High-Throughput Two-Photon 3D Printing Enabled by Holographic Multi-Foci High-Speed Scanning.

The emerging two-photon polymerization (TPP) technique enables high-resolution printing of complex 3D structures, revolutionizing micro/nano additive manufacturing. Various fast scanning and parallel processing strategies have been proposed to promote its efficiency. However, obtaining large numbers of uniform focal spots for parallel high-speed scanning remains challenging, which hampers the realization of higher throughput. We report a TPP printing platform that combines galvanometric mirrors and liquid crystal on silicon spatial light modulator (LCoS-SLM). By setting the target light field at LCoS-SLM's diffraction center, sufficient energy is acquired to support simultaneous polymerization of over 400 foci. With fast scanning, the maximum printing speed achieves 1.49 × 108 voxels s-1, surpassing the existing scanning-based TPP methods while maintaining high printing resolution and flexibility. To demonstrate the processing capability, functional 3D microstructure arrays are rapidly fabricated and applied in micro-optics and micro-object manipulation. Our method may expand the prospects of TPP in large-scale micro/nanomanufacturing.

Recent Advances in Photothermal Therapy at Near-Infrared-II Based on 2D MXenes.

The use of photothermal therapy (PTT) with the near-infrared II region (NIR-II: 1000-1700 nm) is expected to be a powerful cancer treatment strategy. It retains the noninvasive nature and excellent temporal and spatial controllability of the traditional PTT, and offers significant advantages in terms of tissue penetration depth, background noise, and the maximum permissible exposure standards for skin. MXenes, transition-metal carbides, nitrides, and carbonitrides are emerging inorganic nanomaterials with natural biocompatibility, wide spectral absorption, and a high photothermal conversion efficiency. The PTT of MXenes in the NIR-II region not only provides a valuable reference for exploring photothermal agents that respond to NIR-II in 2D inorganic nanomaterials, but also be considered as a promising biomedical therapy. First, the synthesis methods of 2D MXenes are briefly summarized, and the laser light source, mechanism of photothermal conversion, and evaluation criteria of photothermal performance are introduced. Second, the latest progress of PTT based on 2D MXenes in NIR-II are reviewed, including titanium carbide (Ti3 C2 ), niobium carbide (Nb2 C), and molybdenum carbide (Mo2 C). Finally, the main problems in the PTT application of 2D MXenes to NIR-II and future research directions are discussed.

Bioinspired magnetism-responsive hybrid microstructures with dynamic switching toward liquid droplet rolling states.

The functionality of tunable liquid droplet adhesion is crucial for many applications such as self-cleaning surfaces and water collectors. However, it is still a challenge to achieve real-time and fast reversible switching between isotropic and anisotropic liquid droplet rolling states. Inspired by the surface topography on lotus leaves and rice leaves, herein we report a biomimetic hybrid surface with gradient magnetism-responsive micropillar/microplate arrays (GMRMA), featuring dynamic fast switching toward different droplet rolling states. The exceptional dynamic switching characteristics of GMRMA are visualized and attributed to the fast asymmetric deformation between the two different biomimetic microstructures under a magnetic field; they endow the rolling droplets with anisotropic interfacial resistance. Based on the exceptional morphology switching surface, we demonstrate the function of classification and screening of liquid droplets, and thus propose a new strategy for liquid mixing and potential microchemical reactions. It is expected that this intelligent GMRMA will be conducive to many engineering applications, such as microfluidic devices and microchemical reactors.

Microclaw Array Fabricated by Single Exposure of Femtosecond Airy Beam and Self-Assembly for Regulating Cell Migratory Plasticity.

The highly aligned extracellular matrix of metastatic breast cancer cells is considered to be the "highway" of cancer invasion, which strongly promotes the directional migration of cancer cells to break through the basement membrane. However, how the reorganized extracellular matrix regulates cancer cell migration remains unknown. Here, a single exposure of a femtosecond Airy beam followed by a capillary-assisted self-assembly process was used to fabricate a microclaw-array, which was used to mimic the highly oriented extracellular matrix of tumor cells and the pores in the matrix or basement membrane during cell invasion. Through the experiment, we found that metastatic breast cancer MDA-MB-231 cells and normal breast epithelial MCF-10A cells exhibit three major migration phenotypes on microclaw-array assembled with different lateral spacings: guidance, impasse, and penetration, whereas guided and penetrating migration are almost completely arrested in noninvasive MCF-7 cells. In addition, different mammary breast epithelial cells differ in their ability to spontaneously perceive and respond to the topology of the extracellular matrix at the subcellular and molecular levels, which ultimately affects the cell migratory phenotype and pathfinding. Altogether, we fabricated a microclaw-array as a flexible and high-throughput tool to mimic the extracellular matrix during invasion to study the migratory plasticity of cancer cells.

