Remote Stimulation of Sciatic Nerve Using Cuff Electrodes and Implanted Diodes.

We demonstrate a method of neurostimulation using implanted, free-floating, inter-neural diodes. They are activated by volume-conducted, high frequency, alternating current (AC) fields and address the issue of instability caused by interconnect wires in chronic nerve stimulation. The aim of this study is to optimize the set of AC electrical parameters and the diode features to achieve wireless neurostimulation. Three different packaged Schottky diodes (1.5 mm, 500 µm and 220 µm feature sizes) were tested in vivo (n = 17 rats). A careful assessment of sciatic nerve activation as a function of diode⁻dipole lengths and relative position of the diode was conducted. Subsequently, free-floating Schottky microdiodes were implanted in the nerve (n = 3 rats) and stimulated wirelessly. Thresholds for muscle twitch responses increased non-linearly with frequency. Currents through implanted diodes within the nerve suffer large attenuations (~100 fold) requiring 1⁻2 mA drive currents for thresholds at 17 µA. The muscle recruitment response using electromyograms (EMGs) is intrinsically steep for subepineurial implants and becomes steeper as diode is implanted at increasing depths away from external AC stimulating electrodes. The study demonstrates the feasibility of activating remote, untethered, implanted microscale diodes using external AC fields and achieving neurostimulation.

Comparison of Electrical and Ultrasound Neurostimulation in Rat Motor Cortex.

Ultrasound (US) is known to non-invasively stimulate and modulate brain function; however, the mechanism of action is poorly understood. This study tested US stimulation of rat motor cortex (100 W/cm2, 200 kHz) in combination with epidural cortical stimulation. US directly evoked hindlimb movement. This response occurred even with short US bursts (3 ms) and had short latency (10 ms) and long refractory (3 s) periods. Unexpectedly, the epidural cortical stimulation hindlimb response was not altered during the 3-s refractory period of the US hindlimb response. This finding suggests that the US refractory period is not a general suppression of motor cortex, but rather the recovery time of a US-specific mechanism.

Wireless impedance measurements for monitoring peripheral vascular disease.

Wireless microdevices powered by ultrasound energy have been fabricated to measure and telemeter tissue impedance spectrums for applications in peripheral vascular disease monitoring. The system is characterized by simplicity of the implant consisting of only two electrical components. Ex vivo testing shows the potential for constructing tissue impedance spectrum plots over the range from 10 Hz to 10 kHz by a device less than 1 mm in diameter and 1 cm long. The neurostimulator microdevice was powered by continuous waveform 650 kHz ultrasound with a swept-frequency amplitude modulation. The system was operated at safe ultrasound power levels on the order of 10-100 mW/cm(2). The device proved to be sensitive and able to measure tissue impedances over a broad range. Volume conducted signals carrying impedance information from the microdevice were remotely detected by surface biopotential electrodes.

Characterization of simple wireless neurostimulators and sensors.

A single diode with a wireless power source and electrodes can act as an implantable stimulator or sensor. We have built such devices using RF and ultrasound power coupling. These simple devices could drastically reduce the size, weight, and cost of implants for applications where efficiency is not critical. However, a shortcoming has been a lack of control: any movement of the external power source would change the power coupling, thereby changing the stimulation current or modulating the sensor response. To correct for changes in power and signal coupling, we propose to use harmonic signals from the device. The diode acts as a frequency multiplier, and the harmonics it emits contain information about the drive level and bias. A simplified model suggests that estimation of power, electrode bias, and electrode resistance is possible from information contained in radiated harmonics even in the presence of significant noise. We also built a simple RF-powered stimulator with an onboard voltage limiter.

Non-invasive method to detect the changes of glucose concentration in whole blood using photometric technique.

A non-invasive method is developed to monitor rapid changes in blood glucose levels in diabetic patients. The system depends on an optical cell built with a LED that emits light of wavelength 535nm, which is a peak absorbance of hemoglobin. As the glucose concentration in blood decreases, its osmolarity also decreases and the Red Blood Cells (RBCs) swell and decrease the path length absorption coefficient. Decreasing absorption coefficient increases the transmission of light through the whole blood. The system was tested with a constructed optical cell that held whole blood in a capillary tube. As expected the light transmitted to the photodiode increases with decreasing glucose concentration. The average response time of the system was between 30-40 seconds.

Method of locating ultrasound-powered nerve stimulators.

We have previously shown a small simple ultrasound-powered nerve stimulator. The piezoelectric implant receives power from an external driving ultrasound transducer. Focusing the ultrasound beam improves power transfer efficiency, but the implant location must be known to aim the focus. We show that currents driven by the stimulator might be detectable on the skin. By scanning the ultrasound focus and measuring the electrical response, we form an image of the implant location. This could give a feedback signal for aiming the beam, and allow multichannel addressing of several stimulators with no added circuitry in the implant.

A microwave powered injectable neural stimulator.

