Lysine (Lys), Cu2+ and Fe3+ ions and biothiols are essential to a myriad of biological and pathological pathways, and their dysregulation is implicated in a variety of diseases. Development of fluorescent probes capable of detecting multiple analytes may be of great significance for early and accurate diagnosis of diseases and remains a huge challenge. In this context, a novel coumarin-dicyanoisophorone-based probe, engineered for the concurrent sensing of Lys, Cu2+, Fe3+ and biothiols was developed. The probe exhibited turn-on response to Lys, colorimetric and turn-off response to Cu2+ by formation of the probe-Cu2+ complex, and ratiometric sensing of Fe3+. In addition, the probe-Cu2+ complex served colorimetric and fluorescence turn-on sensor for biothiols. The limit of detection (LOD) values for the analytes were in the range of 0.30-4.40 μM. Sensing mechanisms based on intramolecular charge transfer (ICT) and iron-mediated hydrolysis of Schiff base were proposed and substantiated through density functional theory (DFT) calculations. Application of the probe for living cell bioimaging was demonstrated.

Alzheimer's disease (AD) has gradually received enthusiastic attention with the aging process, and studying its biological relevance is expected. Excitingly, fluorescence probes were considered to be powerful tools for exploring biological correlations. Therefore, a highly selective near-infrared (NIR) fluorescent probe (DCM-Cl-Acr) for imaging cysteine (Cys) in AD was designed and synthesized. Through structural optimization, the probe exhibited high fluorescence quantum yield and low detection limit (20 nM) towards Cys. Meanwhile, based on the high selectivity and high sensitivity response exhibited by the probe to Cys, it was successfully applied to visualize endogenous and exogenous Cys in living cells and zebrafish, and showed good discrimination from homocysteine (Hcy) and glutathione (GSH). Further, the correlation between AD and Cys concentration was clarified by imaging studies in hippocampus tissue of AD mouse, and the abnormal accumulation of Cys in the hippocampus of AD brain was demonstrated.

A highly sensitive and selective upconversion near-infrared (NIR) fluorescence and colorimetric dual readout hydrogen sulfide (H2S) nanoprobe was constructed based on the excellent NIR fluorescence emission performance of upconversion nanomaterials (UCNPs), the specific recognition effect of synergistically synthesized gold nanoflowers (trypsin-stabled AuNFs (Try-AuNFs)) and the effective NIR fluorescence quenching capability. In this assay, the sensing strategy included three processes. First of all, the synthesized UCNPs can emit 803 nm NIR fluorescence when they were excited by 980 nm excitation light. Secondly, as a result of the principle of fluorescence resonance energy transfer (FRET), Try-AuNFs can effectively quench the NIR fluorescence of UCNPs at 803 nm, which can effectively improve the signal-to-background ratio of nanoprobes, thereby improving the sensitivity of the probes. Thirdly, in the presence of H2S, the Try protective layer on the surface of Try-AuNFs was specifically penetrated, which will subsequently cleave Try-AuNFs via the strong S-Au bond. As such, the NIR fluorescence of UCNPs will be restored, achieving high selectivity and sensitivity detection of H2S. Under optimized conditions, the linear response range of H2S was 0.1-300 μM, and the detection limit was 53 nM. It is worth noting that the Try on the surface of Try-AuNFs via the synergistic effect can increase the steric hindrance of the probe, and this can effectively prevent the interaction between the probe with biothiols (cysteine (Cys), homocysteine (Hcy)) and other natural amino acids (non-thiol-containing) with resultant in the high selectivity regarding the detection of H2S in human serum, which is unlikely to be achieved by AuNFs synthesized by the gold seed method (Se-AuNFs). This work not only provided a new type of UCNPs fluorescence quencher and recognition unit, but also exemplified that the use of the physical properties (steric hindrance) of protein ligands on the surface of nanoflowers can improve the specificity of the probe. This will provide new ideas for the design of other nanoprobes.

As a biothiol, cysteine (Cys) is essential to both physiological and pathological processes and has been associated with many diseases, including neurological disorders, rheumatoid arthritis, and renal dysfunction. Therefore, the development of a high-performance probe for detecting Cys levels can help prevent and diagnose disease. In this study, a ratiometric fluorescent probe based on a novel fluorophore was developed for detecting Cys, and it showed high specificity and a rapid response time toward Cys. This probe demonstrates excellent biocompatibility and has been utilized effectively for the imaging of Cys in living cells.

Gold nanoclusters (AuNCs) with low toxicity, high photostability, and facile synthesis have attracted great attention. The ligand is of great significance in stabilizing AuNCs and regulating their properties. Ligands consisting of amino acids (proteins and peptides) are an ideal template for synthesizing applicative AuNCs due to their inherent bioactivity, biocompatibility, and accessibility. In this review, we summarize the correlation of the template consisting of amino acids with the properties of AuNCs by analyzing different peptide sequences. The selection of amino acids can regulate the fluorescence excitation/emission and intensity, size, cell uptake, and light absorption. By analyzing the role played by AuNCs stabilized by proteins and peptides in the application, universal rules and detailed performances of sensors, antibacterial agents, therapeutic reagents, and light absorbers are reviewed. This review can guide the template design and application of AuNCs when selecting proteins and peptides as ligands.

Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disorder. Its etiology may be associated with genetic, environmental, and lifestyle factors. With the advancement of technology, the integration of genomics, transcriptomics, and imaging data related to AD allows simultaneous exploration of molecular information at different levels and their interaction within the organism. This paper proposes a hypergraph-regularized joint deep semi-non-negative matrix factorization (HR-JDSNMF) algorithm to integrate positron emission tomography (PET), single-nucleotide polymorphism (SNP), and gene expression data for AD. The method employs matrix factorization techniques to nonlinearly decompose the original data at multiple layers, extracting deep features from different omics data, and utilizes hypergraph mining to uncover high-order correlations among the three types of data. Experimental results demonstrate that this approach outperforms several matrix factorization-based algorithms and effectively identifies multi-omics biomarkers for AD. Additionally, single-cell RNA sequencing (scRNA-seq) data for AD were collected, and genes within significant modules were used to categorize different types of cell clusters into high and low-risk cell groups. Finally, the study extensively explores the differences in differentiation and communication between these two cell types. The multi-omics biomarkers unearthed in this study can serve as valuable references for the clinical diagnosis and drug target discovery for AD. The realization of the algorithm in this paper code is available at https://github.com/ShubingKong/HR-JDSNMF .

Given the growing concerns about nanotoxicity, numerous studies have focused on providing mechanistic insights into nanotoxicity by imaging the intracellular fate of nanoparticles. A suitable imaging strategy is necessary to uncover the intracellular behavior of nanoparticles. Although each conventional technique has its own limitations, scanning transmission electron microscopy (STEM) and three-dimensional structured illumination microscopy (3D-SIM) combine the advantages of chemical element mapping, ultrastructural analysis, and cell dynamic tracking. Gold nanoclusters (AuNCs), synthesized using 6-aza-2 thiothymine (ATT) and L-arginine (Arg) as reducing and protecting ligands, referred to as Arg@ATT-AuNCs, have been widely used in biological sensing and imaging, medicine, and catalyst yield. Based on their intrinsic fluorescence and high electron density, Arg@ATT-AuNCs were selected as a model. STEM imaging showed that both the single-particle and aggregated states of Arg@ATT-AuNCs were compartmentally distributed within a single cell. Real-time 3D-SIM imaging showed that the fluorescent Arg@ATT-AuNCs gradually aggregated after being located in the lysosomes of living cells, causing lysosomal damage. The aggregate formation of Arg@ATT-AuNCs was triggered by the low-pH medium, particularly in the lysosomal acidic environment. The proposed dual imaging strategy was verified using other types of AuNCs, which is valuable for studying nano-cell interactions and any associated cytotoxicity, and has the potential to be a useful approach for exploring the interaction of cells with various nanoparticles.

Copper performs an important role in the brain, but in high levels it can be neurotoxic. Further, some authors have described that copper dyshomeostasis could be related with neurodegenerative diseases. Thus, this review was performed to observe whether high copper levels are related to Alzheimer's and Parkinson's diseases (AD and PD), using the literature published recently. Articles that measured copper levels in AD or PD patients was included, as well as they that measured copper levels in models used to mimic these diseases. Also, results about high copper levels effects and its relationship with AD and PD observed in laboratory animals are considered. In summary, 38 and 24 articles with AD and PD patients were included, respectively. Despite of the heterogeneity between the studies in humans, meta-analysis has demonstrated that there is an increase in free and total copper levels in the blood of AD patients compared to controls, and a decrease in copper levels in PD patients. A decrease in the metal content in postmortem brain tissue was observed in AD and PD. In manuscripts using animal models that mimic AD and PD, it was included seven and three articles, respectively. Two of them have reported an increase in copper concentrations in AD model, and one in PD model. Finally, studies with laboratory animals have concluded that high copper levels are related to oxidative stress, neuroinflammation, mitochondrial dysfunction, changes in neurotransmitter levels, cell death, and reduced both cognitive and locomotor activity, which are also described in AD or PD.

