Design and fabrication of a multilayered polymer microfluidic chip with nanofluidic interconnects via adhesive contact printing

The design and fabrication of a multilayered polymer micro-nanofluidic chip is described that consists of poly(methylmethacrylate) (PMMA) layers that contain microfluidic channels separated in the vertical direction by polycarbonate (PC) membranes that incorporate an array of nanometre diameter cylindrical pores. The materials are optically transparent to allow inspection of the fluids within the channels in the near UV and visible spectrum. The design architecture enables nanofluidic interconnections to be placed in the vertical direction between microfluidic channels. Such an architecture allows microchannel separations within the chip, as well as allowing unique operations that utilize nanocapillary interconnects: the separation of analytes based on molecular size, channel isolation, enhanced mixing, and sample concentration. Device fabrication is made possible by a transfer process of labile membranes and the development of a contact printing method for a thermally curable epoxy based adhesive. This adhesive is shown to have bond strengths that prevent leakage and delamination and channel rupture tests exceed 6 atm (0.6 MPa) under applied pressure. Channels 100 microm in width and 20 microm in depth are contact printed without the adhesive entering the microchannel. The chip is characterized in terms of resistivity measurements along the microfluidic channels, electroosmotic flow (EOF) measurements at different pH values and laser-induced-fluorescence (LIF) detection of green-fluorescent protein (GFP) plugs injected across the nanocapillary membrane and into a microfluidic channel. The results indicate that the mixed polymer micro-nanofluidic multilayer chip has electrical characteristics needed for use in microanalytical systems.     

Microtiter plate based chemistry and in situ screening: a useful approach for rapid inhibitor discovery

The use of libraries extracted from nature or constructed by combinatorial chemistry, have been widely appreciated in the drug discovery area. In this perspective, we present our contribution to the field of enzyme inhibitor discovery using a useful approach that allows diversification of a common core in a microtiter plate followed by in situ screening. Our method relies on an organic reaction that is highly selective, high yielding, amenable to the microscale and preferably can be performed in water. The core can be a designed molecule based on the structural and mechanistic information of the target, a compound with a weak binding affinity, or a natural product. Several reactions were found useful for this approach and were applied to the rapid discovery of potent inhibitors of representative enzymes.     

Alkene cyclopropanation catalyzed by Halterman iron porphyrin: participation of organic bases as axial ligands

With the iron(III) complex of the Halterman iron porphyrin [P*Fe(Cl)] and ethyl diazoacetate (EDA) as catalyst and carbene source, respectively, styrene-type substrates were converted to cyclopropyl esters with high trans/cis ratio (not less than 12) and high enantioselectivity for the trans-isomers (74-86% ee). The isomeric distribution of the cyclopropyl esters so obtained is akin to that obtained from the previously reported Ru(II) counterpart [P*Ru(CO)]. A linear Hammett correlation log(k(X)/k(H)) = sigma(+)rho was observed with rho = -0.57 suggesting the involvement of an electrophilic cyclopropanating species derived from the iron(II) center as the reactive intermediate in the catalytic cycle. This is further supported by a dramatic decrease in the enantioselectivity and trans/cis ratio observed in an experiment of styrene cyclopropanation when the reaction mixture was deliberately exposed to air. Axial ligand effects on the selectivities was also investigated. Substantial improvement in trans/cis ratios could be achieved by addition of organic bases such as pyridine (py) and 1-methylimidazole (MeIm) to the catalytic reaction. The existence of axially ligated iron carbene moieties, [P*Fe(CHCO(2)Et)(py)] and [P*Fe(CHCO(2)Et)(MeIm)], was established by electrospray mass spectrometry. Study of secondary kinetic isotope effect indicated that a more product-like transition state was generated by addition of MeIm.     

Low temperature kinetics and energetics of the electron and hole traps in irradiated TiO2 nanoparticles as revealed by EPR spectroscopy

We have monitored exclusively the dynamics of photogenerated charge carriers trapping in deep traps and trapped electron-hole recombination in UV irradiated anatase TiO2 powders by electron paramagnetic resonance (EPR) spectroscopy at 10 K. The results reveal that the strategy of using low temperatures contributes to the stabilization of the charged pair states for hours by reducing the rate of electron-hole recombination processes. Since only the localized states such as holes trapped at oxygen anions and electrons trapped at coordinatively unsaturated cations are accessible to EPR spectroscopy, the time-dependent population and depopulation of these EPR signals reflect the kinetics and energetics of these trap states. The data support a model of sequential accumulation of deep trap site populations in which the initial fast direct trapping into a deep trap site is followed by slower carrier trap-to-trap hopping until a deep trap is encountered for both photogenerated electrons and holes. Effective modeling of the subsequent decay of trapped-holes is achieved by employing a first-order kinetics, whereas the decay of either surface- or inner-trapped electrons has both a fast and a slow component. The fast component is attributed to a trapped-electron and a free-hole recombination, and the slow component is attributed to trapped electron-hole recombination. The activation energies for the process of diffusion of trapped electrons from their Ti3+ trapping sites are estimated.     

