Lorentz Center - Acoustic Waves for the Control of Microfluidics Flows from 23 Apr 2012 through 27 Apr 2012
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    Acoustic Waves for the Control of Microfluidics Flows
    from 23 Apr 2012 through 27 Apr 2012

 

Abstracts

 

Per Augustsson

Driving cells or microbeads across fluid interfaces in continuous flow acoustophoresis – Experimental conciderations

Joint work with Thomas Laurell, Lund University, Sweden

 

Acoustic standing wave technology combined with ligand complexed microbeads offers means for affinity specific selection of target analytes from complex samples. When realized in a microfluidic format we can capitalize on laminar flow and acoustic forces that can drive cells or microbeads across fluid interfaces. Given this, we have the ability to perform carrier fluid (suspending medium) exchange operations in continuous flow in microfluidic chips solely based on acoustofluidic properties.

A key issue here is to ensure that a minimum of the original carrier fluid follows the cells/particles across the fluid interface. If such systems are designed properly, simple processing protocols can be realized that may outperform macroscale magnetic bead-based sample extraction or centrifugation steps, and which can also be straightforwardly integrated with downstream analytical instrumentation.

We outline some basic fluidic configurations for acoustophoresis based sample decomplexing and details the different system parameters that will impact the outcome of an acoustophoresis based affinity extraction experiment or a cell medium exchange step. Examples are given of both targeted extraction of microbes and selective elusion of molecular species.

 

 

Rune Barnkob

Theoretical and experimental analysis of acoustic energy densities and acoustophoretic particle velocities in microchannels supporting ultrasound resonances

Acoustofluidics and ultrasound handling of particle suspensions is a research field in rapid growth both concerning physical characterization and optimization of the devices as well as biological applications. To further advance this mainly application-driven research field, there is a need for improved experimental techniques and theoretical analyses of the acoustic energy density in ultrasound resonances and of the associated acoustophoretic velocities of suspended particles.

For water-filled microchannels supporting ultrasound resonances, we present three methods based on microparticle acoustophoresis to determine the acoustic energy density in situ: single-particle tracking [1], particle image velocimetry (PIV) [2], and trans-illumination light microscopy [3]. We show how the acoustic energy densities can be used to evaluate the performance of acoustic microchips in terms of resonance strength and Q factor.

We combine theoretical modeling with high-resolution measurements, obtained by our newly-developed automated and temperature-controlled micro-PIV system, to unravel the complex nature of the acoustic resonances underlying the acoustophoretic particle motion in the entire microchannel. Using the same system, we measure the acoustophoretic particle velocity as function of the particle size to estimate the critical particle size for the crossover from radiation-force-dominated motion for large particles to the acoustic-streaming-dominated motion for small particles. Finally, we show how to use the high-resolution measurements of the acoustophoretic particle velocities to determine fundamental acoustophysical properties such as acoustophoretic mobility of different particle and cell species in various buffer media.

[1] R. Barnkob, P. Augustsson, T. Laurell and H. Bruus, Lab Chip , 563-570 (2010). [2] P. Augustsson, R. Barnkob, S. T. Wereley, H. Bruus and T. Laurell, Lab Chip , 4152-4164 (2011). [3] R. Barnkob, I. Iranmanesh, M. Wiklund, and H. Bruus, Lab Chip doi:10.1039/C2LC40120G (2012).

 

 

Almudena Cabańas Sorando

Influence of acoustic streaming on the formation and destruction of particles aggregates

Joint work with Itziar González+ and Jeremy J. Hawkes*
*ManchesterInterdisciplinary Biocentre, The University of Manchester, 131 Princess Street. Manchester M1 7DN, UK +Instituto de Acústica, CSIC, Calle Serrano 144, 28006 Madrid, Spain

 

Latex particles suspended in water move to pressure nodes in a standing wave due to the acoustic radiation force. A current problem is the interaction between direct acoustic forces on particles and viscous drag forces from acoustic streaming.

Our objective is to identify the influence of acoustic streaming on the formation and destruction of particles aggregates in nodal planes.

