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Review

Advancements and Applications of Single-Atom Nanozymes in Sensing Analysis

by
Huiyun Zhang
1,
Shouting Zhang
1,2,* and
Zhicheng Zhang
1,2
1
Key Laboratory of Organic Integrated Circuit, Ministry of Education & Tianjin Key Laboratory of Molecular Optoelectronic Sciences, Department of Chemistry, School of Science, Tianjin University, Tianjin 300072, China
2
Collaborative Innovation Center of Chemical Science and Engineering, Tianjin 300072, China
*
Author to whom correspondence should be addressed.
Chemosensors 2024, 12(10), 209; https://doi.org/10.3390/chemosensors12100209
Submission received: 3 September 2024 / Revised: 3 October 2024 / Accepted: 11 October 2024 / Published: 12 October 2024
(This article belongs to the Special Issue Nanozyme-Enabled Analytical Chemistry)
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Versions Notes

Abstract

:
Single-atom nanozymes, with their atomically dispersed metal active sites, distinctive atom utilization rate, and tunable electronic structure, demonstrate great promise in the field of sensing analysis. This paper reviews the latest research progress on single-atom nanozymes in sensing applications. We classify single-atom nanozymes based on both their structural characteristics, such as carbon-based carriers, frameworks and their derivatives, metal oxides, metal sulfides, and organic polymer carriers, and their unique catalytic properties, including peroxidase, oxidase, catalase, superoxide dismutase, and multi-enzyme mimetic activities. Furthermore, we discuss the application of single-atom nanozymes in the sensitive detection of biological small molecules, antioxidants, ions, enzyme activities and their inhibitors, as well as cells and viruses. Finally, we highlight the opportunities and challenges for advancing the practical application and further research of single-atom nanozymes in the field of sensing analysis.

1. Introduction

The field of sensing analysis is a critical scientific and technological discipline that focuses on the development of highly sensitive and selective sensors for the detection and analysis of complex biochemical samples [1]. The rapid advancement of nanotechnology has unveiled the distinctive advantages and immense potential of nanomaterials in this domain [2]. Nanozymes, which mimic the catalytic activity of natural enzymes, offer exceptional stability, cost-effective production, and versatile catalytic properties. This simplifies enzyme preparation and promotes their extensive utilization in biosensors, medical diagnostics, and environmental monitoring [3]. Despite significant advancements in nanozyme research, the challenges persist due to the low density of active sites and intricate catalytic mechanisms [4,5]. Consequently, it remains arduous to precisely identify the exact active sites and determine the source of enzyme-like activity, thereby impeding the broader application of conventional nanozymes [6,7]. Therefore, the rational design and development of multifunctional nanozymes with well-defined active sites and high catalytic activity remains a formidable challenge.
In recent years, single-atom nanozymes (SANs) have emerged as a prominent focus in the field of nanozyme research due to their optimized atom utilization, exceptionally high catalytic efficiency, and selectivity [8]. SANs facilitate the precise construction and regulation of nanozyme structures at the atomic level, unveiling potential structure–activity relationships [9,10]. Numerous investigations have demonstrated that reducing particles to the atomic scale introduces unique properties, such as significantly increased surface free energy, quantum size effects, unsaturated coordination environments, and enhanced metal-support interactions [11,12]. The physicochemical properties of SANs not only confer exceptional catalytic performance but also significantly enhance atom utilization rates and reduce production costs, making them highly promising for intricate biochemical sample monitoring and analysis [13,14,15].
This paper aims to present a comprehensive overview of recent advancements in the field of sensing analysis by summarizing the latest research progress on single-atom nanozymes. We present a systematic classification of single-atom nanozymes based on their structural characteristics and catalytic properties, comprehensively investigate their applications in sensing analysis, and explore potential future research directions. The objective is to facilitate the rational design and broader utilization of single-atom nanozymes, thereby expanding their applicability not only in sensing analysis but also in other related fields.

2. Classification of SANs

The applications of single-atom nanozymes in sensing analysis are primarily driven by their unique structure and exceptional catalytic performance. The dispersion of metal active sites at the atomic level on carrier materials significantly enhances the enzyme-mimetic activity of SANs, presenting significant potential for a wide range of sensing applications [16]. Table 1 summarizes the enzyme-like activities of SANs supported by various carrier materials and their corresponding detection performances, including linear range and limit of detection (LOD) for different target analytes. These results highlight the influence of carrier structures on the enzyme-like behaviors and detection capabilities of SANs, providing insights into how carrier materials contribute to the catalytic performance of SANs. In the following sections, we will classify SANs according to their carrier structures and enzyme-mimetic activities, discussing how different carriers influence the catalytic performance and stability of SANs.

2.1. Characteristic Structure

The performance of single-atom nanozymes is significantly influenced by the properties of their carrier materials. These carriers not only provide a stable platform for anchoring single atoms but also contribute to enhancing their catalytic activity and selectivity by tuning the electronic structure and surface chemistry of the single atoms. Researchers have developed single-atom nanozymes employing a diverse array of carrier materials, including carbon-based materials, metal−organic frameworks (MOFs) and their derivatives, metal oxides, sulfides, and organic polymers [29].

2.1.1. Carbon-Based Carrier Materials

Carbon-based carrier materials, such as graphene oxide (GO) and its derivatives, carbon quantum dots (CQDs), carbon nanotubes (CNTs), carbon nanospheres (CNSs), and porous carbon (PC), are extensively utilized to support and augment the functionality of SANs [30,31]. These materials possess attributes such as ultra-high electrical conductivity, large specific surface area, excellent chemical stability, and tunable electronic structures, making them ideal carriers for the development of multifunctional SANs [32]. For example, Wang et al. [33] leveraged the abundant hydroxyl groups on the surface of carbon quantum dots to reduce silver ions (Ag+) to silver nanoparticles (Ag NPs). This process was followed by an amination reaction between amino and carboxyl groups from different CDs, which facilitated the formation of carbon dot shells, culminating in the synthesis of silver carbon dot (Ag CD) nanocomposites with peroxidase-mimicking activity. Similarly, Cheng et al. [19] synthesized iron single-atom nanozymes (CNTs/FeNCs) with ultra-high peroxidase mimetic activity by anchoring Fe atoms onto carbon nanotubes. Furthermore, research has shown that heteroatom doping can fundamentally alter the electronic structure and surface polarity of carbon. Commonly used non-metal dopants encompass nitrogen (N), oxygen (O), sulfur (S), boron (B), and phosphorus (P) [34]. Among these, nitrogen-doped carbon nanomaterials are the most widely documented, largely due to the similar atomic radii of N and C atoms. Additionally, nitrogen atoms exhibit valence electrons capable of forming covalent bonds with carbon, making N an ideal choice for heteroatom doping. For instance, Wu et al. [35] synthesized and characterized a nitrogen-doped carbon-supported copper single-atom nanozyme (Cu SA/NC) synthesized using a template-assisted polymerization strategy. The atomically dispersed Cu active sites on the nitrogen-doped carbon substrate confer specific peroxidase-mimicking activity and excellent photothermal conversion efficiency at room temperature.

