Recent advances and perspectives of aggregation-induced emission as an emerging platform for detection and bioimaging

Highlights

• This review summarizes the various AIE based sensors, probes and molecules with respective to their sensing principal.

• Analytical performances of AIE are new paradigm in field of detection and bioimaging.

• Concise the efforts and progress made by the researchers in last three years (2017–2019).

• AIE serve a practical platform to open a new avenue for scientists to explore and paint for wide range of application.

Abstract

The emergent arena of bio-nanotechnology aims at modernizing the detection and bioimaging discipline via the introduction of aggregation-induced emission (AIE)-based tools. AIE is a unique photophysical phenomenon because of the photoemission of the propeller-like molecules that could be significantly enhanced after aggregation. AIE differs immensely from the generally recognized aggregation-caused emission quenching (ACQ) observed in numerous conventional luminophores that own well-conjugated and planar structures. The luminogens with AIE aspects (AIEgens) are more promising to be applied in various research front. Driven by ever-increasing interests for good applicability, fast response, excellent fluorescence and sensitivity, the fluorescent AIE-probes with numerous working methodology and innovative functionalities are prospering at an astonishing speed. In this review, we have presented a brief introduction of AIE with development history, comparison with conventional fluorophores, expected working methodology, discuss the structure-property relationship of the AIEgens and summarized the recent progress of AIE molecular and nanomaterial probe over the past 3 years with their respective mechanism of detection and bioimaging. In addition, this work provides a novel platform for the preparation and potential applications of multifunctional AIE-active nano-systems responsiveness for various detection of analytes and cell bioimaging with respective examples and also encompasses the recent progress, challenges and potential breakthroughs.

Introduction

The great and enormous contributions have been made by the scientific community to nanotechnology-based novel devices and materials, implementing diverse concepts from chemistry, physics, engineering, materials science, agriculture, medical sciences and biology, as well as from other areas [1], [2], [3]. As a result, the last few decades have witnessed the breakthroughs in nanotechnology-based novel sensors, bio-imaging assay and real-time monitoring techniques for sensitive and specific detection of trace metals, toxins and elements, cell bioimaging, diagnosis and treatment of various types of disease [4], [5], [6], [7]. Fluorescence sensors and imaging probes have gained enthusiastic attention and recognized as momentous tools for advanced functional materials in biological sensing and imaging [3], [8], [9], [10], [11].

With the first discovery of fluorescence, the development of luminescent substances has gained much attention and emerged as a powerful tool in the field of visualization of the process down to nanoscale and nanostructures [12]. But these probes tend to aggregate/self-quenched with the introduction of analytes/in high concentration and result in the gradual reductions of the fluorescence signals due to ACQ mechanism [13], [14], [15]. As illustrated in Fig. 1A, Nile red dye emits the strong fluorescence in DMSO but tends to quench in water (aggregation state). The CdSe and conventional dye as “Fluorescein” also tend to partially/totally quench with the addition of water upon aggregation (Fig. 1C) [15]. Fluorescein is an ideal ACQ fluorophore. The poor miscibility in organic solvent outcomes in nanoscopic aggregates. Owing to the severe aggregation, the light emission gets fully quenched [16]. Subsequently, the customary ACQ fluorescent sensors/probes for biosensor applications could be used only at a comparatively low level. The notorious ACQ phenomenon has greatly posed the formidable barrier for trace analysis and bioimaging of biomolecules. Thus, it is highly desirable to conquer the ACQ drawbacks by developing new sensors and bio-probes because it confines the scope of demand [17]. The distinctive AIE platform renders a monotonous clarification to the ACQ problem.

In contrast, new concepts and theories about luminescent material are equally significant. For example, AIE has improved the way of our thinking and created a new research field. In 2001, the new concept called AIE was first coined by Tang et al. in silole derivatives (MPS) [18]. The wet spot of MPS was non-emissive on thin layer chromatography plate but turned to fluorescent after drying. This interesting phenomenon of aggregation played a significant role to generate light emission, which was exactly opposite to conventional organic fluorogens with ACQ effect in the solid-state. In 2017, Liu and Zhang [19] also summarize the three important key millstones of AIE, categorized as discovery, propagation into functional material and booming stages.

