A Flexible Sensor for Vancomycin Fabricated By Depositing Molecularly Imprinted Carbon Paste on a Wire
Authors: Yoshimi Yasuo , Okamura Haruka , Dosaka Keigo , Aaryashree Aaryashree 
Published: February 2024

1. Introduction

Vancomycin (VCM), an antibacterial drug, has a narrow effective blood concentration range, requiring therapeutic drug monitoring (TDM) to measure blood levels and optimize dosing regimens . Neonates, in particular, have large individual differences in the rate of drug metabolism, so strict TDM is necessary, but the dilemma is that the amount of blood drawn must be kept to a minimum. Therefore, we decided to develop a method of TDM without blood sampling by implanting a sensor that detects VCM under the skin. The sensor must be flexible enough not to damage the subcutaneous tissue. We have developed a sensor using a MIP carbon paste (MIP-CP) electrode, in which graphite particles with molecularly imprinted polymers are mixed with oil. Since higher mechanical strength is required for indwelling sensors, we fabricated MIP-carbon dough (MIP-CD) electrodes by mixing MIP with a thermosetting silicon resin prepolymer and thermosetting it. This was applied to a wire to develop a flexible wire-type sensor, and its performance was evaluated. 2.

2. experimental method

2-1. MIP graft polymerization /MIP-CD fabrication
Methacrylic acid, ethylene glycol dimethacrylate, and allylamine carboxypropionic-3-ferrocene were graft copolymerized on the surface of graphite particles with fixed polymerization initiator in the presence of template VCM. Then, after washing and drying with sodium chloride solution and distilled water, the uncured MIP-CD was mixed with thermosetting silicone resin at a weight ratio of 7:3. Non-imprinted polymer (NIP)-CD, which was prepared by the same procedure without adding a template during synthesis, was also prepared for comparison.
2-2. Fabrication of MIP-CD sensor
Carbon ink was applied to a 20 mm tip of a 50 mm tin-plated copper wire, and uncured MIP-CD was applied on top. Then, silicon resin was applied for insulation to limit the effective area of the MIP-CD electrode, and both the insulation and MIP-CD were heat-cured in a dryer to fabricate the wire electrode shown in Fig. 1.
2-3. measurement method
Differential pulse voltammetry was performed on the MIP (or NIP)-CD sensor in phosphate buffer containing VCM or teicoplanin (TEIC), which has a similar structure, and the relationship between current and concentration was plotted.

3. Results and Discussion

A comparison of the sensitivity of MIP-CD and NIP-CD electrodes to VCM is shown in Fig. 2: the current at MIP-CD increased linearly with increasing VCM concentration, while that at NIP-CD was insensitive. This result indicates that the current at the MIP-CD electrode reflects the specific binding of VCM to the imprinted binding site. As shown in Fig. 3, the MIP-CD electrode was not sensitive to TEIC and showed high selectivity.

Conclusion

The electrode with MIP-CD fixed on a wire is strong and flexible, yet has a specific response to VCM, and is expected to be used as an indwelling subcutaneous sensor.
*This work was supported by the Bridging Research Program of the Japan Agency for Medical Research and Development (Keio University Center).

Figure 1