Academic literature on the topic 'Biosensing platform'

As fossil fuel levels are exhausted, building a more sustainable world is an issue that is coming to the fore as a crucial consideration in the development of new technology. The energy needs of the planet's population are immense, and an environmentally friendly source of energy is desperately needed. Energy harvesting from renewable sources is not a new concept - windmills have been around since the first century - but the desire to harness renewable energy has intensified. Energy harvesting technology is the term given to technology used for collecting unused energy from the surrounding environment and converting it into electrical power. Solar, wind and hydroelectric power are perhaps the best-known of these technologies. However, there are many other forms of energy that are under developed and hold much potential for powering the future. These include vibration, pressure, heat and temperature difference. While large-scale power generation cannot be realised using these sources due to their low levels, devices with low power demands may be able to harness such energy sources, potentially eliminating the need for an external power source. Dr Haruichi Kanaya at Kyushu University is leading a team investigating wireless technology.

After the COVID-19 pandemic, the development of an accurate diagnosis and monitoring of diseases became a more important issue. In order to fabricate high-performance and sensitive biosensors, many researchers and scientists have used many kinds of nanomaterials such as metal nanoparticles (NPs), metal oxide NPs, quantum dots (QDs), and carbon nanomaterials including graphene and carbon nanotubes (CNTs). Among them, CNTs have been considered important biosensing channel candidates due to their excellent physical properties such as high electrical conductivity, strong mechanical properties, plasmonic properties, and so on. Thus, in this review, CNT-based biosensing systems are introduced and various sensing approaches such as electrochemical, optical, and electrical methods are reported. Moreover, such biosensing platforms showed excellent sensitivity and high selectivity against not only viruses but also virus DNA structures. So, based on the amazing potential of CNTs-based biosensing systems, healthcare and public health can be significantly improved.

A V-trench biosensor is a sensitive biosensing platform utilizing fluorescence enhancement induced by surface plasmon resonance (SPR). Instruments for the SPR-assisted fluorescence assays, which were complicated and bulky, are drastically simplified and miniaturized by employing sensor chips equipped with prism-integrated microfluidic channels. In this review, the working principle, sensor design, and examples of virus detection of the V-trench biosensor are presented.

The objective of this research was to develop the initial constituents of a highly scalable and label-free electronic biosensing platform. Current immunoassays are becoming increasingly incapable of taking advantage of the latest advances in disease biomarker identification, hindering their utility in the potential early-stage diagnosis and treatment of many diseases. This is due primarily to their inability to simultaneously detect large numbers of biomarkers. The platform presented here - termed the electronic microplate - embodies a number of qualities necessary for clinical and laboratory relevance as a next-generation biosensing tool. Silicon nanowire (SiNW) sensors were fabricated using a purely top-down process based on those used for non-planar integrated circuits on silicon-on-insulator wafers and characterized in both dry and in biologically relevant ambients. Canonical pH measurements validated the sensing capabilities of the initial SiNW test devices. A low density SiNW array with fluidic wells constituting isolated sensing sites was fabricated using this process and used to differentiate between both cancerous and healthy cells and to capture superparamagnetic particles from solution. Through-silicon vias were then incorporated to create a high density sensor array, which was also characterized in both dry and phosphate buffered saline ambients. The result is the foundation for a platform incorporating versatile label-free detection, high sensor densities, and a separation of the sensing and electronics layers. The electronic microplate described in this work is envisioned as the heart of a next-generation biosensing platform compatible with conventional clinical and laboratory workflows and one capable of fostering the realization of personalized medicine.

