微小流路を用いた高機能マイクロカプセルの開発に関する研究

学位の種別: 課程博士審査委員会委員 : (主査)東京大学教授 鳥居 徹, 東京大学教授 神保 泰彦, 東京大学教授 藤井 輝夫, 東京大学准教授 割澤 伸一, 東京大学客員准教授 染矢 聡University of Tokyo(東京大学

Rapid Prototyping of a Nanoparticle Concentrator Using a Hydrogel Molding Method

Nanoparticle (NP) concentration is crucial for liquid biopsies and analysis, and various NP concentrators (NPCs) have been developed. Methods using ion concentration polarization (ICP), an electrochemical phenomenon based on NPCs consisting of microchannels, have attracted attention because samples can be non-invasively concentrated using devices with simple structures. The fabrication of such NPCs is limited by the need for lithography, requiring special equipment and time. To overcome this, we reported a rapid prototyping method for NPCs by extending the previously developed hydrogel molding method, a microchannel fabrication method using hydrogel as a mold. With this, we fabricated NPCs with both straight and branched channels, typical NPC configurations. The generation of ICP was verified, and an NP concentration test was performed using dispersions of negatively and positively charged NPs. In the straight-channel NPC, negatively and positively charged NPs were concentrated >50-fold and >25-fold the original concentration, respectively. To our knowledge, this is the first report of NP concentration via ICP in a straight-channel NPC. Using a branched-channel NPC, maximum concentration rates of 2.0-fold and 1.7-fold were obtained with negatively and positively charged NPs, respectively, similar to those obtained with NPCs fabricated through conventional lithography. This rapid prototyping method is expected to promote the development of NPCs for liquid biopsy and analysis

Hyper Alginate Gel Microbead Formation by Molecular Diffusion at the Hydrogel/Droplet Interface

We report a simple method for forming monodispersed, uniformly shaped gel microbeads with precisely controlled sizes. The basis of our method is the placement of monodispersed sodium alginate droplets, formed by a microfluidic device, on an agarose slab gel containing a high-osmotic-pressure gelation agent (CaCl₂ aq.): (1) the droplets are cross-linked (gelated) due to the diffusion of the gelation agent from the agarose slab gel to the sodium alginate droplets and (2) the droplets simultaneously shrink to a fraction of their original size (<100 μm in diameter) due to the diffusion of water molecules from the sodium alginate droplets to the agarose slab gel. We verified the mass transfer mechanism between the droplet and the agarose slab gel. This method circumvents the limitations of gel microbead formation, such as the need to prepare microchannels of various sizes, microchannel clogging, and the deformation of the produced gel microbeads

Hyper Alginate Gel Microbead Formation by Molecular Diffusion at the Hydrogel/Droplet Interface

We report a simple method for forming monodispersed, uniformly shaped gel microbeads with precisely controlled sizes. The basis of our method is the placement of monodispersed sodium alginate droplets, formed by a microfluidic device, on an agarose slab gel containing a high-osmotic-pressure gelation agent (CaCl₂ aq.): (1) the droplets are cross-linked (gelated) due to the diffusion of the gelation agent from the agarose slab gel to the sodium alginate droplets and (2) the droplets simultaneously shrink to a fraction of their original size (<100 μm in diameter) due to the diffusion of water molecules from the sodium alginate droplets to the agarose slab gel. We verified the mass transfer mechanism between the droplet and the agarose slab gel. This method circumvents the limitations of gel microbead formation, such as the need to prepare microchannels of various sizes, microchannel clogging, and the deformation of the produced gel microbeads

Design, Fabrication, and Performance of an Optimized Flow Reactor with Parallel Micropacked Beds

Herein, we build on the results of our previous studies and describe the design and fabrication of a hybrid glass/silicon flow reactor with 32 parallel packed beds using an eight-inch wafer process. Increasing throughput of the exothermic reaction requires sufficient heat removal for maintaining reasonable productivity as well as for safe operation. In this work, a glass/silicon combination was chosen as reactor materials. We predicted the heat dissipation effect of the bonding of a silicon substrate to the glass microreactor, which was validated by the reaction experiment monitored by IR thermography. The reactor withstood pressures of up to 13 MPa, which ensures safe reactor operation in spite of the brittleness of materials (silicon and glass) used. It was designed to serve for the direct synthesis of hydrogen peroxide (10 wt %) with 0.5 kg/h productivity per single reactor, and its parallel operation was demonstrated. Here we can show that the reactor is well suited for the safe and efficient operation of hazardous processes and their upscaling