Functionalized Chiral Materials for Use in Chiral Sensors.

Chirality represents a fundamental attribute within living systems and is a pervasive phenomenon in the natural world. The identification and analysis of chiral materials within natural environments and biological systems hold paramount importance in clinical, chemical, and biological sciences. Within chiral analysis, there is a burgeoning focus on developing chiral sensors exhibiting exceptional selectivity, sensitivity, and stability, marking it as a forefront area of research. In the past decade (2013-2023), approximately 1990 papers concerning the application of various chiral materials in chiral sensors have been published. Biological materials and nanomaterials have important applications in the development of chiral sensors, which accounting for 26.67% and 45.24% of the material-related applications in these sensors, respectively; moreover, the development of chiral nanomaterials is closely related to the development of portable and stable chiral sensors. Natural chiral materials, utilized as selective recognition units, are combined with carriers characterized by good physical and chemical properties through functionalization to form various functional chiral materials, which improve the recognition efficiency of chiral sensors. In this article, from the perspective of biological materials, polymer materials, nanomaterials, and other functional chiral materials, the applications of chiral sensors are summarized and the research prospects of chiral sensors are discussed.

Development of Levo-Lansoprazole Chiral Molecularly Imprinted Polymer Sensor Based on the Polylysine-Phenylalanine Complex Framework Conformational Separation.

The efficacies and toxicities of chiral drug enantiomers are often dissimilar, necessitating chiral recognition methods. Herein, a polylysine-phenylalanine complex framework was used to prepare molecularly imprinted polymers (MIPs) as sensors with enhanced specific recognition capabilities for levo-lansoprazole. The properties of the MIP sensor were investigated using Fourier-transform infrared spectroscopy and electrochemical methods. The optimal sensor performance was achieved by applying self-assembly times of 30.0 and 25.0 min for the complex framework and levo-lansoprazole, respectively, eight electropolymerization cycles with o-phenylenediamine as the functional monomer, an elution time of 5.0 min using an ethanol/acetic acid/H2O mixture (2/3/8, V/V/V) as the eluent, and a rebound time of 10.0 min. A linear relationship was observed between the sensor response intensity (ΔI) and logarithm of the levo-lansoprazole concentration (l-g C) in the range of 1.0 × 10-13-3.0 × 10-11 mol/L. Compared with a conventional MIP sensor, the proposed sensor showed more efficient enantiomeric recognition, with high selectivity and specificity for levo-lansoprazole. The sensor was successfully applied to levo-lansoprazole detection in enteric-coated lansoprazole tablets, thus demonstrating its suitability for practical applications.

A novel AuNP colorimetric sensor based on a polyadenine probe for ultra-sensitive detection of Ag.

Silver(I) ions (Ag+) are harmful to humans and can be bioaccumulated in organisms. Although numerous methods for Ag+ analysis have been established, new strategies are still in urgent need. Here, we propose a colorimetric sensor based on polyadenine (polyA)-mediated DNA-functionalized gold nanoparticles (AuNPs) for the specific measurement of Ag+ ions. In this strategy, a polyA-modified Au probe with high uniformity was assembled successfully. The method was based on Ag+-induced aggregation of the probe. Ag+ was reflected according to the color variations of solution. Taking advantage of the low cost and convenient assembly of the polyA-based Au probe, our strategy determined Ag+ with high sensitivity and wide range. In addition, by changing probes or nanoparticles, the proposed strategy is expected to be a universal platform for detecting other analytes in environmental and even biological samples.

Research and Application of Highly Selective Molecular Imprinting Technology in Chiral Separation Analysis.

Since residual chiral pollutants in the environment and toxic or ineffective chiral components in drugs can threat human health, there is an urgent need for methods to separation and analyze chiral molecules. Molecular imprinting technology (MIT) is a biomimetic technique for specific recognition of analytes with high potential for application in the field of chiral separation and analysis. However, since MIT has some disadvantages when used for chiral recognition, such as poor rigidity of imprinted materials, a single type of recognition site, and poor stereoselectivity, reducing the interference of conformationally and structurally similar substances to increase the efficiency of chiral recognition is difficult. Therefore, improving the rigidity of imprinted materials, increasing the types of imprinted cavity recognition sites, and constructing an imprinted microenvironment for highly selective chiral recognition are necessary for the accurate identification of chiral substances. In this article, the principle of chiral imprinting recognition is introduced, and various strategies that improve the selectivity of chiral imprinting, using derivative functional monomers, supramolecular compounds, chiral assembly materials, and biomolecules, are reviewed in the past 10 years.

