Perspective on Aggregation-induced Emission (AIE) Materials for Pathogen Detection

The rapid and accurate identification of pathogens plays a crucial role in clinical practice, which helps to prevent, control, and treat pathogenic infections at the initial stage. The current available technologies for pathogen detection appear to be inadequate in dealing with cases such as COVID-19. More importantly, the frequent emergence of drug-resistant bacteria is gradually rendering the existing therapeutic options ineffective. Efforts are urgently required to focus on the development of diagnostic systems for point-of-care (POC) detection and high-throughput pathogen identification. Since 2001, a new class of aggregation-induced emission luminogens (AIEgens) with good photostability, high sensitiv-ity, and improved signal-to-noise ratio has emerged as powerful fluorescent tools for various biosensing and cell imaging. Based on the unique fluorescence of AIEgens that becomes stronger upon aggregation, naked-eye detection in turn-on mode has gained a speedy development. A timely overview can not only provide a summary of the advances and challenges of AIEgens in pathogen detection but also offer sys-tematic ideas for future developments. There are also expectations for in-depth interdisciplinary research in the field of analytical chemistry and microbiology. © 2023 Bentham Science Publishers.

Bis(thio)carbohydrazone Luminogens with AIEE and ACQ Features and Their In Silico Investigations with SARS-CoV-2.

Herein, we report two novel multidentate luminogen proligands bis(3,5-diiodosalicylidene) carbohydrazone (H4L1) and bis(3,5-diiodosalicylidene) thiocarbohydrazone (H4L2), which are suitable candidates for biomedical applications. Though the thiocarbohydrazone H4L2 shows aggregation caused quenching (ACQ), the carbohydrazone H4L1 exhibits stronger fluorescence due to aggregation induced emission enhancement (AIEE). Molecular docking studies of H4L1 and H4L2 along with four similar (thio)carbohydrazones with the active sites of SARS-CoV-2 main protease 3CLpro reveals that the thiocarbohydrazones, in general, are showing better propensity compared to their oxygen analogues. Both the thiocarbohydrazones and the carbohydrazones, however, exhibit better binding potential at the active sites than that of some of the repurposed drugs such as chloroquine, hydroxychloroquine, lopinavir, ritonavir, darunavir and remdesivir. Also, the carbohydrazone H4L1 can be a better bioprobe compared to H4L2 as the former is found to have better binding potential with SARS-CoV-2 spike glycoprotein along with AIEE feature.

Development of fluorescent lateral flow immunoassay for SARS-CoV-2-specific IgM and IgG based on aggregation-induced emission carbon dots.

Understanding the dynamic changes in antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential for evaluating the effectiveness of the vaccine and the stage for the recovery of the COVID-19 disease. A rapid and accurate method for the detection of SARS-CoV-2-specific antibodies is still urgently needed. Here, we developed a novel fluorescent lateral flow immunoassay (LFA) platform for the detection of SARS-CoV-2-specific IgM and IgG by the aggregation-induced emission carbon dots conjugated with the SARS-CoV-2 spike protein (SSP). The aggregation-induced emission carbon dots (AIE-CDs) are one of the best prospect fluorescent probe materials for exhibiting high emission efficiency in both aggregate and solid states. The AIE-CDs were synthesized and displayed dual fluorescence emission, which provides a new perspective for the design of a high sensitivity testing system. In this work, the novel LFA platform adopted the AIE carbon dots, which are used to detect SARS-CoV-2-specific IgM and IgG conveniently. Furthermore, this sensor had a low LOD of 100 pg/ml. Therefore, this newly developed strategy has potential applications in the areas of public health for the advancement of clinical research.

Self-cleaning wearable masks for respiratory infectious pathogen inactivation by type I and type II AIE photosensitizer.

Although face masks as personal protective equipment (PPE) are recommended to control respiratory diseases with the on-going COVID-19 pandemic, improper handling and disinfection increase the risk of cross-contamination and compromise the effectiveness of PPE. Here, we prepared a self-cleaning mask based on a highly efficient aggregation-induced emission photosensitizer (TTCP-PF6) that can destroy pathogens by generating Type I and Type II reactive oxygen species (ROS). The respiratory pathogens, including influenza A virus H1N1 strain and Streptococcus pneumoniae (S. pneumoniae) can be inactivated within 10 min of ultra-low power (20 W/m2) white light or simulated sunlight irradiation. This TTCP-PF6-based self-cleaning strategy can also be used against other airborne pathogens, providing a strategy for dealing with different microbes.

