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In the rapidly emerging field of biomedical applications, multifunctional nanoparticles, especially those containing magnetic and plasmonic components, have gained significant attention due to their combined properties. These hybrid systems, often composed of iron oxide and gold, provide both magnetic and optical functionalities and offer promising avenues for applications in multimodal bioimaging, hyperthermal therapies, and magnetically driven selective delivery. This paper focuses on the implementation of advanced characterization methods, comparing statistical analyses of individual multifunctional particle properties with macroscopic properties as a way of fine-tuning synthetic methodologies for their fabrication methods. Special emphasis is placed on the size-dependent properties, biocompatibility, and challenges that can arise from this versatile nanometric system. In order to ensure the quality and applicability of these particles, various novel methods for characterizing the magnetic gold particles, including the analysis of their morphology, optical response, and magnetic response, are also discussed, with the overall goal of optimizing the fabrication of this complex system and thus enhancing its potential as a preferred diagnostic agent.
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Plasmonic nanoparticles have a wide range of applications in science and industry. Despite the numerous synthesis methods reported in the literature over the last decades, achieving precise control over the size and shape of large nanoparticle populations remains a challenge. Since variations in size and shape significantly affect the plasmonic properties of nanoparticles, accurate metrological techniques to characterize their morphological features are essential. Here, we present a novel spectrophotometric method, called Amplitude-Resolved Single Particle Spectrophotometry, that can measure the individual sizes of thousands of particles with nanometric accuracy in just a few minutes. This new method, based on the measurement of the scattering amplitude of each nanoparticle, overcomes some of the limitations observed in previous works and theoretically allows the characterization of nanoparticles of any size with a simple extra calibration step. As proof of concept, we characterized thousands of spherical nanoparticles of different sizes. This new method shows excellent accuracy, with less than a 3% discrepancy in direct comparison with transmission electron microscopy. Although the effectiveness of this method has been demonstrated with spherical nanoparticles, its real strength lies in its adaptability to more complex geometries by using an alternative analytical method to the one described here.
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Plasmonic nanoparticles are widely used in multiple scientific and industrial applications. Although many synthesis methods have been reported in the literature throughout the last decade, controlling the size and shape of large populations still remains as a challenge. As size and shape variations have a strong impact in their plasmonic properties, the need to have metrological techniques to accurately characterize their morphological features is peremptory. We present a new optical method referred as Dark-Field Single Particle Spectrophotometry which is able to measure the individual sizes of thousands of particles with nanometric accuracy in just a couple of minutes. Our method also features an easy sample preparation, a straightforward experimental setup inspired on a customized optical microscope, and a measurement protocol simple enough to be carried out by untrained technicians. As a proof of concept, thousands of spherical nanoparticles of different sizes have been measured, and after a direct comparison with metrological gold standard electron microscopy, a discrepancy of 3% has been attested. Although its feasibility has been demonstrated on spherical nanoparticles, the true strengthness of the method is that it can be generalized also to nanoparticles with arbitrary shapes and geometries, thus representing an advantageous alternative to the gold-standard electron microscopy.
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Nanopartículas del Metal , Espectrofotometría , Microscopía Electrónica , Tamaño de la PartículaRESUMEN
Hypervalent tellurium compounds have a particular reactivity towards thiol compounds which are related to their biological properties. In this work, this property was assembled to tellurium-functionalized surfaces. These compounds were used as linkers in the immobilization process of thiolated biomolecules (such as DNA) on microcantilever surfaces. The telluride derivatives acted as reversible binding agents due to their redox properties, providing the regeneration of microcantilever surfaces and allowing their reuse for further biomolecules immobilizations, recycling the functional surface. Initially, we started from the synthesis of 4-((3-((4-methoxyphenyl) tellanyl) phenyl) amino)-4-oxobutanoic acid, a new compound, which was immobilized on a silicon surface. In nanomechanical systems, the detection involved a hybridization study of thiolated DNA sequences. Fluorescence microscopy technique was used to confirm the immobilization and removal of the telluride-DNA system and provided revealing results about the potentiality of applying redox properties to chalcogen derivatives at surfaces.
