Model-free robust motion control for biological optical microscopy using time-delay estimation with an adaptive RBFNN compensator.

The field of large numerical aperture microscopy has witnessed significant advancements in spatial and temporal resolution, as well as improvements in optical microscope imaging quality. However, these advancements have concurrently raised the demand for enhanced precision, extended range, and increased load-bearing capacity in objective motion carrier (OMC). To address this challenge, this study introduces an innovative OMC that employs a ball screw mechanism as its primary driving component. Furthermore, a robust nonlinear motion control strategy has been developed, which integrates fast nonsingular terminal sliding mode, experimental estimation techniques, and adaptive radial basis neural network, to mitigate the impact of nonlinear friction within the ball screw mechanism on motion precision. The stability of the closed-loop control system has been rigorously demonstrated through Lyapunov theory. Compared with other enhanced sliding mode control strategies, the maximum error and root mean square error of this controller are improved by 33% and 34% respectively. The implementation of the novel OMC has enabled the establishment of a high-resolution bio-optical microscope, which has proven its effectiveness in the microscopic imaging of retinal organoids.

The power of super-resolution microscopy in modern biomedical science.

Super-resolution microscopy (SRM) technology that breaks the diffraction limit has revolutionized the field of cell biology since its appearance, which enables researchers to visualize cellular structures with nanometric resolution, multiple colors and single-molecule sensitivity. With the flourishing development of hardware and the availability of novel fluorescent probes, the impact of SRM has already gone beyond cell biology and extended to nanomedicine, material science and nanotechnology, and remarkably boosted important breakthroughs in these fields. In this review, we will mainly highlight the power of SRM in modern biomedical science, discussing how these SRM techniques revolutionize the way we understand cell structures, biomaterials assembly and how assembled biomaterials interact with cellular organelles, and finally their promotion to the clinical pre-diagnosis. Moreover, we also provide an outlook on the current technical challenges and future improvement direction of SRM. We hope this review can provide useful information, inspire new ideas and propel the development both from the perspective of SRM techniques and from the perspective of SRM's applications.

Superoscillation focusing with suppressed sidebands by destructive interference.

Optical superoscillation, a phenomenon that the local optical field can oscillate much faster than that allowed by its highest harmonic, can significantly overcome the Abbe diffraction limit. However, as the spot size is compressed below the superoscillation criteria of 0.38λ/NA, huge sidebands will inevitably appear around the central lobe with intensity hundreds of times higher than that of the central lobe. Here, we propose an approach to realize superoscillation by using destructive interference. The central lobe size can be compressed beyond the superoscillation criteria without formation of strong sidebands by destructive interference between focused fields. Such a super-resolution metalens can find its application in label-free far-field super-resolution microscopy.

Monitoring the distribution of internalized silica nanoparticles inside cells via direct stochastic optical reconstruction microscopy.

Understanding the exact localization of nanoparticles within cell is of particular importance for rational design of high-effective nanomedicines. In the present study, direct stochastic optical reconstruction microscopy (dSTORM) is employed to elucidate the precise localization of nanoparticles within cells owing to its superiority of nanometric resolution, multicolour ability and minimal invasiveness. The localization of the Cy5 labelled mesoporous silica nanoparticles (MSNs-Cy5) in MCF-7 cells are monitored by dSTORM and conventional fluorescence microscopy, respectively. The dSTORM images demonstrate much higher spatial resolution for locating MSNs-Cy5 within cells compared to that of the conventional fluorescence images. Moreover, the distribution of MSNs-Cy5 within three cell lines over time are obtained. For the MCF-7 and HeLa cells, MSNs-Cy5 nanoparticles distribute nearly all around the cytoplasm after 5 h incubation. In contrast, MSNs-Cy5 nanoparticles within NIH 3T3 cells are quite different that they are found to be either attached to or embedded into cell membranes, without penetrating into the cytoplasm. Overall, we provide a practical method to reveal the in situ precise imaging of nanoparticles in cells with nanometric resolution precision. This method may open up new opportunities for organelle-specific targeting drug delivery to achieve maximum therapeutic benefit.