We show here that it is possible to identify discrete aggregation patterns depending on the dimensions of the particles. The chamber for these observations was a 50.00 mm long glass capillary with rectangular cross – section (inside dimension: h~4.00 mm and d~0.34 mm), held in a horizontal position with the transducer in one side. The size of the particles used in our experiments was approximately 24 μm, 10 μm and 1 μm diameter.

On the contrary to the radiation force, the theory predicts more intense effects on smaller particles due to the Rayleigh streaming drag forces:  more intense on 1 μm-sized particle suspensions than on the 10 μm-sized, and much more on the 24 μm-sized particles, where the radiation force drift motion dominates.

The theory predicts higher streaming drag forces on smaller particles than the radiation force (~ 1μm diameter) the influence of streaming acting on them is bigger than the acoustic radiation force. When the ultrasound was applied in the frequency range 2 – 3 MHz the experiments showed: for 24μm (ideal behaviour), the particles moved towards the nodal planes (lines along the capillary) due to the acoustic radiation force and afterwards the lateral radiation force made them clumped within the nodal planes; for 10μm, as it occurred with 24 μm particles, the particles moved towards the nodal lines due to the acoustic radiation force and then they were clumped within the nodal planes, however after a while a distortion was noticed, such a effect seems to correspond to a breaking down of the standing wave just before the lines fanned out; for 1μm particles the influence of streaming acting on them is bigger than the acoustic radiation force however, after a long time (5 – 10 min) comparing to the time needed for 24μm and 10μm, finally it is noticed they were collected in the nodal lines. 

 

 

Paul Charette

Surface acoustic waves for improved sensitivity and mixing in miniaturized diagnostic microfluidic devices

 

Micro/nanofabricated biosensors, also known as lab-on-chip devices and micro-total-analysis systems (µTAS), require ever higher degrees of measurement precision and miniaturization. Photonics devices are a prime choice for on-chip integrated detection and interface technology components. In this talk, we will give an overview of on-chip photonics technologies in miniaturized diagnostic devices and focus on surface-based biosensing systems where two particularly difficult challenges can be:

(1) How to overcome sensitivity limitations due to non-specific adsorption. Non-specific adsorption is the weak binding of molecules other than the target analyte to the sensing surface. The non-specifically adsorbed molecules can completely obscure the surface-bound ligands, inhibiting any contact with the target analyte.

(2) How to perform efficient mixing at the microfluidic level for homogeneous and timely analysis. To minimize the quantity of reagents, modern biosensing systems use microfluidics. Because the fluid flow at such small scales is typically laminar, the efficient mixing of reagents is a real challenge in microfluidics.

We propose to use surface acoustic waves to provide active microfluidic mixing in the fluid above the sensor to overcome those two challenges.

 

 

Lawrence Crum

Therapeutic Ultrasound: A potential Revolution in Health Care

Joint work with: Michael Bailey, Tanya Khokhlova, Vera Khokhlova, Wayne Kreider, Julianna Simon, Yak-Nam Wang, and Oleg Sapozhnikov, Center for Industrial and Medical Ultrasound, University of Washington, Seattle, WA 98105 USA

 

The use of ultrasound in medicine is now quite commonplace, especially with the recent introduction of small, portable and relatively inexpensive, hand-held diagnostic imaging devices.  Moreover, ultrasound has expanded beyond the imaging realm, with methods and applications extending to novel therapeutic and surgical uses. These applications broadly include: Tissue ablation, acoustocautery, lipoplasty, site-specific and ultrasound mediated drug activity, extracorporeal lithotripsy, gene therapy and the enhancement of natural physiological functions such as wound healing and tissue regeneration. A particularly attractive aspect of this technology is that diagnostic and therapeutic systems can be integrated to produce totally non-invasive, image-guided therapy. Because therapeutic applications typically require ultrasound to be used at high intensities, these applications require a knowledge of nonlinear acoustics, which often plays an essential role in the physical mechanisms that give rise to a particular therapeutic effect.  In this lecture, some specific examples will be given of some current applications of therapeutic ultrasound that are being used or have the potential for use in clinical medicine.

