Team:HZAU-China/Project

Mixed-Reality CellBidirectional coupling between real and virtual bio-oscillators



Overview


Since the emergence of Computer Science, the life styles and society conditions of human beings have experienced a huge leap. Till now, computers have been widely used in many fields of human life. At the same time, there has been great development in Biological Science as well. Biology is believed to bring another marvel for the world. With the rapid developments of computer science and biology, the connections between them are getting more and more close, manifested as the emergence of the following events: the processing of biological data through computers, the computational simulation of life activities, and even the researches on man-machine interface. There seems a trend that computer science and biology being combined into one. Thus, we wonder what would happen if we combine the life in the real world with the computer-simulated life in the virtual world. Could it be regarded as a new life form that is half-real and half-virtual?


Meanwhile, virtual-reality devices are the major ways to experience the virtual world, like Google-Glass, Holo-Lens and Xbox. However, no matter how cool they may look like, the core of their working mechanisms is just the sense, like your eye-sight that could communicate with the world. The degree that you feel being involved in the virtual world is too shallow to make you believe that you are experiencing a reality. Therefore, we intend to create a new method that a whole real life system would fuse with a whole virtual life system. That's the concept of Mixed-Reality Cell (MR. Cell). We put forward a whole design to make it come true.


To achieve our goal, we chose oscillation, a typical biological process, to represent life activity. A genetic oscillator was built in E. coli as the real part and an e-oscillator was simulated in a computer as the virtual part. The two parts could interact with each other through an interface device composed of microfluidic chip and chemical/optical modulator. At the beginning, the two oscillators work independently in a dual-reality state. With their interaction, they would gradually adjust to each other without human interference to a strongly coupled and synchronized mixed-reality state.


To reach our goal step by step, our project is divided into three phases, virtual-virtual coupling, mixed-reality in physics and mixed-reality of bio-oscillators. Till now, phase 1 that two e-oscillators coupled with each other and phase 2 that an e-oscillator coupled with a physical oscillator represented by the light intensity change of an LED have all been achieved. What's more, we designed several experiments to test the parts we used, including a hybrid promoter and the Light Controlling system; the results showed that these parts can work well. Also, a prototype of MR. Cell was demonstrated in this project which has great potential in a wide range of the future biological research.





Background


As we know, computer technology have created great revolution in humans’ lives from 20th century. And now, we enter into 21th century, a century of life science. The developments of computer science and life science both impact profoundly our world and society. And they also develop production of society. We can’t help imagining what will happen if these two combine. We can’t predict what will happen. However, we believe that the combination has great potential, even creates the next revolution.


Review the development history of computer science and life science development, we can find that these two begin combining gradually. Especially in recent years, with the increasing ability of computer simulation, many scientific research can be carried out by means of computer simulation in the virtual world. And this technology has a lot of applications in life science research. For example, man-machine interaction, artificial intelligence and visual simulation environment of medicine research. It is not exaggerated to claim that we have entered into a mix-reality era [1]. So we are thinking why not create a life form half in the reality, half in the virtual world. The real part and virtual part regulate each other constantly eventually mix a mix-reality system.


A researcher ever explored the concept of mix-reality state [2,3]. He set a simple pendulum in the reality, and designed a simulative programs in the computer. These two simple pendulums coupled in the same conditions limited in a numerical range. On the other hand, in the realm of biology, researchers constructed two genetic oscillator circuits in bacterium. These two genetic oscillator circuits coupled based on queuing theory [4]. We were sparked inspiration by these research achievements. We want to achieve the couple between organisms and computers to create a new united life form. We believe such a life form possesses logic of computers and adaption of organisms will make a difference in the future.







MR. Cell


MR. Cell, a half-real and half-virtual life form, is composed of two parts, the real part in E.coli and the virtual part in computer. These two parts interact with each other through our interface hardware and will be coupled to a unified whole, mixed-reality state.


Real part
A genetic oscillator, as a representative life activity form, was constructed in E.coli as the real part. Besides a light control system associated with the oscillator is adopted to connect the real part in computer, and we can regulate the oscillator by light through computer.
Virtual part
Mixed reality states occur only when a virtual and a real system are sufficiently similar. Therefore, based on the mechanism of the genetic oscillator, we simulate an e-oscillator in a computer as the virtual counterpart. In addition, the state of e-oscillator could be modulated through the parameter adjustment.

Interface device
The two-way interface device is composed of Light Receiving part and Light Controlling part. For the former one, cells were cultivated on a microfluidic chip and observed by fluorescence microscope. And for the last one, light (LED beads) can be controlled by a computer through a Single Chip Micyoco.


The synchronous interreality system — MR. Cell

At the beginning, the two oscillators, bio-oscillator and e-oscillator, work independently in a dual-reality state. When connected by the interface devices, the two parts begin to interact with each other. The state of bio-oscillator in E.coli cultured in a microfluidic chip would be observed through a fluorescence microscope and transmitted to the computer. The computer would analyze and process the received fluorescent data and adjust the state of e-oscillator through parameter modifications. In the meanwhile, based on its own state, the e-oscillator in computer also could regulate the state of bio-oscillator through LED intensity. The LED is controlled by a single-chip, which is linked to the computer. Following the processing cycle, the two parts interact with each other and couple eventually.



Besides, in consideration of the complexity and difficulty of the system, we take three stages to achieve our final goal, MR.Cell. At the first stage, we simulate two e-oscillators, which are of similar characters but have different initial states. And they couple gradually. Next stage, LED lamp replaces the genetic oscillator in E.coli to interact and couple with the e-oscillator. The last stage, our ultimate ambition, is to complete the MR. Cell, the two part of which synchronize and couple strongly.





Future work


Next step, we won't be satisfied with achieving coupling between bacterium's oscillators and computers. We will focus on the coupling between a metabolic system such as Krebs Cycle (Fig.1) and computer. We are interested in cell differentiation (Fig.2). If we could achieve the coupling between cell differentiation and computer, organisms will have more diversities. And the cell differentiation will get more amazing



We chose to couple oscillators because the synchronization is easy to observe. Not only oscillators but also many states can be coupled. In fact, there is the real-time communication and codetermining next behavior in the couple state. Life complexly couple with itself and the environment, that’s why we need to decouple parts in synthetic biology. In our project, we not only plan to achieve to couple between the E.coli and one computer but also dream to achieve couple with everything. We will try to couple different kinds of organisms with different kinds of computers. And we also plan to test the cascade of couples. At last, it may combine the organisms, inorganic environment and virtual world then achieves all in one.



Reference

1. Bin-Guang Ma, About Mechanics of Virtual Reality, written in 2005, published in: The General Science Journal, (August 25, 2006).

2. V Gintautas and A Hubler, Mixed Reality States in a Bidirectionally Coupled Interreality System.[J]. Phys. Rev. E 75, 057201 (2007)

3. A Hubler and V Gintautas. Experimental evidence for mixed reality states [J]. Complexity, 2011, 13(6):7–10.

4. A Prindle, et al., Rapid and tunable post-translational coupling of genetic circuits. [J]. Nature, 2014, 508(7496):387-391.




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