Pyrocatechol violet/copper ion-graphene oxide/alginate (PV/Cu2+-GO/Alg) hydrogel was fabricated and applied as a colorimetric sensor for monitoring urinary cysteine via an indicator-displacement assay (IDA) and Cu2+-cysteine affinity pair. The hydrogel-based sensor was formed by Ca2+ cations cross-linked PV/Cu2+-GO/Alg. The morphologies of hydrogel were characterized by field-emission scanning electron microscopy with energy-dispersive X-ray spectroscopy and Fourier-transform Raman spectroscopy. Incorporating GO into the hydrogel improved its uniformity of porosity, large surface area, and compressive strength, leading to amplified colorimetric signals of the hydrogel sensor. Under optimal conditions, this sensor offered a linear range of 0.0-0.5 g/L with a detection limit of 0.05 g/L for cysteine without interfering effects in urine. Furthermore, this hydrogel-based sensor was applied for urinary cysteine detection and validated with laser desorption ionization mass spectrometry. This platform could be used to determine cysteine at its cutoff (0.25 g/L) in human urine, which was distinguishable between normal and abnormal individuals, to evaluate an early stage of Alzheimer's disease. Eventually, this system was integrated with diapers for a wearable cysteine sensor.

Our study presents an electrochromic sensor that operates without the need for enzymes or multiple oxidant reagents. This sensor is augmented with machine learning algorithms, enabling the identification, classification, and prediction of six different antioxidants with high accuracy. We utilized polyaniline (PANI), Prussian blue (PB), and copper-Prussian blue analogues (Cu-PBA) at their respective oxidation states as electrochromic materials (ECMs). By designing three readout channels with these materials, we were able to achieve visual detection of antioxidants without relying on traditional "lock and key" specific interactions. Our sensing approach is based on the direct electrochemical reactions between oxidized electrochromic materials (ECMsox) as electron acceptors and various antioxidants, which act as electron donors. This interaction generates unique fingerprint patterns by switching the ECMsox to reduced electrochromic materials (ECMsred), causing their colors to change. Through the application of density functional theory (DFT), we demonstrated the molecular-level basis for the distinct multicolor patterns. Additionally, machine learning algorithms were employed to correlate the optical patterns with RGB data, enabling complex data analysis and the prediction of unknown samples. To demonstrate the practical applications of our design, we successfully used the EC sensor to diagnose antioxidants in serum samples, indicating its potential for the on-site monitoring of antioxidant-related diseases. This advancement holds promise for various applications, including the real-time monitoring of antioxidant levels in biological samples, the early diagnosis of antioxidant-related diseases, and personalized medicine. Furthermore, the success of our electrochromic sensor design highlights the potential for exploring similar strategies in the development of sensors for diverse analytes, showcasing the versatility and adaptability of this approach.

Phenylalanine dehydrogenase (PheDH) has been proposed as an ideal protein scaffold for the one-step and green synthesis of highly efficient multifunctional gold nanoclusters. The PheDH-stabilized fluorescent gold nanoclusters (PheDH-AuNCs) with dual emission/single excitation exhibited excellent and long-term stability, high water solubility, large Stokes shift and intense photoluminescence. Selectivity studies demonstrated that the red fluorescence emission intensity of PheDH-AuNCs was obviously decreased in less than 10 min by the addition of mercury, copper, cysteine or glutathione under the single excitation at 360 nm, without significant change in the blue emission of the PheDH-AuNCs. Therefore, the as-prepared PheDH-AuNCs as a new excellent fluorescent probe were successfully employed to develop a simple, rapid, low cost, label- and surface modification-free nanoplatform for the ultrasensitive and selective detection of Hg2+, Cu2+, Cys and GSH through a ratiometric fluorescence system with wide linear ranges and detection limits of 1.6, 2.4, 160 and 350 nM, respectively which were lower than previous reports. In addition, the results showed that PheDH-AuNCs can be used for the detection of toxic heavy metal ions and small biomarker thiols in biological and aqueous samples with acceptable recoveries. Interestingly, PheDH-AuNCs also displayed a promising potential for live-cell imaging due to their low toxicity and great chemical- and photo-stability.

Alzheimer's disease, a progressive neurological condition, is associated with various internal and external risk factors in the disease's early stages. Early diagnosis of Alzheimer's disease is essential for treatment management. Circulating exosomal microRNAs could be a new class of valuable biomarkers for early Alzheimer's disease diagnosis. Different kinds of biosensors have been introduced in recent years for the detection of these valuable biomarkers. Isolation of the exosomes is a crucial step in the detection process which is traditionally carried out by multi-step ultrafiltration. Microfluidics has improved the efficiency and costs of exosome isolation by implementing various effects and forces on the nano and microparticles in the microchannels. This paper reviews recent advancements in detecting Alzheimer's disease related exosomal microRNAs based on methods such as electrochemical, fluorescent, and SPR. The presented devices' pros and cons and their efficiencies compared with the gold standard methods are reported. Moreover, the application of microfluidic devices to detect Alzheimer's disease related biomarkers is summarized and presented. Finally, some challenges with the performance of novel technologies for isolating and detecting exosomal microRNAs are addressed.

