Capillary Alignment Research Articles

Self-alignment of whole wafers using patterning for capillary forces

Three dimensional packaging schemes take advantage of multiple substrate materials, functionality, and reduced area constraints. Alignment of stacks of wafers becomes difficult as the number increases. We investigate full-wafer self-alignment as a means for solving this problem. To date, capillary self-alignment has only been accomplished with tiny, millimeter-sale, objects. Here, wafer-level self-alignment is demonstrated with capillary alignment forces, and we describe several needed, nontrivial advances and considerations compared to the chip alignment. The patterning scheme and the alignment force character are found to be crucial to ensure alignment at the wafer scale. Avoidance of alignment at local minima with the use of multiple length scales, prevention of upper wafer dragging by balancing the wafer and using engineered flow channels, and increased pattern features at small misalignments to combat the decreased alignment force are all discussed. A capture range of a few millimeters in position and several degrees in rotation for the self-alignment is achieved by patterning a hydrophobic self-assembled monolayer. These advances for large structure self-alignment offer a path forward for self-assembly of wafer stacks or other complex, large structures useful for mmWave, 5G antennas, for example. The scheme is compatible with a bonding scheme using the bonding precursor as the alignment fluid.

Mechanical Stimulation Induces Vasa Vasorum Capillary Alignment in a Fibrin-Based Tunica Adventitia.

Generation of bioartificial blood vessels with a physiological three-layered wall architecture is a long pursued goal in vascular tissue engineering. While considerable advances have been made to resemble the physiological tunica intima and media morphology and function in bioartificial vessels, only very few studies have targeted the generation of a tunica adventitia, including its characteristic vascular network known as the vasa vasorum, which are essential for graft nutrition and integration. In healthy native blood vessels, capillary vasa vasorum are aligned longitudinally to the vessel axis. Thus, inducing longitudinal alignment of capillary tubes to generate a physiological tunica adventitia morphology and function may be advantageous in bioengineered vessels as well. In this study, we investigated the effect of two biomechanical stimulation parameters, longitudinal tension and physiological cyclic stretch, on tube alignment in capillary networks formed by self-assembly of human umbilical vein endothelial cells in tunica adventitia-equivalents of fibrin-based bioartificial blood vessels. Moreover, the effect of changes of the biomechanical environment on network remodeling after initial tube formation was analyzed. Both, longitudinal tension and cyclic stretch by pulsatile perfusion induced physiological capillary tube alignment parallel to the longitudinal vessel axis. This effect was even more pronounced when both biomechanical factors were applied simultaneously, which resulted in an alignment of 57.2 ± 5.2% within 5° of the main vessel axis. Opposed to that, a random tube orientation was observed in vessels incubated statically. Scanning electron microscopy showed that longitudinal tension also resulted in longitudinal alignment of fibrin fibrils, which may function as a guidance structure for directed capillary tube formation. Moreover, existing microvascular networks showed distinct remodeling in response to addition or withdrawal of mechanical stimulation with corresponding increase or decrease of the degree of alignment. With longitudinal tension and cyclic stretch, we identified two mechanical stimuli that facilitate the generation of a prevascularized tunica adventitia-equivalent with physiological tube alignment in bioartificial vascular grafts. Impact statement Fibrin-based bioartificial vessels represent a promising regenerative approach to generate vascular grafts with superior biocompatibility and hemocompatibility compared to currently available synthetic graft materials. Precapillarization of bioartificial vascular grafts may improve nutrition of the vessel wall and integration of the graft into the target organism's microvasculature. In native vessels, physiological vasa vasorum alignment is pivotal for proper function of the tunica adventitia. Thus, it is necessary to induce longitudinal capillary alignment in the tunica adventitia of bioengineered vessels as well to secure long-term graft patency and function. This alignment can be reliably achieved by controlled biomechanical stimulation in vitro.

Modified SAMs and templates for achieving self-alignment of full wafers

Self-assembly of structures that are more than a few millimeters in size is a current problem that can have broad applications in new ways to construct the objects that we use. As a step in that direction, fluidic self-alignment at the wafer-to-wafer level is demonstrated, characterized, and modeled. Although self-alignment of millimeter-sized objects has previously been shown, several physical processes become important as the structure size is increased to a whole wafer. These processes are measured and modeled in this paper. Self-assembled monolayers, both natural and modified by oxidation, are used to create surface energy gradients that are used to produce capillary alignment forces. These forces exceed the wafer-edge forces. The measured capillary fluid profile is modeled to predict the alignment forces with no adjustable parameters. Alignment forces are measured and the trends are predicted as the surface tension of the liquid, hence the generated force, is varied. These considerations govern pattern design rules, which are described and ensure a long capture range, high alignment force, and avoidance of wafer-edge dragging.

