A quadruplet 3-D laser scribed graphene/MoS2, functionalised N2-doped graphene quantum dots and lignin-based Ag-nanoparticles for biosensing.

Troponin I is a protein released into the human blood circulation and a commonly used biomarker due to its sensitivity and specificity in diagnosing myocardial injury. When heart injury occurs, elevated troponin Troponin I levels are released into the bloodstream. The biomarker is a strong and reliable indicator of myocardial injury in a person, with immediate treatment required. For electrochemical sensing of Troponin I, a quadruplet 3D laser-scribed graphene/molybdenum disulphide functionalised N2-doped graphene quantum dots hybrid with lignin-based Ag-nanoparticles (3D LSG/MoS2/N-GQDs/L-Ag NPs) was fabricated using a hydrothermal process as an enhanced quadruplet substrate. Hybrid MoS2 nanoflower (H3 NF) and nanosphere (H3 NS) were formed independently by varying MoS2 precursors and were grown on 3D LSG uniformly without severe stacking and restacking issues, and characterized by morphological, physical, and structural analyses with the N-GQDs and Ag NPs evenly distributed on 3D LSG/MoS2 surface by covalent bonding. The selective capture of and specific interaction with Troponin I by the biotinylated aptamer probe on the bio-electrode, resulted in an increment in the charge transfer resistance. The limit of detection, based on impedance spectroscopy, is 100 aM for both H3 NF and H3 NS hybrids, with the H3 NF hybrid biosensor having better analytical performance in terms of linearity, selectivity, repeatability, and stability.

Electrochemical biosensor detection on respiratory and flaviviruses.

Viruses have spread throughout the world and cause acute illness or death among millions of people. There is a growing concern about methods to control and combat early-stage viral infections to prevent the significant public health problem. However, conventional detection methods like polymerase chain reaction (PCR) requires sample purification and are time-consuming for further clinical diagnosis. Hence, establishing a portable device for rapid detection with enhanced sensitivity and selectivity for the specific virus to prevent further spread becomes an urgent need. Many research groups are focusing on the potential of the electrochemical sensor to become a key for developing point-of-care (POC) technologies for clinical analysis because it can solve most of the limitations of conventional diagnostic methods. Herein, this review discusses the current development of electrochemical sensors for the detection of respiratory virus infections and flaviviruses over the past 10 years. Trends in future perspectives in rapid clinical detection sensors on viruses are also discussed. KEY POINTS: • Respiratory related viruses and Flavivirus are being concerned for past decades. • Important to differentiate the cross-reactivity between the virus in same family. • Electrochemical biosensor as a suitable device to detect viruses with high performance.

A Comprehensive Review on Biopolymer Mediated Nanomaterial Composites and Their Applications in Electrochemical Sensors.

Biopolymers are an attractive green alternative to conventional polymers, owing to their excellent biocompatibility and biodegradability. However, their amorphous and nonconductive nature limits their potential as active biosensor material/substrate. To enhance their bio-analytical performance, biopolymers are combined with conductive materials to improve their physical and chemical characteristics. We review the main advances in the field of electrochemical biosensors, specifically the structure, approach, and application of biopolymers, as well as their conjugation with conductive nanoparticles, polymers and metal oxides in green-based noninvasive analytical biosensors. In addition, we reviewed signal measurement, substrate bio-functionality, biochemical reaction, sensitivity, and limit of detection (LOD) of different biopolymers on various transducers. To date, pectin biopolymer, when conjugated with either gold nanoparticles, polypyrrole, reduced graphene oxide, or multiwall carbon nanotubes forming nanocomposites on glass carbon electrode transducer, tends to give the best LOD, highest sensitivity and can detect multiple analytes/targets. This review will spur new possibilities for the use of biosensors for medical diagnostic tests.

Gold-Nanohybrid Biosensors for Analyzing Blood Circulating Clinical Biomacromolecules: Current Trend toward Future Remote Digital Monitoring.

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.

