Microfluidics, a technology characterized by the engineered manipulation of fluids at the submillimetre scale, has shown considerable promise for improving diagnostics and biology research. Certain properties of microfluidic technologies, such as rapid sample processing and the precise control of fluids in an assay, have made them attractive candidates to replace traditional experimental approaches. Here we analyse the progress made by lab-on-a-chip microtechnologies in recent years, and discuss the clinical and research areas in which they have made the greatest impact. We also suggest directions that biologists, engineers and clinicians can take to help this technology live up to its potential.

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The present and future role of microfluidics in biomedical research

Soft materials capable of transforming between three-dimensional (3D) shapes in response to stimuli such as light, heat, solvent, electric and magnetic fields have applications in diverse areas such as flexible electronics1,2, soft robotics3,4 and biomedicine5–7. In particular, magnetic fields offer a safe and effective manipulation method for biomedical applications, which typically require remote actuation in enclosed and confined spaces8–10. With advances in magnetic field control
 11
 , magnetically responsive soft materials have also evolved from embedding discrete magnets
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 or incorporating magnetic particles
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 into soft compounds to generating nonuniform magnetization profiles in polymeric sheets14,15. Here we report 3D printing of programmed ferromagnetic domains in soft materials that enable fast transformations between complex 3D shapes via magnetic actuation. Our approach is based on direct ink writing
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 of an elastomer composite containing ferromagnetic microparticles. By applying a magnetic field to the dispensing nozzle while printing
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 , we reorient particles along the applied field to impart patterned magnetic polarity to printed filaments. This method allows us to program ferromagnetic domains in complex 3D-printed soft materials, enabling a set of previously inaccessible modes of transformation, such as remotely controlled auxetic behaviours of mechanical metamaterials with negative Poisson’s ratios. The actuation speed and power density of our printed soft materials with programmed ferromagnetic domains are orders of magnitude greater than existing 3D-printed active materials. We further demonstrate diverse functions derived from complex shape changes, including reconfigurable soft electronics, a mechanical metamaterial that can jump and a soft robot that crawls, rolls, catches fast-moving objects and transports a pharmaceutical dose.

Printing ferromagnetic domains for untethered fast-transforming soft materials

This Review summarizes recent developments in the field of responsive photonic crystal structures, including principles for design and fabrication and many strategies for applications, for example as optical switches or chemical and biological sensors. A number of fabrication methods are now available to realize responsive photonic structures, the majority of which rely on self-assembly processes to achieve ordering. Compared with microfabrication techniques, self-assembly approaches have lower processing costs and higher production efficiency, however, major efforts are still needed to further develop such approaches. In fact, some emerging techniques such as spin coating, magnetic assembly, and flow-induced self-assembly have already shown great promise in overcoming current challenges. When designing new systems with improved performance, it is always helpful to bear in mind the lessons learnt from natural photonic structures.

Responsive photonic crystals.

This review comprises a detailed survey of ongoing methodologies for soft actuators, highlighting approaches suitable for nanometer- to centimeter-scale robotic applications. Soft robots present a special design challenge in that their actuation and sensing mechanisms are often highly integrated with the robot body and overall functionality. When less than a centimeter, they belong to an even more special subcategory of robots or devices, in that they often lack on-board power, sensing, computation, and control. Soft, active materials are particularly well suited for this task, with a wide range of stimulants and a number of impressive examples, demonstrating large deformations, high motion complexities, and varied multifunctionality. Recent research includes both the development of new materials and composites, as well as novel implementations leveraging the unique properties of soft materials.

Soft Actuators for Small-Scale Robotics.

In the last decade, inertial microfluidics has attracted significant attention and a wide variety of channel designs that focus, concentrate and separate particles and fluids have been demonstrated. In contrast to conventional microfluidic technologies, where fluid inertia is negligible and flow remains almost within the Stokes flow region with very low Reynolds number (Re ≪ 1), inertial microfluidics works in the intermediate Reynolds number range (~1 < Re < ~100) between Stokes and turbulent regimes. In this intermediate range, both inertia and fluid viscosity are finite and bring about several intriguing effects that form the basis of inertial microfluidics including (i) inertial migration and (ii) secondary flow. Due to the superior features of high-throughput, simplicity, precise manipulation and low cost, inertial microfluidics is a very promising candidate for cellular sample processing, especially for samples with low abundant targets. In this review, we first discuss the fundamental kinematics of particles in microchannels to familiarise readers with the mechanisms and underlying physics in inertial microfluidic systems. We then present a comprehensive review of recent developments and key applications of inertial microfluidic systems according to their microchannel structures. Finally, we discuss the perspective of employing fluid inertia in microfluidics for particle manipulation. Due to the superior benefits of inertial microfluidics, this promising technology will still be an attractive topic in the near future, with more novel designs and further applications in biology, medicine and industry on the horizon.

