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  1. Letchumanan I, Arshad MKM, Gopinath SCB
    Curr Med Chem, 2021;28(5):986-1002.
    PMID: 31971105 DOI: 10.2174/0929867327666200123092648
    Cardiovascular disease (CVD) has become one of the leading causes of morbidity and mortality in both men and women. According to the World Health Organization (WHO), ischemic heart disease is the major issue due to the narrowing of the coronary artery by plaque formation on the artery wall, which causes an inadequate flow of oxygen and blood to the heart and is called 'coronary artery disease'. The CVD death rate increased by up to 15% in 2016 (~17.6 million) compared to the past decade. This tremendous increment urges the development of a suitable biomarker for rapid and early diagnosis. Currently, C-reactive protein (CRP) is considered an outstanding biomarker for quick and accurate outcomes in clinical analyses. Various techniques have also been used to diagnose CVD, including surface plasmon resonance (SPR), colorimetric assay, enzyme-linked immunosorbent assay (ELISA), fluoro-immunoassays, chemiluminescent assays, and electrical measurements. This review discusses such diagnostic strategies and how current, cutting-edge technologies have enabled the development of high-performance detection methodologies. Concluding remarks have been made concerning the clinical significance and the use of nanomaterial in medical diagnostics towards nanotheranostics.
  2. Letchumanan I, Gopinath SCB, Arshad MKM
    Mikrochim Acta, 2020 01 14;187(2):128.
    PMID: 31938893 DOI: 10.1007/s00604-020-4115-0
    A method is described for the electrochemical determination of squamous cell carcinoma (SCC) antigen, and by testing the effect of 30 nm gold nanoparticles (GNPs). Three comparative studies were performed in the presence and absence of GNPs, and with agglomerated GNPs. The divalent ion Ca(II) was used to induce a strong agglomeration of GNPs, as confirmed by colorimetry and voltammetry. Herein, colorimetry was used to test the best amount of salt needed to aggregate the GNPs. Despite, voltammetry was used to determine the status of biomolecules on the sensor. The topography of the surface of ZnO-coated interdigitated electrodes was analyzed by using 3D-nano profilometry, scanning electron microscopy, atomic force microscopy and high-power microscopy. The interaction between SCC antigen and antibody trigger vibrations on the sensor and cause dipole moment, which was measured using a picoammeter with a linear sweep from 0 to 2 V at 0.01 V step voltage. The sensitivity level was 10 fM by 3σ calculation for the dispersed GNP-conjugated antigen. This indicates a 100-fold enhancement compared to the condition without GNP conjugation. However, the sensitivity level for agglomerated GNPs conjugated antibody was not significant with 100 fM sensitivity. Specificity was tested for other proteins in serum, namely blood clotting factor IX, C-reactive protein, and serum albumin. The SCC antigen was quantified in spiked serum and gave recoveries that ranged between 80 and 90%. Graphical abstractSchematic representation of SCC (squamous cell carcinoma) antigen determination using divalent ion induced agglomerated GNPs. Sensitivity increment depends on the occurrence of more SCC antigen and antibody binding event via GNPs integration. Notably, lower detection limit was achieved at femto molar with proper orientation of biological molecules.
  3. Letchumanan I, Md Arshad MK, Balakrishnan SR, Gopinath SCB
    Biosens Bioelectron, 2019 Apr 01;130:40-47.
    PMID: 30716591 DOI: 10.1016/j.bios.2019.01.042
    This paper primarily demonstrates the approach to enhance the sensing performance on antigen C-reactive protein (CRP) and anti-CRP antibody binding event. A nanogapped electrode structure with the gap of ~100 nm was modified by the anti-CRP antibody (Probe) to capture the available CRP. In order to increase the amount of antigen to be captured, a gold nanorod with 119 nm in length and 25 nm in width was integrated, to increase the surface area. A comparative study between the existence and non-existence of gold nanorod utilization was evaluated. Analysis of the sensing surface was well-supported by atomic force microscopy, scanning electron microscopy, 3D nano-profilometry, high-power microscopy and UV-Vis spectroscopy. The dielectric voltammetric analysis was carried out from 0 V to 2 V. The sensitivity was calculated based on 3σ and attained as low as 1 pM, which is tremendously low compared to real CRP concentration (119 nM) in human blood serum. The gold nanorod conjugation with antibody has enhanced the sensitivity to 100 folds (10 fM). The specificity of the CRP detection by the proposed strategy was anchored by ELISA and failure in the detection of human blood clotting factor IX by voltammetry. Despite, CRP antigen was further detected in human serum by spiking CRP to run-through the detection with the physiologically relevant samples.
