Smartphone-Integrated Automated Sensor Employing Electrochemically Engineered 3D Bimetallic Nanoflowers for Hydrogen Peroxide Quantification in Milk.

Hydrogen peroxide (H2O2), one of the reactive oxygen species in living beings, serves as a regulator of various cellular processes. However, excessive peroxide concentrations are linked to oxidative stress and promptly disrupt cellular components, leading to several pathological conditions in the body. Moreover, it is extremely reactive and has a limited lifetime; thus, H2O2 sensing remains a prominent focus of research. Enzymatic sensing probes were widely employed to detect H2O2 in the recent past; however, they are susceptible to intrinsic chemical and thermal instabilities, which decrease the reliability and durability of the surface. This research was designed to come up with a feasible solution to this problem. Herein, a novel nonenzymatic peroxidase-mimic three-dimensional (3D) bimetallic nanoflower has been synergistically engineered for quick sensing of H2O2. The sensor platform showed minimal resistance or enhanced charge transfer properties as well as remarkable analytical capability, having a broad linear range between 0.01 and 1 nM and a detection limit of 1.46 ± 0.07 pM. The probe responded to changes in H2O2 concentration in just 2.10 ± 0.02 s, making it a quick sensing platform for H2O2 tracking. This peroxidase-mimic nanozyme probe showed minimal sensitivity to interferants often seen in real-world sample matrices and possessed good recoveries ranging from 92.88 to 99.09% in milk samples. Further, a facile and user-friendly smartphone application (APP) named "HPeroxide-Check" was developed and integrated into the sensor to check the milk adulteration by detecting H2O2. It processes the current output obtained from the sensing interface and provides real-time peroxide concentrations in milk. The entire procedure of fabricating the probe is a single, highly robust step that takes only 10 min and is coupled with a smartphone APP, highlighting the sensor's quick manufacturing and deployment for automated H2O2 monitoring in industrial and point-of-care settings.

Thiazole-Based Silver Ion Sensor for Sequential Colorimetric Visualization of Epinephrine in the Brain Tissues of an Alzheimer's Disease Model of Mouse.

A thiazole-based probe, N'-((2-aminothiazol-5-yl)methylene)benzohydrazide (TBH), has been efficiently synthesized and characterized for the selective and sensitive detection of the neurotransmitter epinephrine (EP). The sensing strategy is based on the use of TBH for sequential colorimetric sensing of Ag+ and EP via in situ formation of Ag nanoparticles (Ag NPs) from the TBH-Ag+ complex. The generated Ag NPs lead to a bathochromic shift in absorption maximum and a change in color of the solution from light brown to reddish brown. TBH-Ag+ shows remarkable selectivity toward EP versus other drugs, common cations, anions, and some biomolecules. Moreover, TBH-Ag+ has a low detection limit for EP at 1.2 nM. The coordination of TBH-Ag+ has been proposed based on Job's plot, Fourier transform infrared spectroscopy (FT-IR), high-resolution mass spectrometry (HRMS), 1H NMR titration, X-ray photoelectron spectroscopy (XPS), energy-dispersive X-ray analysis (EDAX), and density functional theory (DFT) studies. The composition and morphology of the generated Ag NPs have been analyzed by XPS, scanning electron microscopy (SEM), transmission electron microscopy (TEM), and dynamic light scattering (DLS). The proposed sensing mechanism for EP has been supported by XPS of Ag after the reaction. Further, the sensitivity of TBH-Ag+ toward EP in brain tissues of an Alzheimer's disease model of mouse has been evaluated. A thorough comparison was done for evaluation of the proposed method.

Highly electrochemically active Ti3C2Tx MXene/MWCNT nanocomposite for the simultaneous sensing of paracetamol, theophylline, and caffeine in human blood samples.

