Micromolding In Capillaries Research Articles

Organizing Reliable Polymer Electrode Lines in Flexible Neural Networks via Coffee Ring-Free Micromolding in Capillaries.

With an increase in the demand for smart wearable systems, artificial synapse arrays for flexible neural networks have received considerable attention. A synaptic device with a two-terminal configuration is promising for complex neural networks because of its ability to scale to a crossbar array architecture. To realize practical crossbar arrays with a high density, it is essential to achieve reliable electrode lines that act as signal terminals. However, an effective method to develop intrinsically flexible signal lines in artificial neural networks has not been developed. In this study, we achieved reliable polymer signal lines for flexible neural networks using coffee ring-free micromolding in capillaries (MIMIC). In a typical MIMIC, the outward convective flow of the polymer solution inherently deteriorates the pattern fidelity. To achieve reliable conducting polymer (CP) lines, we precisely controlled the flow of the polymer solution in the MIMIC by inducing the Marangoni force. When the convective and Marangoni flows for the solution were balanced in the MIMIC, the CP line patterns were reliably produced with high fidelity. The developed CP lines exhibited superior conductivity and high mechanical flexibility. Moreover, flexible memristor arrays consisting of CP signal lines demonstrated a high potential for realizing practical neuromorphic systems linked to artificial intelligence.

Development of the micro-patterned 3D neuronal-hydrogel model using soft-lithography for study a 3D neural network on a microelectrode array.

In vitro patterned neuronal models have been studied as one of the strategies to investigate the relationship between structural connectivity and functional activity of neural network. Despite the importance of three-dimensional (3D) cell models, most of these studies have been performed on two-dimensional models. In this study, we present a technique to construct the micro-pattern to 3D neuronal-hydrogel model using a micromolding in capillaries (MIMIC) technique on microelectrode array (MEA). Our technique was suitable to prevent the deformation of micro-patterned collagen model against the neuronal contracted tension during the network formation. The relationship between the growth directions of glial cells and micro-pattern direction was investigated. Lastly, we confirmed that our 3D model had synchronized activity among neurons in 3D. This model is expected to be used as a tool to study the relationship between structural connectivity and functional activity in the 3D environment.

Subpore‐Scale Trapping Mechanisms Following Imbibition: A Microfluidics Investigation of Surface Roughness Effects

AbstractSurface roughness is ubiquitous in subsurface formations due to weathering and diagenesis. Yet micromodel studies of porous media have not sufficiently addressed the impact of pore‐wall roughness on multiphase fluid displacement. We investigate the influence of pore‐wall roughness on capillary trapping by implementing surface roughness into glass micromodels and conducting imbibition experiments. Time‐lapse fluorescence microscopy, micromolding in capillaries, and scanning electron microscopy are used to examine flow behavior during spontaneous and forced imbibition experiments with capillary numbers between 10−6 and 10−4. It is found that surface roughness causes interface pinning and irregular displacement fronts within a single pore, promotes latent pore filling following imbibition, enhances snap‐offs, and contributes to interface relaxation. Furthermore, we verify a cooperative effect between corner flow and surface roughness that causes pore filling to occur at over 10 times the channel width ahead of the main bulk front. Consequently, a significant increase in trapped air saturation of up to 60% is observed, especially at lower capillary numbers and narrower pores. Effects of surface roughness also decrease the rate of spontaneous imbibition, which is slower than the prediction from Washburn's equation. Our results emphasize the importance of surface roughness in building conceptual models for capillary trapping when the ratio of surface roughness‐to‐pore size reaches a critical value of about 0.1. Above this critical threshold value, subpore‐scale trapping mechanisms contribute significantly to capillary trapping, which theoretical and numerical models should consider for accurate quantification of fluid‐transport processes.

"Plug-n-Play" Polymer Substrates: Surface Patterning with Reactive-Group-Appended Poly-l-lysine for Biomolecule Adhesion.

The immobilization of biomolecules onto polymeric surfaces employed in the fabrication of biomedical and biosensing devices is generally a challenging issue, as the absence of functional groups in such materials does not allow the use of common surface chemistries. Here we report the use of modified poly-l-lysine (PLL) as an effective method for the selective modification of polymeric materials with biomolecules. Cyclic olefin polymer (COP), Ormostamp, and polydimethylsiloxane (PDMS) surfaces were patterned with modified PLLs displaying either biotin or maleimide functional groups. Different patterning techniques were found to provide faithful microscale pattern formation, including micromolding in capillaries (MIMIC) and a hydrogel-based stamping device with micropores. The surface modification and pattern stability were tested with fluorescence microscopy, contact angle and X-ray photoelectron spectroscopy (XPS), showing an effective functionalization of substrates stable for over 20 days. By exploiting the strong biotin–streptavidin interaction or the thiol–maleimide coupling, DNA and PNA probes were displayed successfully on the surface of the materials, and these probes maintained the capability to specifically recognize complementary DNA sequences from solution. The printing of three different PNA-thiol probe molecules in a microarray fashion allowed selective DNA detection from a mixture of DNA analytes, demonstrating that the modified PLL methodology can potentially be used for multiplexed detection of DNA sequences.

