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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., ACS Nano, 17 (1), ISSN:1936-0851, ISSN:1936-086X

The quantum ground state of a massive mechanical system is a stepping stone for investigating macroscopic quantum states and building high fidelity sensors. With the recent achievement of ground-state cooling of a single motional mode, levitated nanoparticles have entered the quantum domain. To overcome detrimental cross-coupling and decoherence effects, quantum control needs to be expanded to more system dimensions, but the effect of a decoupled dark mode has so far hindered cavity-based ground-state cooling of multiple mechanical modes. Here, we demonstrate two-dimensional ground-state cooling of an optically levitated nanoparticle. Utilizing coherent scattering into an optical cavity mode, we reduce the occupation numbers of two separate centre-of-mass modes to 0.83 and 0.81, respectively. By controlling the frequency separation and the cavity coupling strengths of the nanoparticle’s mechanical modes, we show the transition from 1D to 2D ground-state cooling. This 2D control lays the foundations for quantum-limited orbital angular momentum states for rotation sensing and, combined with ground-state cooling along the third motional axis shown previously, may allow full 3D ground-state cooling of a massive object., Nature Physics, ISSN:1745-2473, ISSN:1745-2481

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., Nano Letters, 23 (7), ISSN:1530-6984, ISSN:1530-6992

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., ACS Nanoscience Au, 2 (6), ISSN:2694-2496

A single levitated nanoparticle is used as a nano-reactor 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 to study how the presence of silanol groups at its surface affects the adsorption and desorption of water from the background gas with unprecedented real time, spatial, and temporal resolution. Here, we demonstrate the unique potential of this versatile platform by studying the Zhuravlev model in silica particles. In contrast to standard methods, our system allowed the first 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.

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. Thermoplasmonics is based on the use of plasmonic nanoparticles as sources of heat remotely controlled by light. This Review discusses its current applications and challenges in a broad range of scientific fields, from nanomedicine to hot-electron chemistry and nanofluidics.

Optical tweezers are tools made of light that enable contactless pushing, trapping, and manipulation of objects ranging from atoms to space light sails. Since the pioneering work by Arthur Ashkin in the 1970s, optical tweezers have evolved into sophisticated instruments and have been employed in a broad range of applications in life sciences, physics, and engineering. These include accurate force and torque measurement at the femtonewton level, microrheology of complex fluids, single micro- and nanoparticle spectroscopy, single-cell analysis, and statistical-physics experiments. This roadmap provides insights into current investigations involving optical forces and optical tweezers from their theoretical foundations to designs and setups. It also offers perspectives for applications to a wide range of research fields, from biophysics to space exploration., Comment: 181 pages, 61 figures

The advent of spatial control over the phase and amplitude of light waves has profoundly transformed photonics, enabling major advances in fields from imaging and information technology to biomedical optics. Here we propose a method of deterministic phase-front shaping using a planar thermo-optical module and designed microheaters to locally shape the refractive index distribution. When combined with a genetic algorithm optimization, this SmartLens can produce free-form optical wavefront modifications. Individually, or in arrays, it can generate complex functions based on either pure or combined Zernike polynomials, including lenses or aberration correctors of electrically tunable magnitude. This simple and compact concept complements the existing optical shaping toolbox by offering low-chromatic-aberration, polarization-insensitive and transmission-mode components that can readily be integrated into existing optical systems. Using microheaters and a genetic algorithm optimization, deterministic phase-front shaping through a planar thermo-optical module can be realized, complementing the existing optical shaping toolbox by offering low-chromatic-aberration, polarization-insensitive and transmission-mode components.

High refractive index dielectric nanoresonators are attracting much attention due to their ability to control both electric and magnetic components of light. Combining confined modes with reduced absorption losses, they have recently been proposed as an alternative to nanoplasmonic biosensors. In this context, we study the use of semi-random silicon nanocylinder arrays, fabricated with simple and scalable colloidal lithography for the efficient and reliable detection of biomolecules in biological samples. Interestingly, electric and magnetic dipole resonances are associated to two different transduction mechanisms: extinction decrease and resonance redshift, respectively. By contrasting both observables, we identify clear advantages in tracking changes in the extinction magnitude. Our data demonstrate that, despite its simplicity, the proposed platform is able to detect prostate specific antigen (PSA) in human serum with limits of detection meeting clinical needs.

