There is a recognized and growing need for rapid and efficient cell assays, where the size of microfluidic devices lend themselves to the manipulation of cellular populations down to the single cell level. An exceptional way to analyze cells independently is to encapsulate them within aqueous droplets surrounded by an immiscible fluid, so that reagents and reaction products are contained within a controlled microenvironment. Most cell encapsulation work has focused on the development and use of passive methods, where droplets are produced continuously at high rates by pumping fluids from external pressure-driven reservoirs through defined microfluidic geometries. With limited exceptions, the number of cells encapsulated per droplet in these systems is dictated by Poisson statistics, reducing the proportion of droplets that contain the desired number of cells and thus the effective rate at which single cells can be encapsulated. Nevertheless, a number of recently developed actively-controlled droplet production methods present an alternative route to the production of droplets at similar rates and with the potential to improve the efficiency of single-cell encapsulation. In this critical review, we examine both passive and active methods for droplet production and explore how these can be used to deterministically and non-deterministically encapsulate cells.

The effects of electroosmotic flow (EOF) on the ionic current rectification (ICR) phenomenon in conical nanopores are studied comprehensively with use of a continuum model, composed of Nernst−Planck equations for the ionic concentrations, the Poisson equation for the electric potential, and Navier−Stokes equations for the flow field. It is found that the preferential current direction of a negatively charged nanopore is toward the base (tip) under a relatively high (low) κR t, the ratio of the tip radius size to the Debye length. The direction also changes with the charge polarity of the nanopore. The EOF effect on the ionic current rectification ratio in a conical nanopore becomes noticeable at an intermediate κR t and surface charge density of the nanopore, meanwhile increasing significantly with the applied voltage.

The ability to manipulate and sort droplets is a fundamental issue in droplet-based microfluidics. Various lab-on-a-chip applications can only be realized if droplets are systematically categorized and sorted. These micron-sized droplets act as ideal reactors which compartmentalize different biological and chemical reagents. Array processing of these droplets hinges on the competence of the sorting and integration into the fluidic system. Recent technological advances only allow droplets to be actively sorted at the rate of kilohertz or less. In this review, we present state-of-the-art technologies which are implemented to efficiently sort droplets. We classify the concepts according to the type of energy implemented into the system. We also discuss various key issues and provide insights into various systems.

Field effect regulation of DNA nanoparticle translocation through a nanopore using a gate electrode is investigated using a continuum model, composed of the coupled Poisson-Nernst-Planck equations for the ionic mass transport and the Navier-Stokes equations for the hydrodynamic field. The field effect regulation of the DNA translocation relies on the induced electroosmotic flow (EOF) and the particle-nanopore electrostatic interaction. When the electrical double layers (EDLs) formed adjacent to the DNA nanoparticle and the nanopore wall are overlapped, the particle-nanopore electrostatic interaction could dominate over the EOF effect, which enables the DNA trapping inside the nanopore when the applied electric field is relatively low. However, the particle-nanopore electrostatic interaction becomes negligible if the EDLs are not overlapped. When the applied electric field is relatively high, a negative gate potential can slow down the DNA translocation by an order of magnitude, compared to a floating gate electrode. The field effect control offers a more flexible and electrically compatible approach to regulate the DNA translocation through a nanopore for DNA sequencing.

Despite increasing demand in the manipulation of nanoscale objects for next generation biological and industrial processes, there is a lack of methods for reliable separation, concentration and purification of nanoscale objects. Acoustic methods have proven their utility in contactless manipulation of microscale objects mainly relying on the acoustic radiation effect, though the influence of acoustic streaming has typically prevented manipulation at smaller length scales. In this work, however, we explicitly take advantage of the strong acoustic streaming in the vicinity of a highly focused, high frequency surface acoustic wave (SAW) beam emanating from a series of focused 6 μm substrate wavelength interdigital transducers patterned on a piezoelectric lithium niobate substrate and actuated with a 633 MHz sinusoidal signal. This streaming field serves to focus fluid streamlines such that incoming particles interact with the acoustic field similarly regardless of their initial starting positions, and results in particle displacements that would not be possible with a travelling acoustic wave force alone. This streaming-induced manipulation of nanoscale particles is maximized with the formation of micro-vortices that extend the width of the microfluidic channel even with the imposition of a lateral flow, occurring when the streaming-induced flow velocities are an order of magnitude larger than the lateral one. We make use of this acoustic streaming to demonstrate the continuous and differential focusing of 100 nm, 300 nm and 500 nm particles.

