Integration of a Dual-Mode Catheter for Ultrasound Image Guidance and HIFU Ablation using a 2-D CMUT Array

Ji Hoon Jang1, Chienliu Chang1, Morten Fischer Rasmussen1, Azadeh Moini1, Kevin Brenner1, Douglas N. Stephens2, Ömer Oralkan3, and Butrus Khuri-Yakub1

1Electrical Engineering, Stanford University, Stanford, CA, USA 2Biomedical Engineering, University of California, Davis, CA, USA

3Electrical and Computer Engineering, North Carolina State University, Raleigh, NC, USA

Abstract— Image-guided high-intensity focused ultrasound (HIFU) is widely used not only for non-invasive therapy but also for a precise approach for tissue ablation. Most HIFU systems use piezoelectric transducers, which are typically bulky due to active cooling, and separate imaging and HIFU transducers, and are therefore impractical for catheter-based applications. Taking advantage of a single 2-D capacitive micromachined ultrasonic transducer (CMUT) array, we developed a dual-mode catheter that can switch between ultrasound imaging mode and HIFU ablation mode. The catheter is equipped with an application-specific integrated circuit (ASIC) and a 32 × 32-element 2-D CMUT array. Both ASIC and CMUT are flip-chip bonded to a custom-designed flexible printed circuit board (flex PCB) via 100-µm and 80-µm solder balls. Then, the flex legs are folded and terminated with pads for a micro zero insertion force (µZIF) connector, allowing easy assembly replacement without the extra cost of coaxial cable assembly. Next, the micro-coaxial cables are assembled at the end of the µZIF connectors. After integration with a 3-D printed tip and encapsulating with polydimethylsiloxane (PDMS), the catheter is finalized in a 22-mm diameter shaft. We successfully validated the functionality of both modes of the dual-mode catheter in oil. We are currently preparing the test for an animal study.

Keywords—Dual-Mode Catheter, Integration, flip-chip bonding, Flexible PCB, Ultrasound Image-guided HIFU

I. INTRODUCTION Most ultrasound applications have been known for their diagnostic nature, but ultrasound can also be used as a treatment tool. Well-known examples of therapeutic ultrasound include lithotripsy, targeted ultrasound drug delivery, cancer therapy, thrombolysis, and high-intensity focused ultrasound (HIFU). HIFU is an FDA-approved, minimally invasive procedure to ablate tissue without affecting the surrounding tissue close to the transducer [1]. This technique has been used clinically to treat uterine fibroids, neurological disorders, prostate cancer, and other types of cancers [2]-[3].

For successful HIFU operation, image guidance to the target is essential. The widely used guidance techniques are Magnetic Resonance Imaging (MRI) and ultrasound imaging. MRI is bulky and expensive, but it is very useful for applications that require precise procedures because it can accurately monitor temperature on the ablation target [4]. On the other hand, ultrasound imaging has advantages in that it can be made low-cost and small, but it may not have the required precision for some operat ions . Each method has advantages and

Figure 1. Conceptual drawing of the dual-mode catheter (a) with dual-mode ASIC and 2-D CMUT array and (b) imaging and HIFU beam.

disadvantages. In this paper, we focus on ultrasound image-guided HIFU.

For typical ultrasound image-guided HIFU procedures, two different ultrasound transducers are used, one for imaging and one for HIFU. In the case that there is no limitation on the size of the ultrasound system for the procedures, it is not a problem to have a cooling system for HIFU transducer and to align the two transducers. However, this is difficult for catheter-based operation. The fundamental reason why two different transducers and the cooling system must be used is due to the use of piezoelectric materials, which are the most commonly used technology of ultrasound transducers. The transducer technology known as Capacitive Micromachined Ultrasound Transducer (CMUT) has a wide bandwidth and low self-heating [5]-[6]. CMUTs are micromachined resonators that have a moving plate on top of a vacuum cavity. They operate with a DC bias voltage that deflects the top plate downwards, which changes the transducers’ frequency response, maximum output pressure, and sensitivity. CMUT’s thin top plates are damped by heavy media such as water and tissue, which leads to their wide bandwidth characteristic. Even though CMUT has loss mechanisms such as elastic loss, substrate loss, and dielectric loss, CMUTs have superior properties for low self-heating, because their material has better thermal conductivity than piezoelectric transducers and they are thermally efficient [5].

