Luminescent Metal–Organic Framework Thin Films: From Preparation to Biomedical Sensing Applications

Abstract

Metal-organic framework (MOF) thin films are receiving increasing attention in a number of different application fields, such as optoelectronics, gas separation, catalysis electronic devices, and biomedicine. In particular, their tunable composition and structure, accessible metal sites and potential for post-synthetic modification for molecular recognition make MOF thin films promising candidates for biosensing applications. Compared with solution-based powdery probes, film-based probes have distinct advantages of good stability and portability, tunable shape and size, real-time detection, non-invasion, extensive suitability in gas/vapor sensing, and recycling. In this review, we summarize the recent advances in luminescent MOF thin films, including the fabrication methods and origins of luminescence. Specifically, luminescent MOF thin films as biosensors for temperature, ions, gases and biomolecules are highlighted.

1. Introduction

The use of biosensors to detect and quantify the presence of targeted compounds is of great significance in diverse fields, such as medicine, pharmacology, agriculture and food safety, environmental monitoring, industry, defense, homeland security, etc. A biosensor is defined as a device with biological sensing elements connected to or integrated within a transducer [1,2]. Biosensors can employ a variety of transduction mechanisms, with luminescence-based sensors being the subject of this review. The luminescent biosensor utilizes changes in the photoluminescence of a fluorescent material induced by analyte-probe interactions or target conditions (e.g., temperature) to quantitate chemical/biological species [3,4]. Luminescent materials can be conjunct with spectrophotometers to identify the sensed material based on the characteristic absorption and emission shifts, and they can quickly and easily give a colorimetric response to stimuli [5,6]. The main advantages of fluorescence-based techniques over other transduction ones are ease of use, non-invasive, technical simplicity, and broad adaptability [7]. Recently, tremendous amounts of luminescent chemo-/bio-probes based on organic luminophores (e.g., small molecules, fluorescent conjugated polymers) [8,9,10,11,12] and inorganic luminophores (e.g., quantum dots and metal nanoclusters) [13,14] have been successfully developed. However, the organic luminophores often own an inherent hydrophobicity, and it is difficult to make them hydrophilic. The inorganic luminophores are often water-soluble and exhibit some congenital shortcomings: (1) inconvenience of store and transport; (2) nonrecycling since they are not easily separated from the analytes in solutions; (3) reagent consumption and environmental pollution; and (4) difficulty in detecting vapor/gas [15,16]. Additionally, these two types of probes have high biotoxicity, which hinders their extensive applications.

Development of film-based luminescent sensors can overcome the drawbacks of the above probes for chemo-/bio-sensing [15,17]. The luminescent films can be easily converted into a device format with several unique advantages: (1) luminescent films with any shape and size (depending on the substrate pattern) can be easily fabricated to meet various needs and occasions; (2) they are easy to store and transport; (3) there is no intrusive interference since the detection is usually carried out in the absence of external addition; (4) luminescent films enable the real-time detection of analytes; (5) luminescent films can be regenerated by washing with a suitable solvent; and (6) luminescent films have less damage to organisms because of the good chemical stability of luminophores in the solid state. Besides, the numbers of defects and grain boundaries in highly oriented quasi-epitaxial films are significantly reduced, and the numbers of binding sites at the outer surface of film are constant and do not depend on the thickness.

Metal–organic frameworks (MOFs), also known as porous coordination polymers (PCPs), which are constructed by the self-assembly of metal ions or clusters and organic ligands, have been widely explored as biosensors because of the unique luminescent properties, diverse advantages from structural and functional components, low biotoxicity, and easy preparation in thin films [18,19,20]. Specifically, MOF sensors have several key advantages over other potential luminescent probe materials: (1) MOFs possess immense potential for tunability and functionalization by altering the metal ions and organic ligands; (2) the inherent crystallinity of MOFs permits exact knowledge of the interactions that may be involved in the detection of analytes; (3) the porosity of MOFs can support the adsorption of analytes into the MOF pores, which can result in preconcentration of the analyte and close-interactions between the MOF and analyte species; (4) the porous frameworks allow the introduction of analyte-selective guest molecules through post synthetic modification into MOF structures for specific recognition. To date, luminescent MOF sensors have been successfully implemented for the detection of vapors/gases [21], explosive chemicals [22,23,24,25], ions [26,27,28], biomarkers [29,30,31] and temperature [32,33]. However, most of them are powdery sensors, which are difficult to operate and hard to recycle, severely limiting their biosensing applications. Fortunately, a variety of strategies, such as solution-based deposition, electrochemical deposition, and coating/casting, have been developed for fabricating MOF thin films. MOF film-based sensors not only retain the intrinsic sensory properties of the corresponding powdery MOFs, but also have the maneuverable nature of film, which shows a broad application prospect in the field of biosensing.

Nowadays, there are a lot of reviews on MOF-based luminescent probes [23,34,35,36,37,38] or the fabrication methods of MOF thin films [39,40,41,42,43,44,45,46]. However, there are no comprehensive reviews on luminescent MOF films for biosensing. In this review, we made such an effort to systematically review the progress of fabrication methods in designing various luminescent MOF films for biosensing. We firstly summarized the main methods for fabrication of MOF thin films followed by a brief introduction of the origins of MOF film luminescence. Finally, we focused on luminescent MOF thin films as biosensors for temperature, ions, gases and biomolecules, and demonstrated the sensory properties of such films that are related to their structures. This review would serve as a guide to better understand and cultivate the design strategies of luminescent MOF film sensors with high sensitivity, selectivity, stability and portability.

2. Methods for the Fabrication of MOF Thin Films

A number of synthetic strategies, including liquid-phase epitaxy (LPE), substrate-seeded heteroepitaxy (SSH), atomic layer deposition (ALD), bottom-up modular assembly (BMA), electrochemical deposition (ECD), and spin coating techniques (SCT), have been developed for the fabrication of MOF thin films. In this review, we divided them into three different categories: (1) deposition from solvothermal mother solutions, a method where a substrate is used (or modified by organic molecules) together with an appropriate growth solution containing the reactants, e.g., metal precursors and organic ligands, (2) electrochemical synthesis, which includes anodic deposition, electrophoretic deposition and cathodic deposition and (3) mixed matrix membranes (MMMs), where essentially powders made using conventional solvothermal synthesis are coated onto a substrate.

It is needed to mention that an appropriate substrate and suitable surface modification are crucial for the deposition of MOF thin films, in particular for the deposition from solvothermal mother solution methods. Different types of substrates, such as planar solid (indium tin oxide (ITO), Si, Au, fluorine-doped tin oxide (FTO)), flexible (plastic, polystyrene fiber), and nonplanar substrates (metal oxide, porous metal), and substrates modified with different functional groups (−COOH, −NH₂, −OH, and –pyridine), have been widely studied for the deposition and support of MOF thin films [41]. These functional groups can be used to anchor the metal/metal-oxo nodes and organic linkers, thereby nucleating the growth of MOF thin films. Using different functional groups or tuning the density of functional groups, the growth orientation of MOF thin films can be systematically controlled and the highly oriented MOF thin films can be obtained under favorable conditions.