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Técnicas Biosensibles , ADN/química , Silicio/química , Telurio/química , Secuencia de Bases/genética , Nanoestructuras/química , Hibridación de Ácido Nucleico , Compuestos de Sulfhidrilo/química , Propiedades de SuperficieRESUMEN
Early detection of HIV infection is the best way to prevent spread of the disease and to improve the efficiency of the antiretroviral therapy. Nucleic acid amplification tests (NAAT) have become the gold-standard for detecting low-concentrations of the virus in blood. However, these methods are technically demanding and cost-prohibitive in developing countries. Immunoassays are more affordable and can be more easily adapted for point-of-care diagnosis. However, the sensitivity so far of these methods has been too low. We here report the development of a sandwich immunoassay that combines nanomechanical and optoplasmonic transduction methods for detecting the HIV-1 capsid antigen p24 in human serum. The immunoreactions take place on the surface of a compliant microcantilever where gold nanoparticles are used as both mechanical and plasmonic labels. The microcantilever acts as both a mechanical resonator and an optical cavity for the transduction of the mechanical and plasmonic signals. The limit of detection of the immunoassay is 10-17 g/mL that is equivalent to one virion in 10 mL of plasma. This is 5 orders of magnitude better than last generation of approved immunoassays and 2 orders of magnitude better than NAAT. This technology meets the demands to be produced en masse at low cost and the capability for miniaturization to be used at the point-of-care.
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Proteína p24 del Núcleo del VIH/sangre , Infecciones por VIH/diagnóstico , VIH-1/metabolismo , Inmunoensayo/métodos , Nanotecnología , Oro/química , Humanos , Inmunoensayo/instrumentación , Límite de Detección , Masculino , Nanopartículas del Metal/química , Microscopía , Sistemas de Atención de Punto , Sensibilidad y Especificidad , Virión/química , Virión/aislamiento & purificaciónRESUMEN
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.
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Surface tethered single-stranded DNA films are relevant biorecognition layers for oligonucleotide sequence identification. Also, hydration induced effects on these films have proven useful for the nanomechanical detection of DNA hybridization. Here, we apply nanomechanical sensors and atomic force microscopy to characterize in air and upon varying relative humidity conditions the swelling and deswelling of grafted single stranded and double stranded DNA films. The combination of these techniques validates a two-step hybridization process, where complementary strands first bind to the surface tethered single stranded DNA probes and then slowly proceed to a fully zipped configuration. Our results also demonstrate that, despite the slow hybridization kinetics observed for grafted DNA onto microcantilever surfaces, ex situ sequence identification does not require hybridization times typically longer than 1 h, while quantification is a major challenge.
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ADN/química , Nanotecnología , Agua/química , Humedad , Cinética , Microscopía de Fuerza Atómica , Propiedades de SuperficieRESUMEN
Mechanical transducers based on nanowires promise revolutionary advances in biological sensing and force microscopy/spectroscopy. A crucial step is the development of simple and non-invasive techniques able to detect displacements with subpicometer sensitivity per unit bandwidth. Here, we design suspended tapered silicon nanowires supporting a range of optical resonances that confine and efficiently scatter light in the visible range. Then, we develop an optical method for efficiently coupling the evanescent field to the regular interference pattern generated by an incoming laser beam and the reflected beam from the substrate underneath the nanowire. This optomechanical coupling is here applied to measure the displacement of 50â nm wide nanowires with sensitivity on the verge of 1â fm/Hz(1/2) at room temperature with a simple laser interferometry set-up. This method opens the door to the measurement of the Brownian motion of ultrashort nanowires for the detection of single biomolecular recognition events in liquids, and single molecule spectroscopy in vacuum.
