{"id":3942,"date":"2023-06-27T11:27:29","date_gmt":"2023-06-27T11:27:29","guid":{"rendered":"https:\/\/innovationisrael.org.il\/en\/?post_type=article&p=3942"},"modified":"2023-11-27T06:14:24","modified_gmt":"2023-11-27T06:14:24","slug":"a-quantum-leap","status":"publish","type":"article","link":"https:\/\/innovationisrael.org.il\/en\/article\/a-quantum-leap\/","title":{"rendered":"A Quantum Leap"},"content":{"rendered":"\n

Large processes sometimes occur on a small scale. \u201cMicrofluidics is the world in which entire processes conducted in the laboratory are miniaturized into tiny containers\u201d, explains Prof. Doron Gerber<\/strong>. In chemistry, biology and other fields, the processes take place in a liquid environment, even when working with miniature dimensions, hence the name \u2018microfluidics\u2019.<\/p>\n\n\n\n

\u2018Laboratory-on-a-chip<\/strong>\u2018, that is based on microfluidics, enables us to simultaneously conduct multiple and complex sets of experiments that generate a high data output such as a survey of biochemical, physical and cell data, with a tremendous saving in the number of samples required and the duration of the experiment. <\/p>\n\n\n\n

A Hair-Sized Canal<\/h3>\n\n\n\n

Prof. Doron Gerber is a researcher in the Nanotechnology Center and Faculty of Life Sciences at Bar Ilan University. \u201cMy background is in biology\u201d, he says. \u201cAfter a doctorate that examined membranal proteins, I decided to do something of a more technological nature. I completed a post doctorate with Prof. Stephen Quake at Stanford \u2013 a researcher who introduced me to the whole field of controlled microfluidics. Prof. Quake invented a new type of microfluidics that enables us to conduct extremely complex experiments and to develop applications in the fields of biology, chemistry, and physics by using flexible switches that enable complete control of whatever happens inside the chip. In other words, the technology allows smart management of small nano-liter quantities of fluids.<\/p>\n\n\n\n

\u201cHow does it all work? Let\u2019s say that we want to conduct 1,000 simultaneous experiments. First, we need a sample of the substance we are studying e.g., a drop of blood. In regular experiments, we only have a limited number of available samples, either because they are taken from a single person or because they are very expensive. <\/p>\n\n\n\n

\u201cMicrofluidics allows us to perform complex procedures with tiny amounts of samples. Let\u2019s imagine that I had an endless quantity of blood to examine: I would take 1,000 test tubes and attempt to perform one experiment using different substances on a blood sample in each one according to the parameter I wanted to test.    <\/p>\n\n\n\n

\u201cHere, we miniaturize the experiment set so that we have 64 micro-cavities instead of test tubes. Each of these cavities contains only one-thousandth of a drop of the patient\u2019s blood. Each cavity is one quarter of a square millimeter and is 20 microns high, so its volume is only a few nano-liters (1 nano-liter is one millionth of a liter). The passages between the micro-cavities are canals, each up to a hairbreadth wide, through which the substances required for the different experiments move. Multiply this set by 64 levels and you can conduct thousands of experiments at the same time.  <\/p>\n\n\n\n

\u201cTo make it work, we need each experiment to remain separate from the others, so we created a \u2018door\u2019 that in addition to separation also allows us to insert and extract things. This door is an elastic switch that opens and closes according to instructions given from a computer software.<\/p>\n\n\n\n

\u201cIn other words, our microfluidic chips are set of extremely small cavities and a system of fully controlled switches (\u2018doors\u2019) capable of timed insertion and extraction of substances from the cavities. An experiment set like this can be used in a wide range of scientific experiments such as searching for substances in the blood like antibodies, pieces of DNA or RNA from a viral source, indicators of cancer etc. A small volume of a patient\u2019s blood can be used as a sample, inserted into the chip so that each of the chip\u2019s many cavities contains a small drop of blood and can \u2018host\u2019 a test to locate the substance under examination, enable its quantification, or a qualitative analysis that indicates its presence in the blood. <\/p>\n\n\n\n

\u201cIn other experiments, such as those that check the connection between proteins of different viruses and human proteins, we can start from the level of the genetic material of a person or a virus, translate it into proteins that are given fluorescent markers (fluorophores)  in the chip\u2019s cavities, and evaluate the degree and strength of the connection created between these proteins. Information such as this is extremely valuable in studying viruses\u2019 operating mechanisms and the way they influence human cells. Finding a strong connection between a viral protein and a human protein hints to the involvement of these proteins in the way the virus infects or spreads and can therefore constitute a target site for the development of a treatment for that virus.<\/p>\n\n\n\n

