Tuning transmission properties of 3D printed metal rod arrays by breaking the structural symmetry.

In this work, one metallic photonic crystal waveguide composed of periodic metal rod arrays (MRAs) is experimentally and numerically demonstrated in terahertz frequencies. Such waveguides fabricated by 3D printers exhibit two resonant modes: the fundamental mode and the high-order mode, separating by a broad bandgap. Compared to the fundamental mode, the high-order mode shows higher field confinement and more sensitive to the geometry changes. By breaking the structure parameter, i.e., increasing or decreasing the metal rod interspace, the spectral positions, bandwidths, as well as the transmittances of high-order modes can be optimized. With broken symmetry in MRAs, the third resonant mode having high transmittance has emerged in the transmission spectrum. Results showing that fine-tuning in the alignment of metal rods leads to a great change in the transmission of high-order modes. These findings suggest that the transportation efficiency of THz waves through an MRA is tunable by breaking the structural symmetry.

Sharp resonances in terahertz free-standing three-dimensional metallic woven meshes.

Free-standing structures that do not require any holder or substrate show high levels of flexibility and stretchability and hence are well-suited for THz applications. In this work, a free-standing three-dimensional metallic woven mesh is experimentally and numerically investigated at terahertz frequencies. Such mesh fabricated by weaving techniques exhibits sharp Fano-like resonances, which has not been found in previous studies. Investigation results indicate that the high Q resonances originate from the bending effect in bent wires, which can be termed as Wood's anomalies. The resonance field longitudinally covers the input and output end faces of the woven mesh, thereby obtaining a large field volume. These properties in this kind of meshes are well suited for wave manipulation and biomolecular sensing in the terahertz regime.

CCD Multi-Ion Image Sensor with Four 128 × 128 Pixels Array.

A semiconductor array pH image sensor consisting of four separated blocks was fabricated using charged coupled device (CCD) and complementary metal oxide semiconductor (CMOS) technologies. The sensing surface of one of the four blocks was Si3N4 and this block responded to H⁺. The surfaces of the other three blocks were respectively covered with cation sensitive membranes, which were separately printed with plasticized poly (vinyl chloride) solutions including Na⁺, K⁺, and Ca2+ ionophores by using an ink-jet printing method. In addition, each block of the image sensor with 128 × 128 pixels could have a calibration curve generated in each independent measurement condition. The present sensor could measure the concentration image of four kinds of ions (H⁺, K⁺, Na +, Ca2+) simultaneously at 8.3 frames per second (fps) in separated regions on a chip.

Investigation of spectral properties and lateral confinement of THz waves on a metal-rod-array-based photonic crystal waveguide.

Terahertz (THz) waves laterally confined in a 1 mm-thick microstructured planar waveguide are demonstrated on a free-standing metal rod array (MRA), and one apparent rejection band of a transmission spectrum, resembling the bandgap of a photonic crystal, is found in 0.1-0.6 THz. The visibility of the photonic bandgap in the spectral width and power distinction can be manipulated by changing the MRA geometry parameters, including the rod diameter, the interspace between adjacent rods, and the propagation length based on the interactive MRA-layer number. THz transmission ratio enhanced by a large interactive length is verified in 30 MRA layers due to the longitudinally resonant guidance of transverse-magnetic-polarized waveguide modes along the MRA length, which is critical to the interspace width of adjacent rods and the metal coating of the rod surface. For an MRA with respective rod diameter and interspace dimensions of about 0.16 and 0.26 mm, the highest transmission of the guided resonant THz waves are performed at 0.505-0.512 THz frequency with strong confinement on the metal rod tips and a low scattering loss of 0.003 cm-1.

Terahertz artificial material based on integrated metal-rod-array for phase sensitive fluid detection.

