Microfluidic S-nitrosothiol Sensor

微流控S-亚硝基硫醇传感器

• 批准号: 9254040
• 负责人: Jonathan Edward McDunn
• 金额: $ 21.55万
• 依托单位: CLINICAL SENSORS, INC.
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-02-01 至 2019-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9254040
• 关键词: Address; Apoptosis; Benchmarking; Biological; Biological Markers; Blood; Blood Vessels; Blood specimen; Buffers; Cell physiology; Chemistry; Cleaved cell; Clinical; Clinical Research; Competence; Detection; Devices; Disease; Electrodes; Ensure; Equilibrium; Functional disorder; Future; Human; Inflammatory; Lab-On-A-Chips; Liquid substance; Literature; Lung diseases; Measurement; Measures; Mediating; Microfluidics; Molecular Weight; Nitrates; Nitric Oxide; Pathology; Performance; Phase; Physiological; Physiology; Plasma; Play; Preparation; Protocols documentation; Reference Values; Research; Research Personnel; Role; S-Nitrosoglutathione; S-Nitrosothiols; Sampling; Signal Transduction; Small Business Innovation Research Grant; Standardization; Talents; Techniques; Technology; Ultraviolet Rays; Visible Radiation; Work; analytical method; base; candidate marker; clinical biomarkers; cost; innovation; oxidation; phase 1 study; photolysis; product development; protocol development; rapid detection; respiratory; sensor; stable isotope; success; tool

PROJECT SUMMARY This Small Business Innovation Research (SBIR) Phase I project aims to develop an accurate, rapid, and commercially available microfluidic sensor that measures low molecular weight S-nitrosothiols in biological samples. S-nitrosothiols (RSNOs), the primary transporters of nitric oxide (NO) in physiology, play a critical role for NO's bioactivity. Homeostatic control of low molecular weight RSNOs, especially S-nitrosoglutathione, is lost in many disease states. Such dysfunction is thought to contribute to the underlying disease pathology. Despite the promise of low molecular weight RSNOs as mechanistic biomarkers, no simple-to-use, standardized tools currently exist for measuring these compounds. There are vast disagreements in the literature regarding the reference ranges for low molecular weight RSNOs, complicating the clinical understanding of these species. As a result, RSNOs have been identified as candidate biomarkers for many inflammatory and respiratory diseases. Yet, little work has validated these findings or determined their clinical utility. A standardized, accurate, facile and commercially ready device to measure RSNOs would enable important clinical research. A simple to use device could resolve fundamental questions regarding the formation and degradation of RSNOs in disease, and help further a general understanding of RSNOs' roles in cellular physiology, signaling and apoptosis. To address the gap in acceptable RSNO measurement techniques, we have begun to develop an innovative, straightforward and inexpensive device for measuring RSNOs in small volumes of biological fluids. The device is based on our core technology—a microfluidic NO sensor. Using a visible light emitting diode (LED), the RSNOs are photolytically broken down to NO which is then detected electrochemically. In this format, the signal generated from NO oxidation is proportional to the RSNO content in the original sample. Employing visible light photolysis along with our microfluidic NO sensor presents several key advantages: (1) our microfluidic sensor requires minimal sample volume (~50 µL) and reduces interference from other common electroactive species; (2) the use of visible light to cleave RSNOs (as opposed to UV light-mediated strategies developed by others) does not generate contamination from photolytic reduction of endogenous nitrate; and (3) our sensor features two working electrodes, providing us with a tool to determine (and thus remove) the background signal associated with each unique sample matrix. Leveraging our core competencies in NO chemistry and measurement, we have assembled a talented team of analytical chemists and clinical researchers to develop a simple-to-use, inexpensive device that can measure RSNOs in biologic samples. Once developed, this device will enable new clinical research that evaluates S-nitrosothiols as clinical biomarkers for disease.

项目摘要 这个小企业创新研究（SBIR）第一阶段项目旨在开发一个准确，快速， 可商购获得的微流体传感器，其测量生物样品中的低分子量S-亚硝基硫醇， 样品S-亚硝基硫醇（RSNOs）是一氧化氮（NO）的主要生理转运体，在体内起着重要的 NO的生物活性。低分子量RSNO，特别是S-亚硝基谷胱甘肽的稳态控制， 在许多疾病状态下都消失了。这种功能障碍被认为有助于潜在的疾病病理学。 尽管低分子量RSNO有望作为机制生物标志物，但没有简单易用的， 目前存在用于测量这些化合物的标准化工具。有巨大的分歧， 关于低分子量RSNO参考范围的文献，使临床 了解这些物种。因此，RSNO已被确定为许多生物标志物的候选者。 炎症和呼吸道疾病。然而，很少有工作证实这些发现或确定其临床意义。 效用一个标准化的、准确的、方便的和商业化的测量RSNO的设备将使 重要的临床研究。一个简单易用的设备可以解决有关 RSNOs在疾病中的形成和降解，并有助于进一步了解RSNOs在疾病中的作用， 细胞生理学、信号传导和凋亡。 为了解决可接受的RSNO测量技术中的差距，我们已经开始开发一种创新的， 用于测量小体积生物流体中的RSNO的简单且廉价的装置。设备 是基于我们的核心技术-微流控NO传感器。使用可见光发射二极管（LED）， RSNO被光解分解为NO，然后被电化学检测。在这种格式中， 由NO氧化产生的信号与原始样品中的RSNO含量成比例。采用 可见光光解沿着我们的微流体NO传感器呈现出几个关键优点：（1）我们的 微流控传感器需要最小的样品体积（约50微升），并减少了其他常见的干扰 电活性物质;（2）使用可见光切割RSNO（与UV光介导的策略相反 （由其他人开发）不会因内源性硝酸盐的光解还原而产生污染; (3)我们的传感器具有两个工作电极，为我们提供了一个工具来确定（从而消除） 背景信号与每个独特的样品矩阵相关联。利用我们的核心竞争力， 我们拥有一支由分析化学家和临床研究人员组成的才华横溢的团队， 开发一种简单易用，价格低廉的设备，可以测量生物样品中的RSNO。一旦开发出来， 该装置将使新的临床研究能够评估S-亚硝基硫醇作为疾病的临床生物标志物。