RESUMEN
By isolating from the environment and precisely controlling mesoscopic objects, levitation in vacuum has evolved into a versatile technique that has already benefited diverse scientific directions, from force sensing and thermodynamics to materials science and chemistry. It also holds great promise for advancing the study of quantum mechanics in the unexplored macroscopic regime. However, most current levitation platforms are complex and bulky. Recent efforts in miniaturization of vacuum levitation set-ups have comprised electrostatic and optical traps, but robustness is still a concern for integration into confined settings, such as cryostats or portable devices. Here we show levitation and motion control in high vacuum of a silica nanoparticle at the surface of a hybrid optical-electrostatic chip. By combining fibre-based optical trapping and sensitive position detection with cold damping through planar electrodes, we cool the particle motion to a few hundred phonons. We envisage that our fully integrated platform is the starting point for on-chip devices combining integrated photonics and nanophotonics with precisely engineered electric potentials, enhancing control over the particle motion towards complex state preparation and read-out.
RESUMEN
Label-free detection of multiple analytes in a high-throughput fashion has been one of the long-sought goals in biosensing applications. Yet, for all-optical approaches, interfacing state-of-the-art label-free techniques with microfluidics tools that can process small volumes of sample with high throughput, and with surface chemistry that grants analyte specificity, poses a critical challenge to date. Here, we introduce an optofluidic platform that brings together state-of-the-art digital holography with PDMS microfluidics by using supported lipid bilayers as a surface chemistry building block to integrate both technologies. Specifically, this platform fingerprints heterogeneous biological nanoparticle populations via a multiplexed label-free immunoaffinity assay with single particle sensitivity. First, we characterise the robustness and performance of the platform, and then apply it to profile four distinct ovarian cell-derived extracellular vesicle populations over a panel of surface protein biomarkers, thus developing a unique biomarker fingerprint for each cell line. We foresee that our approach will find many applications where routine and multiplexed characterisation of biological nanoparticles are required.
Asunto(s)
Nanopartículas , Humanos , Nanopartículas/química , Membrana Dobles de Lípidos/química , Holografía/métodos , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/química , Microfluídica/métodos , Microfluídica/instrumentación , Femenino , Técnicas Analíticas Microfluídicas/instrumentación , Técnicas Analíticas Microfluídicas/métodos , Línea Celular Tumoral , Técnicas Biosensibles/métodos , Técnicas Biosensibles/instrumentación , Biomarcadores/análisisRESUMEN
Label-free thermometry is a pivotal tool for many disciplines. However, most current approaches are only suitable for planar heat sources in steady state, thereby restricting the range of systems that can be reliably studied. Here, we introduce pump probe-based optical diffraction tomography (ODT) as a method to map temperature precisely and accurately in three dimensions (3D) at the single-particle level. To do so, we first systematically characterize the thermal landscape in a model system consisting of gold nanorods in a microchamber and then benchmark the results against simulations and quantitative phase imaging thermometry. We then apply ODT thermometry to resolve thermal landscapes inaccessible to other label-free approaches in the form of nonplanar heat sources embedded in complex environments and freely diffusing gold nanorods in a microchamber. Last, we foresee that our approach will find many applications where routine thermal characterization of heterogeneous nanoparticles samples in 3D or in non-steady state is required.
RESUMEN
Lack of standardization is a systematic problem that impacts nanomedicine by challenging data comparison from different studies. Translation from preclinical to clinical stages indeed requires reproducible data that can be easily accessed and compared. In this work, we propose a series of experimental standards for in vitro plasmonic photothermal therapy (PPTT). This best practice guide covers the five main aspects of PPTT studies in vitro: nanomaterials, biological samples, pre-, during, and postirradiation characterization. We are confident that such standardization of experimental protocols and reported data will benefit the development of PPTT as a transversal therapy.
