A combination of bio-electronic and artificial intelligence technologies and disciplines is facilitating innovative developments including an artificial retina implant that restores vision and an electronic patch that detects neural disease before it develops – developments that will positively influence the health of millions around the world.

Although X-trodes was founded only a year ago, its main technological development – smart systems for monitoring neural activity – will accompany us for years to come and will assist in the early detection of patients with neural diseases. “The technology is in the form of a sticker that enables us to monitor and measure the activity of patients’ muscles and brain, during sleep for example, or while they go about their daily lives”, explains Prof. Yael Hanein, the company’s CTO and the person who led the development together with her team at Tel Aviv University. “The sticker contains special electrodes that transmit two-way signals to and from the nervous system and the muscles. This information is recorded and monitored for early detection of different neural diseases”.   

Prof. Hanein served until recently as the Director of the Tel Aviv University’s Center for Nanoscience and Nanotechnology and she currently leads a research group studying neural engineering that focuses on the development of electronic nanodevices, primarily those that interface with brain cells. “Several years ago, we began studying and working on systems aimed at neural sensing, mainly of muscle activity and electrophysiological monitoring”, Prof. Hanein explains. We received a license from Tel Aviv University to commercialize the technology and are presently working on three central products: an evaluation system for developers, a product in the field of sports, and a neurological diagnosis product in the field of sleep disorders. 

“The sticker is passive and connects to an electronic component that amplifies the electric signal from the body, stores it, and transmits it to a computer. The system itself is made up of three elements: the soft sticker with silver strips for conduction and carbon electrodes that receive the signals and perform electric stimulation, the micro-electronic component that amplifies the signals and transfers them to the app, and the accumulated data which becomes a relevant answer to the medical question”.

Aharon Aharon, CEO of the Israel Innovation Authority: “The world is advancing towards data-based industry and the field of medicine will be one of its primary customers. The Corona crisis has highlighted the importance of assembling environmental and medical databases, the smart use of which will enable prediction of new outbreaks. For example, continuous monitoring of viruses using hybrid engineering-biological sensors together with smart and AI-based data analysis will allow real-time alerts and identification of outbreaks in specific geographic locations and rapid early response of the health system”.

Identifying Parkinson’s Patients While They Sleep

“Sleep disorders are one of the accurate early indicators of neurological diseases, and we believe that our product – the sticker combined with the app – can help in early identification of Parkinson’s, even several years before the appearance of motor symptoms”, declares Prof Hanein.  

The REM sleep of healthy people is typified by reduced muscle activity, while that of most Parkinson’s patients is characterized by its presence. This phenomenon is called RBD and the only way to monitor it is by examining neural and muscle activity during sleep. “This phenomenon is episodic and doesn’t occur every night”, explains Prof. Hanein, “so it is very important to perform the measurements continuously for several nights and at optimal ecological conditions. Using the sticker that we developed, patients can perform the monitoring at home or with the help of a relative and the data is received via the app by the medical team supervising the test. The common current alternative to such tests is a sleep laboratory, which is a costly process that requires medical supervision. 

“The app is for people at high-risk for Parkinson’s disease and seeks to identify the RBD phenomenon. The technology is just the beginning of the process. We need to conduct a clinical trial that proves that the product works. This requires substantial capital and we are currently collaborating productively on this with Prof. Anat Mirelman at the Sourasky Medical Center. In the meantime, an experienced operator must visit the patients’ home and help them connect to the system. We are also working simultaneously on converting the system to be self-operated”. 

According to Prof. Hanein, electrophysiological monitoring is customarily used in many areas of medicine but the process, conducted in a lab or hospital, involves inconvenient electrodes that have many disadvantages: the electrodes tend to fall off, time is limited, and the data received is not always accurate. “Our innovation does not cause the patients discomfort and they can use it for hours, even during the night. Because some patients will use our product as part of their daily routine, we also pay attention to the sticker’s design and appearance”, Prof. Hanein clarifies.

