key: cord-0737409-lewyhiek
authors: Wang, Ying; Hu, Yaqin; He, Qunye; Yan, Jianhua; Xiong, Hongjie; Wen, Nachuan; Cai, Shundong; Peng, Dongming; Liu, Yanfei; Liu, Zhenbao
title: Metal-organic frameworks for virus detection
date: 2020-09-14
journal: Biosens Bioelectron
DOI: 10.1016/j.bios.2020.112604
sha: a2d9e84af63f6fb2f64b6f17e491f12239fd0ffa
doc_id: 737409
cord_uid: lewyhiek

Virus severely endangers human life and health, the detection of virus is essential for the prevention and treatment of associated disease. Metal-organic framework (MOF), a novel hybrid porous material which bridged by the metal clusters and organic linkers, has become a promising biosensor platform for virus detection due to its outstanding properties including high surface area, adjustable pore size, ligands modification, etc. However, the MOF-based sensing platforms for virus detection is rarely summarized. This review systematically divided the detection platforms into nucleic acid and immunological (antigen and antibody) detection and the underlying sensing mechanisms were interpreted. The nucleic acid sensing was discussed based on the properties of MOF (such as metal ion, functional groups, geometry structure, size, porosity, stability, etc.), revealing the relationship between the sensing performance and properties of MOF. Moreover, antibodies sensing based on the fluorescent detection and antigens sensing based on molecular imprinting or electrochemical immunoassay were highlighted. Furthermore, the remaining challenges and future development of MOF for virus detection were further discussed and proposed. This review will provide valuable references for construction of sophisticated sensing platform for the detection of virus, especially 2019 coronavirus.

The outbreak of the arisen viruses, such as human immunodeficiency virus (HIV) , Ebolaviruses (Qin et al. 2016; Yang et al. 2015) , Zika virus , and Dengue virus , as well as the ongoing novel coronavirus (SARS-CoV-2) (Petrosillo et al. 2020) , raised tremendous challenges to public health. The Table 1 . The comparison of MOF with other materials: characteristics, advantages and disadvantages.

Characteristics Nucleic acid detection Immunological detection Refs.

Disadvantages Advantages Disadvantages

(1) 2D planar structure;

(2) Electric conductable;

(3) Thermal conductable;

(4) High surface area (2630 m 2 /g); (5) Chemical stable.

(1) Adsoption of probs;

(2) Fluorescent quencher;

(3) Low cost;

(4) Quick detection

(1) Preparation of single-layer structure is difficult;

(2) Mass production is limited;

(3) Functional groups is limited;

(4) The fluorescence recovery is relative difficult.

(1) Electrochemical sigal;

(2) Signal amplification and label free biosensing;

(3) Low cost.

(1) Lack of modification sites;

(2) Limited material production. (Afsahi et al. 2018) Graphene oxide

(1) 2D planar structure;

(2) Electric conductable;

(3) Thermal conductable; (4) High surface area; (5) Oxygen-rich functional groups (-OH, -COOH).

(1) Adsorption of probs;

(2) Fluorescent quencher;

(3) Low cost.

(4) Quick detection

(1) Detection stability;

(2) Detection Reproducibility;

(3) False positive signal (4) The specificity and sensitivity of the aptamer (1) Rich in hydroxyl and carboxyl groups for probe linkage;

(2) Provide active site for bioreceptor;

(3) Signal amplification (4) Label free biosensing.

(1) Complicated operation;

(2) Interference by functional groups. (Krishnan et al. 2019; Wei 2013; Zhao et al. 2018 )

(1) Superparamagnetism;

(2) Convenient separation;

(3) Large surface area.

(1) The reproducibility and stability are improved;

(2) The adsorption capacity of sensitive molecules are improved.

(3) Low cost.

(1) Low noise background (2) Sensitivity and selectivity.

(1) Facilitates enzyme immobilization;

(2) Signal amplification;

(3) Erichment of substances.

(1) Stability need to be improved;

(2) Easy to aggregate. (Pastucha et al. 2019; Tiwari et al. 2015; Zheng et al. 2020 )

(1) Uniform and controllable particle size; (2) High surface area;

(3) Easily modifiable surface.

(1) Sensitivity;

(2) Selectivity;

(3) Non-toxic and high biological affinity. (4) Low cost. (5) Quick detection (1) Large size;

(2) Poor permeability;

(3) High cost and immunogenicity; (4) High background fluorescence.

(1) Signals Amplification;

(2) Low detection limit (fg/mL);

(3) High stability (4) Easy to synthesis and surface modification.

(1) Difficult to preparate;

(2) Easy to aggregate.

(Kholafazad Kordasht et al. 2020; Luo et al. 2020a; Vandghanooni et al. 2020; Zhou et al. 2014) (1) Biocompatible;

(1) High sensitivity;

(1) Difficult to (1) Electron (1) Easily to (Brunner and Kraemer J o u r n a l P r e -p r o o f

(2) Wide size distribution (1-150 nm);

(3) Photoelectric effect with size and morphology dependence;

(4) Strong covalent bond with thiol; (5) Electric conductable.

(2) Rapid response;

(3) Rich surface active sites; (4) Strong adsorption. metabolize;

(2) Expensive reagents;

(3) The stability of gold nanosol is affected by environmental factors.

(4) non-specific conductable;

(2) Affinity to immunological molecules;

(3) High sensitivity; (4) Non-specific adsorption; (5) Regeneration. aggregate in the electrolyte solution.

2004; Kumar et al. 2015; Steinmetz et al. 2019 )

(1) Electric conductable;

(2) High surface area;

(3) Rich in oxygen functional groups at the end and the side of wall for ligand immobilizing;

(1) Easy to functionalization;

(2) Rich in oxygen functional groups for immobilizing;

(3) Quick detection.

(1) The fluorescence was difficult to recover;

(2) Unmodified CN has poor dispersion:

The retouching process is complicated.

(1) Electronic mobility and biocompatibility;

(2) High sensitivity (3) Significant signal amplification;

(4) Amplify the signal and provide label free sensing.

(1) Poor dispersion;

(2) Lack of uniform length;

(3) Impurities and catalysts are difficult to remove. Wei 2013) Metal organic framework (MOF)

(1) Large specific surface area (10400 m 2 /g);

(2) High porosity (90%);

(3) Tunable pore sizes (from micropore to mesopore); (4) High loading efficiency; (5) Easy functionalization and postsynthetic modification; (6) Biocompatible and biodegradable.

(1) Quick detection;

(2) Adsorption and quenching the fluorophore labelled probes;

(3) Fuorescence quenching ability can be adjusted by ligands or functional groups; (4) Selectivity based on size discrimination capacity.

(5) Low cost.

(1) Unstable in acid;

(2) Detection limit in the range from pM to nM.

(1)

Post-synthesis modification, specific molecular recognition;

(2) Excellent adsorption performance, and easy molecular enrichment;

(3) Efficient molecular immobilization.