Effects of temperature and chemical modification on polymer Langmuir films

We previously reported on a rheological study of Langmuir films of poly(tert-butyl methacrylate) (PtBMA), and this work describes further studies on this system. Here, surface pressure-area (Pi-A) isotherms and interfacial shear rheology experiments are performed to better understand the effects of two modifications: varying the temperature between 5 and 40 degrees C and introducing small amounts of carboxylic acid groups by partially hydrolyzing the polymer. Increased temperature produced isotherms with lower plateau surface pressures, Pip, and Pi values shifted to lower areas above Pip. Film properties transition from being primarily viscous to being dominated by elasticity as Pip is crossed for all temperatures studied, even as the value of Pip changes. Increasing the hydrolysis fraction leads to isotherms shifted to lower areas throughout the curve and higher Pip values. Both temperature variation and chemical modification are believed to affect the relative importance of polymer-polymer and polymer-subphase interactions.     

An embedding method for simulation of immobilized enzyme kinetics and transport in sessile hydrogel drops

A newly-developed embedding method for simulating enzyme kinetics and transport occurring within axisymmetric 3D domains is presented. The physical problem is pertinent to gel-pad microarrays for assessment of enzymatic activity. An enzyme is immobilized uniformly within a hydrogel which is spotted onto a solid surface in the form of a sessile drop, taking on a spherical cap shape. An aqueous solution containing substrate flows slowly past the porous drop. The substrate diffuses into the drop and is converted to product with the help of the enzyme. The product accumulates in and diffuses out of the drop and is taken away by the flow. Spatiotemporal distribution of the product, monitored via fluorescence, can be used to quantify the enzyme kinetics. This process is described by a system of nonlinear reaction-diffusion partial differential equations, modeling the diffusive transport and enzymatic reaction. The computational domain contains both the hydrogel drop and the bulk fluid phases. The embedding method is a computational technique that enables the use of finite differences on a regular Cartesian grid for simulation of multiphase problems with complex interfaces/boundaries. It uses a volume-fraction-based approach, similar to the volume-of-fluid (VOF) method, to implement the boundary conditions that must be applied at the interface between the phases. The main advantage of the embedding method is its simplicity, which results in code generation that can be highly optimized. In the present work, we apply the embedding method to the aforementioned two-phase reaction-diffusion problem and validate the results by comparing to a number of exact solutions available in simpler geometries and to results obtained using a finite-volume method on an unstructured body-fitted mesh. (© 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)     

Design optimization of a damped hybrid vibration absorber

In this article, the H_∞ optimization design of a hybrid vibration absorber (HVA), including both passive and active elements, for the minimization of the resonant vibration amplitude of a single degree-of-freedom (sdof) vibrating structure is derived by using the fixed-points theory. The optimum tuning parameters are the feedback gain, the tuning frequency, damping and mass ratios of the absorber. The effects of these parameters on the vibration reduction of the primary structure are revealed based on the analytical model. Design parameters of both passive and active elements of the HVA are optimized for the minimization of the resonant vibration amplitude of the primary system. One of the inherent limitations of the traditional passive vibration absorber is that its vibration absorption is low if the mass ratio between the absorber mass and the mass of the primary structure is low. The proposed HVA overcomes this limitation and provides very good vibration reduction performance even at a low mass ratio. The proposed optimized HVA is compared to a recently published HVA designed for similar propose and it shows that the present design requires less energy for the active element of the HVA than the compared design.     

Robust dynamic pairs trading with cointegration

This paper investigates the robust optimal pairs trading using the concept of equivalent probability measures and a penalty function associated with the confidence in parameter estimates when the parameters in the drift term of the continuous-time cointegration model are estimated with errors. A closed-form solution is derived for the robust pairs trading rule. We compare the robust pairs trading rule against its non-robust counterpart using simulations and real data. The robust strategy is empirically more stable and less volatile.     

Mapping the first electronic resonances of a Cu phthalocyanine STM tunnel junction

Using a low temperature, ultrahigh vacuum scanning tunneling microscope (STM), dI/dV differential conductance maps were recorded at the tunneling resonance energies for a single Cu phthalocyanine molecule adsorbed on an Au(111) surface. We demonstrated that, contrary to the common assumption, such maps are not representative of the molecular orbital spatial expansion, but rather result from their complex superposition captured by the STM tip apex with a superposition weight which generally does not correspond to the native weight used in the standard Slater determinant basis set. Changes in the molecule conformation on the Au(111) surface further obscure the identification between dI/dV conductance maps and the native molecular orbital electronic probability distribution in space.