Advances in engineered surfaces for functional performance

Microarrays with biomolecules (e.g., DNA and proteins), cells, and tissues immobilized on solid substrates are important tools for biological research, including genomics, proteomics, and cell analysis. In this paper, the current state of microarray fabrication is reviewed. According to spot formation techniques, methods are categorized as "contact printing" and "non-contact printing." Contact printing is a widely used technology, comprising methods such as contact pin printing and microstamping. These methods have many advantages, including reproducibility of printed spots and facile maintenance, as well as drawbacks, including low-throughput fabrication of arrays. Non-contact printing techniques are newer and more varied, comprising photochemistry-based methods, laser writing, electrospray deposition, and inkjet technologies. These technologies emerged from other applications and have the potential to increase microarray fabrication throughput; however, there are several challenges in applying them to microarray fabrication, including interference from satellite drops and biomolecule denaturization.

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Bio-microarray fabrication techniques--a review.

The detachment of liquid droplets from porous material surfaces used with proton exchange membrane (PEM) fuel cells under the influence of a cross-flowing air is investigated computationally and experimentally. CCD images taken on a purpose-built transparent fuel cell have revealed that the water produced within the PEM is forming droplets on the surface of the gas-diffusion layer. These droplets are swept away if the velocity of the flowing air is above a critical value for a given droplet size. Static and dynamic contact angle measurements for three different carbon gas-diffusion layer materials obtained inside a transparent air-channel test model have been used as input to the numerical model; the latter is based on a Navier-Stokes equations flow solver incorporating the volume of fluid (VOF) two-phase flow methodology. Variable contact angle values around the gas-liquid-solid contact-line as well as their dynamic change during the droplet shape deformation process, have allowed estimation of the adhesion force between the liquid droplet and the solid surface and successful prediction of the separation line at which droplets loose their contact from the solid surface under the influence of the air stream flowing around them. Parametric studies highlight the relevant importance of various factors affecting the detachment of the liquid droplets from the solid surface.

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Dynamics of water droplets detached from porous surfaces of relevance to PEM fuel cells.

Of the diverse analytical tools used in proteomics, protein microarrays possess the greatest potential for providing fundamental information on protein, ligand, analyte, receptor, and antibody affinity-based interactions, binding partners and high-throughput analysis. Microarrays have been used to develop tools for drug screening, disease diagnosis, biochemical pathway mapping, protein–protein interaction analysis, vaccine development, enzyme–substrate profiling, and immuno-profiling. While the promise of the technology is intriguing, it is yet to be realized. Many challenges remain to be addressed to allow these methods to meet technical and research expectations, provide reliable assay answers, and to reliably diversify their capabilities. Critical issues include: (1) inconsistent printed microspot morphologies and uniformities, (2) low signal-to-noise ratios due to factors such as complex surface capture protocols, contamination, and static or no-flow mass transport conditions, (3) inconsistent quantification of captured signal due to spot uniformity issues, (4) non-optimal protocol conditions such as pH, temperature, drying that promote variability in assay kinetics, and lastly (5) poor protein (e.g., antibody) printing, storage, or shelf-life compatibility with common microarray assay fabrication methods, directly related to microarray protocols. Conventional printing approaches, including contact (e.g., quill and solid pin), non-contact (e.g., piezo and inkjet), microfluidics-based, microstamping, lithography, and cell-free protein expression microarrays, have all been used with varying degrees of success with figures of merit often defined arbitrarily without comparisons to standards, or analytical or fiduciary controls. Many microarray performance reports use bench top analyte preparations lacking real-world relevance, akin to “fishing in a barrel”, for proof of concept and determinations of figures of merit. This review critiques current protein-based microarray preparation techniques commonly used for analytical and function-based proteomics and their effects on array-based assay performance.

A critical comparison of protein microarray fabrication technologies.

The motion of droplets under the influence of lithographically created anisotropic chemically defined patterns is described and discussed. The patterns employed in our experiments consist of stripes of alternating wettability: hydrophobic stripes are created via fluorinated self-assembled monolayers, and for hydrophilic stripes, the SiO2 substrate is used. The energy gradient required to induce the motion of the droplets is created by varying the relative widths of the stripes in such a way that the fraction of the hydrophilic area increases. The anisotropic patterns create a preferential direction for liquid spreading parallel to the stripes and confine motion to the perpendicular direction, giving rise to markedly higher velocities as compared to nonstructured surface energy gradients. Consequently, the influence of the distinct pattern features on the overall motion as well as suggestions for design improvements from an application point of view are discussed.

Smart Design of Stripe-Patterned Gradient Surfaces to Control Droplet Motion

This work is a fundamental study on the movement of various sized micro-liter droplets on a surface subjected to temperature gradients The histories of droplet movement are recorded by high-speed CCD camera and are simulated by numerical methods based on first principle equations The agreement between computations and experimental observations are obtained The study indicates that temperature gradients, the change of dynamic receding/advancing contact angles across the droplets, and the flowfields inside the droplet are the key parameters determining the moving behavior of the micro-droplet driven by Marangoni and capillary effects