Ultrabright nanoparticle-labeled lateral flow immunoassay for detection of anti-SARS-CoV-2 neutralizing antibodies in human serum.

The level of anti-SARS-CoV-2 neutralizing antibodies (NAb) is an indispensable reference for evaluating the acquired protective immunity against SARS-CoV-2. Here, we established an ultrabright nanoparticles-based lateral flow immunoassay (LFIA) for one-step rapid semi-quantitative detection of anti-SARS-CoV-2 NAb in vaccinee's serum. Once embedded in polystyrene (PS) nanoparticles, the aggregation-induced emission (AIE) luminogen, AIE490, exhibited ultrabright fluorescence due to the rigidity of PS and severe inhibition of intramolecular motions. The ultrabright AIE490-PS nanoparticle was used as a fluorescent marker of LFIA. Upon optimized conditions including incubation time, concentrations of coated proteins and conjugated nanoparticles, amounts of antigens modified on the surface of nanoparticles, dilution rate of serum samples, and so on, the ultrabright nanoparticles-based LFIA could accurately identify 70 negative samples and 63 positive samples from human serum (p < 0.0001). The intra- and inter-assay precisions of the established method are above 13% and 16%, respectively. The established LFIA has tremendous practical value of generalization as a rapid semi-quantitative detection method of anti-SARS-CoV-2 NAb. Meanwhile, the AIE490-PS nanoparticle is also promising to detect many other analytes by altering the protein on the surface.

Fibrous aggregates: Amplifying aggregation-induced emission to boost health protection.

Environmental monitoring and personal protection are critical for preventing and for protecting human health during all infectious disease outbreaks (including COVID-19). Fluorescent probes combining sensing, imaging and therapy functions, could not only afford direct visualizing existence of biotargets and monitoring their dynamic information, but also provide therapeutic functions for killing various bacteria or viruses. Luminogens with aggregation-induced emission (AIE) could be well suited for above requirements because of their typical photophysical properties and therapeutic functions. Integration of these molecules with fibers or textiles is of great interest for developing flexible devices and wearable systems. In this review, we mainly focus on how fibers and AIEgens to be combined for health protection based on the latest advances in biosensing and bioprotection. We first discuss the construction of fibrous sensors for visualization of biomolecules. Next recent advances in therapeutic fabrics for individual protection are introduced. Finally, the current challenges and future opportunities for "AIE + Fiber" in sensing and therapeutic applications are presented.

Prospects of NIR fluorescent nanosensors for green detection of SARS-CoV-2.

The pandemic of the novel coronavirus disease 2019 (COVID-19) is continuously causing hazards for the world. Effective detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can relieve the impact, but various toxic chemicals are also released into the environment. Fluorescence sensors offer a facile analytical strategy. During fluorescence sensing, biological samples such as tissues and body fluids have autofluorescence, giving false-positive/negative results because of the interferences. Fluorescence near-infrared (NIR) nanosensors can be designed from low-toxic materials with insignificant background signals. Although this research is still in its infancy, further developments in this field have the potential for sustainable detection of SARS-CoV-2. Herein, we summarize the reported NIR fluorescent nanosensors with the potential to detect SARS-CoV-2. The green synthesis of NIR fluorescent nanomaterials, environmentally compatible sensing strategies, and possible methods to reduce the testing frequencies are discussed. Further optimization strategies for developing NIR fluorescent nanosensors to facilitate greener diagnostics of SARS-CoV-2 for pandemic control are proposed.

Novel photonic methods for diagnosis of SARS-CoV-2 infection.

The COVID-19 pandemic that began in March 2020 continues in many countries. The ongoing pandemic makes early diagnosis a crucial part of efforts to prevent the spread of SARS-CoV-2 infections. As such, the development of a rapid, reliable, and low-cost technique with increased sensitivity for detection of SARS-CoV-2 is an important priority of the scientific community. At present, nucleic acid-based techniques are primarily used as the reference approach for the detection of SARS-CoV-2 infection. However, in several cases, false positive results have been observed with these techniques. Due to the drawbacks associated with existing techniques, the development of new techniques for the diagnosis of COVID-19 is an important research activity. We provide an overview of novel diagnostic methods for SARS-CoV-2 diagnosis that integrate photonic technology with artificial intelligence. Recent developments in emerging diagnostic techniques based on the principles of advanced molecular spectroscopy and microscopy are considered.