A Modular and Practical Synthesis of Zwitterionic Hydrogels through Sequential Amine-Epoxy "Click" Chemistry and N-Alkylation Reaction.

In this work, the amine-epoxy “click” reaction is shown to be a valuable general tool in the synthesis of reactive hydrogels. The practicality of this reaction arises due to its catalyst-free nature, its operation in water, and commercial availability of a large variety of amine and epoxide molecules that can serve as hydrophilic network precursors. Therefore, hydrogels can be prepared in a modular fashion through a simple mixing of the precursors in water and used as produced (without requiring any post-synthesis purification step). The gelation behavior and final hydrogel properties depend upon the molecular weight of the precursors and can be changed as per the requirement. A post-synthesis modification through alkylation at the nitrogen atom of the newly formed β-hydroxyl amine linkages allows for functionalizing the hydrogels. For example, ring-opening reaction of cyclic sulfonic ester gives rise to surfaces with a zwitterionic character. Finally, the established gelation chemistry can be combined with soft lithography techniques such as micromolding in capillaries (MIMIC) to obtain hydrogel microstructures.

Micromolding in Capillaries와 Microtransfer Molding법을 이용한 역테이퍼 구조물을 가지는 이방성 소유성 표면 제작

Fabrication of inverse-tapered structure remains as a problem in the fabrication of oleophobic surface mostly due to the complications and the high cost of processes. In this paper, we propose a simple and low-cost fabrication method of inverse-tapered structured oleophobic surface using micromolding in capillaries (MIMIC) and microtransfer molding followed by MEMS processes. Silicon wafer molds for the formation of inverse-tapered structure were made using MEMS processes such as photolithography and anisotropic KOH etching of silicon wafer. The geometry of structure could be changed by controlling the etching depth of the silicon wafer mold. After covering the surface of the mold using flat UV tape, the formed space between mold and UV tape was filled with pre-cured PDMS by capillary force and then cured in oven. The tapered structure on UV tape was transferred and bonded to glass wafer by O₂ plasma treatment. The fabricated inverse-tapered structure was coated with a fluoroalkylsilane monolayer to reduce its surface energy. The wetting behaviors were investigated by the contact angle (CA) measurement of hexadecane droplets. This study demonstrates that an inversetapered structure can be fabricated on a substrate using micromolding in capillaries and microtransfer molding, whose surface shows the superoleophobicity.

A Novel Single Cell Culture Chip Based on One-Step Method

More and more basic biology research focus on the single cell level. However, the way to fabricate a chemically patterned surface exist some questions such as complex fabrication process, graphic quality puzzle and so on. In this paper, we present a One-Step method based on Poly 2-hydroxyethyl methacrylate (PolyHEMA) and micromolding in capillaries (MIMIC) technology to fabricate single cell culture chip. Experimental evidence indicates that the integrity and stability of the PolyHEMA pattern can perfectly satisfy the need of long-term cell culture.

Biodegradable neural cell culture sheet made of poly(lactic-co-glycolic acid) thin film with micropatterns of Dulbecco’s phosphate-buffered saline (−) containing laminin layers

In the regenerative medicine field of nervous systems, techniques used to fabricate microstructures of neurons on flexible and biodegradable substrates have attracted attention. In this research, biodegradable and flexible neuron culture thin films that enable the selective axonal outgrowth of neurons were fabricated using poly(lactic-co-glycolic acid) (PLGA) thin films with micropatterns of Dulbecco’s phosphate-buffered saline (D-PBS) (−) containing laminin layers. The 100-µm-thick PLGA thin films were fabricated by diluting PLGA in acetone (5% w/w) and the solution was distributed onto a poly(dimethylsiloxane) (PDMS) mold. D-PBS (−) micropatterns containing laminin layers with widths of 10–150 µm were fabricated by micromolding in capillaries (MIMIC) and the microstencil method. Rat neurons were selectively cultured for 3 d on the laminin micropatterns; using the MIMIC method, the cells properly adhered to a pattern wider than 30 µm, while with the microstencil method, the necessary pattern width for proper adhesion was more than 50 µm.

