Soft tubular microfluidics for 2D and 3D applications

Microfluidics has been the key component for many applications, including biomedical devices, chemical processors, microactuators, and even wearable devices. This technology relies on soft lithography fabrication which requires cleanroom facilities. Although popular, this method is expensive and labor-intensive. Furthermore, current conventional microfluidic chips precludes reconfiguration, making reiterations in design very time-consuming and costly. To address these intrinsic drawbacks of microfabrication, we present an alternative solution for the rapid prototyping of microfluidic elements such as microtubes, valves, and pumps. In addition, we demonstrate how microtubes with channels of various lengths and cross-sections can be attached modularly into 2D and 3D microfluidic systems for functional applications. We introduce a facile method of fabricating elastomeric microtubes as the basic building blocks for microfluidic devices. These microtubes are transparent, biocompatible, highly deformable, and customizable to various sizes and cross-sectional geometries. By configuring the microtubes into deterministic geometry, we enable rapid, low-cost formation of microfluidic assemblies without compromising their precision and functionality. We demonstrate configurable 2D and 3D microfluidic systems for applications in different domains. These include microparticle sorting, microdroplet generation, biocatalytic micromotor, triboelectric sensor, and even wearable sensing. Our approach, termed soft tubular microfluidics, provides a simple, cheaper, and faster solution for users lacking proficiency and access to cleanroom facilities to design and rapidly construct microfluidic devices for their various applications and needs. Keywords: flexible microfluidics, elastomeric microtubes, microfluidic assemblies, inertial focusing chip, microfluidic sensorSingapore-MIT Alliance for Research and Technology (SMART

Fabrication and Characterization of Miniaturized Components Based on Extruded Ceramic-Filled Polymer Blends

The objective of this work is to develop an improved manufacturing process for microstructured ceramic components that is based on co-extrusion. Co-extrusion of structured feedrods holds promise for development of multi-layered, functionally graded and/or textured structures. However, it requires a polymer binder that is difficult to remove before structures can be sintered to full density. A two-step debinding is introduced to eliminate debinding defects that are commonly observed in thermal debinding (TD). Cracking is a major issue due to a lack of pore spaces for outgassing of pyrolysis products in traditional TD. In two-step debinding, a soluble binder is removed partially by solvent extraction (SE) which creates a porous network and allows gases to escape in subsequent TD of remaining binder components. The feasibility of solvent extraction (SE) is documented for the extrusion of solid ceramic rods and co-extrusion of tubes, where alumina powder was batched with polyethylene butyl acrylate (PEBA) as backbone polymer and polyethylene glycol (PEG) as water soluble binder. SE for specimens with varying PEBA:PEG ratios were tested in water at three different temperatures for various times. Experiments were also performed with different grades of PEBA and EVA to investigate the effect of thermoplastics on SE. The 1:1 mixture showed a PEG removal up to 80wt.% of the original PEG content after 6h extraction. After subsequent thermal debinding, rods and tubes were sintered successfully without defects, demonstrating the viability of the process. Scanning electron microscopy and optical analysis were performed to characterize the process. In order to illustrate potential applications, microfluidic devices were manufactured using extrusion followed by hot embossing. Ceramic microfabricated components have advantages over silicon, glass or polymer devices in terms of their ability to sustain high temperatures without compromising their functional capabilities. Flat tapes were extruded to create substrates, which were subsequently embossing micro patterns using a brass metal mold. To seal the microchanneled feature, a glass slide was attached to the chip by thermal bonding. Though a good bond was obtained, small portions were found where poor bonding was observed. To check leakage, colored water was forced to flow through the channel,and no leakage of water was found. A low temperature sintered ceramic material was fabricated as a potential alternative to the commercial low temperature co-fired ceramic (LTCC) tape. Overall, the study describes new possibilities for microstructure fabrication on ceramic based substrate and established the embossing process as a promising technique for fabrication

