Kunihiko Uemura

Industrial lab-on-a-chip: Design, applications and scale-up for drug discovery and delivery

Microfluidics is an emerging and promising interdisciplinary technology which offers powerful platforms for precise production of novel functional materials (e.g., emulsion droplets, microcapsules, and nanoparticles as drug delivery vehicles- and drug molecules) as well as high-throughput analyses (e.g., bioassays, detection, and diagnostics). In particular, multiphase microfluidics is a rapidly growing technology and has beneficial applications in various fields including biomedicals, chemicals, and foods. In this review, we first describe the fundamentals and latest developments in multiphase microfluidics for producing biocompatible materials that are precisely controlled in size, shape, internal morphology and composition. We next describe some microfluidic applications that synthesize drug molecules, handle biological substances and biological units, and imitate biological organs. We also highlight and discuss design, applications and scale up of droplet- and flow-based microfluidic devices used for drug discovery and delivery.

Developing a new apparatus for inactivating Bacillus subtilis spore in orange juice with a high electric field AC under pressurized conditions

An electric inactivating apparatus of micro-organic spores was designed. A continuous AC electric field (20 kHz, 16.3 kV/cm) was applied to orange juice containing Bacillus subtilis spores in order to examine the inactivation effect of electrical equipment. Electrical treatment at 100 °C under atmospheric pressure has a poor ability to inactivate Bacillus subtilis spores. But electrical treatment at 121 °C under pressurized conditions to elevate the boiling point can reduce the viable Bacillus subtilis spores in orange juice four logarithmic orders in <1 s of treatment. 10% of the original ascorbic acid in the orange juice was destroyed after electric treatment. This value compares with 30% that was destroyed by heating in boiling water for 10 min. And the unpalatable flavor of heat-treated Satsuma mandarin juice was not developed in the electric treated juice.

Developing a new apparatus for inactivating Escherichia coli in saline water with high electric field AC

Abstract An electrical apparatus for inactivating microorganisms in saline water was designed. A continuous AC electric field (20 kHz, 14 kV/cm) was applied to 0.1% saline water containing Escherichia coli in order to examine the inactivation effect of the electrical apparatus. After the electric treatment, a reduction of 5 logarithmic orders was observed for E. coli when the final process temperature was controlled at 74 ° C . The temperature was maintained constant by alternating saline concentration with different electric field intensities. A higher electric field at the same process temperature produced a larger decrease of E. coli. Further, a higher process temperature at the same electric field also decreased the number of cells. It was concluded that high electric field combined with high temperature plays an important role in inactivation in a short time treatment.

A new twin-screw press design for oil extraction of dehulled sunflower seeds

Transport of material in a single-screw press depends mainly on friction between the material and the barrel’s inner surface and the screw surface during screw rotation. Thus, a solid core component, like seed hulls, is often necessary to produce the fraction. This sometimes causes excess frictional heat, large energy consumption and oil deterioration. Furthermore, if single-screw presses are not configured with breaker bars or other special equipment, they provide inadequate crushing and mixing.A twin-screw oil press can be expected to solve these problems because of the higher transportation force, similar to a gear pump, and better mixing and crushing at the twin-screw interface. A twin-screw press (screw diameter=136 mm, length/diameter=6.5, screw speed 15–100 rpm, feed rate=50–150 kg/h) was designed with partially intermeshing and counter-rotating screws and was tested on dehulled sunflower seed. The results were compared to a single-screw lab-scale press. Dehulled sun-flower seed (wt, 6.0%; oil, 58.6%) without pretreatments (crushing or cooking) gave 93.6% oil recovery with the twin-screw press, in contrast to 20% oil recovery with the single-screw press. The oil expressed with a twin-screw press had less foreign material than the oil from the single-screw press. Other properties of the oil were also good. Energy consumption of the twin-screw press was more efficient. All results suggested that oil production from dehulled sunflower seed with a twin-screw press is highly efficient.

Architecture of baked breads depicted by a magnetic resonance imaging

The architecture of baked breads made of fresh dough and frozen dough was depicted by magnetic resonance imaging (MRI). Pieces of bread (16 mm cubic cakes) were soaked in organic solvents containing various concentrations of heavy metals (Cu(2+), Co(2+) and Fe(3+)) and images of the grain structure of the breads were obtained. Of the organic solvents tested, acetone was preferable because of its single peak that prevents chemical shift effects on images, the retention of the bread structure, and the solubility of heavy metals. The heavy metals, especially Fe(3+), shortened the overly long relaxation times of acetone to practical lengths for imaging and stained the materials to provide high contrasts. The images obtained in acetone with 8 mM Fe(3+) were suitable for analyzing crumb grain structures. The bread of fresh dough showed a uniform distribution of pores of various sizes made of thin gluten sheets, whereas the pores in the bread of frozen dough were less, prominently large, non-uniformly distributed, and made of thick gluten sheets.

Preparation and Characterization of Water-in-Oil-in-Water Emulsions Containing a High Concentration of L-Ascorbic Acid

This study sought to encapsulate a high concentration of L-ascorbic acid, up to 30% (w/v), in the inner aqueous phase of water-in-oil-water (W/O/W) emulsions with soybean oil as the oil phase. Two-step homogenization was conducted to prepare W/O/W emulsions stabilized by a hydrophobic emulsifier and 30% (v/v) of W/O droplets stabilized by a hydrophilic emulsifier. First-step homogenization prepared W/O emulsions with an average aqueous droplet diameter of 2.0 to 3.0 μm. Second-step homogenization prepared W/O/W emulsions with an average W/O droplet diameter of 14 to 18 μm and coefficients of variation (CVs) of 18% to 25%. The results indicated that stable W/O/W emulsions containing a high concentration of L-ascorbic acid were obtained by adding gelatin and magnesium sulfate in the inner aqueous phase and glucose in both aqueous phases. L-Ascorbic acid retention in the W/O/W emulsions was 40% on day 30 and followed first-order kinetics.

