Stopped/quenched flow system

我们正在申请资金，以获得一个停止/熄灭的流动系统，用于测量各种分子(蛋白质、多肽、药物、核酶)的快速反应动力学(时间尺度为毫秒到分钟)和稳态性质。所要求的设备由两部分组成：1)快速混合设备，用于通过在3个混合步骤中混合多达4种不同的溶液来启动这些分子的各种反应，混合之间的延迟时间可变；2)能够测量荧光、光散射和吸光度的光谱仪，以监控反应的进展。共同申请者(6名生物化学家和化学家，以及1名化学工程师，其小组目前总共包括81名研究人员)需要在日常基础上使用该设备进行广泛的测量，这些测量构成他们研究计划的核心部分：蛋白质折叠、聚集和工程；酶和核酶的催化作用及抑制作用；以及生物纳米材料。因此，这项研究对于了解生物学中的自然和疾病过程，以及由此开发新的疗法非常重要。他们说，共同申请者目前只有一个老化的停止/熄灭的流动系统：由于部件的逐渐失效，这种仪器的能力越来越有限，通常无法更换，并且在操作中变得非常不可靠。这种仪器的状态对共同申请者的研究努力产生了非常负面的影响，因为失败的实验需要使用昂贵的试剂重复进行，故障排除和尝试仪器维修所需的时间，因此，共同申请者迫切需要所需的设备来从事其研究计划的许多关键要素。因此，所需的设备将为许多高素质的人员提供非常有价值的培训，包括本科生、技术人员、研究生和博士后研究员，以使用这一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.