Food Innovations

International Technion Innovation: Technologies to reduce sugar consumption, create healthy plant-based alternatives to unhealthy, animal-based stabilizers, and prevent food poisoning

The EU has allocated millions of euros to three multinational research teams that include researchers from the Technion Faculties of Biotechnology and Food Engineering and Mechanical Engineering. These researchers are participating in EIT-FOOD projects with cumulative budgets of more than 2.25 million, supported by grants of the EU.

The objective: To promote inventions that improve food quality and human health.

Three teams involving Technion – Israel Institute of Technology researchers are running projects of around € 1 million each supported by EU grants from the EIT-Food consortium,  the leading food innovation initiative of the European Union whose goal is to lead a revolution in food innovation, business creation, and education.

Sugar-Out, Prote-In

Professor Yoav D. Livney

A consortium led by Professor Yoav D. Livney, of the Technion Faculty of Biotechnology and Food Engineering, is fighting diabetes and obesity by developing the first healthy sweetener for the food & beverage market. The healthy, zero-glycemic-index protein-based sugar-substitute has the potential to revolutionize the global food and beverage market.

The consortium also includes PepsiCo, Danone, and Amai Proteins, a startup led by Dr. Ilan Samish. Amai Proteins is a member of the “Rising Food Stars” startup club of the EIT-FOOD.

 “The EIT Food, which the Technion is a partner of, is revolutionizing the European food ecosystem. Our project within this consortium is expected to bring to the global market an innovative sweet protein, along with a novel microencapsulation technology, to replace sugar, a major cause of obesity and diabetes (which are also risk factors for COVID-19 mortality). Sugar replacement is a tough challenge, and there is a great need for non-artificial intensive sweeteners, with a sensory profile similar to that of sugar, that is suitable for the huge global food & beverage market,” said Prof. Livney.

High-pressure processing to achieve a healthy plant-based alternative to unhealthy stabilizers 

Assistant Professor Avi Shpigelman

The Laboratory for Novel Food and Bioprocessing, led by Assistant Professor Avi Shpigelman, is partnering with the EIT project “HPHC – Development and application of hydrocolloids functionalized by dynamic high pressure.” The project aims to create healthier nutrition by physically modifying common currently used polysaccharide-based hydrocolloids using high-pressure food processing to achieve an improved range of techno-functionalities. The goal is to replace or reduce currently used additives and stabilizers with plant-based materials. 

The technology is based on ultra-high-pressure homogenization (UHPH), where a liquid is continuously pumped through a narrow valve using high pressures of up to 350 MPa. This results in the modification of biopolymer structure. This technology was originally developed for the pasteurization and sterilization of liquid foods. Specifically, the project aims to physically modify plant-based polysaccharides and fibers with the intention to replace animal-based or unhealthy stabilizers with plant-based, health-promoting ingredients. The German Institute for Food Technology (DIL) is leading the initiative together with the Technion, Herbstreith & Fox, Maspex, ZPOW Agros Nova, and Glucanova.

According to Dr. Spiegelman, “We believe that the project will increase the assimilation of diverse hydrocolloids from plant sources into the food industry and will expand the use of these materials for a healthier diet for the population. “

Lab on a chip – an early warning platform for food safety

Professor Yechezkel Kashi

Professor Yechezkel Kashi of the Faculty of Biotechnology and Food Engineering and Professor Gilad Yossifon of the Faculty of Mechanical Engineering are leading this consortium with six European partners (EUFIC, Grupo AN, Maspex, Energy Pulse Systems, and the University of Queen Belfast) to develop a technology to improve food safety by rapid monitoring of pathogenic bacteria and toxins.

Food poisoning leads to thousands of deaths each year. Food contaminants are mostly monitored in plants using culture-based and time-consuming methods of up to one week. By that time, some of the contaminated products are released to the market and consumed. The Technion team has developed a technology for sensitive and real-time detection of different pathogens and toxins, based on the “lab-on-a-chip” technology developed and verified by the Technion. This technology includes the concentration of bacteria and amplification of their DNA sequences until a measurable signal is obtained. 

Professor Gilad Yossifon

“Our goal is to integrate the technology into food product tests to obtain safety evaluation in real-time,” said Prof. Kashi. “Our solutions will improve societal well-being, minimize recalls and food outbreaks, and improve production efficiency. It is also relatively inexpensive compared to the existing methods, so it will encourage the parties involved in the food market to check products frequently throughout the supply chain, eliminating contaminated raw materials and products in real-time. This will help to avoid recall events, which are harmful for companies and their images.”

 

 

Autonomous Microscope

Technion researchers have developed an innovative microscopic method based on deep learning and self-design of the optical system, enabling the study of dynamic 3D images at super-resolution. The ability to study the dynamics in whole cells over such times scales was rarely possible until now.   



Researchers at Technion – Israel Institute of Technology present a breakthrough in 3D super-resolution microscopy of cells in the journal Nature Methods. The innovative system significantly shortens 3D image acquisition time by using a neural network and deep learning. The researchers experimentally demonstrated system efficiency in 3D mapping of mitochondria (the cell’s energy maker) and volumetric imaging of fluorescently labeled telomeres (chromosome edge regions, which are responsible, among other things, for cell division in the body) in live cells.

