Rapid LFIA blood test for SCD using highly specific monoclonal antibodies

使用高度特异性单克隆抗体对 SCD 进行快速 LFIA 血液检测

基本信息

批准号：
9170967
负责人：
MARK GEISBERG
金额：
$ 50万
依托单位：
SILVER LAKE RESEARCH CORPORATION
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-08-01 至 2018-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9170967
关键词：
Adult Affect Amino Acids Area Awareness Bedside Testings Biological Assay Blood Blood Tests Blood Volume Blood specimen Brazil Clinical Clinical Research Collaborations Communities Consultations Data Detection Developing Countries Development Diagnosis Diagnostic tests Disease Early Intervention Early treatment Environment Head Healthcare Hematology Hemoglobin High Prevalence Home environment Immunoassay Individual Intervention Laboratories Lateral Life Marketing Medical Methods Monoclonal Antibodies Morbidity - disease rate Mutation Neonatal Screening Patient-Focused Outcomes Performance Phase Phenotype Population Postdoctoral Fellow Pregnancy Tests Preparation Price Procedures Production Reporting Research Design Research Personnel Resources Sampling Sickle Cell Anemia Spottings Technology Temperature Test Result Testing Time Translational Research Universities Validation Variant Whole Blood Work base carrier status cost design disease phenotype effective therapy experience hemoglobin AA improved instrument mid-career faculty mortality pediatric department point-of-care diagnostics pre-clinical prevent professor programs prototype screening social trait treatment center trial design validation studies

项目摘要

PROJECT SUMMARY/ABSTRACT This proposal describes Phase II of the development of a rapid immunoassay test kit for the determination of hemoglobin variants in blood, to be used as a point-of-care diagnostic test for sickle cell disease (SCD) and SCD carrier trait in low-resource settings worldwide. Today, determination of SCD and SCD trait requires lengthy and expensive laboratory analyses that are not available in low-resource settings, and >80% of individuals with SCD and SCD trait live in areas where healthcare is provided in those settings. Nevertheless, newborn screening programs have resulted in significant improvement of patient outcomes due to early treatment to prevent complications of the disease. The proposed test kit will be a lateral flow immunoassay, similar in principle to a home pregnancy test. The test design is based on monoclonal antibodies (MAbs) specific for the single-amino-acid differences between SCD-related hemoglobin variants. In Phase I, the applicant developed a working prototype hemotyping test kit which was shown to correctly identify the phenotype of >99% of tested whole blood samples, including each relevant SCD and carrier phenotype. The prototype test requires a 1-microliter volume of blood and the time-to-result is under 20 minutes. In Phase II, the test kit will be further improved and simplified, and a complete manufacturable product will be developed. Clinical validation studies will be carried out to determine the real-world performance of the product, including studies performed in low-resource settings in Brazil. At the successful conclusion of Phase II, the test kit will be ready for manufacturing and submission for approval to regulatory agencies worldwide. The estimated cost of the hemotyping test kit will be $2.00, a price point that will allow widespread acceptance of this test kit in developing countries.

项目概要/摘要该提案描述了快速免疫检测试剂盒开发的第二阶段测定血液中的血红蛋白变异，用作现场护理资源匮乏地区镰状细胞病 (SCD) 和 SCD 携带者特征的诊断测试全球设置。如今，SCD 和 SCD 性状的确定需要漫长且昂贵的实验室分析在资源匮乏的环境中无法进行，并且> 80% 具有 SCD 和 SCD 特征的个体居住在提供医疗保健的地区设置。尽管如此，新生儿筛查计划已取得显着成果通过早期治疗预防并发症，改善患者预后疾病。拟议的检测试剂盒将是侧向流动免疫测定，原理上类似于家用试剂盒妊娠测试。该测试设计基于针对特定疾病的单克隆抗体 (MAb) SCD 相关血红蛋白变体之间的单氨基酸差异。在第一阶段，申请人开发了一种血型分型测试套件的工作原型，该套件被证明可以正确识别 >99% 的测试全血样本的表型，包括每个相关的 SCD 和携带者表型。原型测试需要 1 微升体积血液，出结果时间不到 20 分钟。在第二阶段，测试套件将进一步改进和简化，并且将开发出完整的可制造产品。将进行临床验证研究以确定真实世界的性能该产品，包括在巴西资源匮乏地区进行的研究。在第二阶段成功结束，测试套件将准备好进行制造和提交全球监管机构批准。预计成本血型检测试剂盒售价为 2.00 美元，这个价格点将能够被广泛接受该检测试剂盒适用于发展中国家。