Leslie Y. Yeo

Microfluidic devices for bioapplications.

Harnessing the ability to precisely and reproducibly actuate fluids and manipulate bioparticles such as DNA, cells, and molecules at the microscale, microfluidics is a powerful tool that is currently revolutionizing chemical and biological analysis by replicating laboratory bench-top technology on a miniature chip-scale device, thus allowing assays to be carried out at a fraction of the time and cost while affording portability and field-use capability. Emerging from a decade of research and development in microfluidic technology are a wide range of promising laboratory and consumer biotechnological applications from microscale genetic and proteomic analysis kits, cell culture and manipulation platforms, biosensors, and pathogen detection systems to point-of-care diagnostic devices, high-throughput combinatorial drug screening platforms, schemes for targeted drug delivery and advanced therapeutics, and novel biomaterials synthesis for tissue engineering. The developments associated with these technological advances along with their respective applications to date are reviewed from a broad perspective and possible future directions that could arise from the current state of the art are discussed.

Ultrafast microfluidics using surface acoustic waves

We demonstrate that surface acoustic waves (SAWs), nanometer amplitude Rayleigh waves driven at megahertz order frequencies propagating on the surface of a piezoelectric substrate, offer a powerful method for driving a host of extremely fast microfluidic actuation and microbioparticle manipulation schemes. We show that sessile drops can be translated rapidly on planar substrates or fluid can be pumped through microchannels at 1-10 cms velocities, which are typically one to two orders quicker than that afforded by current microfluidic technologies. Through symmetry-breaking, azimuthal recirculation can be induced within the drop to drive strong inertial microcentrifugation for micromixing and particle concentration or separation. Similar micromixing strategies can be induced in the same microchannel in which fluid is pumped with the SAW by merely changing the SAW frequency to rapidly switch the uniform through-flow into a chaotic oscillatory flow by exploiting superpositioning of the irradiated sound waves from the sidewalls of the microchannel. If the flow is sufficiently quiescent, the nodes of the transverse standing wave that arises across the microchannel also allow for particle aggregation, and hence, sorting on nodal lines. In addition, the SAW also facilitates other microfluidic capabilities. For example, capillary waves excited at the free surface of a sessile drop by the SAW underneath it can be exploited for micronanoparticle collection and sorting at nodal points or lines at low powers. At higher powers, the large accelerations off the substrate surface as the SAW propagates across drives rapid destabilization of the drop free surface giving rise to inertial liquid jets that persist over 1-2 cm in length or atomization of the entire drop to produce 1-10 mum monodispersed aerosol droplets, which can be exploited for ink-jet printing, mass spectrometry interfacing, or pulmonary drug delivery. The atomization of polymerprotein solutions can also be used for the rapid synthesis of 150-200 nm polymerprotein particles or biodegradable polymeric shells in which proteins, peptides, and other therapeutic molecules are encapsulated within for controlled release drug delivery. The atomization of thin films behind a translating drop containing polymer solutions also gives rise to long-range spatial ordering of regular polymer spots whose size and spacing are dependent on the SAW frequency, thus offering a simple and powerful method for polymer patterning without requiring surface treatment or physicalchemical templating.

Emerging Technologies for Next-Generation Point-of-Care Testing

Considerable advances in point-of-care testing (POCT) devices stem from innovations in cellphone (CP)-based technologies, paper-based assays (PBAs), lab-on-a-chip (LOC) platforms, novel assay formats, and strategies for long-term reagent storage. Various commercial CP platforms have emerged to provide cost-effective mobile health care and personalized medicine. Such assay formats, as well as low-cost PBAs and LOC-based assays, are paving the way to robust, automated, simplified, and cost-effective POCT. Strategies have also been devised to stabilize reagent storage and usage at ambient temperature. Nevertheless, successful commercialization and widespread implementation of such clinically viable technologies remain subject to several challenges and pending issues.

Particle concentration and mixing in microdrops driven by focused surface acoustic waves

We report the use of focused surface acoustic waves (SAWs) generated on 128° rotated Y-cut X-propagating lithium niobate (LiNbO3) for enhancing the actuation of fluids and the manipulation of particle suspensions at microscale dimensions. In particular, we demonstrate increased efficiency and speed in carrying out particle concentration/separation and in generating intense micromixing in microliter drops within which acoustic streaming is induced due to the focused SAW beneath the drop. Concentric circular and elliptical single-phase unidirectional transducers (SPUDTs) were used to focus the SAW. We benchmark our results against a straight SPUDT which does not cause focusing of the SAW. Due to the increased wave intensity and asymmetry of the wave, we found both circular and elliptical SPUDTs concentrate particles in under 1 s, which is one order of magnitude faster than the straight SPUDT and several orders of magnitude faster than conventional microscale devices. The concentric circular SPUDT was found ...

Fabrication of microfluidic devices using polydimethylsiloxane

Polydimethylsiloxane (PDMS) is nearly ubiquitous in microfluidic devices, being easy to work with, economical, and transparent. A detailed protocol is provided here for using PDMS in the fabrication of microfluidic devices to aid those interested in using the material in their work, with information on the many potential ways the material may be used for novel devices.

