Novel Microarray System for In Vitro Allergen Testing

描述（由申请人提供）：五千万美国人患有过敏性疾病，包括哮喘、鼻炎、鼻窦炎、皮炎和食物过敏。过敏是慢性病的第六大原因，每年至少涉及200亿美元的医疗保健费用。对于I型变态反应，其表现为血清中IgE水平升高，对于能够使用单滴血快速定量超过300种最常见过敏原的过敏原特异性IgE的体外免疫测定，存在日益增长的需求。这种测试模式可以通过为临床医生提供数据来设计患者特异性的、成本有效的症状管理和治疗程序，从而显著提高过敏诊断的效率。一个有前途的候选人是过敏原微阵列系统。然而，目前的微阵列技术还不足以满足临床诊断在低成本、可靠性和自动化方面的严格要求。 在第一阶段，AmberGen与该项目的分包商Clinical MicroArrays（CMA）合作，计划开发和评估一种集成的微阵列系统，用于同时体外测量数百种过敏原特异性IgE。该集成系统将基于微阵列技术的几个领域的创新，包括阵列基底、变应原固定方法、阵列免疫测定和荧光读出。超低荧光阵列基板将被生产和评估，这将是基于聚苯乙烯和硝化纤维素薄膜。将评估通过与表面共价键合和使用生物素-链霉抗生物素蛋白桥定向结合来附着过敏原的新方法。将评估具有高灵敏度倏逝波检测技术的微阵列读取器。包括一次性微阵列的盒处理的集成系统将是低成本和高度自动化的。Lynda Schneider博士，儿科体外过敏诊断领域的专家，波士顿儿童医院过敏/临床免疫学项目主任，Helen Hollingsworth博士，成人过敏专家，波士顿大学医学中心过敏科主任将担任顾问。在第二阶段，一个完整的集成系统，包括扫描仪和阵列处理器，连同沿着一个原型微阵列含有几百个抗原将开发和评估在临床设置。

DESCRIPTION (provided by applicant): Fifty million Americans suffer from allergic diseases including asthma, rhinitis, sinusitis, dermatitis and food allergy. Allergies constitute the 6th leading cause of chronic disease and involve at least $20 billion in annual health care costs. For type I allergy, which manifests itself by elevated levels of IgE in the serum, there is a growing need for in vitro immunoassays capable of rapidly quantifying allergen-specific IgEs for the over 300 most common allergens using a single drop of blood. Such a testing modality could significantly improve the efficiency of allergy diagnosis by providing the clinician with data to design a patient-specific, cost effective program of symptom management and therapy. One promising candidate is an allergen microarray system. However, current microarray technology is not sufficiently developed to meet the rigorous demands of clinical diagnostics in terms of low cost, reliability and automation. During Phase I, AmberGen in collaboration with Clinical MicroArrays (CMA), a subcontractor on this project, plans to develop and evaluate an integrated microarray system for simultaneous in vitro measurements of hundreds of allergen-specific IgEs. This integrated system will be based on innovations in several areas of microarray technology including array substrates, method for allergen immobilization, array immunoassays and fluorescent readout. Ultra-low fluorescence array substrates will be produced and evaluated which will be based on polystyrene and nitrocellulose thin films. Novel methods of allergen attachment through covalent bonding to surfaces and by directed binding using biotin-streptavidin bridges will be evaluated. A microarray reader which features high sensitivity evanescent wave detection technology will be evaluated. The integrated system including cassette processing of disposable microarrays will be low-cost and highly automated. Dr. Lynda Schneider, an expert in the field of pediatric in vitro allergy diagnostics and Director of the Allergy/Clinical immunology Program at Boston Children's Hospital and Dr. Helen Hollingsworth, an expert in adult allergies and Director of the allergy unit at Boston University Medical Center will serve as consultants. During Phase II, a complete integrated system including a scanner and array processor, along with a prototype microarray containing several hundred antigens will be developed and evaluated in a clinical setting.