1. Introduction 1.1. Overview of luminescent metal-organic frameworks (LMOFs)

Over the past few decades, metal-organic frameworks (MOFs) have risen to prominence in scientific research due to their vast potential across various applications, including gas storage, luminescence, catalysis, and drug delivery [1-8]. MOFs are composed of metal ions or clusters linked with organic ligands to form either two-dimensional (2D) or three-dimensional (3D) frameworks. These structures offer not only structural flexibility and functional diversity but also high porosity, which is a key attribute for their performance in multiple domains [9, 10].

Luminescence, the emission of light following the absorption of energy, is crucial for applications such as sensitive detection and illumination. Luminescent metal-organic frameworks (LMOFs) are a specialized subset of MOFs that, in addition to the general characteristics of MOFs, exhibit unique luminescent properties [11-14]. These properties have made LMOFs a promising material in various fields, especially in luminescent sensing [15]. The framework of LMOFs, constructed from metal ions or clusters connected with organic ligands, can encapsulate guest molecules like lanthanide ions, quantum dots, and organic dyes, which enhance their luminescent performance [16, 17]. This capability is fundamental to the development of multifunctional MOFs-based hybrid materials.

For LMOFs to be effective in luminescent sensing, they must possess strong luminescence, non-toxicity, biodegradability, stability in biological fluids or chemical solutions, and the capacity for post-synthetic modification. However, some LMOFs show instability in aqueous solutions, which can be attributed to the weakening or breaking of hydrogen or coordination bonds between metal ions and water oxygen atoms. The instability of LMOFs in aqueous solution is mainly manifested by structural disintegration, ligand exchange, increased solubility, phase or crystal transformation, and chemical reactions. These problems can lead to the destruction of the frame structure of LMOFs and the significant degradation of material properties, which severely limits their application in aqueous environments. For example, water molecules may attack metal-ligand bonds in LMOFs, triggering a break in the framework or causing the ligand to be replaced by water molecules, thereby altering the original structure [18-20]. The collapse of LMOF is indicated by the gradual disappearance of the diffraction signal in powder X-ray diffraction, additionally, redox and acid-base reactions between water molecules and metal ions within LMOFs may alter the metal ions' coordination environment, further impacting their stability. In order to solve these problems, a series of measures can be taken to improve the stability of LMOFs, including reducing the possibility of water molecules entering the framework by introducing hydrophobic ligands or hydrophobic modifications on the surface of the framework; Select ligands that are insensitive to water molecules or stable in water, such as fluorine-containing ligands; Enhance the stability of the frame structure by crosslinking agents or other methods; Optimizing the synthesis conditions to form a more stable crystal phase; Add waterproof coating to LMOFs surface; Control humidity or avoid direct contact with aqueous solutions during use. Through these strategies, the structural integrity of LMOFs can be effectively maintained, thus extending its application range in wet environments. LMOFs with good biocompatibility and low toxicity usually contain calcium ions (Ca²⁺), magnesium ions (Mg²⁺), zinc ions (Zn²⁺), iron ions (Fe²⁺/Fe³⁺) and titanium ions (Ti⁴⁺). These metal ions are safe in metabolic pathways in living organisms and are widely used in the biomedical field, showing excellent biocompatibility and low toxicity [21-27].

In conclusion, LMOFs, characterized by their distinctive luminescent features and multifunctionality, are gaining attention in scientific research and industrial applications. With an increasing understanding of these materials, it is expected that LMOFs will play an increasingly significant role in the high-tech sectors of the future.

1.2. Advantages of LMOFs in sensing applications

The porous structure of LMOFs has the unique characteristic that the pore sizes can be fine-tuned to selectively trap target analytes. The pore arrangement constrains intermolecular distances, facilitating robust interactions between the MOFs and the luminescent guest molecules, such as organic dyes, quantum dots, and gold nanoparticles [28]. Moreover, LMOFs porosity enhances the adsorption of guest molecules, substantially improving sensor sensitivity and selectivity. We can enlarge the pore size of LMOFs by selecting organic ligands with larger aromatic chains [29]. Structural feature of these ligands is their extended π-electron systems. These systems not only enlarge the ligands themselves but also facilitate the formation of larger pores through π-π stacking interactions between aromatic rings [30-33]. This is because larger aromatic chain ligands have longer molecular structures and greater spatial barrier effects, thus increasing the spacing between ligands and forming larger pores. In addition, the larger aromatic chain ligands can also promote the formation of more complex three-dimensional structures of LMOFs, further expanding the pore size, thereby improving their performance in terms of gas adsorption and drug delivery. Furthermore, this interaction contributes to exceptional luminescent sensing performance during the self-assembly process. In 2022, Zhang's group constructed a flexible ligand, 1, 3, 5-tri(5‑methoxy-1, 3-benzoate)benzene, by connecting three m-phthalates to the benzene ring via a flexible -CH₂–O- bond [34]. The resulting ligands were then combined with Eu³⁺, Tb³⁺, or Gd³⁺ to prepare MOFs, which showed better optical properties for the detection of phosphoric acid. On the other hand, strategically enlarging the pore size in materials can be achieved by intentionally introducing defects during the synthesis phase [35, 36]. In the synthesis process of LMOFs, the intentional introduction of defects can significantly improve their luminous and sensing properties. Defects can enhance luminous efficiency by creating additional optical states in the material or by changing the electronic structure, for example by increasing luminescence quantum yield and luminous stability. In particular, the defect state can improve the excitation and emission mechanism of light, thus optimizing the luminous performance.

In addition, defects can increase the surface active site of LMOFs or adjust their electronic properties, thereby improving the sensitivity and response speed of the sensor. For example, the defect state introduced by manganese ions not only improves the luminous intensity, but also improves the luminescence lifetime and enhances the detection ability of the sensor. At the same time, the defects introduced by ligand deletion can increase the surface active site, thus improving the detection sensitivity of gas molecules. The controlled introduction of such defects can stimulate localized structural rearrangements or distortions, effectively leading to an increase in pore dimensions [37]. In 2019, Huang's team obtained a new defective iron-based MOF, Fe(BDC)(DMF, F)-OA-30 by introducing monocarboxylic acid into the synthesis process [38]. The iron valence state and electrochemical properties before and after degradation revealed that the organic ligand was partially replaced by caprylic acid (OA). By heat treatment and vacuum treatment, defects are formed to generate synergistic unsaturated metal sites and accelerate the original electron transfer, thus enhancing the persulfate activation activity and effectively removing tetrabromobisphenol A (TBBPA). Overall, through defect engineering, researchers can effectively optimize the optical and electronic properties of LMOFs, achieving significant improvements in performance.

Additionally, incorporating photoluminescent entities, including quantum dots and organic dyes, into the nanocavities of MOFs can markedly improve their sensing performance [39, 40]. For instance, a case in point is the integration of CdSe/ZnS quantum dots into the framework of a MOF, which has proven to be highly effective for the recognition of specific metal ions like Cu²⁺ and Pb²⁺ [41-43]. Herein, quantum dots within MOFs serve as energy receptors, with their interaction with metal ions commonly eliciting luminescence [44]. The resultant change in luminescence intensity is determined by the interaction specifics and the MOF's structure. Metal ions can either enhance quantum dot luminescence, possibly acting as luminescence enhancers, or diminish it through surface reactions or competitive light absorption [45-47]. To understand these effects, targeted experiments are essential. Another example is where MOFs loaded with organic dyes can be used for pH sensing, where the absorption and emission of the dye is sensitive to changes in pH. Luminescence enhancement or attenuation depends on the interaction of the dye with the MOF and the effect of pH changes on its structure and properties. The environment provided by MOFs may promote the stability and luminescence efficiency of the dye, resulting in enhanced luminescence. However, changes in pH may lead to structural changes or degradation of the dye, which can affect the luminescence efficiency and lead to reduced luminescence [48, 49]. LMOF's luminescent, chemical, and physical properties can be controlled by various metal centers and organic ligand. In addition, post-synthesis modification (PSM) is a widely-used technique in the field of MOFs, significantly enhancing the capabilities of LMOFs [50]. It has become a key strategy for broadening the applications of MOFs, especially in sensing technologies. PSM methodology involves two primary approaches, the first strategy is the covalent approach which facilitates the targeted interaction between the organic components of the MOFs and specific reagents leading to the incorporation of new functional groups [51, 52]. The second strategy is coordinative method where organic ligands with metal-binding properties are integrated into inorganic structural elements of MOFs known as secondary building units (SBUs). This method also enhances the properties of MOFs through coordination chemistry [53, 54].

PSM plays an important role in improving the application capability of LMOFs biosensing. By chemically or physically modifying LMOFs, PSM can significantly enhance its selectivity and sensitivity to specific biomolecules. For example, the introduction of specific functional groups or biometric elements can improve the recognition capability of the sensor, thus improving the accuracy of the detection.

In addition, PSM can improve the chemical stability and biocompatibility of LMOFs. By modification, LMOFs can better withstand extreme biological environmental conditions, such as changing pH levels or high salt concentrations. This stability enhances the sensor's performance in complex biological samples and expands its range of applications.

The latest research and methods include surface functionalization, nanostructural modification, and smart responsive materials. Surface functionalization technology can introduce various bioactive molecules on the surface of LMOFs to improve its performance. Nanostructured modifications, such as nano-metal particles or quantum dots, further enhance optical and electrochemical properties; Intelligent response materials enable sensors to exhibit different characteristics under specific environmental conditions, improving the accuracy and efficiency of detection.

1.3. Luminescent emission of lanthanide metal-organic frameworks (Ln-MOFs)

Ln-MOFs originates from organic ligands, Lanthanide ions, or guest molecules [55-62]. Ligands with aromatic or π-conjugated backbones play a crucial role in the luminescent emission of MOFs as they can sensitize lanthanide metal ions with fingerprint luminescence emission band which can be utilized to distinguish the lanthanides, comprising the 15 elements from lanthanum (La) to lutetium (Lu) in the periodic table, share similar electronic structures, leading to similar luminescent properties of their ions. Lanthanide ions typically exhibit a + 3 valence [63-69]. However, lanthanide ions may take on a + 2 or +4 valence state under certain conditions. The +2 valence state usually occurs under specific reducing conditions, such as at low redox potential or in contact with a reducing agent. The +4 valence state may occur under oxidation conditions or in contact with an oxidizing agent [70]. The surrounding environment and interactions with ligands often influence these changes. Common lanthanide ions and their luminescent properties include:

- Ce³⁺ (cerium ion): Used in luminescent materials, emitting blue to orange spectra.

- Pr³⁺ (praseodymium ion): Produces red luminescence.

- Nd³⁺ (neodymium ion): Emits red light, utilized in lasers and luminescent materials.

- Sm³⁺ (samarium ion): Emits orange to red light, widely used in luminescent displays.

- Eu³⁺ (europium ion): Emits red and blue light, used in LEDs and luminescent materials.

- Tb³⁺ (terbium ion): Emits green light, employed in phosphors and luminescent displays.

- Er³⁺ (Erbium ion): emits light in the near-infrared region, usually at a wavelength of about 1550 nm, used in optical devices such as fiber amplifiers and lasers.

- Yb³⁺ (ytterbium ion): emits light in the near infrared region, usually at a wavelength of about 980 nm, and is an important doping ion for laser materials and fiber amplifiers.

The Eu and Tb ions of the lanthanides are found in the visible region, where they have a specific electronic structure and energy level jumps that make them exhibit distinct emission spectra in this wavelength range. Such multicolor spectra manifest themselves in the visible region. Emission spectra of europium and terbium are typically characterized by luminescence, a process involving energy level transitions that cause electrons to fall from higher to lower energy levels, emitting photons in the process. Some lanthanide metal ions are weakly luminescent, for example, Sm, Gd are the rare earth elements that do not emissions under common conditions. These two elements are less efficient at emitting light, and the energy is released more through non-radiative processes than in the form of photons. This is because their electronic structures and energy level distributions are not suitable for producing strong emitted light. The characteristics of the electronic structure of these rare earth elements, including the distribution of electrons in the f orbitals, result in an energy level structure that is unsuitable for generating significant, visible light leaps. This means that they usually do not produce significant light emission. In addition, the spectral properties of rare earth elements usually involve the emission of light in a very specific wavelength range [71]. However, MOFs materials based on lanthanide metals are not limited to visible light emission, but also have significant applications in the near infrared (NIR) region. This is because larger aromatic chain ligands have longer molecular structures and greater spatial barrier effects, thus increasing the spacing between ligands and forming larger pores. In addition, the larger aromatic chain ligands can also promote the formation of more complex three-dimensional structures of LMOFs, further expanding the pore size, thereby improving their performance in terms of gas adsorption and drug delivery. In terms of near-infrared luminescence, lanthanide ions such as neodymium (Nd³⁺), erbium (Er³⁺) and ytterbium (Yb³⁺) play a key role due to their unique electronic and energy level structures [72-78]. These near-infrared luminescent MOFs are of great significance in bioimaging and sensing applications, as they can minimize interference from intrinsic luminescence in biological tissues. For example, MOFs doped with Nd³⁺ have demonstrated near-infrared luminescence, enabling deeper tissue penetration in imaging biological samples and reducing interference by spontaneous luminescence [79]. Similarly, MOFs based on Yb³⁺ and Er³⁺ also show near-infrared luminescence properties, helping to enable sensitive detection and imaging of tiny signals in biological systems while reducing the impact of background noise [80-82]. Lanthanide metal MOFs utilizing near-infrared luminescence open new avenues for non-invasive biomedical imaging, biosensing and drug delivery applications, contributing to the development of medical diagnostics and therapies [83, 84].

