Portable, affordable, quantitative microchip electrophoresis system for integrated anemia and hemoglobin variant testing

便携式、经济实惠的定量微芯片电泳系统，用于综合贫血和血红蛋白变异测试

• 批准号: 9909933
• 负责人: PETER GALEN
• 金额: $ 22.5万
• 依托单位: HEMEX HEALTH, INC.
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-05 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9909933
• 关键词: Address; Affect; Africa; Anemia; Bedside Testings; Biological Assay; Blood; Blood Tests; Blood specimen; Clinical; Complete Blood Count; Detection; Diagnosis; Diagnostic tests; Drops; Early Diagnosis; Ensure; Gold; Health; Health Status; Hematological Disease; Hemoglobin; Hemoglobin E Disease; Hemoglobin concentration result; High Pressure Liquid Chromatography; High Prevalence; Human Resources; In Vitro; India; Individual; Infrastructure; Inherited; Laboratories; Malnutrition; Measurement; Measures; Methods; Microchip Electrophoresis; Monitor; Names; Patient Monitoring; Patients; Performance; Persons; Phase; Population; Primary Health Care; Reporting; Sickle Cell Anemia; Small Business Technology Transfer Research; Southeastern Asia; System; Technology; Testing; Thalassemia; Variant; World Health Organization; base; clinical efficacy; clinically relevant; commercialization; diagnostic accuracy; disease diagnosis; genetic variant; hydroxyurea; innovation; low and middle-income countries; novel; performance tests; point of care; portability; primary care setting; research clinical testing

PROJECT SUMMARY Anemia is characterized by low blood hemoglobin levels and has high prevalence affecting over one-third of the world's population or about 2.5 billion people. Anemia has numerous causes, including nutritional deficiencies, oncologic conditions, and hematologic diseases, including hemoglobin gene variants. More than 7% of the world's population carry hemoglobin gene variants, one of which is Sickle Cell Disease (SCD). SCD or sickle cell anemia is one of the most commonly inherited blood anemias. Anemia and SCD diagnosis/monitoring are challenging in low and middle income countries due to lack of laboratory infrastructure and skilled personnel. In a 2019 report, World Health Organization has listed hemoglobin testing (diagnosis and monitoring of anemia) as an essential in vitro diagnostic tests for primary care in low and middle income countries. We have developed a point-of-care (POC) microchip electrophoresis hemoglobin variant testing system, HemeChip. HemeChip has been extensively validated in the US, Africa, India, and South-East Asia, for hemoglobin variants. In this STTR Phase I project, we plan to add total hemoglobin quantification and anemia testing capability to HemeChip system and develop HemeChip+. The proposed HemeChip+ is the first and only single test, POC platform for portable, affordable, accurate, and quantitative hemoglobin quantification, anemia detection, and hemoglobin variant identification. Based on our preliminary findings, we hypothesize that rapid, affordable, integrated, POC testing of anemia and hemoglobin variants is feasible with the proposed HemeChip+ system. To test this hypothesis, we propose the following distinct but interrelated aims: Aim1: To develop the HemeChip+ platform for integrated quantitative hemoglobin testing, anemia detection, and quantitative hemoglobin variant identification. Aim 1 milestone is to achieve, in a single test, accurate total hemoglobin quantification (g/dL), hemoglobin variant identification, and hemoglobin variant percent (%) quantification using a drop of blood, in less than 10 minutes. Aim 2: To perform clinical testing of the integrated HemeChip+ anemia and hemoglobin variant testing system. Aim 2 Milestone is to validate the HemeChip+ performance as an integrated assay for anemia and hemoglobin variant testing platform. Quantitative hemoglobin test performance target is >90% correlation (Pearson correlation coefficient >0.90, p<0.01) with the results of clinical gold standard method, Complete Blood Count. Hemoglobin variant identification performance target is >95% accuracy; and hemoglobin variant % quantification performance target is >90% correlation (Pearson correlation coefficient > 0.90, p<0.01) compared with the results of the clinical gold standard method, High Performance Liquid Chromatography. The proposed HemeChip+ system is the first of its kind, single test solution, which offers an accurate, affordable, portable, and rugged platform for anemia and hemoglobin variant testing in low- and middle- income countries.

项目摘要 贫血的特点是血液血红蛋白水平低，患病率高，影响三分之一以上的人口， 世界人口约25亿。贫血有许多原因，包括营养缺乏， 肿瘤病症和血液病，包括血红蛋白基因变异。超过7%的 世界人口携带血红蛋白基因变异，其中之一是镰状细胞病（SCD）。SCD或镰状细胞 贫血是最常见的遗传性贫血之一。贫血和SCD诊断/监测是 在低收入和中等收入国家，由于缺乏实验室基础设施和熟练人员，这是一个挑战。在 在2019年的一份报告中，世界卫生组织将血红蛋白检测（贫血的诊断和监测）列为 这是低收入和中等收入国家初级保健的基本体外诊断测试。我们已经开发出一种 即时（POC）微芯片电泳血红蛋白变体检测系统，HemeChip。HemeChip具有 已在美国、非洲、印度和东南亚针对血红蛋白变体进行了广泛验证。在本STTR中 第一阶段的项目，我们计划增加总血红蛋白定量和贫血检测能力，血红素芯片 系统和开发HemeChip+。拟议的HemeChip+是第一个也是唯一一个单一的测试，POC平台， 便携、经济、准确和定量的血红蛋白定量、贫血检测和血红蛋白 变体鉴定根据我们的初步研究结果，我们假设快速，负担得起，综合，POC 用所提出的HemeChip+系统测试贫血和血红蛋白变体是可行的。为了验证这一 假设，我们提出了以下不同但相互关联的目标：目标1：开发HemeChip+平台 用于集成的定量血红蛋白检测、贫血检测和定量血红蛋白变体 识别.目标1里程碑是在单次检测中实现准确的总血红蛋白定量（g/dL）， 血红蛋白变体鉴定和使用一滴血的血红蛋白变体百分比（%）定量， 不到十分钟目的2：进行集成的HemeChip+贫血的临床测试， 血红蛋白变体测试系统。目标2里程碑是验证HemeChip+作为 贫血和血红蛋白变体检测平台的集成分析。定量血红蛋白检测性能 目标与临床金标准结果的相关性>90%（Pearson相关系数>0.90，p<0.01） 方法，全血细胞计数。血红蛋白变体鉴定性能目标是>95%准确度;以及 血红蛋白变体%定量性能目标>90%相关性（皮尔逊相关系数> 0.90，p<0.01）与临床金标准方法高效液相色谱法（HPLC）的结果比较， 层析所提出的HemeChip+系统是同类产品中的第一个单一测试解决方案，它提供了一个 准确、经济、便携、坚固的平台，用于中低血糖人群的贫血和血红蛋白变异检测， 收入国家。