 

 

Olivier Couture

Composite droplets for drug-delivery and Ultrasound Super-Localization 

 

This talk will present two medical applications combining both microfluidics and acoustic waves. Firstly, we will describe composite droplets formed by enclosing an aqueous nanoemulsion within a matrix of perfluorocarbon oil that can carry a large payload (2/3 of their volume). This payload can be released with low ultrasound power, attainable by conventional ultrasound scanners. Hence, with the same clinical instrument, both imaging and drug delivery can be performed. A potential application would be to tattoo tissues to be resected under radiological guidance before surgery. Our objective is to demonstrate the release of fluorescein in rats at sufficient concentrations to be macroscopically observable, along with its ultrasound targeting and monitoring. Ultimately, these droplets could also be used to deliver large quantities of drugs in-situ.

 

The second part of the talk will describe super-localization of microbubbles. When distinct sources are generated in a region of interest, their location can be mapped with a resolution beyond the diffraction limit. Such distinct sources can be generated during ultrafast imaging of clouds of clinical contrast agents at the appropriate acoustic pressures. We shall describe experiments on the resolution limit, in-vitro localization of microbubbles and the demonstration that ultrafast events are present in-vivo. Since our resolution limit is less than 10 microns for a 1 MHz transducer, the experiments are performed within microfluidics channels. Mapping distinct events could yield images of vasculature at the micrometer scale. 

 

 

 

David Fernandez Rivas

Ultrasound nucleated bubbles in a microreactor: radical production, sonoluminescence, sonochemiluminescence and cleaning control.

 

We describe the ejection of bubbles from air filled cavities in micromachined pits on a silicon surface when exposed to ultrasound at 200 kHz. Depending on the pressure amplitude different scenarios are observed as the bubbles ejected from the micropits interact in complex ways with each other and the silicon surface.

 We have determined the size distribution of bubbles ejected from one, two and three pits, for three different pressure amplitudes and correlated them with sonochemical OH. radical production.

 Under suitable conditions, the collapse of these bubbles can result in light emission (sonoluminescence, SL). OH. radicals generated during bubble collapse can react with luminol to produce light (sonochemiluminescence, SCL). SL and SCL intensities were recorded for several regimes related to the pressure amplitude for pure water, and aqueous luminol and propanol solutions.

 For imaging SL emitting regions, Argon-saturated water was used under similar conditions. SL emission from aqueous propanol solution (50 mM) provided evidence of transient bubble cavitation. Solutions containing 0.1 mM luminol were also used to demonstrate the radical production by attaining the SCL emission regions.

 Experimental evidence of shock wave emission from the microbubble clusters, deformed microbubble shapes and jetting events that lead to surface erosion are presented.

We also present a new method to generate cavitation in various liquids for fast removal (order of tenths of seconds) of various deposited materials with millimeter control, based on the pits as nucleation sites.

 

Collaborators:

 

Laura Stricker; U.Twente, NL

Bram Verhaagen; U.Twente, NL

Aaldert G Zijlstra; U.Twente, NL

Han J.G.E. Gardeniers; U.Twente, NL

Michel Versluis; U.Twente, NL

Detlef Lohse; U.Twente, NL

Andrea Prosperetti. U.Twente, NL & J.Hopkins, USA Muthupandian Ashokkumar; U.Melbourne, AUS Thomas Leong; U.Melbourne, AUS Sandra Kentish; U.Melbourne, AUS Kyuichi Yasui; AIST, JAP Toru Tuziuti; AIST, JAP Sandra Kentish; U.Melbourne, AUS


Caroline Harfield
Theoretical characterisation of the radial and translational motion of coated microbubbles under acoustic excitation
joint work with N C Ovenden , G Memoli , P H Jones and Eleanor Stride

Microbubbles are used as ultrasound contrast agents for diagnostic imaging and increasingly are being investigated for use in therapeutic applications such as gene and drug therapy. For the latter, an improved understanding of microbubble behaviour under ultrasound excitation is needed to engineer targeted vehicles and optimise interactions with tissue.

