On-line rheological characterization of semi-solid formulations.

The rheological profile of a semi-solid product is a critical quality attribute. To monitor changes of this attribute during manufacturing, it would be beneficial to measure the rheological parameters in an on-line or in-line mode and implement this as a part of a control strategy for manufacturing of semi-solids. None of the process analytical technology (PAT) tools for measuring the rheological parameters have yet been widely accepted in the pharmaceutical area, as most of the equipment can only measure viscosity. Therefore, an automated system based on the measurement of pressure difference across both a topology optimized channel and a tube geometry (capillary viscometer) was investigated. The Pressure Difference Apparatus (PDA) can sample from the bulk intermediate/product stream and press the sample through the apparatus at different flow rates to yield a frequency sweep (G' and G″) and a flow curve (viscosity). A calibration model was successfully prepared and verified with hydroxyethyl cellulose gels with polymer content varying from 1.0 to 1.5% (w/w) resulting in gels of different viscosities. The calibration model was used on-line during manufacturing of a gel and manufacturing changes related to dilution of the product were clearly reflected in the batch evolution profiles. The measurements with the PDA reflected the shear rate and frequency ranges relevant for manufacturing and thereby complemented the rheology measurements obtained with a standard rheometer with real time data.

Parametric optimization of inverse trapezoid oleophobic surfaces.

In this paper, we introduce a comprehensive and versatile approach to the parametric shape optimization of oleophobic surfaces. We evaluate the performance of inverse trapezoid microstructures in terms of three objective parameters: apparent contact angle, maximum sustainable hydrostatic pressure, and mechanical robustness (Im, M.; Im, H:; Lee, J.H.; Yoon, J.B.; Choi, Y.K. A robust superhydrophobic and superoleophobic surface with inverse-trapezoidal microstructures on a large transparent flexible substrate. Soft Matter 2010, 6, 1401-1404; Im, M.; Im, H:; Lee, J.H.; Yoon, J.B.; Choi, Y.K. Analytical Modeling and Thermodynamic Analysis of Robust Superhydrophobic Surfaces with Inverse-Trapezoidal Microstructures. Langmuir 2010, 26, 17389-17397). We find that each of these parameters, if considered alone, would give trivial optima, while their interplay provides a well-defined optimal shape and aspect ratio. The inclusion of mechanical robustness in combination with conventional performance characteristics favors solutions relevant for practical applications, as mechanical stability is a critical issue not often addressed in idealized models.

Dynamic adaption of vascular morphology.

The structure of vascular networks adapts continuously to meet changes in demand of the surrounding tissue. Most of the known vascular adaptation mechanisms are based on local reactions to local stimuli such as pressure and flow, which in turn reflects influence from the surrounding tissue. Here we present a simple two-dimensional model in which, as an alternative approach, the tissue is modeled as a porous medium with intervening sharply defined flow channels. Based on simple, physiologically realistic assumptions, flow-channel structure adapts so as to reach a configuration in which all parts of the tissue are supplied. A set of model parameters uniquely determine the model dynamics, and we have identified the region of the best-performing model parameters (a global optimum). This region is surrounded in parameter space by less optimal model parameter values, and this separation is characterized by steep gradients in the related fitness landscape. Hence it appears that the optimal set of parameters tends to localize close to critical transition zones. Consequently, while the optimal solution is stable for modest parameter perturbations, larger perturbations may cause a profound and permanent shift in systems characteristics. We suggest that the system is driven toward a critical state as a consequence of the ongoing parameter optimization, mimicking an evolutionary pressure on the system.

Experimental characterisation of a novel viscoelastic rectifier design.

A planar microfluidic system with contractions and obstacles is characterized in terms of anisotropic flow resistance due to viscoelastic effects. The working mechanism is illustrated using streak photography, while the diodicity performance is quantified by pressure drop measurements. The point of maximum performance is found to occur at relatively low elasticity levels, with diodicity around 3.5. Based on a previously published numerical work [Ejlebjerg et al., Appl. Phys. Lett. 100, 234102 (2012)], 2D simulations of the FENE-CR differential constitutive model are also presented, but limited reproducibility and uncertainties of the experimental data prevent a direct comparison at low elasticity, where the flow is essentially two-dimensional.

HistoFlex--a microfluidic device providing uniform flow conditions enabling highly sensitive, reproducible and quantitative in situ hybridizations.

