Combination Of Soft Lithography Research Articles

Closed-Loop Diabetes Minipatch Based on a Biosensor and an Electroosmotic Pump on Hollow Biodegradable Microneedles.

Developing a miniaturized, low-cost, and smart closed-loop system for diabetes could significantly improve life quality and benefit millions of people. Conventional closed-loop devices are large in size and exorbitant. Here, we unprecedentedly demonstrate an electrically controlled flexible closed-loop patch for continuous diabetes management by integrating hollow biodegradable microneedles with a biosensing device and an electroosmotic pump. The hollow microneedles were fabricated using a combination of soft lithography and micromachining. The outer layer of the microneedles was functionalized to serve as a biosensing device for the in situ sensitive and accurate monitoring of interstitial glucose. The inner layer of the microneedles was integrated with a flexible electroosmotic pump to deliver insulin, and the delivery rate was electrically controlled by the glucose level from the biosensing device. The closed-loop system successfully stabilized the blood glucose levels of diabetic rats in a normal and safe range. The system is painless, miniaturized, cost-effective, and flexible. It is anticipated that it could open up exciting new avenues for fundamental studies of new closed-loop devices as well as practical applications for diabetes management.

Exploring electrostatic properties of biomolecules by a combination of soft-lithography and Kelvin force microscopy

Electrostatic properties of biomolecules play an important role in a vast myriad of fundamental biological processes. Despite of the great importance of this matter, techniques to directly determine these properties are quite scarce and are still facing technical limitations. To date, Kelvin force microscopy (KFM), a variation of conventional atomic force microscopy which is generally used to study surface potential in semiconductors, is capturing attention due to its capability of mapping electrostatic properties of biomolecules with great sensitivity and spatial resolution at sub-micrometer scale.

Microscale Liquid Metal Conductors for Stretchable and Transparent Electronics

AbstractIntegrated wearable electronics capable of transducing and transmitting biophysical information on complex and dynamic systems are attracting high interest across the consumer electronics, clinical, and research domains. Gallium and gallium‐based liquid metals (LMs) emerge as promising conductor technology for wearables due to their excellent combination of electrical conductivity and mechanical compliance. However, LMs feature complex physical and chemical properties that pose significant manufacturability challenges. Herein, a microtechnology approach is presented to fabricate deformable, microscale LM conductors with high surface density and over large surface areas. Based on a combination of soft lithography, directional patterning, and thermal evaporation of gallium, this new technology enables a range of designs and geometries that can be used to form LM‐based stretchable electronic conductors. The versatility of the technology enables a palette of circuit designs that can offer unrivaled transparency (T > 89%) or large metallization density (2/5 µm line/gap).

Regulation of Myogenic Differentiation by Topologically Microgrooved Surfaces for Skeletal Muscle Tissue Engineering.

Inspired by the natural topological structure of skeletal muscle tissue, the topological surface construction of bionic scaffolds for skeletal muscle repair has attracted great interest. Many previous studies have focused on the effects of the topological structure on myoblasts. However, these studies used only specific repeating sizes and shapes to achieve the myoblast alignment and myotube formation; moreover, the regulatory effects of the size of a topological structure on myogenic differentiation are often neglected, leading to a lack of guidance for the design of scaffolds for skeletal muscle tissue engineering. In this study, we fabricated a series of microgroove topographies with various widths and depths via a combination of soft lithography and melt-casting and studied their effects on the behaviors of skeletal muscle cells, especially myogenic differentiation, in detail. Microgrooved poly(lactic-co-glycolic acid) substrates were found to effectively regulate the proliferation, myogenic differentiation, and myotube formation of C2C12 cells, and the degree of myogenic differentiation was significantly dependent on signals in response to the size of the microgroove structure. Compared with their depth, the width of the microgroove structures can more strongly affect the myogenic differentiation of C2C12 cells, and the degree of myoblast differentiation was enhanced with increasing groove width. Microgroove structures with relatively large groove widths and small groove depths promoted the myogenic differentiation of C2C12 cells. In addition, the integrin-mediated focal adhesion kinase signaling pathway and MAPK signaling pathway were activated in cells in response to the external topological structure, and the size of the topological structure of the material surface effectively regulated the degree of the cellular response to the external topological structure. These results can guide the design of scaffolds for skeletal muscle tissue engineering and the construction of effective bionic scaffold surfaces for skeletal muscle regeneration.

