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

• 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
• 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

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.

项目摘要/摘要 该提案描述了开发快速免疫测定测试套件的第二阶段 血液中血红蛋白变异的测定，用作治疗点 低资源中的镰状细胞病（SCD）和SCD载体性状的诊断测试 全球设置。如今，确定SCD和SCD特质需要冗长，并且 昂贵的实验室分析在低资源环境中不可用，> 80％ 具有SCD和SCD特质的人生活在提供医疗保健的地区 设置。然而，新生儿筛查计划导致了重要的 由于早期治疗而改善患者预后，以防止并发症 疾病。 拟议的测试套件将是横向流量免疫测定，原则上类似于房屋 怀孕测试。测试设计基于针对特定的单克隆抗体（mAb） 与SCD相关的血红蛋白变体之间的单氨基酸差异。在第一阶段， 申请人开发了一个有效的原型血液型测试套件，该试剂盒被证明 正确识别> 99％测试的全血样品的表型，包括每个样品 相关的SCD和载体表型。原型测试需要1-微粒的体积 鲜血和时间的时间不到20分钟。在第二阶段，测试套件将进一步 改进和简化，将开发完整的可制造产品。 将进行临床验证研究以确定现实世界的表现 该产品，包括在巴西低资源环境中进行的研究。在 成功结论第二阶段，测试套件将准备好制造和 提交给全球监管机构的批准。估计的成本 血压测试套件将为2.00美元，这个价格将允许接受广泛接受 该测试套件在发展中国家。