A microfluidic device (the HistoFlex) designed to perform and monitor molecular biological assays under dynamic flow conditions on microscope slide-substrates, with special emphasis on analyzing histological tissue sections, is presented. Microscope slides were reversibly sealed onto a cast polydimethylsiloxane (PDMS) insert, patterned with distribution channels and reaction chambers. Topology optimization was used to design reaction chambers with uniform flow conditions. The HistoFlex provided uniform hybridization conditions, across the reaction chamber, as determined by hybridization to microscope slides of spotted DNA microarrays when applying probe concentrations generally used in in situ hybridization (ISH) assays. The HistoFlex's novel ability in online monitoring of an in situ hybridization assay was demonstrated using direct fluorescent detection of hybridization to 18S rRNA. Tissue sections were not visually damaged during assaying, which enabled adapting a complete ISH assay for detection of microRNAs (miRNA). The effects of flow based incubations on hybridization, antibody incubation and Tyramide Signal Amplification (TSA) steps were investigated upon adapting the ISH assay for performing in the HistoFlex. The hybridization step was significantly enhanced using flow based incubations due to improved hybridization efficiency. The HistoFlex device enabled a fast miRNA ISH assay (3 hours) which provided higher hybridization signal intensity compared to using conventional techniques (5 h 40 min). We further demonstrate that the improved hybridization efficiency using the HistoFlex permits more complex assays e.g. those comprising sequential hybridization and detection of two miRNAs to be performed with significantly increased sensitivity. The HistoFlex provides a new histological analysis platform that will allow multiple and sequential assays to be performed under their individual optimum assay conditions. Images can subsequently be recorded either in combination or sequentially through the ability of the HistoFlex to monitor assays without disassembly.

Topology optimized microbioreactors.

This article presents the fusion of two hitherto unrelated fields--microbioreactors and topology optimization. The basis for this study is a rectangular microbioreactor with homogeneously distributed immobilized brewers yeast cells (Saccharomyces cerevisiae) that produce a recombinant protein. Topology optimization is then used to change the spatial distribution of cells in the reactor in order to optimize for maximal product flow out of the reactor. This distribution accounts for potentially negative effects of, for example, by-product inhibition. We show that the theoretical improvement in productivity is at least fivefold compared with the homogeneous reactor. The improvements obtained by applying topology optimization are largest where either nutrition is scarce or inhibition effects are pronounced.

Optimal homogenization of perfusion flows in microfluidic bio-reactors: a numerical study.

In recent years, the interest in small-scale bio-reactors has increased dramatically. To ensure homogeneous conditions within the complete area of perfused microfluidic bio-reactors, we develop a general design of a continually feed bio-reactor with uniform perfusion flow. This is achieved by introducing a specific type of perfusion inlet to the reaction area. The geometry of these inlets are found using the methods of topology optimization and shape optimization. The results are compared with two different analytic models, from which a general parametric description of the design is obtained and tested numerically. Such a parametric description will generally be beneficial for the design of a broad range of microfluidic bioreactors used for, e.g., cell culturing and analysis and in feeding bio-arrays.

A generalized theoretical model for "continuous particle separation in a microchannel having asymmetrically arranged multiple branches".

In this article we present a generalized theoretical model for the continuous separation of particles using the pinched flow fractionation method. So far the theoretical models have not been able to predict the separation of particles without the use of correction factors. In this article we present a model which is capable of predicting the separation from first principles. Furthermore we comment on the importance of the incorporation of the finite height of the micro fluidic channels in the models describing the system behavior. We compare our model with the experiment obtained by Seki et al. (J. Takagi, M. Yamada, M. Yasuda and M. Seki, Lab Chip, 2005, 5, 778-784).

Scaling behavior of optimally structured catalytic microfluidic reactors.

In this study of catalytic microfluidic reactors we show that, when optimally structured, these reactors share underlying scaling properties. The scaling is predicted theoretically and verified numerically. Furthermore, we show how to increase the reaction rate significantly by distributing the active porous material within the reactor using a high-level implementation of topology optimization.

Universality in edge-source diffusion dynamics.

We show that in edge-source diffusion dynamics the integrated concentration N(t) has a universal dependence with a characteristic time scale tau=(A/P)2pi/(4D), where D is the diffusion constant while A and P are the cross-sectional area and perimeter of the domain, respectively. For the short-time dynamics we find a universal square-root asymptotic dependence N(t)=N0(sqrt)t/tau while in the long-time dynamics N(t) saturates exponentially at N0. The exponential saturation is a general feature while the associated coefficients are weakly geometry dependent.

Reexamination of Hagen-Poiseuille flow: shape dependence of the hydraulic resistance in microchannels.

We consider pressure-driven, steady-state Poiseuille flow in straight channels with various cross-sectional shapes: elliptic, rectangular, triangular, and harmonic-perturbed circles. A given shape is characterized by its perimeter P and area A which are combined into the dimensionless compactness number C= P2/A, while the hydraulic resistance is characterized by the well-known dimensionless geometrical correction factor alpha. We find that alpha depends linearly on C, which points out C as a single dimensionless measure characterizing flow properties as well as the strength and effectiveness of surface-related phenomena central to lab-on-a-chip applications. This measure also provides a simple way to evaluate the hydraulic resistance for the various shapes.

Reaction-diffusion dynamics: confrontation between theory and experiment in a microfluidic reactor.

We confront, quantitatively, the theoretical description of the reaction-diffusion process of a second-order reaction to experiment. The reaction at work is Ca(2+)/CaGreen, a fluorescent tracer for calcium. The reactor is a T-shaped microchannel, 10 microm deep, 200 microm wide, and 2 cm long. The experimental measurements are compared with the two-dimensional numerical simulation of the reaction-diffusion equations. We find good agreement between theory and experiment. From this study, one may propose a method of measurement of various quantities, such as the kinetic rate of the reaction, in conditions yet inaccessible to conventional methods.