This study demonstrated the terminated sialo-sugar chains (Neu5Acα2,6Gal and Neu5Acα2,3Gal) mediated specificity enhancement of influenza virus and chicken red blood cell (RBC) by hemagglutination assay. These glycan chains were immobilized on the gold nanoparticle (GNP) to withhold the higher numbers. With the preliminary optimization, a clear button formation with 0.5% RBC was visualized. On the other hand, intact B/Tokio/53/99 with 750 nM hemagglutinin (HA) displayed a nice hemagglutination. The interference on the specificity of RBC and influenza virus was observed by anti-influenza aptamer at the concentration 31 nM, however, there is no hemagglutination prevention was noticed in the presence of complementary aptamer sequences. Spiking GNP conjugated Neu5Acα2,6Gal or Neu5Acα2,3Gal or a mixture of these two to the reaction promoted the hemagglutination to 63 folds higher with 12 nM virus, whereas under the same condition the heat inactivated viruses were lost the hemagglutination. Neuraminidases from Clostridium perfringens and Arthrobacter ureafaciens at 0.0025 neuraminidase units are able to abolish the hemagglutination. Other enzymes, Glycopeptidase F (Elizabethkingia meningoseptica) and Endoglycosidase H (Streptomyces plicatus) did not show the changes with agglutination. Obviously, sialyl-Gal-terminated glycan conjugated GNP amendment has enhanced the specificity of erythrocyte-influenza virus and able to be controlled by aptamer or neuraminidases. This article is protected by copyright. All rights reserved.
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.
Artificial intelligence of things (AIoT) has become a potential tool for use in a wide range of fields, and its use is expanding in interdisciplinary sciences. On the other hand, in a clinical scenario, human blood-clotting disease (Royal disease) detection has been considered an urgent issue that has to be solved. This study uses AIoT with deep long short-term memory networks for biosensing application and analyzes the potent clinical target, human blood clotting factor IX, by its aptamer/antibody as the probe on the microscaled fingers and gaps of the interdigitated electrode. The earlier results by the current-volt measurements have shown the changes in the surface modification. The limit of detection (LOD) was noticed as 1 pM with the antibody as the probe, whereas the aptamer behaved better with the LOD at 100 fM. The time-series predictions from the AIoT application supported the obtained results with the laboratory analyses using both probes. This application clearly supports the results obtained from the interdigitated electrode sensor as aptamer to be the better option for analyzing the blood clotting defects. The current study supports a great implementation of AIoT in sensing application and can be followed for other clinical biomarkers.
Prostate cancer is one of the predominant cancers affecting men and has been widely reported. In the past, various therapies and drugs have been proposed to treat prostate cancer. Among these treatments, gene therapy has been considered to be an optimal and widely applicable treatment. Furthermore, due to the increased specificity of gene sequence complementation, the targeted delivery of complementary gene sequences may represent a useful treatment in certain instances. Various gene therapies, including tumor-suppressor gene therapy, suicide gene therapy, immunomodulation gene therapy and anti-oncogene therapies, have been established to treat a wide range of diseases, such as cardiac disease, cystic fibrosis, HIV/AIDS, diabetes, hemophilia, and cancers. To this end, several gene therapy clinical trials at various phases are underway. This overview describes the developments and progress in gene therapy, with a special focus being placed on prostate cancer.
Reduced graphene oxide (rGO) is widely utilised to develop various types of biosensors; however, producing self-assembled rGO nanoflake networks through single-droplet drop-casting remains inconsistent. In the present work, we systematically used three different methods to prepare rGO suspensions in order to produce large scale self-assembled rGO nanoflake networks through single-droplet drop-casting. The rGO suspensions were prepared using only deionised water with no added any chemicals/organic solvents, which we considered to be a low-cost method. Subsequently, the most effective preparation method was used to deposit rGO nanoflakes onto commercial gold interdigitated microelectrodes (Au-IDE) to examine their electrical performance. Assessment of the yields, developed methods, surface morphologies, spectroscopy and structural analyses of the as-prepared rGO nanoflakes were conducted. The results revealed that method-3 (involving sonication, centrifugation and post-sonication) produced large self-assembled rGO nanoflake networks with strong adhesion to glass substrates. Furthermore, the as-prepared rGO/Au-IDE modified sensors showed excellent electron mobility where the electrical conductivity was enhanced approximately ~ 1000 fold compared to the bare devices. The present work provided new insights for depositing large self-assembled interconnected rGO nanoflake networks through single-droplet drop-casting which will be beneficial for biosensor development and other downstream applications.
Current developments in sensors and actuators are heralding a new era to facilitate things to happen effortlessly and efficiently with proper communication. On the other hand, Internet of Things (IoT) has been boomed up with er potential and occupies a wide range of disciplines. This study has choreographed to design of an algorithm and a smart data-processing scheme to implement the obtained data from the sensing system to transmit to the receivers. Technically, it is called "telediagnosis" and "remote digital monitoring," a revolution in the field of medicine and artificial intelligence. For the proof of concept, an algorithmic approach has been implemented for telediagnosis with one of the degenerative diseases, that is, Parkinson's disease. Using the data acquired from an improved interdigitated electrode, sensing surface was evaluated with the attained sensitivity of 100 fM (n = 3), and the limit of detection was calculated with the linear regression value coefficient. By the designed algorithm and data processing with the assistance of IoT, further validation was performed and attested the coordination. This proven concept can be ideally used with all sensing strategies for immediate telemedicine by end-to-end communications.