2.1.2. Metal−Organic Frameworks and Their Derivatives

Metal−organic frameworks (MOFs) are porous materials comprising metal nodes or clusters coordinated with organic ligands. They provide tunable pore structures, large specific surface areas, uniform active sites, and strong catalytic activity, rendering them highly suitable for functionalization and integration with other catalytic agents, as demonstrated by examples such as ZIF-8, MIL-101, and UiO-66 [36]. SANs based on MOFs fully leverage the benefits of MOF materials, ensuring the stable dispersion of single metal atoms within the MOF matrix, thereby preventing metal agglomeration and enhancing SANs’ catalytic activity and selectivity [37]. Xu et al. [38] designed and synthesized a highly active single-atom nanozyme incorporating a Zn porphyrin structure derived from the ZIF-8 precursor through a mesoporous silicon protection strategy, proving that Zn played a critical role in the nanozyme’s catalytic function. Wu et al. [27] developed a nanozyme with atomically dispersed monoiron sites using the UiO-67 metal–organic framework as a carrier. The electron transfer (ET) process was effectively enhanced through the synergistic action of multiple customized enzyme-like nanocofactors incorporated into this nanozyme, thereby promoting peroxidase-like catalysis. In this system, the linker-coupled atomic Fe site was pivotal in substrate activation, while the bare linker and zirconia node significantly enhanced the efficiency of electron transfer within the intermediate. The synergistic effect of these three nanocofactors increased catalytic efficiency by 4.29-fold compared to metal-site-based nanozymes, achieving an ultra-low detection limit of 0.21 ng mL−1 in the immunoassay of chlorpyrifos.

2.1.3. Metal Oxide Carriers

Common metal oxide carriers, such as alumina (Al2O3), titanium dioxide (TiO2), zinc oxide (ZnO), and cerium dioxide (CeO2), are renowned for their exceptional thermal stability and mechanical robustness [39,40,41,42]. The presence of abundant defects and oxygen vacancies on their surfaces offers optimal adsorption sites for the stable dispersion of single atoms. These sites not only aid in stabilizing single atoms but also act as reactive centers to enhance catalytic efficiency [43]. Yan et al. [44] strategically employed the lattice structure and oxygen vacancy properties of CeO2 (111) to immobilize single-atom Pt, resulting in a unique structural design with excellent multi-enzyme mimetic catalytic activity, offering a novel and effective approach for non-invasive brain trauma treatment. Similarly, Wang et al. [45] developed and synthesized an Ag single-atom nanozyme (Ag-TiO2-SANs) supported on TiO2 with 1.0 wt% Ag loading. Compared to traditional nano-TiO2 and Ag, Ag-TiO2-SANs demonstrated 99.65% adsorption efficacy against the SARS-CoV2 pseudovirus. Following viral binding, the SANs/viral complex is engulfed by macrophages and colocalizes with lysosomes. Additionally, Ag-TiO2-SANs demonstrated significant peroxidase-like activity and generated reactive oxygen species (ROS), with the acidic lysosomal microenvironment promoting the oxygen reduction reaction effectively destroying the virus.

2.1.4. Metal Sulfide Carriers

Metal sulfide carriers, such as cadmium sulfide (CdS) and molybdenum disulfide (MoS2), are distinguished by their expansive specific surface areas and numerous surface-active sites. These features enable their surfaces to optimize the catalytic performance of single atoms by regulating the oxidation states of sulfur atoms and forming various defect structures [46,47]. Li et al. [47] investigated the catalytic efficacy of single-atom palladium nanozymes (CdS-Pd) with CdS as the carrier. Their findings demonstrated that only Pd-s coordination existed in the CdS-Pd nanocatalyst, indicating a strong interaction between CdS and Pd single atoms, which significantly promoted the rapid migration of electrons from the bulk to the surface, thereby enhancing catalytic activity. Huang et al. [48] synthesized an iron single-atom nanozyme (FexMo1−xS2) using MoS2 as the carrier, thereby achieving optimal adsorption energy to enhance the sulfite-activated electron transfer by adjusting the iron content in the material. The Fe and Mo sites in the synthesized FexMo1−xS2 mimic sulfite oxidase activity through the redox cycles of Fe2+/Fe3+ and Mo4+/Mo5+/Mo6+, substantially enhancing the degradation of organic pollutants.

2.1.5. Organic Polymer Carriers

Common organic polymer carriers, such as polydopamine (PDA), polyaniline (PANI), and polypyrrole (PPy), are recognized for their outstanding biocompatibility, large specific surface areas, porous architectures, and ease of chemical modification and functionalization. These properties make them exceptionally effective carriers for single-atom nanozymes [49,50,51]. Li et al. [49] developed a composite of polydopamine nanotubes (PDANTs) and gold nanoparticles (AuNPs) by loading AuNPs onto PDANTs for in situ growth. After high-temperature calcination, the resulting composite (C-PDANTs@AuNPs) demonstrated markedly enhanced peroxidase and oxidase-mimicking activities, attributable to the synergistic interaction between PDANTs and AuNPs, enabling the sensitive detection of glutathione through its oxidase-like activity. Ye et al. [50] synthesized pegylated mesoporous manganese-based single-atom nanozymes (PmMn/SAEs) using a coordination-assisted synthesis strategy with polydopamine. These nanozymes exhibited superior enzymatic activities, with Mn active sites dispersed at the single-atom level. In vitro and in vivo experiments showed that PmMn/SAEs could effectively eradicate cancer cells through photothermally enhanced catalytic therapy. Similarly, Zeng et al. [51] developed a novel nanozyme (CuP) with catalase, peroxidase, and glutathione peroxidase activities using polypyrrole as the carrier. After PEGylation, the resulting CuPP was demonstrated to effectively regulate hypoxia and induce oxidative stress.