(1) The electric conductivity is poor;

(2) Poor stability in solvents. (Furukawa et al. 2010; Wei 2013; Zhou et al. 2020) J o u r n a l P r e -p r o o f Firstly, fluorophore labelled probes could be adsorbed on MOF through various interactions including electrostatic interactions, hydrogen bonding, and π-π stacking with negatively charged aromatic nucleic acid sequences ). Then, the fluorescence of dyes on probes could be quenched by metal ions, such as Cu 2+ (Liu and Lu 2007) , Fe 3+ (Tian et al. 2015) , Zn 2+ (Zhao et al. 2016a) , Dy 3+ (Qin et al. 2016 ), or coplanar structure (Zhao et al. 2016a ) via the process of fluorescence resonance energy transfer (FRET) (de Silva et al. 1997 ). Subsequently, the specific hybridization of probe DNA (P-DNA) with target virus-related nucleic acids sequences formed stable rigid double-stranded DNA , hybrid DNA/RNA duplexes (Cheatham and Kollman 1997) or triple-stranded DNA structure Wang et al. 2014) , and subsequently be released from the surface of MOF due to their low affinity toward nanomaterials, leading to the recovery of fluorescence. The target sequences of virus and fluorescent dyes labeled complementary probe DNA were summarized in Table 2 . MOF could bind DNA in a variety of ways, mainly including covalent, electrostatic, insert, or groove bonding (Jannesari et al. 2015; Liu et al. 2020b; Yang et al. 2019b) (Fig. 3C) .

Especially, the stable rigid triplex structure can be formed through hydrogen bonding (Lesnik and Freier 1995) , due to the A-T and G-C base pair could bind the T base and C base, respectively Wang et al. 2014) , the P-DNA with reverse Hoogsteen base pairs in the major groove formed the T·A·T and C + ·G·C triplex structures (Moser and Dervan 1987; Sklenár̆ and Felgon 1990) . Nucleic acids sensing platforms are equipped with the ability to distinguish mismatched and complementary sequences ). In the presence of base pair mutated ds-DNA, the fluorescent will not obviously recover owing to the unstable existence of the T·A·T and C + ·G·C triplex structures ).

J o u r n a l P r e -p r o o f HIV-1 ss-DNA 5 '-GCT AGA GAT TTT CCA CAC TGACT-3'  5'-FAM--CATGTGTCCAGCTGATTGCC-3'  (Pan et al. 2018) HIV-1 ds-DNA 5'-CGAGTTAAGAAGAAAAAAGATTGAGC-3' /5'-GCTCAATCTTTTTTCTTCTTAACTCG-3' 5'-FAM-TTCTTCTTTTTTCT-3' Yang et al. 2015) SUDV RNA 5'-GAUGAGGACAAACUUUUUAA-3' 5'-FAM-TTAAAAAGTTTGTCCTCATC-3' Yang et al. 2015) Ebolavirus Ebolavirus conserved sequence of RNA (T 1 ) 5'-GGCAAUCAGUUGGACACAUG-3'

The complementary sequence for T 1 as probe DNA-1 (P-DNA-1) 5'-CATGTGTCCAACTGATTGCC-FAM-3' Ebolavirus-encoded miRNA-like fragment (T 2 ) 5'-UGCUUCAUUAGCACUUUGGGGC-3'

The complementary sequence for T 2 as probe DNA-2 (P-DNA-2) 5'-GCCCCAAAGTGCTAATGAAGCA-ROX-3' Zika virus (ZIKV) 5'-ACUUGGGUGGAUAGGUAGUCCAUGU-3' 5'-TAMRA-ACATGGACTACCTATCCACCCAAGT-3' ) Dengue virus (DENV) 5'-UGGUGCUGUUGAAUCAACAGGUUCU-3' 5'-FAM-AGAACCTGTTGATTCAACAGCACCA-3' ) Hepatitis B virus (HBV) 5'-TTGTCCTGGCTATCGCTGGATGTGTCTGC-3' 5'-TATATAGCAGACACATCCAGCGATAGCCAGGACAATATATA-FAM-3' (Ye et al. 2014) 

Nucleic acid detection is a dominant diagnostic method in window period (Fig. 4) and it's of great significance for effective prevent virus proliferation in clinical treatment of viruses. Many viruses including ss-DNA (such as HIV ss-DNA Zhu et al. 2013) , respiratory syncytial virus (Guo et al. 2015) ), ds-DNA (such as HIV ds-DNA ), ss-RNA (such as Ebolaviruses (Qin et al. 2016) , Sudan virus (Yang et al. 2015) , Zika virus , Dengue virus ), have been successfully detected by MOF based sensing platforms. In this section, nucleic acid detection is divided into single-virus detection and multi-virus detection. 

The properties of MOF, such as metal ion, functional groups, geometry structure, size, porosity, stability, etc, have important influences on the sensing performance.

The efficient quenching ability of metal ions is a critical factor. Unpaired transition-metal ions, such as Cu 2+ (Liu and Lu 2007) , Fe 3+ (Tian et al. 2015) , Zn 2+ (Zhao et al. 2016a) , Dy 3+ (Qin et al. 2016) , Zr 4+ (Zhang et al. 2014a) , etc, can serve as efficient quenchers which possess high electron-accepting ability serving as electron-consuming pools (de Silva et al. 1997) and effectively intercalate into the base pairs of P-DNA to achieve a π-electrostatic interaction with the phosphate backbone, then the FRET process from fluorescent dyes to unsaturated metal ions was subsequently triggered J o u r n a l P r e -p r o o f (Liu and Lu 2007; Xie et al. 2019) . Although these metal ions have inherent higher adsorption and stronger quenching capabilities than MOF, they are not suitable as viral nucleic acid detection platform, mainly because the strong adsorption between metal ions and the P-DNA would lead to a slow fluorescence recover or even no recover Xie et al. 2019; Zhu et al. 2013) . While, the quenching ability can be adjusted by ligands or functional groups.

Copper ion is generally considered to be an outstanding quencher with the Q E being 87.42% (Liu and Lu 2007; , causing Cu-MOFs to be widely studied for nucleic acid detection. Cu-based MOF showed excellent quenching ability (de Silva et al. 1997). The N, N'-bis(2-hydroxy-ethyl)dithiooxamidatocopper(II) [Cu(H 2 dtoa)] n is the first MOF based platform to detect biomolecules (HIV ss-DNA) with the Q E being 84.53% , owing to its two-dimensional (2D) planer structure linked by intermolecular hydrogen bonds, and the metal center Cu 2+ ion. Moreover, the H 2 dtoaCu was consist of Cu 2+ with d 9 electronic structure and the conjugated π-π stacking systems of the dithiooxamide bridging ligand, which strongly adsorbed P-DNA by strongly chemisorb and quenched the fluorescence ). Zhu et al. confirmed that [Cu(H 2 dtoa)] n could effectively detect HIV-1 ssDNA sequences with the detection limit of 3 nM and a good linear relationship in the range of 5-100 nM (Fig. 5A ). Chen and coworkers ) utilized [Cu(H 2 dtoa)] n as a sensing platform to detect HIV ds-DNA in vitro. Unlike forming a rigid dsDNA structure, the FAM-labeled triplex-forming oligonucleotide (TFO) was recognized by the target HIV ds-DNA forming a rigid triplex structure through Hoogsteen hydrogen bonds, leading to the recovery of fluorescence ( Fig. 5B) . The detection platform showed a low detection limit of 1.3 nM and good selectivity, which was lower than that based on the electrochemical-DNA platform or graphene oxide sensor. Zn-based MOF is widely studied in the field of biomedicine due to its good biocompatibility and inherent fluorescence quenching ability of Zn 2+ (Zhao et al. 2016a ). Zeolitic imidazolate framework-8 (ZIF-8) which consists of 2-methylimidazole and Zn 2+ is one of the most frequently used Zn-based MOFs in biomedicine, and it holds a sodalite (SOD)-type structure and large pores of 11.6 Å. ZIF-8 is a good fluorescence quenching material, not only due to the inherent fluorescence quenching ability of Zn 2+ (Q E %=81.5%) but also its functional bridge ligands with Compared with Cu 2+ (87.42%) (Liu and Lu 2007; Zhu et al. 2013) and Zn 2+ (Q E %=81.5%) , the Dy 3+ also has excellent fluorescence quenching ability with Q E % being 85% (Qin et al. 2016) . Moreover, the P-DNA can be adsorbed on the Dy-MOF through hydrogen bonding, π-π stacking and electrostatic interactions. Its fluorescence quenching method is similar to Cu 2+ (Liu and Lu 2007) which decreased the background fluorescence, leading to enhanced sensitivity (Qin et al. 2016) . Many Cr-based MOFs (such as MIL-100 (Cr) (Ferey et al. 2004 ) and MIL-101 (Cr) (Ferey et al. 2005) , MIL-53 (Cr) (Serre et al. 2002) , MIL-88(B) and MIL-88(D) (Surblé et al. 2006) ) which mainly belong to the carboxyl-rich materials of institute Lavoisier family (MIL-n) were synthesized by Férey and coworkers.