Photonic crystals have been shown to be a promising technology for improving the performance of light emitting diodes, solar cells and optical communication components. More recently there has been interest in the application of photonic crystals for bio‐chemical sensing since they provide the potential benefits of high sensitivity, label free, real time detection with low limit of detection. Optical sensing mechanisms such as Surface Plasmon Resonance (SPR), and Evanescent Field (EF) sensing methods are currently popular. These are all sensitive to small changes in refractive index (RI) of part of the device. To date SPR methods provide the highest level of sensitivity but have the disadvantage of requiring an expensive gold coating. AROMA Sensor: As a high sensitivity, low cost alternative to conventional SPR methods, this thesis investigates a new concept for bio‐chemical sensing recently developed at Southampton, which uses vertical projection of leaky transmitted modes of a photonic crystal as the sensing method. We call this Angle Resolved Out‐coupled Mode Analysis (AROMA). This method is highly sensitive to small changes in refractive index at the sidewalls of the holes of a photonic crystal resulting in a strong angular shift of an out coupled beam of light. Changes in RI causes a shift in the projected spot position that can be recorded by a CCD/ CMOS camera. Sensor performance is shown to far exceed normal SPR. Simulation and experimental results demonstrate a sensitivity of 10 degree/RIU from a non‐optimised sensor and simulation results indicate an improved sensitivity of 6500 degree/RIU by optimising the sensor operating point. Responsivity of the sensor was investigated by sequentially depositing a series of sub nm ZnO layers, and was found to be highly linear. Photonic crystal coupler and system integration: Apart from the sensor, a new concept for light coupling is developed and optimised. We extend photonic crystal technology to create a combined light coupler/splitter component allowing arbitrary N‐channel light coupling to a simple slab waveguide device. The coupler is combined with multiple sensors to make a fully functional multi‐channel (4‐12 channels) sensor operating at 785nm. This is integrated into a high refractive index (n=1.7) Silicon Oxynitride (SiON) slab waveguide deposited onto a transparent borosilicate glass substrate. The aim for the slab waveguide was to mimic the refractive index of available polymer materials so that the entire system could eventually be fabricated on a flexible polymer substrate by nanoimprint lithography. Design and modelling: This thesis describes the design and optimisation of each component (sensor, coupler and slab waveguide), presenting in depth background physics and rigorous design methods for each component. 3D models were developed based on Rigorous Coupled Wave Analysis (RCWA) and Finite‐Difference Time‐Domain (FDTD) methods. RCWA models allowed accurate prediction and optimisation of light coupling and projection angles for any selected operating wavelength. FDTD methods allowed careful analysis of the interaction between the light field in the slab waveguide and materials placed in the holes. It also predicts the far‐field projected beam pattern for the sensor. Applications: Capability to detect (dry) monolayer coatings was proven for a simple self‐assembled monolayer molecule coating (p‐tolyltrichlorosilane (TTCS)) and also deoxyribonucleic acid (DNA) was successfully detected, close to physiological levels. To achieve this a complex hybridisation process was developed. Sensor response as a function of self‐assemble molecule (SAM) length and distance from the sidewalls was investigated in detail by using reversible chains of long chain charged molecules (lysine, poly‐lysine, bovine serum albumin protein). A detector surface with a layer of poly‐lysine‐g‐PEG was successfully replaced by a poly‐lysine molecule with larger molecule weight. Sequentially additional bovine serum albumin protein binding with the Polylysine was detected. Capability to detect biomolecules in an aqueous environment is intrinsically difficult for most bio‐sensors. By fabricating the device on a transparent glass substrate, and designing the device to project light backwards through the substrate, it became possible to detect small changes in refractive index for liquids placed on the exposed top surface with no detriment to the readout method. The bulk sensitivity of the sensor for liquids was evaluated by measuring a sequence of glucose solutions with increasing concentrations. A highly linear response was again observed.

