Liquid handling instruments for life science applications based on droplet formation with focused acoustic energy or acoustic droplet ejection (ADE) were introduced commercially more than a decade ...ago. While the idea of "moving liquids with sound" was known in the 20th century, the development of precise methods for acoustic dispensing to aliquot life science materials in the laboratory began in earnest in the 21st century with the adaptation of the controlled "drop on demand" acoustic transfer of droplets from high-density microplates for high-throughput screening (HTS) applications. Robust ADE implementations for life science applications achieve excellent accuracy and precision by using acoustics first to sense the liquid characteristics relevant for its transfer, and then to actuate transfer of the liquid with customized application of sound energy to the given well and well fluid in the microplate. This article provides an overview of the physics behind ADE and its central role in both acoustical and rheological aspects of robust implementation of ADE in the life science laboratory and its broad range of ejectable materials.
DNA shearing is crucial for all genetic based biomedical applications. In this paper, we present the effect of sonication time, one of the main parameters of shearing protocol, on DNA shearing using ...an array of Fresnel Annular Sector Actuator (FASA) piezoelectric transducers. Four 90° FASA piezoelectric transducers are arranged in a circular array to generate acoustic waves with unique effects, in particular, vortexing and converging effects, inside DNA sample. In this paper, we describe the building blocks of proposed DNA shearing system and present results of sonication time-dose shearing experiments performed on two types of DNA - E. Coli lambda DNA and human genomic DNA. In particular, we empirically demonstrate that the length of sheared DNA could be varied from 800 base-pairs to 300 base-pair by increasing the sonication time from 5 mins to 55 mins (< \mathbf{Hr}) .
In this paper, we present an analytical modeling technique for circularly symmetric piezoelectric transducers, also called as Fresnel Lens. We also present the design of a flat/piston transducer that ...can generate unique acoustic wave patterns, having both converging and vortexing effects. The converging effect is generated by designing the transducer electrodes in the shapes of circular rings using Fresnel formula and exciting it with an RF signal of resonant frequency. The vortexing effect is achieved by cutting the rings to different sector angles: 90, 120, 180 and 270 degrees. We use the analytical model to simulate the performance of these transducers.
In this paper, we present the design of a Deoxyribonucleic Acid (DNA) shearing system based on unique acoustic waves generated using a phased-array Fresnel Lens transducer. Four 90-degree ...sector-transducers are used to build a circular array transducer. Acoustic simulation results for particle displacement are provided for cases when one, two, three, and all four transducers in the array are excited with RF signals. Each 90degree-transducer is excited with separate RF signal of same or different phase. The proposed transducer structure generates bulk lateral ultrasonic waves in the DNA sample; the lateral waves produce both convergence and vortexing effects in the sample. The converged lateral acoustic waves are required to break the DNA sample-meniscus inside the tube and the rotational component of acoustic field is used to recirculate the DNA sample to get homogeneous shearing with tight fragment distribution. Finally, we present the experimental results of DNA sheared to different mean fragment sizes using the proposed system and validate the shearing-capability of the proposed system.
In this paper, we present an analytical modeling technique for circularly symmetric piezoelectric transducers. We also present the design of a flat/piston transducer that can generate unique acoustic ...wave patterns, having both converging and vortexing effects. The converging effect is generated by designing the transducer electrodes in the shapes of circular rings using Fresnel formula and exciting it with an RF signal of resonant frequency. The vortexing effect is achieved by cutting the rings to different sector angles: 90°, 180° and 270°. We use the analytical model to simulate the performance of these transducers.
In this paper, we present the design of a Deoxyribonucleic Acid (DNA) shearing system based on unique acoustic waves generated using a phased-array transducer. Four 90° sector-transducers are used to ...build a circular array transducer. Each 90°-transducer is excited with separate RF signal of same or different phase. The proposed transducer structure generates bulk lateral ultrasonic waves in the DNA sample; the lateral waves produce both convergence and vortexing effects in the sample. The converged lateral acoustic waves are required to break the DNA sample-meniscus inside the tube and the rotational component of acoustic field is used to recirculate the DNA sample to get homogeneous shearing with tight fragment distribution. Finally, we present the experimental results of DNA sheared to different mean fragment sizes using the proposed system and validate the shearing-capability of the proposed system.