The facile fabrication is reported of highly electrochemically active Ti3C2Tx MXene/MWCNT (3D/1D)-modified screen-printed carbon electrode (SPE) for the efficient simultaneous electrochemical detection of paracetamol, theophylline, and caffeine in human blood samples. 3D/1D Ti3C2Tx MXene/MWCNT nanocomposite was synthesized using microwave irradiation and ultrasonication processes. Then, the Ti3C2Tx/MWCNT-modified SPE electrode was fabricated and thoroughly characterized towards its physicochemical and electrochemical properties using XPS, TEM, FESEM, XRD, electrochemical impedance spectroscopy, cyclic voltammetry, and differential pulse voltammetry techniques. As-constructed Ti3C2Tx-MWCNT/SPE offers excellent electrochemical sensing performance with good detection limits (0.23, 0.57, and 0.43 µM) and wide linear ranges (1.0 ~ 90.1, 2.0 ~ 62.0, and 2.0-90.9 µM) for paracetamol, caffeine, and theophylline, respectively,  in the human samples. Notably, the non-enzymatic electroactive nanocomposite-modified electrode has depicted a semicircle Nyquist plot with low charge transfer resistance (Rct∼95 Ω), leading to high ionic diffusion and facilitating an excellent electron transfer path. All the above results in efficient stability, reproducibility, repeatability, and sensitivity compared with other reported works, and thus, it claims its practical utilization in realistic clinical applications.

A rapid and sensitive analytical methodology for the simultaneous biomonitoring of two direct oral anticoagulant drugs and their major metabolites in thromboembolic disordered patients samples for clinical evaluations.

Apixaban and dabigatran are the two major direct oral anticoagulant drugs to treat thromboembolic disordered patients. Increasing the clinical application for the thromboembolic disorder and monitoring the concentrations of apixaban, dabigatran, and their metabolites are essential in most clinical circumstances. In this work, we developed a rapid analytical methodology comprising of vortex-assisted salt-enhanced liquid-liquid microextraction technique coupled with UHPLC-MS/MS for the extraction and simultaneous determination of two major direct oral anticoagulant drugs (apixaban, dabigatran), and their two major metabolites from plasma, serum, and urine samples of patients. The developed method was optimized with various procedural steps and validated to study the analytical merits. The developed method yielded a good detection limit of 0.01 ∼ 0.37 ng/mL, 0.01 ∼ 0.32 ng/ml, and 0.01 ∼ 0.27 ng/mL for four target analytes in the plasma, serum, and urine matrices. Moreover, extraction recoveries ranged from 85.11 - 113.57% (for plasma), 89.63 - 110.47% (for serum), and 87.44 -106.79% (for urine samples) with 8.78% RSD. In addition, the method exhibited good R2 values of 0.999 for all four target analytes, and the specificity and carryover study revealed no carryover effect from the UHPLC-MS/MS system for determining the apixaban, dabigatran, and their metabolites. Due to the above advantages, the developed analytical technique was applied to examine 11 real-time clinical patients' samples, and the observed results were satisfactory for all three different sample matrices. Therefore, this analytical method can be applied for biomonitoring apixaban, dabigatran, and their two major metabolites with high sensitivity in a short time for various clinical applications.

Bioengineered cellulosic paper micro-device for serum albumin detection in clinical range.

Chronic Kidney Disease (CKD) is becoming one of the major causes of morbidity and mortalities in 21st century. We have developed a bioengineered cellulosic paper device for the quantification of albumin (ALB) in physiological samples. The paper surface was activated and antibodies specific to target biomarker was immobilized on engineered paper surface. Every step after modification was characterized by FTIR, XPS, SPM and optical analysis. Further, the device model was designed using CAD file, and a 3-D cascade device was fabricated with in-built constant light source to provide proper and controlled environment for in-situ image analysis. After adding the sample on the bioengineered paper, the antigen-antibody reaction takes place, after that addition of dye results in change of color from yellow to blueish-green within 40 s. An optical method was employed for the analysis of the images by recognizing the specific area and the color intensity. Additionally, the immunosensor specificity was evaluated on number of molecules that are usually found in the serum sample. The linear dynamic range of the developed immunosensor has been reported to be 1-60 mg/mL, covering the normal as well as clinical range of ALB in physiological samples with a detection limit of 0.049(±0.002) mg/mL. With good precision and recovery, the device was able to successfully determine the ALB concentrations in serum sample. The developed device has simple and user-friendly interface and it may also help diagnosing CKD in personalized settings.

