Biosensors based on metal/covalent organic framework for detection of nucleic acids (2023)


Nucleic acids are fundamental components of life, which store and transmit genetic information and show a close connection with various diseases such as cancer and viral infections [1], [2]. Therefore, nucleic acid testing plays a key role in disease diagnosis, treatment and prognosis [3], [4], [5]. The coronavirus disease 2019 (COVID-19) pandemic has recently highlighted the importance of nucleic acid testing in a sensitive and accurate manner [6]. Although several technologies, such as polymerase chain reaction (PCR) [7], [8], Southern blot [9], [10], Northern blot [11] and microarrays [12], [13] show high sensitivity to nucleic acid detection, false-positive rates and poor assay reproducibility still limit their application, especially for rapid detection of large-scale samples. Recently, simple and fast detection methods based on fluorescent and colorimetric nanomaterials [14], [15], [16], in which biodetectors and biosensors are constructed from metal-organic frameworks (MOF) and/or covalent-organic frameworks, have attracted much attention. (COF) present unique advantages.

MOFs, known as crystalline coordination polymers, are formed by the coordination of organic ligands and metal ions (or metal clusters) [17], [18]. MOFs have tunable and diverse structures, which makes them promising for applications in various fields such as separation [19], [20], [21], gas storage [22], [23], [24], [25 ], catalysis [26], [27], [28], [29], [30], energy conversion [31], [32], biosensing and bioimaging [33], [34], [35], [36 ], [ 37], [38] and drug administration [39], [40], [41]. For nucleic acid detection, MOFs have become potential candidates due to the following advantages. (1) Large surface area: MOFs are homogeneous or heterogeneous crystal structures with large surface areas, which provide a large interface for nucleic acid binding and improve the sensitivity and detection limit [27]. (2) Tunable Porosity: The unique structure of MOFs offers flexibility and tunable porosity, enabling specific pore sizes and geometries for selective capture and immobilization of targeted nucleic acids. This results in improved specificity and reduces interference from non-target species [42]. (3) Fluorescence quenching: Some MOFs show good quenching characteristics in fluorescence detectors, which favors the fabrication of high-sensitivity fluorescence sensors [43]. (4) Customizable functionality: various organic ligands, metal ions and other functional groups can be selected to adjust the appropriate interaction mode and strength between MOFs and nucleic acids, including hydrogen bonds, van der Waals forces, electrostatics and coordination interactions to achieve the need detection in different nucleic acids. This adaptability allows the incorporation of specific recognition elements or signaling groups, increasing the selectivity and flexibility of MOF sensors for nucleic acid detection [44]. (5) Biocompatibility and biodegradability: Many MOFs are biocompatible and show low toxicity, which can be achieved by rational selection of ligands and metals, making them suitable for biomedical applications, especially for the detection of nucleic acids in biological samples. Their compatibility with living systems enables the development of sensors for diagnostics at the point of care,livemonitoring and detection [45].

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Compared to MOFs, COFs lack metal ion centers and are composed of elements that mainly include C, N, O, and B [46], [47]. With adjustable pore structure and large specific surface area [48], [49], [50], COFs show higher thermal and chemical stability than MOFs due to covalent bonding [51]. Similar to MOFs, COFs can acquire fluorescent properties from the ligand structure, and their intensities are also influenced by environmental photobleaching effects [52]. In particular, COFs exhibit strong and stable fluorescence properties due to the presence of carbon-carbon double bonds. Interestingly, removal of COF from covalent organic nanosheets (CON) can further reduce fluorescence bleaching [53]. The ordered pore structures and specific binding sites of COFs also enable the selective adsorption of specific targets, which induces changes in the optical or electrical properties of the COF material and then results in detectable signals in color, fluorescence, current, or conductivity. These advantages contribute to the biosensor efficiency of COF [54], [55], [56].