Protein synergistic action-based development and application of a molecularly imprinted chiral sensor for highly stereoselective recognition of S-fluoxetine.

In order to improve the recognition performance of MIPs sensors in chiral drug enantiomers, a novel a highly selective molecular recognition method based on protein-assisted immobilization of chiral molecular conformation was developed. S-fluoxetine (S-FLX) as the target chiral molecule, human serum albumin (HSA), which has a high affinity and strong interactions with S-FLX, was screened from 11 proteins to serve as an auxiliary recognition unit for the fixation of chiral conformation. By incorporating HSA into the preparation of molecularly imprinted polymers (MIPs), the natural chirality and high stereoselectivity of the protein were leveraged for the induction and fixation of the stereo conformation of S-FLX, refinement of internal structures of the imprinted cavities. The sensor exhibited excellent chiral recognition ability and high detection sensitivity. The changes of probe signal intensity of the MIPs/HSA sensor were positively correlated with the logarithmic concentration of S-FLX in the range of 1.0 × 10-16-1.0 × 10-11 mol L-1, where a detection limit of 6.43 × 10-17 mol L-1 was achieved (DL = 3δb/K). The selectivity of MIPs/HSA sensor in recognizing S-FLX was increased by 18.5 times and the sensitivity was increased by 2.6 times after the incorporation of HSA. The developed sensor was successfully used for the analysis of S-FLX in fluoxetine hydrochloride capsules.

DNA-Immobilized Special Conformation Recognition of L-Penicillamine Using a Chiral Molecular Imprinting Technique.

A new chiral molecularly imprinted polymer (MIP) sensor with dual recognition ability was developed for the highly selective separation of enantiomers with toxic side effects in drugs. The sensor contains double-stranded deoxyribonucleic acid (dsDNA) as the element that immobilizes the chiral molecular conformation: the dsDNA enables the imprinted cavities to match the three-dimensional structure and functional groups from the chiral molecule. By embedding the spatial orientation of dsDNA in MIPs, one can accurately capture and immobilize the molecular conformation, eliminating the influence of interfering analogues. Herein, L-penicillamine (L-Pen) was selected as the chiral template molecule and embedded into dsDNA to form dsDNA-L-Pen complex, which was then embedded into the MIPs by electropolymerization. After elution, the stereo-selective imprinted cavities were obtained. The ATATATATATAT-TATATATATATA base sequence showed a high affinity for the embedded L-Pen, which endowed the imprinted cavities with a larger number of sites and improved the selectivity toward Pen enantiomers. Under the optimal working conditions, the current response of the MIP/dsDNA sensor exhibited a positive linear relationship with the logarithm of the L-Pen concentration in the range of 3.0 × 10-16 to 3.0 × 10-13 mol/L, and the detection limit was 2.48 × 10-16 mol/L. After the introduction of dsDNA into the MIP, the selectivity of the sensor toward D-Pen increased by 6.4 times, and the sensor was successfully applied in the analysis of L-Pen in penicillamine tablets.

Ultrasensitive detection of DNA methyltransferase activity: a novel dual-amplification fluorescence technique.

DNA methyltransferase (MTase) is an important regulatory enzyme in various biological processes. However, current methods for investigating MTase activity are still limited in terms of sensitivity and/or generality. Herein, we proposed a dual amplification fluorescence strategy for the ultrasensitive detection of DNA adenine methylation methyltransferase (Dam MTase) activity based on strand displacement amplification (SDA) coupled with rolling circle amplification (RCA). In this study, the hairpin probe could not be cleaved by Nt.AlwI nicking endonuclease (Nt.AlwI) in the presence of Dam MTase, and the subsequent SDA-RCA reaction was blocked, resulting in a weak fluorescence signal. Moreover, the blocking effect was more pronounced at a higher concentration of Dam MTase. This assay provides a very low detection limit (down to 0.0067 U ml-1), as well as good selectivity against other types of MTases (e.g., CpG methyltransferase (M.SssI MTase)). In addition, the analytical mode improves the generality and can be extended to the detection of other types of DNA MTases.

Carbon Material-Based Aerogels for Gas Adsorption: Fabrication, Structure Design, Functional Tailoring, and Applications.