The research was carried out by Asst. Prof. Yoav Shechtman and Ph.D. student Elias Nehme, of the Faculty of Biomedical Engineering together with Asst. Prof. Tomer Michaeli of the Viterbi Faculty of Electrical Engineering.

Asst. Prof. Yoav Shechtman

A major challenge in biology today is the super-resolution mapping of dynamic biological processes in living cells. That is, mapping with a resolution 10 times greater than that of a standard optical microscope.

Microscopes, as a rule, produce two-dimensional images. Information is innately missing from such images as the world is three-dimensional. Currently, 3D images are usually obtained through layer scanning – the imaging of different layers in the sample and their computerized integration into a 3D image. This process is problematic as it requires a long scanning time, during which the object being examined must be static. In addition, in classical optical microscopy, the level of resolution (separation capacity) is limited by the “diffraction limit” formulated by German physicist Ernst Karl Abbe in 1873.

Enter DeepSTORM3D – a super-resolution 3D mapping system developed by the researchers. According to Asst. Prof. Yoav Shechtman, who led the development of DeepSTORM3D, “To get depth information from a 2D image we use wavefront shaping – an optical method that encodes the depth of each molecule in the image obtained on the camera. The problem with this method is that if several molecules are close by, their images overlap on the camera, and this drastically impairs spatial and temporal resolution, to the point that some samples cannot produce useful images at all.”

Asst. Prof. Tomer Michaeli

To address this challenge, researchers harnessed the field of deep learning and developed an artificial neural network – a system that performs computational tasks at unprecedented performance and speed. Together with Asst. Prof. Tomer Michaeli, an expert in this field, the researchers developed a neural network able to generate and train itself using a large number of virtual samples, and then produce super-resolution 3D images from microscopy data of real samples.

According to Shechtman, “The new technology has advanced us towards realizing one of the holy grails of biological research – mapping biological processes in living cells in super-resolution. It is important that the life sciences benefit from our instrumentation, and we maintain close relationships with biologists who explain their needs to us.”

Shechtman used the neural networks not only to analyze the images but to also improve the instrumentation. “This is perhaps the most exciting direction to emerge from the current development – the neural network has provided us with the optimal physical design of the optical system. In other words – the computer not only analyzes the data but has shown us how to build the microscope. This concept can also be applied in non-microscopy-related fields, and we are working on it.” 

Ph.D. student Elias Nehme

Research participants include Dr. Daniel Freedman from Google Research, and researchers and students from the Faculty of Biomedical Engineering, the Lorry I. Lokey Interdisciplinary Center for Life Sciences and Engineering, and the Russell Berrie Nanotechnology Institute: Racheli Gordon, Boris Ferdman, Dr. Lucien E. Weiss, Dr. Onit Alalouf, Tal Naor, and Reut Orange. The research was conducted with the support of the European Research Council Horizon 2020 Program, Google, the Israel Science Foundation and the Zuckerman Foundation. Asst. Prof. Yoav Shechtman is a Zuckerman Faculty Scholar and Dr. Lucien E. Weiss is a Zuckerman Postdoctoral Fellow.

Click here for the paper in Nature Methods 

 

UV Light to Limit COVID-19 Transmission

An international team of researchers advocates the use of UV-C light in indoor spaces as a way to reduce the transmission of SARS-CoV-2 viruses

This solution meets the requirements of fast, scalable, and affordable implementation to fulfill the needs of disinfecting workspaces, such as offices, schools, healthcare facilities, and public transportation, to name a few 

Pathways of viral infection in everyday life shown in a simplified scheme (top) and illustrated by pictorial descriptions of exposure to the virus in everyday activities (bottom). Placement of UV-C light sources at ventilation systems and rooms not in use, without direct optical paths to humans, help reduce virus propagation. Image sketches by Nacho Gaubert

The COVID-19 outbreak, caused by the SARS-CoV-2 virus, is posing an extraordinary challenge that requires swift worldwide action for the massive deployment of affordable and ready-to-apply measures to drastically reduce its transmission probabilities in indoor spaces. Doing so will allow for the eventual return to conventional activities such as working at the office, going to school, or even attending entertainment events. 

Studies show that virus transmission follows two main paths. Firstly, the virus can be transmitted through the air in droplets exhaled by infected individuals and inhaled by healthy individuals. Secondly, it can be deposited on surfaces from exhalations or hand contact. Several measures are being adopted to help prevent the transmission of this disease. The most common ones refer to facial masks and other physical barriers that if properly used, have proven to be highly effective. However, such measures depend on the compliance of the population. 

Prof. Ido Kaminer

A long series of studies suggest that virus transmission in indoor spaces is much higher than outdoors. Filters and chemicals have been presented as possible solutions to minimize this problem, but despite their effectiveness in reducing the concentration of contaminated particles and droplets passing through ventilation systems, their installation may be costly and time-consuming. In addition, some chemicals that are very effective for virus disinfection, such as ozone, can be harmful if misused.