Fundamental studies on micro-droplet movement by Marangoni and capillary effects

This paper proposes a novel stamping system using a back-filling Micro-Stamp Chip with discrete dispensing channels to pattern precise and uniform protein microarrays for disease diagnosis or drug screening. Unlike the micro arrayer which spots biosamples in serial, this novel device can simultaneously spot hundreds to thousands of bioreagents into a dense array in 1 min. Surface tension is the major mechanism in reservoir filling, solution transportation, micro/nano printing, and droplet breakdown processes of the micro stamp system. The passive channel design requires no actuation or external energy sources to manipulate the bioreagents. The fabrication of the back-filling Micro-Stamp Chip involves thick photoresist lithography, evaporation, PDMS (polydimethylsiloxane) molding, PDMS dry etching, and oxygen-plasma oxidization for the hydrophilic treatment of stamp surface. The Bio-Assay Chip is prepared by treating the surface of a glass slide with aminopropyltrimethoxysilane (APTS) for amino-derivitization and then with bis-sulfo-succinimidyl suberate (BS3) for surface activation. Both simulation and experiment have demonstrated the capability of this system to accurately transfer proteins in uniform arrays. Experimental results verify that the spot size and intensity variations of spotted protein arrays were less than 5% across the whole chip with 144 protein spots, and the size discrepancy between the imprinted spot and fabricated stamp is about 5%. Simulation results provided the guidelines to generate uniform protein spots, such as the hydrophilic degree of the micro stamp tip and Bio-Assay Chip surface, and the departing speed of the Micro-Stamp Chip from the Bio-Assay Chip.

Simultaneous immobilization of protein microarrays by a micro stamper with back-filling reservoir

This paper proposes a novel passive micromixer design for mixing enhancement by forming a large three-dimensional (3-D) flow vortex in a counterflow microfluidic system. The counterflow fluids are self-driven by surface tension to perform mixing in an open chamber. The chamber design consists of two rectangular bars to house the chamber and to form two opening inlets from opposite directions. The best design is selected from various versions of mixing chambers. The mixing effectiveness is tremendously increased by folds of contacting surface between two fluids induced and enhanced due to the stretching of two fluid contacting interfaces by the formation of a 3-D large size vortex structure inside the mixing chamber itself with unaccountable numbers of fluid layers. Both numerical simulations and experiments are performed and compared to identify the design parameters for maximum utilization in this microfluidic system, such as the length of rectangular bar, microchannel wall height, and mixing chamber size. Compared to traditional micromixers operated by two-dimensional (2-D) vortex, this passive mixer can greatly enhance mixing efficiency and reduce mixing time by tenfold from around 10 s to less than 10 ms by 3-D effective chaotic flow structures in a more compact size. This mixing chamber is also suitable for an H-shape digital fluidic system for parallel mixing process in different mixing ratio simultaneously as a lab-on-a-chip system.

Surface tension driven and 3-D vortex enhanced rapid mixing microchamber

Rapid and parallel protein micro/nano array formation provides a powerful tool for protein chip fabrication and protein preservation. This paper presents the characterization of the surface tension and viscosity effects on the formation of nano-liter droplet arrays by a novel instant micro stamper, which can simultaneously immobilize hundreds of proteins on a chip. Capillary force is the major driving mechanism of the micro stamper, flowing protein solutions through the chip channel for array-registration and droplet-size control. Three important properties have been characterized in this paper, including uniformity of the parallel printing process, surface wettability and solution viscosity effect on micro droplet size and the dynamic sequence of micro droplet formation. Experimental results demonstrated the uniformity of the parallel stamping process for protein micro arrays from area to area and chip to chip. The effects of surface wettability of bioassay chips and solution viscosity on droplet-size variation have been investigated in detail by experiments and simulations. Both simulation and experimental results demonstrate that the spot size increases with increasing surface wettability and decreasing solution viscosity, and they showed similar tends. The dynamic process of droplet formation has also been observed and analyzed by high-speed images, demonstrating that the footprint reduction rate, formation time and necking of the printed micro droplet are lower on the more hydrophobic surface. This is due to the rapid shrinkage of the droplet footprint area on a hydrophobic surface, resulting in smaller droplet formation. The droplet size can shrink up to 50% when the contact angle of the bioassay chip surface increases from 30° to 80°. On the other hand, the variation of solution viscosity from 1.02 to 10.08 cp makes the droplet size shrink to 70%.

Characterization of the surface tension and viscosity effects on the formation of nano-liter droplet arrays by an instant protein micro stamper

Present study demonstrates the head loss and the flow characteristics as the open microchannel makes turns. The microchannels are of various aspect ratios of depth/width ranging from 0.5 to 2, and makes turns with different angles ranging from 60 to 120 degrees. The investigations are performed both by experiments and numerical simulations based on first principle equations. For the open channel system, the flow is mainly driven by surface tension under same pressure atmosphere. For liquid flow in open microchannel without turn, the liquid front velocity decreases but the interface area of liquid-gas increase as flow moves downstream. For turning flows, liquid front velocity is decreased firstly and then increased sharply at the turning point. Furthermore, the liquid front velocity can be increased for higher aspect ratio of channel height and width, and the effect of aspect ratio is significant up to aspect ratio between 1.0–1.5. Detailed flow characteristics as well as the head loss coefficient due to microchannel turning are discussed.Copyright © 2004 by ASME

Yu-Feng Chen

Papers

Fundamental studies on micro-droplet movement by Marangoni and capillary effects

Simultaneous immobilization of protein microarrays by a micro stamper with back-filling reservoir

Surface tension driven and 3-D vortex enhanced rapid mixing microchamber

Characterization of the surface tension and viscosity effects on the formation of nano-liter droplet arrays by an instant protein micro stamper

Head Loss and Flow Characteristics for Turning Flow Driven by Surface Tension Force Inside Open Microchannel