Gestational diabetes and jaundice are the correlated diseases predominantly found in mother and newborn child. Jaundice is a neonatal complication with an increased risk when mother has gestational diabetes. Mothers with diabetes at an early stage of gestational age are at higher risk for hyperbilirubinemia (jaundice) and hypoglycemia. So, it is mandatory to monitor the condition of diabetes and jaundice during the pregnancy period for a healthy child and safest delivery. On the other hand, nanotechnology has displayed a rapid advancement that can be implemented to overcome these issues. The development of high-performance diagnosis using appropriate biomarkers provides their efficacy in the detection gestational diabetes and jaundice. This review covers the aspects from a fast-developing field to generate nanosensors in the nanosized dimensions for the applications to overcome these complications by coupling diagnostics with biomarkers. Further, the serum-based biomarkers have been discussed for these inborn complications and also the diagnosis with the current trend.
Luteinizing hormone (LH)/Lutropin is an interstitial cell stimulating hormone playing a predominant role in the reproductive system, and highly correlated with the infertility treatment in both men and women. This research was concentrated to quantify LH level by using interdigitated electrode sensor. To improve the electric current flow, sensing electrode was modified with graphene oxide (GO) and the aptamer probe was attached on GO through biotin-streptavidin linker. Current responses were measured with aptamer-LH interaction at the target concentrations between 7.5 nM and 1 μM and the detection limit of LH was calculated as 60 nM with the determination co-efficient (R2 ) value, 0.9229 [y = 1.296x - 2.8435] on a linear range from 30 nM until 1 μM. Further, biofouling effect on sensing electrode surface was analysed with complementary aptamer sequence, control proteins (Albumin, and globulin). The above GO-aptamer modified interdigitated electrode sensor helps to quantify LH level and diagnose gynaecological endocrinology related complications. This article is protected by copyright. All rights reserved.
C-reactive protein (CRP) is an acute phase reactant to be a marker of inflammation and has been correlated with the cardiac injury. An immunoassay was performed using anti-human CRP antibody on an InterDigitated electrode (IDE) sensor to determine and specify CRP concentration for diagnosing the condition of myocardial inflammation. To promote the detection, gold nanoparticle (GNP) was seeded on the aminated-IDE surface. Anti-CRP was hitched on the GNP-seeded surface and identified the abundance of CRP. The limit of quantification was found as 100 fM, and the higher current response was noticed by increasing CRP concentrations with the sensitivity at 1 pM. Furthermore, CRP-spiked human serum did not interfere the determination of CRP and increased the current response, indicating suitability for a real-life sample. Similarly, the control experiments with nonimmune antibody Troponin I are not showing the definite current responses, proving the selective identification of CRP. This method of diagnosing is needful to determine the cardiovascular injury at the right time.
The urinary C-terminal telopeptide fragment of type II collagen (uCTX-II) has been reported as the efficient blood-based biomarker for osteoarthritis, which affects knees, hands, spine, and hips. This study reports a sensing strategy with antibody-conjugated gold nanoparticles (GNP) on an interdigitated electrode (IDE) to determine uCTX-II. The GNP-antibody complex was chemically immobilized on the IDE surface through the amine linker. uCTX-II was determined by monitoring the alteration in current upon interacting the GNP-complexed antibody. This strategy was improved the detection by attracting higher uCTX-II molecules, and the detection limit falls in the range of 10-100 pM with an acceptable regression value [y = 0.6254x - 0.4073, R² = 0.9787]. The sensitivity of the detection was recognized at 10 pM. Additionally, upon increasing the uCTX-II concentration, the current changes were increased in a linear fashion. Control detection with nonimmune antibody and control protein do not increase the current level, confirming the specific detection of uCTX-II. This method of detection helps in diagnosing osteoarthritis and its follow-up treatment.
Nanoparticles have been investigated as flagging tests for the sensitive DNA recognition that can be utilized as a part of field applications to defeat restrictions. Gold nanoparticles (AuNPs) have been widely utilized due to its optical property and capacity to get functionalized with a mixed bag of biomolecules. This study exhibits the utilization of AuNPs functionalized with single-stranded oligonucleotide (AuNP-oligo test) for fast the identification of Human Papillomavirus (HPV). This test is displayed on interdigitated electrode sensor and supported by colorimetric assay. DNA conjugated AuNP has optical property that can be controlled for the applications in diagnostics. With its identification abilities, this methodology incorporates minimal effort, strong reagents and basic identification of HPV.
