Three-dimensional continuous particle focusing in a microfluidic channel via standing surface acoustic waves (SSAW)

Three-dimensional (3D) continuous microparticle focusing has been achieved in a single-layer polydimethylsiloxane (PDMS) microfluidic channel using a standing surface acoustic wave (SSAW). The SSAW was generated by the interference of two identical surface acoustic waves (SAWs) created by two parallel interdigital transducers (IDTs) on a piezoelectric substrate with a microchannel precisely bonded between them. To understand the working principle of the SSAW-based 3D focusing and investigate the position of the focal point, we computed longitudinal waves, generated by the SAWs and radiated into the fluid media from opposite sides of the microchannel, and the resultant pressure and velocity fields due to the interference and reflection of the longitudinal waves. Simulation results predict the existence of a focusing point which is in good agreement with our experimental observations. Compared with other 3D focusing techniques, this method is non-invasive, robust, energy-efficient, easy to implement, and applicable to nearly all types of microparticles.     

UV epoxy bonding for enhanced SAW transmission and microscale acoustofluidic integration

Surface acoustic waves (SAWs) are appealing as a means to manipulate fluids within lab-on-a-chip systems. However, current acoustofluidic devices almost universally rely on elastomeric materials, especially PDMS, that are inherently ill-suited for conveyance of elastic energy due to their strong attenuation properties. Here, we explore the use of a low-viscosity UV epoxy resin for room temperature bonding of lithium niobate (LiNbO(3)), the most widely used anisotropic piezoelectric substrate used in the generation of SAWs, to standard micromachined superstrates such as Pyrex? and silicon. The bonding methodology is straightforward and allows for reliable production of sub-micron bonds that are capable of enduring the high surface strains and accelerations needed for conveyance of SAWs. Devices prepared with this approach display as much as two orders of magnitude, or 20 dB, improvement in SAW transmission compared to those fabricated using the standard PDMS elastomer. This enhancement enables a broad range of applications in acoustofluidics that are consistent with the low power requirements of portable battery-driven circuits and the development of genuinely portable lab-on-a-chip devices. The method is exemplified in the fabrication of a closed-loop bidirectional SAW pumping concept with applications in micro-scale flow control, and represents the first demonstration of closed channel SAW pumping in a bonded glass/LiNbO(3) device.     

Recent advances in particle and droplet manipulation for lab-on-a-chip devices based on surface acoustic waves

Manipulation of microscale particles and fluid liquid droplets is an important task for lab-on-a-chip devices for numerous biological researches and applications, such as cell detection and tissue engineering. Particle manipulation techniques based on surface acoustic waves (SAWs) appear effective for lab-on-a-chip devices because they are non-invasive, compatible with soft lithography micromachining, have high energy density, and work for nearly any type of microscale particles. Here we review the most recent research and development of the past two years in SAW based particle and liquid droplet manipulation for lab-on-a-chip devices including particle focusing and separation, particle alignment and patterning, particle directing, and liquid droplet delivery.     

Nebulisation on a disposable array structured with phononic lattices

We demonstrate the use of a phononic crystal to enable the nebulisation of liquid droplets from low-cost disposable arrays, using surface acoustic waves (SAW). The SAWs were generated using interdigitated transducers (IDT) on a piezoelectric surface (LiNbO(3)) and the acoustic waves were coupled into a disposable phononic crystal structure, referred to as a superstrate. Using its excellent reflecting properties, the phononic structures confined the acoustic field within the superstrate, resulting in the concentration of the acoustic energy, in a manner controllable by the excitation frequency. We show that this capability mitigates against coupling losses incurred by the use of a disposable superstrate, greatly reducing the time needed to nebulise a drop of water with respect to an unstructured superstrate for a given power. We also demonstrate that by changing the excitation frequency, it is possible to change the spatial position at which the acoustic energy is concentrated, providing a means to specifically nebulise drops across an array. These results open up a promising future for the use of phonofluidics in high-throughput sample handling applications, such as drug delivery or the "soft" transfer of samples to a mass spectrometer in the field of proteomics.     

Acoustofluidics 2: perturbation theory and ultrasound resonance modes

In the second part of the thematic tutorial series "Acoustofluidics--exploiting ultrasonic standing waves forces and acoustic streaming in microfluidic systems for cell and particle manipulation", we develop the perturbation theory of the acoustic field in fluids and apply the result in a study of acoustic resonance modes in microfluidic channels.     

Acoustofluidic platforms for particle manipulation

There is an increasing interest in acoustics for microfluidic applications. This field, commonly known as acoustofluidics involves the interaction of ultrasonic standing waves with fluids and dispersed microparticles. The combination of microfluidics and the so-called acoustic standing waves (ASWs) led to the development of integrated systems for contact-less on-chip cell and particle manipulation where it is possible to move and spatially localize these particles based on the different acoustophysical properties. While it was initially suggested that the acoustic forces could be harmful to the cells and could impact cell viability, proliferation, or function via phenotypic or even genotypic changes, further studies disproved such claims. This review is summarizing some interesting applications of acoustofluidics in the manipulations of biomaterials, such as cells or subcellular vesicles, in works published mainly within the last 5 years.     

