Distal planar rotary scanner for endoscopic optical coherence tomography.

Optical coherence tomography (OCT) is becoming a more common endoscopic imaging modality for detecting and treating disease given its high resolution and image quality. To use OCT for 3-dimensional imaging of small lumen, embedding an optical scanner at the distal end of an endoscopic probe for circumferential scanning the probing light is a promising way to implement high-quality imaging unachievable with the conventional method of revolving an entire probe. To this end, the present work proposes a hollow and planar micro rotary actuator for its use as an endoscopic distal scanner. A miniaturized design of this ferrofluid-assisted electromagnetic actuator is prototyped to act as a full 360° optical scanner, which is integrated at the tip of a fiber-optic probe together with a gradient-index lens for use with OCT. The scanner is revealed to achieve a notably improved dynamic performance that shows a maximum speed of 6500 rpm, representing 325% of the same reported with the preceding design, while staying below the thermal limit for safe in-vivo use. The scanner is demonstrated to perform real-time OCT using human fingers as live tissue samples for the imaging tests. The acquired images display no shadows from the electrical wires to the scanner, given its hollow architecture that allows the probing light to pass through the actuator body, as well as the quality high enough to differentiate the dermis from the epidermis while resolving individual sweat glands, proving the effectiveness of the prototyped scanner design for endoscopic OCT application.

Electromechanically Functionalized Ureteral Stents for Wireless Obstruction Monitoring.

While millions of ureteral stents are placed in patients with urinary tract issues around the world every year, hydronephrosis still poses great danger to these patients as a common complication. In the present work, an intelligent double-J ureteral stent equipped with a micro pressure sensor and antenna circuitry is investigated and prototyped toward enabling continuous wireless monitoring of kidney pressure to detect a ureteral obstruction and the resultant hydronephrosis via the indwelling stent. This electromechanically functionalized "intelligent" ureteral stent acts as a radiofrequency resonator with a pressure-sensitive resonant frequency that can be interrogated using an external antenna to track the local pressure. The prototype passes mechanical bending tests of up to 15 cm radius of curvature and shows wireless sensing with a sensitivity of 3.1 kHz/mmHg in artificial urine, which represents 25× enhancement over the preceding design, using an in vitro model with test tissue layers and a pressure range that functions within the conditions found in hydronephrotic conditions. These promising results are expected to propel intelligent ureteral stent technology into further clinical research.

Switch mode capacitive pressure sensors.

Switch mode capacitive pressure sensors are proposed as a new class of microfabricated devices that transform pressure into a mechanically switching capacitance to form an analog-to-digital signal with zero power, high sensitivity, and a high signal-to-noise ratio. A pressure-sensitive gold membrane suspended over a capacitive cavity makes ohmic contact with patterned gold leads on the substrate, closing circuits to fixed on-chip capacitors outside the cavity and leading to significant step responses. This function is achieved by allocating the switch leads on the part of the counter electrode area, while the remaining area is used for touch mode analog capacitive sensing. The sensor microchip is prototyped through a novel design approach to surface micromachining that integrates micro-Tesla valves for vacuum sealing the sensor cavity, showing an unprecedented response to applied pressure. For a gauge pressure range of 0-120 mmHg, the sensor exhibits an increase of 13.21 pF with resultant switch events, each of which ranges from 2.53-3.96 pF every 12-38 mmHg, in addition to the touch mode linear capacitive increase between switches. The equivalent sensitivity is 80-240 fF/mmHg, which is 11-600× more than commercial and reported touch mode sensors operating in similar pressure ranges. The sensor is further demonstrated for wireless pressure tracking by creating a resonant tank with the sensor, showing a 32.5-101.6 kHz/mmHg sensitivity with frequency jumps led by the switch events. The developed sensor, with its promising performance, offers new application opportunities in a variety of device areas, including health care, robotics, industrial control, and environmental monitoring.