Dopamine-Mediated Biomineralization of Calcium Phosphate as a Strategy to Facilely Synthesize Functionalized Hybrids.

Organic-inorganic hybrid materials have been considered to be promising carriers or immobilization matrixes for biomolecules due to their high efficiency and significantly enhanced activities and stabilities of biomolecules. Here, the well-defined dopamine/calcium phosphate organic-inorganic hybrids (DACaPMFs) are fabricated via one-pot dopamine-mediated biomineralization, and their structure and properties are also characterized. Direct stochastic optical reconstruction microscopy (dSTORM) is first used to probe the distribution of organic components in these hybrids. Combined with spectroscopic data, the direct observation of dopamine in the hybrids helps to understand the formation of a physical chemistry mechanism of the biomineralization. The obtained DACaPMFs with multiple-level pores allow the loading of doxorubicin with a high loading efficiency and a pH-responsive property. Furthermore, thrombin is entrapped by the hybrids to prove the controlled release. It is expected that such organic-inorganic hybrid materials may hold great promise for application in drug delivery as well as scaffold materials in bone tissue engineering and hemostatic material.

Programmable Dynamic Shapes with a Swarm of Light-Powered Colloidal Motors.

We report robust control over the dynamic assembly, disassembly, and reconfiguration of light-activated molybdenum disulfide (MoS2 ) colloidal motor swarms with features not possible in equilibrium systems. A photochemical reaction produces chemical gradients across the MoS2 colloidal motors to drive them to move. Under illumination of a gradient light, these colloidal motors display a positive phototactic motion. Mesoscale simulations prove that the self-diffusiophoresis induced by the locally consumed oxygen gradient across MoS2 colloidal motors dominates the phototactic process. By programming the structured illumination, the collective migration and well-defined shapes of colloidal motor swarms can be externally regulated. The successful realization of programmable swarm transformation of colloidal motors like the emergent behaviors of living systems in nature provides a direct proof-of-concept for active soft materials and systems, with adaptive and interactive functions.

Cofactor-free oxidase-mimetic nanomaterials from self-assembled histidine-rich peptides.

Natural oxidases mainly rely on cofactors and well-arranged amino acid residues for catalysing electron-transfer reactions but suffer from non-recovery of their activity upon externally induced protein unfolding. However, it remains unknown whether residues at the active site can catalyse similar reactions in the absence of the cofactor. Here, we describe a series of self-assembling, histidine-rich peptides, as short as a dipeptide, with catalytic function similar to that of haem-dependent peroxidases. The histidine residues of the peptide chains form periodic arrays that are able to catalyse H2O2 reduction reactions efficiently through the formation of reactive ternary complex intermediates. The supramolecular catalyst exhibiting the highest activity could be switched between inactive and active states without loss of activity for ten cycles of heating/cooling or acidification/neutralization treatments, demonstrating the reversible assembly/disassembly of the active residues. These findings may aid the design of advanced biomimetic catalytic materials and provide a model for primitive cofactor-free enzymes.

Dynamic Detection of Active Enzyme Instructed Supramolecular Assemblies In Situ via Super-Resolution Microscopy.

Inspired by the self-assembly phenomena in nature, the instructed self-assembly of exogenous small molecules in a biological environment has become a prevalent process to control cell fate. Despite mounting examples of versatile bioactivities, the underlying mechanism remains less understood, which is in large hindered by the difficulties in the identification of those dynamic assemblies in situ. Here, with direct stochastic optical reconstruction microscopy, we are able to elucidate the dynamic morphology transformation of the enzyme-instructed supramolecular assemblies in situ inside cancer cells with a resolution below 50 nm. It indicates that the assembling molecules endure drastically different pathways between cell lines with different phosphatase activities and distribution. In HeLa cells, the direct formation of intracellular supramolecular nanofibers showed slight cytotoxicity, which was due to the possible cellular secretory pathway to excrete those exogenous molecules assemblies. In contrast, in Saos-2 cells with active phosphatase on the cell surface, assemblies with granular morphology first formed on the cell membranes, followed by a transformation into nanofibers and accumulation in cells, which induced Saos-2 cell death eventually. Overall, we provided a convenient method to reveal the in situ dynamic nanomorphology transformation of the supramolecular assemblies in a biological environment, in order to decipher their diverse biological activities.