A terahertz artificial material composed of metal rod array is experimentally investigated on its transmission spectral property and successfully incorporated into microfluidics as a miniaturized terahertz waveguide with an extended optical-path-length for label-free fluidic sensing. Theoretical and experimental characterizations of terahertz transmission spectra show that the wave guidance along the metal rod array originates from the resonance of transverse-electric-polarized waves within the metal rod slits. The extended optical path length along three layers of metal-rod-array enables terahertz waves sufficiently overlapping the fluid molecules embedded among the rods, leading to strongly enhanced phase change by approximately one order of magnitude compared with the blank metal-parallel-plate waveguide. Based on the enhanced phase sensitivity, three kinds of colorless liquid analytes, namely, acetone, methanol, and ethanol, with different dipole moments are identified in situ using the metal-rod-array-based microfluidic sensor. The detection limit in molecular amounts of a liquid analyte is experimentally demonstrated to be less than 0.1 mmol, corresponding to 2.7 µmol/mm2. The phase sensitive terahertz metal-rod-array-based sensor potentially has good adaptability in lab-chip technology for various practical applications, such as industrial toxic fluid detection and medical breath inspection.

Salt effects on the picosecond dynamics of lysozyme hydration water investigated by terahertz time-domain spectroscopy and an insight into the Hofmeister series for protein stability and solubility.

The addition of salts into protein aqueous solutions causes changes in protein solubility and stability, whose ability is known to be ordered in the Hofmeister series. We investigated the effects of Hofmeister salts on the picosecond dynamics of water around a lysozyme molecule using terahertz time-domain spectroscopy. The change in the absorption coefficient for 200 mg mL(-1) lysozyme aqueous solution by the addition of salts was found to depend on the salts used, whereas that for pure water was almost independent of salts. From the difference in the salt concentration dependence for various salts, it has been found that chaotropic anions make the dynamics of water around the lysozyme molecule slower, whereas kosmotropic anions make the dynamics faster. The ability of an anion to slow down the water dynamics was found to have the following order: SCN(-) > Cl(-) > H2PO4(-) > NO3(-) ≈ SO4(2-). This result indicates that the effects of anions on the dynamics of water around the lysozyme molecule are the opposite of those for bulk water. This finding agrees with a prediction from a molecular model proposed by Collins [K. D. Collins, Methods, 2004, 34, 300]. The results presented here are compared with the results from preferential interaction studies and the results from sum frequency generation spectroscopy. These discussions have led to the conclusion that the picosecond dynamics of protein hydration water strongly contributes to protein stability, whereas electrostatic interactions between protein molecules contribute to protein solubility.

Two-dimensional microchemical observation of mast cell biogenic amine release as monitored by a 128 × 128 array-type charge-coupled device ion image sensor.

Available array-type, chemical-sensing image sensors generally only provide on/off responses to the sensed chemical and produce qualitative information. Therefore, there is a need for an array sensor design that can detect chemical concentration changes to produce quantitative, event-sensitive information. In this study, a 128 × 128 array-type image sensor was modified and applied to imaging of biogenic amines released from stimulated rat mast cells, providing recordable responses of the time course of their release and diffusion. The imaging tool was manufactured by an integrated circuit process, including complementary metal oxide semiconductor and charge-coupled device technology. It was fitted with an amine-sensitive membrane prepared from plasticized poly(vinyl chloride) including a hydrophobic anion, which allowed the sensor to detect amines, such as histamine and serotonin, in Tyrode's solution. As mast cells were larger in diameter than the pixel hollows, some pixels monitored amines released from single cells. The image from the array responses yielded sequential snapshots at a practical frame speed that followed amine concentration changes over time, after mast cell amine release was synchronized by chemical stimulation. This sensor was shown to be sensitive to amine release at very low stimulus concentrations and was able to detect localized spots of high amine release. The entire time course of the amine release was recorded, including maximum concentration at 4-6 s and signal disappearance at 30 s after stimulation. With further development, this sensor will increase opportunities to study a variety of biological systems, including neuronal chemical processes.

Determination of galactosamine impurities in heparin sodium using fluorescent labeling and conventional high-performance liquid chromatography.

Heparin is a sulfated glycosaminoglycan (GAG), which contains N-acetylated or N-sulfated glucosamine (GlcN). Heparin, which is generally obtained from the healthy porcine intestines, is widely used as an anticoagulant during dialysis and treatments of thrombosis such as disseminated intravascular coagulation. Dermatan sulfate (DS) and chondroitin sulfate (CS), which are galactosamine (GalN)-containing GAGs, are major process-related impurities of heparin products. The varying DS and CS contents between heparin products can be responsible for the different anticoagulant activities of heparin. Therefore, a test to determine the concentrations of GalN-containing GAG is essential to ensure the quality and safety of heparin products. In this study, we developed a method for determination of relative content of GalN from GalN-containing GAG in heparin active pharmaceutical ingredients (APIs). The method validation and collaborative study with heparin manufacturers and suppliers showed that our method has enough specificity, sensitivity, linearity, repeatability, reproducibility, and recovery as the limiting test for GalN from GalN-containing GAGs. We believe that our method will be useful for ensuring quality, efficacy, and safety of pharmaceutical heparins. On July 30, 2010, the GalN limiting test based on our method was adopted in the heparin sodium monograph in the Japanese Pharmacopoeia.