Figure 2. Optical picture of 2-D 32×32-element CMUT array.

With the aforementioned advantages, it has been shown that a single 2-D CMUT array can perform both ultrasound imaging and HIFU with its custom application-specific integrated circuit (ASIC) [7]-[8].

Many researchers have studied how CMUT arrays can be effectively fabricated for better performance [9] and showed many different shapes of CMUT probes. Among them, intravascular catheters using CMUT arrays have attracted attention for developing potential medical devices. Intravascular ultrasound (IVUS) catheters using CMUT arrays have been shown using 1-D CMUT arrays [10] and ring CMUT arrays [11]. However, there have been fewer studies that use a 2-D CMUT array for IVUS catheters because 2-D CMUT arrays need a larger number of connections, which makes it difficult to achieve reliable integration. However, it is desirable to develop IVUS catheters using 2-D arrays due to benefits such as 3-D imaging and HIFU ablation capability.

In this paper, we show how to integrate a 2-D 32×32-element CMUT array and a dual-mode ASIC into a catheter system using the flip-chip bonding technology and a flexible printed circuit board (flex PCB). The conceptual drawing of the catheter is shown in Figure 1. The following section describes how micro zero insertion force (µZIF) connectors and 3-D printed tips are used for reliable integration. Then, the acoustic test using the catheter is presented in the last section.

II. CHARACTERIZATION OF THE 32×32-ELEMENT CMUT ARRAY

We fabricated the 32×32-element CMUT arrays using the sacrificial release process [9]. This design exploits through silicon vias (TSV) and achieved robust connections from CMUT electrodes to the flip-chip bond pads on the backside as shown in the previous work [12]. The top plate of all cells in all elements are electrically connected together to pads on the CMUT backside and the bottom plates of the 1,024 CMUT elements are connected to individual pads on the backside, as shown in Figure 2.

The CMUT array has a 5-MHz center frequency, 24 cells per element, and an element pitch of 250 µm. Although this CMUT array is designed for use in immersion, the CMUT impedance in the air provides information about its performance. Therefore, CMUT impedance with different DC bias voltages was measured using the impedance analyzer (4294A, Agilent, Santa Clara, CA) and the results are shown in Figure 3. As the DC bias increases using a high voltage DC

Figure 3. CMUT array and cell design parameters and impedance of CMUT element in air with DC bias voltage.

Figure 4. Impedance mapping of 32×32-element CMUT array and the automatic impedance mapping system with XYZ motorized positioner.

supply (PS310, Stanford Research Systems, Inc., Sunnyvale, CA), the resonant frequency decreases due to the spring softening effect. In Figure 3, the table summarizes the parameters of the CMUT array.

Before integration with the ASIC, the impedance of every element needs to be measured. Because all top plates are tied together, if one cell gets shorted due to insulator breakdown, none of the CMUT elements in the array can be biased and used. By increasing the DC bias up to collapse voltage or higher, we can screen for short elements and remove their connections to the ASIC. However, it is time-consuming to measure the impedance of every element with different bias voltages. For example, when every element was measured manually one by one, it took about 1-2 days to measure all elements and analyze the data. Therefore, we utilized a motorized positioner (PT3-Z8, Thorlab, Inc., Newton, NJ) which supports a resolution up to 0.05 µm in the x, y, and z-directions. The probe (ACP40-W-GS-150; Cascade Microtech, Inc., Beaverton, OR) is attached to the positioner as shown in Figure 4. The automatic test sequence is developed using MATLAB, which calibrates for the pad positions, controls the impedance analyzer and the motorized positioner, and analyzes the acquired data. This array impedance mapping system significantly reduces the total time to 8 hours. One of the array mapping results is shown in Figure 4. The red colored elements are the shorted elements and the green colored elements are the open elements. Neither of them gets connected to the ASIC.

