Design of Low Noise Micro Liter Syringe Pump for Quartz Crystal Microbalance Sensor

An injection pump was a critical aspect in the used of Quartz Crystal Microbalance (QCM) biosensor or chemical sensor in liquid. It is required that the pump should have variable speed and doesn't introduce pressure noise to the QCM sensor. In this work, the pump was developed using a micro stepper motor with a microliter syringe. The mechanical transmission transforms the rotational displacement of the motor into a translational displacement of the syringe. The flow rate of the injection pump could affect the signal pattern indicated by a signal spike or instability of the sensor resonance frequency. The developed system successfully minimized the spike signal and improved the stability of the sensor resonance by the used of the microliter syringe pump with optimizing the reaction chamber of the QCM sensor. The flow rate of the pump can be controlled with a minimum speed of 0.7 microliter per second for water. At low flow rate, there was a negligible or none of the spike signal observed during the injection and ejection of the liquid. However, at a high flow rate, few signal spikes may be observed

Bulk and Surface Acoustic Wave Sensor Arrays for Multi-Analyte Detection: A Review

Bulk acoustic wave (BAW) and surface acoustic wave (SAW) sensor devices have successfully been used in a wide variety of gas sensing, liquid sensing, and biosensing applications. Devices include BAW sensors using thickness shear modes and SAW sensors using Rayleigh waves or horizontally polarized shear waves (HPSWs). Analyte specificity and selectivity of the sensors are determined by the sensor coatings. If a group of analytes is to be detected or if only selective coatings (i.e., coatings responding to more than one analyte) are available, the use of multi-sensor arrays is advantageous, as the evaluation of the resulting signal patterns allows qualitative and quantitative characterization of the sample. Virtual sensor arrays utilize only one sensor but combine itwith enhanced signal evaluation methods or preceding sample separation, which results in similar results as obtained with multi-sensor arrays. Both array types have shown to be promising with regard to system integration and low costs. This review discusses principles and design considerations for acoustic multi-sensor and virtual sensor arrays and outlines the use of these arrays in multi-analyte detection applications, focusing mainly on developments of the past decade

Low-Cost Quartz Crystal Microbalance System Platform Designed for Chemical Nanoparticle

QCM sensor is a response to a kind of broad spectrum, high sensitivity, and simple structure, low-cost detection device, and particularly its quality as a type of gas sensor is widely used. With the successful oscillation in liquid phase, QCM sensor has been involved in the application analytical chemistry, surface chemistry, biochemistry and environmental monitoring side and many other scientific fields. With sensitive surface film as the sensitive element, AT-cut quartz crystal as energy transducer components by changes of the relationship between mass of surface film and frequency of QCM sensor transduces signals of mass or concentration into output frequency signal of sensor, thus achieve changes of mass or concentration detection. This paper mainly states how to design a low-cost QCM system platform with Arduino microcontroller board based on QCM sensor specific properties. For the oscillator circuit selection and differential frequency circuit design, the shield board has properly matched Arduino Mega2560, then by programming code to make Arduino acquire frequency of QCM sensor in real-time. Meanwhile, the interface and data store are corresponding convenient for real- time observing and data post-processing. By the tests of anhydrous ethanol evaporation, QCM system platform was calibrated and Sauerbrey equation verification. Moreover, this paper studies that photocatalytic degradation processing of Rhodamine B (RB) and methyl orange solution at the Surface of nanocrystalline TiO2 by QCM sensor