Early and simple detection of aberrant cooper metabolism in diseases with neurological-manifestations and several other conditions, including cancer, becomes an urgent necessity. Instrumental methods used today are limited to high-cost equipment and reagents and demand highly qualified personnel. In this work, we report easy-to-use and cost-effective nano-sized sensors for the selective and quantitative detection of copper ion based on fluorescence quenching. Glutaraldehyde cross-linked albumin nanoparticles with tunable ultraviolet-to-red autofluorescence emissions are developed as dual-agents for sensing and imaging. These albumin nanoparticles show great selectivity towards copper ion when tested against a selection of biochemical components and other metal ions, and a limit of detection as low as 1.9 μM, relevant for sensing in clinical diagnosis, was determined. In addition, a lack of toxicity and good cellular uptake were observed and the ultraviolet-to-red intrinsic fluorescence of the albumin nanoparticles was preserved when tested in vitro on NIH:OVCAR3 cell line. Preliminary studies confirm the albumin nanoparticles' ability to detect Cu²⁺in vitro and establishes their potential for future practical use.

Cysteine is one of the important amino acids that is involved in various physiological processes, food industries, pharmaceuticals, and personal care. It also serves as a biomarker for some diseases. The large use of cysteine necessitates rapid, cheap, and accurate determination of cysteine in a range of samples. Although many techniques have been employed for the detection of cysteine, they suffer from limitations that make them unsuitable for routine analysis. Here we report on a cheap colorimetric method using biosynthesized silver nanoparticles (AgNPs) as nanozymes. The AgNPs were characterized by UV/visible spectrophotometry, scanning electron microscopy (SEM), and surface-enhanced Raman spectroscopy (SERS). The AgNPs exhibit peroxidase-like activity using o-phenylenediamine (OPD) as a chromogenic reagent. The low K_m values observed for OPD and H₂O₂ (0.9133 and 61.56 mM respectively) show strong affinity of the substrates to AgNPs. The peroxidase-like activity of AgNPs, however, was inhibited on the addition of cysteine. The results show that the absorption intensity of the oxidized OPD decreased linearly with the concentration of cysteine in the range of 0.5-20 μM. The limit of detection (LOD) in this linear range was found to be as low as 90.4 nM. The recovery from urine sample (spiked with cysteine) analyses demonstrated the feasibility of the method in real sample application. From our findings, we anticipate that our method can be applied for the analysis of cysteine in various samples.

Alzheimer's disease (AD) is an irreversible neurodegenerative disease with clinical symptoms of memory loss and cognitive impairment. Currently, no effective drug or therapeutic method is available for curing this disease. The major strategy used is to identify and block AD at its initial stage. Thus, early diagnosis is very important for intervention of the disease and assessment of drug efficacy. The gold standards of clinical diagnosis include the measurement of AD biomarkers in cerebrospinal fluid and positron emission tomography imaging of the brain for amyloid-β (Aβ) deposits. However, these methods are difficult to apply to the general screening of a large aging population because of their high cost, radioactivity and inaccessibility. Comparatively, blood sample detection is less invasive and more accessible for the diagnosis of AD. Hence, a variety of assays based on fluorescence analysis, surface-enhanced Raman scattering, electrochemistry, etc., were developed for the detection of AD biomarkers in blood. These methods play significant roles in recognizing asymptomatic AD and predicting the course of the disease. In a clinical setting, the combination of blood biomarker detection with brain imaging may enhance the accuracy of early diagnosis. Fluorescence-sensing techniques can be used not only to detect the levels of biomarkers in blood but also to image biomarkers in the brain in real time due to their low toxicity, high sensitivity and good biocompatibility. In this review, we summarize the newly developed fluorescent sensing platforms and their application in detecting and imaging biomarkers of AD, such as Aβ and tau in the last five years, and discuss their prospects for clinical applications.

Herein, gold nanoclusters (AuNCs@EW@Lzm, AuEL) with the bright red fluorescence at 650 nm were prepared by egg white and lysozyme as double protein ligands, which exhibited good stability and high biocompatibility. The probe displayed highly selective detected pyrophosphate (PPi) based on Cu²⁺-mediated AuEL fluorescence quenching. Specifically, the fluorescence of AuEL was quenched once the Cu²⁺/Fe³⁺/Hg²⁺ is added to chelate with amino acids on the AuEL surface, respectively. Interestingly, the fluorescence of quenched AuEL-Cu²⁺ was significantly recovered by PPi, but not the other two. This phenomenon was attributed to the stronger bond between PPi and Cu²⁺ than that of Cu²⁺ with AuEL nanoclusters. The results demonstrated a good linear relationship between PPi concentration and the relative fluorescence intensity of AuEL-Cu²⁺ in the range of 131.00-685.40 μM with a detection limit of 2.56 μM. In addition, the quench AuEL-Cu²⁺ system can also be recovered in acidic environments (pH ≤ 5). And the as-synthesized AuEL showed excellent cell imaging and target the nucleus. Thus the fabrication of AuEL offers a facile strategy for efficient PPi assay and offers the potential for drug/gene delivery to the nucleus.