2.2. Characteristic Performance

The catalytic functions of single-atom nanozymes closely resemble the catalytic functions of natural enzymes. Based on the type and mechanism of the catalytic reactions, single-atom nanozymes can be categorized into the following types: peroxidase, oxidase, catalase, superoxide dismutase, and multi-enzyme activities.

2.2.1. Peroxidase

Peroxidase (POD) is a peroxidase-mimicking enzyme that utilizes oxidized substrates, such as hydrogen peroxide (H2O2), as electron acceptors to catalyze the oxidation of chromogenic substrates such as 3,3′,5,5′-tetramethylbenzidine (TMB), 2,2′-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS), and o-phenylenediamine (OPD). During this process, the chromogenic substrate loses electrons, which are transferred to H2O2, resulting in the cleavage of the peroxide bond and the generation of hydroxyl radicals (•OH), which are reactive oxygen species with strong oxidizing capacity, facilitating enzymatic reactions [52]. Wang et al. [53] developed a single-atom nanozyme, Ir (III)/GO, which exhibits superior POD-like activity, achieved without the need for nitrogen doping and pyrolysis. This was accomplished through a coordination reaction between an Ir (III) complex and oxygen-containing groups in graphene oxide (GO), with an Ir loading of up to 5.31%. By capitalizing on its remarkable POD-like activity, they created a simple and sensitive colorimetric detection platform for the pesticide PIB, with a linear detection range of 10−300 nM and a limit of detection (LOD) of 2.81 nM. Additionally, this platform was converted into a portable test kit that can detect PIB with an LOD of 3.31 nM, aided by a colorimetric barcode-reading application.

2.2.2. Oxidase

Oxidase (OXD) is an artificial mimetic enzyme that reduces O2 to H2O, H2O2, or O2•− while simultaneously oxidizing various chromogenic substrates, such as TMB, ABTS, and OPD, in the presence of O2 [54]. In contrast to SANs with peroxidase (POD) activity, SANs with OXD activity can catalyze the chromogenic reactions without the need for H2O2. Li et al. [55] synthesized a series of cobalt single-atom catalysts (Co-Nx(C), where x = 2, 3, and 4), each with different nitrogen coordination numbers. The researchers discovered that the OXD-like activity of these single-atom Co catalysts was precisely modulated by adjusting the N-coordination sites. Notably, among the catalysts examined, Co-N3(C) with a triligand N configuration demonstrated the highest OXD-like activity, exceeding the catalytic performance of most reported cobalt-based single-atom nanozymes.

2.2.3. Catalases

Cataloid (CAT) is an artificial mimetic enzyme that catalyzes the decomposition of H2O2 into O2 and H2O through disproportionation reactions [56]. Chen et al. [10] identified promising catalase mimics using DFT theoretical calculations and established a strong correlation between the atomic structure of single-atom nanozymes and their catalase-like properties. They developed a unique hollow carbon polyhedron-supported Co single-atom nanozyme with an optimal Co-N3PS active configuration, which was synthesized through a two-step pyrolysis of MOFs. This study confirmed that the precise atomic-level manipulation of the electronic and geometric structures of single-atom nanozymes is an effective approach to mimicking the catalytic center of natural enzymes.

2.2.4. Superoxide-like Dismutase

Superoxide (SOD) is an artificial mimetic enzyme that catalyzes the disproportionation of superoxide anion radicals (•O2−) into less toxic O2 and H2O molecules [57]. Luo et al. [58] encapsulated monoatomic Mn within a framework of Prussian blue analogues formed on Ti3C2 MXene sheets, using the surfactant PVP. The resulting Mn SANs demonstrated a remarkable loading efficiency of 13.5 wt % (typically <2.0 wt %), exhibiting excellent superoxide anion scavenging capacity, attributed to their SOD-like activity. Furthermore, the Mn SANs demonstrated a synergistic quenching efficiency of up to 98.89% in reactive oxygen species-mediated chemiluminescence (CL) systems, attributed to the broad-spectrum absorption properties of the carrier. This work represents a pioneering effort in demonstrated a synergistic quenching efficiency of up to 98.89%.

2.2.5. Multi-Enzyme-Mimicking Activities

Some single-atom nanozymes possess not only a single enzyme-like activity but also exhibit multiple enzyme-like activities, enabling them to cater to a wider range of applications. Recent research has revealed that many single-atom nanozymes exhibit diverse enzymatic activities [23,59]. For instance, Kim et al. [60] synthesized FeNC-edge structures through H2O2 etching, which created edge sites that significantly enhanced the POD-like and OXD-like activities of the catalyst, achieving 9-fold and 1.3-fold increases in activity compared to single-atom Fe sites at defect sites, respectively. This nanozyme effectively inhibited tumor growth both in vitro and in vivo. Additionally, Liu et al. [61] developed a novel and efficient single-atom nanozyme (Ir-N5 SA) with multiple enzyme-like catalytic activities. The synergistic effect between the central Ir single atom and the axial N-coordination in Ir-N5 SA results in superior catalytic performance relative to Ir-N4. At tumor sites, Ir-N5 SA produces significant levels of ROS through its OXD-like and POD-like catalytic activities. Furthermore, its CAT-like and NADH oxidase-like activities promote the production of O2 and H2O2, enabling efficient nanozyme-catalyzed therapy through a substrate cycling mechanism. This process disrupts the intracellular NADH/NAD+ cycle balance, interfering with the ADH/NAD+ cycle and destabilizing the energy metabolism homeostasis of tumor cells.

