Nanoscale Accuracy Research Articles

BNP-Track: a framework for superresolved tracking

Superresolution tools, such as PALM and STORM, provide nanoscale localization accuracy by relying on rare photophysical events, limiting these methods to static samples. By contrast, here, we extend superresolution to dynamics without relying on photodynamics by simultaneously determining emitter numbers and their tracks (localization and linking) with the same localization accuracy per frame as widefield superresolution on immobilized emitters under similar imaging conditions (≈50 nm). We demonstrate our Bayesian nonparametric track (BNP-Track) framework on both in cellulo and synthetic data. BNP-Track develops a joint (posterior) distribution that learns and quantifies uncertainty over emitter numbers and their associated tracks propagated from shot noise, camera artifacts, pixelation, background and out-of-focus motion. In doing so, we integrate spatiotemporal information into our distribution, which is otherwise compromised by modularly determining emitter numbers and localizing and linking emitter positions across frames. For this reason, BNP-Track remains accurate in crowding regimens beyond those accessible to other single-particle tracking tools.

Millipixel accuracy optical localization for point-like targets on pixelated image sensors

Localizing point-like targets, such as stars and single molecules on pixelated image sensors, are of great importance in optical measurement fields, including astronomy and microscopy. To date, a localization accuracy of 0.01 pixels has been considered high in practical applications. It is difficult to assess or achieve a higher accuracy (e.g., millipixel level) using experimental data due to noise from conventional setups or environment. Here, we propose a millipixel-scale localization accuracy assessment and realization method. The method combines organic light emitting diode subpixel precise motion control and large-ratio optical scaling to form spot array motion with ultrahigh accuracy in digital images for localization assessment and uses effective point spread function (PSF) modeling and maximum likelihood estimation fitting to realize millipixel localization performance. A localization accuracy better than 0.001 pixels has been demonstrated on two types of practical spots. The work not only provides an experimental assessment method for localization techniques with ultrahigh accuracy but also verifies the ability of optical localization as a powerful tool to measure 2D displacements at nano-scale accuracy in advanced manufacturing.

Growth of two-dimensional covalent organic frameworks on substrates: insight from microsecond atomistic simulations.

While growing two-dimensional covalent organic frameworks (2D COFs) on substrates holds promise for producing functional monolayers, the presence of many defects in the resulting crystals often hinders their practical applications. Achieving structural order while suppressing defect formation necessitates a detailed atomic-level understanding. The key lies in understanding the polymerization process with high nano-scale accuracy, which presents significant challenges. Here, we perform microsecond atomistic molecular dynamics simulations to describe the deposition and polymerization of cyclohexa-m-phenylene on metal substrates, closely mimicking experimental conditions. Our improved approach highlights that 2D polymerization occurs through monomer addition and island coalescence, with a pre-bonding stage allowing monomers/oligomers to dynamically adjust their configurations to the expanding island structures. Our results elucidate the mechanisms underlying the formation of vacancy and dislocation defects during 2D polymerization as well as their healing processes. Overall, our findings underscore the significant roles that high surface mobility, effective monomer-substrate anchoring, high framework rigidity, moderate monomer coordination, and low bonding rate play in forming large, extended 2D crystals while suppressing vacancy and dislocation defects. We demonstrate how these factors can be tuned through substrate selection, deposition rate modulation, and temperature control, thereby offering valuable insight for strategically optimizing on-surface 2D polymerizations.

