Body-on-chip: technology perspectives
Each new drug to enter the market goes a few years and billions of dollars, of which more than half is spent on research. Animal testing does not give a definitive answer about the efficacy of drugs: drugs that work on mice may be useless for humans. Drugs that work on the majority of people may not be suitable for one particular patient, which leads to the need for personalization.
One of the ways to solve these problems was the concept of “organ-on-chip”. The group of scientists working with DARPA went further: it is working on creating an “on-a-chip” system to search for drugs that are fully compatible with the patient and to study their side effects.
A group of scientists within the project has created a microfluidic platform to simulate the interaction of up to ten human organs. The system is designed to test drugs. “With our chip, you can inject a drug and test its effect on several organs, measure the drug's metabolism,” says Linda Griffith, the head of the research team. Scientists note that one of the main applications of the system will be the testing of immunotherapeutic drugs: the results of their testing on animals are very difficult to translate into humans.
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When developing new drugs, researchers determine its purpose — answering the question of what the drug should influence, based on knowledge of the disease itself. They then create compounds that have the desired effect on the organ. Preclinical animal trials should demonstrate the safety and efficacy of the drug before testing in humans, but cannot reveal potential side effects. In addition, according to Griffith, drugs may later fail in human trials. In some cases, it is impossible to test the drug in mice or rats - for example, enteroviruses , deadly for infants, these animals do not become infected.
The technology, which Griffith and her colleagues are developing for DARPA, scientists called "physiomy-on-a-chip." The researchers needed a platform that allows tissues to grow, to interact with each other, imitating the functions of human organs.
The organ-on-a-chip is a multichannel microfluidic system, which allows to imitate the interaction of a drug with the heart, lungs, intestines and other organs. For example, heart tissue on a microcircuit after their loading onto the device began to pulsate with the frequency of the normal pulse of an average adult person - from 55 to 80 beats per minute, and after half an hour of exposure to the drug for the treatment of bradycardia, the pulse increased to 124 beats.
Heart tissue pulsation
The thrombosis-on-a-chip model makes it possible to mimic the factors leading to the formation of blood clots. Brain-on-a-Chip has learned how to grow blood vessels on its own. The “packaging” of living cells into a microcircuit in theory may allow one to abandon animal experiments and increase the effectiveness of drug testing.
"Thrombosis-on-chip"
An important factor in favor of working with “organs-on-a-chip” is the ability to personalize drugs. Side effects and efficacy of the drug may depend on the genetics, age, lifestyle, and other indicators of the particular patient. A miniature "body" of a particular person will allow you to understand how the drug will affect it.
The new development develops this direction and makes it possible to understand not only the effect of a drug on one organ, but its effect on a system of several organs, “a person in miniature”. The second difference from the "classic" "organs-on-chip" was the openness of the system: tissues can be removed for their analysis, without interrupting the operation of the device. The system of pumps allows you to regulate the distribution of fluids between organs, to simulate the circulation of blood, immune cells and proteins in the human body. Additional tissues can be introduced into the system, such as a tumor inside the organ.
The result was several versions of the chip, including tissues of up to ten types of organs: liver, lungs, intestines, endometrium, brain, heart, pancreas, kidneys, skin, muscles. Each "body" consists of a cluster of 1-2 million cells. Tissues are not a copy of an organ, but are capable of performing some of its important functions. In the system, you can use cells of a specific person - it is more difficult to work with them, but this approach is more effective for finding personalized drugs.
The device allows researchers to see how a drug that has entered the body through the mouth is transported to other tissues and metabolized. They can check how the drug moves between the organs, affects different tissues and breaks down.
“Microphysiological systems that mimic a single organ can be successfully used for testing in the pharmaceutical industry and for organ research. But the enormous potential of this concept is connected with the integration of several organs on a single chip for in vitro pharmacology. This study illustrates how an approach to a multi-microphysiological system, combining the genetic background of human cells, allows us to accurately predict the pharmacokinetics of drugs, their distribution, metabolism and elimination from the body, ”Kevin Healy, professor of bioengineering at the University of California at Berkeley, comments on the results. not associated with a group of researchers.
"Fizioma-on-chip"
Linda Griffith is now working on a chip in the laboratory to search for drugs from Parkinson's disease: the system includes the brain, liver and tissues of the gastrointestinal tract. With this “body-on-a-chip”, the team will test the hypotheses that bacteria found in the intestine can influence the development of this disease.
Another application is related to the modeling of tumors, turning into metastases in other parts of the body. Among the advantages of the system Griffith calls the ability to scale it and use different configurations. For commercialization, the most promising solution at the moment will be the creation of systems from three to four bodies, since this “minimum” will allow to obtain more valuable information compared to systems from one body.