3. Application of SANs in Sensing Detection

3.1. Application of SANs in Biomolecules Detection

The accurate detection and monitoring of biomolecule concentration and dynamic changes are pivotal in various domains, including disease diagnosis, treatment assessment, drug development, and metabolic research [62]. For instance, blood glucose levels in diabetic patients, tumor marker concentrations in cancer patients, and cholesterol levels in cardiovascular disease patients are all assessed by measuring biomolecules. Single-atom nanozymes, with their high catalytic efficiency, excellent stability, and ease of functionalization, have emerged as promising tools for biomolecule detection due to their potential for widespread application [63,64]. Chen et al. [65] prepared a single-iron-centered nanozyme (Fe SSN) dispersed on a porous nitrogen-doped carbon surface using a sacrificial template method (Figure 1A). Due to its well-defined Fe-N4 coordination structure and high-density active centers, this nanozyme demonstrated outstanding POD-like activity and stability, activating H2O2 into hydroxyl radicals. In the Fe SSN-GOx-tMB system, it achieved precise colorimetric detection of glucose (linear range of 10−100 × 10−3 M, LOD of 8.2 × 10−6 M), establishing a low-cost integrated agarose-based hydrogel colorimetric biosensor for the visual evaluation and quantitative detection of glucose. Sun et al. [21] developed a Mo-sAN with high POD-like activity (Figure 1B). The unique chelation of oxygen-containing functional groups in glucose with metal atoms facilitated the formation of Mo active sites. DFT studies of its enzyme-mimicking catalytic process revealed that the strong oxygen affinity of Mo favors the formation of *OH, with the desorption of •OH being the rate-determining step. Compared to HRP and other peroxidase materials, Mo-sAN exhibited significant advantages in stability, operational conditions, and catalytic kinetics. On one hand, by leveraging Mo-sAN’s robustness and POD-like activity, a paper-based visual sensing platform integrated with a smartphone was constructed for the real-time visual detection of choline levels in human serum (linear range of 0.5−35 μM, LOD of 0.12 μM). On the other hand, the capability of Mo-sAN to catalyze the efficient generation of •OH from endogenous H2O2 in the tumor microenvironment was also validated.
Furthermore, as hydrogen peroxide (H2O2) is an important signaling molecule and marker of oxidative stress in the body, its detection is essential for monitoring various diseases, including cancer and neurodegenerative disorders. Since the POD-like activity of SANs can catalyze the color change of TMB in the presence of H2O2, the quantitative detection of H2O2 concentration can be achieved by measuring changes in absorbance. Based on this principle, Jiao et al. [66] employed synthesized Fe-N-C single-atom nanozymes for in vitro H2O2 detection and in situ detection of H2O2 in Hela cells (Figure 1C). Compared to single-signal response modes, dual-signal response modes offer higher accuracy and sensitivity. Zhang et al. [67] synthesized Fe-SNC, with POD-like and electrocatalytic activities, using ZIF-8 as a carrier (Figure 1D). When aniline was polymerized by Fe atoms to form polyaniline linked to ZIF-8, the aggregation of Fe atoms during calcination was effectively reduced, exposing more active centers for H2O2 catalysis. They proposed a dual-signal detection strategy, involving both colorimetric (linear range of 3–1000 μM, LOD of 1.3 μM) and electrochemical (linear range of 1–8127 μM, LOD of 0.61 μM) methods, for the real-time monitoring of H2O2.

3.2. Application of SANs in Antioxidant Detection

Antioxidants, as free radical scavengers, can counteract the adverse effects of oxidative stress and are essential for maintaining redox homeostasis in the human body [68]. They can be classified into thiol antioxidants, such as glutathione (GSH), and non-thiol antioxidants, such as ascorbic acid (AA), both of which can prevent the conversion of TMB to ox-tMB in the presence of H2O2. Based on this principle, Tao et al. [69] developed a Cu single-atom nanozyme (Cu-N/C) using ZIF-8 as a carrier, drawing on the multi-Cu atomic sites and Cu2+/Cu+ redox electron transfer pathway found in natural ascorbate oxidase (AAO) (Figure 2A). This nanozyme successfully mimicked the function of natural AAO, exhibiting higher catalytic efficiency and improved stability. It enabled the detection of AA in fluorescence mode based on its AAO activity, as well as the detection of total antioxidant capacity (TAC) in colorimetric mode based on its POD activity. Chen et al. [70], inspired by natural metalloenzyme structures, developed a large-scale biomimetic synthesis method for a porous Fe-N3 single-atom nanozyme (pFeSAN) using hemoglobin as the iron source and template (Figure 2B). The inhibition of atomically dispersed Fe aggregation, along with the removal of hemoglobin (2–3 nm) by heat treatment, facilitated species transport and maximized the exposure of active sites within the resulting mesopores. The unique electronic configuration of Fe-N3 supported the oxygen–water oxidation pathway, similar to that of natural cytochrome c oxidase. The OXD-like activity of pFeSAN was found to be 3.3 times and 8791 times higher than that of Fe-N4 and Fe3O4 nanozymes, respectively. This nanozyme was successfully employed for the rapid colorimetric detection of glutathione (linear range of 50 nM−1 mM, LOD of 2.4 nM), and it has been further developed into a real-time, simple, rapid (approximately 6 min), and accurate visual analysis method for tumor detection based on glutathione levels, showing potential for diagnostic and clinical applications.
In addition, Liu et al. [71] also reported a nitrogen-doped carbon-supported Cu single-atom nanozyme (Cu-sAC) with a Cu loading of 7.98 wt%, which exhibited excellent POD-like catalytic activity (Figure 2C). They developed a colorimetric assay for ascorbic acid (AA) detection with a limit of detection of 0.63 μM, utilizing the inhibitory effect of AA on TMB oxidation. The assay exhibited a clear linear relationship between the relative absorbance intensity (ΔA) and AA concentration (1–30 μM), with a distinct transition in color from deep blue to light blue, indicating high sensitivity at low concentrations. The selectivity of the assay was evaluated using common interfering substances, such as carbohydrates, amino acids, and metal ions (1 mM), which caused negligible changes in absorbance and solution color compared to the control. Conversely, the solution with 50 μM AA showed a significantly faded blue color after 10 min, highlighting a marked difference in response. This pronounced contrast in absorbance and color change between AA and the interferents underscores the high selectivity of the proposed assay, establishing its reliability for AA detection in complex sample matrices. Xi et al. [72] employed a Fe-SA/Ti3C2Tx single-atom nanozyme with POD-like activity as a surface-enhanced Raman scattering (SERS) substrate for TMB oxidation (Figure 2D). This nanozyme showed high catalytic efficiency, as the X-ray absorption fine structure (XAFS) analysis confirmed strong electron transport between the Ti3C2Tx support and Fe atoms via Fe-O-Ti coordination bonds. Density functional theory (DFT) calculations further revealed that the spontaneous dissociation of H2O2 facilitated the formation of hydroxyl radicals (OH•), which are crucial for the TMB oxidation reaction, generating a distinct SERS signal of oxidized TMB (TMB+). Leveraging the blocking effects of free radical reactions, a sensitive SERS sensor array was constructed to simultaneously detect five antioxidants—ascorbic acid (AA), uric acid (UA), glutathione (GSH), melatonin (Mel), and tea polyphenols (TPP). Upon introducing 10 μM of each antioxidant, specific fingerprint SERS spectra were obtained, exhibiting distinct Raman shifts at 1190, 1340, and 1606 cm−1 for each antioxidant. Linear discriminant analysis (LDA) was subsequently applied to evaluate the discriminating power of the developed sensor array. The resulting LDA diagram indicated that the first two discriminant factors accounted for 98.9% of the total variance (factor 1 = 97.3%, factor 2 = 1.6%), and each antioxidant formed distinct clusters with large inter-cluster distances, demonstrating excellent separation and classification accuracy. This principle could attain 100% accuracy in distinguishing when combined with linear discriminant analysis (LDA) and heat map data analysis. A wide detection concentration ranges from 10−8 to 10−3 M for five antioxidants was also achieved.

