Direct Synthesis of a Covalently Self-Assembled Peptide Nanogel from a Tyrosine-Rich Peptide Monomer and Its Biomineralized Hybrids.

There has been significant progress in the self-assembly of biological materials, but the one-step covalent peptide self-assembly for well-defined nanostructures is still in its infancy. Inspired by the biological functions of tyrosine, a covalently assembled fluorescent peptide nanogel is developed by a ruthenium-mediated, one-step photo-crosslinking of tyrosine-rich short peptides under the visible light within 6 minutes. The covalently assembled peptide nanogel is stable in various organic solvents and different pH levels, unlike those made from vulnerable non-covalent assemblies. The semipermeable peptide nanogel with a high density of redox-active tyrosine acts as a novel nano-bioreactor, allowing the formation of uniform metal-peptide hybrids by selective biomineralization under UV irradiation. As such, this peptide nanogel could be useful in the design of novel nanohybrids and peptidosomes possessing functional nanomaterials.

Submillisecond organic synthesis: Outpacing Fries rearrangement through microfluidic rapid mixing.

In chemical synthesis, rapid intramolecular rearrangements often foil attempts at site-selective bimolecular functionalization. We developed a microfluidic technique that outpaces the very rapid anionic Fries rearrangement to chemoselectively functionalize iodophenyl carbamates at the ortho position. Central to the technique is a chip microreactor of our design, which can deliver a reaction time in the submillisecond range even at cryogenic temperatures. The microreactor was applied to the synthesis of afesal, a bioactive molecule exhibiting anthelmintic activity, to demonstrate its potential for practical synthesis and production.

Direct Fabrication of Free-Standing MOF Superstructures with Desired Shapes by Micro-Confined Interfacial Synthesis.

Recently, metal-organic frameworks (MOFs) with multifunctional pore chemistry have been intensively investigated for positioning the desired morphology at specific locations onto substrates for manufacturing devices. Herein, we develop a micro-confined interfacial synthesis (MIS) approach for fabrication of a variety of free-standing MOF superstructures with desired shapes. This approach for engineering MOFs provides three key features: 1) in situ synthesis of various free-standing MOF superstructures with controlled compositions, shape, and thickness using a mold membrane; 2) adding magnetic functionality into MOF superstructures by loading with Fe3 O4 nanoparticles; 3) transferring the synthesized MOF superstructural array on to flat or curved surface of various substrates. The MIS route with versatile potential opens the door for a number of new perspectives in various applications.

Covalent Self-Assembly and One-Step Photocrosslinking of Tyrosine-Rich Oligopeptides to Form Diverse Nanostructures.

We present covalently self-assembled peptide hollow nanocapsule and peptide lamella. These biomimetic dityrosine peptide nanostructures are synthesized by one-step photopolymerization of a tyrosine-rich short peptide without the aid of a template. This simple approach offers direct synthesis of fluorescent peptide nanocages and free-standing thin films. The simple crosslinked peptide lamella films provide robust mechanical properties with an elastic modulus of approximately 30 GPa and a hardness of 740 MPa. These nanostructures also allow for the design of peptidosomes. The approach taken here represents a rare example of covalent self-assembly of short peptides into nano-objects, which may be useful as microcompartments and separation membranes.

Multilayered film microreactors fabricated by a one-step thermal bonding technique with high reproducibility and their applications.

We report the versatile uses of multilayered polyimide (PI) film microreactors with various functions including pressure tolerance, three-dimensional mixing and multistep membrane emulsification. Such PI film microreactors were fabricated by a simple one-step thermal bonding technique with high reproducibility. Upon bonding at 300 °C for 1 hour, the thin and flexible film microdevices could withstand pressure up to 8.6 MPa and 16.3 MPa with PI adhesive film or fluoropolymer adhesive, respectively, due to differences in wettability. The hydrophilic and hydrophobic microchannel devices were used to generate monodisperse oil-in-water (O/W) and water-in-oil (W/O) droplets, and polymer micro/nanoparticles at a high generation frequency. A monolithic and chemical resistant film microreactor with a three-dimensional serpentine microchannel was used for the selective reduction of ester to aldehyde by efficient mixing and quenching in a flash chemistry manner, within a several 10(1) millisecond time scale. Furthermore, a novel multilayered film microreactor for organic-aqueous biphasic interfacial reactions was devised by embedding a membrane layer to induce chaotic mixing in both the interface and emulsified phase by flowing through multiple numbers of meshed structures along the hydrophobic channel. This simple and economic fabrication technique significantly facilitates mass production of multilayered film devices that could be useful as a platform for various microfluidic applications in chemistry and biology.

Micro-total envelope system with silicon nanowire separator for safe carcinogenic chemistry.

