Two-Photon Polymerization Lithography for Optics and Photonics: Fundamentals,Materials, Technologies,and Applications

The rapid development of additive manufacturing has fueled a revolution in various research fields and industrial applications. Among the myriad of advanced 3D printing techniques, two-photon polymerization lithography (TPL) uniquely offers a significant advantage in nanoscale print resolution, and has been widely employed in diverse fields, for example, life sciences, materials sciences, mechanics, and microfluidics. More recently, by virtue of the optical transparency of most of the resins used, TPL is finding new applications in optics and photonics, with nanometer to millimeter feature dimensions. It enables the minimization of optical elements and systems, and exploration of light-matter interactions with new degrees of freedom, never possible before. To review the recent progress in the TPL related optical research, it starts with the fundamentals of TPL and material formulation, then discusses novel fabrication methods, and a wide range of optical applications. These applications notably include diffractive, topological, quantum, and color optics. With a panoramic view of the development, it is concluded with insights and perspectives of the future development of TPL and related potential optical applications.     

Customizable and Reconfigurable Surface Properties of Printed Micro-objects by 3D Direct Laser Writing via Nitroxide Mediated Photopolymerization

Photoactivated Reversible Deactivation Radical Polymerization (RDRP) technologies have emerged very recently in the field of 3D printing systems especially at the macroscale in vat-photopolymerization-based processes such as digital light processing (DLP). Contrary to conventional free radical photopolymerization, photoRDRP in 3D printing leads to 3D objects with living character and thus confers them the unique ability to be post-modified after fabrication. While 3D direct laser writing (3D DLW) by two photon polymerization has become a standard for fabrication of complex 3D micro-objects, the use of RDRP and its associated benefits has so far been under-investigated at that scale. Herein, a photoresist suitable for 3D DLW based on nitroxide mediated photopolymerization (NMP2) is developed. The photopolymerization efficiency for fabrication of micro-structures and their subsequent post-modification are investigated regarding the laser power and the wavelength of excitation. Moreover, highly tunable, precise, and successive surface patterning of 2D and 3D multi-material microstructures are demonstrated thanks to the spatial and temporal control offered by the photo-induced post-modification. This work highlights new directions to be explored in order to accelerate the adoption of RDRP in 3D printing based on photopolymerization.     

Recent Advances on High-Speed and Holographic Two-Photon Direct Laser Writing

Two-Photon Lithography, thanks to its very high sub-diffraction resolution, has become the lithographic technique par excellence in applications requiring small feature sizes and complex 3D pattering. Despite this, the fabrication times required for extended structures remain much longer than those of other competing techniques (UV mask lithography, nanoimprinting, etc.). Its low throughput prevents its wide adoption in industrial applications. To increase it, over the years different solutions have been proposed, although their usage is difficult to generalize and may be limited depending on the specific application. A promising strategy to further increase the throughput of Two-Photon Lithography, opening a concrete window for its adoption in industry, lies in its combination with holography approaches: in this way it is possible to generate dozens of foci from a single laser beam, thus parallelizing the fabrication of periodic structures, or to engineer the intensity distribution on the writing plane in a complex way, obtaining 3D microstructures with a single exposure. Here, the fundamental concepts behind high-speed Two-Photon Lithography and its combination with holography are discussed, and the literary production of recent years that exploits such techniques is reviewed, and contextualized according to the topic covered.     

用于纳米器件的电子束与光学混合光刻技术

成功开发出了一种可用于纳米结构及器件制作的电子束与光学光刻的混合光刻工艺。通过两步光刻工艺,在栅结构层上采用大小图形数据分离的方法,使用光学光刻形成大尺寸栅引出电极结构,利用电子束直写形成纳米尺寸栅结构,并通过图形转移工艺解决两次光刻定义的栅结构的叠加问题。此混合光刻工艺技术可以解决纳米电子束直写光刻技术效率较低的问题,同时避免了电子束进行大面积、高密度图形曝光时产生严重邻近效应影响的问题。这项工艺技术已经应用于先进MOS器件的研发,并且成功制备出具有良好电学特性、最小栅长为26 nm的器件。     

