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Background: Digital image analysis (DIA), used to extract information from pathology slides, provides better precision and no limitation regarding different interpretations by observers. Objectives: The present study aimed at evaluating the accuracy of DIA in the interpretation of borderline (2+) human epidermal growth factor receptor 2 (HER2) immunohistochemistry (IHC) slides of invasive ductal carcinoma of the breast. Methods: Sixty pathology samples with invasive ductal carcinoma of the breast were extracted based on HER2 (2+) and their fluorescence in situ hybridization (FISH), and chromogenic in situ hybridization (CISH) responses (as reference standard). The slides were digitized and, then, two pathologists examined the slides and documented diagnosis. DIA was performed by a free web application. Results: Totally, 307 digital images with 298 megabytes volume were extracted. The accuracy, sensitivity, and specificity values of DIA were 86 %, 46.1 %, and 97.8 %, respectively, with 8 false-negative cases. There was moderate agreement between the pathologist 1 (kappa = 0.42) and pathologist 2 (kappa = 0.41) with DIA. Conclusions: DIA had good accuracy and could be used for the interpretation of borderline HER2 IHC method in invasive ductal carcinoma.

Cardiac fibrosis describes the inappropriate proliferation of cardiac fibroblasts (CFs), leading to accumulation of extracellular matrix (ECM) proteins in the cardiac muscle, which is found in many pathophysiological heart conditions. A range of molecular components and cellular pathways, have been implicated in its pathogenesis. In this review, we focus on the TGF-β and WNT signaling pathways, and their mutual interaction, which have emerged as important factors involved in cardiac pathophysiology. The molecular and cellular processes involved in the initiation and progression of cardiac fibrosis are summarized. We focus on TGF-β and WNT signaling in cardiac fibrosis, ECM production, and myofibroblast transformation. Non-coding RNAs (ncRNAs) are one of the main players in the regulation of multiple pathways and cellular processes. MicroRNAs, long non-coding RNAs, and circular long non-coding RNAs can all interact with the TGF-β/WNT signaling axis to affect cardiac fibrosis. A better understanding of these processes may lead to new approaches for diagnosis and treatment of many cardiac conditions.

Focused ultrasound has been shown to be effective at stimulating neurons in many animal models, both in vivo and ex vivo. Ultrasonic neuromodulation is the only noninvasive method of stimulation that could reach deep in the brain with high spatial-temporal resolution, and thus has potential for use in clinical applications and basic studies of the nervous system. Understanding the physical mechanism by which energy in a high acoustic frequency wave is delivered to stimulate neurons will be important to optimize this technology. We imaged the isolated salamander retina of either sex during ultrasonic stimuli that drive ganglion cell activity and observed micron scale displacements, consistent with radiation force, the nonlinear delivery of momentum by a propagating wave. We recorded ganglion cell spiking activity and changed the acoustic carrier frequency across a broad range (0.5–43 MHz), finding that increased stimulation occurs at higher acoustic frequencies, ruling out cavitation as an alternative possible mechanism. A quantitative radiation force model can explain retinal responses and could potentially explain previous in vivo results in the mouse, suggesting a new hypothesis to be tested in vivo. Finally, we found that neural activity was strongly modulated by the distance between the transducer and the electrode array showing the influence of standing waves on the response. We conclude that radiation force is the dominant physical mechanism underlying ultrasonic neurostimulation in the ex vivo retina and propose that the control of standing waves is a new potential method to modulate these effects. SIGNIFICANCE STATEMENT Ultrasonic neurostimulation is a promising noninvasive technology that has potential for both basic research and clinical applications. The mechanisms of ultrasonic neurostimulation are unknown, making it difficult to optimize in any given application. We studied the physical mechanism by which ultrasound is converted into an effective energy form to cause neurostimulation in the retina and find that ultrasound acts via radiation force leading to a mechanical displacement of tissue. We further show that standing waves have a strong modulatory effect on activity. Our quantitative model by which ultrasound generates radiation force and leads to neural activity will be important in optimizing ultrasonic neurostimulation across a wide range of applications.

