Active middle-ear implant based on piezoelectric thin-film cantilevers

In a typical cochlear implant, flexible lead with stimulating electrodes is inserted in the scala tympani, a fluid-filled cavity in the cochlea. When the electrical stimulation is applied, it propagates through fluid in the scala tympani and across the basilar membrane, separating the scala tympani and the scala media, an adjacent compartment of the cochlea containing the hair cells. Such rather remote operation of existing cochlear implants does not allow fine localized targeting of the hair cells, limiting their pitch resolution. Cochlear implants have not undergone significant changes in their design or function since 1985, when the first multi-channel cochlear implant was developed by Cochlear and approved by FDA. Since then, FDA approved similarly-designed cochlear implants by two other companies, one by Advanced Bionics in 1996 and another by MedEl in 2001. An apparent lack of innovation in cochlear implant is partially due to the fact that, despite their limited pitch resolution, they provide rather faithful reproduction of human speech. The remaining “holly grail” of the cochlear implant industry is a device with sufficient pitch resolution for listening to music. So far, that goal remains outside the reach, at least for the devices based on electrical stimulation of cochlea. As a welcome first step toward an alternative method of cochlear stimulation, a group of engineers at the Fraunhofer Institute for Manufacturing Engineering and Automation in Stuttgart, led by Dr. Kaltenbacher, developed a device that can be placed in the middle-ear to bypass the ossicles (the auditory bones) and provide direct acoustic stimulation of the fluid in the scala tympani. In theory, such a design can: 1) be less invasive, 2) be easily implanted in an outpatient procedure, and 3) potentially provide better sound quality than existing cochlear implants. The implant does require that at least some of the hair cells are still present in the cochlea (unlike the other types of cochlear implants). In order to bypass the bones in the middle ear, the sound is picked up by an externally-mounted microphone, converted to infrared light, passed through the tympanic membrane, picked up by a photo diode, and finally converted back to the sound waves with MEMS-based piezoelectric thin-film cantilevers (see the inset). So far, the engineers are testing individual components of the device, with a finished prototype tests planned for 2014.

One-million US$ B.R.A.I.N. Prize to support development of a breakthrough neurotechnology

The Israel Brain Technologies (IBT) has announced the launch of one-million US$ B.R.A.I.N. Prize (Breakthrough Research And Innovation in Neurotechnology) to support the development of a disruptive and medically significant neural technology toward its commercialization. An international judging committee, composed of distinguished leaders in neurotechnology and business including two Nobel Prize Laureates, will select an individual or a group from across the globe to support continued development and commercialization of the technology in collaboration with Israeli researchers and entrepreneurs. The applicants must have already produced a working prototype and be able to demonstrate a clear path to commercialization.

“The B.R.A.I.N. Prize will bring together the best minds across geographic boundaries to create the next generation of brain-related innovation, from Brain Machine Interface to Brain Inspired Computing to urgently-needed solutions for brain disease,” says Dr. Rafi Gidron, Founder and Chairman of IBT. “It’s a global brain-gain. Our aim is to open minds…quite literally.”

“We invite innovators around the world to enter the B.R.A.I.N. Prize competition, so we can tackle some of the most exciting challenges facing our planet,” said IBT Executive Director Miri Polachek. “Our aim is to bring Israeli technology to the world, and the world to Israeli technology. We want to turn the ‘Start-up Nation’ into the ‘Brain Nation.’”

In the words of Israeli President Shimon Peres, a leading proponent of brain research and technology. “There is no doubt that brain research in the next decade will revolutionize our lives and impact such major domains as medicine, education, computing, and the human mind, to name but some. Moreover, it will not only relieve the suffering of patients of such debilitating diseases as Parkinson’s and Alzheimer’s, but it will also engender large economic rewards as well.”

Prize winners could, for example, help treat neurological disorders like Alzheimer’s, Parkinson’s, depression, PTSD or even sports-related brain trauma. Or they could create the next cutting-edge brain-inspired technology that will alter our day-to-day lives.

Interested contestants can visit www.IsraelBrain.org to receive more information and to apply online. The submission deadline is March 15, 2013, and the Prize will be awarded at IBT’s International Brain Technology Conference in October 2013.

