A Disposable Vancomycin Sensor Using Molecularly Imprinted Carbon Paste on a Ceramic Chip

Abstract

Introduction Vancomycin (VCM) is the first-choice drug for the therapy of MRSA infection, which is the most typical nosocomial infection. However, VCM resistant bacteria is a severe worldwide problem [1]. Therapeutic drug monitoring (TDM) of VCM in the blood is useful to prevent the creation of resistant bacteria. Nevertheless, conventional TDM using immunoassay requires economical and labor burdens to hospitals [2]. Thus, an inexpensive disposable sensor that can determine the VCM concentration in blood with simple operation as that of blood sugar-sensor is required. In this study, we developed a VCM sensor using a carbon paste electrode grafted with a molecularly imprinted polymer (MIP) and a ceramic platform. MIPs are a molecular recognition element prepared by simple radical copolymerization in the presence of the target as a template. We have discovered that redox current at a MIP-grafted carbon paste electrode is sensitive to the target [3]. Method Figure 1(a) shows the scheme of the ceramic chip composed of aluminum oxide ceramic body and platinum wiring. It contains three holes for electrodes with 2.0 mm diameter and 0.4 mm depth, connected with platinum wiring at the bottom. The chip also comprises a square sample-reservoir of side 10 mm. VCM imprinted poly(methylene bisacrylamide-co-methacrylic acid-co-Allylaminocarboxypropyonic-3-ferrocene) was grafted on graphite particle surface by a procedure similar to our previous work [3], This grafted graphite was mixed with silicone oil to make a paste to use as the sensing material. A non-treated polymer was also synthesized in a similar way as that of VCM MIP, but without the template. Two of the holes of 2.0 mm diameter were each packed with grafted graphite and Ag/AgCl paste to act as the working electrode a reference electrode, respectively. The Pt wire of the third hole was used as the counter electrode. We performed differential pulse voltammetry with a VCM sample solution (0-60 mgmL-1, both in phosphate buffer and in bovine blood) filled in the sample-reservoir. Results and Conclusions The execution time of each voltammetry was 10 min only. Figure 1(b) shows the influence of the VCM concentration on the redox current at 0.8 V at both non-treated and the MIP-carbon paste electrode. It is quite evident from the figure that only MIP responds to VCM. The dynamic range at the MIP electrode versus the concentration of VCM is seen in the range of 0-60 mgmL-1, which corresponds covers the therapeutically effective vancomycin concentration level in plasma varying from 20 to 40 mgL-1 [4], [5]. Additionally, the R2 value of 0.9963 indicates a linear behavior of the sensor with change in drug concentration. From these results, it can be concluded that the proposed method is useful for quick and straightforward TDM to prevent both of the toxic side effects by overdose and the creation of antibacterials by underdose. References [1] Z.-K. Ye, et. al. PLoS One, vol. 8, no. 10, p. e77169, Oct. 2013,doi:10.1371/journal.pone.0077169. [2] K. Matsumoto, et. al. J. Infect. Chemother., vol. 19, no. 3, pp. 365–380, 2013,doi:10.1007/s10156-013-0599-4. [3] Y. Yoshimi, et. al. Sensors Actuators B Chem., vol. 259, pp. 455–462, Apr. 2018,doi:10.1016/j.snb.2017.12.084. [4] “UCSFMC Adult Vancomycin Dosing and Monitoring Recommendations.” https://idmp.ucsf.edu, 2018. [5] “Vancomycin in adult patients,” vol. 2018, May, 2017. Acknowledgment The research is partially supported by Grant in Aid of JST A-STEP. Figure 1