Metal Nanoparticles as Glucose Sensor

A novel enzyme-free glucose and H2O2 sensor based on 3D graphene aerogels decorated with Ni3N nanoparticles

Chapter 4 - Glucose biosensing with gold and silver nanoparticles for real-time applications

Increased health awareness has called for better health monitoring devices, resulting in continuous research and advancement in glucose sensors. Innovations in both enzymatic and enzyme-free sensors (or non-enzymatic) are revolutionising diabetes control. While enzymatic sensors offer superior sensitivity and selectivity, enzyme-free sensors are preferred for stability and affordability, advancing the quest for rapid and accurate glucose tests. Progress in the development of enzyme-free glucose sensors is being achieved by improvements in electrode materials as well as sensor design. The selection of electrode materials is crucial in these sensors for attaining optimum values of sensing time as well as accuracy. Numerous electrode materials, including graphene, carbon nanotubes, metal oxides (such as platinum and gold), and conductive polymers, have been developed and studied by researchers to be employed in glucose sensors. Among the most critical factors being considered for developing glucose sensor materials is the selectivity for glucose molecules without interference due to the presence of another molecule. This article focuses on tracing recent developments in enzyme-free glucose sensor research, highlighting efforts to overcome limitations and drive innovation in glucose monitoring technology.

A localized surface plasmon resonance (LSPR) based optical fiber biosensor using gold nano rods has been developed. The LSPR optical fiber sensor was fabricated by immobilizing gold nanorods at the distal end of a multimode fiber. The surface of gold nanorods was further functio nalized with human IgG to create a bios ensor to detect anti-human IgG. The peak shift of the longitudinal plasmon wavelength of gold nanorod was monitored as a function of the refractive index change. The results show that refractive index sensitivity of th is sensor is 506 nm/RIU, and the limit of detection for anti-human IgG is 3 nM. Keywords: localized surface plasmon resonance, gold nanorods, optical fiber sensor, biosensor 1. INTRODUCTION Biosensors have been continuing to play an important role in many areas such as in biochemistry, medicine developments, disease detection and health monitoring. However, most of these types of biosensors need to be used in a laboratory environment, where expensive and bulk instruments are often required, and detection by employing these conventional biosensors is often time-consuming. Therefore, a fast, real-time, sensitive, portable and economical technique for developing biosensors is urgently required. Localized surface plasmon resonance (LSPR) is an advanced sensing technology that can be applied to this problem due to the fact that it is highly sensitive to the refractive index change caused by the interactions between small biomolecules, which makes it an ideal candidate for label-free biosensing applications. LSPR is normally generated on the surface of localized metallic nanoparticles when the frequency of incident light is resonant with the collective oscillation of conductive electrons in the metallic nanoparticles [1]. The optical properties of metallic nanoparticles are known to be highly dependent on the materials and their shapes and sizes [2]. Gold nanoparticle s are commonly employed to fabr icate LSPR biosensors due to the close affinity between gold and biomolecules. Among the various types of gold particles, gold nanorods (GNRs) have attracted much attention in recent years due to th eir unique shape and optical pr operties. Being different from the conventional gold nanospheres which have only one plasmon band, GNRs possess two plasmon bands, namely the transverse plasmon wavelength (TPW) and the longitudinal plasmon wavelength (LPW). The LPW is tunable with the aspect ratio of the GNRs and is much more sensitive to the refractive index change than TPW and the plasmon band of gold nanospheres. Fiber-optic based sensor devices, on the other hand, have shown advantages such as small sample volume requirements, a miniaturized and simplified optical design, immunity to el ectromagnetic interference and ca pability for remote sensing. Taking the advantages of both LSPR and optical fiber sensors, LSPR-based optical fiber biosensors offer an alternative solution which would be able to overcome many of the disadvantages of conventional biosensors discussed above. Several studies of LSPR based optical fiber sensors using gold nanospheres have been reported and shown their capability of being biosensors [3]. However, only few resear ch studies into GNRs-based LSPR optical fiber biosensors have been explored so far. In our previous study, a LPSR based optical fiber sensor using GNRs was successfully developed. The results have shown that the device created was highly sensitive to a bulk refractive index change. In this work, a similar GNRs-based LSPR optical fiber sensor has been fabricated based on our previous study. The refractive index sensitivity of the sensor has been investigated under conditions where the sensor was subjected to bulk refractive index change. The sensor was further functionalized with human IgG in order to make a label-free biosensor which is specific to anti-human IgG. The positive results obtained from this work show that the LSPR optical fiber sensor developed has the capability of being a labe l-free biosensor. This shows the poten tial that, based on the same principle demonstrated in this work, biosensors for detecting different targets could be developed effectively.

