High Performance Secondary Ion Mass Spectrometer Upgrade of Advanced Scanning Ion Microprobe

我们提出了一项生物仪器开发计划，旨在从根本上提升芝加哥大学高分辨率扫描离子微探测器(UC SIM)的质量分辨能力和二次离子检测灵敏度。这将通过用高性能的磁扇形质谱计取代现有的RF四极滤质器来实现。为了实现这一目标，需要设计和建造合适的转移光学系统，并对现有的二次离子引出系统进行改造，以及高电压和硬件结构。利用这一仪器在许多受益于成像显微分析的领域取得了实质性进展，在性能水平上大大提高了基础生物学研究，这证明了拟议的升级是合理的。来自几个学术机构的知名生物学家将与我们合作，在所有情况下继续并扩大已经与加州大学SIM进行的成功的先导实验，以应用升级的微探头。这些应用将旨在：(A)对人类染色体中同位素标记的核苷酸的分布进行直接测绘，并评估脆弱部位的核苷酸含量。(B)确定骨形成所涉及的矿物相以及破骨细胞引发骨吸收的机制。这将需要用钙同位素作为示踪剂进行实验，并检测和测量磷。(C)牙齿和骨组织中微量元素的定位和动力学，与显微结构的关系。铝对器官(骨、脑)影响的显微结构研究。(D)以视网膜神经元为模型系统研究钙在神经元缺血中的作用。这些研究将利用钙同位素和同位素标记的核苷酸作为示踪剂。

We propose a biological instrumentation development program aimed at a radical upgrade of the mass discrimination capability and secondary ion detection sensitivity of the University of Chicago high resolution Scanning Ion Microprobe (UC SIM). This is to be accomplished by replacing the existing RF quadrupole mass filter with a high performance magnetic sector mass spectrometer. The design and construction of appropriate transfer optics, and modification to the present secondary ion extraction system, together with high voltage and hardware construction, will be required to implement this goal. The pursuit of fundamental biological studies at a much improved level of performance with this instrument, that has already contributed substantial advances in many areas that benefit from imaging microanalysis, justifies the proposed upgrade. Established biologists from several academic institutions will collaborate with us in exciting applications of the upgraded microprobe, in all cases continuation and amplification of successful pilot experiments already carried out with the UC SIM. These applications will aim at: (a) Director mapping of the distribution of isotope-labelled nucleotides in human chromosomes and evaluation of the nucleotide content of fragile sites. (b) Identification of the mineral phases involved in bone formation and of the mechanism of bone resorption initiated by osteoclasts. This will entail experiments with Ca isotopes as tracers, and the detection and measurement of phosphorus. (c) Localization and kinetics of trace elements in tooth and bone tissues, relative to microstructure. Microstructural study of organs (bone, brain) affected by aluminum. (d) Study of the role of calcium in neuronal ischemia using retinal neurons as model system. These studies will make use of Ca isotopes and isotope-labelled nucleotides as tracers.