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The simplification of localized surface plasmon resonance (LSPR) detection can further promote the development of optical biosensing application in point-of-care testing. In this study, we proposed a simple light emitting diode (LED) based single-wavelength LSPR sensor modulated with bio-electron transfers for the detection of electroactive biomolecules. Indium tin oxide electrode loaded with nanocomposites of polyaniline coated gold nanorod was used as LSPR chip, and the applied electric potential was scanned at the LSPR chip for single-wavelength LSPR biosensing. Under the scanning of applied potentials, biological electron transfer of redox reaction was employed to demonstrate the bioelectronic modulation of single-wavelength LSPR for selective electroactive biomolecule detection. Without any additional recognition material, electroactive biomolecules uric acid and dopamine were detected directly with a sensitivity of 5.05 μmol/L and 7.11 μmol/L at their specific oxidation potentials, respectively. With the simplified optical configuration and selective bioelectronic modulation, the single-wavelength LSPR sensor is promising for the development of simple, low-cost, and high specificity optical biosensor for point-of-care testing of electroactive biomolecules.

Background: This is the first review on Poly(diphenylamine) and its nanohybrids which covers about 181 references demonstrating the brief discussion on the theoretical studies, chemical, electrochemical and other-phase preparation techniques, polymerization and oxidation-reduction (redox) mechanisms, physicochemical and electrochemical properties along with electrochemical sensors and spectroscopic applications on the detection of chemicals and biomolecules analysis applications. Objective: The main aim of this detailed report is merely to afford a survey of the literature existing on this multifunctional conducting organic polymer (poly(diphenylamine)) that provokes a pathway to innovations and discoveries in the near future claim its applications in multidisciplinary fields, especially in the detection of chemicals and bio-molecules applications. Methods: We discussed the overall studies on poly(diphenylamine) and its various nanohybrids, including copolymers, homopolymers, carbon-based, and metal/metal-oxide hybrids. The different synthesis methods of poly(diphenylamine) such as chemical/electrochemical/mechano-chemical polymerization in terms of morphology and electrical conductivity were briefly discussed. Conclusion: This review manuscript deliberates the various synthesis approaches and applications based on the multifunctional conducting polymer poly(diphenylamine) and its nanohybrids. This review provides an outlook and challenges ahead that ignites spotlight to innovations and discoveries in the near future claim its applications in multidisciplinary fields, particularly in electrochemical sensors and spectroscopic applications towards the detection of chemicals and bio-molecules.

The assembly of biomacromole particles with artificial solid matrixes to fabricate hybrid composites has been demonstrated as an efficient strategy to promote both components’ applications. Elaborating matrixes as well as appropriate assembly method is essential for optimal performances of the obtained natural-artificial composites. Herein, we fabricated the Cyt c@COF-42-B microcapsule through a sacrificial templating method and researched their adjustable biocatalysis by precisely adjusting the microenvironments of these assembled enzyme@COF particles. As a result, the hydrophobicity and mass transfer of the COF microcapsule can be controlled by modifying the different amounts of PEG moieties, thus improving the composite's bioactivity. We found that compared with pristine Cyt c@COF-42-B without PEG, the Cyt c@COF-42-B-PEG exhibited a ∼2.2 times higher activity. This study provides a significant step toward designing customizable functional natural-artificial composites for enhanced biomacromolecule's activity.

Detection of nucleoside derivatives has paramount importance because they are the essential biomolecular units for all life. Herein, we report a host-guest approach by using a fluorescent tetraphenylethene-based octacationic cage as host and 8-hydroxypyrene-1,3,6-trisulfonic acid trisodium salt (HPTS) as guest and fluorescent indicator to form non-fluorescent 1:1:1 host-(endo-exo)guest complex in water. This new host-(endo-exo)guest complex can be successfully used for detecting nucleosides (e.g., ATP and GTP), DNA (e.g., sm-DNA), and antibiotics (e.g., Penicillin G) with off-on fluorescence response via a competitive host-guest exchange with HPTS as exo-guest in water. Furthermore, this on-off-on fluorescent host-guest complex is also used for cell imaging based on ATP concentration in HeLa cells. Therefore, this study not only provides insight into the construction of a supramolecular probe with on-off-on fluorescence via host-guest complexation and exchange in solution, but also realizes a universal method for detecting and monitoring biomolecules.

Accurate localization of central nervous system (CNS) drug distribution in the brain is quite challenging to matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI), owing to the ionization competition/suppression of highly abundant endogenous biomolecules and MALDI matrix. Herein, we developed a highly efficient sample preparation technique, laser-assisted chemical transfer (LACT), to enhance the detection sensitivity of CNS drugs in brain tissues. A focused diode laser source transilluminated the tissue slide coated with α-cyano-4-hydroxycinnamic acid, an optimal matrix to highly absorb the laser radiation at 405 nm, and a very thin-layer chemical film mainly containing drug molecule was transferred to the acceptor glass slide. Subsequently, MALDI MSI was performed on the chemical film without additional sample treatment. One major advantage of LACT is to minimize ionization competition/suppression from the tissue itself by removing abundant endogenous lipid and protein components. The superior performance of LACT led to the successful visualization of regional distribution patterns of 16 CNS drugs in the mouse brain. Furthermore, the dynamic spatial changes of risperidone and its metabolite were visualized over a 24-h period. Also, the brain-to-plasma (B/P) ratio could be obtained according to MALDI MSI results, providing an alternative means to assess brain penetration in drug discovery.

