Acoustic Standing Wave Manipulation of Particles and Cells in Microfluidic Chips

The rise of MEMS and µTAS techniques has created a whole new family of microfluidic devices for a wide range of chemical and biomedical analyses to be performed on small Lab-on-a-chip platforms. The operations often include small samples of particle or cell suspensions on which separation, mixing, trapping or sorting is performed. External fields and forces are used for these operations, and this thesis is specifically focused the development of ultrasonic standing wave technology and the use of acoustic force fields to perform bioanalytical unit operations. The combination of acoustic standing waves and the laminar flow in microfluidics has proven to be well suited for performing particle and cell separation. The fundamental acoustic separator used in this thesis consists of a microfluidic flow channel with a three way flow splitter (trifurcation) in the end of the channel. An acoustic standing wave field is applied to the main flow channel by attaching the transducer underneath the chip. The acoustic standing wave is however obtained perpendicular to the axial propagation of the wave field and the direction of the flow. The half wavelength resonance affects rigid particles or cells driving them into the acoustic pressure node while liquid spheres having other density and compressibility properties may move to the pressure antinode. This enables acoustic separation of different particle types. Blood has proven to be very suitable for acoustic cell manipulation. An application where lipid particles can be removed acoustically from shed blood from open heart surgery is demonstrated. An application for acoustic plasmapheresis is also shown where high quality blood plasma is generated. Different separator designs, device material, and the influence of the separation channel cross-section design are also investigated

Efficient Removal of Platelets from Peripheral Blood Progenitor Cell Products Using a Novel Micro-Chip Based Acoustophoretic Platform

Excessive collection of platelets is an unwanted side effect in current centrifugation-based peripheral blood progenitor cell (PBPC) apheresis. We investigated a novel microchip-based acoustophoresis technique, utilizing ultrasonic standing wave forces for the removal of platelets from PBPC products. By applying an acoustic standing wave field onto a continuously flowing cell suspension in a micro channel, cells can be separated from the surrounding media depending on their physical properties

Continuous separation of cells and particles in microfluidic systems

The progress in microfabrication and lab-on-a-chip technologies has been a major area of development for new approaches to bioanalytics and integrated concepts for cell biology. Fundamental advances in the development of elastomer based microfluidics have been driving factors for making microfluidic technology available to a larger scientific community in the past years. In line with this, microfluidic separation of cells and particles is currently developing rapidly where key areas of interest are found in designing lab-on-a-chip systems that offer controlled microenvironments for studies of fundamental cell biology. More recently industrial interests are seen in the development of micro chip based flow cytometry technology both for preclinical research and clinical diagnostics. This critical review outlines the most recent developments in microfluidic technology for cell and particle separation in continuous flow based systems. (130 references

Emerging clinical applications of microchip-based acoustophoresis.

Acoustophoresis is currently in a state of transition from the academic laboratories, moving into the biomedical laboratories and industries. Clear areas of interest are seen in clinical diagnostics and therapeutics, where new approaches to cell handling and purification are emphasized as highly potent areas. This article outlines some of the basic unit operations of acoustophoresis, where applications as cell washing, binary separation, free-flow acoustophoresis, and affinity acoustophoresis are highlighted. The most recent steps to move acoustophoresis into clinical and preclinical applications are also presented

Microscale Acoustofluidics

The manipulation of cells and microparticles within microfluidic systems using external forces is valuable for many microscale analytical and bioanalytical applications. Acoustofluidics is the ultrasound-based external forcing of microparticles with microfluidic systems. It has gained much interest because it allows for the simple label-free separation of microparticles based on their mechanical properties without affecting the microparticles themselves. Microscale Acoustofluidics provides an introduction to the field providing the background to the fundamental physics including chapters on governing equations in microfluidics and perturbation theory and ultrasound resonances, acoustic radiation force on small particles, continuum mechanics for ultrasonic particle manipulation, and piezoelectricity and application to the excitation of acoustic fields for ultrasonic particle manipulation. The book also provides information on the design and characterization of ultrasonic particle manipulation devices as well as applications in acoustic trapping and immunoassays. Written by leading experts in the field, the book will appeal to postgraduate students and researchers interested in microfluidics and lab-on-a-chip applications

Improved ultrasonic micro array separation using far field ultrasonic excitation

This paper reports improved separation efficiency of an ultrasonic standing wave separator microchannel array by means of ultrasonic far field excitation. By putting an aluminium spacer between the transducer and the channel array, the acoustic power transmission region is moved into the ultrasonic far field decreasing the local intensity variations which is induced in close vicinity to the transducer. This generates a more stable acoustic separation, which enables better separation performance and higher separation efficiency

Acoustofluidics 8: Applications of acoustophoresis in continuous flow microsystems

This acoustofluidics tutorial focuses on continuous flow-based half wavelength resonator systems operated in the transversal mode, where the direction of the primary acoustic force acts in plane with the microchip. The transversal actuation mode facilitates integration with up- and downstream microchannel networks as well as visual control of the acoustic focusing experiment. Applications of particle enrichment in an acoustic half wavelength resonator are discussed as well as clarification of the carrier fluid from undesired particles. Binary separation of particle/vesicle/cell mixtures into two subpopulations is outlined based on the different polarities of the acoustic contrast factor. Furthermore, continuous flow separation of different particle/cell types is described where both Free Flow Acoustophoresis (FFA) and binary acoustophoresis are utilized. By capitalizing on the laminar flow regime, acoustophoresis has proven especially successful in performing bead/cell translations between different buffer systems. Likewise, the ability to controllably translate particulate matter across streamlines has opened a route to valving of cells/particles without any moving parts, where event triggered cell sorting is becoming an increasing area of activity. Recent developments now also enable measurements of fundamental cell properties such as density and compressibility by means of acoustophoresis. General aspects on working with live cells in acoustophoresis systems are discussed as well as available means to quantify the outcome of cell and particle separation experiments performed by acoustophoresis