Micropost Arrays Research Articles

Performance optimization of a DLD microfluidic device for separating deformable CTCs.

Deterministic lateral displacement (DLD) microfluidic devices work based on the streamlines created by an array of micro-posts. The configuration of pillars alters the isolation efficiency of these devices. The present paper optimizes the performance of a DLD device for isolating deformable circulating tumor cells. The input variables include cell diameter (d), Young's modulus ( ), Reynolds number (Re), and tan θ, where θ is the tilted angle of micro-posts. The output, which is the response of the system, is DLD. The numerical simulation results are employed to optimize the device using the response surface method, leading to the proposition of a correlation to estimate DLD as a function of input variables. It is demonstrated that the maximum and minimum impacts on cell lateral displacement correspond to and Re, respectively.

Universal correlation for the critical diameter of deterministic lateral displacement devices with polygonal posts.

Deterministic lateral displacement (DLD) is a microfluidic technique that utilizes a specific array of micro-posts to separate cells or particles larger and smaller than a critical diameter. The critical diameter depends on the shape of the posts, the gap between the posts, and the relative shift between the adjacent rows of posts. Here, we present an experimental and numerical investigation to elucidate the functional dependence of the critical diameter of DLD arrays with polygonal posts on the geometric parameters. Based on simulations of fluid flow through DLD devices with varying geometric parameters, we first derived a correlation to predict the critical diameter of DLD arrays with polygonal post shapes having an arbitrary number of sides. We then used a novel experimental approach, wherein we coupled different DLD arrays with an upstream droplet generator to flow droplets of varying sizes and estimate the critical diameter. The critical diameter predicted by the correlation based on simulations compares well with our experimental data and with data available in the literature. The universal correlation for a critical diameter presented here can help design and optimize DLD devices with polygonal posts.

The porous structure induced heterogeneous and localized failure of the biofilm in microfluidic channels.

Understanding the mechanism of biofilm distribution and detachment is very important to effectively improve water treatment and prevent blockage in porous media. The existing research is more related to the local biofilm evolving around one or few microposts and the lack of the integral biofilm evolution in a micropost array for a longer growth period. This study combines microfluidic experiments and mathematical simulations to study the distribution and detachment of biofilm in porous media. Microfluidic chips with an array of microposts with different sizes are designed to simulate the physical pore structure of soil. The research shows that the initial formation and distribution of biofilm are influenced by bacterial transport velocity gradients within the pore space. Bacteria prefer to aggregate areas with smaller microposts, leading to the development of biofilm in those regions. Consequently, impermeable blockage structures form in this area. By analyzing experimental images of biofilm structures at the later stages, as well as coupling fluid flow and porous medium, and the finite element simulation, we find that the biofilm detachment is correlated with the morphology and permeability (kb) (from 10-15 to 10-9 m2) of the biofilm. The simulations show that there are two modes of biofilm detachment, such as internal detachment and external erosion.

Villi Inspired Mechanical Interlocking for Intestinal Retentive Devices.

Intestinal retentive devices have applications ranging from sustained oral drug delivery systems to indwelling ingestible medical devices. Current strategies to retain devices in the small intestine primarily focus on chemical anchoring using mucoadhesives or mechanical coupling using expandable devices or structures that pierce the intestinal epithelium. Here, the feasibility of intestinal retention using devices containing villi-inspired structures that mechanically interlock with natural villi of the small intestine is evaluated. First the viability of mechanical interlocking as an intestinal retention strategy is estimated by estimating the resistance to peristaltic shear between simulated natural villi and devices with various micropost geometries and parameters. Simulations are validated in vitro by fabricating micropost array patches via multistep replica molding and performing lap-shear tests to evaluate the interlocking performance of the fabricated microposts with artificial villi. Finally, the optimal material and design parameters of the patches that can successfully achieve retention in vivo are predicted. This study represents a proof-of-concept for the viability of micropost-villi mechanical interlocking strategy to develop nonpenetrative multifunctional intestinal retentive devices for the future.

