Advancements in Two-Photon Polymerization (2PP) for Micro and Nanoscale Fabrication

Parallel direct laser writing of micro-optical and photonic structures using spatial light modulator

Objective: Two-photon polymerization (TPP) utilizes an optical nonlinear absorption process to initiate the polymerization of photopolymerizable materials. To date, it is the only technique capable of fabricating complex 3D microstructures with finely adjusted geometry on the cell and sub-cell scales. TPP shows a very promising potential in biomedical applications related to high-resolution features, including drug delivery, tissue engineering, microfluidic devices, and so forth. Therefore, it is of high significance to grasp the global scientific achievements in this field. An analysis of publications concerning the applications of TPP in the biomedical field was performed, and the knowledge domain, research hotspots, frontiers, and research directions in this topic were identified according to the research results. Methods: The publications concerning TPP applications in biomedical field were retrieved from WoSCC between 2003 and 2022, Bibliometrics and visual analysis employing CiteSpace software and R-language package Bibliometrix were performed in this study. Results: A total of 415 publications regarding the TPP applications in the biomedical field were retrieved from WoSCC, including 377 articles, and 38 review articles. The studies pertaining to the biomedical applications of TPP began back in 2003 and showed an upward trend constantly. Especially in the recent 5 years, studies of TPP in biomedical field have increased rapidly, with the number of publications from 2017 to 2021 accounting for 52.29% of the total. In terms of output, China was the leading country and Chinese Acad Sci, Tech Inst Phys and Chem was the leading institution. The United States showed the closest cooperation with other countries. ACS applied materials and interfaces was the most prolific journal (n = 13), followed by Biofabrication (n = 11) and Optics express (n = 10). The journals having the top cited papers were Biomaterials, Advanced materials, and Applied physic letters. The most productive author was Aleksandr Ovsianikov (27 articles). Meanwhile, researchers who had close cooperation with other researchers were also prolific authors. “cell behavior”, " (tissue engineering) scaffolds”, “biomaterials,” and “hydrogel” were the main co-occurrence keywords and “additional manufacturing”, “3D printing,” and “microstructures” were the recent burst keywords. The Keyword clusters, “stem cells,” and “mucosal delivery”, appeared recently. A paper reporting unprecedented high-resolution bull models fabricated by TPP was the most locally cited reference (cited 60 times). “Magnetic actuation” and “additive manufacturing” were recently co-cited reference clusters and an article concerning ultracompact compound lens systems manufactured by TPP was the latest burst reference. Conclusion: The applications of TPP in biomedical field is an interdisciplinary research topic and the development of this field requires the active collaboration of researchers and experts from all relevant disciplines. Bringing up a better utilization of TPP as an additive manufacturing technology to better serve the biomedical development has always been the research focus in this field. Research on stem cells behaviors and mucosal delivery based on microstructures fabricated using TPP were becoming new hotspots. And it can be predicted that using TPP as a sourcing technique to fabricate biomedical-related structures and devices is a new research direction. In addition, the research of functional polymers, such as magnetic-driven polymers, was the frontier topic of TPP biomedical applications.

To unleash the full potential of two-photon polymerization (TPP) as a promising technique for three-dimensional (3D) fabrication of functional micro/nanostructures, multi-walled carbon nanotubes (MWNT) as filling materials were incorporated into polymer resins. Scanning electron microscopy images and polarized Raman spectra showed that the MWNTs with concentrations up to 0.2 wt % were uniformly distributed throughout the polymer matrix by thiol functionalization. A near-infrared femtosecond pulsed laser beam was focused into the composite resins, resulting in the 3D fabrication of arbitrary micro/nano architectures. The obtained MWNT-thiol-acrylate (MTA) composite structures exhibited significantly enhanced electrical conductivity and mechanical strength, and maintained high optical transmittance at the same time. Furthermore, MWNTs were self-aligned along the laser scanning direction in thiol-acrylate polymer, resulting in high electrical anisotropic effect of the MTA composites. Based on this highly conductive MTA composite photoresist, various functional micro/nano architectures and devices have been successfully fabricated, including photonic crystals, micromodels, microcapacitors and microresistors. Precise assembly of MWNTs with ∼100 nm spatial resolution was achieved by the combination of TPP and direct pyrolysis. This technique enables 3D precise printing of multifunctional micro/nano devices and holds great potential to pave a way for wide applications of carbon nanotubes, such as 3D electronics, integrated photonics and micro/nanoelectromechanical systems (MEMS/NEMS).