Classical theory of two-dimensional time-domain terahertz spectroscopy.

A general theoretical framework of two-dimensional time-domain second-order and third-order terahertz spectroscopy has been presented. The theoretical treatment is based on a classical and phenomenological model with weak nonlinearities. Three types of nonlinearity sources, anharmonicity, nonlinear coupling, and nonlinear damping, were considered. The second-order THz spectroscopy has an exact correspondence to fifth-order off-resonance Raman spectroscopy, and it has been shown that the present treatment gives exactly the same results as of the quantum mechanical theory under the weak nonlinearity condition. General expressions for the nonlinear signal have been obtained for a single-mode system, and numerical calculations for delta-function incident terahertz pulses were shown. For the third-order signal, two-level systems were also considered for comparison. Contributions of two types of incident pulse sequences have been studied separately in the third-order signals. Profiles of the two-dimensional signals were found to depend on the origin and order of the nonlinearity and also on the pulse sequence. The results of the present study show that the two-dimensional signal features of second- and third-order nonlinear terahertz spectroscopy can clarify the nature of the system which is not accessible using linear spectroscopy.

Heparin identification test and purity test for OSCS in heparin sodium and heparin calcium by weak anion-exchange high-performance liquid chromatography.

Heparin sodium and heparin calcium, which are widely used as anti-coagulants, are known to potentially contain the natural impurity dermatan sulfate (DS). Recently serious adverse events occurred in patients receiving heparin sodium in the US, and a contaminant oversulfated chondroitin sulfate (OSCS) was found to be a cause of the events. To ensure the quality and safety of pharmaceutical heparins, there is need of a physicochemical identification test that can discriminate heparin from the heparin-related substances as well as a sensitive purity test for OSCS. Recently, HPLC with a strong-anion exchange column was proposed as the methods for identifying heparin and determination of OSCS in heparin sodium. Although this method is convenient and easy to perform, the only column suitable for this purpose is the Dionex IonPac AS11-HC column. In this study, we developed alternative identification test and test for OSCS in both heparin sodium and heparin calcium using a weak anion-exchange column. The identification test allowed for separation of heparin from the impurity DS and contaminant OSCS in a shorter time. The purity test provided enough sensitivity, specificity, linearity, recovery and repeatability for OSCS. We believe that our methods will be useful for quality control of pharmaceutical heparins.

Anion sensing properties of electrospun nanofibers incorporating a thiourea-based chromoionophore in methanol.

To sense hydrophilic anions in protic solvents, we fabricated polymethylmethacrylate (PMMA) nanofibers incorporating 4-nitrophenyl azo thiourea polymer as a chromoionophore. When methanol solutions containing anions contacted the PMMA nanofiber, a bathochromic shift from 386 nm was observed in the absorption maximum of the chromoionophore. This spectral change is due to hydrogen bond formation between the urea moiety of the thiourea-based polymer and anions penetrating the nanofiber. This spectral change was not observed in PMMA film incorporating the same anion sensor, and the difference is attributed to the much larger specific surface area of the nanofiber compared to the film. As a result, many anions could react with the anion-sensing polymers in the nanofiber and induce a large spectral response.

Evaluation of Removal Behavior of Cesium in Contaminated Soil Based on Speciation Analysis.

The removal efficiency of Cs from contaminated soil depends on its chemical species bound with the soil components. Therefore, in this study, we observed the elution behavior of Cs based on speciation analysis in a Cs removal experiment conducted on contaminated soils. The treatment method was optimized using simulated contaminated soil and applied to actual contaminated soil on a large scale as well. The elution rate of Cs was approximately 50% or more in both actual and simulated contaminated soil using the optimized treatment method. From the obtained results, a robust treatment method using an eluting reagent and a magnetic adsorbent with low energy costs is proposed. Additionally, the usefulness of speciation analysis in decontamination studies was confirmed.

pH-potentiometirc study of polyion complexes between chitosan and poly(vinyl sulfate) or dodecylbenzene sulfonate.

