Surface-Engineered Nanomaterials for Optical Array Based Sensing.

Array based sensing governed by optical methods provides fast and economic way for detection of wide variety of analytes where the ideality of detection processes depends on the sensor element's versatile mode of interaction with multiple analytes in an unbiased manner. This can be achieved by either the receptor unit having multiple recognition moiety, or their surface property should possess tuning ability upon fabrication called surface engineering. Nanomaterials have a high surface to volume ratio, making them viable candidates for molecule recognition through surface adsorption phenomena, which makes it ideal to meet the above requirements. Most crucially, by engineering a nanomaterial's surface, one may produce cross-reactive responses for a variety of analytes while focusing solely on a single nanomaterial. Depending on the nature of receptor elements, in the last decade the array-based sensing has been considering as multimodal detection platform which operates through various pathway including single channel, multichannel, binding and indicator displacement assay, sequential ON-OFF sensing, enzyme amplified and nanozyme based sensing etc. In this review we will deliver the working principle for Array-based sensing by using various nanomaterials like nanoparticles, nanosheets, nanodots and self-assembled nanomaterials and their surface functionality for suitable molecular recognition.

Time-resolved fluorescence sensor array for the discrimination of phosphate anions using transition metal dichalcogenide quantum dots and Tb(III).

Phosphate detection has garnered widespread attention due to its biological and environmental impact. Among several optical techniques, time-resolved fluorescence (TRF) provides a sensitive way for the discrimination of analytes in a complex mixture as it exhibits less interference from the background, therefore providing a high signal-to-noise ratio. The sensitization of rare earth metal (REM) ions by semiconducting quantum dots (QDs) can help the former overcome the drawback of low absorption coefficient, therefore allowing exploitation of the additional advantage of the REM, namely the long-excited state lifetime. Here, we have developed a TRF-based sensor array consisting of three QDs, i.e. MoS2 , WS2 and MoSe2 as energy sensitizers for Tb3+ ions. Different QDs possess variable energy transfer abilities for Tb3+ ions. Therefore, they can be used to discriminate phosphates. It was also observed that CrO4 2- can competitively bind to Tb3+ and further enhance the efficiency of the sensor array so that it could discriminate six different phosphates at 200 µM concentration in aqueous as well as serum medium with a detection limit of 10 µM in aqueous medium. Therefore, the sensitivity of the TRF-based sensor array is rarely compromised in a complex mixture, which is advantageous over a fluorescence-based sensor array.

Ligand Exchange on MoS2 Nanosheets: Applications in Array-Based Sensing and Drug Delivery.

Two-dimensional MoS2 nanosheets (2D-MoS2) have been widely used in many biological applications due to their distinctive physicochemical properties. Further, the development of surface modification using thiolated ligands allows us to use them for many specific applications. But the effect of possible ligand exchange on 2D-MoS2 has never been explored, which can play an important role in diverse biological applications. In this study, we have observed the ligand-exchange phenomenon on 2D-MoS2 in the presence of different thiolated ligands. The initial study proceeded with boron-dipyrromethene (BODIPY) functionalized MoS2 with different concentrations of glutathione (GSH), which is the most abundant thiol species in the cytoplasm of various cancer cells. It was found that in the presence of GSH the fluorescence of BODIPY can be regenerated, which is time and concentration dependent. We have also examined this phenomenon with different thiol ligands and transition-metal dichalcogenides (TMDs). We observed a variable rate of ligand exchange in different solvents, surface functionality, and receptor environments that helped us to construct sensor arrays. Interestingly, a ligand-exchange process was not observed in the presence of dithiols. Further, this concept was applied to a cancerous cell line for in vitro delivery. We found that BODIPY-functionalized 2D-MoS2 undergoes thiol exchange by intracellular GSH and subsequently enhanced the fluorescence in the cytoplasm of cancer cells. This strategy can be applied to the development of 2D-TMD-based materials for various biological applications related to ligand exchange.

Rapid Discrimination of Bacterial Drug Resistivity by Array-Based Cross-Validation Using 2D MoS2.

The precise discrimination of microbes based on family, class and drug resistivity is essential for the early diagnosis of infectious diseases. Information about the type and strength of drug resistivity can help the analyst to prescribe a suitable antibiotic at the proper dosage to completely eradicate microbes without giving them a chance to gain further resistance. Herein, we propose a sensor array based on the use of cationic two-dimensional MoS2 units and green fluorescence protein as building blocks. Cationic surfaces of receptors with various functionality were suitable for tunable interaction with anionic surfaces of microbes. The array successfully discriminates six different bacterial strains. The versatile ability of the receptors to bind with the wild-type as well as the corresponding ampicillin-resistant strain contributed significantly to rapid detection with high sensitivity. The optimized array was able to classify five different types and three different extents of drug-resistant variants of Escherichia coli by using bacteria cells and lysates. Finally, we have introduced the cross identification method using both bacteria cells and lysates and we found a great enhancement of detection in sensitivity and accuracy. This is the first report of this approach, which can be extended to many other methods for better accuracy in array-based detection.