[eng] Functional diversification in the More than Moore era has attracted an increasing attention on MEMS resonators as sensing devices for system-on-chip applications thanks to its miniaturization capabilities, simple readout schemes, and integration with current ICs fabrication technologies. These advantages make them the perfect candidates to develop biosensing applications in the chemical and biological domains provided its portability, high-throughput, reduced footprint, and minimal processing time. This thesis focuses on analyzing, designing, and developing MEMS resonators oriented and optimized for VOCs detection and calorimetric sensing that are monolithically integrated with a commercial 0-35-μm CMOS technology with on-chip readout via a CMOS-MEMS fabrication approach. An electrostatic actuation scheme and a capacitive readout allow the MEMS structures to operate as a self-sustained oscillator when coupled to a specific amplifier providing a quasidigital output signal. The MEMS resonators are defined using the available CMOS layers. The adopted fabrication approach uses an intra-CMOS post-fabrication wet-etching step to release the mechanical moving parts by removing the surrounding sacrificial oxide, while the readout circuit is protected thanks to the passivation layer. Extensive analytical studies and FEM simulations, together with experimental characterization in open-loop and closedloop configuration of the fabricated CMOS-MEMS devices are addressed, offering an invaluable source of information for design optimization. Four-anchored plate resonators operating in the MHz range are designed and evaluated to work as a gas sensor with specific surface functionalization (via dip-cast immersion and inkjet polymer deposition) achieving a mass resolution per unit area as low as 213 pg·cm-2·Hz-1 and an Allan deviation below 0.5 ppm. Tolerance against environment perturbations such as temperature, humidity and fluid flow are discussed in detail for multiple anchor topologies, providing an optimum folded flexure alternative that alleviates such disturbances by 20-times. After P4V polymer coating, the fabricated system demonstrated acetone detection with a resolution down to 20 ppb that directly points towards non-invasive exhaled breath diagnosis for diabetic patients. In the case of calorimetric sensing, CC-Beams resonators in the MHz range have been designed as the temperature sensor providing extremely high temperature sensitivity up to -7900 ppm·ºC-1 that, together with a fair sub-ppm Allan deviation, achieves an outstanding temperature resolution of 300 μK. In this line, a cointegration of the resonator within a microfluidics PDMS-based platform has been developed that enables a Lab-on-Chip CMOS-compatible system capable of routing a fluid of interest to interact with a CMOS electrode. A conformal 2D planarization process is proposed to increase the IC active surface, combined with a standard wire bonding technique for socket connection. The obtained results confirm micro-calorimetric operation with an experimentally measured thermal efficiency from sample to resonator of 20%, conducting to an energy and heat resolutions as low as of 150 pJ and 630 nW, respectively.
[cat] La diversificació de funcionalitats en un mateix sistema integrat intrínsec a l’aproximació “More than Moore” ha evidenciat un interès creixent en els dispositius basats en ressonadors MEMS per aplicacions tipus “System-on-Chip” gràcies a la seva capacitat de miniaturització, a la implementació directa d’esquemes de lectura elèctrics i a la seva possible integració amb les tecnologies actuals de fabricació de circuits integrats. Aquests avantatges els fan candidats idonis pel desenvolupament d’aplicacions de bio-sensat en l’àmbit de la química i de la biologia donada la seva portabilitat, elevat rendiment, dimensions reduïdes i temps mínim de processat. Aquest treball de tesi es focalitza en l’anàlisi, disseny i desenvolupament de ressonadors MEMS orientats i optimitzats per a la detecció de COVs i pel sensat calorimètric, integrats monolíticament amb circuits CMOS de lectura mitjançant l’ús d’una tecnologia comercial CMOS de 0.35-μm i d’una estratègia de fabricació CMOS-MEMS. Els ressonadors MEMS desenvolupats poden operar en mode oscil·lador, gràcies a la implementació d’un esquema elèctric amb actuació electrostàtica i lectura capacitiva, que permet la seva connexió directa a un circuit amplificador específic obtenint-se així un senyal de sortida quasi digital. Els dispositius MEMS s’han mecanitzat emprant les capes disponibles de la tecnologia CMOS mitjançant una aproximació intra-CMOS per la seva fabricació. Aquesta requereix d’una etapa posterior de gravat humit per a l’alliberació de les parts mecàniques mòbils dels ressonadors basada en l’eliminació de l’òxid de sacrifici tot mantenint-se protegit la resta del circuit integrat gràcies a la capa de passivació. En aquest treball es presenten un gran nombre d’estudis analítics i simulacions FEM que, juntament amb la caracterització experimental tant en llaç obert com en llaç tancat dels diferents dispositius CMOS-MEMS fabricats, suposen una important font d’informació per a l’optimització dels dissenys. S’han dissenyat ressonadors tipus plataforma amb quatre ancoratges que operen dins el rang dels MHz i seguidament, s’han avaluat per la seva operació com a sensors de gas gravimètrics mitjançant una funcionalització superficial específica (ja sigui a través d’immersió en dissolució o bé per deposició d’un polímer emprant impressió de tinta) amb els que s’ha obtingut una resolució en massa per unitat de superfície de 213 pg·cm-2·Hz-1 així com una desviació d’Allan inferior als 0.5 ppm. Addicionalment s’ha analitzat la tolerància que presenten varies topologies de suport front a