Continuous Flow Lithography Research Articles

Preparation of anisotropic multiscale micro-hydrogels via two-photon continuous flow lithography

HypothesisPolymeric anisotropic soft microparticles show interesting behavior in biological environments and hold promise for drug delivery and biomedical applications. However, self-assembly and substrate-based lithographic techniques are limited by low resolution, batch operation or specific particle geometry and deformability. Two-photon polymerization in microfluidic channels may offer the required resolution to continuously fabricate anisotropic micro-hydrogels in sub-10 µm size-range. ExperimentsHere, a pulsed laser source is used to perform two-photon polymerization under microfluidic flow of a poly(ethylene glycol) diacrylate (PEGDA) solution with the objective of realizing anisotropic micro-hydrogels carrying payloads of various nature, including small molecules and nanoparticles. The fabrication process is described via a reactive-convective-diffusion system of equations, whose solution under proper auxiliary conditions is used to corroborate the experimental observations and sample the configuration space. FindingsBy tuning the flow velocity, exposure time and pre-polymer composition, anisotropic PEGDA micro-hydrogels are obtained in the 1–10 μm size-range and exhibit an aspect ratio varying from 1 to 5. Furthermore, 200 nm curcumin-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles and 100 nm ssRNA-encapsulating lipid nanoparticles were entrapped within square PEGDA micro-hydrogels. The proposed approach could support the fabrication of micro-hydrogels of well-defined morphology, stiffness, and surface properties for the sustained release of therapeutic agents.

Scanning two-photon continuous flow lithography for the fabrication of multi-functional microparticles.

In this work, we demonstrate the high-throughput fabrication of 3D microparticles using a scanning two-photon continuous flow lithography (STP-CFL) technique in which microparticles are shaped by scanning the laser beam at the interface of laminar co-flows. The results demonstrate the ability of STP-CFL to manufacture high-resolution complex geometries of cell carriers that possess distinct regions with different functionalities. A new approach is presented for printing out-of-plane features on the microparticles. The approach eliminates the use of axial scanning stages, which are not favorable since they induce fluctuations in the flowing polymer media and their scanning speed is slower than the speed of galvanometer mirror scanners.

Scanning two-photon continuous flow lithography for synthesis of high-resolution 3D microparticles: erratum.

An error in a reference is reported and corrected.

Scanning two-photon continuous flow lithography for synthesis of high-resolution 3D microparticles.

Demand continues to rise for custom-fabricated and engineered colloidal microparticles across a breadth of application areas. This paper demonstrates an improvement in the fabrication rate of high-resolution 3D colloidal particles by using two-photon scanning lithography within a microfluidic channel. To accomplish this, we present (1) an experimental setup that supports fast, 3D scanning by synchronizing a galvanometer, piezoelectric stage, and an acousto-optic switch, and (2) a new technique for modifying the laser's scan path to compensate for the relative motion of the rapidly-flowing photopolymer medium. The result is an instrument that allows for rapid conveyor-belt-like fabrication of colloidal objects with arbitrary 3D shapes and micron-resolution features.

High-Throughput Contact Flow Lithography.

High-throughput fabrication of graphically encoded hydrogel microparticles is achieved by combining flow contact lithography in a multichannel microfluidic device and a high capacity 25 mm LED UV source. Production rates of chemically homogeneous particles are improved by two orders of magnitude. Additionally, the custom-built contact lithography instrument provides an affordable solution for patterning complex microstructures on surfaces.

Fabrication of Free-floating Nanohybrid Microparticles with ZnO Nanowire Surfaces