The MIL-101 (Cr) (Ferey et al. 2005 ) has ultra-large pore characteristics (29 Å-34 Å) and high specific surface area (5900 m 2 /g). Moreover, MIL-101 possesses good adorption of dyes and low-background signal. However, due to the non-specific adsorption, the detection sensitivity was reduced (Brunner and Kraemer 2004; Lee et al. 2008 ). Fang et al. (Fang et al. 2014 ) designed a low background signal platform for decreasing the high background fluorescence of DNA-intercalating dyes/probe DNA complex (Fig. 7A) . The SG/probe DNA complex could be strongly adsorbed by MIL-101 through electrostatic interactions and π-π stacking, leading to the greatly quenching of SG dye. Moreover, the SG dye could insert into dsDNA via minor groove binding, which further enhanced the fluorescence of SG dye and improved the signal-to-background ratio (~8-fold). The HIV dsDNA could be partly adsorbed by MIL-101 leading to the quenching of fluorescence, however, the impact was obviously weaker than that of SG/ssDNA, so the ratio of J o u r n a l P r e -p r o o f signal-to-background could be improved. The detection limit was confirmed to be 73 pM, it was much lower than that of the sensing platform based on the graphene oxide and carbon nanotube.

Fe(III) centers have high electron-accepting ability serving as electron-consuming pools to improve the electronic transfer, which greatly improved the quenching efficiency. By integrating the quenching ability of Fe(III) and the π-conjugated electron structure of benzene-containing molecule, Tian et al. (Tian et al. 2015) developed MIL-88B which consisted of π-conjugated 1,4-benzenedicarboxylic acid (H 2 BDC) ligand and Fe(III) center for the detection of HIV ss-DNA. The quenching efficiency (Q E ) of MIL-88 reached nearly 100% and recovery efficiency (R E ) of 84% and the formation and release of ds-DNA from MOF were also very fast (3 min). On the one hand, the rich micropores on the MIL-88B surface would increase its adsorption capacity and the fluorescence quenching ability of Fe(III). On the other hand, the non-π-conjugated Fe(III) failed to provide continuous interaction sites through π-stacking effects, thus weakening the binding and leading to the quick release and high recovery efficiency. The sensor exhibited a low limit detection of 10 pM and a linear range from 0 to 5 nM.

Besides, Zr-based MOFs are generally highly stable owing to the capacity of the inner Zr 6 -cluster to rearrange reversibly on addition or removal of μ 3 -OH groups, and the combination of strong Zr-O bonds without any changes after connecting carboxylates (Cavka et al. 2008) . Lanthanides (La) metal ions are also developed as sensing platforms.

Lanthanide is a good candidate for sensing virus owing to their high coordination number and high lipophilicity to make structurally intriguing and water-stable MOFs. The fluorescence quenching properties (79.8 ± 6.4%) of La 3+ endow La-MOF with applications for detecting Sudan virus , the performance was consistent with other transition metals (Yang et al. 2015; Zhu et al. 2013) . Besides, indium is also favored due to its integrating cationic functionality (NMe 3+ ) and aromaticity, moreover, it is non-toxicity ). However, nobel metals MOF are rarely synthesized and involved in virus detection, which could be attributed to the disordered state of the nobel metals embedded in MOF materials, the spatial and size distribution of nobel metal nanoparticles cannot be controlled during the synthesis process.

For nucleic acid sensing, the performance can be adjusted by changing various interactions owning to the adsorption of probes mainly relys on various interactions. Functional groups can be introduced into the sensing platform to act as a source for increasing potential function in the detection of viral nucleic acids, such as electrostatic interactions, hydrogen bonding, and π-π stacking with negatively charged nucleic acid sequences (Wei 2013) . The functional groups of MOFs have outstanding merits for sensors (Zhang et al. 2014a ): (1) Enhanced adsorption of P-DNA through various interactions;

(2) Enhanced selectivity and recognition by the interaction of analyte and functional groups (Zhang et al. 2014a) .

From the perspective of electrostatic interaction, the cationic functionality (such as NMe 3+ ) can be introducd into the ligands to constitute electrostatic interactions with the anion DNA nucleobases. Furthermore, the cationic function and aromaticity can be integrated into MOF to simultaneously achieve the interaction of the electrostatic interaction and π-π stacking. For instance, the cationic quaternary amines-decorated metal lophthalocyanines, involving -SCH 2 CH 2 N(Me) 3 , -OCH 2 CH 2 N(Me) 3 and -SH 2 CH 2 N(Et) 3 , which illustrated good binding affinities for H-telo quadruplexes (Ren et al. 2007 ). Based on this strategy, Li and coworker ) reported a set of indium(III)-based In- Tab to be adopted as a source of electrostatic interaction for nucleic acid detection owing to the protonated ligand and the charge reverses in an acidic environment. Besides, designing charged MOF is also an excellent idea (Zhao et al. 2019c) in addition to introduce functional groups (Ali Akbar Razavi and Morsali 2019). Enhanced π-π interactions can be achieved by introducing ligands or auxiliary ligands in a planar structure, or synthesizing 2D multifunctional MOF nanosheets (Li et al. 2019c) . As for hydrogen bonding, some functional groups can be applied, such as -OH and -NH 2 (Zhao et al. 2019a) , quaternary ammonium groups Yang et al. 2017 ), N-carboxymethyl-3,5-dicarboxylpyridinium bromide (H 3 CmdcpBr) (Sun et al. 2017; Yang et al. 2015) . And the structural matching between the probe DNA and MOFs should be taken into account in future MOF design (Sun et al. 2017 ).

Moreover, the functional MOF might be promising for solving the problem of the high "false negative" rates which is

inevitably ( grafting functional groups (such as -NH 2 and -NO 2 ), the pore volume and Brunauer-Emmett-Teller (BET) surface area reduced due to the adding of organic functional groups (Li et al. 2019d) . Grafting functional groups with polar, H-donor, alkaline will lead to a significant increase of payloads, whereas, hydrogen bonds might be related to the releasing process (Cunha et al. 2013) . The relationship between ligand structure and functions/interaction has been summarized in Table 3 .

J o u r n a l P r e -p r o o f Table 3 . Relationships between the structures of ligands and the properties of MOF.

Interactions/Functions Ligands/ functional groups/ structures Refs.

Negatively charged phenolic hydroxyl and carboxyl groups on FAM; negatively charged phosphate backbones of P-DNA; cationic quaternary amines-decorated metal phthalocyanines, involving -SCH 2 CH 2 N(Me) 3 , -OCH 2 CH 2 N(Me) 3 and-SH 2 CH 2 N(Et) 3 , positively charged SYBR Green I (SGI), The geometric structure have an important impact on quenching performance. The quenching performance of planar MOFs are better than stereoscopic MOFs owing to the planar structure holds highly exposed surfaces, abundant functional groups, metal ions (positive charge) and large conjugated system (Zhao et al. 2016a ) and the planar ligands might reduce the steric hindrance of the MOFs leading to the enhanced probe adsorption and hybridization.