Single Photon Emitters in Hexagonal Boron Nitride Fabricated by Focused Helium Ion Beam

AbstractThe 2D layered hexagonal boron nitride (hBN) material is a promising platform for making single photon emitters (SPEs). Integrate SPEs with photonic cavities or waveguides, requires the deterministic positioning of these emitters as accurately as possible. Among all of the alternative techniques, He+ focused ion beam (FIB) theoretically has sub‐nanometer precision, but its practical positioning accuracy in processing SPEs is limited by the inevitable detrimental byproduct defects. So far, it remains challenging to achieve an accuracy below 100 nm for the positioning of SPEs in hBN. Here, we present a two‐step method for creating SPEs at the predetermined positions in hBN that combines the He+ FIB irradiation and thermal annealing under an oxygen atmosphere. With this method, we have realized the positioning accuracy of less than 50 nm, which, to the best of our knowledge, stands as the highest among the currently available hBN SPEs preparation methods. Moreover, the SPE conversion yield was over 35% and the emission brightness of individual SPE achieved up to 3 × 105 counts/s at room temperature. These SPEs fabricated precisely with nanoscale accuracy in hBN are expected to be good candidates for making large‐scale integrated SPEs in photonic circuits.

Influence of Gold Nanoparticle Shape and Single-Cell Localization on Energy Deposition Efficiency and Irradiation Specificity in Photon Radiotherapy

Gold nanoparticles (AuNPs) have been investigated extensively in the past twenty years as a sensitizing agent in photon radiotherapy. Targeted delivery of AuNPs to specific sites in cells and tissues contributes to highly localized radiation dose enhancement, whereby the surrounding healthy structures can be largely spared from the unwanted radiation effects. The efficiency of introduced AuNPs with regard to dose enhancement depends on the properties of the nanoparticles since not all of deposited radiation energy reaches the intended biological target but is partially absorbed within the nanoparticles themselves or distributed elsewhere. The present paper investigates the influence of AuNP shape and localization on the enhancement and intracellular distribution of deposited energy in radiation therapy with photons. Energy deposition patterns are calculated with nanoscale accuracy through Monte Carlo simulations of radiation transport, which are optimized to accommodate a structured geometrical representation of the region loaded with AuNPs, i.e., to allow discrete modeling of individual nanoparticles. Same-volume nanoparticles of three commonly encountered shapes—nanospheres, nanorods, and square nanoplates—are examined, in order to inspect the differences in the propagation and absorption of secondary charged particles produced by the incident photons. Five different spatial distributions of spherical AuNPs at the single-cell level are studied in the simulations and compared according to the energy deposited in the cell nucleus. Photon energy, nanoparticle size, and concentration are also varied across simulation runs, and their influence is analyzed in connection to nanoparticle shape and localization. The obtained results reveal how the investigated nanoparticle properties affect their dose-enhancing ability and irradiation specificity in AuNP-augmented radiotherapy.

Fuzzy adaptive terminal sliding mode control based on recurrent neural network compensation for a maglev system

Reluctance motor has high force density while strong uncertainties. This paper concentrates on the research of the intelligent control method for a reluctance-motor maglev system (RMMS) with limited system information. To this end, we propose a new fuzzy adaptive terminal sliding mode control (FATSMC) method based on a novel full-regulated recurrent neural network (RNN) compensator. The RNN approximates the lumped uncertainty of the RMMS, and the controller handles the residual error and external disturbances. The presented increasing–decreasing fuzzy adaptive law, without the prior knowledge of uncertain upper bound, adjusts the switching gain by the dynamic information of the system. And the overestimation of the switching gain can be reduced. Moreover, the proposed method only uses the nominal parameters and model of the RMMS, thus avoiding complex modeling. This study provides strong support for the application of RMMS in high-precision situations. By constructing a Lyapunov function, the stability of the proposed method is analyzed, which is uniformly and ultimately bounded (UUB). In the experiment, the proposed method is compared with three existing methods in four cases. The results demonstrate that the presented method achieves nanoscale suspension accuracy, suppresses chattering significantly, and has strong robustness.

Magnetic field imaging by hBN quantum sensor nanoarray

Placing a sensor close to the target at the nano-level is a central challenge in quantum sensing. We demonstrate magnetic field imaging with a boron vacancy (VB−) defects array in hexagonal boron nitride with a few 10 nm thickness. VB− sensor spots with a size of (100 nm)2 are arranged periodically with nanoscale accuracy using a helium ion microscope and attached tightly to a gold wire. The sensor array allows us to visualize the magnetic field induced by the current in the straight micro wire with a high spatial resolution. Each sensor exhibits a practical sensitivity of 73.6 μT/Hz0.5, suitable for quantum materials research. Our technique of arranging VB− quantum sensors periodically and tightly on measurement targets will maximize their potential.

