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。研究将建立在最近一段时间的支持期间取得的几项令人兴奋的突破的基础上，这些突破包括：1）快速筛选高电荷密度聚阴离子杂质（例如，2）使用电位聚阴离子传感器技术在商业生物医学级肝素制剂中的过硫酸化硫酸软骨素（OSCS）; 2）使用铑（III）金属卟啉络合物作为迄今为止发现的用于制备电位聚阴离子传感器的最具选择性的结合剂;（和潜在的光学）亚硝酸根离子传感器; 3）采用脉冲电位测量技术提高了阴离子和聚离子敏感聚合物膜电极的分析响应性能。在这个长期计划的下一阶段的努力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定量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，并且还评估先前报道的光学肝素感测聚合物膜技术是否可以用于类似的测量; 2）进一步优化铑（III）金属卟啉在聚合物膜中作为离子载体的效用，用于开发亚硝酸盐的高选择性电化学和光学传感器（使用封端的四苯基卟啉作为离子载体），并且证明了在新型气体/生物传感系统中使用这种传感器作为简单的检测器来监测可能在呼出气中的非常低水平的气相一氧化氮（NO）;和3）评估使用新的pulstrode仪器控制方法来增强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，以及制备完全可逆的聚阴离子/聚阳离子传感器，其可用于连续监测血液中的肝素和检测蛋白酶活性。预计这些领域的研究成果将继续提供一系列新的简单传感器，可用于复杂生理和其他类型样本的重要生物医学测量。 公共卫生相关性：生物医学科学的进步和提高保健质量需要更快、更简单和更便宜的测量技术，用于直接感测复杂样品中的物种。迄今为止，基于聚合物膜的化学传感器已经为许多新的即时检测仪器的开发提供了基础，这些仪器能够在全血和其他样品中进行快速化学测量。本文提出的研究将提供聚合物膜化学的进展，这可能使生物医学级肝素产品中有害污染物的简单检测，在医疗过程中全血中肝素的实时测量，以及用于量化生理上重要的亚硝酸盐和一氧化氮水平的新设备的设计成为可能。

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.