Let's say that an Israeli company wants to adopt technology developed at the world's largest particle accelerator. What are is chances of success? And what if an Israeli company needs the cooperation of giant corporations to develop a sensor capable of changing the world?
Israeli technology companies seeking to develop a competitive advantage sometimes require the cooperation of international research and commercial entities. It was exactly with this objective in mind that the Innovation Authority launched a special program aimed at developing advanced products that are based on Israel's budding infrastructures while cooperating with research institutes and academic bodies abroad.
As a result, the Authority is presently assisting the team at HIL Applied Medical to utilize the information generated in the famous CERN particle accelerator to develop a unique system that will allow the public access to a cancer treatment using a beam of protons. In another example, it is supporting an extraordinary collaboration between the TOWER corporation, the engineering faculty at Tel Aviv University and the Technion, and global and German research teams with the goal of developing a miniature sensor that can identify diseases and be mass-produced.
The Sensor that will Smell Disease
Prof. Yossi Rosenwaks, Dean of the Engineering Faculty at Tel Aviv University, tells of the CC‐Sens research project that was supported by the Innovation Authority in 2017 as part of a joint German-Israeli call for proposals. At the center of the project is a sensor that will change the world of medicine: "The Faculty of Engineering at Tel Aviv University has undertaken to collaborate with industry because we believe that in certain fields, industry is far ahead of the university. Furthermore, there are steps that require tremendous financial investment in which it is better to share rather than to compete.
"There are many examples of such collaboration: industrialists teach courses at the university, award scholarships to students, we listen to their opinions while planning the curriculum, and conduct round-table discussions with them to clarify various research issues and conceive joint programs. We are very attentive to industry and this is a win-win situation for all parties involved. Our IAP (Industrial Affiliates Program) led by Prof. David Mendlovic, has 35 members and boasts a high level of activity.
"The goal of the current project is to develop a sensor for gases or molecules. This sensor is based on an electronic component that can only be created in large factories and not at a university. Furthermore, we also have a commercial purview so that's why we chose to collaborate with leading engineering companies such as Tower Jazz and the German Singulus corporation. Singulus possesses the exclusive capability of applying/submerging the extremely thin layers required for the sensor's operation and to do so in mass-production – something that is impossible to do in other companies and certainly not at a university.
"The sensor is the size of a micrometer (one millionth of a meter) and can in the future be part of a wearable device or a cell-phone. It is compatible for components used in IoT systems (Internet of Things) requiring a large number of sensors. For example, it could be a sensor that reports on the quality of air at the home or on the freshness of food. In the future, it will be able to tell us whether our breath is gassy, thereby providing a different indication of diseases. The project's main goal is to engage in the field of early disease diagnosis.
"The project is led by Prof. Hossam Haick from the Technion, a world-renowned expert in disease diagnosis. Five groups are collaborating on this initiative: our team from Tel Aviv University is designing the sensor, TOWER are responsible for manufacturing it, Prof. Haick provides his expertise, and Singulus manufactures the layers. The fifth group is an academic team from Friedrich-Alexander University (FAU) in Germany which specializes in nanometric characterization of the sensor using extremely advanced microscopes in order to understand its operation and the layers on it.
"These different bodies converged naturally: I have been working with TOWER on a number of subjects for several years while at the same time having a long-standing acquaintance with Prof. Haick who knew the group from Germany. They in turn were acquainted with TOWER from previous projects and established the connection with the German university. It's a kind of natural consortium where everyone works well together.
"The work with the international entities is less convenient than with those in Israel but the German groups possess capabilities that don't exist in Israel so the challenge is definitely worth contending with. We couldn't have launched the project without them. Naturally, because of the significant resources involved, it would also have been impossible without the support of the Innovation Authority.
"Because we are dealing with a chip made from silicon, the cost of the sensor is very low, and it consumes very little electricity. As I said previously, we expect its main applications to be in the fields of disease diagnosis and the Internet of Things. The studies that Prof. Haick has been conducting for years show that cancer patients' breath contains a slightly different molecular composition. His incentive for participating in the project was the fact that it will be possible to mass-produce this sensor which may play a significant role in the early diagnosis of diseases or of air pollution.
