Medtronic introduces the prototype of a tiny wireless pacemaker … but lacks the technology to power the device

Dr. Stephen Oesterle, Medtronic’s senior vice president for medicine and technology, made an announcement about an interesting new device at works at the world’s largest medical device company – the tiny injectable pacemaker. Judging by the provided photo of the prototype, its width is ~2 mm and length is ~6 mm, allowing it to be implanted into the heart via a small catheter rather than an invasive surgery. Medtronic’s R&D department has already developed an ASIC chip featuring most of the components—an oscillator to generate current, a capacitor to store and rapidly dispense charge, memory to store data, and a data telemetry system. “What we don’t have that is fundamental to a pacemaker is a way to power the chip,” said Oesterle. It is not clear whether Medtronic will try to develop this crucial piece of technology in-house or to buy the patent rights from others. Considering that the device would have to deliver tens of mA of current (perhaps more), the power telemetry development might be not an easy task. Additional challenges facing the device developers include deep device placement and limited space for the antenna given the small device size. For these reasons, it might not be feasible to use the existing RF inductive-coupling power telemetry technologies developed for superficially-placed neurostimulation devices, such as the RF-BIONTM Implantable Microstimulator from AMF and the SAINTTM from MicroTransponder Inc. Other possibilities do exist, such as the resonant antennas operating at microwave frequencies, but these technologies have a long way to go before they are applied for any biomedical applications. I guess, we will be more certain about the Medtronic’s plans once they start hiring the microwave antenna engineers.

First clinical trial of a brain-controlled artificial arm to begin by summer’s end

Since 2005, DARPA (the Defense Advanced Research Projects Agency) has invested more than $100M into development of the brain-machine interfaces (BMIs) by sponsoring two programs, Revolutionizing Prosthetics and Human-Assisted Neural Devices. Most of that funding went into creation of two BMI-controlled artificial arms – the 10-degrees-of-freedom (DoF) DEKA “Luke” Arm by DEKA R&D Corp. and the 22-DoF Modular Prosthetic Limb (MPL) by Johns Hopkins University together with University of Pittsburgh and California Institute of Technology. A smaller effort to develop the 3-DoF BMI-controlled artificial arm is also underway in Germany by the company Otto Bock HealthCare GmbH. It now appears that DARPA’s investment into neuroprosthetic control of the arm may begin to materialize as early as this summer. The BMI control of the MPL arm will be made possible by the array of penetrating electrodes implanted into the motor cortex of five quadriplegic patients. The silicon-based array will record the multi-unit activity in the cortical area that controls the arm movement and the recorded information will be used to predict the intended direction and force of movement. Penetrating silicon-based arrays have been already successfully tested in monkeys, demonstrating the feasibility of decoding the intent of different movements from cortical signals. The biggest remaining problem is a rapid deterioration in the quality of neural recordings from cortical arrays, ranging from several months to a year.  A range of strategies can potentially overcome this problem: 1) by making the electrodes less stiff, 2) by removing the wires tethering the array to the skull, and 3) by using a biomimetic array coating to improve its biocompatibility and reduce the immune response. It is unlikely that any of these novel strategies will actually be used in the first generation of cortical arrays for the MPL control. Nevertheless, the upcoming clinical trial will be a positive event for the BMI R&D community after suffering a setback from the failed BrainGate trial three years ago. Progression of the BMI-MPL clinical trial will be closely monitored and guided by the FDA, which, after extensive talks with DARPA, recently created the Innovation Pathway specifically for such pioneering and transformative medical technologies. By utilizing this Pathway, the FDA aims to cut the premarket approval process time in half (to 150 days or less), suggesting a smooth commercialization path for the BMI-MPL after conclusion of its clinical trials.