2.1. Deposition from Solvothermal Mother Solutions

Like the preparation of powdery MOF, the solvothermal method is a main method for preparing MOF thin films. In general, the synthesis of MOF thin films follows one of two approaches: in situ growth or seed-assisted (secondary) growth.

2.1.1. In Situ Growth

The most straightforward method of preparing an MOF thin film is inserting one or several substrate(s) into the mother solution of a given MOF following the usual solvothermal synthesis. The nucleation, growth and interchange of crystals on the substrate occur during the same preparation process. Growth occurs at the surface and sometimes also in solutions at the same time. This growth causes the crystals to adhere to the surface of the substrate in a more or less intergrown and continuous manner. Despite its superficial simplicity, this method can be quite powerful, especially for oxide wafers, metal slices, fibers, and even porous alumina in some cases. In this way, dense, crystalline and homogeneous thin films with micrometer-scale thickness have been obtained.

The first continuous and well-intergrown membrane, MOF-5 membrane, was prepared by Lai and Jeong et al. on a porous α-alumina without substrate modification by in situ solvothermal synthesis [47]. The porous α-alumina is placed in a solution of 1,4-terephthalic acid in DMF for half an hour, followed by addition of dehydrated Zn(NO₃)₂ 0.86·H₂O, and finally heated to 105 °C for solvothermal reaction to obtain an MOF-5 membrane. Figure 1 shows that the continuous and dense MOF-5 membrane was successfully prepared and membranes with different thicknesses were obtained at different synthesis time or at different solvents. Besides MOF-5, other MOF membranes, such as Cu₃(btc)₂ (btc = 1,3,5-benzenetricarboxylate) [48], Zn(bdc)₂(dabco) (bdc = 1,4-benzenedicarboxylate; dabco = 1,4-diazabicyclo[2.2.2]octane) [48], ZIF-8 [49], were also successfully prepared on porous alumina by the same method.

In addition, a dense ZIF-8 membrane with a thickness of approximately 50 μm is directly fabricated on the porous TiO₂ substrate by the microwave heating in situ solvothermal method [50]. Other substrates were also used for deposition of MOF films, and continuous HKUST-1 and ZIF-8 thin films were obtained in silicon slices [51].

However, it is still difficult to prepare continuous MOF membranes on unmodified supports because the heterogeneous nucleation of MOF crystals on support surfaces is not homogeneous and efficient. In addition, MOF grains formed in solutions are difficult to adhere to the surface of the substrate due to the lack of binding sites. There are two main strategies to promote the growth of MOF grains on the substrate and increase the interaction of the MOF thin films with the substrate: “metal source” and substrate surface modification.

The synthesis of MOFs involves the coordination of metal centers with organic ligands, and it is particularly favorable when the substrate is made of the same metal as the MOF. Under the guidance of this idea, Qiu and Zhu et al. successfully produce an HKUST-1 thin film using the “twin copper source” method (Figure 2) [52]. In the in situ solvothermal growth process, the oxidized copper net and the Cu²⁺ in a mother solution provide the metal source for the growth of MOF crystals. At the same time, the oxidized copper net provides a homogeneous nucleation site for the growth of a continuous and dense MOF membrane. In addition, the same group prepared a Zn₃(BTC)₂ thin film by placing an H₂O₂-activated zinc sheet in the aqueous solution of H₃BTC [53]. In 2011, Martens et al. produced a continuous Cu₃(BTC)₂ thin film by an in situ hydrothermal reaction using oxidized copper as a substrate [54]. Furthermore, a simple method of ‘single nickel source’ has been developed by Qiu and Xue et al. to prepare a homochiral Ni₂(L-asp)₂(bipy) (L-asp = L-aspartic acid, bipy = 4,4′-bipyridine) membrane (Figure 3) [55]. The nickel net plays a dual role in the synthesis process as the only nickel source and as a substrate supporting the membrane. Because the nickel net is the only metal source in the reaction system, the growth process stops once a layer of the crystal film is formed, making the final membrane thinner and continuous.

Poor bonding of the MOF thin films to the substrates is a common challenge. In order to improve the bonding force between the MOFs film and the substrate, functional surface modification of the substrate becomes a powerful means. Huang and Caro et al. report a covalent functionalization strategy to prepare ZIF-90 and ZIF-22 membranes by using 3-aminopropyltriethoxysilane (APTES) as covalent linkers between the MOF layers and supports’ surfaces [56,57]. Figure 4 shows the amination of a porous Al₂O₃ substrate and the preparation of ZIF-90 polycrystalline film. In the first step, the ethoxy groups of the APTES react with the hydroxyl groups on the surface of Al₂O₃ support. In the second step, the amino groups react with the aldehyde groups of imidazolate-2-carboxyaldehyde via imines condensation, and then the nucleation and crystal growth of the ZIF-90 start at these fixed sites on the surface of the porous ceramic supports. After solvothermal reaction for 18 h at 100 °C, the ZIF-90 layer is completely covered by the surface of the APTES modified support with a thickness of about 20 μm. In the growth process of the ZIF-22 polycrystalline film, their group believes that the amino groups in 3-aminopropyltriethoxysilane can be coordinated with Zn²⁺, thus connecting the ZIF-22 nanocrystals and the substrate, and finally forming a dense ZIF-22 polycrystalline film [57]. Modifying the surface of porous α-alumina and porous potassium hexatitanate with hydroxyl groups, as well as modifying the surface of silicon with carboxy groups by self-assembled monolayer (SAM), continuous and dense Zn₂(bdc)₂(dabco), Mn(HCOO)₂ and HKUST-1 polycrystalline films are successfully prepared [58,59].

2.1.2. Seed-Assisted Growth

Seeded growth, also known as secondary growth, is a process, in which a seed layer is coated or deposited on a substrate and then on deposited MOF thin films under solvent or hydrothermal conditions. Due to the low heterogeneous nucleation density of many MOF crystals on the porous ceramic carrier substrates, this method is widely used to prepare dense and packed MOF thin films. Seeded growth allows for more effective control of crystal growth and orientation of MOF membranes, and it requires two steps: preparation and deposition of seeds followed by growth into a film. Various materials, such as MOF nanocrystals, non-MOF particles, coordination polymers, even MOF thin films, can be used as seeds [60,61].

Very recently, Qian and Cui et al. developed a strategy, named “in situ secondary growth”, to fabricate a Eu-BDC-NH₂ film on common glass with a UiO-66-NH₂ layer as seed layers [62]. Because of the matched components and structures of Eu-BDC-NH₂ and UiO-66-NH₂, the Eu-BDC-NH₂ film can be successfully fabricated on the UiO-66-NH₂ layer through in situ secondary growth. The space groups of UiO-66-NH₂ and Eu-BDC-NH₂ are F43m and Fm3m, respectively. These similar crystal structures and the same ligand avoid the mismatch between the lattices and components. As shown in Figure 5, a common glass with abundant hydroxylate on the surface is obtained by treating with the piranha solution. The well-intergrown UiO-66-NH₂ with the thickness of about 1 μm is formed on the treated glass after solvothermal synthesis (Figure 6a,c). Then, the washed UiO-66-NH₂ film is vertically put into the mother solution of Eu-BDC-NH₂ and heated to 120 °C for 24 h. After the in situ secondary growth, the observed Eu-BDC-NH₂ grains have a size of around 1–2 μm, and tightly cohere to each other, leading to a crack-free film of around 2 μm in thickness (Figure 6b,d). The [Cu(ndc)(dabco)_0.5] (ndc = 1,4-naphthalenedicarboxylate, dabco = 1,4-diazabicyclo[2.2.2]octane) film with itself as seed layers and IRMOF-3 film with MOF-5 as seed layers are reported by Yusenko et al. and Yoo et al., respectively [63,64].