Marine-Derived Hydrogels for Biomedical Applications

Marine organisms provide novel and broad sources for the preparations and applications of biomaterials. Since the urgent requirement of bio-hydrogels to mimic tissue extracellular matrix (ECM), the natural biomacromolecule hydrogels derived from marine sources have received increasing attention. Benefiting from their outstanding bioactivity and biocompatibility, many attempts have been made to reconstruct ECM components by applying marine-derived natural hydrogels. Moreover, marine hydrogels have been successfully applied in biomedicine by means of microfluidics, electrospray, and bioprinting. In this review, the classification and characteristics of marine-derived hydrogels are summarized. In particular, their role in the development of biomaterials is also introduced. Then, the recent advances in bio-fabrication strategies for various hydrogel materials are focused upon. Besides, the influences of hydrogel types on their functions in biomedical applications are discussed in depth. Finally, critical reflections on the limitations and future development of marine-derived hydrogels are presented.     

Engineered Sulfated Polysaccharides for Biomedical Applications

Sulfated polysaccharides are ubiquitous in living systems and have central roles in biological functions such as organism development, cell proliferation and differentiation, cellular communication, tissue homeostasis, and host defense. Engineered sulfated polysaccharides (ESPs) are structural derivatives not found in nature but generated through chemical and enzymatic modification of natural polysaccharides, as well as chemically synthesized oligo- and polysaccharides. ESPs exhibit novel and augmented biological properties compared with their unmodified counterparts, mainly through facilitating interactions with other macromolecules. These interactions are closely linked to their sulfation patterns and backbone structures, providing a means to fine-tune biological properties and characterize structural–functional relationships by employing well-characterized polysaccharides and strategies for regioselective modification. The following review provides a comprehensive overview of the synthesis and characterization of ESPs and of their biological properties. Through the pioneering research presented here, key emerging application areas for ESPs, which can lead to novel breakthroughs in biomedical research and clinical treatments, are highlighted.     

DNA Hydrogels as Functional Materials and Their Biomedical Applications

With the remarkable development of DNA nanotechnology, interest in DNA molecules has expanded beyond its biological role to building blocks in materials science. As a unique branch of DNA-based materials, DNA hydrogels have exhibited many fascinating characteristics, including broad biocompatibility, precise programmability, convenient modification, and tunable mechanical properties, which make DNA hydrogels ideal biomaterials. Moreover, by combining with functional nucleic acids, such as aptamers, i-motif nanostructures, CpG oligodeoxynucleotides, and DNAzymes, DNA hydrogels can be further tailored to provide additional target recognition, therapeutic potential, and catalytic activities, allowing them to play important roles in biosensing and medical applications. This review, aims to provide readers with an up-to-date overview of the important developments of biomedical DNA hydrogels. First, it introduces different synthetic strategies of hydrogels that utilize DNA as building materials and functional units within the hydrogel networks and discuss their advantages in biomedical applications. Subsequently, new approaches and applications of biomedical DNA hydrogels in the recent years are highlighted, such as therapeutic systems, cell culture platforms, tissue engineering materials, and biosensors. Finally, future perspectives and remaining challenges of DNA hydrogels in biomedicine are presented.     

Stimuli-Responsive Nanocomposite Hydrogels for Biomedical Applications

The complex tissue-specific physiology that is orchestrated from the nano- to the macroscale, in conjugation with the dynamic biophysical/biochemical stimuli underlying biological processes, has inspired the design of sophisticated hydrogels and nanoparticle systems exhibiting stimuli-responsive features. Recently, hydrogels and nanoparticles have been combined in advanced nanocomposite hybrid platforms expanding their range of biomedical applications. The ease and flexibility of attaining modular nanocomposite hydrogel constructs by selecting different classes of nanomaterials/hydrogels, or tuning nanoparticle-hydrogel physicochemical interactions widely expands the range of attainable properties to levels beyond those of traditional platforms. This review showcases the intrinsic ability of hybrid constructs to react to external or internal/physiological stimuli in the scope of developing sophisticated and intelligent systems with application-oriented features. Moreover, nanoparticle-hydrogel platforms are overviewed in the context of encoding stimuli-responsive cascades that recapitulate signaling interplays present in native biosystems. Collectively, recent breakthroughs in the design of stimuli-responsive nanocomposite hydrogels improve their potential for operating as advanced systems in different biomedical applications that benefit from tailored single or multi-responsiveness.     