Unravelling the Drug Encapsulation Ability of Functional DNA Origami Nanostructures: Current Understanding and Future Prospects on Targeted Drug Delivery.

Rapid breakthroughs in nucleic acid nanotechnology have always driven the creation of nano-assemblies with programmable design, potent functionality, good biocompatibility, and remarkable biosafety during the last few decades. Researchers are constantly looking for more powerful techniques that provide enhanced accuracy with greater resolution. The self-assembly of rationally designed nanostructures is now possible because of bottom-up structural nucleic acid (DNA and RNA) nanotechnology, notably DNA origami. Because DNA origami nanostructures can be organized precisely with nanoscale accuracy, they serve as a solid foundation for the exact arrangement of other functional materials for use in a number of applications in structural biology, biophysics, renewable energy, photonics, electronics, medicine, etc. DNA origami facilitates the creation of next-generation drug vectors to help in the solving of the rising demand on disease detection and therapy, as well as other biomedicine-related strategies in the real world. These DNA nanostructures, generated using Watson-Crick base pairing, exhibit a wide variety of properties, including great adaptability, precise programmability, and exceptionally low cytotoxicity in vitro and in vivo. This paper summarizes the synthesis of DNA origami and the drug encapsulation ability of functionalized DNA origami nanostructures. Finally, the remaining obstacles and prospects for DNA origami nanostructures in biomedical sciences are also highlighted.

Fourier ptychographic topography.

Topography measurement is essential for surface characterization, semiconductor metrology, and inspection applications. To date, performing high-throughput and accurate topography remains challenging due to the trade-off between field-of-view (FOV) and spatial resolution. Here we demonstrate a novel topography technique based on the reflection-mode Fourier ptychographic microscopy, termed Fourier ptychograhpic topography (FPT). We show that FPT provides both a wide FOV and high resolution, and achieves nanoscale height reconstruction accuracy. Our FPT prototype is based on a custom-built computational microscope consisting of programmable brightfield and darkfield LED arrays. The topography reconstruction is performed by a sequential Gauss-Newton-based Fourier ptychographic phase retrieval algorithm augmented with total variation regularization. We achieve a synthetic numerical aperture (NA) of 0.84 and a diffraction-limited resolution of 750 nm, increasing the native objective NA (0.28) by 3×, across a 1.2 × 1.2 mm2 FOV. We experimentally demonstrate the FPT on a variety of reflective samples with different patterned structures. The reconstructed resolution is validated on both amplitude and phase resolution test features. The accuracy of the reconstructed surface profile is benchmarked against high-resolution optical profilometry measurements. In addition, we show that the FPT provides robust surface profile reconstructions even on complex patterns with fine features that cannot be reliably measured by the standard optical profilometer. The spatial and temporal noise of our FPT system is characterized to be 0.529 nm and 0.027 nm, respectively.

Design of a redundant actuated 4-PPR planar 3-DOF compliant nanopositioning stage

The compliant planar positioning stage actuated by voice coil motors can obtain nanoscale motion accuracy within a millimeter motion range and has received increasing attention in precision engineering. However, there is always a contradiction between the actuation force and the output stiffness in the design of the stage. This study presents the design of a novel redundant actuated planar 3-DOF-compliant nanopositioning stage. A redundant actuated configuration can increase the output stiffness of the stage and decrease the peak actuating force. The analytical stiffness model, kinetostatic model, and dynamic model of the stage are established, which illustrate the high force transmission efficiency and dynamic decoupling feature of the stage. The geometric parameters were optimized based on the established models, and model validation and performance evaluation of the stage were conducted via finite element analysis. Finally, a prototype positioning stage is fabricated. Experimental results show that the proposed stage can achieve a motion range of up to ±2.5 mm × ±2.5 mm × ±2.5° with a resolution of 80 nm and 0.28″, and the tracking error ratio for a composite Lissajous trajectory is within 0.102%.

