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

Ensamblaje y validación de un "cartridge" basado en un array de sensores HFFQCM para aplicaciones de High-Throughput Screening (HTS)

One of the outstanding challenges in the areas of health and food safety and quality is the development of new High-Throughput Screenig (HTS) techniques that allow the simultaneous monitoring of multiple samples. A key element in this type of system is the cartridge. This element, which contains the multiple samples to analyze, is connected to the analysis system to perform the analytical determination. The cartridge to be assembled and evaluated in this TFM will be formed by three elements: 1) an array of HFFQCM sensors properly functionalized for a key application, 2) a layer of plastic material which traces the microfluidic channels on the different sensors and 3) A printed circuit board (PCB) through which the array of sensors will be connected to the analysis system. Different designs of the array will be proposed. The task of the student will consist in studying and evaluating their pros and cons in order to select the more suitable array design according to the criteria of size, cost and interference between sensors. The array must be attached to the PCB on one side, for this purpose a positioning and dispensing equipment, which will be programmed by the student, will be used. On the other side of the array, a plastic material that will define the microfluidic channels will be fixed by means of the positioning and dispensing equipment. Finally, the response of the complete cartridge will be evaluated, for that, the electrical admittance of each sensor and the effect of the fluidic on the final response will be studiedUno de los retos pendientes dentro de los ámbitos de la salud y la seguridad y calidad alimentaria es el desarrollo de nuevas técnicas de High-Throughput Screenig (HTS) que permitan la monitoriazión de múltiples muestras de forma simultánea. Un elemento clave en este tipo de sistemas es lo que se conoce como el cartridge (cartucho), se trata de un elemento que contiene las múltiples muestras a analizar y que debe ser conectado al sistema de análisis para realizar la determinación analítica. El cartrigde que se ensamblará y evaluará en este TFM estará formado por tres elementos: 1) un array de sensores HFFQCM debidamente funcionalizados en función de la aplicación, 2) una capa de material plástico que trazará los canales de microfluídica sobre los diferentes sensores y 3) una placa de circuito impreso (PCB) en la que irá conectado el array de sensores al sistema de análisis. Desde la dirección del trabajo se propondrán diversos diseños del array que el estudiante tendrá que estudiar y evaluar sus pros y contras, el primer resultado del trabajo será la selección del diseño de array más adecuados atendiendo a los criterios de tamaño, coste e interferencia entre sensores. El array deberá ir fijado a la PCB por una cara, para ello se utilizará un equipo de posicionamiento y dispensación de los epoxys necesarios para realizar la fijación, el estudiante deberá programar dicho equipo. Una vez fijado el array a la PCB, por la otra cara se fijará el material plástico que definirá los canales de microfluídica, el cuál deberá ser diseñado en función del array elegido. Para su fijación también se utilizará el equipo de posicionamiento y dispensación. Por último se evaluará la respuesta del cartucho completo, se estudiará la admitancia eléctrica de cada sensor y el efecto de la fluídica sobre la respuesta final.Calero Alcarria, MDS. (2017). Ensamblaje y validación de un "cartridge" basado en un array de sensores HFFQCM para aplicaciones de High-Throughput Screening (HTS). http://hdl.handle.net/10251/91762TFG

A Real-Time Method for Improving Stability of Monolithic Quartz Crystal Microbalance Operating under Harsh Environmental Conditions

[EN] Monolithic quartz crystal microbalance (MQCM) has recently emerged as a very promising technology suitable for biosensing applications. These devices consist of an array of miniaturized QCM sensors integrated within the same quartz substrate capable of detecting multiple target analytes simultaneously. Their relevant benefits include high throughput, low cost per sensor unit, low sample/reagent consumption and fast sensing response. Despite the great potential of MQCM, unwanted environmental factors (e.g., temperature, humidity, vibrations, or pressure) and perturbations intrinsic to the sensor setup (e.g., mechanical stress exerted by the measurement cell or electronic noise of the characterization system) can affect sensor stability, masking the signal of interest and degrading the limit of detection (LoD). Here, we present a method based on the discrete wavelet transform (DWT) to improve the stability of the resonance frequency and dissipation signals in real time. The method takes advantage of the similarity among the noise patterns of the resonators integrated in an MQCM device to mitigate disturbing factors that impact on sensor response. Performance of the method is validated by studying the adsorption of proteins (neutravidin and biotinylated albumin) under external controlled factors (temperature and pressure/flow rate) that simulate unwanted disturbances.This work was supported by the European Commission Horizon 2020 Programme, Capturing non-Amplified Tumor Circulating DA with Ultrasound Hydrodynamics, under Grant H2020FETOPEN-2016-2017/737212-CATCH-U-DNA. M. Calero is the recipient of the doctoral fellowship BES-2017-080246 from the Ministerio de Economia, Industria y Competitividad de Espana.Fernández Díaz, R.; Calero-Alcarria, MDS.; Jiménez Jiménez, Y.; Arnau Vives, A. (2021). A Real-Time Method for Improving Stability of Monolithic Quartz Crystal Microbalance Operating under Harsh Environmental Conditions. Sensors. 21(12):1-12. https://doi.org/10.3390/s21124166S112211