Capacitive micromachined ultrasonic transducers (CMUTs) with substrate-embedded springs offer highly efficient output pressure performance over conventional CMUTs, owing to their nonflexural parallel plate movement. The embedded silicon springs support thick Si piston plates, creating a large nonflexural average volume displacement efficiency in the operating frequency range from 1&ndash, 3 MHz. Static and dynamic volume displacements of the nonflexural parallel plates were examined using white light interferometry and laser Doppler vibrometry. In addition, an output pressure measurement in immersion was performed using a hydrophone. The device showed a maximum transmission efficiency of 21 kPa/V, and an average volume displacement efficiency of 1.1 nm/V at 1.85 MHz with a low DC bias voltage of 55 V. The device element outperformed the lead zirconate titanate (PZT) ceramic HD3203, in the maximum transmission efficiency or the average volume displacement efficiency by 1.35 times. Furthermore, its average volume displacement efficiency reached almost 80% of the ideal state-of-the-art single-crystal relaxor ferroelectric materials PMN-0.33PT. Additionally, we confirmed that high-efficiency output pressure could be generated from the CMUT device, by quantitatively comparing the hydrophone measurement of a commercial PZT transducer.

We developed a fully-populated 2-D capacitive micromachined ultrasonic transducer (CMUT) array for high intensity focused ultrasound (HIFU) treatment. The 2-D CMUT array, which consists of 20 × 20 square CMUT elements with an element-to-element pitch of 1 mm, was designed and fabricated using the thick-buried-oxide (BOX) fabrication process. It was then assembled on a custom interface board that can provide various array configurations depending on the desired applications. In this study, the interface board groups the CMUT array elements into eight channels, based on the phase delay from the element to the targeted focal point at a 20-mm distance from the array surface, which corresponds to an F-number of 1. An 8-channel phase generating system supplies continuous waves with eight different phases to the eight channels of the CMUT array through bias-tees and amplifiers. This array aperture, grouped into eight channels, gives a focusing gain of 6.09 according to field simulation using Field II. Assuming a...

Touchscreen sensors are widely used in many devices such as smart phones, tablets, and laptops with diverse applications. We present the design, analysis, and implementation of an ultrasonic touchscreen system that utilizes the interaction of transient Lamb waves with objects in contact with the screen. It attempts to improve on the existing ultrasound technologies, with the potential of addressing some of the weaknesses of the dominant technologies, such as the capacitive or resistive ones. Compared with the existing ultrasonic and acoustic modalities, among other advantages, it provides the capability of detecting several simultaneous touch points and also a more robust performance. The localization algorithm, given the hardware design, can detect several touch points with a very limited number of measurements (one or two). This in turn can significantly reduce the manufacturing cost.

High-intensity focused ultrasound (HIFU) has been used as noninvasive treatment for various diseases. For these therapeutic applications, capacitive micromachined ultrasonic transducers (CMUTs) have advantages that make them potentially preferred transducers over traditional piezoelectric transducers. In this paper, we present the design and the fabrication process of an $8 \times 8$ -mm $^{2}~32 \times 32$ -element 2-D CMUT array for HIFU applications. To reduce the system complexity for addressing the 1024 transducer elements, we propose to group the CMUT array elements into eight HIFU channels based on the phase delay from the CMUT element to the targeted focal point. Designed to focus at an 8-mm depth with a 5-MHz exciting frequency, this grouping scheme was realized using a custom application-specific integrated circuit. With a 40-V dc bias and a 60-V peak-to-peak ac excitation, the surface pressure was measured 1.2 MPa peak-to-peak and stayed stable for a long enough time to create a lesion. With this dc and ac voltage combination, the measured peak-to-peak output pressure at the focus was 8.5 MPa, which is expected to generate a lesion in a minute according to the temperature simulation. The following ex vivo tissue experiments successfully demonstrated its capability to make lesions in both bovine muscle and liver tissue.

Synthetic phased array (SPA) beamforming with Hadamard coding and aperture weighting is an optimal option for real-time volumetric imaging with a ring array, a particularly attractive geometry in intracardiac and intravascular applications. However, the imaging frame rate of this method is limited by the immense computational load required in synthetic beamforming. For fast imaging with a ring array, we developed graphics processing unit (GPU)-based, real-time image reconstruction software that exploits massive data-level parallelism in beamforming operations. The GPU-based software reconstructs and displays three cross-sectional images at 45 frames per second (fps). This frame rate is 4.5 times higher than that for our previously-developed multi-core CPU-based software. In an alternative imaging mode, it shows one B-mode image rotating about the axis and its maximum intensity projection, processed at a rate of 104 fps . This paper describes the image reconstruction procedure on the GPU platform and presents the experimental images obtained using this software.

