Singulation for imaging ring arrays of capacitive micromachined ultrasonic transducers.

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.

Ginsenoside CK Inhibits TGF-ß-Induced Epithelial-Mesenchymal Transition in A549 Cell via SIRT1.

Ginsenoside CK is the main metabolite of protopanaxadiol saponins in intestinal bacteria. Previous studies have shown that ginsenoside CK can affect many aspects of tumor development through a variety of mechanisms. However, few studies have reported the antimetastatic effects of ginsenoside CK in non-small-cell lung cancer (NSCLC). In this study, we explored the effect of ginsenoside CK on epithelial-mesenchymal transition (EMT) induced by TGF-ß in A549 cells and the potential molecular mechanisms. Our data showed that ginsenoside CK effectively prevented TGF-ß-induced EMT, as indicated by the upregulation of E-cadherin and downregulation of vimentin. Furthermore, ginsenoside CK inhibited the metastatic ability of A549 cells in the tail vein lung metastasis model of nude mice. Additionally, ginsenoside CK decreased the expression of silent information regulator 2 homolog 1 (SIRT1) in the inhibition of EMT induced by TGF-ß. Moreover, the antimetastatic effect of ginsenoside CK was reversed by SIRT1 overexpression. Generally, our results indicated the antimetastatic effect and underlying mechanism of ginsenoside CK on TGF-ß-induced EMT in A549 cells, suggesting that ginsenoside CK can be used as an effective antineoplastic agent.

Encapsulation of Capacitive Micromachined Ultrasonic Transducers Using Viscoelastic Polymer.

The packaging of a medical imaging or therapeutic ultrasound transducer should provide protective insulation while maintaining high performance. For a capacitive micromachined ultrasonic transducer (CMUT), an ideal encapsulation coating would therefore require a limited and predictable change on the static operation point and the dynamic performance, while insulating the high dc and dc actuation voltages from the environment. To fulfill these requirements, viscoelastic materials, such as polydimethylsiloxane (PDMS), were investigated for an encapsulation material. In addition, PDMS, with a glass-transition temperature below room temperature, provides a low Young's modulus that preserves the static behavior; at higher frequencies for ultrasonic operation, this material becomes stiffer and acoustically matches to water. In this paper, we demonstrate the modeling and implementation of the viscoelastic polymer as the encapsulation material. We introduce a finite element model (FEM) that addresses viscoelasticity. This enables us to correctly calculate both the static operation point and the dynamic behavior of the CMUT. CMUTs designed for medical imaging and therapeutic ultrasound were fabricated and encapsulated. Static and dynamic measurements were used to verify the FEM and show excellent agreement. This paper will help in the design process for optimizing the static and the dynamic behavior of viscoelastic-polymer-coated CMUTs.

Panax notoginsenoside Rb1 Restores the Neurotrophic Imbalance Following Photothrombotic Stroke in Rats.

Mature brain-derived neurotrophic factor (mBDNF) has neuroprotection in cerebral ischemia. Conversely, the precursor of brain-derived neurotrophic factor (proBDNF) has the opposite function to its mature form, inducing apoptosis. However, whether the neuroprotection of Panax notoginsenoside Rb1 (PNS-Rb1) on ischemic stroke is due to, at least partially, its modulation of suppressing proBDNF/P75NTR/sortilin or upregulation of mBDNF is not clear. To test this hypothesis, rats induced by photothrombotic stroke were treated with PNS-Rb1 100 mg/kg or nimodipine 1 mg/kg twice a day until 3, 7, and 14 days. Our data indicate that PNS-Rb1 significantly reduced cerebral infarction rate, proBDNF/P75NTR/sortilin, and plasminogen activator inhibitor-1 (PAI-1) protein levels, and improved sensorimotor dysfunctions induced by ischemic stroke, upregulation of BDNF/TrkB levels, and its processing enzymes (tissue plasminogen activator, tPA) in a time-dependent manner. Taken together, our findings indicate that the improvement of sensorimotor dysfunctions by PNS-Rb1 following ischemic stroke is made, at least partially, by activating the BDNF/TrkB and inhibiting proBDNF/sortilin/P75NTR.