Carbon material-based aerogels (CMBAs) have three-dimensional porous structure, high specific surface area, low density, high thermal stability, good electric conductivity, and abundant surface-active sites, and, therefore, have shown great application potential in energy storage, environmental remediation, electrochemical catalysis, biomedicine, analytical science, electronic devices, and others. In this work, we present recent progress on the fabrication, structural design, functional tailoring, and gas adsorption applications of CMBAs, which are prepared by precursor materials, such as polymer-derived carbon, carbon nanotubes, carbon nanofibers, graphene, graphene-like carbides, fullerenes, and carbon dots. To achieve this aim, first we introduce the fabrication methods of various aerogels, and, then, discuss the strategies for regulating the structures of CMBAs by adjusting the porosity and periodicity. In addition, the hybridization of CMBAs with other nanomaterials for enhanced properties and functions is demonstrated and discussed through presenting the synthesis processes of various CMBAs. After that, the adsorption performances and mechanisms of functional CMBAs towards CO2, CO, H2S, H2, and organic gases are analyzed in detail. Finally, we provide our own viewpoints on the possible development directions and prospects of this promising research topic. We believe this work is valuable for readers to understand the synthesis methods and functional tailoring of CMBAs, and, meanwhile, to promote the applications of CMBAs in environmental analysis and safety monitoring of harmful gases.

Recent Advances in the Fabrication and Environmental Science Applications of Cellulose Nanofibril-Based Functional Materials.

Cellulose is one of the important biomass materials in nature and has shown wide applications in various fields from materials science, biomedicine, tissue engineering, wearable devices, energy, and environmental science, as well as many others. Due to their one-dimensional nanostructure, high specific surface area, excellent biodegradability, low cost, and high sustainability, cellulose nanofibrils/nanofibers (CNFs) have been widely used for environmental science applications in the last years. In this review, we summarize the advance in the design, synthesis, and water purification applications of CNF-based functional nanomaterials. To achieve this aim, we firstly introduce the synthesis and functionalization of CNFs, which are further extended for the formation of CNF hybrid materials by combining with other functional nanoscale building blocks, such as polymers, biomolecules, nanoparticles, carbon nanotubes, and two-dimensional (2D) materials. Then, the fabrication methods of CNF-based 2D membranes/films, three-dimensional (3D) hydrogels, and 3D aerogels are presented. Regarding the environmental science applications, CNF-based nanomaterials for the removal of metal ions, anions, organic dyes, oils, and bio-contents are demonstrated and discussed in detail. Finally, the challenges and outlooks in this promising research field are discussed. It is expected that this topical review will guide and inspire the design and fabrication of CNF-based novel nanomaterials with high sustainability for practical applications.

Chiral molecular imprinted sensor for highly selective determination of D-carnitine in enantiomers via dsDNA-assisted conformation immobilization.

In this paper, a novel approach was established on the basis of a molecularly imprinted technique with the aid of double-stranded deoxyribonucleic acid (dsDNA) embedded in a molecularly imprinted polymer (MIP) membrane as a new functional unit with chiral recognition for highly specific chiral recognition. The chiral molecules were immobilized and anchored in the cavities of the MIP membrane on the basis of the three-dimensional structure of a molecule determined by the functional groups, spatial characterization of the cavities of MIPs, and the spatial orientation with dsDNA embedded in MIPs. D-carnitine was selected as an example of a chiral molecular template, which intercalated into dsDNA immobilized on the gold electrode surface to form dsDNA-D-carnitine complex, and then the complex was embedded in the MIP during electropolymerization. After elution, the stereo-selective cavities were obtained. Our findings have shown that AAAA-TTTT base sequence had high affinity for D-carnitine intercalation. Combined with the electrochemical detection method, MIP sensor was prepared. The selectivity of the MIP sensor to ultratrace D-carnitine was significantly improved; the sensor had remarkable stereo-selectivity and highly chiral specific recognition to D-carnitine, and L-carnitine with a concentration of 10,000 times D-carnitine did not interfere with the detection of D-carnitine in the assay of raceme. The sensor also exhibited high sensitivity to ultratrace D-carnitine determination with a linear response to the concentration of D-carnitine in the range of 3.0 × 10-16 mol/L to 4.0 × 10-13 mol/L, with a detection limit of 2.24 × 10-16 mol/L. The mechanism of chiral recognition was studied, and result showed that apart from the recognition effect of imprinted cavities, dsDNA provided chiral selectivity to the spatial orientation of chiral molecules via the intercalation of chiral molecules with dsDNA and electrostatic interaction with groups of DNA base.

A high sensitive epitope imprinted electrochemical sensor for bovine serum albumin based on enzyme amplifying.