A fast method for monitoring the shifts in resonance frequency and dissipation of the QCM sensors of a Monolithic array in biosensing applications

© 2021 IEEE. Personal use of this material is permitted. Permissíon from IEEE must be obtained for all other uses, in any current or future media, including reprinting/republishing this material for advertisíng or promotional purposes, creating new collective works, for resale or redistribution to servers or lists, or reuse of any copyrighted component of this work in other works.[EN] Improvement of data acquisition rate remains as an important challenge in applications with Quartz Crystal Microbalance (QCM) technology where high throughput is required. To address this challenge, we developed a fast method capable of measuring the response of a large number of sensors and/or overtones, with a high time resolution. Our method, which can be implemented in a low-cost readout electronic circuit, is based on the estimation of fr (frequency shift) and D (dissipation shift) from measurements of the sensor response obtained at a single driving frequency. By replacing slow fitting procedures with a direct calculation, the time resolution is only limited by the physical characteristics of the sensor (resonance frequency and quality factor), but not by the method itself. Capabilities of the method are demonstrated by monitoring multiple overtones with a single 5 MHz sensor and a Monolithic QCM array comprising 24 50MHz-sensors. Accuracy of the method is validated and compared with the state-of-the-art, as well as with a reference method based on impedance analysis.This work was supported in part by the Ministerio de Economía, Industria y Competitividad de España-Agencia Estatal de Investigación with Fondo Europeo de Desarrollo Regional (FEDER) Funds under Grant AGL2016-77702-R and in part by the European Commission Horizon 2020 Programme (Capturing non-amplified tumor circulating DNA with ultrasound hydrodynamics) under Agreement H2020-FETOPEN-2016-2017/737212-CATCH-UDNA. The work of María Calero was supported by the Spanish Ministry of Economy, Industry and Competitiveness, Madrid, Spain, under Grant BES-2017-080246.Fernández Díaz, R.; Calero-Alcarria, MDS.; García Narbón, JV.; Reiviakine, I.; Arnau Vives, A.; Jiménez Jiménez, Y. (2021). A fast method for monitoring the shifts in resonance frequency and dissipation of the QCM sensors of a Monolithic array in biosensing applications. IEEE Sensors Journal. 21(5):6643-6651. https://doi.org/10.1109/JSEN.2020.3042653S6643665121

High Fundamental Frequency (HFF) Monolithic Resonator Arrays for Biosensing Applications: Design, Simulations, Experimental, Characterization

© 2020 IEEE. Personal use of this material is permitted. Permissíon from IEEE must be obtained for all other uses, in any current or future media, including reprinting/republishing this material for advertisíng or promotional purposes, creating new collective works, for resale or redistribution to servers or lists, or reuse of any copyrighted component of this work in other works.[EN] Miniaturized, high-throughput, cost-effective sensing devices are needed to advance lab-on-a-chip technologies for healthcare, security, environmental monitoring, food safety, and research applications. Quartz crystal microbalance with dissipation (QCMD) is a promising technology for the design of such sensing devices, but its applications have been limited, until now, by low throughput and significant costs. In this work, we present the design and characterization of 24-element monolithic QCMD arrays for high-throughput and low-volume sensing applications in liquid. Physical properties such as geometry and roughness, and electrical properties such as resonance frequency, quality factor, spurious mode suppression, and interactions between array elements (crosstalk), are investigated in detail. In particular, we show that the scattering parameter, S 21 , commonly measured experimentally to investigate crosstalk, contains contributions from the parasitic grounding effects associated with the acquisition circuitry. Finite element method simulations do not take grounding effects into account explicitly. However, these effects can be effectively modelled with appropriate equivalent circuit models, providing clear physical interpretation of the different contributions. We show that our array design avoids unwanted interactions between elements and discuss in detail aspects of measuring these interactions that are often-overlooked.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.Fernández Díaz, R.; Calero-Alcarria, MDS.; Reviakine, I.; García, JV.; Rocha-Gaso, MI.; Arnau Vives, A.; Jiménez Jiménez, Y. (2021). High Fundamental Frequency (HFF) Monolithic Resonator Arrays for Biosensing Applications: Design, Simulations, Experimental, Characterization. IEEE Sensors Journal. 21(1):284-295. https://doi.org/10.1109/JSEN.2020.3015011S28429521

