度进行进一步的优化 POC设备的验证将遵循FDA的生物分析方法行业指南 验证。我们的儿科临床合作者将在 在大规模生产之前评估设计控制适宜性的研究能力。 同时，ILS将采集匹配的血清和尿液样本，并进行接收器操作 特性曲线分析，以评估POC原型装置对 预测ID。在商业化前阶段IIB的后续资金中，该设备将是 在多中心临床试验中进行了测试，结果提交给FDA进行510(K)计划的批准。

Summary/Abstract Iron deficiency (ID) is a leading cause of anemia worldwide and affects more than 17 million children in the US alone. However, it is now recognized the even without anemia, ID adversely affects cognitive development, endocrine function, and physical and behavioral growth and development in children. While anemia in the US is prevalent in 3.4% of children ages 0.5-4 years old, the prevalence of non-anemic ID is much greater, estimated to be 15.1% in children from 12-23 months and 16.5% from 2-5 years. Ideally, a non-invasive point-of-care (POC) device to confidently diagnose ID would be of great interest to pediatricians. Hepcidin-25 has been shown to be the principal regulator of systemic iron homeostasis. Measurement of serum hepcidin is a reliable marker for assessment of iron status and can prove a valuable indicator of physiologic ID in adults and children. Urinary hepcidin is strongly correlated with serum hepcidin and would serve as an excellent marker to diagnose ID in children and adolescents employing the non-invasive POC device that we propose to commercialize. Intrinsic LifeSciences (ILS) is requesting Direct to Phase II funding to continue commercialization of a multiplexed POC lateral flow assay (LFA) to quantify urinary hepcidin normalized to urinary creatinine. We have successfully completed proof of principle research resulting in a working prototype of the LFA. To achieve this milestone, ILS contracted with a local San Diego company, NanoComposix (NCX), to utilize their ultra-bright gold nanoshell technology to dramatically enhance diagnostic sensitivity. Reader selection will be a critical next step in the commercial development of this device. End user design input will assist in selecting a suitable strip reader followed by optimization of lateral flow strip geometry for deployment in a cassette compatible with the selected reader. The hepcidin and creatinine assays will be multiplexed on a single strip, further optimization for sensitivity and precision will be undertaken and validation of the POC device will follow FDA industry guidelines for bioanalytical method validation. Our pediatric clinical collaborators will beta test the LFA POC prototype device in a research capacity to assess design control suitability before large scale manufacturing. Concurrently, ILS will procure matched serum and urine samples and perform receiver operator characteristic curve analysis to assess the diagnostic strength of the POC prototype device to predict ID. During pre-commercialization Phase IIB follow-on funding, the device would be tested in a multi-center clinical trial and the results submitted to the FDA for 510(k) clearance.