The luminescence properties of lanthanide metal ions are mainly determined by their unique electronic structure and energy level transition. Lanthanide metal ions have unfilled 4f orbitals, and these 4f electrons are shielded by the outer layer of 5s, 5p and 6s electrons, resulting in their energy levels being less affected by the external environment, and thus have stable luminous properties. Its luminescence mainly comes from 4f-4f transitions, which have low transition probability, long luminescence lifetime and large transition energy level interval due to Laporte prohibition effect, so that the luminescence wavelength covers a wide range from ultraviolet to near-infrared. In metal-organic frameworks (MOFs), ligands can significantly improve the luminous efficiency by absorbing light energy and transferring the energy to lanthanide metal ions (antenna effect). The luminescence wavelength and efficiency of lanthanide metal ions can be regulated by selecting appropriate ligands and frame structures.

However, for individual lanthanide ions, it can be observed that the weak emission which attributed to forbidden f-f transition, low absorption efficiency [85, 86]. To overcome these disadvantage, lanthanide centers can combine with organic ligand to form coordination complexes with organic ligands, these organic molecules act as light absorbers, enhancing emission intensity of lanthanide centers through crystal field effect to decrease the parity degree of 4f-4f transition forbidden (Scheme 1, Scheme 2) [87]. The ligands that contain aromatic or π-conjugated backbones play a particularly crucial role in the luminescence emission of MOFs. This is due to their ability to undergo π-π* transitions, which can be coupled with the metal centers to promote high energy transfer efficiency and further enhance luminescence emission [88, 89].

1.4. Diverse strategies in the design of LMOFs

Compared with typically performed at a later stage of the synthesis process, post-modification offers several significant advantages: (1) Functional modification: Post-modification enables the introduction of diverse functional groups or functionalities into the synthesized product, providing it with specific chemical properties or reactivity. This capability allows for the alteration of molecular hydrophilicity, hydrophobicity, or enhanced affinity towards other molecules or surfaces [90-92] (2) Enhanced stability: Through post-modification, the stability of a synthesized product can be improved, enhancing its resistance to various environmental conditions such as chemical exposure, high temperatures, or oxidative processes [93-95]. This increased stability ensures the product's durability and reliability in practical applications [96, 97]; (3) Surface modification: Surface modification plays a pivotal role in the design of nanomaterials, enabling the precise control of interactions between the material and its environment [98-101]. By tuning the hydrophilic or hydrophobic properties of nanomaterials, their reactivity, solubility, and compatibility with biological systems or other chemical entities can be significantly altered [102, 103]. The process of surface modification involves the introduction or alteration of molecular structures on the surface of nanomaterials. This can be achieved through various techniques such as chemical grafting, plasma treatment, or the formation of self-assembled monolayers [104]. The choice of technique depends on the desired outcomes and the specific characteristics of the nanomaterials. Enhancing the stability of nanomaterials in different media is one of the primary objectives of surface modification [105]. For instance, hydrophobic surface modifications can increase the solubility of nanomaterials in organic solvents, while hydrophilic modifications can improve their dispersion in aqueous environments. This is particularly crucial for applications such as drug delivery, where nanomaterials must remain stable and functional within the complex biological fluids of the body [106-108] (4) Size and shape control: One of the essential advantages of post-modification is its ability to precisely control and adjust the size, shape, and distribution of nanoparticles or nanomaterials. The significance of post-modification lies in its ability to customize and optimize the properties of synthesized products according to specific application needs [109-111]. By fine-tuning the composition, functional groups, stability, surface properties, or size and shape, post-modification empowers scientists and engineers to develop tailored materials that can address key challenges and propel technological advancements [110, 112].

When carrying out post modifications, it is critical to consider a range of factors to ensure successful execution and the achievement of intended outcomes. The selection of suitable reagents or chemicals is pivotal; these must not dissolve or damage the framework of the material in question, and attention should be paid to the reagents' purity and quality. Furthermore, the duration of the post-modification reaction must be regulated to avert any excessive reaction that could occur before the desired level of modification is attained. This reaction time typically requires case-specific optimization. Estimating the pore size of MOFs is a vital step and can be ascertained using methods such as the Brunauer-Emmett-Teller (BET) specific surface area measurements (N₂ and CO₂ adsorption), transmission electron microscopy (TEM), among other characterization techniques. When introducing a guest molecule, care must be taken to ensure that its diameter is smaller than the MOF's pore size to avoid reactions with MOFs. Additionally, guest molecules within the framework can be removed through ion or solvent exchange [113]. Furthermore, it is essential to ensure that the post-modification process is both controlled and reproducible. Thermogravimetric analysis can be utilized to determine the composite ratio.

The application of mixed-metal strategies significantly bolsters the materials' luminescent characteristics, selectivity, and chemical stability, particularly with the integration of lanthanide elements. The unique luminescent colors emitted by various lanthanides enable the design of LMOFs with a diverse range of emission shades, thus paving the way for the creation of multicolor luminescent materials [114, 115]. Specific lanthanide elements, such as europium (Eu) and terbium (Tb), which are well-known for their distinctive electronic transition properties, serve as sensitizers capable of increasing the photoluminescent quantum yield of other metal ions within LMOFs, thereby enhancing the overall luminescent efficiency [116-121]. Luminescent properties of these lanthanides also show promise in the biomedical field, making them applicable for biomarker recognition and image-guided surgical procedures. Consequently, mixed-metal LMOFs incorporating lanthanides have the potential to become powerful tools in biomedicine, possibly increasing the accuracy of diagnostic and therapeutic processes [122].

Moreover, the combination of lanthanide elements with transition metals can lead to the development of multifunctional LMOFs that possess both catalytic activity and luminescent features, thereby expanding their range of applications [123]. The strategic incorporation of lanthanide elements into LMOFs, taking into account their coordination chemistry and interactions with transition metals, allows for the precise modulation of material performance. This approach not only diversifies the luminescent profile of LMOFs but also extends their potential applications in various fields, including environmental sensing and information storage, with a simultaneous consideration for the cost-effectiveness and availability of the lanthanide elements.

Selecting the right ligands is essential in the construction of LMOFs, as this choice greatly affects their structural integrity, porosity, and chemical attributes [124]. Ligands such as 1, 4-benzenedicarboxylic acid and trimesic acid are known to create stable coordination networks with metal cations. Furthermore, polydentate chelating agents like 2, 2′-bipyridine and 4, 4′-bipyridine are particularly effective at forming robust complexes with metal ions, which can lead to LMOFs with customized structures and precisely controlled pore sizes. Nitroxyl-based ligands, including 2-nitroimidazole derivatives and certain amino acids, also play a significant role in establishing coordination bonds with metal ions, which is beneficial for crafting LMOFs with distinctive properties.

In the development of LMOFs with enlarged pores tailored for applications, certain macrocyclic ligands are particularly effective. These include 2, 6-bis(4-pyridylcarbonyl)hexadione (H₂DPOP) and ligands derived from benzodiazepine structures, which contribute to extensive porosity of the frameworks [125, 126]. Carboxylate ligands, distinguished by their carboxylic acid groups such as those found in benzoic acid and phthalic acid, are integral to the formation of LMOFs. They establish stable bonds with lanthanide ions, creating a secure and fundamental structural framework. Moreover, the integration of heterocyclic ligands, such as phenanthroline and imidazoles, during the synthesis process endows LMOFs with unique electronic characteristics and charge-transport properties [127]. Nitrogen-containing ligands, including those derived from 2, 2′-bipyridine and pyridine, are known for their robust coordination with metal ions, which is essential for fine-tuning luminescent properties of LMOFs.

1.5. LMOFs composite material

Encapsulating specific guest molecules within porous structure of MOFs allows for the creation of composite materials with high sensitivity and selectivity, which are highly promising for the luminescence detection of various molecular species [128-134].

Quantum dots (QDs), known for their size-tunable bandgap and high photoluminescence quantum yield, significantly enhance the intensity of the luminescence signal and detection sensitivity when integrated into the MOFs structure. Furthermore, MOF composites, with their efficient energy transfer capabilities, exhibit bright luminescence emission and extended luminescence lifetimes [135]. These characteristics not only broaden the range of detectable luminescence wavelengths but also enhance the selectivity of detection, enabling the simultaneous detection of multiple target substances.

Introduction of luminescent dyes, such as rhodamine or cyanine, which are widely used in biological detection and molecular diagnostics for their high sensitivity and diverse color options, further amplifies the luminescence signal within the MOFs structure, increasing detection sensitivity [136]. The chemical stability and structural adjustability of MOFs provide a protective environment for the dyes, safeguarding them against degradation from external factors such as light, humidity, and temperature. Additionally, the microporous structure of MOFs, combined with the selective modification of luminescent dyes, enhances the adsorption capacity for specific molecules, improving target molecule selectivity and reducing the impact of interfering substances, leading to more precise detection [137, 138]. Composite materials, thoughtfully designed, can offer functionalities beyond luminescence detection, including catalysis and adsorption, thereby expanding their scope in practical applications [139-142].

The combination of MOFs with functional nanomaterials, such as gold nanoparticles or graphene oxide, leverages their localized surface plasmon resonance (LSPR) effects to significantly enhance the luminescence signal of dyes or QDs within the MOFs [143-145]. This enhancement extends the sensitivity and detection range of luminescence assays, making the detection of low-concentration or trace samples more sensitive and reliable. The union of MOFs with functional nanomaterials improves the performance of luminescence detection and endows the material with additional functionalities like catalysis and adsorption, diversifying its potential applications [146-149]. Moreover, the incorporation of functional nanomaterials optimizes the microstructure and surface properties of MOFs, enhancing their selective adsorption and recognition capabilities for target molecules, which improves the selectivity and accuracy of detection. The addition of these nanomaterials also enhances the stability of the composite material, shielding MOFs from environmental factors and ensuring the reliability and durability of detection results [150, 151].

In addition, MOFs can also be combined with metal ions and biomolecules to form composite materials. These can be fabricated into LMOFs membranes using spin-coating or layer-by-layer methods for high-sensitivity and high-selectivity luminescence detection [152]. Biomolecules, such as enzymes, antibodies, or nucleic acids, acting as biological recognition elements, form complexes with MOFs that enable highly selective detection of specific biological molecules, further expanding the application potential of MOFs in the field of luminescence detection.

1.6. Preparation of LMOFs membrane

LMOFs membranes exhibit exceptional potential in the field of luminescence detection, offering several notable advantages over their powdered or solid counterparts. Primarily, LMOFs membranes minimize particle aggregation, maintaining a high utilization rate of active sites, which significantly enhances the sensitivity and efficiency of luminescence detection [153]. Additionally, the membrane form preserves the complete structure of LMOFs, which helps maintain their inherent porous characteristics and chemical composition, avoiding structural damage that can occur during the processing of powders or solids [154].

The membrane form of LMOFs is also more easily integrated into various devices and systems, such as sensors, separators, and optoelectronic devices, simplifying the steps required to combine with existing technologies [155, 156]. They typically exhibit better uniformity and consistency, which is crucial for ensuring the accuracy and repeatability of detection results. Moreover, LMOFs membranes are generally more stable than powdered or solid forms, capable of withstanding harsher operating conditions such as changes in temperature and humidity, thereby extending their service life [157].