Collagen Microfibers Induce Blood Capillary Orientation and Open Vascular Lumen.

Achieving vascularization of engineered tissues or structures is a major challenge in the field of tissue engineering. Hitherto, studies on vascularization have demonstrated limited control of vascular network geometry, such as vasculature direction and network density. An open vascular lumen is crucial to ensure that cells survive and that metabolic activity is fully functional in large-sized tissues. Herein, a method based on high water-dispersible collagen microfibers (CMF) to fabricate capillary orientation-controllable 3D tissue with an open vascular lumen using a dispensing machine is reported. A twenty micrometers-long CMF (CMF-20) with high dispersion property are shown to be more effective for dispensing a homogenous tissue and inducing formation of an interconnected capillary network than two hundred micrometers-long CMF (CMF-200). One of the advantages is the prevention of shrinkage on the z-axis of hydrogel-based tissue which acts as a microscaffold. The gaps between the fibers can support endothelial cell migration and maturation, thus forming a larger vascular lumen compared to CMF-free controls. Besides, shear forces produced by the dispensing process cause the collagen microfibers to align, and these microfibers guide cell alignment by integrin-induced adhesion. The findings based on CMF to allow blood capillary alignment and vascular lumen stabilization will be an important technology in tissue engineering.

Tunable Contact Angle Hysteresis for Component Placement on Stretchable Superhydrophobic Surfaces

AbstractOne of the promising strategies to achieve high performance flexible electronics is to integrate high performance components (micro‐electro‐mechanical systems, integrated circuit, etc.) on a flexible substrate. The heterointegration of fragile high performance components, for example, thinned down 100 GHz silicon technology, necessitate however methodologies to place these components on the substrate while exerting as little force as possible to prevent any damage from occurring. In this work, a novel approach is presented for component positioning by capillary assembly on a smart flexible substrate composed of two layers of polymers. It is shown how the wettability of the surface can be engineered by combining stretching induced deformation of the top layer with plasma treatment. Using magnetically actuated ferrofluid droplets which carry the silicon chip shows how it can be aligned and deposited at predetermined sites on these substrates. It is demonstrated that unlike standard capillary alignment which relies on a hydrophobic/hydrophilic contrast, in this case deposition is controlled by surface adhesion contrast between the site and the rest of the substrate. Furthermore, it is explained how deposition sites can be selectively activated through localized stretching thus producing generic smart substrates on which precise depositions sites can be activated according to the needs of the end user.

The influence of spatial patterns of capillary networks on transverse relaxation

Tissue-inherent relaxation parameters offer valuable information about the arrangement of capillaries: in an external field, capillaries act as magnetic perturbers to generate local inhomogeneous fields due to the susceptibility difference of deoxygenated blood and the surrounding tissue. These field inhomogeneities influence the free induction decay in a characteristic way, and, conversely, the above tissue parameters can be recovered by multi-parametric fits of adequate theoretical models to experimentally sampled free induction decays. In this work we study the influence of different spatial patterns of capillary positions on the free induction decay. Starting from the standard single capillary approximation (Krogh cylinder) for a symmetric array of capillaries, the free induction decay is analyzed for increasingly random capillary positions, using a previously described Gibbs point field model. The effects of diffusion are implemented with a flexible and fast random walk simulation. We find that the asymmetric form of the obtained frequency distribution is more robust against variations of capillary radii than against shifts of capillary positions, and further that, for an inclusion of diffusion effects, the single capillary approximation models the uniform alignment of capillaries in the hexagonal lattice to great accuracy. An increase in randomization of capillary positions then leads to a significant change in relaxation times. This effect, however, is found less pronounced than that of changes in the off-resonance field strengths which are controlled by the oxygen extraction fraction, thus indicating that observed changes in BOLD imaging are more likely to be attributed to changes in oxygenation than to capillary alignment.

