A Review from a Clinical Perspective: Recent Advances in Biosensors for the Detection of L-Amino Acids

Abstract

The field of biosensors is filled with reports and designs of various sensors, with the vast majority focusing on glucose sensing. However, in addition to glucose, there are many other important analytes that are worth investigating as well. In particular, L-amino acids appear as important diagnostic markers for a number of conditions. However, the progress in L-amino acid detection and the development of biosensors for L-amino acids are still somewhat insufficient. In recent years, the need to determine L-amino acids from clinical samples has risen. More clinical data appear to demonstrate that abnormal concentrations of L-amino acids are related to various clinical conditions such as inherited metabolic disorders, dyslipidemia, type 2 diabetes, muscle damage, etc. However, to this day, the diagnostic potential of L-amino acids is not yet fully established. Most likely, this is because of the difficulties in measuring L-amino acids, especially in human blood. In this review article, we extensively investigate the 'overlooked' L-amino acids. We review typical levels of amino acids present in human blood and broadly survey the importance of L-amino acids in most common conditions which can be monitored or diagnosed from changes in L-amino acids present in human blood. We also provide an overview of recent biosensors for L-amino acid monitoring and their advantages and disadvantages, with some other alternative methods for L-amino acid quantification, and finally we outline future perspectives related to the development of biosensing devices for L-amino acid monitoring.

Keywords: amino acids; biosensors; clinical condition; detection; diagnostics; disease.

Figure 1

A scheme demonstrating the significance of L-amino acids detection and/or monitoring for various medical conditions.

Figure 2

A scheme demonstrating different generations of enzymatic biosensors. (A) The first-generation biosensors are based on electron transfer to the electrode via native intermediate of enzymatic reaction (e.g., H₂O₂). (B) The second-generation biosensors are based on electron transfer to the electrode via a redox active intermediate. (C) The third-generation biosensors are based on direct electron transfer between the enzyme and the electrode.

Figure 3

A schematic diagram displaying the enzyme electrode design for the determination of L- and D-amino acids. E-FAD/E-FADH₂—D/L amino acid oxidase (reduced/oxidized), HRP—horseradish peroxidase, M—mediator (ferrocene). Reprinted from Dominguez et al. [81] with permission from Elsevier.

Figure 4

A schematic diagram demonstrating an enzyme-free sensor for D/L-methionine detection in human serum samples based on AgO modified graphite electrode. Reprinted from Odewunmi et al. [82] with permission from Elsevier.

Figure 5

A schematic diagram displaying (A) the preparation of Cu organic framework and (B) electrode modification procedure and electrochemical Cu redox before/after exposure to histidine. Reprinted from Hua et al. [84] with the permission from Royal Society of Chemistry.

Figure 6

A schematic diagram displaying a capacitance-based biosensor for the detection of total L-amino acids operating in human blood serum. Reprinted from Miškinis et al. [3] according to Creative Commons license (CC-BY 4.0.).