亚65 nm及以下节点的光刻技术

由于193 nm浸入式光刻技术的迅速发展,它被业界广泛认为是65 nm和45 nm节点首选光刻技术.配合双重曝光技术,193 nm浸入式光刻技术还可能扩展到32 nm节点,但是光刻成本会成倍增长,成品率会下降.随着ASML在2006年推出全球第一款EUV曝光设备,人们纷纷看好EUV技术应用到32 nm及以下节点,但是它仍需克服很多技术和经济上的挑战.对于22 nm节点,电子束直写是最可行,成本最低的候选方案,业界将在它与EUV技术之间做出抉择.     

一种基于快速自动聚焦的相变光刻系统

为了获得亚衍射级别的光刻图形,设计了一种光、机、电一体化的相变光刻系统。利用脉冲延迟技术产生了分辨率为1ns、脉宽可调的数字信号,对激光器进行驱动以获得相应脉宽的激光脉冲,然后通过LabVIEW软件和单片机,使系统各部件与计算机之间进行通信,以实现系统的全自动光刻过程。以Ge2Sb2Te5薄膜为基材料,利用其光学性质提出了一种针对相变材料的快速自动聚焦方法,并最终在该相变光刻系统上成功地得到了线宽为0.69m的Ge2Sb2Te5晶化图形,该尺寸远小于激光聚焦光斑。结果表明,该方法具有精度高、易操作、实现成本低等优点,这对简易相变光刻系统的设计具有很好的指导意义。     

Ionic Liquid-Mediated Scanning Probe Electro-Oxidative Lithography as a Novel Tool for Engineering Functional Oxide Micro- and Nano-Architectures

Functional oxides have extensively been investigated as a promising class of materials in a broad range of innovative applications. Harnessing the novel properties of functional oxides in micro- to nano-scale applications hinges on establishing advanced fabrication and manufacturing techniques able to synthesize these materials in an accurate and reliable manner. Oxidative scanning probe lithography (o-SPL), an atomic force microscopy (AFM) technique based on anodic oxidation at the water meniscus formed at the tip/substrate contact, not only combines the advantages of both “top-down” and “bottom-up” fabrication approaches, but also offers the possibility of fabricating oxide nanomaterials with high patterning accuracy. While the use of self-assembled monolayers (SAMs) broadened the application of o-SPL, significant challenges have emerged owing to the relatively limited number of SAM/solid surface combinations that can be employed for o-SPL, which constrains the ability to control the chemistry and structure of oxides formed by o-SPL. In this work, a new o-SPL technique that utilizes room-temperature ionic liquids (RTILs) as the functionalizing material to mediate the electrochemistry at AFM tip/substrate contacts is reported. The results show that the new IL-mediated o-SPL (IL-o-SPL) approach allows sub-100 nm oxide features to be patterned on a model solid surface, namely steel, with an initiation voltage as low as −2 V. Moreover, this approach enables high tunability of both the chemical state and morphology of the patterned iron oxide structures. Owing to the high chemical compatibility of ILs, which derives from the possibility of synthesizing ILs able to adsorb on a wide variety of solid surfaces, IL-o-SPL can be extended to other material surfaces and provide the opportunity to accurately tailor the chemistry, morphology, and electronic properties within nanoscale domains, thus opening new pathways to the development of novel micro- and nano-architectures for advanced integrated devices.     

Capillary Force Lithography: A Versatile Tool for Structured Biomaterials Interface Towards Cell and Tissue Engineering

This Feature Article aims to provide an in‐depth overview of the recently developed molding technologies termed capillary force lithography (CFL) that can be used to control the cellular microenvironment towards cell and tissue engineering. Patterned polymer films provide a fertile ground for controlling various aspects of the cellular microenvironment such as cell–substrate and cell–cell interactions at the micro‐ and nanoscale. Patterning thin polymer films by molding typically involves several physical forces such as capillary, hydrostatic, and dispersion forces. If these forces are precisely controlled, the polymer films can be molded into the features of a polymeric mold with high pattern fidelity and physical integrity. The patterns can be made either with the substrate surface clearly exposed or unexposed depending on the pattern size and material properties used in the patterning. The former (exposed substrate) can be used to adhere proteins or cells on pre‐defined locations of a substrate or within a microfluidic channel using an adhesion‐repelling polymer such as poly(ethylene glycol) (PEG)‐based polymer and hyaluronic acid (HA). Also, the patterns can be used to co‐culture different cells types with molding‐assisted layer‐by‐layer deposition. In comparison, the latter (unexposed substrate) can be used to control the biophysical surrounding of a cell with tailored mechanical properties of the material. The surface micropatterns can be used to engineer cellular and multi‐cellular architecture, resulting in changes of the cell shape and the cytoskeletal structures. Also, the nanoscale patterns can be used to affect various aspects of the cellular behavior, such as adhesion, proliferation, migration, and differentiation.     