Acoustofluidics 1: Governing equations in microfluidics

In Part 1 of the thematic tutorial series "Acoustofluidics--exploiting ultrasonic standing waves forces and acoustic streaming in microfluidic systems for cell and particle manipulation", we establish the governing equations in microfluidics. Examples of basic flow solutions are presented, and equivalent circuit modeling for determining flow rates in microfluidic networks is introduced.     

Surface vibration induced spatial ordering of periodic polymer patterns on a substrate

We demonstrate the possibility of producing regular, long-range, spatially ordered polymer patterns without requiring the use of physical or chemical templating through the interfacial destabilization of a thin polymer film driven by surface acoustic waves (SAWs). The periodicity and spot size of the pattern are observed to be dependent on a single parameter, that is, the SAW frequency (or wavelength), therefore offering a rapid, simple, yet novel method for self-organized regular spatial polymer pattern formation that is far more tunable than conventional polymer patterning procedures.     

Acoustofluidics 7: The acoustic radiation force on small particles

In this paper, Part 7 of the thematic tutorial series "Acoustofluidics-exploiting ultrasonic standing waves, forces and acoustic streaming in microfluidic systems for cell and particle manipulation", we present the theory of the acoustic radiation force; a second-order, time-averaged effect responsible for the acoustophoretic motion of suspended, micrometre-sized particles in an ultrasound field.     

Acoustofluidics 10: scaling laws in acoustophoresis

In Part 10 of the thematic tutorial series "Acoustofluidics-exploiting ultrasonic standing waves forces and acoustic streaming in microfluidic systems for cell and particle manipulation", we present and analyze a number of scaling laws relevant for microsystem acoustophoresis. Such laws are useful both in understanding, designing, and analyzing acoustofluidic devices.     

Acoustic resonances in microfluidic chips: full-image micro-PIV experiments and numerical simulations

We show that full-image micro-PIV analysis in combination with images of transient particle motion is a powerful tool for experimental studies of acoustic radiation forces and acoustic streaming in microfluidic chambers under piezo-actuation in the MHz range. The measured steady-state motion of both large 5 microm and small 1 microm particles can be understood in terms of the acoustic eigenmodes or standing ultra-sound waves in the given experimental microsystems. This interpretation is supported by numerical solutions of the corresponding acoustic wave equation.     

Microfluidic waves

The propagation of pressure waves in fluidic channels with elastic covers is discussed in view of applications to flow control in microfluidic devices. A theory is presented which describes pressure waves in the fluid that are coupled to bending waves in the elastic cover. At low frequencies, the lateral bending of the cover dominates over longitudinal bending, leading to propagating, non-dispersive longitudinal pressure waves in the channel. The theory addresses effects due to both the finite viscosity and compressibility of the fluid. The coupled waves propagate without dispersion, as long as the wave length is larger than the channel width. It is shown that in channels of typical microfluidic dimensions, wave velocities in the range of a few 10 m s(-1) result if the channels are covered by films of a compliant material such as PDMS. The application of this principle to design microfluidic band pass filters based on standing waves is discussed. Characteristic frequencies in the range of a few kHz are readily achieved with quality factors above 30.     

DNA concentration modulation on supported lipid bilayers switched by surface acoustic waves

Spatially addressable arrays of molecules embedded in or anchored to supported lipid bilayers are important for on-chip screening and binding assays; however, methods to sort or accumulate components in a fluid membrane on demand are still limited. Here we apply in-plane surface acoustic shear waves (SAWs) to laterally accumulate double-stranded DNA segments electrostatically bound to a cationic supported lipid bilayer. The fluorescently labeled DNA segments are found to segregate into stripe patterns with a spatial frequency corresponding to the periodicity of the standing SAW wave (~10 μm). The DNA molecules are accumulated 10-fold in the regions of SAW antinodes. The superposition of two orthogonal sets of SAW sources creates checkerboard like arrays of DNA demonstrating the potential to generate arrayed fields dynamically. The pattern relaxation time of 0.58 s, which is independent of the segment length, indicates a sorting and relaxation mechanism dominated by lipid diffusion rather than DNA self-diffusion.     

Microfluidics for Miniaturized Laboratories on a Chip

Microfluidic systems promise solutions for high throughput and highly specific analysis for biology, medicine and chemistry while consuming only tiny amounts of reactants and space. On these lab‐on‐a‐chip platforms often multiple physical effects such as electrokinetic, acoustic or capillary phenomena from various disciplines are exploited to gain the optimal functionality. The fluidics on these small length scales differ significantly from our experience of the macroscopic world. In this Review we survey some of the approaches and techniques to handle minute amounts of fluid volumes in microfluidic systems with special focus on surface acoustic wave driven fluidics, a technique developed in our laboratory. Here, we outline the basics of this technique and demonstrate, for example, how acoustic mixing and fluid actuation is realized. Furthermore we discuss the interplay of different physical effects in microfluidic systems and illustrate their usefulness for several applications.     