Improved Mesenchymal Stem Cell Proliferation, Differentiation, Epithelial Transition, and Restrained Senescence on Hierarchically Patterned Porous Honey Silk Fibroin Scaffolds.

We report a significant improvement of adipose-derived mesenchymal stem cells' (ADMSCs) biocompatibility and proliferation on hierarchically patterned porous honey-incorporated silk fibroin scaffolds fabricated using a combination of soft lithography and freeze-drying techniques. Parametric variations show enhanced surface roughness, swelling, and degradation rate with good pore interconnectivity, porosity, and mechanical strength for soft-lithographically fabricated biomimetic microdome arrays on the 2% honey silk fibroin scaffold (PHSF2) as compared to its other variants, which eventually made PHSF2 more comparable to the native environment required for stem cell adhesion and proliferation. PHSF2 also exhibits sustained honey release with remarkable antibacterial efficacy against methicillin-resistant Staphylococcus aureus (MRSA). Honey incorporation (biochemical cue) influences microdome structural features, that is, biophysical cues (height, width, and periodicity), which further allows ADMSCs pseudopods (filopodia) to grasp the microdomes for efficient cell-cell communication and cell-matrix interaction and regulates ADMSCs behavior by altering their cytoskeletal rearrangement and thereby increases the cellular spreading area and cell sheet formation. The synergistic effect of biochemical (honey) and biophysical (patterns) cues on ADMSCs studied by the nitro blue tetrazolium assay and DCFDA fluorescence spectroscopy reveals limited free radical generation within cells. Molecular expression studies show a decrease in p53 and p21 expressions validating ADMSCs senescence inhibition, which is further correlated with a decrease in cellular senescence-associated β galactosidase activity. We also show that an increase in CDH1 and CK19 molecular expressions along with an increase in SOX9, RUNX2, and PPARγ molecular expressions supported by PHSF2 justify the substrate's efficacy of underpinning mesenchymal to epithelial transition and multilineage trans-differentiation. This work highlights the fabrication of a naturally healing nutraceutical (honey)-embedded patterned porous stand-alone tool with the potential to be used as smart stem cells delivering regenerative healing implant.

Time Dependent Lyotropic Chromonic Textures in Microfluidic Confinements

Nematic and columnar phases of lyotropic chromonic liquid crystals (LCLCs) have been long studied for their fundamental and applied prospects in material science and medical diagnostics. LCLC phases represent different self-assembled states of disc-shaped molecules, held together by noncovalent interactions that lead to highly sensitive concentration and temperature dependent properties. Yet, microscale insights into confined LCLCs, specifically in the context of confinement geometry and surface properties, are lacking. Here, we report the emergence of time dependent textures in static disodium cromoglycate (DSCG) solutions, confined in PDMS-based microfluidic devices. We use a combination of soft lithography, surface characterization, and polarized optical imaging to generate and analyze the confinement-induced LCLC textures and demonstrate that over time, herringbone and spherulite textures emerge due to spontaneous nematic (N) to columnar M-phase transition, propagating from the LCLC-PDMS interface into the LCLC bulk. By varying the confinement geometry, anchoring conditions, and the initial DSCG concentration, we can systematically tune the temporal dynamics of the N- to M-phase transition and textural behavior of the confined LCLC. Overall, the time taken to change from nematic to the characteristic M-phase textures decreased as the confinement aspect ratio (width/depth) increased. For a given aspect ratio, the transition to the M-phase was generally faster in degenerate planar confinements, relative to the transition in homeotropic confinements. Since the static molecular states register the initial conditions for LC flows, the time dependent textures reported here suggest that the surface and confinement effects—even under static conditions—could be central in understanding the flow behavior of LCLCs and the associated transport properties of this versatile material.

