Novel Characterization Techniques for Multifunctional Plasmonic-Magnetic Nanoparticles in Biomedical Applications.

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.

Amplitude-Resolved Single Particle Spectrophotometry: A Robust Tool for High-Throughput Size Characterization of Plasmonic Nanoparticles.

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.

Size characterization of plasmonic nanoparticles with dark-field single particle spectrophotometry.

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.

IgG1-b12-HIV-gp120 Interface in Solution: A Computational Study.

The use of broadly neutralizing antibodies against human immunodeficiency virus type 1 (HIV-1) has been shown to be a promising therapeutic modality in the prevention of HIV infection. Understanding the b12-gp120 binding mechanism under physiological conditions may assist the development of more broadly effective antibodies. In this work, the main conformations and interactions between the receptor-binding domain (RBD) of spike glycoprotein gp120 of HIV-1 and the IgG1-b12 mAb are studied. Accelerated molecular dynamics (aMD) and ab initio hybrid molecular dynamics have been combined to determine the most persistent interactions between the most populated conformations of the antibody-antigen complex under physiological conditions. The results show the most persistent receptor-binding mapping in the conformations of the antibody-antigen interface in solution. The binding-free-energy decomposition reveals a small enhancement in the contribution played by the CDR-H3 region to the b12-gp120 interface compared to the crystal structure.

Tethering of the IgG1 Antibody to Amorphous Silica for Immunosensor Development: A Molecular Dynamics Study.

A key factor for improving the sensitivity and performance of immunosensors based on mechanical-plasmonic methods is the orientation of the antibody proteins immobilized on the inorganic surface. Although experimental techniques fail to determine surface phenomena at the molecular level, modern simulations open the possibility for improving our understanding of protein-surface interactions. In this work, replica exchange molecular dynamics (REMD) simulations have been used to model the IgG1 protein tethered onto the amorphous silica surface by considering a united-atom model and a relatively large system (2500 nm2 surface). Additional molecular dynamics (MD) simulations have been conducted to derive an atomistic model for the amorphous silica surface using the cristobalite crystal structure as a starting point and to examine the structure of the free IgG1 antibody in the solution for comparison when immobilized. Analyses of the trajectories obtained for the tethered IgG1, which was sampled considering 32 different temperatures, have been used to define the geometry of the protein with respect to the inorganic surface. The tilt angle of the protein with respect to the surface plane increases with temperature, the most populated values being 24, 66, and 87° at the lowest (250 K), room (298 K), and the highest (380 K) temperatures. This variation indicates that the importance of protein-surface interactions decreases with increasing temperature. The influence of the surface on the structure of the antibody is very significant in the constant region, which is directly involved in the tethering process, while it is relatively unimportant for the antigen-binding fragments, which are farthest from the surface. These results are expected to contribute to the development of improved mechanical-plasmonic sensor microarrays in the near future.

Development of a methodology for reversible chemical modification of silicon surfaces with application in nanomechanical biosensors.

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.

Imaging the surface stress and vibration modes of a microcantilever by laser beam deflection microscopy.

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⁻¹/² 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.

Hidatidosis pediatrica / Pediatric hydatidosis

Con el objeto de conocer la realidad clínica de niños con hidatidosis, los procedimientos terapéuticos usados así como los antecedentes epidemiológicos, se estudiaron 76 casos que acudieron consecutivamente desde 1982 hasta 1990 al Hospital Luis Calvo Mackenna. La edad promedio de los niños fueron 7,9 ñ 5,1 años, correspondiendo 44 casos a hombres (57,9%) y 32 mujeres (42,1%). Compromiso pulmonar hubo en 38 casos (50%), hepático en 27 (35,5%), hepático y pulmonar 6 (7,9%) y 5 renal (6,6%). El tiempo que medió entre que aparecieron los síntomas e ingresaron al hospital, fue de 24,4 ñ 2,5 meses para la hidatidosis pulmonar y 65,5 ñ 5,5 meses para la hepática. El compromiso del estado nutritivo fue más importante en los casos de hidatidosis hepática. Al exámen físico destacó signología de condensación en el 50% de los casos pulmonares y existencia de una masa abdominal en el 63% de los casos hepáticos. En el 80% de los niños se encontraron quistes hidatídicos únicos que se presentaban en forma más frecuente al lado derecho de los órganos. Los quistes pulmonares fueron más pequeños que los de hígado y riñón. Se les practicó quistectomía al 73,7% de los quístes pulmonares, a la totalidad de los hepáticos y a 3 de 5 renales, siendo el resto tratados con lobectomías o nefrectomías según el caso. Eosinofilia se presentó en las hidatidosis mixtas pulmonar-hepática, con un promedio de 1.536 eos/ul

Comparación del rendimiento terapéutico del albendazol y el tiabendazol en síndrome de larva migrans / Comparison of therapeutical behaviour of albendazol and tiabendazol in larva migrans syndrome

En Chile se ha incrementado el diagnóstico de larva migrans visceral, y es así que se ha documentado infección por este agente en el 28%de los pacientes con eosinofilia, en tanto que la posee el 8,8%de la población, presuntamente sana. Se presenta fundamentalmente en niños con antecedentes de geofagia y de contacto con perros y gatos. Los síntomas y signos son de intensidad variables. El objetivo del presente estudio, es dar a conocer la experiencia en relación al tratamiento en 32 pacientes tratados con tiabendazol, a razón de 25 mg/kg por 5 días, y 21 con albendazol, en dosis fija de 400 mg/día por 3 días. La edad, estado nutricional, eosinógilos absolutos y síntomas fueron semejantes en ambos grupos. El tiabendazol mejoró a 29 casos (90,6%), tanto en los aspectos clínicos como en el recuento de eosinófilos absolutos, mientras que el albendazol lo hizo en 18 (85,7%) (p > 0,05). Con ambas drogas, las manifestaciones de intolerancia fueron mínimas. Se concluye que el tratamiento con albendazol es una solución para el síndrome de larva migrans visceral en nuestro medio, en que no se dispone de tiabendazol