(Invited) Cultivation of Rat Nerve Cells on Biodegradable Sheet Made of Poly (lactic-co-glycolic acid) Thin Film with Micropatterns of Polylysine Containing Laminin Layer

Cultivation of Rat Nerve Cells on Biodegradable sheet made of Poly (lactic-co-glycolic acid) thin film with micropatterns of polylysine containing laminin layer Yuki Nakamura, Shunpu Horiuchi, Eiki Koshinuma, Satomitsu Imai, and Yasushiro Nishioka* Department of Precision Machinery Engineering, College of Science and Technology, Nihon University, Funabashi, Chiba 274-8501, Japan Tel & Fax: + 81 – 47 – 469 - 6482 *e-mail: nishioka.yasushiro@nihon-u.ac.jp In regenerative medicine field of nervous system, a technique to fabricate microstructure of neurons on flexible and biodegradable substrates has attracted attention [1]. On the other hand, we have focused on poly lactic-co-glycolic acid (PLGA) as a candidate for the substrate material. The degradation products of PLGA have been reported to be non-cytotoxic and safely removed from host system via normal metabolic activity. Furthermore, it has also been reported that the hydrolysis reaction speed can be modified through controlling the ratio of lactide to glycolide [2]. The characteristics of degradation and removal in vivoare advantageous for regenerative medicine. Neural cell culture on micropatterns of polylysine containing laminin layer has been reported as a technique enabling selective axonal outgrowth of neurons [3]. In this research, biodegradable neuron culture thin films that enable selective axonal outgrowth of neurons were fabricated using PLGA thin films with micro lactic patterns of polylysine with laminin on them. Micro lactic patterns of polylysine with laminin as narrow as 20 μm in width ware defined by using the micromolding in capillaries (MIMIC) technique. Polydimethylsiloxane (PDMS) channel molds used for MIMIC and stencil sheets used for the microstencil method were fabricated by curing a polyether ether ketone mold, which was fabricated by nanoimprinting. The 100µm thick PLGA thin film was fabricated by diluting the PLGA into acetone (5w/w%), packing the solution into a PDMS mold, drawing a vacuum, baking and then cooling it down to cure. The selective growth of neurons on the culture sheet with the micropatterns were confirmed.

Patterning of Nanoclays on Positively Charged Self-Assembled Monolayers via Micromolding in Capillaries.

Nanoclays are nanomaterials with versatile adsorptive properties. This contribution describes the generation of micropatterns of a nanoclay ("laponite") on ammonium-terminated, self-assembled monolayers (SAMs) on glass and silicon. Microstructured immobilization of the laponite was performed using micromolding in capillaries (MIMIC). The immobilization was verified using contact angle goniometry, X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM), scanning electron microscopy (SEM), time-of-flight secondary ion mass spectrometry (ToF-SIMS), and fluorescence microscopy. Furthermore, laponite was modified with Nile red to generate a fluorescence enhancement-based surface sensor for the vitamin choline.

Systematic Study of Functionalizable, Non-Biofouling Agarose Films with Protein and Cellular Patterns on Glass Slides.

Herein we demonstrate a systematic investigation of chemically functionalizable, non-biofouling agarose films over large-area glass surfaces. Agarose films, prepared with various concentrations of aqueous agarose, were activated by using periodate oxidation to generate aldehyde groups at the termini of the agarose chains. The non-biofouling efficacy and binding capabilities of the activated films were evaluated by using protein and cellular patterning, performed by using a microarrayer, microcontact printing, and micromolding in capillaries. Characterization by using a fluorescence slide scanner and a scanning-probe microscope revealed that the pore sizes of the agarose films played an important role in achieving desirable film performance; the 0.2 wt % agarose film exhibited the optimum efficacy in this work.

Long‐Term Stable Poly(acrylamide) Brush Modified Transparent Microwells for Cell Attachment Studies in 3D

The fabrication of 3D cell microenvironments exploiting versatile, long-term stable passivating poly(acryl amide) brushes in a microwell format and the study of the behavior of fibroblast and pancreatic tumor cells in wells of systematically varied shape and size is reported. The microwells, which are obtained by combining micromolding in capillaries with microcontact printing of initiator monolayers for subsequent surface-initiated polymerization of acrylamide and controlled functionalization with fibronectin (FN), expose cell adhesive areas inside the wells and protein and cell resistant brushes on the topside plateaus. NIH 3T3 fibroblast and pancreatic tumor (Patu 8988T) cells adhere and remain viable in the FN coated microwells for more than 1 week. Compared to 2D patterns, both cell lines are observed to attach to the bottom as well as the sidewalls of the microwells. The cytoskeleton alignment is found to be less pronounced compared to 2D patterned substrates, independent of microwell size and geometry.