Fabrication and characterization of three-dimensional silver nanodomes: Application for alkaline water electrolysis

A novel approach to fabricate three-dimensional (3D) silver nanodomes (AgNDs) based on combination of soft lithography and nanosphere lithography was reported. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) were used for the characterization of the 3D nanostructures. The 3D-AgNDs were evaluated for electrochemical hydrogen production in 6 M KOH solution by some electrochemical techniques. It was found that well-structured AgNDs have higher hydrogen evolution activity than Ag bulk. The hydrogen discharge potential (EH2) at the NDs lowered ∼150 mV with respect to that of the bulk Ag electrode which demonstrated that fabrication of NDs favors the hydrogen evolution kinetics and reduces the energy input for activating the HER. The cathodic Tafel slopes of bulk Ag and AgNDs were found to be 108 and 114 mV dec−1, respectively. The related charge transfer coefficients were very close to 0.5. In the case of AgNDs, resistance was reduced from 660 to 197.1 Ω cm2. This electrode was also characterized with higher current density at a fixed overpotential when compared to bulk Ag. The superior hydrogen evolution performance of AgNDs was assigned to their high roughness and large real surface area. Roughness factor (Rf) of the NDs was 22 times higher than that of bulk Ag.

Influence of 3D Microgrooves on C2C12 Cell Proliferation, Migration, Alignment, F-actin Protein Expression and Gene Expression

In this paper, we fabricated three kinds of 3D microgrooves with different depth on biocompatible poly(lactic-co-glycolic acid) (PLGA) substrate via combination of soft-lithography and melt-casting methods, and investigated in detail their influence on C2C12 cell behaviors. It is found that cell proliferation, migration, alignment, spatial distribution, F-actin protein expression and gene expression are all remarkably distinct on these microgrooved samples and the smooth control PLGA substrate. The associated underlying mechanisms were further analyzed and discussed using real-time living cell monitoring, confocal laser scanning microscopy and gene microarray. Our preliminary results suggested that 3D microstructure could affect cell behaviors in a much more extensive manner than what we had understood before.

Fabrication of flexible, transparent silver nanowire electrodes for amperometric detection of hydrogen peroxide

We present a simple method to fabricate flexible, transparent silver nanowire (AgNW) films. Homogenous AgNW networks were formed on a mixed cellulose ester (MCE) membrane by vacuum filtration and were easily transferable to self-adhesive poly(ethylene terephthalate). The opaque, white MCE membrane became transparent after being subjected to hot acetone vapor. The fabricated AgNW films had an average resistivity of 13Ω/sq and a transmittance of approximately 67%. Moreover, the AgNW films showed excellent mechanical properties in repeated adhesion tests and bending tests. The AgNW films also showed good resistance against heat and NaCl solutions. AgNW films were patterned by a combination of soft lithography and a solution-based chemical etching technique. The area under the photoresist polymer maintained its conductivity and transmittance after etching, whereas increased resistance and transparency were observed in the etched area. The suitability of the patterned AgNW electrodes for electronic devices was demonstrated via a simple LED chip array. After using standard photolithography to define the working area, AgNW films were used as sensor electrodes for the electrochemical detection of hydrogen peroxide (H2O2). The AgNW sensors displayed a reasonable detection limit of 46μM (S/N=3), a rapid response time (within 2s), and high sensitivity (749μAmM−1cm−2 and 1640μAmM−1cm−2). Furthermore, the AgNW sensor was resistant to other potential interfering electroactive species commonly present in physiological samples such as l-ascorbic acid, glucose, and sodium oxalate. These results indicate that the AgNW sensor is selective for electroreduction of H2O2. Additionally, the developed sensor exhibited a stable amperometric response to the reduction of H2O2 even after extended storage.