Organic-Inorganic Hybrid Nanoflower Production and Analytical Utilization: Fundamental to Cutting-Edge Technologies.

Over the past decade, science has experienced a growing rise in nanotechnology with ground-breaking contributions. Through various laborious technologies, nanomaterials with different architectures from 0 D to 3 D have been synthesized. However, the 3 D flower-like organic-inorganic hybrid nanomaterial with the most direct one-pot green synthesis method has attracted widespread attention and instantly become research hotspot since its first allusion in 2012. Mild synthesis procedure, high surface-to-volume ratio, enhanced enzymatic activity and stability are the main factor for its rapid development. However, its lower mechanical strength, difficulties in recovery from the reaction system, lower loading capacity, poor reusability and accessibility of enzymes are fatal, which hinders its wide application in industry. This review first discusses the selection of non-enzymatic biomolecules for the synthesis of hybrid nanoflowers followed by the innovative advancements made in organic-inorganic hybrid nanoflowers to overcome aforementioned issues and to enhance their extensive downstream applications in transduction technologies. Besides, the role of hybrid nanoflower has been successfully utilized in many fields including, water remediation, biocatalyst, pollutant adsorption and decolourization, nanoreactor, biosensing, cellular uptake and others, accompanied with several quantification technologies, such as ELISA, electrochemical, surface plasmon resonance (SPR), colorimetric, and fluorescence were comprehensively reviewed.

1,1'-Carbonyldiimidazole-copper nanoflower enhanced collapsible laser scribed graphene engraved microgap capacitive aptasensor for the detection of milk allergen.

The bovine milk allergenic protein, 'ß-lactoglobulin' is one of the leading causes of milk allergic reaction. In this research, a novel label-free non-faradaic capacitive aptasensor was designed to detect ß-lactoglobulin using a Laser Scribed Graphene (LSG) electrode. The graphene was directly engraved into a microgapped (~ 95 µm) capacitor-electrode pattern on a flexible polyimide (PI) film via a simple one-step CO2 laser irradiation. The novel hybrid nanoflower (NF) was synthesized using 1,1'-carbonyldiimidazole (CDI) as the organic molecule and copper (Cu) as the inorganic molecule via one-pot biomineralization by tuning the reaction time and concentration. NF was fixed on the pre-modified PI film at the triangular junction of the LSG microgap specifically for bio-capturing ß-lactoglobulin. The fine-tuned CDI-Cu NF revealed the flower-like structures was viewed through field emission scanning electron microscopy. Fourier-transform infrared spectroscopy showed the interactions with PI film, CDI-Cu NF, oligoaptamer and ß-lactoglobulin. The non-faradaic sensing of milk allergen ß-lactoglobulin corresponds to a higher loading of oligoaptamer on 3D-structured CDI-Cu NF, with a linear range detection from 1 ag/ml to 100 fg/ml and attomolar (1 ag/ml) detection limit (S/N = 3:1). This novel CDI-Cu NF/LSG microgap aptasensor has a great potential for the detection of milk allergen with high-specificity and sensitivity.

Laser-scribed graphene nanofiber decorated with oil palm lignin capped silver nanoparticles: a green biosensor.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (M. tuberculosis), requires a high level of attention and is one of the most infectious diseases in the air. Present methods of diagnosing TB remain ineffective owing to their low sensitivity and time consumption. In this study, we produced a green graphene nanofiber laser biosensor (LSG-NF) decorated with oil palm lignin-based synthetic silver nanoparticles (AgNPs). The resulting composite morphology was observed by field-emission scanning electron microscopy and transmission electron microscopy, which revealed the effective adaptation of the AgNPs to the LSG-NF surface. The successful attachment of AgNPs and LSG-NFs was also evident from X-ray diffraction and Raman spectroscopy studies. In order to verify the sensing efficiency, a selective DNA sample captured on AgNPs was investigated for specific binding with M.tb target DNA through selective hybridisation and mismatch analysis. Electrochemical impedance studies further confirmed sensitive detection of up to 1 fM, where a detection limit of 10-15 M was obtained by estimating the signal-to-noise ratio (S/N = 3:1) as 3σ. Successful DNA immobilisation and hybridisation was confirmed by the detection of phosphorus and nitrogen peaks based on X-ray photoelectron spectroscopy and Fourier-transform infrared spectroscopy. The stability and repeatability of the analysis were high. This approach provides an affordable potential sensing system for the determination of M. tuberculosis biomarker and thus provides a new direction in medical diagnosis.

