Chi Tat Chiu

Acoustic trapping with a high frequency linear phased array

A high frequency ultrasonic phased array is shown to be capable of trapping and translating microparticles precisely and efficiently, made possible due to the fact that the acoustic beam produced by a phased array can be both focused and steered. Acoustic manipulation of microparticles by a phased array is advantageous over a single element transducer since there is no mechanical movement required for the array. Experimental results show that 45 μm diameter polystyrene microspheres can be easily and accurately trapped and moved to desired positions by a 64-element 26 MHz phased array.

Ultrahigh Frequency (100 MHz-300 MHz) Ultrasonic Transducers for Optical Resolution Medical Imagining.

High resolution ultrasonic imaging requires high frequency wide band ultrasonic transducers, which produce short pulses and highly focused beam. However, currently the frequency of ultrasonic transducers is limited to below 100 MHz, mainly because of the challenge in precise control of fabrication parameters. This paper reports the design, fabrication, and characterization of sensitive broadband lithium niobate (LiNbO3) single element ultrasonic transducers in the range of 100–300 MHz, as well as their applications in high resolution imaging. All transducers were built for an f-number close to 1.0, which was achieved by press-focusing the piezoelectric layer into a spherical curvature. Characterization results demonstrated their high sensitivity and a −6 dB bandwidth greater than 40%. Resolutions better than 6.4 μm in the lateral direction and 6.2 μm in the axial direction were achieved by scanning a 4 μm tungsten wire target. Ultrasonic biomicroscopy images of zebrafish eyes were obtained with these transducers which demonstrate the feasibility of high resolution imaging with a performance comparable to optical resolution.

Systematic study of high-frequency ultrasonic transducer design for laser-scanning photoacoustic ophthalmoscopy

Abstract. Photoacoustic ophthalmoscopy (PAOM) is a high-resolution in vivo imaging modality that is capable of providing specific optical absorption information for the retina. A high-frequency ultrasonic transducer is one of the key components in PAOM, which is in contact with the eyelid through coupling gel during imaging. The ultrasonic transducer plays a crucial role in determining the image quality affected by parameters such as spatial resolution, signal-to-noise ratio, and field of view. In this paper, we present the results of a systematic study on a high-frequency ultrasonic transducer design for PAOM. The design includes piezoelectric material selection, frequency selection, and the fabrication process. Transducers of various designs were successfully applied for capturing images of biological samples in vivo. The performances of these designs are compared and evaluated.

Direct and sustained intracellular delivery of exogenous molecules using acoustic-transfection with high frequency ultrasound

Controlling cell functions for research and therapeutic purposes may open new strategies for the treatment of many diseases. An efficient and safe introduction of membrane impermeable molecules into target cells will provide versatile means to modulate cell fate. We introduce a new transfection technique that utilizes high frequency ultrasound without any contrast agents such as microbubbles, bringing a single-cell level targeting and size-dependent intracellular delivery of macromolecules. The transfection apparatus consists of an ultrasonic transducer with the center frequency of over 150 MHz and an epi-fluorescence microscope, entitled acoustic-transfection system. Acoustic pulses, emitted from an ultrasonic transducer, perturb the lipid bilayer of the cell membrane of a targeted single-cell to induce intracellular delivery of exogenous molecules. Simultaneous live cell imaging using HeLa cells to investigate the intracellular concentration of Ca2+ and propidium iodide (PI) and the delivery of 3 kDa dextran labeled with Alexa 488 were demonstrated. Cytosolic delivery of 3 kDa dextran induced via acoustic-transfection was manifested by diffused fluorescence throughout whole cells. Short-term (6 hr) cell viability test and long-term (40 hr) cell tracking confirmed that the proposed approach has low cell cytotoxicity.

Non-contact high-frequency ultrasound microbeam stimulation for studying mechanotransduction in human umbilical vein endothelial cells.

We describe how contactless high-frequency ultrasound microbeam stimulation (HFUMS) is capable of eliciting cytoplasmic calcium (Ca(2+)) elevation in human umbilical vein endothelial cells. The cellular mechanotransduction process, which includes cell sensing and adaptation to the mechanical micro-environment, has been studied extensively in recent years. A variety of tools for mechanical stimulation have been developed to produce cellular responses. We developed a novel tool, a highly focused ultrasound microbeam, for non-contact cell stimulation at a microscale. This tool, at 200 MHz, was applied to human umbilical vein endothelial cells to investigate its potential to elicit an elevation in cytoplasmic Ca(2+) levels. It was found that the response was dose dependent, and moreover, extracellular Ca(2+) and cytoplasmic Ca(2+) stores were involved in the Ca(2+) elevation. These results suggest that high-frequency ultrasound microbeam stimulation is potentially a novel non-contact tool for studying cellular mechanotransduction if the acoustic pressures at such high frequencies can be quantified.

Laser-scanning photoacoustic microscopy with ultrasonic phased array transducer

In this paper, we report our latest progress on proving the concept that ultrasonic phased array can improve the detection sensitivity and field of view (FOV) in laser-scanning photoacoustic microscopy (LS-PAM). A LS-PAM system with a one-dimensional (1D) ultrasonic phased array was built for the experiments. The 1D phased array transducer consists of 64 active elements with an overall active dimension of 3.2 mm × 2 mm. The system was tested on imaging phantom and mouse ear in vivo. Experiments showed a 15 dB increase of the signal-to-noise ratio (SNR) when beamforming was employed compared to the images acquired with each single element. The experimental results demonstrated that ultrasonic phased array can be a better candidate for LS-PAM in high sensitivity applications like ophthalmic imaging.

