Continuous sheath-free magnetic separation of particles in a U-shaped microchannel

Particle separation is important to many chemical and biomedical applications. Magnetic field-induced particle separation is simple, cheap, and free of fluid heating issues that accompany electric, acoustic, and optical methods. We develop herein a novel microfluidic approach to continuous sheath-free magnetic separation of particles. This approach exploits the negative or positive magnetophoretic deflection to focus and separate particles in the two branches of a U-shaped microchannel, respectively. It is applicable to both magnetic and diamagnetic particle separations, and is demonstrated through the sorting of 5 μm and 15 μm polystyrene particles suspended in a dilute ferrofluid.     

Flagellated Janus particles for multimodal actuation and transport

Catalytic Janus particles rely on chemical decomposition to self-propel and have displayed enormous potential for targeted drug delivery and cellular penetration. Catalytic propulsion mechanisms are limiting, however, with fuel requirements and specialized fluid properties being necessary to achieve propulsion. We have improved the dynamic propulsion of catalytic Janus particles by functionalizing flagellar filaments to one of their hemispheres. Flagellated Janus particles, torqued by rotating magnetic fields, swim along their rotation axis using the explicit chirality and flexibility of flagella, mimicking flagellar rotation of live bacteria. Depending on the working fluid, flagellated Janus particles can propel using either catalytic or swimming propulsion. We demonstrate experimentally that flagellated Janus particles behave predictably under the two actuation modes and can precisely follow trajectories under closed-loop feedback control. Flagellated Janus particles were demonstrated to swim in both Newtonian and shear-thickening fluids. These are the first Janus particles developed that can be propelled interchangeably between catalytic and flagellar swimming propulsion, allowing two distinct propulsion mechanisms for future use within in vivo operations.     

Curvature-induced dielectrophoresis for continuous separation of particles by charge in spiral microchannels

The separation of particles from a heterogeneous mixture is critical in chemical and biological analyses. Many methods have been developed to separate particles in microfluidic devices. However, the majority of these separations have been limited to be size based and binary. We demonstrate herein a continuous dc electric field driven separation of carboxyl-coated and noncoated 10 μm polystyrene beads by charge in a double-spiral microchannel. This method exploits the inherent electric field gradients formed within the channel turns to manipulate particles by dielectrophoresis and is thus termed curvature-induced dielectrophoresis. The spiral microchannel is also demonstrated to continuously sort noncoated 5 μm beads, noncoated 10 μm beads, and carboxyl-coated 10 μm beads into different collecting wells by charge and size simultaneously. The observed particle separation processes in different situations are all predicted with reasonable agreements by a numerical model. This curvature-induced dielectrophoresis technique eliminates the in-channel microelectrodes and obstacles that are required in traditional electrode- and insulator-based dielectrophoresis devices. It may potentially be used to separate multiple particle targets by intrinsic properties for lab-on-a-chip applications.     

Microfluidic conformal coating of non-spherical magnetic particles

We present the conformal coating of non-spherical magnetic particles in a co-laminar flow microfluidic system. Whereas in the previous reports spherical particles had been coated with thin films that formed spheres around the particles; in this article, we show the coating of non-spherical particles with coating layers that are approximately uniform in thickness. The novelty of our work is that while liquid-liquid interfacial tension tends to minimize the surface area of interfaces—for example, to form spherical droplets that encapsulate spherical particles—in our experiments, the thin film that coats non-spherical particles has a non-minimal interfacial area. We first make bullet-shaped magnetic microparticles using a stop-flow lithography method that was previously demonstrated. We then suspend the bullet-shaped microparticles in an aqueous solution and flow the particle suspension with a co-flow of a non-aqueous mixture. A magnetic field gradient from a permanent magnet pulls the microparticles in the transverse direction to the fluid flow, until the particles reach the interface between the immiscible fluids. We observe that upon crossing the oil-water interface, the microparticles become coated by a thin film of the aqueous fluid. When we increase the two-fluid interfacial tension by reducing surfactant concentration, we observe that the particles become trapped at the interface, and we use this observation to extract an approximate magnetic susceptibility of the manufactured non-spherical microparticles. Finally, using fluorescence imaging, we confirm the uniformity of the thin film coating along the entire curved surface of the bullet-shaped particles. To the best of our knowledge, this is the first demonstration of conformal coating of non-spherical particles using microfluidics.     