To address this dilemma, an international team of experts in the fields of virology, immunology, aerosols, architecture, and physics studied various methods to prevent SARS-CoV-2 propagation in indoor spaces. Based on their findings, published recently in ACS Nano, they are advocating for one measure that they believe to be “particularly efficient, easily deployable, and economically affordable”: virus inactivation by ultraviolet light

The research was conducted by Technion Professor Ido Kaminer, in collaboration with ICREA Prof. Javier García de Abajo at ICFO, ICREA Profs. Andreas Meyerhans (Universitat Pompeu Fabra) and Joan Rosell-Llompart (University Rovira i Virgili), together with Profs. Rufino Javier Hernández (University of the Basque Country), and Tilman Sanchez-Elsner (University of Southampton). 

After researching currently available UV-C sources, such as fluorescent lamps, microcavity plasmas, and LEDs, the team concluded that applying this type of light on the inside of the ventilation systems of buildings and in shared indoor spaces while not in use, makes it possible to quickly and efficiently deactivate both airborne and surface-deposited SARS-CoV-2 viruses.

The team also explored the cost of deploying such technology and argue that a global capital investment of a few billion dollars in UV-C sources could protect more than a billion indoor workers worldwide.

Click here for the paper in ACS Nano

 

3D Printed Aircraft

The unmanned vehicle was produced using advanced technologies to serve as a cost-effective experimental platform for design aspects pertaining to flexible aircraft and green aviation

Prof. Daniella Raveh with the students. Credit : Assaf Hober

Students from the Technion Faculty of Aerospace Engineering conducted the successful maiden test flight of the A3TB (Active Aeroelastic Aircraft Testbed), an experimental platform for studying phenomena related to wing flexibility and future flexible aircraft design. The flight took place on May 15, two months after the project won the Student Project Competition in memory of Dr. Shlomit Gali, during the 60th Israel Annual Conference on Aerospace Sciences. 

Designing modern aircraft includes numerous challenges, including the economic-environmental challenge of reducing fuel consumption and decreasing pollution. One of the solutions is designing lightweight aircraft structures with a large wingspan, thus reducing the drag forces. Lengthening the wings inevitably leads to increased flexibility, which spurs structural tremors and sometimes even a loss of stability. Engineering solutions, such as control mechanisms, require complex multidisciplinary R&D that combine mathematical and numeric models with simulations in the lab, as well as test flights essential for verifying performance. During these flights, one must also take into account the risk of crashing.


For this reason, there is a need for inexpensive and safe testing platforms which can be “sacrificed” at relatively low cost in both money and project time. With the A3TB platform, optimal production design can be presented at a high speed and low cost. This platform therefore signals a breakthrough in the design of a flexible wing platform manufactured using a 3D printer. 

For the past two years, two groups of students at the Faculty of Aerospace Engineering have been developing an aeroelastic tester of this sort – a light aircraft whose wings are long and flexible, and whose performance can be evaluated during flight so that special control mechanisms can be designed to improve its performance, response to wind gusts, and stability.

The A3TB platform weighs 10 kg, and its wingspan is 3m. It was designed by two groups of students under the guidance of Dr. Lucy Edery-Azulay and Professsor Daniella Raveh, in collaboration with the Directorate of Defense Research and Development (DDR&D) at Israel’s Ministry of Defense. The first test flight that was conducted on May 15 demonstrated that the platform is capable of flying straight and horizontal at sea level, including maneuvers. This flight is an important milestone in the platform’s continued development.

According to Prof. Raveh, “The successful flight signals the starting point of an extensive program of research, testing, and design. The concept we developed, and the possibility of printing the entire aircraft on a 3D printer, offer considerable freedom in designing the airplane and an enormous cost advantage compared to airplanes made of composite materials or metals. Since it is a test airplane that is expected to crash at some point, these features make it possible to make many improvements without large investments. The group is currently working on an automatic control mechanism that will be installed on the second generation of the aircraft, A3TB-G2, in the next few months, and we hope to report on additional interesting results in the near future.”

Prof. Daniella Raveh completed all her academic degrees at Technion’s Faculty of Aerospace Engineering. She is an expert on aeroelastic phenomena. The aircraft being developed will serve as a platform for her continued research and its expansion. 

Dr. Lucy Edery-Azulay received a B.Sc. and M.Sc. from Technion’s Faculty of Civil and Environmental Engineering and is an external lecturer at the Faculty of Aerospace Engineering. For more than 20 years, she has been working on applied R&D in industry in various fields: 3D printing, civil and military aviation, structural strength and advanced technologies. 

 

New Tech for Medical Cannabis

Researchers at the Technion – Israel Institute of Technology and at the Shenkar Institute have developed an innovative drug delivery system that releases medical cannabis slowly to provide tailored treatment with a long-lasting effect.

Professor Dedi Meiri

When medical cannabis is used today to treat conditions such as cancer-related pain, Parkinson’s, post-traumatic disorder, and epilepsy, it is usually inhaled or taken orally. But these methods have disadvantages. The entire amount enters the body all at once, resulting in a short-lived effect of just a few hours. And the decomposition of the treatment in the body depends on various factors, including the type of food consumed before.

