Electrochemical Impedance Spectroscopy Based Biosensors: Mechanistic Principles, Analytical Examples and Challenges towards Commercialization for Assays of Protein Cancer Biomarkers

Impedimetric affinity biosensors are, without any doubt, among the most sensitive analytical devices available, offering low limits of detection and wide linear response ranges. There are, however, only a few papers detailing the application of impedimetric biosensors for the analysis of clinically relevant samples with due clinical performance. The fact that these devices have not found their way to any commercial or clinical use to date might be surprising, since an electrochemical assay platform based on portable potentiostats is a success story for monitoring a range of clinical parameters such as ions, haematological indicators and glucose. This review discusses the reasons behind this discrepancy and addresses the barriers to be overcome in order to achieve the point-of-care diagnostics using such devices for detection of protein oncomarkers approved by FDA. The final part of the review covers the most recent progress in the area.The financial support received from the Slovak Scientific Grant Agency VEGA 2/0137/18 and 2/0090/16 and the Slovak Research and Development Agency APVV 17-0300 and APW-15-0227 is acknowledged. The research received funding from the European Research Council (no. 311532). This publication is the result of the project implementation: Centre for materials, layers and systems for applications and chemical processes under extreme conditions - Stage I, ITMS No.: 26240120007, supported by the ERDF

A graphene-based glycan biosensor for electrochemical label-free detection of a tumor-associated antibody

The study describes development of a glycan biosensor for detection of a tumor-associated antibody. The glycan biosensor is built on an electrochemically activated/oxidized graphene screen-printed electrode (GSPE). Oxygen functionalities were subsequently applied for covalent immobilization of human serum albumin (HSA) as a natural nanoscaffold for covalent immobilization of Thomsen-nouvelle (Tn) antigen (GalNAc-O-Ser/Thr) to be fully available for affinity interaction with its analyte—a tumor-associated antibody. The step by step building process of glycan biosensor development was comprehensively characterized using a battery of techniques (scanning electron microscopy, atomic force microscopy, contact angle measurements, secondary ion mass spectrometry, surface plasmon resonance, Raman and energy-dispersive X-ray spectroscopy). Results suggest that electrochemical oxidation of graphene SPE preferentially oxidizes only the surface of graphene flakes within the graphene SPE. Optimization studies revealed the following optimal parameters: activation potential of +1.5 V vs. Ag/AgCl/3 M KCl, activation time of 60 s and concentration of HSA of 0.1 g L−1. Finally, the glycan biosensor was built up able to selectively and sensitively detect its analyte down to low aM concentration. The binding preference of the glycan biosensor was in an agreement with independent surface plasmon resonance analysis.The financial support received from the Slovak Scientific Grant Agency VEGA 2/0137/18 and 2/0090/16 from the Slovak Research and Development Agency APVV 17-0300 is acknowledged. This publication is the result of the project implementation: Centre for materials, layers and systems for applications and chemical processes under extreme conditions—Stage I, ITMS no.: 26240120007, supported by the ERDF. This publication was supported by Qatar University Collaborative Grant QUCG-CAM-19/20-2. The findings achieved herein are solely the responsibility of the authors.Scopu

Highly stable Ti3C2Tx (MXene)/Pt nanoparticles-modified glassy carbon electrode for H2O2 and small molecules sensing applications

Electrochemical performance of a 2D Ti3C2Tx (MXene, where T: [dbnd]O, –OH, –F) sheets modified with Pt nanoparticles (PtNPs) was investigated. The results showed that Ti3C2Tx/PtNP nanocomposite deposited on the surface of GCE showed much better and stable redox behavior in an anodic potential window as compared to the GCE modified with pristine Ti3C2Tx MXene. For example, the H2O2 sensor of Ti3C2Tx/PtNP on GCE offered LOD of 448 nM with a potential at which reduction starts of ∼+250 mV (vs. Ag/AgCl) in comparison to values of 883 μM and ∼−160 mV observed for Ti3C2Tx modified GCE. Moreover, the Ti3C2Tx/PtNP sensor could detect small redox molecules such as ascorbic acid (AA), dopamine (DA), uric acid (UA) and acetaminophen (APAP) at a potential higher than +250 mV with high selectivity and LOD down to nM level. We proved that selectivity of detection of such molecules (AA, DA, UA and APAP) could be modulated to high extent using external membranes. © 2018 Elsevier B.V.26240120007, ERDF, European Regional Development Fund; 311532, ERC, European Research Council; 9-219-2-105, QNRF, Qatar National Research FundSlovak Scientific Grant Agency VEGA [2/0162/14]; Slovak Research and Development Agency [APVV-15-0227]; European Research Council [311532]; NPRP from the Qatar National Research Fund [9-219-2-105]; ERDF [26240120007

Tailoring electrocatalytic properties of Pt nanoparticles grown on Ti3C2Tx MXene surface