Printed circuit boards: system automation and alternative matrix for biosensing.

Circuit integration has revolutionized the diagnostic sector by improving the sensing ability and rapidity of biosensors. Bioelectronics has led to the development of point-of-care (PoC) devices, offering superior performance compared with conventional biosensing systems. These devices have lower production costs, are smaller, and have greater reproducibility, enabling the construction of compact sensing modules. Flexible upgrades to the fabrication pattern of the printed circuit board (PCB) remains the most reliable and consistent means so far, offering portability, wearability, a lower detection limit, and smart output integration to these devices. This review summarizes the advances in PCB technology for biosensing devices for introducing automation and their emerging application as an alternative matrix material for detecting various analytes.

Insights into the Fabrication and Electrochemical Aspects of Paper Microfluidics-Based Biosensor Module.

Over the past ten years, microfluidic paper-based analytical devices (micro-PADs) have attracted a lot of attention as a viable analytical platform. It is expanding as a result of advances in manufacturing processes and device integration. Conventional microfluidics approaches have some drawbacks, including high costs, lengthy evaluation times, complicated fabrication, and the necessity of experienced employees. Hence, it is extremely important to construct a detection system that is quick, affordable, portable, and efficient. Nowadays, micro-PADs are frequently employed, particularly in electrochemical analyses, to replicate the classic standard laboratory experiments on a miniature paper chip. It has benefits like rapid assessment, small sample consumption, quick reaction, accuracy, and multiplex function. The goal of this review is to examine modern paper microfluidics-based electrochemical sensing devices for the detection of macromolecules, small molecules, and cells in a variety of real samples. The design and fabrication of micro-PADs using conventional and the latest techniques have also been discussed in detail. Lastly, the limitations and potential of these analytical platforms are examined in order to shed light on future research.

Exploring the Potential Applications of Engineered Borophene in Nanobiosensing and Theranostics.

A monolayer of boron known as borophene has emerged as a novel and fascinating two-dimensional (2D) material with exceptional features, such as anisotropic metallic behavior and supple mechanical and optical capabilities. The engineering of smart functionalized opto-electric 2D materials is essential to obtain biosensors or biodevices of desired performance. Borophene is one of the most emerging 2D materials, and owing to its excellent electroactive surface area, high electron transport, anisotropic behavior, controllable optical and electrochemical properties, ability to be deposited on thin films, and potential to create surface functionalities, it has recently become one of the sophisticated platforms. Despite the difficulty of production, borophene may be immobilized utilizing chemistries, be functionalized on a flexible substrate, and be controlled over electro-optical properties to create a highly sensitive biosensor system that could be used for point-of-care diagnostics. Its electrochemical properties can be tailored by using appropriate nanomaterials, redox mediators, conducting polymers, etc., which will be quite useful for the detection of biomolecules at even trace levels with a high sensitivity and less detection time. This will be quite helpful in developing biosensing devices with a very high sensitivity and with less response time. So, this review will be a crucial foundation as we have discussed the basic properties, synthesis, and potential applications of borophene in nanobiosensing, as well as therapeutic applications.

Design and development of opto-electrochemical biosensing devices for diagnosing chronic kidney disease.

Chronic kidney disease (CKD) is emerging as one of the major causes of the increase in mortality rate and is expected to become 5th major cause by 2050. Many studies have shown that it is majorly related to various risk factors, and thus becoming one of the major health issues around the globe. Early detection of renal disease lowers the overall burden of disease by preventing individuals from developing kidney impairment. Therefore, diagnosis and prevention of CKD are becoming the major challenges, and in this situation, biosensors have emerged as one of the best possible solutions. Biosensors are becoming one of the preferred choices for various diseases diagnosis as they provide simpler, cost-effective and precise methods for onsite detection. In this review, we have tried to discuss the globally developed biosensors for the detection of CKD, focusing on their design, pattern, and applicability in real samples. Two major classifications of biosensors based on transduction systems, that is, optical and electrochemical, for kidney disease have been discussed in detail. Also, the major focus is given to clinical biomarkers such as albumin, creatinine, and others related to kidney dysfunction. Furthermore, the globally developed sensors for the detection of CKD are discussed in tabulated form comparing their analytical performance, response time, specificity as well as performance in biological fluids.