  4. Letchumanan I, Md Arshad MK, Gopinath SCB, Rajapaksha RDAA, Balakrishnan SR
    Sci Rep, 2020 Apr 22;10(1):6783.
    PMID: 32321969 DOI: 10.1038/s41598-020-63831-w
    Field of generating a surface thin film is emerging broadly in sensing applications to obtain the quick and fast results by forming the high-performance sensors. Incorporation of thin film technologies in sensor development for the better sensing could be a promising way to attain the current requirements. This work predominantly delineates the fabrication of the dielectric sensor using two different sensing materials (Gold and Aluminium). Conventional photolithography was carried out using silicon as a base material and the photo mask of the dielectric sensor was designed by AutoCAD software. The physical characterization of the fabricated sensor was done by Scanning Electron Microscope, Atomic Force Microscope, High Power Microscope and 3D-nano profiler. The electrical characterization was performed using Keithley 6487 picoammeter with a linear sweep voltage of 0 to 2 V at 0.01 V step voltage. By pH scouting, I-V measurements on the bare sensor were carried out, whereby the gold electrodes conducts a least current than aluminium dielectrodes. Comparative analysis with pH scouting reveals that gold electrode is suitable under varied ionic strengths and background electrolytes, whereas aluminium electrodes were affected by the extreme acid (pH 1) and alkali (pH 12) solutions.
  5. Letchumanan I, Gopinath SCB, Md Arshad MK, Anbu P, Lakshmipriya T
    Biosens Bioelectron, 2019 Apr 15;131:128-135.
    PMID: 30826647 DOI: 10.1016/j.bios.2019.02.006
    This article is clearly presenting the development of a biosensor for human factor IX (FIX) to diagnose the blood clotting deficiency, a so-called 'Royal disease' using an interdigitated electrode (IDE) with the zinc oxide surface modification. Gold nano-urchins (GNUs) with 60 nm in diameter was integrated into a streptavidin-biotinylated aptamer strategy to enhance the active surface area. Two different comparative studies have been done to validate the system to be practiced in the current work holds with a higher capability for the high-performance sense. Whereby, the presence and absence of GNUs in the aptasensing system for FIX interaction were investigated using the amperometric measurement, using a linear sweep voltage of 0-2 V at 0.01 V step voltage. The detection limit was 6 pM based on 3σ calculation when GNUs integrated aptamer assay was utilized for FIX detection, which shows 8 folds sensitivity enhancement comparing the condition in the absence of GNU and 50 folds higher than sensitive radio-isotope and surface plasmon resonance assays. Albeit, the surface and molecular characterizations were well demonstrated by scanning electron microscopy, atomic force microscopy, 3D nano-profilometry and further supports were rendered by UV-Vis spectroscopy and Enzyme-linked apta-sorbent assay (ELASA). Furthermore, the spiking experiment was done by FIX-spikes in human blood serum in order to demonstrate the stability with a higher non-fouling.
  6. Letchumanan I, Gopinath SCB, Md Arshad MK, Mohamed Saheed MS, Perumal V, Voon CH, et al.
    Crit Rev Anal Chem, 2020 Sep 08.
    PMID: 32897761 DOI: 10.1080/10408347.2020.1812373
    Mortality level is worsening the situation worldwide thru blood diseases and greatly jeopardizes the human health with poor diagnostics. Due to the lack of successful generation of early diagnosis, the survival rate is currently lower. To overcome the present hurdle, new diagnostic methods have been choreographed for blood disease biomarkers analyses with the conjunction of ultra-small ideal gold nanohybrids. Gold-hybrids hold varieties of unique features, such as high biocompatibility, increased surface-to-volume ratio, less-toxicity, ease in electron transfer and have a greater localized surface plasmon resonance. Gold-nanocomposites can be physically hybrid on the sensor surface and functionalize with the biomolecules using appropriate chemical conjugations. Revolutionizing biosensor platform can be prominently linked for the nanocomposite applications in the current research on medical diagnosis. This review encloses the new developments in diagnosing blood biomarkers by utilizing the gold-nanohybrids. Further, the current state-of-the-art and the future envision with digital monitoring for facile telediagnosis were narrated.
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