Takahashi and Falcaro et al. demonstrate that the substrate-seeded heteroepitaxy approach can permit the fabrication of large-scale epitaxial MOF thin films with unrestricted substrate size and rigidity [65]. The oriented microcrystalline Cu(OH)₂ nanobelts are used as a source of metal ions, and a substrate-seeded heteroepitaxial growth of Cu₂(BDC)₂ thin film is rapidly fabricated (Figure 7). After immersing the Cu(OH)₂ nanobelt film in a saturated ethanolic solution of H₂BDC, a continuous Cu₂(BDC)₂ MOF film orthogonal to the nanobelts is observed within 5 minutes (see Figure 7e,f). Out-of-plane XRD measurements and in-plane XRD measurements confirm that the (h00) and (0k0) faces of the MOF crystals are aligned and precisely oriented along the metal hydroxide crystallographic directions. Together with the transmission electron microscope (TEM) analyses, the epitaxial Cu₂(BDC)₂ thin film is determined to crystalize in P2 symmetry with lattice parameters (a = 10.90 Å, b = 5.89 Å, and c = 10.90 Å), which are excellently matched with the Cu(OH)₂ nanotubes with P4 symmetry and lattice parameters (a = 10.61 Å, b = 5.80 Å, and c = 10.61 Å), as shown in Figure 7c,d. In addition, since the size and rigidity of the substrate are essentially unrestricted, the substrate-seeded heteroepitaxy approach allows the fabrication of flexible and large-scale MOF thin film-based devices (Figure 7g,h).

2.2. Electrochemical Synthesis

Electrochemical synthesis of HKUST-1 thin films was first introduced by researchers at Badische Anilin-und-Soda-Fabrik (BASF) [66]. Since then, scientists have done a lot of research in the electrochemical preparation of high-quality MOF films [67,68]. Three main approaches have been described for the fabrication of MOF thin films via electrochemical methods: (1) anodic deposition, (2) electrophoretic deposition, and (3) cathodic deposition (Figure 8) [41,67].

In the anodic deposition process (Figure 8a), a metallic electrode is electrochemically oxidized to provide metal ions, and MOF thin films grow on the anode when the electrochemically generated metal ions react with the organic linkers contained in the electrolyte. Ameloot et al. showed that, by carefully optimizing the conditions and in the absence of stirring, the anodic deposition method can be used to grow HKUST-1 on copper anodes [69]. The HKUST-1 layer is formed in 30 min or less by applying an anode voltage to the copper electrode immersed in a BTC solution. Various thicknesses (2–50 μm) and intergrowth degrees could be obtained by variation of the water content of the solution as well as the voltage and frequency of the applied tension. Since metal ions are provided on the surface where nucleation occurs, crystals and the resulting film are highly homogeneous. To the best of our knowledge, various types of MOF thin films, such as Zn₃(BTC)₂ on Zn plates [70], MIL-100(Fe) on Fe anodes [71], and Zn(TPTC) on Zn plates [72], have also been fabricated by this method.

In the electrophoretic deposition process (Figure 8b), two conductive electrodes are immersed in solutions containing surface-charged MOF particles. When a voltage is applied between the two electrodes, the resulting electric field drives the MOF particles toward the oppositely charged electrode, thus leading to the formation of MOF thin films. The electrophoretic deposition method is well suited to the facile and rapid fabrication of MOF films on the traditional substrates, such as ITO and FTO glass and metal plates. HKUST-1, Al-MIL-53, UiO-66, NU-1000, carbon quantum dots (C-QDs)@UiO-66-(COOH)₂, Ln@UiO-66, Eu-NDC and so on, have been successfully fabricated with the electrophoretic deposition method [73,74,75].

During the cathodic deposition process (Figure 8c), two inert electrodes (WE, working electrode; CE, counter electrode) are used as chemically inert separators [76,77]. They are the only source of electrons and do not participate in the MOF-forming reactions. The key step in cathodic deposition is to obtain a local alkaline region near the cathode where the organic ligands are deprotonated. The “deprotonated” organic ligands react with metal precursors in solutions, inducing the crystallization of MOF particles at the cathode surface and forming MOF thin films.

2.3. Mixed Matrix Membranes

There are several possibilities for fabricating MOF thin films from essential powders made using conventional solvothermal synthesis: (1) direct deposition of powdered MOFs onto a substrate by drop-casting or spin-coating methods; (2) coating of an MOF particle suspension containing an additional polymeric binder to obtain MOF-based mixed matrix membranes (MMMs). Eddaoudi et al. implemented the spin-coating method to construct various MOF thin films, ranging in thickness from a few micrometers down to the nanometer scale including Cu₂(bdc)₂·xH₂O, Zn₂(bdc)₂·xH₂O, HKUST-1, and ZIF-8 [78]. Zhang et al. synthesize a continuous and smooth lanthanide MOF films, Eu_1-xTb_x-MOF, via spin-coating deposition [79]. Similarly, MIL-101(Cr) and MIL-101(Cr)-NH₂ films are prepared on alumina supports by Burrows et al. with the polyethylenimine (PEI)-assisted dip-coating method [80,81].

Besides, given the vast possibilities that MOFs offer in terms of design together with their intrinsic hybrid nature, research into MOF-based MMMs has experienced an unprecedented explosion since the first report in 2004 [82,83,84,85]. The lab-scale manufacture of MOF-based MMM is similar to the one applied for the synthesis of other MMMs [86]. In the general procedure, the first step is the dispersion of powdery MOFs in the solvent in an ultrasonic bath. A polymer (such as polymethyl methacrylate, PMMA; polyvinylidene fluoride, PVDF; polyacrylonitrile, PAN) is then added. The whole mixture is stirred overnight. Before the casting, different intervals of sonication and stirring take place to ensure good dispersion. Subsequently, the membranes are cast on a flat surface, and then left overnight for evaporation of solvent at room temperature. Once dried, the films are placed in a vacuum oven for 24 h at a specific temperature (depending on the polymer glass transition temperature) high enough to remove the remaining solvent.

In a recent paper, Cohen et al. achieve the integration of a wide range of MOF particles (UiO-66, UiO-66-NH₂, MIL-101(Cr), MIL-101(Fe), HKUST-1, MIL-53(Fe), ZIF-8) in an MMM with a high MOF content (≈67 wt %) (see Figure 9a) [87]. These synthesized MMMs retain high specific surface areas of the parent MOFs and readily undergo post-synthetic modification (PSM) and post-synthetic exchange (PSE) producing. In addition, these MMMs can be fabricated on a large scale and are easy to handle and manipulate (Figure 9b).