The study of microbubble dynamics has faced a significant challenge due to the difficulties involved in isolating and controlling the spatial distribution of individual or populations of microbubbles for detailed characterisation. The lack of repeatable experimental data has made it difficult to reliably validate theoretical models. Therefore an experimental method for observing individual microbubbles and/or populations in well characterized surroundings is required.

A further problem is that whilst there has been significant attention paid to developing theoretical models describing radial microbubble oscillations, the associated translational motion has been largely neglected. Moreover those models have a number of inconsistencies, these included the frame of reference used and the treatment of the relative velocity between the bubble and the liquid. The present study is concerned with developing a full theoretical description of a coated microbubble under ultrasound excitation that addresses these omissions. The model will ultimately be used to inform the development of an experimental system based on optical and acoustic traps for microbubble characterisation.

In addition, the uniqueness of the solution to this model, for a given set of parameters describing the bubble coating material, will be demonstrated. This is essential if modelling is to be used in the interpretation of experimental results for microbubble characterisation, since the properties of the coating dominate the bubble’s response and hence its effectiveness as a diagnostic and/or therapeutic agent. 

 

Jeremy Hawkes and Almudena Cabańas Sorando

Acoustic streaming Live. An interactive demonstration of acoustic streaming

 

We will demonstrate one or maybe two types of acoustic streaming. Geometries for producing streaming and standing waves will be identified experimentally. Frequency dependence will be measured.  Control and suppression methods will be demonstrated. Suggestions for experiments will be welcomed. The approach could be developed as a teaching aid if sufficient attention to noise suppression is given.

 

 

Frank Holsteyns

Introduction of acoustic actuation in semiconductor processing

Joint work with Robert Mettin, Philipp Frommhold, Till Nowak, Carlos Cairos (CDLCME, DPI, Georg-August University Göttingen) Xi Xu, Frederic Cegla (Imperial College London), Alex Lippert ,Dieter Frank and Harald Okorn-Schmidt (Lam Research AG, Villach)

 

Surface preparation via wet processing is a critical step in semiconductor processing and must be repeated many times. It covers typically chemical processes such as etching (partial removal of dielectric or metal films), cleaning (removal of particulate and metallic contamination), stripping (photoresist removal) or even thin film deposition. As a matter of fact, the wet chemical processing that was traditionally done in batch systems is now migrating towards single wafer processing tools, which means that the substrate is only covered with a 500-2000 mm thick process liquid film. The interest in single wafer wet processing is mainly driven by process advantages such as the isolation of front- and back side of the wafer, the lowering of cross-contamination… Furthermore, it also allows the introduction of various acoustic resonators on either front- or backside that may induce any type of acoustic actuation within the process liquid, which fills the gap between substrate and resonator. This acoustic actuation, in the form of either acoustic cavitation or acoustic streaming, may support the transition from a pure chemical process towards a physically assisted chemical process that may lead to the further improvement of process efficiency, uniformity and selectivity and the reduction of process costs. In this presentation, different types of resonators -that cover a wide range of frequencies (20 kHz to 2 GHz) - will be discussed how they induce and control acoustic cavitation or acoustic streaming. To improve processes based on acoustic cavitation such as the removal of nanoparticulate contamination, several aspects of multi bubble systems and structures will be discussed, in order to deliver a damage free and highly efficient cleaning step. Regarding the generation of acoustic streaming, BAW-resonators at GHz frequencies will be discussed and their impact on semiconductor processing steps such as rinsing and thin film deposition.

 

Ida Sadat Iranmanesh

Measuring acoustic energy density in microchannel acoustophoresis using a simple and rapid light-intensity method

 

Poster

 

Thomas Laurell

Advancing microchip acoustophoretic cell handling in life science and medical applications

 

Microchip acoustophoresis have in recent years become a viable strategy for advanced cell manipulation in life science applications, including cell separation, buffer switching, valving, affinity bead extraction, cell interaction studies. Cells undergoing acoustophoresis experience a low mechanical stress and display unaffected viability if the acoustophoresis is operated properly. This opens the route to a wide range of clinical applications. 

