Team:BostonU HW/Silver
MEDAL CRITERIA: SILVER
Silver Medal Requirements
Validate that something you created (art & design, hardware, software, etc) performs its intended function. Provide thorough documentation of this validation on your team wiki.
As described in the Bronze Medal section, we developed a fully integrated, end-to-end design suite for microfluidic devices. We also designed 3D printed hardware infrastructure for controlling these devices, and we designed a new and original hardware solution to controlling fluid dispension using servo motors. Putting the cherry on top, we also contributed to developing algorithms that help translate LFR specifications of microfluidic devices to lower level MINT descriptions. Ultimately, the intended function of our software and hardware is to enable researchers to design, fabricate and use microfluidics with a single, coherent workflow. Furthermore, this single workflow needs to interface with low cost tools, it needs to be simple and robust, and it should allow any researcher to make a microfluidic chip with ease.
The best way to validate our workflow, our software and our hardware, would be to explore some of the microfluidic projects we did this summer. The following microfluidic designs were made within Neptune, using the LFR and MINT specifications to create the design schematics. Further, we obtained the 3D print schematics for the control infrastructure for these projects from Neptune. We designed the control infrastructure using the tutorials and specifications detailed by Neptune. Finally, we ran control tests to validate the function of our device through Neptune's control interface.
The best way to validate our workflow, our software and our hardware, would be to explore some of the microfluidic projects we did this summer. The following microfluidic designs were made within Neptune, using the LFR and MINT specifications to create the design schematics. Further, we obtained the 3D print schematics for the control infrastructure for these projects from Neptune. We designed the control infrastructure using the tutorials and specifications detailed by Neptune. Finally, we ran control tests to validate the function of our device through Neptune's control interface.
Convince the judges you have helped any registered iGEM team from high school, a different track, another university, or another institution in a significant way by, for example, mentoring a new team, characterizing a part, debugging a construct, modeling/simulating their system or helping validate a software/hardware solution to a synbio problem.
MIT Collaboration
Our most significant collaboration was that with the MIT iGEM team. In this collaboration, the MIT team had the opportunity to explore the possibility of using microfluidic chips to culture mammalian cells. In return, we had the the opportunity to validate the performance of our microfluidic chips with mammalian cell cultures.
The goal in our collaboration was to feed mammalian cells into a cell trap on a microfluidic chip, and then to culture those mammalian cells with an nutrient solution that we could control the input of. The design idea is simple: we would have a single fluid input, and a single output. This fluid would be gated by a valve, after which it would pass over a cell trap bank, and then be gated by another valve. After the valve the fluid is allowed to exit. The design would look something as follows:
The red portion is the control layer, in other words, the valves that block or allow fluid to pass. The blue part is the flow layer, where our actual fluid is allowed to flow, and where our experiment is run. And the purple portion is the cell trap, where the mamalian cells will be cultured. To validate our workflow, we used Neptune to create the chip design schematic. The LFR code to create the chip is included below.
With this LFR file, we generated the below design schematic. Note that this is a to-scale design schematic that we fed directly into the CNC mill for fabrication. You may also notice that in this design schematic, the cell traps are much smaller than in the design above. This is because this design schematic is to scale, and the real chip has small traps, appropriate for the size of the mammalian cells. We milled this chip out using the OtherMill, following the MakerFluidics protocol. In brief, this entails milling that channels of the flow and control layer out of a thermoplastic substrate, and then bonding the layers with a inner layer of PDMS. Our final chip looked as follows:
Now, our first visit to the MIT iGEM team’s lab space was to give the newly fabricated chip a initial test run just to see how the mammalian cells would fare. Since our chip is very simple, with only one port, we ran the experiment without Neptunes control interface, instead manually generating flow with a syringe pump. We were able to successfully insert mammalian cells into the microfluidic chip. We were able to verify this by visualizing the cells through a microscope, we included the results below, in what is an image of the MIT mammalian cell culture in our microfluidic chip cell trap.
Although we had this initial success, the mammalian cells did not sustain themselves in the cell trap for long.