Penetrating electrode arrays for retinal stimulation

On the heеls of the previous post, here is another news bit on the topic of retinal implants. Over the years, we have witnessed a variety of approaches being applied for retinal stimulation, including the epiretinal, subretinal, and suprachoroidal. One feature, however, remained unchanged in those varied types of implants – a planar geometry of the stimulation array.  At least until now. As the competition in the retinal implant sector is heating up,  the issues of low-power operation and improved electrode contact with retinal neurons is fueling the development of stimulation arrays featuring the 3D geometries. Improved charge delivery to retinal neurons has been achieved a few years ago by fabricating the protruding 3D nanoelectrodes in Daniel Palanker’s lab at Stanford University and at Dong-Il Dan Cho’s and Sung June Kim’s labs at Seoul National University. Now, preparing to reach even deeper into the retina, the Israeli company Nano-Retina Inc., co-founded by Rainbow Medical Ltd. and Zyvex Labs. , is developing the Bio-Retina implant featuring the array of 100-µm-sized penetrating electrodes. Their length should allow the electrodes to reach the layer of bipolar cells that are spared in AMD and other degenerating retinal disorders. The first-generation array will have 24×24 electrodes and the second – 72×72. Power to the device will be delivered wirelessly using the infrared light beamed from the glasses. To expedite their efforts in developing the low-power IC chip with the built-in photodetector array and power telemetry, Nano-Retina has teamed up with CMES (Centre Suisse d’Electronique et de Microtechnique), a non-profit R&D center in Switzerland. According to their (perhaps too optimistic) estimates they plan to have the functional device ready for clinical trials by 2013 and even have estimated the target price of $60K for the Bio-Retina implant. We wish the best of luck to this young ambitious company, hoping it has what it takes to develop a device from scratch in such a short period of time.

Organic film photodetectors for retinal implants

An important issue for the realization of retinal prosthetic devices is a conversion of light into electrical energy using photodetectors. The existing implants utilize the photodetectors made from semiconductors, either silicon or GaAs/AlGaAs, which exhibt moderate efficiency of photovoltaic energy conversion. Recently, the photodiodes based on nanoscale photo-ferroelectric thin films have been evaluated in order to overcome the charge injection limit of semiconductor photodiodes, imposed by the band gap of the p-n junction. However, the photovoltaic conversion efficiency of ferroelectric materials is too small to make them a viable option for retinal implants. The silicon-based photodetectors, although practical, provide the quantum efficiency of about 1000 times lower than the retinal photoreceptors, so that an intense eye irradiation, required for their operation, may be damaging (phototoxic) to remaining retinal photoreceptors. Faced with this challenge, Dr. Lanzani from Istituto Italiano di Tecnologia and Politecnico di Milano in Italy decided to evaluate the soft organic film photodetectors, which have the advantages of biocompatibility, flexibility, minimal heat dissipation, and inexpensive deposition by ink-jet printers. Dr. Lanzani used the fullerene–polythiophene film, commonly used in organic solar cells, patterned on one side with the indium tin oxide to form a transparent electrode for neuronal stimulation. The organic film photodetectors remained functional after a month of in vitro testing. Let’s hope that an upcoming in vivo testing in the eye will validate the efficacy and safety of novel photodetectors.

Innovative research in the field of brain-computer interface (BCI)

The BCI encompasses multiple types of neural technology united by a common purpose of assisting, augmenting, or repairing human cognitive or sensory-motor functions at the cortical level.  Taking its roots from the EEG interfaces in early 1970s, the BCI field has gradually grown to include other non-invasive techniques, such as the NIRS (near infrared-spectroscopy), fMRI (functional magnetic resonance imaging), and MEG (magnetoencephalogram). It has also evolved to include the invasive technologies, such as the electrocorticogram (ECoG) and penetrating cortical electrodes. In 2010, an international committee, headed by Dr. Gerwin Schalk of the Wadsworth Center (Albany, NY), critically evaluated the trends and developments in the BCIs by focusing on its novel applications and technological improvements. The  committee examined 57 submissions and selected the winner of 2010 BCI Research Award – a team led by Dr. Guan Cuntai from A*STAR, Singapore – for his work on motor-imagery based BCI coupled to a robotic arm and used for rehabilitation after stroke. The 2011 BCI Research Award will be awarded during the 5th International BCI Workshop on Sept. 22-24, 2011 in Graz, Austria. In the analysis of nominations for the 2010 award, the EEG is clearly the predominant technology accounting for 75% of nominations, while the fMRI and ECoG accounting for 3.5% each, NIRS accounting for 1.8%, and penetrating electrodes accounting for 0.9%. Current philosophy in the BCI development is dominated by four assumptions, stated in a recent article by Prof. Jon Wolpaw of the Wadsworth Center: (1) intended actions are fully represented in the cerebral cortex; (2) neuronal action potentials can provide the best picture of an intended action; (3) the best BCI is one that records action potentials and decodes them; and (4) ongoing mutual adaptation by the BCI user and the BCI system is not very important. According to Prof. Wolpaw, these assumptions are flawed. Indeed, much of the motor control occurs at the spinal cord, brainstem, and deep brain levels. Further complication for BCI is that the cortical involvement in the motor control is state-dependent and continually adapts to optimize the performance in different tasks. Present generation of BCI algorithms do not account for such state-dependent and performance-driven adaptations therefore their effectiveness quickly degrades over a period of several days. Yet another level of complexity for decoding of cortical signals stems from the profound slowly-developing plasticity in the motor cortex after the stroke or spinal cord injury. Fortunately, novel adaptive learning algorithms, like those in the IBM’s Jeopardy-winning computer Watson, continue to grow in sophistication and eventually should attain the adaptability needed for handling the challenges of BCI.

