Abstract
Glycine monitoring is gaining importance as a biomarker in clinical analysis due to its involvement in multiple physiological functions, which results in glycine being one of the most analyzed biomolecules for diagnostics. This growing demand requires faster and more reliable, while affordable, analytical methods that can replace the current gold standard for glycine detection, which is based on sample extraction with subsequent use of liquid chromatography or fluorometric kits for its quantification in centralized laboratories. This work discusses electrochemical sensors and biosensors as an alternative option, focusing on their potential application for glycine determination in blood, urine, and cerebrospinal fluid, the three most widely used matrices for glycine analysis with clinical meaning. For electrochemical sensors, voltammetry/amperometry is the preferred readout (10 of the 13 papers collected in this review) and metal-based redox mediator modification is the predominant approach for electrode fabrication (11 of the 13 papers). However, none of the reported electrochemical sensors fulfill the requirements for direct analysis of biological fluids, most of them lacking appropriate selectivity, linear range of response, and/or capability of measuring at physiological conditions. Enhanced selectivity has been recently reported using biosensors (with an enzyme element in the electrode design), although this is still a very incipient approach. Currently, despite the benefits of electrochemistry, only optical biosensors have been successfully reported for glycine detection and, from all the inspected works, it is clear that bioengineering efforts will play a key role in the embellishment of selectivity and storage stability of the sensing element in the sensor.
Highlights
Amino acids (AAs) play a key role in regulating the whole-body metabolism, which is essential for human health, growth, development, and survival [1]
This theory was well proved through isotopic studies that confirmed that glycine turnover occurs during body metabolism, resulting in glycine converting into different compounds and flowing to different body parts [5,6,7]
Glycine analysis for clinical purposes is currently performed at centralized laboratories by means of time and cost consuming methodologies, mainly involving chromatography or fluorometric kits
Summary
Amino acids (AAs) play a key role in regulating the whole-body metabolism, which is essential for human health, growth, development, and survival [1]. Blood-derived fluids rare accessible clinical information regarding human glycine levels. The simultaneous collection (within 2 h) of CSF and plasma is necessary to provide diagnostic information [33,45]: in the collection of CSF, some precaution should be taken to avoid blood contamination, because this will generate erroneous elevation of glycine level in the CSF sample, given the much higher blood glycine range, leading to an invalid result [24]. Blood plasma analysis is currently the preferred assay for clinical glycine detection [25], because it is informative, relatively easy to access, and reproducible [46]. Considering that the combination of different matrix detections is of great significance in clinical applications, an ideal glycine sensing platform should be compatible with a variety of biological fluids
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