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STABLE ISOTOPES AS BIOTRACERS BY NOVEL LASER METHODS

通过新颖的激光方法将稳定同位素作为生物示踪剂

基本信息

批准号：
2180662
负责人：
WILLIAM G. TONG
金额：
$ 0.8万
依托单位：
SAN DIEGO STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1989
资助国家：
美国
起止时间：
1989-01-01 至 1998-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/2180662
关键词：
biomedical equipment development circular dichroism evaluation /testing laser spectrometry stable isotope

项目摘要

The main objectives of the proposed research are (a) design and study of new degenerate four-wave mixing (D4WM) laser spectroscopic methods in high-resolution measurement of stable isotopes important for biotracer studies, (b) careful comparison of these methods with currently available methods, and (c) the demonstration of the effectiveness and the usefulness of these methods in biotracer studies using real biomedical samples. Although many isotopes have been used in studying mineral absorption and metabolism in human subjects, there is no simple, routine analytical method for measurement of stable isotope enrichment. Currently available methods such as mass spectrometry or ICP-MS have limitations including slow sample throughput, high cost, isobaric or matrix interferences, and time-consuming sample purification or modification (chelation) steps. Safe and reliable biotracer studies can be performed by measuring stable non-radioactive isotopes at trace-concentration levels using D4WM. Laser D4WM offers excellent sub-Doppler (and Lorentzian minimized) spectral resolution, and hence, it can resolve not only isotopes, but also hyperfine lines of individual isotopes. A hyperfine structure, the atomic spectroscopic fingerprint, is unique and no two structures are identical, and hence, it offers unambiguous measurements. Hence, spectral and chemical interference problems are negligible in these high-resolution studies, even when a mixture of many elements is present in the sample. Isotope ratios can be measured by simply comparing the peak intensities in many well-resolved and spread-out hyperfine structures. when hyperfine structures are convoluted, rich isotope information can still be extracted by using spectral deconvolution schemes based on theoretical D4WM calculations. Both stable and radioactive isotopes can be measured simultaneously, since all types of isotopes present are measured in a hyperfine structure. Some of the advantages over conventional methods include: excellent sensitivity, selectivity, reproducibility, relatively inexpensive instrumentation, simple and safe operation, and fast sample throughput. The effectiveness and the accuracy of these new laser methods will be investigated for some of the most important elements in biotracer isotope studies, such as Ca, Pb, Mg, Cu, Ni, Ag, Fe, Cd, Zn, Pd, Re, Os, Li, Ba, Al, and Rb, using different atomizers including discharge, graphite furnace and flame. Careful and detailed studies on the reliability and the usefulness of these new laser-based methods will be performed for many real biosamples while comparing them to currently available methods for biotracer studies. The PI will prove, compare and demonstrate that the D4WM isotope analysis method is an important alternative method if not one of the most effective methods for safe, cost effective, simple and unambiguous biotracer studies, without the use of undesirable radioactive isotopes. The PI will also study new laser methods for measuring circular dichroism in the gas-phase samples using thermal or polarization-grating based D4WM setups. Successful detection and analysis of optically active chiral biomedical substances at trace-concentration levels promise many applications in various biomedical areas.

拟议研究的主要目标是（a）设计和研究新的简并四波混频（D4 WM）激光光谱方法，对生物示踪剂重要稳定同位素的高分辨率测量研究，（B）仔细比较这些方法与目前可用的方法，以及（c）证明有效性和有用性这些方法在使用真实的生物医学样品的生物示踪剂研究中的应用。虽然许多同位素已被用于研究矿物质的吸收，在人类受试者的代谢中，没有简单的，常规的分析方法。稳定同位素富集度的测量方法当前可用诸如质谱法或ICP-MS的方法具有局限性，缓慢的样品通量、高成本、同量异位素或基质干扰，以及耗时的样品纯化或修饰（螯合）步骤。安全可靠的生物示踪剂研究可以通过测量稳定的使用D4 WM的痕量浓度水平的非放射性同位素。激光 D4 WM提供出色的亚多普勒（和洛伦兹最小化）频谱因此，它不仅可以分辨同位素，单个同位素的超精细线。一种超精细结构，光谱指纹，是唯一的，没有两个结构是相同的，因此，它提供了明确的测量。因此，光谱和在这些高分辨率中，化学干扰问题可以忽略不计即使样品中存在许多元素的混合物，也可以进行研究。同位素比可以通过简单地比较许多分辨率很高且分布广泛的超精细结构。当超精细尽管结构错综复杂，但仍然可以提取丰富的同位素信息，通过使用基于理论D4 WM的光谱去卷积方案，计算。稳定同位素和放射性同位素都可以测量同时，由于存在的所有类型的同位素都是在超精细结构与传统方法相比，包括：优异灵敏度、选择性、再现性、相对仪器价格低廉，操作简单安全，取样快速吞吐量这些新的激光方法的有效性和准确性将研究生物示踪剂中一些最重要的元素同位素研究，如Ca、Pb、Mg、Cu、Ni、Ag、Fe、Cd、Zn、Pd、Re、Os， Li、Ba、Al和Rb，使用不同的雾化器，包括放电，石墨炉和火焰。仔细和详细的研究，这些新的基于激光的方法的可靠性和实用性将是对许多真实的生物样品进行了测试，同时将它们与目前的生物示踪剂研究的可用方法。PI将证明、比较和证明D_4WM同位素分析方法是一种重要的替代方法，如果不是最有效的方法之一，安全，成本有效，简单和明确的生物示踪剂研究，而不使用不受欢迎的放射性同位素。 PI还将研究测量圆二色性的新激光方法在气相样品中，使用基于热或偏振光栅的D4 WM 设置。成功检测和分析光学活性手性微量浓度水平的生物医学物质承诺许多在各种生物医学领域的应用。