Engineering tissue barrier models on hydrogel microfluidic platforms

Tissue barriers play a crucial role in human physiology by establishing tissue compartmentalization and regulating organ homeostasis. At the interface between the extracellular matrix (ECM) and flowing fluids, epithelial and endothelial barriers are responsible for solute and gas exchange. In the past decade, microfluidic technologies and organ-on-chip devices became popular as in vitro models able to recapitulate these biological barriers. However, in conventional microfluidic devices, cell barriers are primarily grown on hard polymeric membranes within polydimethylsiloxane (PDMS) channels that do not mimic the cell¿ECM interactions nor allow the incorporation of other cellular compartments such as stromal tissue or vascular structures. To develop models that accurately account for the different cellular and acellular compartments of tissue barriers, researchers have integrated hydrogels into microfluidic setups for tissue barrier-on-chips, either as cell substrates inside the chip, or as self-contained devices. These biomaterials provide the soft mechanical properties of tissue barriers and allow the embedding of stromal cells. Combining hydrogels with microfluidics technology provides unique opportunities to better recreate in vitro the tissue barrier models including the cellular components and the functionality of the in vivo tissues. Such platforms have the potential of greatly improving the predictive capacities of the in vitro systems in applications such as drug development, or disease modeling. Nevertheless, their development is not without challenges in their microfabrication. In this review, we will discuss the recent advances driving the fabrication of hydrogel microfluidic platforms and their applications in multiple tissue barrier models

Development of a PDMS Based Micro Total Analysis System for Rapid Biomolecule Detection

The emerging field of micro total analysis system powered by microfluidics is expected to revolutionize miniaturization and automation for point-of-care-testing systems which require quick, efficient and reproducible results. In the present study, a PDMS based micro total analysis system has been developed for rapid, multi-purpose, impedance based detection of biomolecules. The major components of the micro total analysis system include a micropump, micromixer, magnetic separator and interdigitated electrodes for impedance detection. Three designs of pneumatically actuated PDMS based micropumps were fabricated and tested. Based on the performance test results, one of the micropumps was selected for integration. The experimental results of the micropump performance were confirmed by a 2D COMSOL simulation combined with an equivalent circuit analysis of the micropump. Three designs of pneumatically actuated PDMS based active micromixers were fabricated and tested. The micromixer testing involved determination of mixing efficiency based on the streptavidin-biotin conjugation reaction between biotin comjugated fluorescent microbeads and streptavidin conjugated paramagnetic microbeads, followed by fluorescence measurements. Based on the performance test results, one of the micromixers was selected for integration. The selected micropump and micromixer were integrated into a single microfluidic system. The testing of the magnetic separation scheme involved comparison of three permanent magnets and three electromagnets of different sizes and magnetic strengths, for capturing magnetic microbeads at various flow rates. Based on the test results, one of the permanent magnets was selected. The interdigitated electrodes were fabricated on a glass substrate with gold as the electrode material. The selected micropumps, micromixer and interdigitated electrodes were integrated to achieve a fully integrated microfluidic system. The fully integrated microfluidic system was first applied towards biotin conjugated fluorescent microbeads detection based on streptavidin-biotin conjugation reaction which is followed by impedance spectrum measurements. The lower detection limit for biotin conjugated fluorescent microbeads was experimentally determined to be 1.9 x 106 microbeads. The fully integrated microfluidic system was then applied towards immuno microbead based insulin detection. The lower detection limit for insulin was determined to be 10-5M. The total detection time was 20 min. An equivalent circuit analysis was performed to explain the impedance spectrum results

Microfluidic on-chip biomimicry for 3D cell culture: a fit-for-purpose investigation from the end user standpoint

A plethora of 3D and microfluidics-based culture models have been demonstrated in the recent years with the ultimate aim to facilitate predictive in vitro models for pharmaceutical development. This article summarizes to date the progress in the microfluidics-based tissue culture models, including organ-on-a-chip and vasculature-on-a-chip. Specific focus is placed on addressing the question of what kinds of 3D culture and system complexities are deemed desirable by the biological and biomedical community. This question is addressed through analysis of a research survey to evaluate the potential use of microfluidic cell culture models among the end users. Our results showed a willingness to adopt 3D culture technology among biomedical researchers, although a significant gap still exists between the desired systems and existing 3D culture options. With these results, key challenges and future directions are highlighted.This work has been supported by The Engineering and Physical Sciences Research Council (EPSRC) UK under the grant number EP/M018989/1, and a Royal Society Research Grant. Y Liu received a studentship from the Schlumberger Foundation, and E Gill received a scholarship from the WD Armstrong Trust