Transport and separation of micron sized particles at isotachophoretic transition zones

Conventionally, isotachophoresis (ITP) is used for separation of ionic samples according to their electrophoretic mobilities. We demonstrate that the scope of ITP applications may be extended toward particle concentration and separation. Owing to the distributions of electrolyte concentration and electric field inside a transition zone between two electrolytes, a number of different forces act on a small particle. As far as possible, we provide estimates for the order of magnitude of these forces and analyze their scaling with the particle size and the electric-field strength. Furthermore, we experimentally demonstrate that polymer beads of 5 μm diameter dispersed in a high mobility “leading” electrolyte are picked up and carried along by an ITP transition zone which is formed with a low mobility “trailing” electrolyte. By studying the particle positions and trajectories, we show that impurities in the electrolytes play a significant role in the experiments. Additionally, it is experimentally shown that different types of beads can be separated at an ITP transition zone. In particular, beads of 1 μm diameter are not carried along with the transition zone, in contrast to the 5 μm beads. The presented technique thus adds to the portfolio of electrokinetic transport, concentration, and separation methods in microfluidics.     

Pressure-driven transport of particles through a converging-diverging microchannel

Pressure-driven transport of particles through a symmetric converging-diverging microchannel is studied by solving a coupled nonlinear system, which is composed of the Navier–Stokes and continuity equations using the arbitrary Lagrangian–Eulerian finite-element technique. The predicted particle translation is in good agreement with existing experimental observations. The effects of pressure gradient, particle size, channel geometry, and a particle’s initial location on the particle transport are investigated. The pressure gradient has no effect on the ratio of the translational velocity of particles through a converging-diverging channel to that in the upstream straight channel. Particles are generally accelerated in the converging region and then decelerated in the diverging region, with the maximum translational velocity at the throat. For particles with diameters close to the width of the channel throat, the usual acceleration process is divided into three stages: Acceleration, deceleration, and reacceleration instead of a monotonic acceleration. Moreover, the maximum translational velocity occurs at the end of the first acceleration stage rather than at the throat. Along the centerline of the microchannel, particles do not rotate, and the closer a particle is located near the channel wall, the higher is its rotational velocity. Analysis of the transport of two particles demonstrates the feasibility of using a converging-diverging microchannel for passive (biological and synthetic) particle separation and ordering.     

Microfluidic size separation of cells and particles using a swinging bucket centrifuge

Biomolecular separation is crucial for downstream analysis. Separation technique mainly relies on centrifugal sedimentation. However, minuscule sample volume separation and extraction is difficult with conventional centrifuge. Furthermore, conventional centrifuge requires density gradient centrifugation which is laborious and time-consuming. To overcome this challenge, we present a novel size-selective bioparticles separation microfluidic chip on a swinging bucket minifuge. Size separation is achieved using passive pressure driven centrifugal fluid flows coupled with centrifugal force acting on the particles within the microfluidic chip. By adopting centrifugal microfluidics on a swinging bucket rotor, we achieved over 95% efficiency in separating mixed 20 μm and 2 μm colloidal dispersions from its liquid medium. Furthermore, by manipulating the hydrodynamic resistance, we performed size separation of mixed microbeads, achieving size efficiency of up to 90%. To further validate our device utility, we loaded spiked whole blood with MCF-7 cells into our microfluidic device and subjected it to centrifugal force for a mere duration of 10 s, thereby achieving a separation efficiency of over 75%. Overall, our centrifugal microfluidic device enables extremely rapid and label-free enrichment of different sized cells and particles with high efficiency.     

AC-dielectrophoretic characterization and separation of submicron and micron particles using sidewall AgPDMS electrodes

The recent development of microfluidic “lab on a chip” devices requires the need to continuously separate submicron particles. Here, we present a PDMS microfluidic device with sidewall conducting PDMS (AgPDMS) composite electrodes capable of separating submicron particles in hydrodynamic flow. In particular, the device can service dual functions. First, the AgPDMS composite electrodes embedded in a sidewall of the device channel allow for performing AC-dielectrophoretic (DEP) characterization through direct microscopic observation of particle behavior. Characterization experiments are carried out for numerous parameters including particle size, medium conductivity, and AC field frequency to reveal important dielectrophoresis DEP information in terms of the crossover frequency and positive/negative DEP behavior under specific frequencies. Second, the device offers an advantage that sidewall AgPDMS composite electrodes can produce strong DEP effects throughout the entire channel height, and thus the robustness of the on-chip particle separation is demonstrated for continuous separation in a flowing mixture of 0.5 and 5 μm particles with 100% separation efficiency.     