pertorbacions ambientals com la temperatura, la humitat i el flux d’un gas constatant que les estructures tipus “U” minimitzen aquests efectes fins 20 vegades. Mitjançant la deposició del polímer P4V sobre els sistemes fabricats, s’ha demostrat la capacitat de detectar acetona amb una resolució de 20 ppb el que capacita per la seva potencial aplicació en el diagnosi clínic de pacients diabètics de forma no invasiva per mitjà de l’exhalat. En el cas dels sensors calorimètrics, s’han dissenyat ressonadors tipus pont amb dos ancoratges que operen dins el rang dels MHz i funcionen com a sensors de temperatura de molt alta sensibilitat assolint un valors de fins a -7900 ppm·ºC-1 que, juntament amb una desviació Allan de l’oscil·lador inferior a ppm, s’assoleix una excel·lent resolució tèrmica de 300 μK. En aquesta línia d’actuació, s’ha desenvolupat tot un procés de co-integració dels ressonadors juntament amb una plataforma de microfluídica basada en PDMS amb el que s’obté un sistema tipus “Lab-on-Chip” compatible amb circuits integrats i que permet dirigir un fluid d’interès per a la seva interacció sobre un elèctrode CMOS. Es presenta un procés de planarització 2D, que permet incrementar la superfície efectiva del xip, juntament amb la utilització de la tècnica “wire bonding” estàndard per a la connexió elèctrica amb l’encapsulat. Els resultats experimentals confirmen l’operació del sistema com a micro-calorímetre obtenint una eficiència tèrmica de la mostra cap al ressonador del 20%, que esdevé en una resolució d’energia i calor de 150 pJ i 630 nW, respectivament.
[spa] La diversificación de funcionalidades en un mismo sistema integrado intrínseca a la aproximación “More than Moore” ha evidenciado un interés creciente en los dispositivos basados en resonadores MEMS para aplicaciones tipo “System-on-Chip” gracias a su capacidad de miniaturización, a la implementación directa de esquemas de lectura eléctricos y a su posible integración con las tecnologías actuales de fabricación de circuitos integrados. Estas ventajas los hacen candidatos idóneos para el desarrollo de aplicaciones de bio-sensado en el ámbito de la química y de la biología dada su portabilidad, elevado rendimiento, tamaño reducido y tiempo mínimo de procesado. Este trabajo de tesis se focaliza en el análisis, diseño y desarrollo de resonadores MEMS, orientados y optimizados para la detección de COVs y para sensado calorimétrico, integrados monolíticamente con circuitos CMOS de lectura mediante el uso de una tecnología comercial CMOS de 0.35-μm y de una estrategia de fabricación CMOS-MEMS. Los resonadores MEMS desarrollados pueden operar como oscilador, gracias a la implementación de un esquema eléctrico con actuación electrostática y lectura capacitiva, que permite su conexión directa a un circuito amplificador específico obteniéndose así una señal de salida casi digital. Los dispositivos MEMS se han mecanizado utilizando las capas disponibles de la tecnología CMOS mediante una aproximación intra-CMOS para su fabricación. Esta requiere de una etapa posterior de gravado húmedo para la liberación de las partes mecánicas móviles de los resonadores basada en la eliminación del óxido de sacrificio manteniéndose protegido el resto del circuito integrado gracias a una capa de pasivación. En este trabajo se presentan un gran número de estudios analíticos y simulaciones FEM que, junto con la caracterización experimental tanto en lazo abierto como lazo cerrado de los diferentes dispositivos CMOSMEMS fabricados, suponen una importante fuente de información para la optimización de los diseños. Se han diseñado resonadores tipo plataforma con cuatro anclajes que operan en el rango de los MHz y seguidamente, se han evaluado para su operación como sensores de gas gravimétricos mediante una funcionalización superficial específica (ya sea a través de inmersión en disolución o bien por deposición de un polímero usando impresión de tinta) con los que se ha obtenido una resolución en masa por unidad de superficie de 213 pg·cm-2·Hz-1 así como una desviación Allan inferior a los 0.5 ppm. Adicionalmente se ha analizado la tolerancia que presentan varias topologías de anclaje frente a perturbaciones ambientales como la temperatura, la humedad y el flujo de un gas constatándose que las estructuras tipo “U” minimizan estos efectos hasta 20 veces. Mediante la deposición del polímero P4V sobre los sistemas fabricados, se ha demostrado la capacidad de detectar acetona con una resolución de 20 ppb lo que capacita para su potencial aplicación en el diagnóstico clínico de pacientes diabéticos de forma no invasiva a través del exhalado. En el caso de los sensores calorimétricos, se han diseñado resonadores tipo puente de doble anclaje que operan en el rango de los MHz y funcionan como sensores de temperatura de muy alta sensibilidad alcanzando valores de hasta -7900 ppm·ºC-1 que, junto con una desviación Allan del oscilador inferior a ppm, se consigue una excelente resolución térmica de hasta 300 μK. En esta línea de actuación, se ha desarrollado todo un proceso de co-integración de los resonadores junto con una plataforma de microfluídica basada en PDMS con lo que se obtiene un sistema tipo “Lab-on-Chip” compatible con circuitos integrados y que permite dirigir un fluido de interés para su interacción sobre un electrodo CMOS. Se presenta un proceso de planarización 2D, que permite incrementar la superficie efectiva del chip, junto con la utilización de la técnica “wire bonding” estándar para la conexión eléctrica con el encapsulado. Los resultados experimentales confirman la operación del sistema como micro-calorímetro obteniendo una eficiencia térmica de la muestra hacia el resonador del 20%, lo que supone una resolución de energía y calor de 150 pJ y 630 nW, respectivamente.