A thermosensitive material coated resonant stent for drug delivery on demand.

An electromagnetic energy source in the radio-frequency range delivers power to a stent circuit via resonant inductive coupling, allowing a thermally triggered release of gel via Joule heating. A gold-electroplated, medical-grade stainless steel stent, serving as the base of the prototype device, melts a coating made from an emulsion composed mainly of dodecanoic acid. These coated devices produce wirelessly controllable releases of a gel into thermally regulated, stirred water that is near body temperature. The gel is made from salt, water, and gelatine from porcine skin and used to simulate drug release in this study. Thus, this system serves as a proof of concept to show the viability of controlling local drug delivery using this prototype device. Dodecanoic acid, a fatty acid, has a phase transition from solid to liquid near 43[Formula: see text]C and has relatively good biocompatibility. The average melting temperature of two different emulsions was 40.8±0.7[Formula: see text]C, a suitable value for the targeted application. Demonstration of controllable releases used electromagnetic pulses of approximately 180 seconds in duration, illustrating reproducibility of a controllable release phase while remaining relatively inert in the absence of stimuli. Releases were observable through measuring the conductivity of the water, the water temperature, and the stent temperature. This electrothermally active stent device enables wirelessly controlled local delivery with controlled dosage and timing, a concept with a wide range of potential applications. Some relevant examples include inhibiting restenosis or cancer treatment via targeted chemotherapy.

Electrothermally Driven Hydrogel-on-Flex-Circuit Actuator for Smart Steerable Catheters.

This paper reports an active catheter-tip device functionalized by integrating a temperature-responsive smart polymer onto a microfabricated flexible heater strip, targeting at enabling the controlled steering of catheters through complex vascular networks. A bimorph-like strip structure is enabled by photo-polymerizing a layer of poly(N-isopropylacrylamide) hydrogel (PNIPAM), on top of a 20 × 3.5 mm2 flexible polyimide film that embeds a micropatterned heater fabricated using a low-cost flex-circuit manufacturing process. The heater activation stimulates the PNIPAM layer to shrink and bend the tip structure. The bending angle is shown to be adjustable with the amount of power fed to the device, proving the device's feasibility to provide the integrated catheter with a controlled steering ability for a wide range of navigation angles. The powered device exhibits uniform heat distribution across the entire PNIPAM layer, with a temperature variation of <2 °C. The operation of fabricated prototypes assembled on commercial catheter tubes demonstrates their bending angles of up to 200°, significantly larger than those reported with other smart-material-based steerable catheters. The temporal responses and bending forces of their actuations are also characterized to reveal consistent and reproducible behaviors. This proof-of-concept study verifies the promising features of the prototyped approach to the targeted application area.

Wireless Hyperthermia Stent System for Restenosis Treatment and Testing With Swine Model.

This paper reports the first in vivo testing of a resonant-heating stent toward wireless hyperthermia treatment of in-stent restenosis. The stent, made of gold-coated medical-grade stainless steel, is designed to function as an electrical inductor and forms a radiofrequency (RF) resonant circuit with an integrated capacitor microchip. Upon implantation and deployment with the balloon catheter, the stent device serves as a wireless heater as part of the resonant wireless power transfer system, which allows for the device to produce mild heat only when the stent is resonated with a tuned RF electromagnetic field supplied from the external antenna. The wireless power transmitter includes an independent omnidirectional booster antenna that enhances the power delivery to the implanted stent device. The entire stent device is packaged with 40-µm-thick Parylene C film that is shown to be essential for minimizing electrothermal damping in a conductive liquid like blood. The in vitro tests of the prototype system show a temperature increase of 3.3 °C in the stent device couple in a flow loop of saline pumped at a flow rate relevant to the condition of coronary stenosis. In swine models, the system demonstrates RF heating of the stent devices expanded to different diameters, in live blood stream, achieving temperature rises of up to 2.6 °C in a consistent and repeatable manner. These results bring the technology one step closer toward clinical realization of wireless thermal therapy of in-stent restenosis.