Electrochemical and surface plasmon bioassays for circulating biomarkers

To address analytical detection needs, sensitive and selective assay methodologies are of great importance. Compared to simple buffer medium, a great challenge exists in detecting ultra-low levels of biomarkers in clinical matrices due to their inherent complexity and interferences posed by non-specific molecules. In addition, small molecules do not yield measurable assay signal changes compared to large biomolecules. My thesis research is focused on designing nano-biological interfaces to detect small and large molecules at low parts-per-billion and femto/picomolar concentrations in complex biofluids (serum and urine samples). Compared to harsh and tedious chemical carboxylation, non-covalent carboxylation of multiwalled carbon nanotubes by π-π stacking 1-pyrenebutyric acid retains the innate sp2 structure and electronic properties of the nanotubes and offers surface carboxyl groups for stable covalent amine coupling of a large amount of enzymes, thus improving the sensitivity of the assay. Chapter 2 demonstrates the first pyrenyl carbon nanostructure modified enzymatic bioelectrode for amperometric detection of urine formaldehyde at clinically relevant parts-per-billion levels with selectivity and wide dynamic range. Subsequently, we explored the low dielectric permittivity and intrinsic plasmonics of graphene for the detection of serum glutamic acid decarboxylase autoantibody (GADA). Graphene-based electrochemical immunosensing approach is advantageous due to its additional applicability for surface plasmon based validation and binding strength analysis with surface immobilized GAD-65 antigens (Chapter 3). My thesis focused on the third class of biomarkers, microRNAs, which are small oligonucleotides with 21-25 bases. To develop the microRNA assay with quantitative characterization, surface plasmon resonance imaging (SPRi) coupled with quartz crystal microbalance (QCM) was designed (Chapter 4). Gold nanoparticles (Au NPs) were linked to the oligonucleotides to increase the detection sensitivity upon hybridization with the selective capture oligonucleotide immobilized on the sensor surface with minimal non-specific signals. Often, cancer and other similar health disorders have been shown to be related to various types of biomarkers. Hence, in Chapter 5, we designed a multiplex assay platform for combined measurement of proteins and microRNAs. For this multiplex assay, we synthesized iron-gold bimetallic core/shell nanoparticles (Fe3O4@Au NPs) that displayed a greater plasmonic signal amplification than either Fe3O4 or Au NPs.Chemistr

Development of a novel high resolution and high throughput biosensing technology based on a Monolithic High Fundamental Frequency Quartz Crystal Microbalance (MHFF-QCM). Validation in food control

