Molecularly Imprinted Carbon-Paste for Theophylline Sensing on a Disposable Paper Chip Sensor
Authors: Aaryashree Aaryashree , Nakane Yui , Takeda Yuuto , Abe Masaki , Ohishi Tomoji , Yoshimi Yasuo 
Published: July 2021

Introduction

Molecularly imprinted polymers (MIPs) are recognition elements with specific cavities designed for a particular target molecule. Recently, MIPs have been used in various applications explicitly requiring molecular recognition. In MIPs, the crosslinking monomers and functional monomers, having an affinity with a target molecule, are copolymerized in the presence of the target or the template molecule. Upon selective removal of the template molecule, imprinted cavities are formed. MIPs provide a wide range of benefits, including mechanical reliability, cost-effectiveness, and rapid mass production, and have recently been used for various applications, especially in biosensing areas [1]–[3].
Theophylline (THO) is a drug commonly used for the therapy of respiratory diseases. However, owing to its highly toxic nature, an overdose can induce paralysis, seizures, and even death.[4] Additionally, the therapeutic window of THO is relatively small (5-15 mgmL-1) [4],[5], and therefore, the therapeutic drug monitoring (TDM) of theophylline is highly significant [5]. In this study, molecularly imprinted polymers grafted carbon pastes were prepared for THO sensing. The commonly used functional monomer, methacrylic acid, crosslinking monomers, N, N’-methylenebisacrylamide (MBAA), and ethylene glycol dimethacrylate (EDMA) were used, and the MIPs thus formed were evaluated using differential pulse voltammetry on a paper chip.

Methods

Fig. 1 shows the scheme of the paper chip along with the sensing response of theophylline MIP. The paper chip composed of a photo-paper base with electrodes printed using conductive ink through an inkjet printer. The holes for electrodes (working electrode, a reference electrode, and counter electrode) and reservoir are cut on laminating sheets using a laser cutter. The three parts are then attached using the laminator. The reference electrode is packed with Ag/AgCl ink and dried overnight at 60 ℃. The counter electrode with the printed conductive ink is used as it is. The MIP-grafted carbon paste is packed in the working electrode with the help of a glass tube. The theophylline imprinted poly(methylene bisacrylamide-co-ethylene dimethacrylate-co-methacrylic acid) was grafted on the graphite particle surface by a procedure similar to our previous work [3], [6]. This grafted graphite was mixed with ferrocene containing silicone oil to make a paste used as the sensing material. We performed the differential pulse voltammetry with theophylline sample solution (in saline buffer with pH 7.4, 0-40 mgmL-1 and whole bovine blood) filled in the sample-reservoir.

Results and Conclusions

The execution time of each voltammetry was 2 min only. The plot in Fig. 1 shows the influence of the theophylline concentration on the redox current at 0.8 V at the MIP-carbon paste electrode in both buffer saline and whole bovine blood. It is quite evident from the figure that MIP is sensitive towards theophylline in both buffer and whole blood. It indicates that MIP activates the electrocatalytic behavior of the carbon-paste electrode. The dynamic range at the MIP electrode versus the concentration of theophylline is seen in the range of 0-40 mgmL-1, which covers the therapeutically effective theophylline concentration level in plasma varying from 5 to 15 mgmL-1. The DPV measurements at each concentration has been done using a new chip every time, i.e. ‘single-use’ of the chip. Additionally, no reagents have been added during the analysis, thus making the procedure of drug level measurement simple. From the results of this study, it can be concluded that the proposed method is useful for quick and straightforward real-time TDM to prevent the toxic side effects of an overdose.

References

[1] T. Sakata, et al.
RSC Adv., 10(29),16999–17013, 2020; doi:10.1039/d0ra02793f.
[2] Y. Yoshimi, et al.
Sensors, 19(10), 2415, 2019; doi:10.3390/s19102415.
[3] Y. Yoshimi, et al.
Sensors Actuators, B Chem., 259, 455–462, 2018; doi:10.1016/j.snb.2017.12.084.
[4] R. Vassallo, et al.
Mayo Clin. Proc., 73(4), 346–354, 1998; doi:10.1016/s0025-6196(11)63701-4.
[5] A. Peng, Int. J. Electrochem. Sci., 12(1), 330–346, 2017; doi:10.20964/2017.01.03.
[6] Aaryashree et al., Sensors, 20(20), 5847, 2020; doi:10.3390/s20205847

Figure 1