High-resolution harmonic motion imaging (HR-HMI) for tissue biomechanical property characterization.

BACKGROUND Elastography, capable of mapping the biomechanical properties of biological tissues, serves as a useful technique for clinicians to perform disease diagnosis and determine stages of many diseases. Many acoustic radiation force (ARF) based elastography, including acoustic radiation force impulse (ARFI) imaging and harmonic motion imaging (HMI), have been developed to remotely assess the elastic properties of tissues. However, due to the lower operating frequencies of these approaches, their spatial resolutions are insufficient for revealing stiffness distribution on small scale applications, such as cancerous tumor margin detection, atherosclerotic plaque composition analysis and ophthalmologic tissue characterization. Though recently developed ARF-based optical coherence elastography (OCE) methods open a new window for the high resolution elastography, shallow imaging depths significantly limit their usefulness in clinics. METHODS The aim of this study is to develop a high-resolution HMI method to assess the tissue biomechanical properties with acceptable field of view (FOV) using a 4 MHz ring transducer for efficient excitation and a 40 MHz needle transducer for accurate detection. Under precise alignment of two confocal transducers, the high-resolution HMI system has a lateral resolution of 314 µm and an axial resolution of 
147 µm with an effective FOV of 2 mm in depth. RESULTS The performance of this high resolution imaging system was validated on the agar-based tissue mimicking phantoms with different stiffness distributions. These data demonstrated the imaging systems improved resolution and sensitivity on differentiating materials with varying stiffness. In addition, ex vivo imaging of a human atherosclerosis coronary artery demonstrated the capability of high resolution HMI in identifying layer-specific structures and characterizing atherosclerotic plaques based on their stiffness differences. CONCLUSIONS All together high resolution HMI appears to be a promising ultrasound-only technology for characterizing tissue biomechanical properties at the microstructural level to improve the image-based diseases diagnosis in multiple clinical applications.

Design of matching layers for high-frequency ultrasonic transducers.

Matching the acoustic impedance of high-frequency (≥100 MHz) ultrasound transducers to an aqueous loading medium remains a challenge for fabricating high-frequency transducers. The traditional matching layer design has been problematic to establish high matching performance given requirements on both specific acoustic impedance and precise thickness. Based on both mass-spring scheme and microwave matching network analysis, we interfaced metal-polymer layers for the matching effects. Both methods hold promises for guiding the metal-polymer matching layer design. A 100 MHz LiNbO3 transducer was fabricated to validate the performance of the both matching layer designs. In the pulse-echo experiment, the transducer echo amplitude increased by 84.4% and its -6dB bandwidth increased from 30.2% to 58.3% comparing to the non-matched condition, demonstrating that the matching layer design method is effective for developing high-frequency ultrasonic transducers.

Fabrication and characterization of a 20 MHz microlinear phased array transducer for intervention guidance

This paper describes the design and fabrication of a miniature ultrasonic phased array transducer used for intervention guidance. Interventional procedures such as biopsy have been widely carried out in clinics for both diagnostic and therapeutic purposes of many different kinds of diseases, including cancer and cardiovascular disease. Due to its real-time imaging capability and non-radiating nature, ultrasound has been one of the common guiding tools for interventional procedures. However, currently the ultrasound probes are often placed at the body surface, which leads to several drawbacks including the limitations of image depth and quality. In this work, a miniature phased array transducer that can be placed adjacent to the intervention device has been developed. The array transducer comprised 48 elements and was placed in a 4-mm needle housing. The measured average center frequency and the bandwidth were around 18.5 MHz and 61% respectively. The measured axial and lateral image resolutions of the transducer were 80 μm and 210 μm respectively. The imaging capability of the transducer was evaluated by acquiring the B-mode images of a needle in a cow liver. The performance of the proposed phased array transducer demonstrates the feasibility of such an approach for interventional guidance.

Low cross-talk kerfless annular array ultrasound transducers using 1–3 piezocomposites with pseudo-random pillars

This paper describes the design and fabrication of a high-frequency kerfless annular array transducer utilizing a novel 1-3 piezocomposite which was designed to reduce inter-element cross-talk. 1-3 piezocomposites have significant advantages over bulk piezoelectric materials and other types of piezocomposites; however, their benefits come at the expense of introducing more undesired interpillar resonances. At high frequencies, this is especially detrimental to kerfless annular array transducers. We have previously shown that this unwanted coupling effect (high inter-element crosstalk), can be further reduced by employing a pseudo-random pillar geometry. Utilizing the 1-3 composites with the pseudo-random pillars, a 40 MHz annular array transducer was fabricated. Each annular array was designed to have six equal-area elements and a center frequency of 40 MHz. The average center frequency estimated from the measured pulse-echo responses of array elements was 38.7 MHz and the -6 dB bandwidth was 51 %. The average insertion loss recorded was 23.1 dB, and the maximum combined crosstalk between the adjacent elements was less than -31 dB. These results demonstrate that the 1-3 piezocomposite with the pseudo-random pillars may be a better choice for fabricating enhanced high frequency linear array ultrasound transducers; especially when mechanical dicing is used.