Scalable Patterning of MoS2 Nanoribbons by Micromolding in Capillaries.

In this study, we report a facile approach to prepare dense arrays of MoS2 nanoribbons by combining procedures of micromolding in capillaries (MIMIC) and thermolysis of thiosalts ((NH4)2MoS4) as the printing ink. The obtained MoS2 nanoribbons had a thickness reaching as low as 3.9 nm, a width ranging from 157 to 465 nm, and a length up to 2 cm. MoS2 nanoribbons with an extremely high aspect ratio (length/width) of ∼7.4 × 10(8) were achieved. The MoS2 pattern can be printed on versatile substrates, such as SiO2/Si, sapphire, Au film, FTO/glass, and graphene-coated glass. The degree of crystallinity of the as-prepared MoS2 was discovered to be adjustable by varying the temperature through postannealing. The high-temperature thermolysis (1000 °C) results in high-quality conductive samples, and field-effect transistors based on the patterned MoS2 nanoribbons were demonstrated and characterized, where the carrier mobility was comparable to that of thin-film MoS2. In contrast, the low-temperature-treated samples (170 °C) result in a unique nanocrystalline MoSx structure (x ≈ 2.5), where the abundant and exposed edge sites were obtained from highly dense arrays of nanoribbon structures by this MIMIC patterning method. The patterned MoSx was revealed to have superior electrocatalytic efficiency (an overpotential of ∼211 mV at 10 mA/cm(2) and a Tafel slope of 43 mV/dec) in the hydrogen evolution reaction (HER) when compared to the thin-film MoS2. The report introduces a new concept for rapidly fabricating cost-effective and high-density MoS2/MoSx nanostructures on versatile substrates, which may pave the way for potential applications in nanoelectronics/optoelectronics and frontier energy materials.

Single cell migration dynamics mediated by geometric confinement

The migration dynamics of cells plays a key role in tissue engineering and regenerative medicine. Previous studies mostly focus on regulating stem cell fate and phenotype by biophysical cues. In contrast, less is known about how the geometric cues mediate the migration dynamics of cells. Here, we fabricate graphene oxide (GO) microstripes on cell non-adhesive PEG substrate by using micromolding in capillary (MIMIC) method. Such micropatterns with alternating cell adhesion and cell resistance enable an effective control of selective adhesion and migration of single cells. The sharp contrast in cell adhesion minimizes the invasion of cells into the PEG patterns, and thereby strongly confines the cells on GO microstripes. As a result, the cells are forced to adapt highly polarized, elongated, and oriented geometry to fit the patterns. A series of pattern widths have been fabricated to modulate the extent of cell deformation and polarization. Under strong confinement, the cytoskeleton contractility, intracellular traction, and actin filament elongation are highly promoted, which result in enhanced cell migration along the patterns. This work provides an important insight into developing combinatorial graphene-based patterns for the control of cell migration dynamics, which is of great significance for tissue engineering and regenerative medicine.

Fast and Simple Preparation of Patterned Surfaces with Hydrophilic Polymer Brushes by Micromolding in Capillaries.

Micropatterns of hydrophilic polymer brushes were prepared by micromolding in capillaries (MIMIC). The polymers are covalently bound to the surfaces by a rapid hetero Diels-Alder reaction, constituting the first example of polymers grafted to surfaces in a defined pattern by MIMIC. The polymers [poly(acrylic acid), poly(hydroxyethyl acrylate), and poly(tetraethylene glycol acrylate) ranging in molecular weight from 1500 to 6000 g mol(-1)] were prepared with narrow dispersities via the reversible addition-fragmentation chain transfer (RAFT) process using a highly electron deficient RAFT agent that can react with surface-anchored dienes such as cyclopentadiene. We demonstrate that the anchoring method is facile to perform and highly suitable for preparing patterned surfaces that are passivated against biological impact in well-defined areas.

Amorphous Aggregation of Amyloid Beta 1-40 Peptide in Confined Space.

The amorphous aggregation of Aβ1-40 peptide is addressed by using micromolding in capillaries. Both the morphology and the size of the aggregates are modulated by changing the contact angle of the sub-micrometric channel walls. Upon decreasing the hydrophilicity of the channels, the aggregates change their morphology from small aligned drops to discontinuous lines, thereby keeping their amorphous structure. Aβ1-40 fibrils are observed at high contact angles.