Integration of 2D CMUT arrays with front-end electronics for volumetric ultrasound imaging.

For three-dimensional (3D) ultrasound imaging, connecting elements of a two-dimensional (2D) transducer array to the imaging system's front-end electronics is a challenge because of the large number of array elements and the small element size. To compactly connect the transducer array with electronics, we flip-chip bond a 2D 16 x 16-element capacitive micromachined ultrasonic transducer (CMUT) array to a custom-designed integrated circuit (IC). Through-wafer interconnects are used to connect the CMUT elements on the top side of the array with flip-chip bond pads on the back side. The IC provides a 25-V pulser and a transimpedance preamplifier to each element of the array. For each of three characterized devices, the element yield is excellent (99 to 100% of the elements are functional). Center frequencies range from 2.6 MHz to 5.1 MHz. For pulse echo operation, the average - 6-dB fractional bandwidth is as high as 125%. Transmit pressures normalized to the face of the transducer are as high as 339 kPa and input-referred receiver noise is typically 1.2 to 2.1 mPa/pHz. The flip-chip bonded devices were used to acquire 3D synthetic aperture images of a wire-target phantom. Combining the transducer array and IC, as shown in this paper, allows for better utilization of large arrays, improves receive sensitivity, and may lead to new imaging techniques that depend on transducer arrays that are closely coupled to IC electronics.

Integration of Trench-Isolated Through-Wafer Interconnects with 2D Capacitive Micromachined Ultrasonic Transducer Arrays.

This paper presents a method to provide electrical connection to a 2D capacitive micromachined ultrasonic transducer (CMUT) array. The interconnects are processed after the CMUTs are fabricated on the front side of a silicon wafer. Connections to array elements are made from the back side of the substrate via highly conductive silicon pillars that result from a deep reactive ion etching (DRIE) process. Flip-chip bonding is used to integrate the CMUT array with an integrated circuit (IC) that comprises the front-end circuits for the transducer and provides mechanical support for the trench-isolated array elements. Design, fabrication process and characterization results are presented. The advantages when compared to other through-wafer interconnect techniques are discussed.

Comparison of conventional and collapsed region operation of capacitive micromachined ultrasonic transducers.

We report experimental results from a comparative study on collapsed region and conventional region operation of capacitive micromachined ultrasonic transducers (CMUTs) fabricated with a wafer bonding technique. Using ultrasonic pulse-echo and pitch-catch measurements, we characterized single elements of 1-D CMUT arrays operating in oil. The experimental results from this study agreed with the simulation results: a CMUT operating in the collapsed region produced a higher maximum output pressure than a CMUT operated in the conventional region at 90% of its collapse voltage (3 kPa/V vs. 16.1 kPa/V at 2.3 MHz). While the pulse-echo fractional bandwidth (126%) was higher in the collapsed region operation than in the conventional operation (117%), the pulse-echo amplitude in collapsed region operation was 11 dB higher than in conventional region operation. Furthermore, within the range of tested bias voltages, the output pressure monotonously increased with increased bias during collapsed region operation. It was also found that in the conventional mode, short AC pulses (larger than the collapse voltage) could be applied without collapsing the membranes. Finally, while no significant difference was observed in reflectivity of the CMUT face between the two regions of operation, hysteretic behavior of the devices was identified in the collapsed region operation.

Capacitive micromachined ultrasonic transducers: fabrication technology.