Bionic Vision Australia reaches significant milestone with its first human retinal implant

Bionic Vision Australia is a consortium of Australian scientists who are working together on suprachoroidal retinal stimulation device for restoring the lost vision. This effort involves about 150 researchers at the Bionics Institute, Centre for Eye Research Australia, NICTA, University of Melbourne, and University of New South Wales in Sydney. The suprachoroidal approach shares some similarities with the cochlear implants, as in both cases the implants are placed in a fluid-based cavity adjacent to the compartment with sensory neurons. The suprachoroid approach is considered safer and easier than surgically-challenging placements directly above the retina (epiretinal) or below it (subretinal). The analogy with the cochlear implants is not a coincidence, as the Australian researchers have leveraged from their extensive experience in developing the first FDA-approved multi-channel cochlear stimulation device for restoring the hearing more than 30 years ago.
Toward their ultimate aim of implanting the 98-electrode suprachoroidal implant, in May 2012, the Australian researchers reached a significant milestone with an implantation of the early-prototype device in three patients with profound vision loss due to retinitis pigmentosa, an inherited condition. While the functionality of the prototype is rather limited (24-electrodes and a lack of wireless interface to the camera), it will enable psychophysics studies to carefully examine the visual percepts and allow researchers to develop appropriate visual processing strategies in preparation to implantation of the fully-functional device in 2013 or 2014. The R&D effort is being supported by a $42 million grant from the Australian government and technology-sharing agreements from Cochlear Ltd.

Magnetically-induced electrical stimulation with sub-millimeter coils

Transcranial magnetic stimulation (TMS) is a well-established method of modulating neuronal activity in the brain. The TMS coil usually spans several centimeters and produces a lot of heating, making it unsuitable for intracranial implantation. The study, led by Dr. Fried at the Massachusetts General Hospital, aimed to develop a sub-millimeter sized coil that can be implanted into deep brain targets, such as the basal ganglia. Their prototype micro-coil was based on a commercial multilayer copper coil (ELJ-RFR10JFB, Panasonic) that was coated with a dielectric varnish, placed on a tip of a needle, and manually positioned above the freshly dissected rabbit retina. With the photoreceptor side down and the ganglion cell layer on top, the patch electrode was positioned on a ganglion cell to record the light-stimulated activity of individual retinal neurons. The micro-coil was oriented in two positions, either parallel or perpendicular to the retinal surface, and the DC voltage (0.5-10 V) was applied for 20 μs to induce a circulating electric field (E-field) in the retinal tissue (see the figure).  The parallel orientation was considerably more effective in inducing the neuronal activation that the perpendicular one. The train of action potentials was readily induced in the parallel orientation as far as 1.1 mm from the retinal surface.  Even more intriguingly, essentially the same amount of DC voltage (6V) was required at the micro-coil to induce the neuronal response at different distance from the retina, ranging from 0.3 to 1.1 mm. The finite element method (FEM) modeling of the electric field distribution around the micro-coil indicated that the magnetically-induced E-field was ~1 V/m at a radial distance of 1 mm from the coil core and was only slightly decreasing with distance. In contrast, the E-field decreased rather rapidly in the vertical dimension form the coil, being only 0.1 V/m at a 1 mm distance. This study provides an initial ex vivo proof of the principle and opens up a possibility of developing novel implantable neuroprosthetic devices with several features that are superior to the electrical stimulation. Among such desirable features are: 1) less steep E-field gradient, resulting in more uniform stimulation of neurons over a larger volume, and 2) absence of electrochemical reactions at the electrode-tissue interface, resulting in longer electrode lifetime and healthier tissue. Other, perhaps unexpected, benefits of the magnetically-induced electrical stimulation may become evident once the in vivo evaluation study is completed.