飞秒激光组装一维纳米材料及其应用

一维纳米材料具有众多优异的特性,是构建微纳米功能性器件的基石。实现一维纳米材料在二维和三维空间的高精度和高定向组装是充分发挥其应用潜力的关键,同时也是制造难点。在众多纳米材料组装技术中,飞秒激光直写诱导组装技术具有独特优势,可实现一维纳米材料在任意三维结构中的可设计、高定向及高精度的组装。首先简要介绍了一维纳米材料组装研究的背景,并总结了非激光直写组装技术的研究现状和存在的挑战,然后较详细介绍了飞秒激光直写技术在一维纳米材料组装研究中的进展,重点回顾了金属(包括Au和Ag纳米线)、半导体(包括CNTs和ZnO)一维纳米材料的飞秒激光直写组装及微纳光电子功能器件的制造。并讨论了诱导一维纳米材料定向排布的光学力和非光学力(包括剪切力、体积收缩应力和空间限制)的作用机理,理论计算和实验研究结果验证了飞秒激光诱导的非光学力作用是导致一维纳米材料定向排布的主要原因。最后探讨了目前飞秒激光组装技术面临的一些问题和未来在高精度纳米材料组装和三维功能器件集成方面的发展趋势。     

Functionalized TiO2 Based Nanomaterials for Biomedical Applications

As baby boomers age, diabetes mellitus, cancer, osteoarthritis, cardiovascular diseases, and orthopedic disorders are more widespread and the demand for better biomedical devices and functional biomaterials is increasing rapidly. Owing to the good biocompatibility, chemical stability, catalytic efficiency, plasticity, mechanical properties, as well as strength‐to‐weight ratio, titanium dioxide (TiO₂) based nanostructured materials are playing important roles in tissue reconstruction and diagnosis of these diseases. Here, recent advance in the research of nanostructured TiO₂ based biomaterials pertaining to bone tissue engineering, intravascular stents, drug delivery systems, and biosensors is described.     

3D Micropatterned Functional Surface Inspired by Salvinia Molesta via Direct Laser Lithography for Air Retention and Drag Reduction

Bioinspired functional surfaces are attracting increasing interest in surface engineering, mostly in the field of wettability. The Salvinia-effect is a remarkable example of superficial air retention and drag force reduction caused by selective chemical coating (super-hydrophobic wax and hydrophilic dead cells) and peculiar 3D hierarchical morphological structures. The replication of Salvinia-like patterns at the microscale has always been prevented by limitations in microfabrication techniques, thus hindering relevant technological applications at this dimensional scale. Integrating 3D laser lithography and traditional microfabrication techniques, dimensionally downscaled, 3D micropatterned surfaces inspired for the first time by both morphology and chemical coating of the hairs present on the Salvinia Molesta leaves are reproduced. The effect of design and different surface energies (bare hydrophilic, hydrophobic, selective hydrophilic/hydrophobic coating) on the wettability are modeled and investigated. Bioinspired surfaces demonstrated to be super-hydrophobic in terms of apparent static contact angle (up to 170°) and provide tunable adhesion with roll-off angle from less than 10° to 90°. They successfully proved remarkable underwater air retention capability, sustained by stable Cassie-Baxter state under external hydrostatic pressure up to 4 atm. The proposed surfaces are tested in hydrodynamic conditions: drag force reduction is successfully demonstrated with up to 40% of energy saved.     

Functional Nanomaterials on 2D Surfaces and in 3D Nanocomposite Hydrogels for Biomedical Applications

An emerging approach to improve the physicobiochemical properties and the multifunctionality of biomaterials is to incorporate functional nanomaterials (NMs) onto 2D surfaces and into 3D hydrogel networks. This approach is starting to generate promising advanced functional materials such as self‐assembled monolayers (SAMs) and nanocomposite (NC) hydrogels of NMs with remarkable properties and tailored functionalities that are beneficial for a variety of biomedical applications, including tissue engineering, drug delivery, and developing biosensors. A wide range of NMs, such as carbon‐, metal‐, and silica‐based NMs, can be integrated into 2D and 3D biomaterial formulations due to their unique characteristics, such as magnetic properties, electrical properties, stimuli responsiveness, hydrophobicity/hydrophilicity, and chemical composition. The highly ordered nano‐ or microscale assemblies of NMs on surfaces alter the original properties of the NMs and add enhanced and/or synergetic and novel features to the final SAMs of the NM constructs. Furthermore, the incorporation of NMs into polymeric hydrogel networks reinforces the (soft) polymer matrix such that the formed NC hydrogels show extraordinary mechanical properties with superior biological properties.     