Researchers at the Technion, led by Professor Dedi Meiri, along with scientists at Shenkar College of Engineering, Design, and Art, have developed a platform for the slow and controlled release of a full spectrum of cannabinoids into the body. Tiny polymer microbeads, called microdepots, are loaded with phytocannabinoids, the naturally occurring chemicals in cannabis. When injected into the patient, the microdepots gradually release a specific combination of phytocannabinoids over a period of two weeks or more. The result is a long-lasting effect that is tailored to its specific treatment targets, such as seizures.

“The idea is that we could possibly treat children with severe forms of epilepsy, where instead of being treated with oil twice a day, they can get an injection once a month,” said Shenkar’s Dr. Dan Lewitus of the college’s Polymer Engineering Department.

To prove the efficacy of this cannabis delivery technology, one set of mice was injected directly with oil extracts while a second set was injected with microdepots. One week later, epileptic seizures were induced in the mice. Researchers found the microdepots reduced the occurrence of tonic-clonic seizures, the most severe kind of seizure, by 40%. The microdepots also increased the seizure survival rate by 50%.

Cannabis treatment using similar microbeads currently exists, but is only suitable for specific cannabis molecules, not the full spectrum. Because individual cannabinoids are desirable for different treatments, the medical effects of previous microbeads were limited.

“In previous studies, we have found that, for the treatment of epilepsy, CBD-rich cannabis extracts are much more therapeutically effective than specific molecules,” said Prof. Meiri. “In other words, [this technology] is a whole lot greater than the sum of its parts … allowing for an enhanced therapeutic effect.”

Prof. Meiri’s Laboratory of Cancer Biology and Cannabinoid Research in the Faculty of Biology is the largest of its kind in academia, with 44 researchers developing methods for analyzing the active compounds in over 900 different types of cannabis plants. They work with cannabis growers to identify almost every strain of marijuana grown in Israel, with the goal of matching specific strains to the diseases it affects.

This research was supported by the Israeli Ministry of Economy Innovation Authority and was published in ACS Applied Materials & Interfaces.

Flexible, Durable Algae Inspirations

Coralline red alga is characterized by a combination of flexibility and durability.  New findings on its structure by researchers at the Technion have shed light on what in its unique structure gives mineralized coralline red alga its remarkable resilience within strong sea currents. Such insight into nature’s designs can be used to develop new low‐weight, high‐compliance structures.

Prof. Boaz Pokroy and PhD student Nuphar Bianco‐Stein from the Department of Materials Science and Engineering have uncovered the unique structure of the articulated coralline red alga Jania sp., a type of sea plant. The research was published in the journal of Advanced Science.

Prof. Boaz Pokroy

Coralline red algae (phylum Rhodophyta) are widespread throughout the world’s oceans and seas, where they play an important role in coral reef ecology. One main group, articulated coralline red algae, grows upright in an anchored branched structure which must endure stress from strong waves and currents. Its durability is based on a unique micrometric structure that combines great flexibility with strength. In the present study, the team sought to uncover the unique structure of Jania sp. and how its structure embodies both strength and flexibility.

In recent years, Prof. Pokroy’s research has focused on biomineralization – a process in which living things form minerals. Through controlled biomineralization, various forms of life create complex structures to serve their own needs. The present study focuses on the biomineralization of Mg-calcite (Magnesium – calcite) in algae.

Calcite, which is a very stable version of calcium carbonate, is a very common ingredient in the skeletal parts of many sea creatures, giving them their hard exoskeleton. Man can make artificial calcite, but nature-produced calcite is characterized by complex and unique forms that give it high durability and other unique features. 

In a previous study on these algae, the researchers found that the uncalcified joints that connect the calcified segments of articulated coralline red algae, give the algae flexibility to endure outer stresses from waves. In the current study, the researchers studied the calcified segments of Jania sp. from the macroscale to the nanoscale at the ESRF Synchrotron in Grenoble, France. 

PhD student Nuphar Bianco‐Stein

The ESFR Synchrotron is an 844-meter circular particle accelerator, and it is the world’s strongest synchrotron in terms of the light intensity it produces; with the ability, for example, to produce X-rays that are 100 billion times stronger than an X-ray in a hospital. 

Through chemical analysis and confirmed using high resolution powder X‐ray diffraction (XRD) using the synchrotron radiation, the researchers discovered that the calcite that the coralline red algae secretes and crystalizes on an organic framework as part of its skeleton, contains a large amount of high-Mg Calcite. 

High‐resolution scanning electron microscopy (HRSEM) of the alga’s cross section, revealed a highly porous structure (as high as 64% of its volume). This porosity enhances the algae’s strength per weight. Moreover, the microstructure of the porous crystalized Mg Calcite is not random: Higher resolution X‐ray nanotomography of Jania sp., performed at the ESRF’s ID16B beamline, demonstrated that the microstructure of high‐Mg calcite is helical, rather than cylindrical. The pores spiral in a helical structure! This is the first known report of such a helical structure in these types of algae. Using a finite element analysis model, the team showed that the helical nature of the red algae increases their compliance and therefore their resilience to the outer stresses they experience underwater.