\u201cIn addition to work with different molecules, the microfluidic platform also enables us to work with whole cells. <\/p>\n\n\n\n

\u201cIn the field of cancer research, there is a good correlation between the results of the laboratory experiment and clinical results. Nevertheless, the main problem is that a sample taken from a cancer patient contains many cancer cells and there is no way to cultivate them in such a way as to be able to conduct dozens of experiments and analyze their influence on a range of possible treatments. In an attempt to overcome this obstacle, scientists are trying to grow the tumor cells in the lab and increase their number and only then expose them to different treatments, but this is a race against time. <\/p>\n\n\n\n

\u201cWe have developed a microfluidic chip for culturing the cells. Each of the chip\u2019s cavities can accommodate a tiny quantity of cancer cells taken from a specific patient and allows us to expose each group of cells to a different pharmaceutical treatment and check their reaction to it. This method enables us to know which treatment the cancer cells are resistant or sensitive to and how they respond, all within just a couple of days.<\/p>\n\n\n\n

\u201cAlthough there are currently many drugs for treating cancer, it\u2019s not clear how each patient will respond to each of them. A specific drug may cause harsh side effects and be ineffective in treating the disease so the window of opportunity for treating these patients is extremely limited. The results of an experiment using our chip can help direct the patient\u2019s physician to choose the most efficient treatment for him, thereby saving precious time and unnecessary suffering. <\/p>\n\n\n\n

\u201cA year ago, we published an initial paper in which we proved the theory and presented the system\u2019s capabilities. We have now begun checking patient samples. The paper gained considerable interest, and many have expressed a wish to examine samples using our system.<\/p>\n\n\n\n

\u201cWe recently began collaborating with Dr. Amir Onn<\/strong>, Head of the Institute of Pulmonary Oncology at the Sheba Medical Center and Dr. Limor Broday<\/strong> from Tel Aviv University. The time limit with lung cancer is especially short. From the moment the patient stops responding to treatment, a doctor needs to receive the relevant knowledge and make a very quick informed decision regarding alternative treatment. In our joint study, we attempt to assess whether our method can facilitate a swift and accurate decision, thereby enhancing the results of the treatment administered to the patient. <\/p>\n\n\n\n

\u201cThere is a tremendous need in this field, and we are attempting to get financing from scientific grants that will enable us to survey about 300 patients over the next two years. This will, in turn, allow us to characterize the system in relation to a set of lung cancer medications while simultaneously upgrading the system that checks the vitality and mortality data following exposure to the medication. In the future, we hope to add a further capability to the system that will facilitate the measurement of metabolic indices which report on processes within the cells such as glucose and energy levels, and that provide more in-depth information. <\/p>\n\n\n\n

\u201cThe device\u2019s complexity means that the need for large-scale investment is a fundamental issue in the chips\u2019 production processes. Our dream is to enable biologists to take an idea and bring it to engineering implementation: lab production of a chip. This for me is the essence of Bio-convergence \u2013 a biologist using sophisticated engineering to create innovative solutions. <\/p>\n\n\n\n

\u201cWe built a factory at Bar Ilan University for producing microfluidic chips, not only for my laboratory but also for additional labs at Bar Ilan and other institutions as well as for Israeli industry, but we belong to academia and it\u2019s only a small factory with limited human and financial resources. As of now, our largest challenge is to enable industry to utilize the potential of the infrastructure we have constructed.<\/p>\n\n\n\n

The Future of Microfluidics<\/h4>\n\n\n\n

Prof. Gerber predicts a rosy future for the tiny chips: “It’s happening all around the world \u2013 microfluidics is entering the world of diagnostics and the field of developing tools for scanning medications and substance synthesis e.g., therapeutic antibodies or antibodies for genetic engineering of viruses etc. <\/p>\n\n\n\n

“The industry needs microfluidic chips to produce therapeutic antibodies and to market them as drugs and increasingly more microfluidic tools are appearing in manufacturing or development processes. As of now, this kind of research only exists on a small scale in Israel, primarily in academia, with large-scale microfluidic centers needed to integrate the technology into the industry. If, for instance, we assume that a startup company receiving a limited initial sum of money wants to use a microfluidic tool, its chances of success are slight. Among the reasons for this is the lack of appropriate infrastructures \u2013 production of a simple microfluidic chip requires a manufacturing plant with clean rooms, equipment for creating molds by lithographic processes, equipment for coating molds, and equipment for producing the chips.  <\/p>\n\n\n\n