Microfluidic separation of viruses from blood cells based on intrinsic transport processes

Clinical analysis of acute viral infection in blood requires the separation of viral particles from blood cells, since the cytoplasmic enzyme inhibits the subsequent viral detection. To facilitate this procedure in settings without access to a centrifuge, we present a microfluidic device to continuously purify bionanoparticles from cells based on their different intrinsic movements on the microscale. In this device, a biological sample is layered on top of a physiological buffer, and both fluids are transported horizontally at the same flow rate in a straight channel under laminar flow. While the micron sized particles such as cells sediment to the bottom layer with a predictable terminal velocity, the nanoparticles move vertically by diffusion. As their vertical travel distances have a different dependence on time, the micro- and nanoparticles can preferentially reside in the bottom and top layers respectively after certain residence time, yielding purified viruses. We first performed numerical analysis to predicate the particle separation and then tested the theory using suspensions of synthetic particles and biological samples. The experimental results using dilute synthetic particles closely matched the numerical analysis of a two layer flow system containing different sized particles. Similar purification was achieved using diluted blood spiked with human immunodeficiency virus. However, viral purification in whole blood is compromised due to extensive bioparticle collisions. With the parallelization and automation potential offered by microfluidics, this device has the potential to function as an upstream sample preparation module to continuously provide cell depleted bio-nanoparticles for downstream analysis.     

Isolation of target DNA using synergistic magnetic bead transport and electrokinetic flow

The advent and dissemination of next-generation sequencing (NGS) technologies such as Illumina''s sequencing platforms has brought forth vast reductions in the cost, time, and technical difficulties associated with DNA and RNA sequencing. Despite this trend, the workflow required to generate nucleic acid libraries for sequencing remains time-consuming and laborious. The following research proposes a method for simplifying and streamlining this process by replacing the manual washing steps of the common magnetic bead-based cleanup with a novel microfluidic method by integrating magnetic separation and electrokinetic purification (MSEP). Requiring no pumps, pipette mixing, vortexing, or centrifugation, MSEP relies on selective adsorption of target DNA onto the magnetic beads with subsequent transport of beads through a microchannel undergoing an antiparallel electroosmotic flow. The synergetic flow conditions were optimized using a simple electrohydrodynamic flow model. This work demonstrates that MSEP is as effective in eliminating adapter-dimers from the post-ligation library mix as the manual method while also greatly reducing the hands-on time and amount of pipetting required. Although MSEP has been applied specifically toward NGS library preparation at this time, it has the potential to be adapted and employed for any bead-based separation scheme, namely, solid phase extraction, sequence-specific hybridization, and immunoprecipitation on a microscale.     

Reconfiguring confined magnetic colloids with tunable fluid transport behavior

Collective dynamics of confined colloids are crucial in diverse scenarios such as self-assembly and phase behavior in materials science, microrobot swarms for drug delivery and microfluidic control. Yet, fine-tuning the dynamics of colloids in microscale confined spaces is still a formidable task due to the complexity of the dynamics of colloidal suspension and to the lack of methodology to probe colloids in confinement. Here, we show that the collective dynamics of confined magnetic colloids can be finely tuned by external magnetic fields. In particular, the mechanical properties of the confined colloidal suspension can be probed in real time and this strategy can be also used to tune microscale fluid transport. Our experimental and theoretical investigations reveal that the collective configuration characterized by the colloidal entropy is controlled by the colloidal concentration, confining ratio and external field strength and direction. Indeed, our results show that mechanical properties of the colloidal suspension as well as the transport of the solvent in microfluidic devices can be controlled upon tuning the entropy of the colloidal suspension. Our approach opens new avenues for the design and application of drug delivery, microfluidic logic, dynamic fluid control, chemical reaction and beyond.     

Phaseguide-assisted blood separation microfluidic device for point-of-care applications

We propose a blood separation microfluidic device suitable for point-of-care (POC) applications. By utilizing the high gas permeability of polydimethylsiloxane (PDMS) and phaseguide structures, a simple blood separation device is presented. The device consists of two main parts. A separation chamber with the phaseguide structures, where a sample inlet, a tape-sealed outlet, and a dead-end ring channel are connected, and pneumatic chambers, in which manually operating syringes are plugged. The separation chamber and pneumatic chambers are isolated by a thin PDMS wall. By manually pulling out the plunger of the syringe, a negative pressure is instantaneously generated inside the pneumatic chamber. Due to the gas diffusion from the separation chamber to the neighboring pneumatic chamber through the thin permeable PDMS wall, low pressure can be generated, and then the whole blood at the sample inlets starts to be drawn into the separation chamber and separated through the phaseguide structures. Reversely, after removing the tape at the outlet and manually pushing in the plunger of the syringe, a positive pressure will be created which will cause the air to diffuse back into the ring channel, and therefore allow the separated plasma to be recovered at the outlet on demand. In this paper, we focused on the study of the plasma separation and associated design parameters, such as the PDMS wall thickness, the air permeable overlap area between the separation and pneumatic chambers, and the geometry of the phaseguides. The device required only 2 μl of whole blood but yielding approximately 0.38 μl of separated plasma within 12 min. Without any of the requirements of sophisticated equipment or dilution techniques, we can not only separate the plasma from the whole blood for on-chip analysis but also can push out only the separated plasma to the outlet for off-chip analysis.     