Simple optical encryption and decryption strategy based on bilayer soft actuator and laser-induced structural color.

Advanced encryption and decryption strategies are of great significance for information protection and data security. Visual optical information encryption and decryption technology plays an important role in the field of information security. However, the current optical information encryption technologies have shortcomings such as the need for external decryption equipment, the inability to read out repeatedly, and information leakage, which hinder their practical application. By combining the excellent thermal response characteristics of the MXene-isocyanate propyl triethoxy silane (IPTS)/polyethylene (PE) bilayer and the structural color generated from the laser fabricated biomimetic structural color surface, an approach of encrypt, decrypt, and transmit information has been proposed. The microgroove-induced structural color is attached to the MXene-IPTS/PE bilayer to form a colored soft actuator (CSA) to realize information encryption and decryption, and information transmission. Benefiting from the unique photon-thermal response of the bilayer actuator and the precise spectrum response of the microgroove-induced structural color, the information encryption and decryption system has the advantages of being simple and reliable, which has the potential application in the field of optical information security.

Functional Shape-Morphing Microarchitectures Fabricated by Dynamic Holographically Shifted Femtosecond Multifoci.

Functional microdevices based on responsive hydrogel show great promise in targeted delivery and biomedical analysis. Among state-of-the-art techniques for manufacturing hydrogel-based microarchitectures, femtosecond laser two-photon polymerization distinguishes itself by high designability and precision, but the point-by-point writing scheme requires mechanical apparatuses to support focus scanning. In this work, by predesigning holograms combined with lens phase modulation, multiple femtosecond laser spots are holographically generated and shifted for prototyping of three-dimensional shape-morphing structures without any moving equipment in the construction process. The microcage array is rapidly fabricated for high-performance target capturing enabled by switching environmental pH. Moreover, the built scaffolds can serve as arrayed analytical platforms for observing cell behaviors in normal or changeable living spaces or revealing the anticancer effects of loaded drugs. The proposed approach opens a new path for facile and flexible manufacturing of hydrogel-based functional microstructures with great versatility in micro-object manipulation.

Real-time capture of single particles in controlled flow by a rapidly generated foci array with adjustable intensity and pattern.

We propose a new, to the best of our knowledge, technique to capture single particles in real-time in a microfluidic system with controlled flow using micro-pillar traps fabricated by one-step. The micro pillars are fabricated in parallel by femtosecond multi-foci laser beams, which are generated by multiplexing gratings. As the generation process does not need integration loops, the pattern and the intensity distribution of the foci array can be controlled in real-time by changing the parameters of gratings. The real-time control of the foci array enables rapidly fabricating microtraps in the microchannel with adjustment of the pillar spaces and patterns according to the sizes and shapes of target particles. This technology provides an important step towards using platforms based on single-particle analysis, and it paves the way for the development of innovative microfluidic devices for single-cell analysis.

Magnetically driven rotary microfilter fabricated by two-photon polymerization for multimode filtering of particles.

In this Letter, a magnetically driven rotary microfilter that enables switching the modes of filtering and passing is fabricated in microfluidic devices via two-photon polymerization using a femtosecond laser for selective filtering of particles. The high-quality integration of a microfilter is ensured by accurately formulating the magnetic photoresist and optimizing the processing parameters. By changing the direction of the external magnetic field, the fabricated microfilter can be remotely manipulated to rotate by desired angles, thereby achieving the "filtering" or "passing" mode on demand. Taking advantage of this property, the magnetically rotary microfilter realizes multi-mode filtering functions such as capturing 8 µm particles/passing the 2.5 µm particles and passing both particles. More importantly, the responsive characteristic increases the reusability of the microchip. The lab-on-chip devices integrated with remotely rotary microfilters by the femtosecond laser two-photon polymerization with the functional photoresist will offer extensive applications in chemical and biological studies.

Controllable double-helical microstructures by photonic orbital angular momentum for chiroptical response.

Three-dimensional helical microstructures are abundant in nature and can be applied as chiral metamaterials for advanced nanophotonics. Here we report a flexible method to fabricate double-helical microstructures with single exposure by recording the chirality of incident optical vortices. Two coaxial optical vortices can interfere to generate a helical optical field, confirmed by the numerical simulation. The diameters of double-helical microstructures can be tailored by the magnitude of topological charges. This fast manufacturing strategy provides the opportunity to efficiently yield helical microstructures. Finally, the chirality of double-helical microstructures can be reversibly read by optical vortices, demonstrating a strong chiroptical response.