Engineered Liposomes in Interventional Theranostics of Solid Tumors.

Engineered liposomal nanoparticles have unique characteristics as cargo carriers in cancer care and therapeutics. Liposomal theranostics have shown significant progress in preclinical and clinical cancer models in the past few years. Liposomal hybrid systems have not only been approved by the FDA but have also reached the market level. Nanosized liposomes are clinically proven systems for delivering multiple therapeutic as well as imaging agents to the target sites in (i) cancer theranostics of solid tumors, (ii) image-guided therapeutics, and (iii) combination therapeutic applications. The choice of diagnostics and therapeutics can intervene in the theranostics property of the engineered system. However, integrating imaging and therapeutics probes within lipid self-assembly "liposome" may compromise their overall theranostics performance. On the other hand, liposomal systems suffer from their fragile nature, site-selective tumor targeting, specific biodistribution and premature leakage of loaded cargo molecules before reaching the target site. Various engineering approaches, viz., grafting, conjugation, encapsulations, etc., have been investigated to overcome the aforementioned issues. It has been studied that surface-engineered liposomes demonstrate better tumor selectivity and improved therapeutic activity and retention in cells/or solid tumors. It should be noted that several other parameters like reproducibility, stability, smooth circulation, toxicity of vital organs, patient compliance, etc. must be addressed before using liposomal theranostics agents in solid tumors or clinical models. Herein, we have reviewed the importance and challenges of liposomal medicines in targeted cancer theranostics with their preclinical and clinical progress and a translational overview.

Chemically engineered unzipped multiwalled carbon nanotube and rGO nanohybrid for ultrasensitive picloram detection in rice water and soil samples.

Picloram (4-Amino-3,5,6-trichloro pyridine-2-carboxylic acid) is a chlorinated herbicide that has been discovered to be tenacious and relatively durable in both soil and water. It is known to have adverse and unpleasant effects on humans causing several health complications. Therefore, the determination of picloram is profoundly effective because of its bio-accumulative and persistent nature. Because of this, a sensitive, rapid, and robust detection system is essential to detect traces of this molecule. In this study, we have constructed a novel nanohybrid system comprising of an UZMWCNT and rGO decorated on AuNPs modified glassy carbon electrode (UZMWCNT + rGO/AuNPs/GCE). The synthesized nanomaterials and the developed system were characterized using techniques such as SEM, XRD, SWV, LSV, EIS, and chronoamperometry. The engineered sensor surface showed a broad linear range of 5 × 10-2 nM to 6 × 105 nM , a low limit of detection (LOD) of 2.31 ± 0.02 (RSD < 4.1%) pM and a limit of quantification (LOQ) of 7.63 ± 0.03 pM. The response time was recorded to be 0.2 s, and the efficacy of the proposed sensor system was studied using rice water and soil samples collected from the agricultural field post filtration. The calculated recovery % for picloram in rice water was found to be 88.58%-96.70% (RSD < 3.5%, n = 3) and for soil it was found to be 89.57%-93.24% (RSD < 3.5%, n = 3). In addition, the SWV responses of both the real samples have been performed and a linear plot have been obtained with a correlation coefficient of 0.97 and 0.96 for rice and soil samples, respectively. The interference studies due to the coexisting molecules that may be present in the samples have been found to be negligible. Also, the designed sensor has been evaluated for stability and found to be highly reproducible and stable towards picloram detection.

Electrochemical Nano-Imprinting of Trimetallic Dendritic Surface for Ultrasensitive Detection of Cephalexin in Pharmaceutical Formulations.

