A Sensor for quantification of hydrogen sulfide

项目摘要 硫化氢是一种具有生物学和临床意义的气体传递器。在哺乳动物中 生理学上，硫化氢参与了某些细胞过程的调节，在 神经、心血管和内分泌系统。虽然存在于健康的细胞功能中， 它的存在和浓度被认为是某些病理状态的指示。为 例如，它被怀疑在与人类健康相关的疾病中发挥重要作用 包括糖尿病、高血压、动脉粥样硬化、心力衰竭、炎症、 神经变性、败血症和哮喘。然而，关于这一事件的准确信息缺失 可能指示疾病状态的硫化氢的实际数量。估计 某些组织中的健康/正常水平差异很大，部分原因是两者都缺乏 灵敏、快速测定体内硫化氢水平的方法。开发这样一种 方法/工具对于提高我们对硫化氢生物学的了解并最终 对其临床重要性的认识。 硫化氢测量的一个重要且主要被忽视的考虑是，在生理上 PH时，大多数H_2S实际上以其共轭碱HS-的形式存在。很少测量，如果有测量的话 技术试图利用这种平衡。换句话说，很少有人考虑过检测 硫化氢阴离子直接作为总硫化物的一种测定方法。我们打算利用这一点 令人惊讶的是，硫化氢定量的途径还不发达。与这种方法相一致， Johnson/Pluth/Haley实验室已经证明了第一类受体分子可以结合HS- 通过独有的非共价、可逆、高特异性和选择性可逆 互动。这些芳基乙炔受体首次使化学FET的发展成为可能。 对HS-具有特异性和敏感性。由丰特诺博士领导的研究团队集结在一起， 最近展示了类似的发育途径，通过产生选择性硝酸盐 ChemFET传感器，利用类似的针对硝酸盐的芳乙炔受体。考虑到这段过去 用类似的分析物和技术成功，我们假设HS受体来自 Pluth/Johnson/Haley实验室可用于生产HS-ChemFET。如果成功，这将是 为生物医学研究人员提供实时测量HS的机会 最低限度的样品准备。我们预计这些工具将立即在 生物医学研究及其在医疗诊断中长期应用的潜力 检测和监测与硫化氢失调相关的疾病状态的方法。

Project Summary Hydrogen Sulfide is a gasotransmitter of biological and clinical relevance. In mammalian physiology, H2S is involved in regulation of certain cellular processes, playing significant roles in neuronal, cardiovascular and endocrine systems. While present during healthy cellular function, its presence and concentration are thought to be indicative of certain pathological states. For example, it is suspected to play important roles in conditions associated with human health including diabetes, hypertension, atherosclerosis, heart failure, inflammation, neurodegeneration, sepsis, and asthma. However, precise information is missing regarding the actual amounts of hydrogen sulfide that may be indicative of disease states. Estimates of healthy/normal levels in certain tissues vary widely, which is in part due to the lack of both sensitive and rapid methods to quantify the levels of H2S in vivo. Developing such a method/tool is critical to improving our knowledge regarding the biology of H2S and to eventual recognition of its clinical importance. An important and mainly overlooked consideration of H2S measurement is that, at physiological pH, most H2S is actually present as its conjugate base, HS–. Few, if any, measurement techniques seek to exploit this equilibrium. In other words, few have looked at detecting the hydrosulfide anion directly as a total sulfide measurement. We propose to exploit this surprisingly underdeveloped pathway for H2S quantification. Aligned with this approach, the Johnson/Pluth/Haley labs have demonstrated the first class of receptor molecules that bind HS– reversibly with high specificity and selectivity through exclusively non-covalent, reversible interactions. These arylethynyl receptors enable for the first time the development of ChemFETs with specificity and sensitivity for HS–. The assembled team of researchers, led by Dr. Fontenot, has recently demonstrated a similar development pathway by creating nitrate-selective ChemFET sensor that utilizes a similar arylethynyl receptor specific for nitrate. Given this past success with a similar analyte and technology, we hypothesize that the HS– receptor from Pluth/Johnson/Haley labs can be used to produce a HS– ChemFET. If successful, this will provide biomedical researchers with the opportunity to measure HS– in real-time and with minimal sample preparation. We expect that these tools will have immediate applications in biomedical research and the potential for longer-term applications in point-of-care diagnostic methods for detecting and monitoring disease states associated with H2S misregulation.