A wearable AIEgen-based lateral flow test strip for rapid detection of SARS-CoV-2 RBD protein and N protein.

Accurate and rapid detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is significant for early tracing, isolation, and treatment of infected individuals, which will efficiently prevent large-scale transmission of coronavirus disease 2019 (COVID-19). Here, two kinds of test strips for receptor binding domain (RBD) and N antigens of SARS-CoV-2 are established with high sensitivity and specificity, in which AIE luminogens (AIEgens) are utilized as reporters. Because of the high brightness and resistance to quenching in aqueous solution, the limit of detection can be as low as 6.9 ng/mL for RBD protein and 7.2 ng/mL for N protein. As an antigen collector, an N95 mask equipped with a test strip with an excellent enrichment effect would efficiently simplify the sampling procedures. Compared with a test strip based on Au nanoparticles or fluorescein isothiocyanate (FITC), the AIEgen-based test strip shows high anti-interference capacity in complex biosamples. Therefore, an AIEgen-based test strip assay could be built as a promising platform for emergency use during the pandemic.

Assessing Differential Binding of Aggregation-Induced Emission-Based Luminogens to Host Interacting Surface Proteins of SARS-CoV-2 and Influenza Virus-An in silico Approach.

Early detection of asymptomatic cases through mass screening is essential to constrain the coronavirus disease 2019 (COVID-19) transmission. However, the existing diagnostic strategies are either resource-intensive, time-consuming, or less sensitive, which limits their use in the development of rapid mass screening strategies. There is a clear pressing need for simple, fast, sensitive, and economical diagnostic strategy for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) screening even in resource-limited settings. In the current work, we assessed the in silico feasibility of directly labeling virus surface proteins using fluorogenic molecules with aggregation-induced emission (AIE) property. Here, we present the results for binding of two such AIE probes, phosphonic acid derivative of tetraphenyl ethylene (TPE-P) and sulfonic acid derivative of tetraphenyl ethylene (TPE-S), to SARS-CoV-2 spike protein based on in silico docking studies. Our results show that both TPE-P and TPE-S bind to angiotensin converting enzyme 2 (ACE2)-binding, and N-terminal domains of SARS-CoV-2 spike protein. Molecular dynamic simulations have revealed specific nature of these interactions. We also show that TPE-P and TPE-S bind to hemagglutinin protein of influenza virus, but the interaction strength was found to be different. This difference in interaction strength may affect the emission spectrum of aforementioned AIE probes. Together, these results form a basis for the development of AIE-based diagnostics for differential detection of SARS-CoV-2 and influenza viruses. We believe that these in silico predictions certainly aid in differentially labeling of the both viruses toward the development of rapid detection by AIE probes.

Soot-Based Reduced Graphene Quantum Dot/Hemin Conjugate for Favipiravir Sensing

A conjugated system was synthesized from reduced graphene quantum dot (rGQD) and hemin for the selective detection of favipiravir (Fav), an antiviral drug that has come into much attention during the year 2020 for its use as a drug against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The required rGQD was prepared from soot particles using Hummers' method followed by the amino-hydrothermal process. At the first step, its fluorescence was quenched by preparing the conjugate with hemin. Interestingly, the fluorescence intensity gradually increases (turn-on) with increasing concentration of Fav, and develops 9-fold higher fluorescence at 15.6 nM of Fav. The fluorescence enhancement is selective, and the limit of detection (LOD) was calculated to be about 1.96 nM. The fluorescence turn-on is governed by aggregation-induced emission (AIE), which originates from electrostatic interactions between the sensor-analyte systems. A similar fluorescence turn-on was observed for Fav in human blood plasma (BP) as well as in artificial urine (AU), which indicates that the sensor is viable in real-sample analysis. In addition to Fav, its 1:1 cocrystals with theophylline (Theo) and ferulic acid (FRA) also enhance the fluorescence in real samples with an LOD of 3.47 and 12.2 nM, respectively. Therefore, the cocrystals remain intact in biological medium and the sensor interacts with cocrystals too. The detection of Fav and its cocrystals, and the development of cocrystals as alternatives in the pharmaceutical industry, is essential considering the current COVID-19 pandemic worldwide. Therefore, the findings of this work will certainly help in developing fluorescence sensors for quantitative determination of active pharmaceutical ingredients (APIs) in real samples. © 2021 American Chemical Society.

