In optoacoustic imaging, short laser pulses irradiate highly scattering human tissue and adiabatically heat embedded absorbing structures, such as blood vessels, to generate ultrasound transients by means of the thermoelastic effect. We present an optoacoustic vascular imaging system that records these transients on the skin surface with an ultrasound transducer array and displays the images online. With a single laser pulse a complete optoacoustic B-mode image can be acquired. The optoacoustic system exploits the high intrinsic optical contrast of blood and provides high-contrast images without the need for contrast agents. The high spatial resolution of the system is determined by the acoustic propagation and is limited to the submillimeter range by our 7.5-MHz linear array transducer. A Q-switched alexandrite laser emitting short near-infrared laser pulses at a wavelength of 760 nm allows an imaging depth of a few centimeters. The system provides real-time images at frame-rates of 7.5 Hz and optionally displays the classically generated ultrasound image alongside the optoacoustic image. The functionality of the system was demonstrated in vivo on human finger, arm and leg. The proposed system combines the merits and most compelling features of optics and ultrasound in a single high-contrast vascular imaging device.

Several cell-based biological applications in microfluidic systems require simultaneous high-throughput and individual handling of cells or other bioparticles. Available chip-based tools for contactless manipulation are designed for either high-precision handling of individual particles, or high-throughput handling of ensembles of particles. In order to simultaneously perform both, we have combined two manipulation technologies based on ultrasonic standing waves (USWs) and dielectrophoresis (DEP) in a microfluidic chip. The principle is based on the competition between long-range ultrasonic forces, short-range dielectrophoretic forces and viscous drag forces from the fluid flow. The ultrasound is coupled into the microchannel resonator by an external transducer with a refractive element placed on top of the chip, thereby allowing transmission light microscopy to continuously monitor the biological process. The DEP manipulation is generated by an electric field between co-planar microelectrodes placed on the bottom surface of the fluid channel. We demonstrate flexible and gentle elementary manipulation functions by the use of USWs and linear or curved DEP deflector elements that can be used in high-throughput biotechnology applications of individual cells.

Various techniques exerting mechanical stress on cells have been developed to investigate cellular responses to externally controlled stimuli. Fundamental mechanotransduction processes, how applied physical forces are converted into biochemical signals, have often been examined by transmitting such forces through cells and probing its pathway at cellular levels. In fact, many cellular biomechanics studies have been performed by trapping (or immobilizing) individual cells, either attached to solid substrates or suspended in liquid media. In that context, we demonstrated two-dimensional acoustic trapping, where a lipid droplet of 125 μm in diameter was directed transversely towards the focus (or the trap center) similar to that of optical tweezers. Under the influence of restoring forces created by a 30 MHz focused ultrasound beam, the trapped droplet behaved as if tethered to the focus by a linear spring. In order to apply this method to cellular manipulation in the Mie regime (cell diameter > wavelength), the availability of sound beams with its beamwidth approaching cell size is crucial. This can only be achieved at a frequency higher than 100 MHz. We define ultrasound beams in the frequency range from 100 MHz to a few GHz as ultrasound microbeams because the lateral beamwidth at the focus would be in the micron range (reviewer #1). Hence a zinc oxide (ZnO) transducer that was designed and fabricated to transmit a 200 MHz focused sound beam was employed to immobilize a 10 μm human leukemia cell (K-562) within the trap. The cell was laterally displaced with respect to the trap center by mechanically translating the transducer over the focal plane. Both lateral displacement and position trajectory of the trapped cell were probed in a two-dimensional space, indicating that the retracting motion of these cells was similar to that of the lipid droplets at 30 MHz. The potential of this tool for studying cellular adhesion between white blood cells and endothelial cells was discussed, suggesting its capability as a single cell manipulator.

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