The development of architectural components with the capabilities of biological systems could lead to the realization of biofunctional, dynamic, interactive, and self-sustaining “living” architecture. One route to interfacing biological systems with architectural materials is functionalization with biomolecules. In particular, functionalization of surfaces with DNA incorporates both informational and active properties such as the ability to produce proteins. However, direct conjugation to surfaces can degrade biomolecule activity, reduce reaction kinetics, and limit available binding sites. Integration of DNA into a hydrogel matrix that is conjugated to the surface can overcome these limitations. Here, DNA encoding genetic information is converted into a hydrogel matrix, termed Meta P-gel. The unique mechanical properties of Meta P-gel allow it to adsorb to patterned ceramic surfaces in a spatially controlled manner. Simultaneously, Meta P-gel retains the biological ability to produce proteins, achieving spatial control over protein synthesis for potential applications in living architecture. Finally, Meta P-gel-based functionalization is applied to create stable protein gradients in situ, further exemplifying its applicability beyond architecture. These experiments are a first step toward continuous and stable protein expression from spatially controlled DNA hydrogels that would enable applications in biotechnological fields such as biosensor development and screening, and more broadly, in architectural fields such as fabrication of bioactive and bio-responsive ceramics for building facade design.

Magnetic particles (MPs) are the most widely used commercialized engineering particles, which gained great success in various biological applications. Inspired by their intrinsic Fe isotope composition, we discovered a commercialized MPs-internal standard's novel function to realize the accurate quantification of biomolecules. The bioassay of carcinoembryonic antigen (CEA) was chosen as a modal system. The Fe isotope in MPs and Au isotope in report probes were simultaneously and sensitively detected by the elemental mass spectrometry. 197Au/57Fe isotopic ratios and CEA concentrations showed good linearity in the range of 0.6–300 ng/mL, with a detection limit of 0.09 ng/mL (3σ). The accuracy and precision of the proposed MPs-based immunoassay were greatly improved, by eliminating potential MPs loss during magnetic separation and absolute intensity fluctuations. Considering the exceptional availability and universality of commercialized MPs, the proposed method might open a new avenue for MPs' biological applications.

Molecular aspects of living systems are important because it is the most basic aspects of life as exemplified in biochemistry and structural biology. Since molecules move due to interactive forces between atoms, physics plays an important role to understand the dynamic phenomena of living systems. Here we review our multiscale approaches for computationally treating different levels of molecular motions: vibrational dynamics of molecules, conformational change of biomolecules, and cellular dynamics using statistical-mechanics-based models.

Extremely high sensitivity is the long-time pursing goal for the surface plasmon resonance (SPR) sensor, which means the capability to detect analytes with lower concentrations or interactions for smaller biomolecules. It was suggested that a flat dispersion for the plasmon material enables to enhance the sensitivity dramatically. However, the regulation ability of inherent dispersion in natural materials is limited. With the appearance of hyperbolic metamaterials (HMMs), the management of the plasmon materials dispersion becomes possible. In this paper, the HMMs with metal/dielectric multilayer structure are proposed to construct the SPR sensors. Through numerical simulations and theoretical analysis, we find that the flat dispersion in the HMM structure could significantly benefit the sensitivity improvement for HMM-SPR sensors. As a result, the proposed HMM-SPR sensor obtains an ultrahigh sensitivity of 34.00 m/RIU in the experiment, which is one order higher in magnitude than that of the conventional monolayer metallic SPR sensors. Thus, this research shows insight into understanding the dependence of the HMM-SPR sensitivity on dispersion management and provides a practical methodology to develop extremely high-sensitivity SPR sensors based on artificial plasmon materials.

Native mass spectrometry (MS) is aimed at preserving and determining the native structure, composition, and stoichiometry of biomolecules and their complexes from solution after they are transferred into the gas phase. Major improvements in native MS instrumentation and experimental methods over the past few decades have led to a concomitant increase in the complexity and heterogeneity of samples that can be analyzed, including protein-ligand complexes, protein complexes with multiple coexisting stoichiometries, and membrane protein-lipid assemblies. Heterogeneous features of these biomolecular samples can be important for understanding structure and function. However, sample heterogeneity can make assignment of ion mass, charge, composition, and structure very challenging due to the overlap of tens or even hundreds of peaks in the mass spectrum. In this review, we cover data analysis, experimental, and instrumental advances and strategies aimed at solving this problem, with an in-depth discussion of theoretical and practical aspects of the use of available deconvolution algorithms and tools. We also reflect upon current challenges and provide a view of the future of this exciting field.

Magnesium is an indispensable cofactor in countless vital processes. In order to understand its functional role, the characterization of the binding pathways to biomolecules such as RNA is crucial. Despite the importance, a molecular description is still lacking since the transition from the water-mediated outer-sphere to the direct inner-sphere conformation is on the millisecond timescale and therefore out of reach for conventional simulation techniques. To fill this gap, we use transition path sampling to resolve the binding pathways and to elucidate the role of the solvent in the reaction. The results reveal that the molecular void provoked by the leaving phosphate oxygen of the RNA is immediately filled by an entering water molecule. In addition, water molecules from the first and second hydration shell couple to the concerted exchange. To capture the intimate solute-solvent coupling, we perform a committor analysis as basis for a machine learning algorithm that derives the optimal deep learning model from thousands of scanned architectures using hyperparameter tuning. The results reveal that the properly optimized deep network architecture recognizes the important solvent structures, extracts the relevant information and predicts the commitment probability with high accuracy. Our results provide a quantitative description of solute-solvent coupling which is ubiquitous for kosmotropic ions and governs a large variety of biochemical reactions in aqueous solutions.