The operation of an acoustic microscope having a resolution of 15 mm has been demonstrated. It uses as a coupling medium superfluid /sup 4/He colder than 0.9 K and pressurized to greater than 20 bar. ...The microscope has been used to image objects that show little or no contrast on a scanning electron microscope. In addition, the acoustic microscope has been used to study the properties of sound propagation in the coupling fluid. At low acoustic intensities, the coupling fluid has very low acoustic attenuation at the microscope's operating frequency (15.3 GHz), but near the focal point the acoustic intensity can be high enough that the helium behaves with extreme nonlinearity. In fact, this medium is capable of entering new regimes of nonlinear interaction. Plots of the received signal versus input power display a nearly complete source depletion at certain input power levels and a reconversion to the source frequency at higher power levels. Arguments that the process underlying this nonlinear behavior is harmonic generation are presented.< >
This work discusses advancements in the fields of high resolution water and superfluid helium acoustic microscopy. The reflection acoustic microscope using water as the coupling fluid has been ...operated at frequencies as high as 5 gigahertz by using ultrashort rf-pulses and acoustic lenses as small as 12 microns in radius. The smallest sound wavelength used for imaging was 3000 Angstroms and the microscope presents a resolution of better than 2000 Angstroms when a nonlinear resolution improvement technique is used. The design and fabrication of the high frequency acoustic transducers are presented. These transducers feature high conversion efficiency and wide bandwidth, and they operate at high input power levels. Several acoustic micrographs are compared with images taken with optical and electron microscopes. We can now state that the resolution of the water acoustic microscope is at least as good as that of the very best optical instruments. The operating frequency of the acoustic microscope using liquid helium at temperatures less than 0.2 K has been increased to 8 gigahertz. The design and fabrication of acoustic transducers to operate at low temperatures are described. Transducers with superconducting electrodes have been demonstrated to give superior performance as compared to similar ones fabricated with conventional techniques. A pulse compression system has been used in the electronics of the microscope to improve the signal-to-noise ratio of the instrument. The sound wavelength in liquid helium at 8 gigahertz is only 300 Angstroms and the microscope demonstrates a resolution of 200 Angstroms. The images taken with the microscope compare well to scanning and transmission electron microscope images. The use of the liquid helium microscope at much higher frequencies is also considered. Work is now underway to build a helium microscope at 96 gigahertz with sub-30 Angstroms resolution. A theoretical analysis for the operation of the 96 gigahertz acoustic transducers and matching networks is presented.
Actuation of microcantilevers in fluids has applications such as atomic force microscopy, fluid mixing and mechanical property characterization in microchannels. In this paper of a microfluidic ...actuator, which utilizes acoustic radiation pressure (ARP) to exert DC and AC forces on a microcantilever is discussed. An atomic force microscope (AFM) cantilever has been used to demonstrate the capabilities of this actuator. The method allows the application of a localized force at a desired location on a cantilever with a 5 MHz bandwidth. The localized nature of the applied force allows the characterization of flexural and torsional oscillation modes of the AFM cantilevers. Tapping mode atomic force microscopy was also carried out using the ARP actuator.
This paper reports an actuation method for atomic force microscope (AFM) cantilevers in liquids utilizing acoustic radiation pressure (ARP) generated by a focused acoustic transducer. This new method ...allows the application of a localized force of controlled amplitude at a desired location on a cantilever over a wide bandwidth (10 MHz). The localized nature of the applied forces allows the characterization of flexural and torsional oscillation modes of the AFM cantilevers. It is also demonstrated that the ARP actuator can be used for tapping mode atomic force microscope imaging.
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