Detailed SEM images of a UiO-66 MMM with an MOF content of about 67 wt % are shown in Figure 10. The octahedral UiO-66 microcrystals clearly remain intact and are well integrated with the polymer binder. The torn edge of MMM in Figure 10b highlights the integration of UiO-66 crystals with the polyvinylidene fluoride (PVDF) strands. The MOF particles are densely packed within the film with approximately 35 mm in thickness.

3. Luminescence Behavior in MOF Thin Films

The ability to load a deposited MOF thin layer with luminescent materials provides many interesting options. The most obvious one is to check morphology and texture of the deposited MOF film, e.g., to check for holes, incompletely covered areas, cracks, scratches and even to determine the thickness. In addition, the luminescent MOF thin films open up the possibility to use such materials for optical data storage, color displays, luminescence detecting and mapping. Like the powdery MOFs, luminescence of MOF thin films can generate from the luminescent metal ions or clusters, organic ligands, and charge-transfer, such as ligand-to-metal charge transfer (LMCT) and metal-to-ligand charge transfer (MLCT), as well as the loaded guest molecules.

3.1. Lanthanide Luminescence

In the past decades, lanthanide MOF thin films have attracted extensive attention due to their unique luminescence properties, such as high luminescence quantum yield, long-lived emission, large Stokes shifts, and characteristically sharp line emissions. Most of the reported luminescent MOF thin films are based on lanthanide luminescence. Due to the parity-forbidden f–f transitions, it is hard to yield strong luminescence with direct excitation of the lanthanide ions. The luminescence of lanthanide ions is often generated from the energy transfer processes, known as “luminescence sensitization” or “antenna effect” [88,89]. The mechanism of luminescence sensitization within lanthanide MOF thin films is comprised of three steps: (1) light is absorbed by the organic ligands around the lanthanide ions; (2) energy is transferred to the lanthanide ions from organic ligands; and (3) luminescence is generated from the lanthanide ions.

In 2010, Zhang et al. synthesized a continuous and smooth lanthanide MOF film with high mechanical stability via spin-coating deposition [79]. In this study, they first synthesize a series of shape-and-size adjustable bimetallic Ln-MOFs nanocrystals by the capping method. The nanometer-sized crystals are then used to deposit continuous and smooth Eu_1-xTb_xMOF thin films on ITO-coated glass substrates with spin-coating deposition. The fabricated films show strong luminescence of Eu³⁺ and Tb³⁺, and are characterized by an efficient Tb³⁺-to-Eu³⁺ energy transfer (see Figure 11). Since then, different types of lanthanide MOF films, such as europium-based MOF films, terbium-based MOF films, and mixed lanthanide MOF films, have been reported [90,91,92].

3.2. Ligand-Based Luminescence

The ligand-based luminescence is usually observed in two cases: (1) transition-metal-based MOF films, such as zirconium-based and zinc-based MOF films; (2) lanthanide-based MOF films with insufficient antenna sensitization.

Qiu and Zhu et al. synthesize an MOF Zn₃(BTC)₂ film on the substrate of zinc wafer by a direct conversion technique [53]. The reaction between the substrate-generated zinc source and the H₃BTC solution yields the inter-growth of crystals, and then forms a compact and continuous Zn₃(BTC)₂ film. Upon excitation at 327 nm, Zn₃(BTC)₂ film exhibits a strong and broad emission of ligand with the peak at about 390 nm, and the fluorescence property of Zn₃(BTC)₂ film is utilized to detect dimethylamine.

In lanthanide-based MOF films, if antenna sensitization is not very efficient, both remaining ligand fluorescence and the lanthanide-centered luminescence can be observed [93]. In addition, if the amount of energy acceptor (lanthanide ions) is not high enough, the fluorescence of the ligand is strong and obvious. Recently, Cao et al. reported a Tb@UiO-66-Hybrid film, featuring with two typical emission peaks of ligand and lanthanide ions upon excitation at 330 nm (Figure 12) [75]. The peak at 430 nm is derived from the ligand (H₂NDC). In addition, the peaks at 489, 544, 584, and 620 nm (⁵D₄-⁷F_J, J = 6, 5, 4, 3,) correspond to characteristic Tb³⁺ emissions. Similarly, the Eu@UiO-66-Hybrid film features two typical emissions based on the ligand (H₂NDC) and Eu³⁺ with characteristic sharp lines at 578, 592, 616, 650, and 699 nm (⁵D₀-⁷F_J, J = 1, 2, 3, 4). The dual-emitting Tb@UiO-66-Hybrid and Eu@UiO-66-Hybrid films are further applied to detect temperature changes.

3.3. Luminescence Generated from Guest Molecules

Because of the highly regular channel structures, controllable pore sizes and abundant modifiable sites, the MOF films can serve as hosts for the encapsulation of the guest luminescent species, such as lanthanide ions/complexes, fluorescent dyes and fluorescent quantum dots. Qian and Cui et al. introduced the Tb³⁺ ions into the two indium MOF films, [(CH₃)₂NH₂][In₃O(BTC)₂(H₂O)₃]₂[In₃(BTC)₄] (CPM-5) and In₃O(OH)(H₂O)₂[BTC]₂ (MIL-100(In)) through the post-functionalization [94]. The presence or absence of extra carboxylate acid in these two films makes adjustment on energy transfer processes and thereby oxygen sensitivities possible. Recently, MIL-124@Eu³⁺ film was successfully prepared via post-synthetic modification of the MIL-124 film with europium ions by the same group [95].

Besides lanthanide ions, small lanthanide complexes can be encapsulated into the pores of MOF films. Europium chelate [Eu(bzac)₃bipy] (bzac = 1-benzoylacetone, bipy = 2,2′-bipyridine) is loaded into a three-dimensional (3D) porous MOF film, HKUST-1 by Wickleder and Woll et al. (Figure 13) [96]. The loading process is carried out by immersion of the deposited MOF films into ethanolic solutions of Eu(bzac)₃bipy. XRD data recorded reveals the loading process does not destroy the porous framework. Room-temperature emission spectra of powdered Eu(bzac)₃bipy and powdered Cu₃(btc)₂-MOF loaded with Eu(bzac)₃bipy reveal that optical excitation can be transferred from the MOF ligands to the Eu-atoms embedded in the MOF pores.

In recent years, fluorescent C-QDs@MOFs composites have attracted the attention of scientists for display lighting, fluorescence imaging, and chemical sensing. Cao et al. employ a UiO-66 based MOF, UiO-66-(COOH)₂ with uncoordinated carboxylic group, to load the C-QDs (Figure 14) [74]. UiO-66-(COOH)₂ MOFs can absorb C-QDs from the solution and prevent C-QDs from aggregating, and the well-dispersed C-QDs impart fluorescence characteristics to composites. C-QDs@UiO-66-(COOH)₂ composites are deposited on zinc plates by electrophoretic deposition. In addition, different kinds of guest luminescent molecules (Eu³⁺ and C-QDs) can be loaded simultaneously and the resulted Eu@C-QDs@UiO-66-(COOH)₂ exhibits white fluorescence in the temperature range from 77 to 363 K upon excitation of 365 nm.