Bond graphs for thermal energy transport and entropy flow

The transport of thermal energy in thermodynamics is described as the product of entropy flow and of the absolute temperature, in analogy to the volume flow and pressure in oil hydraulics and to electric charge flow (= current) and voltage in electronics. Bond graphs are shown to be especially suitable to describe the splitting of applied thermal energy into internal energy and external mechanical work. Transformers and the 0- and 1-junctions of Paynter can illustrate various entropy flow processes, including Carnot engines and heat exchangers. Entropy flow in heat conduction is distinguished from entropy convection, or transport by moving mass, where the entropy/temperature characteristic or equation of state is important. Irreversibilities are represented by impedance transformers reducing temperature and increasing entropy flow but conserving power.     

Three-dimensional printing-based electro-millifluidic devices for fabricating multi-compartment particles

In this work, we demonstrate the use of stereolithographic 3D printing to fabricate millifluidic devices, which are used to engineer particles with multiple compartments. As the 3D design is directly transferred to the actual prototype, this method accommodates 3D millimeter-scaled features that are difficult to achieve by either lithographic-based microfabrication or traditional macrofabrication techniques. We exploit this approach to produce millifluidic networks to deliver multiple fluidic components. By taking advantage of the laminar flow, the fluidic components can form liquid jets with distinct patterns, and each pattern has clear boundaries between the liquid phases. Afterwards, droplets with controlled size are fabricated by spraying the liquid jet in an electric field, and subsequently converted to particles after a solidification step. As a demonstration, we fabricate calcium alginate particles with structures of (1) slice-by-slice multiple lamellae, (2) concentric core-shells, and (3) petals surrounding the particle centers. Furthermore, distinct hybrid particles combining two or more of the above structures are also obtained. These compartmentalized particles impart spatially dependent functionalities and properties. To show their applicability, various ingredients, including fruit juices, drugs, and magnetic nanoparticles are encapsulated in the different compartments as proof-of-concepts for applications, including food, drug delivery, and bioassays. Our 3D printed electro-millifluidic approach represents a convenient and robust method to extend the range of structures of functional particles.     

Microfluidic platform for separation and extraction of plasma from whole blood using dielectrophoresis

Microfluidic based blood plasma extraction is a fundamental necessity that will facilitate many future lab-on-a-chip based point-of-care diagnostic systems. However, current approaches for providing this analyte are hampered by the requirement to provide external pumping or dilution of blood, which result in low effective yield, lower concentration of target constituents, and complicated functionality. This paper presents a capillary-driven, dielectrophoresis-enabled microfluidic system capable of separating and extracting cell-free plasma from small amounts of whole human blood. This process takes place directly on-chip, and without the requirement of dilution, thus eliminating the prerequisite of pre-processed blood samples and external liquid handling systems. The microfluidic chip takes advantage of a capillary pump for driving whole blood through the main channel and a cross flow filtration system for extracting plasma from whole blood. This filter is actively unblocked through negative dielectrophoresis forces, dramatically enhancing the volume of extracted plasma. Experiments using whole human blood yield volumes of around 180 nl of cell-free, undiluted plasma. We believe that implementation of various integrated biosensing techniques into this plasma extraction system could enable multiplexed detection of various biomarkers.     

Laser separation of isotopes

Laser separation of isotopes was first shown to be scientifically practicable at the start of the 1970s, when the isotopes of nitrogen, chlorine, hydrogen, and many other elements were successfully separated. Its most important applications are for uranium and plutonium enrichment. Enriched uranium is used as fuel for nuclear power stations, while enriched plutonium can be used to design more effective nuclear weapons. Ninety-eight per cent of all enriched uranium is now produced in gaseous diffusion installations, the remaining 2 per cent being produced by gaseous centrifugation. Research into laser separation is being conducted in numerous countries and will lead to the production of enriched plutonium on an industrial scale by the end of this decade.