A reproducible approach to the assembly of microcapillaries for double emulsion production

Double emulsions attract considerable interest for their utility in applications as diverse as drug delivery, contrast agents, and compartmentalizing analytes for fluorescence-activated cell sorting. Microfluidic platforms offer a particularly elegant approach to generating these structures, but the construction of devices to provide reproducible and stable production of double emulsions remains challenging. PDMS-based systems require specialized surface treatments that are difficult to implement and lack long-term stability, and current glass microcapillary systems, while offering some advantages, lack flexible and reproducible methods for capillary alignment. This article describes a microcapillary-based approach that addresses these key challenges. Our approach utilizes translational stage elements and alignment end caps that are fixed in place once configured, rather than tightly fitting capillaries. This new approach enables alignment to within ±10 µm and allows greater flexibility in choosing the dimensions of the capillary, which contributes to the size and stability of formation of the double emulsion. Importantly, it also allows the user to compensate for the deviations from ideal shape that occur in pulled glass capillaries, which has been a source of failure with previous methods. A detailed description of the critical design and operational parameters that affect double emulsion generation in these capillary microfluidic devices is provided.

Mixing injector enables time-resolved crystallography with high hit rate at X-ray free electron lasers.

Knowledge of protein structure provides essential insight into function, enhancing our understanding of diseases and enabling new treatment development. X-ray crystallography has been used to solve the structures of more than 100 000 proteins; however, the vast majority represent long-lived states that do not capture the functional motions of these molecular machines. Reactions triggered by the addition of a ligand can be the most challenging to detect with crystallography because of the difficulty of synchronizing reactions to create detectable quantities of transient states. The development of X-ray free electron lasers (XFELs) and serial femtosecond crystallography (SFX) enables new approaches for solving protein structures following the rapid diffusion of ligands into micron sized protein crystals. Conformational changes occurring on millisecond timescales can be detected and time-resolved. Here, we describe a new XFEL injector which incorporates a microfluidic mixer to rapidly combine reactant and sample milliseconds before the sample reaches the X-ray beam. The mixing injector consists of bonded, concentric glass capillaries. The fabrication process, employing custom laser cut centering spacers and UV curable epoxy, ensures precise alignment of capillaries for repeatable, centered sample flow and dependable mixing. Crystal delivery capillaries are 50 or 75 μm in diameter and can contain an integrated filter depending on the demands of the experiment. Reaction times can be varied from submillisecond to several hundred milliseconds. The injector features rapid and uniform mixing, low sample dilution, and high hit rates. It is fully compatible with existing SFX beamlines.

Hydrodynamic confinement and capillary alignment of gold nanorods

Controlling the alignment and orientation of nanorods on various surfaces poses major challenges. In this work, we investigate hydrodynamic confinement and capillary alignment of gold nanorod assembly on chemically stripe-patterned substrates. The surface patterns consist of alternating hydrophilic and hydrophobic micrometer wide stripes; a macroscopic wettability gradient enables controlling the dynamics of deposited suspension droplets. We show that drying of residual liquid on the hydrophilic stripes gives rise to spatially localized deposition and alignment of the nanorods. Moreover, a universal relation between the extent of order within the single layers of nanoparticles and the lateral dimension of the deposits is presented and discussed.

Transmural variation and anisotropy of microvascular flow conductivity in the rat myocardium.

Transmural variations in the relationship between structural and fluid transport properties of myocardial capillary networks are determined via continuum modeling approaches using recent three-dimensional (3D) data on the microvascular structure. Specifically, the permeability tensor, which quantifies the inverse of the blood flow resistivity of the capillary network, is computed by volume-averaging flow solutions in synthetic networks with geometrical and topological properties derived from an anatomically-detailed microvascular data set extracted from the rat myocardium. Results show that the permeability is approximately ten times higher in the principal direction of capillary alignment (the "longitudinal" direction) than perpendicular to this direction, reflecting the strong anisotropy of the microvascular network. Additionally, a 30% increase in capillary diameter from subepicardium to subendocardium is shown to translate to a 130% transmural rise in permeability in the longitudinal capillary direction. This result supports the hypothesis that perfusion is preferentially facilitated during diastole in the subendocardial microvasculature to compensate for the severely-reduced systolic perfusion in the subendocardium.