We decided with the MIT team to continue this collaboration in an effort to successfully culture and sustain mammalian cells in a microfluidic chip. Our goals are to iterate over new microfluidic designs and to practice better methods of inserting the cells into the chip. We are currently still in collaboration with the MIT iGEM team.
NEU Collaboration
Our second big collaboration was with the NEU iGEM team in designing a microfluidic gradient generator for a cell culture system. The idea is as follows: the NEU team wanted to test a hypothetical genetic circuit and its performance under variable levels of environmental stress. Namely, they were interested in seeing how the expression of certain circuit outputs varied when the bacterial cells received a variable amount of nutrients from the environment.
The NEU team wanted a microfluidic device with the following function: The device would take two fluid inputs, one fluid with a concentrated nutrient solution, and the other input with water. The microfluidic device would contain ten cell traps, each cell trap would contain an individual cell culture. The function of the microfluidic chip would be to generate a gradient of nutrient solution such that the first cell trap receives the full concentration of solution, the second cell trap receives a little less solution, the third even less and so forth. The final cell trap would have no nutrient solution. Thus this chip would generate a gradient of nutrients for all the cells, and then the NEU team would be able to easily analyze the expression of their circuit under variable nutrient inputs. The design schematic was as follows:
This clearly was a much more complicated microfluidic to design, so we considered it a strong test bench for Neptune’s back-end algorithms. We attempted to generate this chip using the gradient generator primitive that was built into MINT. We iterated over several design attempts with MINT.
We ultimately found that MINT’s gradient generator primitive has a few limitations and bugs, which we have since proceeded to work out. Our collaboration with NEU unfortunately was put on hold because the NEU team informed us that they could not realize their hypothetical genetic circuit, so they had no need for our device. We have not given up though! Our goal is to update and iron out any bugs in MINT to ensure that Neptune can handle the gradient generator designs.
Our most significant collaboration was that with the MIT iGEM team. In this collaboration, the MIT team had the opportunity to explore the possibility of using microfluidic chips to culture mammalian cells. In return, we had the the opportunity to validate the performance of our microfluidic chips with mammalian cell cultures.
The goal in our collaboration was to feed mammalian cells into a cell trap on a microfluidic chip, and then to culture those mammalian cells with an nutrient solution that we could control the input of. The design idea is simple: we would have a single fluid input, and a single output. This fluid would be gated by a valve, after which it would pass over a cell trap bank, and then be gated by another valve. After the valve the fluid is allowed to exit. The design would look something as follows:
The red portion is the control layer, in other words, the valves that block or allow fluid to pass. The blue part is the flow layer, where our actual fluid is allowed to flow, and where our experiment is run. And the purple portion is the cell trap, where the mamalian cells will be cultured. To validate our workflow, we used Neptune to create the chip design schematic. The LFR code to create the chip is included below.
With this LFR file, we generated the below design schematic. Note that this is a to-scale design schematic that we fed directly into the CNC mill for fabrication. You may also notice that in this design schematic, the cell traps are much smaller than in the design above. This is because this design schematic is to scale, and the real chip has small traps, appropriate for the size of the mammalian cells. We milled this chip out using the OtherMill, following the MakerFluidics protocol. In brief, this entails milling that channels of the flow and control layer out of a thermoplastic substrate, and then bonding the layers with a inner layer of PDMS. Our final chip looked as follows:
Now, our first visit to the MIT iGEM team’s lab space was to give the newly fabricated chip a initial test run just to see how the mammalian cells would fare. Since our chip is very simple, with only one port, we ran the experiment without Neptunes control interface, instead manually generating flow with a syringe pump. We were able to successfully insert mammalian cells into the microfluidic chip. We were able to verify this by visualizing the cells through a microscope, we included the results below, in what is an image of the MIT mammalian cell culture in our microfluidic chip cell trap.
Although we had this initial success, the mammalian cells did not sustain themselves in the cell trap for long.