Emerging technologies for a more sustainable future: Preface for emerging technologies and new directions in chemistry research

Keywords: Aggregation-induced emission;chemistry Nobel Prize;emerging technologies;liquid gating technology;new directions in chemistry research;organocatalysts;Top Ten Emerging Technologies in Chemistry EN Aggregation-induced emission chemistry Nobel Prize emerging technologies liquid gating technology new directions in chemistry research organocatalysts Top Ten Emerging Technologies in Chemistry 1351 1352 2 12/15/21 20211201 NES 211201 Many demanding challenges threaten mankind. Aggregation-induced emission, chemistry Nobel Prize, emerging technologies, new directions in chemistry research, Top Ten Emerging Technologies in Chemistry, organocatalysts, liquid gating technology. [Extracted from the article] Copyright of Pure & Applied Chemistry is the property of De Gruyter and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Fabrics Attached with Highly Efficient Aggregation-Induced Emission Photosensitizer: Toward Self-Antiviral Personal Protective Equipment.

Personal protective equipment (PPE) is vital for the prevention and control of SARS-CoV-2. However, conventional PPEs lack virucidal capabilities and arbitrarily discarding used PPEs may cause a high risk for cross-contamination and environmental pollution. Recently reported photothermal or photodynamic-mediated self-sterilizing masks show bactericidal-virucidal abilities but have some inherent disadvantages, such as generating unbearable heat during the photothermal process or requiring additional ultraviolet light irradiation to inactivate pathogens, which limit their practical applications. Here, we report the fabrication of a series of fabrics (derived from various PPEs) with real-time self-antiviral capabilities, on the basis of a highly efficient aggregation-induced emission photosensitizer (namely, ASCP-TPA). ASCP-TPA possesses facile synthesis, excellent biocompatibility, and extremely high reactive oxygen species generation capacity, which significantly outperforms the traditional photosensitizers. Meanwhile, the ASCP-TPA-attached fabrics (ATaFs) show tremendous photodynamic inactivation effects against MHV-A59, a surrogate coronavirus of SARS-CoV-2. Upon ultralow-power white light irradiation (3.0 mW cm^-2), >99.999% virions (5 log) on the ATaFs are eliminated within 10 min. Such ultralow-power requirement and rapid virus-killing ability enable ATaFs-based PPEs to provide real-time protection for the wearers under indoor light irradiation. ATaFs' virucidal abilities are retained after 100 washings or continuous exposure to office light for 2 weeks, which offers the benefits of reusability and long-term usability. Furthermore, ATaFs show no toxicity to normal skin, even upon continuous high-power light illumination. This self-antiviral ATaFs-based strategy may also be applied to fight against other airborne pathogens and holds huge potential to alleviate global PPE supply shortages.

Advances in aggregation induced emission (AIE) materials in biosensing and imaging of bacteria.

With their ubiquitous nature, bacteria have had a significant impact on human health and evolution. Though as commensals residing in/on our bodies several bacterial communities support our health in many ways, bacteria remain one of the major causes of infectious diseases that plague the human world. Adding to this, emergence of antibiotic resistant strains limited the use of available antibiotics. The current available techniques to prevent and control such infections remain insufficient. This has been proven during one of greatest pandemic of our generation, COVID-19. It has been observed that bacterial coinfections were predominantly observed in COVID-19 patients, despite antibiotic treatment. Such higher rates of coinfections in critical patients even after antibiotic treatment is a matter of concern. Owing to many reasons across the world drug resistance in bacteria is posing a major problem i. According to Center for Disease control (CDC) antibiotic report threats (AR), 2019 more than 2.8 million antibiotic resistant cases were reported, and more than 35,000 were dead among them in USA alone. In both normal and pandemic conditions, failure of identifying infectious agent has played a major role. This strongly prompts the need to improve upon the existing techniques to not just effective identification of an unknown bacterium, but also to discriminate normal Vs drug resistant strains. New techniques based on Aggregation Induced Emission (AIE) are not only simple and rapid but also have high accuracy to visualize infection and differentiate many strains of bacteria based on biomolecular variations which has been discussed in this chapter.