An extravascular fluid transport system based on structural framework of fibrous connective tissues in human body.

OBJECTIVE: Interstitial fluid in extracellular matrices may not be totally fixed but partially flow through long-distance oriented fibrous connective tissues via physical mechanisms. We hypothesized there is a long-distance interstitial fluid transport network beyond vascular circulations. MATERIALS AND METHODS: We first used 20 volunteers to determine hypodermic entrant points to visualize long-distance extravascular pathway by MRI. We then investigated the extravascular pathways initiating from the point of thumb in cadavers by chest compressor. The distributions and structures of long-distance pathways from extremity ending to associated visceral structures were identified. RESULTS: Using fluorescent tracer, the pathways from right thumb to right atrium wall near chest were visualized in seven of 10 subjects. The cutaneous pathways were found in dermic, hypodermic and fascial tissues of hand and forearm. The perivascular pathways were along the veins of arm, axillary sheath, superior vena cava and into the superficial tissues on right atrium. Histological and micro-CT data showed these pathways were neither blood nor lymphatic vessels but long-distance oriented fibrous matrices, which contained the longitudinally assembled micro-scale fibres consistently from thumb to superficial tissues on right atrium. CONCLUSIONS: These data revealed the structural framework of the fibrous extracellular matrices in oriented fibrous connective tissues was of the long-distance assembled fibres throughout human body. Along fibres, interstitial fluid can systemically transport by certain driving-transfer mechanisms beyond vascular circulations.

Assembled Vitamin B2 Nanocrystals with Optical Waveguiding and Photosensitizing Properties for Potential Biomedical Application.

Great success has been achieved in recent years in the development of synthetic or assembled nanobiomaterials. Among these, biomolecule-based nanoarchitectures with special optical property are of particular interest. Here, we demonstrate that vitamin B2 nanocrystals assembled as nanorods can be obtained with precise control. Excitingly, such one-dimensional nanostructures not only exhibit intrinsic optical waveguiding properties but also the ability to sensitize oxygen to produce reactive oxygen species. With these properties, we applied the obtained vitamin B2 nanorods under remotely localized light illumination into single tumour cells in vitro for anticancer photodynamic therapy. Further, vitamin B2 nanorods were explored for in vivo photodynamic therapy by using a tumour model. With such bionanostructures, new features and functions of vitamin B2 and its derivatives have been developed.

Broadband quarter-wave birefringent meta-mirrors for generating sub-diffraction vector fields.

Independent manipulation of phase and polarization of optical fields is of great interest in various applications, including vector-field generation, optical tweezers, and nanolithography. The integration of phase and polarization manipulation on a single optical device may greatly simplify optical systems and eases optical alignment. In this Letter, a family of reflective cross-shaped quarter-wave birefringent metasurfaces is proposed to achieve full control of polarization and phase of reflected waves. Based on the proposed metasurfaces, two meta-mirrors are designed with integrated functions of polarization conversion and sub-diffraction focusing. Numerical investigations also reveal the achromatic focusing performance of the two meta-mirrors. The proposed metasurfaces with independent manipulation of polarization and phase provide flexible building blocks for constructing complicated vector optical fields.

Unidirectional Branching Growth of Dipeptide Single Crystals for Remote Light Multiplication and Collection.

Herein, we report on the unidirectional branched assembly of diphenylalanine dipeptide through a one-step rapid evaporation process. Large numbers of crystalline tubular branches with smooth surfaces are developed from a hexagonal solid microrod mimicking a "Christmas tree". Density functional theory suggests the formation of tubular diphenylalanine aggregates with cis isomers. The diphenylalanine branched assembly shows good optical waveguide properties that can transmit light homogeneously along the crystal fibers as well as harvest light from the tips of branches to the microrod terminals. These findings hold importance in the development of bioinspired optical fibers for information transmission in a microscale.

