Multifunctional single beam acoustic tweezer for non-invasive cell/organism manipulation and tissue imaging.
ABSTRACT: Non-contact precise manipulation of single microparticles, cells, and organisms has attracted considerable interest in biophysics and biomedical engineering. Similar to optical tweezers, acoustic tweezers have been proposed to be capable of manipulating microparticles and even cells. Although there have been concerted efforts to develop tools for non-contact manipulation, no alternative to complex, unifunctional tweezer has yet been found. Here we report a simple, low-cost, multifunctional single beam acoustic tweezer (SBAT) that is capable of manipulating an individual micrometer scale non-spherical cell at Rayleigh regime and even a single millimeter scale organism at Mie regime, and imaging tissue as well. We experimentally demonstrate that the SBAT with an ultralow f-number (f#?=?focal length/aperture size) could manipulate an individual red blood cell and a single 1.6?mm-diameter fertilized Zebrafish egg, respectively. Besides, in vitro rat aorta images were collected successfully at dynamic foci in which the lumen and the outer surface of the aorta could be clearly seen. With the ultralow f-number, the SBAT offers the combination of large acoustic radiation force and narrow beam width, leading to strong trapping and high-resolution imaging capabilities. These attributes enable the feasibility of using a single acoustic device to perform non-invasive multi-functions simultaneously for biomedical and biophysical applications.
Project description:The optical tweezer has become a popular device to manipulate particles in nanometer scales and to study the underlying principles of many cellular or molecular interactions. Theoretical analysis was previously carried out at the authors' laboratory, to show that similar acoustic trapping of microparticles may be possible with a single beam ultrasound. This article experimentally presents the transverse trapping of 125 microm lipid droplets under an acoustically transparent mylar film, which is an intermediate step toward achieving acoustic tweezers in three-dimension. Despite the lack of axial trapping capability in the current experimental arrangement, it was found that a 30 MHz focused beam could be used to laterally direct the droplets toward the focus. The spatial range within which acoustic traps may guide droplet motion was in the range of hundreds of micrometers, much greater than that of optical traps. This suggests that this acoustic device may offer an alternative for manipulating microparticles in a wider spatial range.
Project description:Similar to optical tweezers, a tightly focused ultrasound microbeam is needed to manipulate microparticles in acoustic tweezers. The development of highly sensitive ultrahigh frequency ultrasonic transducers is crucial for trapping particles or cells with a size of a few microns. As an extra lens would cause excessive attenuation at ultrahigh frequencies, two types of 200-MHz lensless transducer design were developed as an ultrasound microbeam device for acoustic tweezers application. Lithium niobate single crystal press-focused (PF) transducer and zinc oxide self-focused transducer were designed, fabricated and characterized. Tightly focused acoustic beams produced by these transducers were shown to be capable of manipulating single microspheres as small as 5 µm two-dimensionally within a range of hundreds of micrometers in distilled water. The size of the trapped microspheres is the smallest ever reported in the literature of acoustic PF devices. These results suggest that these lensless ultrahigh frequency ultrasonic transducers are capable of manipulating particles at the cellular level and that acoustic tweezers may be a useful tool to manipulate a single cell or molecule for a wide range of biomedical applications.
Project description:Single-beam acoustic tweezers (SBAT), used in laboratory-on-a-chip (LOC) device has promising implications for an individual micro-particle contactless manipulation. In this study, a freestanding hydrothermal PZT thick film with excellent piezoelectric property (d33 = 270pC/N and kt = 0.51) was employed for SBAT applications and a press-focusing technology was introduced. The obtained SBAT, acting at an operational frequency of 50MHz, a low f-number (?0.9), demonstrated the capability to trap and manipulate a micro-particle sized 10?m in the distilled water. These results suggest that such a device has great potential as a manipulator for a wide range of biomedical and chemical science applications.
Project description:Techniques that can dexterously manipulate single particles, cells, and organisms are invaluable for many applications in biology, chemistry, engineering, and physics. Here, we demonstrate standing surface acoustic wave based "acoustic tweezers" that can trap and manipulate single microparticles, cells, and entire organisms (i.e., Caenorhabditis elegans) in a single-layer microfluidic chip. Our acoustic tweezers utilize the wide resonance band of chirped interdigital transducers to achieve real-time control of a standing surface acoustic wave field, which enables flexible manipulation of most known microparticles. The power density required by our acoustic device is significantly lower than its optical counterparts (10,000,000 times less than optical tweezers and 100 times less than optoelectronic tweezers), which renders the technique more biocompatible and amenable to miniaturization. Cell-viability tests were conducted to verify the tweezers' compatibility with biological objects. With its advantages in biocompatibility, miniaturization, and versatility, the acoustic tweezers presented here will become a powerful tool for many disciplines of science and engineering.
