Analytical Micro-Systems for Personalized Health Monitoring

---

Electrochemical lab-on-a-chip for neuropsychiatric health management

Schizophrenia is a lifelong mental disorder with few recent advances in treatment. Clozapine is the most effective antipsychotic for schizophrenia treatment. However, it remains underutilized since frequent blood draws are required to monitor adverse side effects, and maintain clozapine concentrations in a therapeutic range. Micro-system technology utilized towards real-time monitoring of efficacy and safety will enable personalized medicine and better use of this medication. Although work has been reported on clozapine detection using its electrochemical oxidation, no in situ monitoring of clozapine has been described. In this work, we present a new concept for clozapine in situ sensing based on amplifying its oxidation current. Specifically, we use a biofabricated catechol-modified chitosan redox cycling system to provide a significant amplification of the generated oxidizing current of clozapine through a continuous cycle of clozapine reduction followed by re-oxidation. The amplified signal has improved the signal-to-noise ratio and provided the required limit-of-detection and dynamic range for clinical applications with minimal pre-treatment procedures. This new biosensing approach can be further developed towards its integration in miniaturized devices for improved personalized mental health care.

Selected Accomplishments:

• The first demonstration of an electrochemical lab-on-a-chip for in situ detection of the antipsychotic clozapine
• Detection of clozapine in undiluted blood samples of Schizophrenia patients

Students and Postdocs:

• Mr. Thomas Winkler
• Ms. Sheryl Chocron
• Mr. George Banis
• Dr. Eunkyoung Kim

Collaborators:

Professor Deanna L. Kelly (University of Maryland School of Medicine)
Professor Gregory F. Payne (University of Maryland College Park)
Professor Reza Ghodssi (University of Maryland College Park)

Support:

• The Maryland Innovation Initiative (MII), TEDCO
• National Institute of Mental Health (NIMH), National Institute of Health (NIH)

Selected Publications:

• Kelly, D. L., Ben-Yoav, H., Payne, G. F., Winkler, T. E., Chocron, S. E., Kim, E., Stock, V., Vyas, G., Love, R. C., Wehring, H. J., Sullivan, K. M., Feldman, S., Liu, F., McMahon, R. P., and Ghodssi, R. Blood draw barriers for treatment with clozapine and development of point-of-care monitoring device. Clinical Schizophrenia & Related Psychoses, 2015 (In Press).
  
• Ben-Yoav, H., Chocron, S. E., Winkler, T. E., Kim, E., Kelly, D. L., Payne, G. F., and Ghodssi, R. An electrochemical micro-system for clozapine antipsychotic treatment monitoring. Electrochimica Acta 163, pp. 260-270, 2015.
  
• Kim, E., Chocron, S. E., Ben-Yoav, H., Winkler, T. E., Liu, Y., Glassman, M., Wolfram, C., Kelly, D. L., Ghodssi, R., and Payne, G. F. Programmable "semismart" sensor: relevance to monitoring antipsychotics. Advanced Functional Materials, 2015.
  
• Chocron, S. E., Weisberger, B. M., Ben-Yoav, H., Winkler, T. E., Kim, E., Kelly, D. L., Payne, G. F., and Ghodssi, R. Multidimensional mapping method using an arrayed sensing system for cross-reactivity screening. PLoS ONE 10, pp. e0116310, 2015.
  
• Kim, E., Xiong, Y., Cheng, Y., Wu, H.-C., Liu, Y., Morrow, B., Ben-Yoav, H., Ghodssi, R., Rubloff, G., Shen, J., Bentley, W., Shi, X., and Payne, G. Chitosan to connect biology to electronics: fabricating the bio-device interface and communicating across this interface. Polymers special issue on "Chitin and Chitosans" 7, pp. 1-46, 2015.
  
• Winkler, T. E., Ben-Yoav, H., Chocron, S. E., Kim, E., Kelly, D. L., Payne, G. F., and Ghodssi, R. Electrochemical study of the catechol-modified chitosan system for clozapine treatment monitoring. Langmuir 30, pp. 14686-14693, 2015.
  
• Ben-Yoav, H., Dykstra, P. H., Bentley, W. E., and Ghodssi, R. A controlled microfluidic electrochemical lab-on-a-chip for label-free diffusion-restricted DNA hybridization analysis. Biosensors and Bioelectronics 64, pp. 579-585, 2015. Click to download article
  
• Ben-Yoav, H., Winkler, T. E., Kim, E., Chocron, S. E., Kelly, D. L., Payne, G. F., and Ghodssi, R. Redox cycling-based amplifying electrochemical sensor for in situ clozapine antipsychotic treatment monitoring. Electrochimica Acta 130, pp. 497-503, 2014. Click to download paper