Capacitive micromachined ultrasonic transducer (cMUT) technology is a prime candidate for next generation imaging systems. Medical and underwater imaging and the nondestructive evaluation (NDE) societies have expressed growing interest in cMUTs over the years. Capacitive micromachined ultrasonic transducer technology is expected to make a strong impact on imaging technologies, especially volumetric imaging, and to appear in commercial products in the near future. This paper focuses on fabrication technologies for cMUTs and reviews and compares variations in the production processes. We have developed two main approaches to the fabrication of cMUTs: the sacrificial release process and the recently introduced wafer-bonding method. This paper gives a thorough review of the sacrificial release processes, and it describes the new wafer-bonding method in detail. Process variations are compared qualitatively and quantitatively whenever possible. Through these comparisons, it was concluded that wafer-bonded cMUT technology was superior in terms of process control, yield, and uniformity. Because the number of steps and consequent process time were reduced (from six-mask process to four-mask process), turn-around time was improved significantly.

A solution to the charging problems in capacitive micromachined ultrasonic transducers.

We report on a capacitive micromachined ultrasonic transducer (CMUT) featuring isolation posts (PostCMUT) as a solution to the charging problems caused by device fabrication and operation. This design improves the device reliability. The PostCMUTs were fabricated using a newly developed process based on the wafer-bonding technique. Paired tests showed the superior reliability characteristics of the PostCMUT design compared to those of conventional CMUT designs. No deleterious effect of the new design was seen in preliminary ultrasonic tests or in process yield. PostCMUTs, a design that serves as a solution to the aforementioned reliability problem, constitutes a major contribution to CMUT commercialization.

Reconfigurable mosaic annular arrays.

Mosaic annular arrays (MAA) based on reconfigurable array (RA) transducer electronics assemblies are presented as a potential solution for future highly integrated ultrasonic transducer subsystems. Advantages of MAAs include excellent beam quality and depth of field resulting from superior elevational focus compared with 1-D electronically scanned arrays, as well as potentially reduced cost, size, and power consumption resulting from the use of a limited number of beamforming channels for processing a large number of subelements. Specific design tradeoffs for these highly integrated arrays are discussed in terms of array specifications for center frequency, element pitch, and electronic switch-on resistance. Large-area RAs essentially function as RC delay lines. Efficient architectures which take into account RC delay effects are presented. Architectures for integration of the transducer and electronics layers of large-area array implementations are reviewed.

Packaging and modular assembly of large-area and fine-pitch 2-D ultrasonic transducer arrays.

A promising transducer architecture for largearea arrays employs 2-D capacitive micromachined ultrasound transducer (CMUT) devices with backside trench-frame pillar interconnects. Reconfigurable array (RA) application-specified integrated circuits (ASICs) can provide efficient interfacing between these high-element-count transducer arrays and standard ultrasound systems. Standard electronic assembly techniques such as flip-chip and ball grid array (BGA) attachment, along with organic laminate substrate carriers, can be leveraged to create large-area arrays composed of tiled modules of CMUT chips and interface ASICs. A large-scale, fully populated and integrated 2-D CMUT array with 32 by 192 elements was developed and demonstrates the feasibility of these techniques to yield future large-area arrays. This study demonstrates a flexible and reliable integration approach by successfully combining a simple under-bump metallization (UBM) process and a stacked CMUT/interposer/ASIC module architecture. The results show high shear strength of the UBM (26.5 g for 70-µm balls), high interconnect yield, and excellent CMUT resonance uniformity (s = 0.02 MHz). A multi-row linear array was constructed using the new CMUT/interposer/ASIC process using acoustically active trench-frame CMUT devices and mechanical/ nonfunctional Si backside ASICs. Imaging results with the completed probe assembly demonstrate a functioning device based on the modular assembly architecture.

Large Area MEMS Based Ultrasound Device for Cancer Detection.

We present image results obtained using a prototype ultrasound array which demonstrates the fundamental architecture for a large area MEMS based ultrasound device for detection of breast cancer. The prototype array consists of a tiling of capacitive Micro-Machined Ultrasound Transducers (cMUTs) which have been flip-chip attached to a rigid organic substrate. The pitch on the cMUT elements is 185 um and the operating frequency is nominally 9 MHz. The spatial resolution of the new probe is comparable to production PZT probes, however the sensitivity is reduced by conditions that should be correctable. Simulated opposed-view image registration and Speed of Sound volume reconstruction results for ultrasound in the mammographic geometry are also presented.