Free Flow Acoustophoresis, FFA, utilizes the migration speed of different cell types in the acoustic field. This enables e.g. the separation of erythrocytes, leukocytes and thrombocytes. More recently FFA has been developed to target clinical use where purification of circulating tumor cells (CTC) from white blood cell fractions is accomplished. Further optimised CTC separation conditions will be demonstrated by multidimensional acoustic actuation.

Rapid buffer exchange of cells in laminar flow can be realised by means of acoustophoresis. This has been realised in a system for on-line cell washing in flow-cytometry applications.

Acoustic standing wave resonators can also be designed in microfluidic systems to retain/trap and enrich cellular, bacterial or other bioparticle species prior to down stream diagnostic readout. Recent advances have furthered the ability to trap particles in the submicrometer domain.

 

Detlef Lohse

Acoustic cavitation

 

abstract will follow

 

Philippe Marmottant

Microbubbles under ultrasound: from a self-organised "ballet" to controlled manipulation and propulsion

 

Because of their high compressibility microbubbles have the unique property of vibrating intensely under ultrasound. This vibration is at the origin of the emission of secondary waves that allow a collection of bubbles to interact with each other. In soft microchannels, this interaction is mediated by low velocity surface waves and is especially strong. We have evidenced a new phenomenon that manifests itself by a self-organization of bubbles into a periodic arrangement of positions. This bubble "crystal" moves independently of the acoustic standing wave. The crystal self-assembly leads to temporary "ballet" like motions.

Because of the high contrast in acoustic properties between bubbles and the liquid, they are also ideal as model objects to study acoustic radiation forces. We show how to push them very locally by focusing high frequency surface acoustic waves on a few dozens of micrometers. We also show the first steps towards acoustic tweezers, which can hold bubbles and displace them at a desired location.

In the last part, we trap bubbles inside an open capsule created by 3D lithography. Under ultrasound, these bubbles therefore do not move but push the surrounding fluid. This provides the principle of very localized pumps when capsules are attached to a boundary, and the hope to create micro-swimmers powered by ultrasound for free standing capsules.

 

Jorick van ‘t Oever

Ultrasonic concentration enhancement for early pathogen detection in microfluidic systems

 

Quality control of drinking water has been and will be an important technology. The evaluation of water quality based on microbacterial with current main-stream technology takes too long for use as in-line detection. The project goal is to detect and distinguish between pathogens by optical means in a continuous system that samples in-line. The initial aim is for a sensitivity of 1 bacterium or cyst per 10 ml of water where 10ml is sampled within 1 hour.

Our approach consists of two steps: a microfluidic concentration step to increase the concentration of particles within the target range by a factor of 100 and detection by non-linear spectroscopy. Two concentration methods (deterministic ratchet and ultra-sonic concentration) will be compared and preliminary experimental results will be discussed.

 

 

Mathias Ohlin

Fluid and particle manipulation by multi-frequency ultrasound in microchannels and microplates

 

Poster

 

Alan Renaudin

Improved biosensing by microfluidic SAW mixer integration: application to SPR and Microcalorimetry

 

Micro-/nanofabricated biosensors require ever higher degrees of measurement precision and miniaturization. In this poster, we give an overview of on-chip integrated surface acoustic wave and biosensing technologies in miniaturized diagnostic devices where two particularly difficult challenges can be:

(1) How to overcome sensitivity limitations due to non-specific adsorption. Non-specific adsorption is the weak binding of molecules other than the target analyte to the sensing surface. The nonspecifically adsorbed molecules can completely obscure the surface-bound ligands, inhibiting any contact with the target analyte.

(2) How to perform efficient mixing at the microfluidic level for homogeneous and timely analysis. To minimize the quantity of expensive reagents, modern biosensing systems use microfluidics. Because the fluid flow at such small scales is laminar, the efficient mixing of reagents is a real challenge in microfluidics.

