73 research outputs found
Graphene as a signal amplifier for preparation of ultrasensitive electrochemical biosensors
Early diagnostics of diseases performed with minimal money and time consumption has become achievable due to recent advances in development of biosensors. These devices use biorecognition elements for selective interaction with an analyte and signal readout is obtained via different types of transducers. Operational characteristics of biosensors have been reported to improve substantially, when a diverse range of nanomaterials was employed. This review presents construction of electrochemical biosensors based on graphene, atomically thin 2D carbon crystals, which is currently intensively studied nanomaterial. The most attractive directions of graphene applications in biosensor preparation are discussed here including novel detection and amplification schemes exploiting graphene’s unique electrochemical, physical and chemical properties. The future of graphene-based biosensors is most likely bright, but there is still a lot of work to do to fulfill high expectations.Slovak scientific grant agency VEGA 2/0162/14 and from the Slovak research and development agency APVV 0282-11 is acknowledged. The research leading to these results has received funding from the European Research Council under the European Union’s Seventh Framework Programme (FP/2007-2013)/ERC Grant Agreement No. 311532 and this work has received funding from the European Union’s Seventh Framework Programme for research, technological development and demonstration under grant agreement no 317420. This work was funded by the National Priorities Research Program (Qatar National Research Fund), NPRP 6-381-1-078
Glycoprofiling of cancer biomarkers: Label-free electrochemical lectin-based biosensors
Glycosylation of biomolecules is one of the most prevalent post- and co-translational modification in a human body, with more than half of all human proteins being glycosylated. Malignant transformation of cells influences glycosylation machinery resulting in subtle changes of the glycosylation pattern within the cell populations as a result of cancer. Thus, an altered terminal glycan motif on glycoproteins could provide a warning signal about disease development and progression and could be applied as a reliable biomarker in cancer diagnostics. Among all highly effective glycoprofiling tools, label-free electrochemical impedance spectroscopy (EIS)-based biosensors have emerged as especially suitable tool for point-of-care early-stage cancer detection. Herein, we highlight the current challenges in glycoprofiling of various cancer biomarkers by ultrasensitive impedimetric-based biosensors with low sample consumption, low cost fabrication and simple miniaturization. Additionally, this review provides a short introduction to the field of glycomics and lectinomics and gives a brief overview of glycan alterations in different types of cancer.Slovak research and development agency APVV 0282-11 and VEGA 2/0162/14 is acknowledged. The research leading to these results has received funding from the European Research Council under the European Union’s Seventh Framework Program (FP/2007-2013)/ERC Grant Agreement no 311532 and this work has received funding from the European Union’s Seventh Framework Program for research, technological development and demonstration under grant agreement no 317420.This publication was made possible by NPRP grant # 6-381-1-078 from the Qatar National Research Fund (a member of Qatar Foundation)
Carboxybetaine Ester Feature as a Platform for Switchable Surface Properties
A lot of strategies for smart approaches on surfaces were applied such as hydrogel layer, polymer brushes or self-assembly monolayers (SAM). [1] Nowadays switchable zwitterionic materials consisting of molecules with internally balanced charge between positive ammonium and negative carboxy group are promising candidates for this application. [2] They can combine antifouling properties of their zwitterion state and complexation or sticky character in their pre-zwitterionic carboxybetaine ester form. Zwitterionic forms possess antibiofouling properties due to electrostatic interaction between charged moieties, highly hydration capability and overall neutral charge in material as well as biomimetic character because zwitterions are structural similarity to biomembranes. We showed that modifications of surface by zwitterionic based self-assemble monolayer allow enhance detection limit of biosensors down to 10–15 M for analyte, [3,4] or improve electrorheological response. [5]
Carboxybetaine esters have cationic character and permit complexation with polyanionic bioabsorbents as well as character of counter ion can adjust wettability and interaction with biomolecules.
These studies will present on the utilization of pre-zwiterionic molecules: carboxybetaine based derivates formed from lipoic acid precursor in order to modify surface for construction of impedimetric lectin biosensors and for tuning wettability and interaction with DNA and other charged (bio)molecules.
Novel pre-zwitterionic carboxybetaine ester (hydrolysable and photolysable) derivates were synthetized by protocol consists of several synthetic steps and fully characterized. Subsequently, modification of a gold surface was performed by a self-assembled monolayer deposited from a solution containing prezwitterion molecules. Self-assembly monolayer, formed from derivates, was characterized by set instrumentation as atomic force microscopy, quartz crystal microbalance XPS, contact angle etc.