This work describes synthesis of gold nanoparticles (AuNPs) of tunable size using the seeding growth method. High concentration of AuNPs of various sizes was synthesized by varying synthesis parameters. The properties were observed using transmission electron microscope (TEM), zetasizernanoZS, X-ray diffractometer (XRD) and UV Vis spectrophotometers. The produced AuNPs were then used in fabrication of glucose sensors with the following structure; Nafion/GOx/AuNPs/ITO. The effect of AuNPs size on glucose sensor properties was studied by measuring electrocatalytic activity of the prepared AuNPs/ITO electrodes using cyclic voltammetry in the range of -0.5 to 0.5 V versus Ag/AgCl reference electrode. Cyclic voltammograms of various sizes of AuNPs tested in 10 mM glucose in 0.01 M PBS. UV-Vis analysis shows the wavelength of AuNPs increases from 518, 519, 523, 525 and 529 for 15 (Au seed), 20, 30, 40 and 50 nm, respectively. Particle size analysis using the zetasizer gave z-average for expected size 20, 30, 40 and 50 nm AuNPs of 29.97, 42.61, 44.16 and 58.78 nm, respectively. All of the z-average is larger than the size expected. The polydispersity index (PDI) for size 20, 30, 40 and 50 nm AuNPs are 0.372, 0.096, 0.112 and 0.102, respectively. XRD analysis matched with (111), (200), (220) and (311) face centered cubic Au planes (ICDD 98-005-0876). The result confirmed that AuNPs is in crystalline structure. For glucose sensor, 30 nm AuNPs has the highest electrocatalytic activity as it has the highest anodic and cathodic peak currents compared to other size of AuNPs. The results obtained could be caused by low PDI value measured using zeta-sizer and the uniform particles size distribution as observed in TEM images.This work describes synthesis of gold nanoparticles (AuNPs) of tunable size using the seeding growth method. High concentration of AuNPs of various sizes was synthesized by varying synthesis parameters. The properties were observed using transmission electron microscope (TEM), zetasizernanoZS, X-ray diffractometer (XRD) and UV Vis spectrophotometers. The produced AuNPs were then used in fabrication of glucose sensors with the following structure; Nafion/GOx/AuNPs/ITO. The effect of AuNPs size on glucose sensor properties was studied by measuring electrocatalytic activity of the prepared AuNPs/ITO electrodes using cyclic voltammetry in the range of -0.5 to 0.5 V versus Ag/AgCl reference electrode. Cyclic voltammograms of various sizes of AuNPs tested in 10 mM glucose in 0.01 M PBS. UV-Vis analysis shows the wavelength of AuNPs increases from 518, 519, 523, 525 and 529 for 15 (Au seed), 20, 30, 40 and 50 nm, respectively. Particle size analysis using the zetasizer gave z-average for expected size 20, 30, 40...