“This coil shape,” said Prof. Pokroy, “increases the resilience of flexural bending by up to 20%. We hope that, based on these findings, we can use innovative methods to produce artificial materials with similar properties – coil pores – which will be as light, flexible, and strong as the skeleton of Jania sp.”

The group concluded that it is the combination of high porosity and a helical configuration that gives Jania sp. it’s sophisticated, lightweight, compliant structure. It is anticipated that these findings will be of value for future design of manmade lightweight structures with superior mechanical properties.

Prof. Pokroy is a member of the Scientific Advisory Board of the ESRF the European Synchrotron Radiation Facility – Grenoble, and he emphasizes that the current research relies on many years of collaboration with the Synchrotron in Grenoble.

Click here for the paper in Advanced Science

 


Zombie Attack? To Your Health!

Researchers at the Technion and their partners in Europe have developed escape games designed to improve the Western population’s quality of nutrition 

In recent years, Western countries have seen a significant increase in obesity and intestinal illnesses, affecting human health and endangering their lives. These phenomena are largely due to the Western lifestyle, which is characterized by a decrease in physical activity and high consumption of processed foods, rich in sugar and salt.

One of the ways to improve this lifestyle is through education, which is the basis of the “Games of Food” – an innovative European project led by Professor Miri Barak of the Technion’s Faculty of Education in Science and Technology. The project is supported by EIT-Food, the European Food Innovation and Technology Institute, which is run by the EU.

According to Prof. Barak, “Games are an important educational tool, used by people since the dawn of history. In this project, we chose an escape game – a very popular genre. Escape games are a learning experience organized around an interesting frame story, and the participants are integral to the development of the plot.”

The two escape games developed as part of the initiative are: “The Zombie Attack” and “Nutrition Mission”. The first game, depicting an apocalyptic future where zombies have taken over the world, requires participants to solve puzzles associated with a healthy diet. The second game, where humanity lives in a giant spacecraft, requires the disclosure of information related to a balanced diet: Identifying food groups, calculating calorific value, detecting nutritious foods, planning a balanced meal, and more.

To test the effectiveness of the “games of food” in different cultures, they were tested by young people from Israel, England, Poland, Finland, and Belgium. The participants stated that they greatly enjoyed the multisensory experience and teamwork in the puzzle-solving process and that they learned very important facts about a healthy diet, as well as reducing environmental damage.

The project includes researchers from the University of Reading, the University of Warsaw, the University of Helsinki, the European Food Information Council in Belgium and the Center for Food Research (VTT) in Finland. The Technion’s involvement in the international project was initiated by Prof. Yoav Livni of the Faculty of Biotechnology and Food Engineering. The project is accompanied by empirical research led by Mrs. Tal Yachin, as part of her Doctoral dissertation, under the guidance of Prof. Barak.

Learn more about the project, the games and the participants’ learning experience HERE

The project’s website: https://www.gamesoffood.com 

 

The Future of Li-ion Batteries

Are we headed for a post-Lithium battery era? Not so fast. Lithium battery technology will remain alongside new power storage technologies, say leading experts from Israel and Germany 

 

Lithium-ion (Li-ion) batteries will remain with us for many more years, according to a group of leading experts from Israel and Germany, who discussed the issue at length for three days at a conference in Berlin. The group’s findings were recently published in Advanced Energy Materials in an article led by Professor Yair Ein-Eli, dean of the Technion Faculty of Materials Science and Engineering and partners from the Hebrew University, the Helmholtz Institute in Ulm, and the Jülich Energy Institute in Germany.

Professor Yair Ein-Eli

Lithium (Li) is the lightest and most active metal in the elemental periodic table. It was first used for power storage with the goal of finding an alternative to fossil fuel in the 1970s, with the development of the first lithium battery at Exxon. Since then, the technology has undergone many changes, including the Li-ion battery developed in 1993, which earned its inventors the 2019 Nobel Prize in Chemistry.

The Li-ion battery is a rechargeable, lightweight battery founded on the flow of Li-ions between the anode and cathode, as opposed to corroding chemical reactions. Li-ion batteries are the basis of our wireless society, they are used in cell phones, laptops, electric cars, and more. However, over the past decade, battery experts have been talking about an imminent “post-lithium” era. In this new article, Israeli-German experts in the field show that the rumors of the death of lithium batteries are premature.

According to Prof. Ein-Eli, “Our article is based on a meeting about batteries with the best experts in the field, which took place in Berlin last year for five days as part of GIBS4 – the German-Israeli school in the field of batteries. Li-ion batteries will remain with us for many more years, however, they will thrive alongside other storage technologies, so we propose to speak in terms of ‘complementary technologies’ and of a multi-technology future as opposed to a post-Lithium future. It is a complex future and so it is important to deliver optimal solutions for different technological needs – such as electric cars, electricity storage at home and at a national level, and so on. “

The meeting in Germany and the publication of the article was supported by German Federal Ministry of Education and Research (BMBF), the Helmholtz Association, the Israeli Ministry of Science and Technology (MOST), the Planning & Budgeting Committee/ISRAEL Council for Higher Education (CHE), and Fuel Choice Initiative (Prime Minister Office of ISRAEL) within the framework of “the 2nd Israel National Research Centre for Electrochemical Propulsion” (INREP 2), and by the Grand Technion Energy Program (GTEP).