III. FLIP-CHIP BONDING The flip-chip bonding technology is chosen to integrate the CMUT array with the ASIC and the flex PCB, which was designed to interface the ASIC to the back-end system. Because the CMUT array and ASIC have many pads to be connected, the flip-chip bonding is used instead of the wire bonding. The

Figure 5. Assembly steps: (a) Flip-chip bonding of ASIC onto the flex PCB. (b) Flip-chip bonding of CMUT array onto ASIC and filling the gap with underfill epoxy. (c) Integration of the assembly with 3-D printed tip and encapsulation of the surface of CMUT array with PDMS. (d) Connecting folded flex PCB legs to uZIF connector.

Figure 6. Optical picture of dual-mode ASIC with solder balls for flip-chip bonding of CMUT array and the flex PCB.

bonding sequence starts with ASIC onto flex PCB, and then CMUT array onto ASIC as shown in Figure 5.

A flip-chip bonding machine (Model D8; Research Devices Inc., Piscataway, NJ) was used to align and bond the devices using upward and downward-facing cameras for alignment and applying 4 g/bump during bonding. Prior to the alignment, we used a no-clean tacky flux (TSF-6592, Kester, Inc., Itasca, IL) to etch native oxide layer to enhance the bonding. Then, the device was placed inside a reflow oven in which temperature increases up to 190˚C. After the bonding was completed, underfill epoxy (Hysol FP4549SI, Henkel Co., Berkeley, CA) was used to enhance the mechanical strength in the gap between CMUT array, ASIC, and flex PCB.

As the under bump metallurgy (UBM) required for flip-chip bonding, a 10/250/150-nm Ti/Ni/Au metal stack was evaporated on the pads for the CMUT array to enhance the electrical contact using Stanford Nanofabrication Facility (Stanford, CA). Also, UBM was formed on the pads of ASIC and the eutectic Sn/Pb 63/37 solder balls were formed by jetting (Pac Tech USA, Santa Clara, CA). The diameter of the solder balls on the dual-mode ASIC is 80 µm on 60 µm × 60 µm pads for the CMUT array and it is 100 µm on 80 µm × 80 µm pads for the flex PCB as shown in Figure 6.

IV. FLEXIBLE PRINTED CIRCUIT BOARD DESIGN The catheter-based application requires miniaturizing size

of the probe. Thus, instead of using the rigid PCB board,

Figure 7. Optical picture of (a) Flex PCB (b) the pads for flip-chip bonding with ASIC, and (c) the pads for µZIF connector.

the flex PCB is chosen to interface the ASIC with the back-end system. In the flip-chip bonding process, the pads of flex PCB

are aligned and matched with the ASIC’s staggered pads whose size is 80 µm x 80 µm with a 250-µm pitch. It requires the flex design to have at least 2 mils (50 µm) width of the trace and the space to avoid shorting between the traces as shown in figure 7(b). Moreover, the tolerance of X-Y registration should be less than about ± 10 µm to make a good alignment to ASIC. The board is fabricated as a double-sided board with micro vias, whose diameter is 1 mil (25 µm) (Tech-Etch, Inc., Fall River, MA). One side of the board is used for routing traces and the other side is used for the ground shield. As shown in Figure 7(b), the solder mask covers the traces close to the pads to avoid wicking the solders into the traces. Four legs of the flex are folded and terminated with pads for the µZIF connector. Each leg has about 41 connector pads to the back-end system.