Self-Locomotive Soft Actuator Based on Asymmetric Microstructural Ti3C2Tx MXene Film Driven by Natural Sunlight Fluctuation.

Soft actuators and microrobots that can move spontaneously and continuously without artificial energy supply and intervention have great potential in industrial, environmental, and military applications, but still remain a challenge. Here, a bioinspired MXene-based bimorph actuator with an asymmetric layered microstructure is reported, which can harness natural sunlight to achieve directional self-locomotion. We fabricate a freestanding MXene film with an increased and asymmetric layered microstructure through the graft of coupling agents into the MXene nanosheets. Owing to the excellent photothermal effect of MXene nanosheets, increased interlayer spacing favoring intercalation/deintercalation of water molecules and its caused reversible volume change, and the asymmetric microstructure, this film exhibits light-driven deformation with a macroscopic and fast response. Based on it, a soft bimorph actuator with ultrahigh response to solar energy is fabricated, showing natural sunlight-driven actuation with ultralarge amplitude and fast response (346° in 1 s). By utilizing continuous bending deformation of the bimorph actuator in response to the change of natural sunlight intensity and biomimetic design of an inchworm to rectify the repeated bending deformation, an inchwormlike soft robot is constructed, achieving directional self-locomotion without any artificial energy and control. Moreover, soft arms for lifting objects driven by natural sunlight and wearable smart ornaments that are combined with clothing and produce three-dimensional deformation under natural sunlight are also developed. These results provide a strategy for developing natural sunlight-driven soft actuators and reveal great application prospects of this photoactuator in sunlight-driven soft biomimetic robots, intelligent solar-energy-driven devices in space, and wearable clothing.

High-Performance Unidirectional Manipulation of Microdroplets by Horizontal Vibration on Femtosecond Laser-Induced Slant Microwall Arrays.

The high-performance unidirectional manipulation of microdroplets is crucial for many vital applications including water collection and bioanalysis. Among several actuation methods (e.g., electric, magnetic, light, and thermal actuation), mechanical vibration is pollution-free and biocompatible. However, it suffers from limited droplet movement mode, small volume range (VMax /VMin  < 3), and low transport velocity (≤11.5 mm s-1 ) because the droplet motion is a sliding state caused by the vertical vibration on the asymmetric hydrophobic microstructures. Here, an alternative strategy is proposed-horizontal vibration for multimode (rolling, bouncing/reverse bouncing, converging/diffusing, climbing, 90o turning, and sequential transport), large-volume-range (VMax /VMin  ≈ 100), and high-speed (≈22.86 mm s-1 ) unidirectional microdroplet manipulation, which is ascribed to the rolling state on superhydrophobic slant microwall arrays (SMWAs) fabricated by the one-step femtosecond laser oblique ablation. The unidirectional transport mechanism relies on the variance of viscous resistance induced by the difference of contact area between the microdroplet and the slant microwalls. Furthermore, a circular, curved, and "L"-shaped SMWA is designed and fabricated for droplet motion with particular paths. Finally, sequential transport of large-volume-range droplets and chemical mixing microreaction of water-based droplets are demonstrated on the SMWA, which demonstrates the great potential in the field of microdroplet manipulation.

Structural Color Surface on Transparent PDMS Fabricated by Carbon-Assisted Laser Interference Lithography for Real-Time Quantification of Soft Actuators Motion.

Dynamic and real-time monitoring of the motion state of soft actuators is of great significance for optimizing their performance. However, present noncontact measurement approaches based on diffractive groove arrays fabricated by imprinting have some limitation, e.g., the grooves should be processed before the solidification of soft materials or the depth and period of grooves cannot be flexibly adjusted. Here, a flexible and high-efficiency fabrication approach carbon-assisted laser interference lithography (CLIL) for periodical groove structures with structural color is proposed. This technique is to irradiate the interference laser on the PDMS surface coated by a carbon layer, which is used for enhanced laser absorption. The processing parameters are systematically studied and optimized to achieve a bright structural color. Benefiting from the advantages of CLIL, the structural color can be processed on a solidified transparent surface with controllable characteristics such as groove period and depth. Lastly, the motion of an electric-driven actuator can be real-time quantified by calibrating the relationship between the observation angle and the observed structural color.

Efficient full-path optical calculation of scalar and vector diffraction using the Bluestein method.