Tesis por compendio[ES] La sociedad actual demanda un mayor control en la seguridad y calidad de los alimentos que se consumen. Esta preocupación se ve reflejada en los diferentes planes estatales y europeos de investigación científica, los cuales, plantean la necesidad de innovar y desarrollar nuevas técnicas analíticas que cubran los requerimientos actuales. En el presente documento se aborda el problema de la presencia de residuos químicos en la miel. El origen de los mismos se debe, fundamentalmente, a los tramientos veterinarios con los que se tratan enfermedades y parásitos en las abejas, y a los tratamientos agrícolas con los que las abejas se ponen en contacto cuando recolectan el néctar en cultivos próximos a las colmenas. La Agencia Europea de Seguridad Alimentaria (EFSA) confirma esta realidad al notificar numerosas alertas sanitarias en la miel. En los últimos años, los métodos de análisis basados en inmunosensores piezoeléctricos se han posicionado como la base de una técnica de cribado muy prometedora, la cual puede ser empleada como técnica complementaria a las clásicas de cromatografía, gracias a su sencillez, rapidez y bajo coste. La tecnología de resonadores High-Fundamental Frequency Quartz Crystal Microbalance with Dissipation (HFF-QCMD) combina la detección directa en tiempo real, alta sensibilidad y selectividad con un fácil manejo y coste reducido en comparación con otras técnicas. Además, está tecnología permite aumentar el rendimiento del análisis mediante el diseño de arrays de resonadores en un mismo sustrato (Monolithic HFF-QCMD). En este documento se presenta el diseño de un array de 24 sensores HFF-QCMD, junto con un cartucho de micro-fluídica que traza diversos microcanales sobre los diferentes elementos sensores, a los que hace llegar la muestra de miel diluida a analizar. El cartucho actúa también como interfaz para realizar la conexión entre el array de resonadores y el instrumento de caracterización de los mismos. Para obtener el máximo partido del array diseñado, se desarrolla un método de medida robusto y fiable que permite elevar la tasa de adquisición de datos para facilitar la toma de registros eléctricos de un elevado número de resonadores de forma simultánea, e incluso en varios armónicos del modo fundamental de resonancia. La gran sensibilidad de la tecnología HFF-QCMD a los eventos bioquímicos a caracterizar se extiende también a otro tipo eventos externos, como son los cambios de temperatura o presión, lo que es necesario minimizar con el fin de reducir el impacto que estas perturbaciones no deseadas provocan en la estabilidad y fiabilidad de la medida. Con este fin, se desarrolla un algoritmo de procesado de señal basado en la Discrete Transform Wavelet (DTW). Finalmente, todos los desarrollos tecnológicos realizados se validan mediante la implementación de un inmunoensayo para la detección simultánea, en muestras de mieles reales, de residuos químicos de naturaleza química muy diferente, a saber, el fungicida tiabendazol y el antibiótico sulfatiazol.[CA] La societat actual demanda un major control en la seguretat i qualitat dels aliments que es consumeixen. Aquesta preocupació es veu reflectida en els diferents plans estatals i europeus d'investigació científica, els quals, plantegen la necessitat d'innovar i desenvolupar noves tècniques analítiques que cobrisquen els requeriments actuals. En el present document s'aborda el problema de la presència de residus químics en la mel. L'origen dels mateixos es deu, fonamentalment, als tractaments veterinaris amb els quals es tracten malalties i paràsits en les abelles, i als tractaments agrícoles amb els quals les abelles es posen en contacte quan recol·lecten el nèctar en cultius pròxims als ruscos. L'Agència Europea de Seguretat Alimentària (EFSA) confirma aquesta realitat notificant nombroses alertes sanitàries en la mel. En els últims anys, els mètodes d'anàlisis basades en immunosensors piezoelèctrics s'han posicionat com la base d'una tècnica de garbellat molt prometedora, la qual pot ser emprada com a tècnica complementària a les clàssiques de cromatografia, gràcies a la seua senzillesa, rapidesa i baix cost. La tecnologia de ressonadors High-Fundamental Frequency Quartz Crystal Microbalance with Dissipation (HFF-QCMD) combina la detecció directa en temps real, alta sensibilitat i selectivitat amb un fàcil maneig i cost reduït en comparació amb altres tècniques. A més, està tecnologia permet augmentar el rendiment del anàlisi mitjançant el disseny d'arrays de ressonadors en un mateix substrat (Monolithic HFF-QCMD). En aquest document es presenta el disseny d'un array de 24 sensors HFF-QCMD, juntament amb un cartutx de microfluídica que estableix diversos microcanals sobre els diferents elements sensors, als quals fa arribar la mostra de mel diluïda a analitzar. El cartutx actua també com a interfície per a realitzar la connexió entre l'array de ressonadors i l'instrument de caracterització d'aquests. Per a traure el màxim partit a l'array dissenyat, es desenvolupa un mètode de mesura robust i fiable que permet elevar la taxa d'adquisició de dades per a facilitar la presa de registres elèctrics d'un elevat nombre de ressonadors de manera simultània, i fins i tot en diversos harmònics del mode fonamental de ressonància. La gran sensibilitat de la tecnologia HFF-QCMD als esdeveniments bioquímics a caracteritzar s'estén també a un altre tipus esdeveniments externs, com són els canvis de temperatura o pressió, la qual cosa és necessari minimitzar amb la finalitat de reduir l'impacte que aquestes pertorbacions no desitjades provoquen en l'estabilitat i fiabilitat de la mesura. A aquest efecte, es desenvolupa un algorisme de processament de senyal basat en la Discrete Transform Wavelet (DTW). Finalment, tots els desenvolupaments tecnològics realitzats es validen mitjançant la implementació d'un immunoassaig per a la detecció simultània, en mostres de mel reals, de residus químics de naturalesa química molt diferent, a saber, el fungicida tiabendazol i l'antibiòtic sulfatiazol.