To improve the sensitivity of the molecular imprinting sensor detection of protein, a new strategy based on enzyme amplification was proposed. The determination of bovine serum albumin (BSA) was achieved by using the epitope imprinted techniques coupling with electrochemical measurement method. Nonapeptide, separated from BSA, was selected as a template molecule to prepare the molecularly imprinted polymer (MIP) film, and it could bind with the cavities of the MIP. By the use of epitope imprinted techniques, BSA can be recognized by the MIP via the nonapeptide on the surface of BSA. The synthesized horseradish peroxidase-labeled nonapeptide (HRP-nonapeptide) can also be recognized by the MIP. After the competitive reaction between HRP-nonapeptide and BSA, the enzymatic reaction derived from labeled HRP on the H2O2-hydroquinone system make the electrochemical current of hydroquinone change, then the concentration of BSA can be indirectly determined. BSA in the range of 1.0-150 ng/mL exhibited a linear relationship with the differential pulse voltammetric current variation and the detection limit was 0.02 ng/mL. The sensor has high sensitivity, good selectivity, and reproducibility. It has been applied to the determination of residual bovine serum albumin in human rabies vaccine with the recovery rate of 98.3%-102.5%.

A molecularly imprinted electrochemiluminescence sensor based on the mimetic enzyme catalytic effect for ultra-trace Ni2+ determination.

A novel molecularly imprinted polymer (MIP) electrochemiluminescence (MIP-ECL) sensor was developed for the highly sensitive and selective determination of ultra-trace levels of Ni2+. The complex Ni2+-dimethylglyoxime (Ni-DMG) was chosen as the template molecule to construct the MIP and then acted as a mimetic enzyme to catalyse the oxidisation of luminol to enhance the ECL signal. When the imprinted cavities were occupied by Ni-DMG in the rebinding process, the ECL intensities produced by the luminol-H2O2 ECL system on the MIP-modified electrode surface increased with increased concentration of the Ni-DMG complex. The highly sensitive determination of Ni2+ was achieved through a catalytic reaction. This technique could be used for the quantitative analysis of Ni2+ with concentrations from 3.0 × 10-12 mol L-1 to 6.0 × 10-9 mol L-1. The detection limit was 1.01 × 10-12 mol L-1, which is much lower than that reported previously. In addition, the allowable amounts of interference ions in the MIP-ECL sensor were higher than that in other common molecularly imprinted sensors because of its excellent recognition of 3D cavity-to-complex molecules and ligand-to-metal ions. This method was successfully used to determine Ni2+ in real samples, such as apples, carrots and grapes, and has been proven feasible for practical applications.

Progress of Mimetic Enzymes and Their Applications in Chemical Sensors.

The need to develop innovative and reformative approaches to synthesize chemical sensors has increased in recent years because of demands for selectivity, stability, and reproducibility. Mimetic enzymes provide an efficient and convenient method for chemical sensors. This review summarizes the application of mimetic enzymes in chemical sensors. Mimetic enzymes can be classified into five categories: hydrolases, oxidoreductases, transferases, isomerases, and induced enzymes. Potential and recent applications of mimetic enzymes in chemical sensors are reviewed in detail, and the outlook of profound development has been illustrated.

Highly sensitive and doubly orientated selective molecularly imprinted electrochemical sensor for Cu(2.).

Studies on molecularly imprinted electrochemical sensors for metal ions determination have been widely reported. However, the sensitivity and selectivity of the sensors needs to be improved urgently. In the current work, a novel molecularly imprinted electrochemical sensor was originally developed for selective determination of ultratrace Cu(2+) by combining the metal-ligand chelate orientated recognition with enzyme amplification effect. The detection relied on a competition reaction between Cu(2+)-glycine (Cu-Gly) and horse radish peroxidase (HRP)-labeled Cu-Gly on the imprinted polymer membrane modified electrode. The sensitivity of this sensor was promoted by enzyme amplification. Selectivity was improved by the double-specificity derived from ligand-to-metal ion and metal-ligand chelate orientated recognition of 3D imprinted cavities. This technique was quantitatively sensitive to Cu(2+) concentrations ranging from 0.5nmol/L to 30nmol/L, with a detection limit of 42.4pmol/L. which was lower than those in most of the reported methods. The allowable amounts of interference ions were higher when it compared to other common molecularly imprinted sensors. Moreover, the results of assaying several real samples have proven its feasibility for practical applications.

Reconfiguration and search of social networks.

Social networks tend to exhibit some topological characteristics different from regular networks and random networks, such as shorter average path length and higher clustering coefficient, and the node degree of the majority of social networks obeys exponential distribution. Based on the topological characteristics of the real social networks, a new network model which suits to portray the structure of social networks was proposed, and the characteristic parameters of the model were calculated. To find out the relationship between two people in the social network, and using the local information of the social network and the parallel mechanism, a hybrid search strategy based on k-walker random and a high degree was proposed. Simulation results show that the strategy can significantly reduce the average number of search steps, so as to effectively improve the search speed and efficiency.