3.3. Application of SANs in Ions Detection

In recent years, the rapid development of China’s industrial and mining sectors has led to the extensive discharge of industrial wastewater, causing severe environmental pollution. Particularly concerning are the inorganic ions, especially heavy metal ions, in the wastewater, which pose significant risks to human health [73]. Consequently, real-time monitoring of these ions is crucial.
Mao et al. [74] developed SA-fe/NG as peroxidase mimetics by anchoring Fe single atoms onto a monolayer of nitrogen-doped graphene (Figure 3A). This material, featuring 100% atom utilization and an Fe-NC structure, demonstrates exceptional catalytic oxidation activity. By using TMB as a colorimetric sensing probe and 8-hydroxyquinoline (8-hQ) as an inhibitor of TMB oxidation, the detection of Cr (VI) was successfully achieved. This method, with a linear range of 30–3 μM and a limit of detection of 3 nM, was effectively employed to measure Cr (VI) in actual samples, such as tap water and tuna, thanks to the specific interaction between Cr (VI) and 8-hQ that results in the oxidative chromogenic development of TMB. Li et al. [75] synthesized Fe-N/S-C SAzymes using peanut shells, a biological waste product, as sources of carbon, nitrogen, and sulfur (Figure 3B). The sulfur doping introduces geometric and electronic effects, enhancing the OXD-like activity of these SAzymes. They efficiently oxidize colorless TMB to blue oxTMB, while also inhibiting TMB oxidation due to GSH, leading to blue fading. When Hg2+ is introduced, the high affinity between GSH and Hg2+ forms Hg2+-sH, which releases TMB and results in blue color reproduction. This phenomenon enabled the development of a visual colorimetric sensor based on Fe-N/S-C, capable of detecting GSH and Hg2+ simultaneously through various modes, such as the naked eye, ultraviolet−visible spectroscopy, and smartphones. The sensor is user-friendly, suitable for on-site inspections, and does not require sophisticated detection instruments, making it ideal for resource-limited areas. It has been successfully used for analyzing GSH (a linear range of 10–80 μM, a LOD of 3.92 μM) and Hg2+ (a linear range of 1 nM−10 μM, a LOD of 0.17 nM) in real-world samples, proving to be effective for routine laboratory applications. In addition to cation detection, Zhu et al. [76] designed and synthesized a single-atom nanozyme with an FeN5 configuration, which efficiently activates H2O2 by closely mimicking the axial amino acid residues found in natural peroxidases (Figure 3C). This enabled the construction of a UO22+ colorimetric sensing platform in seawater, utilizing the excellent POD-like activity of FeN5–SA, with a LOD of 3.12 ppb. Lang et al. [77] prepared Fe-N-P-C nanozymes from sweet potatoes, a high-yielding crop, which provided abundant active sites with a metal loading of 0.95 wt% (Figure 3D). These nanozymes demonstrated excellent POD-like activity and were used to develop a smartphone-based colorimetric sensor for S2− detection (linear range of 1–800 μM, LOD of 0.23 μM). This sensor successfully quantified S2− in environmental water samples, showing good recovery and reproducibility.