A microfluidic device was developed to separate heterogeneous particle or cell mixtures in a continuous flow using acoustophoresis. In this device, two identical surface acoustic waves (SAWs) generated by interdigital transducers (IDTs) propagated toward a microchannel, which accordingly built up a standing surface acoustic wave (SSAW) field across the channel. A numerical model, coupling a piezoelectric effect in the solid substrate and acoustic pressure in the fluid, was developed to provide a better understanding of SSAW-based particle manipulation. It was found that the pressure nodes across the channel were individual planes perpendicular to the solid substrate. In the separation experiments, two side sheath flows hydrodynamically focused the injected particle or cell mixtures into a very narrow stream along the centerline. Particles flowing through the SSAW field experienced an acoustic radiation force that highly depends on the particle properties. As a result, dissimilar particles or cells were laterally attracted toward the pressure nodes at different magnitudes, and were eventually switched to different outlets. Two types of fluorescent microspheres with different sizes were successfully separated using the developed device. In addition, Escherichia coli bacteria premixed in peripheral blood mononuclear cells (PBMCs) were also efficiently isolated using the SSAW-base separation technique. Flow cytometric analysis on the collected samples found that the purity of separated E. coli bacteria was 95.65%.

Concentration and separation of particles and biological specimens are fundamental functions of micro/nanofluidic systems. Acoustic streaming is an effective and biocompatible way to create rapid microscale fluid motion and induce particle capture, though the >100 MHz frequencies required to directly generate acoustic body forces on the microscale have traditionally been difficult to generate and localize in a way that is amenable to efficient generation of streaming. Moreover, acoustic, hydrodynamic, and electrical forces as typically applied have difficulty manipulating specimens in the submicrometer regime. In this work, we introduce highly focused traveling surface acoustic waves (SAW) at high frequencies between 193 and 636 MHz for efficient and highly localized production of acoustic streaming vortices on microfluidic length scales. Concentration occurs via a novel mechanism, whereby the combined acoustic radiation and streaming field results in size-selective aggregation in fluid streamlines in the vicinity of a high-amplitude acoustic beam, as opposed to previous acoustic radiation induced particle concentration where objects typically migrate toward minimum pressure locations. Though the acoustic streaming is induced by a traveling wave, we are able to manipulate particles an order of magnitude smaller than possible using the traveling wave force alone. We experimentally and theoretically examine the range of particle sizes that can be captured in fluid streamlines using this technique, with rapid particle concentration demonstrated down to 300 nm diameters. We also demonstrate that locations of trapping and concentration are size-dependent, which is attributed to the combined effects of the acoustic streaming and acoustic forces.

The extraordinary properties of layered graphene and its successful applications in electronics, sensors, and energy devices have inspired and renewed interest in other two-dimensional (2D) layered materials. Particularly, a semiconducting analogue of graphene, molybdenum disulfide (MoS2), has attracted huge attention in the last few years. With efforts in exfoliation and synthetic techniques, atomically thin films of MoS2 (single- and few-layer) have been recently prepared and characterized. 2D MoS2 nanosheets have properties that are distinct and complementary to those of graphene, making it more appealing for various applications. Unlike graphene with an indirect bandgap, the direct bandgap of single-layer MoS2 results in better semiconductor behavior as well as photoluminescence, suggesting its great suitability for electronic and optoelectronic applications. Compared to their applications in energy storage and optoelectronic devices, the use of MoS2 nanosheets as a sensing platform, especially for biosensing, is still largely unexplored. Here, we present a review of the preparation of 2D atomically thin MoS2 nanosheets, with an emphasis on their use in various sensing applications.