Rapid methods to identify bacteria in biological samples are important for prompt antimicrobial therapy. The current detection methods are classical biological sample cultures and biochemical tests, which are however, time-consuming and not highly sensitive. A novel and highly performing approach is offered by aptamers acting as recognition elements able to detect epitopes on the surface of a bacterium. Aptamers interacting with specific bacteria are known and then could provide a solid base for developing promising solutions for this issue. With this PhD work I intended to tackle one drawback of aptamer-based biosensor: the lack of platforms for high density aptamers immobilization. Cluster-assembled thin films, have been optimized as supports to demonstrate that aptamers, targeting Staphylococcus aureus, well adhere on these substrates and keep their functionality. Moreover, the characteristics of the nanostructured zirconium oxide thin film: thermal stability, good reactivity towards -OH and -COOH groups and nano-morphology, make this material a suitable candidate for the realization of platforms for general screening and biosensing applications. This strategy will offer a promising way for the development of an user-friendly aptamer-based biosensors for screening biological samples. Furthermore, I focused on a technological problem, regarding the need of substrates to perform correlative light-electron microscopy(CLEM), designing, developing and testing a device which improve the feasibility of correlative fluorescence/confocal and scanning electron microscopy.

Thesis (Ph.D.)--Boston University
Label-free optical biosensors have been established as proven tools for monitoring specific biomolecular interactions. However, compact and robust embodiments of such instruments have yet to be introduced in order to provide sensitive, quantitative, and high-throughput biosensing for low-cost research and clinical applications. Here we present the interferometric reflectance-imaging sensor (IRIS). IRIS allows sensitive label free analysis using an inexpensive and durable multi-color LED illumination source on a silicon based surface. IRIS monitors biomolecular interaction through measurement of biomass addition to the sensor's surface. We demonstrate the capability of this system to dynamically monitor antigen-antibody interactions with a noise floor of 5.2 pg/mm^2 and DNA single mismatch detection under isothermal melting conditions in an array format. Ensemble detection of binding events using IRIS did not provide the sensitivity needed for detection of infectious disease and biomarkers at clinically relevant concentrations. Therefore, a new approach was adapted to the IRIS platform that allowed the detection and identification of individual nanoparticles on the sensor's surface. The new detection method was te1med single-particle IRIS (SP-IRIS). We developed two detection modalities for SP-IRIS. The first modality is when the target is a nanoparticle such as a virus. We verified that SP-IRIS can accurately detect and size individual viral particles. Then we demonstrated that single nanoparticle counting and sizing methodology on SP-IRIS leads to a specific and sensitive virus sensor that can be multiplexed. Finally, we developed an assay for the detection of Ebola and Marburg. A detection limit of 3 x 10^3 PFU/ml was demonstrated for vesicular stomatitis virus (VSV) pseudotyped with Ebola or Marburg virus glycoprotein. We have demonstrated that virus detection can be done in human whole blood directly without the need for sample preparation. The second modality of SP-IRIS we developed was single molecule counting of biomarkers utilizing a sandwich assay with detection probes labeled with gold nanoparticles. We demonstrated the use of single molecule counting in a nucleic acid assay for melanoma biomarker detection. We showed that a single molecule counting assay can lead to detection limits in the attomolar range. The improved sensitivity of IRIS utilizing single nanoparticle detection holds promise for a simple and low-cost technology for rapid virus detection and multiplexed molecular screening for clinical applications.

