Portable, affordable, quantitative microchip electrophoresis for hemoglobin A1C testing

项目摘要 糖尿病是世界上最重要的健康问题之一。糖尿病患者的数量 自1980年以来，艾滋病毒/艾滋病感染率翻了两番，低收入和中等收入国家的感染率增幅最大。不仅 糖尿病是发病率和死亡率的主要原因，但它也会使家庭经济状况恶化， 国家的财政资源。世界卫生组织要求各国政府减少25% 到2025年，糖尿病和其他非传染性疾病的死亡率。世卫组织计划的一个关键部分要求， 改善初级保健中糖尿病的诊断和管理。多年来，血红蛋白A1 C 由于它是葡萄糖的最佳指标，因此已被用作糖尿病和前驱糖尿病的可靠标志物 控制时间。由于A1 C与空腹血糖测试相比相对容易测试，因此通常是 发展中国家的首选。然而，目前的A1 C测试可能不准确， 血红蛋白病，其可用性有限。尽管糖尿病患者的A1 C监测得到改善， 结果，当前的测试选项是：（a）昂贵的实验室测试，结果延迟，（B）昂贵的点- 不适合偏远地区的护理（POC）选项，或（c）昂贵且难以使用的家庭监测套件。我们 开发了一种POC微芯片电泳系统，可以准确识别和定量血红蛋白 变种血红素芯片该系统由Hemex Health Inc.以产品名称“Gazelle™”商业化。 它已在美国、非洲、印度和东南亚得到广泛验证，重点是镰状细胞病 和β地中海贫血Gazelle目前在13个国家销售，并计划在更多地点销售。 在STTR第一阶段项目中，我们成功地完成了两个里程碑：（1）一个易于使用的 用于糖基化血红蛋白HbA 1的改良功能HemeChip原型设计，和（2）定量 算法来检测和定量HbA 1和非糖基化血红蛋白的相对百分比。 在这个STTR II期项目中，我们计划：（1）开发一种新的方法来检测HbA 1C成分， HbA 1条带，其包含总糖化血红蛋白组分，以符合国家标准 糖化血红蛋白标准化计划（NGSP）诊断标准，（2）全面实施修改设计 将检测盒插入Gazelle平台，并调整系统以供入门级医疗保健在POC中使用 工人，和（3）临床验证HemeChip A1 C测定的性能。 具体目标是：目标1：完成测试盒的开发并修改Gazelle阅读器， 支持A1 C检测和定量。目的2：证明HemeChip A1 C的诊断准确性 根据NGSP指南进行认证前试验。目的3：进行临床试验， 在美国和加纳进行验证。由于其易用性和可负担性，拟议的POC A1 C测试 将提供一个解决方案，满足发展中国家和其他服务不足地区的需求。

PROJECT SUMMARY Diabetes is one of the most important health issues in the world. The number of people living with diabetes has quadrupled since 1980, with the greatest increase in prevalence in low and middle-income countries. Not only is diabetes a major cause of morbidity and mortality, but it can also devastate the finances of families and strain countries’ financial resources. World Health Organization is challenging governments to achieve a 25% reduction in deaths by diabetes and other non-communicable diseases by 2025. A key part of the WHO program calls for improved diagnosis and management of diabetes in primary healthcare. For many years, the hemoglobin A1C test has been used as a reliable marker for diabetes and prediabetes, since it is the best indicator of glucose control over time. Due to the relative ease of testing of A1C versus the fasting plasma glucose test, it is often the preferred option in developing countries. Current A1C tests, however, may be inaccurate due to hemoglobinopathies, and their availability has been limited. Although monitoring of A1C in diabetics improves outcomes, current testing options are: (a) expensive laboratory tests with delayed results, (b) expensive point- of-care (POC) options not suitable for remote areas, or (c) expensive and hard-to-use home monitoring kits. We have developed a POC microchip electrophoresis system that accurately identifies and quantifies hemoglobin variants, HemeChip. This system is commercialized under the product name “Gazelle™” by Hemex Health Inc. It has been extensively validated in the US, Africa, India, and South-East Asia, with a focus on sickle cell disease and beta thalassemia. Gazelle is currently selling in 13 countries with more locations planned. In the STTR Phase I project, we successfully completed two milestones by developing (1) an easy-to-use modified functional HemeChip prototype design for glycosylated hemoglobin HbA1, and (2) a quantification algorithm to detect and quantify the relative percentages of the HbA1 and non-glycosylated hemoglobin. In this STTR phase II project we plan to: (1) develop a new approach to detect the HbA1C component within the HbA1 band which incorporates the total glycosylated hemoglobin components to comply with the National Glycohemoglobin Standardization Program (NGSP) diagnostic standard, (2) fully implement the modified design of the test cartridge into the Gazelle platform and adapt the system for use at the POC by entry level healthcare workers, and (3) clinically validate the performance of the HemeChip A1C assay. Specific aims are: Aim 1: To complete the development of a test cartridge and modify the Gazelle reader to support the A1C detection and quantification. Aim 2: To demonstrate diagnostic accuracy of the HemeChip A1C test by performing a pre-certification trial according to NGSP guidelines. Aim 3: To perform clinical testing and validation in the United States and Ghana. With its ease-of-use and affordability, the proposed POC A1C test will offer a solution that meets the needs of the developing world and other underserved regions.