An Ultrasonically Powered Implantable Microprobe for Electrolytic Ablation.

Electrolytic ablation (EA) is a promising nonthermal tumor ablation technique that destroys malignant cells through induction of a locoregional pH change. EA is typically performed by inserting needle electrodes inside the tumor followed by application of direct current (DC), thus inducing electrolysis and creating localized pH changes around the electrodes. In this paper, we report an ultrasonically powered implantable EA microprobe that may increase the clinical relevance of EA by allowing wireless control over device operation (capability to remotely turn the device on and off) and providing flexibility in treatment options (easier to administer fractionated doses over a longer period). The wireless EA microprobe consists of a millimeter-sized piezoelectric ultrasonic receiver, a rectifier circuit, and a pair of platinum electrodes (overall size is 9 × 3 × 2 mm3). Once implanted through a minimally invasive procedure, the microprobe can stay within a solid tumor and be repeatedly used as needed. Ultrasonic power allows for efficient power delivery to mm-scale devices implanted deep within soft tissues of the body. The microprobe is capable of producing a direct current of 90 µA at a voltage of 5 V across the electrodes under low-intensity ultrasound (~200 mW/cm2). The DC power creates acidic (pH < 2) and alkaline (pH > 12.9) regions around the anode and the cathode, respectively. The pH change, measured using tissue-mimicking agarose gel, extends to 0.8 cm3 in volume within an hour at an expansion rate of 0.5 mm3/min. The microprobe-mediated EA ablative capability is demonstrated in vitro in cancer cells and ex vivo in mouse liver.

A nanofluidic channel with embedded transverse nanoelectrodes.

In this paper, we demonstrate fabrication and characterization of a nanofluidic channel with embedded transverse nanoelectrodes using a combination of conventional photolithography and focused ion beam technologies. Glass-capped silicon dioxide nanochannels having 20 nm depth, 50 nm width, and 2 microm length with embedded platinum nanoelectrodes were fabricated. Channel patency was verified through measurements of the resistivity in phosphate buffered saline and electrostatic action on charged fluorescent nanospheres. Platinum nanoelectrode functionality was also tested using transverse resistance measurements in nanochannels filled with air, deionized water, and saline solution.

A diaper-embedded disposable nitrite sensor with integrated on-board urine-activated battery for UTI screening.

This paper reports a low-cost solution to the early detection of urinary nitrite, a common surrogate for urinary tract infection (UTI). We present a facile method to fabricate a disposable and flexible colorimetric [1] nitrite sensor and its urine-activated power source [2] on a hydrophobic (wax) paper through laser-assisted patterning and lamination. Such device, integrated with interface circuitry and a Bluetooth low energy (BLE) module can be embedded onto a diaper, and transmit semi-quantitative UTI monitoring information in a point-of-care and autonomous fashion. The proposed nitrite sensing platform achieves a sensitivity of 1.35 ms/(mg/L) and a detection limit of 4 mg/L.

A GENERIC PACKAGING TECHNIQUE USING FLUIDIC ISOLATION FOR LOW-DRIFT IMPLANTABLE PRESSURE SENSORS.

This paper reports on a generic packaging method for reducing drift in implantable pressure sensors. The described technique uses fluidic isolation by encasing the pressure sensor in a liquid-filled medical-grade polyurethane balloon; thus, isolating it from surrounding aqueous environment that is the major source of baseline drift. In-vitro tests using commercial micromachined piezoresistive pressure sensors show an average baseline drift of 0.006 cmH2O/day (0.13 mmHg/month) for over 100 days of saline soak test, as compared to 0.101 cmH2O/day (2.23 mmHg/month) for a non-fluidic-isolated one soaked for 18 days. To our knowledge, this is the lowest reported drift for an implantable pressure sensor.

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 mm(3), 2 ×2 ×2 mm(3), and 2 ×4 ×2 mm(3) 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/cm(2)). 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 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.

Intraocular pressure measurement at the choroid surface: a feasibility study with implications for implantable microsystems.

