Label-Free Morpho-Molecular Imaging for Studying the Differential Interaction of Black Phosphorus with Tumor Cells.

Black phosphorus nanosheets (2D BP) are emerging as very promising, highly selective chemotherapeutic agents due to their fast degradation in the intracellular matrix of cancer cells. Here, optical diffraction tomography (ODT) and Raman spectroscopy were exploited as a powerful label-free approach to achieve integrated insights into the processes accompanying the administration of exfoliated 2D BP flakes in human prostatic adenocarcinoma and normal human prostate epithelial cells. Our ODT experiments provided unambiguous visualization of the 2D BP internalization in cancer cells and the morphological modifications of those cells in the apoptotic phase. The cellular internalization and damaging occurred, respectively, 18 h and 36-48 h after the 2D BP administration. Changes in the chemical properties of the internalized 2D BP flakes were monitored by Raman spectroscopy. Interestingly, a fast oxidation process of the 2D BP flakes was activated in the intracellular matrix of the cancer cells after 24 h of incubation. This was in sharp contrast to the low 2D BP uptake and minimal chemical changes observed in the normal cells. Along with the understanding of the 2D BP fate in the cancer cells, the proposed label-free morpho-molecular approach offers a powerful, rapid tool to study the pharmacokinetic properties of engineered nanomaterials in preclinical research.

Label-Free Spectroscopic SARS-CoV-2 Detection on Versatile Nanoimprinted Substrates.

Widespread testing and isolation of infected patients is a cornerstone of viral outbreak management, as underscored during the ongoing COVID-19 pandemic. Here, we report a large-area and label-free testing platform that combines surface-enhanced Raman spectroscopy and machine learning for the rapid and accurate detection of SARS-CoV-2. Spectroscopic signatures acquired from virus samples on metal-insulator-metal nanostructures, fabricated using nanoimprint lithography and transfer printing, can provide test results within 25 min. Not only can our technique accurately distinguish between different respiratory and nonrespiratory viruses, but it can also detect virus signatures in physiologically relevant matrices such as human saliva without any additional sample preparation. Furthermore, our large area nanopatterning approach allows sensors to be fabricated on flexible surfaces allowing them to be mounted on any surface or used as wearables. We envision that our versatile and portable label-free spectroscopic platform will offer an important tool for virus detection and future outbreak preparedness.

Nanowire Assisted Mechanotyping of Cellular Metastatic Potential.

Nanotechnology has provided tools for next generation biomedical devices which rely on nanostructure interfaces with living cells. In vitro biomimetic structures have enabled observation of cell response to various mechanical and chemical cues, and there is a growing interest in isolating and harnessing the specific cues that three-dimensional microenvironments can provide without the requirement for such culture and the experimental drawbacks associated with it. Here we report a randomly oriented gold coated Si nanowire substrate with patterned hydrophobic-hydrophilic areas for differentiation of isogenic breast cancer cells of varying metastatic potential. When considering synthetic surfaces for the study of cell-nanotopography interfaces, randomly oriented nanowires more closely resemble the isotropic architecture of natural extracellular matrix as compared to currently more widely used vertical nanowire arrays. In the study reported here, we show that primary cancer cells preferably attach to the hydrophilic region of randomly oriented nanowire substrate while secondary cancer cells do not adhere. Using machine learning analysis of fluorescence images, cells were found to spread and elongate on the nanowire substrates as compared to a flat substrate, where they mostly remain round, when neither surface was coated with extracellular matrix (ECM) proteins. Such platforms can not only be used for developing bioassays but also as stepping stones for tissue printing technologies where cells can be selectively patterned at desired locations.

Spectroscopy-Assisted Label-free Molecular Analysis of Live Cell Surface with Vertically Aligned Plasmonic Nanopillars.