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link. Estimations of accurate and reliable NMR chemical shift values, coupling patterns and constants within a reasonable timeframe remain significantly challenging, and the unavailability of reliable software strategies for the prediction of low-field (e.g., 60 MHz) spectra from those acquired at higher operating frequencies hampers their direct comparison. Hence, this study explored the applications of accessible software options for predicting these parameters in the 1H NMR profiles of analytes as a function of magnetic field strength; this was performed for individual analytes and also for complex biofluid matrices featured in metabolomics investigations. For this purpose, results from the very first successful experimental acquisition and simulation of the 1H NMR profiles of intact human salivary supernatant samples on a 60 MHz benchtop spectrometer were evaluated. Using salivary metabolite concentrations determined at 400 MHz, it was demonstrated that simulation of the low-field spectra of five biomolecules with the most prominent 1H resonances detectable allowed multiple component fits to be applied to experimental spectra. Hence, these salivary 1H NMR profiles could be successfully predicted throughout the 45–600 MHz operating frequency range. With the exception of propionate resonance multiplets, which revealed more complex coupling patterns at low field and required more astute computational and fitting options, valuable quantitative metabolomics data on salivary acetate, formate, methanol and glycine could be attained from low-field spectrometres. These studies are both timely and pertinent in view of the recent advancement of low-field benchtop NMR facilities for diagnostically significant biomarker tracking in biofluids. Experiments performed with added ammonium chloride to facilitate the release of salivary metabolites from biopolymer binding sites provided evidence that a small but nevertheless significant proportion of propionate, but not lactate, was bound to such sites, an observation of much relevance to biomolecule quantification in salivary metabolomics investigations.

Bacterial extracellular vesicles (EVs) are nanoscale lipid-enclosed packages that are released by bacteria cells and shuttle various biomolecules between bacteria or host cells. They are implicated in playing several important roles, from infectious disease progression to maintaining proper gut health, however the tools available to characterise and classify them are limited and impractical for many applications. Surface-enhanced Raman Spectroscopy (SERS) provides a promising means of rapidly fingerprinting bacterial EVs in a label-free manner by taking advantage of plasmonic resonances that occur on nanopatterned surfaces, effectively amplifying the inelastic scattering of incident light. In this study, we demonstrate that by applying machine learning algorithms to bacterial EV SERS spectra, EVs from cultures of the same bacterial species Escherichia coli can be classified by strain, culture conditions, and purification method. While these EVs are highly purified and homogeneous compared to complex samples, the ability to classify them from a single species demonstrates the incredible power of SERS when combined with machine learning, and the importance of considering these parameters in future applications. We anticipate that these findings will play a crucial role in developing the laboratory and clinical utility of bacterial EVs, such as the label-free, noninvasive, and rapid diagnosis of infections without the need to culture samples from blood, urine, or other fluids.

Triarylboranes have been known for more than 100 years and have found potential applications in various fields such as anion sensors and optoelectronics, for example in organic light emitting diodes (OLEDs), field effect transistors (OFETs), and organic photovoltaic devices. However, biological applications, such as bioimaging agents and biomolecule sensors have evolved much more recently. This review summarises progress in this relatively young field and highlights the potential of triarylboranes in biological applications.

A breadth of strategies are needed to efficiently modify oligonucleotides with peptides or lipids to capitalize on their therapeutic and diagnostic potential, including the modulation of in vivo chemical stability and for applications in cell-targeting and cell-permeability. The chemical linkages typically used in peptide oligonucleotide conjugates (POCs) have limitations in terms of stability and/or ease of synthesis. Herein, we report an efficient method for POC synthesis using a diselenide-selenoester ligation (DSL)-deselenization strategy that rapidly generates a stable amide linkage between the two biomolecules. This conjugation strategy is underpinned by a novel selenide phosphoramidite building block that can be incorporated into an oligonucleotide by solid-phase synthesis to generate diselenide dimer molecules. These can be rapidly ligated with peptide selenoesters and, following in situ deselenization, leads to the efficient generation of POCs. The diselenide within the oligonucleotide also serves as a flexible functionalisation handle that can be leveraged for fluorescent labelling, as well as for alkylation to generate micelles.

Imaging biomolecules within the single bacterial cell is crucial for understanding cellular genetic mechanisms. Herein, we exploited a surface-enhanced Raman spectroscopy (SERS) imaging strategy for single cell analysis. The cellular biosynthesized Ag nanoparticles (NPs) provided the necessary enhancement for SERS imaging. Multiple complementary techniques, including high-resolution transmission electron microscopy (HR-TEM), high-angle annular dark-field (HAADF)-scanning transmission electron microscopy (STEM), and energy-dispersive X-ray spectroscopy (EDX), were used to characterize the biogenic Ag NPs in cells. Three-dimensional SERS imaging maps displayed biomolecules spectral information of the single cell. Multivariate curve resolution (MCR) model and principal component analysis (PCA) model were used to analyze the cellular SERS imaging maps. MCR model, with specific constraint of non-negativity, resulted in meaningful identification of biomolecules associated with Ag reduction. Focusing on the molecular level reveals that Pantoea sp. IMH utilizes several mechanisms to synthesize Ag NPs, including cytoplasm reduction by glucose or nicotinamide adenine dinucleotide (NADH)-dependent reductase, and extracellular reduction by electron transfer chain containing quinone and cytochrome C. Our results shed new light on Ag NPs biosynthesis mechanism and single cell Raman analysis.

The green synthesis of nanoparticles using plant extracts plays an important role in the field of nanotechnology. The potential of biomolecules present in plant extracts in reducing metal ions to nanoparticles in a single step of green synthesis process is very important. In this study we report on synthesis of Chromium oxide nanoparticles (Cr2O3) by reduction of potassium chromate solution with Manihot esculenta leaf extract. The presence of water soluble carbohydrates which have an aldehyde group may lead the formation of Cr2O3 nanoparticles. The fabricated Chromium oxide nanoparticles were confirmed by UV–Vis spectroscopy, X-ray diffraction (XRD), Fourier transform-infrared spectroscopy (FTIR) and Scanning electron microscopy (SEM).XRD and UV–Visible absorption studies. The images showed that the size of NPs of Cr2O3 varied with average crystalline size 85–100 nm of nanosized Cr2O3.