Wirelessly Heating Stents via Radiofrequency Resonance toward Enabling Endovascular Hyperthermia.

Thermal therapy known as hyperthermia has served as an effective method for cancer treatment. This therapeutic approach has also been attracting attention for treatment of in-stent restenosis, the most common complication of stenting. Mild heating of stents has been shown to be a possible path to addressing this problem. Despite various studies on stent-based thermotherapy, this area still lacks a clinically viable method and technology. Here, a radiofrequency-powered "hot" stent prototype is reported in vitro and in vivo. An implantable stent device based on medical-grade stainless steel acts as an electrical resonator, or an efficient wireless heater operating only when resonated using tuned external electromagnetic fields. The system architecture uses a custom-developed power transmitter for wireless resonant powering/heating of the stent. An eight-shaped antenna is shown to be highly effective for near-field power transfer to the device and potentially to other smart implants, revealing stent heating efficiencies of up to 120 °C W-1 , 206% of the level provided by a conventional loop antenna. Testing with swine models, the prototyped system achieves stent heating in blood flow by powering through air and skin tissue in vivo in a fully controlled manner. The results advance stent hyperthermia technology toward possible future clinical application.

Enabling Angioplasty-Ready "Smart" Stents to Detect In-Stent Restenosis and Occlusion.

Despite the multitude of stents implanted annually worldwide, the most common complication called in-stent restenosis still poses a significant risk to patients. Here, a "smart" stent equipped with microscale sensors and wireless interface is developed to enable continuous monitoring of restenosis through the implanted stent. This electrically active stent functions as a radiofrequency wireless pressure transducer to track local hemodynamic changes upon a renarrowing condition. The smart stent is devised and constructed to fulfill both engineering and clinical requirements while proving its compatibility with the standard angioplasty procedure. Prototypes pass testing through assembly on balloon catheters withstanding crimping forces of >100 N and balloon expansion pressure up to 16 atm, and show wireless sensing with a resolution of 12.4 mmHg. In a swine model, this device demonstrates wireless detection of blood clot formation, as well as real-time tracking of local blood pressure change over a range of 108 mmHg that well covers the range involved in human. The demonstrated results are expected to greatly advance smart stent technology toward its clinical practice.

Wireless implantable chip with integrated nitinol-based pump for radio-controlled local drug delivery.

We demonstrate an active, implantable drug delivery device embedded with a microfluidic pump that is driven by a radio-controlled actuator for temporal drug delivery. The polyimide-packaged 10 × 10 × 2 mm(3) chip contains a micromachined pump chamber and check valves of Parylene C to force the release of the drug from a 76 µL reservoir by wirelessly activating the actuator using external radio-frequency (RF) electromagnetic fields. The rectangular-shaped spiral-coil actuator based on nitinol, a biocompatible shape-memory alloy, is developed to perform cantilever-like actuation for pumping operation. The nitinol-coil actuator itself forms a passive 185 MHz resonant circuit that serves as a self-heat source activated via RF power transfer to enable frequency-selective actuation and pumping. Experimental wireless operation of fabricated prototypes shows successful release of test agents from the devices placed in liquid and excited by radiating tuned RF fields with an output power of 1.1 W. These tests reveal a single release volume of 219 nL, suggesting a device's capacity of ~350 individual ejections of drug from its reservoir. The thermal behavior of the activated device is also reported in detail. This proof-of-concept prototype validates the effectiveness of wireless RF pumping for fully controlled, long-lasting drug delivery, a key step towards enabling patient-tailored, targeted local drug delivery through highly miniaturized implants.

Wireless displacement sensing of micromachined spiral-coil actuator using resonant frequency tracking.