It is interesting and meaningful to explore fluorescent probes for novel rapid detection methods. In this study, we discovered a natural fluorescence probe, bovine serum albumin (BSA), for the assay of ascorbic acid (AA). Due to clusterization-triggered emission (CTE), BSA has the character of clusteroluminescence. AA shows an obvious fluorescence quenching effect on BSA, and the quenching effect increases with increasing concentrations of AA. After optimization, a method for the rapid detection of AA is established by the AA-caused fluorescence quenching effect. The fluorescence quenching effect reaches saturation after 5 min of incubation time and the fluorescence is stable within more than one hour, suggesting a rapid and stable fluorescence response. Moreover, the proposed assay method shows good selectivity and a wide linear range. To further study the mechanisms of AA-caused fluorescence quenching effect, some thermodynamic parameters are calculated. The main intermolecular force between BSA and AA is electrostatic, presumably leading to the inhibiting CTE process of BSA. This method also shows acceptable reliability for the real vegetable sample assay. In summary, this work will not only provide an assay strategy for AA, but also open an avenue for the application expansion of CTE effect of natural biomacromolecules.

Histidine (His) is a natural amino acid that plays very important roles in biota. However, the low concentrations of His in biological fluids and the similar structures and properties of other amino acids mean it is difficult to selectively determine His concentrations in biological fluids with a high degree of sensitivity. A novel ratiometric fluorescence probe for detecting His in aqueous solutions is described here. The method involves carbon dots (CDs) and calcein/Ni²⁺ complexes. At an excitation wavelength of 480 nm, the CD/calcein system emits green fluorescence (maximum emission from calcein at 512 nm) and red fluorescence (maximum emission from CDs at 617 nm). The presence of Ni²⁺ decreases the calcein fluorescence intensity because of static quenching caused by the formation of calcein/Ni²⁺ complexes but the CD fluorescence intensity remains almost unchanged. Fluorescence of calcein/Ni²⁺ complexes provides the response, and the presence of His binds to Ni²⁺ via cooperative chelation and produces free calcein causing fluorescence to be recovered. CDs provide a self-calibration fluorescence signal, the intensity of which remains almost unchanged in the presence of His. The ratio of the fluorescence intensities at 512 and 617 nm (I₅₁₂/I₆₁₇) was strongly related to the His concentration in the range 0.5-22 μM, and the detection limit was 0.16 μM. The specificity of Ni²⁺/His interactions allows His to be determined without interference from other species. The method was successfully used to determine His in diluted human urine. The recovery was acceptable, suggesting that the biosensor can be used to determine His in real samples.

Free copper ions (Cu⁺ and Cu²⁺) have critical toxicity to cells, although copper is an essential element for human body. Hence, sensitive monitoring is crucial to avoid over intake of Cu⁺/Cu²⁺. We herein designed a ssDNA sequence (A₃₁) for synthetizing A₃₁-templated silver nanoclusters (AgNCs), and demonstrated that Cu⁺/Cu²⁺ can induce the aggregation of A₃₁-templated AgNCs and thus greatly enhanced the fluorescence emission of A₃₁-templated AgNCs. Based on Cu⁺/Cu²⁺-induced fluorescence enhancement effect of A₃₁-templated AgNCs, a label-free and signal-on fluorescent sensing platform was developed for the specific and sensitive detection of Cu⁺/Cu²⁺ in biological samples and intracellular imaging of Cu⁺/Cu²⁺ in cells. The signal-on fluorescent sensing platform could be used to rapidly detect Cu⁺ and Cu²⁺ with a detection limit of 0.1 µM within 30 min., and to perform the intracellular imaging of Cu⁺ and Cu²⁺ in cells with good cell permeability and biocompatibility. By using the signal-on fluorescent sensing platform, we have successfully detected Cu⁺ and Cu²⁺ in cells fluids and human serum with a recovery of 90-104% and a RSD (n = 5) < 5%, and performed the imaging of Cu⁺/Cu²⁺ in Hela cells. The developed fluorescent sensing platform has obvious analytical and imaging advantages such as signal-on, simple operation, short analysis time, both Cu⁺ and Cu²⁺ detection, similar or higher sensitivity, good cell permeability and biocompatibility, which promising a reliable approach for the rapid and on-site detection or imaging of free copper ions in biological samples in clinical diagnosis.

Ascorbic acid (AA) is an essential nutrient for humans, which must be obtained from vegetables, fruits, and other foods. The content of AA has become an important standard to evaluate the quality and nutritional value of food. The fluorescence sensing method based on nanomaterials is a good alternative for the rapid detection of AA. In this study, we developed an inner filter effect-based fluorescent probe that hybridized nitrogen-doped carbon dots (NCDs) with cobalt oxyhydroxide nanoflakes (CoOOH NFs).