With the rapid development of MOF and COF materials in recent years, considerable attention has been paid to their preparation methods, property tuning, and potential applications in catalysis, enzyme immobilization, and biomedicine [50], [57], [58], 59 ], [60]. However, the potential application in life analysis, especially the detection of critical biomarkers such as nucleic acids, has been overlooked. Moreover, compared to other nanomaterial-based functional sensors, the above advantages of MOFs and COFs have not yet been fully exploited in nucleic acid detection. So far, the development of MOF- and COF-based sensors for nucleic acid detection is still at an early stage [61], [62]. Uniform protocols, test conditions, and performance metrics are lacking. This makes it difficult to directly compare results between studies and draw definitive conclusions about the overall effectiveness of these sensors. In this review, we aim to present bioprobes and biosensors fabricated from MOF/COF that meet the requirements for nucleic acid detection (Figure 1). Detection mechanisms and typical cases of their application will be presented and discussed. The essential role of rational MOF/COF design in achieving optimal performance for nucleic acid detection will also be summarized. Strategies include the design or selection of organic ligands and metal centers used in MOFs, as well as the building blocks, bond types, and stacking distances used in COFs. In addition, the combination of MOF/COF-based biosensors with signal amplification strategies such as hybridization chain reaction (HCR) and catalytic hairpin assembly (CHA) will be developed to improve the sensitivity of nucleic acid detection. Finally, this review provides insight into the future prospects of MOFs and COFs in nucleic acid sensing.

Unit extracts

Design and synthesis of MOF/COF biosensors

By tailoring metal elements, ligands and synthesis methods, MOFs and COFs can be fine-tuned in terms of their structures and properties. Identification of target nucleic acids can be achieved by high-affinity labeling of specific molecules, such as artificial single-stranded DNA or RNA, in and/or on these materials. However, the labeling ability of these materials is affected by various factors, such as synthesis method, linker property, node size, solvent, reaction time,

Mechanisms of interaction between MOF/COF and nucleic acids

The mechanism of biosensors produced by MOF/COF usually involves the processes of adsorption and dissociation of nucleic acid molecules. Nucleic acids can bind to MOF/COF by various forces, including hydrogen bonding, van der Waals interactions, π–π stacking, electrostatic interactions, coordination interactions, and pore adsorption (Figure 5). The nature and strength of these interactions is determined by the specific structures of both the MOF/COF and the nucleic acids and

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Strategies for detection of nucleic acids using MOF/COF

MOFs/COFs are rapidly emerging as promising platforms for the development of sensitive and selective biosensors. Their physical and chemical properties can be tuned to an extraordinary level, which makes them particularly attractive for nucleic acid detection applications. In order to achieve the goal of nucleic acid detection, various strategies can be used (Figure 6), including fluorescence, electrochemical and colorimetric detection methods. The flexibility of MOF/COF enables precise and

Detection of the volume of circulating DNA (ctDNA).

CtDNAs are fragmented DNAs produced by apoptosis, necrosis or secretion of cancer cells. It is a valuable biomarker for tumor detection and treatment due to its non-invasive nature, high detection accuracy, sensitivity and specificity compared to traditional cancer diagnosis methods [1], [128], [129]. For example, ctDNAs are a type of biomarker for the diagnosis of lung cancer [130], [131]. In a recent study, Bai and colleagues developed a simple DNA electrochem

Summary and perspective

This review highlighted the rational design and recent research progress of MOF/COF in nucleic acid sensing. The structure design, synthesis methods, and fabrication of MOF/COF biosensors are summarized and discussed to elaborate their potential in fulfilling various sensing needs in various nucleic acids, including ctDNA, miRNA, mRNA, genes, and other nucleic acid molecules. Current progress shows that both MFs and COFs have promising prospects for development in this area

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Statement of competing interests

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

Thank you

This work was supported by grants from the National Natural Science Foundation of China (32271453, 22104060, and 31870946), the Double First Class University Plan (CPU2022QZ12), the Natural Science Foundation of Jiangsu Province (BK20200716), the Natural Science Foundation of Jiangsu Higher Education Institution of China (20KJB150019 ), Doctoral Program of Innovation and Entrepreneurship of Jiangsu Province (JSSCBS20210317).

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© 2023 Elsevier B.V. All rights reserved.

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1. Innovation in Biology: Development of Improved Biosensors
(St. Francis College)
2. SENSOR AND MEASUREMENT SYSTEM (41): Biosensors (Part 2)
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3. Disposable Sensors for Detection of Biomolecules, BCHES102/202, Engineering Chemistry for CSE
4. STTP - Nanotechnology and Functional Materials - Phase - III / Day 4 - Session 2
(Kiran Kumar _ME)
5. Fiber-optic immunosensors and genosensors
6. DNA Nanotechnology
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