AIMS: To demonstrate that a sensor, which is inserted through the sclera and placed in intimate contact with the choroid, can reliably detect changes in the intraocular pressure (IOP). METHODS: A manometer was used to control the IOP of three cadaver eyes in steps of 7 mm Hg. A piezoresistive pressure sensor was used to measure the pressure at the choroid through a 2.5 mm diameter hole that was surgically removed from the sclera. Data were collected for two configurations; with the sensor: (i) rigidly attached to a miniature positioning stage, and (ii) sutured to the sclera. RESULTS: Both configurations accurately tracked the manometer pressure from 10 mm Hg to 47 mm Hg. For the fixed sensor cases, the average difference between the pressure measured at the choroid and in the anterior chamber was 0.8 mm Hg for the three eyes. For the sutured sensor case, the average difference was 2.1 mm Hg-although a significant portion of this was attributed to an initial offset. The standard deviations at each pressure level for all of the choroid measurements were under 1.0 mm Hg. CONCLUSIONS: Small changes in IOP can be accurately measured by a sensor in contact with the surface of the choroid, for both a fixed sensor configuration and for a sensor sutured to the sclera. These results are the first step in the realisation of a surgically implantable microsensor to monitor IOP for patients suffering from low tension and other difficult to manage forms of glaucoma.

An ultralight biotelemetry backpack for recording EMG signals in moths.

A two-channel FM biopotential recording system fabricated on a foldable, lightweight, polyimide substrate is presented. Each channel consists of a biopotential amplifier followed by a Colpitts oscillator with operating frequency tunable in the 88-108 MHz commercial FM band. The overall system measures 10 mm X 10 mm X 3 mm, weighs 0.74 g, uses two 1.5-V batteries, dissipates about 2 mW, and has a transmission range of 2 m. Using this system, electromyogram signals have been recorded from the dorsal ventral muscle and the dorsal longitudinal muscle of a giant sphinx moth (manduca sexta).

A single-channel implantable microstimulator for functional neuromuscular stimulation.

This paper describes a single-channel implantable microstimulator for functional neuromuscular stimulation. This device measures 2 x 2 x 10 mm3 and can be inserted into paralyzed muscle groups by expulsion from a hypodermic needle. Power and data to the device are supplied from outside by RF telemetry using an amplitude-modulated 2-MHz RF carrier generated using a high-efficiency class-E transmitter. The transmitted signal carries a 5-b address which selects one of the 32 possible microstimulators. The selected device then delivers up to 2 microC of charge store in a tantalum chip capacitor for up to 200 microseconds (10 mA) into loads of < 800 omega through a high-current thin-film iridium-oxide (IrOx) electrode (approximately 0.3 mm2 in area). A bi-CMOS receiver circuitry is used to: generate two regulated voltage supplies (4.5 and 9 V), recover a 2-MHz clock from the carrier, demodulate the address code, and activate the output current delivery circuitry upon the reception of an external command. The overall power dissipation of the receiver circuitry is 45-55 mW. The implant is hermetically packaged using a custom-made glass capsule.

A self-oscillating detuning-insensitive class-E transmitter for implantable microsystems.

This paper describes a low-cost, self-oscillating, detuning-in-sensitive, class-E driver for transcutaneous power and data transmission to implantable microsystems. A voltage feedback scheme using a fast comparator for zero-crossing detection and a CMOS start-up circuit were used to stabilize the class-E operation for various transmitter coil inductance values. This technique solves the common problem of mismatch between the switching frequency of the driving device and the resonant frequency of the load network, which can cause excessive power loss and damage to the active device. Data is transmitted by AM modulation of the carrier through switching the power supply between two levels. The transmitter uses a 9-V supply, consumes 212 mA, operates at 3.9 MHz, and has an efficiency of 71%. The efficiency is stable (< 2% change) against 13% variations in the inductance value of a pancake shaped transmitter coil. Index Terms-Biomedical microsystems, class-E transmitter, implantable electronics, inductive powering, transcutaneous links.

A modular micromachined high-density connector system for biomedical applications.

This paper presents a high-density, modular, low-profile, small, and removable connector system developed using micromachining technologies for biomedical applications. This system consists of a silicon or polyimide electrode with one end in contact with the biological tissue and its back-end supported in a titanium base (12.5 mm in diameter and 2.5 mm in height) that is fixed on the test subject. An external glass substrate (6 x 6 x 0.75 mm3), which supports a flexible polyimide diaphragm and CMOS buffers, is attached to the titanium base whenever electrical contact is required. The polyimide flexible diaphragm contains high-density gold electroplated pads (32 pads, each having an area of 100 x 100 micron 2 and separated by 150 microns) which match similar pads on the electrode back-end. When vacuum is applied between the two, the polyimide diaphragm deflects and the corresponding gold pads touch, therefore, establishing electrical connection. In vitro electrical tests in saline solution have been performed on a 32-site connector system demonstrating < 5 omega contact resistance, which remained stable after 70 connections, and -55 dB crosstalk at 1 kHz between adjacent channels. In vivo experiments have also confirmed the establishment of multiple contacts and have produced simultaneous biopotential recordings from the guinea pig occipital cortex.