Self-healing Electronic Skin

A doctoral student at the Technion – Israel Institute of Technology has invented a soft polymer that is elastic and waterproof, and that knows how to heal itself in the event of an “injury,” such as a scratch, cut, or twist.

The self‐healing stretchable conductive pathways were prepared by embedding silver nanowires (AgNWs) or carbon nanotubes into the surface of PBPUU.

The student, Muhammad Khatib, used the new polymer to develop advanced sensors that can monitor temperature, pressure, and acidity, and that are likely to be beneficial to a range of applications in the fields of robotics, prosthetics, and wearable devices. The innovative platform can heal itself not only on a mechanical level – repairing the tear in the polymer sheet – but also in terms of physical and chemical capabilities such as electrical conductivity and chemical sensing.

Khatib, who conducts his research at the Wolfson Faculty of Chemical Engineering at the Technion under the guidance of Professor Hossam Haick, presented his innovative inventions in two papers in the journals Advanced Materials and Advanced Functional Materials.

Muhammad Khatib

During millions of years of evolution, the skin of mammals developed into a sensory platform characterized on the one hand by high sensitivity to environmental stimuli and, on the other hand, by great resistance to hostile conditions such as temperature, salinity, heat, stretching, and folding. Inspired by natural skin, a great deal of effort has been invested in developing artificial electronic materials and devices with similar properties – due to the huge potential for applications in fields such as soft robotics and human-machine interfaces. 

These types of systems require developing soft materials whose functioning is not harmed by distortions or tears. The problem is that soft materials tend to be damaged over time, and their functionality becomes impaired. Consequently, researchers are motivated to develop new materials and systems that can heal themselves, just like human skin does after an injury. 

Khatib’s first project, presented in Advanced Functional Materials, describes the planning, building and implementation of elastomer – elastic and resilient polymer – with unique traits. The new elastomer is hydrophobic (water resistant), strong, and very elastic. It can stretch to 1,100% of its original length without tearing. One of its unique attributes is that it can heal itself, even when soaked in tap water, sea water, and water with varying levels of acidity. This elastomer has a huge potential for use in soft, dynamic electronic devices that come into contact with water. In the event that the mechanical damage to the polymer occurs when it is submerged in water, it knows how to heal itself and prevent electrical leakages (current flow from the device to the water). 

Khatib took advantage of the new polymer’s promising traits to develop artificial electronic skin – a project which he presents in Advanced Materials. Numerous attributes and capabilities are incorporated into the invention, including selective sensing, resistance to water, self-monitoring, and self-healing. The artificial skin contains a sensory system composed of nanometric materials that selectively and simultaneously monitors various environmental variables such as pressure, temperature, and acidity. Finally, inspired by the healing process of human skin, Khatib included an innovative autonomous self-healing system in the artificial skin. This system consists of neuron-like components that monitor damage to the system’s electronic parts, and other components that accelerate the self-healing process in the damaged places. This mechanism of self-healing enables the smart electronic systems to self-monitor their activities and repair functional problems caused by mechanical damage.

“The new sensory platform is a universal system that displays stable functioning in both dry and wet environments, and it is capable of containing additional types of chemical and physical (electronic) sensors,” Khatib explained. “Both projects that were now published pave the way for new paths and new strategies in the development of skin-inspired electronic sensing platforms that can be integrated into wearable devices and electronic skins for advanced robots and artificial organs.”

Khatib’s partners in the research are lab director Walaa Saliba; researcher Orr Zohar, who worked on developing the sensors and their attributes; and Prof. Simcha Srebnik, who worked on molecular simulations that clarify the capabilities of the new polymer.

The research was carried out with the support of the Bill and Melinda Gates Foundation and a grant from the A-Patch project (part of the Horizon 2020 program).


Biomarkers for COVID-19

Researchers at the Technion – Israel Institute of Technology and Rambam Health Care Campus have developed a toolbox that will help analyze the information gleaned from the physiological time series of oximeters increasingly being used during the ongoing COVID-19 pandemic.

Assistant Professor Joachim Behar

During the pandemic, many individuals with suspected or confirmed, but mild cases of COVID-19 are told to monitor their symptoms at home or from government managed locations (hotels in Israel). Hospitalization is only an option if there is a medical need, in particular shortness of breath. As a result, there has been an increase in purchases of low-cost commercial oximeters for people to self-monitor their oxygen saturation.

A low oxygen level in the blood means low oxygen in the body’s tissues, a condition that can ultimately lead to organ failure.

While monitoring the blood oxygen level may be a meaningful way to remote monitor individuals with mild COVID-19, a number of these commercial devices, even if CE or FDA approved, have limited accuracy. As a result, their practical use in this specific context is debatable.

More importantly, patients in the intensive care unit (ICU) with pneumonia, a common complication of the coronavirus, are continuously monitored with oximeters. However, there is a lack of smart algorithms that can exploit the information encrypted within these oxygen saturation physiological time series. The development of such algorithms could better support the continuous monitoring of ICU patients and predict eventual deterioration.