3.4. Detection of Enzyme Activity and Its Inhibitors

Enzymes play crucial roles in various physiological processes in organisms, and many diseases are closely linked to changes in the activity of specific hydrolase enzymes [78,79,80,81,82,83]. Mao et al. [78] developed iron-manganese double-monoatomic nanozymes (FeMn DSA/N-CNTs) with peroxidase (POD)-like activity using nitrogen-doped carbon nanotubes as carriers (Figure 4A). The binmonoatoms in these nanozymes exhibited a lower energy barrier (0.079 eV), and their interaction with N-CNTs was essential for generating oxygen radicals. Acetylcholinesterase (AChE) can hydrolyze thioacetylcholine (ATCh) to thiocholine (TCh), which significantly inhibits the POD-like activity of FeMn DSA/N-CNTs, thereby blocking the catalytic oxidation of TMB to ox-tMB and resulting in decreased absorbance. Consequently, these nanozymes were effectively used for the sensitive colorimetric detection of AChE (linear range of 0.1–30 U L−1, LOD of 0.066 U L−1) and its inhibitor Huperzine A (linear range of 5–500 nM, LOD of 4.17 nM). Chen et al. [79] drew inspiration from the heme site of cytochrome c oxidase (Ccos) and created a single-atom nanozyme with an Fe-N5 coordination by introducing axial N-doping (Figure 4B). This design aimed to bind with O2 to generate an active metal−oxygen intermediate. Hierarchical porous carbon nanoskeletons (Fe SAs/N5-pC-4) with Fe-N5 active centers were prepared through polymerization–pyrolysis–evaporation–etching. The potential enzyme-like mechanisms were explored using experimental and density functional theory calculations. The high metal atom utilization, increased active sites, accelerated mass transfer, excellent hydrophilicity, and electron-driven mechanism of axial N enhanced the OXD-like activity of these nanozymes, achieving a catalytic rate constant (0.398 s−1) that is 569 times greater than that of commercial Pt/C catalysts. The catalytic mechanism mimics that of Ccos, allowing O2 to be converted into reactive oxygen species, thus avoiding the use of H2O2. When AChE hydrolyzes iodide acetylthiocholine (ATChI), it produces small TCh molecules containing sulfhydryl groups, which inhibit the activity of Fe SAs/N5-pC-4 by forming Fe-S bonds, while organophosphorus pesticides (OPs) effectively inhibit AChE activity. A novel AChE/ATChI/Fe SAs/N5-pC-4 biosensor (a linear range of 0.001–20 μg mL−1, a LOD of 0.0006 μg mL−1) was constructed for the indirect determination of OPs.
In addition, Niu et al. [80] reported a Fe-N-C single-atom nanozyme with ZIF-8 as the carrier, which exhibited excellent POD-like activity, with a specific activity of 57.76 U mg−1, nearly comparable to natural horseradish peroxidase (HRP) (Figure 4C). Butyrylcholinesterase (BChE) catalyzes the substrate S-butyrylthiocholine iodide (BTCh) to produce TCh. TCh products, which have reducing properties, inhibit the chromogenic reaction by competing with TMB for oxidation. Thus, the absorbance of the solution decreases with increasing BChE activity, enabling the highly sensitive detection of BChE (a linear range of 0.1−10 U L−1, a LOD of 0.054 U L−1). Su et al. [81] prepared a Co-N-C single-atom nanozyme, which was successfully employed for sensitive colorimetric and fluorescence dual-mode detection of BChE (Figure 4D). The nanozyme’s excellent OXD-like catalytic activity and remarkable stability allowed for the sensitive detection of BChE (a linear range of 0.5−40 U L−1, a LOD of 0.16 U L−1 for colorimetric and 0.21 U L−1 for fluorescence modes). Huang et al. [82] developed a Fe-N-C single-atom nanozyme with OXD-like activity using L-ascorbic acid 2-phosphate (AAP) as the substrate (Figure 4E). This nanozyme catalyzes the hydrolysis of AAP to produce ascorbic acid (AA) in the presence of ALP, triggering an enzyme cascade reaction for the colorimetric detection of ALP (a linear range of 0.05–100 U L−1, a LOD of 0.02 U L−1). Inspired by the ion substitution strategies, Zhou et al. [83] created an Fe/C NS single-atom nanozyme where the “fence” effect of Zn and the stabilization effect of the nitrogen source prevented excessive Fe agglomeration during pyrolysis (Figure 4F). This resulted in Fe/C NS having excellent POD-like activity, capable of catalyzing the decomposition of H2O2 to produce superoxide radicals (O2–•) and singlet oxygen (1O2). ALP can hydrolyze phenyl phosphate disodium (PPDS) to phenol (PO), which, in the presence of ROS, reacts with 4-aminoantipyrine (4-aAP) to form a red product (quinoneimine). Based on this principle, an ALP colorimetric sensor was successfully constructed (a linear range of 0.05−6.00 U L−1, a LOD of 0.03 U L−1).

3.5. Application of SANs in ELISA

The enzyme-linked immunosorbent assay (ELISA) is a biochemical technique used for the detection and quantification of antigens or antibodies that specifically bind to enzyme-labeled antibodies or antigens, which are immobilized on a solid carrier (e.g., microplates) [84,85]. Upon addition of the substrate, the enzyme catalyzes a chromogenic reaction, producing a measurable light signal whose intensity is proportional to the concentration of the target molecule in the sample. The SANs-based ELISA technology is gradually replacing traditional ELISAs due to its high stability, lower production cost, higher sensitivity, and faster reaction rate [22,86,87]. Ding et al. [86] synthesized a novel single-atom nanozyme (Fe-Nx SANs) with 100% atom utilization and superior peroxidase-like activity, achieving a specific activity of up to 64.79 U mg−1 by doping Fe onto polypyrrole (Figure 5A). The Fe-Nx SANs-eLISA platform successfully detected Aβ 1–40, a typical biomarker of Alzheimer’s disease (AD), with a linear range of 1−2000 pg mL−1 and a LOD of 0.88 pg mL−1, showing results significantly better than those of commercial ELISA kits (9.98 pg mL−1). This study confirms that Fe-Nx SANs can serve as a satisfactory alternative to enzyme markers, demonstrating significant potential in ultrasensitive colorimetric immunoassays. Guo et al. [87] employed ZIF-8 as a carrier and incorporated heme to synthesize Fe-N-C SANs with an optimal doping ratio of 5% (Figure 5B). These SANs exhibited substantial affinity for the substrate TMB, demonstrated notable peroxidase-like activity, and achieved the quantitative colorimetric detection of aflatoxin AFB1 in food (a linear range of 0.0084−0.358 ng mL−1, a LOD of 0.0033 ng mL−1), with a short detection time (only 50 min) and high sample recovery. This work presents a viable strategy for the rapid detection of food safety. In addition, as shown in Figure 5C, Yu et al. [22] synthesized Fe0.7/NC SANSs with enhanced OXD-like activity by adjusting the content of metal active sites, achieving a Km value as low as 0.09 mM, and integrated it with an ELISA platform (Fe0.7/NC@PSS-eLISA) to perform the immunosensing detection of capsaicin (CAP) in spicy foods (a linear range of 0.01–1000 ng mL−1, a LOD of 0.046 ng. mL−1).