“Today, when it is obvious to everyone that there is a need to connect biology and high-tech, it is also clear that most of the major tools for doing so actually exist in academia far more than in industry. On the other hand, academia lacks the large-scale infrastructures required to transform technology into an off-the-shelf product like production of a chip prototype. Since entering academia, I have established, and am still establishing, a microfluidic chip center capable of producing different kinds of chips and providing support to new researchers seeking to make use of microfluidic technology, all subject to the limitations of the existing support in academia. <\/p>\n\n\n\n

“There is no doubt that large-scale investment and significant financial incentives directed at the development of basic infrastructures are required for the field of microfluidics to transcend the walls of academia and penetrate industrial realms. In contrast to biology for example, where you can buy a robot to perform large quantity tasks, microfluidics is characterized by a scarcity of companies that develop these tools for others. Investment in this infrastructure will enable companies to make use of off-the-shelf products and to integrate these innovative technologies into their applications. Young industry must also be connected to academic capabilities. <\/p>\n\n\n\n

“Many companies who come to our nanotechnology center for example, use our equipment and at the same time, receive good counseling. But this happens at an academic pace. We must invest a little more in this infrastructure so that it serves industry better, for example, in the establishment of a consortium which we aspire to be a member of”.<\/p>\n\n\n\n

Dr. Itai Kela, Scientific Director of the Bio-Convergence Program:<\/strong> “The integration of microfluidics used for discovering new medicines and ‘lab-on-a-chip’ systems creates an amazing technology that enables to dramatically reduce the use of lab animals when developing drugs and constitutes an engineering technological platform for the scanning and more rapid and efficient detection of new medicines and treatments”.          <\/em><\/p><\/blockquote><\/figure>\n\n\n\n

The Sensors that Discover Why Medications Fail<\/h3>\n\n\n\n

When discussing Bio-convergence and the combination of industry and academia, it is important to learn about the work of Prof. Yaakov “Koby” Nahmias.<\/strong> Prof. Nahmias, Founding Director of the Bioengineering Center at the Hebrew University in Jerusalem<\/strong>, is a serial entrepreneur and Chief Scientist of the Tissue Dynamics corporation which he founded a year ago. <\/p>\n\n\n\n

“Bio-convergence \u2013 the structured combination of engineering biology and medicine \u2013 is a very important part of projects’ technological maturity and enables amazing breakthroughs”, he says. “In practice, one of the main reasons behind the establishment of the Bioengineering Center at the Hebrew University was the desire to provide an academic response to the growing need for engineers who understand biology and vice versa”.<\/p>\n\n\n\n

As an example of the importance of Bio-convergence, Prof. Nahmias relates to the Corona virus: “When the ‘Hepatitis C’ virus was discovered in the year 2000, it took 3-4 years to sequence it and then an entire year to grow it. The first medication arrived only several years later. In other words, it took about a decade to develop molecules capable of contending with ‘Hepatitis C’. <\/p>\n\n\n\n

“In contrast, the new Corona virus was only discovered in November and was more or less sequenced already in December. Its first tissue cultures were ready in January-February with the first molecules being introduced to clinical research around March. What took years with ‘Hepatitis C’ is being done in just weeks and a few short months with Corona. This is much more than an exponential increase \u2013 it’s a quantum leap. <\/p>\n\n\n\n

“Today’s world moves extremely fast and investors need to take into account that the pharma industry is going to reverse itself. The 1970s and 1980s were characterized by a lot of mediocre pharma companies, most of which were swallowed up by a small number of pharma giants that are the only ones with the massive resources necessary to bring a new drug to the market. The next technological revolution will enable an entire community of small pharma companies to compete with the giants. <\/p>\n\n\n\n

“I am a member of the Innovation Authority’s Bio-convergence Committee that will lead a dramatic breakthrough in Israel’s technological capabilities. The Authority helps the academic world penetrate industry, receive necessary resources, and transform theoretical solutions into practical applications. If until 15 years ago the world of academia was extremely theoretical and did not view the connection with industry as something positive, I believe that this view has changed over the last decade. Today, both the universities and their academic staff are very interested in industry and are working closely with the Authority. The attitude has changed even more in recent years during which young faculty members are themselves beginning to lead startup companies to the market and I hope that this trend will continue. <\/p>\n\n\n\n

Tissue Dynamics operates in the ‘organ-on-a-chip’ field and seeks to change the world of pharma development.<\/p>\n\n\n\n

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