Jeremy Levy

What remains unclear is how exactly the information contained in the oxygen saturation physiological time series may be useful. Are trends or absolute values or the occurrence of specific patterns the most meaningful information to identify the disease and predict its course?

With these questions in mind, the laboratory for Artificial Intelligence in Medicine (AIMLab., https://aim-lab.github.io/) in the Technion Faculty of Biomedical Engineering has developed a toolbox of oximetry biomarkers to analyze these physiological time series. The toolbox, developed by master’s student Jeremy Levy and Assistant Professor Joachim Behar together with Dr. Ronit Almog and Dr. Danny Eytan  from Rambam Health Care Campus, has been integrated into the open-source software PhysioZoo developed jointly by the AIMLab and the Bio-electric and Bio-energetic Systems Laboratory headed by Professor Yael Yaniv. The software PhysioZoo can be freely downloaded at (https://physiozoo.com/).

Precision Personalized Medicine

Four research groups at Technion have been awarded grants from the Israel Science Foundation for personalized precision medicine research

The studies include improving cancer treatments and healing wounds in diabetics.

Four Technion research groups have been awarded ISF grants for research into personalized precision medicine. This is the second round of grants given by the Israel Science Foundation (ISF). In this round of the program, 16 research grants totaling approximately NIS 60 million were awarded to research groups from universities in Israel. The selected research projects are expected to lead to major breakthroughs in the field, increasing understanding of disease, and promoting new therapeutic approaches.

The four Technion projects are:

  • Defining sensitivity and overcoming resistance to PARP inhibition in pancreatic ductal adenocarcinoma using combined genomics and metabolomics tools. Prof. Eyal Gottlieb, and Prof. Keren Yizhak of the Technion Rappaport Faculty of Medicine, and their colleagues at Sheba Medical Center (Oncology Institute).
  • Overcoming Resistance to CAR-T cell Therapy due to Antigen Loss or Modulation by New Chimeric Receptors Targeting Intracellular-derived HLA Peptidome. Prof. Yoram Reiter, Technion Faculty of Biology, Prof. Myriam Ben-Arush, and Dr. Adi Shapira, Rambam Health Care Campus (Pediatric Hemato-oncology).
  • Understanding the relation of cellular and immunosenescence in aging and its relevance to the dynamics and clinical outcomes of severe infections. The study is conducted in cooperation with the Maccabi Health Data Science Institute. Prof. Shai Shen-Orr, Technion Faculty of Medicine, Prof. Valery Krizhanovsky, Weizmann Institute of Science (Molecular Cell Biology), and Prof. Mical Paul, Rambam Health Care Campus (Institute of Infectious Diseases)
  • A personalized 3D oxygen-sensing skin graft for the diagnosis and treatment of chronic wounds in patients with diabetes. Prof. Aharon Blank, Technion Faculty of Chemistry, Prof. Mogher Khamaisi, Rambam Health Care Campus (Internal Medicine D and Endocrinology), Prof. Marcelle Machluf, Technion Faculty of Biotechnology and Food Engineering and Prof. Yaron Fuchs, Technion Faculty of Biology.

The 16 winning research proposals in the current round were selected from 75 submitted proposals on a wide range of topics related to human biology as it applies to medicine. This program enables further expansion and deepening of personalized medicine in Israel. The winning bids were selected in a competitive process, based on scientific excellence, by an international judging committee chaired by the Nobel laureate for Chemistry, Professor Roger Kornberg of Stanford University. 

Research in the field of Precision Medicine is based on broad interdisciplinary collaborations that integrate scientific and medical knowledge, theory, in-depth analysis of medical big data, and extensive experimental work. The research program is based on a pooling of resources, which is part of the Planning and Budgeting Committee of the Council for Higher Education, the Ministry of Health, Israel’s digital project of the Ministry of Social Equality, the Yad Hanadiv and the Kellerman Family Foundation (Boston). The program is run and operated by the National Science Foundation (ISF).

Professor Yuval Dor, Head of ISF’s Life Sciences and Medicine division: “In IPMP’s second program cycle, we have witnessed a wealth of outstanding research programs that reflect the scientific depth and spirit of collaboration among researchers and physicians in Israel, and among universities, hospitals, and health funds. We were pleased to have been able to conduct the competitive evaluation process without delay, despite disruptions caused by the coronavirus pandemic. The winning proposals are from a range of universities and medical institutions, address fundamental questions in human health, and are expected to generate important scientific insights and medical applications.”

Professor Yaffa Zilbershats, Chair of the Council for Higher Education’s Planning and Budgeting Committee: “The IPMP program is a source of pride and satisfaction. By the end of the first cycle, it emerged that the program had exceeded all expectations. The second cycle reinforces this understanding. I am excited to see the content of the winning projects, their scientific quality, and the collaborations between scientists from academia and physicians and researchers from health organizations. There is no doubt that the program will make a huge contribution to advancing research and medicine in Israel and around the world. I thank the members of the Israel Science Foundation (ISF), who rose up to the challenge of evaluating the proposals within the timetables, despite the coronavirus outbreak.”