The planar and aromatic ring structure are more beneficial for nucleic acids sensing, which is mainly achieved by affecting various interactions. Zhao et al. (Zhao et al. 2016a ) synthesized a novel series of water-stable zinc (II)-based zwitterionic MOFs for selective and sensitive sensing of HIV-1 ds-DNA sequences with the detection limit of 10 pM (S/N=3). Among them, complex 2 which consists of Zn 2+ and Cbdcp 2exhibited the best quenching performance due to its appropriate pore size and planar structure. For complex 1, the weak quenching ability was attributed to the anion carboxylate group on the 1D zigzag chain since it might form electrostatic repulsion with the DNA. While for complex 3

and 5, the relatively small pore size (5.4×0.8 Å) of them was not suitable for a long chain of FAM-labeled P-DNA (9.4 Å), resulting in the low adsorption of P-DNA. Considering the formed 2D network structures were not coplanar, complex 4 and 6 were also not suitable. (Fig. 6A) In contrast, complex 2 equipped with the 2D plane structure, abundant carboxylic acid groups, functional aromatic rings, positively charged pyridinium, and Zn 2+ cation centers (+11.3 mV), might provide hydrogen bonding, electrostatic interaction and π-π stacking with P-DNA to promote the quenching of fluorescence through a FRET process. (Fig. 6B ) The quenching efficiency of MOF was not only affected by metal ions but also affected by the structural characteristics. The 2D layer structure was more effective for the fluorescence quenching in HIV-1 ds-DNA detection than those of the 1D chain and the 1D/2D co-crystal (Zhao et al. 2016b ). The 2D

layer net structural contributed to their biological performances even compositional similarity of Cu-MOF, the results were consistent with Zn-based MOF (Zhao et al. 2016a ).

J o u r n a l P r e -p r o o f Compared with coplanar structure, 3D MOFs with large surface areas and high porosity can also achieve successful detection of longer nucleic acid sequences by designing longer carboxylate ligands loaded quaternary ammonium centers.

From the perspective of the structure of MOF, the multidentate carboxylate ligands with sp 3 methylene groups generally reduce the symmetry of ligands including H3CmdcpBr (Qin et al. 2016 ). However, the irregularity of the ligands can be effectively compensated to make up high-dimensional networks with larger surfaces or larger pore size when low-symmetry ligands are combined with high coordination number La ions. Yang and coworkers found that the quenching efficiencies of {[La 4 (Cmdcp) 6 (H 2 O) 9 ]} n (1, 3D) (70.2 ± 5.3%) was higher in comparison to layer {[La 2 (Cbdcp) 3 (H 2 O) 10 ]} n (2, 2D) (57.3 ± 5.3%), due to the edges channel of 1 was decorated by positively charged quaternary ammonium nitrogen atoms which could provide stronger electrostatic interaction with probe DNA than 2 with 2D layer structure, aromatic rings, free carboxylates, and positively charged pyridinium. The fluorescence was recovery via the formation of the DNA@RNA duplex, in which the larger pore size of 1 and the large layer of 2 was critical. These sensing platforms exhibited high specificity with detection limits of 112 pM and 67 pM and discriminated single-base mismatch SUDV RNA sequences.

However, many synthesized MOFs with moderate quenching efficiency are time-consuming. To address this issues, many π-conjugated ancillary ligands including 2,2'-bipyridine (bipy) (Sun et al. 2017 ), 1,10-phenanthroline (phen) (Sun (2) detected HIV-1 ds-DNA with good selectivity and sensitivity, which should be mainly attributed to its 1D chain structure carrying aromatic bipy ancillary. Therefore, the structural matching between P-DNA and MOFs is a critical feature for improving quenching efficiency.

Besides , MIL-101 promoted the dsDNA to rotate faster and irregular, resulting in a smaller FA of dsDNA (r 2 ). Thus, the FA valve ∆r (∆r=r 1 -r 2 ) was dually amplified (Fig. 7B) . Moreover, the circular dichroism confirmed that the introduction of MIL-101 prevented the decomposition of the structure of DNA.

J o u r n a l P r e -p r o o f 

The pore size of MOF can be rationally tailored from micropore to mesopore by modulating the length of the ligand, which is the unique advantage of MOF (Deng et al. 2012; Eddaoudi et al. 2002) . 

The pore size can adjust the sensing time while improving the selectivity. Yang and coworkers (Yang et al. 2015) synthesized a water-stable, highly sensitive, cost-effective and macroporous 3D [Cu 3 (Cmdcp) 2 (dps) 4 (H 2 O) 4 (SO 4 )] n to detect Sudan ebolavirus (SUDV) RNA sequences with detection limits of 73 pM (Fig. 7C) . The SUDV RNA sequences formed a stable DNA@RNA hybrid duplex with FAM-marked complementary sequences, causing fluorescence recovery (Guo et al. 2015) . However, the fluorescence recovery of the P Table 4 . 

Compared with single viral nucleic acid detection, multi-viral nucleic acid detection can achieve simultaneous detection of multiple nucleic acids based on fluorescent biosensing technology, which saves the detection time and improves the diagnostic accuracy. Some studies show that simultaneous detection can provide a lower detection limit The cross-reaction is an important issue worthy of investigation when assessing the reliability and specificity of multiplex detection (Ye et al. 2014 ). Chen and coworkers (Xie et al. 2019) studied the cross-reaction between three conserved RNA sequences of the Zika virus on the MOF-based sensing platform (Fig. 8B, 8C and 8D) , no cross-reaction was observed during the simultaneously detection of three conserved RNA sequences of Zika virus by using 2D

water-stable Cu-based MOF of [Cu(Dcbb)(bipy)(OH)] n with low detection limits of 0.56 ± 0.02, 0.16 ± 0.04, and 0.19 ± 0.05 nM. Three conserved sequences T 1 , T 2 , T 3 triggered the fluorescence recovery, which proved that simultaneous detection did not interfere with each other. The detection sensitive was related to the structural characteristics of MOF.

The positively charged MOF (+11.7 mV) provided possibilities for electrostatically interacting with negatively charged P-DNA. The conjugate structures of H 2 DcbbBr and bipy in ligands were benefited for π-π stacking with the nucleobases.

And the uncoordinated N atoms and carboxylates were also hydrogen-bonding acceptors for promoting interactions with the P-DNA. , which was related to its unique structural flexibility, and conjugate structure of benzene, pyridinium and bipy rings, as well as varied hydrogen bond acceptor of uncoordinated N atoms and carboxylates.

Overall, fluorescence sensing is the main technology for detecting viral nucleic acid. The sensing performance (such as selectivity, sensitivity, stability, detection time etc.) is related to the structure/property of MOF (such as metal ion, particle size, functional group of ligand, pore, geometric structure, stability etc). The transition-metal ions, coplanar structure, functional group/ ligand, small size can improve the selectivity by adjusting the interaction between the nucleic acids and MOF, while the porosity has a positive effect on the improvement of selectivity. Compared with single viral nucleic acid detection, multiple viral nucleic acid detection can achieve simultaneous detection of multiple nucleic acids based on fluorescent biosensing technology, which saves the detection time and improves the diagnostic accuracy ( Table 5) .

Research proves that MOFs can not only detect two or even three viruses simultaneously, but also avoid cross-reaction and have a shorter detection time, which are related to the unique structure of MOF ).

