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.
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[Show abstract] [Hide abstract] ABSTRACT: Translation of any inventions into products requires manufacturing. Development of drug/gene/cell delivery systems will eventually face manufacturing challenges, which require the establishment of standardized processes to produce biologically-relevant products of high quality without incurring prohibitive cost. Microfluidicu technologies present many advantages to improve the quality of drug/gene/cell delivery systems. They also offer the benefits of automation. What remains unclear is whether they can meet the scale-up requirement. In this perspective, we discuss the advantages of microfluidic-assisted synthesis of nanoscale drug/gene delivery systems, formation of microscale drug/cell-encapsulated particles, generation of genetically engineered cells and fabrication of macroscale drug/cell-loaded micro-/nano-fibers. We also highlight the scale-up challenges one would face in adopting microfluidic technologies for the manufacturing of these therapeutic delivery systems.
- "A non-wetting elastomeric mold containing cavities of predefined shapes is used to contain precursor solution for gelling or crosslinking that allows high-throughput production of NP. In contrast to the static production of PRINT, continuous flow lithography combines the advantages of photolithography and microfluidics to continuously form morphologically complex particles . Precursor solution flows along a microfluidic channel underneath which a photomask with defined shapes is placed and pulses of UV light are applied. "
[Show abstract] [Hide abstract] ABSTRACT: In vitro experiments of blood flow are usually performed with blood analogue fluids due to ethical and practical considerations. The ideal analogue must match the rheology of blood in multiple scales. Ideally, the blood analogue fluid should be a suspension of transparent particles with similar properties to red blood cells. PDMS particles are an interesting candidate because they are transparent, have a low refractive index and can be produced through polymerization by heating. Here we present a study to produce PDMS microparticles, to be used in biomimetic fluids, by droplet microfluidics. A microfluidic flow focusing device was employed to produce the droplets. A polymeric fluid (PDMS) was squeezed by two counter-flowing water streams (with 2% of SDS). The flow rate of the disperse phase (Qdis) was 1 μl min-1 and that of the continuous phase (Qcont) 5 μ min-1. Both liquids were forced to flow through a narrow slit (25 μm × 100 μm) located downstream the channels where PDMS stream breaks into droplets. In these conditions, the device operated in the jetting regime, forming polydispersed droplets. Monodispersed microparticles were also obtained in the dripping regime. The droplets were then cured thermally to form microparticles. The process of droplet formation was filmed with a high-speed camera and the movies were analyzed to relate the flow pattern to particle size distribution.
- "The ability to synthesize monodisperse droplets, of controlled size and shape, has numerous potential applications in areas such as the production of emulsions, drug delivery, catalysis or medical imaging. Microfluidics offers also a promising path to synthetize microparticles, enabling the production of highly uniform particles in the micrometer size range123456. Microfluidic research devices are generally fabricated in polydimethylsiloxane (PDMS) [1, 4,910 18]. "
[Show abstract] [Hide abstract] ABSTRACT: We present the synthesis of hydrogel microbeads based on telechelic poly(2-oxazoline) (POx) crosslinkers and the methacrylate monomers (HEMA, METAC, SPMA) by inverse emulsion polymerization. While in batch experiments only irregular and ill-defined beads were obtained, the preparation in a microfluidic (MF) device resulted in highly defined hydrogel microbeads. Variation of the MF parameters allowed to control the microbead diameter from 50 to 500 μm. Microbead elasticity could be tuned from 2 to 20 kPa by the POx:monomer composition, the POx chain length, net charge of the hydrogel introduced via the monomer as well as by the organic content of the aqueous phase. The proliferations of human mesenchymal stem cells (hMSCs) on the microbeads were studied. While neutral, hydrophilic POx-PHEMA beads were bioinert, excessive colonization of hMSCs on charged POx-PMETAC and POx-PSPMA was observed. The number of proliferated cells scaled roughly linear with the METAC or SPMA comonomer content. Additional collagen I coating further improved the stem cell proliferation. Finally, a first POx-based system for the preparation of biodegradable hydrogel microcarriers is described and evaluated for stem cell culturing.
- "Variation of reaction conditions including change of the emulsifier or emulsifier content, oil phase (n-heptane, paraffin, dodecane) did not significantly improve the microbead morphology to a degree that would allow a later systematic investigation. An intriguing alternative to produce hydrogel microbeads of defined morphology, narrow size distribution, tunable sizes and even various shapes is their formation by microfluidics in which an aqueous phase is constantly injected into a flow of oil to form droplets of defined sizes in the range of tens to some hundreds of micrometers [1,12,46,61] . Such devices are relatively easy to prepare by rapid prototyping using PDMS . "