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Light has profoundly impacted modern medicine and healthcare, with numerous luminescent agents and imaging techniques currently being used to assess health and treat diseases. As an emerging concept in luminescence, aggregation-induced emission (AIE) has shown great potential in biological applications due to its advantages in terms of brightness, biocompatibility, photostability, and positive correlation with concentration. This review provides a comprehensive summary of AIE luminogens applied in imaging of biological structure and dynamic physiological processes, disease diagnosis and treatment, and detection and monitoring of specific analytes, followed by representative works. Discussions on critical issues and perspectives on future directions are also included. This review aims to stimulate the interest of researchers from different fields, including chemistry, biology, materials science, medicine, etc., thus promoting the development of AIE in the fields of life and health.

Hydrogels have various promising prospects as a successful platform for detecting biomarkers, and human serum albumin (HSA) is an important biomarker in the diagnosis of kidney diseases. However, the difficult-to-control passive diffusion kinetics of hydrogels is a major factor affecting detection performance. This study focuses on using hydrogels embedded with aggregation-induced emission (AIE) fluorescent probe TC426 to detect HSA in real time. The vortex fluidic device (VFD) technology is used as a rotation strategy to control the reaction kinetics and micromixing during measurement. The results show that the introduction of VFD could significantly accelerate its fluorescence response and effectively improve the diffusion coefficient, while VFD processing could regulate passive diffusion into active diffusion, offering a new method for future sensing research.

β-Glucosidase (β-Glu) is a ubiquitous enzyme which has multiple roles in medical diagnosis, food production, agriculture, etc. Existing β-Glu assays have limitations such as complex operation, long running time, and high background noise. Here we report a red-emissive probe TBPG for measuring the activity of β-Glu. The probe was synthesized through conjugating a β-Glu targeting glucoside to an aggregation-induced emission (AIE) fluorophore. In the presence of β-Glu, TBPG was hydrolyzed and exhibited a fluorescence turn-on process. The detection conditions including time, temperature, pH value, buffer, and probe concentration were optimized systematically. Afterwards, fluorescence titration was conducted showing an excellent linearity (R 2  = 0.998), a wide linear dynamic range (0-5.0 U/mL), and a limit of detection as low as 0.6 U/L. The detection specificity and ion interference were evaluated by adding various biological species and ions to probe without or with β-Glu. Next, we demonstrate the applicability of probe TBPG in determining the β-Glu activity in living cells using confocal microscopy and flow cytometry. Finally, this newly established assay was applied to real soil samples. Comparable results were obtained as the commercial assay, manifesting its great potential in soil enzyme analysis., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Yuning Hong reports financial support was provided by Australian Research Council and Department of Industry, Innovation and Science, Australia. Zhe H. Weng reports financial support was provided by La Trobe University, Australia., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Although molecular design strategies for highly bright near-infrared II (NIR-II) fluorophores were proposed, the lack of solid structural identification (single crystal) hinders the further development of this field. This thorny issue is addressed by performing the structure-function relationship of NIR-II dyes, as confirmed by molecular single crystal engineering. Single crystal structure analysis confirms that twisted architectures (large dihedral angles ∼70°) and loose packing patterns (intermolecular distance of ∼3.4-4.5 Å) are key elements to enhance the absolute quantum yield (QY) in the solid state. Through regulating donor-acceptor distance and donor-acceptor interactions, the resultant well-defined TBP- b -DFA fluorophore displays an absolute QY of 0.4% with an emission extending to 1400 nm, which is favorable for NIR-II bioimaging. The cerebrovascular function, including cerebral blood flow and cerebrovascular reactivity of different conditions, is accurately quantified by a NIR-II fluorescence wide-field microscope. Our study provides a sight for designing NIR-II fluorophores, which is useful for studying cerebrovascular function.