Highly sensitive and selective acute myocardial infarction detection using aptamer-tethered MoS2 nanoflower and screen-printed electrodes.

Acute myocardial infarction (AMI) is one of the leading causes of death worldwide. Cardiac troponin I (cTn1) is a commonly used biomarker for the diagnosis of AMI. Although there are various detection methods for the rapid detection of cTn1 such as optical, electrochemical, and acoustic techniques, electrochemical aptasensing techniques are commonly used because of their ease of handling, portability, and compactness. In this study, an electrochemical cTn1 biosensor, MoS2 nanoflowers on screen-printed electrodes assisted by aptamer, was synthesized using hydrothermal technique. Field emission scanning electron microscopy revealed distinct 2D nanosheets and jagged flower-like 3D MoS2 nanoflower structure, with X-ray diffraction analysis revealing well-stacked MoS2  layers. Voltammetry aptasensing of cTn1 ranges from 10 fM to 1 nM, with a detection limit at 10 fM and a sensitivity of 0.10 nA µM-1  cm-2 . This is a ∼fivefold improvement in selectivity compared with the other proteins and human serum. This novel aptasensor retained 90% of its biosensing activity after 6 weeks with a 4.3% RSD and is a promising high-performance biosensor for detecting cTn1.

Self-assembled silver nanoparticle-DNA on a dielectrode microdevice for determination of gynecologic tumors.

Nanoscale materials have been employed in the past 2 decades in applications such as biosensing, therapeutics and medical diagnostics due to their beneficial optoelectronic properties. In recent years, silver nanoparticles (AgNPs) have gained attention due to their higher plasmon excitation efficiency than gold nanoparticles, as proved by sharper and stronger plasmon resonance peaks. The current work is focused on utilizing self-assembled DNA-AgNPs on microdevices for the detection of gynecological cancers. Human papilloma virus (HPV) mostly spreads through sexual transmittance and can cause various gynecological cancers, including cervical, ovarian and endometrial cancers. In particular, oncogene E7 from the HPV strain 16 (HPV-16 E7) is responsible for causing these cancers. In this research, the target sequence of HPV-16 E7 was detected by an AgNP-conjugated capture probe on a dielectrode sensor. The detection limit was in the range between 10 and 100 aM (by 3σ estimation). The sensitivity of the AgNP-conjugated probe was 10 aM and similar to the sensitivity of gold nanoparticle conjugation sensors, and the mismatched control DNA failed to detect the target, proving selective HPV detection. Morphological assessments on the AgNPs and the sensing surfaces by high-resolution microscopy revealed the surface arrangement. This sensing platform can be expanded to develop sensors for the detection various clinically relevant targets.

MicroRNA-155 complementation on a chemically functionalized dual electrode surface for determining breast cancer.

This study correlated and quantified the expression of microRNA-155 with breast cancer to determine breast cancer progression. The target microRNA-155 sequence was identified by complementation on a capture-probe sequence-immobilized interdigitated dual electrode surface. The sensitivity was found to be 1 fM, and the limit of detection fell between 1 and 10 fM. The specific sequence selectivity with single mismatches, triple mismatches, and noncomplementary bases failed to complement the capture-probe sequence. The obtained results demonstrate the selective determination of the microRNA-155 sequence and can help to diagnose breast cancer.

Human papilloma virus DNA-biomarker analysis for cervical cancer: Signal enhancement by gold nanoparticle-coupled tetravalent streptavidin-biotin strategy.