We propose to use Surface Acoustic Waves to provide active microfluidic mixing in the fluid above the sensor to overcome those two challenges.

 

 

Massimiliano Rossi

Estimation of flow velocity and fluid interface topology using astigmatism particle tracking velocimetry: prospects and applications to acoustofluidic microflows
Joint work with Marin A, Cierpka C, Kähler CJ.

In the past few years, significant improvements have been achieved in the calibration and application of the astigmatism particle tracking velocimetry (APTV), that is nowadays a robust and reliable method to track the 3D position of tracer particles in microfluidic systems. Additionally, it has been recently demonstrated how APTV can be extended to estimate the topology of fluid interfaces (liquid-liquid, liquid-air ). In this contribution, the latest improvements of the APTV and APTV-based surface reconstruction methods, as well as their applications and future prospects to the field of acoustofluidic in microfluidic flows will be discussed.

Gianluca Memoli

Characterisation of a multi-frequency reference vessel for cavitation

 

 

Michael Schindler

Droplet-based microfluidics driven by surface-acoustic waves:

Deformation of free surfaces and transport of particles

 

I present a numerical method to solve the combined problem of finding the acoustically driven internal circulation in a droplet and the determination of its shape. The method is based on finite elements that adapt themselves to the free surface of the droplet, which allows to efficiently find a stationary state. The numerical values and comparison with experimental data allow to estimate the relative importance of viscous drag and pressure on particles transported in the flow.

 

Oleksandr Shpak

Acoustically driven vaporization of superheated droplets

Liquid emulsion droplets composed of perfluorocarbon (PFC) and a drug (Doxorubicin) are currently being studied as a potential highly efficient system for tumor imaging and for local drug delivery. The droplets have the ability to extravasate through hyperpermeable tumor blood vessel walls, and to accumulate into interstitial tissue. The extravasated droplets can be triggered and vaporized with focused ultrasound, converting them into gas bubbles while the encapsulated drugs are released during the explosive evaporation of the droplet. The motivation of this work was to investigate nucleation and grows of the newly created bubbles during the first microsecond following the vaporization and to study the influence of ultrasound on it.

Tim Segers and Michel Versluis
Acoustic bubble sorting: contrast enrichment by primary radiation forces

Ultrasound contrast agents consist of a suspension of encapsulated microbubbles with radii ranging from 1 to 10 µm. Medical transducers typically operate at a single frequency, consequently only a small selection of bubbles resonates to the driving ultrasound frequency. Thus, the sensitivity can be improved by narrowing down the size distribution. Here, a simple lab-on-a-chip method is presented to acoustically sort microbubbles on-line by a piezoelectric actuator positioned perpendicular to a microfluidic channel in a PDMS chip. Bubbles are produced in a flow focusing geometry at a rate of 500 bubbles per second. The bubbles are characterized in the unbounded fluid to provide physical input parameters for a force balance model. Good agreement is found with the experimentally observed displacement as a function of the bubble radius in free space as well as in the confinement of the sorting chip. This novel sorting strategy may lead to an overall improvement of the sensitivity of contrast echo by at least an order of magnitude.

 

 

Ton van der Steen

Intravascular imaging of atherosclerosis

 

Intravascular ultrasound (IVUS) is a technology that uses an ultrasound element on the tip of a catheter[1, 2]. This catheter is advanced through the groin into the coronary arteries. In this way a tomographic image of the vascular wall and atherosclerotic plaques can be produced. The steering of the ultrasound beam can be done by mechanically rotating a single ultrasound transducer, or electronically, using an array of 64 elements in the tip. 

Historically is has been used to assess the level of occlusion, the atherosclerotic plaque burden and the native size of the vessel. This information can be used to decide to treat or not and to determine the diameter and length of the stent to be used for treatment. It has also been used extensively to determine if the stent was well deployed.