The electrochemical sensor fused with the principle of immunoassay can recognize the specific binding reaction of antigen and antibody, and transduce it directly into an electrical signal, realizing the rapid detection of relevant disease markers in the liquid sample. In this study, an electrochemical sensor for detecting eosinophil cationic protein (ECP), a marker of allergic rhinitis, was constructed based on a chemically modified electrode, and the surface of the carbon electrode was modified with semiconductor colloidal quantum dots (CQDs). Owing to the remarkable surface effect, size effect and unique quantum effect of CQDs, which can improve the enrichment of biomolecules and signal transduction on the surface of the carbon electrode, the lead sulfide (PbS) CQDs have good adhesion to the carbon electrode. On the basis of the ECP antibody coating and sealing treatment on the surface of the CQDs modified working electrode, combined with the differential pulse voltammetry (DPV) that can significantly reduce the background current for electrochemical performance testing, then the quantitative detection of ECP antigen of different concentrations can be achieved. The detection time of the electrochemical sensor for ECP was about 30 seconds, and the detection limit was 0.508 pg mL−1. The electrochemical sensor has the characteristics of high sensitivity, convenience and non-invasiveness, showing the potential for early screening of diseases such as allergic rhinitis.

The concept of multivalency finds various applications in the fields of chemistry and biology, relying on the principle that multiple weak interactions can lead to strong adhesive forces. Polymeric carriers are promising tools to translate these properties into the field of biomedicine, especially upon functionalization by active biomolecules, such as antibodies. In this study we report on the synthesis of dendritic polyglycerol (dPG) and dPG-based nanogels (NGs) as platforms for the multivalent display of molecules and their potential application as carrier units. Macromolecules based on dPG were synthesized and NGs were generated by strain-promoted azide-alkyne cycloaddition (SPAAC) by inverse nanoprecipitation under mild conditions. Scale-up screening rendered a reproducible method for a batch size of up to 50 mg for the formation of NGs in a size range of 150 nm with narrow dispersity. Dye-labelled bovine serum albumin (FITC-BSA) was chosen as model protein and showed successful conjugation to the carriers, while the protein’s secondary structure was not affected. Consequently, cyanine-5-amine (Cy5-NH2) and avidin (Av) were conjugated in order to exploit the strong avidin-biotin interaction, facilitating the directed attachment of a myriad of biotinylated (bio)molecules. As a proof-of-concept, the biotinylated monoclonal antibodies (mAbs) α-CD3 and α-CD28 were attached to the platforms and their capability to activate T cells was assessed. Experiments were performed with a Jurkat reporter cell line which expresses green fluorescent protein (GFP) upon activation, providing a rapid and reliable readout by flow cytometry. Carriers clearly outperformed conventional compounds for activation (i.e. antibodies crosslinked with anti-IgG antibody) at significantly lower dosages. These findings could be confirmed by confocal laser scanning microscopy (CLSM), showing accumulation of the functional nanoplatforms at the cell surface and cytoplasmic GFP expression (>95% activation of cells for the multivalent conjugates at 10 µg mL-1 compared to 37% activation with conventionally crosslinked mAbs at 25 µg mL-1), whereas carriers without mAbs could not activate cells. As the attachment of biotinylated molecules to the functional nanoplatforms is straightforward, the results obtained show their great potential of our platforms for a broad range of applications.

The building blocks of life – nucleotides, amino acids and saccharides – give rise to a large variety of components and make up the hierarchical structures found in Nature. Driven by chirality and non-covalent interactions, helical and highly organised structures are formed and the way in which they fold correlates with specific recognition and hence function. A great amount of effort is being put into mimicking these highly specialised biosystems as biomaterials for biomedical applications, ranging from drug discovery to regenerative medicine. However, as well as lacking the complexity found in Nature, their bio-activity is sometimes low and hierarchical ordering is missing or underdeveloped. Moreover, small differences in folding in natural biomolecules (e.g., caused by mutations) can have a catastrophic effect on the function they perform. In order to develop biomaterials that are more efficient in interacting with biomolecules, such as proteins, DNA and cells, we speculate that incorporating order and handedness into biomaterial design is necessary. In this review, we first focus on order and handedness found in Nature in peptides, nucleotides and saccharides, followed by selected examples of synthetic biomimetic systems based on these components that aim to capture some aspects of these ordered features. Computational simulations are very helpful in predicting atomic orientation and molecular organisation, and can provide invaluable information on how to further improve on biomaterial designs. In the last part of the review, a critical perspective is provided along with considerations that can be implemented in next-generation biomaterial designs.

Recent emergence of FTIR spectromicroscopy (micro-FTIR) as a dynamic spectroscopy for imaging to the study of biological chemistry has opened new possibilities for investigating in situ drug release, redox chemistry effects with biological molecules, DNA and drug interactions, membranes dynamic, and redox reaction with proteins at the single cell level. Micro-FTIR applied to metallodrugs have been playing important role in the last decade because of its great potential to achieve more robust and controlled pharmacological effects against several diseases, including cancer. An important aspect in the development of these drugs is to understand their cellular properties, such as uptake, accumulation, activity, and toxicity. In this review, we present the potential application of the micro-FTIR and its importance for studying metal-based drugs, highlighting the prospective of chemistry of living cells. We also present a bioimaging emphasis, which is therefore of high importance to localize the cellular processes, for the proper understanding of the mechanism of action.