A Multichannel Microfluidic Sensing Cartridge for Bioanalytical Applications of Monolithic Quartz Crystal Microbalance

[EN] Integrating acoustic wave sensors into lab-on-a-chip (LoC) devices is a well-known challenge. We address this challenge by designing a microfluidic device housing a monolithic array of 24 high-fundamental frequency quartz crystal microbalance with dissipation (HFF-QCMD) sensors. The device features six 6-µL channels of four sensors each for low-volume parallel measurements, a sealing mechanism that provides appropriate pressure control while assuring liquid confinement and maintaining good stability, and provides a mechanical, electrical, and thermal interface with the characterization electronics. We validate the device by measuring the response of the HFF-QCMD sensors to the air-to-liquid transition, for which the robust Kanazawa¿Gordon¿Mason theory exists, and then by studying the adsorption of model bioanalytes (neutravidin and biotinylated albumin). With these experiments, we show how the effects of the protein¿surface interactions propagate within adsorbed protein multilayers, offering essentially new insight into the design of affinity-based bioanalytical sensorsThis work was supported in part by Ministerio de Economía, Industria y Competitividad de España Agencia Estatal de Investigación with FEDER (Fondo Europeo de Desarrollo Regional) funds under Project AGL2016-77702-R and in part by the European Commission Horizon 2020 Programme, Capturing non-Amplified Tumor Circulating DA with Ultrasound Hidrodynamics, under Grant H2020-FETOPEN-2016-2017/737212-CATCH-U-DNA. M. Calero is the recipient of the doctoral fellowship BES-2017-080246 from the Ministerio de Economía, Industria y Competitividad de España.Calero-Alcarria, MDS.; Fernández Díaz, R.; Garcia Molla, P.; García Narbón, JV.; García, M.; Gamero-Sandemetrio, E.; Reviakine, I.... (2020). 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Acoustic Array Biochip Combined with Allele-Specific PCR for Multiple Cancer Mutation Analysis in Tissue and Liquid Biopsy

[EN] Regular screening of point mutations is of importance to cancer management and treatment selection. Although techniques like next-generation sequencing and digital polymerase chain reaction (PCR) are available, these are lacking in speed, simplicity, and cost-effectiveness. The development of alternative methods that can detect the extremely low concentrations of the target mutation in a fast and cost-effective way presents an analytical and technological challenge. Here, an approach is presented where for the first time an allele-specific PCR (AS-PCR) is combined with a newly developed high fundamental frequency quartz crystal microbalance array as biosensor for the amplification and detection, respectively, of cancer point mutations. Increased sensitivity, compared to fluorescence detection of the AS-PCR amplicons, is achieved through energy dissipation measurement of acoustically ¿lossy¿ liposomes binding to surface-anchored dsDNA targets. The method, applied to the screening of BRAF V600E and KRAS G12D mutations in spiked-in samples, was shown to be able to detect 1 mutant copy of genomic DNA in an excess of 104 wild-type molecules, that is, with a mutant allele frequency (MAF) of 0.01%. Moreover, validation of tissue and plasma samples obtained from melanoma, colorectal, and lung cancer patients showed excellent agreement with Sanger sequencing and ddPCR; remarkably, the efficiency of this AS-PCR/acoustic methodology to detect mutations in real samples was demonstrated to be below 1% MAF. The combined high sensitivity and technology-readiness level of the methodology, together with the ability for multiple sample analysis (24 array biochip), cost-effectiveness, and compatibility with routine workflow, make this approach a promising tool for implementation in clinical oncology labs for tissue and liquid biopsy.This work was supported by the European Union's Horizon H2020-FETOPEN-1-2016-2017 under grant agreement no. 737212 (CATCH-U-DNA).Naoumi, N.; Michaelidou, K.; Papadakis, G.; Simaiaki, AE.; Fernández Díaz, R.; Calero-Alcarria, MDS.; Arnau Vives, A.... (2022). Acoustic Array Biochip Combined with Allele-Specific PCR for Multiple Cancer Mutation Analysis in Tissue and Liquid Biopsy. ACS Sensors. 7(2):495-503. https://doi.org/10.1021/acssensors.1c02245S4955037

OSTEMER polymer as a rapid packaging of electronics and microfluidic system on PCB