Shai-Lee Spigelman, CEO, Digital Israel, Ministry of Social Equality: “The IPMP program is a significant part of the Digital Health initiative as an engine of growth, positioning Israel at the forefront of the digital health revolution. It demonstrates the tremendous value of the medical information generated in Israel. The outstanding research studies that won the second cycle of the program will expand our understanding of a variety of diseases and help prevent and treat them. Equally important, they will strengthen the excellent existing collaboration between Israel’s academia and health system. This collaboration underpins Israel’s excellence in health and is one of the reasons for Israel’s success in battling the first wave of the coronavirus pandemic.”

Last year, grants were also awarded to Technion scholars: Prof. Roy Kishony of the Faculty of Biology (Development of customized antibiotic treatment for urinary tract infections); Prof. Tomer Shlomi of the Faculty of Biology (Early diagnosis of cancer in the population; Prof. Amit Mellar of the Faculty of Medicine (Prediction of retinal disease); and Prof. Yael Mandel-Gutfreund of the Biology Faculty (Prenatal diagnosis of birth defects).

 

Melanoma Therapy Breakthrough

Technion researchers present a new approach to overcoming anticancer drug resistance in melanoma.

Melanoma often presents a rapid resistance to molecular anti-cancer therapies. Now, in a discovery that can one day help address this major clinical challenge, researchers from the Technion’s Rappaport Faculty of Medicine have uncovered two proteins which, together, play a major role in drug resistant Melanoma.

The research was published in the Journal of Investigative Dermatology and was led by Prof. Amir Orian of the Rappaport Faculty of Medicine and Dr. Emily Avitan-Hersh of the Faculty of Medicine and Rambam Dermatology Department (as part of a doctoral dissertation) in collaboration with Prof. Ze’ev A. Ronai of the Sanford Burnham Prebys Medical Discovery Institute in California.

According to world statistics, melanoma is the deadliest form of skin cancer, killing one person every hour. In the U.S. alone, about 6,850 people are expected to die from the disease this year, most of them men. Although there have been advances in targeted and immunotherapy melanoma treatments in recent years, a substantial percentage of patients fail to respond or develop resistance to such therapies.

Professor Amir Orian

In many cases, melanoma results from a mutation in a gene coding for an enzyme called BRAF. This mutation promotes uncontrolled cell division and prevents programmed cell death, resulting in the development of cancer/melanoma tumors. Several years ago, new drugs that inhibit BRAF became available. These drugs are currently at the forefront of treating the disease, but unfortunately, melanoma cells develop rapid resistance to the same drugs − reducing their effectiveness and patients’ survival rates.

A “hallmark” observation in melanoma tumors from the patients are “stabilized oncoproteins.” Oncoproteins are cancer-causing proteins, which have the ability to turn healthy cells into cancerous cells. They are usually short-lived, however in such melanoma tumors they abnormally stabilize, thereby increasing their levels and pro-cancer activity. In previous experiments by Prof. Orian’s group, the oncoproteins were found to be protected against their natural protein degradation process by a protein called RNF4.

The team observed that high RNF4 levels in melanoma tumors correlate with poor prognosis and treatment resistance. Even more notably, they found that the tumorigenic properties (tumor growth, formation, and therapy resistance) of RNF4 in melanoma requires another protein: the translation initiation factor, eIF2α. RNF4 binds to eIF2α and stabilizes it, increasing p-eIF2α levels. In turn, p-eIF2α is required for RNF4 activities including the development of resistance, creating a devastating positive feedback loop.

The study spans the entire spectrum between basic research and clinics, from cell culture to xenografts in model mice to melanoma patients. The findings showed that increased levels of RNF4 characterize about 40% of melanoma patient tumors.

Dr. Emily Avitan-Hersh

The elucidation of the RNF4-dependant pathway in melanoma and its dependency on eIF2α has the potential to enable doctors to predict how a patients’ melanoma will respond to targeted therapies, allowing doctors to better personalize treatments for individual patients. The findings also present an opportunity for researchers to find a new pharmacological treatment to selectively block this pathway, effectively destroying such treatment-resistant melanoma tumors.

The study was conducted together with graduate students Yamen Abu Ahmad and Avital Oknin Vaisman of the Orian Lab and Rambam Senior Pathologist Yaniv Zohar, MD, PhD.

The research was supported by Fine and Wolf Fellowships, an Atidim research grant, National Cancer Institute Grants, the Israel Cancer Research Fund (ICRF) project grant, the German‒Israeli Foundation for Scientific Research and Development, and the Flinkman-Marandy Family Cancer Research Grants.

Prof. Amir Orian MD/PhD is the head of the Stan and Ruth Flinkman Laboratory for the Study of Genetic Networks at the Faculty of Medicine and a member of the Technion’s Integrated Cancer Research Center (TICC).

Dr. Emily Avitan-Hersh MD/PhD is a Lecturer in the Technion Faculty of Medicine, Deputy Director of the Department of Dermatology, and a member of the Rambam Clinical Research Institute, Rambam Medical Center.

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