The Next Stage – Processing Emotions and Facial Expressions  

The sports product being developed by X-trodes also places importance on the design aspect with the aim of creating a compelling appearance. “We are still working on integrating additional sensors to the system”, says Prof. Hanein, “but at present the electrode can successfully record muscle, eye, heart, neural and diaphragm cells. We are still checking how to adapt the length of time the sticker is worn to ongoing or intensive activity”. This endeavor has received financial support from the Innovation Authority. 

According to Prof. Hanein, development of the company’s products was made possible thanks to three fields that have evolved dramatically in recent years, the combination of which created a real bio-convergence opportunity – printed electronics, the miniaturization of specially designated electronics for electrophysiological signals, and artificial intelligence. “This is a consolidation of technologies and not just of disciplines. Israel has many advantages in this field and an impressive presence at important conferences and in scientific developments”.

The smart sticker technology developed by X-trodes can be used in different areas: “Psychiatry, psychology, behavioral science, business management, motor problems, stuttering, autism and others”, Prof. Hanein says. “We established many diverse collaborations from the very beginning. We understood that there was great interest in checking and trying out our technology, and when we founded the company we decided to build and develop a research system in addition to developing the company’s primary products”.

One of the interesting areas still being studied in the research labs that Hanein heads is the processing of facial expressions and monitoring of emotions. As she explains, the initiative focuses on identifying objective indices for defining emotions and their intensity among different people. “There are physiological indices such as perspiration and pulse acceleration, but these are not definitive. Using different sensors, we try to measure facial expressions and to combine the data with analysis of additional physiological indices to make it useful”.

Bio-Convergence – A Growth Engine for Israel

Prof. Hanein also serves as VP of Scientific Affairs at Nano Retina, a company that has developed an artificial retina implant that mimics the natural physiological processes of the human eye and restores functional vision to people blinded by retinal degenerative diseases. 

Nano Retina is part of Rainbow Medical Group, an innovation and investment company that invents and develops innovative medical technologies addressing the most significant unmet clinical needs, including Alzheimer’s Disease, blindness, diabetes, heart failure, hypertension, pain and more. “Rainbow Medical’s diverse portfolio of medical device companies are the epitome of the bio-convergence concept, fully utilizing the different fields of expertise and strengths in Israel’s workforce”, says Yuval Mandelbaum, the company’s Director of Operations. “Rainbow researches and invents inhouse, unique proprietary solutions for the most pressing and burdensome medical conditions. Once a new solution is vetted by physicians and has a solid proof-of-concept, a subsidiary company is incorporated, and a diversified and experienced team is recruited to transform the idea into a commercial product. To allow portfolio companies to focus on product development and clinical studies and reach the market as fast as possible, Rainbow supports its portfolio both financially as well as with expert hands-on guidance and centralized services, on-going market validation and access to its vast network of Key Opinion Leaders (KOLs) and strategic partners worldwide. This lean, unique model has been designed to allow for both capital efficiency and time efficiency – cutting costs and expediting processes, thereby helping our portfolio companies meet their goals faster and maximize their potential. The company’s internal ideation stems primarily from the inventions and innovations of Yossi Gross, a luminary medical device entrepreneur with multiple success stories under his belt as well as more than 750 patents to his name.
“Bio-convergence is part of the Rainbow Medical Group’s DNA, and we believe that when you have a truly diversified team you gain access to a “higher-level” of innovation and the whole business becomes much greater than the sum of its parts. As such, our personnel is made up of multi-disciplinary professionals from different walks of life, with knowledge in various fields and with diverse capabilities”, says Mandelbaum. “We have biologists, engineers, physicists, and programmers working in unison as part of one team, with experts in fields such as nanotechnology, materials science, genetic engineering, and neurobiology. This is the same idea that stands behind the Innovation Authority’s decision to define Bio-convergence as one of Israel’s next growth engines. The strengths of Israel’s industry are in areas like engineering, big data, and AI, alongside the fields of science that have flourished over the past 20 years and the rise of medical device and digital health that has characterized the last decade. Combine all these together and we will truly have a growth engine that will drive the economy for years”.