In mixed-matrix membranes, high loadings of MOFs contribute to improved separation efficiency and selectivity. Several specialized techniques are employed for the fabrication of these membranes, including the sol-gel method, layer-by-layer deposition, and in situ growth, each approach has its own unique advantages and limitations [158]. The sol-gel method is a wet chemical technique that polymerizes small molecular precursors into nanoparticles by hydrolysis and condensation of metallic alkane oxides or salts to form ordered porous structures. This approach helps to create a material that is uniform and compatible with a variety of substrates and allows for precise control of the composition and porosity of the film. However, this method can require a long gel time and is sensitive to environmental conditions, and the post-treatment steps need to be precisely controlled to prevent the collapse of the porous structure. The layered MOF films were constructed by alternating deposition of positively charged metal ions and negatively charged organic ligands. This method can create a membrane with a well-defined layered structure, with good control and consistency. However, in large-scale production, the layer-by-layer deposition method may be less efficient and the interlayer bonding force may not be sufficient to withstand mechanical stress, which limits its scope of application. In situ growth is the direct growth of MOF films on a substrate, such as a porous support or a functionalized surface. This method ensures a strong bond between the film and the substrate, helping to maintain the structural integrity of the film during use. Nevertheless, the in-situ growth method requires higher pretreatment of the substrate, and the growth conditions must be strictly controlled to prevent defects and inhomogeneity, which makes the thickness and porosity of the film difficult to accurately control.

However, these fabrication methods also have certain limitations. The sol-gel method may require a long gelation time and is sensitive to environmental conditions, with post-treatment steps needing precise control to prevent the collapse of the porous structure. Layer-by-layer deposition may be less efficient for large-scale production, and the interlayer binding force may not be sufficient to withstand mechanical stress. In situ growth requires high substrate pretreatment standards, and growth conditions must be strictly controlled to prevent defects and non-uniformity, which can also make it difficult to precisely control the thickness and porosity of the membrane [159-162].

The sol-gel preparation of LMOFs films faces several challenges, including structural control during gelation and drying, control of film thickness and consistency, and mechanical strength and stability of the films. During gelation and drying, uneven gelation or drying may lead to defects in membrane structure. The film thickness is uneven or does not meet the requirements will affect the performance; During the drying process, the film may become fragile, affecting the mechanical strength and stability.

These challenges can be addressed by optimizing sol-gel formulations, precisely controlling deposition methods (such as spin coating or dip coating), introducing enhancers or modifiers to improve the mechanical strength of the film, and adjusting precursor chemistry and post-treatment steps to precisely regulate the porosity and surface properties of the film. These measures are helpful to improve the uniformity, pore structure, mechanical properties and practical application effect of the film.

In summary, each preparation method has its applicable scenarios and limitations. Sol-gel method is suitable for creating uniform porous structures, but the processing requirements are high. Layer-by-layer deposition method is suitable for finely controlled layered structures, but not suitable for large-scale production. In situ growth method can ensure the structural integrity of the membrane, but it is difficult to control. Depending on the specific application needs and technical requirements, researchers often combine multiple approaches or improve existing techniques to optimize the performance and applicability of LMOFs membranes.

To overcome these challenges, researchers are exploring new synthesis strategies and post-treatment techniques to enhance the performance and applicability of the membranes. Continuous optimization and improvement of existing methods are also key to enhancing the performance of LMOFs membranes [163-165]. By carefully adjusting synthesis parameters such as temperature, time, solvent ratios, and precursor concentrations, the thickness and morphology of the membranes can be precisely controlled. Post-synthesis treatments, including thermal annealing or chemical vapor deposition, are also used to further refine the membranes' physicochemical properties, enhancing the intensity and stability of the luminescence signal, thereby improving the sensitivity and accuracy of detection [166-168].

Highly ordered porous structure of LMOFs membranes enhances the interaction between luminescent probes and target molecules, improving detection sensitivity and selectivity. Direct contact between the MOF membrane and the sample accelerates the reaction rate and increases detection efficiency. Compared to solution-based detection methods, this direct contact approach minimizes the effects of diffusion and dilution, enhancing the accuracy and sensitivity of the detection [169].

Chemical stability and structural controllability of MOF membranes allow them to maintain consistent detection performance under various environmental conditions, ensuring the repeatability of experiments and the reliability of results. Surface modification and functionalization of MOF membranes, through the introduction of specific functional groups, enable highly selective recognition of target molecules, further enhancing the accuracy and sensitivity of luminescence detection [170-173].

In summary, MOFs membranes serve as a platform for luminescence detection by effectively adsorbing and interacting specifically with target molecules [174-177]. These membranes achieve sensitive, rapid, and accurate detection of target molecules by monitoring changes in the emission signal of the luminescent probe. The excellent chemical stability and reproducibility of MOFs membranes provide a solid foundation for reliable luminescence detection [178-182].

1.7. Integrating LMOFs with portable analytical techniques

Portable luminescence detection devices have revolutionized on-site rapid testing, offering significant convenience across various fields. The importance of these devices is highlighted in several key aspects:

Firstly, the portability of these devices eliminates the need for laboratory settings, enabling them to be taken to any location requiring testing, whether it is outdoors, remote areas, or disaster sites [183, 184]. This capability drastically reduces sample analysis time and enhances the response to emergencies, which is crucial for food safety, environmental monitoring, and medical diagnostics. Biosensors based on LMOFs show significant application potential in food safety management. Due to the excellent luminescence characteristics and high specific surface area of LMOFs, these sensors are capable of highly sensitive detection of contaminants or harmful substances in food, such as pesticide residues, heavy metals and pathogens, at low concentrations. They also enable real-time monitoring and rapid response, improving the efficiency and timeliness of food safety testing. In addition, the high selectivity and stability of the LMOFs sensor enables it to handle complex food samples through functionalization and structural adjustment, ensuring the accuracy of the detection results.

However, researchers face several challenges in developing and applying these sensors. First, how to maintain the stability and repeatability of the sensor in complex food samples is a key issue, because interfering substances can affect the detection performance. Second, the synthesis and modification processes of LMOFs are complex and costly, which limits the economics of their large-scale application. The tedious pre-processing steps of food samples also increase the complexity of the analysis, while environmental factors such as temperature and humidity can have an impact on the performance of the sensor. To address these issues, researchers need to develop more economical production methods, optimize sample pretreatment processes, and improve the environmental adaptability of sensors to improve the effectiveness of LMOFs-based biosensors in practical food safety management. For instance, Zhao et al. introduced a portable luminescence sensor based on a zinc-organic framework material, Tb@Zn-TDA-80, which incorporates terbium ions (Tb³⁺) as a dual-emission center for high-sensitivity and selective detection of plant alkaloids (CTS) [185]. The sensor allows for direct visual monitoring of CTS concentration through smartphone scanning, with color changes that exhibit a linear relationship with concentration, suitable for home medication safety monitoring. However, to enhance practical application, the long-term stability and environmental adaptability of such sensors need further improvement, as well as expanding their detection capabilities to a broader range of target molecules.

Secondly, the user-friendliness and intuitive operation interface of portable devices simplify the testing process, reducing the need for professional operators and enabling non-specialists to perform accurate tests easily. This not only increases the accessibility of testing technology but also enhances public scientific literacy. Additionally, the low cost and high efficiency of portable devices make them ideal for resource-limited environments, reducing testing costs and improving economic benefits [186-189]. For example, Wei et al. presented a portable smartphone luminescence detection platform based on a luminescent metal-organic framework (LMOF), enhanced by RecJf exonuclease for ratiometric luminescence detection of arsenic(Ⅲ) ions. Using PCN-224-cDNA as a luminescence quencher and FAM-labeled oligonucleotide probes, the method demonstrated excellent sensitivity and accuracy with a detection limit as low as 0.021 ng/mL. The integration of 3D printing technology and smartphone capabilities provides the potential for rapid on-site testing. Nonetheless, to meet broader field testing needs, the technology should be further improved for environmental stability, cost reduction, user interface optimization, multi-target detection capability expansion, and the development of more precise data analysis tools [190].

In the field of luminescence detection, the application of LMOFs has led to diverse innovations and breakthroughs through integration with modern technologies. These portable devices, being compact and lightweight, integrate specific optical sensors and electronic components that interact with LMOFs membranes, detecting target molecules through changes in luminescence signals, particularly in water quality testing where they demonstrate rapid identification and quantification of pollutants or pathogens in water samples [191-193].

Nano-sensors based on LMOFs leverage their high surface area and tunable pore structure for highly sensitive detection of specific molecules, suitable for integration into microchips for rapid screening of trace harmful substances in the environment or food. Optical biosensors using LMOFs as molecular recognition elements exhibit excellent luminescence properties and biocompatibility, binding specifically to target biomolecules for applications in disease marker detection and biomolecular analysis [194-196].

The combination of microfluidic chip technology and LMOFs provides an efficient detection method, precisely controlling minute volumes of fluids for rapid analysis and screening of biological samples such as cells and proteins. Smartphone applications innovate by transforming smartphones into powerful luminescence detection tools through specific apps and accessories, enabling on-site testing for food safety and environmental pollutants [197, 198].

Furthermore, LMOFs-integrated sensors can be embedded into wearable devices like watches or bracelets, enabling real-time monitoring of health indicators such as heart rate, blood pressure, or blood sugar. Home health monitoring kits allow users to regularly test indoor air quality and drinking water safety with simple, easy-to-use designs. Education and research fields also benefit from LMOFs technology, providing students and researchers with intuitive, interactive learning tools [199-202].

Through these innovative applications, LMOFs have not only promoted the popularization of luminescence detection technology but also provided new tools and methods for scientific research and solving practical problems in various fields. With continuous technological advancements, LMOFs are expected to demonstrate their unique value and potential in an increasingly wider range of applications.

2. Working mechanism of LMOFs-based sensor 2.1. Förster resonance energy transfer (FRET)

Förster Resonance Energy Transfer (FRET) process is a mechanism for energy transfer between two chromophoric entities [203]. This transfer occurs when the donor chromophore and the acceptor chromophore are brought into close proximity, typically within a distance not exceeding 10 nanometers. Upon excitation, the donor, when appropriately stimulated by light of a specific wavelength and in an excited state, can transfer energy to the acceptor through non-radiative dipole-dipole coupling [204-209].

FRET is not limited to luminescence processes; phosphorescence can also participate in FRET under suitable conditions. The luminescence emitted by the acceptor upon excitation of the donor serves as an indicator of successful energy transfer. In FRET systems, the donor typically refers to luminescent molecules or luminescent nanoparticles, while the acceptor refers to molecules capable of absorbing the emission light from the donor, including metal ions, organic ligands, and quantum dots [210].

In the application of LMOFs, the utilization of FRET is particularly ingenious. LMOFs contain luminescent metal centers or organic ligands that can serve as donors, while organic molecules embedded in their nanopores act as acceptors. Such systems enable us to delve into the internal FRET mechanisms of composite materials. Additionally, by introducing luminescent groups, luminescent proteins, or quantum dots into MOFs as luminescent tags, further exploitation of FRET phenomena is possible, provided there is sufficient overlap between the excitation/absorption spectrum of these tags and the emission spectrum of the donor in MOFs [211].

The binding of luminescent proteins to MOFs materials, along with the adjustment of the emission spectrum of these proteins, can facilitate FRET with specific portions of MOFs, thereby endowing them with potential applications in cellular imaging or biosensing. The multifunctionality of FRET is evident in its applications in organic optoelectronics, studies of molecular dynamics, and the understanding of energy transfer phenomena, highlighting its wide applicability in the scientific field [212].

2.2. Photoelectron induced transfer (PET)

Photoinduced electron transfer (PET) system is a luminescence quenching mechanism widely employed in luminescence detection and biosensing fields [213, 214]. This system comprises a receptor (typically an electron-accepting molecule), a spacer unit (linking the receptor and the luminescent label), and a luminescent probe (fluorophore). Under PET, the luminescent probe is excited by light, causing electrons to transition from the highest occupied molecular orbital (HOMO) of the fluorophore (donor) to the receptor molecule, forming an unstable charge transfer state. As this state typically has lower energy, the system rapidly returns to its ground state through non-radiative pathways rather than photon emission, thus suppressing the luminescence of the fluorophore [215, 216].

According to the Frontier Molecular Orbital theory, the working principle of PET luminescent probes can be explained as follows: upon excitation, electrons from the HOMO of the fluorophore can transition to the lowest unoccupied molecular orbital (LUMO). If the HOMO level of the receptor is situated between the HOMO and LUMO levels of the fluorophore, the lone pair electrons on the HOMO of the receptor will transfer to the HOMO of the fluorophore. This process prevents the electrons on the LUMO of the fluorophore from returning to the HOMO, thereby impeding the direct return of the excited-state electrons of the fluorophore to the ground state, resulting in PET effects and luminescence quenching.