Intracellular delivery of biomolecules and nanoscale materials to individual cells has gained remarkable attention in recent years owing to its wide applications in drug delivery, clinical diagnostics, bio-imaging, and single-cell analysis. It remains a challenge to control and measure the delivered amount in one cell. In this work, we developed a multifunctional nanopipette-containing both nanopore and nanoelectrode (pyrolytic carbon) at the apex- as a facile, minimal-invasive, and effective platform for both controllable single-cell intracellular delivery and single-entity counting. While controlled by a micromanipulator, the baseline changes of nanopore ionic current (I) and nanoelectrode open circuit potential (V) help to guide the nanopipette tip insertion and positioning processes. The delivery from the nanopore barrel can be facilely controlled by the applied nanopore bias. To optimize the intracellular single-entity detection while delivery, we studied the effects of nanopipette tip geometry and solution salt concentration in controlled experiments. We have successfully delivered gold nanoparticles and biomolecules into the cell, as confirmed by the increased scattering and fluorescence signals, respectively. The delivered entities have also been detected at the single-entity level by using either one or both transient I and V signals. We found the sensitivity of the single-entity electrochemical measurement was greatly affected by the local environment of the cell and varied between cell lines.

Many biomarkers for early diagnosis of cancer and other diseases are difficult to detect because they often exist in body fluids in very low concentrations and are masked by high-abundance proteins such as albumin and immunoglobulins. At the same time, water pollution is one of the most serious environmental problems, but the existing adsorption materials have many shortcomings such as slow kinetics, small adsorption capacity and low adsorption efficiency. Nanotraps, mixed with gases or liquids, can capture and concentrate target substances, such as biomolecules, metal ions and oxoanions. Using nanotraps is a versatile sample pre-processing approach and it can improve the sensitivity of downstream analysis techniques. Herein, the preparations and applications of different types of nanotraps are mainly introduced. What's more, the shortcomings of using nanotraps in practical applications are also discussed. Using nanotraps is a promising sample pre-processing technology, which is of great significance for biomarkers discovery, diseases diagnosis, sewage purification and valuable ions recovery. STATEMENT OF SIGNIFICANCE: This review collates and summarizes the preparations and applications of different types of nanotraps, and discusses the shortcomings of using nanotraps in practical applications. Nanotraps, mixed with gases or liquids, can capture and concentrate target materials, such as biomolecules, metal ions and oxoanions. Using nanotraps is a versatile sample pre-processing approach and it can improve the sensitivity of downstream analysis techniques. During the COVID-19 pandemic, hydrogel nanotraps were successfully utilized for RT-PCR analysis with the FDA Emergency Used Authorization for COVID-19. Using nanotraps is a promising sample pre-processing technology, which is of great significance for biomarkers discovery, diseases diagnosis, sewage purification and valuable ions recovery.

Abstract Oxidized tannic acid (OTA) is a useful biomolecule with a strong tendency to form complexes with metals and proteins. In this study we open the possibility to further the application of OTA when assembled as supramolecular systems, which typically exhibit functions that correlate with shape and associated morphological features. We used machine learning (ML) to selectively engineer OTA into particles encompassing one-dimensional to three-dimensional constructs. We employed Bayesian regression to correlate colloidal suspension conditions (pH and pKa) with the size and shape of the assembled colloidal particles. Fewer than 20 experiments were found to be sufficient to build surrogate model landscapes of OTA morphology in the experimental design space, which were chemically interpretable and endowed predictive power on data. We produced multiple property landscapes from the experimental data, helping us to infer solutions that would satisfy, simultaneously, multiple design objectives. The balance between data efficiency and the depth of information delivered by ML approaches testify to their potential to engineer particles, opening new prospects in the emerging field of particle morphogenesis, impacting bioactivity, adhesion, interfacial stabilization, and other functions inherent to OTA. Impact statement Tannic acid is a versatile bio-derived material employed in coatings, surface modifiers, and emulsion and growth stabilizers, which also imparts mild anti-viral health benefits. Our recent work on the crystallization of oxidized tannic acid (OTA) colloids opens the route toward further valuable applications, but here the functional properties tend to depend strongly on particle morphology. In this study, we eschew trial-and-error morphology exploration of OTA particles in favor of a data-driven approach. We digitalized the experimental observations and input them into a Gaussian process regression algorithm to generate morphology surrogate models. These help us to visualize particle morphology in the design space of material processing conditions, and thus determine how to selectively engineer one-dimensional or three-dimensional particles with targeted functionalities. We extend this approach to visualize other experimental outcomes, including particle yield and particle surface-to-volume ratio, which are useful for the design of products based on OTA particles. Our findings demonstrate the use of data-efficient surrogate models for general materials engineering purposes and facilitate the development of next-generation OTA-based applications. Graphic abstract

Blocking non-specific binding of fluorescent biomolecules in single-molecule detection is one of the most important approach to minimize the background noise. Polyethylene glycol (PEG) and its derivatives are the most frequently-used self-assembled monolayers (SAMs) for surface passivation because they are particularly effective at reducing the adsorption of a majority of fluorescent biomolecules. Most studies about mechanism focus only on biomolecules themselves and sparse literature exists examining the interactions between commercial fluorophores and organosilane SAMs. The objective of this study was studying the interactions between fluorescein isothiocyanate (FITC) and PEG SAMs in solutions with different ionic strengths. Total internal reflection microscopy (TIRM) was utilized for quantitative analysis of the interactions. In low ionic strength solution, strong electrostatic attractions between PS-silica-FITC particles and PEG500 SAMs were detected even though both bodies were negatively charged. The origin of the attractive force was the charge correlations between the heterogeneous surfaces. In high ionic strength, the electrostatic attractions were completely screened, only left with the van der Waals attractions between the PS-silica-FITC particles and PEG SAMs. Due to the polarizability of FITC molecule, Hamaker constant was enlarged and the measured attractive forces depended on the thickness of PEG SAMs. The phenomenon can be explained by the mechanism of biomolecular resistance, including steric repulsion and hydration shell. The energy penalty of a small molecule is much less than that of a large biomolecule while penetrating into the PEG layers. This work reveals that the PEG SAMs not only fail to prevent the non-specific binding of FITC molecules, but also attract the fluorophores through van der Waals interactions.