The insertion of an implant in the body of a patient raises the risk of a posterior infection and formation of a biofilm, which can have critical consequences on the patient's health and be associated with a high sanitary cost. While antibacterial agents can be used to prevent the infection, such a strategy is time-limited and causes bacteria resistance. As an alternative to biochemical approaches, we propose here to use light-induced local hyperthermia with plasmonic nanoparticles. This strategy is implemented on surgical meshes, extensively used in the context of hernia repairing, one of the most common general surgeries. Surgical meshes were homogeneously coated with gold nanorods designed to efficiently convert near-infrared light into heat. The modified mesh was exposed to a biofilm of Staphylococcus aureus ( S. aureus) bacteria before being treated with a train of light pulses. We systematically study how the illumination parameters, namely fluence, peak intensity and pulse length, influence the elimination of attached bacteria. Additionally, fluorescence confocal microscopy provides us some insight on the mechanism involved in the degradation of the biofilm. This proof-of-principle study opens a new set of opportunities for the development of novel disinfection approaches combining light and nanotechnology.

Owing to their unique combination of chemical and physical properties, inorganic nanoparticles show a great deal of potential as suitable agents for early diagnostics and less invasive therapies. Yet, their translation to the clinic has been hindered, in part, by the lack of non-invasive methods to quantify their concentration in vivo while also assessing their effect on the tissue physiology. In this work, we demonstrate that diffuse optical techniques, employing near-infrared light, have the potential to address this need in the case of gold nanoparticles which support localized surface plasmons. An orthoxenograft mouse model of clear cell renal cell carcinoma was non-invasively assessed by diffuse reflectance and correlation spectroscopies before and over several days following a single intravenous tail vein injection of polyethylene glycol-coated gold nanorods (AuNRs-PEG). Our platform enables to resolve the kinetics of the AuNR-PEG uptake by the tumor in quantitative agreement with ex vivo inductively coupled plasma mass spectroscopy. Furthermore, it allows for the simultaneous monitoring of local tissue hemodynamics, enabling us to conclude that AuNRs-PEG do not significantly alter the animal physiology. We note that the penetration depth of this current probe was a few millimeters but can readily be extended to centimeters, hence gaining clinical relevance. This study and the methodology presented here complement the nanomedicine toolbox by providing a flexible platform, extendable to other absorbing agents that can potentially be translated to human trials.

Fever is an evolutionary conserved response able to stimulate and boost both innate and adaptive immunity. Temperature variations in general modify the homeostatic setpoint such as blood flow in warm blooded animals and can change gene-expression patterns on the single cell level [1] . Neutrophils and dendritic cells (DCs) patrol tissues under various temperature levels and their effective encounter and response to ‘danger signals’ is key for optimal immune defence [2] . Still, the thermo-regulation of immune cell dynamics remains largely elusive. Here we show that the local temperature controls immune cell dynamics, such as shape changes, cell migration speed and persistence in 2D/2.5D/3D biomimetic micro-environments.

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., Biosensors, 11 (5), ISSN:2079-6374

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 β (PDGFRβ) 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-PDGFRβ specifically target activated hepatic stellate cells in vivo. Additionally, gold nanorods-PDGFRβ-mediated photothermal therapy decreases fibrosis, hepatic inflammation, and hepatocyte injury in the experimental model of CCl4-induced liver fibrosis in mice.

Plasmonic photothermal therapy is an emerging complementary method for treating tumors usually studied pre-clinically in mice with small subcutaneous tumors. In this project, it is conducted on a more realistic orthotopic xenograft renal carcinoma mouse model, while tissue optical properties are monitored non-invasively by diffuse optics. Hybrid diffuse reflectance spectroscopy and diffuse correlation spectroscopy are used to quantify tissue hemodynamics, the accumulated plasmonic nanoparticle concentration and therapy induced physiological changes. The results show the need for personalization and the predictive capabilities of the monitoring, which, in turn, would allow for therapy optimization.

This Conference Presentation, “Dielectric nanophotonics for reconfigurable planar optics and biosensing,” was recorded for the Photonics West 2021 Digital Forum.

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., Nature Communications, 12 (1), ISSN:2041-1723

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. ISSN:0031-9007 ISSN:1079-7114

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 (, Science Advances, 6 (45), ISSN:2375-2548

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., Research, 2020

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 the one 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, which 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., Comment: 23 pages, 7 figures