RESUMEN
Label-free detecting multiple analytes in a high-throughput fashion has been one of the long-sought goals in biosensing applications. Yet, for all-optical approaches, interfacing state-of-the-art label-free techniques with microfluidics tools that can process small volumes of sample with high throughput, and with surface chemistry that grants analyte specificity, poses a critical challenge to date. Here, we introduce an optofluidic platform that brings together state-of-the-art digital holography with PDMS microfluidics by using supported lipid bilayers as a surface chemistry building block to integrate both technologies. Specifically, this platform fingerprints heterogeneous biological nanoparticle populations via a multiplexed label-free immunoaffinity assay with single particle sensitivity. Herein, we first thoroughly characterise the robustness and performance of the platform, and then apply it to profile four distinct ovarian cell-derived extracellular vesicle populations over a panel of surface protein biomarkers, thus developing a unique biomarker fingerprint for each cell line. We foresee that our approach will find many applications where routine and multiplexed characterisation of biological nanoparticles is required.
RESUMEN
Label-free detecting multiple analytes in a high-throughput fashion has been one of the long-sought goals in biosensing applications. Yet, for all-optical approaches, interfacing state-of-the-art label-free techniques with microfluidics tools that can process small volumes of sample with high throughput, and with surface chemistry that grants analyte specificity, poses a critical challenge to date. Here, we introduce an optofluidic platform that brings together state-of-the-art digital holography with PDMS microfluidics by using supported lipid bilayers as a surface chemistry building block to integrate both technologies. Specifically, this platform fingerprints heterogeneous biological nanoparticle populations via a multiplexed label-free immunoaffinity assay with single particle sensitivity. Herein, we first thoroughly characterise the robustness and performance of the platform, and then apply it to profile four distinct ovarian cell-derived extracellular vesicle populations over a panel of surface protein biomarkers, thus developing a unique biomarker fingerprint for each cell line. We foresee that our approach will find many applications where routine and multiplexed characterisation of biological nanoparticles is required.
RESUMEN
We propose to introduce additional control in levitated optomechanics by trapping a meta-atom, i.e., a subwavelength and high-permittivity dielectric particle supporting Mie resonances. In particular, we theoretically demonstrate that optical levitation and center-of-mass ground-state cooling of silicon nanoparticles in vacuum is not only experimentally feasible but it offers enhanced performance over widely used silica particles in terms of trap frequency, trap depth, and optomechanical coupling rates. Moreover, we show that, by adjusting the detuning of the trapping laser with respect to the particle's resonance, the sign of the polarizability becomes negative, enabling levitation in the minimum of laser intensity, e.g., at the nodes of a standing wave. The latter opens the door to trapping nanoparticles in the optical near-field combining red and blue-detuned frequencies, in analogy to two-level atoms, which is of interest for generating strong coupling to photonic nanostructures and short-distance force sensing.
Asunto(s)
Nanopartículas , Nanoestructuras , Nanoestructuras/química , Nanopartículas/química , Rayos Láser , Luz , FotonesRESUMEN
Reconfigurable metasurfaces offer great promises to enhance photonics technology by combining integration with improved functionalities. Recently, reconfigurability in otherwise static metasurfaces has been achieved by modifying the electric permittivity of the meta-atoms themselves or their immediate surrounding. Yet, it remains challenging to achieve significant and fast tunability without increasing bulkiness. Here, we demonstrate an ultrathin tunable metalens whose focal distance can be changed through optomechanical control with moderate continuous wave intensities. We achieve fast focal length changes of more than 5% with response time of the order of 10 µs.
