Biacore T100 SPR system for studying and characterizing biomolecular interaction

描述（由申请人提供）：表面等离子体共振（SPR）是用于研究和表征无标记状态下大分子相互作用的通用工具。该系统通过监测芯片表面质量浓度的变化来检测真实的结合反应;结合和解离速率常数直接从反应轨迹中确定。从小分子到粗提物、脂质囊泡、病毒、细菌和真核细胞的样品都可以进行实时研究，而无需使用标签，也无需或仅需少量样品制备。 申请资金用于最先进的SPR生物传感器Biacore T100，以取代已有16年历史的Biacore 1000仪器。所要求的仪器和服务将取代旧系统，并将位于一个核心设施，生物物理资源凯克实验室，并将提供给任何人需要在他或她的研究应用SPR。耶鲁大学医学院副院长已承诺支付60，000美元，用于购买所要求的T100系统的维护服务合同，这将在很大程度上确保该仪器至少4年的平稳运行。 目前在耶鲁大学医学院校园内没有类似的仪器;因此，新仪器将大大提高当地SPR的能力。将利用所要求的SPR仪器的研究项目的研究需求已经超过了旧SPR系统作为核心设施环境中的"开放获取"仪器的能力。这些需要包括：连续寻址的细胞，其允许真实的时间参照、检测与低分子量（<1000 Da）分子的相互作用的更好灵敏度、缓冲液转换能力和筛选与药物文库的相互作用的更高通量。 所要求的Biacore T100系统是多功能的，将支持由耶鲁大学医学院15名研究人员指导的14个NIH资助的项目。这些研究人员建议使用SPR技术来推进各种生物医学研究：免疫应答，药物滥用，沙门氏菌病（这仍然是一个主要的世界范围的健康问题，估计每年对美国的经济影响为30亿美元），催乳素受体，一种与获得性长QT综合征有关的钾通道蛋白质，一种危及生命的心脏综合征，抗HIV感染的疫苗的设计，发现可能对多种细菌病原体有效的广谱疗法，以及开发与微生物感染、创伤、自身免疫性疾病和癌症相关的蛋白质靶点药物。这项研究的进展可能会提高我们对如何最好地理解，预防和治疗人类疾病的认识。所要求的T100系统将是耶鲁大学独有的，但它也将开放给任何感兴趣的研究人员使用，因为它放置在一个接受来自世界各地样本的核心设施中;因此，所要求的T100肯定会对耶鲁大学以外的生物医学研究做出重大贡献。

DESCRIPTION (provided by applicant): Surface plasmon resonance (SPR) is a universal tool for studying and characterizing macromolecular interaction in a label-free state. The system detects the binding reaction in real time by monitoring changes in mass concentration at the chip surface; the association and dissociation rate constants are determined directly from the reaction traces. Samples ranging from small molecules to crude extracts, lipid vesicles, viruses, bacteria and eukaryotic cells can be studied in real-time, without the use of labels and with little or no prior sample preparation. Funding is requested for the state-of-the-art SPR biosensor, Biacore T100 to replace a 16 year old Biacore 1000 instrument. The requested instrument and service will replace the old system and will be located in a core facility, the Biophysics Resource of Keck Laboratory, and will be available to anyone needing application of SPR in his or her research. The Deputy Dean of Yale School of Medicine has committed $60,000 for the purchase of a service contract for maintenance of the requested T100 system, which will largely ensure the smooth operation of the instrument for at least 4 years. There is currently no comparable instrument on the campus of Yale School of Medicine; thus the new instrument will significantly enhance the local SPR capabilities. The research needs of the research projects that will utilize the requested SPR instrument have exceeded the capabilities of the old SPR system available as an "open access" instrument in the core facility setting. These needs include: serially addressed cells that allow referencing in real time, better sensitivity to detect interactions with molecules of low molecular weight (<1000 Da), buffer switching capabilities, and higher throughput for screening interactions with drug libraries. The requested Biacore T100 system is versatile and would support 14 NIH-funded projects directed by 15 investigators from Yale School of Medicine. These investigators propose to use the SPR technology to advance diverse biomedical research on: immune response, drug abuse, Salmonellosis (which continues to be a major world-wide health concern and has an estimated annual economic impact on the U.S. of $3 billion), prolactin receptor, a potassium channel protein involved in acquired long QT syndrome, a life-threatening heart syndrome, design of vaccines against HIV infection, discovery of broad-spectrum therapeutics that may be effective against multiple bacterial pathogens, and the development of drugs for protein targets that are associated with microbial infections, trauma, autoimmune diseases, and cancer. Progress in this research will likely advance our knowledge of how best to understand, prevent, and treat human diseases. The requested T100 system would be unique to Yale University, but it will be also open for use to any interested investigator due to its placement in a core facility that accepts samples from all over the world; thus, the requested T100 would surely make a significant contribution to biomedical research that would extend beyond Yale University.