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XJTLU-CHINA/Education

automation

Ensuring that each product has the same quality is an important part of the production of synthetic bio-based quantitative biosensors, which is sensitive to the quantity of biological components as well as to reaction time and external interference. Therefore, we designed a collaborative robotic workstation in Robotstudio to automate the kit reagents adding, lyophilization, and assembly process as a complementary part of our project. We also want to use this workstation to demonstrate the potential of collaborative robots in the automation of synthetic biology. This workstation will show our excellence in automation, the design and implications for synthetic biology products will be described in detail below.

Specification

Fig.1&2 Schematic of the workstation Fig.3 End-effector with pipette and vacuum of cobot Fig.4 Schematic of the workstation

The robot workstation consists of the following components:

ABB CRB15000 GoFa collaborative robot (cobot)
End-effector with pipette and vacuum （Fig.3）
-20 degrees Celsius Refrigerator with automatic door
-80 degrees Celsius Refrigerator with automatic door
Liquid nitrogen tank with automatic door
Freeze dryer
Empty kit with 3 reaction tank and
Kit lid

Workflow

The workflow of this workstation is mainly based on the experimental procedure of lyophilized cell free system on paper (Pardee et al., 2014), and our own experimental protocol.

1.Cobot’s controller sends the opening signal, the -80 degree refrigerator receives and opens, then the cobot uses the pipette on the end-effector to aspirate a certain amount of cell-free system as required for three reaction tanks.

2.The pipette finishes aspirating, moves to the position above of the empty kit No.1 reaction tank and the cobot’s controller sends the closing signal, the -80 degree refrigerator receives the signal and closes.

3.Pipette aligns to reaction tank No.1 and add a dose of cell-free system

4.Pipette aligns to reaction tank No.2 and add a dose of cell-free system

5.Pipette aligns to reaction tank No.3 and add a dose of cell-free system

6.Cobot’s controller sends the opening signal, the -20 degree refrigerator receives and opens, then the cobot uses the pipette on the end-effector to aspirate a certain amount of DNA elements as required for three reaction tanks.

7.The pipette finishes aspirating, moves to the position above of the kit No.1 reaction tank and the cobot’s controller sends the closing signal, the -20 degree refrigerator receives the signal and closes.

8.Pipette aligns to reaction tank No.1 and add a dose of DNA elements

9.Pipette aligns to reaction tank No.2 and add a dose of DNA elements

10.Pipette aligns to reaction tank No.3 and add a dose of DNA elements

11.Cobot’s controller sends the opening signal, the liquid nitrogen tank receives and opens, then the cobot uses the vacuum on the end-effector to transfer the kit into the liquid nitrogen tank for flash freeze.

13.When the flash freeze is finished, the automated liquid nitrogen tank sends a completion signal and opens. The cobot receives this signal and uses the vacuum on the end-effector to remove the kit. After the kit is removed, the cobot's controller sends a closing signal, and the liquid nitrogen tank receives and closes.

14.Cobot’s controller sends the opening signal, the freeze dryer receives and opens. Then the cobot uses the vacuum on the end-effector to put the kit into the freeze dryer

15.Cobot's end-effector leaves the freeze dryer, and cobot’s controller sends a closing signal, the freeze dryer receives and closes. The kit will be freeze dried overnight.

16.After the freeze drying process fishing, the automated freeze dryer sends a finshing signal and opens, the cobot receives the finishing signal and removes the kit using the vacuum on the end-effector, after removal the cobot's controller sends a closing signal, the freeze dryer receives and closes.

17.Cobot places the kit on the holder and use the vacuum on the end-effector to take the kit lid, mount it on the kit.

Please refer to demonstration video for details

Why we need automation in synthetic biology

Automated workstation boosts efficiency

In the production design of kits, the experimenter often needs to build a product prototype several times, which is a mechanized and repetitive process. Automated workstations can automate this work, reducing lab technician work and increasing efficiency.

Collaborative robots can be programmed to perform multiple tasks and quickly transform the production process.

Automated workstation boosts product accuracy

Automated pipettes allow precise control of the amount of reagent added to the product, reducing production errors caused by human factors and thus boosting the accuracy of the product.

Compared to human operation, automated workstations are better able to repeat the same work perfectly, thus ensuring consistent quality of the product produced.

Automated workstations can work in a sterile and closed environment, thus blocking out external interfering factors. Before our kits are assembled, contamination by external bacteria will interfere with future quantitative assays. Our automated workstations can complete the previous steps of assembly in a closed, sterile environment, thereby eliminating interference.

Automated workstation ensures biosafety

Automated workstations can work in a completely enclosed environment. If the product includes biohazardous components such as phage in our design, closed environment automated production can effectively reduce the risk of leakage.

Automated workstations can also perform some risky steps, thus ensuring the safety of the experimenter. For example, in the production of our kits, liquid nitrogen is required for flash freeze, which reduces the safety risk to the experimenter.

Why collaborative robots (cobots)

In the previous section, we described the implications of using automation in synthetic biology. There are various means of automation, and there are already several commercially available laboratory automation workstations depending on different experimental needs, while we would like to introduce collaborative robotics as a new means of automation in synthetic biology automation.

Compared to traditional automation workstations, collaborative robots are also highly automated and fast and accurate. Current commercial collaborative robots have end-effectors that can perform movements with a precision of 10 microns at a speed of 2.2m/s under a 5kg load.

Collaborative robots can perform more complex tasks. Most of the collaborative robots are 6-degree of freedom robotic arms, and the high-degree of freedom robotic arms can imitate human to perform more complex operations than the traditional automated workstations that perform simple tasks. In our designed workstations, collaborative robots can be used with automated laboratory instruments to perform precise spiking and freeze-drying operations.

Collaborative robots are more flexible. While traditional automated workstations can often perform only a single task, collaborative robots can be programmed to perform many different tasks. For a laboratory, a collaborative robot can be flexible enough to automate various parts of synthetic biology work.

Demonstration

Reference

Pardee K, Green AA, Ferrante T, Cameron DE, DaleyKeyser A, Yin P, Collins JJ. Paper-based synthetic gene networks. Cell. 2014 Nov 6;159(4):940-54. doi: 10.1016/j.cell.2014.10.004. Epub 2014 Oct 23. PMID: 25417167; PMCID: PMC4243060.

Team:XJTLU-CHINA/Cooperative Manipulator