These luminescence MOFs act as the fluorophore in PET systems, utilizing guest molecules in the pores as receptors to detect the presence and changes of guests through luminescence variations. When the receptor binds with a guest molecule, if the HOMO level of the receptor is lower than that of the fluorophore, electron transfer is impeded, weakening or eliminating the PET effect, allowing the electrons on the LUMO of the fluorophore to directly transition back to the HOMO, thus restoring luminescence. This change in luminescence serves as a signal for detecting specific molecules and finds important applications in biosensing and environmental monitoring fields.

2.3. Luminescence reverse energy transfer process

Thermally activated energy back transfer (BENT) is a unique mechanism of energy transfer, primarily involving the transfer of energy from a metal to its ligands. The BENT process is highly sensitive to changes in environmental temperature, with elevated temperatures significantly affecting the rates of both forward and backward energy transfer.

Forward energy transfer, wherein energy is transferred from the excited-state donor molecule to the acceptor molecule, typically accelerates with increasing temperature. This acceleration is attributed to heightened molecular vibrations and thermal motion, which increase the collision frequency between the excited-state donor and acceptor molecules. However, there may exist a potential upper limit, beyond which the rate of forward energy transfer may plateau or decline.

As temperature increases, there may be a redistribution of molecular energy levels, with more molecules occupying higher energy states, potentially reducing the efficiency of forward energy transfer. Conversely, for backward energy transfer wherein energy returns from the acceptor molecule to the donor molecule-elevated temperature may enhance molecular vibrations and thermal motion, thereby increasing the rate of backward energy transfer. Furthermore, changes in the distribution of molecular energy states induced by temperature elevation may also impact the efficiency of backward energy transfer.

In 2015, Yan's group synthesized a UiO-type framework material [217], Eu³⁺@UiO-bpydc, and investigated its temperature-dependent photoluminescent properties. The study revealed that the thermal response of Eu³⁺@UiO-bpydc was opposite to that of the ligands and Eu³⁺ions. With increasing temperature, the emission intensity of Eu³⁺ ions significantly decreased, while that of the ligands markedly increased, suggesting a potential energy back transfer from Eu³⁺ cations to ligands at high temperatures. The emission of Eu³⁺ ions remained unchanged with temperature variation, while the emission of UiO-bpydc as a single component decreased with increasing temperature, further confirming the presence of dynamic energy transfer between Eu³⁺ ions and ligands. This energy transfer mechanism is crucial for applications relying on the optical properties of these materials, as understanding and controlling the mechanism of energy transfer can drive the development of sensing and luminescent devices.

2.4. Solvent effect and inner filter effect

Typically, solvent polarity affects the emission spectra of fluorophores, causing spectral shifts. When molecules transition from the ground state to the excited state, an increase in the dielectric constant of the solvent medium leads to a red shift in luminescence emission, resulting in longer emission wavelengths [218]. Conversely, a decrease in the dielectric constant induces a blue shift, shortening the emission wavelengths [219]. Notably, in non-polar solvents, luminescence wavelengths generally blue-shift, whereas in polar solvents, they red-shift. This has significant implications for luminescence detection techniques, as changes in solvent environment or molecular interactions can be inferred by observing spectral shifts.

During the process of transitioning from the ground state to the excited state and back again upon external stimuli (such as photoexcitation), luminescence molecules experience energy loss, known as internal effects. In luminescence sensing, internal effects can alter the generation and intensity of luminescence signals. For instance, receptor-ligand or receptor-target molecule binding may weaken or enhance luminescence signals by altering the molecular environment of the luminescence molecule and affecting the charge transfer between its excited and ground states. Additionally, environmental factors such as solvent polarity, ionic strength, and temperature can influence internal effects. Therefore, understanding and controlling internal effects are crucial for designing and optimizing luminescence sensors to ensure high sensitivity and selectivity for target molecule detection.

Solute interactions can diminish luminescence intensity, a phenomenon referred to as quenching. In the absence of external solute interactions, high local concentrations of luminescent groups may lead to self-quenching or inner filter effects. At higher concentrations, luminescent molecules may aggregate or come into close proximity, facilitating non-radiative energy transfer within clusters, resulting in energy dissipation without luminescence emission. This phenomenon, known as concentration quenching, is particularly noticeable in solutions containing high-density luminescent labels or dyes. Aggregation-induced emission (AIE) is a phenomenon where luminescence enhancement occurs upon aggregation of luminescent molecules. Unlike non-radiative energy transfer, AIE may lead to an increase in luminescence intensity with increasing concentration. Conducting prior UV spectroscopy can help minimize the inner filter effect, typically with an absorbance below 0.1 suggesting a reduced likelihood of this effect. Therefore, preventing inner filter quenching is crucial when constructing and utilizing luminescent probes to ensure the accuracy and robustness of luminescence-based applications.

In order to effectively prevent internal filter quenching (IFE) in luminscent-based LMOFs sensors, several strategies can be adopted. Optimizing the excitation and emission wavelengths is the key. By selecting the wavelength of excitation light source and luminescence probe, avoiding overlapping with the absorption peak of the target molecule, the luminescence signal attenuation caused by internal filtering can be reduced.

In addition, improving the design and structure of the sensor is also an effective strategy. For example, increasing the porosity of LMOFs or adopting a multilayer membrane structure can extend the path of light, improve the detection sensitivity of the signal, and mitigate the impact of internal filtering. At the same time, the implementation of data correction and compensation technology, through the standard curve or controlled experiment to adjust the difference between the actual signal and the theoretical signal, help to improve the accuracy of the sensor. In addition, optimizing the selection of samples and media, using high-transparency media or decreasing the samples' concentration can also reduce the absorption of light by the medium, thereby reducing the quenching effect of the internal filter. By combining these strategies, the performance and reliability of luminescent LMOFs sensors can be significantly improved.

2.5. Hydrogen bonding interactions

To enhance the luminescence properties of materials, scientists often design intricate conjugated π-systems and promote the formation of rigid, planar configurations in organic molecules, which aids in luminescence generation. Among numerous non-covalent intermolecular forces, π-π stacking interactions are prevalent, while hydrogen bonding is a crucial type of non-covalent interaction. For instance, Bai and colleagues synthesized three novel single-crystal luminescent materials based on isophorone: DCDSC, DCDH₃C, and DCDH₄C. These materials exhibit diverse hydrogen bonding interactions, with DCDH₃C (containing a hydroxyl group at position 3) showing a redshift of emission wavelength by 27 nanometers, while DCDH₄C (containing a hydroxyl group at position 4) displays a 45-nanometer redshift. These observations reveal the critical role of hydrogen bonding in modulating the properties of luminescent materials, as hydrogen bond formation may lead to changes in molecular orbital energy levels, thereby influencing the emission wavelength.

In metal-organic frameworks (MOFs), the presence of hydrogen bonding can be detected through various methods:

(1) Crystallographic techniques: Advanced crystallographic methods such as X-ray and neutron diffraction provide detailed information about crystal structure, including atomic positions and bond lengths, thereby revealing the presence, characteristics, and geometric configurations of hydrogen bonds.

(2) Infrared spectroscopy (IR spectroscopy): IR spectroscopy is adept at detecting intermolecular interactions, and by evaluating the IR spectra of MOFs samples, researchers can identify hydrogen bonding interactions and determine their absorption frequencies, thus assessing the nature and strength of bonds.

(3) Nuclear magnetic resonance (NMR) spectroscopy: NMR spectroscopy can reveal molecular structures and interactions, and through NMR, the effects of hydrogen bonding interactions in MOFs can be observed, deepening the understanding of intermolecular interactions.

(4) Raman spectroscopy: The formation of hydrogen bonds causes changes in molecular vibrational frequencies, which manifest as specific peak positions or frequency shifts in Raman spectra, thereby enabling the determination of the presence or absence of hydrogen bonds and providing detailed information about their properties and formation [220, 221].

(5) Influence on molecular properties: The effects of hydrogen bonding on molecular properties such as solubility, stability, and reactivity can indirectly indicate their presence and role in MOFs.

(6) Computational chemistry techniques: Particularly density functional theory (DFT), can simulate molecular structures and interactions in MOFs, including hydrogen bonding situations. By calculating molecular electronic structures and energies, the presence and characteristics of hydrogen bonds can be revealed [222].

By precisely controlling the number and distribution of hydrogen bonds, scientists can effectively tune the emission wavelength of luminescent materials, which is significant for developing novel luminescent materials with specific properties. These materials hold promising applications in various fields such as lighting technology, sensing, and biomedical imaging.

3. Luminescent MOFs as versatile platforms for biosensing applications

In the field of luminescence sensing, the engineering and assembly of MOFs based detection platforms have made significant progress. These innovative platforms are systematically classified based on the properties of the analytes they are designed to detect and the specific applications they serve.

(1) Firstly, there are MOFs designed specifically for biosensing, aimed at detecting key biomolecules including amino acids, carbohydrates, and enzymes. These frameworks have emerged as strong competitors in the field of biosensors due to their outstanding selectivity and enhanced sensitivity. Relevant data is comprehensively presented in Table 1.

(2) Secondly, some MOFs sensors are finely tuned for the identification of biomarkers associated with diseases. These systems are crucial for early detection and continuous monitoring of various health conditions. They are capable of reliably identifying biomarkers associated with malignant tumors and infectious diseases, with specific information recorded in Table 2.

(3) Furthermore, progress has been made in the application of MOFs in drug detection, as described in Table 3. These MOFs exhibit high specificity for various drugs, including antibiotics, and can detect them in various matrices such as urine and milk. Combining MOFs-based sensors with existing detection technologies has brought significant advancements in medical diagnostics and environmental analysis.

Additionally, to better integrate innovative materials with practical applications, MOFs embedded in PVDF membranes are being developed into user-friendly formats, enhancing their practicality in daily clinical, pharmaceutical, and environmental monitoring. To aid in understanding these latest developments, Table 4 provides a compilation of the MOFs ligand-related abbreviations discussed in this paper. This compilation offers a comprehensive perspective on the potential of MOFs to innovate detection methods across multiple fields.

3.1. Detection of amino acids

In the detection of amino acids by LMOF, the strategies to improve the detection sensitivity include: Functional ligands were designed to enhance the specific interaction, metal nanoparticles or quantum dots were doped to increase the active site, the binding ability was improved by surface-modified luminescent probes, the co-assembly strategy was used to bind high-sensitivity materials, the detection environmental conditions were optimized, and signal amplification techniques (such as electrochemical amplification, FRET, SERS) were adopted. Select LMOFs with large specific surface area and high porosity, as well as build responsive sensors. These methods can significantly improve the detection sensitivity and enhance the reliability and accuracy of detection.

Cysteine (Cys) and homocysteine (Hcy) are extensively studied amino acids due to their biological importance. Wu et al. developed an advanced signal amplification method to detect SPARC, a cysteine-rich secreted protein, utilizing a peptide-decorated metal-organic framework (MOF) [223]. This MOF nanocomposite integrates Horseradish Peroxidase (HRP) with ZIF-90, providing a stable matrix for anchoring HRP. A custom-designed peptide within this system exclusively targets SPARC, ensuring high specificity in detection. Upon exposure to acidic environments, rapid release of HRP from the composite triggers a chromogenic reaction, enabling the sensitive detection of SPARC with a limit of detection as low as 30 fg/mL. Fig. 1 illustrates this detection mechanism.

Additionally, trace cysteine in biological cells can be identified by a novel assay combining gold-silver (Au-Ag) nanospheres with the ZIF-8 framework. Cai and colleagues pioneered the formation of luminescent bimetallic Au-Ag nanoclusters through a protein-directed biomineralization process, followed by a desolvation step to generate nanospheres with potent luminescence [224]. Cys specifically quenches the luminescence of these nanospheres, potentially due to the interaction between etched Ag on the Au-Ag nanosphere surface and the nanosphere matrix. A luminescent Cys test strip was fabricated by affixing these luminescent nanospheres onto a strip and subsequently fusing them with ZIF-8. This versatile strip accurately detects Cys across a variety from 0.0032 µmol/L to 32.0 µmol/L in both serum and cellular contexts, demonstrating exceptional sensitivity and specificity. Such detailed detection, even at minimal Cys concentrations, offers opportunities for the early clinical identification of various diseases, including cancers.

Further expanding this field, Yu et al. have successfully synthesized a cutting-edge luminescent probe, UIO-66-NH-BQB, demonstrating a remarkable ability to selectively enhance luminosity in the presence of H₂S or l-Cys [225]. The ultra-low detection limit for H₂S using this probe is around 1.74 µmol/L. With its high selectivity and biocompatibility, UIO-66-NH-BQB presents a promising tool for investigating the pathogenesis of disorders such as diabetes, along with cardiovascular and cerebrovascular diseases. It provided vital and reliable data for clinical diagnosis and management. While these advancements have been proven in laboratory settings and cytotoxicity assays suggest safety for further development, the translation into specific functional devices suitable for widespread clinical use is an ongoing challenge, with significant potential for impacting thiol detection and sensing in vivo.

