Optical Microsphere Nano-Imaging:Progress and Challenges

The optical diffraction effect imposes a radical obstacle preventing conventional optical microscopes from achieving an imaging resolution beyond the Abbe diffraction limit and thereby restricting their usage in a multitude of nanoscale applications.Over the past decade,the optical microsphere nanoimaging technique has been demonstrated to be a cost-effective solution for overcoming the diffraction limit and has achieved an imaging resolution of up to about k6k8 in a real-time and label-free manner,making it highly competitive among numerous super-resolution imaging technologies.In this review,we summarize the underlying nano-imaging mechanisms of the microsphere nanoscope and key advancements aimed at imaging performance enhancement:first,to change the working environment or modify the peripheral hardware of a single microsphere nanoscope at the system level;second,to compose the microsphere compound lens;and third,to engineer the geometry or ingredients of microspheres.We also analyze challenges yet to be overcome in optical microsphere nano-imaging,followed by an outlook of this technique.

Fano Resonance Enabled Infrared Nano-Imaging of Local Strain in Bilayer Graphene

Detection of local strain at the nanometer scale with high sensitivity remains challenging.Here we report near-field infrared nano-imaging of local strains in bilayer graphene by probing strain-induced shifts of phonon frequency.As a non-polar crystal,intrinsic bilayer graphene possesses little infrared response at its transverse optical phonon frequency.The reported optical detection of local strain is enabled by applying a vertical electrical field that breaks the symmetry of the two graphene layers and introduces finite electrical dipole moment to graphene phonon.The activated phonon further interacts with continuum electronic transitions,and generates a strong Fano resonance.The resulted Fano resonance features a very sharp near-field infrared scattering peak,which leads to an extraordinary sensitivity of-0.002%for the strain detection.Our results demonstrate the first nano-scale near-field Fano resonance,provide a new way to probe local strains with high sensitivity in non-polar crystals,and open exciting possibilities for studying strain-induced rich phenomena.

Remote-mode microsphere nano-imaging：new boundaries for optical microscopes

Optical microscope is one of the most popular characterization techniques for general purposes in many fields. It is distinguishedfrom the vacuum or tip-based imaging techniques for its flexibility, low cost, and fast speed. However, its resolutionlimits the functionality of current optical imaging performance. While microspheres have been demonstrated forimproving the observation power of optical microscope, they are directly deposited on the sample surface and thus theapplications are greatly limited. We develop a remote-mode microsphere nano-imaging platform which can scan freelyand in real-time across the sample surfaces. It greatly increases the observation power and successfully characterizesvarious practical samples with the smallest feature size down to 23 nm. This method offers many unique advantages,such as enabling the detection to be non-invasive, dynamic, real-time, and label-free, as well as leading to more functionalitiesin ambient air and liquid environments, which extends the nano-scale observation power to a broad scope inour life.

Infrared Nano-Imaging of Electronic Phase across the Metal–Insulator Transition of NdNiO_(3) Films

NdNiO_(3) is a typical correlated material with temperature-driven metal–insulator transition. Resolving the local electronic phase is crucial in understanding the driving mechanism behind the phase transition. Here we present a nano-infrared study of the metal–insulator transition in NdNiO_(3) films by a cryogenic scanning near-field optical microscope. The NdNiO_(3) films undergo a continuous transition without phase coexistence. The nano-infrared signal shows significant temperature dependence and a hysteresis loop. Stripe-like modulation of the optical conductivity is formed in the films and can be attributed to the epitaxial strain. These results provide valuable evidence to understand the coupled electronic and structural transformations in NdNiO_(3) films at the nano-scale.

Nano-imaging agents for brain diseases: Environmentally responsive imaging and therapy

Precise imaging is essential for the accurate diagnosis and surgical guidance of brain diseases but it is challenging due to the difficulties in crossing the blood-brain barrier(BBB),the difficulties in disease lesion targeting,and the limited contrast in the brain environment.Nano-imaging agents were characterized by functionalized modifications,high contrast,small size,and high biocompatibility,thus providing advantages in BBB crossing,brain targeting,imaging resolution,and real-time monitoring,holding great potential in brain disease imaging.Specific characteristics in brain environment and brain diseases(e.g.,marker proteins on the BBB,the pathogenic proteins in the neurodegenerative diseases or brain tumors,and the tumor and inflammatory microenvironment)provide opportunities for the functionalized nano-imaging agents to improve BBB crossing and disease targeting.Moreover,the versatile nano-imaging agents are endowed with therapeutic agents to facilitate the theranostics of brain diseases.Here,we summarized the common materials and imaging techniques of nano-imaging agents and their imaging treatment applications.We discussed their BBB penetration,environmental response for disease targeting,and therapeutic effects.We also provided insights on the advantages,challenges,and application of nano-imaging agents in detecting and treating brain diseases such as neurodegenerative diseases,brain tumors,stroke,and traumatic brain injury.These discussions will help develop nano-imaging agents-based theranostic platforms for the precise diagnosis and treatment of brain diseases.

Ultrastructural analysis of neuronal synapses using state-of-the-art nano-imaging techniques

Neuronal synapses are functional nodes in neural circuits.Their organization and activity define an individual＇s level of intelligence,emotional state and mental health.Changes in the structure and efficacy of synapses are the biological basis of learning and memory.However,investigation of the molecular architecture of synapses has been impeded by the lack of efficient techniques with sufficient resolution.Recent developments in state-of-the-art nano-imaging techniques have opened up a new window for dissecting the molecular organization of neuronal synapses with unprecedented resolution.Here,we review recent technological advances in nano-imaging techniques as well as their applications to the study of synapses,emphasizing super-resolution light microscopy and 3-dimensional electron tomography.

Full-field x ray nano-imaging system designed and constructed at SSRF

Full-field x ray nano-imaging（FXNI） is one of the most powerful tools for in-situ, non-destructive observation of the inner structure of samples at the nanoscale. Owing to the high flux density of the third-generation synchrotron radiation facility, great progress is achieved for FXNI and its applications. Up to now, a spatial resolution of20 nm for FXNI is achieved. Based on the user operation experiences over the years at the Shanghai Synchrotron Radiation Facility（SSRF） x ray imaging beamline, we know lots of user experiments will rely on a large range of spatial resolutions and fields of view（FOVs）. In particular, x ray microscopes with a large FOV and a moderate spatial resolution of around 100 nm have a wide range of applications in many research fields. Driven by user requirements, a dedicated FXNI system is designed and constructed at the SSRF. This microscope is based on a beam shaper and a zone plate, with the optimized working energy range set to 8–10 ke V. The experimental test results by a Siemens star pattern demonstrate that a spatial resolution of 100 nm is achieved, while an FOV of50 μm is obtained.