Accuracy improvement of surface measurement through phase correction in spectrally resolved interferometer

The spectrally resolved interferometer (SRI) is used to measure the surface profile by the linear fitting line of its phase distribution of spectral interference signal. However, the noise existed in the phase cannot be ignored if the nano-scale measurement accuracy is required. In this paper, a novel algorithm is proposed to improve the measurement accuracy by using the constant term oflinear fitting line of phase distribution in wavenumber domain. The simulations indicate that the algorithm achieves the similar measurement accuracy under the influence of three kinds of noise. Even though the proposed algorithm has the possibility of 4% to bring the additional minor error, it provides a better performance on measurement of entire surface in different SNRs compared with the other two common algorithms. In experiments, the variations of surface less than 10 nm and 30 nm and the repeatability of 2.2 nm and 4.9 nm are obtained in the measurements of a protected aluminium mirror with and without proposed algorithm. A smooth profile with a step shape of nearly 3 μm height is tested, where the maximum repeatability of step height and maximum magnitude of variations of the surfaces reaches to 3.8 nm and 10 nm from the 15.3 nm and 30 nm by using this algorithm. Both the simulations and experimental results demonstrate that the proposed algorithm is feasible for high-precision measurement.

Printed Hybrid Upconversion/Perovskite Nanoparticle Cluster and Its Individual Photoluminescence Imaging

AbstractA versatile strategy to print hybrid upconversion/perovskite nanoparticle clusters based on nanoxerography has been developed. The individual hybrid cluster can be tuned by different upconversion nanoparticles (UCNPs), perovskite quantum dots (QDs), and their combinations to visualize multicolor. Based on the precise positioning of the array system, the structural and optical properties of each cluster in the array can be in situ and simultaneously characterized. This approach provides a straightforward and robust platform for high‐throughput preparation and characterization of the hybrid clusters, and the ability to position functional nanoparticles at a desired area with nanoscale accuracy exhibits great potential in fabricating advanced nanodevices.

DNA Origami‐Based Single‐Molecule CRISPR Machines for Spatially Resolved Searching

AbstractRepurposing the RNA‐guided endonuclease Cas9 to develop artificial CRISPR molecular machines represents a new direction toward synthetic molecular information processing. The operation of CRISPR‐Cas9‐based machines, nevertheless, relies on the molecular recognition of freely diffused sgRNA/Cas9, making it practically challenging to perform spatially regulated localized searching or navigation. Here, we develop a DNA origami‐based single‐molecule CRISPR machine that can perform spatially resolved DNA cleavage via either free or localized searching modes. When triggered at a specific site on the DNA origami with nanoscale accuracy, the free searching mode leads to searching activity that gradually decays with the distance, whereas the localized mode generates spatially‐confined searching activity. Our work expands the function of CRISPR molecular machines and lays foundations to develop integrated molecular circuits and high‐throughput nucleic acid detection.

DNA Origami-Based Single-Molecule CRISPR Machines for Spatially Resolved Searching.

Repurposing the RNA-guided endonuclease Cas9 to develop artificial CRISPR molecular machines represents a new direction toward synthetic molecular information processing. The operation of CRISPR-Cas9-based machines, nevertheless, relies on the molecular recognition of freely diffused sgRNA/Cas9, making it practically challenging to perform spatially regulated localized searching or navigation. Here, we develop a DNA origami-based single-molecule CRISPR machine that can perform spatially resolved DNA cleavage via either free or localized searching modes. When triggered at a specific site on the DNA origami with nanoscale accuracy, the free searching mode leads to searching activity that gradually decays with the distance, whereas the localized mode generates spatially-confined searching activity. Our work expands the function of CRISPR molecular machines and lays foundations to develop integrated molecular circuits and high-throughput nucleic acid detection.