Low-cost fabrication of paper-based microfluidic devices by one-step plotting.

In this technical note, we describe a facile method for one-step fabrication of paper-based microfluidic devices, by simply using commercially available permanent markers and metal templates with specific patterns. The fabrication process involves only a single step of plotting pattern in paper; it can be typically finished within 1 min. The ink marks formed in the patterned paper will act as the hydrophobic barriers to define the hydrophilic flow paths or separate test zones. Various paper devices can be created by using different templates with corresponding patterns. Transparent adhesive tape-sandwiched devices could protect their assay surfaces from potential contamination. In the proof-of-concept experiments, circular paper test zones (~3 mm diameter) were fabricated for colorimetric and quantification detection of prostate-specific antigen (PSA) as a model target, based on dot-immunogold staining assays coupled with gold enhancement amplification. Several serum specimens were additionally evaluated with this new approach and the results were compared with the commercial chemiluminescence immunoassay, validating its feasibility of practical applications. Such a one-step plotting method for paper patterning does not require any specialized equipments and skills, is quite inexpensive and rapid, and thus holds great potential to find wide applications especially in remote regions and resource-limited environments such as small laboratories and private clinics.

TEPITOPEpan: extending TEPITOPE for peptide binding prediction covering over 700 HLA-DR molecules.

MOTIVATION: Accurate identification of peptides binding to specific Major Histocompatibility Complex Class II (MHC-II) molecules is of great importance for elucidating the underlying mechanism of immune recognition, as well as for developing effective epitope-based vaccines and promising immunotherapies for many severe diseases. Due to extreme polymorphism of MHC-II alleles and the high cost of biochemical experiments, the development of computational methods for accurate prediction of binding peptides of MHC-II molecules, particularly for the ones with few or no experimental data, has become a topic of increasing interest. TEPITOPE is a well-used computational approach because of its good interpretability and relatively high performance. However, TEPITOPE can be applied to only 51 out of over 700 known HLA DR molecules. METHOD: We have developed a new method, called TEPITOPEpan, by extrapolating from the binding specificities of HLA DR molecules characterized by TEPITOPE to those uncharacterized. First, each HLA-DR binding pocket is represented by amino acid residues that have close contact with the corresponding peptide binding core residues. Then the pocket similarity between two HLA-DR molecules is calculated as the sequence similarity of the residues. Finally, for an uncharacterized HLA-DR molecule, the binding specificity of each pocket is computed as a weighted average in pocket binding specificities over HLA-DR molecules characterized by TEPITOPE. RESULT: The performance of TEPITOPEpan has been extensively evaluated using various data sets from different viewpoints: predicting MHC binding peptides, identifying HLA ligands and T-cell epitopes and recognizing binding cores. Among the four state-of-the-art competing pan-specific methods, for predicting binding specificities of unknown HLA-DR molecules, TEPITOPEpan was roughly the second best method next to NETMHCIIpan-2.0. Additionally, TEPITOPEpan achieved the best performance in recognizing binding cores. We further analyzed the motifs detected by TEPITOPEpan, examining the corresponding literature of immunology. Its online server and PSSMs therein are available at http://www.biokdd.fudan.edu.cn/Service/TEPITOPEpan/.

Toward more accurate pan-specific MHC-peptide binding prediction: a review of current methods and tools.

Binding of short antigenic peptides to major histocompatibility complex (MHC) molecules is a core step in adaptive immune response. Precise identification of MHC-restricted peptides is of great significance for understanding the mechanism of immune response and promoting the discovery of immunogenic epitopes. However, due to the extremely high MHC polymorphism and huge cost of biochemical experiments, there is no experimentally measured binding data for most MHC molecules. To address the problem of predicting peptides binding to these MHC molecules, recently computational approaches, called pan-specific methods, have received keen interest. Pan-specific methods make use of experimentally obtained binding data of multiple alleles, by which binding peptides (binders) of not only these alleles but also those alleles with no known binders can be predicted. To investigate the possibility of further improvement in performance and usability of pan-specific methods, this article extensively reviews existing pan-specific methods and their web servers. We first present a general framework of pan-specific methods. Then, the strategies and performance as well as utilities of web servers are compared. Finally, we discuss the future direction to improve pan-specific methods for MHC-peptide binding prediction.