RESUMEN
Rapid and reliable characterization of heterogeneous nanoparticle suspensions is a key technology across the nanosciences. Although approaches exist for homogeneous samples, they are often unsuitable for polydisperse suspensions, as particles of different sizes and compositions can lead to indistinguishable signals at the detector. Here, we introduce holographic nanoparticle tracking analysis, holoNTA, as a straightforward methodology that decouples size and material refractive index contributions. HoloNTA is applicable to any heterogeneous nanoparticle sample and has the sensitivity to measure the intrinsic heterogeneity of the sample. Specifically, we combined high dynamic range k-space imaging with holographic 3D single-particle tracking. This strategy enables long-term tracking by extending the imaging volume and delivers precise and accurate estimates of both scattering amplitude and diffusion coefficient of individual nanoparticles, from which particle refractive index and hydrodynamic size are determined. We specifically demonstrate, by simulations and experiments, that irrespective of localization uncertainty and size, the sizing sensitivity is improved as our extended detection volume yields considerably longer particle trajectories than previously reported by comparable technologies. As validation, we measured both homogeneous and heterogeneous suspensions of nanoparticles in the 40-250 nm size range and further monitored protein corona formation, where we identified subtle differences between the nanoparticle-protein complexes derived from avidin, bovine serum albumin, and streptavidin. We foresee that our approach will find many applications of both fundamental and applied nature where routine quantification and sizing of nanoparticles are required.
Asunto(s)
Nanopartículas , Refractometría , Suspensiones , Tamaño de la Partícula , Nanopartículas/análisis , Albúmina Sérica BovinaRESUMEN
The Duffing oscillator is a nonlinear extension of the ubiquitous harmonic oscillator and as such plays an outstanding role in science and technology. Experimentally, the system parameters are determined by a measurement of its response to an external excitation. When changing the amplitude or frequency of the external excitation, a sudden jump in the response function reveals the nonlinear dynamics prominently. However, this bistability leaves part of the full response function unobserved, which limits the precise measurement of the system parameters. Here, we exploit the often unknown fact that the response of a Duffing oscillator with nonlinear damping is a unique function of its phase. By actively stabilizing the oscillator's phase we map out the full response function. This phase control allows us to precisely determine the system parameters. Our results are particularly important for characterizing nanoscale resonators, where nonlinear effects are observed readily and which hold great promise for next generation of ultrasensitive force and mass measurements. We demonstrate our approach experimentally with an optically levitated particle in high vacuum.
RESUMEN
A single levitated nanoparticle is used as a nanoreactor for studying surface chemistry at the nanoscale. Optical levitation under controlled pressure, surrounding gas composition, and humidity provides extreme control over the nanoparticle, including dynamics, charge, and surface chemistry. Using a single nanoparticle avoids ensemble averages and allows studying how the presence of silanol groups at its surface affects the adsorption and desorption of water from the background gas with excellent spatial and temporal resolution. Herein, we demonstrate the potential of this versatile platform by studying the Zhuravlev model in silica particles. In contrast to standard methods, our system allowed the observation of an abrupt and irreversible change in scattering cross section, mass, and mechanical eigenfrequency during the dehydroxylation process, indicating changes in density, refractive index, and volume.
RESUMEN
We theoretically show that strong mechanical quantum squeezing in a linear optomechanical system can be rapidly generated through the dynamical instability reached in the far red-detuned and ultrastrong coupling regime. We show that this mechanism, which harnesses unstable multimode quantum dynamics, is particularly suited to levitated optomechanics, and we argue for its feasibility for the case of a levitated nanoparticle coupled to a microcavity via coherent scattering. We predict that for submillimeter-sized cavities the particle motion, initially thermal and well above its ground state, becomes mechanically squeezed by tens of decibels on a microsecond timescale. Our results bring forth optical microcavities in the unresolved sideband regime as powerful mechanical squeezers for levitated nanoparticles, and hence as key tools for quantum-enhanced inertial and force sensing.
