Procedimiento de bioanálisis de moléculas de ácido nucleico en una muestra y biosensor para su implementación

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Physics of nanomechanical spectrometry of viruses

There is an emerging need of nanotools able to quantify the mechanical properties of single biological entities. A promising approach is the measurement of the shifts of the resonant frequencies of ultrathin cantilevers induced by the adsorption of the studied biological systems. Here, we present a detailed theoretical analysis to calculate the resonance frequency shift induced by the mechanical stiffness of viral nanotubes. The model accounts for the high surface-to-volume ratio featured by single biological entities, the shape anisotropy and the interfacial adhesion. The model is applied to the case in which tobacco mosaic virus is randomly delivered to a silicon nitride cantilever. The theoretical framework opens the door to a novel paradigm for biological spectrometry as well as for measuring the Young's modulus of biological systems with minimal strains.We acknowledge financial support from the Spanish Science Ministry (MINECO) through projects MAT2012-36197 and from European Research Council through Starting Grant NANOFORCELLS (ERC-StG-2011-278860).Peer Reviewe

Spatially Multiplexed Micro-Spectrophotometry in Bright Field Mode for Thin Film Characterization

Thickness characterization of thin films is of primary importance in a variety of nanotechnology applications, either in the semiconductor industry, quality control in nanofabrication processes or engineering of nanoelectromechanical systems (NEMS) because small thickness variability can strongly compromise the device performance. Here, we present an alternative optical method in bright field mode called Spatially Multiplexed Micro-Spectrophotometry that allows rapid and non-destructive characterization of thin films over areas of mm2 and with 1 μm of lateral resolution. We demonstrate an accuracy of 0.1% in the thickness characterization through measurements performed on four microcantilevers that expand an area of 1.8 mm2 in one minute of analysis time. The measured thickness variation in the range of few tens of nm translates into a mechanical variability that produces an error of up to 2% in the response of the studied devices when they are used to measure surface stress variations.The authors acknowledge the financial support by European Research Council through Starting Grant NANOFORCELLS (ERC-StG-2011-278860). P. M. Kosaka acknowledges funding from the Fundación General CSIC ComFuturo program. We acknowledge support by the CSIC Open Access Publication Initiative through its Unit of Information Resources for Research (URICI

Development of nanomechanical biosensors for the determination of cell mechanical properties

Póster presentado en el GEM4 Summer school, celebrado en Londres del 10 al 14 de septiembre de 2012.Peer Reviewe

Optomechanical devides for mechanobiological fingerprinting

Resumen del trabajo presentado en el Frontiers of Nanomechanical Systems (FSN2021), celebraod de forma virtual del 19 al 21 de enero de 2021Twenty years have passed since the first detection of biomolecular recognition using micromechanical systems[1]. In the last two decades, micro- nanomechanical systems have been refined to achieve amazing detection limits in force and mass that have enabled different schemes for ultrasensitive measurements of biological interactions as well as new ways of biological spectrometry. More recently, these figures of merit have been improved by coupling optical cavities to mechanical systems. In this talk, I will review the use of micro- nanomechanical systems for mechanobiological fingerprinting of biological entities, particularizing in the contributions of our group [2]. An essential core of this topic is the discussion about the mechanical coupling between a biological particle and a mechanical resonator, an issue that it is has been often oversimplified. We show that the biomechanical coupling that emerges between a bioparticle and a mechanical resonator is more complex than previously expect and it can give rise to different interaction regimes, in which the resonator response is dominated by different physical parameters of the analyte [3-4]. In particular, we will show experiments done with a variety of micro- nano- optomechanical systems using different measurement schemes where the mass, the stiffness and even the vibration modes of single biological entities can be measured with high sensitivity. It is now widely appreciated the essential role of mechanics in relevant biological processes and how disease can be revealed as changes in the mechanical properties of biological matter. I am pretty sure that future developments in optomechanical devices will contribute for major understanding of diseases as well as for new avenues in diagnosis and therapy

High-Throughput Mass Measurement Of Single Bacterial Cells By Silicon Nitride Membrane Resonators

Trabajo presentado en la 36th International Conference on Micro Electro Mechanical Systems (MEMS), celebrada en Munich (Alemania), del 15 al 19 de enero de 2023.© 2023 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other uses, in any current or future media, including reprinting/republishing this material for advertising 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.We present a technological approach to precisely measure the dry mass of many individual cells of a bacteria colony. In this technique, bacteria are transported from aqueous solution into gas phase and subsequently guided to the surface of a silicon nitride membrane resonator. Abrupt downshifts in the membrane eigenfrequencies are measured upon every bacterium adhesion and are related to the dry mass of the cell by theoretical methods. We measure the dry mass of Escherichia coli K-12 and Staphylococcus epidermidis with an unprecedented throughput of 20 cells/min and with a mass resolution of ⁓1%. Finally, we apply the Koch & Schaechter model to assess the intrinsic sources of growth stochasticity.This work was supported by the European Union’s Horizon 2020 Research and Innovation Program under Grant Agreement No. 731868-VIRUSCAN and by the ERC CoG Grant 681275 “LIQUIDMASS”. We acknowledge the service from the Micro and Nanofabrication Laboratory an X-SEM laboratory at IMNCNM funded by the Comunidad de Madrid (Project S2018/NMT-4291 TEC2SPACE) and by MINECO (Project CSIC12-4E-1794 with support from FEDER, FSE). E. G. S. acknowledges financial support by the Spanish Science and Innovation Ministry through Ramón y Cajal grant RYC-2019-026626-I

Multifrequency Nanomechanical Mass Spectrometer Prototype for Measuring Viral Particles Using Optomechanical Disk Resonators

Nanomechanical mass spectrometry allows characterization of analytes with broad mass range, from small proteins to bacterial cells, and with unprecedented mass sensitivity. In this work, we show a novel multifrequency nanomechanical mass spectrometer prototype designed for focusing, guiding and soft-landing of nanoparticles and viral particles on a nanomechanical resonator surface placed in vacuum. The system is compatible with optomechanical disk resonators, with an integrated optomechanical transduction method, and with the laser beam deflection technique for the measurement of the vibrations of microcantilever resonators. The prototype allows the in-vacuum alignment of resonators thanks to a dedicated visualization system. Finally, in this work, we have demonstrated the detection of gold nanoparticles, polystyrene nanoparticles and phage G viruses with optomechanical disks and microcantilever resonators.Peer reviewe

Ultrasensitive detection of biomarkers in blood using a hybrid nanomechanical and optoplasmonic sensor

Trabajo presentado en las Sesiones Docentes CIOCC - Nanosensores, organizadas en el Hospital Universitario HM Sanchinarro, Madrid, el 17 de mayo de 2017Peer reviewe

Development of nanomechanical systems for biological analysis

Comunicación presentada en el 2nd Workshop on Nanobioscience, celebrado en Madrid el 18 de mayo de 2012.Peer Reviewe

Ultrasensitive detection of p24 antigen for HIV-1 detection using an optomechanoplasmionic nanosensor

Trabajo presentado en el Technologies for HIV Self-Testing: Detection of Acute or Rebound Viremia, celebrado en Rockville (Maryland, Estados Unidos), el 19 de junio de 2017Peer reviewe