Using light to manipulate fluids has been a long-sought-after goal for lab-on-a-chip applications to address the size mismatch between bulky external fluid controllers and microfluidic devices. Yet, this goal has remained elusive due to the complexity of thermally driven fluid dynamic phenomena, and the lack of approaches that allow comprehensive multiscale and multiparameter studies. Here, we report an innovative optofluidic platform that fulfills this need by combining digital holographic microscopy with state-of-the-art thermoplasmonics, allowing us to identify the different contributions from thermophoresis, thermo-osmosis, convection, and radiation pressure. In our experiments, we demonstrate that a local thermal perturbation at the microscale can lead to mm-scale changes in both the particle and fluid dynamics, thus achieving long-range transport. Furthermore, thanks to a comprehensive parameter study involving sample geometry, temperature increase, light fluence, and size of the heat source, we showcase an integrated and reconfigurable all-optical control strategy for microfluidic devices, thereby opening new frontiers in fluid actuation technology., Nature Communications, 12 (1), ISSN:2041-1723

From its beginnings, nanomedicine research has encountered several challenges that have slowed down its clinical translation. The first part of this chapter focuses on the targeted delivery of nanoparticles, examining their biodistribution and toxicity and how these factors have influenced progress in nanomedicine. In the second part of the chapter, the use of gold nanoparticles in photothermal therapy for cancer treatment is reviewed, from its conception to current status, with special emphasis on its limitations. The chapter summarizes by discussing the key areas needing improvement in order to move this promising therapy closer to the clinics.

We discuss the use of a levitated mesoscopic particle in vacuum as a optomechanical system with unique features and performance.

We investigate the nonlinear optical response of suspended one-dimensional (1D) photonic crystal nanocavities fabricated on a silicon nitride chip. Strong thermo-optical nonlinearities are demonstrated for input powers as low as $2\phantom{\rule{4pt}{0ex}}\ensuremath{\mu}\text{W}$ and a self-sustained pulsing regime is shown to emerge with periodicity of several seconds. As the input power and laser wavelength are varied the temporal patterns change in period, duty cycle, and shape. This dynamics is attributed to the multiple timescale competition between thermo-optical and thermo-optomechanical effects and closely resembles the relaxation oscillations states found in mathematical models of neuronal activity. We introduce a simplified model that reproduces all the experimental observations and allows us to explain them in terms of the properties of a 1D critical manifold which governs the slow evolution of the system.

The levitation of condensed matter in vacuum allows the study of its physical properties under extreme isolation from the environment. It also offers a venue to investigate quantum mechanics with large systems, at the transition between the quantum and classical worlds. In this work, we study a novel hybrid levitation platform that combines a Paul trap with a weak but highly focused laser beam, a configuration that integrates a deep potential with excellent confinement and motion detection. We combine simulations and experiments to demonstrate the potential of this approach to extend vacuum trapping and interrogation to a broader range of nanomaterials, such as absorbing particles. We study the stability and dynamics of different specimens, such as fluorescent dielectric crystals and gold nanorods, and demonstrate stable trapping down to pressures of 1 mbar.

Biosensing based on optical micro- and nanoresonators integrated in a microfluidic environment is a promising approach to lab-on-a-chip platforms capable of detecting low concentrations of analytes...

The use of photothermal sensitizers to facilitate the sintering of polymer powders is rapidly becoming a pivotal additive manufacturing technology, impacting multiple sectors of industry. However, conventional carbon-based sensitizers can only produce black or gray objects. To create white or colorful prints with this method, visibly transparent equivalents are needed. Here, we address this problem by designing resonant photothermal sensitizers made of plasmonic nanoparticles that strongly absorb in the near-infrared, while only minimally interacting with visible light. Gold nanorods were coated with silica before being mixed with polyamide powders to create stable colorful nanocomposite powders. At resonance, these composites showed greatly improved light-to-heat conversion compared with equivalent composites using the industry standard carbon black as a sensitizer and could be sintered using low-power light sources. Furthermore, they appear much whiter and can produce brightly colored 3D objects when mixed with dyes. Our results open a new route to utilize plasmonic nanoparticles to produce colorful and functional 3D-printed objects.

Noble metal nanoparticles (NPs) supporting localized surface plasmon resonances are widely used in the context of biotechnology as optical and absorption contrast agents with great potential applicability to both diagnostics and less invasive therapies. In this framework, it is crucial to have access to simple and reliable microscopy techniques to monitor the NPs that have internalized into cells. While dark field (DF) microscopy takes advantage of the enhanced NP scattering at their plasmon resonance, its use in cells is limited by the large scattering background from the internal cell compartments. Here, we report on a novel two-color dark field microscopy that addresses these limitations by significantly reducing the cell scattering contribution. We first present the technique and demonstrate its enhanced contrast, specificity and reliability for NP detection compared to a standard optical dark field. We then demonstrate its potential suitability in two different settings, namely wide-field parallel screening of circulating cells in microfluidic chips and high-resolution tracking of internalized NPs in cells. These proof of principle experiments show a promising capability of this approach with possible extension to other kinds of targeted systems like bacteria and vesicles.