Li et al. have introduced a novel approach in the detection of cysteine using a terephthalate-linked copper metal-organic framework (CuBDC) [226]. This CuBDC structure offers enhanced mass transfer efficiency and supports a series of reactions involving cysteine and peroxidase within its porous framework, confining the reaction to a localized space. As depicted in Fig. 2, the cysteine sensing mechanism unfolds in the following stages: Initially, when oxygen is present, CuBDC serves as a mimic of cysteine oxidase, catalyzing the oxidation of cysteine into cystine. Concurrently, the H₂O₂ formed demonstrates a high localized concentration within the pores of the CuBDC framework, where it is further catalyzed by enzyme-like constituents intrinsic to CuBDC. These constituents facilitate the conversion of H₂O₂ into hydroxyl radicals. Subsequent to their generation, these hydroxyl radicals promote the disassembly of CuBDC and induce a detectable luminescence emission through the oxidation of the framework's ligands. The CuBDC thus embodies a multifaceted entity, integrating the roles of a peroxidase, a cysteine oxidase, and as a responsive agent in luminescence activation. Through employing this versatile 3-in-1 CuBDC construct, a sophisticated system for cysteine detection has been achieved, characterized by an expansive dynamic range, robust performance, and a flexible paradigm for luminescent sensing. The sensitivity of this system has been honed to detect cysteine levels as low as 0.67 µmol/L. However, the research group has not fully elucidated the underlying mechanisms by which CuBDC achieves such selectivity and sensitivity towards cysteine detection.

Expanding on similar research, Wang et al. synthesized MOF-Eu-pydc through an innovative synthetic method [227]. This creation exhibits a high level of sensitivity and efficiency in detecting cysteine via a novel colorimetric assay, relying on MOFs as enzymatic mimics that catalyze the color-developing substrate, 3, 3′, 5, 5′-tetramethylbenzidine (TMB). Based on the color changes observed in TMB, they have developed a cysteine sensor with a detection threshold of 0.28 µmol/L. The sensitivity of this method positions it as highly advantageous for potential applications in the diagnosis of diseases, alongside benefits such as cost-efficiency, speed, and user-friendliness.

Ma's research collective has developed a core-shell metal-organic framework (referred to as Zr-MOF) using zirconium as the central metal to synthesize the compound SiO₂@50BenzCys [228]. The creation process involves a solvent-assisted ligand exchange technique, enabling the incorporation of mercury-ion binding sites within the material and enhancing its affinity for mercury ions. The team utilized the supernatant derived from SiO₂@50BenzCys for detecting Homocysteine (Hcy), showcasing a rapid response with heightened sensitivity and selectivity specifically for Hcy. Their detection system identified Hcy concentrations as low as 4 nmol/L. Elevated homocysteine levels have been linked to an increased risk of radiation-induced toxicity. Thus, this Zr-MOF structure could potentially function as an effective luminescent sensor, crucial for monitoring during antioxidant therapies. However, further research is necessary to assess its viability for real biomedical applications, including optimizing its efficiency and readiness for deployment in clinical settings to monitor homocysteine as a marker for radiation exposure or other pathological conditions.

Histidine is an essential amino acid with a pivotal role in various biological processes. Aberrant levels of histidine are known to be associated with the risk of neurological disorders. Xiao's research team has crafted a pH-responsive luminescence and colorimetric system by integrating rare earth elements to create a metal-organic framework designated as Eu³⁺@Mn-MOF [229]. This composite was forged using straightforward hydrothermal technique. The framework is characterized by its robust structure and dual-emission luminescent properties. Notably, Eu³⁺@Mn-MOF can change its emitted light's color under acidic and basic conditions, making it a compelling feature in luminous color transformation. The Eu³⁺@Mn-MOF has been envisioned as a viable chemical sensor to measure histidine levels by leveraging its pH-dependent luminescence and color change capabilities. The sensor excels with impressive detection speed, heightened sensitivity, and low detection thresholds. When histidine interacts with the sensor, it induces a luminescent shift from a yellow to a gentle pink hue correlating with histidine concentrations. The enhanced Eu³⁺@Mn-MOF demonstrates substantial potential for both chemical sensing and monitoring health-related biomarkers.

Concurrently, Song's team delved into the synthesis of a luminescent material by embedding Eu³⁺ ions into a bismuth-based metal-organic framework (Eu/Bi-MOF) [230]. Initially, the energy transfer from the framework's ligands to Eu³⁺ ions was restricted during the creation process, establishing a luminescence-quenched system in an aqueous medium. The introduction of histidine reactivated this energy transfer within the Eu/Bi-MOF. As histidine was introduced, the previously quiescent luminescent system was reactivated, leading to the quenching of ligand emission. This enabled the Eu/Bi-MOF to function as a ratiometric luminescent sensor, providing a "trun-on" signal in the presence of histidine. The synthesized sensor exhibits a low detection limit of up to 0.18 µmol/L, high selectivity for histidine, and rapid responsiveness. Additionally, a practical and stable film has been developed, which holds significant promise for clinical and biological analyses. This film provides a prospective tool for diagnosing and monitoring health conditions across various environments. However, it is worth noting that current research lacks simulated testing in real-world scenarios, especially concerning human bodily fluids. Therefore, further validation under physiological conditions is necessary to ascertain the practicality and effectiveness of these novel sensors in real clinical diagnostics.

The synthesis of the microporous metal-organic framework JNU-200, developed by Wu's team, marked a significant advancement in MOF construction through meticulous regulation of pH levels during the reaction process [231]. By incorporating BTTB, an organic emitter known for its aggregation-induced emission traits, the structure utilizes the imidazole groups present in histidine to establish robust coordinative interactions with cobalt ions. This precise coordination promotes displacement within JNU-200 via a competitive coordination-substitution mechanism, making it a potential luminescent sensor with heightened sensitivity to histidine, boasting a lower detection threshold of 0.1 mmol/L. JNU-200 demonstrates exceptional convenience, sensitivity, and rapid detection capabilities due to its unique colorimetric response and luminescence 'turn-on' feature. These attributes make it an efficient platform for histidine monitoring.

Pioneering a new frontier, Yang et al. ensemble engineered a three-dimensional metal-organic framework through a hydrothermal synthesis approach, yielding {[Eu(L)(H₂O)₂]·DMF}_n [232]. As a luminescent probe, this structured MOF exhibits selective detection capabilities for histidine and aspartic acid (Asp). With histidine, the MOF's lower detection limit reaches 10⁻⁴ mol/L when the MOF suspension interacts with this amino acid. In contrast, for aspartic acid, the probe discerns Asp with a detection limit as low as 2.88×10⁻³ mol/L. Remarkably, the MOF's recyclable nature ensures its usability, maintaining efficacy for a minimum of five cycles. Moving beyond fundamental research, the exploitation of MOFs in crafting functional devices remains an avenue less traversed. Enhancements in this domain could catalyze the transition towards more favorable practical applications.

Building on this progress, Ji et al. introduced the Cu/Tb@Zn-MOF, which is ingeniously synthesized by successively encapsulating Cu²⁺ and Tb³⁺ ions within the Zn-MOF matrix [233]. This novel model has established itself as a pioneering 'turn-on' luminescent probe for aspartic acid. Upon association with Asp, Cu²⁺ ions trigger the liberation of the Tb³⁺ luminescent signature, thus utilizing the luminescence traits of the material to identify target molecules. With its 'turn-on' configuration, the MOF not only shows high sensitivity and selectivity towards Asp but also demonstrates rapid detection capabilities with an impressively low detection threshold of 4.132 µmol/L. This innovation further refines analytical methods through an 'open-close-open' model, assimilating implication logic gates to construct a comprehensively advanced analysis paradigm. The MOF's detection prowess for both histidine and aspartic acid is unmatched by existing sensor technologies and its capability to magnify lanthanide luminescence demands further exploration. Delving into the operative mechanisms underlying this distinct augmentation within the lanthanide series could open doors to novel applications and deeper understanding.

Glutamic acid (Glu) plays a pivotal role as an excitatory neurotransmitter within the central nervous system and its elevated levels are implicated in certain neuropathic conditions. To address the sensitive detection of Glu, Fan et al. ingeniously synthesized two distinct three-dimensional cadmium-based metal-organic frameworks (Cd-MOFs), coded as [Cd(L)(bbibp)]_n (1) and [Cd(L)(bbibp)_0.5]_n (2) (Fig. 3) [234]. Both frameworks are characterized by their exceptional selectivity and sensitivity to luminescence quenching by glutamate, demonstrating a robust acid-induced luminescence enhancement effect. When an aqueous solution of glutamate was introduced to these Cd-MOFs, the resulting mix exhibited a notable decrease in luminescence, reaching a low detection threshold of merely 1.03×10⁻⁶ mol/L, displaying their potential applications for Glu monitoring.

On the other hand, Xia et al. has crafted isomorphic microporous rare earth metal-organic frameworks known as ZJU-168, which feature a formula of [(CH₃)₂NH₂]₂[Ln₆(µ₃–OH)₈(BDC–OH)₆(H₂O)₆]·(solv)_x with variations ZJU-168 (Eu) and ZJU-168 (Tb) [235]. These MOFs show selective responses to Glu, with the luminescence signals of the organic ligands increasing upon Glu addition, while the rare earth ion emissions remain comparatively stable. This distinct behavior allows the use of ligand emission as a reliable signal for detection and rare earth ion emission as an internal standard, offering a potential ratiometric luminescence sensor with built-in calibration for Glu. These suspensions exhibit a strong linear relationship between luminescence intensity ratio and glutamate concentration, with detection limits of 3.6 µmol/L for ZJU-168 (Tb) and 4.3 µmol/L for ZJU-168 (Eu), respectively, potentially useful for practical detection of Glu.

Qin's team extended their investigation into chiral recognition by employing l-dibenzoyl tartric acid as a chiral modifier to create zirconium-based MOFs with chiral luminescence properties [236]. Through a solvent-assisted ligand integration method, they synthesized a series of porous coordination networks labeled PCN-128Y. Among these, PCN-128Y-1 and PCN-128Y-2 exhibited highly stable luminescence and unique chiral selectivity towards the enantiomers of glutamine (Gln), attributed to emission induced by hetero-chiral interactions and aggregation. They developed a rapid luminescence detection method for enantiomeric determination of Gln. Using the Stern-Volmer quenching plot, the chiral MOF PCN-128Y-1 demonstrated enantioselective quenching in the presence of d-Gln, with an enantioselectivity ratio of 2.0 at pH 7.0 within just 30 s, further demonstrating its selectivity. The chiral detection achieved impressively low limits, detecting l-Gln and d-Gln at concentrations as low as 3.3 × 10⁻⁴ mol/L and 6.6 × 10⁻⁴ mol/L, respectively. Through these innovative strategies, such MOFs not only offer a pathway for selective detection and quantification of Glu and Gln with chiral precision but also present broad potential applications in clinical diagnostics and neuroscience research, where understanding neurotransmitter levels is crucial.

Tryptophan (Trp) is among the eight essential amino acids crucial for human health, playing a vital role in organisms and biological systems. Improper tryptophan metabolism can result in stress, anxiety, hallucinations, and delusions. Therefore, in food nutrition analysis and disease diagnosis, quantitatively detecting tryptophan holds significant importance. Zhang et al. designed and successfully synthesized a water-stabilized metal-organic framework, ZJU-108, serving as a luminescent activation sensor [237]. This sensor enables the discrimination of tryptophan from other natural amino acids. Given that the singlet level of tryptophan is notably lower than that of other amino acids, a light-emitting sensor was devised utilizing the singlet-singlet Förster resonance energy transfer mechanism. The MOF luminescence sensor selectively detects tryptophan by choosing ligands with appropriate singlet energy levels, as depicted in Fig. 4. Upon immersion in a tryptophan aqueous solution, ZJU-108 exhibited excellent luminescence enhancement effects on tryptophan, with a detection limit of 42.9 nmol/L. However, this set of MOFs has yet to be explored for detecting simulated human serum samples.