This paper reports a method that enables real-time displacement monitoring and control of micromachined resonant-type actuators using wireless radiofrequency (RF). The method is applied to an out-of-plane, spiral-coil microactuator based on shape-memory-alloy (SMA). The SMA spiral coil forms an inductor-capacitor resonant circuit that is excited using external RF magnetic fields to thermally actuate the coil. The actuation causes a shift in the circuit's resonance as the coil is displaced vertically, which is wirelessly monitored through an external antenna to track the displacements. Controlled actuation and displacement monitoring using the developed method is demonstrated with the microfabricated device. The device exhibits a frequency sensitivity to displacement of 10 kHz/µm or more for a full out-of-plane travel range of 466 µm and an average actuation velocity of up to 155 µm/s. The method described permits the actuator to have a self-sensing function that is passively operated, thereby eliminating the need for separate sensors and batteries on the device, thus realizing precise control while attaining a high level of miniaturization in the device.

Intelligent telemetric stent for wireless monitoring of intravascular pressure and its in vivo testing.

This paper reports a sensor-integrated telemetric stent targeted at wireless detection and monitoring of restenosis, a common vascular complication induced by stent implantation. The developed "smart" stent incorporates the design and fabrication approaches that raise the practicality of the device, being tested in an in vivo study that validates its operating principle. The stent is produced to have a gold-coated helical-like structure that serves as a high-performance inductor/antenna and integrated with a novel capacitive pressure sensor chip, all based on medical-grade stainless steel. The stent device forms an inductor-capacitor resonant tank that enables radio-frequency (RF) wireless pressure sensing in an operating frequency range of 30-80 MHz. With an overall length of 20 mm, the device is designed to be compatible with standard balloon catheters and necessary crimping process. The balloon-expanded devices are characterized in saline and blood to determine selective coating of passivation layer, Parylene C, with tailored thicknesses in order to maximize both RF and sensing abilities. In vitro testing of the devices reveals a frequency sensitivity up to 146 ppm/mmHg over a pressure range of 250 mmHg. Tests in pig models show wireless detection of device's resonance and frequency response to variations in local blood pressure, the targeted function of the device.

Wirelessly addressable heater array for centrifugal microfluidics and Escherichia coli sterilization.

Localized temperature control and heater interface remain challenges in centrifugal microfluidics and integrated lab-on-a-chip devices. This paper presents a new wireless heating method that enables selective activation of micropatterned resonant heaters using external radiofrequency (RF) fields and its applications. The wireless heaters in an array are individually activated by modulating the frequency of the external field. Temperature of 93 °C is achieved in the heater when resonated with a 0.49-W RF output power. The wireless method is demonstrated to be fully effective for heating samples under spinning at high speeds, showing its applicability to centrifugal systems. Selective sterilization of Escherichia coli through the wireless heating is also demonstrated. Healthcare applications with a focus on wound sterilization are discussed along with preliminary experiments, showing promising results.

An experimental study of electrochemical polishing for micro-electro-discharge-machined stainless-steel stents.

This paper reports electrochemical polishing (EP) of 316L stainless-steel structures patterned using micro-electro-discharge machining (µEDM) for application to stents including intelligent stents based on micro-electro-mechanical-systems technologies. For the process optimization, 10 µm deep cavities µEDMed on the planar material were polished in a phosphoric acid-based electrolyte with varying current densities and polishing times. The EP condition with a current density of 1.5 A/cm(2) for an EP time of 180 s exhibited the highest surface quality with an average roughness of 28 nm improved from~400 nm produced with high-energy µEDM. The EP of µEDMed surfaces was observed to produce almost constant smoothness regardless of the initial roughness determined by varying discharge energies. Energy-dispersive X-ray spectroscopy was performed on the µEDMed surfaces before and after EP. A custom rotational apparatus was used to polish tubular test samples including stent-like structures created using µEDM, demonstrating uniform removal of surface roughness and sharp edges from the structures.

Radio aneurysm coils for noninvasive detection of cerebral embolization failures: a preliminary study.