"So, how does a molecule sensor work? If we emit a gas such as ammonia in a certain area, when the transistor we are developing comes into contact with an ammonia molecule, its electric current changes. This happens even if only a single molecule lands on it. But in order for this to happen, the sensor must be in contact with the air so it's more challenging at this stage to install it in a cell-phone rather than on a bracelet or a sticker.
We have made significant progress since the consortium was set up. We have met the goals we set ourselves and are now at the half-way point. I believe that by the project's completion in 18 months, we will be able to present a prototype that combines all the capabilities. Similar things to what we are doing exist overseas but there is no other sensor that is based on a silicon chip, which can be mass-produced at negligible cost, with such a tiny electricity consumption, that can do this job. Once we have a functioning prototype, no-one will be able to compete with us."
The Particle Accelerator Has Shrunk
"We heard a lot about CERN - the world's largest particles institute located on the Swiss-French border – at the Authority", says Lital Burian, Mobility Sector Director of the Innovation Authority. "We tried for years to understand how to cooperate with it and although Israel is a full member state alongside 21 other countries, it was difficult to characterize an appropriate model. A year ago, we contacted their commercialization company and they accepted the challenge. We sent an initial delegation of 12 representatives from industry and academia for talks and the result was 4 collaborations in different fields."
One of these was established with the HIL Allied Medical corporation which was founded in 2010 by the senior physicist Prof. Arie Zigler and Dr. Shmulik Eisenman from the Hebrew University as an incubator company of the Innovation Authority. The 2 researchers focused on developing a technology to accelerate protons using a laser, with an emphasis on treating cancer by projection of a beam of protons.
The company's current CEO is Engineer Sagi Brink-Danan who served as its VP Business Development when the company was founded. "Radiotherapy is currently the most common treatment for cancer – in the United States, approximately 66% of cancer patients undergo this treatment. A special form of this treatment – proton beam therapy – is considered the most advanced type of radiotherapy in the world today. Proton therapy is a very focused and precise treatment that enables us to radiate a tumor efficiently and to reduce the number of treatments that affect the surrounding healthy tissue. These radiations allow the patient a higher quality of life and reduce complications and side-effects common with "traditional" radiotherapy that uses x-rays or gamma-rays, both during treatment and long-term.
"Radiotherapy with proton beams is not new and has already been in clinical use for 30 years. Nevertheless, there is still no such machine in Israel. There is a high demand for such treatments form all the relevant parties: doctors, patients, and the health systems. And yet, less than 5% of the patients who should be receiving this treatment actually receive it. The remaining patients receive standard radiation treatments with x-rays or gamma-rays – a very efficient treatment for cancerous tumors but half the radiation is absorbed not by the tumor itself but rather by healthy tissue, leading to implications and complications for the rest of the patients' lives.
"The reason that so few patients are treated with proton beams is because these systems are extremely large. The most compact systems that exist are 4-5 story buildings the size of a tennis court, have concrete walls 6- meters thick and cost 30-40 million dollars. The core of these systems is a particles accelerator that weighs 2000 tons – the same as 747 Jumbo.
"The devices themselves are based on very old technology developed during the 1930s and 1940s and have since undergone many processes of improvement, streamlining, descaling and lowering in cost. Unfortunately, there are no new technologies that can replace proton beams, but their dimensions and weight make the systems unattainable for many medical entities.
"This is where HIL Applied Medical enters the picture. The technology we have developed can bring to the market technology identical to that of the proton accelerator – on half the area needed for the original system, a quarter of the volume, a third of the cost and only one thousandth of the weight. Our accelerator does not weigh 200 tons but rather, 200 kilograms and is the size of an office chair. This is 21st century technology that aims to make this important treatment accessible to every medium and large-size hospital and to make it available for every patient in need.