Glucose-harvesting fuel cell for powering neuroprosthetic devices

The team of MIT researchers, led by Rahul Sarpeshkar and Jakub Kedzierski, reported developing a Si-based fuel cell that can break down glucose and harvest its energy. The device operates by collecting the electrons liberated during electrooxidation of glucose at the anode, while the liberated protons travel to the cathode through the solution. The subsequent reduction of protons and electrons, catalyzed at the cathode, restores the net charge neutrality in the solution (or tissue). Since glucose is present in the brain and spinal cord, including the cerebrospinal fluid, the fuel cell can operate autonomously at the implantation site, without the need for supplying the fuel. Moreover, the catalyzing agent for the anodic reaction can be produced by a bacterial biofilm, which has a self-regenerating capability (although this approach might not be suitable for humans due to the biosafety concerns). Researchers calculate that a very small fraction of available glucose will be used, therefore not impacting normal brain consumption of glucose. The prototype device was able to harvest the energy at the power density up to 100 µW/cm2, which is sufficient for operation of the ultra-low-power analog electronics that is also being developed by Dr. Sarpeshkar. Harvesting the biological energy is important for removing the batteries or inductive coils from the implanted neuroprosthetic device, and consequently shrinking its size and reducing the number of feedthoughs and leads from the device. Harvesting the energy of organic compounds, such as glucose, it just one possible method of collecting the energy from biological environment, while other groups are evaluating the absorption of light, heat and mechanical vibration.

A dedicated radiofrequency spectrum is allocated for medical devices in the United States

The FCC recently allocated a dedicated RF spectrum for Medical Body Area Network (MBAN) technologies. The MBAN spectrum can be used for low-power and short-range medical applications as well as other, perhaps unprecedented, uses in consumer electronics, personal entertainment, gaming, sport training, and social network applications. The transmitting/emitting devices can be implanted or placed on the surface or around the body of humans (or animals). The MBAN adheres to IEEE 802.15.6-2012 standard and supports the data rates up to 10 Mbps. The allocated frequency bands include 402–405, 420 –450, 863 –870, 902 –928, 950 –956, 2360 –2400, and 2400 –2483.5MHz. Creation of the MBAN spectrum has been driven by the “last meter” challenge of untethering the patient from the bedside monitoring and treatment equipment. In addition to the bedside applications of MBAN spectrum, the neural interface devices are also likely to benefit from the new bandwidth. MBAN can spur the development of novel data-intensive neural interfaces, ranging from EEG and ECoG to cochlear and retinal implants. The newly-allocated bandwidth can be readily utilized for sending the wide-band neural signals from hundreds of recording electrodes or for sending the control signals to hundreds of stimulation electrodes. Use of the bandwidth reduces the need for incorporating the multiplexing and signal-processing circuits inside the implantable device and, instead, sending the raw data to an external controller, such as a body-worn smartphone-like device. My personal hope is that simplification and standardization of the implantable electronics will lead to the considerable price reduction and eventual emergence of consumer-oriented implantable neural interfaces for non-medical use.

Combination Therapies: Is this the next generation of rehabilitation?

Combining several therapies to build a rehabilitation treatment plan for neurological conditions is nothing new.  However, combining a variety of technologies into a treatment plan to produce functional outcomes is an emerging theme among innovative rehabilitation professionals. The roots of combining the rehabilitation with electrical stimulation to improve motor re-learning come from the pioneering work by Dr. Randolph Nudo and Dr. Alvaro Pascual-Leone in 1990es.

Recently, this approach was applied by combining the robotic therapy with electrical or magnetic stimulation by a team of researchers lead by Dr. Lumy Sawaki at the University of Kentucky in Lexington. This new neural rehabilitation technique capitalizes on “neuroplasticity,” which refers to the brain’s ability to reorganize itself by forming new neural connections to compensate for injury and disease.  Dr. Lumy Sawaki, MD, PhD, an Associate Professor in the Department of Physical Medicine and Rehabilitation at the University of Kentucky, has been exploring how combining technologies in the rehabilitation setting may help her patients regain functional movements. This new therapy is based on previous work she had done involving CIMT, constraint-induced movement therapy.  Dr. Sawaki was the lead author on a CIMT study published in the journal Neurorehabilitation and Neural Repair.   In this study, each of the 30 participants was evaluated using transcranial magnetic stimulation (TMS), a non-invasive method to excite neurons in the primary motor cortex. In the CIMT therapy study, Dr. Sawaki and collaborators used TMS to map the area of the brain that controls a particular muscle and compared this map to previous patterns of activity. As the patient’s ability to perform a certain movement improves, these brain maps confirm the reorganization of the associated area of the brain. Focusing on hand motor function of sub-acute stroke survivors, they observed changes within the functional activity of the brain for those who used CIMT.

