A peptide-based point-of-care vertical flow assay for the rapid diagnosis of Lyme disease
基于肽的即时垂直流检测用于快速诊断莱姆病
基本信息
- 批准号:10404209
- 负责人:
- 金额:$ 100万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-06-24 至 2024-06-30
- 项目状态:已结题
- 来源:
- 关键词:AddressAntibioticsAntibodiesAntigen TargetingAntigensBacterial ProteinsBindingBinding ProteinsBiological AssayBorrelia burgdorferiBorrelia miyamotoiCellsCellular PhoneCenters for Disease Control and Prevention (U.S.)ClinicalClinical TreatmentCoupledDBL OncoproteinDataDefectDetectionDevelopmentDiagnosisDiagnosticDiseaseDisease ProgressionEarly DiagnosisEarly treatmentEpitopesFamilyGenerationsGoalsITGB3 geneImProvImmunoglobulin GImmunoglobulin MIndividualInfectionInterventionLaboratoriesLaboratory DiagnosisLegal patentLyme DiseaseMachine LearningMapsMeasuresMembraneMethodsMicrobeMusculoskeletal SystemNatureNervous system structureOspC proteinPaperPatient-Focused OutcomesPatientsPeptidesPhasePhysiciansProteinsReaderReportingResearchSamplingSerologySignal TransductionSmall Business Innovation Research GrantSpecificitySpeedSpottingsSystemTechnologyTestingTimeWorkantibody detectionbasebiological systemsblindclinical Diagnosiscostcost effectivecross reactivitydecorin binding protein Bdesigndetection assaydetection platformdiagnostic assayefficacy testingimprovedinnovationmembermultiplex detectionnovel strategiespoint of carepoint of care testingpoint-of-care detectionpoint-of-care diagnosticsportabilitypreservationpreventprototypepublic health relevancerapid diagnosisrapid testrelapsing fever borreliascreening
项目摘要
Abstract
Project Summary There is an obvious need for new approaches and better assays for the laboratory diagnosis of Lyme disease. All attempts to develop a practical assay for the direct detection of Borrelia burgdorferi in infected patients have failed. Thus far, all proposed alternatives to serology have been unsuccessful, not cost-effective, or are still in early development. Improving serological detection in early disease is the fastest and most effective way to improve patient outcomes in Lyme disease. The antigen targets utilized in current serodiagnostic assays have considerable defects. They often contain conserved epitopes that cross-react with antibodies raised to other antigens, reducing specificity and requiring the use of a two-tier seroassay paradigm that preserves specificity at the cost of poor sensitivity in the detection of early disease. The use of peptides as serodiagnostic targets demonstrate improved efficacy, but the use of one or two peptides containing single epitopes still provides re- duced sensitivity in early disease. Putting the same old antigen targets into new platforms, no matter how in- novative the platform, will not succeed in improving serodiagnostics for Lyme disease. Both the target anti- gens and assays need an innovative approach. By incorporating unique peptides containing linear epitopes highly specific to B. burgdorferi, into a cutting-edge, multiplex, portable paper-based point-of-care diagnostic assay that uses a cost-effective smartphone-based reader, we aim to transform the diagnosis of Lyme disease. An ideal test for Lyme disease could be performed in a single step and yield an answer on the spot to support diagnosis and direct the course of clinical treatment. We have developed an innovative vertical-flow assay which allows for the multiplexed detection of IgM and IgG binding of up to 25 independent antigen targets in a point-of-care setting. The VFA design allows for uniform flow of sample across the target membrane, creating uniform binding conditions and maximizing developed signal. We coupled this design with a cost-effective portable smart-phone based reader allowing for quantitative measure of antibody binding, eliminating subjectiv- ity. By multiplexing peptide antigens each containing 1-2 epitopes unique to B. burgdorferi from multiple differ- ent antigens expressed at different stages during mammalian infection we can generate a single tier, POC as- say that can specifically and sensitively detect patient antibody at all stages of the disease. The assay can be completed in less than 25 min allowing for rapid in office results to support clinical diagnosis, thereby improving patient outcomes.
摘要
项目概述莱姆病的实验室诊断显然需要新的方法和更好的分析方法。所有试图开发一种实用的方法来直接检测感染患者中的伯氏疏螺旋体的尝试都失败了。到目前为止,所有提出的血清学替代方案都是不成功的,不符合成本效益的,或者仍处于早期开发阶段。改进早期疾病的血清学检测是改善莱姆病患者预后的最快和最有效的方法。目前血清诊断分析中使用的抗原靶标存在相当大的缺陷。它们通常包含保守的表位,与针对其他抗原的抗体发生交叉反应,降低了特异性,需要使用两级血清分析范例来保持特异性,但代价是检测早期疾病的敏感度较低。使用多肽作为血清学诊断靶点显示了更好的疗效,但使用包含单个表位的一个或两个多肽在早期疾病中仍然提供了降低的敏感性。将相同的旧抗原靶点放入新的平台,无论平台多么创新,都不会成功地改善莱姆病的血清诊断。无论是目标抗原法还是化验方法都需要创新。通过将包含伯氏杆菌高度特异的线性表位的独特多肽结合到使用经济高效的智能手机阅读器的尖端、多路、便携式纸质医疗点诊断分析中,我们的目标是改变莱姆病的诊断。理想的莱姆病检测可以一步完成,并当场得出答案,以支持诊断和指导临床治疗过程。我们开发了一种创新的垂直流动检测方法,它允许在护理点设置中对多达25个独立的抗原目标的IgM和IgG结合进行多重检测。VFA设计允许样品在目标膜上均匀流动,创造均匀的结合条件并使显影信号最大化。我们将这一设计与一种经济高效的便携式智能手机阅读器结合在一起,允许定量测量抗体结合,消除了主观性。通过从哺乳动物感染过程中不同阶段表达的多个不同抗原中分别含有伯氏杆菌特有的1-2个表位的多肽抗原,我们可以产生一个单层,也就是说,POC,它可以在疾病的所有阶段特异性和灵敏地检测患者抗体。该分析可以在不到25分钟的时间内完成,允许快速的办公室结果支持临床诊断,从而改善患者的结果。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Paul Michael Arnaboldi其他文献
Paul Michael Arnaboldi的其他文献
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A peptide-based point-of-care vertical flow assay for the rapid diagnosis of Lyme disease
基于肽的即时垂直流检测用于快速诊断莱姆病
- 批准号:
10452660 - 财政年份:2020
- 资助金额:
$ 100万 - 项目类别:
A peptide-based point-of-care vertical flow assay for the rapid diagnosis of Lyme disease
基于肽的即时垂直流检测用于快速诊断莱姆病
- 批准号:
10080510 - 财政年份:2020
- 资助金额:
$ 100万 - 项目类别:
A peptide-based point-of-care vertical flow assay for the rapid diagnosis of Lyme disease
基于肽的即时垂直流检测用于快速诊断莱姆病
- 批准号:
10653862 - 财政年份:2020
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$ 100万 - 项目类别:
A peptide-based point-of-care vertical flow assay for the rapid diagnosis of Lyme disease
基于肽的即时垂直流检测用于快速诊断莱姆病
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