Dual Role of MoS2 Quantum Dots in a Cross-Dehydrogenative Coupling Reaction.

Modern day research focuses on the development of greener and eco-friendlier protocols to fabricate biologically relevant targets with minimal waste generation. C-C bond formation reactions are of prime importance in this regard. In a typical photocatalytic hydrogen evolution reaction, three components are used, viz, catalyst, photosensitizer, and sacrificial amine donor. Among these, the photosensitizer and sacrificial amine donors are wasted at the end of the reaction. Considering these drawbacks, in this work, we have developed a methodology targeted at the utilization of sacrificial amine donors for C-H functionalization with MoS2 quantum dots (QDs) as the catalyst as well as the photosensitizer. QDs indeed emerged to be an active participant in the heterogeneous electron transfer process. This concept opens up new possibilities in the field of nanomaterial-based photomediated organic transformations without the aid of any external photosensitizers via a clean and sustainable protocol with no side product.

Machine Learning-Assisted Array-Based Detection of Proteins in Serum Using Functionalized MoS2 Nanosheets and Green Fluorescent Protein Conjugates.

Abnormal concentrations of a specific protein or the presence of some biomarker proteins may indicate life-threatening diseases. Pattern-based detection of specific analytes using affinity-regulated receptors is one of the potential alternatives to specific antigen-antibody-based detection. In this report, we have schemed a sensor array by using various functionalized two-dimensional (2D)-MoS2 nanosheets and green fluorescent protein (GFP) as the receptor and the signal transducer, respectively. Two-dimensional MoS2 has been used as a promising candidate for recognition of the bioanalytes because of its high surface-to-volume ratio compared to those of other nanomaterials. Easy surface tunability of this material provides additional advantages to analyze the target of interest. The optimized 2D-MoS2-GFP conjugates are able to discriminate 15 different proteins at 50 nM concentration with a detection limit of 1 nM. Moreover, proteins in the binary mixture and in the presence of serum were discriminated successfully. Ten different proteins in serum media at relevant concentrations were classified successfully with 100% jackknifed classification accuracy, which proves the potentiality of the above system. We have also implemented and discussed the implication of using different machine learning models on the pattern recognition problem associated with array-based sensing.

Nano-Graphene Oxide Based Multichannel Sensor Arrays towards Sensing of Protein Mixtures.

Optical array-based sensors are attractive candidates for the detection of various bio-analytes due to their convenient fabrication and measurements. For array-based sensors, multichannel arrays are more advantageous and used frequently in many electronic sensors. But most reported optically array based sensors are constructed on a single channel array. This difficulty is mainly instigated from the overlap in optical responses. In this report we have used nano-graphene oxide (nGO) and suitable fluorophores as sensor elements to construct a multichannel sensor array for the detection of protein analytes. By using the optimized multichannel array we are able to detect different proteins and mixtures of proteins with 100 % classification accuracy at sub-nanomolar concentration. This modified method expedites the sensing analysis as well as minimizes the use of both analyte and sensor elements in array-based protein sensing. We have also used this system for the single channel array-based sensing to compare the sensitivity and the efficacy of these two systems for other applications. This work demonstrated an intrinsic trade-off associated with these two methods which may be necessary to balance for array-based analyte detections.

In Situ Synthesis of Amino Acid Functionalized Carbon Dots with Tunable Properties and Their Biological Applications.

Emissive carbon dots (C-Dots) are known for displaying versatile properties, which have been widely utilized in many applications such as bioimaging, light-emitting devices, and photocatalysis. Further functionalization can tune their physical and chemical properties, which play the key role in many biologically and chemically relevant applications. Amino acids provide an attractive means for introducing functionality with a structural diversity. In this work, water-soluble emissive C-Dots were synthesized from pyrolysis of citric acid in the presence of various amino acids under hydrothermal conditions. We established that the diverse functionality-bearing polyamides and the polyester backbone of C-Dots are the origin of optical properties with a high quantum yield. The amino acid based C-Dots were systematically characterized using various analytical methods to confirm the core structure as well as the functionality. The results show that, depending on functionalization, the quantum yield can be varied and enhanced up to 62% and surface charge and hydrophobicity can be tuned. Most importantly, we observed a correlation between the quantum yield and properties of the side chain residue of amino acids such as hydrophobicity index and volume. Furthermore, it was found that the synthesized, diversely functionalized C-Dots exhibit no cellular toxicity and can be used for cell imaging. Due to variable surface functionality, we have also applied these C-Dots for array-based protein sensing. Overall, based on this reported method, we can easily tune the optical as well as surface properties of C-Dots, which will be suitable for many future applications.