Abstract

Two-photon polymerized poly(caprolactone) retinal cell delivery scaffolds and their systemic and retinal biocompatibility

Two-photon polymerization (TPP) is of increasing interest due to its unique combination of truly three-dimensional (3D) fabrication capability and ultrahigh spatial resolution of ~40 nm. However, the stringent requirements of non-linear resins seriously limit the material functionality of 3D printing via TPP. Precise fabrication of 3D micro/nanostructures with multi-functionalities such as high electrical conductivity and mechanical strength is still a long-standing challenge. In this work, TPP fabrication of arbitrary 3D micro/nanostructures using multi-walled carbon nanotube (MWNT)-thiolacrylate (MTA) composite resins has been developed. Up to 0.2 wt% MWNTs have been incorporated into thiol-acrylate resins to form highly stable and uniform composite photoresists without obvious degradation for one week at room temperature. Various functional 3D micro/nanostructures including woodpiles, micro-coils, spiral-like photonic crystals, suspended micro-bridges, micro-gears and complex micro-cars have been successfully fabricated. The MTA composite resin offers significant enhancements in electrical conductivity and mechanical strength, and on the same time, preserving high optical transmittance and flexibility. Tightly controlled alignment of MWNTs and the strong anisotropy effect were confirmed. Microelectronic devices including capacitors and resistors made of the MTA composite polymer were demonstrated. The 3D micro/nanofabrication using the MTA composite resins enables the precise 3D printing of micro/nanostructures of high electrical conductivity and mechanical strength, which is expected to lead a wide range of device applications, including micro/nano-electromechanical systems (MEMS/NEMS), integrated photonics and 3D electronics.

Two-photon polymerization (TPP) is a micro/nano-fabrication technology for additive manufacturing, enabling 3D printing of polymeric materials using ultrafast laser pulses. In this work, two-photon polymerization is realized inside a metal-organic framework (MOF) crystal. Intricate structures are built in the porous crystal to create a microstructure-in-crystal hybrid. Furthermore, the MOF can be removed by acid treatment to release the printed structure. The two-photon polymerization inside the crystal has the potential for MOF sensing device fabrication and data storage applications. In the future development, printing different materials in the same MOF crystal for creating functional 3D devices is hoped.

Filigree structures can be manufactured via two-photon polymerization (2PP) operating in the regime of nonlinear light absorption. For the first time, it is possible to apply this technique to the powder processing of ceramic structures with a feature size in the range of the critical defect sizes responsible for brittle fracture and, thus, affecting fracture toughness of high-performance ceramics. In this way, tailoring of advanced properties can be achieved already in the shaping process. Traditionally, 2PP relies on transparent polymerizable resins, which are diametrically opposed to the usually completely opaque ceramic resins and slurries. Here a transparent and photocurable suspension of nanoparticles (resin) with very high mass fractions of yttria-stabilized zirconia particles (YSZ) is presented. Due to the extremely well-dispersed nanoparticles, scattering of light can be effectively suppressed at the process-relevant wavelength of 800nm. Sintered ceramic structures with a resolution of down to 500nm are obtained. Even at reduced densities of 1-4g cm-3 , the resulting compressive strength with 4.5GPa is equivalent or even exceeding bulk monolithic yttria-stabilized zirconia. A ceramic metamaterial is born, where the mechanical properties of yttria-stabilized zirconia are altered by changing geometrical parameters, and gives access to a new class of ceramic materials.

Two-photon polymerization (TPP) enables us to fabricate three-dimensional structures with feature sizes beyond the diffraction limit. In TPP, since near-infrared femtosecond pulsed laser has been used for two-photon excitation, photo-initiators are added into a resin to trigger the TPP reaction. Here, we propose a photo-initiator free TPP by utilizing monomer’s intrinsic absorption in the deep-UV (DUV) region. Chemical bonds in monomer molecules are directly two-photon-excited with a visible femtosecond pulsed laser at 400-nm wavelength. We fabricated 3D nano-structures of acrylic oligomer, inorganic materials, and biomaterials without a photo-initiator. Raman spectroscopy study clarified chemical structure changes upon DUV two-photon excitation.

In this paper, approaches for the realization of high-resolution periodic structures with gap sizes at sub-100 nm scale by two-photon polymerization (2PP) are presented. The impact of laser intensity on the feature sizes and surface quality is investigated. The influence of different photosensitive materials on the structure formation is compared. Based on the elliptical geometry character of the voxel, the authors present an idea to realize high-resolution structures with feature sizes less than 100 nm by controlling the laser focus position with respect to the glass substrate. This investigation covers structures fabricated respectively in the plane along and perpendicular to the major axis of voxel. The authors also provide a useful approach to manage the fabrication of proposed periodic structure with a periodic distance of 200 nm and a gap size of 65 nm.