Efficient calculation of the light diffraction in free space is of great significance for tracing electromagnetic field propagation and predicting the performance of optical systems such as microscopy, photolithography, and manipulation. However, existing calculation methods suffer from low computational efficiency and poor flexibility. Here, we present a fast and flexible calculation method for computing scalar and vector diffraction in the corresponding optical regimes using the Bluestein method. The computation time can be substantially reduced to the sub-second level, which is 105 faster than that achieved by the direct integration approach (~hours level) and 102 faster than that achieved by the fast Fourier transform method (~minutes level). The high efficiency facilitates the ultrafast evaluation of light propagation in diverse optical systems. Furthermore, the region of interest and the sampling numbers can be arbitrarily chosen, endowing the proposed method with superior flexibility. Based on these results, full-path calculation of a complex optical system is readily demonstrated and verified by experimental results, laying a foundation for real-time light field analysis for realistic optical implementation such as imaging, laser processing, and optical manipulation.

Rapid fabrication of high-resolution multi-scale microfluidic devices based on the scanning of patterned femtosecond laser.

Femtosecond-laser-induced two-photon polymerization has distinct advantages in micro-nanofabrication due to its intrinsic three-dimensional processing capability and high precision with sub-100 nanometer fabrication resolution. However, the high resolution causes a drawback in fabricating large-scale structures due to unacceptably long processing times. To solve this problem, we applied the patterned focus as the basic element for scanning processing. Theoretically, the relationship between patterned-focus scanning parameters and the uniformity of scanned light field was analyzed and optimized. Experimentally, we quantitatively investigated the relationship between the microstructure surface quality and the parameters of patterned-focus scanning. Based on above, we put forward a hybrid method that combines the femtosecond laser patterned exposure with direct-writing fabrication to rapidly fabricate large-scale microfluidic devices for various practical applications.

Multilayered skyscraper microchips fabricated by hybrid "all-in-one" femtosecond laser processing.

Multilayered microfluidic channels integrated with functional microcomponents are the general trend of future biochips, which is similar to the history of Si-integrated circuits from the planer to the three-dimensional (3D) configuration, since they offer miniaturization while increasing the integration degree and diversifying the applications in the reaction, catalysis, and cell cultures. In this paper, an optimized hybrid processing technology is proposed to create true multilayered microchips, by which "all-in-one" 3D microchips can be fabricated with a successive procedure of 3D glass micromachining by femtosecond-laser-assisted wet etching (FLAE) and the integration of microcomponents into the fabricated microchannels by two-photon polymerization (TPP). To create the multilayered microchannels at different depths in glass substrates (the top layer was embedded at 200 µm below the surface, and the underlying layers were constructed with a 200-µm spacing) with high uniformity and quality, the laser power density (13~16.9 TW/cm2) was optimized to fabricate different layers. To simultaneously complete the etching of each layer, which is also important to ensure the high uniformity, the control layers (nonlaser exposed regions) were prepared at the upper ends of the longitudinal channels. Solvents with different dyes were used to verify that each layer was isolated from the others. The high-quality integration was ensured by quantitatively investigating the experimental conditions in TPP, including the prebaking time (18~40 h), laser power density (2.52~2.94 TW/cm2) and developing time (0.8~4 h), all of which were optimized for each channel formed at different depths. Finally, the eight-layered microfluidic channels integrated with polymer microstructures were successfully fabricated to demonstrate the unique capability of this hybrid technique.

Large area metal micro-/nano-groove arrays with both structural color and anisotropic wetting fabricated by one-step focused laser interference lithography.

Artificial bioinspired surfaces are attracting increasing attention because of their fascinating characteristics, such as the structural color of a butterfly wing and the anisotropic wetting of a rice leaf. However, realization of the multicolor biomimetic metal surfaces with controlled anisotropy by using a simple, inexpensive and efficient method remains a challenge. Herein, we propose a focused laser interference lithography processing method, which has sufficient energy density and high processing efficiency to directly fabricate the groove structures on the metal surface. The surface is multicolor due to the diffraction grating effect of the regular groove structures, and exhibits anisotropic wetting due to its single-direction morphology. The influence of the observation angle on the diversity of colors and the anisotropic wetting under different heights and periods of grooves have been quantitatively investigated. A variety of patterns (e.g., leaf, crab, windmill, letter and so on) can be processed on various metals (e.g., stainless steel, Ti, Ni, Cu, Fe, Zn and so on) by this focused laser interference lithography because of its excellent flexibility and wide range of suitable materials. This multi-functional metal surface has broad applications in identification code, decorative beautification, anti-counterfeiting, information storage, bionic application design and so on.

Femtosecond Mathieu Beams for Rapid Controllable Fabrication of Complex Microcages and Application in Trapping Microobjects.