Transmural variation and anisotropy of microvascular flow conductivity in the rat left ventricular myocardium (675.4)

Three‐dimensional (3D) ex vivo data on microvascular anatomy in the myocardium is used to determine the transmural gradient in fluid transport properties via mathematical averaging methods. The 3D capillary network is modeled as a porous medium, whose conductivity is quantified in terms of a permeability tensor. This metric is directly computed by volume‐averaging blood flow solutions in model networks with geometrical and topological properties derived from an anatomically‐detailed data set recently extracted from the rat left ventricular myocardium using confocal microscopy, high‐precision sectioning and image processing techniques.Results showed that the permeability was strongly anisotropic: the network was approximately ten times more permeable in the principal direction of capillary alignment (the ‘longitudinal’ direction) than perpendicular to this direction. Structural properties of the network varied smoothly from subepicardium to subendocardium, with a 30% transmural increase in capillary diameter translating to a 130% rise in permeability in the longitudinal direction. This supports the hypothesis that perfusion is preferentially facilitated during ventricular diastole in the subendocardial microvasculature to compensate for severely‐reduced systolic perfusion in the subendocardium.Grant Funding Source: Supported by NIH GM094503‐1, EPSRC EP/F043929/1 and EP/G007527/2, and Award KUK‐C1‐013‐0 from KAUST.

Role of substrate aspect ratio on the robustness of capillary alignment

Capillary forces associated with liquid bridges formed across solid substrates are routinely exploited to align and assemble micro- and nanoscale devices. The magnitude of these forces plays a critical role in minimizing substrate misalignment and therefore should be controlled for robust and reliable fabrication process. We explore through simulations and experiments the role of the substrate aspect ratio (L/W) on capillary restoring forces and torques. Simulations show that increasing the aspect ratio of the substrates increases the capillary torques and forces when the substrates are misaligned through either lateral or rotational perturbations. The effect of substrate area, perimeter, and liquid volume are also systematically explored to show that the increase in restoring torque is caused by an increase in aspect ratio. A simple theoretical model based on the geometry of the system shows excellent agreement with Surface Evolver simulations. Finally, parameters from experimental flip-chip devices [Josell, D. Wallace, W.E. Warren, J.A. Wheeler, D. Powell, A.C. J. Electron. Packag. 124, 227, (2002)] are used in our simulations to show how current capillary self-alignment schemes could benefit from using rectangular substrate shapes with aspect ratio greater than one.

Microprism using capillary alignment

When a microstructure is placed on a droplet, the structure is positioned and remains at a particular position due to capillary forces. By using this phenomenon, two-dimensional arrangements on droplets have been widely developed. In this study, we fabricate a three-dimensional structure (prism shape) by placing two circular plates on a droplet. The paper explains the dynamics of the positioning both experimentally and numerically. Through experiment and simulation, we found that the rotational positioning is determined by surface tension and the two plates are supported by internal pressure and surface tension. The apex angle of the prism can be easily tuned by changing its volume. As described at the end of the paper, a prism composed of a droplet of silicone oil and two transparent circular SU-8 plates is encapsulated by depositing an organic Parylene membrane. The shape of the liquid is fixed, and a non-evaporative and non-deformable prism is formed with a volume of less than 1 mm3.

Performance of capillary gel electrophoretic analysis of oligonucleotides coupled on-line with electrospray mass spectrometry

Synthetic oligonucleotides (ODNs) are routinely analyzed using capillary gel electrophoresis (CGE) for size-sieving based separations as well as electrospray mass spectrometry (ESI-MS) for identification. On-line coupling of these methods is therefore desired in order to combine the analytical capabilities provided by both methods. Performance of on-line CGE–ESI-MS systems is influenced by various parameters, and choice of optimal conditions is crucial for successful coupling experiments. In this study, we explore characteristics of the on-line coupled CGE–ESI-MS system for ODN analysis. Effects of CGE buffer concentration, capillary length, separation and orifice voltage on CGE separation and MS detection of a phosphodiester ODN mixture were examined. Attention was paid to the influence of the interface, such as geometry of capillary alignment, sheath liquid flow-rate and sheath liquid composition on performance of the system.

Quantitative analysis of low molecular weight polar compounds by continuous flow liquid secondary ion tandem mass spectrometry.

Quantitative analyses of low molecular weight (100-200) polar compounds [1-methyl-4-phenylpyridine (MPP+), 2-amino-3-(methylamino)propanoic acid (synonyms, beta-(methyl-amino)-L-alanine or BMAA), and tryptophan] were conducted on a triple-stage quadrupole mass spectrometer configured for continuous flow liquid secondary ion mass spectrometry ionization (CF L-SIMS). It is shown that quantification by CF L-SIMS at subnanogram sensitivity can be precise (correlation coefficients greater than 0.99), accurate, specific, and routine for compounds not measurable by static L-SIMS. Successful analyses, however, are strongly dependent upon the stability of the film formed by the mobile phase on the probe tip. In our system, film stability is affected by mobile phase composition and flow rate, ion source and probe tip temperature, probe-tip and capillary alignment, film thickness, and sample composition.