The current study describes a new technology, effective for readily preparing a fluorescent (FL) nanoprobe-based on hyperbranched polymer (HB) and aggregation-induced emission (AIE) fluorogen with high brightness to ultimately develop FL hydrogels. We prepared the AIE nanoprobe using a microfluidic platform to mix hyperbranched polymers (HB, generations 2, 3, and 4) with AIE (TPE-2BA) under shear stress and different rotation speeds (0-5 K RPM) and explored the FL properties of the AIE nanoprobe. Our results reveal that the use of HB generation 4 exhibits 30-times higher FL intensity compared to the AIE alone and is significantly brighter and more stable compared to those that are prepared using HB generations 3 and 2. In contrast to traditional methods, which are expensive and time-consuming and involve polymerization and post-functionalization to develop FL hyperbranched molecules, our proposed method offers a one-step method to prepare an AIE-HB nanoprobe with excellent FL characteristics. We employed the nanoprobe to fabricate fluorescent injectable bioadhesive gel and a hydrogel microchip based on polyvinyl alcohol (PVA). The addition of borax (50 mM) to the PVA + AIE nanoprobe results in the development of an injectable bioadhesive fluorescent gel with the ability to control AIEgen release for 300 min. When borax concentration increases two times (100 mM), the adhesion stress is more than two times bigger (7.1 mN/mm 2 ) compared to that of gel alone (3.4 mN/mm 2 ). Excellent dimensional stability and cell viability of the fluorescent microchip, along with its enhanced mechanical properties, proposes its potential applications in mechanobiology and understanding the impact of microstructure in cell studies.

Human serum albumin (HSA) is a broadly used biomarker for the diagnosis of various diseases such as chronic kidney disease. Here, a fluorescent probe TC426 with aggregation-induced emission (AIE) characteristics is reported as a sensitive and specific probe for HSA. This probe is non-emissive in aqueous solution, meanwhile it shows bright fluorescence upon interacting with HSA, which makes it applicable in detecting HSA with a high signal to noise ratio. Besides, the fluorescence of TC426 exhibits a high linear correlation with the concentration of albumin in the range of microalbumin (20-200 mg/L), which has a significant importance for the early diagnosis of glomerulus related diseases. Compared with previously reported HSA probes TPE-4TA and BSPOTPE, TC426 shows comparable anti-interference ability towards creatinine and other major components in urine but is excited by a longer excitation wavelength at the visible light range. Finally, with the established assay, TC426 shows excellent performance in detecting HSA in real human urine, indicating its great potential in practical urinalysis., (© 2021 Wiley-VCH GmbH.)

The development of fluorescent gels, if not the current focus, is at the center of recent efforts devoted to the invention of a new generation of gels. Fluorescent gels have numerous properties that are intrinsic to the gel structure, with additional light-emitting properties making them attractive for different applications. This review focuses on current studies associated with the development of fluorescent gels using aggregation-induced emission fluorophores (AIEgens) to ultimately suggest new directions for future research. Here, we discuss major drawbacks of the methodologies used frequently for the fabrication of fluorescent gels using traditional fluorophores compared to those using AIEgens. The fabrication strategies to develop AIE-based fluorescent gels, including physical mixing, soaking, self-assembly, noncovalent interactions, and permanent chemical reactions, are discussed thoroughly. New and recent findings on developing AIE-active gels are explained. Specifically, physically prepared AIE-based gels including supramolecular, ionic, and chemically prepared AIE-based gels are discussed. In addition, the intrinsic fluorescent properties of natural gels, known as clustering-triggered fluorescent gel, and new and recent relevant findings published in peer-reviewed journals are explained. This review also revealed the biomedical applications of AIE-based fluorescent hydrogels including drug delivery, biosensors, bioimaging, and tissue engineering. In conclusion, the current research situation and future directions are identified.

We developed a facile strategy for the fabrication of dual-emission carbon nanodots (CDs) and demonstrated their applications for ratiometric glutathione (GSH) sensing and for differentiating cancer cells from normal cells. Dual-emission CDs were synthesized using a simple hydrothermal treatment of alizarin carmine as the carbon source, manifesting intriguing dual-emission behavior at 430 and 642 nm. With increasing GSH concentration, the fluorescence band at 430 nm increased gradually, whereas that at 642 nm decreased slightly. With monitoring of the intrinsic ratiometric fluorescence variation ( I 430nm / I 642nm ), as-prepared CDs were developed as an effective platform for ratiometric fluorescent GSH sensing, with a linear range of 1-10 to 25-150 μM and a detection limit of 0.26 μM. More importantly, confocal fluorescent imaging of cancer cells and normal cells indicated that obtained CDs could be implemented as an effective tool to visualize cancer cells with overexpressing GSH.