Uniform mixing in paper-based microfluidic systems using surface acoustic waves

Paper-based microfluidics has recently received considerable interest due to their ease and low cost, making them extremely attractive as point-of-care diagnostic devices. The incorporation of basic fluid actuation and manipulation schemes on paper substrates, however, afford the possibility to extend the functionality of this simple technology to a much wider range of typical lab-on-a-chip operations, given its considerable advantages in terms of cost, size and integrability over conventional microfluidic substrates. We present a convective actuation mechanism in a simple paper-based microfluidic device using surface acoustic waves to drive mixing. Employing a Y-channel structure patterned onto paper, the mixing induced by the 30 MHz acoustic waves is shown to be consistent and rapid, overcoming several limitations associated with its capillary-driven passive mixing counterpart wherein irreproducibilities and nonuniformities are often encountered in the mixing along the channel--capillary-driven passive mixing offers only poor control, is strongly dependent on the paper's texture and fibre alignment, and permits backflow, all due to the scale of the fibres being significant in comparison to the length scales of the features in a microfluidic system. Using a novel hue-based colourimetric technique, the mixing speed and efficiency is compared between the two methods, and used to assess the effects of changing the input power, channel tortuousity and fibre/flow alignment for the acoustically-driven mixing. The hue-based technique offers several advantages over grayscale pixel intensity analysis techniques in facilitating quantification without limitations on the colour contrast of the samples, and can be used, for example, for quantification in on-chip immunochromatographic assays.     

Chip integrated strategies for acoustic separation and manipulation of cells and particles

Acoustic standing wave technology combined with microtechnology opens up new areas for the development of advanced particle and cell separating microfluidic systems. This tutorial review outlines the fundamental work performed on continuous flow acoustic standing wave separation of particles in macro scale systems. The transition to the microchip format is further surveyed, where both fabrication and design issues are discussed. The acoustic technology offers attractive features, such as reasonable throughput and ability to separate particles in a size domain of about tenths of micrometers to tens of micrometers. Examples of different particle separation modes enabled in microfluidic chips, utilizing standing wave technology, are described along a discussion of several potential applications in life science research and in the medical clinic. Chip integrated acoustic standing wave separation technology is still in its infancy and it can be anticipated that new laboratory standards very well may emerge from the current research.     

An Acoustically Driven Microliter Flow Chamber on a Chip (μFCC) for Cell–Cell and Cell–Surface Interaction Studies

A novel method for pumping very small volumes of liquid by using surface acoustic waves is employed to create a microfluidic flow chamber on a chip. It holds a volume of only a few μl and its planar design provides complete architectural freedom. This allows for the reconstruction of even complex flow scenarios (e.g. curvatures, bifurcations and stenosis). Addition of polymer walls to the planar fluidic track enables cell culturing on the chip surface and the investigation of cell–cell adhesion dynamics under flow. We demonstrate the flexibility of the system for application in many areas of microfluidic investigations including blood clotting phenomena under various flow conditions and the investigation of different stages of cell adhesion.     

Acoustofluidics 16: acoustics streaming near liquid-gas interfaces: drops and bubbles

In this sixteenth part of the series on "Acoustofluidics-exploiting ultrasonic standing waves forces and acoustic streaming in microfluidic systems for cell and particle manipulation," we continue our discussion on the analytical aspects of the streaming phenomenon. In particular, the use of the singular perturbation technique for this class of problems is delineated with a set of examples where fluid-fluid interaction takes place. In this category, we focus on drops and bubbles, and deal specifically with the effect of interfacial mobility on the streaming flow.     

Polydimethylsiloxane-LiNbO3 surface acoustic wave micropump devices for fluid control into microchannels

This paper presents prototypical microfluidic devices made by hybrid microchannels based on piezoelectric LiNbO(3) and polydimethylsiloxane. This system enables withdrawing micropumping by acoustic radiation in microchannels. The withdrawing configuration, integrated on chip, is here quantitatively investigated for the first time, and found to be related to the formation and coalescence dynamics of droplets within the microchannel, primed by surface acoustic waves. The growth dynamics of droplets is governed by the water diffusion on LiNbO(3), determining the advancement of the fluid front. Observed velocities are up to 2.6 mm s(-1) for 30 dBm signals applied to the interdigital transducer, corresponding to tens of nl s(-1), and the micropumping dynamics is described by a model taking into account an acoustic power exponentially decaying upon travelling along the microchannel. This straighforward and flexible micropumping approach is particularly promising for the withdrawing of liquids in lab-on-chip devices performing cycling transport of fluids and biochemical reactions.