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      Optical DNA Biosensor Based on Square-Planar Ethyl Piperidine Substituted Nickel(II) Salphen Complex for Dengue Virus Detection

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          Abstract

          A sensitive and selective optical DNA biosensor was developed for dengue virus detection based on novel square-planar piperidine side chain-functionalized N, N′-bis-4-(hydroxysalicylidene)-phenylenediamine-nickel(II), which was able to intercalate via nucleobase stacking within DNA and be functionalized as an optical DNA hybridization marker. 3-Aminopropyltriethoxysilane (APTS)-modified porous silica nanospheres (PSiNs), was synthesized with a facile mini-emulsion method to act as a high capacity DNA carrier matrix. The Schiff base salphen complexes-labelled probe to target nucleic acid on the PSiNs renders a colour change of the DNA biosensor to a yellow background colour, which could be quantified via a reflectance transduction method. The reflectometric DNA biosensor demonstrated a wide linear response range to target DNA over the concentration range of 1.0 × 10 −16–1.0 × 10 −10 M (R 2 = 0.9879) with an ultralow limit of detection (LOD) at 0.2 aM. The optical DNA biosensor response was stable and maintainable at 92.8% of its initial response for up to seven days of storage duration with a response time of 90 min. The reflectance DNA biosensor obtained promising recovery values of close to 100% for the detection of spiked synthetic dengue virus serotypes 2 (DENV-2) DNA concentration in non-invasive human samples, indicating the high accuracy of the proposed DNA analytical method for early diagnosis of all potential infectious diseases or pathological genotypes.

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          Trends in DNA biosensors

          Biosensors have witnessed an escalating interest nowadays, both in the research and commercial fields. Deoxyribonucleic acid (DNA) biosensors (genosensors) have been exploited for their inherent physico-chemical stability and suitability to discriminate different organism strains. The main principle of detection among genosensors relies on specific DNA hybridization, directly on the surface of a physical transducer. This review covers the main DNA immobilization techniques reported so far, new micro- and nanotechnological platforms for biosensing and the transduction mechanisms in genosensors. Clinical applications, in particular, demand large-scale and decentralized DNA testing. New schemes for DNA diagnosis include DNA chips and microfluidics, which couples DNA detection with sample pretreatment under in vivo-like hybridization conditions. Higher sensitivity and specificity may arise from nanoengineered structures, like carbon nanotubes (CNTs) and DNA/protein conjugates. A new platform for universal DNA biosensing is also presented, and its implications for the future of molecular diagnosis are argued.
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            Molecular basis of structure-activity relationships between salphen metal complexes and human telomeric DNA quadruplexes.

            The first X-ray crystal structures of nickel(II) and copper(II) salphen metal complexes bound to a quadruplex DNA are presented. Two structures have been determined and show that these salphen-metal complexes bind to human telomeric quadruplexes by end-stacking, with the metal in each case almost in line with the potassium ion channel. Quadruplex and duplex DNA binding is presented for these two and other related salphen complexes, all with side-chains terminating in pyrrolidino end-groups and differing patterns of substitution on the salphen core. The crystal structures are able to provide rationalizations for the structure-activity data, and in particular for the superior quadruplex-binding of the nickel complexes compared to that of the copper-containing ones. The complexes show significant antiproliferative activity for the compounds in a panel of cancer cell lines. They also show telomerase inhibitory activity in the telomerase TRAP-LIG assay.
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              Optimization of DNA immobilization on gold electrodes for label-free detection by electrochemical impedance spectroscopy.

              The ability to immobilize DNA probes onto gold substrates at an optimum surface density is key in the development of a wide range of DNA biosensors. We present a method to accurately control probe DNA surface density by the simultaneous co-immobilization of thiol modified probes and mercaptohexanol. Probe surface density is controlled by the thiol molar ratio in solution, with a linear relationship between thiol molar ratio and probe density spanning (1-9) x10(12)/cm2. The probe surface density per microscopic surface area was determined using chronocoulometry, and a detailed analysis of the method presented. Using this sample preparation method, the effect of probe density and hybridization on the charge transfer resistance with the negatively charged ferri/ferrocyanide redox couple was determined. Above a threshold probe surface density of 2.5 x 10(12)/cm2, electrostatic repulsion from the negatively charged DNA modulates the charge transfer resistance, allowing hybridization to be detected. Below the threshold density no change in charge transfer resistance with probe density or with hybridization occurs. The probe surface density was optimized to obtain the maximum percentage change in charge transfer resistance with hybridization.
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                Author and article information

                Journal
                Sensors (Basel)
                Sensors (Basel)
                sensors
                Sensors (Basel, Switzerland)
                MDPI
                1424-8220
                12 April 2018
                April 2018
                : 18
                : 4
                : 1173
                Affiliations
                [1 ]School of Chemical Sciences and Food Technology, Faculty of Science and Technology, University Kebangsaan Malaysia, Bangi 43600, Selangor D.E., Malaysia; edayu_hanna@ 123456yahoo.com (E.Y.A.); nurulhuda@ 123456ukm.edu.my (N.H.A.K.); leeyookheng@ 123456yahoo.co.uk (L.Y.H.)
                [2 ]Southeast Asia Disaster Prevention Research Initiative (SEADPRI-UKM), Institute for Environment and Development (LESTARI), Universiti Kebangsaan Malaysia, Bangi 43600, Selangor D.E., Malaysia
                Author notes
                [* ]Correspondence: babybabeoo@ 123456gmail.com ; Tel.: +60-3-8921-7636; Fax: +60-3-8927-5629
                Article
                sensors-18-01173
                10.3390/s18041173
                5948868
                29649118
                da824028-c08d-4c55-bfc9-c90850168b50
                © 2018 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 02 March 2018
                : 02 April 2018
                Categories
                Article

                Biomedical engineering
                dengue virus detection,nickel(ii) salphen complex,optical dna biosensor,porous silica nanospheres,reflectance measurement,synthetic dna binder

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