A generalized label-free platform for surface-selective molecular sensing in living cells can transform the ability to examine complex events in the cell membrane. While vertically aligned semiconductor and metal-semiconductor hybrid nanopillars have rapidly surfaced for stimulating and probing the intracellular environment, the potential of such constructs for selectively interrogating the cell membrane is surprisingly underappreciated. In this work, a new platform, entitled nano-PROD (nano-pillar based Raman optical detection), enables molecular recording by probing fundamental vibrational modes of membrane constituents of cells adherent on a large-area silver-coated silicon nanopillar substrate fabricated using a precursor solution-based nanomanufacturing process. It is shown that the nano-PROD platform sustains live cells in near-physiological conditions, which can be directly profiled using surface-enhanced Raman spectroscopy due to the confined electromagnetic field enhancement. The experimental results highlight the utility of the platform in probing specific cell surface markers for accurately recognizing the phenotypically identical prostate cancer cells, differing only in prostate-specific membrane antigen expression. Due to its tunability, nano-PROD has the promise to be readily extendable to other applications that can leverage its unique combination of nanoscale topographic features and molecular sensing capabilities, from stain-free cytopathology inspection to understanding spatio-mechanical regulation in membrane receptor function.

Unconventional plasmonic sensitization of graphene in mid-infrared.

Light-matter interaction in graphene can be engineered and substantially enhanced through plasmonic sensitization, which has led to numerous applications in photodetection, sensing, photocatalysis and spectroscopy. The majority of these designs have relied on conventional plasmonic materials such as gold, silver and aluminum. This limits the implementation of such devices to the ultraviolet and visible regimes of the electromagnetic spectrum. However, for many practical applications, including those relevant to security and defense, the development of new strategies and materials for sensing and detection of infra red (IR) light is crucial. Here we use surface enhanced Raman spectroscopy (SERS), for direct visualization and estimation of enhanced light-matter interaction in graphene in the mid-IR regime, through sensitization by an unconventional plasmonic material. Specifically, we fabricate a hybrid device consisting of a single layer graphene and a two-dimensional array of nanodiscs of aluminum doped zinc oxide (AZO), which is a highly doped semiconductor, exhibiting plasmonic resonance in the mid-IR. We find that the enhancement in the SERS signal of graphene is of similar magnitude to what has been achieved previously in the visible using conventional plasmonic materials. Our results establish the potential of such hybrid systems for graphene-based optical and optoelectronic applications in the mid-IR.

Silver-coated silicon nanowire platform discriminates genomic DNA from normal and malignant human epithelial cells using label-free Raman spectroscopy.

Genomic deoxyribonucleic acid (DNA) stores and carries the information required to maintain and replicate cellular life. While much efforts have been devoted in decoding the sequence of DNA basis to detect the genetic mutations related to cancer disease, it is becoming clear that physical properties, like structural conformation, stiffness and shape, can play an important role to recognize DNA modifications. Here, silver-coated silicon nanowires (Ag/SiNWs) are exploited as Raman spectroscopic platform to easily discriminate healthy and cancer genomic DNA, extracted from human normal skin and malignant melanoma cells, respectively. In particular, aqueous DNA droplets are directly deposited onto a forest of Ag/SiNWs and Raman maps are acquired after sample dehydration. By applying principal component analysis (PCA) to the Raman spectra collected within the droplets, healthy and cancer cell DNA can be distinguished without false negative identifications and with few false positive results (< 2%). The discrimination occurs regardless the analysis of specific DNA sequencing, but through Raman bands strictly related to the interfacing of the DNA and the NWs. The observed phenomenon can be ascribed to conformational differences and/or diverse charge properties between healthy and cancer cell DNA determining a different arrangement of the molecules adsorbed onto the NWs upon water evaporation. The unique interaction with DNA and facile fabrication technology make Ag/SiNWs an effective platform for a robust, rapid and label-free cancer diagnosis, as well as a potential tool to investigate physical properties of DNA.

Molecular Radiative Energy Shifts under Strong Oscillating Fields.

Coherent manipulation of light-matter interactions is pivotal to the advancement of nanophotonics. Conventionally, the non-resonant optical Stark effect is harnessed for band engineering by intense laser pumping. However, this method is hindered by the transient Stark shifts and the high-energy laser pumping which, by itself, is precluded as a nanoscale optical source due to light diffraction. As an analog of photons in a laser, surface plasmons are uniquely positioned to coherently interact with matter through near-field coupling, thereby, providing a potential source of electric fields. Herein, the first demonstration of plasmonic Stark effect is reported and attributed to a newly uncovered energy-bending mechanism. As a complementary approach to the optical Stark effect, it is envisioned that the plasmonic Stark effect will advance fundamental understanding of coherent light-matter interactions and will also provide new opportunities for advanced optoelectronic tools, such as ultrafast all-optical switches and biological nanoprobes at lower light power levels.