Glycine (Gly), known for its simplicity among amino acids, is important not only for enhancing the palatability of foods, making it a common additive in the culinary and feed industries, but also for its use in pharmaceutical formulations. The concentration of glycine in the human body reflects a person's health status. Elevated levels of glycine may disrupt the delicate balance of amino acid absorption, posing a potential risk to metabolic harmony. Given Gly's critical role, developing a detection paltform with superior selectivity, heightened sensitivity, and a minimal detection limit is crucial for safeguarding human health. Wang and colleagues synthesized a novel composite, RhB@ZrT-1-OH, by incorporating Rhodamine B (RhB) into a zirconium-based metal-organic cage [238]. This composite functions as an "on-switch" luminescent probe for glycine detection, leveraging electron transfer and intermolecular hydrogen bonding interactions. Upon interaction with glycine, the probe's luminescence undergoes a notable colorimetric shift from orange to pink, culminating in purple, achieving a detectable concentration as low as 0.3747 µmol/L. While Wang's study marks a significant milestone in glycine detection, elucidating more underlying detection mechanism could be more helpful. Enhancing the transparency of the mechanism would bolster the scientific foundation and reinforce practical applications of this composite as a sensitive biosensor. Integrating the analysis of simulated human serum samples into the research framework would be more advisable which confirm that this sensor can be applied in real conditions. This step would validate the probe's efficacy within a complex biological matrix, underscoring its potential for clinical diagnostics and monitoring human health comprehensively. Such an integrative approach would extend the applicability of RhB@ZrT-1-OH, cementing its position as an invaluable asset in the arena of biochemical sensing and diagnostics.

Amino thiols have been significantly implicated in chronic kidney diseases, however, their urinary concentrations in patients with IgA vasculitis with nephritis (IgAVN) have not been extensively studied. In an effort to address this knowledge gap, Ma's team utilized a novel approach by employing a solvent-assisted ligand exchange technique to create an innovative Zr-MOF composite, named SiO₂@50Benz-Cys. This MOF composite demonstrates exceptional ability to selectively isolate aminothiols from the urine of patients with elevated levels of IgAVN. Leveraging its impressive chelating properties for mercury ions, SiO₂@50Benz-Cys predominantly captures homocysteine (Hcy) and glutathione (GSH), both of which are clinically significant aminothiols. The detection thresholds for Hcy and GSH achieved with this composite were notably low, recorded at 0.5 and 1 nmol/L, respectively. Furthermore, when examining urine samples spiked with known quantities of these compounds, SiO₂@50Benz-Cys exhibited good recovery rates ranging from 79.5%−103% for Hcy and 85.3%−105% for GSH across three varying levels of concentration, attesting to the composite's high accuracy and precision. The application of this testing methodology revealed that Hcy levels in IgAVN patients were elevated compared to those in healthy individuals, indicating a potential biomarker for the disease. In contrast, GSH concentrations observed in the IgAVN patient group were consistently lower than those detected in the control group. This distinct pattern of aminothiol levels could offer new insights into the pathophysiological mechanisms of IgAVN and may inform the development of targeted treatments or management strategies for this kidney disorder. These findings represent a significant advancement in the detection and understanding of aminothiol profiles in renal diseases, particularly offering a new perspective on the biochemical landscape associated with IgAVN. The strategic assembly of SiO₂@50Benz-Cys as an affinity material for Hcy and GSH underscores the potential for this approach to be adapted for broader clinical applications, including early diagnosis, progression monitoring, and possibly the evaluation of therapeutic interventions in chronic kidney diseases.

3.2. Detection of biomarkers

Biomarkers are measurable substances within an organism that serve as critical indicators for assessing the presence of drug metabolites or exogenous toxic chemicals, whose abnormal levels may lead to dysfunction in bodily functions. In the field of medical health, the determination of biomarkers is crucial for predicting diseases, diagnosing conditions, evaluating treatment efficacy, and monitoring disease recurrence, making it a key tool in medical diagnostics. For instance, biomarkers such as serum markers, ascorbic acid, prostate-specific antigen, alpha-fetoprotein, bilirubin, pyridinoline, rhodamine, polycyclic aromatic hydrocarbons, vinyl chloride monomer, and thiodiglycolic acid can be monitored using highly sensitive and selective sensing technologies. Particularly in the context of chronic disease management and chemical exposure, these detection techniques demonstrate their significance.

Biomarker detection technology has far-reaching significance in chronic disease management and chemical exposure monitoring. It not only helps in early diagnosis of chronic diseases and assessment of chemical exposure risks, but also effectively monitors disease progression and treatment effects, supporting the development of individualized medicine and preventive measures. Through the regular detection of biomarkers, doctors can adjust the treatment plan in time to improve the treatment effect, and in the chemical exposure monitoring, the change of biomarkers can reflect the dynamic change of exposure level, helping to develop personalized protective measures. In addition, the data generated by these technologies is critical for public health policy making, providing the scientific basis for assessing the burden of disease, developing intervention strategies and safety standards, thereby reducing the health impact of environmental pollution and chemicals, and improving the overall efficiency and effectiveness of health management.

The definition of biomarkers in the International Chemical Safety Program underscores their importance in interdisciplinary research, as they serve as crucial indicators of the interaction between biological systems and external chemical, physical, and biological factors. With ongoing research, the discovery of new biomarkers continuously enhances our understanding of the pathophysiological processes of diseases and paves the way for personalized medicine. Consequently, there is an urgent need to develop highly sensitive detection technologies capable of accurately identifying and quantifying these biomarkers, which holds significant implications for medical diagnostics and environmental health research in the real world.

The scope of research and application of biomarkers is constantly expanding, encompassing early disease detection, assessment of treatment responses, and monitoring of disease recurrence, among others, further emphasizing their increasingly significant role in medical and environmental health fields. Monitoring biomarkers also involves various biological molecules such as phosphatidylserine, carnitine, and serotonin, which play core roles in diverse biological processes. With the continuous discovery and application of biomarkers, there is a growing demand for advanced engineered sensing systems, indicating the potential for significant breakthroughs in medical diagnostics and environmental health fields in the future.

AFP is one of the most active biomarkers in the clinical diagnosis of liver diseases, being a glycoprotein synthesized by embryonic liver cells. During fetal development, AFP levels in the blood are high, but they rapidly decrease after birth, with AFP levels in adult serum usually being low. The determination of AFP levels is of great significance for the diagnosis of primary liver cancer. Compared to other detection methods, luminescence sensing technology demonstrates higher efficiency and sensitivity in detecting AFP in vivo, while ensuring high selectivity and accuracy. Sheta et al. synthesized a novel metal-organic framework material named Cu-MOF-NPs by reacting organic nano-connectors with copper chloride, and named it for its nanomagnetic properties [239]. Experimental results showed that different concentrations of AFP have varying effects on the photoluminescence intensity of Cu-MOF-NPs, indicating its effectiveness as a biosensor (Fig. 5). However, further exploration of this detection mechanism remains insufficient, requiring future research to clarify.

Ovarian cancer has a higher incidence rate among gynecological malignancies, yet it has the lowest survival rate. This grim reality largely stems from the fact that it is often diagnosed in advanced stages in clinical practice, complicating effective therapeutic interventions. Among numerous phospholipids, lysophosphatidic acid (LPA) is recognized for its simple structure and diverse functional roles in different cellular environments, particularly in promoting tumor cell proliferation. In vivo, a series of genetic alterations, molecular dynamics, and biochemical events lead to an elevation in plasma LPA concentration, which is associated with the pathogenesis of ovarian cancer.

The urgent need for early detection of ovarian cancer has prompted the search for sensitive diagnostic methods to track LPA levels in plasma. In the innovative work by Zhang et al., a luminescence-based method was established [240]. This method utilizes a methanol suspension of mixed crystal Tb/Eu-ZMOFs, capable of selectively and sensitively detecting LPA, with a detection limit as low as 1.4 micromoles. The use of these MOFs marks a leap forward in efforts for early diagnosis of ovarian cancer and offers significant potential for a range of biochemical sensing applications. Despite these advancements, further detailed exploration of the exact mechanism by which LPA is detected by these MOFs is needed to refine and optimize the detection process. These insights reinforce the importance of strengthening research efforts aimed at improving early diagnosis methods for ovarian cancer, which could significantly alter patient treatment outcomes and efficacy.

Prostate cancer (PCa) originates from malignant proliferation of prostate glandular epithelial cells and typically progresses without apparent clinical symptoms. In the detection of PCa, the metabolite sarcosine (SAR) found in human urine has attracted attention as a potential biomarker. Detecting SAR in biological fluids such as urine is crucial for the early diagnosis of prostate cancer. The highlight of this detection process lies in the high selectivity and sensitivity to sarcosine, unaffected by the presence of commonly occurring substances in urine, making it an effective method for analyzing sarcosine levels.

The study by Sun et al. proposes a novel luminescent probe based on Cu²⁺-Tb³⁺-Ga³⁺ heterometallic organic frameworks (MOFs) for detecting sarcosine [241]. This sensor operates in an "open-switch-open" mode, with a rapid response and high specificity and sensitivity to sarcosine. The method cleverly integrates sarcosine-responsive sites into the framework, utilizing Cu²⁺ sites to recognize sarcosine molecules. Cu²⁺-Tb³⁺-Ga³⁺ MOFs exhibit significantly enhanced luminescence intensity in response to sarcosine, with a detection range of 0–1200 micromoles and a detection limit as low as 0.23 micromoles. These lanthanide-based metal-organic frameworks demonstrate potential sensing capabilities applicable to clinical diagnosis and monitoring of prostate cancer. Additionally, the sensor exhibits good pH stability and reproducibility, further facilitating practical detection of sarcosine in bodily fluids.

Another significant advancement by Shen's research team, involves the synthesis of boric acid-modified MOF, MIL-100(Fe)-BA, through a microwave-assisted co-assembly strategy involving metal ligands and fragments [242]. This heteroporous structure, MIL-100(Fe)-BA, exhibits numerous binding sites suitable for enzyme immobilization, minimizing protein leakage and effectively serving as a scaffold for single (such as myosin oxidase) or dual enzymes (e.g., acetylcholinesterase/choline oxidase), guiding multi-enzyme cascade reactions efficiently. MIL-100(Fe)-BA combines the benefits of synthetic and natural nanoenzymes, setting the foundation for a multi-enzyme cascade nanoplatform. It offers impressive cascade activity, robust stability, and enhanced sensitivity for the monitoring of sarcosine or acetylcholine (ACh), with detection limits of 0.26 µmol/L for sarcosine, and 1.18 µmol/L for ACh. Moreover, the MIL-100(Fe)-BA also serves as a bioanalytical tool with inherent oxidase/peroxidase-like activity, suitable for the detection of biomolecules like glutathione and ascorbate, with detection thresholds of 0.12 µmol/L and 0.09 µmol/L, respectively. The research detailed a comprehensive mechanism of action for each detection scenario, along with potential strategies for optimizing the synthesis steps of the testing sample. This level of detail paves the way for simplifying the testing process, ultimately facilitating easier sample preparation for practical application.

Bilirubin (BR) is a primary heme metabolite in humans and is categorized as an endogenous toxin with the potential to cause irrevocable harm to the human brain and nervous system. Despite this, BR possesses antioxidant traits that enable it to thwart the oxidation of substances like phospholipids and linoleic acid. Clinically, assessing BR levels is crucial for evaluating liver health; excessive concentrations of BR are associated with cognitive dysfunction, brain damage, jaundice, and potential liver failure.

Yi's team developed a novel water-stable luminescent probe based on Tb³⁺@MOF-808, crafted via a coordination-driven post-synthetic modification approach [243]. This probe displayed a prominent quenching effect in luminescence upon incremental addition of BR, coupled with a rapid response time, strong specificity, and heightened sensitivity. The luminescence probe had a notably low detection threshold of around 0.026 µmol/L. The Tb³⁺@MOF-808 probe proved its effectiveness by accurately detecting BR levels in human serum and urine, holding promise for the development of portable testing devices for BR, such as diagnostic test papers.

Following a similar pursuit, Du et al. engineered a luminescently tagged MOF, namely UIO-66-PSM [244]. This sensor employs the luminescence resonance energy transfer (FRET) method to detect free bilirubin, a critical biomarker for jaundice. In instances of jaundice, free bilirubin substantially quenches the luminescence emitted by UIO-66-PSM, facilitating the identification of this biomarker. The luminescent probe boasts a broad linear detection range, swift reaction times, and high sensitivity, achieving outstanding selectivity and an exceptionally low detection limit of 0.59 pmol/L for free bilirubin. Moreover, the sensor system is adept at the sensitive tracking of free bilirubin in human serum. A noted limitation of the experiment is the MOF's non-conversion into a functional device for direct bilirubin detection.