J o u r n a l P r e -p r o o f (1) High selectivity;

(2) No interference; (3) Low detection limit; (4) Early detection (window period); (5) High specificity.

(1) Time-consuming;

(2) Complicated Sample preparation;

(3) Expensive; (4) Unsuitable for extensive and preliminary detection. (Guo et al. 2015; Qin et al. 2016; Tian et al. 2015; Zhang et al. 2014a; Zhu et al. 2013 (1) Repeated sample preparation is unneeded;

(2) Time-saving;

(3) Selective; (4) Accurate; (5) Early detection (window period).

(1) Iterference;

(2) Real samples application is challenging. Qiu et al. 2018; Xie et al. 2018; Xie et al. 2019; Yang et al. 2015; Ye et al. 2014) Immunological detection

Japanese encephalitis virus; Hepatitis A virus; HIV p24; ALV-J MIL-101, Ce(ff) coordination polymer, eZIF, etc.

(1) Selective;

(2) Sensitive;

(3) Low cost, fast and accurate; (4) Stable and reproducible;

(1) Unsuitable for the determination of hapten and small molecule monovalent antigen;

(2) Hard to find imprint layer and functional monomers. (1) Sensitivity;

(2) Fast and time-saving;

(3) Cracking and stable periods detection;

(4) Simple operation; (5) Cost-effective.

(1) The detection limit is in the range from pM to nM;

(2) Accuracy is lower than nucleic acid detection. J o u r n a l P r e -p r o o f

Although nucleic acid detection is the "gold standard" for diagnosis, it suffers from the "false negatives" results, risk of contamination, high cost, and long time for real-time fluorescent RT-PCR detection. The immunological detection method, which is based on the specific binding of antigen and antibody, has the advantages of simple operation, short detection time, and is very suitable for on-site detection. The MOF-based virus immunological detection can be divided into two categories: antigen-based detection and antibody-based detection.

Antigen can stimulate the immune response to produce antibodies, mainly including the proteins on the virus surface (such as the capsid protein p24 of HIV ). Considering the high infectivity and pathogenicity of viruses, the vaccines which have been attenuated or inactivated but maintain the structure of the outer shell of virus (Luo et al. 2020b; Yang et al. 2020 ) and the specific proteins on the surface of virus are usually adopted to replace the viruses or actual samples (Liu et al. 2018a Electrochemical immunoassay has many advantages, including good reproducibility, high sensitivity, low cost, fast and accurate analysis, which has attracted widespread attention in virus detection. However, the application of MOF in electrochemical immunosensors has many constraints. For example, the functional groups on MOF are generally limited by the covalent binding of biomolecules, and the electron transfer is inhibited by weak molecular permeability of MOF.

To solve these problems, Liu et al. (Liu et al. 2018a ) developed an excellent sandwich-type electrochemical immunosensor for Avian leukosis virus (ALV-J) detection. (Fig. 9A) The MOF of hollow zeolitic imidazolate framework (eZIF) carried horseradish peroxidase (HRP) and secondary antibodies (Ab 2 ), and functionalized with TA for signal amplification ( Fig. 9B and 9C) . The immunosensor was highly selective for ALV-J with a low detection limit (140 J o u r n a l P r e -p r o o f TCID 50 mL −1 , TCID 50 was 50% tissue culture infective dose). The chemical-etched hollow ZIF-8 enhanced the electron transfer properties of MOF, and the research proved practicability in avian serum samples. show excellent selectivity for viruses owing to the imprinted sites are generated during imprinting (Luo et al. 2020b ).

However, detecting viruses in molecular imprinting is facing a challenge brought by large size viruses of 20-900 nm. The effective way to overcome this obstacle is to find an imprinted carrier with sufficient surface area for providing additional imprinting sites. Compared with other molecular imprinting materials SiO 2 (only 57.4 m 2 ·g -1 ), MOF is a typical material with high surface area, which is mainly related to its porous structure (Furukawa et al. 2010) . Materials of the institute Lavoisier (MIL-n) family usually have a high specific surface area. For instance, MIL-100 (Cr) (Ferey et al. 2004 ) and

MIL-101 (Cr) (Ferey et al. 2005 ) have a large pore of 2.5~2.9 and 2.9~3.4 nm, respectively. Especially, the Langmuir specific surface area of MIL-101 was (5900±300) m 2 /g. The larger surface area of the MOF can provide more imprinting sites for virus detection, which is beneficial to expand the linear range and improve sensitivity (Luo et al. 2020b ).

Moreover, molecularly imprinted polymers have great promising as artificial receptors that recognize viruses, however, the problems, such as poor imprinting effects, long analysis time and non-specific adsorption, may limit the wide application. To solve the problems, Yang and coworkers through the RLS technique (Fig. 10C) . The HM@MIP was constructed with MIL-101 for increasing the specific surface area which is conducive to increase the adsorption ability and pH-responsive polymer (dimethylaminoethyl methacrylate (DMA)) for adjusting the pH and promoting the release and capture of HAV via HM@MIPs nanoprobes as anticipated.

J o u r n a l P r e -p r o o f When exposed to an acidic environment, the Me 2 N-groups in cationic acid labile polymer protonated to increase the repulsive interactions between the DMA side chains, and then the hydrophilicity of polymers was enhanced, leading to the polymeric layer to swell, which benefited eluting of the templates. The nanoprobes could detect HAV within 20 min with a low limit detection of 0.1 pmol·L -1 , particularly, the result could be directly displayed through the RLS output signal. And the nanoprobes quantitatively detected HAV added to human serum, revealing the potential in practical applications of the virus.

Compared with viral nucleiMNBVc acid and antigen detection, antibody is mainly utilized in the detection of cracking period and stable period with a short detection time (5 min MOF-based fluorescence biosensor has a suitable adsorption capacity for molecular probes compared with analogical materials, such as SWCNTs, which is more conducive to fluorescence recovery. Antibody detection has high selectivity which is mainly based on the specific recognition of antibodies and antigens ).

Based on the fluorescence quenching properties of Cu-MOF and the inhibition of Exonuclease I (Exo I) hydrolysis by macromolecule, Wei and coworkers developed a novel biosensor based on H 2 dtoaCu for the influenza H 5 N 1 antibody with a detection limit of 1.6×10 -9 mol·L -1 (S/N=3) and a linear range of 1.0×10 -6 -5.0×10 -9 mol·L -1 ). The ss-DNA linked with H 5 N 1 antigens and fluorescent dye 5' 6-carboxyfluorescein were adsorbed by the MOF, resulting in the quenching of fluorescence. Subsequently, the hydrolysis of Exo I was inhibited when the H 5 N 1 antibody was specifically recognized by H 5 N 1 antibody, so the fluorescence of FAM did not recover. (Fig. 10D) In contrast, in the absence of H 5 N 1 antibody, the DNA probe was hydrolyzed and the fluorescent dye FAM was released from the MOF, leading to the recovery of fluorescence. This antibody detection method was fast (5 min) and cost-efficient (Chen et al. 2010 ).