Intracellular components (including organelles and biomolecules) at the submicron level are typically analyzed in situ by special preparation or expensive setups. Here, a label-free and cost-effective approach of screening microalgal single-cells at a subcellular resolution is available based on impedance cytometry. To the best of our knowledge, it is the first time to show the relationships between impedance signals and submicron intracellular organelles and biomolecules. Experiments were performed on Euglena gracilis (E. gracilis) cells incubated under different incubation conditions (i.e., aerobic and anaerobic) and 15 μm polystyrene beads (reference) at two distinct stimulation frequencies (i.e., 500 kHz and 6 MHz). Based on the impedance detection of tens of thousands of samples at a throughput of 900 cells/s, three metrics were used to track the changes in biophyscial properties of samples. As a result, the electrical diameters of cells showed a clear shrinkage in cell volume and intracellular components, as observed under microscope. The morphology metric of impedance pulses (i.e., tilt index) successfully characterized the changes in cell shape and intracellular composition distribution. Besides, the electrical opacity showed the stable ratio of the intracellular components to cell volume under the cellular self-regulation. Additionally, simulations were used to support these findings and to elucidate how submicron intracellular components and cell morphology affect impedance signals, providing a basis for future improvements. This work opens up a label-free and high-throughput way to analyze single-cell intracellular components by impedance cytometry.

The typical aza-BODIPYs in the dye family are known for bright fluorescence, excellent stability, and tunable absorption wavelengths. Hence, these dyes are attracting the increasing attention. Aza-BODIPYs having the maxima absorption in the near-infrared (NIR) region (650–900 nm) are very favorable for bioimaging in vivo due to the less photo-damage, deeper tissue penetration, and less interference from background auto-fluorescence by biomolecules in the living systems. Many strategies have been employed to modify the structures of the aza-BODIPY core to provide the NIR absorbing dyes. Among these, the most effective method is the fusion of the aromatic rings in aza-BODIPY system. This review allsidedly summarizes the recent development of ring-fused aza-BODIPY dyes (λabs> 700 nm) focusing on the design, synthesis, and potential applications in the NIR region since 2002.

In the information age, data storage technology has become the key to improving computer systems. Since traditional storage technologies cannot meet the demand for massive storage, new DNA storage technology based on biomolecules attracts much attention. DNA storage refers to the technology that uses artificially synthesized deoxynucleotide chains to store and read all information, such as documents, pictures, and audio. First, data are encoded into binary number strings. Then, the four types of base, A(Adenine), T(Thymine), C(Cytosine), and G(Guanine), are used to encode the corresponding binary numbers so that the data can be used to construct the target DNA molecules in the form of deoxynucleotide chains. Subsequently, the corresponding DNA molecules are artificially synthesized, enabling the data to be stored within them. Compared with traditional storage systems, DNA storage has major advantages, such as high storage density, long duration, as well as low hardware cost, high access parallelism, and strong scalability, which satisfies the demands for big data storage. This manuscript first reviews the origin and development of DNA storage technology, then the storage principles, contents, and methods are introduced. Finally, the development of DNA storage technology is analyzed. From the initial research to the cutting edge of this field and beyond, the advantages, disadvantages, and practical applications of DNA storage technology require continuous exploration.

Biotin is widely used in biological applications due to its highly selective and stable interaction with avidin, which highlights the great potential value of the quantitative determination of biotin concentration. However, the currently reported methods have many defects such as complicated operation process and low sensitivity. Here, the time-resolved fluorescence resonance energy transfer (TR-FRET) assay is introduced to establish a convenient, rapid and sensitive biotin quantitative detection strategy. Europium cryptate (Eu3+) acts as an energy donor to label streptavidin, while APC acts as an energy acceptor to label biotin. Biotin in aqueous solution interacts with streptavidin in a competition model. The obtained biotin detection range is 0.05-100 nM and an optimal limit of detection (LOD) of 0.03 nM biotin is obtained. Furthermore, the enzyme digestion test and competition mode test are implemented to analyze biotin in different states. The method involved in this work has greatly improved the sensitivity of biotin quantitative detection. And it’s the first time to systematically study the difference between free and bound biotin on concentration results. It can be furtherly extended to the detection of other biological molecules, or multiplex detection of other small molecules.

Covalent organic frameworks (COFs) have emerged as highly crystalline porous organic materials and proved to be the potential candidates for various interesting applications, such as gas adsorption and separation, catalysis, energy storage, and sensing, etc. Fluorescence-based sensing has gained great attention due to its high selectivity, rapid response time, and real-time monitoring. Lately, luminescent COFs have come to the fore as sensing probes to detect the various target molecules. In this review, we have targeted a comprehensive account of the chronological development of the field of COFs starting from 2005 till date. We have described the design principle with a focus on various topologies reported, classification of their structural diversity on the basis of thirty-two linkages and dimensionality, methods of synthesis with examples, and the use of various characterization techniques. Interestingly, almost one-half of the COFs contains linkages that are nitrogen-rich. With a background in different processes involved for fluorescence sensing, we have illustrated the potential applicability of nitrogen-rich COFs as sensors for numerousanalytes, such as explosives, volatile organic molecules, pH, temperature, toxic anions, metal ions and biomolecules from different media utilizing the striking features of COFs with predesigned structures and diverse functionality.

Sulfated biomolecules are known to influence numerous biological processes in all living organisms. Particularly, they contribute to prevent and inhibit the hypercoagulation condition. The failure of polymeric implants and blood contacting devices is often related to hypercoagulation and microbial contamination. Here, bioactive sulfated biomacromolecules are mimicked by sulfation of poly(glycerol glycidyl ether) (polyGGE) films. Autoclaving, gamma-ray irradiation and ethylene oxide (EtO) gas sterilization techniques were applied to functionalized materials. The sulfate group density and hydrophilicity of sulfated polymers were decreased while chain mobility and thermal degradation were enhanced post autoclaving when compared to those after EtO sterilization. These results suggest that a quality control after sterilization is mandatory to ensure the amount and functionality of functionalized groups are retained.