A method is introduced to monitor cardiac ablative therapy by examining slope changes in the thermal strain curve caused by speed of sound variations with temperature. The sound speed of water-bearing tissue such as cardiac muscle increases with temperature. However, at temperatures above about 50°C, there is no further increase in the sound speed and the temperature coefficient may become slightly negative. For ablation therapy, an irreversible injury to tissue and a complete heart block occurs in the range of 48 to 50°C for a short period in accordance with the well-known Arrhenius equation. Using these two properties, we propose a potential tool to detect the moment when tissue damage occurs by using the reduced slope in the thermal strain curve as a function of heating time. We have illustrated the feasibility of this method initially using porcine myocardium in vitro. The method was further demonstrated in vivo, using a specially equipped ablation tip and an 11-MHz microlinear intracardiac echocardiography (ICE) array mounted on the tip of a catheter. The thermal strain curves showed a plateau, strongly suggesting that the temperature reached at least 50°C.

Minimally invasive catheter-based electrophysiological (EP) interventions are becoming a standard procedure in diagnosis and treatment of cardiac arrhythmias. As a result of technological advances that enable small feature sizes and a high level of integration, nonfluoroscopic intracardiac echocardiography (ICE) imaging catheters are attracting increasing attention. ICE catheters improve EP procedural guidance while reducing the undesirable use of fluoroscopy, which is currently the common catheter guidance method. Phased-array ICE catheters have been in use for several years now, although only for side-looking imaging. We are developing a forward-looking ICE catheter for improved visualization. In this effort, we fabricate a 24-element, fine-pitch 1-D array of capacitive micromachined ultrasonic transducers (CMUT), with a total footprint of 1.73 mm x 1.27 mm. We also design a custom integrated circuit (IC) composed of 24 identical blocks of transmit/ receive circuitry, measuring 2.1 mm x 2.1 mm. The transmit circuitry is capable of delivering 25-V unipolar pulses, and the receive circuitry includes a transimpedance preamplifier followed by an output buffer. The CMUT array and the custom IC are designed to be mounted at the tip of a 10-Fr catheter for high-frame-rate forward-looking intracardiac imaging. Through-wafer vias incorporated in the CMUT array provide access to individual array elements from the back side of the array. We successfully flip-chip bond a CMUT array to the custom IC with 100% yield. We coat the device with a layer of polydimethylsiloxane (PDMS) to electrically isolate the device for imaging in water and tissue. The pulse-echo in water from a total plane reflector has a center frequency of 9.2 MHz with a 96% fractional bandwidth. Finally, we demonstrate the imaging capability of the integrated device on commercial phantoms and on a beating ex vivo rabbit heart (Langendorff model) using a commercial ultrasound imaging system.

This brief analyzes the effect of load capacitor mismatch on the offset of a regenerative latch comparator. Two analytical models are presented and compared with HSpice simulations. Our results indicate that in a typical 0.18-mum CMOS latch, a capacitive imbalance of only 1 fF can lead to offsets of several tens of millivolts