Functionalization of bamboo pulp fabrics with noble metal nanoparticles

Fast and reliable detection of glucose is of great scientific and technological importance both in clinical diagnostics and analytical practices industrial applications. Besides the necessity of glucose detection and quantization as an application in environmental pollution monitoring, biotechnology, and food industry, it is essential for the detection and regular monitoring of diabetes mellitus in clinical diagnostics. This metabolic disorder results from the deficiency of insulin and hyperglycemia and results in the fluctuation of blood glucose level with a value falling outside the normal range of 4.4 – 6.6 mM. In detail, blood sugar concentration for healthy people range between 4.0 and 5.4 mM in fasting and up to 7.8 mM in postprandial glucose. A prolonged increase in the blood glucose concentration, will cause severe damage to essential human body organs. Thus affordable, efficient and regular monitoring of blood glucose level is necessary to avoid major health complications.Presently, enzyme-based glucose sensors are the most widely distributed and commercially produced devices for monitoring glucose level at home and clinics. Despite the prompt sensitivity and selectivity, enzymatic glucose sensors suffer from drawbacks due to denaturization of enzymes, higher cost, lesser reproducibility, and lack of stability from temperature fluctuations, pH variation, and humidity. These drawbacks were overcome by the non-enzyme sensors, particularly, the metal based amperometric sensors with direct detection of glucose, owing to its good stability, simplicity, and reproducibility. However, detection of glucose using non-enzymatic metal-based sensors via direct oxidation have their own set of challenges. Precious metal-based sensors, besides being expensive, have recorded narrow linear current response ranges, limited sensitivity and selectivity, and surface poisoning from the adsorbed intermediates and interferences from chloride ions.In this work fabrication of non-enzymatic transition metal-based glucose sensors with good stability, linear range of response covering the normal glucose levels of human, lower detection limit, faster response, workable sensitivity and low cost, were studied. Here, we have researched thin film electrodes of single transition metal as well as bimetallic nanostructures to enhance the surface area, catalytic active sites and electrochemical properties via synergic effects. A two-stage electrochemical deposition technique was used to fabricate bimetallic thin films. A uniform film of nickel (Ni) crystals were formed on the titanium (Ti) cathode. Post the deposition of Ni coating, another two set of samples were prepared with a second-stage electrochemical reduction of silver (Ag) and copper (Cu) nanoparticles on the surface on Ni-coated Ti plate. Scanning electron microscopy images revealed a uniform film of transition-metal nanocrystals with varying diameter depending on the deposition conditions.The electrochemical behavior and the electrocatalytic properties of the as-prepared bimetallic films towards glucose oxidation were studied using cyclic voltammetry and amperometric techniques. The three metallic films investigated, namely, Ni, NiAg, and NiCu showed a fast response towards non-enzymatic glucose oxidation and detected amperometric signals that were linearly proportional in the 0.2-1.8 mM, 0.2-6.4 mM, and 0.2-12.2 mM ranges, respectively and with sensitivity values of 110 μm mM-1 cm-2, 320 μm mM-1 cm-2, and 420 μm mM-1 cm-2, respectively. The sensitivity of the bimetallic films was recorded higher than the monolayer of Ni nanocrystals due to higher surface area and low detection limits were recorded for all the samples. Besides that, for all the three samples, both the cathodic reduction peak current (Ipc) and anodic oxidation peak current (Ipa) increased linearly with the square root of the scan rate between 10 mV/s and 100 mV/s signifying that the electrocatalytic reaction is limited by the diffusion of the glucose molecules into the electrode/electrolyte interface. The as-fabricated bimetallic films are thus promising candidates for electrocatalytic glucose oxidation reaction with wide linear detection range covering the physiological levels of glucose.

This work presents a comprehensive review on gas sensors based on localized surface plasmon resonance (LSPR) phenomenon, including the theory of LSPR, the synthesis of nanoparticle-embedded oxide thin films, and strategies to enhance the sensitivity of these optical sensors, supported by simulations of the electromagnetic properties. The LSPR phenomenon is known to be responsible for the unique colour effects observed in the ancient Roman Lycurgus Cup and at the windows of the medieval cathedrals. In both cases, the optical effects result from the interaction of the visible light (scattering and absorption) with the conduction band electrons of noble metal nanoparticles (gold, silver, and gold–silver alloys). These nanoparticles are dispersed in a dielectric matrix with a relatively high refractive index in order to push the resonance to the visible spectral range. At the same time, they have to be located at the surface to make LSPR sensitive to changes in the local dielectric environment, the property that is very attractive for sensing applications. Hence, an overview of gas sensors is presented, including electronic-nose systems, followed by a description of the surface plasmons that arise in noble metal thin films and nanoparticles. Afterwards, metal oxides are explored as robust and sensitive materials to host nanoparticles, followed by preparation methods of nanocomposite plasmonic thin films with sustainable techniques. Finally, several optical properties simulation methods are described, and the optical LSPR sensitivity of gold nanoparticles with different shapes, sensing volumes, and surroundings is calculated using the discrete dipole approximation method.

