Integrated Microfluidic Platform for Point-of-Care Serodiagnostics

用于护理点血清诊断的集成微流控平台

• 批准号: 8393163
• 负责人: Abraham P. Lee
• 金额: $ 30万
• 依托单位: IMMPORT THERAPEUTICS, INC.
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-01 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8393163
• 关键词: Acoustics; Address; Air; Antibiotics; Antibodies; Antigens; Automobile Driving; Bartonella henselae; Bedside Testings; Biological Assay; Biological Warfare; Borrelia burgdorferi; Brucella melitensis; Brucellosis; Burkholderia pseudomallei; Chlamydia; Clinical; Collaborations; Collection; Communicable Diseases; Country; Coxiella burnetii; DNA; Data; Dengue; Detection; Development; Devices; Diagnosis; Diagnostic; Disasters; Disease; Disease Outbreaks; Electronics; Emergency Situation; Enzyme Immunoassay; Enzyme-Linked Immunosorbent Assay; Equipment; Evaluation; Francisella tularensis; Funding; Future; Generations; Genomics; Hand; Healthcare; Hepatitis B Virus; Hour; Housing; Human Papillomavirus; Immune response; Immunoassay; Immunodominant Antigens; Immunological Diagnosis; Individual; Infection; Infectious Agent; Laboratories; Lateral; Liquid substance; Location; Lyme Disease; Malaria; Melioidosis; Methods; Microarray Analysis; Microfabrication; Microfluidics; Miniaturization; Modeling; Mycobacterium tuberculosis; National Institute of Allergy and Infectious Disease; Natural Disasters; Orientia tsutsugamushi; Patients; Phase; Plasmodium falciparum; Plastics; Population; Power Sources; Poxviridae; Production; Protein Microchips; Proteins; Proteome; Pump; Reagent; Research Infrastructure; Rickettsia rickettsii; Role; Salmonella enterica; Sampling; Scanning; Screening procedure; Sensitivity and Specificity; Serological; Serum; Simplexvirus; Smallpox; Source; Speed; Spottings; Staging; Symptoms; System; Technical Expertise; Techniques; Technology; Testing; Time; Toxoplasma gondii; Training; Transducers; Tularemia; United States National Institutes of Health; Vaccines; Validation; West Nile virus; base; clinical Diagnosis; cost; cost effective; design; emergency service responder; experience; improved; instrumentation; meetings; micro-total analysis system; microorganism; microsystems; nano; new technology; novel; novel diagnostics; pathogen; point of care; point-of-care diagnostics; portability; prevent; prototype; rapid detection; rural area; tool; trend

DESCRIPTION (provided by applicant): We aim to develop a fully integrated microfluidic immunodiagnostic platform utilizing a novel air-liquid cavity acoustic transducer (ALCAT) technology pioneered in the lab of Dr Abe Lee. The diagnosis platform is based on the well-established clinical diagnostic tool, the enzyme immunoassay (eg ELISA). ELISAs are an integral platform for clinical diagnosis because they are rapid, robust, and provide results that are highly sensitive and specific. Additionally, ELISAs rely on the inherent humoral immune response of the host to produce antibodies indicative of pathological status. In this proposal, we will form a strategic partnership of expertise in protein microarrays (Antigen Discovery, Inc. and Dr Phil Felgner) and in microfluidics (Dr Abe Lee) to develop a point-of-care diagnostic system consisting of a cost-effective disposable microfluidic plastic chip and a portable analyzer that can be driven by a mobile computing device for rapid serological evaluation of Melioidosis. By synergistically incorporating novel ALCAT-based approaches into these arrays we will have the versatility and power to reduce enzymatic development times, limit production costs, and fully integrate all components into a disposable assay. From previous NIH/NIAID funding we have discovered serodiagnostic antigens for 12 NIAID priority agents (Brucella melitensis, Francisella tularensis, Burkholderia pseudomallei, Coxiella burnetii, Salmonella enterica typhi, Rickettsia rickettsii, Orientia tsutsugamushi, Toxoplasma gondii, M. tuberculosis, variola major related pox viruses, Dengue, and West Nile). We have also identified serodiagnostic antigens for non-biodefense targets including: Bartonella henselae, Borrelia burgdorferi, Hepatitis B Virus, Chlamydia, Plasmodium falciparum, Human papillomavirus, and Herpes simplex virus. This approach will leverage our existing content of serodiagnostic antigens (and appropriate banked sera collection) to produce a multiplex device that will contain multiple antigens from numerous pathogens and enable clinicians to determine which pathogen an individual was exposed to. We believe the platform takes advantage of this wealth of content, and marries it to a versatile ALCAT-based microfluidics approach to produce a true lab-on-a- chip tool that is equipment free, technical expertise unrestricted, and useful for both developed and undeveloped countries. This approach produces a an immensely powerful diagnostic platform that will compliment current assays, provide diagnosis for a broad range of diseases, and is capable of utilizing additional enzyme immunoassay-based content. This proposal is an effective integration of emerging microarray technologies and will set the stage for future serological detection systems. PUBLIC HEALTH RELEVANCE: Centralized testing in well-resourced reference laboratories cannot adequately address the unpredictable demand for rapid diagnostics during mass disasters, natural disease outbreaks, and bioterrorist threats. During such emergencies, first responders must rely on accurate diagnostics that are quickly and efficiently deployable to patients who may not have easily recognizable signs or symptoms of an infection. Point-of-care (POC) multiplex diagnostics are well-suited to fill this important role as they are highly portable do not require extensive training, and provide prompt sample-to-answer times.