Simultaneous thickness and surface profiling of blank mask and its experimental verification using robust harmonic fringe-iterative algorithm and Fizeau interferometer

The quality of blank masks should be assessed with nano-scale accuracy to achieve the efficiency improvement of semiconductor devices. In this study, we proposed a harmonic fringe-iterative method that uses seven-frame interferograms for simultaneous thickness and surface assessment of blank masks. The incorporation of the noble convergence formula and pixel array into the proposed method was found to eliminate harmonics-related errors and significantly increase the computational ability. For verification, the numerical simulation and simultaneous assessment of a blank mask using a multi-surface Fizeau interferometer with wavelength scanning were performed using a seven-frame harmonic fringe-iterative method. The results of the simulations and experiments verify that the harmonic fringe-iterative method has a better phase-extraction ability than the conventional fringe-iterative and Fourier window methods in terms of computational ability and suppression of non-target harmonic signals and nonlinearity of phase-modulation errors.

Dynamic Augmented Reality Display by Layer‐Folded Metasurface via Electrical‐Driven Liquid Crystal

AbstractHeading toward the next‐generation versatile meta‐devices and meta‐systems with increasing complexity, it inevitably demands the cascading and coupling between multi‐layer metasurfaces to create new design space for meta‐optics. However, the accurate requirement for multilayer alignment at the nanoscale is significantly challenging due to the actual fabrication limitation, thus hindering the state‐of‐the‐art meta‐optics device integration and its practical application. Herein, a dynamic meta‐system for augmented reality (AR) holographic display functionality based on a layer‐folded metasurface integrated with an electrical‐driven liquid crystal (LC) platform is originally proposed and realized. By ingeniously folding the optical path between meta‐device vertical space, a beam‐steering metasurface in parallel with the other two holographic metasurfaces placed on a single surface is successfully cascaded. Such a layer‐folded scheme enjoys single‐time lithography processing for multi‐patterning with nanoscale alignment accuracy and avoids any vertical alignment issue. Furthermore, by combining with an electrical‐driven LC tuning scheme, the integrated meta‐system could actively switch independent‐encoded holographic images in real‐time floating in the actual‐world scene. Overall, it is envisioned that such a compact dynamic meta‐system suggests a feasible route for dynamic tunable wearable AR displays, intelligent dynamic displays, multi‐functional devices, etc.

Programmable DNA Circuits for Flexible and Robust Exciton-Plasmon Interaction-Based Photoelectrochemical Biosensing.

DNA circuits as one of the dynamic nanostructures can be rationally designed and show amazing geometrical complexity and nanoscale accuracy, which are becoming increasingly attractive for DNA entropy-driven amplifier design. Herein, a novel and elegant exciton-plasmon interaction (EPI)-based photoelectrochemical (PEC) biosensor was developed with the assistance of a programmable entropy-driven DNA amplifier and superparamagnetic nanostructures. Low-abundance miRNA-let-7a as a model can efficiently initiate the operation of the entropy-driven DNA amplifier, and the released output DNAs can open the partially hybridized double-stranded DNA anchored on Fe3O4@SiO2 particles. The liberated Au nanoparticles (NPs)-cDNA can completely hybridize with CdSe/ZnS quantum dots (QDs)-cDNA-1 and result in proportionally decreased photocurrent of CdSe/ZnS QDs-cDNA-1. This unique entropy-driven amplification strategy is beneficial for reducing the reversibility of each step reaction, enables the base sequence invariant and the reaction efficiency improvement, and exhibits high thermal stability and specificity as well as flexible design. These features grant the PEC biosensor with ultrasensitivity and high selectivity. Also, instead of solid-liquid interface assembly for conventional EPI-based PEC biosensors, herein, DNA hybridization in the solution phase enables the improved hybridization efficiency and sensitivity. In addition, superparamagnetic Fe3O4@SiO2 particles further ensure the enhancement of the selectivity and reliability of the as-designed PEC biosensor. Particularly, this single-step electrode modification procedure evidently improves the electrode fabrication efficiency, reproducibility, and stability.

