A fully autonomous method of creating highly monodispersed emulsion droplets with a low sample dead volume was realized using a degassed poly(dimethylsiloxane) (PDMS) microfluidic chip possessing a simple T-junction channel geometry with two inlet reservoirs for oil and water to be loaded and one outlet reservoir for the collection of generated droplets. Autonomous transport of oil and water phases in the channel was executed by permeation of air confined inside the outlet reservoir into the degassed PDMS. The only operation required for droplet creation was simple pipetting of oil and aqueous solutions into the inlet reservoirs. Long-lasting fluid transport in the current system enabled us to create ca. 51,000 monodispersed droplets (with a coefficient of variation of <3% for the droplet diameter) in 80 min with a maximum droplet generation rate of ca. 12 Hz using a PDMS chip that had been degassed overnight. With multiple time-course measurements, the reproducibility in the current method of droplet preparation was confirmed, with tunable droplet sizes achieved simply by changing the cross-sectional dimensions of the microchannel. Furthermore, it was verified that the resultant droplets could serve as microreactors for digital polymerase chain reactions. This hands-free technique for preparing monodispersed droplets in a very facile and inexpensive fashion is intended for, but not limited to, bioanalytical applications and is also applicable to material syntheses.

Experimental results for methane and carbon dioxide diffusion in coal, as reported in the literature, often lead to diffusion rates of CO2 appearing to be much greater than that of CH4. The interpretation sometimes offered that the diffusion coefficient for CO2 is 1–2 orders of magnitude higher than that of CH4, violates fundamental principles. Nevertheless, the experimental observations require explanation. In this article, we: (a) Develop simplified models for the fast estimation of transport coefficients. These are compared with comprehensive grand canonical Monte Carlo (GCMC) and molecular dynamic (MD) simulations, collectively defined as molecular simulations (MS), which provide theoretical adsorption isotherms and various transport coefficients based on multicenter potential energy equations. The simplified models are shown to have acceptable accuracies. (b) Use the simplified models to compare diffusivities of CO2 and CH4 in carbon nanopores. For all cases examined, the diffusivity of CH4 is always larger than that of CO2. (c) Offer two explanations for the apparently contradictory experimental observations (that CO2 sometimes appears to diffuse much faster than the CH4 molecule, even though CH4 is lighter and has smaller adsorption affinity): (i) CH4 mobility could be significantly reduced by directional forces resulting from irregular pore geometries; and (ii) if pores contain throats with sizes close to the CH4 molecular diameter, the energy barrier that the methane molecules must overcome to proceed through is much larger than that required for CO2. (d) Demonstrate that both mobility and connectivity issues can be addressed using kinetic theory in association with percolation analysis. Furthermore, this method of understanding pore networks provides a number of important quantitative measures including percolation threshold, size of largest cluster, shortest path and tortuosity. Separating different transport mechanisms, as we propose here, provides improved insights into the complex transport phenomena that occur in carbonaceous porous media. In many cases, diffusivities reported in the literature with mixed mechanisms are better named “apparent transport coefficients,” because they lump in other unrelated phenomena, violating the fundamental basis of, or mathematical assumptions imposed on, the definition of diffusion. © 2011 American Institute of Chemical Engineers AIChE J, 2012

A PDMS microfluidic chip with T-junction channel geometry, two inlet reservoirs, and one outlet reservoir was reversibly adhered on a glass plate through the viscoelastic properties of PDMS. This formed a detachable microfluidic device for creation of water-in-oil emulsion droplets that were used as discrete reaction compartments for the droplet digital PCR. The PDMS/glass device could continuously produce monodisperse droplets without leakage of fluids using a vacuum-driven autonomous micropumping method. This droplet preparation technique only required evacuation of air dissolved in the PDMS before loading of oil and aqueous phases into separate inlet reservoirs. Degassing of the PDMS chip at approximately 300 Pa for 1.5 h in a vacuum desiccator gave 40 000 droplets in 80 min, which corresponded to a generation frequency of up to nine droplets per second. Over multiple runs the droplet creation was very reproducible, and the size reproducibility of generated droplets (polydispersity of up to 4.1%) was comparable to that acquired using other microfluidic droplet preparation techniques. Because the PDMS chip can be peeled off the glass plate, blocked channels can easily be fixed when they arise, and this extends the lifetime of the chip. Single DNA molecules partitioned into the droplets were successfully amplified by PCR. In addition, the droplet digital PCR platform allowed absolute quantification of low copy numbers of target DNA, and was robust against instrumental variance.