Interfacial destabilization and atomization driven by surface acoustic waves

Surface acoustic wave atomization is a rapid means for generating micron and submicron aerosol droplets. Little, however, is understood about the mechanisms by which these droplets form due to the complex hydrodynamic processes that occur across widely varying length and time scales. Through experiments, scaling theory, and simple numerical modeling, we elucidate the interfacial destabilization mechanisms that lead to droplet formation. Using a millimeter-order fluid drop exposed to surface acoustic waves as it sits atop a single-crystal lithium niobate piezoelectric substrate, large aerosol droplets on the length scale of the parent drop dimension are ejected through a whipping and pinch-off phenomenon, which occurs at the asymmetrically formed crest of the drop due to leakage of acoustic radiation at the Rayleigh angle. Smaller micron order droplets, on the other hand, are formed due to the axisymmetric breakup of cylindrical liquid jets that are ejected as a consequence of interfacial destabilization. ...

Electrospinning carbon nanotube polymer composite nanofibers

The unique and exceptional physical properties of carbon nanotubes have inspired their use as a filler within a polymeric matrix to produce carbon nanotube polymer composites with enhanced mechanical, thermal and electrical properties. A powerful method of synthesising nanofibers comprising these polymer composites is electrospinning, which utilises an applied electric stress to draw out a thin nanometer-dimension fiber from the tip of a sharp conical meniscus. The focussing of the flow due to converging streamlines at the cone vertex then ensures alignment of the carbon nanotubes along the fiber axis, thus enabling the anisotropic properties of the nanotubes to be exploited. We consider the work that has been carried out to date on various aspects encompassing preprocessing, synthesis and characterisation of these electrospun polymer composite nanofibers as well as the governing mechanisms and associated properties of such fibers. Particular attention is also dedicated to the theoretical modelling of these fiber systems, in particular to the electrohydrodynamic modelling of electrospinning polymer jets.

Microparticle collection and concentration via a miniature surface acoustic wave device

The ability to detect microbes, pollens and other microparticles is a critically important ability given the increasing risk of bioterrorism and emergence of antibiotic-resistant bacteria. The efficient collection of microparticles via a liquid water droplet moved by a surface acoustic wave (SAW) device is demonstrated in this study. A fluidic track patterned on the SAW device directs the water droplets motion, and fluid streaming induced inside the droplet as it moves along is a key advantage over other particle collection approaches, because it enhances microparticle collection and concentration. Test particles consisted of 2, 10, 12 and 45 microm diameter monodisperse polystyrene and melamine microparticles; pollen from the Populus deltoides, Kochia scoparia, Secale cerale, and Broussonetia papyrifera (Paper Mulberry) species; and Escherichia coli bacteria. The collection efficiency for the synthetic particles ranged from 16 to 55%, depending on the particle size and surface tension of the collection fluid. The method was more effective in collecting pollen and the bacteria with an efficiency of 45-68% and 61.0-69.8%, respectively. Pollen collection was strongly influenced by its diameter, size, and surface geometry in a manner contrary to initial expectations. Reasons for the consistent yet unexpected collection results include leaky SAW pressure boundary segregation and shear-induced concentration of larger particles, and the subtle effects of wetting interactions. These results demonstrate a new method for collecting microparticles requiring only about one second per run, and illustrate the inadequacy of using synthetic microparticles as a substitute for their biological counterparts in experiments studying particle collection and behavior.

Paper-based microfluidic surface acoustic wave sample delivery and ionization source for rapid and sensitive ambient mass spectrometry

A surface acoustic wave-based sample delivery and ionization method that requires minimal to no sample pretreatment and that can operate under ambient conditions is described. This miniaturized technology enables real-time, rapid, and high-throughput analysis of trace compounds in complex mixtures, especially high ionic strength and viscous samples that can be challenging for conventional ionization techniques such as electrospray ionization. This technique takes advantage of high order surface acoustic wave (SAW) vibrations that both manipulate small volumes of liquid mixtures containing trace analyte compounds and seamlessly transfers analytes from the liquid sample into gas phase ions for mass spectrometry (MS) analysis. Drugs in human whole blood and plasma and heavy metals in tap water have been successfully detected at nanomolar concentrations by coupling a SAW atomization and ionization device with an inexpensive, paper-based sample delivery system and mass spectrometer. The miniaturized SAW ionization unit requires only a modest operating power of 3 to 4 W and, therefore, provides a viable and efficient ionization platform for the real-time analysis of a wide range of compounds.

Rapid fluid flow and mixing induced in microchannels using surface acoustic waves

Very-high-frequency surface acoustic waves, generated and transmitted along single-crystal lithium niobate, are used to drive homogeneous aqueous suspensions of polystyrene nanoparticles along microchannels. At a few hundred milliwatts, uniform and mixing flows with speeds of up to 10 mm/s were obtained in centimetres-long rectangular channels with cross-sectional dimensions of tens to a few hundreds of microns. A transition from uniform to mixing flow occurs as the channel width grows beyond the wavelength of sound in the fluid at the chosen excitation frequency. At far lower input powers, the suspension agglomerates into equally spaced, serpentine lines coincident with nodal lines in the acoustic pressure field. We expose the physics underlying these disparate phenomena with experimental results aided by numerical models.