A conventional capacitive micromachined ultrasonic transducer (CMUT) is composed of many cells connected in parallel. Since the plate in each CMUT cell is anchored at its perimeter, the average displacement is several times smaller than the displacement of an equivalent ideal piston transducer. In addition, the post areas, where the plates are anchored to, are non-active and, thus, do not contribute to the transduction. We propose a CMUT structure that resembles an ideal capacitive piston transducer, where the movable top plate only undergoes translation rather than deflection. Our proposed CMUT structure is composed of a rigid plate connected to a substrate using relatively long and narrow posts, providing the spring constant for the movement of the plate. Rather than the flexure of the plate as in a conventional CMUT, this device operates based on the compression of the compliant posts. For a capacitive transducer, a thin electrostatic gap is provided under the top plate. We used finite element analysis (FEA) to design and verify the structure's functionality. The simulation results show a fractional bandwidth of over 100% in immersion for all the designs. They also confirm that the average displacement of the top plate is above 90% of its peak displacement. We fabricated the first prototype based on this idea, which only requires a simple 3-mask fabrication process. In addition to 128-element 1-D arrays, we fabricated a variety of 240 µm × 240 µm, single-element transducers with different post configurations. We successfully measured the electrical input impedance of the fabricated devices and confirmed their resonant behavior in air. Further, we measured the acoustic pressure using a calibrated hydrophone at a known distance. Using this measurement, we calculated a peak-to-peak pressure of 1.5 MPa at the face of the transducer. Our results show that it is possible to fabricate CMUTs that exhibit ideal piston-like plate movement. Because of the substrate-embedded spring elements, the plate does not need to be operated in flexural mode, as in a conventional CMUT, resulting in a significantly improved fill-factor, and, thus, a more efficient device.

A ring array provides a very suitable geometry for forward-looking volumetric intracardiac and intravascular ultrasound imaging. We fabricated an annular 64-element capacitive micromachined ultrasonic transducer (CMUT) array featuring a 10-MHz operating frequency and a 1.27-mm outer radius. A custom software suite was developed to run on a PC-based imaging system for real-time imaging using this device. This paper presents simulated and experimental imaging results for the described CMUT ring array. Three different imaging methods--flash, classic phased array (CPA), and synthetic phased array (SPA)--were used in the study. For SPA imaging, two techniques to improve the image quality--Hadamard coding and aperture weighting--were also applied. The results show that SPA with Hadamard coding and aperture weighting is a good option for ring-array imaging. Compared with CPA, it achieves better image resolution and comparable signal-to-noise ratio at a much faster image acquisition rate. Using this method, a fast frame rate of up to 463 volumes per second is achievable if limited only by the ultrasound time of flight; with the described system we reconstructed three cross-sectional images in real-time at 10 frames per second, which was limited by the computation time in synthetic beamforming.

Electrophysiologic interventions have had increasing popularity as treatment options for arrhythmias, particularly atrial fibrillation.1 Atrial fibrillation is the most common arrhythmia, with an incidence of 2 to 3 per 1000 people aged 55 to 64 years annually,2 and is associated with considerable morbidity and mortality.3,4 There are at least 3 techniques available to interventionalists that can accurately locate intracardiac regions of interest, with fluoroscopy being the most established technique. However, the exposure to ionizing radiation, as well as the inability of fluoroscopy to clearly delineate subsurface intracardiac regions and confirm catheter contact with the endocardium, has made echocardiography and electroanatomic mapping (EAM) the most attractive as adjunct modalities.5–9 Intracardiac echocardiography (ICE), in particular, has found multiple uses in the electrophysiology laboratory, providing real-time display of intracardiac structures.6–8 The use of ultrasound image guidance for interventional radiofrequency ablation (RFA) procedures in the heart has begun to play a more important role in the minimization of fluoroscopic radiation exposure to the patient while imaging important intracardiac features, eg, the membranous fossa of the interatrial septum for puncture access to the left atrium, the pulmonary veins, and Doppler blood velocities associated with pulmonary vein stenosis.10 Important considerations in the design of ICE catheters are the (1) imaging and handling performance features, (2), compatibility with current interventional practice, and (3) cost in both procedural time and purchasing expense. Overall, a catheter that can be itself guided into place with EAM, perform high-quality image guidance of RFA therapy, and improve procedural throughput at a lower cost is a worthwhile goal. As a general guide, Table 1 compares the common RFA catheter with an “ideal” catheter and with the initial features of a proposed progenitor, a microlinear capacitive micromachined ultrasound transducer (ML-CMUT) catheter. Table 1 Performance Parameter Objectives for Catheters Used in Radiofrequency Ablation Procedures The miniaturization of ICE catheters has revolutionized interventional procedures by integrating ultrasound transducers onto flexible, low-profile catheters, which allow imaging in the restricted spaces of vascular and cardiac structures.11–13 Two distinctly different ICE catheter prototypes, descriptively referred as ML catheters because of their small ultrasonic array designs, have been developed within a program to build a series of miniaturized high-frequency forward-looking transducer arrays.14 Piezoceramic arrays, namely those made with lead zirconate titanate (PZT), are considered standard design types for most ultrasound applications. Currently in their third generation of development, our early ML devices are called ML-PZT array catheters. The second array transducer type is the CMUT, now in its second generation of development15; these CMUT arrays are used in the assembly of the ML-CMUT array catheter (Figure 1). By comparison to PZT, the CMUT as an acoustic transducer is relatively new as an ultrasound transceiver. This silicon-based array, however, has several design aspects that may yield a considerable advantage over the PZT array type, especially at small sizes. The small-element CMUT array in combination with a local buffer-preamplifier offers excellent transmit and receive sensitivity with a wide bandwidth, allows special element shaping, does not require acoustic matching layers, and may be considerably less expensive in large-scale manufacturing. Figure 1 Prefinished distal tip (a) of the 9F microlinear capacitive micromachined ultrasound transducer (CMUT) intracardiac imaging catheter with a metal radiofrequency ablation tip electrode, and the 24-element CMUT array (b) with silicon die dimensions of 1.9 ... The principal objective of this work is to describe the first in vivo use of a forward-looking ML-CMUT array catheter in a true 9F profile, the catheter compatibility with EAM guidance, and the use of a specially integrated RFA tip capable of both monitoring and delivery of intracardiac ablation. This work represents the first in vivo ablation and direct simultaneous collection of tissue echo data for the thermal strain temperature at the exact ablation site. In addition, we describe the initial use of the ML-CMUT catheter in exploratory cardiac imaging from the perspective of the epicardial surface from within the pericardium.