3-D Deep Penetration Photoacoustic Imaging with a 2-D CMUT Array.

In this work, we demonstrate 3-D photoacoustic imaging of optically absorbing targets embedded as deep as 5 cm inside a highly scattering background medium using a 2-D capacitive micromachined ultrasonic transducer (CMUT) array with a center frequency of 5.5 MHz. 3-D volumetric images and 2-D maximum intensity projection images are presented to show the objects imaged at different depths. Due to the close proximity of the CMUT to the integrated frontend circuits, the CMUT array imaging system has a low noise floor. This makes the CMUT a promising technology for deep tissue photoacoustic imaging.

Capacitive micromachined ultrasonic transducers with piston-shaped membranes: fabrication and experimental characterization.

Capacitive micromachined ultrasonic transducers (CMUTs) featuring piston-shaped membranes (piston CMUTs) were developed to improve device performance in terms of transmission efficiency, reception sensitivity, and fractional bandwidth (FBW). A piston CMUT has a relatively flat active moving surface whose membrane motion is closer to ideal piston-type motion compared with a CMUT with uniformly thick membranes (classical CMUT). Piston CMUTs with a more uniform surface displacement profile can achieve high output pressure with a relatively small electrode separation. The improved device capacitance and gap uniformity also enhance detection sensitivity. By adding a center mass to the membrane, a large ratio of second-order resonant frequency to first-order resonant frequency was achieved. This improved the FBW. Piston CMUTs featuring membranes of different geometric shapes were designed and fabricated using wafer bonding. Fabricating piston CMUTs is a more complex process than fabricating CMUTs with uniformly thick membranes. However, no yield loss was observed. These devices achieved ~100% improvement in transduction performance (transmission and reception) over classical CMUTs. For CMUTs with square and rectangular membranes, the FBW increased from ~110% to ~150% and from ~140% to ~175%, respectively, compared with classical CMUTs. The new devices produced a maximum output pressure exceeding 1 MPa at the transducer surface. Performance optimization using geometric membrane shape configurations was the same in both piston CMUTs and classical CMUTs.

Wafer-bonded 2-D CMUT arrays incorporating through-wafer trench-isolated interconnects with a supporting frame.

This paper reports on wafer-bonded, fully populated 2-D capacitive micromachined ultrasonic transducer (CMUT) arrays. To date, no successful through-wafer via fabrication technique has been demonstrated that is compatible with the wafer-bonding method of making CMUT arrays. As an alternative to through-wafer vias, trench isolation with a supporting frame is incorporated into the 2-D arrays to provide through-wafer electrical connections. The CMUT arrays are built on a silicon-on-insulator (SOI) wafer, and all electrical connections to the array elements are brought to the back side of the wafer through the highly conductive silicon substrate. Neighboring array elements are separated by trenches on both the device layer and the bulk silicon. A mesh frame structure, providing mechanical support, is embedded between silicon pillars, which electrically connect to individual elements. We successfully fabricated a 16 x 16-element 2-D CMUT array using wafer bonding with a yield of 100%. Across the array, the pulse-echo amplitude distribution is uniform (rho = 6.6% of the mean amplitude). In one design, we measured a center frequency of 7.6 MHz, a peak-to-peak output pressure of 2.9 MPa at the transducer surface, and a 3-dB fractional bandwidth of 95%. Volumetric ultrasound imaging was demonstrated by chip-to-chip bonding one of the fabricated 2-D arrays to a custom-designed integrated circuit (IC). This study shows that through-wafer trench-isolation with a supporting frame is a viable solution for providing electrical interconnects to CMUT elements and that 2-D arrays fabricated using waferbonding deliver good performance.