The MOF-based detection strategies still face many challenges, the detection limit (range from pM to nM) is not enough to detect a low level of viruses in the real samples. With the aim to improve the detection sensitivities for the practical application, multiple strategies should be considered: (1) From the perspective of structure and properties, MOFs with unique structure, high quenching efficiency and good selectivity should be designed. For example, reducing the particle size to amplify fluorescence signal (Guo et al. 2015) ;

(2) Combined with other novel devices, such as lab-on-a-chip (Roy et al. 2020) , or technologies, such as electrochemistry (de Eguilaz et al. 2020; Shetti et al. 2019a )), to generate ultrasensitive biosensors with the characteristics of large-scale, automation, high-throughput screening, etc.;

(3) Utilizing nanoparticles, such as MOF-derived porous carbon (Jia et al. 2019; Li et al. 2019b) , to develop novel sensors (Shetti et al. 2019c ); (4) Oxide enhances the sensing performance, the binding ability and biological activity (Shetti et al. 2019b) , the combination of MOF with metal oxides, metal particles, or carbon materials for the electrochemical detection of viruses is also a promising direction ( Additionally, the detection performace and safety of MOF-based biosensing need to be further verified in vivo due to the complex in vivo environment, and the long-term biological toxicity of metal ion in MOF need to be further evaluated in vivo , some biocompatible metal ions, such as Fe 2+ /Fe 3+ , Ni 3+ , Zr 4+ , Mn 2+ , Mg 2+ , Ca 2+ , Zn 2+ , or biomaterials, such as liposomal (Dunne et al. 2019) , bioconjugates (Malfanti et al. 2019) , and green synthetic routes also should be considered. The functional modification of MOFs with target ligands, such as aptamers (Cai et al. 2018; He et al. 2020b; Liu et al. 2014a; Liu et al. 2015; Xiong et al. 2019) would endow the MOFs with more functionalities, with detection performces even better than the biosensor platforms based on graphene oxide (Du et al. 2020; Liu et al. 2014b) ).

Since the biosensors for virus detection are becoming increasing important, the commercialization should be taken into consideration. The qualcomm, automation, miniaturization and low cost are the trend of future, such as wearable skin patches . And the sensor disposal, large-scale synthesis, fabrication, cost-effectiveness, and recycling are directions in the future (Liu et al. 2018b; Yi et al. 2016) . For instance, the magnetic metal ions (Terzopoulou et al. 2019) (such as Fe 2+ , Co 2+ , and Ni 3+ ) or magnetic particle (i.e., alginate ferrogel ( through the magnetic properties of magnetic materials/field. Moreover, a comprehensive quality assessment standard to assess the accuracy and reliability of the virus detection is also need to be established (Cruz et al. 2020) . Water stability is a factor that must be considered in practical applications of MOF. Water-stable MOFs can be constructed with zwitterionic carboxylate ligands (Yang et al. 2015) or zwitterionic thiolate ) and some metal ions including Zr 4+ (Cavka et al. 2008) and Zn 2+ (Zhao et al. 2016a ). What's more, the instability of MOF in complex physiological environments should also be taken seriously ( SARS-CoV-2 has similar gene sequences with SARS, SARS-CoV and MERS-CoV ). In theory, general detection techniques may also be applicable. Various diagnostic methods based on gold nanoparticles or carbon nanotubes have been proposed as efficacious approaches for sensing SARSCoV-1 and MERS-CoV and other respiratory viruses (Nasrollahzadeh et al. 2020; Palestino et al. 2020; Zhang et al. 2020b ), which can serve as prominent models to guide the development of SARS-CoV-2 biosensors based on MOF. As a potential detection platform for SARS-CoV-2, J o u r n a l P r e -p r o o f MOF has the following advantages: (1) MOF can be used as a adsorption and fluorescence quenching platform; (2) MOFs can serve as a simple and effective fluorescence anisotropy amplification platform (Guo et al. 2015) ; (3) MOF with unique structure can be designed using molecular imprinting technology.

In this review, MOF-based virus detection has been summarized. For viral nucleic acid detection, the relationship between the sensing performance and properties of MOF, involving metal ions, functional groups, geometry structure, size, porosity, stability, etc. has been revealed. For antigen detection, the attention mainly focuses on the fluorescent technique and molecular imprinting technology, and for antibody, the specific recognition of antibodies has been emphasized. This review focuses on the structure and properties of MOF and its relationship to virus detection performace which will provide a better understanding and valuable guidance for the development of efficient diagnosis and dealing with the challenges encountered in SARS-CoV-2 and conventional chemotherapy. This review will provide valuable references for designing sophisticated platform for viruses based on the promising material of the MOF.

The authors declare no conflicts of interest.

Metal organic frameworks modified mesoporous silica nanoparticles (MSN): A nano-composite system to inhibit uncontrolled chemotherapeutic drug delivery from Bare-MSN

Novel graphene-based biosensor for early detection of Zika virus infection

A "green" strategy to construct non-covalent, stable and bioactive coatings on porous MOF nanoparticles

Multimetal organic frameworks as drug carriers: aceclofenac as a drug candidate

Linker functionalized metal-organic frameworks

Luminescent metal-organic frameworks

Cancer biomarkers in HIV patients

Highly sensitive bioaffinity electrochemiluminescence sensors: Recent advances and future directions

Copper(II)-Quenched Oligonucleotide Probes for Fluorescent DNA Sensing

Electrochemical behavior of an anticancer drug 5-fluorouracil at methylene blue modified carbon paste electrode

Electrochemical Sensor for the Determination of Anticancer Drug 5-Fluorouracil at Glucose Modified Electrode

Novel ruthenium doped TiO2/reduced graphene oxide hybrid as highly selective sensor for the determination of ambroxol

Investigations on the interface of nucleic acid aptamers and binding targets

Metal-Organic Frameworks for the Development of Biosensors: A Current Overview

A new zirconium inorganic building brick forming metal organic frameworks with exceptional stability

A multi-species indirect ELISA for detection group-specific antibodies against VP7 protein of bluetongue virus

Molecular Dynamics Simulations Highlight the Structural Differences among DNA:DNA, RNA:RNA, and DNA:RNA Hybrid Duplexes

In Vitro Toxicity Study of a Porous Iron(III) MetalOrganic Framework

Ratiometric fluorescence sensing of metal-organic frameworks: Tactics and perspectives

Quantum-dots-based fluoroimmunoassay for the rapid and sensitive detection of avian influenza virus subtype H5N1

Metal-organic frameworks-based biosensor for sequence-specific recognition of double-stranded DNA

Emerging coronaviruses: Genome structure, replication, and pathogenesis

Detection of 2019 J o u r n a l P r e -p r o o f novel coronavirus (2019-nCoV) by real-time RT-PCR

Evaluation of accuracy of hepatitis B virus antigen and antibody detection and relationship between epidemiological factors using dried blood spot

Rationalization of the entrapping of bioactive molecules into a series of functionalized porous zirconium terephthalate MOFs

Role of conducting polymer and metal oxide-based hybrids for applications in ampereometric sensors and biosensors

A new photoactive crystalline highly porous titanium(IV) dicarboxylate

Signaling Recognition Events with Fluorescent Sensors and Switches

Large-pore apertures in a series of metal-organic frameworks

TiO2 nanowires as an effective sensing platform for rapid fluorescence detection of single-stranded DNA and double-stranded DNA

Photoluminescent metal-organic frameworks and their application for sensing biomolecules

Self-assembled fluorescent Ce(Ⅲ) coordination polymer as ratiometric probe for HIV antigen detection

Tumor microenvironment and NIR laser dual-responsive release of berberine 9-O-pyrazole alkyl derivative loaded in graphene oxide nanosheets for chemo-photothermal synergetic cancer therapy

State-of-the-Art and Prospects of Biomolecules: Incorporation in Functional Metal-Organic Frameworks

Heat-activated drug delivery increases tumor accumulation of synergistic chemotherapies

Systematic design of pore size and functionality in isoreticular MOFs and their application in methane storage

Metal-organic framework MIL-101 as a low background signal platform for label-free DNA detection