Structured laser beam based microfabrication technology provides a rapid and flexible way to create some special microstructures. As an important member in the propagation of invariant structured optical fields, Mathieu beams (MBs) exhibit regular intensity distribution and diverse controllable parameters, which makes it extremely suitable for flexible fabrication of functional microstructures. In this study, MBs are generated by a phase-only spatial light modulator (SLM) and used for femtosecond laser two-photon polymerization (TPP) fabrication. Based on structured beams, a dynamic holographic processing method for controllable three-dimensional (3D) microcage fabrication has been presented. MBs with diverse intensity distributions are generated by controlling the phase factors imprinted on MBs with a SLM, including feature parity, ellipticity parameter q, and integer m. The focusing properties of MBs in a high numerical aperture laser microfabrication system are theoretically and experimentally investigated. On this basis, complex two-dimensional microstructures and functional 3D microcages are rapidly and flexibly fabricated by the controllable patterned focus, which enhances the fabrication speed by 2 orders of magnitude compared with conventional single-point TPP. The fabricated microcages act as a nontrivial tool for trapping and sorting microparticles with different sizes. Finally, culturing of budding yeasts is investigated with these microcages, which demonstrates its application as 3D cell culture scaffolds.

Photoacoustic microscopy of obesity-induced cerebrovascular alterations.

Cerebral small vessel disease has been linked to cognitive, psychiatric and physical disabilities, especially in the elderly. However, the underlying pathophysiology remains incompletely understood, largely due to the limited accessibility of these small vessels in the live brain. Here, we report an intravital imaging and analysis platform for high-resolution, quantitative and comprehensive characterization of pathological alterations in the mouse cerebral microvasculature. By exploiting multi-parametric photoacoustic microscopy (PAM), microvascular structure, blood perfusion, oxygenation and flow were imaged in the awake brain. With the aid of vessel segmentation, these structural and functional parameters were extracted at the single-microvessel level, from which vascular density, tortuosity, wall shear stress, resistance and associated cerebral oxygen extraction fraction and metabolism were also quantified. With the use of vasodilatory stimulus, multifaceted cerebrovascular reactivity (CVR) was characterized in vivo. By extending the classic Evans blue assay to in vivo, permeability of the blood-brain barrier (BBB) was dynamically evaluated. The utility of this enabling technique was examined by studying cerebrovascular alterations in an established mouse model of high-fat diet-induced obesity. Our results revealed increased vascular density, reduced arterial flow, enhanced oxygen extraction, impaired BBB integrity, and increased multifaceted CVR in the obese brain. Interestingly, the 'counterintuitive' increase of CVR was supported by the elevated active endothelial nitric oxide synthase in the obese mouse. Providing comprehensive and quantitative insights into cerebral microvessels and their responses under pathological conditions, this technique opens a new door to mechanistic studies of the cerebral small vessel disease and its implications in neurodegeneration and stroke.

Comprehensive Characterization of Cerebrovascular Dysfunction in Blast Traumatic Brain Injury Using Photoacoustic Microscopy.

Blast traumatic brain injury (bTBI) is a leading contributor to combat-related injuries and death. Although substantial emphasis has been placed on blast-induced neuronal and axonal injuries, co-existing dysfunctions in the cerebral vasculature, particularly the microvasculature, remain poorly understood. Here, we studied blast-induced cerebrovascular dysfunctions in a rat model of bTBI (blast overpressure: 187.8 ± 18.3 kPa). Using photoacoustic microscopy (PAM), we quantified changes in cerebral hemodynamics and metabolism-including blood perfusion, oxygenation, flow, oxygen extraction fraction, and the metabolic rate of oxygen-4 h post-injury. Moreover, we assessed the effect of blast exposure on cerebrovascular reactivity (CVR) to vasodilatory stimulation. With vessel segmentation, we extracted these changes at the single-vessel level, revealing their dependence on vessel type (i.e., artery vs. vein) and diameter. We found that bTBI at this pressure level did not induce pronounced baseline changes in cerebrovascular diameter, blood perfusion, oxygenation, flow, oxygen extraction, and metabolism, except for a slight sO2 increase in small veins (<45 µm) and blood flow increase in large veins (≥45 µm). In contrast, this blast exposure almost abolished CVR, including arterial dilation, flow upregulation, and venous sO2 increase. This study is the most comprehensive assessment of cerebrovascular structure and physiology in response to blast exposure to date. The observed impairment in CVR can potentially cause cognitive decline due to the mismatch between cognitive metabolic demands and vessel's ability to dynamically respond to meet the demands. Also, the impaired CVR can lead to increased vulnerability of the brain to metabolic insults, including hypoxia and ischemia.