Fabrication and Characterization of Flexible and Tunable Plasmonic Nanostructures

We present a novel method to fabricate flexible and tunable plasmonic nanostructures based on combination of soft lithography and nanosphere lithography, and perform a comprehensive structural and optical characterization of these structures. Spherical latex particles are uniformly deposited on glass slides and used as molds for polydimethylsiloxane to obtain nanovoid structures. The diameter and depth of the nanostructures are controlled by the size of the latex particles. These surfaces are coated with a thin Ag layer for fabrication of uniform plasmonic nanostructures. Structural characterization of these surfaces is performed by SEM and AFM. Optical properties of these plasmonic nanostructures are evaluated via UV/Vis absorption spectroscopy, dark field microscopy, and surface–enhanced Raman spectroscopy (SERS). Position of the surface plasmon absorption depends on the diameter and depth of the nanostructures. SERS enhancement factor (measured up to 1.4 × 106) is dependent on the plasmon absorption wavelength and laser wavelength used in these experiments.

Fabrication of hierarchical hybrid structures using bio‐enabled layer‐by‐layer self‐assembly

Development of versatile and flexible assembly systems for fabrication of functional hybrid nanomaterials with well-defined hierarchical and spatial organization is of a significant importance in practical nanobiotechnology applications. Here we demonstrate a bio-enabled self-assembly technique for fabrication of multi-layered protein and nanometallic assemblies utilizing a modular gold-binding (AuBP1) fusion tag. To accomplish the bottom-up assembly we first genetically fused the AuBP1 peptide sequence to the C'-terminus of maltose-binding protein (MBP) using two different linkers to produce MBP-AuBP1 hetero-functional constructs. Using various spectroscopic techniques, surface plasmon resonance (SPR) and localized surface plasmon resonance (LSPR), we verified the exceptional binding and self-assembly characteristics of AuBP1 peptide. The AuBP1 peptide tag can direct the organization of recombinant MBP protein on various gold surfaces through an efficient control of the organic-inorganic interface at the molecular level. Furthermore using a combination of soft-lithography, self-assembly techniques and advanced AuBP1 peptide tag technology, we produced spatially and hierarchically controlled protein multi-layered assemblies on gold nanoparticle arrays with high molecular packing density and pattering efficiency in simple, reproducible steps. This model system offers layer-by-layer assembly capability based on specific AuBP1 peptide tag and constitutes novel biological routes for biofabrication of various protein arrays, plasmon-active nanometallic assemblies and devices with controlled organization, packing density and architecture.

Plasma functionalized PDMS microfluidic chips: towards point-of-care capture of circulating tumor cells

The main challenge in the isolation of circulating tumor cells (CTCs) resides in their extreme rarity in blood. Here we report on the design of efficient and disposable microfluidic CTC capture devices based on the plasma functionalization of PDMS and its subsequent conjugation with the anti-epithelial-cell adhesion-molecule (EpCAM) mAb. Model studies on planar surfaces demonstrated excellent immuno-specificity of cancer-cell capture using NCI H69 small-cell lung cancer cells and SK-Br-3 breast cancer cells. Taking advantage of the transparency of the PDMS device, direct observation of the capture events on the internal 3D microstructure of the device could be achieved. At a flow rate of 16 μL min−1, an overall capture efficiency of 80 to 90% is determined in cell-spiking experiments in PBS. In accordance with direct microscopic observations, an increased flow rate (48 μL min−1) only has a minor effect (30% reduction) on cell-capture efficiency. Capture efficiency of the device using cancer cells spiked in whole blood is above 70%. The combination of soft lithography and plasma-based functionalization described in this work enables the facile fabrication of efficient and disposable CTC capture devices based on PDMS, which could facilitate the transition of this new technology into the clinical environment.