4. Biomedical Sensing Application of Luminescent MOF thin Films

To date, various types of luminescent MOFs have been reported and realized in sensing of metal ions, anions, gas molecules, nitro explosives, small molecules and temperature [21,22,23,24,25,26,27,28,29,30,31,32,33]. However, most of them are brittle crystals or loose powders synthesized by hydrothermal/solvothermal methods, which require specific solvent conditions to detect analytes. The operation is difficult and seriously limits their practical in-field applications. MOF thin films grown on solid substrates have many advantages over powdery and solution-based samples, such as: they are easily separated from liquid media; the numbers of defects and grain boundaries of highly oriented quasi-epitaxial layers are obviously reduced; and the numbers of binding sites at the outer surface of the MOF film are constant and do not depend on the thickness of MOF film. In the following section, we will discuss the luminescent MOF thin films as biosensors for detecting temperature, ions, gases and biomolecules, and some related powdery probes are also mentioned.

4.1. Temperature Sensing

Temperature is a critical parameter in both scientific research and industry. Since the first MOF-thermometer [Eu_0.0069Tb_0.9931-DMBDC] (H₂DMBDC = 2,5-dimethoxy-1,4-benzenedicarboxylic acid) was reported by Chen and Qian et al. [97], MOF-based luminescence thermometers have drawn great attention [98,99]. By designing a thin film of such a luminescence thermometer on a suitable substrate, a novel device can be developed, with which the surface temperature distribution can be easily mapped via a non-invasive method. Recently, Cao et al. prepared two Ln@UiO-66-Hybrid films and studied their temperature detection performances [75]. The smooth and uniform MOF films with a thickness of approximately 50 μm are fabricated by stepwise PSE and PSM, followed by the electrophoretic deposition method on unmodified FTO glass (Figure 15a,b). The Tb@UiO-Hybrid film features two typical emission peaks: the peak at 430 nm is derived from the ligand (H₂NDC), and the peaks at 489, 544, 584 and 620 nm correspond to characteristic Tb³⁺ emissions. Similarly, the Eu@UiO-66-Hybrid film features two typical emissions based on the ligand (H₂NDC) and Eu³⁺ with characteristic sharp lines at 578, 592, 616, 650 and 699 nm. When the temperature gradually increases from 303 to 403 K, the intensity at 430 nm in the Eu@UiO-66-Hybrid film decreases by about 15% of pristine intensity, while the intensity at 616 nm based on the europium ions gradually increases by approximately 2.5 times of pristine intensity (Figure 15c,d). There is a good function relationship between the intensity ratio at 613–430 nm and temperature with a relative sensitivity of 4.26% K⁻¹ in the temperature range of 303–403 K (Figure 15e). In addition, the Tb@UiO-66-Hybrid film exhibit good temperature sensing properties with a relative sensitivity of 2.76% K⁻¹ in the temperature range of 303–353 K. In a recent article, the same group reported a C-QDs functionalized MOF composite film C-QDs@UiO-66-(COOH)₂ film, which is also fabricated by the electrophoretic deposition method. Based on the emission of C-QDs, this film can detect temperature in the range of 97–297 K with a relative sensitivity of 1.3% K⁻¹ at 297 K.

Other groups have also reported some types of MOF film thermometers. Yan et al. fabricate a polymer hybrid thin film based on rare earth complexes RE(BPDC)(Ad) (BPDC = biphenyl-4,4′-dicarboxylic acid, Ad = adenine) via polymerization reaction of ethyl methacrylate (EMA) and 4-vinylpyridine (VPD) [100]. The resulted polymer thin film can act as a luminescent thermometer based on the energy transfer from Tb³⁺ to Eu³⁺. With the one-step direct solvothermal synthesis method, Bouwman et al. deposit a series of lanthanoid MOF LnHL (Ln = Tb, Gd, and Gd_0.9Tb_0.1; H₄L = 5-hydroxy-1,2,4-benzenetricarboxylic acid) films on a Gd₂O₃ substrate [101]. As the temperature increases from 110 to 270 K, the intensity of the Tb^III-based emission in the Gd_0.9Tb_0.1HL film only changes slightly, but the intensity of the ligand-based phosphorescence decreases dramatically. A good linear relationship is found based on the ratio between the intensities I_Tb (541 nm) and I_(phos+Tb) (the total emission intensity from 350 to 650 nm). The relative sensitivity of Gd_0.9Tb_0.1HL film is 0.8% K⁻¹, which can be enhanced with a lower Tb content and the relative sensitivity of Gd_0.99Tb_0.01HL compound reaches up to 4.4% K⁻¹ at 110 K.

4.2. Ion Detection

With the development of modern industry, heavy metal ions, such as Cu²⁺, Hg²⁺, Cr³⁺ from industrial wastes, have increasingly released into the environment, which causes a series of ecological and health-care issues [102]. Wastewater containing high concentrations of Cu²⁺ will seriously pollute the soil and endanger the ecosystem of the natural water system. For human bodies, excessive intake of copper ion may cause gastrointestinal distress, liver and kidney failure, even DNA damage [91,103,104,105,106]. Hg²⁺ is among the most toxic metal ions, which is harmful to humans and can cause many diseases, such as digestive, kidney, and neurological diseases, even in a very low concentration. It is very difficult to be replaced in a short period of time when mercury enters the human body [107,108,109,110,111,112,113,114]. As for Cr³⁺, a trace amount of Cr³⁺ is necessary and has a huge impact on the metabolism of carbohydrates, fats, proteins, and nucleic acids. The deficiency of Cr³⁺ can trigger diabetes, atherosclerosis, and cardiovascular diseases. However, excess Cr³⁺ is still toxic and harmful to human health, which can incorporate with DNA and result in mutations and malignant cells [115,116]. Besides, anions have important roles in a wide variety of environmental, industrial, biological and clinical fields. For example, the carbonate ion concentration in blood maintains an approximation of the acid-base balance and aids in elucidating abnormal conditions [77,117,118]. Therefore, it is urgently needed to develop simple, fast, visual techniques for detecting these ions.

4.2.1. Cu²⁺ Sensing

Several reports have manifested the potential applications of luminescent MOFs in the bio-sensing of Cu²⁺ ion. In 2010, Chen and Qian et al. reported a microporous luminescent MOF Eu₂(FMA)₂(OX)(H₂O)₄·4H₂O (FMA = fumarate; OX = oxalate) for the sensing of Cu²⁺ [103]. The luminescent intensity of Eu₂(FMA)₂(OX)(H₂O)₄·4H₂O largely quenches in the presence of Cu²⁺, and the sensing ability under simulated physiological conditions is explored. Zhu et al. report a europium-based MOF probe with a high quenching coefficient of Cu²⁺ among reported MOFs [104]. The exchange of Cu²⁺ with the cationic guest molecule causes decomposition of the skeleton, resulting in quenching of the luminescent. Employing special chemical reaction is designed for specific Cu²⁺ probe by Oh et al. [105]. They synthesize a pyrene-functionalized organic building block CPP-16 with three functional parts: a framework construction part, a detecting part and a fluorophore part. The interaction of Cu²⁺ with amide groups results in change of the dangled pyrene groups from the stacked excimer state to the quenched excimer state, leading to significant quenching of the fluorescence.