Optimization-free approach for generating sub-diffraction quasi-non-diffracting beams.

Sub-diffraction quasi-non-diffracting beams with sub-wavelength transverse size are attractive for applications such as optical nano-manipulation, optical nano-fabrication, optical high-density storage, and optical super-resolution microscopy. In this paper, we proposed an optimization-free design approach and demonstrated the possibility of generating sub-diffraction quasi-non-diffracting beams with sub-wavelength size for different polarizations by a binary-phase Fresnel planar lens. More importantly, the optimization-free method significantly simplifies the design procedure and the generation of sub-diffracting quasi-non-diffracting beams. Utilizing the concept of normalized angular spectrum compression, for wavelength λ0 = 632.8 nm, a binary-phase Fresnel planar lens was designed and fabricated. The experimental results show that the sub-diffraction transverse size and the non-diffracting propagation distances are 0.40λ0-0.54λ0 and 90λ0, 0.43λ0-0.54λ0 and 73λ0, and 0.34λ0-0.41λ0 and 80λ0 for the generated quasi-non-diffracting beams with circular, longitudinal, and azimuthal polarizations, respectively.

Self-Propelled Nanomotors for Thermomechanically Percolating Cell Membranes.

We report a near-infrared (NIR) light-powered Janus mesoporous silica nanomotor (JMSNM) with macrophage cell membrane (MPCM) cloaking that can actively seek cancer cells and thermomechanically percolate cell membrane. Upon exposure to NIR light, a heat gradient across the Janus boundary of the JMSNMs is generated by the photothermal effect of the Au half-shells, resulting in a self-thermophoretic force that propels the JMSNMs. In biological medium, the MPCM camouflaging can not only prevent dissociative biological blocks from adhering to JMSNMs but also improve the seeking sensitivity of the nanomotors by specifically recognizing cancer cells. The biofriendly propulsion and recognition capability enable JMSNMs to achieve the active seeking and bind to the membrane of cancer cells. Subsequent illumination with NIR then triggers the photothermal effect of MPCM@JMSNMs to thermomechanically perforate the cytomembranes for guest molecular injection. This approach integrates the functions of active seeking, cytomembranes perforating, and thermomechanical therapy in nanomotors, which may pave the way to apply self-propelled motors in biomedical fields.

Generating a three-dimensional hollow spot with sub-diffraction transverse size by a focused cylindrical vector wave.

A three-dimensional (3D) hollow spot is of great interest for a wide variety of applications such as microscopy, lithography, data storage, optical manipulation, and optical manufacturing. Based on conventional high-numerical-aperture objective lenses, various methods have been proposed for the generation of 3D hollow spots for different polarizations. However, conventional optics are bulky, costly, and difficult to integrate. More importantly, they are diffraction-limited in nature. Owing to their unique properties of small size, light weight, and ease of integration, planar lenses have become attractive as components in the development of novel optical devices. Utilizing the concept of super-oscillation, planar lenses have already shown great potential in the generation of sub-diffraction, or even of super-oscillatory features, in propagating optical waves. In this paper, we propose a binary-phase planar lens with an ultra-long focal length (300λ) for the generation of a 3D hollow spot with a cylindrical vector wave. In addition, we experimentally demonstrate the formation of such a hollow spot with a sub-diffraction transverse size of 0.546λ (smaller than the diffraction limit of 0.5λ/NA, where NA denotes the lens numerical aperture) and a longitudinal size of 1.585λ. The ratio of central minimum intensity to the central ring peak intensity is less than 3.7%. Such a planar lens provides a promising way to achieve tight 3D optical confinement for different uses that might find applications in super-resolution microscopy, nano-lithography, high-density data storage, nano-particle optical manipulation, and nano-optical manufacturing.

Magnetic Mesoporous Silica Nanoparticles Cloaked by Red Blood Cell Membranes: Applications in Cancer Therapy.