Project description:The purpose of this paper is to present a rapid and simple method to evaluate the trapping performance of high frequency focused ultrasonic transducers for acoustic tweezer applications. The method takes into consideration the friction between the particle to be trapped and the surface that it resides on. As a result it should be more reliable and accurate than the methods proposed previously. The trapping force produced by a 70-MHz press-focused transducer was measured to evaluate the performance of this approach. This method demonstrates its potential in optimizing the excitation conditions for acoustic tweezer applications and the design of acoustic tweezers.
Project description:Acoustic micro-beams produced by highly focused ultrasound transducer have been investigated for micro-particle and cell manipulation. Here we report the selective trapping of microspheres via the acoustic force using the single acoustical beam. The forbidden band theory of acoustic radiation force trapping is proposed, which indicates that the trapping of particles via the acoustic beam is directly related to the particle diameter-to-beam wavelength ratio as well as excitation frequency of the ultrasonic acoustic tweezers. Three tightly focused LiNbO<sub>3</sub> transducers with different center frequencies were fabricated for use as selective single beam acoustic tweezers (SBATs). These SBATs were capable of selectively manipulating microspheres of sizes 5-45 ?m by adjusting the wavelength of acoustic beam. Our observations could introduce new avenues for research in biology and biophysics by promoting the development of a tool for selectively manipulating microspheres or cells of certain selected sizes, by carefully setting the acoustic beam shape and wavelength.
Project description:Acoustic tweezers have recently raised great interest across many fields including biology, chemistry, engineering, and medicine, as they can perform contactless, label-free, biocompatible, and precise manipulation of particles and cells. Here, we present wave number-spiral acoustic tweezers, which are capable of dynamically reshaping surface acoustic wave (SAW) wavefields to various pressure distributions to facilitate dynamic and programmable particle/cell manipulation. SAWs propagating in multiple directions can be simultaneously and independently controlled by simply modulating the multitone excitation signals. This allows for dynamic reshaping of SAW wavefields to desired distributions, thus achieving programmable particle/cell manipulation. We experimentally demonstrated the multiple functions of wave number-spiral acoustic tweezers, among which are multiconfiguration patterning; parallel merging; pattern translation, transformation, and rotation; and dynamic translation of single microparticles along complex paths. This wave number-spiral design has the potential to revolutionize future acoustic tweezers development and advance many applications, including microscale assembly, bioprinting, and cell-cell interaction research.
Project description:The ability of surface acoustic waves to trap and manipulate micrometer-scale particles and biological cells has led to many applications involving "acoustic tweezers" in biology, chemistry, engineering, and medicine. Here, we present 3D acoustic tweezers, which use surface acoustic waves to create 3D trapping nodes for the capture and manipulation of microparticles and cells along three mutually orthogonal axes. In this method, we use standing-wave phase shifts to move particles or cells in-plane, whereas the amplitude of acoustic vibrations is used to control particle motion along an orthogonal plane. We demonstrate, through controlled experiments guided by simulations, how acoustic vibrations result in micromanipulations in a microfluidic chamber by invoking physical principles that underlie the formation and regulation of complex, volumetric trapping nodes of particles and biological cells. We further show how 3D acoustic tweezers can be used to pick up, translate, and print single cells and cell assemblies to create 2D and 3D structures in a precise, noninvasive, label-free, and contact-free manner.
Project description:This paper describes an acoustic trap consisting of a multi-foci Fresnel lens on 127 μm thick lead zirconate titanate sheet. The multi-foci Fresnel lens was designed to have similar working mechanism to an Axicon lens and generates an acoustic Bessel beam, and has negative axial radiation force capable of trapping one or more microparticle(s). The fabricated acoustic tweezers trapped lipid particles ranging in diameter from 50 to 200 μm and microspheres ranging in diameter from 70 to 90 μm at a distance of 2 to 5 mm from the tweezers without any contact between the transducer and microparticles.
Project description:Contactless manipulation of microparticles using acoustic waves holds promise for applications ranging from cell sorting to three-dimensional (3D) printing and tissue engineering. However, the unique potential of acoustic trapping to be applied in biomedical settings remains largely untapped. In particular, the main advantage of acoustic trapping over optical trapping, namely the ability of sound to propagate through thick and opaque media, has not yet been exploited in full. Here we demonstrate experimentally the use of the recently developed technique of single-beam acoustical tweezers to trap microbubbles, an important class of biomedically relevant microparticles. We show that the region of vanishing pressure of a propagating vortex beam can confine a microbubble by forcing low-amplitude, nonspherical, shape oscillations, enabling its full 3D positioning. Our interpretation is validated by the absolute calibration of the acoustic trapping force and the direct spatial mapping of isolated bubble echos, for which both find excellent agreement with our theoretical model. Furthermore, we prove the stability of the trap through centimeter-thick layers of bio-mimicking, elastic materials. Finally, we demonstrate the simultaneous trapping of nanoparticle-loaded microbubbles and activation with an independent acoustic field to trigger the release of the nanoparticles. Overall, using exclusively acoustic powering to position and actuate microbubbles paves the way toward controlled delivery of drug payloads in confined, hard-to-reach locations, with potential in vivo applications.