"The potential is huge: for decades, there has been a tremendous gap between the market demand and the ability to satisfy it. During the 16 years in which I have been working in the field of medical devices, I have never seen a field in which the entire ecosystem exists, the treatment is recognized, proven and accepted, and the demand so high – and yet 30 years later, there is still such a disparity between supply and demand. We believe that we possess the technological key to surmounting this hurdle and opening the floodgates."
The Magic Beam
"The core of the existing systems is the particles accelerator", explains Brink-Danan. "The particle accelerators built in the last 80 years are large and heavy. The particles make 100,000 rotations in strong electro-magnetic fields, gaining increased acceleration with each rotation – until they reach approximately 2/3 the speed of light. They then exit to the second part of the system which is an array of magnets that function like a telescope lens. This is the stage in which the beam is focused on the tumor in a non-invasive manner.
"The particles accelerator at the heart of our technology is a completely new generation. It doesn't use large fields and magnets but rather, an extremely high-powered laser – a technology that won its inventors the Nobel Prize for physics only a few months ago! We shoot the laser at a physical target using an interaction of nanometric characteristics and microns and the result is the emission of a beam of energetic protons. It's just like a "magic mirror": you shoot a laser at a target and receive a proton beam. We are also focusing on development of advanced magnetic technologies that will reduce the size and lower the cost of all proton transfer systems.
"As I mentioned, our company was originally founded as an incubator company of the Innovation Authority which provided most of the capital. We subsequently received another grant as part of the Authority's "Early Stage Companies" Incentive Program. Thanks to their initiative, we are now collaborating with the CERN particles accelerator, something that is very important, both technologically and from a branding perspective. This is also partly financed by the Innovation Authority.
"CERN is currently the world's largest research institute for the study of particles. Dozens of countries are partners in this special project, all of whom participate in its financing and in sending scientists and researchers to work there. It's actually a giant research institute spread over hundreds of square kilometers in Switzerland, hosting more than 10,000 researchers from all over the world.
"The foundation of our relationship with CERN is their transfer to us of new technologies being constantly developed there. As a non-profit international institute, they don't have any commercial projects. One of their missions is to distribute the knowledge for the benefit of mankind. This is where we come into the picture. There are three different technologies that may be relevant for us. The first stage is to understand what technologies they have and their present stage of development. The second stage will be to build a prototype and to assimilate them in our research laboratory and alpha system, currently under construction in Jerusalem. At the end of the second stage, if everything works as we expect, we will receive a license for these technologies so that we can use them.
"The company's first patents were written together with the Hebrew University via 'Yissum' – the university's commercialization company. In practice, 'Yissum' invested in the company even before it was founded via the Baby Seed Fund for small investments in promising initiatives. 'Yissum's venture capital fund – Integra Goldings – has also invested in our company.
"We work with the Hebrew University on a number of fronts. Our offices are located at the university and we use many of its scientific infrastructures, such as the 3-D Printing Center, the Nanotechnology Center and the Microscopic Center. This cooperation is productive for all parties. Most of our employees are graduates of Hebrew University. They sometimes come to us as part of a summer or research project and this is a win-win situation for everyone that enables us access to super high-quality manpower. It's also good for Jerusalem as a city that young people engaged in science, technology and development are attracted to live here.
"We currently have two development centers – one in Israel and the other in the US. We have functioning prototypes and two months ago we signed an agreement with the Hebrew University to rent a building on campus that will be our new development center and later, a manufacturing facility for the first systems. We are now establishing an alpha system there and its performance will be close to that of an operational clinical system. This process takes about two and a half years. Our vision is to begin selling the first beta systems to hospitals within 2-3 years. We already have signed letters of intent – one from the famous Thomas Jefferson Medical Center.
"HIL is a global company with a global market and with global strategic partners. The world's leading company in the field of proton radiation – IBA from Belgium – has invested in us, and its founder is a member of our scientific advisory committee. HIL is definitely a company with a global orientation."