Considering that the biosensing of Cu²⁺ ions is usually in the liquid phase, the portable MOF films can apparently make the detection procedure simpler. Yang et al. utilize the one-step electrodeposition method to fabricate a luminescent water stable Tb-Succinate MOF film on FTO conductive glass. The photoluminescence experiment suggests that the Tb-Succinate MOF film exhibits characteristic luminescence of Tb³⁺ ion, and presents high sensitive and selective sensing ability toward Cu²⁺ ion [91]. The quenching percentage of the luminescence can be linearly fit to the concentration of the Cu²⁺ ions with a K_SV value of 6298 M⁻¹. As shown in Figure 16, the luminescent quenching effects are eye-distinguishable under UV-light when the concentration of Cu²⁺ ions is between 1 × 10⁻⁵ to 1 × 10⁻³ M. Compared with the powder sample, the Tb-Succinate MOF film not only has brighter luminescence, but also exhibits faster luminescent response of Cu²⁺ in the first 10 min. The film provides potential for semi-quantitative in-field detection of Cu²⁺ ion in aqueous environments or biosystems. The same group also demonstrates the potential of luminescent Ln–CP film Tb₂(BDC)₃(H₂O)₄ for Cu²⁺ ions sensing [106].

4.2.2. Hg²⁺ Sensing

The mercury ion (Hg²⁺) has a higher affinity to nitrogen atoms and MOFs containing uncoordinated pyridyl nitrogen atoms are usually used to sense Hg²⁺ ions [107]. Yang et al. reported a robust MOF thin films [Eu₂(bqdc)₃(H₂O)(DMF)₃]·0.5DMF·H₂O (bqdc = 2,2′-biquinoline-4,4′-dicarboxylate) for Hg²⁺ ion sensing [108]. The film of [Eu₂(bqdc)₃(H₂O)(DMF)₃]·0.5DMF·H₂O with a thickness of about 10 μm is developed by electrodeposition in combination with subsequent solvothermal synthesis (Figure 17). Due to the diffusion of Hg²⁺ into the channels and coordination with the pyridyl atom on bqdc²⁻, the energy transfer from the antenna of bqdc²⁻ to Eu³⁺ is interfered, resulting in the quenching of the Eu³⁺ luminescence. This sensor can measure the concentration of Hg²⁺ in the range from 1 × 10⁻⁵ to 1 × 10⁻³ M with a detection limit of 1 × 10⁻⁸ M. Besides, the change in the photoluminescence intensity of this sensor before and after the exposure to Hg²⁺ is distinguishable even with the naked eye. In addition, the performance of film for Hg²⁺ sensing is superior to that of emulsion and powder in practicability and data reproducibility.

Some other nitrogen-containing groups are also incorporated into the MOFs for Hg²⁺ ion detection. By immobilizing melamine groups into the organic linker 4,4′,4″-s-triazine-1,3,5-triyltri-p-aminobenzoic acid (H₃TATAB), Qian and Cui et al. synthesize a lanthanide MOF Tb(TATAB)·(DMF)₄(H₂O)(MeOH)_0.5 for Hg²⁺ sensing [109]. The suitable space between multiple nitrogen atoms from triazine and imino groups is beneficial for chelating with Hg²⁺ ions, and this sensor is successfully applied to detect Hg²⁺ ions in natural water samples. Gu et al. utilize a PCN-224 containing porphyrin ring to detect Hg²⁺ in the 4-(2-hydroxyethyl)-piperazine-1-ethanesulfonic acid (HEPES) buffer solution [110]. The Hg²⁺ ions bind to the porphyrin center, providing a fluorescent quenching effect in the visible region. The fluorescence quenching shows a linear correlation in the Hg²⁺ concentration range from 0.1 to 10 μM with the calculated limit of detection (LOD) of 6 nM. In addition, amino [111], triazole unit [112], sulfone [113] and thiol [114] are introduced into MOFs for Hg²⁺ sensing.

4.2.3. Cr³⁺ Sensing

Cao et al. demonstrate the potential of Ln-BTC MOFs films to detect chromium ions (Cr³⁺) [115]. First, dense and continuous Tb-BTC, Eu-BTC and Eu_0.45Tb_0.55-BTC MOF films are fabricated directly on the unmodified zinc, FTO and ITO-substrates by the electrophoretic deposition method. The thicknesses of these three films are 55, 67, and 33.5 μm, respectively, and the film thickness can be controlled by the DC voltage. When excited with UV light at 254 nm, Tb-BTC, Eu-BTC, and Eu_0.45Tb_0.55-BTC films exhibit strong green, red, and yellow luminescence, respectively. Then, the prepared Tb-BTC film is used to detect Cr³⁺. Fluorescence titration experiments show that the Tb-BTC film could successfully detect Cr³⁺ at a concentration of 10⁻⁴ mM (0.11 ppb) with the fast response time of 10 s. In another case, Zhang et al. synthesize a stable fluorescent framework [Me₂NH₂]₄[Zn₆(qptc)₃(trz)₄]·6H₂O (H₄qptc = terphenyl-2,5,2′5′-tetracarboxylic acid, trz = 1,2,4-triazole), which exhibits selective adsorption and recyclable detection of the Cr³⁺ ion with K_SV = 4.39 × 10⁴ M⁻¹ [116].

4.2.4. CO₃²⁻ Sensing

Yang et al. fabricate a luminescent Ln-MOF-based thin film [Eu(HBPTC)(H₂O)₂]·2DMF (BPTC = benzophenone-3,3′,4,4′-tetracarboxylic) via electrodeposition for the detection of CO₃²⁻ [77]. The thin films of Eu–HBPTC are deposited at the cathode trough by a mechanism of electrochemical generation of the base in a nitrate solution. As shown in Figure 18a, the reduction of NO³⁻ causes the local increase of HO⁻ concentration, followed by the hydrolysis of benzophenone-3,3′,4,4′-tetracarboxylic dianhydride (BTDA) and the consequent growth of MOFs directly on the FTO surface. Upon the excitation at 317 nm, the Eu-HBPTC film exhibits the characteristic emission of Eu³⁺ ions. The emission intensity can be exclusively quenched by CO₃²⁻ (Figure 18b), which might be attributed to the impediment of the energy transfer between the linkers and Eu³⁺ ions. In a recent work, Yan et al. present a robust and porous Eu/Pt-MOF for the ratiometric sensing towards CO₃²⁻. With the increase of CO₃²⁻, the luminescence of Eu³⁺ is enhanced while the ligand emission is suppressed significantly [117]. The intensity ratio of two emissions linearly increases as the concentration of CO₃²⁻ with a detection limit of 0.021 μM increases. The same group further establishes an orthogonal pattern based on luminescent intensity and quantum yields of MIL-125(Ti)-AM-Eu in response to various anions [118]. The ratiometric luminescence and the quantum yields of the MOF show a one-to-one correspondence with the accommodated anions, which provides a simple identification method to recognize different anions by reading the coordinates on the pattern.