RESUMEN
In plasmonic photothermal therapy (PPTT), illuminated gold nanoparticles are locally heated to produce selective damage in cells. While PPTT is expected to strongly depend on the cell line, available data are sparse and critical parameters remain unclear. To elucidate this pivotal aspect, we present a systematic study of diseased and nondiseased cells from different tissues to evaluate cytotoxicity, uptake of gold nanorods (AuNRs), and viability after PPTT. We identified differences in uptake and toxicity between cell types, linking AuNR concentrations to toxicity. Furthermore, the cell death mechanism is shown to depend on the intensity of the irradiated light and hence the temperature increase. Importantly, the data also underline the need to monitor cell death at different time points. Our work contributes to the definition of systematic protocols with appropriate controls to fully comprehend the effects of PPTT and build meaningful and reproducible data sets, key to translate PPTT to clinical settings.
RESUMEN
Organ-on-a-chip (OOC) devices offer new approaches for metabolic disease modeling and drug discovery by providing biologically relevant models of tissues and organs in vitro with a high degree of control over experimental variables for high-content screening applications. Yet, to fully exploit the potential of these platforms, there is a need to interface them with integrated non-labeled sensing modules, capable of monitoring, in situ, their biochemical response to external stimuli, such as stress or drugs. In order to meet this need, we aim here to develop an integrated technology based on coupling a localized surface plasmon resonance (LSPR) sensing module to an OOC device to monitor the insulin in situ secretion in pancreatic islets, a key physiological event that is usually perturbed in metabolic diseases such as type 2 diabetes (T2D). As a proof of concept, we developed a biomimetic islet-on-a-chip (IOC) device composed of mouse pancreatic islets hosted in a cellulose-based scaffold as a novel approach. The IOC was interfaced with a state-of-the-art on-chip LSPR sensing platform to monitor the in situ insulin secretion. The developed platform offers a powerful tool to enable the in situ response study of microtissues to external stimuli for applications such as a drug-screening platform for human models, bypassing animal testing.
Asunto(s)
Técnicas Biosensibles , Secreción de Insulina , Animales , Diabetes Mellitus Tipo 2 , Descubrimiento de Drogas , Evaluación Preclínica de Medicamentos , Humanos , Insulinas , Dispositivos Laboratorio en un Chip , Análisis de Secuencia por Matrices de Oligonucleótidos , Resonancia por Plasmón de SuperficieRESUMEN
Liver fibrosis is a major health problem with multiple associated complications, which, to date, has no effective treatment. Hepatic stellate cells are the main responsible cells for fibrosis formation; upon their activation, excess accumulation of extracellular matrix and collagen deposits occurs. The mitogen platelet-derived growth factor (PDGF) and its receptor ß (PDGFRß) play a major role in hepatic stellate cells activation and are, therefore, promising targets for antifibrotic therapies. Gold nanorods hold great potential for diseased liver treatments, since their passive hepatic accumulation enhances active targeting strategies, hence increasing therapeutic efficiency. In addition, gold nanorods have photothermal properties that, combined with specific cell delivery, can be exploited to induce localized near-infrared light-mediated thermal ablation. Here, we demonstrate that gold nanorods coated with anti-PDGFRß specifically target activated hepatic stellate cells in vivo. Additionally, gold nanorods-PDGFRß-mediated photothermal therapy decreases fibrosis, hepatic inflammation, and hepatocyte injury in the experimental model of CCl4-induced liver fibrosis in mice.
Asunto(s)
Hipertermia , Cirrosis Hepática , Animales , Células Estrelladas Hepáticas/patología , Hígado/patología , Cirrosis Hepática/patología , Cirrosis Hepática/terapia , Ratones , Receptor beta de Factor de Crecimiento Derivado de PlaquetasRESUMEN
Quantum control of a system requires the manipulation of quantum states faster than any decoherence rate. For mesoscopic systems, this has so far only been reached by few cryogenic systems. An important milestone towards quantum control is the so-called strong coupling regime, which in cavity optomechanics corresponds to an optomechanical coupling strength larger than cavity decay rate and mechanical damping. Here, we demonstrate the strong coupling regime at room temperature between a levitated silica particle and a high finesse optical cavity. Normal mode splitting is achieved by employing coherent scattering, instead of directly driving the cavity. The coupling strength achieved here approaches three times the cavity linewidth, crossing deep into the strong coupling regime. Entering the strong coupling regime is an essential step towards quantum control with mesoscopic objects at room temperature.