A chromium terephthalate-based solid with unusually large pore volumes and surface area

A hybrid solid with giant pores prepared by a combination of targeted chemistry, simulation, and powder diffraction

Ultrahigh porosity in metal-organic frameworks

A review on production of metal organic frameworks (MOF) for CO2 adsorption

A new metal-organic framework with ultra-high surface area

Dual amplifying fluorescence anisotropy for detection of respiratory syncytial virus DNA fragments with size-control synthesized metal-organic framework MIL-101

PEG functionalized zirconium dicarboxylate MOFs for docetaxel drug delivery in vitro

Aptamer-Based Targeted Drug Delivery Systems: Current Potential and Challenges

Thermostable enzyme-immobilized magnetic responsive Ni-based metal-organic framework nanorods as recyclable biocatalysts for efficient biosynthesis of S-adenosylmethionine

Recent progress in nanoscale metal-organic frameworks for drug release and cancer therapy

Interfacing DNA with nanoparticles: Surface science and its applications in biosensing

Fluorescent immunochromatographic assay for quantitative detection of the foot-and-mouth disease virus serotype O antibody

A mononuclear zinc(II) complex with piroxicam: crystal structure, DNA-and BSA-binding studies; in vitro cell cytotoxicity and molecular modeling of oxicam complexes

NiCo2O4 spinel embedded with carbon nanotubes derived from bimetallic NiCo metal-organic framework for the ultrasensitive detection of human immune deficiency virus-1 gene

Low cost synthesis of reduced graphene oxide using biopolymer for influenza virus sensor

Synergistic antioxidant activity and anticancer effect of green tea catechin stabilized on nanoscale cyclodextrin-based metal-organic frameworks

Multifunctional aptasensors based on mesoporous silica nanoparticles as an efficient platform for bioanalytical applications: Recent advances

Controlling the porous structure of alginate ferrogel for anticancer drug delivery under magnetic stimulation

Heteroassembled gold nanoparticles with sandwich-immunoassay LSPR chip format for rapid and sensitive detection of hepatitis B virus surface antigen (HBsAg)

A simple technique for the detection of dengue antigen in mosquitoes by immunofluorescence

Graphene, carbon nanotubes, zinc oxide and gold as elite nanomaterials for fabrication of biosensors for healthcare

Electrochemical Sensors and Biosensors Based on Graphene Functionalized with Metal Oxide Nanostructures for Healthcare Applications

A new metal-organic polymeric system capable of stimuli-responsive controlled release of the drug ibuprofen

Sensitive and Selective Label-Free DNA Detection by Conjugated Polymer-Based Microarrays and Intercalating Dye

Relative Thermodynamic Stability of DNA, RNA, and DNA:RNA Hybrid Duplexes: Relationship with Base Composition and Structure

Metal-organic frameworks for catalysis: State of the art, challenges, and opportunities

Nanomedicine Assembled by Coordinated Selenium-Platinum Complexes Can Selectively Induce Cytotoxicity in Cancer Cells by Targeting the Glutathione Antioxidant Defense System

Counterintuitive Solid-State Syntheses of Indium-Thiolate-Phen Cations as Efficient and Selective Fluorescent Biosensors for HIV-1 ds-DNA and Sudan Ebolavirus RNA Sequences

Design and synthesis of an exceptionally stable and highly porous metal-organic framework

Nitrogen-doped porous carbon-based fluorescence sensor for the detection of ZIKV RNA sequences: fluorescence image analysis

Advances in transition-metal (Zn, Mn, Cu)-based MOFs and their derivatives for anode of lithium-ion batteries

Label-Free Electrochemical Detection of Short Sequences Related to the Hepatitis B Virus Using 4,4′-Diaminoazobenzene Based on Multiwalled Carbon Nanotube-Modified GCE

2020b. Metal-Ligand Coordination Nanomaterials for Biomedical Imaging

Aptamers-Based Sensing Strategy for 17beta-Estradiol Through Fluorescence Resonance Energy Transfer Between Oppositely Charged CdTe Quantum Dots and Gold Nanoparticles

Metal-organic framework nanosheets: Preparation and applications

Development and clinical application of a rapid IgM-IgG combined antibody test for SARS-CoV-2 infection diagnosis

Functional groups influence and mechanism research of UiO-66-type metal-organic frameworks for ketoprofen delivery

Effective loading of cisplatin into a nanoscale UiO-66 metal-organic framework with preformed defects

An electrochemical immunosensor based on an etched zeolitic imidazolate framework for detection of avian leukosis virus subgroup

Strain-promoted "click" modification of a mesoporous metal-organic framework

A DNAzyme Catalytic Beacon Sensor for Paramagnetic Cu2+ Ions in Aqueous Solution with High Sensitivity and Selectivity

A novel immunochromatographic assay using ultramarine blue particles as visible label for quantitative detection of hepatitis B virus surface antigen

The Applications of Metal−Organic Frameworks in Electrochemical Sensors

The Applications of Metal-Organic Frameworks in Electrochemical Sensors

Cu(ii)-TACN complexes selectively induce antitumor activity in HepG-2 cells via DNA damage and mitochondrial-ROS-mediated apoptosis

Intracellular Detection of ATP Using an Aptamer Beacon Covalently Linked to Graphene Oxide Resisting Nonspecific Probe Displacement

Fluorescent sensors using DNA-functionalized graphene oxide

Aptamer density dependent cellular uptake of lipid-capped polymer nanoparticles for polyvalent targeted delivery of vinorelbine to cancer cells

Development of an indirect ELISA for detecting porcine deltacoronavirus IgA antibodies

Functional silica nanospheres for sensitive detection of H9N2 avian influenza virus based on immunomagnetic separation

Molecular imprinting resonance light scattering nanoprobes based on pH-responsive metal-organic framework for determination of hepatitis A virus

Electrochemiluminescent immunosensing of prostate-specific antigen based on silver nanoparticles-doped Pb (II) metal-organic framework

Curcumin-graphene quantum dots for dual mode sensing platform: Electrochemical and fluorescence detection of APOe4, responsible of Alzheimer's disease

Virus Detection by High-Throughput Sequencing of Small RNAs: Large-Scale Performance Testing of Sequence Analysis Strategies

Metal-organic frameworks as biosensors for luminescence-based detection and imaging

Sequence-specific cleavage of double helical DNA by triple helix formation

Controlled Release of Doxycycline by Magnetized Microporous MIL53(Fe); Focus on Magnetization and Drug Loading

Nanomaterials and Nanotechnology-Associated Innovations against Viral Infections with a Focus on Coronaviruses

Magnetic bio-metal-organic framework nanocomposites decorated with folic acid conjugated chitosan as a promising biocompatible targeted theranostic system for cancer treatment

Development of double-antibody sandwich ELISA for rapidly quantitative detection of antigen concentration in inactivated SCRV vaccine

Nucleic acids biosensors based on metal-organic framework (MOF): Paving the way to clinical laboratory diagnosis

Zeolitic imidazolate framework-based biosensor for detection of HIV-1 DNA

Evaluation of novel multiplex qPCR assays for diagnosis of pathogens associated with the bovine respiratory disease complex

Exceptional chemical and thermal stability of zeolitic imidazolate frameworks

Magnetic nanoparticles for smart electrochemical immunoassays: a review on recent developments

COVID-19, SARS and MERS: are they closely related?