Capacitive micromachined ultrasonic transducer (CMUT) arrays are conveniently integrated with frontend integrated circuits either monolithically or in a hybrid multichip form. This integration helps with reducing the number of active data processing channels for 2D arrays. This approach also preserves the signal integrity for arrays with small elements. Therefore CMUT arrays integrated with electronic circuits are most suitable to implement miniaturized probes required for many intravascular, intracardiac, and endoscopic applications. This paper presents examples of miniaturized CMUT probes utilizing 1D, 2D, and ring arrays with integrated electronics.

State-of-the-art 3-D medical ultrasound imaging requires transmitting and receiving ultrasound using a 2-D array of ultrasound transducers with hundreds or thousands of elements. A tight combination of the transducer array with integrated circuitry eliminates bulky cables connecting the elements of the transducer array to a separate system of electronics. Furthermore, preamplifiers located close to the array can lead to improved receive sensitivity. A combined IC and transducer array can lead to a portable, high-performance, and inexpensive 3-D ultrasound imaging system. This paper presents an IC flip-chip bonded to a 16 x 16-element capacitive micromachined ultrasonic transducer (CMUT) array for 3-D ultrasound imaging. The IC includes a transmit beamformer that generates 25-V unipolar pulses with programmable focusing delays to 224 of the 256 transducer elements. One-shot circuits allow adjustment of the pulse widths for different ultrasound transducer center frequencies. For receiving reflected ultrasound signals, the IC uses the 32-elements along the array diagonals. The IC provides each receiving element with a low-noise 25-MHz-bandwidth transimpedance amplifier. Using a field-programmable gate array (FPGA) clocked at 100 MHz to operate the IC, the IC generated property timed transmit pulses with 5-ns accuracy. With the IC flip-chip bonded to a CMUT array, we show that the IC can produce steered and focused ultrasound beams. We present 2-D and 3-D images of a wire phantom and 2-D orthogonal cross-sectional images (B-scans) of a latex heart phantom. This work was supported by NIH grant CA99059. Work was performed in part at the Stanford Nanofabrication Facility (a member of the National Nanotechnology Infrastructure, Network) which is supported by the National Science Foundation under Grant ECS-9731293. Publisher's Version Q2 WOS:000270592000011 PubMed ID: 19942502