Introduction Incident lights interact with noble metal nanoparticles (NPs) to form collective oscillations of free electrons, creating a strong electromagnetic field on their surface. This phenomenon is called localized surface plasmon resonance (LSPR). Recently metal oxide NPs with appreciable concentration of free electrons have been also reported to exhibit LSPR peaks, the peak wavelengths of which were controlled from the visible to near-IR regions.[1] When a plasmonic NP was combined with a semiconductor, the excitation of LSPR could cause the injections of electrons and/or holes from plasmonic NPs to the semiconductor, that is, the plasmon-induced charge separation (PICS).[2] Since the PICS was reported using plasmonic metal oxide NPs,[3] the intense research has been devoted to studying plasmonic metal and metal oxide NPs for the application to photovoltaics, photocatalyts, and biosensors.Recently we reported the preparation of noble metal NPs by metal sputtering deposition onto room-temperature ionic liquids (RTIL) under a reduced pressure (RTIL/metal sputtering), where NPs of several nanometers in size were stably and uniformly dispersed without additional stabilizing agents.[4] This technique enabled the clean preparation of plasmonic metal NPs, such as Au[4], Ag[5], and AgAu alloy[6]. In this study, we apply the RTIL/metal sputtering to the preparation of molybdenum oxide (MoOx) NPs. Thus-obtained NPs exhibited the LSPR peak, the excitation of which induced the PICS. Experimental The sputter deposition of molybdenum were carried out on the surface of 1-hydroxyethyl-3-methylimidazolium tetrafluoroborate (HyEMI-BF4) and 1-ethyl-3-methylimidazolium tetrafluoroborate (EMI-BF4) used as RTILs for 1 h with a discharge current of 30 mA under an argon pressure of 3.0 Pa. The deposited NPs were partially oxidized by the heat treatment at 473 K for 30 min in air, resulting in the formation of MoOx NPs. The photoelectrochemical properties were measured in a 0.5 M Na2SO4 aqueous solution with the ITO electrode immobilized with MoOx NPs as working electrodes, a Pt counter electrode and a Ag/AgCl reference electrode. The photocurrents were detected with monochromatic light irradiation under the potential application at +0.5 V vs Ag/AgCl. Results and Discussion TEM measurements revealed that Mo NPs sputter-deposited in HyEMI-BF4 had an average diameter of 6.8 nm and then the heat treatment at 473 K increased the particle size to ca. 65 nm. XPS spectra of thus-obtained particles indicated that the thus-obtained NPs were composed of MoOx containing Mo(V) and Mo(VI) species. The MoOx NPs prepared in HyEMI-BF4 showed a LSPR peak at around 840 nm, the peak wavelength of which was close to that of LSPR reported for chemically synthesized MoO3-x NPs.[1] On the other hand, MoOx NPs prepared in EMI-BF4 showed no LSPR peak in the visible and near-IR regions. Anodic photocurrents were observed by the irradiation to MoOx NP-immobilized ITO electrodes with wavelength shorter than ca. 1000 nm. Regardless of the kinds of MoOx NPs, the action spectra of photocurrents showed the increase of IPCE at the wavelength below 600 nm due to the photoexcitation of interband transition of MoO3, being in agreement with their extinction spectra. Furthermore, the MoOx NPs prepared in HyEMI-BF4 showed a peak at 840 nm, the peak wavelength of which agreed with that of their LSPR peak. In contrast, MoOx NPs formed in EMI-BF4 exhibited no photocurrent by the irradiation of near-IR lights.Conclusively, we successfully prepared the MoOx NPs with RTIL/metal sputtering technique followed by the heating treatment. The NPs formed in HyEMI-BF4 showed the LSPR peak in near-IR region, the photoexcitation of which induced the PICS from the MoOx NPs to the ITO electrodes. References (1) A. Agrawal, S. H. Cho, O. Zandi, S. Ghosh, R. W. Johns, and D. J. Milliron, Chem. Rev., 118, 3121 (2018).(2) Y. Tian and T. Tatsuma, J. Am. Chem. Soc., 127, 7632 (2005).(3) S. H. Lee, H. Nishi, and T. Tatsuma, Nanoscale, 10, 2841 (2018).(4) T. Torimoto, K. Okazaki, T. Kiyama, K. Hirahara, N. Tanaka, and S. Kuwabata, Appl. Phys. Lett., 89, 243117 (2006).(5) T. Suzuki, K. Okazaki, T. Kiyama, S. Kuwabata, and T. Torimoto, Electrochemistry, 77, 636 (2009).(6) K. Okazaki, T. Kiyama, K. Hirahara, N. Tanaka, S. Kuwabata, and T. Torimoto, Chem. Commun., 6, 691 (2008).

Glucose sensors have been extensively researched in patent studies and manufactured a tool for clinical diabetes diagnosis. Although some kinds of electrochemical enzymatic glucose sensors have been commercially successful, there is still room for improvement, in selectivity and reliability of these sensors. Because of the intrinsic disadvantages of enzymes, such as high fabrication cost and poor stability, non-enzymatic glucose sensors have recently been promoted as next generation diagnostic tool due to their relatively low cost, high stability, prompt response, and accuracy. In this research, a novel free standing and binder free non-enzymatic electrochemical sensor was manufactured using in situ grown copper (Cu) and cobalt (Co) on a silicon (Si) substrate. Scanning High-Energy Electron Diffraction (SHEED) and Edward deposition methods were used to synthesise the sensors. Morphological observations showed that Cu and Co homogeneously formed nanorod-like shapes over the Si substrate. The elemental composition and structure of the prepared sensors were identified by Reflection High-Energy Electron Diffraction (RHEED). In terms of electrochemical properties, for the enzyme-free glucose sensor, voltammograms showed that the peak currents increased when the glucose solution was injected into the electrolytic cell. The electrical relation of voltage versus current was linear, as shown in the experimental data. Another effective parameter changed the magnetic field; and the linear behaviour of the electrical resistance of Co remained unaltered. In the optimum annealing temperature, where the magnetic field increased, the properties of the samples remained constant. In other words, in the selected annealing temperature, resistance and stability of the layers increased in a significant manner.

