Guided and fluidic self-assembly of microstructures using railed microfluidic channels

Fluidic self-assembly is a promising pathway for parallel fabrication of devices made up of many small components. Here, we introduce 'railed microfluidics' as an agile method to guide and assemble microstructures inside fluidic channels. The guided movement of microstructures in microfluidic channels was achieved by fabricating grooves ('rails') on the top surface of the channels and also creating complementary polymeric microstructures that fit with the grooves. Using the rails as a guiding mechanism, we built complex one- and two-dimensional microsystems in which all the microstructures initially involved in the fabrication method were incorporated as components in the final product. Complex structures composed of more than 50 microstructures (each sized smaller than 50 microm) were fluidically self-assembled with zero error. Furthermore, we were able to use the rails to guide microstructures through different fluid solutions, successfully overcoming strong interfacial tension between solutions. On the basis of rail-guided self-assembly and cross-solution movement, we demonstrated heterogeneous fluidic self-assembly of polymeric microstructures and living cells. In addition to such assembly of in situ polymerized structures, we also guided and assembled externally fabricated silicon chips-demonstrating the feasible application of railed microfluidics to other materials systems.     

High‐Throughput Fabrication and Modular Assembly of 3D Heterogeneous Microscale Tissues

3D hydrogel microstructures that encapsulate cells have been used in broad applications in microscale tissue engineering, personalized drug screening, and regenerative medicine. Recent technological advances in microstructure assembly, such as bioprinting, magnetic assembly, microfluidics, and acoustics, have enabled the construction of designed 3D tissue structures with spatially organized cells in vitro. However, a bottleneck exists that still hampers the application of microtissue structures, due to a lack of techniques that combined high‐throughput fabrication and flexible assembly. Here, a versatile method for fabricating customized microstructures and reorganizing building blocks composed of functional components into a combined single geometric shape is demonstrated. The arbitrary microstructures are dynamically synthesized in a microfluidic device and then transferred to an optically induced electrokinetics chip for manipulation and assembly. Moreover, building blocks containing different cells can be arranged into a desired geometry with specific shape and size, which can be used for microscale tissue engineering.     

Microfluidic separation and gateable fraction collection for mass-limited samples

Integrating multiple analytical processes into microfluidic devices is an important research area required for a variety of microchip-based analyses. A microfluidic system is described that achieves preparative separations by intelligent fraction collection of attomole quantities of sample. The device consists of a main microfluidic channel used to perform electrophoresis, which is interconnected at 90 degrees to two vertically displaced channels via a nanocapillary array membrane. The membrane interconnect contains nanometer-diameter pores that provide fluidic communication between the channels. Sample injection and analyte collection are controlled by application of an electrical bias between the microfluidic channels across the nanocapillary array. After the separation, the automated transfer of the FITC-labeled Arg, Gln, and Gly bands occurs; a fluorescence detector located at the separation/collection channel interconnect is used to generate a triggering signal that initiates suitable voltages to allow near-quantitative transfer of analyte from the separation channel to the second fluidic layer. The ability to achieve such sample manipulations from mass-limited samples enables a variety of postseparation processing events.     

Microfluidics: Accelerated Biofluid Filling in Complex Microfluidic Networks by Vacuum‐Pressure Accelerated Movement (V‐PAM) (Small 33/2016)

Rapid fluid transport and exchange are critical operations involved in many microfluidic applications. However, conventional mechanisms used for driving fluid transport in microfluidics, such as micropumping and high pressure, can be inaccurate and difficult for implementation for integrated microfluidics containing control components and closed compartments. Here, a technology has been developed termed Vacuum–Pressure Accelerated Movement (V‐PAM) capable of significantly enhancing biofluid transport in complex microfluidic environments containing dead‐end channels and closed chambers. Operation of the V‐PAM entails a pressurized fluid loading into microfluidic channels where gas confined inside can rapidly be dissipated through permeation through a thin, gas‐permeable membrane sandwiched between microfluidic channels and a network of vacuum channels. Effects of different structural and operational parameters of the V‐PAM for promoting fluid filling in microfluidic environments have been studied systematically. This work further demonstrates the applicability of V‐PAM for rapid filling of temperature‐sensitive hydrogels and unprocessed whole blood into complex irregular microfluidic networks such as microfluidic leaf venation patterns and blood circulatory systems. Together, the V‐PAM technology provides a promising generic microfluidic tool for advanced fluid control and transport in integrated microfluidics for different microfluidic diagnosis, organs‐on‐chips, and biomimetic studies.     