The rupture of a cerebral aneurysm is the most common cause of subarachnoid hemorrhage. Endovascular embolization of the aneurysms by implantation of Guglielmi detachable coils (GDC) has become a major treatment approach in the prevention of a rupture. Implantation of the coils induces formation of tissues over the coils, embolizing the aneurysm. However, blood entry into the coiled aneurysm often occurs due to failures in the embolization process. Current diagnostic methods used for aneurysms, such as X-ray angiography and computer tomography, are ineffective for continuous monitoring of the disease and require extremely expensive equipment. Here we present a novel technique for wireless monitoring of cerebral aneurysms using implanted embolization coils as radiofrequency resonant sensors that detect the blood entry. The experiments show that commonly used embolization coils could be utilized as electrical inductors or antennas. As the blood flows into a coil-implanted aneurysm, parasitic capacitance of the coil is modified because of the difference in permittivity between the blood and the tissues grown around the coil, resulting in a change in the coil's resonant frequency. The resonances of platinum GDC-like coils embedded in aneurysm models are detected to show average responses of 224-819 MHz/ml to saline injected into the models. This preliminary demonstration indicates a new possibility in the use of implanted GDC as a wireless sensor for embolization failures, the first step toward realizing long-term, noninvasive, and cost-effective remote monitoring of cerebral aneurysms treated with coil embolization.

Implantable drug delivery device using frequency-controlled wireless hydrogel microvalves.

This paper reports a micromachined drug delivery device that is wirelessly operated using radiofrequency magnetic fields for implant applications. The controlled release from the drug reservoir of the device is achieved with the microvalves of poly(N-isopropylacrylamide) thermoresponsive hydrogel that are actuated with a wireless resonant heater, which is activated only when the field frequency is tuned to the resonant frequency of the heater circuit. The device is constructed by bonding a 1-mm-thick polyimide component with the reservoir cavity to the heater circuit that uses a planar coil with the size of 5-10 mm fabricated on polyimide film, making all the outer surfaces to be polyimide. The release holes created in a reservoir wall are opened/closed by the hydrogel microvalves that are formed inside the reservoir by in-situ photolithography that uses the reservoir wall as a photomask, providing the hydrogel structures self-aligned to the release holes. The wireless heaters exhibit fast and strong response to the field frequency, with a temperature increase of up to 20°C for the heater that has the 34-MHz resonant frequency, achieving 38-% shrinkage of swelled hydrogel when the heater is excited at its resonance. An active frequency range of ~2 MHz is observed for the hydrogel actuation. Detailed characteristics in the fabrication and actuation of the hydrogel microvalves as well as experimental demonstrations of frequency-controlled temporal release are reported.

A Micromachined Capacitive Pressure Sensor Using a Cavity-Less Structure with Bulk-Metal/Elastomer Layers and Its Wireless Telemetry Application.

This paper reports a micromachined capacitive pressure sensor intended for applications that require mechanical robustness. The device is constructed with two micromachined metal plates and an intermediate polymer layer that is soft enough to deform in a target pressure range. The plates are formed of micromachined stainless steel fabricated by batch-compatible micro-electro-discharge machining. A polyurethane roomtemperature- vulcanizing liquid rubber of 38-µm thickness is used as the deformable material. This structure eliminates both the vacuum cavity and the associated lead transfer challenges common to micromachined capacitive pressure sensors. For frequency-based interrogation of the capacitance, passive inductor-capacitor tanks are fabricated by combining the capacitive sensor with an inductive coil. The coil has 40 turns of a 127-µmdiameter copper wire. Wireless sensing is demonstrated in liquid by monitoring the variation in the resonant frequency of the tank via an external coil that is magnetically coupled with the tank. The sensitivity at room temperature is measured to be 23-33 ppm/KPa over a dynamic range of 340 KPa, which is shown to match a theoretical estimation. Temperature dependence of the tank is experimentally evaluated.