Tea is a very important source of the terepenoid [Formula: see text]-ionone, which is much appreciated as a medicinal beverage. Schiff bases are a very important class of organic compounds usually formed by the condensation of carbonyl compounds with amines. [Formula: see text]-ionone is a carbonyl terpenoid obtained from Schiff bases on condensation with nucleobases like adenine and cytosine and the amino acid [Formula: see text]-leucine. We synthesized these three Schiff bases and characterized them using UV, FTIR, and H1 and C13-NMR spectra. The molecules were optimized using B3LYP/6-311+G(2d,p) level followed by the simulation of FT-IR spectra, of which the simulated and experimental spectra showed complete agreement. The UV spectra were simulated using TD-DFT, and the electronic excitations were carefully analyzed. Natural bond orbitals provided an analysis of the stability of the compound, which is supplemented by the data from frontier molecular orbital analysis. Detailed wavefunction analysis is reported which predicts the active centers, reactivity profile, and the extent of non-covalent interactions. PASS indicated that compounds show antieczemic properties and antiarthritic properties, which is confirmed with the help of molecular docking results.

Background: Peptides and peptide-based therapeutics are biomolecules that demarcate a significant chemical space to bridge small molecules with biological therapeutics, such as antibodies, recombinant proteins, and protein domains. Introduction: Cyclooligopeptides and depsipeptides, particularly cyanobacteria-derived thiazoline-based polypeptides (CTBCs), exhibit a wide array of pharmacological activities due to their unique structural features and interesting bioactions, which furnish them as promising leads for drug discovery. Methods: In the present study, we comprehensively review the natural sources, distinguishing chemistries, and pertinent bioprofiles of CTBCs. We analyze their structural peculiarities counting the mode of actions for biological portrayals which render CTBCs as indispensable sources for emergence of prospective peptide-based therapeutics. In this milieu, metal organic frameworks and their biomedical applications are also briefly discussed. To boot, the challenges, approaches, and clinical status of peptide-based therapeutics are conferred. Results: Based on these analyses, CTBCs can be appraised as ideal drug targets that have always remained a challenge for traditional small molecules, like those involved in protein- protein interactions or to be developed as potential cancer-targeting nanomaterials. Cyclization-induced reduced conformational freedom of these cyclooligopeptides contribute to improved metabolic stability and binding affinity to their molecular targets. Clinical success of several cyclic peptides provokes the large library-screening and synthesis of natural product-like cyclic peptides to address the unmet medical needs. Conclusion: CTBCs can be considered as the most promising lead compounds for drug discovery. Adopting the amalgamation of advanced biological and biopharmaceutical strategies might endure these cyclopeptides to be prospective biomolecules for futuristic therapeutic applications in the coming times.

Chemiluminescence (CL) has been widely used for bioanalysis owing to its high sensitivity, low background and simplicity. However, most of the CL systems need acidic/alkaline conditions or organic solvent to enhance their luminescent efficiency, and the non-physiological conditions can usually lead to the misfunction of biomolecules during biosensing. Herein, we report a highly luminous CL system under physiological conditions based on carbon dots-bis(2-carbopentyloxy-3,5,6-trichlorophenyl) oxalate (CDs-CPPO) micelles, and further used it in biosensing application. In the CL system, the amphiphilic surfactant packed CPPO and hydrophobic CDs together to form CDs-CPPO micelles. Such micelles solution not only isolated the CPPO from water to prevent its hydrolysis but also made the close proximity between CPPO and CDs, thus significantly enhancing the CDs quantum yield. The CL quantum yield was calculated to be 5.26 × 10−4 einsteins/mol, about 200-fold higher than that of the most commonly used luminol CL system. The oxidases (e.g., glucose oxidase) were tested to be susceptible to the organic solvent and non-physiological pH. Hence, the CL system was used for the detection of oxidase substrates (exemplified by glucose) in serum samples, and the limit of detection was as low as 8.4 nmol/L. The highly luminous CL system that can work under physiological conditions is promising for biosensing applications

Building compatible surface on perovskite quantum dots (PQDs) for applications like sensing analytes in aqueous medium is highly challenging and if achieved by simple means can revolutionize disease diagnostics. The present work reports the surface engineering of CsPbBr3 QDs via "simple ligand exchange process" to achieve water-compatible QDs towards detection of biomolecules. The monodentate oleic acid ligand in CsPbBr3 QDs is exchanged with dicarboxylic acid containing (bidentate) ligands such as folic acid (FA), ethylenediamine tetra-acetic acid (EDTA), succinic acid (SA) and glutamic acid (GA) to develop an efficient water-compatible PQD-ligand system. optical and theoretical studies showed the existence of a stronger binding between the perovskite and succinic acid ligand as compared to oleic acid (OA) and all other ligands. Replacement of OA with SA and retention of crystal structure is validated using spectroscopic and microscopic tools. It is observed that SA ligands facilitate better electronic coupling with PQDs and show significant improvement in fluorescence and stability. Further N-Hydroxy succinimide (NHS), which is a well-known compound to activate carboxyl groups, is used to bind onto SA PQDs as multidentate ligand, to form water stable PQDs. SA PQDs react with NHS (in water) to form multidentate ligand passivated PQDs that show very high photoluminescence (PL) as compared to OA PQDs in toluene. This also results in the formation of an NHS ester that allows bioconjugation with PQDs. This simple probe in water is further utilized for sensing a highly hydrophilic bovine serum albumin (BSA) protein as a model target to demonstrate the potential and effectiveness of this process to create compatible QDs for the successful conjugation of biomolecules. Although the focus of this work is to demonstrate bioconjugation and not achieving higher sensitivity levels, the intrinsic sensing level of these compatible QDs towards BSA shows a detection limit of 51.47 nM, which is above par with other reports in literature.

