Electrochemical chemosensor for asymmetric dimethylarginine detection with molecularly imprinted recognition layer

Early diagnosis of renal diseases is extremely important for their effective curing. Biomarkers present in body fluids, which are currently used for diagnosis of this illness, are strongly affected by different non-renal factors (e.g. patient gender, age, diet etc.). Consequently, searching for new biomarkers, and methods of their determination, is still a very important task. One of such promising biomarkers of renal dysfunctions is asymmetric dimethyl arginine (ADMA)¹ as its normal concentration level in blood serum is independent of age, gender, and diet.

The aim of this work was to develop a chemical sensor with molecularly imprinted polymer (MIP) layer as recognition unit for selective determination of ADMA. To develop the ADMA-imprinted polymer, benzoic acid and 18-crown-6-appended bis(bithienyl)methane derivatives were used as functional monomers. Structure of pre-polymerization complex of ADMA with these monomers was optimized with Gaussian 09 software using the B3LYP/6-31G functional and basis set. These calculations indicated formation of a very stable complex with ΔG of −499 kJ/mol. Subsequently, the MIP and NIP films were deposited on Pt disk electrode by electrochemical polymerization in potentiodynamic conditions in the presence of crosslinking monomer. Extraction of template was proved by Surface Enhanced Raman Spectroscopy (SERS) and differential pulse voltammetry (DPV). The response of the devised chemosensor toward the analyte was subsequently tested by using DPV and electrochemical impedance spectroscopy (EIS) as transduction techniques. The sensor showed sensitivity reaching about 52 nA/µM, linear dynamic concentration range 0.3-2.2 µM, and limit of detection of 0.3 µM when DPV was used as transduction technique, while impedimetric sensor exhibited sensitivity of 86.1 Ω/µM, linear dynamic concentration range 0.4-2.2 µM and limit of detection 0.4 µM. This ADMA chemosensor was also found to work in the presence of large excess of interfering compounds indicating its potential use in in-vivo and in-vitro monitoring of ADMA.

Fig. 1. (a) Electrochemical impedance spectra recorded in solutions of 0.1 M K₄[Fe(CN)₆] and 0.1 M K₃[Fe(CN)₆] with different ADMA concentrations at open circuit potential. (b) Calibration plot for MIP and NIP coated electrode with EIS as transduction technique.

Fig. 2. DPV peak current changes in 1 mM K₄[Fe(CN)₆], 0.1 M KNO₃ solution recorded for MIP-coated Pt electrode in (1, 1’) ADMA-containing solution, (2,2’)ADMA-containing solution in the presence of 40 μM arginine, (3,3’)ADMA-containing solution in the presence of 40 μM glucose, and (4,4’) NIP-coated electrode in solution of ADMA. Concentration of ADMA was (a) 0.4 μM and (b) 2.0μM.

This work was partially supported by the Polish National Science Centre grant No. 2014/15/B/ST4/04642.

Results of the present work are published in V Malyshev, et al. ECS J. Solid State Sci. Technol. 2018, 7: Q3189-Q3195 (open access).

1. C. Fleck, F. Schweitzer, E. Karge, M. Busch, G. Stein, Clinica Chimica Acta, 2003, 336: 1-12.