Patterned growth of ZnO nanorods and enzyme immobilization toward the fabrication of glucose sensors

Optical plasmonic sensing based on nanomaterials integrated in solid supports. A critical review

Glucose sensors are essential tools for monitoring blood glucose concentration in diabetic patients. In recent years, with the increasing number of individuals suffering from diabetes, blood glucose monitoring has become extremely necessary, which expedites the iteration and upgrade of glucose sensors greatly. Currently, two main types of glucose sensors are available for blood glucose testing: enzyme-based glucose sensor (EBGS) and enzyme-free glucose sensor (EFGS). For EBGS, several progresses have been made to comprehensively improve detection performance, ranging from enhancing enzyme activity, thermostability, and electron transfer properties, to introducing new materials with superior properties. For EFGS, more and more new metallic materials and their oxides are being applied to further optimize its blood glucose monitoring. Here the latest progress of electrochemical glucose sensors, their manufacturing methods, electrode materials, electrochemical parameters, and applications were summarized, the development glucose sensors with various noninvasive sampling modes were also compared.

Due to a relation between glucose in sweat and blood, there is an opportunity to monitor patients' glucose levels non-invasively through sweat. There is a high demand for developing highly selective and sensitive biosensors in order to sense biomarkers like glucose and, therefore, the diseases based on those biomarkers. However, enzymatic sensors are selective to specific biomarkers; they are suffering from high sensitivity to the fluctuation of temperature, oxygen, pH, humidity, detergents, organic reagents, and toxic chemicals, affecting their stability and sensitivity, and reproducibility. Therefore, developing non-enzymatic glucose (or other biomarkers) sensors is getting significant attention to fulfill higher sensitivity and selectivity as well as minimized susceptibility to fouling by enzyme-ageing and adsorbed intermediates. Here we have proposed a combination of two sensors that can help us improve these non-enzymatic sensors' selectivity. Two electrochemical arrayed sensors have been developed. The first electrochemical sensor has been achieved by controlled growth of cobalt nanowire and copper nanoparticles on carbon substrate in order to measure the glucose level at low concentrations, and the second electrochemical sensor has been modified by MWCNT-CO-NH-cyanuric-NH2 and Fe3O4 in order to measure the uric acid and eliminate the interference of it in glucose measurement results. In order to show the morphology of the glucose sensor, the SEM and EDX have been conducted. Also, the FT-IR test has been shown to confirm the functionalization of MWCNT. The electrocatalytic and electrochemical performance of each sensor have been evaluated in the presence of the various contaminants of sweat. The glucose sensor showed less than 5% interference toward ascorbic acid, sodium bicarbonate, and the lactic acid at their max range of presence in the sweat. For eliminating the interference of uric acid, the second sensor has developed, which has no response to the glucose and high sensitivity to the uric acid. The calibration curve of each sensor has been provided in the 3D form, and a simple method of arraying has been applied to improve the sensors' selectivity. The arrayed sensors showed a highly glucose-selective sweat-based sensor with minimized error imposed by the uric acid interference. The glucose sensor's reproducibility and durability have also been tested, which showed less than 5% and 10% variations, respectively. In the end, the arrayed sensor's performance has been evaluated by real sweat samples of a male and a female, analyzed by Clarke’s error grid analysis showing less than 20% deviation from the glucose levels measured by the commercial glucometers.

The work was aimed to prepare and characterize a binder-free, low cost, linear and sensitive non-enzymatic glucose (NEG) sensor. An enzyme-free glucose sensor was prepared by spin coating a nanocomposite solution consisting of one-dimensional copper nanowires and two-dimensional reduced graphene oxide nanosheets (CuNWs/rGO) on an ITO coated glass substrate. One dimensional smooth and uniform copper nanowires with an average diameter of 100 nm and length 10 μm anchored to reduced graphene oxide nanosheets were synthesized as illustrated from FESEM results. The crystallite size of the CuNWs/rGO nanocomposite obtained from XRD results was in the range 16-31 nm. The EDX results indicated the presence of copper, carbon, and oxygen in different proportions in the nanocomposite. The CV results showcased an electrocatalytic ability of the prepared nanocomposite. The prepared CuNWs/rGO/ITO electrode exhibited a high sensitivity of 9.3 μA mM <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-1</sup> cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-2</sup> in linear glucose range 0-5 mM.