Seung Hyun Song

An Ultrasonically Powered Implantable Micro-Oxygen Generator (IMOG)

In this paper, we present an ultrasonically powered implantable micro-oxygen generator (IMOG) that is capable of in situ tumor oxygenation through water electrolysis. Such active mode of oxygen generation is not affected by increased interstitial pressure or abnormal blood vessels that typically limit the systemic delivery of oxygen to hypoxic regions of solid tumors. Wireless ultrasonic powering (2.15 MHz) was employed to increase the penetration depth and eliminate the directional sensitivity associated with magnetic methods. In addition, ultrasonic powering allowed for further reduction in the total size of the implant by eliminating the need for a large area inductor. IMOG has an overall dimension of 1.2 mm × 1.3 mm × 8 mm, small enough to be implanted using a hypodermic needle or a trocar. In vitro and ex vivo experiments showed that IMOG is capable of generating more than 150 μA which, in turn, can create 0.525 μL/min of oxygen through electrolytic disassociation. In vivo experiments in a well-known hypoxic pancreatic tumor models (1 cm3 in size) also verified adequate in situ tumor oxygenation in less than 10 min.

Omnidirectional Ultrasonic Powering for Millimeter-Scale Implantable Devices

In addition to superior energy-conversion efficiency at millimeter-scale dimensions, ultrasonic wireless powering offers deeper penetration depth and omnidirectionality as compared to the traditional inductive powering method. This makes ultrasound an attractive candidate for powering deep-seated implantable medical devices. In this paper, we investigate ultrasonic powering of millimeter-scale devices with specific emphasize on the output power levels, efficiency, range, and omnidirectionality. Piezoelectric receivers 1 × 5 × 1 mm3, 2 × 2 × 2 mm3, and 2 × 4 × 2 mm3 in size are able to generate 2.48, 8.7, and 12.0 mW of electrical power, while irradiated at 1.15 and 2.3 MHz within FDA limits for medical imaging (peak acoustic intensity of 720 mW/cm2). The receivers have corresponding efficiencies of 0.4%, 1.7%, and 2.7%, respectively, at 20-cm powering distance. Due to the form factor and reflections from tissue-air boundaries, the output power stays constant to within 92% when the angular positions of the transmitter and receiver are varied around a cylindrical shell.

A thermophone on porous polymeric substrate

In this Letter, we present a simple, low-temperature method for fabricating a wide-band (>80 kHz) thermo-acoustic sound generator on a porous polymeric substrate. We were able to achieve up to 80 dB of sound pressure level with an input power of 0.511 W. No significant surface temperature increase was observed in the device even at an input power level of 2.5 W. Wide-band ultrasonic performance, simplicity of structure, and scalability of the fabrication process make this device suitable for many ranging and imaging applications.

A wireless intracranial brain deformation sensing system for blast-induced traumatic brain injury

Blast-induced traumatic brain injury (bTBI) has been linked to a multitude of delayed-onset neurodegenerative and neuropsychiatric disorders, but complete understanding of their pathogenesis remains elusive. To develop mechanistic relationships between bTBI and post-blast neurological sequelae, it is imperative to characterize the initiating traumatic mechanical events leading to eventual alterations of cell, tissue, and organ structure and function. This paper presents a wireless sensing system capable of monitoring the intracranial brain deformation in real-time during the event of a bTBI. The system consists of an implantable soft magnet and an external head-mounted magnetic sensor that is able to measure the field in three dimensions. The change in the relative position of the soft magnet WITH respect to the external sensor as the result of the blast wave induces changes in the magnetic field. The magnetic field data in turn is used to extract the temporal and spatial motion of the brain under the blast wave in real-time. The system has temporal and spatial resolutions of 5 μs and 10 μm. Following the characterization and validation of the sensor system, we measured brain deformations in a live rodent during a bTBI.

An ultrasonically powered implantable micro-light source for localized photodynamic therapy

In this work, we introduce an ultrasonically powered light source which can provide in situ localized light for photodynamic therapy. The implants are 2×2×2 mm³ and 2×4×2 mm³ in dimensions and consist of two red LEDs mounted on a piezoelectric energy source. Such device is small enough to be easily implanted inside solid tumors using a biopsy needle. In vitro light intensity measurements show an output power density of 48 μW/cm² from the 2×2×2 mm³ and 1.1 mW/cm² from the 2×4×2 mm³ light source. The results indicate that implanting multiple sources and powering them for 1 hour can provide optimal energy for localized photodynamic therapy.