Cephalexin (CFX), a first-generation cephalosporin, is used to treat various infectious diseases. Although antibiotics have achieved considerable progress in the eradication of infectious diseases, their incorrect and excessive usage has contributed to various side effects, such as mouth soreness, pregnancy-related pruritus, and gastrointestinal symptoms, including nausea, epigastric discomfort, vomiting, diarrhoea, and haematuria. In addition to this, it also causes antibiotic resistance, one of the most pressing problems in the medical field. The World Health Organization (WHO) claims that cephalosporins are currently the most commonly used drugs for which bacteria have developed resistance. Hence, it is crucial to detect CFX in complex biological matrices in a highly selective and sensitive way. In view of this, a unique trimetallic dendritic nanostructure comprised of cobalt, copper, and gold was electrochemically imprinted on an electrode surface by optimising the electrodeposition variables. The dendritic sensing probe was thoroughly characterised using X-ray photoelectron spectroscopy, scanning electron microscopy, chronoamperometry, electrochemical impedance spectroscopy, and linear sweep voltammetry. The probe displayed superior analytical performance, with a linear dynamic range between 0.05 nM and 105 nM, limit of detection of 0.04 ± 0.01 nM, and response time of 4.5 ± 0.2 s. The dendritic sensing probe displayed minimal response to interfering compounds, such as glucose, acetaminophen, uric acid, aspirin, ascorbic acid, chloramphenicol, and glutamine, which usually occur together in real matrices. In order to check the feasibility of the surface, analysis of a real sample was carried out using the spike and recovery approach in pharmaceutical formulations and milk samples, yielding current recoveries of 93.29-99.77% and 92.66-98.29%, respectively, with RSD < 3.5%. It only took around 30 min to imprint the surface and analyse the CFX molecule, making it a quick and efficient platform for drug analysis in clinical settings.

Clinically Deployable Bioelectronic Sensing Platform for Ultrasensitive Detection of Transferrin in Serum Sample.

Varying levels of transferrin (Tf) have been associated with different disease conditions and are known to play a crucial role in various malignancies. Regular monitoring of the variations in Tf levels can be useful for managing related diseases, especially for the prognosis of certain cancers. We fabricated an immunosensor based on graphene oxide (GO) nanosheets to indirectly detect Tf levels in cancer patients. The GO nanosheets were deposited onto an indium tin oxide (ITO)-coated glass substrate and annealed at 120 °C to obtain reduced GO (rGO) films, followed by the immobilization of an antibody, anti-Tf. The materials and sensor probe used were systematically characterized by UV-Visible spectroscopy (UV-Vis), X-ray diffraction (XRD), atomic force microscopy (AFM), and Fourier transform infrared spectroscopy (FTIR). Cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), and differential pulse voltammetry (DPV) were also used for the stepwise sensor probe characterizations and Tf detection in serum samples, respectively. The anti-Tf/rGO/ITO immunosensor DPV output demonstrated an excellent Tf detection capability in the linear range of 0.1 mg mL-1 to 12 mg mL-1 compared to the enzyme-linked immunosorbent assay (ELISA) detection range, with a limit of detection (LOD) of 0.010 ± 0.007 mg mL-1. Furthermore, the results of the fabricated immunosensor were compared with those of the ELISA and autobioanalyzer techniques, showing an outstanding match with < 5% error and demonstrating the immunosensor's clinical potential.

Nanobiosensors Design Using 2D Materials: Implementation in Infectious and Fatal Disease Diagnosis.

Nanobiosensors are devices that utilize a very small probe and any form of electrical, optical, or magnetic technology to detect and analyze a biochemical or biological process. With an increasing population today, nanobiosensors have become the broadly used electroanalytical tools for the timely detection of many infectious (dengue, hepatitis, tuberculosis, leukemia, etc.) and other fatal diseases, such as prostate cancer, breast cancer, etc., at their early stage. Compared to classical or traditional analytical methods, nanobiosensors have significant benefits, including low detection limit, high selectivity and sensitivity, shorter analysis duration, easier portability, biocompatibility, and ease of miniaturization for on-site monitoring. Very similar to biosensors, nanobiosensors can also be classified in numerous ways, either depending on biological molecules, such as enzymes, antibodies, and aptamer, or by working principles, such as optical and electrochemical. Various nanobiosensors, such as cyclic voltametric, amperometric, impedimetric, etc., have been discussed for the timely monitoring of the infectious and fatal diseases at their early stage. Nanobiosensors performance and efficiency can be enhanced by using a variety of engineered nanostructures, which include nanotubes, nanoparticles, nanopores, self-adhesive monolayers, nanowires, and nanocomposites. Here, this mini review recaps the application of two-dimensional (2D) materials, especially graphitic carbon nitride (g-C3N4), graphene oxide, black phosphorous, and MXenes, for the construction of the nanobiosensors and their application for the diagnosis of various infectious diseases at very early stage.