Building on this previous work, Dr. Sawaki and her research team are evaluating the combined approach to stimulate the brain with two painless and non-invasive methods: the magnetic stimulation with TMS and the electrical stimulation with transcranial direct current stimulation (tDCS), to develop a new neural rehabilitation therapy for chronic survivors of neurological trauma from stroke, brain and spinal cord injuries. In this new therapy, the TMS and tDCS is applied along with robotic movement therapy, such as body weight supported treadmill training. Dr. Sawaki is using TMS and tDCS to stimulate the area inside the motor cortex that controls movement of a targeted muscle. By applying multiple stimuli and monitoring the muscle response combined with robotic therapy, the investigators are attempting to determine if this combination will result in higher functional benefit.

Conclusive evidence is still lacking but it brings the promise of combined neural rehabilitation therapies paving a new path for how we approach complex neurological conditions in the rehabilitation setting.  Click here to read more about Dr. Lumy Sawaki’s research and new neurorehabilitation therapy.

Build your own amplifier for electrophysiological recording @ US$10 per channel!

It is well known that building a setup for recording neural spikes is not trivial. Many older electrophysiological systems are bulky, expensive and difficult to use. Their system components require elaborate shielding and grounding  to reduce the electromagnetic interference. Recently, the technology advances have been quite rapid. It has become possible to build the millimeter-scale electrophysiology amplifiers from commercial off-the-shelf components. Here, I would like to share an amplifier design that is capable of intracellular and extracellular recording, as well as LFP, EMG, and EEG. It is small, easy to build and extremely cheap. The system uses differential mode of recording, thus eliminating the need of extensive shielding from environmental noise. The circuit had been tested on freely-moving animal exposed to their regular environment and was able to record neural spikes with a good signal-to-noise ratio (SNR).

The amplifier is divided into two stages. The first stage is an Instrumentation Amplifier (IA) with the differential input. The input signals have DC removed (with a high-pass filter) with highly tuned RC components. It is important to have very closely matched components to have high Common Mode Rejection Ratio (CMRR). The capacitors Cpf and Cnf are for power supply regulation with typical value of 0.1µF. The gain of the instrumentation amplifier is typically set in the range from 100 to 1000. The second stage is a second order low-pass filter (sellen-key). The gain of this filter should be maintained about 10; resulting in a total gain of the amplifier of ~10,000.

Following are the example values for the filter amplifier:

Chp1 = CHR = 100nF, RH1 = RHR = 4.68MΩ; Low Cut-off frequency = 0.34Hz;

R1= 10kΩ, R2= 150kΩ, C1= 1nF, C2= 1nF, R3= 10kΩ, R4= 100kΩ; High Cut-off frequency = 4,109Hz;

NOTE: For multiple channels build the same circuit and use them in parallel. For single reference electrode just short all the inverting terminals (-) of all instrumentation amplifiers and use only one reference high-pass filter (CHR, RHR) instead.

First flexible organic transistor to withstand considerable heating

An international research team from Japan, Germany, and United States reported creating a flexible organic transistor that features good thermal stability at temperatures up to 150°C. The new transistor has been fabricated with a biocompatible polymeric substrate (Parylene), making it potentially useful for ECoG and other types of implants. Fabrication of many implantable devices involves some steps that have to be performed at elevated temperatures (e.g. parylene annealing). In addition, device sterilization is also commonly done at elevated temperatures of 130-170°C and (optionally) an elevated chamber pressure, in a process called autoclaving. The autoclaving, done at 150°C and atmospheric pressure, takes less than 3 hours, faster than room-temperature sterilization using ethylene oxide (24 hours).

The key technological achievement in the reported study is the use of an ultrathin (2 nm) heat-resistant monolayer film for insulation between the organic semiconductor and its gate. The monolayer is synthesized by a self-assembly of long-tailed phosphonic acids and has a densely packed crystalline (rather than amorphous) structure. Such ordered chemical structure prevents a formation of pinholes during heating. The use of ultrathin monolayer between the semiconductor and its gate instead of thicker dielectric films allowed the researchers to reduce the transistor driving voltage from 20V to 2V, making it more suitable for neuroprosthetic applications. Main limitation of the reported study is the short duration of the applied heat stress (20 sec), which does not evaluate a possibility of a slow heat-induced degradation of the self-assembled monolayer.