4.3. Gas Detection

Compared with the luminescent sensors in the form of powders and suspensions, film-based probes have significant advantages in gas detection. The dispersion of MOF powders into solutions is time-consuming, and the powdery samples and suspensions are hard to be recycled. In addition, the powdery samples cannot stand the blast of gas flux. Therefore, luminescent MOF film-based probe is a good choice for gas detection.

Qian and Cui et al. recently reported two indium MOF films, [(CH₃)₂NH₂][In₃O(BTC)₂(H₂O)₃]₂[In₃(BTC)₄] (CPM-5) and In₃O(OH)(H₂O)₂[BTC]₂ (MIL-100(In)), for oxygen sensing [94,119]. The CPM-5 and MIL-100(In) films are prepared by the in situ solvothermal synthesis method on ITO glass with the “twin indium source” strategy, and Tb³⁺ ions are introduced into these two films through the post-functionalization. As shown in Figure 19, the prepared films are continuous and dense with the thickness of about 2.5 μm, and the modifications barely change the structures and the morphology of the MOF films.

Both CPM-5⊃Tb³⁺ and MIL-100(In)⊃Tb³⁺ thin films exhibit the characteristic emission bands of Tb³⁺, and the luminescence of these films can be gradually quenched by the increasing pressure of O₂ (Figure 20b). Although the lanthanide ions are sensitized by the same organic ligand, the quenching efficiencies of CPM-5⊃Tb³⁺ and MIL-100(In)⊃Tb³⁺ films are about 47% and 88% at 1 atm of O₂, respectively. It might be because of different energy transfers in these two films. In CPM-5⊃Tb³⁺, Tb³⁺ ions serve as balancing cations in the pores, leading to long-distance intermolecular energy transfer, while MIL-100(In) possesses exposed carboxylate acids to form Tb-O bonds with metal ions, leading to the intramolecular energy transfer (see Figure 20a). As a result, the MIL-100(In)⊃Tb³⁺ film shows higher oxygen sensitivity (K_SV = 7.59) and shorter response/recovery time (6 and 53 s) than those of CPM-5⊃Tb³⁺ film (see Figure 20c,d).

By introducing the Pt(II)-porphyrin ligand into the frameworks, Lin’s group report the first self-calibrating oxygen probe to be utilized in living cells [120]. Two different linkers with a similar length, named H₂DBP-Pt (DBP-Pt = Pt-5,15-di(p-benzoato)porphyrin) and H₂QPDC-NH₂, (H₂QPDC-NH₂ = amino-quaterphenyldicarboxylaic acid), are successfully introduced into one NMOF. Then, Rhodamine-B isothiocyanate (RITC) is conjugated in QPDC-NH₂ linkers via thiourea bonds. The DBP-Pt ligand acts as an O₂-sensitive probe and a Rhodamine-B isothiocyanate ligand acts as an O₂-insensitive reference probe. The modified NMOF shows a linear correlation between the intensity ratio and P_O2 and is further used to probe oxygen in living cells.

MOF film-based probes for other gases, such as ammonia, sulfur dioxide, nitrobenzene (NB) and trinitrotoluene (TNT) in gas phases, and gaseous HCl, have been explored. Qian and Cui et al. prepare an MIL-124 film by the in situ synthesis method on a porous α-Al₂O₃ ceramic plate, and introduce europium ions into the film via post-synthetic modification [95]. The luminescent MOF film MIL-124@Eu³⁺ can detect ammonia based on the chemical reaction between NH₃ and the free -COOH in the framework. The same group recently reported a Eu-BDC-NH₂ film for detecting sulfur dioxide with a detection limit of 0.65 ppm [62]. Yang et al. design an electrodeposited luminescent MOF thin film [Eu₂(TDC)₃(CH₃OH)₂]·CH₃OH (Eu-TDC, TDC = thiophene-2,5-dicarboxylate) for detecting nitrobenzene vapor [121]. Cao et al. synthesize a Tb-BTC film to detect NB and TNT in the gas phase [115]. Dong et al. report a porous Cu₄I₄–MOF-based MMM for visual and luminescent detection of gaseous HCl [122].

4.4. Biomolecule Detection

4.4.1. Formaldehyde

Formaldehyde (HCHO) is widely used in construction, and furniture, particleboard and other industries. However, it is very harmful to human being and can result in watery eyes, asthma and respiratory irritation. However, some unscrupulous vendors, driven by economic interests, often add HCHO to the soaking solution to extend the keeping life of waterishlogged food products. Therefore, it is necessary to monitor them in light of their importance not only as air pollutants but also as indicators of food quality. Yang et al. recently designed a luminescent thin film of Eu-NDC@HPAN for self-calibrating formaldehyde sensing [123]. The Eu-NDC@HPAN film is fabricated on polyacrylonitrile (PAN) via a layer by the layer strategy (see Figure 21). A hydrolyzed polyacrylonitrile (HPAN) film is immersed in a Eu(NO₃)₃·6H₂O solution, causing the binding of Eu³⁺ ions to -COO on the surface of HPAN. After removing unreacted Eu³⁺ ions, the HPAN film is put into the NDC solution to make the binding between Eu³⁺ and NDC. By subsequently repeating and alternating the immersion of HPAN film in the solution of Eu(NO₃)₃·6H₂O and NDC, square Eu-NDC particles with the size of 2–4 μm grow on the surface of HPAN homogeneously (see Figure 22a,b).

Upon excitation at 360 nm, the Eu-NDC@HPAN film exhibits characteristic emission of the Eu³⁺ ion. When exposed to HCHO, the luminescence intensity of the emission at 616 nm is significantly quenched, while luminescence intensity of the emission at 453 nm becomes conspicuous, but other small molecules (propanol, acetone, DMF, H₂O MeOH, and EtOH) show weak influence (see Figure 22c). There is a linear relationship between the emission ratios (I₄₅₃/I₆₁₆) and the concentrations of HCHO from 0.05 to 1% (see Figure 22d). The Eu-NDC@HPAN film is further used to detect HCHO in an aquatic product and an HCHO vapor. These results suggest that the Eu-NDC@HPAN can be potentially applied in practical applications for the quantitative determination of HCHO.

4.4.2. Pharmaceuticals

The recognition and detection of pharmaceuticals are important in biological and environmental systems. Wang et al. recently reported a luminescent mixed-crystal Ln-MOF thin film, Eu_xTb_1-x-BTC, for the sensing of pharmaceuticals [92]. The nanocrystals Eu_xTb_1-x-BTC is first synthesized with sodium acetate as a modulator. Then, the monodisperse nanocrystals are dip-coated on ITO glass to obtain the large-scale, uniform and continuous thin film with a thickness of 4–5 μm (Figure 23a,b). Prepared films exhibit the characteristic transitions of Eu³⁺ and Tb³⁺, and different pH conditions (4–9) and different solutions (pure water, river water, saline and simulated body fluid) have little effect on the emissions. However, due to the different host–guest interactions, the emission intensity of Eu_0.1Tb_0.9-BTC film is largely dependent on the pharmaceutical molecules, such as antipyrine, benzafibrate, caffeine, clofibrate, clotetracycline, coumarin, diclofenac, fluorouracil, nalidixic acid, naproxen, sulfachinoxalin, and tetracycline. The parameter (R−R₀)/R₀ is used to fingerprint correlations between each different pharmaceutical molecule, where R₀ is the initial intensity ratio without an analyte and R is the intensity ratio in the presence of an analyte (Figure 23c). Moreover, the Eu_0.1Tb_0.9-BTC film emits different guest-dependent light colors, which can be distinguished by the naked eye (Figure 23d).

