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

用于检测儿童和青少年缺铁情况的新型尿铁调素护理点设备

• 批准号: 10709598
• 负责人: Vaughn E Ostland
• 金额: $ 78.87万
• 依托单位: INTRINSIC LIFESCIENCES, LLC
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-25 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10709598
• 关键词: 4 year old; Acute Renal Failure with Renal Papillary Necrosis; Address; Adolescent; Adoption; Adult; Affect; Affinity; Age; Amino Acids; Anemia; Behavioral; Biological Assay; Biological Sciences; Blood Banks; Characteristics; Child; Childhood; Classification; Clinic; Clinical; Clinics and Hospitals; Code; Contracts; Creatinine; Current Procedural Terminology; Custom; Data; Development; Device or Instrument Development; Devices; Diagnosis; Diagnostic; Diagnostic Equipment; Diagnostic Sensitivity; Dialysis procedure; Discrimination; Endocrine; Engineering; Enzyme-Linked Immunosorbent Assay; Equipment; Funding; Geometry; Goals; Growth; Growth and Development function; Guidelines; Homeostasis; Hormones; Human; Immunoassay; Industry; Institution; Insurance; Iron; Iron Metabolism Disorders; Iron deficiency anemia; Knowledge; Laboratories; Lateral; Liver; Measurement; Measures; Medical; Medical Device; Methods; Monitor; Monoclonal Antibodies; Multi-Institutional Clinical Trial; Neonatal; Outcome; Patients; Pediatrics; Performance; Phase; Physiological; Prevalence; Public Health; Reader; Receiver Operating Characteristics; Research; Research Design; SARS-CoV-2 exposure; Sales; Sampling; Sensitivity and Specificity; Serum; Signal Transduction; Sodium Chloride; Sports Medicine; Target Populations; Technology; Testing; Urine; Validation; Venipunctures; Venous blood sampling; Visit; Work; cognitive development; commercial application; commercialization; commercialization readiness; cost; design; follow-up; hepcidin; improved; in-vitro diagnostics; innovation; interest; iron deficiency; large scale production; lateral flow assay; manufacture; nanoGold; nanoshell; novel; pediatrician; peptide hormone; point of care; prototype; rapid diagnosis; research and development; technology validation; urinary

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.

摘要/摘要 缺铁 (ID) 是全世界贫血的主要原因，影响超过 17 仅在美国就有 100 万儿童。然而，现在人们认识到即使没有贫血，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。在美国，3.4% 的儿童普遍患有贫血症 0.5-4岁年龄段，非贫血性ID的患病率更高，估计为15.1% 12-23 个月的儿童和 2-5 岁的儿童占 16.5%。理想情况下，非侵入性护理点 儿科医生对能够自信地诊断 ID 的 (POC) 设备非常感兴趣。铁调素-25 已被证明是全身铁稳态的主要调节剂。测量 血清铁调素是评估铁状态的可靠标志物，并且可以证明是有价值的 成人和儿童生理 ID 的指标。尿铁调素与 血清铁调素可作为诊断儿童和青少年 ID 的极好标志物 青少年使用我们建议商业化的非侵入性 POC 设备。 Intrinsic LifeSciences (ILS) 正在请求直接进入第二阶段资金以继续 用于定量尿铁调素的多重 POC 侧流测定 (LFA) 的商业化 标准化为尿肌酐。我们已成功完成原理研究证明 产生了 LFA 的工作原型。为了实现这一里程碑，ILS 与一家 圣地亚哥当地公司 NanoComposix (NCX) 利用其超亮金纳米壳 技术显着提高诊断灵敏度。读者选择将是接下来的关键 该设备的商业开发迈出一步。最终用户设计输入将有助于选择 合适的试纸条读取器，然后优化侧流试纸条几何形状，以便在 与所选读卡器兼容的盒式磁带。铁调素和肌酐测定将 多路复用在单个条带上，将进一步优化灵敏度和精度 POC 设备的验证将遵循 FDA 生物分析方法行业指南 验证。我们的儿科临床合作者将在一个实验室中对 LFA POC 原型设备进行 Beta 测试 在大规模制造之前评估设计控制适用性的研究能力。 同时，ILS将采购匹配的血清和尿液样本并进行接收操作员 特征曲线分析以评估 POC 原型设备的诊断强度 预测ID。在预商业化阶段 IIB 后续资金期间，该设备将 经过多中心临床试验测试，并将结果提交给 FDA 进行 510(k) 审批。