Plinabulin (1) is a potent anti-microtubule agent, however, its low water solubility has to be improved for the advantage in pharmacokinetics and chemotherapy. In this report, the replaceable water-solubilizing moiety of the water-soluble prodrug of plinabulin (1) was investigated. The properties of the water-soluble prodrugs of plinabulin (1), in which the water-solubilizing part was replaced with a new functionality, were evaluated. The newly introduced water-solubilizing moiety provided interesting effects on the water solubility and half-life of the prodrugs.Key words water-soluble prodrug; anti-microtubule agent; click chemistry; plinabulin; monolactim 'Prodrug' research is one of the most important fields of medicinal chemistry. In particular, improvements in water solubility have been studied extensively.1) Paclitaxel, for example, exhibited potent anti-microtubule activity 2) as intravenous (i.v.) injection. Due to its low water solubility (0.25 µg/mL), 3) it was initially formulated with the detergent cremophor EL, which induced hypersensitivity. 4) Therefore, a variety of water-soluble paclitaxel prodrugs have been developed to improve the patient's burden. 5-9)Previously, we reported the design and synthesis of a water-soluble prodrug of plinabulin (1) 10) as a monolactim serine-type derivative 2 11) using click chemistry 12-14) (Fig. 1). Plinabulin (NPI-2358) (1) (cytotoxic activity: IC 50 =15 nM in HT-29 cells) is a derivative of S-(−)-phenylahistin 15,16) and phase II clinical trials have been undertaken worldwide [17][18][19] by way of i.v. injection as a promising vascular disrupting agent (VDA). [20][21][22][23][24] Plinabulin (1) showed low water solubility (<0.1 µg/mL), which forced the co-injection of a solubilizing agent, such as paclitaxel. To improve the pharmacokinetics and chemotherapeutic index, the water-soluble prodrug 2 was developed. The water solubility of α-amino acid type derivative 2 was determined to be 6.38 mg/mL, and the in vitro halflife (t 1/2 ) in the presence of porcine liver esterase was found to be 59.9 min. These values make the compound appropriate for i.v. injection without inclusion of a solubilizing agent. Furthermore, the water-solubilizing triazole auxiliary, which was cleaved from the mother skeleton via an esterase hydrolysis reaction, was shown to be cellularly non-toxic.11) These results suggested that it was worthwhile to pursue further optimization of this prodrug system.In this paper, we investigated the replaceable water-solubilizing moiety to evaluate its influence on prodrug water solubility and half-life. As a water-solubilizing moiety, we focused on two types of polar groups. One was L-carnitine (3), 25) which is an γ-amino acid derivative involved in lipid metabolism in the human body. The unprotected polar functional group of the azide 4 26) is a β-hydroxycarboxylic acid moiety, that is similar to the serine-type structure used in prodrug 2, with a higher number of carbon atoms. These slight changes were expected to provide interesting effects on th...

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As a way to improve optical feeding antennas with a wide bandwidth above 1 GHz for evaluation of radiated emission test sites, we developed a tears drop type antenna composed of biconical type antenna elements and a sphere that utilizes a unitraveling-carrier photodiode (UTC-PD) as a photo detector instead of the usual PIN photo diode. The radiated electric field was measured and compared with values calculated from the finite integration (FI) method. A numerical simulation revealed that the calculated frequency characteristics and directivities of the electric field radiated from the tears drop type antenna agreed very well with the measured values. In addition, the measured frequency characteristics of the electric field radiated from the antenna were almost flat within 9 dB in the frequency range from 1 GHz to 6 GHz, and the measured electric field levels were from 97 dBμV/m to 106 dBμV/m. The radiation directivities in the ș direction almost complied with those specified by CISPR16-1-4 Ed.2. Our examinations showed that the tears drop type antenna is superior to a biconical type antenna.