(401f) Lock Release Lithography (LRL)

3D functional particles hold distinct advantages as sorting media, smart materials and building blocks for self-assembled, dynamic structures with complex functionality. Despite enormous their potentials, 3D and composite particles are not widely used because current methodologies have limitations in large scale, facile production and suffer from constraints of functionality and morphology. Multiphoton fabrication is a well-known method for synthesizing micro/nano 3D structures as it provides unparalleled control of morphology in all dimensions. In spite of the advantage, this direct drawing technique is prohibitively time-consuming. This method also has not been used to generate multifunctional structures. For higher throughput, 3D particles can be generated using a layer-by-layer process with photo resistst. Unfortunately, these materials are not ideal for many applications, the chemistries are extremely restricted, and the chemical patterning is limited to layered motifs. Three-dimensional particles can alternatively be generated using the PRINT method, where particles are shaped using a 3D mold. While Janus PRINT particles can be made by sequentially filling the mold with different materials, this approach will only yield simple ?striped? material patterns on a particle and, to the best of our knowledge, particles with more than 2 stripes have not been synthesized. Here, we introduce lock release lithography (LRL), built off of continuous-flow and stop-flow lithography (SFL). LRL utilizes a combination of channel topography, mask design, and pressure-induced channel deformation to form and release particles in a cycled fashion. This technique provides a means for the high-throughput production of particles with complex 3D morphologies and composite particles with configurable chemistries. The process consists of (1) stopping the flow of a UV-sensitive monomer stream through a microfliudic channel, (2) lithographically printing structures that are ?locked? into regions with multi-level channel topography, and (3) inducing channel deformation via high pressure to release structures for harvesting. In the example shown in Figure 1, we use a channel with positive relief features in the topography (ie. post structures protruding from the channel ceiling) to lock in an array of particles that are formed by 75ms of UV exposure through a transparency mask using a standard fluorescence microscope. Particle morphology is defined by a combination mask feature shape and channel topography. Locked into the three-dimensional relief, particles remain immobilized until a relatively high pressure (~ 5 psi) is applied to the poly(dimethylsiloxane) (PDMS) channel to initiate flow and deflect the channel beyond the point of particle release. Using an automated valving system, the flow is then stopped via pressure release, and the process is repeated, thus allowing the formation of 3D particles in an automated, semi-continuous manner. We synthesize a variety of 3D particles such as dishes, cups and table-like structures with unique mask shapes and channel topographies. LRL can be more complicated depending on the mold used to generate the channel topographies, and the mask used to polymerize the particles. Molds generated using standard lithography can be multi-tiered, rounded, or slanted, while virtually any topography can be achieved using multiphoton fabrication. The transparency masks used to generate particles can have virtually any two-dimensional shape, can be greyscale to provide variability in height along particles, and can be used in conjugation with interference masks to give finely tuned microporous structures. However, LRL is not suitable for the preparation of interlocking (like chain links) features or particles with internal hollow structures. Perhaps the most attractive feature of lock release lithography is that the release time is controllable. Because particle release occurs at a critical pressure (related to deformation), lower pressures can be used to exchange monomer without unlocking particles ? this allows subsequent addition of new chemistries. As such, LRL can be used efficiently to generate composite particles with multiple precisely engineered chemistries. The process is shown schematically in Figure 2a. First, the multi-inlet channel is filled with chemistry #1 and locked 3D structures are polymerized. Then, by adjusting the pressures of the inlet streams (but keeping them below ~ 1 psi), a second chemistry replaces the first without displacing the locked particle structure. A unique mask can be used with this chemistry to polymerize distinct particle features that are covalently linked to the locked particles via overlap. Finally, a high pressure flow (~ 10 psi) is used to release the composite particles (Fig. 2b-d). This approach can be applied to any number of unique chemistries. Using the process, we generate composite particles with ?autumn trees? in a frame (Fig. 2e-g). We also demonstrate a diverse set of functional particles including those displaying heterogeneous swelling characteristics and containing functional entities such as nucleic acids, proteins and beads. The length scales in LRL are ideally suited to generating tissue engineering mesoconstructs each containing multiple cell lines which are precisely positioned within the particle. In addition, the juxtaposition of swelling and stiff materials can be exploited to create particles that can undergo dramatic shape changes. Degradable polymers can be used to create microparticles which controllably evolve or fragment over time. We have believed that this technology will provide a simple but powerful means to mass-produce functional units for microfluidic operations, filtration systems, and tissue engineering constructs.