Coumarin and caffeine are selected as target compounds to investigate the quantitative relationship between the concentration and intensity ratio of Eu_0.1Tb_0.9-BTC. As the concentration increases, the (R − R₀)/R₀ of coumarin increases linearly with a slope of about 0.0276 ± 0.0006, while the (R − R₀)/R₀ of caffeine decreases linearly with a slope of −0.0045 ± 0.002. The values of (R − R₀)/R₀ obtained from simulated samples are basically consistent with the detection curves, indicating that the Eu_0.1Tb_0.9-BTC film is a luminescent sensor candidate in practical applications.

4.4.3. Nitrofuran Antibiotics

Nitrofuran antibiotics (NFAs) have effective therapeutic value for the treatment of protozoan and bacterial infections in human and prevent the infection of intestinal tract bacteria in food-producing animals. However, due to the mutagenicity and carcinogenicity, NFAs have been banned in the United States, China, and most other countries. Development of rapid and effective methods for the detection of NFAs is very necessary on ecosystem and human health. Recently, Yang et al. fabricated two MOF films [Eu₂(BCA)₃(H₂O)(DMF)₃]·0.5DMF·H₂O (Eu-BCA, BCA = 2,2′-biquinoline-4,4′-dicarboxylate) and [Tb₂(AIP)₂(H₂O)₁₀]·(AIP)·4H₂O (Tb-AIP, AIP = 5-aminoisophthalate) for NFA detection [124,125].

The Eu-BCA film is coated by vertically inserting the Co₃O₄ nanowire-coated stainless steel wire mesh (SSWM) into the MOF precursor solution [124]. When the bare SSWM is used directly, the film cannot be formed on the SSWM. These Co₃O₄ motifs act as anchors and nucleation centers to fix the MOF crystals on every stainless steel wire firmly. The concentration of MOF precursor solution has a significant influence on the resulting films. Relatively low concentrations of precursor solution (0.005 M and 0.01 M) lead to some scattered MOF crystal blocks piled up on the modified SSWM. With the increasing concentrations to 0.015 M and 0.02 M, a continuous and compact Eu-BCA thin-film is formed on the substrate (Figure 24).

The Eu-BCA film exhibits the characteristic emission of Eu³⁺ when excited with UV light, which is dramatically quenched by nitrofurans antibiotics nitrofurazone (NFZ) and nitrofurantoin (NFT). The K_sv value are 2.2 × 10⁻⁴ M⁻¹ for NFZ and 1.6 × 10⁻⁴ M⁻¹ for NFT. The corresponding limits of detection for NFZ and NFT are estimated to be 0.21 and 0.16 μM, respectively. The Eu-BCA film can selectively detect NFAs even in the presence of a high concentration of other antibiotics, such as metronidazole (MDZ), dimetridazole (DTZ), sulfadiazine (SDZ), sulfamethazine (SMZ), chloramphenicol (CAP), thiamphenicol (THI), and penicillin (PCL) (Figure 25). Further, this thin film can detect NFAs in real samples, and can also be recycled.

The Tb-AIP film is fabricated by the MMM method with poly(methyl methacrylate) (PMMA) as the polymer and Tb-AIP as the fillers (Figure 26) [125]. Tb-AIP MOF powder fillers are added to the PMMA chloroform solution and then ultrasonically dispersed in ice water for 30 min to get PMMA-MOF ink. The luminescent MMMs are formed by dropping the above ink on slide glasses, followed by drying in an oven overnight. The freestanding luminescent sensor is obtained by peeling off the MMMs from slide glass.

Upon excitation at 360 nm, the emission spectrum of Tb-AIP MMMs exhibits four characteristic transitions of the Tb³⁺ ions. Tb-AIP MMMs can selectively and sensitively detect NFZ and NFT via the inner filter effect (IFE). Other common antibiotics, metal ions and anions have little interference with the detective results. The limits of detection for NFT and NFZ are 0.30 and 0.35 μM, respectively.

5. Conclusions and Outlook

Based on the above discussion, it is obvious that luminescent MOF thin films have received tremendous attention in a wider range of applications in biosensing. Various methods of assembling the luminescent MOF thin films are the foundation of these achievements. However, deposited films from solvothermal mother solutions are out of universality and the obtained films are often discontinuous. Preparing highly oriented single crystal and polycrystalline MOF films remains a significant challenge. Owing to the facile operation and general applicability, the electrochemical synthesis and drop-casting method are increasingly employed. However, they suffer from some inborn weaknesses including poor uniformity and adhesion, and their sensing performances are significantly influenced by the film thickness. In addition, in the MMMs, the MOF particles are encapsulated by the organic polymer and cannot sufficiently interact with the analytes, which loses the porosity of MOFs and leads to poor sensitivity.

The development of luminescent MOF film-based biosensors yields significant advancements in environmental monitoring, and biomedical diagnostics. However, the study of luminescent MOF film-based biosensors is a relatively new field and more research work is needed. Current challenges in the application of luminescent MOF films as biosensors include reversible binding to analytes, which would realize continuous detection. To achieve this goal, advanced structural design based on a thorough investigation of the structure–property relationship of MOFs is required. The fluorescent efficiency of MOFs still restrains the LOD in biomedical sensing fields, and development of more efficient luminescent MOF films can further increase the detection limit. In addition, most of the MOF film sensors are based on the intensity change of single emission, which is greatly affected by the concentration of probe, excitation power, and the drifts of the optoelectronic system. The strategy utilizing the ratio between the intensities of two transitions of the same probe has been established and thus opened a new strategy for high-accuracy luminescent sensors. Moreover, the development of a new multi-dimensional sensing strategy utilizing intensity, life, wavelength, and polarization could be an attractive future direction for improving sensor accuracy.

There are numerous essential metals (e.g., Cr, Mn, Co, Ni, Mo) and toxic metals (e.g., Cd, Hg, Pb) to be detected and monitored in the biomedical field. In this regard, development of new MOF sensors will be attractive in the future. Research on biomedical sensing applications of MOF thin films is gaining momentum and this emerging new class of materials is likely to replace the traditional film materials in the future. Systematic investigations concerning critical issues, such as the stability of MOFs under humid environment and toxicology, will be necessary and speed up the development of luminescent MOF films. Besides, further efforts should focus on the preparation of biologically compatible luminescent MOF films and the integration of different functions, such as luminescence sensing, imaging, molecular targeting, and so on. More research effort is needed to prepare MOF films that meet different testing requirements, and there is still a long way to go before these materials can be industrialized and commercialized.