Mixing enhancement has drawn great attention from designers of micromixers, since the flow in a microchannel is usually characterized by a low Reynolds number (Re) which makes the mixing quite a difficult task to accomplish. In this paper, a novel integrated efficient micromixer named serpentine laminating micromixer (SLM) has been designed, simulated, fabricated and fully characterized. In the SLM, a high level of efficient mixing can be achieved by combining two general chaotic mixing mechanisms: splitting/recombination and chaotic advection. The splitting and recombination (in other terms, lamination) mechanism is obtained by the successive arrangement of "F"-shape mixing units in two layers. The advection is induced by the overall three-dimensional serpentine path of the microchannel. The SLM was realized by SU-8 photolithography, nickel electroplating, injection molding and thermal bonding. Mixing performance of the SLM was fully characterized numerically and experimentally. The numerical mixing simulations show that the advection acts favorably to realize the ideal vertical lamination of fluid flow. The mixing experiments based on an average mixing color intensity change of phenolphthalein show a high level of mixing performance was obtained with the SLM. Numerical and experimental results confirm that efficient mixing is successfully achieved from the SLM over the wide range of Re. Due to the simple and mass producible geometry of the efficient micromixer, SLM proposed in this study, the SLM can be easily applied to integrated microfluidic systems, such as micro-total-analysis-systems or lab-on-a-chip systems.

An invariant-based optimal fitting (IBOF) closure approximation is proposed to approximate the fourth order structural orientation tensor in terms of the second order structural orientation tensor and its invariants. IBOF adopts the most general expression of a full symmetric fourth order tensor using a symmetric second order tensor and an identity tensor. The six coefficients that appear in the expression are represented by polynomial expansions in terms of the second and third invariants of the second order orientation tensor, similar to in the natural (NAT) closure approximation. Unknown parameters in the polynomial expansions are determined by following the method introduced by an orthotropic fitted closure approximation, which is a least-square optimization fitting technique of various flow data generated from solutions of the probability distribution function. IBOF is a hybrid of the NAT and the orthotropic fitted approximations, which are types of eigenvalue-based optimal fitting (EBOF) closure approximations. The accuracy of IBOF is as good as EBOF, and IBOF requires less computational time to obtain a solution. Also, IBOF does not suffer from the singularity problems encountered in using the NAT approximations.

Blood typing is the most important test for both transfusion recipients and blood donors. In this paper, a low cost disposable blood typing integrated microfluidic biochip has been designed, fabricated and characterized. In the biochip, flow splitting microchannels, chaotic micromixers, reaction microchambers and detection microfilters are fully integrated. The loaded sample blood can be divided by 2 or 4 equal volumes through the flow splitting microchannel so that one can perform 2 or 4 blood agglutination tests in parallel. For the purpose of obtaining efficient reaction of agglutinogens on red blood cells (RBCs) and agglutinins in serum, we incorporated a serpentine laminating micromixer into the biochip, which combines two chaotic mixing mechanisms of splitting/recombination and chaotic advection. Relatively large area reaction microchambers were also introduced for the sake of keeping the mixture of the sample blood and serum during the reaction time before filtering. The gradually decreasing multi-step detection microfilters were designed in order to effectively filter the reacted agglutinated RBCs, which show the corresponding blood group. To achieve the cost-effectiveness of the microfluidic biochip for disposability, the biochip was realized by the microinjection moulding of COC (cyclic olefin copolymer) and thermal bonding of two injection moulded COC substrates in mass production with a total fabrication time of less than 20 min. Mould inserts of the biochip for the microinjection moulding were fabricated by SU-8 photolithography and the subsequent nickel electroplating process. Human blood groups of A, B and AB have been successfully determined with the naked eye, with 3 microl of the whole sample bloods, by means of the fabricated biochip within 3 min.

Mixing enhancement has drawn a great attention to designing of micromixers, since the flow in a microchannel is usually characterized by a low Reynolds number (Re) which makes mixing quite a difficult task to complete. In this regard, we present a new chaotic passive micromixer, called a barrier embedded micromixer (BEM). In the BEM, chaotic flow is induced by periodic perturbation of the velocity field due to periodically inserted barriers along the top surface of the channel while a helical type of flow is obtained by slanted grooves on the bottom surface in the pressure driven flow. A T-channel and a microchannel with only slanted grooves were fabricated for the purpose of experimental comparison. Mixing performance has been experimentally characterized in two ways: (i) change of average mixing intensity by means of phenolphthalein and (ii) mixing patterns via a confocal microscope. Experimental results showed that BEM has better mixing performance than the other two. A characteristic required mixing length, defined in view of intensity change, increases logarithmically with Re in BEM. The confocal microscope images indicated that BEM could achieve almost complete mixing. The chaotic mixing mechanism, proposed in this study can be easily applied to integrated microfluidic systems, such as micro-total-analysis-systems, lab-on-a-chip and so on.