Direct‐Write Assembly of Microperiodic Silk Fibroin Scaffolds for Tissue Engineering Applications

Three–dimensional, microperiodic scaffolds of regenerated silk fibroin have been fabricated for tissue engineering by direct ink writing. The ink, which consisted of silk fibroin solution from the Bombyx mori silkworm, was deposited in a layer‐by‐layer fashion through a fine nozzle to produce a 3D array of silk fibers of diameter 5 µm. The extruded fibers crystallized when deposited into a methanol‐rich reservoir, retaining a pore structure necessary for media transport. The rheological properties of the silk fibroin solutions were investigated and the crystallized silk fibers were characterized for structure and mechanical properties by infrared spectroscopy and nanoindentation, respectively. The scaffolds supported human bone marrow‐derived mesenchymal stem cell (hMSC) adhesion, and growth. Cells cultured under chondrogenic conditions on these scaffolds supported enhanced chondrogenic differentiation based on increased glucosaminoglycan production compared to standard pellet culture. Our results suggest that 3D silk fibroin scaffolds may find potential application as tissue engineering constructs due to the precise control of their scaffold architecture and their biocompatibility.     

Ascidian‐Inspired Fast‐Forming Hydrogel System for Versatile Biomedical Applications: Pyrogallol Chemistry for Dual Modes of Crosslinking Mechanism

Exploitation of unique biochemical and biophysical properties of marine organisms has led to the development of functional biomaterials for various biomedical applications. Recently, ascidians have received great attention, owing to their extraordinary properties such as strong underwater adhesion and rapid self‐regeneration. Specific polypeptides containing 3,4,5‐trihydroxyphenylalanine (TOPA) in the blood cells of ascidians are associated with such intrinsic properties generated through complex oxidative processes. In this study, a bioinspired hydrogel platform is developed, demonstrating versatile applicability for tissue engineering and drug delivery, by conjugating pyrogallol (PG) moiety resembling ascidian TOPA to hyaluronic acid (HA). The HA–PG conjugate can be rapidly crosslinked by dual modes of oxidative mechanisms using an oxidant or pH control, resulting in hydrogels with different mechanical and physical characteristics. The versatile utility of HA–PG hydrogels formed via different crosslinking mechanisms is tested for different biomedical platforms, including microparticles for sustained drug delivery and tissue adhesive for noninvasive cell transplantation. With extraordinarily fast and different routes of PG oxidation, ascidian‐inspired HA–PG hydrogel system may provide a promising biomaterial platform for a wide range of biomedical applications.     

Nanosphere Lithography as a Versatile Method to Generate Surface‐Imprinted Polymer Films for Selective Protein Recognition

A versatile approach based on nanosphere lithography is proposed to generate surface‐imprinted polymers for selective protein recognition. A layer of 750 nm diameter latex bead‐protein conjugate is deposited onto the surface of gold‐coated quartz crystals followed by the electrosynthesis of a poly(3,4‐ethylenedioxythiophene)/poly(styrenesulfonate) (PEDOT/PSS) film with thicknesses on the order of the bead radius. The removal of the polymer bead‐protein conjugates, facilitated by using a cleavable protein‐nanosphere linkage is shown to result in 2D arrays of periodic complementary size cavities. Here it is demonstrated by nanogravimetric measurements that the imprinting proceeds further at molecular level and the protein (avidin) coating of the beads generates selective recognition sites for avidin on the surface of the PEDOT/PSS film. The binding capacity of such surface‐imprinted polymer films is ca. 6.5 times higher than that of films imprinted with unmodified beads. They also exhibit excellent selectivity against analogues of avidin, i.e., extravidin, streptavidin, and neutravidin, the latter being in fact undetectable. This methodology, if coupled with properly oriented conjugation of the macromolecular template to the nanoparticles, offers the possibility of site‐directed imprinting.