How to open the imagination space of precision medicine with “chip”?

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With the development of AI technology, “personalized medicine” has been mentioned frequently in recent years. The “accuracy”, “efficiency” and “intelligence” symbolized by “personalized” make it an effective entry point to change the current situation of the medical industry. For example, intelligent guidance can interact with patients, and intelligent monitoring equipment can help track and customize medical services. So, can personalized medical care only be defined by AI medical products? I’m afraid not. Today, the theory of intelligent relativity (aixdlun) wants to talk to you about another level of personalized medical technology – “organ chip”.
Break the whole into parts, and truly “personalized” medical treatment
Speaking of personalized medicine, the first thing we think of in our mind is genetic medicine, which is a customized medical model that designs the best treatment plan for patients based on personal genome information and relevant internal environment information.
Although gene detection and treatment can provide a basis for personalized medicine, there are also cases of cancer and diabetes found through gene detection, and then precision medical measures are taken to delay the disease. However, from the perspective of the development process of gene medicine, except for a few diseases, it is difficult to determine the relationship between genes and diseases, such as “progressive frostbite” (ALS). Data shows that only a small part of ALS is related to gene defects, The cause of 90% of sporadic cases is still unknown.
Therefore, it is not reliable to include the whole genetic program of the human body in the reference list of personalized medical treatment. At this time, the emergence of organ chips gave people new reference indicators.
The concept of “organ chip” has a long history and was listed as one of the “top ten emerging technologies” by the Davos Forum in 2016. According to the journal of the Chinese Academy of Sciences, organ chip refers to an organ physiological microsystem built on a chip. It takes microfluidic chip as the core, and can simulate and build a tissue organ microenvironment containing a variety of living cells, functional tissue interfaces, biological fluids, mechanical force stimulation and other complex factors in vitro by combining with cell biology, biomaterials, engineering and other methods,, It reflects the main structure and functional signs of human tissues and organs.
To put it simply, it is to build a simplified version of biological tissues and organs in human body in vitro, only preserving the organ functions and human pathobiological characteristics. The significance of “organ chip” in personalized medicine is to break the human body into parts, replace the accurate diagnosis of “human body” with the accurate diagnosis of “organ”, and provide more effective and targeted treatment.
Through the use of patient-derived stem cells, the engineering construction of induced pluripotent stem cell-derived organ model is realized, which makes the individualized disease risk prediction, drug efficacy evaluation, toxicological evaluation and prognosis analysis more accurate. At present, there are also scientists who use the stem cells of specific patients to build functional heart tissue to simulate the cumulative genetic heart disease model.
In addition to realizing personalized medical treatment for human beings, organ chips also have an obvious advantage, namely, drug testing. In this regard, changes in animal experiments will be revolutionary.
For a long time, people have tested drugs through animals, regardless of whether it is humane to test drugs with animals. From the perspective of experimental accuracy, although the proportion of genes shared by animals and humans is as high as 99%, the remaining 1% will still cause huge variables, resulting in huge physiological differences between the two species. The reactions of the same drug in animals and humans may be different. Even the smallest difference in expression will be magnified with the progress of drug research and development, and eventually lead to the failure of the whole project.
Because “organ chip” is closer to the human body, it can be more effectively used for drug testing. On October 11, the Progress of Science reported a 3D method of making neurons and muscle tissue on a microfluidic chip. With this chip, scientists can test new drugs for “gradually frozen human”.
Emulation, cost, connection… problems faced by organ chips
The concept of organ chip has been put forward for a long time, but the process of industrialization is very slow. To explore the reasons, it can be roughly divided into three points.
First of all, even the most advanced organ chips cannot fully represent the functions of living organs. After all, all organs cannot exist independently of the body. Although it is of constructive significance to break up the whole into parts, the whole is larger than the part. Only relying on organ chips can not replicate the disease organism, especially a series of functional changes caused by the endocrine environment.
Therefore, we must consider the relevance of the human body as a whole. In this regard, we can use a single chip to form a highly integrated 3D tissue and organ microfluidic chip system. The research team of Dalian University of Technology has developed such a chip system. The chip system is composed of multiple modules stacked from top to bottom, integrating cells or tissues such as intestine, blood vessels, liver, tumor, heart, lung, muscle and kidney, with “digestive fluid”, “blood” and “urine” running through it. In this way, the organ chip is like a building block. By stacking all the building blocks, we can create a “human body building” to the greatest extent, restore the functional environment in the human body, and achieve drug testing and other functions.
Secondly, organ chip is still a growing technology, and the immaturity of the industrial chain will lead to increased costs. Oxford’s CNBio company uses a chip containing 12 miniature livers to conduct toxicity tests on drugs. At present, the price of a unit is 22000, in US dollars. In fact, the price is much lower than that of animal experiment. You know, the price of mice for the same experiment is $50000.
However, in the process of industrialization, the so-called “low price” is still a question mark. At present, organ chips are mostly used in scientific research, and the scientific research funds are sufficient to support the use of such tools. But our greater hope for organ chips is to be based on the medical treatment of ordinary people. If organ chips are to be industrialized, it is still necessary to control costs. Of course, with the improvement of the industrial chain, its advantages will gradually emerge, and the cost problem will be solved accordingly.
Before that, we may be able to use 3D printing technology as an important supplement to the organ chip production method. 3D printing technology will affect organ chips in at least two aspects, one is chip preparation, and the other is bioprinting. Especially in chip preparation, 3D printing has been able to produce chips with high resolution and complex structure, and also has the advantages of short production cycle, simple unit operation and low cost. Researchers from Wyss Institute of Bioengineering of Harvard University and Harvard John A. Paulson Institute of Engineering and Applied Sciences have used 3D printing to produce the first complete organ chip with integrated sensor system.
Finally, there is a common problem in microfluidic chips, that is, the connection between macro samples and microchips is not easy. At present, the injection of samples on the chip is mostly done manually, which is inefficient and unreliable. It is very easy to affect the vitality of cells, and thus affect the real-time detection of cell processes and biological characteristics. Therefore, we also need to develop more auxiliary products, such as continuous injection systems, to ensure automation, miniaturization and integration in the preparation.
So far, personalized medical care has accumulated many technical achievements. With the continuous development of technology, we also put forward more requirements for “personalization” and “accuracy”. The significance of organ chip to human is that people can really “apply the medicine to the case” without “damaging” other tissues and organs. With the deepening of research, organ chip technology will be widely used in the research of life science, medicine, pharmacy and other fields, bringing more possibilities for personalized medicine.

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