We decided with the MIT team to continue this collaboration in an effort to successfully culture and sustain mammalian cells in a microfluidic chip. Our goals are to iterate over new microfluidic designs and to practice better methods of inserting the cells into the chip. We are currently still in collaboration with the MIT iGEM team.
NEU Collaboration
Our second big collaboration was with the NEU iGEM team in designing a microfluidic gradient generator for a cell culture system. The idea is as follows: the NEU team wanted to test a hypothetical genetic circuit and its performance under variable levels of environmental stress. Namely, they were interested in seeing how the expression of certain circuit outputs varied when the bacterial cells received a variable amount of nutrients from the environment.
The NEU team wanted a microfluidic device with the following function: The device would take two fluid inputs, one fluid with a concentrated nutrient solution, and the other input with water. The microfluidic device would contain ten cell traps, each cell trap would contain an individual cell culture. The function of the microfluidic chip would be to generate a gradient of nutrient solution such that the first cell trap receives the full concentration of solution, the second cell trap receives a little less solution, the third even less and so forth. The final cell trap would have no nutrient solution. Thus this chip would generate a gradient of nutrients for all the cells, and then the NEU team would be able to easily analyze the expression of their circuit under variable nutrient inputs. The design schematic was as follows:
This clearly was a much more complicated microfluidic to design, so we considered it a strong test bench for Neptune’s back-end algorithms. We attempted to generate this chip using the gradient generator primitive that was built into MINT. We iterated over several design attempts with MINT.
We ultimately found that MINT’s gradient generator primitive has a few limitations and bugs, which we have since proceeded to work out. Our collaboration with NEU unfortunately was put on hold because the NEU team informed us that they could not realize their hypothetical genetic circuit, so they had no need for our device. We have not given up though! Our goal is to update and iron out any bugs in MINT to ensure that Neptune can handle the gradient generator designs.
iGEM projects involve important questions beyond the lab bench, for example relating to (but not limited to) ethics, sustainability, social justice, safety, security, and intellectual property rights. Demonstrate how your team has identified, investigated, and addressed one or more of these issues in the context of your project. Your activity could center around education, public engagement, public policy issues, public perception, or other activities (see the human practices hub for more information and examples of previous teams' exemplary work).
NONA Partnership
Nona is a nonprofit organization established to help document, maintain, and increase community access to open source synthetic biology software tools. The motivation behind Nona stems from the observation that a large portion of synthetic biology software tools that are created, despite being incredibly useful for their purpose, often see only limited support, development, and often they never come to full fruition. Too often, a large proportion of software tools made in academia will only see a limited amount of updates and support before the original creators of the tool move onto different project; when this happens, the software tool loses all use, documentation ends, and old or new issues don’t get resolved. To many synthetic biology software tools do not receive enough support and community attention to reach fruition.
Nona gives support to synthetic biology software by providing a platform to archive, document, host and distribute these tools. More so, Nona has a goal of culturing a community of researchers and developers around these tools: Nona aims to have a form where members of the synthetic biology community can discuss, ask and answer questions, and provide feedback about these software tools. And because the tools that Nona supports are all open source, there is a goal of fostering the growth of a developer community around these synthetic biology tools. Nona is a home for open source synthetic biology software tools, and we are proud to have partnered with Nona this summer as just a small part of our human practices ventures.
What did we do? Well, to start off, Neptune is already under the Nona umbrella of software tools. This summer our team met with members of the Nona board to discuss the future of Neptune and Nona, as well other ways in which our team could contribute to the Nona community. We had a total of 3 main meetings, with a couple smaller correspondences in between. The following conclusions were reached regarding our collaboration:
Building With Biology
We will continue to discuss our partnership with Nona under the gold medal requirements for integrated human practices. For now, we will look at a handful of other “beyond the bench” activities that we did. The first of these is the Building With Biology event at the Boston Museum of Science. This Building With Biology event is part of a NSF funded effort to stimulate synthetic biology public engagement and community outreach. Indeed, there is a big gap between the general public’s perception of synthetic biology, and the perception that researchers and engineers have toward synthetic biology; the Building with Biology event is one way we are trying to bridge that gap. During this daylong event, our iGEM team, as well as a number of other iGEM teams including our sister foundational research team and the MIT team, came to join the public in a day of conversation, education and outreach.
