Polymer Membrane Ion/Gas/Polyion Sensors: New Frontiers

描述(由申请人提供)：提出了新型阴离子/气体/聚离子选择性聚合物膜/膜基电化学和光学传感器的持续开发、研究和分析应用。研究将在最近一段时间内取得的几项令人振奋的突破的基础上进行，这些突破包括：1)利用电位型聚阴离子传感器技术快速筛选商业生物医用级肝素制剂中含有高电荷密度的聚阴离子杂质(如过硫酸软骨素)的能力；2)使用Rh(III)金属卟啉配合物作为迄今发现的最具选择性的结合剂，用于制备电位型(及潜在光学)亚硝酸盐离子传感器；3)采用一种新型的Pulstrod型电位测量技术，以增强阴离子和多离子灵敏聚合物膜电极的分析响应性能。这一长期计划下一阶段的工作将包括基础和应用研究，并将集中在：1)检查使用新的基于聚阴离子传感器的方法来量化生物医学肝素制剂中OSCS和潜在的其他高电荷密度聚阴离子杂质的浓度的方法，并评估以前报道的光学肝素传感聚合物膜技术是否可以用于类似的测量；2)进一步优化Rh(III)金属卟啉在聚合物薄膜中作为离子载体的作用，以开发高选择性的亚硝酸盐电化学和光学传感器(使用带帽的四苯基卟啉作为离子载体)，并展示在新型气体/生物传感系统中作为简单检测器的这种传感器的使用，以监测潜在在呼气中的极低水平的气相一氧化氮(NO)；以及3)评估一种新的Pulstrode仪器控制方法的使用，以提高各种基于离子载体的聚合物膜阴离子传感器的电位选择性，并制备可用于连续监测血液中的肝素和检测蛋白酶活性的完全可逆的聚阴离子/聚阳离子传感器。预计这些领域的研究成果将继续提供一系列新的、简单的传感器，可用于复杂生理和其他类型样本的重要生物医学测量。 与公共卫生的相关性：生物医学科学的进步和提高卫生保健的质量要求提供更快、更简单和更便宜的测量技术，用于直接检测复杂样品中的物种。到目前为止，基于聚合物膜的化学传感器已经为许多新的能够快速测量全血和其他样本的化学成分的护理点测试仪器的开发提供了基础。本文提出的研究将提供聚合物膜化学的进展，使其能够简单地检测生物医用级肝素产品中的有害污染物，在医疗过程中实时测量全血中的肝素，并设计新的定量生理上重要的亚硝酸盐和一氧化氮水平的设备。

DESCRIPTION (provided by applicant): The continued development, study, and analytical applications of novel anion/gas/polyion selective polymer membrane/film-based electrochemical and optical sensors are proposed. Research will build upon several exciting breakthroughs made during the most recent period of support that have included: 1) the ability to rapidly screen for the presence of high charge density of polyanion impurities (e.g., oversulfated chondroitin sulfate (OSCS)) within commercial biomedical grade heparin preparations using potentiometric polyanion sensor technology; 2) the use of rhodium (III) metalloporphyrin complexes as the most selective binding agents discovered to date for preparing potentiometric (and potentially optical) nitrite ion sensors; and 3) the adaptation of a new pulstrode type potentiometric measurement technology to enhance the analytical response properties of anion and polyion sensitive polymeric membrane electrodes. Efforts during the next phase of this long-term program will include both fundamental and applied studies and will concentrate on: 1) examining approaches to use the new polyanion sensor-based method to quantify the concentration of OSCS and potentially other high-charge density polyanion impurities in biomedical heparin preparations, and also assess whether a previously reported optical heparin sensing polymer film technology can be employed for similar measurements; 2) further optimize the utility of rhodium(III) metalloporphyrins as ionophores in polymeric films for developing highly selective electrochemical and optical sensors for nitrite (using capped tetraphenylporphyrins as ionophores), and demonstrating the use of such sensors as simple detectors in a novel gas/biosensing system to monitor very low levels of gas phase nitric oxide (NO), potentially in exhaled breath; and 3) assessing the use of a new pulstrode instrumental control method to enhance the potentiometric selectivity of various ionophore-based polymeric membrane anion sensors, and also to prepare fully reversible polyanion/polycation sensors that can be used to continuously monitor heparin in blood and for detecting protease activities. It is anticipated that results derived from the research in these areas will continue to provide an array of new and simple sensors that can be employed for important biomedical measurements in complex physiological and other types of samples. PUBLIC HEALTH RELEVANCE: Progress in biomedical sciences and enhancing the quality of health care requires the availability of faster, simpler and less expensive measurement technologies for direct sensing of species in complex samples. To date, polymer membrane-based chemical sensors have provided the foundation for the development of many new point-of-care test instruments capable of rapid chemical measurements in whole blood and other samples. The research proposed herein will provide advances in polymer membrane chemistries that may enable the simple detection of harmful contaminants in biomedical grade heparin products, the real-time measurement of heparin in whole blood during medical procedures, and the design of new devices for quantifying physiologically important nitrite and nitric oxide levels.