Development of an automated IVD for the ultra-sensitive, direct, molecular detection of Borrelia for early Lyme Disease

开发自动化 IVD，用于对早期莱姆病的疏螺旋体进行超灵敏、直接的分子检测

• 批准号: 10077755
• 负责人: Alon Singer
• 金额: $ 100万
• 依托单位: HELIXBIND, INC.
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-15 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10077755
• 关键词: Address; Allergic Reaction; Anaplasma phagocytophilum; Antibiotics; Area; Arthralgia; Arthritis; Babesia; Bacteria; Biological; Biological Assay; Blinded; Blood; Blood Circulation; Blood Volume; Borrelia; Borrelia Infections; Borrelia burgdorferi Group; Borrelia miyamotoi; Budgets; Carditis; Cells; Chronic; Clinic; Clinical; Clinical Microbiology; Clinical Research; Clinical Sensitivity; Clinical Trials; Clinical assessments; Collaborations; Communicable Diseases; Data; Detection; Development; Devices; Diagnosis; Diagnostic; Disease; Early Diagnosis; Ehrlichia; Endemic Diseases; Ensure; Exanthema; Fever; Future; General Population; Gold; Growth; Headache; Health; Hour; Human; Immunoglobulin G; Immunoglobulin M; In Vitro; Infection; Intervention; Laboratories; Lutheran Church; Lyme Disease; Manuals; Medical; Medical center; Methods; Microbiology; Molecular; Molecular Diagnostic Techniques; Molecular Diagnostic Testing; Multi-site clinical study; Myalgia; New England; New York; Order Spirochaetales; Outcome; Pathology; Patients; Performance; Phase; Recovery; Relapsing Fever; Sampling; Sensitivity and Specificity; Sepsis; Serologic tests; Serological; Specimen; Symptoms; System; Test Result; Testing; Tick-Borne Diseases; TimeLine; Tissues; Traction; Translating; Vector-transmitted infectious disease; Whole Blood; acute infection; assay development; cost effectiveness; design; diagnostic assay; effectiveness testing; erythema migrans; experience; improved; innovation; instrument; medical schools; member; molecular diagnostics; novel; point of care; seropositive; standard of care; success; tick-borne; tick-borne pathogen; verification and validation

PROJECT SUMMARY Lyme disease (LD), caused by the tick-borne bacteria Borrelia, is the most common vector-borne infectious disease in the US with 300,000 new cases annually. If diagnosed early and treated with appropriate antibiotics, outcomes for LD are typically excellent, but delays in treatment result in arthritis, carditis, or neuroborreliosis. The most telling manifestation of early LD is the erythema migrans (EM); however, the EM is often difficult to distinguish from an allergic reaction, and 30% of those infected never develop the rash. Displaying non-specific symptoms which mimic those of other diseases, LD can only be confirmed by laboratory tests. Current laboratory tests rely on serological methods which are ineffective at diagnosing early LD and cannot distinguish between an active and previous infection. Molecular diagnostic tests for direct detection of Borrelia from blood have demonstrated poor sensitivity and have thus not gained traction (or FDA clearance). The end result is that no test today can detect early LD with confidence. To address this unmet need for improved detection of LD, HelixBind has developed RaPID/LD – an ultra- sensitive test specifically designed for the direct detection of Borrelia from whole-blood. RaPID/LD displays a limit of detection (LoD) well below a single cell/ml of human blood, orders of magnitude more sensitive than existing molecular diagnostics. RaPID/LD will only detect active infections and incorporates a broad menu of Lyme Disease inducing and Relapsing Fever inducing Borrelia, inclusive of B. miyamotoi, and provides results in roughly 2.5-hours. It has undergone initial testing with clinical specimens and demonstrated superior capabilities. This proposal focuses on: (1) Completing assay development and initial verification testing, (2) Translating the current manual assay to a fully automated test; comprising of single-use plastic devices operated by a small, bench-top, instrument – capable of placement in any setting inclusive of the Point-of-Care, and (3) Completing an extensive study with clinical specimens to establish performance metrics. In order to succeed in this endeavor, we have assembled a team of experts in the development of automated diagnostics supported by world-class advisors with expertise in pathology, infectious diseases, clinical microbiology, Lyme Disease, and Borrelia microbiology. Together, we will build upon our capabilities and deliver an automated assay, culminating in a blinded, multi-site, clinical study in collaboration with our clinical partners. Having achieved our Specific Aims, we will begin verification and validation efforts under an ISO 13485 Quality System, scale manufacturing, and complete clinical trials for regulatory clearance. RaPID/LD will represent the initial test for a planned multiplex panel covering a range of tickborne diseases (TBDs).

项目摘要 由tick传播的细菌引起的莱姆病（LD）是最常见的矢量传播感染 美国疾病每年有30万例新病例。如果早点诊断并接受适当的抗生素治疗， LD的结局通常非常好，但是治疗的延迟会导致关节炎，心脏炎或神经性脂肪性病。 早期LD最有说服力的表现是红斑迁移（EM）；但是，EM通常很难 与过敏反应区分开来，而感染者中有30％从未发展出皮疹。显示非特异性 模仿其他疾病，LD的症状只能通过实验室测试来确认。当前的 实验室测试取决于在早期LD诊断中无效的血清学方法，无法区分 在活动和先前的感染之间。分子诊断测试直接从血液中直接检测 表现出敏感性不佳，因此没有获得关注（或FDA清除率）。最终结果是 今天没有测试可以自信地检测早期LD。 为了满足改善LD检测的未满足的需求，Helixbind已发展快速/LD - 一种超级 敏感的测试专为直接检测全血疏松岩而设计。快速/LD显示A。 检测限（LOD）远低于单个细胞/ml人体血液，比敏感的数量级比 现有的分子诊断。 Rapid/LD仅检测主动感染，并包含一个广泛的菜单 莱姆病诱导和复发发烧诱导疏螺旋体，包括宫林氏芽孢杆菌，并提供结果 大约2.5小时。它已经对临床标本进行了初步测试，并证明了优越 功能。该建议的重点是：（1）完成评估开发和初步验证测试，（2） 将当前的手动测定转换为完全自动化的测试；完成单使用塑料设备的完成 通过一个小型的台式工具 - 能够在包括护理点的任何设置中放置，（3） 通过临床标本完成一项广泛的研究，以建立性能指标。 为了在这项工作中取得成功，我们组建了一个专家团队 由世界一流顾问支持具有病理学专业知识，传染病，临床方面的诊断。 微生物学，莱姆病和伯罗利微生物学。一起，我们将建立我们的能力和 与我们的临床合作进行自动测定 合作伙伴。达到了我们的具体目标后，我们将在ISO下开始验证和验证工作 13485质量系统，规模制造和完整的临床试验，以进行监管清除。快速/LD会 表示涵盖一系列滴答疾病（TBD）的计划多重面板的初始测试。