Effects of the micro-post array on the maximum allowable input power for a micro pulsating heat pipe

This study is performed to experimentally investigate the effects of the micro-post array (MPA) and its arrangements on the maximum allowable input power for a micro pulsating heat pipe (MPHP). The maximum allowable input powers for MPHPs with the MPAs in three different arrangements are measured and compared to that for the conventional MPHP (without the MPA). To do this, ten-turn MPHPs with and without the MPA are fabricated using MEMS techniques. The overall dimensions of the MPHPs are 53 × 38 × 1.5 mm3, and the width and the height of the meandering rectangular channels are 1500 µm and 660 µm, respectively. The MPA in each case is placed on the bottom surfaces of the channels. The dimensions of the MPA are analytically determined in such a way to maximize the rate of the capillarity-induced flow by solving the Brinkman-extended Darcy's equation: the diameter, the pitch and the height are determined to be 33 µm, 97 µm, and 80 µm, respectively. The MPA is placed in three different arrangements: in alternating pairs of channels, in alternating channels, or in all channels. Ethanol is selected as the working fluid. The experiments are conducted in a horizontal orientation, and the flow is visualized with high-speed photography. The experimental results show that the MPA can have either a favorable or an adverse effect depending on its arrangement. If the MPA is placed in alternating channels, the maximum allowable input power is enhanced by 44%, compared to that for the conventional MPHP, and if it is placed in alternating pairs of channels, the maximum allowable input power is enhanced by 36%. On the other hand, the MPHP does not operate at all at any input power if the MPA is placed in all channels. Therefore, in case of the MPHP where a vapor plug oscillates in its own channel, the MPA should be placed in alternating pairs of channels or in alternating channels to enhance the maximum allowable input power for an MPHP.

Measuring Cytoskeletal Mechanical Fluctuations and Rheology with Active Micropost Arrays.

The dynamics of the cellular actomyosin cytoskeleton are crucial to many aspects of cellular function. Here, we describe techniques that employ active micropost array detectors (AMPADs) to measure cytoskeletal rheology and mechanical force fluctuations. The AMPADS are arrays of flexible poly(dimethylsiloxane) (PDMS) microposts with magnetic nanowires embedded in a subset of microposts to enable actuation of those posts via an externally applied magnetic field. Techniques are described to track the magnetic microposts’ motion with nanometer precision at up to 100 video frames per second to measure the local cellular rheology at well‐defined positions. Application of these high‐precision tracking techniques to the full array of microposts in contact with a cell also enables mapping of the cytoskeletal mechanical fluctuation dynamics with high spatial and temporal resolution. This article describes (1) the fabrication of magnetic micropost arrays, (2) measurement protocols for both local rheology and cytoskeletal force fluctuation mapping, and (3) special‐purpose software routines to reduce and analyze these data. © 2022 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Fabrication of magnetic micropost arrays Basic Protocol 2: Data acquisition for cellular force fluctuations on non‐magnetic micropost arrays Basic Protocol 3: Data acquisition for local cellular rheology measurements with magnetic microposts Basic Protocol 4: Data reduction: determining microposts’ motion Basic Protocol 5: Data analysis: determining local rheology from magnetic microposts Basic Protocol 6: Data analysis for force fluctuation measurements Support Protocol 1: Fabrication of magnetic Ni nanowires by electrodeposition Support Protocol 2: Configuring Streampix for magnetic rheology measurements

Design and numerical simulation analysis of three multifunctional microfluidic chips in isolation of CTCs

Circulating tumor cells (CTCs) are tumor cells that dissociate from the origin tumors and disseminate in the bloodstream and lymphatic circulation systems. CTCs carry a remarkably similar constituent to the original tumor, which makes CTCs have a significant value in the biological molecular analysis of cancer. However, CTCs are extremely rare and heterogeneous in blood. Therefore, CTC separation is highly challenging. In the present work, we designed a fan-shaped symmetric microfluidic chip, a multifunctional capturing and co-culture chip, and an immunomagnetic chip in isolation of CTCs. The first chip is composed of two-faced fans placed symmetrically. Inside, there are arc-shaped arrays composed of numerable circular microposts. CTCs could be captured by antibody-modified microposts, and blood constituents flow away. Pressure, velocity, streamline, and shear stress simulations were performed theoretically. The second chip is a multifunctional capturing and co-culture chip. Patient blood samples are filtered by a W-shaped structure, and isolated viable CTCs could co-culture with several normal cells of the same type to mimic the real microenvironment. The third microfluidic chip is a combination of both immunomagnetic and physical-based. Many electronic coils are wound around the chip to produce a strong magnetic field when electrified. CTCs are incubated with magnetic beads. Magnetized CTCs would be oriented to be enriched. Those CTCs without conjugating beads would be captured by two interlace arrays of square microposts. These three delicate designs and theoretical explanation clarify feasibility for further experiments of CTC enumeration, clinical analysis, and evaluation of cancer therapy.

