Nanomaterials for Healthcare Biosensing Applications

In recent years, an increasing number of nanomaterials have been explored for their applications in biomedical diagnostics, making their applications in healthcare biosensing a rapidly evolving field. Nanomaterials introduce versatility to the sensing platforms and may even allow mobility between different detection mechanisms. The prospect of a combination of different nanomaterials allows an exploitation of their synergistic additive and novel properties for sensor development. This paper covers more than 290 research works since 2015, elaborating the diverse roles played by various nanomaterials in the biosensing field. Hence, we provide a comprehensive review of the healthcare sensing applications of nanomaterials, covering carbon allotrope-based, inorganic, and organic nanomaterials. These sensing systems are able to detect a wide variety of clinically relevant molecules, like nucleic acids, viruses, bacteria, cancer antigens, pharmaceuticals and narcotic drugs, toxins, contaminants, as well as entire cells in various sensing media, ranging from buffers to more complex environments such as urine, blood or sputum. Thus, the latest advancements reviewed in this paper hold tremendous potential for the application of nanomaterials in the early screening of diseases and point-of-care testing

Optical Fiber, Nanomaterial, and THz-Metasurface-Mediated Nano-Biosensors: A Review

The increasing use of nanomaterials and scalable, high-yield nanofabrication process are revolutionizing the development of novel biosensors. Over the past decades, researches on nanotechnology-mediated biosensing have been on the forefront due to their potential application in healthcare, pharmaceutical, cell diagnosis, drug delivery, and water and air quality monitoring. The advancement of nanoscale science relies on a better understanding of theory, manufacturing and fabrication practices, and the application specific methods. The topology and tunable properties of nanoparticles, a part of nanoscale science, can be changed by different manufacturing processes, which separate them from their bulk counterparts. In the recent past, different nanostructures, such as nanosphere, nanorods, nanofiber, core–shell nanoparticles, nanotubes, and thin films, have been exploited to enhance the detectability of labelled or label-free biological molecules with a high accuracy. Furthermore, these engineered-materials-associated transducing devices, e.g., optical waveguides and metasurface-based scattering media, widened the horizon of biosensors over a broad wavelength range from deep-ultraviolet to far-infrared. This review provides a comprehensive overview of the major scientific achievements in nano-biosensors based on optical fiber, nanomaterials and terahertz-domain metasurface-based refractometric, labelled and label-free nano-biosensors

Self referencing SPR sensor by simultaneous excitation of long and short range surface plasmon modes

A novel surface plasmon resonance sensor is fabricated to evaluate its use in biochemical sensing. The sensor can differentiate between bulk refractive index changes and surface binding reactions of interest. There has been a great interest in developing sensors to differentiate biological or chemical agents from interfering effects, but they still remain in research phase. In this work, a prism coupler is used to simultaneously excite both long and short range surface plasmon modes of the sensor. The differing sensitivities of the long and short range modes allow one to distinguish surface binding reactions of interest from refractive index fluctuations. In this thesis, we have demonstrated the sensors self referencing capability by detecting the formation of an octadecanethiol self assembled monolayer while varying solution refractive index

Applications and Properties of Magnetic Nanoparticles

This Special Issue aimed to cover the new developments in the synthesis and characterization of magnetic nanoconstructs ranging from conventional metal oxide nanoparticles to novel molecule-based or hybrid multifunctional nano-objects. At the same time, the focus was on the potential of these novel magnetic nanoconstructs in several possible applications, e.g. sensing, energy storage, and nanomedicine

Fiber optics based surface plasmon resonance for label-free optical sensing

With the advancement in the laser technology and availability of low cost optical fibers, there is an increasing trend towards adoption of optical fibers as sensing element for development of optical sensors probes especially point-of-care sensing for environmental, biomedical and clinical application. Refractive index measurement through surface plasmon resonance has evolved to be, one of the most sensitive transducer for label-free sensing with high sensitivity. Surface plasmon resonance is a surface sensitive optoelectronic phenomenon, where light incident on a plasmonic metal surface at a given angle can excite a surface-bound electromagnetic wave, a surface plasmon. Associated with the surface plasmon is an evanescent field that probes local changes in the refractive index of the ambient medium that are used for monitoring analyte- supramolecular/ bio-molecular ligand interactions. Present review outlines a concise view on theoretical aspects of fiber optics based surface plasmon resonance phenomenon and comprehensive updated review on research and development for progression in the design of fiber optics based SPR sensors

Electrospun fiber based colorimetric probes for aspartate aminotransferase and I7ß-estradiol