Solvent Effect on the Potential Energy Surfaces of the F- + CH3CH2Br Reaction.

Although substantial work has been undertaken on reaction pathways involved in base-promoted elimination reactions and bimolecular nucleophilic substitution reaction of F- on CH3CH2X (X = Cl, Br, I), the effect of solvents with varying dielectric constants on the stereochemistry of each of the reaction species involved across the reaction profile have not yet been clearly understood. The present investigation reports the effect of solvents on the potential energy surfaces (PES) and structures of the species appearing in the reaction pathway of F- with bromoethane. The PESs in the gas phase have been computed at MP2 level and CCSD(T) level. The performance of several hybrid density functional, such as B3LYP, M06, M06L, BHandH, X3LYP, M05, M05-2X, and M06-2X have also been investigated toward describing the elimination and nucleophilic substitution reactions. With respect to MAE values and to make the computation cost-effective, we have explored the implicit continuum solvent model, CPCM in solvents like cyclohexane, methanol, acetonitrile, dimethyl sulfoxide and water. The reactant complexes proceed through the subsequent steps to produce fluoroethane as the substitution product and ethylene as one of the elimination products. For elimination reaction both syn and anti elimination have been explored. The calculated relatives energies values, which are negative in the gas phase, are found to be positive in polar solvents since the point charge in the separated reactants are more stabilized than the dispersed charge in the transient complex, which has also been analyzed through NBO analysis.

Effect of different polymers on in vitro and ex vivo permeability of Ofloxacin from its mucoadhesive suspensions.

Considering the importance of drug permeation from formulations, in vitro and ex vivo drug permeation characteristics of three oral mucoadhesive suspensions of Ofloxacin were designed and compared. Three suspensions of Ofloxacin were prepared by taking two grades of Carbopol polymer such as Carbopol 934 (C934) and Carbopol 940 (C940); and Hydroxypropyl methylcellulose. The permeability study was performed by using a Franz diffusion cell through both synthetic cellulose acetate membrane and excised goat gastrointestinal membranes in acidic as well as alkaline pH. To know the permeability of the drug from control/formulations through different membranes in acidic/alkaline pH, cumulative percentage drug permeation, apparent permeability (Papp) and flux (J) were calculated. In addition, enhancement ratio (ER) of each formulation was also determined. From our results, it is evident that formulation containing C940 was the best suspension considering Papp and J values of all formulations. Moreover, it was the most beneficial formulation for improving permeation and diffusivity of Ofloxacin even after 16 h. Hence, this suspension was probably the most suitable formulation to obtain prolonged release action of the drug. The ER values of all formulations through the excised goat intestinal mucus membrane in alkaline pH were higher than those formulations through the goat stomach mucosal membrane in acidic pH. ER values of those formulations indicate that the permeability of the drug was more enhanced by the polymers in the intestinal part, leading to more bioavailability and prolonged action in that portion of the gastrointestinal tract. It may also be concluded from our results that in addition to formulation containing C940, other formulations may also show effective controlled release action.

Role of different biodegradable polymers on the permeability of ciprofloxacin.

Since permeability across biological membranes is a key factor in the absorption and distribution of drugs, drug permeation characteristics of three oral suspensions of ciprofloxacin were designed and compared. The three suspensions of ciprofloxacin were prepared by taking biodegradable polymers such as carbopol 934, carbopol 940, and hydroxypropyl methylcellulose (HPMC). The permeability study was performed by using a Franz diffusion cell through both synthetic cellulose acetate membrane and excised goat gastrointestinal membranes in acidic as well as alkaline pH. To know the permeability of drug from control/formulations through different membranes in acidic/alkaline pH, cumulative percentage drug permeation, apparent permeability (Papp), flux, and enhancement ratio (ER) were calculated. Considering Papp and flux values of all formulations, it is evident that formulation containing HPMC was the most beneficial for improving permeation and diffusivity of ciprofloxacin even after 16 h. Hence, this preparation may be considered as the most suitable formulation to obtain prolonged release action of the drug. The ER values of all formulations, through excised goat intestinal mucosal membrane in alkaline pH, were higher than those formulations through goat stomach mucosal membrane in acidic pH. Enhancement ratio values of those formulations indicate that the permeability of the drug was more enhanced by the polymers in the intestinal part, leading to more bioavailability and prolonged action in that portion of the gastrointestinal tract. It may also be concluded from our results that HPMC containing formulation was the best suspension, which may show effective controlled release action. Even carbopol containing formulations might also produce controlled release action.