An optimal NCDs was successfully selected because it has a strong fluorescence at 430 nm and the most significant quenching phenomenon with CoOOH NFs due to the inner filter effect. When adding AA into the NCDs-CoOOH NFs probe solution, a specific redox reaction will occur between the enediol group of AA and the CoOOH NFs to interfere with the quenching ability of CoOOH NFs and recover the fluorescence of NCDs. The recovered fluorescence intensities demonstrated a linear relationship with the concentrations of AA. The assay based on the NCDs-CoOOH NFs probe allows AA to be tested in a wide range of 5-200 μmol L^-1 with a detection limit of 2.31 nmol L^-1 . Furthermore, to evaluate its practical application, the NCDs-CoOOH NFs fluorescence probe was utilized to analyze AA in vegetable, fruit, and serum matrixes with satisfactory results.

An inner filter effect-based fluorescence probe for the rapid detection of AA was developed, and it has a good potential to be applied in both food and clinical testing. © 2022 Society of Chemical Industry.

A trace element copper (Cu2+) ion is the third most plentiful metal ion that necessary for all living organisms and playing a critical role in several processes. Nonetheless, according to cellular needs, deficient or excess Cu2+ ion cause various diseases. For all these reasons, optical sensors have been focused rapid Cu2+ ion detection in real-time with high selectivity and sensitivity. Optical sensors can measure fluorescence in the refractive index-adsorption from the relationships between light and matter. They have gained great attention in recent years due to the excellent advantages of simple and naked eye recognition, real-time detection, low cost, high specificity against analytes, a quick response, and the need for less complex equipment in analysis. This review aims to show the significance of Cu2+ ion detection and electively current trends in optical sensors. The integration of optical sensors with different systems, such as microfluidic systems, is mentioned, and their latest studies in medical and environmental applications also are depicted. Conclusions and future perspectives on these advances is added at the end of the review.

Cysteine is an essential biothiol that plays various functions in the human body. Decrease or exceeding of this excellent antioxidant from the expected range will lead to so many problems. Thus, appropriate sensing of it would be of great importance. Sulfur-doped carbon Dots(S-CDs) owe excellent fluorescence emission. Therefore, designing a Fluorescence resonance energy transfer (FRET) system between S-CDs as donor and Au nanoparticles (AuNPs) decorated tungsten disulfide nanosheet (WS2 NSs) would be a perfect strategy for cysteine detection. Excitation at 340 nm will give the maximum quantum yield of S-CDs (21%) and fluorescence emission peak at 460 nm. In the presence of cysteine, the FRET mechanism inhibited through the affinity of cysteine's functional groups (-SH and -NH2) toward AuNPs and S-CDs fluorescence emission was recovered. To find the best efficiency of the system, optimization of pH, temperature, and time was investigated. Here the linear range of 3-275 µM and limit of detection of 0.01 µM was obtained. Finally, the fluorescence method was applied to the analysis of cysteine in human blood serum, which poses the potential of rapid and sensitive sensing. It can detect both lower and higher amounts of serum cysteine.

In this project, poly (citric acid) (PCA) functionalized on nano Ag/Cu was synthesized by chemical analysis method. The nano probe was applied to detection of cysteine by using the magnesium (II) ions as a cross linker. The characterization of Ag/Cu/PCA nano probe was studied by using the UV-visible, morphological microscopy, dynamic light scattering, and zeta potential analyzer. The zeta potential and size of Ag/Cu/PCA were -38.0 mV and 18.0 nm, respectively. The prepared nano probe shows rapid response for detection of cysteine. The detection limit of Ag/Cu/PCA nano probe was 0.07 nM. Additional, the Ag/Cu/PCA nanoparticles was applied to cysteine detection from real samples in the presence of amino acids compounds. Rapidly and sensitive determination of Streptococcus pneumoniae is substantial for food safety and human health. The DNA-Ag/Cu/PCA were prepared as a template in chemical method and experimented as a bio-receptor for the cell bacteria detection as peroxidase-like catalytic process. The DNA-Ag/Cu/PCA nano probe shows a linear dynamic concertation range of Streptococcus pneumoniae via detection limit about 65 CFU/mL. The project presents that the DNA-Ag/Cu/PCA could detect the biological and bacterial samples via high accuracy.