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Fundamentals and applications of inertial microfluidics: a review

Many creatures in nature, such as butterflies and peacocks, display unique brilliant colours, known as ‘structural colours’, which result from the interaction of light with periodic nanostructures on their surfaces. Mimicking such nanostructures found in nature, however, requires state-of-the-art nanofabrication techniques that are slow, expensive and not scalable. Herein, we demonstrate high-resolution patterning of multiple structural colours within seconds, based on successive tuning and fixing of colour using a single material along with a maskless lithography system. We have invented a material called ‘M-Ink’, the colour of which is tunable by magnetically changing the periodicity of the nanostructure and fixable by photochemically immobilizing those structures in a polymer network. We also demonstrate a flexible photonic crystal for the realization of structural colour printing. The simple, controllable and scalable structural colour printing scheme presented may have a significant impact on colour production for general consumer goods. Maskless high-resolution patterning of structural colours is demonstrated using a new material called ‘M-Ink’. The period of the material is patterned magnetically and a photochemical process immobilizes the structure in a polymer network.

Structural colour printing using a magnetically tunable and lithographically fixable photonic crystal

Polymeric microcomponents are widely used in microelectromechanical systems (MEMS) and lab-on-a-chip devices, but they suffer from the lack of complex motion, effective addressability and precise shape control To address these needs, we fabricated polymeric nanocomposite microactuators driven by programmable heterogeneous magnetic anisotropy Spatially modulated photopatterning was applied in a shape-independent manner to microactuator components by successive confinement of self-assembled magnetic nanoparticles in a fixed polymer matrix By freely programming the rotational axis of each component, we demonstrate that the polymeric microactuators can undergo predesigned, complex two- and three-dimensional motion

Programming magnetic anisotropy in polymeric microactuators.

A QR-coded microtaggant for the anti-counterfeiting of drugs is proposed that can provide high capacity and error-correction capability. It is fabricated lithographically in a microfluidic channel with special consideration of the island patterns in the QR Code. The microtaggant is incorporated in the drug capsule ("on-dose authentication") and can be read by a simple smartphone QR Code reader application when removed from the capsule and washed free of drug.

Lithographically Encoded Polymer Microtaggant Using High‐Capacity and Error‐Correctable QR Code for Anti‐Counterfeiting of Drugs

We have investigated the focusing and dynamics of non-spherical polymeric particles in microfluidic flows at finite Reynolds number. The rotational diameter, Dmax, of a particle, regardless of its cross-sectional shape, was found to determine the final focused position, except for the case of asymmetric disks. Additionally, elongated particles with larger Dmax exhibited longer residence times in a horizontal orientation than those with smaller Dmax. These findings inform approaches to hydrodynamically control shaped and barcoded particles for multiplexed biochemical assays.

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Inertial focusing of non-spherical microparticles

In order to offer an easier way to study interactions between multiple cellular populations, we have developed a novel method to precisely place cells in a variety of nonoverlapping patterns using surface tension in laterally open microchannels. Our design is fundamentally different from previous strategies such as compartmentalization, stamping, stenciling, or mechanical approaches. It relies on capillary action or the propensity for liquid to move more readily through narrow spaces as a result of surface tension. Until now, capillary based patterning has been limited to coating chemically isolated areas. Here, we demonstrate, through use of surface tension and controlled flooding, that it is possible to pattern multiple cells and proteins using laterally open channels in a variety of designs. We demonstrate the relevance of the concept by coculturing different mammalian cell types and evaluating the behavior of engineered quorum sensing circuits in E. coli. In the future, we believe the laterally open channel designs shown here can be useful for rapidly creating and studying cellular ecologies using simple pipetting.

Sung-Eun Choi

Papers

Structural colour printing using a magnetically tunable and lithographically fixable photonic crystal

Programming magnetic anisotropy in polymeric microactuators.

Lithographically Encoded Polymer Microtaggant Using High‐Capacity and Error‐Correctable QR Code for Anti‐Counterfeiting of Drugs

Inertial focusing of non-spherical microparticles

Capillary Based Patterning of Cellular Communities in Laterally Open Channels