Zhuochen Wang

Recent advances in particle and droplet manipulation for lab-on-a-chip devices based on surface acoustic waves.

Manipulation of microscale particles and fluid liquid droplets is an important task for lab-on-a-chip devices for numerous biological researches and applications, such as cell detection and tissue engineering. Particle manipulation techniques based on surface acoustic waves (SAWs) appear effective for lab-on-a-chip devices because they are non-invasive, compatible with soft lithography micromachining, have high energy density, and work for nearly any type of microscale particles. Here we review the most recent research and development of the past two years in SAW based particle and liquid droplet manipulation for lab-on-a-chip devices including particle focusing and separation, particle alignment and patterning, particle directing, and liquid droplet delivery.

Disruption of microalgal cells using high-frequency focused ultrasound.

The objective of this study was to evaluate the effectiveness of high-frequency focused ultrasound (HFFU) in microalgal cell disruption. Two microalgal species including Scenedesmus dimorphus and Nannochloropsis oculata were treated by a 3.2-MHz, 40-W focused ultrasound and a 100-W, low-frequency (20kHz) non-focused ultrasound (LFNFU). The results demonstrated that HFFU was effective in the disruption of microalgal cells, indicated by significantly increased lipid fluorescence density, the decrease of cell sizes, and the increase of chlorophyll a fluorescence density after treatments. Compared with LFNFU, HFFU treatment was more energy efficient. The combination of high and low frequency treatments was found to be even more effective than single frequency treatment at the same processing time, indicating that frequency played a critical role in cell disruption. In both HFFU and LFNFU treatments, the effectiveness of cell disruption was found to be dependent on the cell treated.

Design, Fabrication, and Characterization of a Bifrequency Colinear Array

Ultrasound imaging with high resolution and large penetration depth has been increasingly adopted in medical diagnosis, surgery guidance, and treatment assessment. Conventional ultrasound works at a particular frequency, with a - 6-dB fractional bandwidth of ~ 70% , limiting the imaging resolution or depth of field. In this paper, a bifrequency colinear array with resonant frequencies of 8 and 20 MHz was investigated to meet the requirements of resolution and penetration depth for a broad range of ultrasound imaging applications. Specifically, a 32-element bifrequency colinear array was designed and fabricated, followed by element characterization and real-time sectorial scan (S-scan) phantom imaging using a Verasonics system. The bifrequency colinear array was tested in four different modes by switching between low and high frequencies on transmit and receive. The four modes included the following: 1) transmit low, receive low; 2) transmit low, receive high; 3) transmit high, receive low; and 4) transmit high, receive high. After testing, the axial and lateral resolutions of all modes were calculated and compared. The results of this study suggest that bifrequency colinear arrays are potential aids for wideband fundamental imaging and harmonic/subharmonic imaging.

A 3 MHz/18 MHz dual-layer co-linear array for transrectal acoustic angiography

In this paper, a novel dual layer co-linear array ultrasound transducer was developed for transrectal dual-frequency superharmonic imaging. The KLM model and Field II were used for the acoustic stack design and simulation of the acoustic field of the array, respectively. The newly designed and fabricated probe consists of 50 transmit elements with a center frequency of 3 MHz and 100 receive elements with a center frequency of 18 MHz. The dimensions of the array are 15 mm in azimuth and 9 mm in elevation. The pitch is 270 μm for the transmitting elements and 135 μm for the receiving element. Pulse-echo testing of TX/RX elements corresponded with the simulation results. Real-time contrast imaging was tested using a multi-channel imaging system. The non-linear responses from microbubble contrast agents flowing through a 200 μm cellulose tube at a distance of 30 mm from the probe were clearly observed and displayed in the image. The axial beam width and CNR were calculated to be 200 μm and 18 dB, respectively. These results suggest that the prototyped co-linear array is capable of performing dual-frequency superharmonic imaging of microbubbles (“acoustic angiography”) for prostate cancer assessment.

Anti-Matching Design for Wave Isolation in Dual Frequency Transducer for Intravascular Super-Harmonic Imaging

Intravascular super-harmonic imaging of microvessels is expected to assist understanding of atherosclerotic cardiovascular disease. A dual frequency intravascular (IVUS) ultrasound transducer is a core component transmitting at low frequency and receiving high order harmonics. A significant challenge in developing high performance dual frequency IVUS transducers is the isolation of the high frequency ultrasound echoes from the low frequency element while keeping the low frequency transmission pressure. An anti-matching layer with low impedance and quarter wavelength thickness was designed based on wave propagation theory. In both KLM modeling and prototype validation, the anti-matching layer successfully suppressed the aliasing echo to less than −20 dB. Transmission pressure of the prototype transducer was still high enough for microbubble nonlinear responses. High resolution ( 12 dB) image was generated from super-harmonic imaging, which elucidated the capability of the transducer for intravascular microvessel detection.Copyright

Acoustic radiation force (ARF) generation with a novel dual-frequency intravascular transducer