[EN] A new heterogeneous integration method is presented that allows the integration of a microfluidic platform and a multi-channel quartz crystal microbalance array on a printed circuit board (PCB) using a dry adhesive bonding method. In this work, the microfluidic platform is a replica molded using a UV-curable OSTEMER 322 Crystal Clear polymer. The OSTEMER acts both as a final package for the cartridge and as a functional material for hosting molded microfluidic channels, the input reservoirs and the waste reservoir. The method is demonstrated by the integration of an array of 24 of a 150 MHz high fundamental frequency quartz crystal microbalance (HFF-QCM) to the OSTEMER microfluidic packaging. The resulting bond interface is shown to be completely homogeneous and void free, and the package is tested to a differential pressure of up to 4 bars. The leak test of the cartridge is performed by pressurizing a microfluidic channel with an aqueous solution using an external peristaltic pump for more than 4 h. The cartridge performance is evaluated by the electrical characterization. Q-factor values of 9507 and of 650are achieved in air and DI water, respectively. Results show that this simple integration method of the HFF-QCM is a promising way to integrate microfluidics into the more complex heterogeneous system.This work was funded by the European Commission Horizon 2020 Programme under the Grant Agreement number ICT-28-2015/687785-LIQBIOPSENS (Reliable Liquid Biopsy technology for early detection of colorectal cancer).El Fissi, L.; Fernández Díaz, R.; García Molla, P.; Calero-Alcarria, MDS.; García Narbón, JV.; Jiménez Jiménez, Y.; Arnau Vives, A.... (2019). OSTEMER polymer as a rapid packaging of electronics and microfluidic system on PCB. Sensors and Actuators A Physical. 285:511-518. https://doi.org/10.1016/j.sna.2018.11.050S51151828

Implementación de un método para la extracción de los parámetros físicos y geométricos de materiales depositados sobre un sensor de cuarzo

En este Trabajo Fin de Grado se ha desarrollado un módulo de extracción de las propiedades físicas y geométricas de los materiales depositados sobre un sensor de cuarzo. El módulo desarrollado proporciona las propiedades del material depositado sobre el cristal a partir de una serie de modelos matemáticos que se han programado, y de las medidas eléctricas proporcionadas por el sistema de caracterización del sensor.Calero Alcarria, MDS. (2015). Implementación de un método para la extracción de los parámetros físicos y geométricos de materiales depositados sobre un sensor de cuarzo. http://hdl.handle.net/10251/79561.Archivo delegad

High Fundamental Frequency (HFF) Monolithic Quartz Crystal Microbalance with Dissipation Array for the Simultaneous Detection of Pesticides and Antibiotics in Complex Food

[EN] As in the case of the food industry in general, there is a global concern about safety and quality in complex food matrices, such as honey, which is driving the demand for fast, sensitive and affordable analytical techniques across the honey-packaging industry. Although excellent techniques such as liquid chromatography-tandem mass spectrometry (LC-MS/MS) are available, these are located in centralized laboratories and are still lacking in speed, simplicity and cost-effectiveness. Here, a new approach is presented where a competitive immunoassay is combined with a novel High Fundamental Frequency Quartz Crystal Microbalance with Dissipation (HFF-QCMD) array biosensor for the simultaneous detection of antibiotics and pesticides in honey. Concretely, thiabendazole and sulfathiazole residues were monitored in spiked honey samples. Results revealed that HFF-QCMD arrays provide a complementary and reliable tool to LC-MS/MS for the analysis of contaminants in these kinds of complex matrices, while avoiding elaborate sample pre-treatment. The good sensitivity achieved (I50 values in the 70¿720 µg/kg range) and the short analysis time (60 min for 24 individual assays), together with the ability for multiple analyte detection (24 sensor array) and its cost-effectiveness, pave the way for the implementation of a fast on-line, in situ routine control of potentially hazardous chemical residues in honey.This work was supported by Ministerio de Economía, Industria y Competitividad de España-Agencia Estatal de Investigación with FEDER (Fondo Europeo de Desarrollo Regional) funds under Grants AGL2016-77702-R and AGL2013-48646-R. M. Calero is the recipient of the doctoral fellowship BES-2017-080246 from the Ministerio de Economía, Industria y Competitividad de España.Calero-Alcarria, MDS.; Fernández Díaz, R.; García, M.; Juan-Borras, MDS.; Escriche Roberto, MI.; Arnau Vives, A.; Montoya, Á.... (2022). High Fundamental Frequency (HFF) Monolithic Quartz Crystal Microbalance with Dissipation Array for the Simultaneous Detection of Pesticides and Antibiotics in Complex Food. Biosensors. 12(6):1-12. https://doi.org/10.3390/bios1206043311212