Patterning of Hierarchically Aligned Single-Walled Carbon Nanotube Langmuir−Blodgett Films by Microcontact Printing

We present a patterning method for hierarchically aligned assembly of single-walled carbon nanotubes (SWNTs) using a combination of the Langmuir-Blodgett (LB) technique and soft lithography. The LB technique allows one to control the alignment and the surface density of SWNTs by adjusting surface pressure of the film at the air-water interface. The aligned SWNT Langmuir films are successfully transferred onto the polydimethylsiloxane (PDMS) or silicon substrate with unidirectional alignment, and SWNT patterns with various shapes are fabricated on silicon and flexible poly(ethylene terephthalate) (PET) substrates by contacting and peeling off the PDMS stamp from the substrates via microcontact printing or lift-up methods. The SWNT patterning technique using the combination of soft lithography and the LB method can be applied in various fields, such as flexible high-speed transistors, high-efficiency solar cells, and transparent electrodes.

Micropatterning of sulfonated polyaniline using a soft lithography based lift-off process

A combination of soft lithography and lift-off processing is presented for the fabrication of sulfonated polyaniline (SPAN) microstructures. A soft lithography based micromolding process was used to pattern sacrificial layers using a thermoplastic polymer. SPAN was then polymerized in situ to coat the patterned substrate. The sacrificial layer was removed by lift-off in an organic solvent, leaving the patterned SPAN on the substrate. This process was performed on several rigid and flexible substrates including glass, silicon, and polyimide. The film thickness and roughness were measured as a function of reaction time using atomic force microscopy. Patterns were also imaged using scanning electron microscopy. This process provides a cost effective and versatile method of patterning SPAN and has potential applications in a number of conducting polymer devices.

Self-Folding of Three-Dimensional Hydrogel Microstructures

This letter describes the fabrication of three-dimensional particulate-like hydrogel microstructures using a combination of soft lithography and volume expansion induced self-folding. Bilayer structures are produced by solvent casting and photocuring of liquid resins. They curl into three-dimensional (3D) structures upon contacting with water due to differential swelling of the two layers. The curvature can be controlled by adjusting the polymer composition of the primary swelling layer. A simple semiempirical mathematical model is used to predict this self-folding behavior. By designing the two-dimensional (2D) shapes of the bilayers, this technique can lead to complicated 3D microstructures.

Selective Growth of Aligned Carbon Nanotubes on a Silver-Patterned Substrate by the Silver Mirror Reaction

It was found that carbon nanotubes prepared by the pyrolysis of iron(II) phthalocyanine (FePc) can selectively grow on a SiO2 surface when the SiO2 wafer is patterned by silver. A combination of the micro-contact printing (μCP) technique and chemical reaction (classical silver tollens reaction, also called silver mirror reaction) has been applied to generate a silver pattern with micro/nanoscale resolution on a quartz glass substrate (silver selectively deposits on hydrophilic regions), and an aligned carbon nanotubes (CNTs) pattern with the same resolution can be fabricated by the pyrolysis of FePc on the basis of the selective growth. This new method represents a great advantage of controlled fabrication of a micro/nanoscale aligned CNT pattern on a conducting surface (silver) by combination of soft-lithography and chemical approach for various device applications, requiring high-resolution pattern and conducting surface.

Colloidal photonic crystal microchannel array with periodically modulated thickness

Here we report on the optical properties of a micrometer scale array of periodically modulated thickness colloidal crystals. A combination of soft-lithography, micromolding, and microfluidics techniques is employed to form rectangular microchannels that can impose a periodic modulation of the thickness of colloidal crystals grown within them. Correspondingly, a periodic fluctuation of the photonic band structure occurs at distances of the order of a few microns. Experimental evidence of this effect is obtained by optical microspectroscopy. Results are analyzed in terms of finite crystal size theoretical calculations.