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The aim of this paper is to review the present status of novel MRI techniques as a new important instrument for functional ventilation imaging. The current status and future perspectives in research and clinical applications are summarized. Morphological lung imaging is based on chest radiography and computed tomography, whereas scintigraphy is used for ventilation imaging. During recent years, MRI has emerged as a new means for functional imaging of ventilation. Aerosolized contrast agents and oxygen are used in proton imaging, whereas non-proton imaging relies on fluorine compounds, such as sulfur hexafluoride and perfluorcarbons, or on hyperpolarized noble gases, such as helium-3 or xenon-129. All the gases are administered as inhaled "contrast agents" for imaging of the airways and airspaces. In general, straightforward images demonstrate the homogeneity of ventilation in a breath-hold and allow for determination of ventilated lung. The different properties of the different compounds enable the measurement of additional functional parameters. They comprise airspace size, regional oxygen partial pressure, and analysis of ventilation distribution, ventilation/perfusion ratios, and gas exchange, including oxygen uptake. Novel MRI techniques provide the potential for functional imaging of ventilation. The next steps include definition of the value and the potential of the different contrast mechanisms as well as determination of the significance of the functional information with regard to physiological research and patient management in chronic obstructive pulmonary disease and others.

Purpose:To elucidate the ability of 3 He-MRI to detect ventilation defects in lung transplant recipients, 3 He-MRI was compared to CT for concordance. Materials and Methods:We examined 14 lung recipients using 3 He-MRI on a 1.5 T MR scanner. CT served as a reference method. Up to four representative ventilation defects were defined for each lung on 3 He-MRI and compared to corresponding areas on CT.Results: Altogether, 59 representative ventilation defects were defined on 3 He-MRI. Plausible CT correlates were found for 29 ventilation defects; less plausible CT correlates were found for eight defects. In 22 defects (37%) no corresponding CT changes were detected. CT demonstrated correlates for ventilation defects seen on 3 He-MRI in only 63% of the cases. Conclusion:3 He-MRI yields a clear increase in the number of detected ventilation defects compared to CT. This may have an important impact on the early detection of bronchiolitis obliterans in lung transplant recipients.

A new microfluidic valve or a "v-type valve" which can be flexibly actuated to focus a fluid flow and block a specific area of a microchannel is demonstrated. Valves with different design parameters were fabricated by multilayer soft lithography and characterized at various operating pressures. To evaluate the functionality of the valve, single microparticles (∅ 7 μm and ∅ 15 μm) and single cells were trapped from flowing suspensions. Continuous processes of particle capture and release were achieved by controlling the actuation and deactuation of the valve. Integration of the v-type valve with poly(dimethyl siloxane) (PDMS) monolithic valves in microfluidic devices was demonstrated to illustrate the potential of the system in various applications such as the creation of a solid phase column, the isolation of a specific number of particles in reactors, and the capture and release of particles or cells in the flow of two immiscible liquids. We believe that this new valve system will be suitable for manipulating particles and cells in a broad range of applications.

A microfluidic platform or “microfluidic mapper” is demonstrated, which in a single experiment performs 36 parallel biochemical reactions with 36 different combinations of two reagents in stepwise concentration gradients. The volume used in each individual reaction was 36 nl. With the microfluidic mapper, we obtained a 3D enzyme reaction plot of horseradish peroxidase (HRP) with Amplex Red (AR) and hydrogen peroxide (H2O2), for concentration ranges of 11.7 μM to 100.0 μM and 11.1 μM to 66.7 μM for AR and H2O2, respectively. This system and methodology could be used as a fast analytical tool to evaluate various chemical and biochemical reactions especially where two or more reagents interact with each other. The generation of dual concentration gradients in the present format has many advantages such as parallelization of reactions in a nanoliter-scale volume and the real-time monitoring of processes leading to quick concentration gradients. The microfluidic mapper could be applied to various problems in analytical chemistry such as revealing of binding kinetics, and optimization of reaction kinetics.

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The correlation between the dimensionless retention times (DRT) of proteins in hydrophobic interaction chromatography (HIC) and their surface properties were investigated. A ternary atomic-level hydrophobicity scale was used to calculate the distribution of local average hydrophobicity across the proteins surfaces. These distributions were characterized by robust descriptive statistics to reduce their sensitivity to small changes in the three-dimensional structure. The applicability of these statistics for the prediction of protein retention behaviour was looked into. A linear combination of robust statistics describing the central tendency, heterogeneity and frequency of highly hydrophobic clusters was found to have a good predictive capability (R2  = 0.78), when combined a factor to account for protein size differences. The achieved error of prediction was 35% lower than for a similar model based on a description of the protein surface on an amino acid level. This indicates that a robust and mathematically simple model based on an atomic description of the protein surface can be used for the prediction of the retention behaviour of conformationally stable globular proteins with a well determined 3D structure in HIC. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:372-381, 2016.

Knowledge-based development of chromatographic separation processes requires efficient techniques to determine the physicochemical properties of the product and the impurities to be removed. These characterization techniques are usually divided into approaches that determine molecular properties, such as charge, hydrophobicity and size, or molecular interactions with auxiliary materials, commonly in the form of adsorption isotherms. In this study we demonstrate the application of a three-dimensional liquid chromatography approach to a clarified cell homogenate containing a therapeutic enzyme. Each separation dimension determines a molecular property relevant to the chromatographic behavior of each component. Matching of the peaks across the different separation dimensions and against a high-resolution reference chromatogram allows to assign the determined parameters to pseudo-components, allowing to determine the most promising technique for the removal of each impurity. More detailed process design using mechanistic models requires isotherm parameters. For this purpose, the second dimension consists of multiple linear gradient separations on columns in a high-throughput screening compatible format, that allow regression of isotherm parameters with an average standard error of 8%. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:1283-1291, 2016.