A Comprehensive Review of Advanced Lactate Biosensor Materials, Methods, and Applications in Modern Healthcare

Abstract

Lactate is a key metabolite in cellular respiration, and elevated levels usually indicate tissue hypoxia or metabolic dysregulation. The real-time detection of lactate levels is particularly important in situations such as exercise, shock, severe trauma, and tissue injury. Conventional lactate assays are insufficient to address today's complex and variable testing environments, and thus, there is an urgent need for highly sensitive biosensors. This review article provides an overview of the concept and composition of electrochemical lactate biosensors, as well as their recent advances. Comparisons of popular studies on enzymatic and non-enzymatic lactate sensors, the surface-related materials used for modifications to electrochemical lactate biosensors, and the detection methods commonly used for sensors are discussed separately. In addition, advances in implantable and non-implantable miniaturized lactate sensors are discussed, emphasizing their application for continuous real-time monitoring. Despite their potential, challenges such as non-specific binding, biomaterial interference, and biorecognition element stability issues remain during practical applications. Future research should aim to improve sensor design, biocompatibility, and integration with advanced signal processing techniques. With continued innovation, lactate sensors are expected to revolutionize personalized medicine, helping clinicians to increase treatment efficiency and improve the experience of their use.

Keywords: biosensor; electrochemical; enzyme; lactate; medical.

Figure 4

(A) SEM images of RGO/GCE (a) and AuNPs/RGO/GCE (b) [66]; (B) SEM images of the etched PC nanoporous membrane electrode [69]; (C) SEM images of the epinephrine MIPs SPCE sensor and lactate MIPs SPCE sensor [72]; and (D) SEM images of SPCE/NDG/Gox and SPCE/NDG/GOx/PMM70 [76].

Figure 5

(A) Nyquist response plots (a), fitted Randles circuits (b), and lactate-calibrated dose responses (c) for GO/PANHS/LOD lactate sensor at different lactate concentrations were reported by Lin et al. [77]; (B) amperometric detection response plots (a) and their linear correlation curves (inset) for G-PU-RGO-PB/LOx lactate sensor at different lactate concentrations, amperometric detection response plots (b) and their linear correlation curves (c) for human and artificial sweat, and differential pulse voltammograms (d) including linear calibration curves (inset) at different lactate concentrations, as reported by Khan et al. [83]; (C) cyclic voltammetry response plots obtained by the CV method of AuE/rGO-AgNPs/MIPs lactate sensor for detection between −0.2 and 0.6 V at lactate concentrations ranging from 0 to 250 µM lactate, and their linear correlation plots of the current variations of the anodic (a) and cathodic (b) peaks, as reported by Ben Moussa et al. [86]; and (D) amperogram (a) and calibration plot (b) between versus current response obtained for 0 to 25 mM lactate concentration by LOx/PtNPs/rGO lactate sensor reported by Phamonpon et al. [60].

Figure 6

(A) Schematic illustration of the multiplexed microneedle-based wearable sensor system and its subcomponents reported by Tehrani et al. [95]; (B) overall design of the multiplexed microneedle-based wearable sensor system reported by Zhong et al. [100]; (C) schematics and images of the sensor patch reported by Dai et al. [101]; (D) wearable sweat analysis patch based on SilkNCT reported by He et al. [102]; and (E) osmotic wearable for lactate sensing in sweat for continuous biochemical monitoring reported by Saha et al. [105].

Figure 7

(A) Schematic diagram of OECT sensor. Scheme of the device geometry (a), experimental setup employed for the gate electrode modification (b), processes occurring at the gate electrode, where nitrate reduction induces an increase in OH⁻ concentration, resulting in the precipitation of the LDH/enzyme composite (c) [108]; (B) characterization of core materials for nanozyme–enzyme co-immobilized sensors. (a) High-resolution transmission electron microscopy image of catalytically synthesized Prussian Blue nanozyme. Inset: selected area electron diffraction pattern. (b) High-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM) of the γ-aminopropyltriethoxysilane-perfluorosulfonated ionomer membrane, containing lactate oxidase, Prussian Blue-based nanozyme and carbon black nanoparticles, and (c) energy-dispersive X-ray spectroscopy maps for the same spot, indicating distribution of elements in the sensing layer [109]; and (C) illustration for achieving highly specific nonenzymatic electrochemical sensing by the neural network [111].

Figure 1

Lactate sensors are used for clinical detection.

Figure 2

Schematics illustrating the detection principle of enzyme/non-enzyme lactate sensors.

Figure 3

(A) Schematic diagram of LDH-NAD+/PyrOx biosensor centered on lactate oxidase [49]; (B) schematic illustration of lactate oxidation on the dual active site of bimetallic Ni-based LDHs with various transition metals [44]; (C) schematic illustration of ZIF-67-derived NiCo LDH for lactate detection by wearable biosensors [45]; and (D) schematic preparation of MIPs-AgNW electrochemical biosensors for epidermal monitoring of lactate [46].