Increasing the Dimensionality of Soft Microstructures through Injection‐Induced Self‐Folding

Devices fabricated using soft materials have been a major research focus of late, capturing the attention of scientists and laypersons alike in a wide range of fields, from microfluidics to robotics. The functionality of such devices relies on their structural and material properties; thus, the fabrication method is of utmost importance. Here, multilayer soft lithography, precision laser micromachining, and folding to establish a new paradigm are combined for creating 3D soft microstructures and devices. Phase‐changing materials are exploited to transform actuators into structural elements, allowing 2D laminates to evolve into a third spatial dimension. To illustrate the capabilities of this new fabrication paradigm, the first “microfluidic origami for reconfigurable pneumatic/hydraulic” device is designed and manufactured: a 12‐layer soft robotic peacock spider with embedded microfluidic circuitry and actuatable features.     

Optically fabricated three dimensional nanofluidic mixers for microfluidic devices

This paper describes a simple technique for fabricating complex, but well defined, three-dimensional (3D) networks of nanoscale flow paths in the channels of microfluidic systems. Near field scanning optical measurements reveal the optics associated with the fabrication process and the key features that enable its application to the area of microfluidics. Confocal studies of microfluidic devices that incorporate 3D nanostructures formed using this approach show that they function as efficient passive mixing elements, particularly at low Reynolds numbers. This application and others such as separation and extraction inmicrofluidic total analysis systems or lab on a chip devices represent promising areas for 3D nanostructures of this general type.     

Cover Picture: Microsolidics: Fabrication of Three‐Dimensional Metallic Microstructures in Poly(dimethylsiloxane) (Adv. Mater. 5/2007)

Flexible metallic wires embedded in poly(dimethylsiloxane) are produced with microscale dimensions by injecting heated, liquid solder into microfluidic channels and cooling, as reported by George Whitesides and co‐workers on p. 727. This approach is used to fabricate complex, metallic microstructures that are twisted (as shown), rolled, or woven into fabrics. The structures can be rigid or flexible, depending on the type of solder used, and breaks in the metal can be “healed” by reheating the device. This method of fabrication may find applications in flexible electronic circuits, 3D metallic microstructures, and hybrid electronic–microfluidic devices.     

Desktop‐Stereolithography 3D‐Printing of a Poly(dimethylsiloxane)‐Based Material with Sylgard‐184 Properties

The advantageous physiochemical properties of poly(dimethylsiloxane) (PDMS) have made it an extremely useful material for prototyping in various technological, scientific, and clinical areas. However, PDMS molding is a manual procedure and requires tedious assembly steps, especially for 3D designs, thereby limiting its access and usability. On the other hand, automated digital manufacturing processes such as stereolithography (SL) enable true 3D design and fabrication. Here the formulation, characterization, and SL application of a 3D‐printable PDMS resin (3DP‐PDMS) based on commercially available PDMS‐methacrylate macromers, a high‐efficiency photoinitiator and a high‐absorbance photosensitizer, is reported. Using a desktop SL‐printer, optically transparent submillimeter structures and microfluidic channels are demonstrated. An optimized blend of PDMS‐methacrylate macromers is also used to SL‐print structures with mechanical properties similar to conventional thermally cured PDMS (Sylgard‐184). Furthermore, it is shown that SL‐printed 3DP‐PDMS substrates can be rendered suitable for mammalian cell culture. The 3DP‐PDMS resin enables assembly‐free, automated, digital manufacturing of PDMS, which should facilitate the prototyping of devices for microfluidics, organ‐on‐chip platforms, soft robotics, flexible electronics, and sensors, among others.     

Microfabricated polymer analysis chip for optical detection

A coupling between multimode polymer waveguides and microfluidic channels on a polymethylmethacrylate (PMMA) capillary electrophoresis (CE)-chip for optical analytical applications has been successfully realised. This technology allows the integration of polymer optical waveguides together with hermetically sealed fluidic channels. The microchannels and waveguides are made in PMMA by the approved hot-embossing technology. The technology developed for the fabrication of polymer waveguides on the microfluidic chip offers the possibility of great flexibility in the choice of core materials, design and alignment of the polymer waveguides. The integration of polymer waveguides on an analysis chip enables highly spatially resolved optical detection without the large and expensive conventionally used apparatus. The optical properties of the analytical system developed are verified by transmission and propagation loss measurements. The results of measurements prove the suitability of the presented device for optical applications between 440 and 800 nm. This was shown with absorbance measurements of the dye Sulfanilazochromotrop (SPADNS) within 50 microm fluidic channels.     