An electret-biased resonant radiation sensor

Resonance-based microcantilevers have been widely explored for various sensing applications. Subjecting the cantilever to an electrets-generated electrostatic field allows for self-resonant sensing of ionizing radiation. This paper reports the development of the resonant radiation sensor consisting of a ZnO microcantilever and a Teflon electret. The electrostatic force generated by the electric field shifts the self-resonant frequency of the cantilever. For a 125 (L), 55 (W), and 4 (T) μm (length) cantilever, the sensor displayed a sensitivity of 24.24Hz/Gy when exposed to 2Gy of gamma radiation.

Radiosensitizing Pancreatic Cancer Xenografts by an Implantable Micro-Oxygen Generator

Over the past decades, little progress has been made to improve the extremely low survival rates in pancreatic cancer patients. Extreme hypoxia observed in pancreatic tumors contributes to the aggressive and metastatic characteristics of this tumor and can reduce the effectiveness of conventional radiation therapy and chemotherapy. In an attempt to reduce hypoxia-induced obstacles to effective radiation treatment, we used a novel device, the implantable micro-oxygen generator (IMOG), for in situ tumor oxygenation. After subcutaneous implantation of human pancreatic xenograft tumors in athymic rats, the IMOG was wirelessly powered by ultrasonic waves, producing 30 μA of direct current (at 2.5 V), which was then utilized to electrolyze water and produce oxygen within the tumor. Significant oxygen production by the IMOG was observed and corroborated using the NeoFox oxygen sensor dynamically. To test the radiosensitization effect of the newly generated oxygen, the human pancreatic xenograft tumors were subcutaneously implanted in nude mice with either a functional or inactivated IMOG device. The tumors in the mice were then exposed to ultrasonic power for 10 min, followed by a single fraction of 5 Gy radiation, and tumor growth was monitored thereafter. The 5 Gy irradiated tumors containing the functional IMOG exhibited tumor growth inhibition equivalent to that of 7 Gy irradiated tumors that did not contain an IMOG. Our study confirmed that an activated IMOG is able to produce sufficient oxygen to radiosensitize pancreatic tumors, enhancing response to single-dose radiation therapy.

An Implantable Wireless Interstitial Pressure Sensor With Integrated Guyton Chamber: in vivo Study in Solid Tumors

A wireless implantable interstitial fluid pressure (IFP) sensor with an integrated Guyton chamber is presented. This implantable device enables noninvasive and continuous measurements of IFP. The Guyton chamber allows for an accurate measurement of IFP without the interference from various cellular/tissue components. The sensor consists of a coil, an air chamber, a silicone membrane embedded with a nickel plate, and a Guyton chamber. The fabricated device is 3 mm in diameter and 1 mm in thickness. The sensor shows a linear response to the pressure with a sensitivity of 60 kHz/mmHg and a resolution of 1 mmHg. Experiments in human prostate cancer tumors grown in mice confirm the sensors capability to operate in vivo and provide continuous wireless measurement of IFP, a surrogate parameter indicating the “window of opportunity” for delivering chemo- and radio-therapeutic agents.

A wireless chemical sensing scheme using ultrasonic imaging of microbubble embeded hydrogel

In this paper, we demonstrate a wireless chemical sensing scheme using ultrasonic imaging of a microbubble-functionalized hydrogel, which we call “bubblegel.” By incorporating oxygen microbubbles into a hydrogel, its volume transition, which is responsive to its chemical microenvironment, can be wirelessly monitored by ultrasonic imaging; measuring volume directly or measuring the reflected acoustic intensity from the surface of the bubblegel. Here a bubblegel fabricated with pH-sensitive poly (methacrylic acid-co-acrylamide) hydrogel is investigated in vitro. The sensor shows a sensitivity of 19.49 gray-scale intensity/pH and a resolution of 0.25 pH unit in the linear response region (between pH 4 and 6). It is expected that the concept can be adapted to hydrogels sensitive to other stimuli (e.g., glucose, biomarkers, etc.).