Waterproof active paper via laser surface micropatterning of magnetic nanoparticles.

Paper is one of the oldest and most abundant materials known to man. Recently, there has been a considerable interest in creating paper devices by combining paper with other functional materials. In this letter, we demonstrate a simple fabrication technique to create water-resistant ferro-patterns on wax paper using CO(2) laser ablation. A resolution of about 100 µm is achieved which is mostly limited by the cellulose fiber size (~50 µm) in the wax paper and can be improved by using a smaller cellulose matrix. Laser ablation results in modification of surface morphology and chemistry, leading to a change in surface energy. We also present a 2D model for ferrofluid deposition relating the size of the pattern to the amount of ferroparticles deposited on the surface. Finally, a paper gripper is presented to demonstrate advantages of our technique, which allows microscale patterning and machining in a single step.

Microsystems technology in radiation therapy.

In this paper, we present several implantable micro-devices targeted towards improving the efficacy of radiation therapy. Three micro-devices are discussed: a self-biased solid state dosimeter to be used for wireless monitoring of the delivered dose, an electromagnetic tracking system to locate the position of tumor in real-time, and a Guyton-chamber-embedded capacitive pressure sensor for wireless measurement of interstitial pressure inside a tumor. Dosimeter and tracking systems are developed to be integrated together to achieve a track-able radiation sensor. Guyton chamber of the pressure sensor will eliminate the sensor drift due to the interaction of cells and fibrous tissue with sensor's membrane. The dosimeter has a sensitivity of up to 9 kΩ/Gy and a dynamic range of 10 Gy, when operating with a zero bias voltage. The tracking system is able to track a tumor that is 60 cm away with a resolution of 2 mm and a dynamic range of up to 5 cm. Finally, the capacitive pressure sensor has a sensitivity of 75 fF/kPa and a dynamic range of 60 mmHg.

Stretchable bioelectrodes.

In this paper, we present a stretchable electrode array for studying cell behavior subjected to mechanical strain. The electrode array consists of four gold nail-head pins (250 microm tip diameter and 1.75 mm spacing) inserted into a polydimethylsiloxane (PDMS) platform (25.4 x 25.4mm(2)). Fusible indium alloy (liquid at room temperature) filled microchannels are used to connect the electrodes to the outside, thus providing the required stretchability. The electrode platform is biocompatible and can withstand strains of up to 40%. We tested these electrodes by repeatedly (100 times) subjecting them to 35% strain and did not notice any failure. We also successfully cultured mice cardiomyocytes onto the platform and performed electrical pacing.

An optical microsystem for wireless neural recording.

In this paper, we describe an optical microsystem for wireless neural recording. The system incorporated recording electrodes, integrated electronics, surface-mount LEDs, and a CCD camera. The components were mounted on a PCB platform having a total dimension of 2.2 x 2.2 cm(2), 4 integrated biopotential amplifiers (IBA) and 16 LEDs. The IBAs having a bandwidth of 0.1-93.5Hz with the midband gain of 38 dB were fabricated using AMI 1.6microm technology. The simulated local field potentials (LFP) were amplified and used to drive the LEDs. A CCD camera with a temporal resolution of 30FPS was used to capture the image and retrieve the signal.

A motorized microdrive for recording of neural ensembles in awake behaving rats.

The recording of neural ensembles in awake, behaving rats has been an extremely successful experimental paradigm, providing demonstrable scientific advances. Dynamic control of the position of the implanted electrodes is of key importance as mobile electrodes provide a better signal-to-noise ratio and a better cell/ electrode yield than nonmobile electrodes. Here we describe the use of low cost, soon to be commercially available dc motors to successfully control the depth of electrodes. The prototype designed is approximately 30 mm in diameter and 50 mm in length and weighed about 30 gms. This paper presents the results of linear displacements of electrodes achievable with this motorized microdrive.