The article is from the public number: Nutshell (ID: Guokr42) , author: Fushi Bo, thematic map from: ” ET alienPeople “ .

Recently, a research team from the University of Vermont and Tufts University published a (PNAS) in the top journal “Academy of Sciences”. A very impressive and innovative study-living biological robots. Many people who eat melon exclaimed, this is simply the powerful mysterious creature in the science fiction movie “Awakening of the Other Stars”, or the nanoparticle killer that devours everything in “Special Forces”. While praising the advancement of science and technology, everyone began to worry, lest scientists accidentally ruin the future of mankind.

However, the existing media often confuses the future application prospects and current status of this invention technology, and erroneously produces a feeling of “the future has come”. Next, we will disassemble the support technology and the problems that need to be solved behind this seemingly “tall” biological robot.


Ins and outs of artificial meatballs

First, the concept of this micro-living robot is very new: the researchers used a supercomputer simulation to select the best cell arrangement. Then the embryonic stem cells of Xenopus laevis were used to differentiate cardiomyocytes and epidermal cells, and the two cells were assembled into a biological robot according to the optimal structure simulated by the computer. These small meat balls show multiple functions such as directional movement, collection of small particles, and transfer of substances in the medium.

Biological Robot Mobile Demo | https://www.inverse.com/

Next, let ’s take apart each itemThe supporting technology behind this seemingly “tall and tall” biological robot.

First, an embryonic stem cell can differentiate into hundreds of cells. Why did you choose epidermal cells and cardiomyocytes independently?

This is because the robot must move first, so skeletal muscle cells and cardiac muscle cells will move among the hundreds of cells. Although skeletal muscle cells can move, they need external electrochemical signals to stimulate them to contract. Myocardial cells are different. As long as the chemical composition of the external environment is stable, it can maintain continuous voluntary contraction.

Epithelial cells and cardiomyocytes are derived from different germ layers. It is not easy to mix with cardiomyocytes when constructing a biological robot. Instead, a group of epidermal cells and a group of cardiomyocytes are tightly adhered to each other to form a certain function structure. In the future, if this biological robot is required to perform other functions, epidermal cells can be replaced with other cells, and even one or two can be added in addition to these two cells.

The authors of the paper refer to non-moving epidermal cells as “passive cells” and moving myocardial cells as “active cells”. The former provides the latter with a lever for contraction, and the latter provides the former with power. In this way, the two cells form a complex cell cluster that can move.

Red is cardiomyocytes and green is epidermal cells. A: Structural model of computer simulation; B: Morphology of biological robot observed under fluorescence microscope | www.wired.com

So how to make myocardial cell clusters and epidermal cells grow together according to a certain binding pattern?

The answer is very simple and rude-the extracellular matrix secreted by the cells will stick the two clumps of cells together, and take very fine tweezers to shape it like a plasticine under the microscope: p>

Demonstration of bio-robot shaping process | https: //www.inverse.com/

But How can we make this little flesh move in the form we need? This is where the cleverness and innovation of this research lies—computer simulation architecture . Rather than blindly experimenting with one structure and one structure, the research team chose computer simulation to allow different matching structures to perform fluid mechanics motion tests in a computer simulation environment.

Building different forms of biological robots and then putting them into the culture medium for exercise testing is passive screening, and researchers asking the computer to do the work greatly improves the efficiency. Let ’s take a look at the “tip of the iceberg” disclosed in the paper:

Red myocardial cells and blue epidermal cells are countlessly matched with different quantity ratios and different matching methods, and then handed over to the computer for calculations to analyze the movement force and movement track in the liquid environment . In this way, the structure that meets the design requirements is coarsely screened and verified by in vitro experiments.

The future is beautiful, and the reality is very skinny

According to the outlook in the paper, researchers believe that the characteristics of biological robots show their infinite possibilities in the future. They can be used to clean up microplastic pollution in the ocean, locate and digest toxic substances, or enter human blood vessels, accurately deliver drugs, remove plaque on the arterial wall, etc.

But the authors also do not deny that the current version 1.0 of the biological robot is far from these great application prospects.It is still far away, at least the following problems still need to be solved:

1 Cannot rely on mass production

At present, according to the methods in this document, all biological robots are “fabricated” by researchers. If it needs to be applied to the human body in the future, obviously a few robots are definitely not enough. How to produce tens of thousands of these small meat balls to make them close in structure and function is obviously not purely artificial.

Maybe biological 3D printing technology or micro robot operation is a feasible strategy. After all, the current 3D bioprinting technology has been able to produce living tissues / organs such as ear cartilage, trachea cartilage and even the bladder and kidney. It is not difficult to print a biorobot composed of only two cells.