Hydrolysable carboxybetaine derivate was able to from complex with polycationic DNA molecules to preconcentrate and release at pH dependent manner. During course of hydrolysis carboxybetaine ester is transferred to carboxybetaine zwitterionic form to promote DNA release due to formation of carboxylate negative charge. Additionally, gradient in wettability can be observed within progress of hydrolysis and present of long perfluorinated or aliphatic types of counter ions. For example switch in wettability can be achieved only by simple and rapid couterion exchange between superhydrophilic (contact angle (CA) below 10° (to very high hydrophobilic (CA over 140°) on rough gold surface. After completed hydrolyses zwitterionic surface can be utilized as a platform for biosensor surface with nonfouling properties. Carboxylic functionality allows immobilizing sensing molecules as lectins for electrochemical impedance spectroscopy by means of EDC/NHS chemistry. This methodology provides opportunity for ultrasensitive detection up to 10–15 M of lectins which may result of a biomarker discovery on several diseases in whole media.
Moreover utilization of photolabile ester of carboxybetaine derivates allowing spatially control wettability and pattering with photomask was performed. Photolabile 2-nitrophenyl methyl ester group was introduced to pre-zwitterionic molecule and after irradiation of prepared surface with light at 365 nm was transformed from carboxybetaine ester group to zwitterionic carboxybetaine. Progress of photolysis can be observed by change of surface zeta potential, quartz crystal microbalance and contact angle measurement. This irreversible switch along with different interaction of biological species before and after photolysis will be discussed in this contribution as well.
This contribution was made possible by NPRP grant 6-381-1-078 from the Qatar National Research Fund (a member of the Qatar Foundation). The statements contained are entirely the responsibility of the authors.qscienc
Ti<sub>3</sub>C<sub>2</sub> MXene-Based Nanobiosensors for Detection of Cancer Biomarkers
This chapter provides information about basic properties of MXenes (2D nanomaterials) that are attractive for a design of various types of nanobiosensors. The second part of the chapter discusses MXene synthesis and various protocols for modification of MXene making it a suitable matrix for immobilization of bioreceptors such as antibodies, DNA aptamers or DNA molecules. The final part of the chapter summarizes examples of MXene-based nanobiosensors developed using optical, electrochemical and nanomechanical transducing schemes. Operational characteristics of such devices such as sensitivity, limit of detection, assay time, assay reproducibility and potential for multiplexing are provided. In particular MXene-based nanobiosensors for detection of a number of cancer biomarkers are shown here
Carboxybetaine Modified Interface for Electrochemical Glycoprofiling of Antibodies Isolated from Human Serum
Impedimetric lectin biosensors capable of recognizing two different carbohydrates (galactose and sialic acid) in glycans attached to antibodies isolated from human serum were prepared. The first step entailed the modification of a gold surface by a self-assembled monolayer (SAM) deposited from a solution containing a carboxybetaine-terminated thiol applied to the subsequent covalent immobilization of lectins and to resist nonspecific protein adsorption. In the next step, Sambucus nigra agglutinin (SNA) or Ricinus communis agglutinin (RCA) was covalently attached to the SAM, and the whole process of building a bioreceptive layer was optimized and characterized using a diverse range of techniques including electrochemical impedance spectroscopy, cyclic voltammetry, quartz crystal microbalance, contact angle measurements, zeta-potential assays, X-ray photoelectron spectroscopy, and atomic force microscopy. In addition, the application of the SNA-based lectin biosensor in the glycoprofiling of antibodies isolated from the human sera of healthy individuals and of patients suffering from rheumatoid arthritis (RA) was successfully validated using an SNA-based lectin microarray. The results showed that the SNA lectin, in particular, is capable of discriminating between the antibodies isolated from healthy individuals and those from RA patients based on changes in the amount of sialic acid present in the antibodies. In addition, the results obtained by the application of RCA and SNA biosensors indicate that the abundance of galactose and sialic acid in antibodies isolated from healthy individuals is age-related.Slovak Scientific Grant Agency VEGA 2/0162/14 and from the Slovak Research and Development Agency APVV 0282-11. The European Research Council under the European Union’s Seventh Framework Programme (FP/2007-2013)/ERC Grant Agreement no. 311532. This publication was made possible by NPRP grant no. 6-381-1-078 from the Qatar National Research Fund (a member of the Qatar Foundation)
Tandem osmotic engine based on hydrogel particles with antipolyelectrolyte and polyelectrolyte effect fuelled by both salinity gradient modes
In this study, we propose a new approach to attain energy by salinity gradient engines with pistons based on hydrogels possessing polyelectrolyte and antipolyelectrolyte effects in a tandem arrangement, providing energy in each salinity gradient mode in a repeatable manner. The swelling of hydrogel with a polyelectrolyte effect and shrinking of hydrogel particles possessing an antipoly-electrolyte effect in desalinated water, and subsequent shrinking of hydrogel with polyelectrolyte and swelling of hydrogel antipolyelectrolyte effect in saline water, generate power in both increasing and decreasing salinity modes. To investigate the energy recovery, we scrutinized osmotic engine assemblies by a setup arrangement of pistons with hydrogel particles, with polyelectrolyte and antipolyelectrolyte effects, in tandem. The energy recovery from the tandem engine setup (calculated based on dry form for each polyelectrolyte polyacrylate-based hydrogel-SPA) and antipolyelectrolyte– sulfobetaine-based gel with methacrylate polymeric backbone-SBE) up to 581 J kg−1 and a mean power of 0.16 W kg−1 was obtained by the tandem setup of SPA and SBE hydrogel containing 3% crosslinking density and particle size of 500 microns with an external load of 3.0 kPa. Exchange of sulfobetaine with methacrylamide (SBAm), the main polymer backbone, revealed a positive increase in energy recovery of 670 J kg−1 with a mean power of 0.19 W kg−1 for the tandem system operating under the same parameters (SPA@SBAm). The energy recovery can be controlled, modulated and tuned by selecting both hydrogels with antipolyelectrolyte and polyelectrolyte effects and their performing parameters. This proof of concept provides blue energy harvesting by contributing both polyelectrolyte and antipolyelectrolyte effects in a single tandem setup; together with easy accessibility (diaper-based materials (SPA)) and known antibiofouling, these properties offer a robust alternative for energy harvesting.- Qatar National Research Fund (QNRF) - grant # NPRP13S-0202-200228.