V. MICRO ZIF CONNECTOR AND COAX CABLING In the previous work on the IVUS catheter using CMUT

array [9], the pads on flex PCB were directly connected to the micro-coaxial cables. This made it difficult to replace the probe when the probe was damaged or the performance had degraded. Due to the high cost of coax cabling, the probe cannot be re-assembled many times. Thus, a µZIF connector (Hirose Electric USA, Inc., San Jose, CA) is introduced between the probe and the coax cables, which is generally used in display connectors for commercial electronics such as laptop computers and smart phones. The advantage of using this µZIF connector is that not only does it enable the replacement of the probe without extra cost for coaxial cabling but it also does not require any mating connectors on the flex PCB, which would require an additional process step on the flex. Also, it provides low profile and reliable connections to the following board. As shown in Figure 7, the edge of the flex board should be designed to mate with µZIF connectors and it connects to the flex seamlessly with zero force needed to insert. The pitch between the pads is 0.2 mm and the number of pads per connector is 41. The width of each of the four legs of the flex PCB is 8.5 mm. The current capacity per pad is about 0.2 A, so HIFU channels are assigned 4 pins.

Four small custom printed circuit boards (PCB) were designed to interface the µZIF connectors with 160 38-AWG micro coaxial cables as shown in Figure 8. Cable termination for the catheter was performed by Precision Interconnect (Tyco Electronics, Wilsonville, OR).

Figure 8. Optical picture of (a) µZIF connectors and micro coaxial cables and (b) the assembled dual-mode catheter before PDMS encapsulation.

Figure 9. (a) Measured peak-to-peak pressure of the focused array at the focus with different AC and DC voltage. (b) Acquired pressure waveform by hydrophone at AC 60V and DC 95V.

VI. PROBE ASSEMBLY After the flip-chip bonding process is completed, the assembly is integrated onto the 3-D printed tip. The 3-D printed tip is designed to set the thickness of PDMS encapsulation and align the legs of the flex to the micro ZIF connector as shown in Figure 8. The housing is made by a 3-D printer in iLab of Stanford University. Next, 150 µm of PDMS encapsulates the surface of the CMUT array. Then, the four legs of the flex are folded and connected to the µZIF connector. The catheter is finalized in a 22-mm shaft. The optical picture of the assembly after the final step is shown in Figure 8.

VII. MEASUREMENT RESULTS To validate the acoustic performance of the probe, it was

bonded to the tank. The experimental setup is described in [7]. Imaging mode of the catheter is tested with a wire phantom. For HIFU mode, a hydrophone (HGL0200, Onda, Co., Sunnyvale, CA) attached to the XYZ positioner was immersed in oil to measure the pressure at the focus. We carefully set the phase and amplitude of all 8 HIFU channels with different AC and DC voltages in Figure 9(a). As shown in Figure 9(b), the maximum pressure at the focus with 60-V AC and 95-V DC was measured as 13 MPa peak-to-peak. In steady state, the pressure was measured to 12.3 MPa peak-to-peak. From the previous study, we know this pressure would be high enough to ablate the tissue [8]. The next step is to perform imaging-guided ablation by switching between imaging mode and HIFU mode of the dual-mode catheter.

VIII. CONCLUSION In this paper, we presented the integration method of a dual-mode catheter, whose main components are a 32×32-element CMUT array, a dual-mode ASIC for imaging and HIFU, and a flex PCB. The flip-chip bonding technology was used to assemble the components. After it was integrated onto a 3-D printed tip, PDMS encapsulated the surface of the CMUT array. The assembly was connected to the back-end system via µZIF connectors and coaxial cables. The catheter was acoustically tested to check its performance. This dual-mode catheter that can perform both ultrasound imaging and HIFU will open new possibilities to treat various diseases.

ACKNOWLEDGMENT This work was supported by the National Institutes of Health under grant R01HL117740. We would like to thank Maxim Corporation for their valuable support in the fabrication of the ASIC. CMUT fabrication was done at the Stanford Nanofabrication Facility (Stanford, CA), a member of National Nanotechnology Infrastructure Network.

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