Formulation characteristics of triacylglycerol oil-in-water emulsions loaded with ergocalciferol using microchannel emulsification

Ergocalciferol is one important form of vitamin D that is needed for proper functioning of the human metabolic system. The study formulates monodisperse food grade ergocalciferol loaded oil-in-water (O/W) emulsions by microchannel emulsification (MCE). The primary characterization was performed with grooved MCE, while the storage stability and encapsulating efficiency (EE) were investigated with straight-through MCE. The grooved microchannel (MC) array plate has 5 × 18 μm MCs, while the asymmetric straight-through MC array plate consists of numerous 10 × 80 μm microslots each connected to a 10 μm diameter circular MC. Ergocalciferol at a concentration of 0.2–1.0% (w/w) was added to various oils and served as the dispersed phase, while the continuous phase constituted either of 1% (w/w) Tween 20, decaglycerol monolaurate (Sunsoft A-12) or β-lactoglobulin. The primary characterization indicated successful emulsification in the presence of 1% (w/w) Tween 20 or Sunsoft A-12. The average droplet diameter increased slowly with the increasing concentration of ergocalciferol and ranged from 28.3 to 30.0 μm with a coefficient of variation below 6.0%. Straight-through MCE was conducted with 0.5% (w/w) ergocalciferol in soybean oil together with 1% (w/w) Tween 20 in Milli-Q water as the optimum dispersed and continuous phases. Monodisperse O/W emulsions with a Sauter mean diameter (d3,2) of 34 μm with a relative span factor of less than 0.2 were successfully obtained from straight-through MCE. The resultant oil droplets were physically stable for 15 days (d) at 4 °C without any significant increase in d3,2. The monodisperse O/W emulsions exhibited an ergocalciferol EE of more than 75% during the storage period.

Monodisperse aqueous microspheres encapsulating high concentration of l-ascorbic acid: insights of preparation and stability evaluation from straight-through microchannel emulsification

Stabilization of l-ascorbic acid (l-AA) is a challenging task for food and pharmaceutical industries. The study was conducted to prepare monodisperse aqueous microspheres containing enhanced concentrations of l-AA by using microchannel emulsification (MCE). The asymmetric straight-through microchannel (MC) array used here constitutes 11 × 104 μm microslots connected to a 10 μm circular microholes. 5–30% (w/w) l-AA was added to a Milli-Q water solution containing 2% (w/w) sodium alginate and 1% (w/w) magnesium sulfate, while the continuous phase constitutes 5% (w/w) tetraglycerol condensed ricinoleate in water-saturated decane. Monodisperse aqueous microspheres with average diameters (dav) of 18.7–20.7 μm and coefficients of variation (CVs) below 6% were successfully prepared via MCE regardless of the l-AA concentrations applied. The collected microspheres were physically stable in terms of their dav and CV for >10 days of storage at 40°C. The aqueous microspheres exhibited l-AA encapsulation efficiency exceeding 70% during the storage. Straight-through microchannel emulsification has ability to produce monodisperse emulsions. l-AA is encapsulated in aqueous microspheres and has encapsulation efficiency of over 70% after 10 days of storage at 40oC.

Large microchannel emulsification device for mass producing uniformly sized droplets on a liter per hour scale

Abstract We report the mass production of uniformly sized droplets on a liter per hour scale using a large microchannel (MC) emulsification device developed in this study. This MC emulsification device includes a newly designed 40×40-mm silicon MC array chip with 24,772 asymmetric MCs, each consisting of a circular microhole (17-μm diameter and 200-μm depth) and a microslot (17×119-μm cross-section and 60-μm depth). The oil-in-water (O/W) system was composed of n-tetradecane as the dispersed phase and a Milli-Q water solution containing 2.0 wt% Tween-20 as the continuous phase. The MC emulsification results demonstrated the stable mass production of uniformly sized oil droplets with average diameters of 87 μm and coefficients of variation below 2% over a wide range of volumetric flow rates of the dispersed phase up to 1.4 l/h. Analyses of shear stress at the chip surface and droplet generation via an asymmetric MC verified that the resultant droplet size and size distribution was not influenced by the volumetric flow rate of each phase. The large MC emulsification device has a potential droplet productivity exceeding several tons per year, which could satisfy a minimum industrial-scale production of monodisperse microdispersions containing emulsion droplets, microparticles, and microcapsules.

Microchannel emulsification study on formulation and stability characterization of monodisperse oil-in-water emulsions encapsulating quercetin

The study used microchannel emulsification (MCE) to encapsulate quercetin in food grade oil-in-water (O/W) emulsions. A silicon microchannel plate (Model WMS 1-2) comprised of 10,300 discrete 10×104μm microslots was connected to a circular microhole with an inner diameter of 10μm. 1% (w/w) Tween 20 was used as optimized emulsifier in Milli-Q water, while 0.4mgml(-1) quercetin in different oils served as a dispersed phase. The MCE was carried by injecting the dispersed phase at 2mlh(-1). Successful emulsification was conducted below the critical dispersed phase flux, with a Sauter mean diameter of 29μm and relative span factor below 0.25. The O/W emulsions remained stable in terms of droplet coalescence at 4 and 25°C for 30days. The encapsulation efficiency of quercetin in the O/W emulsions was 80% at 4°C and 70% at 25°C during the evaluated storage period.