A. James Clark School of Engineering

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Author: search.filters.author.Chocron, Sheryl E.

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    The Binding Effect of Proteins on Medications and Its Impact on Electrochemical Sensing: Antipsychotic Clozapine as a Case Study
    (MDPI, 2017-08-01) Banis, George E.; Winkler, Thomas; Barton, Patricia; Chocron, Sheryl E.; Kim, Eunkyoung; Kelly, Deanna L.; Payne, Gregory F.; Ben-Yoav, Hadar; Ghodssi, Reza
    Clozapine (CLZ), a dibenzodiazepine, is demonstrated as the optimal antipsychotic for patients suffering from treatment-resistant schizophrenia. Like many other drugs, understanding the concentration of CLZ in a patient’s blood is critical for managing the patients’ symptoms, side effects, and overall treatment efficacy. To that end, various electrochemical techniques have been adapted due to their capabilities in concentration-dependent sensing. An open question associated with electrochemical CLZ monitoring is whether drug–protein complexes (i.e., CLZ bound to native blood proteins, such as serum albumin (SA) or alpha-1 acid-glycoprotein (AAG)) contribute to electrochemical redox signals. Here, we investigate CLZ-sensing performance using fundamental electrochemical methods with respect to the impact of protein binding. Specifically, we test the activity of bound and free fractions of a mixture of CLZ and either bovine SA or human AAG. Results suggest that bound complexes do not significantly contribute to the electrochemical signal for mixtures of CLZ with AAG or SA. Moreover, the fraction of CLZ bound to protein is relatively constant at 31% (AAG) and 73% (SA) in isolation with varying concentrations of CLZ. Thus, electrochemical sensing can enable direct monitoring of only the unbound CLZ, previously only accessible via equilibrium dialysis. The methods utilized in this work offer potential as a blueprint in developing electrochemical sensors for application to other redox-active medications with high protein binding more generally. This demonstrates that electrochemical sensing can be a new tool in accessing information not easily available previously, useful toward optimizing treatment regimens.
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    The Binding Effect of Proteins on Medications and Its Impact on Electrochemical Sensing: Antipsychotic Clozapine as a Case Study
    (Multidisciplinary Digital Publishing Institute (MDPI), 2017-08-01) Banis, George E.; Winkler, Thomas; Barton, Patricia; Chocron, Sheryl E.; Kim, Eunkyoung; Kelly, Deanna L.; Payne, Gregory F.; Ben-Yoav, Hadar; Ghodssi, Reza
    Clozapine (CLZ), a dibenzodiazepine, is demonstrated as the optimal antipsychotic for patients suffering from treatment-resistant schizophrenia. Like many other drugs, understanding the concentration of CLZ in a patient’s blood is critical for managing the patients’ symptoms, side effects, and overall treatment efficacy. To that end, various electrochemical techniques have been adapted due to their capabilities in concentration-dependent sensing. An open question associated with electrochemical CLZ monitoring is whether drug–protein complexes (i.e., CLZ bound to native blood proteins, such as serum albumin (SA) or alpha-1 acid-glycoprotein (AAG)) contribute to electrochemical redox signals. Here, we investigate CLZ-sensing performance using fundamental electrochemical methods with respect to the impact of protein binding. Specifically, we test the activity of bound and free fractions of a mixture of CLZ and either bovine SA or human AAG. Results suggest that bound complexes do not significantly contribute to the electrochemical signal for mixtures of CLZ with AAG or SA. Moreover, the fraction of CLZ bound to protein is relatively constant at 31% (AAG) and 73% (SA) in isolation with varying concentrations of CLZ. Thus, electrochemical sensing can enable direct monitoring of only the unbound CLZ, previously only accessible via equilibrium dialysis. The methods utilized in this work offer potential as a blueprint in developing electrochemical sensors for application to other redox-active medications with high protein binding more generally. This demonstrates that electrochemical sensing can be a new tool in accessing information not easily available previously, useful toward optimizing treatment regimens.
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    Interference Studies Using Multidimensional Mapping of Cross-Reactive Sensors: Applications in Blood Monitoring of Clozapine
    (2014) Chocron, Sheryl E.; Ghodssi, Reza; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
    Point-of-care sensors are used in clinical applications for diagnosing and monitoring health conditions. For example, a point-of-care sensor for therapeutic drug monitoring of the clozapine antipsychotic can reduce burdens from guidelines suggesting routine monitoring of this medication. However, when measuring chemical markers in complex fluids, there are challenges related to decreased sensor performance due to chemical interference. This work presents a methodology for identifying individual interfering species. A set of cross-reactive electrochemical sensors were developed, whose diversified responses provide a fingerprint-type pattern capable of differentiating various species. By mapping the multidimensional responses, patterns from complex solutions were discerned and matched to those of individual species. Applying this methodology to clozapine sensing in blood, a major source of chemical interference was identified. The understanding matrix components that cause interference can guide the design of reliable sensing systems and can be integrated with pattern recognition tools that can account for it.