An unexpectedly simple implantable device that can achieve wireless neurostimulation consists of a short 1 cm long dipole platinum wire antenna, a Schottky diode, and a pulsed microwave transmitter. Fabricated into a 1 cm long by polyimide tubing, the implant can have a sub-millimeter diameter form factor suited to introduction into tissue by injection. Experiments that chronically implant the device next to a rat sciatic nerve show that a 915 MHz microwave transmitter emitting an average power of 0.5 watts has an ability to stimulate motor events when spaced up to 7 cm from the body surface. Tissue models consisting of saline filled tanks show the possibility of delivering milliampere pulsed current to neurosimulators though 5 centimeters or more of tissue. Such a neurostimulation system driven by microwave energy is limited in functional tissue depth by microwave SAR exposure. This report discusses some of the advantages and limitations of such a neurostimulation approach.

A Fully-Passive Wireless Microsystem for Recording of Neuropotentials using RF Backscattering Methods.

The ability to safely monitor neuropotentials is essential in establishing methods to study the brain. Current research focuses on the wireless telemetry aspect of implantable sensors in order to make these devices ubiquitous and safe. Chronic implants necessitate superior reliability and durability of the integrated electronics. The power consumption of implanted electronics must also be limited to within several milliwatts to microwatts to minimize heat trauma in the human body. In order to address these severe requirements, we developed an entirely passive and wireless microsystem for recording neuropotentials. An external interrogator supplies a fundamental microwave carrier to the microsystem. The microsystem comprises varactors that perform nonlinear mixing of neuropotential and fundamental carrier signals. The varactors generate third-order mixing products that are wirelessly backscattered to the external interrogator where the original neuropotential signals are recovered. Performance of the neuro-recording microsystem was demonstrated by wireless recording of emulated and in vivo neuropotentials. The obtained results were wireless recovery of neuropotentials as low as approximately 500 microvolts peak-to-peak (µV(pp)) with a bandwidth of 10 Hz to 3 kHz (for emulated signals) and with 128 epoch signal averaging of repetitive signals (for in vivo signals).

Wireless ultrasound-powered biotelemetry for implants.

A miniature piezoelectric receiver coupled to a diode is evaluated as a simple device for wireless transmission of bioelectric events to the body surface. The device converts the energy of a surface-applied ultrasound beam to a high frequency carrier current in solution. Bioelectrical currents near the implant modulate the carrier amplitude, and this signal is remotely detected and demodulated to recover the biopotential waveform. This technique achieves millivolt sensitivity in saline tank tests, and further attention to system design is expected to improve sensitivity.

A miniature fully-passive microwave back-scattering device for short-range telemetry of neural potentials.

This paper describes a fully passive telemetry technique based on microwave backscattering. In this technique, a subharmonically-pumped passive mixer is coupled to a bio-probe and one or two miniature antennas. When interrogated by an RF excitation, this device generates an amplitude modulated RF backscattering component centered at twice the frequency of excitation. An external sensitive receiver can be used to demodulate the backscattering component and recover the bio-potential. A simple prototype based on solid state diodes has been fabricated and tested for 2.4/4.8 GHz and has the dimensions of 11.5x4.6 mm2 and thickness of approximately 1 mm. Experiments with this very simple device show that low-frequency signals (fm<1 kHz) as low as 1 mV can results in double-sideband levels of greater than -126 dBm for an incident RF power of less than 1 mW/cm2. The proposed device is intended to be coated with an insulating bio-compatible coating and serve as a telemetry chip for chronic implantation inside the body.

Ultrasonic cardiac pacing in the porcine model.

Periodic pulses of intense ultrasound energy at 70 kHz with 5-ms duration at 3 MPa SPL applied to the exposed pig myocardium at physiologic rhythms were observed to produce cardiac pacing. Ten animals were successfully paced at pulse width and energy conditions above a certain threshold. Sigmoid strength-duration curves characterizing ultrasound's effectiveness in pacing were observed to resemble those of electrical stimulation. We suggest that bioelectrical stimulatory effects of ultrasound on the heart are a radiation pressure effect and a manifestation of the known myocyte sensitivity to stretch.

Piezoelectric contrast materials for ultrasound imaging.

Piezoelectric ceramics and polymers can be used as a type of marker and contrast material for medical ultrasound imaging systems. High-frequency electrical signals are detected from surface electrodes when these materials are introduced into conducting media such as tissue and scanned by ultrasound imaging systems. Detected signals are applied to the imaging circuits of a modified ultrasound system such that they display a unique type of electrical image that shows the piezomaterial's polarization, shape, and position at arbitrarily high contrast compared to the conventional ultrasound acoustic image. The resulting piezoelectric image can be merged in real-time with conventional ultrasound acoustic imaging to form a composite image. This approach is of interest in the development of improved techniques for imaging medical devices that are implanted or otherwise introduced into the body.

Ultrasonically-assisted intracortical microstimulation of the rat.

High frequency tone bursts of ultrasound are capable of increasing the sensitivity of rat motor cortex to electrical stimulation. In this study, 11.75 MHz ultrasound pre-stimuli were delivered to the forelimb motor region of the rat cortex followed by an electrical pulse train to assess changes in cortical activation. The temporal peak intensity of the ultrasound delivered to the brain ranged from 100 to 150 W/cm(2). Tone bursts of 10 to 50 ms in duration were delivered once per second over periods of 30 to 240 seconds. The intracortical microstimulation (ICMS) current needed for forepaw motor response decreased by as much as 40% when applying 50 ms ultrasound pulses. Brain excitability changes were seen with a thermal index (TI) as low as 2.0. Ultrasound application alone was not able to induce motor responses.