Three-dimensional photoacoustic imaging using a two-dimensional CMUT array.

In this paper, we describe using a 2-D array of capacitive micromachined ultrasonic transducers (CMUTs) to perform 3-D photoacoustic and acoustic imaging. A tunable optical parametric oscillator laser system that generates nanosecond laser pulses was used to induce the photoacoustic signals. To demonstrate the feasibility of the system, 2 different phantoms were imaged. The first phantom consisted of alternating black and transparent fishing lines of 180 mum and 150 mum diameter, respectively. The second phantom comprised polyethylene tubes, embedded in chicken breast tissue, filled with liquids such as the dye indocyanine green, pig blood, and a mixture of the 2. The tubes were embedded at a depth of 0.8 cm inside the tissue and were at an overall distance of 1.8 cm from the CMUT array. Two-dimensional cross-sectional slices and 3-D volume rendered images of pulse-echo data as well as photoacoustic data are presented. The profile and beamwidths of the fishing line are analyzed and compared with a numerical simulation carried out using the Field II ultrasound simulation software. We investigated using a large aperture (64 x 64 element array) to perform photoacoustic and acoustic imaging by mechanically scanning a smaller CMUT array (16 x 16 elements). Two-dimensional transducer arrays overcome many of the limitations of a mechanically scanned system and enable volumetric imaging. Advantages of CMUT technology for photoacoustic imaging include the ease of integration with electronics, ability to fabricate large, fully populated 2-D arrays with arbitrary geometries, wide-bandwidth arrays and high-frequency arrays. A CMUT based photoacoustic system is proposed as a viable alternative to a piezoelectric transducer based photoacoustic systems.

Evaluation of wafer bonded CMUTs with rectangular membranes featuring high fill factor.

Increasing fill factor is one design approach used to increase average output displacement, output pressure, and sensitivity of capacitive micromachined ultrasonic transducers (CMUTs). For rectangular cells, the cell-to-cell spacing and the aspect ratio determine the fill factor. In this paper, we explore the effects of these parameters on performance, in particular the nonuniformity of collapse voltage between neighboring cells and presence of higher order modes in air or immersed operation. We used a white light interferometer to measure nonuniformity in deflection between neighboring cells. We found that reducing the cell-to-cell spacing could cause bending of the center support post, which amplifies nonuniformities in collapse voltage to 18.4% between neighboring cells. Using a 2-D finite element model (FEM), we found that for our designs, increasing the support post width to 1.67 times the membrane thickness alleviated the post bending problem. Using impedance and interferometer measurements to observe the effects of aspect ratio on higher order modes, we found that the (1,3) modal frequency approached the (1,1) modal frequency as the aspect ratio of the rectangles increased. In air operation, under continuous wave (CW) excitation at the center frequency, the rectangular cells behaved in the (1,1) mode. In immersion, because of dispersive guided modes, these cells operated in a higher order mode when excited with a CW signal at the center frequency. This contributed to a loss of output pressure; for this reason our rectangular design was unsuitable for CW operation in immersion.

Capacitive micromachined ultrasonic transducers (CMUTs) with isolation posts.

In this paper, an improved design of a capacitive micromachined ultrasonic transducer (CMUT) is presented. The design improvement aims to address the reliability issues of a CMUT and to extend the device operation beyond the contact (collapse) voltage. The major design novelty is the isolation posts in the vacuum cavities of the CMUT cells instead of full-coverage insulation layers in conventional CMUTs. This eliminates the contact voltage drifting due to charging caused by the insulation layer, and enables repeatable CMUT operation in the post-contact regime. Ultrasonic tests of the CMUTs with isolation posts (PostCMUTs) in air (electrical input impedance and capacitance vs. bias voltage) and immersion (transmission and reception) indicate acoustic performance similar to that obtained from conventional CMUTs while no undesired side effects of this new design is observed.