Ion-selective electrodes for manipulating cation availability in nerve stimulation and for neural conduction block

During stimulation, the applied electrical charge induces similar flows of multiple extracellular cations (K+,Na+ and Ca2+) in the electrode vicinity. This is rather counter-productive as these cations play varying roles in the initiation and propagation of action potentials. As a result, a significant percentage of applied electric charge is being wasted. Now, scientists at MIT and Harvard Medical School have reported a way to alter the cation concentrations using commercially available cation-selective resin solutions deposited on planar electrodes. In one experiment, they applied small positive DC current (≤1µA, 10 to 100 times below the nerve activation threshold)  to a centrally-located calcium-selective electrode for 1 min to deplete Ca2+ concentration from the fluid surrounding the nerve. Immediately thereafter, they applied the supra-threshold electrical pulses between two lateral uncoated electrodes, while the central electrode was off. The researchers achieved a 70% decrease in the amount of current required for reaching the nerve activation threshold. In another experiment, the K+– and Na+-selective electrodes were used to deplete the concentrations of these ions at some distance from the stimulating electrode. Such cation depletion caused a complete conduction block for 10 min after applying a cation-depleting DC current of 1µA for 5 min. Both K+– and Na+-selective electrodes were equally effective in blocking the action potential propagation. This finding could have important applications in shutting off the nociceptive neural activity in relieving chronic pain. Finally, the developed cation-selective electrodes have two important features making them attractive for neuroprosthetic applications: 1) they can be microfabricated and 2) they do not require a chemical reservoir for their operation.

Blood entry sensor for cerebral embolization using RF resonance of micro-coils

About 3 -4% of the general population has or will develop a cerebral aneurysm, with most are without any symptoms. Aneurysm is an enlarged area of a blood vessel that usually develops at a branching point of artery and is caused by constant pressure from blood flow. It often grows gradually and becomes weaker as it stretches. Rupture of a cerebral aneurysm causes bleeding into the brain, often leading to a stroke. Endovascular embolization using micro-coils has emerged as a successful preventive treatment for aneurysms. The micro-coils are made from platinum wire (thickness 20–120 μm) wound at diameters of 200–500 μm for length up to 50 cm. Once the coil is inserted through the artery into the aneurysm, it forms a randomly tangled globe that promotes clotting of blood, thus preventing further inflow of blood and pressure rise. In about half of implanted patients,
the embolization process fails within 18 months, requiring frequent checks for the blood entry into the aneurysm using expensive, invasive, and potentially toxic methods, such as X-ray angiography and computer tomography. The group of Dr. Takahata at the University of British Columbia has reported a new method for monitoring blood entry into aneurysms, which is simple and inexpensive enough for frequent monitoring at home. In their method, the RF resonance of the micro-coils is used as a moisture sensor.  The RF resonant circuit is formed by self-inductance combined with parasitic capacitance, which is affected by tissue permittivity around the coil. At 100 MHz, for example, the dielectric constant of blood is 25 times higher than that of fibrous tissue. The RF coupling of the micro-coils would be done with an external antenna attached to the head of a patient. The present study was conducted using animal muscle tissues, with a clinical device
anticipated in 2-3 years.

Protonic transistor for more natural neuronal stimulation

As described in the September issue of Nature Communications, Prof. Rolandi ‘s team at the University of Washington, Seattle has created the first solid-state transistor that controls the flow of protons instead of electrons. This is much more practical for transmission of information in biological tissues than electrons, as protons can freely interact with ions.  The key challenges in developing proton-based electronics are to find the right materials for pumping and conducting the protons. In the developed prototype transistor, the pumping action is mediated by palladium, which can absorb hydrogen and create a hydride that easily accepts and donates protons. The protons then flow through a 3.5-micrometer-wide channel made from nanofibers of chitosan, a polysaccharide extracted from the chitin shells of crustaceans (such as crabs and shrimp). The prototype is built on the silicon substrate, but the final device would probably use a more biocompatible material. The protonic transistor behaves like a traditional field-effect transistor, with the current flowing between the source and drain under the control of the gate. The ability to modulate the current flow in this protonic transistor is rather limited (by a factor of 10) compared to high gain ratios in conventional electronic transistors (x10,000). Unlike these conventional transistors, the protonic one does not have a p-n junction to block the current when the device is off. So, the protonic transistor functions more like a variable resistor than a switch. Despite its limitations, it is a big step toward more natural neuronal stimulation, as the device is easy to fabricate and is more stable than previous attempts, using microfluidics and thin films.