Recent advances in technology are expected to increase our current understanding of neuroscience. Nanotechnology and nanomaterials can alter and control neural functionality in both in vitro and in vivo experimental setups. The intersection between neuroscience and nanoscience may generate long-term neural interfaces adapted at the molecular level. Owing to their intrinsic physicochemical characteristics, gold nanostructures (GNSs) have received much attention in neuroscience, especially for combined diagnostic and therapeutic (theragnostic) purposes. GNSs have been successfully employed to stimulate and monitor neurophysiological signals. Hence, GNSs could provide a promising solution for the regeneration and recovery of neural tissue, novel neuroprotective strategies, and integrated implantable materials. This review covers the broad range of neurological applications of GNS-based materials to improve clinical diagnosis and therapy. Sub-topics include neurotoxicity, targeted delivery of therapeutics to the central nervous system (CNS), neurochemical sensing, neuromodulation, neuroimaging, neurotherapy, tissue engineering, and neural regeneration. It focuses on core concepts of GNSs in neurology, to circumvent the limitations and significant obstacles of innovative approaches in neurobiology and neurochemistry, including theragnostics. We will discuss recent advances in the use of GNSs to overcome current bottlenecks and tackle technical and conceptual challenges.

This is the first report on the simple preparation of gold nanoclusters stabilized with pregabalin (PREG) as a capping and reducing agent. PREG is an active pharmaceutical ingredient of the commercially available drug "Lyrica" used to treat different diseases like epilepsy and anxiety. PREG has never been used before in the synthesis of any nanoparticles or nanoclusters. The prepared gold nanoclusters (PREG-stabilized gold nanoclusters [PREG-AuNCs]) have blue fluorescence with excitation/emission at 365/425 nm, respectively. The reaction conditions were optimized for the synthesis of the as-prepared AuNCs. Different tools were used for the characterization of the synthesized nanoclusters in terms of size and surface properties. The PREG-AuNCs were exploited as a sensitive and selective fluorescent nanosensor for Cu²⁺ detection. The quenching of AuNC fluorescence intensity in the presence of Cu²⁺ is due to the aggregation-induced fluorescence quenching mechanism. The detection limit of Cu²⁺ ions was found to be 1.11 × 10^-7 M. The selectivity of the PREG-AuNCs was studied and proved to be excellent. The drug entrapment efficacy and in vitro drug diffusion studies along with drug release kinetics helped to understand more about the pharmaceutical approaches of PREG-AuNCs. Moreover, we think that PREG-AuNCs open new opportunities as a promising candidate material for drug delivery systems and medical applications.

Metal-organic gel (MOG), as a novel type of metallic organic hybrid material, exhibits diverse properties. However, its application in fluorescence detection for specific metal ions has rarely been exploited. In this work, we have designed and synthesized a MOG based on Al-carboxylate coordination assemblies (denoted as MOG-Al). The resultant MOG-Al shows good specific fluorescence signal response to trace Cu²⁺. Under optimal conditions, the fluorescence quenching degrees (F₀ - F) of the MOG-Al have a linear correlation with Cu²⁺ concentration ranging from 0.05 to 100 μM, and the limit of detection (LOD) is 45.00 nM. The proposed sensing platform was also applied for the detection of Cu²⁺ in real samples. Satisfactory recoveries (92-116%) for Cu²⁺ in rice, soybean milk powder and pork liver were obtained. These results indicate that MOG-Al is a promising material for the specific and sensitive sensing of Cu²⁺.

Excessive copper ions (Cu²⁺) cause serious environmental pollution and even endanger the health of organisms. Fluorescence chemosensing materials are widely used in the detection of metal ions due to their simple operation and high sensitivity. In this study, SiO₂-encapsulated single perovskite quantum dot (PQD@SiO₂) core-shell nanostructures which show strong, stable, and green fluorescence are synthesized and composited with gold nanoclusters (AuNCs) which show Cu²⁺-sensitive and red light-emitting fluorescence to obtain a visualized ratiometric fluorescence sensor (AuNCs/PQD@SiO₂) for the detection of Cu²⁺. In the visualized detection of Cu²⁺, the green fluorescence emitted from the ion-insensitive PQD@SiO₂ component is used as a reference signal and the red fluorescence emitted by ion-sensitive AuNC component is adopted as a sensing signal. In the presence of Cu²⁺, the red fluorescence is quenched whereas the green fluorescence remains stable, which results in a visualized fluorescence color change from orange-red to yellow and finally to green with increasing Cu²⁺ concentration. The significant change in the fluorescence color of AuNCs/PQD@SiO₂ in response to Cu²⁺ enables a rapid, sensitive, and visualized detection of Cu²⁺. Further accurate and sensitive ratiometric fluorescence analysis of Cu²⁺ can be accomplished by measuring the ratio of fluorescence intensities at 643 and 520 nm (I₆₄₃/I₅₂₀) at a certain Cu²⁺ level. The developed AuNCs/PQD@SiO₂-based sensor has been validated by its satisfactory application in the detection of Cu²⁺ in human serum and environmental water samples.