Fabrication, characterization and application of electrospun polymer composite based colorimetric probes are presented in this thesis. The first part of the thesis involved the development of a protocol for in situ reduction of gold trication (Au³+) into metallic gold atoms with sodium borohydride. The prepared PS-Au NPs showed an SPR band at 542 nm. Furthermore the absorbance of the colloidal Au NPs in polystyrene exhibited a good linear correlation (r2 = 0.9934) to E2 concentration in the range 5 to 50 ppb. The lowest naked eye detection limit was found to be 0.5 ppb and could further be easily monitored by UV-vis spectrophotometer. Upon interaction with E2 Au NPs aggregated to give nanoparticle clusters, confirmed through TEM analysis. Different concentrations of Au NPs were found to have a significant effect on the conductivity of the PS-Au NPs solution. At low concentrations of Au NPs (0.002, 0.015 and 0.025% w/v) PS-Au NPs solution could be electrospun without clogging. The FE-SEM images showed a non-beaded morphology of PS-Au NPs composite fibers. Upon interaction of the colorimetric probe strips with various E2 concentrations it was observed that with increasing E2 concentrations (50 ng/ml to 1000 µg/ml) the colour of the probe changed gradually from white to shades of pink and eventually to shades of blue at higher E2 concentrations. The visible cut-off concentration was 100 ng/ml. The second component of the thesis focussed on the development of diazonium dye-nylon 6 colorimetric probe for aspartate aminotransferase. At optimal pH 7.4 the enzyme was stable, highly active and catalyzed a reaction that was susceptible to detailed kinetic analysis by continuous optical methods. The KM values for L-aspartate, a- ketoglutarate and oxaloacetate were 2.60, 0.59 and 0.066 mM, respectively. On the basis of these KM values the solid-state colorimetric probe was developed. A colour change occurred when an electrospun dye-N 6 probes were exposed to visibly detectable concentrations of oxaloacetate, an AST-catalyzed reaction product. While monitoring AST activity at 530 run, a linear relation was obtained between oxaloacetate concentrations ranging from 0.4 - 7.4 µg/ml. Naked eye detection limit of 2.4 µg/ml oxalaoacetate equivalence of 10 times the normal AST activity was attained. The colorimetric probe was in addition, tested against co-substrates aspartate, ketoglutarate and a variety of other compounds such as alanine, pryruvate, as well as glutamic, malaic and succinic acids known to interfere with AST activity. Each compound elicited a distinct and unambiguous colour change upon interaction with the colorimetric probe. Further X-ray powder diffraction (XRD), duNouy ring tensiometer, Brunauer- Emmett- Teller (BET) and energy dispersive X-ray spectroscopy (EDS/EDX) characterization confirmed composition and stability of the colorimetric probes. Colorimetric probes developed in this thesis are relatively cost effective, simple and "rugged" for measurement of analytes with visual detection without sample pretreatment in matrices, such as plasma and dairy effluents. The probes warrant further investigation as they have shown potential and offer a promising solid-state platform for both clinical diagnostics and environmental monitoring

A numerical approach into new designs for SPR sensors in D-type optical fibers

This thesis investigates how to improve the performance of current designs of optical fiber sensors based on Surface Plasmon Resonance, and how to use a better understanding of the physical and sensing principles behind them to propose new sensing concepts and ideas. We adopt a methodology based on numerical simulations because they provide a better insight onto the operation of these sensors and because they allow an easy and quick way of testing new designs and concepts without the need to fabricate the sensors. We also show that these simulations have a good agreement with experimental results. We adopt a systematic approach to investigate the various parameters that influence the sensor performance, and present different sensors designs, where we study the localization, optical properties, shape and size of the metal components, combined with different type of fibers, resulting in the coupling between the plasmon and optical modes. Furthermore, we verify that choosing the optical modes used in sensing in multimode fibers can also have advantages. We investigate the use of modern artificial materials, such as metamaterials, as well as the inclusion of multiple wires in the fiber to enhance the performance of the SPR sensor. At a more fundamental level, we show that the control of the coupling between multiple plasmon modes in metal components and the optical modes in the fiber constitutes a new way to improve the performance of the sensor and can be inclusively used to develop a new type of SPR sensors capable of measuring simultaneously two variables, such as the external refractive index and temperatureEsta tese investiga como é possível melhorar o desempenho das estruturas atuais dos sensores de fibra ótica baseados em Ressonância Plasmónica de Superfície (SPR), bem como compreender melhor os princípios físicos e de sensorização na base do seu funcionamento, permitindo propor novos conceitos de sensores. Foi utilizada uma metodologia baseada em simulações numéricas, pois proporcionam um melhor entendimento do funcionamento desses sensores, constituindo uma maneira simples e rápida de testar novas estruturas e conceitos, sem a necessidade de fabricar os sensores. Mostra-se também que essas simulações têm uma boa concordância com os resultados experimentais. Foi adotada uma abordagem em que se investiga sistematicamente os diversos parâmetros que influenciam o desempenho do sensor e se apresentam diferentes estruturas de sensores onde foram estudadas a localização, propriedades óticas, forma e tamanho dos componentes metálicos, combinados com diferentes tipos de fibras, resultando no acoplamento entre os modos plasmónicos e os modos óticos. Também foi verificado que a escolha dos modos óticos utilizados na deteção em fibras multimodo pode apresentar vantagens. Foi investigado ainda o uso de materiais artificiais recentemente desenvolvidos, de que são exemplo os metamateriais, bem como, a inclusão de múltiplos fios metálicos na fibra, de forma a melhorar o desempenho dos sensores SPR. A um nível mais fundamental, foi demonstrado que o controlo do acoplamento entre os múltiplos modos plasmónicos gerados nos componentes metálicos e os modos óticos propagados na fibra constitui uma nova forma de melhorar o desempenho do sensor. Tal pode ser inclusivamente utilizado para desenvolver um novo tipo de sensores SPR capazes de medir simultaneamente duas variáveis, como por exemplo o índice de refração externo e a temperatura