Silver-Coated Disordered Silicon Nanowires Provide Highly Sensitive Label-Free Glycated Albumin Detection through Molecular Trapping and Plasmonic Hotspot Formation.

Glycated albumin (GA) is rapidly emerging as a robust biomarker for screening and monitoring of diabetes. To facilitate its rapid, point-of-care measurements, a label-free surface-enhanced Raman spectroscopy (SERS) sensing platform is reported that leverages the specificity of molecular vibrations and signal amplification on silver-coated silicon nanowires (Ag/SiNWs) for highly sensitive and reproducible quantification of GA. The simulations and experimental measurements demonstrate that the disordered orientation of the nanowires coupled with the wicking of the analyte molecules during the process of solvent evaporation facilitates molecular trapping at the generated plasmonic hotspots. Highly sensitive detection of glycated albumin is shown with the ability to visually detect spectral features at as low as 500 × 10-9 m, significantly below the physiological range of GA in body fluids. Combined with chemometric regression models, the spectral data recorded on the Ag/SiNWs also allow accurate prediction of glycated concentration in mixtures of glycated and non-glycated albumin in proportions that reflect those in the bloodstream.

Optical properties of symmetry-breaking tetrahedral nanoparticles.

Spectrally rich but geometrically simple plasmonic metallic nanoparticles are highly favored in nanophotonics. However, they remain elusive owing to the symmetry-induced mode degeneracy and interband transition-induced plasmonic damping. Hence, most nanoparticles exhibit a single major extinction peak originating from the lowest-order dipole resonance. In this study, we uncover that even a simple tetrahedral nanoparticle supports rich spectral features due to symmetry breaking. This discovery runs counter to the reported gold tetrahedral nanoparticles, where only a single extinction peak was observed. We find that, in the case of a tetrahedral nanoparticle, the plasmonic quadrupole vertex mode becomes a bright mode and hybridizes with the dipole vertex mode, which splits the extinction peak and contributes to spectral diversity and tunability. The peak splitting is also found to be sensitively dependent on the roundness of vertices and edges. Furthermore, the tetrahedral depolarization factors are determined using the previously generalized absorption coefficient. We envision that this work will not only help fill the gap in understanding the optical properties enriched by symmetry breaking but also guide the superior probe design by combining spectral tunability with geometric simplicity of the nanoparticle.

Towards rational design and optimization of near-field enhancement and spectral tunability of hybrid core-shell plasmonic nanoprobes.

In biology, sensing is a major driver of discovery. A principal challenge is to create a palette of probes that offer near single-molecule sensitivity and simultaneously enable multiplexed sensing and imaging in the "tissue-transparent" near-infrared region. Surface-enhanced Raman scattering and metal-enhanced fluorescence have shown substantial promise in addressing this need. Here, we theorize a rational design and optimization strategy to generate nanostructured probes that combine distinct plasmonic materials sandwiching a dielectric layer in a multilayer core shell configuration. The lower energy resonance peak in this multi-resonant construct is found to be highly tunable from visible to the near-IR region. Such a configuration also allows substantially higher near-field enhancement, compared to a classical core-shell nanoparticle that possesses a single metallic shell, by exploiting the differential coupling between the two core-shell interfaces. Combining such structures in a dimer configuration, which remains largely unexplored at this time, offers significant opportunities not only for near-field enhancement but also for multiplexed sensing via the (otherwise unavailable) higher order resonance modes. Together, these theoretical calculations open the door for employing such hybrid multi-layered structures, which combine facile spectral tunability with ultrahigh sensitivity, for biomolecular sensing.

Controlling Evolution: The Nobel Prize in Chemistry 2018.

2018 was a revolutionary year in the field of chemistry as the Royal Swedish Academy of Sciences awarded the Nobel Prize in Chemistry 2018 to three brilliant chemists (Figure 1): Dr. Frances H. Arnold-"for the directed evolution of enzymes "; Dr. George P. Smith and Sir Gregory P. Winter (jointly)-"for the phage display of peptides and antibodies" [1]. Their phenomenal contribution in controlling the evolution of enzymes and binding proteins and using them for the benefit of humankind has revolutionized the industry and academia alike for the past few decades.

Composite-Scattering Plasmonic Nanoprobes for Label-Free, Quantitative Biomolecular Sensing.