4. Perspectives and Challenges

Single-atom nanozymes are advancing the frontiers of catalysis and sensing, offering remarkable potential across various fields. One major advantage of SANs is their exceptional catalytic efficiency and specificity, which can be harnessed for a wide range of applications. In sensing, SANs enable highly sensitive and selective detection of biomolecules, pollutants, and environmental toxins. This capability is particularly valuable in fields such as medical diagnostics and environmental monitoring, where precision and reliability are crucial. In terms of development, SANs provide opportunities for innovation in material design and functionalization. By leveraging advanced synthesis techniques and novel support materials, SANs can be tailored to enhance their stability, activity, and compatibility with different substrates. This adaptability facilitates the creation of specialized sensors that are finely tuned to detect specific analytes with high accuracy. Additionally, integrating SANs into sensor platforms allows for the development of portable and user-friendly devices that can operate under various conditions, expanding their applicability to on-site and real-time monitoring.
Despite their promising potential, several critical challenges need to be addressed to fully harness the capabilities of SANs and SAN-based sensors for practical applications. Although numerous synthesis strategies—including mass separation soft landing, one-pot pyrolysis, co-precipitation, impregnation, step reduction, atomic layer deposition (ALD), and organometallic complexation—have been developed to enhance SAN stability, maintaining the uniform dispersion and structural integrity of single atoms under various operational conditions remains a major challenge, particularly at high metal loadings or elevated temperatures. Single atoms are particularly prone to migration and aggregation due to their high surface energy, an issue further exacerbated by environmental fluctuations such as changes in temperature, humidity, and pH. To address these limitations, future research should prioritize the development of more robust stabilization strategies, including self-healing materials and adaptive frameworks, to preserve the integrity of active sites under harsh or fluctuating conditions.
Furthermore, achieving reproducibility in SAN synthesis poses a major challenge. The atomic-level precision necessary to control single-atom configurations is highly susceptible to minor variations in precursor concentration, reaction temperature, and the properties of the support material. Such sensitivity can lead to inconsistencies in atomic distribution and coordination environments, which complicate the transition from laboratory-scale to industrial-scale production. To address this limitation, incorporating real-time monitoring and feedback control systems into the synthesis process could enable the precise regulation of reaction parameters, thereby ensuring reproducibility and consistent quality during scale-up.
Another significant challenge is achieving high sensitivity and selectivity in SAN-based sensors, especially when deployed in complex sample environments. Environmental factors, including competing ions, organic contaminants, and pH fluctuations, can disrupt sensor responses by competing for active sites or altering the local chemical environment around the single atoms. Although strategies such as surface functionalization have been employed to tailor the electronic properties of active sites, these approaches still face limitations under highly complex or fluctuating conditions. Future research should focus on developing multifunctional surface coatings or adaptive nanostructures capable of dynamically adjusting their properties in response to environmental changes, thereby maintaining high selectivity and sensitivity across diverse sample environments.
Finally, the integration of SANs into practical sensing devices must address challenges related to reproducibility, scalability, and long-term stability. Developing robust sensors that can reliably perform across diverse conditions and sample types is crucial for practical applications. This requires refining synthesis methods to achieve high yield and uniformity, while preserving the unique atomic configurations critical for their catalytic performance. In addition, advanced encapsulation techniques can protect active sites from environmental fluctuations, thereby improving the durability of SANs under harsh operational conditions. Continued research into these stabilization and integration strategies is essential for facilitating the large-scale adoption of SAN-based sensors in diverse fields, including environmental monitoring, biomedical diagnostics, and industrial catalysis.

5. Conclusions

Single-atom nanozymes (SANs) represent a transformative advancement in sensing technology, offering unparalleled catalytic efficiency and specificity due to their precisely engineered metal active sites. This review has explored the diverse classifications of SANs based on their structural frameworks and catalytic properties, highlighting their potential across a wide array of sensing applications. From detecting biological molecules and antioxidants to monitoring ions and enzyme activities, SANs have demonstrated exceptional performance in both qualitative and quantitative analyses. In summary, while SANs offer significant promise in advancing sensing technologies, continued research and development are crucial for overcoming existing limitations and unlocking their full potential. The evolving landscape of SAN technology, coupled with advancements in related fields, holds the promise of more effective, sensitive, and versatile sensing solutions in the future.

Author Contributions

Conceptualization, H.Z.; writing—original draft preparation, H.Z.; writing—review and editing, S.Z.; investigation, H.Z.; supervision, S.Z. and Z.Z.; funding acquisition, S.Z. All authors have read and agreed to the published version of the manuscript.

Funding

This research was funded by the Youth Project of the National Natural Science Foundation of China, grant number 22104109.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Not applicable.

Conflicts of Interest

The authors declare no conflicts of interest.