Human papillomavirus (HPV) is a double-standard DNA virus, as well as the source of infection to the mucous membrane. It is a sexually transmitted disease that brings the changes in the cervix cells. Oncogenes, E6 and E7 play a pivotal role in the HPV infection. Identifying these genes to detect HPV strains, especially a prevalent HPV16 strain, will bring a great impact. Among different sensing strategies for pathogens, the dielectric electrochemical biosensor shows the potential due to its higher sensitivity. In this research, HPV16-E7 DNA sequence was detected on the carbodiimidazole-modified interdigitated electrode (IDE) surface with the detection limit of 1 fM. To enhance the sensitivity, the target sequence was conjugated on gold nanoparticle (GNP) and attained detection to the level of 10 aM. This produced ~100 folds improvement in detecting HPV16-E7 gene and 4 folds increment in the current flow. The stability of HPV16-E7 DNA sequences on GNP was verified by the salt-induced GNP aggregation. The current system has shown the higher specificity by comparing against non-complementary and triple-mismatched DNA sequences of HPV16-E7. This demonstration in detecting HPV16-E7 using dielectric IDE sensing system with a higher sensitivity can be recommended for detecting a wide range of disease-causing DNA-markers.

Gold nanorod embedded novel 3D graphene nanocomposite for selective bio-capture in rapid detection of Mycobacterium tuberculosis.

Tuberculosis (TB) is a chronic and infectious airborne disease which requires a diagnosing system with high sensitivity and specificity. However, the traditional gold standard method for TB detection remains unreliable with low specificity and sensitivity. Nanostructured composite materials coupled with impedimetric sensing utilised in this study offered a feasible solution. Herein, novel gold (Au) nanorods were synthesized on 3D graphene grown by chemical vapour deposition. The irregularly spaced and rippled morphology of 3D graphene provided a path for Au nanoparticles to self-assemble and form rod-like structures on the surface of the 3D graphene. The formation of Au nanorods were showcased through scanning electron microscopy which revealed the evolution of Au nanoparticle into Au islets. Eventually, it formed nanorods possessing lengths of ~ 150 nm and diameters of ~ 30 nm. The X-ray diffractogram displayed appropriate peaks suitable to defect-free and high crystalline graphene with face centered cubic Au. The strong optical interrelation between Au nanorod and 3D graphene was elucidated by Raman spectroscopy analysis. Furthermore, the anchored Au nanorods on 3D graphene nanocomposite enables feasible bio-capturing on the exposed Au surface on defect free graphene. The impedimetric sensing of DNA sequence from TB on 3D graphene/Au nanocomposite revealed a remarkable wide detection linear range from 10 fM to 0.1 µM, displays the capability of detecting femtomolar DNA concentration. Overall, the novel 3D graphene/Au nanocomposite demonstrated here offers high-performance bio-sensing and opens a new avenue for TB detection.

Diagnosing human blood clotting deficiency.

There are different clotting factors present in blood, carries the clotting cascade and excessive bleeding may cause a deficiency in the clotting Diagnosis of this deficiency in clotting drastically reduces the potential fatality. For enabling a sensor to detect the clotting factors, suitable probes such as antibody and aptamer have been used to capture these targets on the sensing surface. Two major clotting factors were widely studied for the diagnosis of clotting deficiency, which includes factor IX and thrombin. In addition, factor IX is considered as the substitute for heparin and the prothrombotic associated with the increased thrombin generation are taking into account their prevalence. The biosensors, surface plasmon resonance, evanescent-field-coupled waveguide-mode sensor, metal-enhanced PicoGreen fluorescence and electrochemical aptasensor were well-documented and improvements have been made for high-performance sensing. We overviewed detecting factor IX and thrombin using these biosensors, for the potential application in medical diagnosis.

Nanoscaled Surface Modification of Poly(dimethylsiloxane) Using Carbon Nanotubes for Enhanced Oil and Organic Solvent Absorption.