Dopamine ranks as a crucial neurotransmitter within the human brain, facilitating essential signal transmission across neurons. Insufficient levels of dopamine in humans can precipitate depression, lack of focus, Alzheimer's disease, schizophrenia, and Parkinson's disease. Conversely, an overproduction of dopamine may lead to hallucinations, delusions, mania, spikes in heart rate, hypertension, and even heart failure. Hence, the precise monitoring of dopamine in various bodily fluids stands as a key measure for the early diagnosis and management of such conditions. Ghosh's team has innovatively devised a biocompatible and water-stable boric acid functionalized aluminum(Ⅲ) MOF [Al(OH)(IPA-B(OH)₂)]·H₂O·0.5DMF [245]. This MOF serves as a luminescence sensor with the capability for highly selective and ultrasensitive detection of dopamine. With an impressive low detection threshold of 3.5 nmol/L (Fig. 6), this material can pinpoint dopamine levels in aqueous solutions or in HEPES buffered environments, maintaining consistent responsiveness in authentic biological samples like human serum and urine. The sensor's substantial potential for clinical dopamine detection applications is thus established. Meanwhile, Pradip Chowdhury has conveyed the remarkable responsiveness of the NH₂−MIL-125(Ti) MOF towards dopamine, displaying a detection limitation down to 10 nmol/L [246]. In another development, Jiajun Sonhas recounted the innovation of an MOF-based transistor, the 2D Cu₃(HHTP)₂ [245]. This device has been adapted to function as a dopamine sensor, requiring only a low operational voltage in the range of tens of millivolts to attain both high selectivity and sensitivity for dopamine, with a detection limit to 100 nmol/L.

As a substance derived from the cyclopentanopoly hydro phenanthrene structure, cholesterol is abundant in animals, especially in brain tissue, and its level deviation can lead to serious health problems, so the establishment of an effective, sensitive and easy-to-operate cholesterol quantification method is critical to the maintenance of public health. The research team led by Hassanzadeh developed a refined probe that applies a ChOx-MOF and a pseudo-peroxidase AgNC/MoS₂NS for cholesterol sensing, after enzymatic oxidation of cholesterol using encapsulated ChOx in MOFs, the generated H₂O₂ is used to oxidize terephthalic acid in the presence of AgNC/MoS₂–NS nanocomposites, yielding an impressive detection performance with a threshold of 0.03 µmol/L [247]. Despite these results, the experiment would benefit from an expanded investigation into the underlying detection mechanism. Moving forward, Zhao et al. employed a water-stable MOF featuring a high surface area and voluminous cavities, known specifically as PCN-333 (Al), capturing cholesterol oxidase (ChOx) and encapsulating horseradish peroxidase (HRP) to generate a colorimetric biosensor [248]. This biosensor was crafted harnessing the cascading catalytic reactions from the tandem enzymes, and it presents a reduced detection limit of 0.6 µmol/L. Lastly, Yao et al. elected europium to be the dopant and integrated it within the MIL-53 (Fe) structure [249]. The inclusion of Eu³⁺ ions into the MIL-53 (Fe) matrix substantively advanced the response sensitivity, diminishing the detectable limit to 0.33 mmol/L. Regardless, these studies indicate a residual need to delve into further functional device optimization for cholesterol detection.

Metallothionein, a protein capable of binding metal ions, is present across various forms of life. The investigative team led by Sha has engineered a colorimetric bioassay platform that employs His-MIL-101 for the precise quantification of metallothionein [250]. This approach takes advantage of the dual-action mechanism wherein metallothionein simultaneously affects metal active site obstruction and the quenching of free radicals. As a result, this interaction facilitates a sensitive detection of the protein, boasting a lower detection limit that has been recorded at 10.49 nm, which is detailed in Fig. 7 of their publication. The innovation demonstrated by this approach lies in the application of His-MIL-101, a metal-organic framework noted for its high affinity towards metal ions, which allows for a selective and potent interaction with metallothionein. This sensitivity is not only indicative of the potential of His-MIL-101 in bioassays but also highlights the effectiveness of leveraging biological molecules in concert with engineered materials for enhanced detection capabilities.

Diabetes, a prevalent global health issue, has catalyzed significant research efforts aimed at advancing glucose monitoring technologies. Amidst the myriad of detection devices on the market and within research, the operational principle for most is predicated on tracking the activity of glucose oxidase (GOD), a widely accepted standard for glucose measurements. However, these devices often encounter limitations due to the inherent fragility of the GOD enzyme, which has prompted continued investigation into GOD-based glucose sensing systems [251, 252].

In pursuit of more robust alternatives, the research team led by Lin put forth a novel approach involving a spheroidal metal-organic framework, GOD@Cu hemin MOFs, which functions as a dual-enzyme (bi-enzyme) catalyst. They devised an Aga/GOD@Cu-hemin MOF/TMB sensor, seamlessly incorporated within an agarose hydrogel membrane, for the purpose of colorimetric glucose quantification. This sensor demonstrated a remarkable sensitivity with a detection threshold set at 0.01 mmol/L. Complementarily, Ortiz-Gomez presented a distinct glucose assay methodology grounded in the use of the Fe-MIL-101 MOF. This particular assay boasts exceptional sensitivity, suitable for measuring glucose levels in biological fluids such as serum and urine, reaching detection limits as low as 2.5 µmol/L. Both advancements reflect the dynamic nature of glucose detection research, where innovative material science applications, such as metal-organic frameworks, are reshaping the landscape of diabetes management by enabling more accurate and sensitive monitoring solutions.

Carcinoid tumors, a subset of neuroendocrine tumors, are a rarity and grow at a slow pace. They originate from chromaffin cells and can affect various organs. Of all the biomarkers, serotonin (5-hydroxytryptamine, HT), a central nervous system neurotransmitter, stands out for its distinctiveness in detecting carcinoids efficiently. Its crucial role extends beyond clinical medicine and into numerous biological processes. The accurate and sensitive quantification of HT is particularly pivotal in a clinical setting, especially for carcinoids that produce this compound at low rates. Moreover, urinary levels of 5-hydroxyindole-3-acetic acid (HIAA), a principal metabolite of HT, are known to surge when released from carcinoid tumors. This makes both HT and HIAA significant in vivo indicators of carcinoids, aiding in the plasma detection of HT and urinary detection of HIAA. These measures are instrumental for the early diagnosis of the tumor and for the surveillance of patients with carcinoid syndrome. Building on these insights, Wu et al. has engineered a cutting-edge luminescent sensor utilizing a Eu-MOF. This sensor relies on a water-stable lanthanide metal-organic framework, tailored to quantitatively assess levels of HT and HIAA. The research findings underscore that the sensor experiences pronounced luminescence quenching upon the introduction of HT and HIAA. Furthermore, the Eu-MOF sensor exhibits remarkable sensitivity. The detection threshold is impressively low, registering at 0.54 µmol/L for HT and 6.6 × 10⁻⁷ mol/L for HIAA, highlighting its potential for clinical applications in monitoring neuroendocrine tumor markers.

3.3. Detection of pharmaceuticals

Medications, chemical compounds developed for the prevention and treatment of diseases, play a crucial role in the field of medicine. LMOFs can be used to detect a variety of drugs, including antibiotics, anticancer drugs, cardiovascular drugs, and central nervous system drugs.

The application of LMOFs is particularly critical in antibiotic detection. The widespread and high-dose use of antibiotics in animal husbandry has promoted the emergence of antibiotic-resistant strains, posing a serious threat to human health [253, 254]. The misuse of antibiotics in agriculture not only exacerbates the proliferation of resistant bacteria but also leads to the widespread presence of these drugs in meat and other animal products, increasing the risk of antibiotic intake through the food chain. Therefore, the development of efficient antibiotic detection platforms is crucial for controlling the spread of resistance and protecting public health. The high selectivity and sensitivity of LMOFs make them ideal tools for detecting antibiotic residues. By designing specific functional ligands, LMOFs sensors can specifically identify β-lactams, aminoglycosides, tetracyclines, and other classes of antibiotics. These sensors can accurately detect antibiotic residues in meat, dairy products, and other foods, as well as detect extremely low concentrations of drugs in clinical samples, thereby enhancing food safety and the accuracy of clinical medication.

LMOFs also have tremendous potential in detecting other drugs. In the detection of anticancer drugs, LMOFs sensors can identify and quantify chemotherapy drugs, which are crucial for assessing cancer treatment efficacy and drug metabolism research. In the field of cardiovascular drugs, LMOFs sensors can detect drugs used to treat hypertension, heart disease, and other conditions, assisting physicians in more accurate drug management. Furthermore, LMOFs technology has unique advantages in detecting illegal drugs and stimulants. Customized LMOFs sensors provide customs and anti-doping agencies with rapid and accurate detection methods, helping to combat illegal drug trafficking and safeguard the fairness of sports competitions.

In conclusion, the application prospects of LMOFs in drug detection are very broad. Their high customizability and excellent detection performance provide extensive possibilities for developing new detection platforms. With further research, LMOFs are expected to play a more critical role in ensuring drug safety, promoting personalized medicine, and enhancing disease treatment efficacy.

Xie et al. developed luminescent sensor arrays constructed from metal-organic frameworks (MOFs) dually doped with europium (Eu³⁺) and terbium (Tb³⁺). These specialized MOFs demonstrated varying luminescent intensity ratios (F₅₄₅/F₆₁₆) at wavelengths of 545 nm and 616 nm in response to different stimuli. Such variations were successfully differentiated through the application of principal component analysis (PCA) [255]. PCA is a widely used method for reducing data dimensionality and extracting key features. It aims to convert original datasets into a new coordinate system of orthogonally aligned variables called principal components through a linear transformation process. This selection process is predicated on the data's variance, aiming to retain the most significant information by choosing components with the greatest variance. PCA method can condense data to its core, minimizing dimensions while retaining vital information from the original dataset. This process is particularly beneficial in data exploration, improving visualization, and trimming redundant data attributes. PCA applications in data exploration include reduction and data simplification, feature extraction and data compression, data visualization, noise removal, and pattern recognition. By projecting high-dimensional data into low-dimensional space, PCA not only simplifies complex data, making it easier to process and analyze, but also extracts the most important features, reducing storage and computational complexity. In data visualization, PCA helps reduce the dimensionality of data to two dimension or three dimensions, making it easy to visualize the structure and pattern of the data. In addition, PCA can also remove noise by preserving the main sources of variation, improve the accuracy of data analysis, and reveal the main patterns and relationships in the data, supporting pattern recognition and feature analysis.

Despite its efficacy, PCA may not be universally applicable. In scenarios that involve non-linear patterns, non-normally distributed datasets, outlier-sensitive data, or incomplete data, the effectiveness of PCA might be compromised. Hence, the choice of a dimensionality reduction technique must be tailored to the nature of the data and the objective of the analysis at hand. Occasionally, other reduction methods or specialized approaches might be more suited to the task. In experiments where 25 different antibiotics were dissolved in aqueous solutions of varying concentrations-with 1 mmol/L representing a higher concentration and 100 µmol/L a more diluted one-PCA adeptly managed to distinguish these solutions, even in the presence of confounding substances. Furthermore, sensor arrays comprised of the three Eu³⁺ and Tb³⁺ incorporated MOFs hold promising potential for the detection of antibiotics in complex mediums such as milk or pharmaceutical products. However, it is crucial to note that comprehending the detection mechanism of these sensor arrays fully necessitates additional clarification to grasp the underlying processes involved.

Building on these findings, the Mukherjee research group launched an advanced nanoscale MOF sensor [256]. Their design, [{Dy(2N₃-TPA)₂(H₂O)(CH₃OH)}] (NMOF), emerged from the hydrothermal synthesis combining lanthanide oxides with two distinct carboxylic acid ligands. As depicted in Fig. 8, this NMOF sensor exhibits exceptional sensitivity towards PA, largely thanks to its luminescence response mechanism. It is especially noteworthy that this selectivity persists even amid various other nitro compound analytes with similar structural characteristics. Moreover, the MOF-based sensor platform demonstrates outstanding reusability, underlining its potential as a robust tool for practical applications in the monitoring and detection of PA. The innovative RGH-Eu(BTC) and NMOF sensor platforms represent significant strides in the sensitive detection of picric acid. The high specificity, low detection limits, and potential for reusability make these MOF-based sensors promising candidates for environmental monitoring and public safety assessments, particularly in contexts where explosive and toxic substances must be accurately identified and measured.

Tetracycline (TC) is a widely utilized antibiotic that is prescribed for treating various infections in both animals and humans. The overuse of TC, particularly in aquaculture and animal husbandry, has led to its accumulation in animal-derived food products, such as milk and meat. This residual presence of TC poses a health risk as it can be ingested by humans through their diet, potentially leading to adverse health effects. Consequently, methods for the sensitive detection and removal of TC are becoming increasingly important to ensure food safety and public health.