Attracted by the interesting perspectives of AIE with their responsive fluorescence, scientists are enthusiastically engaged and are working on the development and engineering of new AIEgens systems, deciphering the working mechanism and exploring their new practical applications [20], [21], [22], [23], [24]. In the AIE systems, weakly luminescent chromogens are prompted to emit intensely by the aggregate formation in concentration solution. A number of AIEgens with propeller-shaped have been observed to display the pronounced AIE effect [16]. A comparison of AIEgens with conventional fluorophore is presented in Table 1. TPE is a typical example of AIE phenomenon as exhibited in Fig. 1B. TPE has a propeller-like structure whose double bond is bounded with four peripheral phenyls (aromatic rotors) with central olefin. Additionally, TEP is non-luminous in dilute solution since the relatively free rotation of phenyl rings around the core can quench the excited states. However, it can display high fluorescence in aggregate state, due to the restriction of intramolecular rotation (RIR) by physical stacking that prevents the strong π –π relations. Collectively, the TPE molecules non-emissive in the molecular state; exhibit strong fluorescence upon aggregate formation and in the solid-state (Fig. 1D) due to restriction of intermolecular rations (RIR) (Fig. 1B). The RIR and propeller-shaped result in the strong fluorescence emission of AIEgens in the aggregation state [15], [16], [25].

Considering the massive advantages, a large number of AIEgens have been modified into smart materials/devices that are responsive to fluorescence, phosphorescent, chemo and colorimetric sensing, image guider and therapies [26]. AIEgens can be modified into sensor because of outstanding functionalities such as ease of synthesis, simple structure and modification. Furthermore, AIE can be transformed into sensor by manipulating aggregation/dis-aggregation [27], [28], chemical modification, enzymatic reactions [29], combination through coordination groups (e.g., carboxylic acid and pyridines) [30], making complexes [31], supermolecular interaction [32] and self-assembly [33], polymerization, encapsulation [34], macro-/micro-/miniemulsion and nanoprecipitation [35], [36], [37], [38]. Mechanistic understanding of the AIE marvel proposes that the F.I of AIE luminogens can be prompted by RIR. Rely on this phenomenon, a number of AIE luminogens have been synthesized and developed as sensors implicated in different research areas. The incorporation of the AIE concept leads towards the recent advancement in the development of ‘turn-on’ probes and label-free detection systems.

Fluorescence AIE techniques are widely cast-off due to their advantages of noninvasiveness, simplicity, high spatiotemporal resolution and sensitivity. Therefore, a number of AIE based active probes and sensors have been fabricated and advanced for detection and bioimaging based on various fluorescence turn on mechanisms as summarized in Fig. 2 as follows (A) conjugation of AIE fluorophores with selective ligands to distinguish the analytes and switch-on the fluorescence by RIR (Fig. 2A) and inhibition effect on the activity of AIE by making them Switch-off fluorescence sensor (Fig. 2B); (B) self-assembly with specific substances through numerous noncovalent interactions, including metal-ligand, van der Waals, hydrogen bonds and electrostatic interactions to customize the highly missive aggregates (Fig. 2C); (C) response with specific chemical moieties or enzymes to sever the adjournment-indorsing ligands and reduce the solubility to aggregate (Fig. 2D); (D) disruption of the photophysical quenching processes by changing the nature or transferring the charge such as intramolecular charge transfer (ICT) [39], photo induced electron-transfer (PET) [40], [41], planar intramolecular charge transfer (PICT) [42] (Fig. 2E), excimer, chelation enhanced fluorescence (CHEF) [43] (Fig. 2F), twisted intramolecular charge transfer (TICT), fluorescence resonance energy transfer (FRET) as illustrated in Fig. 2G [44], chemiluminescence resonance energy transfer (CRET) [45], excited-state intramolecular proton transfer [46] (ESIPT) (Fig. 2H), through-bond energy transfer (TBET) (Fig. 2I), excited-state double-bond reorganization (ESDBR), dark resonance energy transfer (DRET) [47], aggregation-induced enhanced emission (AIEE) [48] (Fig. 2J) and the conversion from non-conjugated to conjugated compounds. Knowledge of the reaction coordinate to access the intersection provides useful guidelines for the design of more efficient luminescent compounds.

The numerous efforts have been carried out on the development of luminescent materials with AIE functionalities. Recently, some basic information about synthesis, mechanism and application of AIEgens have been reported exceptionally in the literature. This topical review will cover up a complete overview on the introduction of AIE about history, their advantages over others luminophores, mechanism understanding and the application of AIE sensor and probe in the field of detection and cell bio-imaging with their respective emerging principles. Herein, this review will provide some demonstrative examples of AIE molecular and nanomaterial sensors and probes used in the past three years together with metal ions and anions, explosive materials, minor biological molecules, pH sensing, Reactive oxygen species (ROS), bacterial detection and discrimination, diseases biomarker and cell bio-imaging. Moreover, the latest exemplary illustrations are enclosed in the review to make it attractive for the reader and shorten the length of articles and also discuss the recent progress, challenges and potential breakthroughs.