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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
5R01EB000784-32
Application #
8418772
Study Section
Special Emphasis Panel (ZRG1-BCMB-B (03))
Program Officer
Korte, Brenda
Project Start
1981-04-01
Project End
2015-01-31
Budget Start
2013-02-01
Budget End
2015-01-31
Support Year
32
Fiscal Year
2013
Total Cost
$263,741
Indirect Cost
$80,193
Name
University of Michigan Ann Arbor
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Yang, Si; Wo, Yaqi; Meyerhoff, Mark E (2014) Polymeric optical sensors for selective and sensitive nitrite detection using cobalt(III) corrole and rhodium(III) porphyrin as ionophores. Anal Chim Acta 843:89-96
Bell-Vlasov, Andrea K; Zajda, Joanna; Eldourghamy, Ayman et al. (2014) Polyion selective polymeric membrane-based pulstrode as a detector in flow-injection analysis. Anal Chem 86:4041-6
Kang, Youngjea; Gwon, Kihak; Shin, Jae Ho et al. (2011) Highly sensitive potentiometric strip test for detecting high charge density impurities in heparin. Anal Chem 83:3957-62
Gemene, Kebede L; Meyerhoff, Mark E (2011) Detection of protease activities by flash chronopotentiometry using a reversible polycation-sensitive polymeric membrane electrode. Anal Biochem 416:67-73
Gemene, Kebede L; Meyerhoff, Mark E (2010) Reversible detection of heparin and other polyanions by pulsed chronopotentiometric polymer membrane electrode. Anal Chem 82:1612-5
Ramanathan, Madhumati; Wang, Lin; Wild, James R et al. (2010) Monitoring of diisopropyl fluorophosphate hydrolysis by fluoride-selective polymeric films using absorbance spectroscopy. Anal Chim Acta 667:119-22
Wang, Lin; Meyerhoff, Mark E (2010) Quantitative Determination of High Charge Density Polyanion Contaminants in Biomedical Heparin Preparations Using Potentiometric Polyanion Sensors. Electroanalysis 22:26-30
Pietrzak, Mariusz; Meyerhoff, Mark E (2009) Polymeric membrane electrodes with high nitrite selectivity based on rhodium(III) porphyrins and salophens as ionophores. Anal Chem 81:3637-44
Gorski, Lukasz; Matusevich, Alexey; Pietrzak, Mariusz et al. (2009) Influence of Inner Transducer Properties on EMF Response and Stability of Solid-Contact Anion Selective Membrane Electrodes Based on Metalloporphyrin Ionophores. J Solid State Electrochem 13:157-164
Wang, Lin; Meyerhoff, Mark E (2008) Polymethacrylate polymers with appended aluminum(III)-tetraphenylporphyrins: Synthesis, characterization and evaluation as macromolecular ionophores for electrochemical and optical fluoride sensors. Anal Chim Acta 611:97-102

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