A photopolymerization technique with UV-photocurable materials using optofluidic maskless lithography (OFML) provides great flexibility in generating microstructure in microfluidic channels, such as continuous flow lithography and optofluidic lithography. These techniques enable the production of various microstructures with freeform shapes and high throughput because of its continuous synthetic process. Photocurable materials can generate polymeric microstructures with tunable internal structures, shapes, and surface properties. They have potential applications in particle-based technologies such as encoded chemical-laden microparticles, QR-encoded polymeric microparticles, and functional microparticles with complex nanostructured compartments. Recently, polymeric microstructures have been widely used in cell biology, including in scaffolding materials, tissue regeneration, and cellular studies, they can be used as three-dimensional (3D) tissue-like structures assembled by biological structures. Most researches on nanowire technology for cellular physiology have been based on nanowires on a two-dimensional planar substrate. For more flexible and scalable expansion of biomimetic surface for cellular study, we have focused on three-dimensional tissue-like structures assembled with microscale building blocks. In bottom-up approach for forming biomimetic extracellular matrix including nanowires, the unit of the structure is required to have nanowires on its surface. We present a novel nanohybrid microparticle inspired by a natural extracellular matrix composed of an interlocking mesh of fibrous proteins and carbohydrate polymers that can be used as a biomimetic material. The novel polymeric microparticle is a 3D shape with spiked ZnO nanowires on its surface. ZnO nanowires have been used for biochemical sensing devices that detect proteins, viruses and pH levels. Moreover, ZnO nanowire structures are an effective extracellular matrix to guide cell migration or control cell differentiation. Herein, we introduce fabrication of free-floating nanohybrid microparticles with a ZnO nanowire surface. The fabrication process of nanohybrid microparticles is composed of two main steps. First, freeform shapes of microparticles are generated by photopolymerization using an OFML system. After preparation of the microparticles, silica layers are deposited to provide texture seeds for the ZnO nanowires. Then, the ZnO nanowires are grown on the surface of microparticles via a hydrothermal reaction process. We can control the density of the ZnO nanowires on the microparticle during seeding processes. In order to produce nanohybrid microparticles, we prepare an UV-photocurable resin, ethoxylated trimethylolpropane triacrylate (ETPTA, Sigma-Aldrich, St. Louis, MO) and UV photoinitiator (2,2-dimethoxy-2-phenylacetophenone, SigmaAldrich, St. Louis, MO) for synthesis of polymeric microparticles. For silica layer deposition, we also prepare 98% tetraethyl orthosilicate (TEOS, Sigma-Aldrich, St. Louis, MO) and a mixed solution that consists of deionized water, 99% ethanol (Daejung, Korea), and 25-28% ammonium hydroxide (Daejung, Korea). After synthesizing polymeric microparticles by photopolymerization of the mixture consisting of ETPTA and 10 wt % photoinitiator using maskless lithography, polymeric particles are incubated in solution for the silica-coating reaction by periodically injecting TEOS into the mixed solution using the Stober method. The surface of elastic polymer microparticles is coated with an inelastic silica film forming a core–shell structure. Texture seeds are used for ZnO nanowire synthesis on the surface of the microparticles. A solution that contains 0.005

6PM3-PMN-002 三次元微細造形のための垂直方向の流れを利用したフローリングラフィー(OS2 三次元の微細形状創成技術,ポスターセッション)

We achieved three-dimensional (3D) fabrication of heterogeneous microstructures using an in situ photo-polymerization method, vertical continuous flow lithography (VCFL). Utilizing a projection system including a Digital Mirror Device, 3D microstructures were fabricated in a layer-by-layer fashion with the thickness of each layer controlled by UV absorber and exposure time. In addition, VCFL fabricated heterogeneous microstructures by exposing light patterns to multiple laminar flows. We demonstrated three-layered structures and long fibers whose cross-sectional geometries were changed. We also fabricated two-layered Janus structures. We believe that VCFL will be applicable to making anisotropic microparticles for material science and bottom up tissue engineering.

Microfluidics: Two‐Photon Continuous Flow Lithography (Adv. Mater. 10/2012)

Polymeric fibers and helical and bow-tie particles are generated by A. Camposeo, D. Pisignano and co-workers on page 1304, using the combination of two-photon lithog-raphy and microfluidics. The two-photon continuous flow lithography enables the creation of polymeric micro-objects with 3D features and sub-diffraction resolution. The particle synthesis throughput is improved, thanks to the combination of polymerization by multiple laser beams under continuous flow.

Two‐Photon Continuous Flow Lithography

A new approach for microfluidics-based production of polymeric particles, namely two-photon continuous flow lithography, is reported. This technique takes advantage of two-photon lithography to create objects with sub-micrometer and 3D features, and overcomes the traditional process limitations of two-photon lithography by using multiple beam production under continuous flow. Polymeric fibers, helical and bow-tie particles with sub-diffraction resolution and surface roughness as low as 10 nm are demonstrated.