Biosensing based on localized surface plasmon resonance (LSPR) relies on concentrating light to a nanometeric spot and leads to a highly enhanced electromagnetic field near the metal nanostructure. Here, a design of plasmonic nanostructures based on rationally structured metal-dielectric combinations is presented, called composite scattering probes (CSPs), to generate an integrated multimodal biosensing platform featuring LSPR and surface-enhanced Raman spectroscopy (SERS). Specifically, CSP configurations are proposed, which have several prominent resonance peaks enabling higher tunability and sensitivity for self-referenced multiplexed analyte sensing. Using electron-beam evaporation and thermal dewetting, large-area, uniform, and tunable CSPs are fabricated, which are suitable for label-free LSPR and SERS measurements. The CSP prototypes are used to demonstrate refractive index sensing and molecular analysis using albumin as a model analyte. By using partial least squares on recorded absorption profiles, differentiation of subtle changes in refractive index (as low as 0.001) in the CSP milieu is demonstrated. Additionally, CSPs facilitate complementary untargeted plasmon-enhanced Raman measurements from the sample's compositional contributors. With further refinement, it is envisioned that the method may lead to a sensitive, versatile, and tunable platform for quantitative concentration determination and molecular fingerprinting, particularly where limited a priori information of the sample is available.

Graphene-silver hybrid devices for sensitive photodetection in the ultraviolet.

The weak light-matter interaction in graphene can be enhanced with a number of strategies, among which sensitization with plasmonic nanostructures is particularly attractive. This has resulted in the development of graphene-plasmonic hybrid systems with strongly enhanced photodetection efficiencies in the visible and the IR, but none in the UV. Here, we describe a silver nanoparticle-graphene stacked optoelectronic device that shows strong enhancement of its photoresponse across the entire UV spectrum. The device fabrication strategy is scalable and modular. Self-assembly techniques are combined with physical shadow growth techniques to fabricate a regular large-area array of 50 nm silver nanoparticles onto which CVD graphene is transferred. The presence of the silver nanoparticles resulted in a plasmonically enhanced photoresponse as high as 3.2 A W-1 in the wavelength range from 330 nm to 450 nm. At lower wavelengths, close to the Van Hove singularity of the density of states in graphene, we measured an even higher responsivity of 14.5 A W-1 at 280 nm, which corresponds to a more than 10 000-fold enhancement over the photoresponse of native graphene.

Ultrahigh field enhancement and photoresponse in atomically separated arrays of plasmonic dimers.

Combining oblique angle deposition with standard graphene transfer protocols, two planar arrays of metal nanoparticles are fabricated that are vertically separated by atomic dimensions, corresponding precisely to the thickness of a single layer of graphene, i.e., 0.34 nm. Upon illumination of light at an appropriate wavelength, the local electromagnetic field at the junction of the dimers can be increased dramatically, thereby resulting in the most sensitive graphene-plasmonic hybrid photodetector reported to date.

Velocity Fluctuations in Helical Propulsion: How Small Can a Propeller Be.

Helical propulsion is at the heart of locomotion strategies utilized by various natural and artificial swimmers. We used experimental observations and a numerical model to study the various fluctuation mechanisms that determine the performance of an externally driven helical propeller as the size of the helix is reduced. From causality analysis, an overwhelming effect of orientational noise at low length scales is observed, which strongly affects the average velocity and direction of motion of a propeller. For length scales smaller than a few micrometers in aqueous media, the operational frequency for the propulsion system would have to increase as the inverse cube of the size, which can be the limiting factor for a helical propeller to achieve locomotion in the desired direction.

Dynamical configurations and bistability of helical nanostructures under external torque.

We study the motion of a ferromagnetic helical nanostructure under the action of a rotating magnetic field. A variety of dynamical configurations were observed that depended strongly on the direction of magnetization and the geometrical parameters, which were also confirmed by a theoretical model, based on the dynamics of a rigid body under Stokes flow. Although motion at low Reynolds numbers is typically deterministic, under certain experimental conditions the nanostructures showed a surprising bistable behavior, such that the dynamics switched randomly between two configurations, possibly induced by thermal fluctuations. The experimental observations and the theoretical results presented in this paper are general enough to be applicable to any system of ellipsoidal symmetry under external force or torque.