Novel platform technology for neuromodulation applications

The present-day neuromodulation technology has been around for 25 years despite the advances in microfabricaion methods and electronics. In part that is due to a lack of novel scalable platform technologies with proven reliability of electrode-tissue interface, interconnects, and packaging. One of such platform technologies is now being developed by Dr. John Parker at the Sydney-based Implant Systems Group of the Australian research center NICTA. Leveraging from the cochlear implant technology, developed by the Cochlear Corp., Parker and his coworkers are developing a modular platform consisting of the multi-channel electrodes, sensors, actuators, processing elements, and packaging. Among the novel features of this platform are: a novel method for microfabrication of the electrode arrays involving the wire electrodes sawn into polymer yarn, novel biocompatible chip-scale hermetic packaging, and novel ASIC architecture for highly distributed neurostimulation systems employing optical data transmission. Targeted neuromodulation applications for this platform technology range from movement disorders (Parkinson’s disease and essential tremor) to obesity and depression. Perhaps because of a relative simplicity of epidural spinal implantation and a limited number of required stimulation channels, the chronic intractable pain was chosen as the first target application of the technology.  The INS2 device will include all key components of the platform including the yarn-woven electrodes with recording and stimulation capability, the ASIC chip, and a rechargeable battery with power telemetry. The human trials will begin sometime in 2011. If successful, the technology will be commercialized by a new spin-out company Saluda Medical.

Harvesting light and heat energy from the body with a hybrid device

Rechargeable batteries are increasingly more common in neural implants, removing the need for multiple surgeries to replace a depleted battery. Alternative strategies are being developed for replenishing the energy of the battery. The most established method of energy delivery is via radio waves. Recent shift toward the use of higher frequencies in the 0.1-1 GHz band made the rectenna (receiving antenna) extremely small. This allowed the implant to fit within an injectable needle for a minimally invasive delivery at a location near a peripheral nerve. In order to eliminate the need for coupling the implant with an external charging device, methods are being developed for harvesting the energy from the human body. These methods utilize the energy of light (visible or infrared), heat, or vibration.  Harvesting of visible light can be done most efficiently in the retina, while infrared light can penetrate the skin and be used for transcutaneous powering of the implants. In the body, amount of energy available for harvesting is rather limited, so that multiple forms of energy – such as light and heat, or light and vibrations – can be used simultaneously in order to collect a sufficient amount for practical use. This can be achieved by combining different kinds of energy transducers. In pursuit of this approach, Fujitsu Laboratories has developed a new hybrid harvesting device that captures energy from either light or heat in a single device. Their device is manufactured from inexpensive organic materials, keeping the production costs low. The device contains two types of semiconductor materials – P-type and N-type semiconductors – allowing it to function as a photovoltaic cell or thermoelectric generator. Importantly, their hybrid device can be fabricated on flexible substrate for easy accommodation into different implant shapes.  The company is currently refining the technology to increase its performance, and aims to commercialize it by around 2015.