Next-generation optoelectronic devices and photonic circuitry will have to incorporate on-chip compatible nanolaser sources. Semiconductor nanowire lasers have emerged as strong candidates for integrated systems with applications ranging from ultrasensitive sensing, to data communication technologies. Despite significant advances in their fundamental aspects, the integration within scalable photonic circuitry remains challenging. Here we report on the realization of hybrid photonic devices consisting of nanowire lasers integrated with wafer-scale lithographically designed V-groove plasmonic waveguides. We present experimental evidence of the lasing emission and coupling into the propagating modes of the V-grooves, enabling on-chip routing of coherent and sub-diffraction confined light with room temperature operation. Theoretical considerations suggest that the observed lasing is enabled by a waveguide hybrid photonic-plasmonic mode. This work represents a major advance towards the realization of application-oriented photonic circuits with integrated nanolaser sources., 24 pages, 4 figures

This document is the unedited Author’s version of a Submitted Work that was subsequently accepted for publication in Nano letters, copyright © American Chemical Society after peer review. To access the final edited and published work see https://pubs.acs.org/doi/10.1021/acs.nanolett.9b04334 Chiro-sensitive molecular detection is highly relevant as many biochemical compounds, the building blocks of life, are chiral. Optical chirality is conventionally detected through circular dichroism (CD) in the UV range, where molecules naturally absorb. Recently, plasmonics has been proposed as a way to boost the otherwise very weak CD signal and translate it to the visible/NIR range, where technology is friendlier. Here, we explore how dielectric nanoresonators can contribute to efficiently differentiate molecular enantiomers. We study the influence of the detuning between electric (ED) and magnetic dipole (MD) resonances in silicon nanocylinders on the quality of the CD signal. While our experimental data, supported by numerical simulations, demonstrate that dielectric nanoresonators can perform even better than their plasmonic counterpart, exhibiting larger CD enhancements, we do not observe any significant influence of the optical chirality.

We present a novel plasmonic sensor configuration that allows the discrimination of chiral molecules. The sensor consists of handed gold nanostructures of gammadion shape, distributed in a racemic (50/50 mixture) matrix with C4 symmetry. Its optical response enhances the interaction with molecules thus circular dichroism can be measured in the visible range. The bare sensors exhibit a flat CD signal, providing background-free CD measurements for molecular detection. We have used a chiral molecular model based on L-, D-, and the racemic mixture of phenylalanine, which allows us to evaluate the opposite chiral effects while having a reference system. Additionally, we have used molecular thermal evaporation technique to deposit a dense molecular layer on top of the sensors in a controllable and reproducible way. Our results show the discrimination of phenylalanine enantiomers through positive or negative peaks while the racemic mixture shows a flat signal. In addition, we present preliminary results that show that this approach is also suitable for microfluidics systems with a much lower density of chiral molecules.

Physical Review Letters, 123 (15), ISSN:0031-9007, ISSN:1079-7114

Nanomedicine has emerged as a promising strategy to address some of the limitations of traditional biomedical sensing, imaging and therapy modalities. Its applicability and efficacy are, in part, hindered by the difficulty in both controllably delivering nanoparticles to specific regions and accurately monitoring them in tissue. Gold nanoparticles are among the most extensively used inorganic nanoparticles which benefit from high biocompatibility, flexible functionalization, strong and tunable resonant absorption, and production scalability. Moreover, their capability to enhance optical fields at their plasmon resonance enables local boosting of non-linear optical processes, which are otherwise very inefficient. In particular, two-photon induced luminescence (TPL) in gold offers high signal specificity for monitoring gold nanoparticles in a biological environment. In this article, we demonstrate that TPL microscopy provides a robust sub-micron-resolution technique able to quantify accumulated gold nanorods (GNRs) both in cells and in tissues. First, the temporal accumulation of GNRs with two different surface chemistries was measured in 786-O cells during the first 24 hours of incubation, and at different nanoparticle concentrations. Subsequently, GNR accumulation in mice, 6 h and 24 hours after tail vein injection, was quantified by TPL microscopy in biopsied tissue from kidney, spleen, liver and clear cell renal cell carcinoma (ccRCC) tumors, in good agreement with inductively coupled mass spectroscopy. Our data suggest that TPL microscopy stands as a powerful tool to understand and quantify the delivery mechanisms of gold nanoparticles, highly relevant to the development of future theranostic medicines.