Engineered Biosensors for Diagnosing Multidrug Resistance in Microbial and Malignant Cells.

To curtail pathogens or tumors, antimicrobial or antineoplastic drugs have been developed. These drugs target microbial/cancer growth and survival, thereby improving the host's health. In attempts to evade the detrimental effects of such drugs, these cells have evolved several mechanisms over time. Some variants of the cells have developed resistances against multiple drugs or antimicrobial agents. Such microorganisms or cancer cells are said to exhibit multidrug resistance (MDR). The drug resistance status of a cell can be determined by analyzing several genotypic and phenotypic changes, which are brought about by significant physiological and biochemical alterations. Owing to their resilient nature, treatment and management of MDR cases in clinics is arduous and requires a meticulous approach. Currently, techniques such as plating and culturing, biopsy, gene sequencing, and magnetic resonance imaging are prevalent in clinical practices for determining drug resistance status. However, the major drawbacks of using these methods lie in their time-consuming nature and the problem of translating them into point-of-care or mass-detection tools. To overcome the shortcomings of conventional techniques, biosensors with a low detection limit have been engineered to provide quick and reliable results conveniently. These devices are highly versatile in terms of analyte range and quantities that can be detected to report drug resistance in a given sample. A brief introduction to MDR, along with a detailed insight into recent biosensor design trends and use for identifying multidrug-resistant microorganisms and tumors, is presented in this review.

Personalized biosensors for point-of-care diagnostics: from bench to bedside applications.

The most significant feature of translational point-of-care technology "Personalized biosensors" is that it can be done quickly and by clinical staff who are not trained in clinical laboratory sciences. Rapid test results can quickly give a doctor or other medical worker answers that can help them decide what to do or how to treat a patient. This is helpful almost everywhere, from the emergency room to a patient getting care at home. When a doctor meets a patient for the first time, during a flare-up of a known problem or when a new symptom shows up in a patient who is already being treated, having faster access to test results gives the doctor answers when they are with the patient or are about to see the patient which indicate the importance of point-of-care technologies and their future scope.

Drug Encapsulated Lipid-Polymeric Nanohybrid as a Chemo-therapeutic Platform of Cancer.

The focus of this research is to design a bioengineered drug delivery vehicle that is efficient in anti-cancer drug delivery in a controlled manner. The experimental work focuses on constructing a methotrexate-loaded nano lipid polymer system (MTX-NLPHS) that can transport methotrexate (MTX) in MCF-7 cell lines in a controlled manner through endocytosis via phosphatidylcholine. In this experiment, MTX is embedded with polylactic-co-glycolic acid (PLGA) in phosphatidylcholine, which acts as a liposomal framework for regulated drug delivery. Scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and dynamic light scattering (DLS) were utilized to characterize the developed nanohybrid system. The particle size and encapsulation efficiency of the MTX-NLPHS were found to be 198 ± 8.44 nm and 86.48 ± 0.31 %, respectively, which is suitable for biological applications. The polydispersity index (PDI) and zeta potential of the final system were found to be 0.134 ± 0.048 and -28 ± 3.50 mV, respectively. The lower value of PDI showed the homogenous nature of the particle size, whereas higher negative zeta potential prevented the system from agglomeration. An in vitro release kinetics was conducted to see the release pattern of the system, which took 250 h for 100% drug release This kind of system may carry the drug for a long time in the circulatory system and prevent the drug discharge. Other cell culture assays such as 3-(4, 5-dimethyl thiazolyl-2)-2, 5-diphenyltetrazolium bromide (MTT) and reactive oxygen species (ROS) monitoring were used to see the effect of inducers on the cellular system. MTT assay showed cell toxicity of MTX-NLPHS reduced at the lower concentration of the MTX, however, toxicity increased at the higher concentration of the MTX as compared to free MTX. ROS monitoring c revealed more scavenging of ROS using MTX-NLPHS as compared to free MTX. Confocal microscopy suggested the MTX-NLPHS induced more nuclear elongation with cell shrinkage comparatively.