The composition and morphology of an atherosclerotic lesion are currently considered more important determinants of acute coronary ischemic syndromes that the degree of stenosis[3]. When a lesion is unstable, it can rupture and cause an acute thrombotic reaction. An unstable plaque can be characterized by a lipid core that is covered by a thin fibrous cap, which has been locally weakened by inflammatory cells.

The last decade serious effort has been put in developing IVUS towards identifying these unstable plaques. This lecture will focus on the development of measuring the elastic properties of the plaque as a marker for plaque instability[4] and measuring the vascularization in the plaque[5], which plays an important role in the pathogenesis of unstable plaque. Furthermore the role of combined ultrasound/light catheters will be discussed[6, 7]. These will allow to image the luminal plaque at a resolution of around 10 µm, while maintaining the full overview. Furthermore photoacoustics and combination of NIR spectroscopy and imaging will be possible.

Technology development in the elements, the echomachines and the signal processing will be presented as well as their validation and the role of IVUS to provide imaging biomarkers in natural history studies and trials for the development of new cardiovascular drugs[8, 9].

 

References

 

[1]            A. F. W. van der Steen, E. I. Cespedes, C. L. de Korte, S. G. Carlier, W. Li, F. Mastik, C. T. Lancee, J. Borsboom, F. Lupotti, R. Krams, P. W. Serruys, and N. Bom, "Novel developments in intravascular imaging," in Proceedings 1998 IEEE Ultrasonics Symposium, pp. 1733-1742.

[2]            Vascular Ultrasound. A.F.W. van der Steen, Y. Saijo eds. Tokio: Springer, 2004.

[3]            J. A. Schaar, J. E. Muller, E. Falk, R. Virmani, V. Fuster, P. W. Serruys, A. Colombo, C. Stefanadis, W. S. Casscells, P. R. Moreno, A. Maseri, and A. F. W. van der Steen, "Terminology for high-risk and vulnerable coronary artery plaques," European Heart Journal, vol. 25, pp. 1077-1082, 2004.

[4]            C. L. de Korte, M. J. Sierevogel, F. Mastik, C. Strijder, J. A. Schaar, E. Velema, G. Pasterkamp, P. W. Serruys, and A. F. W. van der Steen, "Identification of atherosclerotic plaque components with intravascular ultrasound elastography in vivo - A Yucatan pig study," Circulation, vol. 105, pp. 1627-1630, 2002.

[5]            D. E. Goertz, M. E. Frijlink, D. Tempel, L. C. van Damme, R. Krams, J. A. Schaar, F. J. Ten Cate, P. W. Serruys, N. de Jong, and A. F. van der Steen, "Contrast harmonic intravascular ultrasound: a feasibility study for vasa vasorum imaging," Invest Radiol, vol. 41, pp. 631-8, 2006.

[6]            A. F. van der Steen, R. A. Baldewsing, F. Levent Degertekin, S. Emelianov, M. E. Frijlink, Y. Furukawa, D. Goertz, M. Karaman, P. T. Khuri-Yakub, K. Kim, F. Mastik, T. Moriya, O. Oralkan, Y. Saijo, J. A. Schaar, P. W. Serruys, S. Sethuraman, A. Tanaka, H. J. Vos, R. Witte, and M. O'Donnell, "IVUS beyond the horizon," EuroIntervention, vol. 2, pp. 132-42, 2006.

[7]            S. Garg, P. Serruys, M. v. d. Ent, C. Schultz, F. Mastik, G. v. Soest, A. v. d. Steen, M. Wilder, J. Muller, and E. Regar, "First use in patients of a combined near infra-red spectroscopy and intra-vascular ultrasound catheter to identify composition and structure of coronary plaque," EuroIntervention, vol. 5, pp. 755-756, 2010.

[8]            P. W. Serruys, H. M. Garcia-Garcia, P. Buszman, P. Erne, S. Verheye, M. Aschermann, H. Duckers, O. Bleie, D. Dudek, H. E. Botker, C. von Birgelen, D. D'Amico, T. Hutchinson, A. Zambanini, F. Mastik, G. A. van Es, A. F. van der Steen, D. G. Vince, P. Ganz, C. W. Hamm, W. Wijns, and A. Zalewski, "Effects of the direct lipoprotein-associated phospholipase A(2) inhibitor darapladib on human coronary atherosclerotic plaque," Circulation, vol. 118, pp. 1172-82, 2008.