In the context of this concern, research teams have been investigating innovative approaches to detect and remove TC from food and environmental samples. For instance, Zhao et al. synthesized a novel bifunctional europium MOF [Eu₂(BIPA)₃(H₂O)] [257]. This framework not only serves as a sensor for TC detection but also functions as an adsorbent to remove TC from solutions. Upon the presence of tetracycline in a solution, the [Eu₂(BIPA)₃(H₂O)] exhibited a notable enhancement in luminescence at 615 nm. The detection of TC by this MOF is feasible over a wide concentration range of 0.05–60 µmol/L, with a detection limit reaching as low as 3 nmol/L. This study indicates a promising avenue for monitoring tetracycline effectively.

Another significant contribution from Chen et al. demonstrated an efficacious and sensitive luminescence detection method employing a Zn-based MOF [258]. The unique Zn-N coordination chemistry facilitates the adsorption of nitrogen-rich tetracycline antibiotics into the MOF's pores, triggering an aggregation-induced luminescence effect. This interaction enables the otherwise non-luminescent Zn-MOF to emit yellow luminescence rapidly, thereby providing a means to detect tetracycline antibiotics in aqueous solutions, which can be achieved with a detection limit of 0.017 µmol/L within a linear range of 0.02–13 µmol/L. Though their findings are noteworthy, the mechanistic details of the detection process could be further investigated to enhance the technique's overall understanding and effectiveness. Furthermore, Zhang et al. utilized a microwave-assisted synthetic route to create a zinc(Ⅱ) based MOF with trimeric acid (Zn-BTC) [259]. The binding of tetracycline to Zn-BTC resulted in an increased luminescence signal, setting the detection limit for this MOF material at 24 nmol/L. This suggests potential for practical applications in TC detection, given the ease of the synthesis method. Li's group synthesized a multi-nuclear lanthanide metal-organic skeleton (Tb-L1) with one-dimensional channels [260]. Tb-L1 has a high specific surface area and chemical stability and shows good selectivity and sensitivity to TC with a detection limit (LOD) of 8 ng/mL. Finally, Liu et al. has crafted MOFs, notably BUT-179, to detect tetracycline antibiotics [261, 262]. The MOF BUT-179 demonstrated favorable luminescence properties in the presence of tetracycline and exhibited a high sensitivity to detecting this antibiotic. Additionally, the sensor displayed commendable chemical stability with a detection limit registering at 19.8 nmol/L. Nonetheless, to fully capitalize on the benefits of Zn-BTC and similar materials in detecting tetracycline, more research is essential to elucidate the underlying detection mechanisms and to validate their utility with biological samples in real-world scenarios. In sum, these research endeavors underscore the vital importance of developing reliable, sensitive, and conveniently implementable detection methods for tetracycline residues in environmental and food matrices as a pivotal step toward preserving human health and well-being.

Rising concerns regarding public health and environmental contamination necessitate efficient methods for detecting and eliminating pollutants in wastewater. Nitrofuran, employed extensively due to its effectiveness, affordability, and efficiency in treating bacterial infections, is now recognized as an emerging organic contaminant in aquatic environments. Zhao et al. innovatively designed and synthesized a set of Cd (Ⅱ)-based metal-organic frameworks (MOFs) exemplified by (MOFs) [NaCd₂(L)(BDC)_2.5]·9H₂O (3), [Cd₂(L)(2, 6-NDC)₂]·DMF·5H₂O (4), [Cd₂(L)(BPDC)₂]·DMFS·9H₂O (5) [263]. These structures exhibit luminescence quenching upon interaction with nitrofurantoin, thereby serving as sensitive sensors for this pollutant. Remarkably, the detection limits of compounds 3, 4, and 5 for nitrofurantoin are 162 ppb, 75 ppb, and 60 ppb, respectively. Concurrently, Lei et al. developed two distinct Zn(Ⅱ)-based metal-organic frameworks, namely {[Zn₃(Cbbi)₂(bpe)(H₂O)₆]·2H₂O}_n and {[Zn₄(OH)₂(cbbi)₂(bpee)(H₂O)₄]·2H₂O}_n. These frameworks exhibit detection limits for nitrofurantoin of 0.22 ppm and 0.15 ppm, respectively. The paper offers a comprehensive analysis of the underlying detection mechanisms and extends its investigation to actual sample analysis. The introduction of array sensing technology coupled with advanced statistical data techniques marks a significant advancement in broadening the scope of analytical subjects.

Flavonoids are key constituents in numerous herbal remedies, known for their broad spectrum of biological effects. To assess their therapeutic potential effectively, it is crucial to establish reliable methods for both qualitative and quantitative flavonoid analysis. The research conducted by Liu et al. has led to the development of an innovative array of luminescent sensors derived from luminescent metal-organic frameworks (MOFs) specifically engineered for flavonoid detection [264]. This array has demonstrated not only high sensitivity in the detection of flavonoids but also exhibited impressive quantitative capabilities. To construct this array, Liu et al. selected five distinct luminescent MOFs, each with a different fluorophore, as the foundation for their sensor technology. The array is tailored for the analysis of flavonoids, using the unique response patterns of the MOFs. By employing a combination of methods, including a tailored MOFs response model, linear discriminant analysis, and hierarchical cluster analysis as statistical tools, the array can accurately differentiate among nine structurally similar flavonoids. The varying detection capabilities of individual luminescent MOFs within the array were notable: In-aip demonstrated a detection limit for isoliquiritigenin of 0.24 µmol/L, Zn-ata showcased a detection limit for rutin at 0.59 µmol/L, In-sbdc proved capable of detecting baicalein with a limit of 0.22 µmol/L, the Gd-bct sensor had a detection limit for quercetin of 0.31 µmol/L, and MOF-525 achieved a detection threshold for fisetin of 0.22 µmol/L. This array represents a significant advancement in flavonoid analysis, offering a sophisticated approach to deciphering the nuanced medicinal contributions of these compounds.

The chemotherapeutic agent 6-mercaptopurine (6-MP) plays a crucial role in the treatment of acute lymphoblastic leukemia, though its use is associated with considerable adverse side effects. As 6-MP effectively disrupts purine metabolism and can interfere with the synthesis of nucleic acids within the body, monitoring its serum concentration is essential for patient safety and treatment efficacy. Sun et al. has pioneered an innovative approach to quantify 6-MP by introducing a rapid luminescence spectrometry technique that employs the luminescent metal-organic framework Fe-MIL-88NH₂ as a probe. Characterized by a robust luminescent emission at 430 nm, Fe-MIL-88NH₂ is sensitive to the presence of 6-MP, which acts to quench this luminescence swiftly, with a reported detection limit of 1.17 µmol/L. Notably, this method has been tested and displays compatibility with human serum samples, showcasing significant potential for integration into clinical diagnostic routines for real-time 6-MP monitoring.

Felodipine is an effective drug for controlling high blood pressure. However, overuse may lead to excessive peripheral vascular dilation, triggering adverse reactions such as hypotension and angina. In order to better monitor the serum concentration of non-lodipine in patients, in 2023, Jiang et al. synthesized Nd-MOF@Yb-MOF@SiO₂@Fe₃O₄ by layer by layer method, which can be used for sensitivity detection of felodipine, the LOD is 6.39 nmol/L [265].

Pregabalin is an effective drug for treating epilepsy, however, excessive use of pregabalin can cause serious side effects, including confusion, attention disorders, and blurred vision. In 2023, Ding's team successfully synthesized a new Gd-MOF using solvothermal method [266]. Using Gd-MOF as a base framework, they further functionalized it into Gd-MOF-1, and by introducing chiral carbon atoms with amino groups, a chiral compound (L-3-Br-PHE-OH) can be embedded into Gd-MOF. This new compound can use the reaction between the amino and carboxyl groups of pregabalin and l-3-Br-PHE-OH to achieve efficient detection of pregabalin. The detection limit of this method is 2.4 nmol/L.

4. Conclusion and prospect

The emergence of luminescent metal-organic frameworks (LMOFs) has brought about breakthroughs in the field of biosensing, showing tremendous potential in detecting various amino acids, biomarkers, and drugs with high sensitivity and selectivity. By virtue of their unique structure, LMOFs can interact with analyte molecules at the interface, leading to changes in their optical properties when analyte molecules are adsorbed onto their surfaces, thereby affecting the intensity or spectral position of luminescent signals. This versatility endows biosensing technologies based on LMOFs with extensive application prospects.

Despite significant achievements in LMOF-based biosensors, several challenges persist. The stability of LMOFs under different environmental conditions remains a major limiting factor, directly impacting the accuracy and reliability of biosensors. Additionally, integrating LMOF-based biosensors into practical applications faces challenges such as long-term stability, scalability, and compatibility with existing detection technologies. Effectively translating laboratory research into commercial products is crucial for the widespread adoption of LMOF-based biosensors. Furthermore, enhancing the selectivity and specificity of sensors, especially in detecting target biomolecules in complex biological samples, is a current research hotspot. Enhancing the molecular recognition capability of LMOFs to reduce non-specific binding interference is essential for improving the overall performance and reliability of biosensors based on LMOFs.

To address these challenges, researchers have proposed the following strategies:

(1) Stability improvement: Researchers are actively exploring strategies to enhance the stability of LMOFs under diverse environmental conditions. This involves developing novel LMOF structures with improved stability and investigating protective coatings or encapsulation techniques to mitigate degradation. By addressing stability concerns, the accuracy and reliability of LMOF-based biosensors can be significantly enhanced.

(2) Optimization of synthesis and functionalization processes: Researchers are striving to simplify and optimize the synthesis and functionalization processes of LMOFs, including developing efficient and reproducible synthesis methods and exploring scalable, automated techniques to enhance the repeatability and scalability of LMOF-based biosensors, laying the foundation for their widespread application.

(3) Integration into practical applications: Successful integration of LMOF-based biosensors into practical applications requires addressing compatibility issues with existing detection technologies. This involves developing standardized protocols and interfaces to achieve seamless integration with existing detection platforms, as well as conducting long-term stability studies and performance optimization under real-world conditions to ensure the reliable and continuous operation of sensors in various applications.

(4) Improving selectivity and specificity: Ongoing research aims to enhance the selectivity and specificity of LMOF-based biosensors. This includes rational design of LMOF structures with tailored pore sizes and functionalities for selective binding of target biomolecules. Advanced surface modification techniques, such as molecular imprinting or bioconjugation, are also explored to improve the molecular recognition capabilities of LMOFs. Achieving higher selectivity and specificity enables more accurate and reliable detection of target analytes using LMOF-based biosensors.

(5) Application of machine learning algorithms to optimize LMOF performance: The application of machine learning algorithms in optimizing LMOF performance is multifaceted. They can handle large datasets, quickly identify LMOFs with the desired performance, particularly demonstrating their utility in high-throughput screening. Machine learning models can predict the structural properties of different LMOFs, such as pore size, shape, and distribution, guiding the design of LMOFs with specific pore characteristics to meet specific application requirements. Additionally, machine learning algorithms can predict the sensing performance of LMOFs based on their chemical composition and structure, aiding in the rapid screening of potential sensing materials and reducing the number of experiments. These applications not only accelerate the discovery and optimization of LMOFs but also improve the precision and efficiency of material design. With the advancement of computational capabilities and the accumulation of datasets, the application prospects of machine learning in the field of LMOFs are expected to be broader.

The application prospects of LMOFs show significant significance in the social, environmental and healthcare fields. They can improve the sensitivity and accuracy of food safety tests including cancerogen and food additives detection to protect the health of consumers; Effective detection of pollutants including chemicals and germs in environmental monitoring to support environmental protection and sustainable development; In terms of health care, early diagnosis of diseases including biomarker's detection and the development of personalized medicine programs to improve treatment effectiveness and reduce costs. With relentless efforts in materials science and biotechnology, these sensors are anticipated to achieve a series of innovative breakthroughs, including realizing real-time monitoring, integrating microfluidic devices for automated sample handling, and developing portable and low-cost biosensors for on-site rapid detection. With the continuous advancement of relevant technologies, LMOF-based biosensors will play a more significant role in promoting human health, enhancing environmental protection, and improving food safety management in the future.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

CRediT authorship contribution statement

Xinhui Fang: Writing – original draft, Formal analysis. Xinrui Wang: Writing – review & editing and design writing framework. Bin Ding: Writing – review & editing, Conceptualization.

Acknowledgments

This work was supported financially by Natural Science Foundation of Tianjin (No. 18JCYBJC89700) and Science & Technology Development Fund of Tianjin Education Commission for Higher Education (No. 2019ZD15).