Polyion complexes of three chitosans with poly(vinyl sulfate) (PVS) and dodecylbenzene sulfonate (DBS) were examined by a potentiometric study that was to separately measure the pH of sample solutions individually prepared. Apparent formation constants (Ki) of ion association between the protonated amines of chitosan and the sulfates of PVS or the sulfonates of DBS were determined. The effects of pH, coexistent salt concentration, and molecular weight on the values of Ki were investigated in order to reveal the properties of the complexation. The values of Ki for chitosan-PVS were quite larger than that for chitosan-DBS. The deducing effect of the coexistent salt was strong against chitosan-PVS, but was weak against chitosan-DBS. Thus, chitosan-PVS complexes possessed a strong electrostatic binding, and chitosan-DBS complexes included a hydrophobic interaction. For chitosan-PVS complexes the effect of the coexistent salt was weaker for a high molecular weight of chitosan than for a low molecular weight.

Potentiometric titration of polyhexamethylene biguanide hydrochloride with potassium poly(vinyl sulfate) solution using a cationic surfactant-selective electrode.

A potentiometric titration method using a cationic surfactant as an indicator cation and a plasticized poly(vinyl chloride) membrane electrode sensitive to the cationic surfactant is proposed for the determination of polyhexamethylene biguanide hydrochloride (PHMB-HCl), which is a cationic polyelectrolyte. A sample solution of PHMB-HCl containing an indicator cation (hexadecyltrimethylammonium ion, HTA) was titrated with a standard solution of an anionic polyelectrolyte, potassium poly(vinyl sulfate) (PVSK). The end-point was detected as a sharp potential change due to an abrupt decrease in the concentration of the indicator cation, HTA, which is caused by its association with PVSK. The effects of the concentrations of HTA ion and coexisting electrolytes in the sample solution on the degree of the potential change at the end-point were examined. A linear relationship between the concentration of PHMB-HCl and the end-point volume of the titrant exists in the concentration range from 2.0 x 10(-5) to 4.0 x 10(-4) M in the case that the concentration of HTA is 1.0 x 10(-5) M, and that from 1.0 x 10(-6) to 1.2 x 10(-5) M in the case that the concentration of HTA is 5.0 x 10(-6) M, respectively. The proposed method was applied to the determination of PHMB-HCl in some contact-lens detergents.

Extracellular Bio-imaging of Acetylcholine-stimulated PC12 Cells Using a Calcium and Potassium Multi-ion Image Sensor.

In biochemistry, Ca2+ and K+ play essential roles to control signal transduction. Much interest has been focused on ion-imaging, which facilitates understanding of their ion flux dynamics. In this paper, we report a calcium and potassium multi-ion image sensor and its application to living cells (PC12). The multi-ion sensor had two selective plasticized poly(vinyl chloride) membranes containing ionophores. Each region on the sensor responded to only the corresponding ion. The multi-ion sensor has many advantages including not only label-free and real-time measurement but also simultaneous detection of Ca2+ and K+. Cultured PC12 cells treated with nerve growth factor were prepared, and a practical observation for the cells was conducted with the sensor. After the PC12 cells were stimulated by acetylcholine, only the extracellular Ca2+ concentration increased while there was no increase in the extracellular K+ concentration. Through the practical observation, we demonstrated that the sensor was helpful for analyzing the cell events with changing Ca2+ and/or K+ concentration.

A bio-image sensor for simultaneous detection of multi-neurotransmitters.

We report here a new bio-image sensor for simultaneous detection of spatial and temporal distribution of multi-neurotransmitters. It consists of multiple enzyme-immobilized membranes on a 128 × 128 pixel array with read-out circuit. Apyrase and acetylcholinesterase (AChE), as selective elements, are used to recognize adenosine 5'-triphosphate (ATP) and acetylcholine (ACh), respectively. To enhance the spatial resolution, hydrogen ion (H+) diffusion barrier layers are deposited on top of the bio-image sensor and demonstrated their prevention capability. The results are used to design the space among enzyme-immobilized pixels and the null H+ sensor to minimize the undesired signal overlap by H+ diffusion. Using this bio-image sensor, we can obtain H+ diffusion-independent imaging of concentration gradients of ATP and ACh in real-time. The sensing characteristics, such as sensitivity and detection of limit, are determined experimentally. With the proposed bio-image sensor the possibility exists for customizable monitoring of the activities of various neurochemicals by using different kinds of proton-consuming or generating enzymes.