Multifunctional Encoded Particles for High-Throughput Biomolecule Analysis

High-throughput screening for genetic analysis, combinatorial chemistry, and clinical diagnostics benefits from multiplexing, which allows for the simultaneous assay of several analytes but necessitates an encoding scheme for molecular identification. Current approaches for multiplexed analysis involve complicated or expensive processes for encoding, functionalizing, or decoding active substrates (particles or surfaces) and often yield a very limited number of analyte-specific codes. We present a method based on continuous-flow lithography that combines particle synthesis and encoding and probe incorporation into a single process to generate multifunctional particles bearing over a million unique codes. By using such particles, we demonstrate a multiplexed, single-fluorescence detection of DNA oligomers with encoded particle libraries that can be scanned rapidly in a flow-through microfluidic channel. Furthermore, we demonstrate with high specificity the same multiplexed detection using individual multiprobe particles.

Stop-flow lithography in a microfluidic device

Polymeric particles in custom designed geometries and with tunable chemical anisotropy are expected to enable a variety of new technologies in diverse areas such as photonics, diagnostics and functional materials. We present a simple, high throughput and high resolution microfluidic method to synthesize such polymeric particles. Building off earlier work that we have done on continuous flow lithography (CFL) (D. Dendukuri, D. C. Pregibon, J. Collins, T. A. Hatton, P. S. Doyle, Nat. Mater., 2006, 5, 365-369; ref. 1), we have devised and implemented a new setup that uses compressed air driven flows in preference to syringe pumps to synthesize particles using a technique that we call stop-flow lithography (SFL). A flowing stream of oligomer is stopped before polymerizing an array of particles into it, providing for much improved resolution over particles synthesized in flow. The formed particles are then flushed out at high flow rates before the cycle of stop-polymerize-flow is repeated. The high flow rates enable orders-of-magnitude improvements in particle throughput over CFL. However, the deformation of the PDMS elastomer due to the imposed pressure restricts how quickly the flow can be stopped before each polymerization event. We have developed a simple model that captures the dependence of the time required to stop the flow on geometric parameters such as the height, length and width of the microchannel, as well as on the externally imposed pressure. Further, we show that SFL proves to be superior to CFL even for the synthesis of chemically anisotropic particles with sharp interfaces between distinct sections.

Synthesis and Self-Assembly of Amphiphilic Polymeric Microparticles

We report the synthesis and self-assembly of amphiphilic, nonspherical, polymeric microparticles. Wedge-shaped particles bearing segregated hydrophilic and hydrophobic sections were synthesized in a microfludic channel by polymerizing across laminar coflowing streams of hydrophilic and hydrophobic polymers using continuous flow lithography (CFL). Particle monodispersity was characterized by measuring both the size of the particles formed and the extent of amphiphilicity. The coefficient of variation (COV) was found to be less than 2.5% in all measured dimensions. Particle structure was further characterized by measuring the curvature of the interface between the sections and the extent of cross-linking using FTIR spectroscopy. The amphiphilic particles were allowed to self-assemble in water or at water-oil interfaces. In water, the geometry of the particles enabled the formation of micelle-like structures, while in emulsions, the particles migrated to the oil-water interface and oriented themselves to minimize their surface energy.

Continuous-flow lithography for high-throughput microparticle synthesis

Precisely shaped polymeric particles and structures are widely used for applications in photonic materials, MEMS, biomaterials and self-assembly. Current approaches for particle synthesis are either batch processes or flow-through microfluidic schemes that are based on two-phase systems, limiting the throughput, shape and functionality of the particles. We report a one-phase method that combines the advantages of microscope projection photolithography and microfluidics to continuously form morphologically complex or multifunctional particles down to the colloidal length scale. Exploiting the inhibition of free-radical polymerization near PDMS surfaces, we are able to repeatedly pattern and flow rows of particles in less than 0.1 s, affording a throughput of near 100 particles per second using the simplest of device designs. Polymerization was also carried out across laminar, co-flowing streams to generate Janus particles containing different chemistries, whose relative proportions could be easily tuned. This new high-throughput technique offers unprecedented control over particle size, shape and anisotropy.