[EN] Currently, society demands greater control over the safety and quality of the food consumed. This concern is reflected in the different states and European plans for scientific research, which establish the necessity to innovate and develop new analytical techniques that meet current requirements. This document addresses the problem of the presence of chemical residues in honey. Its origin is fundamentally due to the veterinary treatments against diseases and parasites in bees, and also to the agricultural treatments with which the bees come into contact when they collect the nectar in crops close to the hives. The European Food Safety Agency (EFSA) confirms this reality by notifying numerous health alerts in honey. In recent years, analysis methods based on piezoelectric immunosensors have been positioned as the basis of a very promising screening technique, which can be used as a complementary technique to the classic chromatography, thanks to its simplicity, speed and low cost. High-Fundamental Frequency Quartz Crystal Microbalance with Dissipation (HFF-QCMD) resonator technology combines direct real-time detection, high sensitivity and selectivity with easy handling and low cost compared to other techniques. In addition, this technology allows increasing the performance of the analysis through the design of resonator arrays on the same substrate (Monolithic HFF-QCMD). This document presents the design of an array of 24 HFF-QCMD sensors, together with a microfluidic cartridge that establish various microchannels on the different sensor elements, to provide them the diluted honey sample to be analyzed. The cartridge also acts as an interface to make the connection between the array of resonators and the characterization instrument. To get the most out of the designed array, a robust and reliable measurement method has been developed that allows increasing the data acquisition rate to facilitate electrical parameters readout from a high number of resonators simultaneously, and even in several harmonics of the fundamental resonance mode. The great sensitivity of the HFF-QCMD technology to the biochemical events to be characterized also is extended to other types of external events, such as changes in temperature or pressure, which must be minimized in order to reduce the impact that these unwanted disturbances cause in the stability and reliability of the measurement. To this end, a signal processing algorithm based on the Discrete Transform Wavelet (DTW) is developed. Finally, all the technological developments carried out are validated through the implementation of an immunoassay for the simultaneous detection, in real honey samples, of chemical residues of very different chemical nature, namely, the fungicide thiabendazole and the antibiotic sulfathiazole.The authors would also like to thank Jorge Martínez from the Laboratory of High Frequency Circuits (LCAF) of the Universitat Politècnica de València (UPV) for assistance with profilometry, and Manuel Planes, José Luis Moya, Mercedes Tabernero, Alicia Nuez and Joaquin Fayos from the Electron Microscopy Services of the UPV for helping with the AFM, and SEM measurements. M.Calero is the recipient of the doctoral fellowship BES-2017-080246 from the Spanish Ministry of Economy, Industry and Competitiveness (Madrid, Spain). This research was funded by Spanish Ministry of Economy and Competitiveness with FEDER funds (AGL 2016-77702-R) and European Commission Horizon 2020 Programme (Grant Agreement number H2020-FETOPEN-2016-2017/737212-CATCH-U-DNA - Capturing non-Amplified Tumor Circulating DNA with Ultrasound Hydrodynamics) for which the authors are grateful. Román Fernández is with the Center for Research and Innovation in Bioengineering (Ci2B), Universitat Politècnica de València, València, Spain and with Advanced Wave Sensors S.L., Paterna, València, Spain. (e-mail: [email protected]); Yolanda Jiménez, Antonio Arnau and María Calero are with the Center for Research and Innovation in Bioengineering (Ci2B), Universitat Politècnica de València, València, Spain; Ilya Reiviakine is with Advanced Wave Sensors S.L., Paterna, Valencia, Spain and with the Department of Bioengineering, University of Washington, Seattle, WA, 98150 USA; María Isabel Rocha-Gaso and José Vicente García are with Advanced Wave Sensors S.L., Paterna, València, Spain.Calero Alcarria, MDS. (2022). Development of a novel high resolution and high throughput biosensing technology based on a Monolithic High Fundamental Frequency Quartz Crystal Microbalance (MHFF-QCM). Validation in food control [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/182652TESISCompendi

