Using Multi-Spectral Imaging with Microchip Electrophoresis to Accurately Screen Newborns for Sickle Cell Disease

使用多光谱成像和微芯片电泳准确筛查新生儿镰状细胞病

基本信息

批准号：
10255480
负责人：
PETER GALEN
金额：
$ 25.66万
依托单位：
HEMEX HEALTH, INC.
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-04-01 至 2022-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10255480
关键词：
Africa Africa South of the Sahara Age Birth Blood Caring Child Cities Clinical Clinical Research Country Data Analyses Decentralization Detection Development Disease Disease Management Drops Early Diagnosis Economically Deprived Population Electrophoresis Ensure Environment Equipment Fetal Hemoglobin Gender Gene Mutation Genetic Counseling Genotype Ghana Gold Health Health Status Hemoglobin Hemoglobin E Disease Hemoglobin concentration result Hemoglobinopathies High Pressure Liquid Chromatography Hospitals Human Resources India Infant Inherited Laboratories Machine Learning Mendelian disorder Microchip Electrophoresis Modernization Mutation Names Neonatal Screening Newborn Infant Phase Phenotype Point of Care Technology Point-of-Care Systems Population Race Reagent Reference Standards Reporting Resources Sickle Cell Anemia Sickle Cell Trait Small Business Innovation Research Grant Southeastern Asia Specificity System Teaching Hospitals Technology Testing Thalassemia Training Validation Variant Work World Health Organization base beta Globin commercialization cost cost effective treatment detection limit diagnostic accuracy genetic variant improved in-vitro diagnostics innovation innovative technologies low and middle-income countries machine learning algorithm miniaturize mortality novel point of care point of care testing portability preventable death research clinical testing screening screening program sickling spectrograph trait

项目摘要

PROJECT SUMMARY Hemoglobin (Hb) disorders are among the world's most common monogenic diseases. Nearly 7% of the world’s population carry Hb gene variants. Sickle cell disease (SCD) arises when Hb mutations are inherited homozygously (HbSS) or paired with another β-globin gene mutation. Globally, an estimated 400,000 babies are born annually with SCD, and 70%-75% are in sub-Saharan Africa (SSA). It is estimated that 50-90% in SSA die by their 5th birthday, 70% of these deaths are preventable. Effective management of SCD involves early diagnosis, and genetic counselling, and, importantly, nationwide newborn screening (NBS). NBS programs utilizing centralized laboratories have dramatically reduced SCD mortality in high-resource countries. NBS requires sensitive detection of relatively low levels of Hb variants in the presence of high fetal Hb (HbF). Normal HbA and sickle HbS should be accurately identified in the presence of high levels (up to 90%) of HbF. The current gold standard for Hb variant testing is high-performance liquid chromatography (HPLC), which requires expensive equipment and reagents, highly trained personnel, and modern laboratories. In low- resource regions, very few centralized laboratories can perform costly Hb testing. Testing is not available to the large percentage of infants born outside of a major hospital or city. There is an unmet need for affordable, portable, easy-to-use, accurate, point-of-care (POC) tests to facilitate decentralized Hb testing to enable nationwide NBS programs. In 2019, the World Health Organization (WHO) listed Hb electrophoresis as an essential in vitro diagnostic in low- and middle-income countries. We have developed a POC microchip electrophoresis Hb variant testing system, MicroChip Electrophoresis (MCE), under the product name “Gazelle Hb Variant” by Hemex Health, Inc. MCE reports Hb phenotype, Hb quantification (%Hb), and an interpretive statement showing genotype (such as SCD, Sickle Cell Trait, or Normal). MCE has been extensively validated for hemoglobinopathies, including SCD, hemoglobin E disease, and thalassemia. Newborns and infants below 6 weeks of age have very low concentrations of Hb variants other than Hb F which is high, therefore an improvement to lower the limit of detection (LoD) is needed to support NBS programs worldwide. By decreasing the LoD from the current 10% to 2%, newborns and infants can be screened with this affordable system. The innovation in this SBIR Phase I is the integration of multi-spectral imaging and machine learning based data analysis capability to MCE to develop MCE+ to accurately screen newborns for common Hb variants. We propose the following aims: Aim 1: Integrate multi-spectral imaging and machine learning algorithm into the MCE platform to enable identification and quantification of hemoglobin variants in newborns. Aim 2: Perform clinical testing of the MCE+ multi-spectral newborn screening system. Significance of this project is that MCE+ is the only affordable POC system for quantitative and objective hemoglobin variant testing that allows screening at birth.

项目概要血红蛋白 (Hb) 疾病是世界上最常见的单基因疾病之一。世界人口携带 Hb 基因变异，当 Hb 突变遗传时就会出现镰状细胞病 (SCD)。纯合子 (HbSS) 或与另一种 β-珠蛋白基因突变配对全球估计有 400,000 名婴儿。每年出生的人都患有 SCD，其中 70%-75% 发生在撒哈拉以南非洲 (SSA)，估计其中 50-90% 发生在撒哈拉以南非洲地区。 SSA 在 5 岁生日时死亡，其中 70% 的死亡是可以预防的，有效管理 SCD。早期诊断、遗传咨询，以及重要的是全国新生儿筛查 (NBS)。利用集中实验室的项目大大降低了资源丰富国家的猝死死亡率。 NBS 需要在胎儿 Hb (HbF) 高的情况下灵敏地检测相对较低水平的 Hb 变异。在存在高水平（高达 90%）HbF 的情况下，应准确识别正常 HbA 和镰状 HbS。目前 Hb 变异检测的黄金标准是高效液相色谱 (HPLC)，需要昂贵的设备和试剂、训练有素的人员和现代化的实验室。资源地区很少有集中实验室可以进行昂贵的血红蛋白检测。很大一部分婴儿是在大医院或城市之外出生的，对负担得起的、廉价的婴儿的需求尚未得到满足。便携式、易于使用、准确的即时护理 (POC) 测试，以促进分散的 Hb 测试，从而实现 2019 年，世界卫生组织 (WHO) 将 Hb 电泳列为国家统计局计划。低收入和中等收入国家必不可少的体外诊断。我们开发了 POC 微芯片。电泳 Hb 变异检测系统，MicroChip Electrophoresis (MCE)，产品名称为“Gazelle Hemex Health, Inc. 的“Hb 变异体”。MCE 报告 Hb 表型、Hb 定量 (%Hb) 和解释显示基因型（例如 SCD、镰状细胞性状或 MCE）的声明已得到广泛验证。用于血红蛋白病，包括 SCD、血红蛋白 E 病和地中海贫血。 6 周龄时，除 Hb F 浓度较高外，Hb 变异体的浓度非常低，因此需要改进以降低检测限 (LoD) 以支持全球 NBS 计划。将 LoD 从当前的 10% 降低至 2%，新生儿和婴儿可以通过这种经济实惠的方式进行筛查 SBIR 第一阶段的创新在于多光谱成像和基于机器学习的集成。我们向 MCE 提供数据分析能力，以开发 MCE+，以准确筛查新生儿的常见 Hb 变异。提出以下目标：目标 1：将多光谱成像和机器学习算法集成到 MCE 平台可实现新生儿血红蛋白变异的识别和量化目标 2：执行。 MCE+多光谱新生儿筛查系统的临床测试该项目的意义在于MCE+是。唯一经济实惠的用于定量和客观血红蛋白变异测试的 POC 系统，可在出生。