This article demonstrates a novel nanoscale surface modification method to enhance the selectivity of porous poly(dimethylsiloxane) (PDMS) in removing oil from water. The surface modification method is simple and low cost by using sugar as a sacrificial template for temporal adhering of carbon nanotubes (CNT) before addition of PDMS prepolymer to encapsulate the CNT on its surface once polymerized. The PDMS-CNT demonstrated a tremendous increase in absorption capacity up to 3-fold compared to previously reported absorbents composed solely of PDMS. Besides showcasing excellent absorption capacity, the PDMS-CNT also shows a faster absorption rate (25 s) as compared to that of pure PDMS (40 s). The enhanced absorption rate is due to the incorporation of CNT, which roughens the surface of the polymer at the nanoscale and lowers the surface energy of porous PDMS while at the same time increasing the absorbent hydrophobicity and oleophilicity. This property makes the absorbent unique in absorbing only oil but repelling water at the same time. The PDMS-CNT is an excellent absorbent material with outstanding recyclability and selectivity for removing oil from water.

Fabrication of interdigitated high-performance zinc oxide nanowire modified electrodes for glucose sensing.

Diabetes is a metabolic disease with a prolonged elevated level of glucose in the blood leads to long-term complications and increases the chances for cardiovascular diseases. The present study describes the fabrication of a ZnO nanowire (NW)-modified interdigitated electrode (IDE) to monitor the level of blood glucose. A silver IDE was generated by wet etching-assisted conventional lithography, with a gap between adjacent electrodes of 98.80 µm. The ZnO-based thin films and NWs were amended by sol-gel and hydrothermal routes. High-quality crystalline and c-axis orientated ZnO thin films were observed by XRD analyses. The ZnO thin film was annealed for 1, 3 and 5 h, yielding a good-quality crystallite with sizes of 50, 100 and 110 nm, and the band gaps were measured as 3.26, 3.20 and 3.17 eV, respectively. Furthermore, a flower-modeled NW was obtained with the lowest diameter of 21 nm. Our designed ZnO NW-modified IDE was shown to have a detection limit as low as 0.03 mg/dL (correlation coefficient = 0.98952) of glucose with a low response time of 3 s, perform better than commercial glucose meter, suitable to instantly monitor the glucose level of diabetes patients. This study demonstrated the high performance of NW-mediated IDEs for glucose sensing as alternative to current glucose sensors.

Characterization of Gold-Sputtered Zinc Oxide Nanorods-a Potential Hybrid Material.

Generation of hybrid nanostructures has been attested as a promising approach to develop high-performance sensing substrates. Herein, hybrid zinc oxide (ZnO) nanorod dopants with different gold (Au) thicknesses were grown on silicon wafer and studied for their impact on physical, optical and electrical characteristics. Structural patterns displayed that ZnO crystal lattice is in preferred c-axis orientation and proved the higher purities. Observations under field emission scanning electron microscopy revealed the coverage of ZnO nanorods by Au-spots having diameters in the average ranges of 5-10 nm, as determined under transmission electron microscopy. Impedance spectroscopic analysis of Au-sputtered ZnO nanorods was carried out in the frequency range of 1 to 100 MHz with applied AC amplitude of 1 V RMS. The obtained results showed significant changes in the electrical properties (conductance and dielectric constant) with nanostructures. A clear demonstration with 30-nm thickness of Au-sputtering was apparent to be ideal for downstream applications, due to the lowest variation in resistance value of grain boundary, which has dynamic and superior characteristics.

A new nano-worm structure from gold-nanoparticle mediated random curving of zinc oxide nanorods.