Solid-supported membranes present a biomimetic platform that can be adapted for bio-physical, biochemical and electrophysiological studies. In addition to this they offer an environment to host membrane proteins for the purposes of biosensing. This thesis examines the use of such a system and the possibilities it presents for the studies of ion channels and their potential applications in biosensing. Electrochemical impedance spectroscopy (EIS) is a powerful technique in the study of solid-supported membranes giving access to capacitance and resistance data, and as such was employed as the main method of characterisation. Electrodes were designed for this purpose in conjunction with Philips Research, and the suitability of the surface for the formation of insulating tethered bilayer lipid membranes (tBLMs). The development of these electrodes led to the incorporation of a SiO2 insulating layer, however its addition resulted in diculties with the formation of self-assembled monolayers (SAMs). However, further refinement of the manufacturing process should resolve these issues. Despite these diffculties, studies were performed using first generation electrodes (P1). Two ionophores, valinomycin and gramicidin, were employed in the characterisation of the ion transport properties of the tBLM system. These studies yielded important information about the structure of the tBLM system under investigation, as well as the ways ion transport can be presented in EIS. Using the work on ionophores as a foundation, an investigation into the incorporation and characterisation of ion channels in tBLM was conducted. Three channels were studied - a ligand-gated eukaryotic Ca2+-permeant channel (TRPC5), a voltage-gated prokaryotic Na+-permeant channel (NavCbt), and a pH-gated K+-permeant channel (KcsA). The success of these studies varied, but provided strong evidence that ion channel incorporation is possible. Further investigation of channel function in the tBLM is required as measured activity is lower than that suggested by literature.

Au cours de ma thèse, j'ai développé un procédé de fabrication spécifique capable de produire un biocapteur qui combine deux techniques de biodétection différentes, la réponse plasmonique basée sur la résonance de plasmon de surface localisée (LSPR) et la réponse électrochimique. Les méthodes et les résultats qui sont présentés dans ce manuscrit ont été définis pour converger vers un dispositif fluidique unique combinant ces deux approches de détection différentes. Afin de trouver la configuration permettant l'excitation des résonances plasmoniques, la géométrie des nanocavités MIM (métal/isolant/métal) en réseau de lignes interdigitées a été optimisée par des simulations électromagnétiques. La fabrication par nanoimpression douce assistée UV (SoftUV-NIL) a été optimisée et, finalement, la caractérisation optique de ces nanocavités a été comparée avec succès aux simulations théoriques. Parallèlement à la réalisation de ce dispositif nanostructuré, des dispositifs électrochimiques fluidiques plus simples qui intègrent des microélectrodes classiques ont également été développés. L'objectif était d'abord de développer une chimie innovante pour le couple « biotine/streptavidine » et de comprendre ensuite comment les paramètres fluidiques peuvent affecter l'efficacité de capture des biomolécules. Ce manuscrit se termine par une discussion sur le rôle des paramètres fluidiques concernant l’efficacité de la biodétection sur la base de la théorie de Squires
During my thesis, I worked on the development of a specific fabrication process able to produce a device that combines two different biodetection techniques, plasmonic response based on Localized Surface Plasmon Resonance (LSPR) and electrochemical response. Methods and results that are presented in this manuscript were defined to converge towards a unique fluidic device combining these two different sensing approaches. This device integrates interdigitated array of MIM nanocavities. In order to find the easier working configuration allowing the excitation of plasmonic resonances, their geometry has been optimized through electromagnetic simulations. The fabrication of these dual devices has been optimized based on Soft-UV NIL and, finally, optical characterization of these nanocavities has been successfully compared with theoretical simulations. In parallel to this challenging goal, simpler fluidic electrochemical devices that integrate conventional microelectrodes have also been developed. The goal was first to develop an innovative chemistry for the couple biotin/streptavidin and secondly to learn how fluidic parameters can affect the capture efficiency of molecules. This manuscript ends with a discussion on the role of the fluidic parameters on the biodetection efficiency based on the theory of Squires