Simulation study on cascaded terahertz pulse generation in electro-optic crystals.

We studied cascaded optical rectification processes for intense terahertz (THz) pulse generation in electro-optic crystals using simulations based on one-dimensional coupled propagation equations of THz and optical fields. We found that under ideal conditions of perfect phase matching and no absorption, cascaded optical rectification processes produce intense THz pulses with efficiencies exceeding the Manley-Rowe limit. Large red shifting of the pump light spectrum was observed. Effects of finite optical and THz absorption, phase mismatches, and pulse width were examined using parameters of a ZnTe crystal pumped by 800 nm pulses. THz field enhancement by multiple pulse pumping was also studied.

Visual detection of anions by a novel isothiourea-based chromophore.

S-Methyl-N-methyl-N'-(4-(N",N"-dimethylamino)phenyl)isothiourea, a novel isothiourea-based chromoionophore for anions, was synthesized. The reactivity for several anions was estimated by a visual method and UV-vis spectroscopy. By the addition of acetate ion, a blue shift in the absorption spectrum was observed in CHCl3, and the solvent color changed from yellow to colorless. These changes indicated that bound acetate ion interfered with the intramolecular charge transfer from the nitrogen atom of the diethylamino group to the isothiourea moiety. The addition of chloride ion caused a red shift of the chromophore and solvent color remained yellow. By the addition of dihydrogenphosphate ion, the precipitate was formed immediately. These anion-dependent natures of the chromoionophore allowed us to detect acetate and phosphate ions easily.

Adsorptive voltammetry of 2-(5-bromo-2-pyridyl)azo-5-[N-n-propyl-N-(3-sulfopropyl)amino]phenol on a carbon paste electrode in the presence of organic cations and polycation.

The adsorption of ion-association complexes on a carbon paste electrode (CPE) was investigated by cyclic voltammetry using an electroactive hydrophobic anion probe. The redox reactions of 2-(5-bromo-2-pyridyl)azo-5-[N-n-propyl-N-(3-sulfopropyl)amino]phenol (5-Br-PAPS), the analytical probe, were irreversible. The reduction of the azo group and the oxidation of the phenol were observed at -0.1 V and 0.9 V vs. SCE, respectively, in a 0.1 mol L(-1) H(2)SO(4) solution. The peak currents for the redox reaction increased with the concentration of the cationic surfactant and the accumulation time. The increase in the ratio of the peak current to the concentration of cationic surfactants was proportional to the hydrophobicity. The peak current for 5-Br-PAPS also increased when a polycation, polyhexamethylene biguanide hydrochloride, was added and was strongly dependent on the ionic strength and pH, in contrast to cationic surfactants.

Development of an ATP and hydrogen ion image sensor using a patterned apyrase-immobilized membrane.

A bio-image sensor using a patterned apyrase-immobilized membrane was developed to visualize the activities of adenosine triphosphate (ATP) and H+ ion in real-time. An enzymatic membrane patterning technique was suggested to immobilize apyrase on a specific sensing area of a charge coupled device (CCD)-type image sensor. It was able to observe the spatiotemporal information of ATP and H+ ion. The smallest size of a patterned membrane is 250×250µm2. The fabrication parameters of the patterned membrane, such as its thickness and the intensity of the incident light used for photolithography, were optimized experimentally. The sensing area under the patterned apyrase-immobilized membrane revealed a linear response up to 0.6mM of ATP concentration with a sensitivity of 37.8mV/mM. Meanwhile, another sensing area without the patterned membrane measured the diffused H+ ion from nearby membranes. This diffusion characteristics were analyzed to determine a measurement time that can minimize the undesirable impact of the diffused ions. In addition, the newly developed bio-image sensor successfully reconstructed ATP and H+ ion dynamics into sequential 2-dimensional images.