Background Phenolic compounds are secondary metabolites with wide biological activities, and their biological activity is inseparable from their interactions with proteins. Phenolic-protein interactions will occur at the moment they are mixed, and this interaction will continue during food processing, handling, ingestion, digestion, metabolism and bioutilization, leading to a profound impact on the structure and properties of phenols and proteins. Scope and approach This review summarizes current knowledge of the contributions of phenolic-protein interactions to the bioactivities and functional mechanism of phenolic-containing foods. We firstly provide a comprehensive review of the interactions between phenolic ingredients and dietary proteins, and the multi-step interactions between ingested phenolics or derived phenolic products and functional proteins (like enzymes, transporters, receptors and transcription factors (TFs)) inside the human body, along with the involved intermolecular forces. In addition, we have proposed the use of molecular docking for predicting such interactions, and demonstrated some docking results of dietary phenolics (or their derived metabolites) with human TFs. Key finding and conclusions The phenolic-protein interactions in foods and post ingestion may function as multi-switches empowering health outcomes. This review asserts the need for increasing the knowledge of the interactions between the ingested phenolics or their derived products and all the protein biomolecules inside the human body.

Contamination caused by the accumulation of petrochemical-based plastics has reached worrying magnitudes and led to the development of biopolymers as an option to mitigate the problem. This work thus presents a bibliometric analysis of all that concerns the development of such bionanocomposite materials, using ScientoPy and SciMAT software to establish associations between the number of published documents, countries, institutions and most relevant topics. The bionanocomposites topic was found to throw up the biggest number of documents associated (2008) with the different types of raw materials and methods used to obtain nanoparticles and their combination with biopolymeric materials, the result known as a “bionancomposite*”. Analysis of the documents related to the application for development of packaging materials from biological molecules, carbohydrate polymers, compounds, conjugates, gels, glucans, hydrogels, membranes, mucilage (source unspecified), mucoadhesives, paper, polymers, polysaccharide, saccharides etc, is also presented, emphasizing mechanical, thermal and barrier properties, which, due to the inclusion of nanoparticles mainly from natural sources of cellulose, show increases of up to 30%. The inclusion of nanoparticles, especially those derived from cellulose sources, generally seeks to increase the properties of bionanocomposite materials. Regarding an increase in mechanical properties, specifically tensile strength, inclusions at percentages not exceeding 10 wt% can register increases that exceed 30% were reported.

It is important to clarify the transport of biomolecules and chemicals to tissues. Herein, we present an electrochemical imaging method for evaluating the endothelial permeability. In this method, the diffusion of electrochemical tracers, [Fe(CN)6]4–, through a monolayer of human umbilical vein endothelial cells (HUVECs) was monitored using a large-scale integration-based device containing 400 electrodes. In conventional tracer-based assays, tracers that diffuse through an HUVEC monolayer into another channel are detected. In contrast, the present method does not employ separated channels. In detail, a HUVEC monolayer is immersed in a solution containing [Fe(CN)6]4– on the device. As [Fe(CN)6]4– is oxidized and consumed at the packed electrodes, [Fe(CN)6]4– begins to diffuse through the monolayer from the bulk solution to the electrodes and the obtained currents depend on the endothelial permeability. As a proof-of-concept, the effects of histamine on the monolayer were monitored. Also, an HUVEC monolayer was cocultured with cancer spheroids, and the endothelial permeability was monitored to evaluate the metastasis of the cancer spheroids. Unlike conventional methods, the device can provide spatial information, allowing the interaction between the monolayer and the spheroids to be monitored. The developed method is a promising tool for organs-on-a-chip and drug screening in vitro.

Nanomaterials have applications in almost every field and among them, green nanomaterials have various biological applications. Green nanomaterials are specifically useful for drug and DNA delivery applications. Considering that cellulose is the most abundant and easily available biomolecule, it has been used for preparing greener cellulose nanomaterials. Cellulosic nanowhiskers are a cost-effective and green alternative to chemical non-viral gene delivery systems. Cellulose nanowhiskers are commonly extracted from plant sources, and they are generally prepared by sulfuric and hydrochloric acid hydrolysis of plant cellulose. In this review, the topic of cellulose nanowhiskers as green biocompatible materials for gene and drug delivery is discussed with several practical examples.

© 2021 The Authors., Bacterial infection of implanted scaffolds may have fatal consequences and, in combination with the emergence of multidrug bacterial resistance, the development of advanced antibacterial biomaterials and constructs is of great interest. Since decades ago, metals and their ions had been used to minimize bacterial infection risk and, more recently, metal-based nanomaterials, with improved antimicrobial properties, have been advocated as a novel and tunable alternative. A comprehensive review is provided on how metal ions and ion nanoparticles have the potential to decrease or eliminate unwanted bacteria. Antibacterial mechanisms such as oxidative stress induction, ion release and disruption of biomolecules are currently well accepted. However, the exact antimicrobial mechanisms of the discussed metal compounds remain poorly understood. The combination of different metal ions and surface decorations of nanoparticles will lead to synergistic effects and improved microbial killing, and allow to mitigate potential side effects to the host. Starting with a general overview of antibacterial mechanisms, we subsequently focus on specific metal ions such as silver, zinc, copper, iron and gold, and outline their distinct modes of action. Finally, we discuss the use of these metal ions and nanoparticles in tissue engineering to prevent implant failure., M.G-G and U.E have received funding from the postdoctoral fellowship programme Beatriu de Pinós, funded by the Secretary of Universities and Research (Government of Catalonia) and by the Horizon 2020 programme of research and innovation of the European Union under the Marie Sklodowska-Curie grant agreement No 801370. R.A.P is supported by the Spanish Ministry by the Ramón y Cajal Program (RYC2018-025977-I). Additional financial support was provided by the Government of Catalonia (2017 SGR 708) and MINECO/FEDER project (RTI2018-096088-J-100).