The purpose of this study is to demonstrate the ability of surface enhanced Raman scattering (SERS) active particles to enable multiplexed immunoassays in a lateral flow format for point of care (POC) testing. The SERS particles used for this study are chemically active glass coated gold particles, containing tracer molecules which in principle can be chosen to provide Raman Spectra with unique features allowing multiple tracers to be simultaneously measured and distinguished without interference between each other. Lateral flow immunoassay technology is the important part of this study and can be conveniently packaged for the use of other than highly skilled technicians outside of the laboratory. A well-known (single channel - simplex) device for the pregnancy test is a typical example of the lateral flow assay. Similar formats have been/are being developed by others for a range of POC applications – but most diagnostic applications require simultaneous determination of a range of biomarkers and multiplexed assays are difficult to achieve without significant interference between the individual assays. This is where SERS particles may provide some advantages over existing techniques. Cardiac markers are the growing market for point of care technology therefore biomarkers of cardiac injury (Troponin, myoglobin and CRP) have been chosen as a model. The object of the study is to establish the proof of concept multiplexing assay using these chosen biomarkers. Thus, initially all different particles were characterised in single and mixture form. Also development of conjugate chemistry between antibodies for each analyte that have been purchased from commercial sources and SERS particles were analysed using different conditions like buffer, pH and antibody loading concentration to get the optimum intensity. The selected SERS particles and their conjugates were tested for size, aggregation and immune quality using a range of techniques: ultraviolet-visible (UV/Vis) absorption spectroscopy, dynamic light scattering (DLS) and lateral flow assay. These characterisations methodologies gave the understanding of optimum conditions of the each conjugates and individual’s behaviour in mixture conditions as well. After the characterisation all conjugates were tested singularly on the lateral flow assay using buffers and serum. The results of this single analyte immunoassay explained the individual’s bioactivity on the lateral flow strip. Further in study, multiplex assay have been demonstrated in serum. These outcomes have described each candidate characteristic in a mixture form on the lateral flow strip. In order to get the optimum Raman intensity from multiplex assay, the detection and capture antibodies loading concentrations were tuned in the assay. Later on different combinations (high, medium and low concentrations) of all three analytes were analysed and has found some interferences in multiplex assay. To investigate these issues various aspect were considered. First of all, different possibilities of non-specific interactions between the co-analytes and antibodies were tested. In addition, steric hindrance and optical interference investigations were performed via several assays and analysis using Scanning electron microscopy. The outcomes have confirmed related optical interferences. Therefore other assay (wound biomarkers) established to eliminate the interferences. In summary, the works reported here have built and test the equipment and necessary reagents for individual assays before moving on the more complicated task. In addition, the entire study has given a deep knowledge of multiplex assay on a single test line including the investigation of the issues for selected cardiac biomarkers and their applications in the future.

Biosensors and biosensing practices collect and share living data, data concerning changes in body states. Health biosensing emerges where devices, health experience, scientific and medical knowledges and online platforms meet around bodies. This book contrasts forms of health biosensing in significant life events ranging from conception to ageing. It explores practicalities, histories and promises of fertility and hormonal biosensing, stress biosensing, DNA genotyping platforms, and old-age biosensing. While the biosensing industries promote promise-horizons of the ‘soon’, ethnographic stories of failure and disappointment abound. ‘Living data’ may be about health for many people, but still happens mostly outside biomedicine or clinical practice. Yet biosensing has the potential to change human bodies and lives in barely imagined ways. This book argues for thinking about biosensing platforms and bodies together to understand that potential and to recognise harms and limitations.

We demonstrate the utilization of an interferometrically created nanoporous polymeric gratings as a platform for biosensing applications. Aminopropyltriethoxysilane (APTES)-functionalized nanoporous polymeric gratings was fabricated by combining holographic interference patterning and APTES-functionalization of pre-polymer syrup. The successful detection of multiple biomolecules indicates that the biofunctionalized nanoporous polymeric gratings can act as biosensing platforms which are label-free, inexpensive, and applicable as high-throughput assays.

A novel flexible electrochemical biosensor for protein biomarker detection was successfully designed and fabricated on a nanoporous polyimide membrane using zinc oxide (ZnO). Nanostructures of ZnO were grown on microelectrode platform using aqueous solution bath. Electrochemical measurements were performed using gold, ZnO seed and nanostructured electrodes to study the influence of electrode surface area on biosensing performance. Feasibility analysis of sensor platforms was evaluated using high concentrations (in ng/mL) of troponin-T. The results showed that improved performance can be obtained on nanostructured platform by careful optimization of growth conditions. This study demonstrates the development of nanostructured ZnO flexible biosensors towards ultra-sensitive protein biosensing.