Enzyme Linked Immunosorbent Assay (ELISA) is a standard assay that has been used widely to validate the presence of analyte in the solution. With the advancement of ELISA, different strategies have shown and became a suitable immunoassay for a wide range of analytes. Herein, we attempted to provide additional evidence with ELISA, to show its suitability for multi-analyte detection. To demonstrate, three clinically relevant targets have been chosen, which include 16kDa protein from Mycobacterium tuberculosis, human blood clotting Factor IXa and a tumour marker Squamous Cell Carcinoma antigen. Indeed, we adapted the routine steps from the conventional ELISA to validate the occurrence of analytes both in homogeneous and heterogeneous solutions. With the homogeneous and heterogeneous solutions, we could attain the sensitivity of 2, 8 and 1nM for the targets 16kDa protein, FIXa and SSC antigen, respectively. Further, the specific multi-analyte validations were evidenced with the similar sensitivities in the presence of human serum. ELISA assay in this study has proven its applicability for the genuine multiple target validation in the heterogeneous solution, can be followed for other target validations.
Early cancer diagnosis remains the holy-grail in the battle against cancers progression. Tainted with debates and medical challenges, current therapeutic approaches for prostate cancer (PCa) lack early preventive measures, rapid diagnostic capabilities, risk factors identification, and portability, i.e. the inherent attributes offered by the label-free biosensing devices. Electronic assisted immunosensing systems inherit the high sensitivity and specificity properties due to the predilection of the antigen-antibody affinity. Bioelectronic immunosensor for PCa has attracted much attentions among the researchers due to its high-performance, easy to prepare, rapid feedback, and possibility for miniaturization. This review explores the current advances on bioelectronic immunosensors for the detection of PCa biomarker revealed in the past decade. The research milestones and current trends of the immunosensors are reported to project the future visions in order to propel their "lab-to-market" realization.
The effect of 0.1-0.7% (w/w) of polyglycerol esters (PGEmix-8) on palm oil crystallization was studied using focused beam reflectance measurement (FBRM) to analyze the in-line changes of crystal size distribution during the crystallization. FBRM results show that 0.1-0.5% (w/w) of PGEmix-8 did not significantly affect nucleation but slightly retarded crystal growth. The use of 0.7% (w/w) additive showed greater heterogeneous nucleation compared to those with lower dosages of additive. Crystal growth was also greatly reduced when using 0.7% (w/w) dosage. The morphological study indicated that the palm oil crystals were smaller and more even in size than when more additive was added. Isothermal crystallization studies using differential scanning calorimetry (DSC) showed increased inhibitory effects on palm oil crystal growth with increasing concentration of PGEmix-8. These results imply that PGEmix-8 is a nucleation enhancing and crystal growth retarding additive in palm oil crystallization at 0.7% (w/w) dosage.
Electrostatic attraction, covalent binding, and hydrophobic absorption are spontaneous processes to assemble and disassemble the molecules of gold nanoparticles (GNP). This dynamic change can be performed in the presence of ions, such as NaCl or charged molecules. Current research encompasses the GNP in mediating non-biofouling and investigating the molecular attachment and detachment. Experiments were performed with different sizes of GNP and polymers. As a proof of concept, poly(ethylene glycol)-b-poly(acrylic acid), called PEG-PAAc, attachment and binding events between factor IX and factor IX-bp from snake venom were demonstrated, and the variations with these molecular attachment on GNP were shown. Optimal concentration of NaCl for GNP aggregation was 250 mM, and the optimal size of GNP used was 30 nm. The polymer PEG-PAAc (1 mg/ml) has a strong affinity to the GNP as indicated by the dispersed GNP. The concentration of 5800 nM of factor IX was proved to be optimal for dispersion of GNP, and at least 100 nM of factor IX-bp was needed to remove factor IX from the surface of GNP. This study delineates the usage of unmodified GNP for molecular analysis and downstream applications.
Cervical cancer is a life-threatening complication, appearing as the uncontrolled growth of abnormal cells in the lining of the cervix. Every year, increasing numbers of cervical cancer cases are reported worldwide. Different identification strategies were proposed to detect cervical cancer at the earlier stages using various biomarkers. Squamous cell carcinoma antigen (SCC-Ag) is one of the potential biomarkers for this diagnosis. Nanomaterial-based detection systems were shown to be efficient with different clinical biomarkers. In this study, we have demonstrated strontium oxide-modified interdigitated electrode (IDE) fabrication by the sol-gel method and characterized by scanning electron microscopy and high-power microscopy. Analysis of the bare devices indicated the reproducibility with the fabrication, and further pH scouting on the device revealed that the reliability of the working pH ranges from 3 to 9. The sensing surface was tested to detect SCC-Ag against its specific antibody; the detection limit was found to be 10 pM, and the sensitivity was in the range between 1 and 10 pM as calculated by 3σ. The specificity experiment was carried out using major proteins from human serum, such as albumin and globulin. SCC-Ag was shown to be selectively detected on the strontium oxide-modified IDE surface.
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.
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.
Cerebral air embolism is potentially a catastrophic event that occurs as a consequence of air entry into the vasculature. We report a mechanically ventilated 72-year-old woman who underwent multiple procedures during intensive care stay with few possible sources of emboli postulated. We also discuss regarding the preventive measures to minimise the risk of air embolism.