A novel triple templates molecularly imprinted biosensor assisted by second-order calibration methods based on generation of second-order hydrodynamic linear sweep voltammetric data for simultaneous biosensing of insulin, proinsulin and C-peptide: Application to comparing PARAFAC2 and PARASIAS

Abstract

In this work, a novel, very sensitive and selective electrochemical biosensor was fabricated based on excellent modification of a thick-film boron doped diamond electrode (TFBDDE) for simultaneous biosensing of insulin (IN), proinsulin (PIN) and C-peptide (CPT). The TFBDDE was modified with multiwalled carbon nanotubes-fullerene C60-graphene-ionic liquid (MWCNTs-C60-GR-IL). Then, IN, PIN and CPT as template molecules were mixed with N-methacryloyl-(L) 3-histidine methyl ester, 2-hydroxyethyl methacrylate and ethylene glycol dimethacrylate, and drop-casted onto the sensor surface for the synthesis of triple templates molecularly imprinted polymers (TTMIPs) by ultraviolet polymerization method. After individual immersion of the biosensor with IN, PIN and CPT, its hydrodynamic linear sweep voltammetric (HLSV) responses were recorded. Immersion of the biosensor in a ternary solution of IN, PIN and CPT generated a single HLSV response which forced us to use multi-way calibration methods for simultaneous determination of IN, PIN and CPT based on generation of second-order HLSV data at different step potentials. Building three-way calibration models by PARAFAC2 and PARASIAS was performed, and the results confirmed superiority of PARASIAS than PARAFAC2 in simultaneous determination of IN, PIN and CPT in the ranges of 1–16 pM, 4–25 pM and 8–88 pM, respectively, in both artificial and real human serum samples. According to the results obtained in this work, the biosensor assisted by PARASIAS can be used as a reliable device for simultaneous determination of IN, PIN and CPT in serum samples.