Alginate-based hydrogels are extensively used for different biomedical applications. While the swelling and degradation of alginate-based hydrogels affect their structure-property relationship, many studies employed gravimetric analysis to characterize the swelling-degradation process. Accurate or not, this traditional method is difficult to be consistently performed with minimized errors, especially at the late stage of the process. For the first time, this study introduced a reliable, accurate and cost-effective method to minimize the human-sourced errors during repetitive measurement of swelling and degradation of alginate-based hydrogels based on Ca 2+ specified aggregation-induced emission fluorogen technology. This study provides an approach for characterization of different properties of alginate-based tissue engineered scaffolds. The established relation between the changes in released Ca 2+ into the swelling environment and its relative intensity identified the potential application of the proposed method for prediction of swelling and degradation behaviour in alginate-based hydrogels., (Copyright © 2019 Elsevier B.V. All rights reserved.)

This paper employs a specially designed aggregation-induced emission fluorogen (AIEgen) to in vivo visualize the process of Hg 2+ bioaccumulation in a common species of freshwater zooplankton Daphnia carinata (D. carinata) by two methods, direct Hg 2+ absorption and ingestion of Hg 2+ contaminated food. We analysed the relevance between photoluminescence (PL, I 595 /I 480 ) ratios and Hg 2+ (C Hg2+ ) and developed the master curve for Hg 2+ determination based on measuring the PL intensity of the solution. Meanwhile, fluorescent image analysis showed that the major recipient organs of Hg 2+ in D. carinata were the compound eyes and carapace, followed by the intestine and shell gland, but not the brain or heart. The response of D. carinata to Hg 2+ via uptake from surrounding water differed distinctly from that through food intake of the algae (Euglena gracilis) contaminated by mercury. When Hg 2+ was encapsulated by algae membrane, no fluorescence was detected, and the carapace morphology remained intact after ingesting algae for 80 min, in contrast to the rapid carapace deformation by direct Hg 2+ absorption. The D. carinata showed higher mortality by direct Hg 2+ immersion than via food ingestion. The reason for the high mortality after Hg 2+ immersion was possibly due to carapace deformity after chemical reaction between chitin and mercury, but the biochemical pathway leading to morality needs further study., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Early detection and appropriate management of chronic kidney disease can reduce the progression of kidney failure and cardiovascular disease. The urine albumin to creatinine ratio (UACR) test is a standard urine test for identifying individuals at high risk of developing progressive kidney disease. In this study, IDATPE, a novel fluorescent probe with aggregation-induced emission (AIE) features, is successfully developed for creatinine detection and quantitation. An excellent correlation between fluorescent light intensity and creatinine concentration is achieved. In addition, BSPOTPE, a reported excellent AIE bioprobe for human serum albumin (HSA) quantitation, is used together with IDATPE in artificial urine for UACR testing. The mutual interference of HSA and creatinine when the bioprobes are used for quantitation is characterised, with promising results. Further improvements and potential applications in CKD quantitation are highlighted.

Microalgae can be a valuable indicator for monitoring water pollution due to their sensitivity to the changes induced by pollutants in the environment. In this study, an aggregation-induced emission fluorogen was used as a novel tool to differentiate dead and live microalgae and quantify the link between live algal concentration and fluorogen intensity. Protein in the cell protoplasm is the key component contributing to fluorescence emission in algae.

We report a fluorophore, TPE-TPP, with AIE characteristics which is utilized as a fluorescence probe to monitor the α-synuclein (α-Syn) fibrillation process. Compared with ThT, TPE-TPP shows a higher sensitivity in the detection of α-Syn oligomers as well as fibrils with a stronger fluorescence. The performance of TPE-TPP was evaluated using fluorescence, AFM, dot blot, and SEC.

"United we stand, divided we fall."--Aesop. Aggregation-induced emission (AIE) refers to a photophysical phenomenon shown by a group of luminogenic materials that are non-emissive when they are dissolved in good solvents as molecules but become highly luminescent when they are clustered in poor solvents or solid state as aggregates. In this Review we summarize the recent progresses made in the area of AIE research. We conduct mechanistic analyses of the AIE processes, unify the restriction of intramolecular motions (RIM) as the main cause for the AIE effects, and derive RIM-based molecular engineering strategies for the design of new AIE luminogens (AIEgens). Typical examples of the newly developed AIEgens and their high-tech applications as optoelectronic materials, chemical sensors and biomedical probes are presented and discussed., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)