Neurotech exploration setup for a curious child: price – $100, experience – priceless

Take a look at this self-explanatory video from Backyard Brains, a web store founded by two grad students at U. Michigan. It shows how to teach the basics of neural stimulation and recording on a slim budget. Their Spikerbox setup consists of a simple op-amp circuit, a few filters, an A/D, and a speaker, all connected to an iPhone for stimulus generation or recording. If you have a kid interested in neuroscience, don’t pass up this opportunity for a fun educational evening with the Spikerbox.

Neural probe with integrated microfluidics and pumps for intracranial drug delivery

Chemical stimulation using channels in a so-called “puffer” neural probe has been a challenging endeavor, originated by Prof. Kendal Wise’s laboratory in U. Michigan back in 1997. The early probes were fabricated using the reactive ion etching (RIE) technology, and despite their initial promise, so far have not been successfully used in chronic animal studies.  Multiple issues, ranging from the outlet biofouling to the hydraulic resistance inside a microfluidic channel, have been identified. A commercial probe combining the drug delivery and electrical recording/stimulation was recently developed by the NeuroNexus Technologies (D/DM-series); it consists of the silicone probe glued to the fused silica fluidic channel. Opting for an integrated probe solution, engineers at the Institute of Micromachining and Information Technology and the Institute of Microsystem Technology at the University of Freiburg etched the channels with heights of 50 µm and more inside the wafer using the deep RIE (DRIE) technology. Their effort is a part of the NeuroProbes project, funded by a European Sixth Framework Programme (FP6), which includes 13 other partners from Belgium, Germany, Sweden, Switzerland, UK, Italy, France, Hungary, Spain, and Netherlands. The probes, fabricated by German engineers, remained unclogged in an acute in vivo test, while the chronic implant studies are still ongoing. The fluid pumping action inside the microfluidic channels was achieved by a MEMS device built into the probe. The MEMS device functions by constricting fluid-filled micro-chambers (volume = 0.25 μL each) using a thermally expandable material coupled to heating microelements. The microchambers are connected in series and can be constricted individually with a 3-second temporal precision. Having the chemical stimulation and electrical recording on the same probe, may soon allow a detailed examination the chemical signaling inside the brain in vivo with a high spatiotemporal precision.

“Active Book” – an implant with active electronics for recording from and stimulation of lumbar spinal roots

the Active Book implant uses novel shape for implantation into spinal column to record from and stimulate the spinal roots.

A device prototype has been fabricated for implantation into human spinal column. It rests over the posterior and anterior (sensory and motor) spinal roots and allows recording from as well as selective stimulation of multiple spinal roots. The work is spearheaded by Prof. Nick Donaldson and Prof. Andreas Demosthenous at the University College London, UK. In collaboration with engineers from Freiburg University and the Tyndall Institute in Cork, they developed a device that includes a VLSI chip for processing the neural recordings and generating the electrical stimulation pulses. The VLSI chip is hermetically sealed into a can enclosure. Hermeticity of the enclosure is monitored using a humidity sensor. The chip feedthroughs are interconnected with the electrodes using wire bonds. The chip, wires, and electrodes are encapsulated into a soft shell, made presumably from silicone or epoxy. The electrodes are fabricated from platinum foil using laser etching and folded into a slot shape. There are four slots at the bottom of the implant, designed to bring the spinal roots (perhaps two anterior and two posterior ones) into close apposition with the electrodes. Such top placement of a neural interface is rather unusual as existing spinal root electrodes (e.g. Finetech-Brindley stimulators) have employed the cuff design. In order to be able to record neural activity and efficiently deliver the electrical current, the slots must be well-matched in size to the diameter of spinal roots. The initial application for the Active Book implant would be the control of bladder voiding in spinal cord injury. The effectiveness of the prosthetic bladder voiding will be similarly limited as in other sacral root stimulators, including the sensory perception of stimulation in people with residual below-injury sensation and concomitant activation of the bladder and urethral sphincter muscles, as well as other pelvic floor muscles. Other applications in paralyzed humans, such as the control of arm or leg muscles, are not unlikely to be successful with this implant as the applied surface stimulation would not be able to selectively activate a specific arm/leg muscle. Such lack of selectivity is inherent to the anatomy of the anterior spinal roots, which are comprised of mixed axonal bundles innervating different, sometimes antagonistic, muscles.