Creating novel nanostructures is a primary step for high-performance analytical sensing. Herein, a new worm like nanostructure with Zinc Oxide-gold (ZnO/Au) hybrid was fabricated through an aqueous hydrothermal method, by doping Au-nanoparticle (AuNP) on the growing ZnO lattice. During ZnO growth, fine tuning the solution temperature expedites random curving of ZnO nanorods and forms nano-worms. The nano-worms which were evidenced by morphological, physical and structural analyses, revealed elongated structures protruding from the surface (length: 1 µm; diameter: ~100 nm). The appropriate peaks for the face centred cubic gold were (111) and (200), as seen from X-ray diffractogram. The strong interrelation between Au and ZnO was manifested by X-ray photoelectron spectroscopy. The combined surface area increment from the nanoparticle radii and ZnO nanorod random curving gives raise an enhancement in detection sensitivity by increasing bio-loading. 'Au-decorated hybrid nano-worm' was immobilized with a probe DNA from Vibrio Cholera and duplexed with a target which was revealed by Fourier Transform Infrared Spectroscopy. Our novel Au-decorated hybrid nano-worm is suitable for high-performance bio-sensing, as evidenced by impedance spectroscopy, having higher-specificity and attained femtomolar (10 fM) sensitivity. Further, higher stability, reproducibility and regeneration on this sensing surface were demonstrated.

Thickness Dependent Nanostructural, Morphological, Optical and Impedometric Analyses of Zinc Oxide-Gold Hybrids: Nanoparticle to Thin Film.

The creation of an appropriate thin film is important for the development of novel sensing surfaces, which will ultimately enhance the properties and output of high-performance sensors. In this study, we have fabricated and characterized zinc oxide (ZnO) thin films on silicon substrates, which were hybridized with gold nanoparticles (AuNPs) to obtain ZnO-Aux (x = 10, 20, 30, 40 and 50 nm) hybrid structures with different thicknesses. Nanoscale imaging by field emission scanning electron microscopy revealed increasing film uniformity and coverage with the Au deposition thickness. Transmission electron microscopy analysis indicated that the AuNPs exhibit an increasing average diameter (5-10 nm). The face center cubic Au were found to co-exist with wurtzite ZnO nanostructure. Atomic force microscopy observations revealed that as the Au content increased, the overall crystallite size increased, which was supported by X-ray diffraction measurements. The structural characterizations indicated that the Au on the ZnO crystal lattice exists without any impurities in a preferred orientation (002). When the ZnO thickness increased from 10 to 40 nm, transmittance and an optical bandgap value decreased. Interestingly, with 50 nm thickness, the band gap value was increased, which might be due to the Burstein-Moss effect. Photoluminescence studies revealed that the overall structural defect (green emission) improved significantly as the Au deposition increased. The impedance measurements shows a decreasing value of impedance arc with increasing Au thicknesses (0 to 40 nm). In contrast, the 50 nm AuNP impedance arc shows an increased value compared to lower sputtering thicknesses, which indicated the presence of larger sized AuNPs that form a continuous film, and its ohmic characteristics changed to rectifying characteristics. This improved hybrid thin film (ZnO/Au) is suitable for a wide range of sensing applications.

'Spotted Nanoflowers': Gold-seeded Zinc Oxide Nanohybrid for Selective Bio-capture.

Hybrid gold nanostructures seeded into nanotextured zinc oxide (ZnO) nanoflowers (NFs) were created for novel biosensing applications. The selected 'spotted NFs' had a 30-nm-thick gold nanoparticle (AuNP) layer, chosen from a range of AuNP thicknesses, sputtered onto the surface. The generated nanohybrids, characterized by morphological, physical and structural analyses, were uniformly AuNP-seeded onto the ZnO NFs with an average length of 2-3 µm. Selective capture of molecular probes onto the seeded AuNPs was evidence for the specific interaction with DNA from pathogenic Leptospirosis-causing strains via hybridization and mis-match analyses. The attained detection limit was 100 fM as determined via impedance spectroscopy. High levels of stability, reproducibility and regeneration of the sensor were obtained. Selective DNA immobilization and hybridization were confirmed by nitrogen and phosphorus peaks in an X-ray photoelectron spectroscopy analysis. The created nanostructure hybrids illuminate the mechanism of generating multiple-target, high-performance detection on a single NF platform, which opens a new avenue for array-based medical diagnostics.