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Figure 1. Application of single-atom nanozymes in the detection of small biological molecules. (A) Schematic diagram of ultra-sensitive detection of glucose by Fe SSN [65]. Copyright: John Wiley and Sons. (B) Synthesis process of Mo-sAN and its application in visual detection of serum choline levels and induction of intracellular ROS production [21]. Copyright: American Chemical Society. (C) H2O2 detection released from Hela cells by Fe-N-C SAzyme [66]. Copyright: American Chemical Society. (D) Schematic diagram of dual-signal detection by Fe-SNC (colorimetric and electrochemical platforms) [67]. Copyright: American Chemical Society.
Figure 1. Application of single-atom nanozymes in the detection of small biological molecules. (A) Schematic diagram of ultra-sensitive detection of glucose by Fe SSN [65]. Copyright: John Wiley and Sons. (B) Synthesis process of Mo-sAN and its application in visual detection of serum choline levels and induction of intracellular ROS production [21]. Copyright: American Chemical Society. (C) H2O2 detection released from Hela cells by Fe-N-C SAzyme [66]. Copyright: American Chemical Society. (D) Schematic diagram of dual-signal detection by Fe-SNC (colorimetric and electrochemical platforms) [67]. Copyright: American Chemical Society.
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Chemosensors 12 00209 g002
Figure 2. Application of single-atom nanozymes in the detection of antioxidants. (A) Cu-N/C enables simultaneous AA detection in fluorescence mode based on its AAO activity and total antioxidant capacity detection in colorimetric mode utilizing its POD activity [69]. Copyright: American Chemical Society. (B) Schematic illustration of the synthesis process and detection effects of pFeSAN [70]. Copyright: Springer Nature. (C) Cu-sAC used for total antioxidant capacity detection [71]. Copyright: American Chemical Society. (D) Fe-SA/Ti3C2Tx enables simultaneous discrimination of multiple antioxidants [72]. Copyright: Springer Nature.
Figure 2. Application of single-atom nanozymes in the detection of antioxidants. (A) Cu-N/C enables simultaneous AA detection in fluorescence mode based on its AAO activity and total antioxidant capacity detection in colorimetric mode utilizing its POD activity [69]. Copyright: American Chemical Society. (B) Schematic illustration of the synthesis process and detection effects of pFeSAN [70]. Copyright: Springer Nature. (C) Cu-sAC used for total antioxidant capacity detection [71]. Copyright: American Chemical Society. (D) Fe-SA/Ti3C2Tx enables simultaneous discrimination of multiple antioxidants [72]. Copyright: Springer Nature.
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Chemosensors 12 00209 g003
Figure 3. Application of single-atom nanozymes in the detection of ions. (A) Scheme of colorimetric detection of Cr (VI) [74]. Copyright: Elsevier. (B) Schematic diagram of colorimetric sensor based on Fe-N/S-C for simultaneous multimode detection of GSH and Hg2+ [75]. Copyright: Elsevier. (C) Schematic diagram of colorimetric sensor based on FeN5–SA for detection of UO22+ in seawater [76]. Copyright: American Chemical Society. (D) Schematic diagram of colorimetric sensor based on Fe-P/N-C for detection of S2− [77]. Copyright: Elsevier.
Figure 3. Application of single-atom nanozymes in the detection of ions. (A) Scheme of colorimetric detection of Cr (VI) [74]. Copyright: Elsevier. (B) Schematic diagram of colorimetric sensor based on Fe-N/S-C for simultaneous multimode detection of GSH and Hg2+ [75]. Copyright: Elsevier. (C) Schematic diagram of colorimetric sensor based on FeN5–SA for detection of UO22+ in seawater [76]. Copyright: American Chemical Society. (D) Schematic diagram of colorimetric sensor based on Fe-P/N-C for detection of S2− [77]. Copyright: Elsevier.
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Chemosensors 12 00209 g004
Figure 4. Application of single-atom nanozymes in the detection of enzyme activity and their inhibitors. (A) Schematic illustration of FeMn DSAs/N-CNTs nanozyme used for colorimetric assays of AChE and its inhibitor [78]. Copyright: American Chemical Society. (B) Schematic diagram of the constructed biosensor for determination of OPs by Fe SAs/N5-pC-4 [79]. Copyright: American Chemical Society. (C) Schematic diagram of a paper-based bioassay integrated with a smartphone for sensing BChE activity [80]. Copyright: Elsevier. (D) Schematic illustration of Co-N-C for BChE biosensing detection [81]. Copyright: Springer Nature. (E) Schematic diagram of Fe-N-C for ALP biosensing detection [82]. Copyright: Elsevier. (F) Schematic diagram of colorimetric and smartphone assays for ALP activity based on Fe/C NS [83]. Copyright: American Chemical Society.
Figure 4. Application of single-atom nanozymes in the detection of enzyme activity and their inhibitors. (A) Schematic illustration of FeMn DSAs/N-CNTs nanozyme used for colorimetric assays of AChE and its inhibitor [78]. Copyright: American Chemical Society. (B) Schematic diagram of the constructed biosensor for determination of OPs by Fe SAs/N5-pC-4 [79]. Copyright: American Chemical Society. (C) Schematic diagram of a paper-based bioassay integrated with a smartphone for sensing BChE activity [80]. Copyright: Elsevier. (D) Schematic illustration of Co-N-C for BChE biosensing detection [81]. Copyright: Springer Nature. (E) Schematic diagram of Fe-N-C for ALP biosensing detection [82]. Copyright: Elsevier. (F) Schematic diagram of colorimetric and smartphone assays for ALP activity based on Fe/C NS [83]. Copyright: American Chemical Society.
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Chemosensors 12 00209 g005
Figure 5. Application of single-atom nanozymes in ELISA bioassays. (A) Schematic illustration of SANS-eLISA for the detection of Aβ 1−40 [86], licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0). Copyright: Science and Technology Review Publishing House. (B) Schematic diagram of Fe-N-C single-atom nanozyme-linked immunosorbent assay for AFB1 detection [87]. Copyright: Elsevier. (C) Schematic illustration of Fe/NC@PSS immunosensor for CAP detection [22]. Copyright: American Chemical Society.
Figure 5. Application of single-atom nanozymes in ELISA bioassays. (A) Schematic illustration of SANS-eLISA for the detection of Aβ 1−40 [86], licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0). Copyright: Science and Technology Review Publishing House. (B) Schematic diagram of Fe-N-C single-atom nanozyme-linked immunosorbent assay for AFB1 detection [87]. Copyright: Elsevier. (C) Schematic illustration of Fe/NC@PSS immunosensor for CAP detection [22]. Copyright: American Chemical Society.
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Table 1. Classification and applications of SANs in sensing (SAN: single-atom nanozyme; LOD: limit of detection).
Table 1. Classification and applications of SANs in sensing (SAN: single-atom nanozyme; LOD: limit of detection).
SANCarrierEnzyme-likeTargetLinear Range (μM)LOD (μM)Ref
FeN/GQDsGQDsPODH2O2
glucose		5–100
1–300		0.78
0.36		[17]
Cu-NS-rGOrGOPODCh
Ach		0.02–0.2
0.02–0.1		2.5 × 10−3
5.0 × 10−3		[18]
CNT/FeNCCNTPODH2O2
glucose
AA		0.1–100
100–1.0 × 104
0.1–10		0.03
20
0.03		[19]
Co-NC/PS@CCCCPODH2O21–17,3280.1687[20]
Mo-SANPCPODCh0.5–350.12[21]
Fe/NCZIF-8PODCAP0.01–1000 ng mL−10.046 ng mL−1[22]
MnSA-N3-CZIF-8POD
OXD
GSHOx		GA
CA
NOR		1.0–70
0.2–15
0.4–18		0.1
0.07
0.05		[23]
CeN4-SAzymeZIF-8PODH2O2
D-glucos
ACh
OPs		100–1.0 × 104
30–2.0 × 103
10–8.0 × 103
1–1000 ng mL−1		77
24
5.3
0.56 ng mL−1		[24]
Co SANsZIF-8POD5-fu0.001–1000 ng mL−12.9 × 10−3[25]
Co-N-CZIF-67OXDGSH
Cys		0.1–40
0.1–20		0.07
0.06		[26]
UiO-67-FeUiO-67PODchlorpyrifos1.67–333.33 ng mL−10.21 ng mL−1[27]
SA Co-MoS2MoS2PODH2O20.05–17,2410.01[28]
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Zhang, H.; Zhang, S.; Zhang, Z. Advancements and Applications of Single-Atom Nanozymes in Sensing Analysis. Chemosensors 2024, 12, 209. https://doi.org/10.3390/chemosensors12100209

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Zhang H, Zhang S, Zhang Z. Advancements and Applications of Single-Atom Nanozymes in Sensing Analysis. Chemosensors. 2024; 12(10):209. https://doi.org/10.3390/chemosensors12100209

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Zhang, Huiyun, Shouting Zhang, and Zhicheng Zhang. 2024. "Advancements and Applications of Single-Atom Nanozymes in Sensing Analysis" Chemosensors 12, no. 10: 209. https://doi.org/10.3390/chemosensors12100209

APA Style

Zhang, H., Zhang, S., & Zhang, Z. (2024). Advancements and Applications of Single-Atom Nanozymes in Sensing Analysis. Chemosensors, 12(10), 209. https://doi.org/10.3390/chemosensors12100209

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