Metal-organic frameworks-based sensitive electrochemiluminescence biosensing

Highlights

• Three different strategies for preparing ECL-active MOF composites are summarized.

• Different functions of MOF composites for ECL sensing are presented.

• Structure-function relationship of ECL-active MOF composites is discussed.

• Recent developments of MOF composites-based ECL sensing are highlighted.

• Future outlooks of MOF composites-based ECL sensing are concluded.

Abstract

Metal-organic frameworks (MOFs) as porous materials have attracted much attention in various fields such as gas storage, catalysis, separation, and nanomedical engineering. However, their applications in electrochemiluminescence (ECL) biosensing are limited due to the poor conductivity, lack of modification sites, low stability and specificity, and weak biocompatibility. Integrating the functional materials into MOF structures endows MOF composites with improved conductivity and stability and facilitates the design of ECL sensors with multifunctional MOFs, which are potentially advantageous over their individual components. This review summarizes the strategies for designing ECL-active MOF composites including using luminophore as a ligand, in situ encapsulation of luminophore within the framework, and post-synthetic modification. As-prepared MOF composites can serve as innovative emitters, luminophore carriers, electrode modification materials and co-reaction accelerators in ECL biosensors. The sensing applications of ECl-active MOF composites in the past five years are highlighted including immunoassays, genosensors, and small molecule detection. Finally, the prospects and challenges associated with MOF composites and their related materials for ECL biosensing are tentatively proposed.

Introduction

Electrochemiluminescence (ECL), also defined as electrogenerated chemiluminescence, is a process in which light emitting excited states are formed through high-energy electron-transfer reactions of electrode-generated species (Miao, 2008; Richter, 2004). A Web of Science-based literature survey reveals the publication of about 7400 ECL journal articles since the first ECL study by Hercules and Bard et al. in the mid-1960s (Hercules, 1964; Santhanam and Bard, 1965). In recent years, extensive research has been performed on ECL, particularly in bioanalysis, bioimaging, nanomaterials and detection devices owing to its high sensitivity and selectivity, low background and simplified optical setup (Irkham et al., 2016; Liu et al., 2015). In 2002, Bard et al. performed the pioneering work on the ECL property of quantum dots (QDs) (Ding et al., 2002), and since then, many research efforts have been devoted to the ECL behaviors of various nanomaterials, including zero-dimensional (0D) nanomaterials, one-dimensional nanomaterials (1D), two-dimensional (2D) nanomaterials, and three-dimensional (3D) nanomaterials. Nanomaterials have been used as ECL emitters or coreaction accelerators for their versatile physical and chemical properties. For ECL emitters, QDs-based systems have been reviewed comprehensively (Zhao et al., 2015b). Coreaction accelerator could interact with the coreactant to produce more reactive intermediates and promote the reaction rate between luminophore and co-reactant, thereby producing an amplified ECL signal.

Metal-organic frameworks (MOFs) are emerging porous and crystalline materials built from metal ions/clusters and organic linkers, and have excited intense interest during the past decades (Osman et al., 2019; Wu and Yang, 2017). The brilliant features of MOFs, such as large surface area, tailorable structure and high porosity, tunable size and versatile functionality, make them promising candidates in bioanalysis and biomedical research (Gülbağça et al., 2019; Wang, 2017; Liao et al., 2019; Raza et al., 2019; Stassen et al., 2017). Despite successful development of MOFs in ECL applications, there is no comprehensive review of this topic, leading to the poor understanding of different applications of MOFs. One of the primary restraints is their low water stability, which tends to cause the breakdown of the framework when exposed to moisture (Aguilera-Sigalat and Bradshaw, 2016; Ge et al., 2013). Additionally, most MOFs have poor conductivity intrinsically. These defects can be overcome via MOF composites by integrating a variety of functional materials into MOFs or by loading guests (luminol, quantum dots, ruthenium, etc.) into MOFs (Hu et al., 2018; Xiong et al., 2015, 2017; Yang et al., 2018).

MOF composites bearing tunable pore sizes and high biocompatibility combine the advantages of both MOFs and various types of functional materials, thus integrating the individual attributes and overcoming the defects of single components. For example, Xiong et al. designed a “signal-on” ECL immunosensor by integrating Ru(bpy)₃²⁺ into MOFs to fabricate Ru(bpy)₃²⁺@UiO-66-NH₂ composites as the signal probes (Xiong et al., 2019). In addition to direct use of MOF composites as reporters, some MOFs that can accelerate ECL reactions can also enhance the ECL signal between luminophores and coreactants. For example, isoreticular MOF-3 (IRMOF-3) not only allows for immobilization of plentiful CdTe QDs, but also functions as self-accelerated ECL reporters, which was further utilized for cTnΙ immunoassay (Yang et al., 2018). Also, by using cobalt-based MOFs (Co-MOFs) as the scaffold of ECL luminophores and the co-reaction accelerator, a self-catalyzed ECL biosensor was designed for amyloid-β protein (Aβ) quantification (Wang et al., 2019a).

These composites have many distinct advantages. Firstly, emerging MOF composites, with diverse morphologies, compositions, sizes, and multifunctional capabilities, are the foundation of many applications (Hu et al., 2014). It is worth noting that the introduction of such functional materials has not significantly altered their intrinsic properties. Secondly, large surface areas and intrinsic permanent porosities endow MOF composites with high loading capacity. Thirdly, integrating luminophores and coreaction accelerators within MOF composites improves the luminous efficiency because of a short electron-transfer path. In short, the benefits of MOFs combining with various types of functional materials in MOF composites can integrate advantages from both and compensate for the disadvantages of their individual components, thus achieving synergistic effects and novel potentialities never attainable by individual parts.

The attractive characteristics of MOF composites favor the development of novel materials and their applications. In this review, we focus on MOF composites-based ECL biosensors (Fig. 1). Firstly, the basic strategies for synthesis of ECL-based MOF composites are summarized (Table 1). Secondly, the different functions of MOF composites in ECL applications are discussed. Thirdly, the illustrative examples of MOF composites-based ECL biosensors are presented. Finally, the challenges for future research are concluded, with an emphasis on the relationship between structures and functionalities of MOF composites, and the design of new devices for practical ECL applications. Different from a broad perspective on luminescent MOFs in previous reviews, this review highlights the ECL-active MOF composites from synthetic strategies to applications in multifunctional bioanalysis.