One of the ways to solve these problems was the concept of “organ-on-chip”. The group of scientists working with DARPA went further: it is working on creating an “on-a-chip” system to search for drugs that are fully compatible with the patient and to study their side effects.
A group of scientists within the project has created a microfluidic platform to simulate the interaction of up to ten human organs. The system is designed to test drugs. “With our chip, you can inject a drug and test its effect on several organs, measure the drug's metabolism,” says Linda Griffith, the head of the research team. Scientists note that one of the main applications of the system will be the testing of immunotherapeutic drugs: the results of their testing on animals are very difficult to translate into humans.
')
When developing new drugs, researchers determine its purpose — answering the question of what the drug should influence, based on knowledge of the disease itself. They then create compounds that have the desired effect on the organ. Preclinical animal trials should demonstrate the safety and efficacy of the drug before testing in humans, but cannot reveal potential side effects. In addition, according to Griffith, drugs may later fail in human trials. In some cases, it is impossible to test the drug in mice or rats - for example, enteroviruses , deadly for infants, these animals do not become infected.
The technology, which Griffith and her colleagues are developing for DARPA, scientists called "physiomy-on-a-chip." The researchers needed a platform that allows tissues to grow, to interact with each other, imitating the functions of human organs.
The organ-on-a-chip is a multichannel microfluidic system, which allows to imitate the interaction of a drug with the heart, lungs, intestines and other organs. For example, heart tissue on a microcircuit after their loading onto the device began to pulsate with the frequency of the normal pulse of an average adult person - from 55 to 80 beats per minute, and after half an hour of exposure to the drug for the treatment of bradycardia, the pulse increased to 124 beats.
Heart tissue pulsation
The thrombosis-on-a-chip model makes it possible to mimic the factors leading to the formation of blood clots. Brain-on-a-Chip has learned how to grow blood vessels on its own. The “packaging” of living cells into a microcircuit in theory may allow one to abandon animal experiments and increase the effectiveness of drug testing.
"Thrombosis-on-chip"
An important factor in favor of working with “organs-on-a-chip” is the ability to personalize drugs. Side effects and efficacy of the drug may depend on the genetics, age, lifestyle, and other indicators of the particular patient. A miniature "body" of a particular person will allow you to understand how the drug will affect it.
The new development develops this direction and makes it possible to understand not only the effect of a drug on one organ, but its effect on a system of several organs, “a person in miniature”. The second difference from the "classic" "organs-on-chip" was the openness of the system: tissues can be removed for their analysis, without interrupting the operation of the device. The system of pumps allows you to regulate the distribution of fluids between organs, to simulate the circulation of blood, immune cells and proteins in the human body. Additional tissues can be introduced into the system, such as a tumor inside the organ.
The result was several versions of the chip, including tissues of up to ten types of organs: liver, lungs, intestines, endometrium, brain, heart, pancreas, kidneys, skin, muscles. Each "body" consists of a cluster of 1-2 million cells. Tissues are not a copy of an organ, but are capable of performing some of its important functions. In the system, you can use cells of a specific person - it is more difficult to work with them, but this approach is more effective for finding personalized drugs.
The device allows researchers to see how a drug that has entered the body through the mouth is transported to other tissues and metabolized. They can check how the drug moves between the organs, affects different tissues and breaks down.
“Microphysiological systems that mimic a single organ can be successfully used for testing in the pharmaceutical industry and for organ research. But the enormous potential of this concept is connected with the integration of several organs on a single chip for in vitro pharmacology. This study illustrates how an approach to a multi-microphysiological system, combining the genetic background of human cells, allows us to accurately predict the pharmacokinetics of drugs, their distribution, metabolism and elimination from the body, ”Kevin Healy, professor of bioengineering at the University of California at Berkeley, comments on the results. not associated with a group of researchers.
"Fizioma-on-chip"
Linda Griffith is now working on a chip in the laboratory to search for drugs from Parkinson's disease: the system includes the brain, liver and tissues of the gastrointestinal tract. With this “body-on-a-chip”, the team will test the hypotheses that bacteria found in the intestine can influence the development of this disease.
Another application is related to the modeling of tumors, turning into metastases in other parts of the body. Among the advantages of the system Griffith calls the ability to scale it and use different configurations. For commercialization, the most promising solution at the moment will be the creation of systems from three to four bodies, since this “minimum” will allow to obtain more valuable information compared to systems from one body.
Source: https://habr.com/ru/post/374347/
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