Infrared light for possible treatment of neuroinflammatory diseases

According to a recent MedGadget post, a Colorado-based company Clarimedix has developed a BandAid-looking device that can be attached on the neck’s skin and emits infrared light onto the carotid artery. The device is being evaluated for treatment of Alzheimer’s disease. The company’s website provides scant scientific explanation for its therapeutic action indicating just that light modulates the production of nitric oxide (NO) in the brain . To expand on their rationale, I examined recent literature on this subject and sketched the diagram (see the image) illustrating the hypothetical mechanism of device’s action. According to one recent review, NO has two opposing effects on neurons. On one hand, NO is involved in neuroprotection by activating the Akt, Bcl-2, and MAP kinase survival pathways. On the other hand, NO inhibits mitochondrial respiration (by blocking the activity of cytochrome c oxidase), therefore depleting neurons of energy and ultimately leading to their inflammation and death. The harmful effect of NO on mitochondrial respiration can be reversed by light, at least in vitro. So, by illuminating the carotid artery, the Clarimedix device modulates the NO release and possibly helps to suppress the progression of neuroinflammatory diseases, such as multiple sclerosis,  Alzheimer’s and Parkinson’s diseases. The evidence for its therapeutic action is very weak at the moment but non-invasive nature of the therapy will hopefully allow for a quick and inexpensive clinical trial.

Treating brain glioblastoma with alternating electric fields

Glioblastoma is the most common type of brain tumor affecting 0.002-0.003% of general population. In glioblastoma, the astrocytes (neuron-supporting glial cells) turn into cancerous cells, start to divide frequently  and gradually form a large mass pressing against the brain. Glioblastoma is a challenging disease to treat as dosages of radiotherapy and chemotherapy are limited by their toxicity to the brain tissue. The use of alternating electrical fields is a novel approach that aims to suppress the division (mitosis) of malignant cells while sparing non-dividing neuronal cells in their vicinity. An Israeli-based company NovoCure Ltd. developed a stimulation device, Novo-TTF, which delivers alternating electric fields through insulated electrodes attached on the scalp surface. The scientific foundation of this approach comes from the study by the Technion scientists showing that alternating electrical fields can stop the cells from dividing and can even destroy them, if the cells are oriented roughly along the field direction. Importantly, the dividing cells inside the blood vessels appear to be unaffected. The key concern for the therapeutic use of alternating electric fields relates to their effects on neurons. At low frequencies, under 1 kHz, alternating electric fields stimulate neurons. As the frequency of the electric field increases above 1 kHz, the field can better penetrate through the cellular membrane, and its effect on neuronal excitability is diminished. At even higher frequencies, above 100 MHz, the brain exposure becomes localized and significant local heating can occur. Faced with these possible side-effects of low and high frequencies, the scientists decided to stick with intermediate frequencies of 100–200 kHz.  The electric fields at these frequencies might be relatively safe as long as their intensity is kept below the threshold for inducing the pore formation in the cellular membrane, through a phenomenon called electroporation. A recently completed phase III trial of the Novo-TTF device alleviates some of these concerns by showing no change in incidences of headaches or seizures in patients. The device is likely to be approved for use in the US within the next three months.

Video of the fabrication steps for Argus III retinal prosthetic device

The US Department of Energy-funded Artificial Retina project is geared toward developing an epi-retinal prosthesis. To date, the effort resulted in fabrication of Argus I and Argus II devices with, respectively, 16 and 60 sites for retinal stimulation. The Argus II device has been commercialized by the company Second Sight and already gained the marketing approval in Europe with plans for the US approval in 2012.  Meanwhile, the continued effort is underway at the Center for Microtechnology and Nanotechnology at the Lawrence Livermore National Labs (LLNL) to fabricate the third-generation device, Argus III, that will have 1000 or more stimulation sites.  Those who are curious about the advanced microfabrication steps involved in making the Argus III can have a look at this video produced by the LLNL. The video is shot at spectacular 1080p and details all major steps from patterning the layers to device release from the wafer and its integration with a wireless chip.