Dynamic detection of the bio-molecular interaction at the surface of plasmonic nanoarrays

Nanophysics and plasmonics have recently become fields of relevant interest in the world of research and, in particular, in biosensing and biochemistry. Nanoparticles of noble metals interact with incident light giving rise to the Localized Surface Plasmon Resonance (LSPR), a sharp peak of the extinction spectra of the nanoparticles as a result of the collective oscillation at a resonant frequency of the conduction electrons. The shape of the peak and its position strongly depend on both nano system properties, as composition, size, shape, orientation, and on the local dielectric environment. A change in the medium in which the nanoparticle is embedded is indeed detected and transduced as a distortion and shift of the peak. This mechanism is at the basis of the biosensing application of plasmonic structures, revealing binding events of molecules to the surface or extremely small variation in concentration of substances in the proximity. For this reason, LSPR plasmonic biosensors gained great popularity in a broad range of applications, in particular as diagnostic devices able to quantitatively detect biomarker molecules. MicroRNA, among the others, are biomolecules of prominent interest associated to thumoral or other kind of diseases. The aim of this project is to realize and test a sensitive, specific and label-free plasmonic nanobiosensor able to detect microRNA target molecules and to investigate the dynamics of the binding of the biomolecules on the surface of the optical transducers. To accomplish this task, Au nanoprisms arrays (NPA) are chosen as reference structure, with a LSPR wavelength around 800 nm and nanofabricated via NanoSphere Lithography (NSL) and thermal evaporation deposition. All the samples are morphologically characterized with AFM or SEM microscopy. Post-treating procedure and functionalization protocols are employed to allow the binding of the analyte molecule to be detected to the sensor, and all the functionalization signals are detected by linear optical spectroscopy in the visible or near-infrared spectral range. Static measurements are performed to control the peak shift of the sample after each functionalization step, and dynamic measurements in a microfluidic setup allow to monitor the temporal evolution of the optical signal and to reconstruct in real-time the hybridization kinetics at the surface of the plasmonic sensor. A 217nm/RIU bulk sensitivity and 50fMoles limit of detection is reached with the employed structures, indicating that both the nanofabrication and functionalization strategy are successful in the detection of analyte molecules down to low concentration limits. Of course, optimization is desirable, to push even further the sensitivity and solve challenges as for example the aspecific target binding on the sensor surface. Another purpose of the work is to extract interesting information about the dynamics of the hybridization reaction that takes place when the analyte microRNA is bound to the surface of the nanoarray. Hybridization kinetics is studied, determining the time and affinity constants characterizing the reaction. The results obtained will prove the non- ideal behaviour of the association, laying the basis for future and advanced outlook about the building of a non-Langmuir association model able to analytically describe the bi-molecular binding system

Molecular Imprinted Polymers Coupled to Photonic Structures in Biosensors: The State of Art

Optical sensing, taking advantage of the variety of available optical structures, is a rapidly expanding area. Over recent years, whispering gallery mode resonators, photonic crystals, optical waveguides, optical fibers and surface plasmon resonance have been exploited to devise different optical sensing configurations. In the present review, we report on the state of the art of optical sensing devices based on the aforementioned optical structures and on synthetic receptors prepared by means of the molecular imprinting technology. Molecularly imprinted polymers (MIPs) are polymeric receptors, cheap and robust, with high affinity and selectivity, prepared by a template assisted synthesis. The state of the art of the MIP functionalized optical structures is critically discussed, highlighting the key progresses that enabled the achievement of improved sensing performances, the merits and the limits both in MIP synthetic strategies and in MIP coupling