Deterministic Lateral Displacement Microfluidic Chip for Minicell Purification.

Deterministic lateral displacement (DLD) is a well-known microfluidic technique for particle separation with high potential for integration into bioreactors for therapeutic applications. Separation is based on the interaction of suspended particles in a liquid flowing through an array of microposts under low Reynolds conditions. This technique has been used previously to separate living cells of different sizes but similar shapes. Here, we present a DLD microchip to separate rod-shaped bacterial cells up to 10 µm from submicron spherical minicells. We designed two microchips with 50 and 25 µm cylindrical posts and spacing of 15 and 2.5 µm, respectively. Soft lithography was used to fabricate polydimethylsiloxane (PDMS) chips, which were assessed at different flow rates for their separation potential. The results showed negligible shear effect on the separation efficiency for both designs. However, the higher flow rates resulted in faster separation. We optimized the geometrical parameters including the shape, size, angle and critical radii of the posts and the width and depth of the channel as well as the number of arrays to achieve separation efficiency as high as 75.5% on a single-stage separation. These results pave the way for high-throughput separation and purification modules with the potential of direct integration into bioreactors.

Pervasive cytoquakes in the actomyosin cortex across cell types and substrate stiffness.

The actomyosin cytoskeleton enables cells to resist deformation, crawl, change their shape and sense their surroundings. Despite decades of study, how its molecular constituents can assemble together to form a network with the observed mechanics of cells remains poorly understood. Recently, it has been shown that the actomyosin cortex of quiescent cells can undergo frequent, abrupt reconfigurations and displacements, called cytoquakes. Notably, such fluctuations are not predicted by current physical models of actomyosin networks, and their prevalence across cell types and mechanical environments has not previously been studied. Using micropost array detectors, we have performed high-resolution measurements of the dynamic mechanical fluctuations of cells' actomyosin cortex and stress fiber networks. This reveals cortical dynamics dominated by cytoquakes-intermittent events with a fat-tailed distribution of displacements, sometimes spanning microposts separated by 4μm, in all cell types studied. These included 3T3 fibroblasts, where cytoquakes persisted over substrate stiffnesses spanning the tissue-relevant range of 4.3kPa-17kPa, and primary neonatal rat cardiac fibroblasts and myofibroblasts, human embryonic kidney cells and human bone osteosarcoma epithelial (U2OS) cells, where cytoquakes were observed on substrates in the same stiffness range. Overall, these findings suggest that the cortex self-organizes into a marginally stable mechanical state whose physics may contribute to cell mechanical properties, active behavior and mechanosensing.

Divisions in a Fibrillar Adhesive Increase the Adhesive Strength.

To realize the potential of bioinspired fibrillar adhesive applications ranging from biomedical devices to robotic grippers, there has been a significant effort to improve their adhesive strength and understanding of the underlying adhesion and detachment mechanisms. These efforts include changes to the backing layer, which connects the roots of all of the pillars in the fibrillar adhesive. However, previous approaches such as thickness or elastic modulus changes are selectively advantageous to the adhesive strength depending on the substrate condition because of the trade-off between conformity to misaligned/rough surfaces and increased interfacial stress concentrations. In this work, we explore mechanical divisions (cuts) in the backing layer as a new approach to improve the adhesive strength without this trade-off. We combine experiments and finite element analysis (FEA) to study the effect of the divisions, which decouples the mechanical interaction between the pillars on the divided layers, and show that the adhesive strength can be improved regardless of the substrate condition. Tensile adhesion experiments show increased adhesive strength with cuts to a micropost array (150 μm diameter posts) by approximately 25% for 4 divisions. In situ imaging of pillar detachment shows a transition of the detachment process from a peel-like detachment to a random detachment sequence. FEA simulations of the detachment process suggest that the increased strength may originate from a simultaneous enhancement of the load distribution between the pillars and the compliance of the backing layer.