Our Bioengineering Research Partnership grant, “High Frequency Ultrasound Arrays for Cardiac Imaging”, including the individuals cited at the end of this paper - Douglas N. Stephens (UC Davis), Matthew O’Donnell (UW Seattle), Kai Thomenius (GE Global Research), Aaron M. Dentinger (GE Global Research), Douglas Wildes (GE Global Research), Peter Chen (St. Jude Medical), K. Kirk Shung (University of Southern California), Jonathan M. Cannata (University of Southern California), Butrus (Pierre) T. Khuri-Yakub (Stanford University), Omer Oralkan (Stanford University), Aman Mahajan (UCLA School of Medicine), Kalyanam Shivkumar (UCLA School of Medicine) and David J. Sahn (Oregon Health & Science University) – is in its sixth year of NIH funding, having proposed to develop a family of high frequency miniaturized forward and side-looking ultrasound imaging devices equipped with electrophysiology mapping and localization sensors and eventually to include a family of capactive micromachined ultrasonic transducer (cMUT) devices – a forward-looking cMUT MicroLinear array and a ring array capable of 3-dimensional imaging and a 5Fr lumen large enough to admit an electrode and ablation devices.

A family of 3 multifunctional intracardiac imaging and electrophysiology (EP) mapping catheters has been in development to help guide diagnostic and therapeutic intracardiac EP procedures. The catheter tip on the first device includes a 7.5 MHz, 64-element, side-looking phased array for high resolution sector scanning. The second device is a forward-looking catheter with a 24-element 14 MHz phased array. Both of these catheters operate on a commercial imaging system with standard software. Multiple EP mapping sensors were mounted as ring electrodes near the arrays for electrocardiographic synchronization of ultrasound images and used for unique integration with EP mapping technologies. To help establish the catheters' ability for integration with EP interventional procedures, tests were performed in vivo in a porcine animal model to demonstrate both useful intracardiac echocardiographic (ICE) visualization and simultaneous 3-D positional information using integrated electroanatomical mapping techniques. The catheters also performed well in high frame rate imaging, color flow imaging, and strain rate imaging of atrial and ventricular structures. The companion paper of this work discusses the catheter design of the side-looking catheter with special attention to acoustic lens design. The third device in development is a 10 MHz forward-looking ring array that is to be mounted at the distal tip of a 9F catheter to permit use of the available catheter lumen for adjunctive therapy tools.

Real-time catheter-based ultrasound imaging tools are needed for diagnosis and image-guided procedures. The continued development of these tools is partially limited by the difficulty of fabricating two-dimensional array geometries of piezoelectric transducers. Using capacitive micromachined ultrasonic transducer (CMUT) technology, transducer arrays with widely varying geometries, high frequencies, and wide bandwidths can be fabricated. A volumetric ultrasound imaging system based on a two-dimensional, 16×16-element, CMUT array is presented. Transducer arrays with operating frequencies ranging from 3 MHz to 7.5 MHz were fabricated for this system. The transducer array including DC bias pads measures 4 mm by 4.7 mm. The transducer elements are connected to flip-chip bond pads on the array back side with 400-µm long through-wafer interconnects. The array is flip-chip bonded to a custom- designed integrated circuit (IC) that comprises the front-end electronics. Integrating the front-end electronics with the transducer array reduces the effects of cable capacitance on the transducer's performance and provides a compact means of connecting to the transducer elements. The front-end IC provides a 27-V pulser and 10-MHz bandwidth amplifier for each element of the array. An FPGA-based data acquisition system is used for control and data acquisition. Output pressure of 230 kPa was measured for the integrated device. A receive sensitivity of 125 mV/kPa was measured at the output of the amplifier. Amplifier output noise at 5 Mhz is 112 nV/√Hz. Volumetric images of a wire phantom and vessel phantom are presented. Volumetric data for a wire phantom was acquired in real-time at 30 frames per second. Keywords-ultrasound imaging, catheter, capacitive micromachined ultrasonic transducer, CMUT, integrated electronics, volumetric, real-time

Electrostatic transducers are usually operated under a DC bias below their collapse voltage. The same scheme has been adopted for capacitive micromachined ultrasonic transducers (cMUTs). DC bias deflects the cMUT membranes toward the substrate, so that their centers are free to move during both receive and transmit operations. In this paper, we present time-domain, finite element calculations for cMUTs using LS-DYNA, a commercially available finite element package. In addition to this DC bias mode, other new cMUT operations (collapse and collapse-snapback) have recently been demonstrated. Because cMUT membranes make contact with the substrate in these new operations, modeling of these cMUTs should include contact analysis. Our model was a cMUT transducer consisting of many hexagonal membranes; because it was symmetrical, we modeled only one-sixth of a hexagonal cell loaded with a fluid medium. The finite element results for both conventional and collapse modes were compared to measurements made by an optical interferometer; a good match was observed. Thus, the model is useful for designing cMUTs that operate in regimes where membranes make contact with the substrate.