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Microcantilever biosensors in the static operation mode translate molecular recognition into a surface stress signal. Surface stress is derived from the nanomechanical cantilever bending by applying Stoney's equation, derived more than 100 years ago. This equation ignores the clamping effect on the cantilever deformation, which induces significant errors in the quantification of the biosensing response. This leads to discrepancies in the surface stress induced by biomolecular interactions in measurements with cantilevers with different sizes and geometries. So far, more accurate solutions have been precluded by the formidable complexity of the theoretical problem that involves solving the two-dimensional biharmonic equation. In this paper, we present an accurate and simple analytical expression to quantify the response of microcantilever biosensors. The equation exhibits an excellent agreement with finite element simulations and DNA immobilization experiments on gold-coated microcantilevers.
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Técnicas Biosensibles/instrumentación , ADN/química , Algoritmos , Técnicas Biosensibles/métodos , Oro/química , Estrés Mecánico , Propiedades de SuperficieRESUMEN
There is a need for noninvasive techniques for simultaneous imaging of the stress and vibration mode shapes of nanomechanical systems in the fields of scanning probe microscopy, nanomechanical biological and chemical sensors and the semiconductor industry. Here we show a novel technique that combines a scanning laser, the beam deflection method and digital multifrequency excitation and analysis for simultaneous imaging of the static out-of-plane displacement and the shape of five vibration modes of nanomechanical systems. The out-of-plane resolution is at least 100 pm Hz⻹/² and the lateral resolution, which is determined by the laser spot size, is 1-1.5 µm. The capability of the technique is demonstrated by imaging the residual surface stress of a microcantilever together with the shape of the first 22 vibration modes. The vibration behavior is compared with rigorous finite element simulations. The technique is suitable for major improvements in the imaging of liquids, such as higher bandwidth and enhanced spatial resolution.
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Rayos Láser , Microscopía Confocal/instrumentación , Microscopía de Sonda de Barrido/instrumentación , Nanotecnología/instrumentación , Técnicas Biosensibles/instrumentación , Técnicas Biosensibles/métodos , Electroquímica/instrumentación , Electroquímica/métodos , Análisis de Elementos Finitos , Microscopía Confocal/métodos , Microscopía de Sonda de Barrido/métodos , Nanotecnología/métodos , Semiconductores/instrumentación , Propiedades de Superficie/efectos de la radiación , VibraciónRESUMEN
The optomechanical coupling that emerges in an optical cavity in which one of the mirrors is a mechanical resonator has allowed sub-Kelvin cooling with the prospect of observing quantum phenomena and self-sustained oscillators with very high spectral purity. Both applications clearly benefit from the use of the smallest possible mechanical resonator. Unfortunately, the optomechanical coupling largely decays when the size of the mechanical system is below the light wavelength. Here, we propose to exploit the optical resonances associated to the light confinement in subwavelength structures to circumvent this limitation, efficiently extending optomechanics to nanoscale objects. We demonstrate this mechanism with suspended silicon nanowires. We are able to optically cool the mechanical vibration of the nanowires from room temperature to 30-40 K or to obtain regenerative mechanical oscillation with a frequency stability of about one part per million. The reported optomechanical phenomena can be exploited for developing cost-optimized mass sensors with sensitivities in the zeptogram range.
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Sistemas Microelectromecánicos , Nanocables/química , Silicio/química , Campos Electromagnéticos , TemperaturaRESUMEN
The detection back-action phenomenon has received little attention in physical, chemical, and biological sensors based on nanomechanical systems. We show that this effect is very significant in ultrathin bimetallic cantilevers, in which the laser beam that probes the picometer scale vibration largely modifies the resonant frequencies of the system. The light back-action effect is nonlinear, and some resonant frequencies can even be reduced to a half with laser power intensities of 2 mW. We demonstrate that this effect arises from the stress and strain generated by the laser heating. The experiments are explained by two-dimensional nonlinear elasticity theory and supported by finite element simulations. The found phenomenology is intimately connected to the old unsolved problem about the effect of surface stress on the resonance frequency of singly clamped beams. The results indicate that to achieve the ultimate detection limits with nanomechanical resonators one must consider the uncertainty due to the detection back-action.