Lithographically Defined Micropost Arrays for Programmable Actuation and Interfacial Hydrodynamics

Magnetically actuating surface-attached post (ASAP) arrays have great potential in microfluidic flow control, including mixing and pumping. Both passive (nonactuating) and active (actuating) micropillar arrays can also be used to control pressure-driven flow and the motion of microscopic particles carried by the fluid through microfluidic channels. Molding techniques are popular for generating these microstructures. However, fabricating high aspect ratio elastomeric microstructures over large surface areas suffers from practical problems such as damage incurred in the demolding process. Here, we report on a fabrication protocol that generates ASAP with an aspect ratio as high as 23:1 and a cross-sectional area less than 1 μm2 using straightforward photolithography processes. We generated 50 unique ASAP arrays, each occupying an area of 1 mm2 on a silicon mold; these arrays have varied cross-sectional shape and size, aspect ratio, and spacings between neighboring posts. Our protocol also controls the level of magnetic material in the ASAP tips with a centrifugation step. Using a herringbone pattern ASAP array, we have demonstrated control over the relative phase of actuation between neighboring posts. Such ASAP serve as an experimental platform to test current models predicting that reciprocal actuators in close proximity can successfully drive flow in a low Reynolds (Re) number environment.

Polycarbonate Masters for Soft Lithography.

Fabrication of microfluidic devices by soft lithography is by far the most popular approach due to its simplicity and low cost. The approach relies on casting of elastomers, such as polydimethylsiloxane (PDMS), on masters fabricated from photoresists on silicon substrates. These masters, however, can be expensive, complicated to fabricate, and fragile. Here we describe an optimized replica molding approach to preserve the original masters by heat molding of polycarbonate (PC) sheets on PDMS molds. The process is faster and simpler than previously reported methods and does not result in a loss of resolution or aspect ratio for the features. The generated PC masters were used to successfully replicate a wide range of microfluidic devices, including rectangular channels with aspect ratios from 0.025 to 7.3, large area spiral channels, and micropost arrays with 5 µm spacing. Moreover, fabrication of rounded features, such as semi-spherical microwells, was possible and easy. Quantitative analysis of the replicated features showed variability of <2%. The approach is low cost, does not require cleanroom setting or hazardous chemicals, and is rapid and simple. The fabricated masters are rigid and survive numerous replication cycles. Moreover, damaged or missing masters can be easily replaced by reproduction from previously cast PDMS replicas. All of these advantages make the PC masters highly desirable for long-term preservation of soft lithography masters for microfluidic devices.

Impacting Droplet Can Mitigate Dust from PDMS Micro-Post Array Surfaces

In this paper, the impact mechanisms of a water droplet on hydrophobized micro-post array surfaces are examined and the influence of micro-post arrays spacing on the droplet behavior in terms of spreading, retraction, and rebounding is investigated. Impacting droplet behavior was recorded using a high-speed facility and flow generated in the droplet fluid was simulated in 3D geometry accommodating conditions of the experiments. Micro-post arrays were initially formed lithographically on silicon wafer surfaces and, later, replicated by polydimethylsiloxane (PDMS). The replicated micro-post arrays surfaces were hydrophobized through coating by functionalized nano-silica particles. Hydrophobized surfaces result in a contact angle of 153° ± 3° with a hysteresis of 3° ± 1°. The predictions of the temporal behavior of droplet wetting diameter during spreading agree with the experimental data. Increasing micro-post arrays spacing reduces the maximum spreading diameter on the surface; in this case, droplet fluid penetrated micro-posts spacing creates a pinning effect while lowering droplet kinetic energy during the spreading cycle. Flow circulation results inside the droplet fluid in the edge region of the droplet during the spreading period; however, opposing flow occurs from the outer region towards the droplet center during the retraction cycle. This creates a stagnation zone in the central region of the droplet, which extends towards the droplet surface onset of droplet rebounding. Impacting droplet mitigates dust from hydrophobized micro-post array surfaces, and increasing droplet Weber number increases the area of dust mitigated from micro-post arrays surfaces.