描述（由申请人提供）：我们的目标是利用 Abe Lee 博士实验室首创的新型气液腔声换能器 (ALCAT) 技术开发完全集成的微流体免疫诊断平台。该诊断平台基于成熟的临床诊断工具——酶免疫分析（例如ELISA）。 ELISA 是临床诊断不可或缺的平台，因为它们快速、稳定，并提供高度敏感和特异的结果。此外，ELISA 依赖于宿主固有的体液免疫反应来产生指示病理状态的抗体。在此提案中，我们将在蛋白质微阵列（Antigen Discovery, Inc. 和 Phil Felgner 博士）和微流体（Abe Lee 博士）方面的专业知识之间建立战略合作伙伴关系，以开发一种护理点诊断系统，该系统包括具有成本效益的一次性微流控塑料芯片和便携式分析仪，可由移动计算设备驱动，对类鼻疽进行快速血清学评估。通过将基于 ALCAT 的新型方法协同整合到这些阵列中，我们将拥有减少酶开发时间、限制生产成本并将所有组件完全集成到一次性检测中的多功能性和能力。从之前的 NIH/NIAID 资助中，我们发现了 12 种 NIAID 优先病原体（布鲁氏菌、土拉弗朗西斯菌、类鼻疽伯克霍尔德菌、伯克氏体、伤寒沙门氏菌、立克次体、恙虫病东方体、弓形虫、结核分枝杆菌、天花相关痘）的血清诊断抗原。病毒，登革热和西尼罗河）。我们还鉴定了非生物防御目标的血清诊断抗原，包括：汉赛巴尔通体、伯氏疏螺旋体、乙型肝炎病毒、衣原体、恶性疟原虫、人乳头瘤病毒和单纯疱疹病毒。这种方法将利用我们现有的血清诊断抗原内容（以及适当的血清库）来生产多重设备，该设备将包含来自多种病原体的多种抗原，并使临床医生能够确定个体暴露于哪种病原体。我们相信该平台能够利用这些丰富的内容，并将其与基于 ALCAT 的多功能微流体方法相结合，以生产出真正的芯片实验室工具，该工具无需设备，技术专业知识不受限制，并且对开发和应用都很有用。不发达国家。这种方法产生了一个非常强大的诊断平台，它将补充当前的检测方法，为广泛的疾病提供诊断，并且能够利用额外的基于酶免疫分析的内容。该提案是新兴微阵列技术的有效整合，将为未来的血清学检测系统奠定基础。 公共卫生相关性：资源丰富的参考实验室的集中检测无法充分满足大规模灾难、自然疾病爆发和生物恐怖威胁期间对快速诊断的不可预测的需求。在此类紧急情况下，急救人员必须依赖准确的诊断，这些诊断可以快速有效地应用于可能不易识别感染体征或症状的患者。护理点 (POC) 多重诊断非常适合填补这一重要角色，因为它们高度便携，不需要大量培训，并且提供快速的样本到答案时间。