HYDROGEL-INTEGRATED ELECTROCHEMICAL BIOSENSORS FOR POINT-OF-CARE MONITORING IN MENTAL HEALTH

Hadar Ben-Yoav ^1,2 Thomas E. Winkler ³ Sheryl E. Chocron ³ Eunkyoung Kim ⁴ Deanna L. Kelly ⁵ Gregory F. Payne ^3,4 Reza Ghodssi ^2,3

¹Department of Biomedical Engineering, Ben-Gurion University of the Negev, Beer-Sheva
²Department of Electrical and Computer Engineering, Institute for Systems Research, University of Maryland College Park, College Park, Maryland
³Fischell Department of Bioengineering, University of Maryland College Park, College Park, Maryland
⁴Institute for Bioscience and Biotechnology Research, University of Maryland College Park, College Park, Maryland
⁵Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, Maryland

We present the first demonstration of a hydrogel-integrated electrochemical micro-system for real-time biosensing of the antipsychotic clozapine (CLZ) towards point-of-care Schizophrenia treatment monitoring. The biosensor is based on a multi-sensor approach that integrates hydrogel chitosan-modified semi-selective sensors, i.e. a catechol-chitosan redox cycling system and a carbon nanotubes (CNTs) –chitosan composite (Figure 1). Here, we show the development of the microfabricated biosensor and the miniaturization of the redox-cycling system that results in the amplification of the electrochemical signal generated by CLZ (Figure 2). The catechol-chitosan integrated biosensor demonstrates a sensitivity of 54 µC×mL/cm²×µg and a limit-of-detection of 0.8 µg/mL (Figure 3), that enables detection in high interference biological samples such as Schizophrenia patients’ serum.

Scheme of the multi-sensor approach that is based on chitosan-modified amplification and differentiation electrochemical biosensors. Photograph of the microfabricated biosensor (3 cm × 4.5 cm). CLZ dose response characteristics of the biosensor integrated with bare and catechol-chitosan modified gold electrodes.

Figure 1 (top): Scheme of the multi-sensor approach that is based on chitosan-modified amplification and differentiation electrochemical biosensors.
Figure 2 (bottom left): Photograph of the microfabricated biosensor (3 cm × 4.5 cm).
Figure 3 (bottom right): CLZ dose response characteristics of the biosensor integrated with bare and catechol-chitosan modified gold electrodes.

References:

1. H. Ben-Yoav, T.E. Winkler, E. Kim, S.E. Chocron, D.L. Kelly, G.F. Payne, R. Ghodssi, Redox cycling-based amplifying electrochemical sensor for in situ clozapine antipsychotic treatment monitoring, Electrochimica Acta 130, p. 497, 2014.
2. H. Ben-Yoav, S.E. Chocron, T.E. Winkler, E. Kim, D.L. Kelly, G.F. Payne, R. Ghodssi, An electrochemical micro-system for clozapine antipsychotic treatment monitoring, Electrochimica Acta 163, p. 260, 2015.
3. D. L. Kelly, H. Ben-Yoav, G. F. Payne, T. E. Winkler, S. E. Chocron, E. Kim, V. Stock, G. Vyas, R. C. Love, H. J. Wehring, K. M. Sullivan, S. Feldman, F. Liu, R. P. McMahon, and R. Ghodssi, Blood draw barriers for treatment with clozapine and development of point-of-care monitoring device, Clinical Schizophrenia & Related Psychoses, 2015 (In Press).