Separation of circulating tumor cells from blood using dielectrophoretic DLD manipulation.

Circulating Tumor Cells (CTCs) play a prominent role in early cancer detection. Emerging label-free techniques can be promising to CTC detection due to advantages in preserving cell integrity and minimal sample consumption. Deterministic Lateral Displacement (DLD) is a size-based label-free technique employing laminar flow for continuous sorting of suspended cells. However, separation based solely on size is challenging as the size distributions of CTCs tend to overlap with blood cells. Moreover, the rarity of CTCs in blood requires high throughput processing of samples for clinical utility. In this work, a dielectrophoretic DLD technique is presented to segregate CTCs from blood. This technique utilizes the cell size and dielectric properties as well as particle movement caused by polarization effect to accomplish continuous separation at high flow rates. A numerical model is developed and validated to investigate the effects of various parameters related to the fluid flow, micro-post array, and electric field. It is demonstrated that the dielectrophoretic DLD with specific post arrangement can continuously separate A549 lung CTCs from WBCs by applying a field frequency close to the crossover frequency of CTCs. The analysis further indicates that such a device can perform well despite uncertainties of CTC crossover frequencies. Additionally, efficient separation with minimum clogging can be achieved by setting the electric field perpendicular to fluid flow. The presented platform offers distinct advantages and can be potentially combined with techniques such as antibody-based immune-binding methods for rapid detection of CTCs.

Water droplet can mitigate dust from hydrophobized micro-post array surfaces

Water droplet rolling motion over the hydrophobized and optically transparent micro-post array surfaces is examined towards dust removal pertinent to self-cleaning applications. Micro-post arrays are replicated over the optically transparent polydimethylsiloxane (PDMS) surfaces. The influence of micro-post array spacing on droplet rolling dynamics is explored for clean and dusty surfaces. The droplet motions over clean and dusty micro-post array surfaces are monitored and quantified. Flow inside the rolling droplet is simulated adopting the experimental conditions. Findings reveal that micro-post gap spacing significantly influences droplet velocity on clean and dusty hydrophobized surfaces. Air trapped within the micro-post gaps acts like a cushion reducing the three-phase contact line and interfacial contact area of the rolling droplet. This gives rise to increased droplet velocity over the micro-post array surface. Droplet kinetic energy dissipation remains large for plain and micro-post arrays with small gap spacings. A Rolling droplet can pick up dust particles from micro-post array gaps; however, few dust residues are observed for large gap spacings. Nevertheless, dust residues are small in quantity over hydrophobized micro-post array surfaces.

A microchannel flow with presence of micro-post arrays on channel top wall

A microchannel flow is considered and the influence of the micro-post arrays and air trapped on velocity and temperature increase of the working fluid is examined experimentally and numerically incorporating 3-D simulations. The channel bottom plate is considered to be smooth and hydrophilic, which moves with a constant velocity, while channel top wall is stationary and it has staggered arrangement of micro-post arrays with hydrophobic wetting state. An experiment is carried out to validate velocity and temperature predictions while setting simulation conditions in line with the experiments. It is found that the flow field in top channel wall vicinity is influenced by the micro-post arrays; hence, wavy flow field is generated in this region. Flow circulation in the trapped air in between the micro-post arrays influences the heat transfer rates. The Nusselt number reduces slightly with increasing pitch size of the micro-post arrays. In addition, increasing the microchannel height lowers the Nusselt number. The pressure drop between the channel inlet and exit is influenced significantly by the micro-post arrays. Increasing pitch size of the micro-post arrays reduces the pressure drop; however, further increase of the pitch size beyond 12 μm does not alter the pressure drop across the microchannel.