L-Cysteine (L-cys) plays very crucial role in biological systems. The study reports the colorimetric detection of L-cys at nanomolar level using chitosan capped Ag decorated NiS nanocomposite (chit-Ag/NiS NCs).The chemical reduction and co-precipitation methods were adopted to prepare chit-Ag/NiS NCs. The fabricated NCs was characterized by X-ray diffraction (XRD), fourier-transform infrared spectroscopy (FT-IR), FT-Raman, scanning electron microscopy (SEM), thermogravimetric analysis (TGA), high-resolution transmission electron microscopy (HR-TEM), energy-dispersive X-ray spectroscopy (EDS) and X-ray photoelectron spectroscopy (XPS). The chit-Ag/NiS NCs particularly detect L-cys even in other amino acids presence. The chit-Ag/NiS NCs showed the surface charge of -26 ± 39.9 mV. The detection of L-cys was indicated by disappearance of yellowish-brown color of Chit-Ag/NiS NCs to colorless. A good linear correlation was found between absorbance vs logarithmic concentration of L-cys (1 μM to 1 nM) with R² value of 0.99. The chit-Ag/NiS NCs impregnated cotton swabs was prepared for real time detection of L-cys and the prepared probe was found to be highly selective and specific. The effect of pH, temperature and salinity influencing the L-cys detection was studied. Also, the antimicrobial activity of Chit-Ag/NiS NCs was investigated against gram negative (E. coli) and gram positive (B. subtilis) bacteria.

The content of deferasirox (DEF) in plasma is significant in β-thalassemia patient that needs long-term transfusion therapy, while the effective and simple strategy for DEF monitoring is still limited. The carbon dots (CDs) prepared from citric acid monohydrate and glutathione exhibit weakly modulated fluorescence intensity to several common metal ions containing Cu²⁺. Interestingly, the process of interaction of Cu²⁺ and DEF forms the chelation of Cu²⁺ and DEF (Cu-DEF) with the absorbance wavelength of DEF at 320 nm shifting to 332 nm for Cu-DEF. And the obtained Cu-DEF will effectively quench CDs through inner filter effect (IFE). Accordingly, a facile signal-off fluorescent method based on CDs as probe is developed for DEF detection using Cu²⁺ as medium. And the proposed method exhibits linear range of 0.5-20 μg/mL with the detection limit of 0.33 μg/mL for DEF under the optimized conditions. Moreover, the developed assay is further expanded to test the content of DEF in dispersible tablet and plasma with accuracy and reproducibility. Such cost-effective and sensitive fluorescent assay just through simple mixing operation present a valuable strategy for drug monitoring.

Herein, fluorescent gold nanoclusters (AuNCs) and horseradish peroxidase (HRP) were simultaneously embedded into self-assembled dipeptide supramolecular films of N-fluorenylmethoxycarbonyl diphenylalanine (Fmoc-FF) on the surface of ITO electrodes (Fmoc-FF/AuNCs/HRP) by using a simple single-step process. In the films, both the fluorescence property of AuNCs and the bioelectrocatalytic property of HRP were well maintained and could be reversibly regulated by pH-sensitive structural changes in the Fmoc-FF hydrogel films. Cu(II)/EDTA in the solution could lead to the aggregation/disaggregation of AuNCs and further quenching/dequenching the fluorescence signal from the films. Meanwhile, the blue complexes formed by Cu(II) and EDTA could produce a UV-vis signal in the solution. In addition, the coordinated Cu(II) in the films enhanced the electrocatalytic capacity toward the reduction of H₂O₂ and could switch the current signal. A biomolecular logic circuit was built based on the smart film electrode system by using pH, the concentrations of EDTA, Cu(II) and H₂O₂ as inputs, while the fluorescence intensity (FL), current (I) and UV-vis extinction (E) of the solution as outputs. Various logic devices were fabricated using the uniform platform, consisting of an encoder/decoder, demultiplexer, dual-transfer gate, keypad lock, digital comparator, half adder, and controlled NOT (CNOT) gate. Specifically, an electronic three-value logic gate, gullibility (ANY) gate, was first mimicked in this biocomputing system. This work not only demonstrated the construction of a new type of multivalued logic gate by using a dipeptide micromolecular matrix but also provided a new approach for designing sophisticated biologic functions, establishing smart multianalyte biosensing or fabricating biology information processing through the use of a simple film system.

Stable fluorescent silver nanoclusters (AgNCs) were synthesized through one-step UV photoreduction using the multiple carboxyl copolymer poly(methacrylic acid-co-itaconic acid) P(MAA-co-IA) as a novel template. The fluorescence lifetime and the quantum yield of the obtained AgNCs were 1.84 ns and 8.9% in an aqueous solution, respectively. Owing to the multiple carboxyls of the protective P(MAA-co-IA) template, the obtained AgNCs have excellent advantages such as good dispersity, and high stability, which make them suitable for highly sensitive and selective detection of Cu²⁺ by fluorescence quenching. A good linear relationship exists between the degree of fluorescence quenching for silver nanoclusters and Cu²⁺ concentration ranging from 0 to 10 μM. The limit of detection (LOD) is 6.36 nM. The result implies that the as-synthesized AgNCs show great potential in the analysis field.