Validation of a Phase-Mass Characterization Concept and Interface for Acoustic Biosensors

Acoustic wave resonator techniques are widely used in in-liquid biochemical applications. The main challenges remaining are the improvement of sensitivity and limit of detection, as well as multianalysis capabilities and reliability. The sensitivity improvement issue has been addressed by increasing the sensor frequency, using different techniques such as high fundamental frequency quartz crystal microbalances (QCMs), surface generated acoustic waves (SGAWs) and film bulk acoustic resonators (FBARs). However, this sensitivity improvement has not been completely matched in terms of limit of detection. The decrease on frequency stability due to the increase of the phase noise, particularly in oscillators, has made it impossible to increase the resolution. A new concept of sensor characterization at constant frequency has been recently proposed based on the phase/mass sensitivity equation: Δφ/Δm ≈ −1/mL, where mL is the liquid mass perturbed by the resonator. The validation of the new concept is presented in this article. An immunosensor application for the detection of a low molecular weight pollutant, the insecticide carbaryl, has been chosen as a validation model

Design and Analysis of High-Frequency Quartz Crystal Microbalance Sensor Array with Concentric Electrodes and Dual Inverted Mesa Structure for Multiple Gas Detection

Lung Cancer is one of the most deadly diseases which claim millions of lives all around the world every year. One of the major reasons that make the treatment process of lung cancer hard is that the patients are diagnosed only during the later stages. Lung cancer patients exhales volatile organic compounds in their breath in low concentration even during the early stages of the disease. There are many gas sensors available to detect these volatiles. However, there are certain disadvantages which make most of the conventional gas sensors unsuitable for early detection. Quartz crystal microbalance (QCM) is one of the promising candidates for volatile organic compounds detection. This thesis describes the design and analysis of the high-frequency quartz crystal microbalance sensor array with a novel concentric electrode and dual inverted mesa structure. Conventional QCM sensors are limited with circular electrodes and single channel design which limits the sensing ability. The proposed QCM sensor array has advantages of a uniform displacement profile with the concentric electrodes and multiple channels on a high frequency monolithic quartz substrate without interference with the dual inverted mesa design. This high frequency multiple channels make the multiple gas detection feasible. Therefore, in this thesis the critical design parameters of this proposed design are analyzed and optimized through a comprehensive finite element analysis in COMSOL Multiphysics and analytical modelling. In addition, the interference between multiple QCM channels has been further eliminated. Furthermore, the fabrication procedure for the proposed high frequency QCM gas sensor array has been proposed and analyzed

Simple and ultrafast resonance frequency and dissipation shift measurements using a fixed frequency drive

A new method for determination of resonance frequency and dissipation of a mechanical oscillator is presented. Analytical expressions derived using the Butterworth-Van Dyke equivalent electrical circuit allow the determination of resonance frequency and dissipation directly from each impedance datapoint acquired at a fixed amplitude and frequency of drive, with no need for numerical fitting or measurement dead time unlike the conventional impedance or ring-down analysis methods. This enables an ultrahigh time resolution and superior noise performance with relatively simple instrumentation. Quantitative validations were carried out successfully against the impedance analysis method for inertial and viscous loading experiments on a 14.3 MHz quartz crystal resonator (QCR). Resonance frequency shifts associated with the transient processes of quick needle touches on a thiol self-assembled-monolayer functionalised QCR in liquid were measured with a time resolution of 112 μs, which is nearly two orders of magnitude better than the fastest reported quartz crystal microbalance. This simple and fast fixed frequency drive (FFD) based method for determination of resonance frequency and dissipation is potentially more easily multiplexable and implementable on a single silicon chip delivering economies of scale

Implantable Piezoresistive Microcantilever-based Wireless Cocaine Biosensors

Cocaine is a well-known, illegal, recreational drug that is addictive due to its effects on the mesolimbic reward pathway in the human body. Accurate and real-time measurement of the concentration of cocaine in the body as a function of time and physiological factors is a key requirement for the understanding of the use of this drug. Current methods for such measurements involve taking samples from the human body (such as blood, urine, and hair) and performing analytical chemistry tests on these samples. This techniques are relatively expensive, time consuming, and labor intensive. To address this issue, a new implantable sensor for the automated detection and measurement of the relative cocaine concentration is presented here. The device is more economical and provides for higher sampling frequencies than the current methods. The active sensor elements consist of piezoresistive microcantilever arrays, which are coated with an oligonucleotide-based aptamer, i.e. a short sequence of RNA with high affinity for specific target molecules, as the cocaine receptor. A Wheatstone bridge is used to convert the biosensor signal into an electronic signal. This signal is transmitted wireless at an operating frequency of 403.55 MHz, which complies with the US Medical Implant Communication System (MICS) FCC 47CFR Part 95. The limit of detection for the in vitro experiment is found to be 1 ng/ml. The device has successfully measured the relative concentration of cocaine upon implantation in the subcutaneous interstitial fluid of male Wistar rats