Microfluidic Platforms toward Rational Material Fabrication for Biomedical Applications

The emergence of micro/nanomaterials in recent decades has brought promising alternative approaches in various biomedicine‐related fields such as pharmaceutics, diagnostics, and therapeutics. These micro/nanomaterials for specific biomedical applications shall possess tailored properties and functionalities that are closely correlated to their geometries, structures, and compositions, therefore placing extremely high demands for manufacturing techniques. Owing to the superior capabilities in manipulating fluids and droplets at microscale, microfluidics has offered robust and versatile platform technologies enabling rational design and fabrication of micro/nanomaterials with precisely controlled geometries, structures and compositions in high throughput manners, making them excellent candidates for a variety of biomedical applications. This review briefly summarizes the progress of microfluidics in the fabrication of various micro/nanomaterials ranging from 0D (particles), 1D (fibers) to 2D/3D (film and bulk materials) materials with controllable geometries, structures, and compositions. The applications of these microfluidic‐based materials in the fields of diagnostics, drug delivery, organs‐on‐chips, tissue engineering, and stimuli‐responsive biodevices are introduced. Finally, an outlook is discussed on the future direction of microfluidic platforms for generating materials with superior properties and on‐demand functionalities. The integration of new materials and techniques with microfluidics will pave new avenues for preparing advanced micro/nanomaterials with enhanced performance for biomedical applications.     

Fast Dynamic Visualizations in Microfluidics Enabled by Fluorescent Carbon Nanodots

Microfluidic systems have become a superior platform for explorations of fascinating fluidic physics at microscale as well as applications in biomedical devices, chemical reactions, drug delivery, etc. Exploitations of this platform are built upon the fundamental techniques of flow visualizations. However, the currently employed fluorescent materials for microfluidic visualization are far from satisfaction, which severely hinders their widespread applications. Here fluorescent carbon nanodots are documented as a game‐changer, applicable in versatile fluidic environment for the visualization in microfluidics with unprecedented advantages. One of the fastest fluorescent imaging speeds up to 2500 frames per second under a normal contionous wave (CW) laser line is achieved by adopting carbon nanodots in microfluidics. Besides better visualizations of the fluid or interface, fluorescent carbon nanodots‐based microparticles enable quantitative studies of high speed dynamics in fluids at microscale with a more than 90% lower cost, which is inaccessible by traditionally adopted fluorescent dye based seeding particles. The findings hold profound influences to microfluidic investigations and may even lead to revolutionary changes to the relevant industries.     

Micro-infiltration of three-dimensional porous networks with carbon nanotube-based nanocomposite for material design

Epoxy composite beams reinforced with a complex three-dimensional (3D) skeleton structure of nanocomposite microfibers were fabricated via micro-infiltration of 3D porous microfluidic networks with carbon nanotube nanocomposites. The effectiveness of this manufacturing approach to design composites microstructures was systematically studied by using different epoxy resins. The temperature-dependent mechanical properties of these multifunctional beams showed different features which cannot be obtained for those of their individual components bulks. The microfibers 3D pattern was adapted to offer better performance under flexural solicitation by the positioning most of the reinforcing microfibers at higher stress regions. This led to an increase of 49% in flexural modulus of a reinforced-epoxy beam in comparison to that of the epoxy bulk. The flexibility of this method enables the utilization of different thermosetting materials and nanofillers in order to design multifunctional composites for a wide variety of applications such as structural composites and components for micro-electromechanical systems.     

Fracture‐Based Fabrication of Normally Closed,Adjustable, and Fully Reversible Microscale Fluidic Channels

Adjustable fluidic structures play an important role in microfluidic systems. Fracture of multilayered materials under applied tension has been previously demonstrated as a convenient, simple, and inexpensive approach to fabricate nanoscale adjustable structures; here, it is demonstrated how to extend this concept to the microscale. This is achieved by a novel pairing of materials that leverages fracture mechanics to limit crack formation to a specified region, allowing to create size‐controllable and adjustable microfluidic structures. This technique can be used to fabricate “normally closed” microfluidic channels that are completely reversible, a feature that is challenging to achieve in conventional systems without careful engineering controls. The adjustable microfluidic channels are then applied to mechanically lyse single cells, and subsequently manipulate the released nuclear chromatin, creating new possibilities for epigenetic analysis of single cells. This simple, versatile, and robust technology provides an easily accessible pathway to construct adjustable microfluidic structures, which will be useful in developing complex assays and experiments even in resource‐limited settings.     

Gateable nanofluidic interconnects for multilayered microfluidic separation systems

The extension of microfluidic devices to include three-dimensional fluidic networks allows complex fluidic and chemical manipulations but requires innovative methods to interface fluidic layers. Externally controllable interconnects, employing nuclear track-etched polycarbonate membranes containing nanometer-diameter capillaries, are described that produce hybrid three-dimensional fluidic architectures. Controllable nanofluidic transfer is achieved by controlling applied bias, polarity, and density of the immobile nanopore surface charge and the impedance of the nanocapillary array relative to the microfluidic channels. Analyte transport between vertically separated microchannels has three stable transfer levels, corresponding to zero, reverse, and forward bias. The transfer can even depend on the properties of the analyte being transferred such as the molecular size, illustrating the flexible character of the analyte transfer. In a specific analysis implementation, nanochannel array gating is applied to capillary electrophoresis separations, allowing selected separated components to be isolated for further manipulation, thereby opening the way for preparative separations at attomole analyte mass levels.     

