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.

总结/摘要 缺铁（ID）是全球贫血的主要原因，影响超过17 仅在美国就有100万儿童。然而，现在公认即使没有贫血，ID 对认知发育、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16.5%。理想情况下，一个非侵入性的护理点 (POC)能够自信地诊断ID的设备将引起儿科医生的极大兴趣。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， 成人和儿童生理ID指标。尿铁调素与 血清hepcidin，并将作为一个很好的标志物，以诊断ID的儿童， 青少年使用我们建议商业化的非侵入性POC设备。 Intrinsic LifeSciences（ILS）正在申请直接进入第二阶段的资金， 用于定量尿铁调素的多路POC侧流测定（LFA）的商业化 以尿肌酸酐标准化。我们成功完成了原理验证研究 从而产生LFA的工作原型。为了实现这一里程碑，ILS与一个 当地圣地亚哥公司，NanoComposix（NCX），利用他们的超亮金纳米壳 技术，以显着提高诊断灵敏度。读者的选择将是一个关键的下一步 迈出了该设备商业开发的一步。最终用户设计输入将有助于选择 合适的条带读取器，随后优化侧向流动条带几何形状，以用于在 与所选读卡器兼容的卡匣。铁调素和肌酸酐测定将在 在单个条带上进行多路复用，将对灵敏度和精确度进行进一步优化 POC装置的验证将遵循FDA生物分析方法行业指南 验证。我们的儿科临床合作者将对LFA POC原型设备进行beta测试， 在大规模生产前评估设计控制适用性的研究能力。 同时，ILS将获得匹配的血清和尿液样本，并执行接收操作 特征曲线分析，以评估POC原型器械的诊断强度， 在商业化前的IIB期后续资助期间，该器械将 在多中心临床试验中进行测试，并将结果提交给FDA进行510（k）批准。