FABRICATION OF MAGNETIC TWO-DIMENSIONAL AND THREE-DIMENSIONAL MICROSTRUCTURES FOR MICROFLUIDICS AND MICROROBOTICS APPLICATIONS

Micro-electro-mechanical systems (MEMS) technology has had an increasing impact on industry and our society. A wide range of MEMS devices are used in every aspects of our life, from microaccelerators and microgyroscopes to microscale drug-delivery systems. The increasing complexity of microsystems demands diverse microfabrication methods and actuation strategies to realize. Currently, it is challenging for existing microfabrication methods—particularly 3D microfabrication methods—to integrate multiple materials into the same component. This is a particular challenge for some applications, such as microrobotics and microfluidics, where integration of magnetically-responsive materials would be beneficial, because it enables contact-free actuation. In addition, most existing microfabrication methods can only fabricate flat, layered geometries; the few that can fabricate real 3D microstructures are not cost efficient and cannot realize mass production. This dissertation explores two solutions to these microfabrication problems: first, a method for integrating magnetically responsive regions into microstructures using photolithography, and second, a method for creating three-dimensional freestanding microstructures using a modified micromolding technique. The first method is a facile method of producing inexpensive freestanding photopatternable polymer micromagnets composed NdFeB microparticles dispersed in SU-8 photoresist. The microfabrication process is capable of fabricating polymer micromagnets with 3 µm feature resolution and greater than 10:1 aspect ratio. This method was used to demonstrate the creation of freestanding microrobots with an encapsulated magnetic core. A magnetic control system was developed and the magnetic microrobots were moved along a desired path at an average speed of 1.7 mm/s in a fluid environment under the presence of external magnetic field. A microfabrication process using aligned mask micromolding and soft lithography was also developed for creating freestanding microstructures with true 3D geometry. Characterization of this method and resolution limits were demonstrated. The combination of these two microfabrication methods has great potential for integrating several material types into one microstructure for a variety of applications

Magnetic Micro-Origami

Microscopic origami figures can be created from thin film patterns using surface tension of liquids or residual stresses in thin films. The curvature of the structures, direction of bending, twisting, and folding of the patterns can be controlled by their shape, thickness, and elastic properties and by the strength of the residual stresses. Magnetic materials used for micro- and nano-origami structures play an essential role in many applications. Magnetic force due to applied magnetic field can be used for remote actuation of microrobots. It can also be used in targeted drug delivery to direct cages loaded with drugs or microswimmers to transport drugs to specific organs. Magnetoelastic properties of free-standing micro-origami patterns can serve for stress or magnetic field sensing. Also, the stress-induced anisotropy and magnetic shape anisotropy provide a convenient method of tuning magnetic properties by designing a shape of the micro-origami figures instead of varying the composition of the films. Micro-origami figures can also serve as building blocks for two- and three-dimensional meta-materials with unique properties such as negative index of refraction. Micro-origami techniques provide a powerful method of self-assembly of magnetic circuits and integrating them with microelectro-mechanical systems or other functional devices

Recent progress in extrusion 3D bioprinting of hydrogel biomaterials for tissue regeneration: a comprehensive review with a focus on advanced fabrication techniques

Over the last decade, 3D bioprinting has received immense attention from research communities for developing functional tissues. Thanks to the complexity of tissues, various bioprinting methods are exploited to figure out the challenges of tissue fabrication, in which hydrogels are widely adopted as a bioink in cell printing technologies based on the extrusion principle. Thus far, there is a wealth of the literature proposing the crucial parameters of extrusion-based bioprinting of hydrogel biomaterials (e.g., hydrogel properties, printing conditions, and tissue scaffold design) toward enhancing performance. Despite the growing research in this field, numerous challenges that hinder advanced applications still exist. Herein, the most recently reported hydrogel-based bioprinted scaffolds, i.e., skin, bone, cartilage, vascular, neural, and muscular (including skeletal, cardiac, and smooth), are systematically discussed with an emphasis on the advanced fabrication techniques from tissue engineering perspective. Methods covered include the multiple-dispenser, coaxial, and hybrid 3D bioprinting. The present work is a unique study to figure out the opportunities of the novel techniques to fabricate complicated constructs with structural and functional heterogeneity. Finally, the principal challenges of current studies and a vision of future research are presented