2 Nutrition needs to be provided from outside

Although in the dissertation, the bio-robot has demonstrated the ability to work continuously without sleep and the ability to repair mechanical damage. But all this depends on a stable external environment-these small meat balls are all immersed in nutrient-rich, oxygen-containing medium. So it is conceivable that if this technology is applied to the human body in the future, robots may only be able to operate in blood vessels, relying on nutrients and oxygen in the blood to maintain life and specific functions.

3 Human applications must also solve the problem of cell origin

If this technology is to be applied to the human body in the future, it will definitely not be able to differentiate active and passive cells from embryonic stem cells. After all, that embryo is already an adult. If other human embryonic stem cells are used, these stem cells will produce mature histocompatibility complexes after the differentiation (MHC) antigens, used in other human bodies Immune rejection will occur and preoperative matching may be required. Specifically similar to the matching of organ transplants.

If we do not follow the path of embryonic stem cell differentiation, it will be necessary to isolate cells from human tissues that have already matured and then expand them for the production of biological robots.

But it faces a more difficult problem: cardiomyocytes take tissue from the heart, and cardiomyocytes are difficult to expand in vitro. Since there is no reliable study on the induction of adult stem cells into differentiated cardiomyocytes, in the future human application, the path of allogeneic embryonic stem cell differentiation and proliferation may be easier.Do transplant matching.

An alien monster? You think too much!

Stills from the movie Awakening of the Other Stars | https://moviesandshakers.com

This biorobot has only two types of cells, and can only survive for less than ten days in a nutrient-rich medium, and it can only do the simplest movements in the culture medium. But the dreaded alien creatures in The Awakening of Other Stars are different. Not only do each cell have motor, digestive, and sensory functions, but it also has obvious self-awareness. In contrast, biological robots are more like artificial meat.

Artificial meat has been on the market for decades, and most of it stays on the modification of plant protein to make it have meat-like taste, aroma and nutrients. The latest artificial meat manufacturing technology is to clone the muscle cells of cattle in vitro to produce artificial meat that is infinitely close to real beef from macro to micro, from taste to nutrition. So from this point of view, the biorobot is just a small, moving, artificial meatball—the taste of a bullfrog, if the Xenopus and the bullfrog taste similar.

Although biological robots still have such shortcomings, this research is still a very innovative synthetic tissue engineering research. In particular, the use of computer simulation technology to assist the structural design of robots has greatly accelerated the process of structural optimization. In fact, the use of computer technology has accelerated the evolution of biological structures. The evolution of life on earth has always been the fine-tuning of the structure caused by random genetic mutations, and the competition for survival in the waves and sands has been in the change of the natural environment. A significant trait change may need to wait for tens of thousands of years, and when humans design biological robots, they use computer simulation to screen out the robot structure we want in a short time.

Biological robots may be simple and fragile. But the seed of this imagination has been quietly buried in the soil.

Expert Reviews


Sun Tianqi | Member of Science Squirrel Society, founder of robot company Vincross

This is a very interesting study, playing Lego with biological structures. However, some media interpreted it as “AI creature”, “living robot”, “alien” and so on.

I don’t think this invention was made by creatures or robots. Because in a strict sense, living things are stressful and capable of reproduction, and this synthetic biological robot does not have such basic biological characteristics. It just uses the rhythmic actions of cardiac muscle cells to form a mobile shape.

And what we usually call a robot is an organism or a mechanical device that can either be adaptive or programmable, but this so-called “biological robot” does not have such a function for the time being.

So, instead of being a creature or a robot, it’s more like a clockwork frog-it can jump blindly for a while. Of course, this technology or invention has very important value and inspiration, but some media’s deliberate pursuit of its report is not right.

Li Jingyu | Shanghai Siweidi Biomedical Technology Co., Ltd.


This is actually not strictly a biological robot. (Although they use the wording of a living machine) . More precisely, it is a multi-cell robot. Use cardiomyocytes that can beat on their own as motors. Using ectoderm-derived skin cells to achieve the morphological structure constructed by AI technology, similar to the wood used for the fuselage when we make model aircraft. The pulsation of myocardial cells causes the regular contraction and relaxation of the entire multicellular robot, allowing the cell mass to move.

But we know that what this cell mass looks like has a great influence on its athletic ability. This team uses AIComputer simulations of how cell clusters of various phases will move have proved to be effective. How to move the cell mass in the future can be designed using this method, and then produce this cell mass.

In general, it is still research at the concept stage.

References:

[1] Sam Kriegman, Douglas Blackiston, Michael Levin, et al. A scalable pipeline for designing reconfigurable organisms. PNAS first published January 13, 2020.


The article is from the public number: husk (ID: Guokr42) , author: Fu Shibo