Abstract3D hydrogel structures fabricated by two‐photon polymerization (TPP) have become attractive in biomedical fields. Generally, conventional organic solvents are toxic and the residues left in the fabricated 3D structures are harmful to cells. Hence, anion ionic carbazole‐based water‐soluble two‐photon initiator (TPI) 3,6‐bis[2‐(1‐methylpyridinium)vinyl]‐9‐methylcarbazole ditosylate (BT) is proposed to construct arbitrary 3D hydrogel structures. Cucurbit[7]uril (CB7) and BT form a host‐guest complex (CB7/BT) with a binding ratio of 1:1, which further improves the water solubility, biocompatibility and nonlinear absorption property of TPI. A water‐soluble photoresist consisting of photoinitiator CB7/BT and monomer poly(ethylene glycol) diacrylate is prepared to explore the TPP fabrication capacity. The electron paramagnetic resonance measurement shows that CB7/BT initiates photopolymerization by alkyl radicals. The laser threshold power of the photoresist is 6.3 mW and the feature size is 127 nm in TPP at 780 nm. The initiator with p‐toluenesulfonate anion exhibits higher binding energy, larger two‐photon absorption cross‐section and two‐photon fabrication resolution compared with the previous work using iodide as an anion, indicating a promising way to improve the fabrication capacity of water‐soluble TPI through changing the anion ionic group. The proposed strategy will provide high potential for the further application in the biomedical field.

Two-photon polymerization (TPP) is a promising micro/nanofabrication technique, which is capable of fabricating 3D micro/nanostructures beyond the diffraction limit of light. However, the study of TPP process with a focus on the dependence of degree of conversion on TPP parameters using a non-destructive and efficient method is still lacking. We studied the quantitative relationships between the TPP parameters and the cross-linking of an acrylic-based IP-L 780 photoresist via systematic Raman characterization. The differences in the Raman spectra between the non-polymerized and the polymerized IP-L 780 photoresists were observed by probing the excitation of carbon-carbon double bond (C=C) vibrations. We obtained the relationship between the degree of conversion in TPP and the Raman spectra of the IP-L 780 resin, in which the intensity of the characteristic Raman peak of IP-L 780 at 1635 cm-1 decreases with the increase of the TPP laser dose. A mathematic model of the degree of conversion with respective to the TPP parameters, including laser average power and writing speed, has been established. The method provides a simple and effective way to characterize and optimize the TPP micro/nanofabrication processes. The established model for the degree of conversion as the function of TPP parameters will contribute to the advanced 3D TPP micro/nanofabrication by providing a guidance to optimize the laser doses, voxel sizes, and the mechanical strength of the polymers.

Functional polymers by two-photon 3D lithography

The interaction between an ultra-fast pulse laser and a material's surface has become a research hotspot in recent years. Micromachining of titanium alloy with an ultra-fast pulse laser is a very important research direction, and it has very important theoretical significance and application value in investigating the ablation threshold of titanium alloy irradiated by ultra-fast pulse lasers. Irradiated by a picosecond pulse laser with wavelengths of 1064 nm and 532 nm, the surface morphology and feature sizes, including ablation crater width (i.e. diameter), ablation depth, ablation area, ablation volume, single pulse ablation rate, and so forth, of the titanium alloy were studied, and their ablation distributions were obtained. The experimental results show that titanium alloy irradiated by a picosecond pulse infrared laser with a 1064 nm wavelength has better ablation morphology than that of the green picosecond pulse laser with a 532 nm wavelength. The feature sizes are approximately linearly dependent on the laser pulse energy density at low energy density and the monotonic increase in laser pulse energy density. With the increase in energy density, the ablation feature sizes are increased. The rate of increase in the feature sizes slows down gradually once the energy density reaches a certain value, and gradually saturated trends occur at a relatively high energy density. Based on the linear relation between the laser pulse energy density and the crater area of the titanium alloy surface, and the Gaussian distribution of the laser intensity on the cross section, the ablation threshold of titanium alloy irradiated by an ultra-fast pulse laser was calculated to be about 0.109 J/cm2.

Two-photon polymerization (TPP) is a sub-classification of vat photopolymerization. It has been widely used to fabricate micro/nano hierarchical structures that have the potential to be used to tune the fluid flow in chips. The present work first studied the influence of laser power on the feature size of TPP-fabricated 2D structures. It was found that the increase of laser power from 1.0 μW to 1.4 μW leads to the feature size increasing from 203 nm to 307 nm. Then, the effect of scanning parameters on the accuracy and surface quality of 3D structures was investigated. The arrangement of the voxels at different scanning strategies explains the mechanisms of the variation of accuracy and surface roughness. Finally, the pinecone structures with micro/nano hierarchical features were built and evaluated for their water repellence. The increase in the number of rows of pinecone structures significantly enhances the water-repellent performance.