We present the design of an integrated circuit (IC) that will be flip-chip bonded to a 16 x 16-element CMUT array. The IC provides 16 receive channels which can be configured to receive along either of the array diagonals or on any single row of the array. On transmit, all 256 elements can be used to transmit arbitrarily focused beams. Focused transmission with the full array is made possible by on-chip pulsers and memory. A 25-V pulser and 8-bit shift register is provided for each element of the array. Prior to each transmit, new values are loaded into the shift registers. Current-con trolled one-shots control the transmit pulse widths. Circuit simulations and the IC layout are presented. Simulations predict that delay values can be loaded in less than 1.3 mu s and show the generation of precisely timed pulses. The IC is being prepared for submission to National Semiconductor for fabrication in a high-voltage BiCMOS process.

This paper describes the development of an ultrasonic imaging system based on a two-dimensional capacitive micromachined ultrasonic transducer (CMUT) array. The transducer array and front-end electronics are designed to fit in a 5-mm endoscopic channel. A custom-designed integrated circuit, which comprises the front-end electronics, will be connected with the transducer elements via through-wafer interconnects and flip-chip bonding. FPGA-based signal-processing hardware will provide real-time three-dimensional imaging. The imaging system is being developed to demonstrate a means of integrating the front-end electronics with the transducer array and to provide a clinically useful technology. Integration of the electronics can improve signal-to-noise ratio, reduce the number of cables connecting the imaging probe to a separate processing unit, and provide a means of connecting electronics to large two-dimensional transducer arrays. This paper describes the imaging system architecture and the progress we have made on implementing each of its components: a 16×16 CMUT array, custom-designed integrated circuits, a flip-chip bonding technique, and signal-processing hardware. Publisher's Version

We have designed, fabricated, and characterized two-dimensional 16x16-element capacitive micromachined ultrasonic transducer (CMUT) arrays. The CMUT array elements have a 250-μm pitch, and when tested in immersion, have a 5 MHz center frequency and 99% fractional bandwidth. The fabrication process is based on standard silicon micromachining techniques and therefore has the advantages of high yield, low cost, and ease of integration. The transducers have a Si3N4 membrane and are fabricated on a 400-μm thick silicon substrate. A low parasitic capacitance through-wafer via connects each CMUT element to a flip-chip bond pad on the back side of the wafer. Each through wafer via is 20 μm in diameter and 400 μm deep. The interconnects form metal-insulator-semiconductor (MIS) junctions with the surrounding high-resistivity silicon substrate to establish isolation and to reduce parasitic capacitance. Each through-wafer via has less than 0.06 pF of parasitic capacitance. We have investigated a Au-In flip-chip bonding process to connect the 2D CMUT array to a custom integrated circuit (IC) with transmit and receive electronics. To develop this process, we fabricated fanout structures on silicon, and flip-chip bonded these test dies to a flat surface coated with gold. The average series resistance per bump is about 3 Ohms, and 100% yield is obtained for a total of 30 bumps.

Singulation of MEMS is a critical step in the transition from wafer-level to die-level devices. As is the case for capacitive micromachined ultrasound transducer (CMUT) ring arrays, an ideal singulation must protect the fragile membranes from the processing environment while maintaining a ring array geometry. The singulation process presented in this paper involves bonding a trench-patterned CMUT wafer onto a support wafer, deep reactive ion etching (DRIE) of the trenches, separating the CMUT wafer from the support wafer and de-tethering the CMUT device from the CMUT wafer. The CMUT arrays fabricated and singulated in this process were ring-shaped arrays, with inner and outer diameters of 5 mm and 10 mm, respectively. The fabricated CMUT ring arrays demonstrate the ability of this method to successfully and safely singulate the ring arrays and is applicable to any arbitrary 2D shaped MEMS device with uspended microstructures, taking advantage of the inherent planar attributes of DRIE.