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

基本信息

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
项目类别：
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

项目摘要

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.

项目概要贫血的特点是血红蛋白水平低，患病率很高，影响了三分之一以上的人。世界人口约25亿。贫血有多种原因，包括营养缺乏、肿瘤疾病和血液疾病，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/监测由于缺乏实验室基础设施和技术人员，低收入和中等收入国家面临挑战。在世界卫生组织在 2019 年报告中将血红蛋白检测（贫血的诊断和监测）列为低收入和中等收入国家初级保健的基本体外诊断测试。我们开发了一个护理点 (POC) 微芯片电泳血红蛋白变异测试系统 HemeChip。血红素芯片有已在美国、非洲、印度和东南亚针对血红蛋白变异体进行了广泛验证。在这个STTR中一期项目，我们计划为HemeChip增加总血红蛋白定量和贫血检测能力系统并开发HemeChip+。拟议的 HemeChip+ 是第一个也是唯一一个单一测试 POC 平台便携式、经济实惠、准确、定量的血红蛋白定量、贫血检测和血红蛋白变体识别。根据我们的初步发现，我们假设快速、负担得起、集成的 POC 使用提议的 HemeChip+ 系统可以测试贫血和血红蛋白变异。为了测试这个假设，我们提出以下不同但相互关联的目标：目标 1：开发 HemeChip+ 平台用于综合定量血红蛋白测试、贫血检测和定量血红蛋白变异鉴别。目标 1 里程碑是在一次测试中实现准确的总血红蛋白定量 (g/dL)，使用一滴血进行血红蛋白变异鉴定和血红蛋白变异百分比 (%) 定量不到10分钟。目标 2：对集成 HemeChip+ 贫血和贫血进行临床测试血红蛋白变异测试系统。目标 2 里程碑是验证 HemeChip+ 的性能贫血和血红蛋白变异检测平台的综合测定。血红蛋白定量测试性能目标是与临床金标准结果的相关性 >90%（皮尔逊相关系数 >0.90，p<0.01）方法，全血细胞计数。血红蛋白变异识别性能目标准确度>95%；和血红蛋白变异 % 量化性能目标为 >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性能液体的结果相比色谱法。拟议的 HemeChip+ 系统是同类中第一个单一测试解决方案，它提供了准确、经济实惠、便携式且坚固耐用的平台，用于低中度和中度贫血和血红蛋白变异测试收入国家。