Molecularly imprinted solid‐phase extraction combined with molecularly imprinted polymer‐sensor: a diagnostic tool applicable to creatine deficiency syndrome

Abstract

Primary creatine deficiency syndromes (CDS) are a new group of disorders caused by guanidinoacetate methyltransferase (GAMT) deficiency, which affects endogenous creatine biosynthesis with depletion of body creatine. A deficiency in creatine can be corrected by treatment with oral creatine supplementation and this necessitates a simple and sensitive screening method for early detection of creatine in dilute physiologic fluids. In this work an artificial receptor, molecularly imprinted polymer (MIP), for creatine was used both as a material for solid-phase extraction (SPE) and as a sensing element in a voltammetric sensor. Using the combination of molecularly imprinted solid-phase extraction (MISPE) with a complementary MIP sensor, the minimum detectable amount was found to be 0.0015 ng mL −1 (RSD = 1.3%, S/N = 3). The MISPE-MIP sensor combination provided up to 60-fold preconcentration, which was more than sufficient for achieving the required quantification limit 50 ng mL −1 (or 0.0025 ng mL −1 after 2 × 10 4 -fold dilution) for creatine in human blood serum.

Proton Transfer Pathways, Energy Landscape, and Kinetics in Creatine–Water Systems

“…The creatine zwitterionic structure is the dominant species at pH 7.3 according to the CHEBI database, 65−68 and through a pH range of 4−12. 10,69 Our simulations therefore correspond to this regime.…”

“…to OH – would be mediated by the water shell, producing a combinatorial number of routes for proton transfer from a specific water complex to OH – . The creatine zwitterionic structure is the dominant species at pH 7.3 according to the CHEBI database, − and through a pH range of 4–12. , Our simulations therefore correspond to this regime.…”

“…It plays a significant role in energy metabolism, and is seen at a depressed concentration in the tissues of patients with severe pathological conditions, such as guanidinoacetate methyltransferase (GAMT) deficiency. 9,10 Furthermore, creatine analogues have proved to be anticancer agents that act synergistically with currently used chemotherapeutics. 11 The purpose of this study is to understand the chemicalexchange process between creatine and water from computer simulation, and especially to investigate the mechanism of proton transfer and the associated kinetics.…”

“…Creatine possesses NH and NH 2 groups, which can exchange protons with water. It plays a significant role in energy metabolism, and is seen at a depressed concentration in the tissues of patients with severe pathological conditions, such as guanidinoacetate methyltransferase (GAMT) deficiency. , Furthermore, creatine analogues have proved to be anticancer agents that act synergistically with currently used chemotherapeutics …”

Electrochemical layer-by-layer modified imprinted sensor based on multi-walled carbon nanotubes and sol–gel materials for sensitive determination of thymidine

“…7B-b) and nonimprinted sol-gel/MWCNTs electrode (Fig. 7B-c) were shown in slope (m) of the linear regression for lower concentration of analyte, using the equation [22]:…”