[9]            C. A. G. Van Mieghem, E. P. McFadden, P. J. de Feyter, N. Bruining, J. A. Schaar, N. R. Mollet, F. Cademartiri, D. Goedhart, S. de Winter, G. R. Granillo, M. Valgimigli, F. Mastik, A. F. van der Steen, W. J. van der Giessen, G. Sianos, B. Backx, M. A. M. Morel, G. A. van Es, A. Zalewski, and P. W. Serruys, "Noninvasive detection of subclinical coronary atherosclerosis coupled with assessment of changes in plaque characteristics using novel invasive imaging modalities," Journal of the American College Of Cardiology, vol. 47, pp. 1134-1142, 2006.

 

 

Martin Wiklund

Ultrasonic manipulation of single cells: Principles and applications

 

Methods for manipulating single cells date back to the early 20th century when Barber and coworkers demonstrated how to grasp a cell with suction through a hollow glass micropipette tip, a method that is still widely used. More recently, methods based on external force fields have emerged as a contactless alternative. Two such established techniques – negative dielectrophoresis (nDEP) and laser tweezers – are based on electrical and optical forces, respectively. Their main advantage is the high spatial accuracy defined by, e.g., micro-electrodes or a focused laser beam, both having length scales of the order of a single cell or even smaller.

Ultrasonic manipulation is a method that was successfully implemented in microscale devices about one decade ago. In contrast to nDEP and optical tweezers, this technique is generally not used as a single-cell manipulation method. The reason is that the ultrasonic radiation force field is more difficult to spatially confine into a volume small enough. On the other hand, ultrasonic manipulation seems to be a much more gentle method for long-term cell handling compared to available alternatives. For that reason we have developed a platform for single-cell handling based on combining multi-frequency ultrasonic manipulation, high-resolution optical microscopy and microfluidics. In the present talk, we describe the implementation of single-cell ultrasonic manipulation into microfluidic chips and microplates, and we report on novel results where the method is used for quantifying the heterogeneity in immune cell – cancer cell interaction.

 

 

Achim Wixforth

The perfect wave

 

After having worked with Surface Acoustic Waves (SAW) for many years in various fields of nanoscience, we started to use them for microfluidic applications about 12 years ago. So far, our SAW studies concentrated on the dynamic piezoelectric fields accompanying a SAW at the speed of sound. These fields can strongly interact with mobile charges in, e.g., semiconductor nanosystems. This way, we were able to probe the dynamical conductivity of low dimensional systems, to efficiently convey charges, to ionize excitons, and to actually delay and store photonic signals in a semiconductor heterostructure. This eventually results in a sound driven single photon source. To also exploit the purely mechanical part of a SAW, we employed them to study various nano electro mechanical systems (NEMS) and finally: to actuate small amounts of fluids on a chip.

 

Here, we made use of the well known effects of acoustic streaming and applied them to SAW driven microfluidic systems. Together with either a modulation of the chip surface chemistry or by combining SAW and elastormer based microfluidic devices, we were able to create SAW driven microfluidic processors with unpreceeded properties for many different applications in chemistry, biology and medicine.

 

In my talk, I plan to review our major developments and give representative examples for the application of SAW in microfluidics over the last decade or so. These include acoustic mixers and stirrers for biological and medical applications, various SAW driven hybridization reactors, single droplet manipulation for, e.g., polymerase chain reaction on a chip, cell assays and various flow chambers for cell investigations and cell sorting on a chip. Some of these applications have already made it into the market, some will do so, soon!

 

 

Regis Wunenburger

Liquid-liquid interface deformation by acoustic radiation pressure

 

I will present how acoustic radiation pressure deforms liquid-liquid interfaces and how the feedback of the deformation on the acoustic waves can be used to inhibit or trigger hydrodynamic interfacial instabilities.

 



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