Micromixers have a variety of applications in chemical and biological processes, becoming an important component in microfluidic systems. The present work aims at understanding detailed mixing behaviour of micromixers by developing a numerical analysis scheme, which ultimately facilitates efficient micromixer design. A systematic numerical method has been developed, enabling visualization of detailed mixing patterns and quantification of the mixing performance in chaotic micromixers. The overall numerical scheme is named ‘colored particle tracking method’ (CPTM), consisting of three steps: (i) a flow analysis to obtain a periodic velocity field of a periodic mixing protocol by the Galerkin/least-squares (GLS) method; (ii) a particle tracking step, particles being labeled by a specific color at the inlet according to fluid species, to obtain a distribution of colored particles at the end of the final period; (iii) a quantification of the degree of mixing from the obtained particle distribution. For the last step we propose a new mixing measure based on the information entropy. The CPTM has successfully been applied to three examples of micromixers with patterned grooves to evaluate their mixing performance both qualitatively and quantitatively. The CPTM seems promising as a practically attractive numerical scheme for mixing analysis of chaotic micromixers.

We developed improved models (called ORW and ORW3) of existing “orthotropic fitted” closure approximations (ORF or ORL) for use with a wide range of fiber‐fiber interaction coefficients. Closure approximation refers to the approximation of a higher order tensor in terms of a lower order tensor. Principal values of the 4th order tensor are assumed in terms of polynomial expansions of the eigenvalues of the 2nd order tensor. Unknown parameters are determined by a least‐square fitting technique with assumed exact solutions. Flow data for the optimal fitting were designed to cover the entire domain of the orientation triangle as uniformly as possible to eliminate non‐physical oscillation. Shear/biaxial stretching combined flow turns out to play an important role in covering the orientation triangle, thereby increasing the accuracy of fiber orientation prediction. When tested for a variety of flow cases, neither ORW nor ORW3 shows any of the non‐physical oscillatory behaviors that ORF and ORL frequently suffer from.

BackgroundCyclic GMP-dependent protein kinases (PKGs) are central mediators of the NO-cGMP signaling pathway and phosphorylate downstream substrates that are crucial for regulating smooth muscle tone, platelet activation, nociception and memory formation. As one of the main receptors for cGMP, PKGs mediate most of the effects of cGMP elevating drugs, such as nitric oxide-releasing agents and phosphodiesterase inhibitors which are used for the treatment of angina pectoris and erectile dysfunction, respectively.Methodology/Principal FindingsWe have investigated the mechanism of cyclic nucleotide binding to PKG by determining crystal structures of the amino-terminal cyclic nucleotide-binding domain (CNBD-A) of human PKG I bound to either cGMP or cAMP. We also determined the structure of CNBD-A in the absence of bound nucleotide. The crystal structures of CNBD-A with bound cAMP or cGMP reveal that cAMP binds in either syn or anti configurations whereas cGMP binds only in a syn configuration, with a conserved threonine residue anchoring both cyclic phosphate and guanine moieties. The structure of CNBD-A in the absence of bound cyclic nucleotide was similar to that of the cyclic nucleotide bound structures. Surprisingly, isothermal titration calorimetry experiments demonstrated that CNBD-A binds both cGMP and cAMP with a relatively high affinity, showing an approximately two-fold preference for cGMP.Conclusions/SignificanceOur findings suggest that CNBD-A binds cGMP in the syn conformation through its interaction with Thr193 and an unusual cis-peptide forming residues Leu172 and Cys173. Although these studies provide the first structural insights into cyclic nucleotide binding to PKG, our ITC results show only a two-fold preference for cGMP, indicating that other domains are required for the previously reported cyclic nucleotide selectivity.

The present work suggests a mass-producible and large-scale fabrication method of superhydrophobic polymeric surfaces by means of material processing equipments which can maximize productivity and cost effectiveness. We fabricated two types of polymeric lotus leaf replicas using a nickel mold, i.e. R1 from intrinsically hydrophobic polydimethylsiloxane by means of polymer casting (PC) and R2 from an intrinsically hydrophilic UV-curable photopolymer by means of UV-nanoimprint lithography (UV-NIL). In the case of R1 from PC, although the nano-scaled structures were not well reproduced, the contact angle (CA) was remarkably high and the sliding angle (SA) was also close to that of the original lotus leaf, resulting in a superhydrophobic surface. In contrast to R1, in the case of R2 from UV-NIL, the nano-scaled structures as well as micro-scaled structures were also relatively well reproduced and the CA was increased noticeably by around 99° in comparison to a flat photopolymer. However, unexpectedly, the SA of R2 was much higher than that of R1. This work provides useful tips of polymeric material selection for the industrial mass production of the superhydrophobic polymer surface.