In this work, the spontaneous and NaBH4-induced reduction of chloroplatinic acid on the surface of Ti3C2TX MXene was investigated to synthesize a hybrid PtNP-decorated MXene nanomaterial (MX-Pt) with potential as hydrogen evolution (HER) or oxygen reduction reaction (ORR) catalyst properties. The initial Pt concentration, reduction time and presence of additional reducing agents were varied, and as-synthesized nanocomposites were characterized thoroughly by XRD, EDX, SEM and XPS analysis and by electrochemical methods. Composites containing 14 wt% Pt showed HER with an onset potential of −75.9 mV and a current density of −10 mA cm−2 achieved at −226 mV. The spontaneous deposition of PtNPs on MXene improved the electrocatalytic properties over using an external reducing agent to form PtNP, which was explained based on the different rates of oxidation of Ti in the initial MXene support. Furthermore, good stability of the electrode modified by the MX-Pt was achieved without any polymeric binder and the HER reaction achieved only a negligible decrease over 3 000 potentiodynamic cycles.- Qatar National Research Fund (a member of The Qatar Foundation) NPRP grant # 9-219-2-105

Glycomics meets artificial intelligence – Potential of glycan analysis for identification of seropositive and seronegative rheumatoid arthritis patients revealed

In this study, one hundred serum samples from healthy people and patients with rheumatoid arthritis (RA) were analyzed. Standard immunoassays for detection of 10 different RA markers and analysis of glycan markers on antibodies in 10 different assay formats with several lectins were applied for each serum sample. A dataset containing 2000 data points was data mined using artificial neural networks (ANN). We identified key RA markers, which can discriminate between healthy people and seropositive RA patients (serum containing autoantibodies) with accuracy of 83.3%. Combination of RA markers with glycan analysis provided much better discrimination accuracy of 92.5%. Immunoassays completely failed to identify seronegative RA patients (serum not containing autoantibodies), while glycan analysis correctly identified 43.8% of these patients. Further, we revealed other critical parameters for successful glycan analysis such as type of a sample, format of analysis and orientation of captured antibodies for glycan analysis. 2018 Elsevier B.V.Financial support received from the Slovak Scientific Grant Agency VEGA 2/0137/18 and Slovak Research and Development Agency APVV 14-0753 is acknowledged. The research received funding from the European Research Council (No. 311532 ). This publication was made possible by NPRP grant no. 6-381-1-078 from the Qatar National Research Fund. This publication is the result of the project implementation: Centre for materials, layers and systems for applications and chemical processes under extreme conditions � Stage I, ITMS No.: 26240120007, supported by the ERDF. Appendix

2D MXenes as Perspective Immobilization Platforms for Design of Electrochemical Nanobiosensors

MXenes are a new group of 2D nanomaterials with fascinating properties including high electrical conductivity, hydrophilic nature, easily tunable structure and high surface area. This is why MXene modified interfaces are extremely promising for the preparation of sensitive electrochemical biosensors. While there are numerous reports on MXene-based enzymatic biosensors for detection of a wide range of analytes, application of MXene for construction of affinity biosensors is in its infancy. The review article summarizes current state-of the-art in the field with a focus on MXene modifications needed for construction of robust and high performance MXene electrochemical biosensors. - 2019 Wiley-VCH Verlag GmbH & Co. KGaA, WeinheimThe authors would like to acknowledge the financial support received from the Slovak Research and Development Agency APVV 17-0300. This work was supported by Ministry of Health of the Slovak Republic under the project registration number 2018/23-SAV-1. P. K. thanks that this work was also made possible by BPRP grant #9-219-2-105 from the Qatar National Research Fund (A Member of The Qatar Foundation). The finding achieved herein is solely the responsibility of the authors.Scopu

Advanced antifouling zwitterionic layer based impedimetric HER2 biosensing in human serum: Glycoprofiling as a novel approach for breast cancer diagnostics

There are two key novel components presented here behind identification of potential novel breast cancer (BCa) diagnostic approach: 1. application of photoimmobilizable zwitterionic hydrogels resisting non-specific protein adsorption for preparation of the biosensor interfaces and 2. integration of lectins (carbohydrate recognizing proteins) within biosensors to evaluate changes in the glycan profile of HER2 protein on the molecular level. A disposable, electrochemical biosensor based on screen printed carbon electrodes (SPCEs) with a deposited hydrogel layer was applied for covalent attachment of antibodies for a specific interaction with HER2. In the subsequent step, HER2 molecules were in situ glycoprofiled using lectins. The impedimetric immunosensor was able to detect HER2 down to 5 pg mL?1 (?77 fM) with a minimal non-specific protein adsorption. The biosensor was then combined with lectins to glycoprofile HER2 in two serum samples (one from a healthy, high BCa risk woman and the other from a woman with a 2nd stage BCa). The results obtained by the glycoprofiling via the impedimetric biosensor were successfully verified by independent lectin-based enzyme-linked immunosorbent assays (ELISA). To our best knowledge it is a very first biosensor applying zwitterionic polymeric hydrogel-modified interface for glycoprofiling of a cancer biomarker.Financial support received from the Slovak Scientific Grant Agency VEGA 2/0162/14 and Slovak Research and Development Agency APVV 17-0300 is acknowledged. The research received funding from the European Research Council (No. 311532 ). This publication is the result of the project implementation: Centre for materials, layers and systems for applications and chemical processes under extreme conditions Stage I, ITMS No.: 26240120007, supported by the ERDF . Appendix AScopu