Highly-sensitive, rapid and low cost plasmonic assay platform for Lyme disease diagnosis

用于莱姆病诊断的高灵敏度、快速且低成本的等离子体检测平台

• 批准号: 10546574
• 负责人: Nathaniel Charles Cady
• 金额: $ 25.96万
• 依托单位: CIENCIA, INC.
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-12 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10546574
• 关键词: 3D Print; Acute; Address; Adoption; Advisory Committees; Algorithms; Antibiotic Therapy; Antibodies; Antibody Response; Antibody titer measurement; Antigens; Benchmarking; Biocompatible Materials; Biological Assay; Blinded; Blood; Blood Volume; Borrelia; Borrelia burgdorferi; Businesses; Centers for Disease Control and Prevention (U.S.); Chronically Ill; Clinical; Complex; Comprehensive Health Care; Computer software; Consultations; Consumption; Coupled; Data Analyses; Detection; Development; Device Designs; Devices; Diagnostic; Disease; Early Diagnosis; Endemic Diseases; Environment; Enzyme-Linked Immunosorbent Assay; European; Fluorescence; Funding; Goals; Gold; Health; Immune response; Immunity; Immunoglobulin Class Switching; Immunoglobulin G; Immunoglobulin M; Individual; Infection; Institutes; Investments; Laboratories; Liquid substance; Lyme Disease; Lyme disease diagnosis; Lyme disease diagnostic; Methods; Monitor; Multiple Sclerosis; Needs Assessment; Order Spirochaetales; Patients; Phase; Preparation; Price; Process; Protocols documentation; Publishing; Reagent; Research; Research Personnel; Rheumatoid Arthritis; SARS-CoV-2 antibody; SARS-CoV-2 infection; Sampling; Sensitivity and Specificity; Serology; Serology test; Serum; Signal Transduction; Silicon; Site; Small Business Technology Transfer Research; Specificity; Spottings; Streptavidin; Syphilis; System; Technology; Test Result; Testing; Tick-Borne Diseases; Time; United States; Vaccination; Variant; Vector-transmitted infectious disease; Western Blotting; Work; base; clinically relevant; cohort; consumer demand; cost; cross reactivity; design; detection limit; diagnostic algorithm; diagnostic assay; diagnostic strategy; diagnostic value; flexibility; health care service; improved; interest; next generation; plasmonics; point of care; programs; prototype; response; screening; sensor; success

Project Summary/Abstract Lyme disease (LD) is the most common vector-borne illness in the United States and represents a considerable diagnostic challenge. 1-3 The current benchmark for LD diagnosis is the standard two-tiered test (STTT), although the modified two-tier test (MTTT) is rapidly becoming an acceptable alternative. 6 These assays are highly specific but have poor sensitivity, especially early in the infection. 6, 7 Traditional testing is limited by each patient's heterogenous immune response to Borrelia burgdorferi (Bb) antigens. While the paired ELISAs of the MTTT are sensitive and simple to perform, some patients respond weakly to screening reagents. The STTT addresses variation in humoral response by combining an initial ELISA with a confirmatory IgG/IgM Western Blot (WB), yet WB sensitivity is modest against any single antigen. This is especially true with IgM results, which also lack the specificity enhancement associated with class switching. 8 Given these limitations, the ideal serologic assay will combine features of ELISA and WB, but will provide quantitative and specific results against all major LD antigens. Using current technologies, this approach is cost prohibitive. Ciencia Inc. has developed a low-cost, highly-sensitive, fluorescence-based assay platform that supports exactly this type of quantitative multi-antigen serologic Lyme assay. 4, 9, 10 Dr. Cady at SUNY Poly has used our grating-coupled fluorescent plasmonics (GC-FP) assay platform to define antibody responses against a suite of Bb antigens. This preliminary work demonstrates superior sensitivity/specificity compared to STTT (90%/100% vs 60%/100%; n=34 validated samples) and an earlier time to result. Our approach offers a linear response across the full dynamic range, a rapid time to result, low reagent costs. Antigen spots may be added for a negligible cost, so a broader tickborne disease (TBD) panels could be performed for the price of one ELISA. With this Phase I STTR, Ciencia will partner with Dr. Cady (SUNY Polytechnic Institute) and Dr. Strle (Wadsworth Center) to build upon our preliminary self-funded exploration of Lyme serodiagnostics. We aim to validate our preliminary results using a larger set of well-characterized LD samples and appropriate controls from the CDC and NY State DoH, including an estimate of time to positivity using samples collected longitudinally. In parallel, Ciencia aims to improve sample handling and overall ease of use by implementing a cartridge-based system and automated processing that will make GC-FP a viable alternative to methods such as the STTT and MTTT, both of which are cumbersome and time consuming. The ultimate goal is to provide a rapid, easy-to-use, and highly accurate test that can be used outside traditional clinical laboratories. Based on the success of Phase I, the Phase II effort would optimize the test for diagnosis of Lyme disease caused by European Borrelia strains and expand it to other tickborne diseases. Phase II would also permit design refinements and initiation of the FDA approval process.

项目摘要/摘要 莱姆病（LD）是美国最常见的媒介传播疾病，代表 很大的诊断挑战。 1-3当前的LD诊断基准是标准的两层测试 （STTT），尽管经过修改的两层测试（MTTT）迅速成为可接受的替代方案。 6这些 测定最特异性，但敏感性较差，尤其是在感染的早期。 6，7 传统测试受到每个患者对Borrelia burgdorferi（BB）的异质免疫反应的限制 抗原。虽然MTTT的配对ELISA敏感且易于执行，但一些患者反应 对于筛选试剂弱。 STTT通过结合初始 ELISA具有确认性IgG/IgM Western印迹（WB），但WB敏感性对任何单个抗原都是适中的。 IGM结果尤其如此，这也缺乏与类相关的特异性增强 交换。 8鉴于这些局限性，理想的血清学测定将结合ELISA和WB的特征，但 针对所有主要LD抗原提供定量和具体的结果。使用当前的技术，这 方法的成本较高。 Ciencia Inc.开发了一个低成本，高敏感的基于荧光的测定平台，该平台支持 正是这种定量多抗原血清学莱姆测定法。 SUNY POLY的4，9，10 Cady博士使用了我们 光栅耦合荧光等离子间（GC-FP）测定平台，以定义针对一套套件的抗体反应 BB抗原。与STTT相比 vs 60％/100％； n = 34个验证的样本）和较早的结果。我们的方法提供了线性响应 在整个动态范围内，很快就会产生低的试剂成本。可以添加抗原斑点 可忽略不计的成本，因此可以以一个ELISA的价格进行更广泛的滴答疾病（TBD）面板。 Ciencia将在I阶段ISTTR上与Cady博士（SUNY POYTECHNIC INSTICE）和Strle博士合作 （Wadsworth Center）以我们对莱姆血清诊断的初步自筹资金探索为基础。我们的目标 使用较大的特征良好的LD样品和适当的对照来验证我们的初步结果 从疾病预防控制中心和纽约州DOH，包括收集样品的阳性时间的估计。 纵向。同时，Ciencia旨在通过实施一个 基于墨盒的系统和自动处理，将使GC-FP成为此类方法的可行替代品 作为STTT和MTTT，它们都很繁琐且耗时。最终目标是提供 可以在传统临床实验室之外使用快速，易于使用且高度准确的测试。基于 第一阶段的成功，第二阶段的努力将优化诊断莱姆病诊断的测试 欧洲波雷利亚菌株并将其扩展到其他tick虫疾病。第二阶段还允许设计 FDA批准过程的改进和启动。