A robust host-guest interaction controlled probe immobilization strategy for the ultrasensitive detection of HBV DNA using hollow HP5-Au/CoS nanobox as biosensing platform

A water-stable metal-organic framework of a zwitterionic carboxylate with dysprosium: a sensing platform for Ebolavirus RNA sequences

Synchronous detection of ebolavirus conserved RNA sequences and ebolavirus-encoded miRNA-like fragment based on a zwitterionic copper (II) metal-organic framework

Quaternary ammonium zinc phthalocyanine: Inhibiting telomerase by stabilizing G quadruplexes and inducing G-quadruplex structure transition and formation

Metal-organic frameworks: a new class of porous materials

Modernization of Biosensing Strategies for the Development of Lab-on-Chip Integrated Systems

Very large breathing effect in the first nanoporous chromium(III)-based solids: MIL-53 or Cr(III)(OH) x

A novel approach for the synthesis of phospholipid bilayer-coated zeolitic imidazolate frameworks: preparation and characterization as a pH-responsive drug delivery system

Nanostructured titanium oxide hybrids-based electrochemical biosensors for healthcare applications

ZnO-based nanostructured electrodes for electrochemical sensors and biosensors in biomedical applications

Skin-Patchable Electrodes for Biosensor Applications: A Review

Sensors based on ruthenium-doped TiO2 nanoparticles loaded into multi-walled carbon nanotubes for the detection of flufenamic acid and mefenamic acid

Chapter 10 -Graphene-Clay-Based Hybrid Nanostructures for Electrochemical Sensors and Biosensors

Duplex DNA-functionalized graphene oxide: A versatile platform for miRNA sensing

Development of a dual monoclonal antibody sandwich enzyme-linked immunosorbent assay for the detection of swine influenza virus using rabbit monoclonal antibody by Ecobody technology

Detection of chikungunya virus DNA using two-dimensional MoS2 nanosheets based disposable biosensor

Formation of a stable triplex from a single DNA strand

A sensitive label-free impedimetric DNA biosensor based on silsesquioxane-functionalized gold nanoparticles for Zika Virus detection

Sequence-specific fluorometric recognition of HIV-1 ds-DNA with zwitterionic zinc(II)-carboxylate polymers

Recent progress in the synthesis of metal-organic frameworks

Magnetic porous carbon nanocomposites derived from metal-organic frameworks as a sensing platform for DNA fluorescent detection

Synthetic and structural chemistry of groups 11 and 12 metal complexes of the zwitterionic ammonium thiolate ligands

Water-alcohol adsorptive separations using metal-organic frameworks and their composites as adsorbents

Mineralization-Inspired Synthesis of Magnetic Zeolitic Imidazole Framework Composites

Rapid, sensitive, and selective fluorescent DNA detection using iron-based metal-organic framework nanorods: Synergies of the metal center and organic linker

Biomedical applications based on magnetic nanoparticles:DNA interactions

Synthesis of a superparamagnetic iron oxide based nano-complex for targeted cell death of glioblastoma cells

Aptamer-conjugated mesoporous silica nanoparticles for simultaneous imaging and therapy of cancer

Degradation of ZIF-8 in phosphate buffered saline media

Integrated Antibody with Catalytic Metal-Organic Framework for Colorimetric Immunoassay

Two luminescent metal-organic frameworks for the sensing of nitroaromatic explosives and DNA strands

Zirconium-Based Metal-Organic Framework Nanocarrier for the Controlled Release of Ibuprofen

Metal-organic frameworks for biosensing and bioimaging applications

Insight into the Unique Fluorescence Quenching Property of Metal-Organic Frameworks upon DNA Binding

MOFBOTS: Metal-Organic-Framework-Based Biomedical Microrobots

A pH-responsive silica-metal-organic framework hybrid nanoparticle for the delivery of hydrophilic drugs, nucleic acids, and CRISPR-Cas9 genome-editing machineries

Metal-organic frameworks for stimuli-responsive drug delivery

Fluorescence biosensor for the H₅N₁ antibody based on a metal-organic framework platform

Metal-Organic Framework (MOF)-Based Drug/Cargo Delivery and Cancer Therapy

A highly sensitive and selective fluorescence biosensor for hepatitis C virus DNA detection based on delta-FeOOH and exonuclease III-assisted signal amplification

Simultaneous detection of Dengue and Zika virus RNA sequences with a three-dimensional Cu-based zwitterionic metal-organic framework, comparison of single and synchronous fluorescence analysis

Synchronous sensing of three conserved sequences of Zika virus using a DNAs@MOF hybrid: experimental and molecular simulation studies

Comparison of different samples for 2019 novel coronavirus detection by nucleic acid amplification tests

Cancer protein biomarker discovery based on nucleic acid aptamers

An integrated targeting drug delivery system based on the hybridization of graphdiyne and MOFs for visualized cancer therapy

Selective binding and removal of guests in a microporous metal-organic framework

A novel fluorescence molecularly imprinted sensor for Japanese encephalitis virus detection based on metal organic frameworks and passivation-enhanced selectivity

Metal-Organic Framework Nanoparticles with Near-Infrared Dye for Multimodal Imaging and Guided Phototherapy

Copper(ii) complexes with NNO ligands: synthesis, crystal structures, DNA cleavage, and anticancer activities

Platforms Formed from a Three-Dimensional Cu-Based Zwitterionic Metal-Organic Framework and Probe ss-DNA: Selective Fluorescent Biosensors for Human Immunodeficiency Virus 1 ds-DNA and Sudan Virus RNA Sequences

Lanthanum-Based Metal-Organic Frameworks for Specific Detection of Sudan Virus RNA Conservative Sequences down to Single-Base Mismatch

Reduction-Responsive Codelivery System Based on a Metal-Organic Framework for Eliciting Potent Cellular Immune Response

Metal-organic framework-based molecular beacons for multiplexed DNA detection by synchronous fluorescence analysis

Chemical Sensors Based on Metal-Organic Frameworks

Functionalized gold nanoparticles for ultrasensitive DNA detection

pH-sensitive MOF integrated with glucose oxidase for glucose-responsive insulin delivery

An amine-functionalized metal-organic framework as a sensing platform for DNA detection

Water-stable metal-organic frameworks with intrinsic peroxidase-like catalytic activity as a colorimetric biosensing platform

Recent advances in the detection of respiratory virus infection in humans

An Electrochemical Immunosensor with Graphene-Oxide-Ferrocene-based Nanocomposites for Hepatitis B Surface Antigen Detection

Adsorption and pH-Responsive Release of Tinidazole on Metal-Organic Framework CAU-1

Persistent luminescent metal-organic frameworks with long-lasting near infrared emission for tumor site activated imaging and drug delivery

A zinc(II)-based two-dimensional MOF for sensitive and selective sensing of HIV-1 ds-DNA sequences

A zwitterionic 1D/2D polymer co-crystal and its polymorphic sub-components: a highly selective sensing platform for HIV ds-DNA sequences

Design strategies and applications of charged metal organic frameworks

Ultrasensitive fluorescent detection of HTLV-II DNA based on magnetic nanoparticles and atom transfer radical polymerization signal amplification

An aluminum adjuvant-integrated nano-MOF as antigen delivery system to induce strong humoral and cellular immune responses

Nanomedicines based on nanoscale metal-organic frameworks for cancer immunotherapy

A cost-effective sandwich electrochemiluminescence immunosensor for ultrasensitive detection of HIV-1 antibody using magnetic molecularly imprinted polymers as capture probes

Metal-organic frameworks-based sensitive electrochemiluminescence biosensing

Metal-organic framework (MOF): a novel sensing platform for biomolecules

Exceptionally water stable heterometallic gyroidal MOFs: tuning the porosity and hydrophobicity by doping metal ions

We gratefully acknowledge the financial support from the Huxiang Young Talent Support Program of Hunan Province