AIEgen-loaded nanofibrous membrane as photodynamic/photothermal antimicrobial surface for sunlight-triggered bioprotection.

The outbreak of infectious diseases such as COVID-19 causes an urgent need for abundant personal protective equipment (PPE) which leads to a huge shortage of raw materials. Additionally, the inappropriate disposal and sterilization of PPE may result in a high risk of cross-contamination. Therefore, the exploration of antimicrobial materials possessing both microbe interception and self-decontamination effects to develop reusable and easy-to-sterilize PPE is of great importance. Herein, an aggregation-induced emission (AIE)-active luminogen-loaded nanofibrous membrane (TTVB@NM) sharing sunlight-triggered photodynamic/photothermal anti-pathogen functions are prepared using the electrospinning technique. Thanks to its porous nanostructure, TTVB@NM shows excellent interception effects toward ultrafine particles and pathogenic aerosols. Benefiting from the superior photophysical properties of the AIE-active dopants, TTVB@NM exhibits integrated properties of wide absorption in visible light range, efficient ROS generation, and moderate photothermal conversion performance. A series of antimicrobial evaluations reveal that TTVB@NM could effectively inactivate pathogenic aerosols containing bacteria (inhibition rate: >99%), fungi (~88%), and viruses (>99%) within only 10 min sunlight irradiation. This study represents a new strategy to construct reusable and easy-to-sterilize hybrid materials for potential bioprotective applications.

A Membrane-Targeting Photosensitizer with Aggregation-Induced Emission Characteristics for Highly Efficient Photodynamic Combat of Human Coronaviruses.

COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2, has resulted in global social and economic disruption, putting the world economy to the largest global recession since the Great Depression. To control the spread of COVID-19, cutting off the transmission route is a critical step. In this work, the efficient inactivation of human coronavirus with photodynamic therapy (PDT) by employing photosensitizers with aggregation-induced emission characteristics (DTTPB) is reported. DTTPB is designed to bear a hydrophilic head and two hydrophobic tails, mimicking the structure of phospholipids on biological membranes. DTTPB demonstrates a broad absorption band covering the whole visible light range and high molar absorptivity, as well as excellent reactive oxygen species sensitizing ability, making it an excellent candidate for PDT. Besides, DTTPB can target membrane structure, and bind to the envelope of human coronaviruses. Upon light irradiation, DTTPB demonstrates highly effective antiviral behavior: human coronavirus treated with DTTPB and white-light irradiation can be efficiently inactivated with complete loss of infectivity, as revealed by the significant decrease of virus RNA and proteins in host cells. Thus, DTTPB sensitized PDT can efficiently prevent the infection and the spread of human coronavirus, which provides a new avenue for photodynamic combating of COVID-19.

The Promise of Aggregation-Induced Emission Luminogens for Detecting COVID-19.

The long-term pandemic of coronavirus disease 2019 (COVID-19) requires sensitive and accurate diagnostic assays to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus and SARS-CoV-2 antibodies in infected individuals. Currently, RNA of SARS-CoV-2 virus is mainly detected by reverse transcription-polymerase chain reaction (RT-PCR)-based nucleic acid assays, while SARS-CoV-2 antigen and antibody are identified by immunological assays. Both nucleic acid assays and immunological assays rely on the luminescence signals of specific luminescence probes for qualitative and quantitative detection. The exploration of novel luminescence probes will play a crucial role in improving the detection sensitivity of the assays. As innate probes, aggregation-induced emission (AIE) luminogens (AIEgens) exhibit negligible luminescence in the free state but enhanced luminescence in the aggregated or restricted states. Moreover, AIEgen-based nanoparticles (AIE dots) offer efficient luminescence, good biocompatibility and water solubility, and superior photostability. Both AIEgens and AIE dots have been widely used for high-performance detection of biomolecules and small molecules, chemical/biological imaging, and medical therapeutics. In this review, the availability of AIEgens and AIE dots in nucleic acid assays and immunological assays are enumerated and discussed. By building a bridge between AIE materials and COVID-19, we hope to inspire researchers to use AIE materials as a powerful weapon against COVID-19.