Atherosclerosis and coronary artery disease remain the leading cause of death in the US. Coronary plaque is visualized with intravascular ultrasound (IVUS) and is typically implemented with high center frequencies (>20 MHz) for superior spatial resolution. Coronary plaque characterization may be improved by implementing elasticity imaging techniques such as acoustic radiation force impulse (ARFI) imaging using IVUS transducers. In this work we propose to extend ARFI imaging to a novel, dual-frequency small-aperture transducer design that includes a low-frequency “pushing” element and a high-frequency “tracking” element. A 40 MHz element (0.6 mm × 0.6 mm) was integrated onto a 5 MHz element (0.6 mm × 3 mm). Both elements of the transducer were fabricated from single crystal PMN-PT and the whole transducer was mounted on a 20 gauge needle tip. ARF-induced motion from the low-frequency element was quantified using optical tracking methods in a translucent phantom (~8 kPa) containing embedded graphite microparticles. Displacements induced by ARF excitations with 300, 600, 900, and 1200 cycles (5 MHz, 190 V) were captured and compared to baseline. Median (inter-quartile range) peak displacements for 300, 600, 900, and 1200 cycles were 0.33 (0.27 - 0.39) μm, 0.72 (0.62 - 0.87) μm, 1.1 (1.0 - 1.3) μm, and 1.6 (1.43 - 1.75) μm, respectively. In another phantom, 40 MHz pulse/echo RF lines were captured to demonstrate backscatter sensitivity. The results of this study show that ARF generation and high-resolution tracking is feasible on a small-aperture transducer fit for IVUS implementation.

Design, fabrication, and test of a small aperture, dual frequency ultrasound transducer

High resolution ultrasound medical imaging requires high frequency transducers, which usually are known with decreased penetration depth because of high loss in two-way-loop at high frequencies. To obtain high resolution imaging at large depth, a dual frequency transducer was designed for contrast imaging. Specifically, a 35 MHz receiving transducer with aperture of 0.6 mm x 0.6 mm was integrated into a 6.5 MHz transmitting transducer with aperture of 0.6 mm x 3 mm. High pressure ultrasound at low frequency was generated by the transducer to excited microbubbles in tissue. High frequency component of the nonlinear response from microbubbles were received by the 35 MHz transducer for high resolution imaging at a relatively large depth. The prototyped transducer showed the ability of transmitting about 2 MPa pressure at 6.5 MHz, under an input of 5-cycle burst at 250 Vpp, which is high enough to generate nonlinear oscillation of microbubbles. The pulse-echo test showed that the -6 dB bandwidth of the 35 MHz transducer is 34.4% and the loop sensitivity is -38.3 dB. The small aperture, dual frequency ultrasound transducers developed in this paper are promising for high resolution ultrasound medical imaging.

Design, fabrication and characterization of a bi-frequency co-linear array (7.5MHz/15MHz)

Ultrasound imaging with high resolution and large field of depth is important in disease diagnosis, surgery guidance and post-surgery assessment. Conventional ultrasound imaging arrays work at a particular frequency, with -6dB fractional bandwidth of <; 100%, limiting the resolution or field of depth in many ultrasound imaging cases. This paper presented design of a 7.5 MHz / 15 MHz bi-frequency co-linear array prototype with a wide bandwidth of 5MHz-20 MHz, which can be significant in a broad range of biomedical ultrasound imaging applications. To demonstrate the concept, a 32-element 1-D linear sub-array was fabricated, followed by element characterization and beamforming tests using a Verasonics system. Beam steering at +/- 40 degree was achieved without obvious side lobes. The initial results suggest great potential of this bi-frequency co-linear array for medical imaging with high resolution and large field of depth.

A dual-frequency co-linear array for prostate acoustic angiography

Approximately 80% of men who reach 80-years of age will have some form of prostate cancer. The challenge remains to differentiate indolent from aggressive disease. Based on recent research, acoustic angiography, a novel contrast enhanced ultrasound imaging technique, can provide high-resolution visualization of tissue microvasculature and has demonstrated the ability to differentiate vascular characteristics between healthy and tumor tissue. We hypothesize that transrectal acoustic angiography may enhance assessment of prostate cancer. In this paper, we describe the development of a dual layer co-linear array ultrasound transducer for transrectal acoustic angiography. The KLM model and Field II were used for the element design and acoustic field simulation, respectively. The probe consists of 64 transmit elements with a center frequency of 3 MHz and 128 receive elements with a center frequency of 15 MHz. The dimensions of the array are 18 mm in azimuth and 8 mm in elevation. The pitch is 280 μm for transmitting (TX) elements and 140 μm for receiving (RX) elements. Pulse-echo test of TX/RX elements were conducted and compared with the simulation results. Real-time contrast imaging was tested using a Verasonics system. Non-linear responses from microbubble contrast agents at a depth of 18 mm were clearly observed. The axial beam width (-6 dB) and CTR were calculated from the measured signals to be 400 μm and 20 dB, respectively. These results suggest that the prototype co-linear array is capable of performing dual-frequency superharmonic imaging of microbubbles for prostate cancer assessment.

Dual-frequency IVUS array for contrast enhanced intravascular ultrasound imaging

Recent studies suggest that contrast enhanced intravascular ultrasound (CE-IVUS) may be used for identifying vulnerable plaques through molecular imaging or detecting neovascularizations within a growing atherosclerotic lesion. However, typical intravascular ultrasound (IVUS) transducers operate at a high frequency band (20-60 MHz) which makes them not ideal for imaging microbubble contrast agents due to the less effective microbubble excitation at high frequencies. In this paper, a prototyped dual-frequency array for CE-IVUS was developed and tested. The prototype flat transducer array consists of a receiving array (32 elements, 30 MHz) built on the top of a transmitting array (8 sub-elements, 2.25 MHz) to achieve real-time superharmonic contrast enhanced imaging. The size of the receiving aperture was varied, tested and resultant images were compared. Images of a contrast-filled microtube can be observed clearly with only 4 receiving elements at an excitation voltage of 55 V, which indicates feasibility of CE-IVUS imaging after circularly wrapping the array for catheter integration.