- Qatar University grant #IRCC-2020-004
Metabolic Phenotype and Adipose Tissue Inflammation in Patients with Chronic Obstructive Pulmonary Disease
Potential links between metabolic derangements and adipose tissue (AT) inflammation in patients with chronic obstructive pulmonary disease (COPD) are unexplored. We investigated AT expressions of interleukin (IL)-6, tumor necrosis factor (TNF)-α, CD68 (macrophage cell surface receptor), caspase-3, and Bax, and their relationships to the metabolic phenotype in nine cachectic, 12 normal-weight, 12 overweight, and 11 obese patients with COPD (age 62.3 ± 7.2 years). With increasing body mass index, increases in AT expressions of IL-6, TNF-α, and CD68 were observed (P < .001; P = .005; P < .001, resp.), in association with reduced insulin sensitivity (P < .001). No differences were observed between cachectic and normal-weight patients in AT expressions of inflammatory or proapoptotic markers. Adipose tissue CD68 and TNF-α expressions predicted insulin sensitivity independently of known confounders (P = .005; P = .025; R2 = 0.840). Our results suggest that AT inflammation in obese COPD patients relates to insulin resistance. Cachectic patients remain insulin sensitive, with no AT upregulation of inflammatory or proapoptotic markers
Novel analysis of glycan structures: Nanoscale approach
Glycans are complex saccharide moieties covering all cell surfaces - presented on different biomolecules. Almost 75% of all proteins are glycosylated, and these glycans can form thousands of different structures.[1] Moreover, these structures may slightly change during a specific disease progress - depending on the biomarker observed, there is a possibility to distinguish between healthy individuals and people suffering from a specific disease, mostly cancer (prostate cancer using PSA as a biomarker)[2] or autoimmune diseases (rheumatoid arthritis, system sclerosis observing IgG N-glycosylation).[3] Viral adhesion on cell surface and subsequent penetration is also dependent on the glycan epitopes present on a cell surface.[4, 5] Using nanoscale manipulation of biorecognition elements (antibodies, lectins as glycan-bindnig proteins or glycans) using self-assembled monolayers (SAMs) allowed to prepare highly sensitive, reproducible and robust biosensors for detection of various analytes - from glycoproteins and whole viral particles to intact cells. Moreover, using SAMs allows to control a biorecognition element's density, orientation and anti-fouling properties of our surfaces.[6] Using nanomaterials like gold nanoparticles of different size or graphene oxide flakes leads to improved characteristics of prepared devices - electrochemical and impedimetric biosensors in this case. Electrochemical devices, mainly in combination with different nanostructures, provide cheap, highly reliable and sensitive platform for glycomic analyses.[7] We present here a novel approach for a glycoprofilation of various analytes (antibodies, PSA, viral hemagglutinins and viruses and eukaryotic cell lines) using small, low cost, highly sensitive electrochemical devices based on different platforms compared to standardly used LC, CE or MS methods for the glycan analysis. Beside electrochemical impedance spectroscopy and voltammetry, other methods for the surface characterization were used (quartz crystal microbalance, surface plasmon resonance, atomic force and scanning electron microscopy and x-ray photoelectron spectroscopy) and our results were compared to outputs from other analytical methods (protein microarray, enzyme-linked lectin assay and MALDI-TOF MS).Scopu
Recovery of High Specific Activity Molybdenum-99 From Accelerator-Induced Fission on Low-Enriched Uranium for Technetium-99m Generators
A new process was developed to recover high specific activity (no carrier added) 99Mo from electron-accelerator irradiated U3O8 or uranyl sulfate targets. The process leverages a novel solvent extraction scheme to recover Mo using di(2-ethylhexyl) phosphoric acid following uranium and transuranics removal with tri-n-butyl phosphate. An anion-exchange concentration column step provides a final purification, generating pure 99Mo intended for making 99Mo/99mTc generators. The process was demonstrated with irradiated uranium targets resulting in more than 95% 99Mo recovery and without presence of fission products or actinides in the product
Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial
Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie
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