29. Nanomapping with Cas9: A new high-resolution and efficient method for characterizing chromosomal rearrangements

Improvements in the genomic tools available for detecting chromosomal rearrangements (CREA) have resulted in the recognition of many new pathognomonic CREA/cancer associations, with these discoveries providing a basis for the development of new treatment modalities and prognostic stratifications. Excitement regarding the application of this CREA knowledge for patient management is accompanied by the recognition of a growing need for an improved assay that can yield a precise, high-resolution characterization of these CREA in a manner that is time-, cost- and specimen-use-efficient. To address this need, we developed “nanomapping”: a technique in which we (1) develop a unique “barcode” for a region of interest using nuclease-inhibited Cas9 molecules as stable and specific programmable labels; and (2) measure the lengths of DNA fragments and distances between Cas9 landmarks with nanoscale accuracy using high-speed atomic force microscopy. By comparing the barcode to a reference sequence, one can identify alterations in “long read” (≥100kb) DNA molecules at high speed and low cost ($1 per sample). To adapt this technique for CREA characterization, we: (1) used inverse PCR to amplify a translocation site of interest with multiplexed endonucleases to yield a characteristic profile of amplicon lengths; (2) nanomapped the resulting amplicons; and (3) compared the nanomaps to predicted reference maps generated in silico to obtain precise (high accuracy/specificity) identification of the chromosomal origin/breakpoints of fusion partners. As “proof of principle” for the utility of this new assay, to date, we have correctly identified IGH fusion partners in 4 neoplasms (including IGH/BCL2 translocations in 3/3 specimens and an IGH/MAFB translocation in 1/1 specimen). In summary, our data demonstrates the feasibility of using nanomapping to characterize CREA that have recurrent breakpoints. Moreover, it not only provides a means for enhancing our efficiency/accuracy in known CREA identification, but has potential to allow for the recognition of novel CREA.

Deep learning-based moiré-fringe alignment with circular gratings for lithography.

In lithography, misalignment measurement with a large range and high precision in two dimensions for the overlay is a fundamental but challenging problem. For moiré-based misalignment measurement schemes, one potential solution is considered to be the use of circular gratings, whose formed moiré fringes are symmetric, isotropic, and aperiodic. However, due to the absence of proper analytical arithmetic, the measurement accuracy of such schemes is in the tens of nanometers, resulting in their application being limited to only coarse alignments. To cope with this problem, we propose a novel deep learning-based misalignment measurement strategy inspired by deep convolutional neural networks. The experimental results show that the proposed scheme can achieve nanoscale accuracy with micron-scale circular alignment marks. Relative to the existing strategies, this strategy has much higher precision in misalignment measurement and much better robustness to fabrication defects and random noise. This enables a one-step two-dimensional nanoscale alignment scheme for proximity, x-ray, extreme ultraviolet, projective, and nanoimprint lithographies.

Arrays of Si vacancies in 4H-SiC produced by focused Li ion beam implantation

Point defects in SiC are an attractive platform for quantum information and sensing applications because they provide relatively long spin coherence times, optical spin initialization, and spin-dependent fluorescence readout in a fabrication-friendly semiconductor. The ability to precisely place these defects at the optimal location in a host material with nano-scale accuracy is desirable for integration of these quantum systems with traditional electronic and photonic structures. Here, we demonstrate the precise spatial patterning of arrays of silicon vacancy ({V}_{Si}) emitters in an epitaxial 4H-SiC (0001) layer through mask-less focused ion beam implantation of Li+. We characterize these arrays with high-resolution scanning confocal fluorescence microscopy on the Si-face, observing sharp emission lines primarily coming from the {V1}^{{prime}} zero-phonon line (ZPL). The implantation dose is varied over 3 orders of magnitude, leading to {V}_{Si} densities from a few per implantation spot to thousands per spot, with a linear dependence between ZPL emission and implantation dose. Optically-detected magnetic resonance (ODMR) is also performed, confirming the presence of V2 {V}_{Si}. Our investigation reveals scalable and reproducible defect generation.