A Microfluidic Device to Acquire Gaseous Samples Via Surface Tension Held Gas-Liquid Interface

We present a relatively simple and effective method for acquiring gaseous samples into microfluidic channels. Hydrophobic polymers are photopatterned on hydrophilic substrates. Due to surface tension, aqueous liquid is confined by the hydrophobic polymers, but not completely blocked by a physical wall, thus allowing an interface for gas-liquid interaction. Here, the mechanism is demonstrated by using hydrophobic (poly)iso-bornyl acrylate polymer patterns on hydrophilic glass substrates, and through a Nessler's reagent-ammonia reaction that exhibits changes in color and electrical resistance.     

Microfluidic mixers: from microfabricated to self-assembling devices

This paper begins with a survey of both passive and active microfluidic mixers that have been implemented in recent years. It then describes a micromixing device based on dynamic self-assembly. This device is easy to fabricate and has excellent working characteristics in the continuous-flow mode. The paper concludes with a brief discussion of possible applications of self-assembly in microfluidics.     

Microfluidic analogy of the wheatstone bridge for systematic investigations of electro-osmotic flows

A microfluidic analogy of the electric Wheatstone Bridge has been developed for electrokinetic study of miscellaneous liquid-solid interfaces. By using an optimized glass-PDMS-glass device technology, microfluidic channels with well-controlled surface properties can be fabricated, forming an "H" shaped fluidic network. After solving a set of linear equations, the electro-osmotic flow rate in the center channel can be deduced from indirect measurement of flow rates in the lateral channels. Experimentally, we demonstrate that the electro-osmotic mobility can be monitored every 30 s with accuracy better than 3% for a large dynamic range of electric fields. The results obtained with a borosilicate glass (D-263) and several standard biological buffers are also shown to illustrate the capability of this high throughput method.     

Flexographically printed fluidic structures in paper

This Technical Note demonstrates a simple method based on flexographic printing of polystyrene to form liquid guiding boundaries and layers on paper substrates. The method allows formation of hydrophobic barrier structures that partially or completely penetrate through the substrate. This unique property enables one to form very thin fluidic channels on paper, leading to reduced sample volumes required in point-of-care diagnostic devices. The described method is compatible with roll-to-roll flexography units found in many printing houses, making it an ideal method for large-scale production of paper-based fluidic structures.     

Continuous-flow lithography for high-throughput microparticle synthesis

Precisely shaped polymeric particles and structures are widely used for applications in photonic materials, MEMS, biomaterials and self-assembly. Current approaches for particle synthesis are either batch processes or flow-through microfluidic schemes that are based on two-phase systems, limiting the throughput, shape and functionality of the particles. We report a one-phase method that combines the advantages of microscope projection photolithography and microfluidics to continuously form morphologically complex or multifunctional particles down to the colloidal length scale. Exploiting the inhibition of free-radical polymerization near PDMS surfaces, we are able to repeatedly pattern and flow rows of particles in less than 0.1 s, affording a throughput of near 100 particles per second using the simplest of device designs. Polymerization was also carried out across laminar, co-flowing streams to generate Janus particles containing different chemistries, whose relative proportions could be easily tuned. This new high-throughput technique offers unprecedented control over particle size, shape and anisotropy.     

Self-regulated, droplet-based sample chopper for microfluidic absorbance detection

Akin to optical beam chopping, we demonstrate that formation and routing of aqueous droplets in oil can chop a fluidic sample to permit phase sensitive detection. This hand-operated microfluidic sample chopper (μChopper) greatly reduces the detection limit of molecular absorbance in a 27 μm optical path. With direct dependence on path length, absorbance is fundamentally incompatible with microfluidics. While other microfluidic absorbance approaches use complex additions to fabrication, such as fiber coupling and increased optical paths, this self-regulated μChopper uses opposing droplet generators to passively alternate sample and reference droplets at ~10 Hz each. Each droplet's identity is automatically locked-in to its generator, allowing downstream lock-in analysis to nearly eliminate large signal drift or 1/f noise. With a lock-in time constant of 1.9 s and total interrogated volume of 59 nL (122 droplets), a detection limit of 3.0 × 10(-4) absorbance units or 500 nM bromophenol blue (BPB) (29 fmol) was achieved using only an optical microscope and a standard, single-depth (27 μm) microfluidic device. The system was further applied to nanoliter pH sensing and validated with a spectrophotometer. The μChopper represents a fluidic analog to an optical beam chopper, and the self-regulated sample/reference droplet alternation promotes ease of use.