RESUMEN
Fluorescence microscopy is the method of choice in biology for its molecular specificity and super-resolution capabilities. However, it is limited to a narrow z range around one observation plane. Here, we report an imaging approach that recovers the full electric field of fluorescent light with single-molecule sensitivity. We expand the principle of digital holography to fast fluorescent detection by eliminating the need for phase cycling and enable three-dimensional (3D) tracking of individual nanoparticles with an in-plane resolution of 15 nm and a z-range of 8 mm. As a proof-of-concept biological application, we image the 3D motion of extracellular vesicles (EVs) inside live cells. At short time scales (<4 s), we resolve near-isotropic 3D diffusion and directional transport. For longer lag times, we observe a transition toward anisotropic motion with the EVs being transported over long distances in the axial plane while being confined in the horizontal dimension.
RESUMEN
Enzyme-powered motors self-propel through the catalysis of in situ bioavailable fuels, which makes them excellent candidates for biomedical applications. However, fundamental issues like their motion in biological fluids and the understanding of the propulsion mechanism are critical aspects to be tackled before a future application in biomedicine. Herein, we investigated the physicochemical effects of ionic species on the self-propulsion of urease-powered micromotors. Results showed that the presence of PBS, NaOH, NaCl, and HEPES reduced self-propulsion of urease-powered micromotors pointing towards ion-dependent mechanisms of motion. We studied the 3D motion of urease micromotors using digital holographic microscopy to rule out any motor-surface interaction as the cause of motion decay when salts are present in the media. In order to protect and minimize the negative effect of ionic species on micromotors' performance, we coated the motors with methoxypolyethylene glycol amine (mPEG) showing higher speed compared to noncoated motors at intermediate ionic concentrations. These results provide new insights into the mechanism of urease-powered micromotors, study the effect of ionic media, and contribute with potential solutions to mitigate the reduction of mobility of enzyme-powered micromotors.
RESUMEN
Over the past two decades, there has been a growing interest in the use of plasmonic nanoparticles as sources of heat remotely controlled by light, giving rise to the field of thermoplasmonics. The ability to release heat on the nanoscale has already impacted a broad range of research activities, from biomedicine to imaging and catalysis. Thermoplasmonics is now entering an important phase: some applications have engaged in an industrial stage, while others, originally full of promise, experience some difficulty in reaching their potential. Meanwhile, innovative fundamental areas of research are being developed. In this Review, we scrutinize the current research landscape in thermoplasmonics, with a specific focus on its applications and main challenges in many different fields of science, including nanomedicine, cell biology, photothermal and hot-electron chemistry, solar light harvesting, soft matter and nanofluidics.
RESUMEN
Light absorption and scattering of plasmonic metal nanoparticles can lead to non-equilibrium charge carriers, intense electromagnetic near-fields, and heat generation, with promising applications in a vast range of fields, from chemical and physical sensing to nanomedicine and photocatalysis for the sustainable production of fuels and chemicals. Disentangling the relative contribution of thermal and non-thermal contributions in plasmon-driven processes is, however, difficult. Nanoscale temperature measurements are technically challenging, and macroscale experiments are often characterized by collective heating effects, which tend to make the actual temperature increase unpredictable. This work is intended to help the reader experimentally detect and quantify photothermal effects in plasmon-driven chemical reactions, to discriminate their contribution from that due to photochemical processes and to cast a critical eye on the current literature. To this aim, we review, and in some cases propose, seven simple experimental procedures that do not require the use of complex or expensive thermal microscopy techniques. These proposed procedures are adaptable to a wide range of experiments and fields of research where photothermal effects need to be assessed, such as plasmonic-assisted chemistry, heterogeneous catalysis, photovoltaics, biosensing, and enhanced molecular spectroscopy.