Hydrodynamic focusing lithography.

Anisotropic multifunctional particles hold great promise for drug delivery, imaging, and construction of building blocks for dynamic mesostructures such as self-assembled tissues and 3-D electrical circuits. Of particular interest, multifunctional particles with unique barcodes have been suggested as diagnosis tools for rapid screening of biomolecules. For these applications, particle design is at least as important as size and requires a fabrication technique with precise control over shape and chemical patchiness. Methods currently used to generate multifunctional particles include microcutting, co-jetting, core–shell systems, photo resist-based lithography, and the PRINT method (particle replication in non-wetting templates). The morphology of particles prepared by co-jetting, microcutting, and core–shell systems has been limited to spheres and cylinders. Although multilayer lithography overcomes this limitation, the use of photoresist materials renders this approach suboptimal for many applications. While the PRINT method has its strength in producing small sub-mm particles, to date multiphasic particles beyond a 1-D stripe have not been synthesized. Furthermore, during multifunctional particle synthesis, the technique needs multiple steps and does not provide flexibility as particle shapes are restricted to the pre-defined stamping molds. Previously, we have shown that flow lithography (FL) can be used to generate multifunctional particles—we exploited several microfluidic characteristics such as co-flow of liquid monomers, rapid fluidic exchange, and simple controllability. In FL, we can use a combination of adjacent flowing photocurable monomers with lithographic masks to simultaneously define the shape and chemical pattern of particles. Recently, we also developed lock release lithography (LRL) to extend chemical patterning to multiple dimensions. However, these FL-based approaches for generating particles with patterned chemistries require precise alignment of masks at flow interfaces and concomitant modest particle throughput. Currently, FL cannot be used to synthesize multifunctional particles with chemical anisotropy in the channel height direction (z direction in this article, c.f. Figure 1A). Here, we introduce a new method called hydrodynamic focusing lithography (HFL) that harnesses flow focusing to create stacked flows in two-layered channels for particle synthesis. Contrary to our prior methods to create multilayered particles, here the fluid interface can be perpendicular to the UV light propagation direction and precise mask alignment at the interface is no longer needed. This change in geometry also allows us to polymerize 2-D arrays, compared to 1-D in the prior method, which can increase throughput substantially. In HFL, multiple monomer streams can be simultaneously stacked in both the z and y direction leading to more complex particles than before. Finally, we demonFigure 1. Hydrodynamic focusing lithography (HFL) for high-throughput synthesis of Janus microparticles. A) Microfluidic device used in HFL. P1 and P2 represent the inlet pressures of top and bottom channel respectively. All inlet dimensions are 40 40 mm. Particles are synthesized after layered flows are widened up to 1 mm in a 40 mm tall region of the channel. B) A side view of flow focusing and particle polymerization. C) A fluorescent image of 50 mm triangular particles with green (200 nm, green fluorescent beads) and red (rhodamine A) layers. H1 and H2 are the heights of top (red) and bottom (green) layer in a particle. D) Comparison of measured H2/H1 versus estimated flow ratio Q2/Q1 (see Supporting Information). The dashed line is the prediction from a hydrodynamic model (Eq. (12) in Supporting Information). E) Uniformity of Janus particles synthesized at a, b, c, d, and e spots across a 1 mm width channel. The intervals between spots are 100 mm. Scale bars are 50 mm (C,E) and 20 mm (D).