Stopped/quenched flow system

我们正在申请资金，以获得一个停止/淬灭流动系统，用于测量快速反应动力学（在毫秒到分钟的时间尺度上）和各种分子（蛋白质，肽，药物，核酶）的稳态特性。所要求的设备由两部分组成：1)快速混合装置，通过混合多达4种不同的溶液，在3个混合步骤中启动这些分子的各种反应，混合之间有可变的延迟时间；2)能够测量荧光、光散射和吸光度的光谱仪，以监测反应的进展。共同申请者（6名生物化学家和化学家，1名化学工程师，他们的小组目前共有81名研究人员）需要在日常工作中使用该设备进行广泛的测量，这些测量构成了他们研究项目的核心部分：蛋白质折叠、聚集和工程；酶和核酶的催化功能及抑制作用；和bio-nanomaterials。这项研究对于理解生物学中的自然和疾病过程，并由此开发新的治疗方法具有重要意义。共同申请者目前只有一个老化的停止/淬火流动系统：由于组件的逐渐失效，该仪器的功能越来越有限，并且通常无法更换，并且在运行中变得非常不可靠。该仪器的状态对共同申请人的研究工作产生了非常负面的影响，因为需要使用昂贵的试剂重复失败的实验，需要时间来排除故障并尝试修理仪器，以及仪器停机时间。因此，共同申请人迫切需要所需的设备来追求他们的研究计划的许多关键要素。所要求的设备将为包括本科生、技术人员、研究生和博士后在内的许多高素质人员提供非常有价值的培训，以使用这种功能强大且广泛适用的仪器。

We are requesting funding to obtain a stopped/quenched flow system for measuring rapid reaction kinetics (on a timescale of millisecond to minute) and steady-state properties of a wide range of molecules (proteins, peptides, drugs, ribozymes). The requested equipment consists of 2 components: 1) a rapid mixing apparatus, for initiating various reactions of these molecules by mixing up to 4 different solutions, in 3 mixing steps, with variable delay times between mixing, and 2) a spectrometer capable of measuring fluorescence, light scattering and absorbance, to monitor the progress of the reactions.  The co-applicants  (6 biochemists and chemists, and 1 chemical engineer, whose groups currently include a total of 81 researchers) need to use this equipment on a routine, daily basis for making extensive measurements that form a central part of their research programs on: protein folding, aggregation, and engineering; enzyme and ribozyme catalyst function and inhibition; and  bio-nanomaterials.  This research is important for understanding natural and disease processes in biology, and from this developing new therapeutics.        The co-applicants currently have just one aging stopped/quenched flow system: this instrumentation has increasingly limited capabilities due to the progressive failure of components, which often cannot be replaced, and it is becoming very unreliable in its operation.  The state of this instrumentation is very negatively impacting the research efforts of the co-applicants, due to failed experiments that need to be repeated using costly reagents, time required to trouble shoot and attempt instrument repairs, and instrument down-time.  Thus, the co-applicants urgently require the requested equipment to pursue many key elements of their research programs.  The requested equipment will provide very valuable training for many highly qualified personnel, including undergraduate students, technicians, graduate students, and postdoctoral fellows, in using this powerful and widely applicable instrumentation.