Constrained Sintering of Alumina Stripes on Rigid Substrates: Effect of Substrate Roughness and Coating

Micromolding in capillaries has been used to fabricate alumina stripes on smooth (Ra = 0.5 nm) and rough substrates (Ra = 900 nm). Different lateral (10–500 μm) and vertical stripe dimensions (8–27 μm) were used to study the influence of substrate roughness (smooth and rough sapphire) and substrate material (platinum coated and plain sapphire) on sintering behavior. Alumina stripes experience edge delamination during sintering on a rigid substrate independent of substrate roughness. However, enhanced substrate roughness reduced delamination length by half and lowered lateral strains by up to 0.10. Grooves in the rough substrate were found to be responsible for this feature as they act as crack propagation barriers and generate local density minima. Accompanying discrete element simulations revealed a localized triaxial stress state at the grooves of a sinusoidal‐shaped substrate interface as the main cause of the density minima. Platinum interlayers also resulted in reduced delamination by 40% in some stripe geometries while density was enhanced by 4% and lateral strains doubled in some geometries. Creep of the metal layer during sintering is thought to be the reason for this seemingly contradictory behavior.

Improved single-cell culture achieved using micromolding in capillaries technology coupled with poly (HEMA).

Cell studies at the single-cell level are becoming more and more critical for understanding the complex biological processes. Here, we present an optimization study investigating the positioning of single cells using micromolding in capillaries technology coupled with the cytophobic biomaterial poly (2-hydroxyethyl methacrylate) (poly (HEMA)). As a cytophobic biomaterial, poly (HEMA) was used to inhibit cells, whereas the glass was used as the substrate to provide a cell adhesive background. The poly (HEMA) chemical barrier was obtained using micromolding in capillaries, and the microchannel networks used for capillarity were easily achieved by reversibly bonding the polydimethylsiloxane mold and the glass. Finally, discrete cell adhesion regions were presented on the glass surface. This method is facile and low cost, and the reagents are commercially available. We validated the cytophobic abilities of the poly (HEMA), optimized the channel parameters for higher quality and more stable poly (HEMA) patterns by investigating the effects of changing the aspect ratio and the width of the microchannel on the poly (HEMA) grid pattern, and improved the single-cell occupancy by optimizing the dimensions of the cell adhesion regions.

3D Micromolding of Arrayed Waveguide Gratings on Upconversion Luminescent Layers for Flexible Transparent Displays without Mirrors, Electrodes, and Electric Circuits

A new technique for the fabrication of arrayed waveguide gratings on upconversion luminescent layers for flexible transparent displays is reported. Ho3+‐ and Yb3+‐codoped NaYF4 nanoparticles are synthesized by hydrothermal techniques. Transparent films consisting of two transparent polymers on the NaYF4 nanoparticle films exhibit mechanical flexibility and high transparence in visible region. Patterned NaYF4 nanoparticle films are fabricated by calcination‐free micromolding in capillaries. Arrayed waveguide gratings consisting of the two transparent polymers are formed on the patterned NaYF4 nanoparticle films by micromolding in capillaries. Green and red luminescence is observed from the upconversion luminescent layers of the NaYF4 nanoparticle films in the arrayed waveguide gratings under excitation at 980 nm laser light. Arrayed waveguide gratings on the upconversion luminescent layers are fabricated with Er3+‐doped NaYF4 nanoparticles which can convert two photons at 850 and 1500 nm into single photon at 550 nm. These results demonstrate that flexible transparent displays can be fabricated by constructing arrayed waveguide gratings on upconversion luminescent layers, which can operate in nonprojection mode without mirrors, transparent electrodes, and electric circuits.

Calcination-free micromolding in capillaries for nanopatterning of inorganic upconversion luminescent layers on flexible plastic sheets

We report calcination-free micromolding in capillaries for the nanopatterning of inorganic upconversion luminescent layers on flexible plastic sheets. We prepared Er3+- and Yb3+-codoped NaYF4 nanoparticles modified with a cationic polymer to improve dispersion stability of aqueous dispersion of the NaYF4 nanoparticles. We controlled the line width and density of nanoparticles in the NaYF4 nanoparticle films on flexible plastic sheets by adjusting the concentrations of the NaYF4 nanoparticle dispersion and the channel sizes of silicone stamps, resulting in the formation of nanopatterned NaYF4 nanoparticle films at the line width of the nanoparticle size (50nm). Visible upconversion luminescence and near-infrared fluorescence appeared from the NaYF4 nanoparticle films excited with a near-infrared laser beam. These results demonstrate that calcination free micromolding in capillaries using aqueous dispersion of NaYF4 nanoparticles modified with a cationic polymer allows for the nanopatterning of inorganic upconversion luminescent layers on flexible plastic sheets.