A microcolumn coated with polydimethylsiloxane functionalized by graphene oxide quantum dots for the gas chromatographic separation of characteristic markers of advanced fibrosis

In this paper, the serpentine-shaped semi-packed chromatographic columns embedded with the micro-post array were developed to separate the characteristic markers of advanced fibrosis. The 3 m long micro separation columns with a rectangular channel cross-sectional dimension of 250 μm × 200 μm and the micropost diameter of 30 μm were prepared by the micro-electromechanical system (MEMS) technology. Based on the static coating process, two kinds of microcolumns (Sp1 and Sp2) with different stationary phase coatings were prepared for comparison. In detail, the Sp1 column was only coated with polydimethylsiloxane (PDMS), and the Sp2 column was coated with PDMS functionalized by graphene oxide quantum dots (GOQDs). GOQDs is a carbon-based nanomaterial that had similar properties to graphene oxide (GO). Moreover, the microcolumns are connected to a conventional gas chromatograph for testing. Alkanes (C5–C14) and benzene series (benzene, toluene, o-xylene, 1,3,5- trimethylbenzene) were used to evaluate the separation characteristics of microcolumns, and the effect of constant column temperature and heating rate on chromatographic performance was studied. The experimental results show that the potential characteristic markers of advanced fibrosis (pentane and benzene) could be effectively separated in alkanes and benzene series, respectively, and the separation effect of Sp2 was better than that of Sp1. In addition, the Sp2 column also showed good repeatability. Therefore, the GOQDs-functionalized PDMS coated column could assist the microdetector of the microsystem under development to rapidly, accurately and effectively distinguish the markers, and is expected to become a candidate for micro gas chromatography (μGC) column for micro-system integration.

Lithographically Defined Micropost Arrays for Programmable Actuation and Interfacial Hydrodynamics

Lithographically Defined Micropost Arrays for Programmable Actuation and Interfacial Hydrodynamics

Fabrication of Ag nanorods on micropost array for a metal-enhanced fluorescence substrate with a high signal-to-background ratio

Selective fabrication of metallic nanostructures at the spotting area is required to increase the signal-to-background noise ratio (SBR) of the metal-enhanced fluorescence (MEF) substrate. As a simple and cost-effective fabrication method for MEF substrate with high SBR, a glancing angle deposition (GLAD) process of Ag material on the UV-imprinted micropost array (50 μm in height, 300 μm in diameter, and 600 μm in pitch) was proposed to selectively fabricate Ag nanorods on the top of micropost structure (spotting area). Ag nanorod formation at the bottom of the micropost decreased as the deposition angle in Ag GLAD increased. A deposition angle of 89° and deposition thickness of 500 nm were selected as the optimum GLAD conditions to maximize the SBR. The optimum Ag nanorods on micropost array (AgNMPA) MEF substrate provided 71-fold fluorescence signal enhancement and 25-times higher SBR than the bare glass substrate. It also provided 7-times higher SBR than the Ag nanorod MEF substrate, which has a similar Ag nanorod structure but is not selectively formed. The detection limit of AgNMPA was 16- and 4-times lower than that of the amine-functionalized glass substrate and commercial epoxy slide, respectively. Although the fluorescence signal of AgNMPA was similar to that of Ag nanorod substrate, the detection limit was 2-times lower because of the low signal standard deviation caused by the low background noise and clear spot shape.

A Continuous Cell Separation and Collection Approach on a Microfilter and Negative Dielectrophoresis Combined Chip.

Cell separation plays an important role in the fields of analytical chemistry and biomedicine. To solve the blockage problem and improve the separation throughput in the traditional microstructure filtration-based separation approach, a continuous cell separation and collection approach via micropost array railing on a microfilter and negative dielectrophoresis combined chip is proposed. By tilting the micropost array at a certain angle, microparticles or cells enter the collection area under micropost array railing. The effects of the inclination angle of the micropost array and the electrode distance on the microparticle collection efficiency were investigated. Based on the optimized microfluidic chip structure, 37- and 16.3-μm particles were collected with 85% and 89% efficiencies, respectively. Additionally, algal cells were separated and collected by using the optimized microchip. The chip also had good separation and collection effects on biological samples, which effectively solved the blockage problem and improved the separation throughput, laying a foundation for subsequent microstructure filtration separation-based research and application.