Exploration and expansion of the chemistries involving toxic or carcinogenic reagents are severely limited by the health hazards their presence poses. Here, we present a micro-total envelope system (µ-TES) and an automated total process for the generation of the carcinogenic reagent, its purification and its utilization for a desired synthesis that is totally enveloped from being exposed to the carcinogen. A unique microseparator is developed on the basis of SiNWs structure to replace the usual exposure-prone distillation in separating the generated reagent. Chloromethyl methyl ether chemistry is explored as a carcinogenic model in demonstrating the efficiency of the µ-TES that is fully automated so that feeding the ingredients for the generation is all it takes to produce the desired product. Syntheses taking days can be accomplished safely in minutes with excellent yields, which bodes well for elevating the carcinogenic chemistry to new unexplored dimensions.

A monolithic and flexible fluoropolymer film microreactor for organic synthesis applications.

A photocurable and viscous fluoropolymer with chemical stability is a highly desirable material for fabrication of microchemical devices. Lack of a reliable fabrication method, however, limits actual applications for organic reactions. Herein, we report fabrication of a monolithic and flexible fluoropolymer film microreactor and its use as a new microfluidic platform. The fabrication involves facile soft lithography techniques that enable partial curing of thin laminates, which can be readily bonded by conformal contact without any external forces. We demonstrate fabrication of various functional channels (~300 µm thick) such as those embedded with either a herringbone micromixer pattern or a droplet generator. Organic reactions under strongly acidic and basic conditions can be carried out in this film microreactor even at elevated temperature with excellent reproducibility. In particular, the transparent film microreactor with good deformability could be wrapped around a light-emitting lamp for close contact with the light source for efficient photochemical reactions with visible light, which demonstrates easy integration with optical components for functional miniaturized systems.

Three-dimensional flash flow microreactor for scale-up production of monodisperse PEG-PLGA nanoparticles.

We present a pressure-tolerant 3D parallel polyimide (PI) film microreactor operating at up to ~160 bars with direct 3D flow focusing geometry for mass production of PEG-PLGA nanoparticles in a ~10(1) gram-scale (g h(-1)).

Odorless isocyanide chemistry: an integrated microfluidic system for a multistep reaction sequence.

Can't smell this: An integrated continuous-flow microfluidic setup enables in situ generation, extraction, separation, and reaction of foul-smelling isocyanides with little exposure to the surroundings. Isocyanides were generated by dehydration of the corresponding N-substituted formamides, and several representative isocyanide-based organic reactions were successfully performed. DIPEA = N,N-diisopropylethylamine.

A doubly cross-linked nano-adhesive for the reliable sealing of flexible microfluidic devices.

Along with the expansion of microfluidics into many areas of applications such as sensors, microreactors and analytical tools, many other materials besides poly(dimethylsiloxane) (PDMS) have been suggested such as poly(imide) (PI) or poly(ethylene terephthalate) (PET). However, the sealing methods for these materials are not reliable in that many of the methods are specific to the substrate materials. Here, we report a novel robust doubly cross-linked nano-adhesive (DCNA) for bonding of various heterogeneous substrates. By depositing 200 nm of epoxy-containing polymer, poly(glycidyl methacrylate), via initiated chemical vapour deposition (iCVD) onto various substrates and cross-linking them with ethylenediamine, a strong adhesion was obtained between the substrates. This adhesive system was not only able to bond various difficult-to-bond substrates, such as PET or PI, but it could also preserve the complicated morphology of the surfaces owing to the thin nature of the DCNA system. The DCNA allowed fabrication of microfluidic devices using both rigid substrates, such as silicon wafer and glass, and flexible substrates, such as PDMS, PET and PI. The burst pressure of the devices sealed with DCNA exceeded 2.5 MPa, with a maximum burst pressure of 11.7 MPa. Furthermore, the adhesive system demonstrated an exceptional chemical and thermal resistance. The adhesion strength of the adhesive sandwiched between glass substrates remained the same even after a 10 day exposure to strong organic solvents such as toluene, acetone, and tetrahydrofuran (THF). Also, exposure to 200 °C for 15 h was not able to damage the adhesion strength. Using the high adhesive strength and flexibility of DCNA, flexible microfluidic devices that can be completely folded or rolled without any delamination during the operation were fabricated. The DCNA bonding is highly versatile in the sealing of microfluidic systems, and is compatible with a wide selection of materials, including flexible and foldable substrates, even upon sealing few-µm-sized channels.

Fabrication of novel transparent inorganic polymer derived microchannels and application for photopolymerization.

The present work describes fabrication of novel inorganic microfluidic channels derived from commercially available inorganic polymer allylhydridopolycarbosilane (AHPCS) by UV imprinting lithography process. The UV transparency and solvent resistance of the microfluidic channels was measured when the polymer was cured at various conditions. The microchannel cured at 160 degrees C for 3 h showed excellent transparency, especially in visible region. The photopolymerization of trimethylolpropanetriacrylate (TMPTA) in the microchannel resulted in greater yield and 20 times faster reaction than that in batch process. These preliminary results demonstrated that novel AHPCS derived microchannel can be useful as an alternative platform for optical and photochemical microfluidic devices.

Novel inorganic polymer derived microreactors for organic microchemistry applications.

Microreactors fabricated with optically transparent inorganic polymers from two types of precursors using a UV-microimprinting process demonstrated reliable solvent resistance and capability for performing three model organic synthetic reactions, which were compared with batch systems and glass based microreactors.