Artificial Retina Restoring Sight to the Blind

Nano Retina developed a miniature, high-resolution artificial retina with low energy consumption designed to restore vision and independent functionality to people suffering from degeneration of the retina’s photoreceptor layer. The implant is equipped with an imager chip that receives external visual input from the environment and converts it to electrical signals that are delivered to healthy layers of the retina via a dense array of hundreds of micro-electrodes that stimulate the bi-polar layer of the retina. The stimulation of the bi-polar cells allows the device to bypass the degenerated layer of photoreceptor cells and for visual signals from the outside environment to once again be detected as electric signals by the retina and optic nerve, thus restoring functionality to the visual system.   

“At this stage, the company is focused on two first indications – Retinitis Pigmentosa and Age-Related Muscular Degeneration (AMD)”, says Mandelbaum. “These diseases cause people in mid-life to gradually lose their sight, until they eventually suffer from complete vision loss. Over 170 million people suffer from these diseases worldwide.

“Nano Retina’s device has entered the clinical phase and first patients were implanted earlier this year. Early results are remarkable, as patients who were completely in the dark prior to the implantation now experience visual perception and are able to identify objects around them and carry out different daily life activities unaided. The team will continue to work with the patients and visual perception is expected to continue improving over the coming months. This does not mean that patients’ vision will return to 100% of what is once was, but going from total darkness to being able to identify a doorway or recognize the face of a person talking to you and regaining independence is an exciting achievement with incredible benefit to patients that I am proud to be a part of”, he says. 
Over the last several years, Nano Retina has been granted research grants from the Innovation Authority.

A Rainbow of Achievements

Additional Bioelectronics and Neuromodulation Companies of Rainbow Medical 

BlueWind: A neuromodulation platform, based on a miniature, wireless implant for the treatment of multiple neurological disorders. The device was granted CE Mark for the treatment of Over-Active Bladder (OAB) and Chronic Neuropathic Pain. The company is currently performing a Pivotal Trial to secure regulatory approval in the U.S. 

Vascular Dynamics: A miniature, minimally invasive implant treating Resistant Hypertension by amplifying the natural baroreceptor response in the Carotid Sinus. The device has been implanted in >80 patients and has shown consistent reductions of systolic values by >20 mmHg on average, maintained over years.

Enopace: Developed the world’s first Endovascular neuromodulation device for the treatment of Heart-Failure. The minimally invasive device is placed trans-catheterly placed in the Descending Aorta and improves the efficiency of the heart’s function by restoring autonomic balance and Ventricular-Arterial compliance. The company is performing a clinical study in several clinical sites in Europe and in Israel.

ChroniSense: A medical grade wearable solution for chronic disease management and remote monitoring of patient’s vital signs, including blood pressure, SpO2, temperature, respiratory rate, E.C.G. and more. The device allows for hospital grade patient monitoring from afar and enables early detection of life-threatening conditions.

GluSense: A fully implantable, truly long-term (<2 years) Continuous Glucose Monitor (CGM), with biological sensors, designed to allow Type 1 & Type 2 Diabetes patients to accurately monitor glucose levels without the hassles associated with an external device. 

BrainBalance: An innovative, medical device approach for the treatment of Alzheimer’s Disease (AD). The minimally invasive device creates a directional electric field that enhances the natural clearance process of Amyloid-Beta proteins (Aβ) out of the brain and into Cerebrospinal Fluid (CSF). The unregulated buildup of Aβ in the brain is associated with the symptoms of AD.

DisCure: A miniature implant for the treatment of Disc Degeneration Disease – one of the most common causes of lower back pain. The implant actively regulates the inflow of fluid and nutrients into the disc, restoring the cushioning function, improving inner disc-cell conditions, and reducing lactic acid and associated pain. DisCure is the only treatment designed to not only reduce pain but reverse the degenerative process of the disease.