Mark Meyerhoff

Current research efforts in our laboratory are focused on: 1) the design and study of novel electrochemical and optical chemical sensors (as well as microfluidic systems) based on thin polymeric films or liquid organic phases doped with highly selective host compounds; 2) the synthesis, characterization and biomedical applications of polymeric materials that release/generate nitric oxide (NO) to prevent clotting and infection; and 3) development of implantable chemical sensors for real-time  in vivo monitoring  of critical care analytes that utilize NO release chemistry to enhance analytical accuracy.

In the area of chemical sensors we are investigating the use of various metal-ligand complexes (including metalloporphyrins) as anion/gas recognition agents within thin polymeric films to create new electrochemical and optical anion and gas selective sensors. Selective anion or gas molecule coordination to the metal ion center of these complexes can yield changes in membrane potentials (voltage across the polymeric films) and/or the optical absorbance or fluorescence spectra of the complexes within the polymeric phase. We are also adapting these ion-selective extraction chemistries, including similar ones for cations using well-known cation selective ionophores, to microfluidic systems that use organic liquid phases to separate segments of blood or other aqueous samples.  The addition of a fluorescent organic pH indicator into the organic phase segments can be used to generate fluorescent signals from the organic phase segments that are dependent on the concentration of target anion or cation within the aqueous sample phase.

Over the past 20+ years we have been examining the use of novel nitric oxide (NO) releasing polymers to prevent clotting and infections for biomedical catheters (both intravascular and urinary catheters) and other medical devices.  Nitric oxide is an endogenous gas molecule produced by endothelial cells that line the inner walls of all blood vessels to prevent activation of platelets (prevent clotting) and is also produced by macrophages in our bodies to help kill bacteria and viruses.   We utilize novel S-nitrosothiol type species as the NO release agents, such as S-nitroso-N-acetyl-penicillamine (SNAP), impregnated into various polymers and study the rate of NO release of these materials, and also examine the antimicrobial activities of these new polymeric materials (including catheters).  The most promising materials are then tested in animal models in the ECMO Laboratory at the University of Michigan Medical School.

We are also developing methods to utilize the NO release chemistry described above to improve the biocompatibility of implantable electrochemical/optical gas/ion sensors via use of novel nitric oxide (NO) release polymers (based on SNAP and other NO release species) for more accurate real time monitoring of blood gases, glucose, lactate, and other species in blood. Owing to the potent anti-platelet aggregating activity of NO, the resulting implanted sensors exhibit a dramatic decrease in platelet adhesion (compared to control sensors without NO release) during in vivo experiments.  Since adhered activated platelets consume oxygen and glucose, and liberate CO₂, platelet adhesion causes the in vivo sensors to yield inaccurate results.  However, with NO release we have found that these intravascular sensors yield much more accurate analytical results over extended time periods. 

Awards

Association of Analytical Chemists (ANACHEM) Award, 2021
ACS Award in Analytical Chemistry, 2020
Ralph N. Adams Award in Bioanalytical Chemistry, 2013
Rackham Distinguished Faculty Achievement Award, 2011
Charles N. Reilley Award in Electroanalytical Chemistry, 2006
Rackham Distinguished Graduate Mentor Award, 2006
ACS Analytical Chemistry Award in Electrochemistry, 2003
Philip J. Elving Collegiate Professor of Chemistry, 2004-present

Representative Publications

Y. Qin, J. Zajda, H. Ren, J. Toomasian, T. Major, A. Rojas-Pena, B. Carr, T. Johnson , J. Haft, R. H. Bartlett, A. Hunt, N. Lehnert, and M. E. Meyerhoff, “Low Cost Portable Gas Phase Nitric Oxide (NO) Generator Based on Electrochemical Reduction of Nitrite for Potential Applications in Inhaled NO Therapy and Within the Sweep Gas/Cardiotomy Suction Air During Cardiopulmonary Bypass Surgery,” Mol. Pharmaceutics, 14, 3762-3771 (2017).

X. Wang, Q. Zhang, C. Nam, M. Hickner, M. Mahoney, and M. E. Meyerhoff, “Ionophore-Based Optode Printed on Cellulose Paper for Polymer/Plasticizer Free Anion Analysis,” Angew. Chem. Int. Ed., 56, 11826-11830 (2017).

K. K. Konopińska, N. J. Schmidt, A. Hunt, N. Lehnert, J. Wu, C. Xi, and M. E. Meyerhoff, “Comparison of Copper(II)-Ligand Complexes as Mediators for Preparing Electrochemically Modulated Nitric Oxide-Releasing Catheters,” ACS Appl. Mater. Interfaces, 10, 25047 -25055 (2018).

X. Wang, M. Sun, S. A. Ferguson, J. D. Hoff, Y. Qin, R. C. Bailey, and M. E. Meyerhoff, “Ionophore-Based Biphasic Chemical Sensing in Droplet Microfluidics,” Angew. Chem. Int. Ed., 58, 8092 –8096 (2019).

J. C. Doverspike, S. J. Mack, A. Luo, B. Stringer, S. Reno, M. S. Cornell, A. Rojas-Pena, J. Wu, C. Xi, A. Yevzlin, M. E. Meyerhoff, “Hub Region Disinfecting Nitric Oxide Releasing Insert for Tunneled Dialysis Catheters,” ACS Appl. Mater & Interfaces, 12(40), 44475-44484 (2020). 

Q. Zhang, G. P. Murray, J. E. Hill, S. L. Harvey, A. Rojas-Pena, J. Choi, Y. Zhou, R. H. Bartlett, M. E. Meyerhoff, “Enhanced Hemocompatability and In Vivo Analytical Accuracy of Intravascular Potentiometric Carbon Dioxide Sensors Via Nitric Oxide Release,” Anal. Chem., 92(20), 13541-13646 (2020).

Q. Zhang, M. E. Meyerhoff, “Nitric Oxide. Release for Enhanced Biocompatibility and Analytical Performance of Implantable Electrochemical Sensors,” Electroanalysis, 33(9), 1997-2015 (2021).

Research Areas(s)

• Analytical Chemistry
  Bioanalytical Chemistry
  Materials Chemistry
  Optics and Imaging
  Sensor Science
  Electrochemical and Optical Sensors
  Biomaterials