Diagnostics for Sepsis and Community-Acquired Pneumonia

败血症和社区获得性肺炎的诊断

• 批准号: 7091568
• 负责人: WILLIAM G WEISBURG
• 金额: $ 46.78万
• 依托单位: NANOGEN, INC.
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7091568
• 关键词: bacterial DNA; bioengineering /biomedical engineering; biomarker; biomedical automation; biomedical equipment development; clinical biomedical equipment; clinical research; communicable disease diagnosis; consumable /disposable biomedical equipment; cooperative study; diagnosis design /evaluation; diagnostic tests; early diagnosis; human subject; microarray technology; miniature biomedical equipment; nucleic acid amplification techniques; nucleic acid hybridization; patient oriented research; pneumonia; septicemia; virus DNA

DESCRIPTION (provided by applicant): Identifying the etiological agent of sepsis or community-acquired pneumonia (CAP) greatly improves the clinician's ability to manage the patient. Even with all of the newly developed technologies of molecular diagnostics, there have been essentially no recent innovations in diagnostic testing for these significant and often life threatening diseases. Blood culture, microbial sugar utilization-based identification, and empirical chemotherapy have dominated diagnostics and patient management decisions for several years. Empirical treatment - often inappropriate - is partially responsible for the epidemic spread of multidrug resistant pathogens. Bacterial, fungal, and viral agents can all be concurrently detected and identified with nucleic acid amplification and hybridization methods. Innovative approaches to nucleic acid isolation from clinical samples, coupled with multiplex PCR amplification, and detection on electronic microarrays has the potential to significantly advance the ability of the clinician to correctly identify the underlying pathogen and manage the disease. This proposal describes a program to merge innovative, yet proven technology for sample preparation, high multiplex amplification, and detection and differentiation with biomarkers identifying at least 17 agents of CAP and sepsis with an automated system for the clinical microbiology laboratory. The investigators have all made significant contributions in commercializing new molecular diagnostic systems for detection and identification of pathogens in the areas of: respiratory viruses, blood banking, sexually transmitted disease, bioterrorism, CAP, and sepsis. The specific aims are: (1) Optimize a multiplex PCR system including bacterial and viral CAP and sepsis agent targets; (2) Select a suitable sample preparation chemistry; (3) Optimize the assay on electronic microarrays; (4) Develop self-contained modules for the three assay steps; (5) Integrate the modules into a prototype disposable, on a prototype instrument; (6) Develop processes and specifications for critical raw materials; and (7) Test the prototype integrated assay in a clinical study. At the completion of the research program, a number of useful tools will be available to improve molecular diagnostic methods for CAP and sepsis (and potentially other diseases), and a fully integrated automated assay that will be in the final stages of commercialization.

描述（由申请人提供）：识别败血症或社区获得性肺炎（CAP）的病因学代理可大大提高临床医生管理患者的能力。即使有了所有新开发的分子诊断技术，对于这些严重且经常威胁生命的疾病的诊断测试，基本上也没有创新。几年来，血液培养，基于微生物糖使用的鉴定和经验化疗已经主导了诊断和患者管理决策。经验治疗（通常不合适）是抗多药的流行病的部分原因 病原体。细菌，真菌和病毒剂均可通过核酸扩增和杂交方法同时检测和鉴定。从临床样品中分离核酸的创新方法，再加上多重PCR扩增，并且对电子微阵列的检测有可能显着提高临床医生正确识别潜在病原体并管理疾病的能力。该提案描述了一项计划，以合并创新但经过验证的技术，用于样本制备，高多重扩增以及与生物标志物的检测和分化，以识别至少17个CAP和败血症的代理与临床微生物学实验室的自动化系统。研究人员在将新的分子诊断系统商业化方面做出了重大贡献，用于检测和鉴定：呼吸道病毒，血液库，性传播疾病，生物恐怖主义，CAP和败血症地区的病原体。具体目的是：（1）优化一个多重PCR系统，包括细菌和病毒帽和败血症剂靶标； （2）选择合适的样品制备化学； （3）优化电子微阵列的测定； （4）为三个测定步骤开发独立的模块； （5）将模块集成到原型仪器上的原型座椅上； （6）开发关键原材料的过程和规格； （7）在一项临床研究中测试原型集成测定法。研究计划完成时，将有许多有用的工具来改善CAP和败血症（以及可能的其他疾病）的分子诊断方法，并完全 综合自动化测定将处于商业化的最后阶段。