Analogue and structure based approaches for modelling HIV-1 integrase inhibitors.

A set of 220 inhibitors belonging to different structure classes and having HIV-1 integrase activity were collected along with their experimental pIC50 values. Geometries of all the inhibitors were fully optimized using B3LYP/6-31 + G(d) level of theory. These ligands were docked against 4 different HIV-1 integrase receptors (PDB IDs: 4LH5, 5KRS, 3ZSQ and 3ZSV). 30 docked poses were generated for all 220 inhibitors and ligand interaction of the first docked pose and the docked pose with the highest score were analysed. Residue GLU170 of 4LH5 receptor shows the highest number of interactions followed by ALA169, GLN168, HIS171 and ASP167 residues. Hydrogen bonding and stacking are mainly responsible for the interactions of these inhibitors with the receptor. We performed Molecular Dynamics (MD) simulation to observe the root-mean-square deviation (RMSD), for measure the average change of displacement between the atoms for a particular frame with respect to a reference and The Root Mean Square Fluctuation (RMSF) for characterization of local changes along the protein chain of the docked complexes. Analogue based models were generated to predict the pIC50 values for integrase inhibitors using various types of descriptors such as constitutional, geometrical, topological, quantum chemical and docking based descriptors. The best models were selected on the basis of statistical parameters and were validated by training and test set division. A few new inhibitors were designed on the basis of structure activity relationship and their pIC50 values were predicted using the generated models. All the designed new inhibitors a very high potential and may be used as potent inhibitors of HIV integrase. These models may be useful for further design and development of new and potent HIV integrase inhibitors.Communicated by Ramaswamy H. Sarma.

Bioengineering of bone tissues using bioreactors for modulation of mechano-sensitivity in bone.

Since the last decade, significant developments have been made in the area of bone tissue engineering associated with the emergence of novel biomaterials as well as techniques of scaffold fabrication. Despite all these developments, the translation from research findings to clinical applications is still very limited. Manufacturing the designed tissue constructs in a scalable manner remains the most challenging aspect. This bottleneck could be overcome by using bioreactors for the manufacture of these tissue constructs. In this review, a current scenario of bone injuries/defects and the cause of the translational gap between laboratory research and clinical use has been emphasized. Furthermore, various bioreactors being used in the area of bone tissue regeneration in recent studies have been highlighted along with their advantages and limitations. A vivid literature survey on the ideal attributes of bioreactors has been accounted, viz. dynamic, versatile, automated, reproducible and commercialization aspects. Additionally, the illustration of computational approaches that should be combined with bone tissue engineering experiments using bioreactors to simulate and optimize cellular growth in bone tissue constructs has also been done extensively.

Development of a palm-sized bioelectronic sensing device for protein detection in milk samples.

The present study relates a portable optical sensing device supported by a small single-board (SBC) computer. The electronic architectural avenue connects the SBC with a camera, LED lights and a monitor. A 'sensor integration unit' has been linked with the device where the biological reactions were performed and assessed based on the concentration-dependent optical signal outputs. This setup can detect the generation of colors and distinguish their changes in the RGB intensity scale with an accuracy of a single pixel unit. A predefined range of values was obtained and fed to the device that can quantitatively sense the molecule of interest on the sensing matrix. The device has a touchscreen interactive panel that allows users to manually set experimental conditions and connect the entire measurement process to the cloud storage for backup information. We have considered detecting Alkaline Phosphatase (ALP) quantitatively from standard solutions as well as in milk samples as a proof-of-concept protein molecule. The device has shown exceptional analytical performance for lower and higher concentration ranges (0-100 U/mL and 100-1000 U/mL) with correlation coefficient values of 0.99. The detection limit of ALP was determined to be 0.1 U/mL, and the average time of a sample assessment was recorded to be 15 s. The device has also been tested against ALP-spiked milk samples to check its effectiveness and commercial viability. The outcome of the real-time assessment was sensitive and efficient, indicating its direct commercial and clinical importance towards colorimetric detection for diverse macromolecules.