Targeted drug delivery is an emerging technological strategy that enables nanoparticle systems to be responsive for tumor therapy. Magnetic mesoporous silica nanoparticles (MMSNs) were cloaked with red blood cell membrane (RBC). This integrates long circulation, photosensitizer delivery, and magnetic targeting for cancer therapy. In vivo experiments demonstrate that RBC@MMSNs can avoid immune clearance and achieve magnetic field (MF)-induced high accumulation in a tumor. When light irradiation is applied, singlet oxygen rapidly generates from hypocrellin B (HB)-loaded RBC@MMSN and leads to the necrosis of tumor tissue. Such a RBC-cloaked magnetic nanocarrier effectively integrates immunological adjuvant, photosensitizer delivery, MF-assisted targeting photodynamic therapy, which provides an innovative strategy for cancer therapy.

Directed Self-Assembly of Dipeptide Single Crystal in a Capillary.

Controlled growth of one-dimensional nanostructures is playing a key role in creating types of materials for functional devices. Here, we report procedures for controlled assembly of the dipeptide diphenylalanine (FF) into aligned and ultralong single crystals in a capillary. With the evaporation of solvent, nucleation of the crystal occurred in the confined region, and the crystal grew continuously with a supply of molecules from the concentration gradient system inside the capillary. Based on the "Knudsen regime", an ultralong aligned individual FF single crystal possessing an active optical waveguide property at macroscopic length scale could be obtained. Moreover, capillary is also an effective microdevice to investigate the disassembly process of the FF single crystals. This strategy has potentials to broaden the range of applications of aligned organic nanomaterials.

Bioinspired Platform Conjugated Active Drug Delivery.

BACKGROUND: The rapid emergence of nanotechnology and biotechnology has enabled revolutionary developments for drug delivery systems. Recently, drug delivery has attracted extensive research interest; applied to improve the functions of these carriers and their applications. OBJECTIVE: Active drug delivery is currently approved as an ideal approach for targeted transport in a biological entity and can cooperate with therapeutic mediums in transporting cargoes. RESULTS AND CONCLUSION: In this review, several active targeted cargomediated drug delivery patterns have been summarized, including molecular motors, bio-camouflaged particles, and self-propelled nanomotors. Subsequently, a series of active targeted carriers for drug delivery were introduced, and their ability for targeted binding was discussed. Furthermore, the mechanism of active targeted transport was exposited in detail, and some promising works are highlighted.

Synthesis of sub-diffraction quasi-non-diffracting beams by angular spectrum compression.

Quasi-non-diffracting beams are attractive for various applications, including optical manipulation, super-resolution microscopes, and materials processing. However, it is a great challenge to design and generate super-long quasi-non-diffracting beams with sub-diffraction and sub-wavelength size. In this paper, a method based on the idea of compressing a normalized angular spectrum is developed, which makes it possible and provides a practical tool for the design of a quasi-non-diffracting beam with super-oscillatory sub-wavelength transverse size. It also presents a clear physical picture of the formation of super-oscillatory quasi-non-diffracting beams. Based on concepts of a local grating and super-oscillation, a lens was designed and fabricated for a working wavelength of λ = 632.8 nm. The validity of the idea of normalized angular spectrum compression was confirmed by both numerical investigations and experimental studies. An optical hollow needle with a length of more than 100λ was experimentally demonstrated, in which an optical hollow needle was observed with a sub-diffraction and sub-wavelength transverse size within a non-diffracting propagation distance of 94λ. Longer non-diffracting propagation distance is expected for a lens with larger radius and shorter effective wavelength.

Self-Assembly of Ultralong Aligned Dipeptide Single Crystals.

Oriented arrangement of single crystals plays a key role in improving the performance of their functional devices. Herein we describe a method for the exceptionally fast fabrication (mm/min) of ultralong aligned dipeptide single crystals (several centimeters). It combines an induced nucleation step with a continuous withdrawal of substrate, leading to specific evaporation/composition conditions at a three-phase contact line, which makes the growth process controllable. These aligned dipeptide fibers possess a uniform cross section with active optical waveguiding properties that can be used as waveguiding materials. The approach provides guidance for the controlled arrangement of organic single crystals, a family of materials with considerable potential applications in large-scale functional devices.