Portable, affordable, quantitative microchip electrophoresis for hemoglobin A1C testing

项目总结 糖尿病是世界上最重要的健康问题之一。患有糖尿病的人数有 自1980年以来翻了两番，低收入和中等收入国家的流行率增幅最大。不仅是因为 糖尿病是发病率和死亡率的主要原因，但它也会摧毁家庭的财务状况和压力 各国的财政资源。世界卫生组织正在挑战各国政府实现25%的减排目标 到2025年，死于糖尿病和其他非传染性疾病的人数将减少。世卫组织项目的一个关键部分呼吁 改进初级卫生保健中的糖尿病诊断和管理。多年来，血红蛋白A1C 试验已被用作糖尿病和糖尿病前期的可靠标记物，因为它是血糖的最佳指示器 随着时间的推移进行控制。由于A1C与空腹血糖测试相比相对容易，因此通常是 发展中国家的首选方案。然而，目前的A1C测试可能不准确，因为 血红蛋白疾病，其可获得性一直有限。尽管糖尿病患者的A1C监测有所改善 结果，目前的检测选择是：(A)昂贵的实验室检测结果延迟，(B)昂贵的点- 护理(POC)选项不适合偏远地区，或(C)昂贵且难以使用的家庭监控套件。我们 开发了一种POC微芯片电泳系统，可以准确地识别和定量血红蛋白 变种，血芯片。该系统由HEMEX Health Inc.以“Gazelle™”的产品名称进行商业化。 它已经在美国、非洲、印度和东南亚得到了广泛的验证，重点是镰状细胞疾病 和贝塔地中海贫血。瞪羚目前在13个国家销售，并计划在更多的地点销售。 在STTR第一阶段项目中，我们成功地完成了两个里程碑：(1)开发了一个易于使用的 糖化血红蛋白HbA1的改良功能血细胞芯片原型设计和(2)定量 检测和量化HbA1和非糖化血红蛋白的相对百分比的算法。 在这个STTR第二阶段项目中，我们计划：(1)开发一种新的方法来检测HbA1C组件 结合总糖化血红蛋白成分的HbA1条带符合国家 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 将测试墨盒放入Gazelle平台，并通过入门级医疗保健使系统适应POC的使用 以及(3)在临床上验证血芯片A1C检测的性能。 具体目标是：目标1：完成测试墨盒的开发，并将瞪羚阅读器改装为 支持A1C检测和量化。目的2：验证血液芯片A1C的诊断准确性 根据NGSP指南进行认证前试验进行测试。目标3：进行临床测试和 在美国和加纳进行了验证。凭借其易用性和经济实惠，拟议的POC A1C测试 将提供一个满足发展中世界和其他服务不足地区需求的解决方案。

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.