Let us paint a picture of what this event was like, what we accomplished, and why this human practices activity is important.
The first portion of this event was centered around having us the “scientific community” host little synthetic biology activities that are geared toward a range of audiences: The activities were simple such that they could be enjoyed by kids under the age of 10 (sometimes as young as 5,) but these activities had embedded in them big synthetic biology ideas, ideas that adults could ponder, and even people with a scientific background could enjoy.
Summer Pathways
In much of the same spirit as in our participation in Building With Biology, our team collaborated with the BU foundational research team to host several activities for a group of high school students from areas all over New England. We taught a group of young women interested in STEM fields of study about basic principles of synthetic biology, electric circuits and microprocessors and engaged them in a discussion of engineering ethics.
Blog Collaboration
In one last collaboration with the BU foundational research team, together we published a reference blog to discuss the history and significance of patent practices in relation to synthetic biology.
Nona is a nonprofit organization established to help document, maintain, and increase community access to open source synthetic biology software tools. The motivation behind Nona stems from the observation that a large portion of synthetic biology software tools that are created, despite being incredibly useful for their purpose, often see only limited support, development, and often they never come to full fruition. Too often, a large proportion of software tools made in academia will only see a limited amount of updates and support before the original creators of the tool move onto different project; when this happens, the software tool loses all use, documentation ends, and old or new issues don’t get resolved. To many synthetic biology software tools do not receive enough support and community attention to reach fruition.
Nona gives support to synthetic biology software by providing a platform to archive, document, host and distribute these tools. More so, Nona has a goal of culturing a community of researchers and developers around these tools: Nona aims to have a form where members of the synthetic biology community can discuss, ask and answer questions, and provide feedback about these software tools. And because the tools that Nona supports are all open source, there is a goal of fostering the growth of a developer community around these synthetic biology tools. Nona is a home for open source synthetic biology software tools, and we are proud to have partnered with Nona this summer as just a small part of our human practices ventures.
What did we do? Well, to start off, Neptune is already under the Nona umbrella of software tools. This summer our team met with members of the Nona board to discuss the future of Neptune and Nona, as well other ways in which our team could contribute to the Nona community. We had a total of 3 main meetings, with a couple smaller correspondences in between. The following conclusions were reached regarding our collaboration:
- NONA would distribute Neptune, allowing Neptune to have a “home” where is can easily be found (beyond GitHub.)
- NONA is dedicated to integrating all open synthetic biology software tools under one umbrella, thus building a community of researchers and developers who who will use and support these tools. Thus, NONA will be a medium through which other developers can contribute to Neptune, and NONA will be a place researchers can go to learn more about how to use Neptune, ask for help, and so forth.
- Overall, by having a dedicated community and website where Neptune will always have a place, we are making it very hard for Neptune to be abandoned. Quite the opposite, with NONA will ensure Neptune is sustained for years to come, while also providing the opportunity for a community to flourish around Neptune and similar software tools.
Building With Biology
We will continue to discuss our partnership with Nona under the gold medal requirements for integrated human practices. For now, we will look at a handful of other “beyond the bench” activities that we did. The first of these is the Building With Biology event at the Boston Museum of Science. This Building With Biology event is part of a NSF funded effort to stimulate synthetic biology public engagement and community outreach. Indeed, there is a big gap between the general public’s perception of synthetic biology, and the perception that researchers and engineers have toward synthetic biology; the Building with Biology event is one way we are trying to bridge that gap. During this daylong event, our iGEM team, as well as a number of other iGEM teams including our sister foundational research team and the MIT team, came to join the public in a day of conversation, education and outreach.
Let us paint a picture of what this event was like, what we accomplished, and why this human practices activity is important.
The first portion of this event was centered around having us the “scientific community” host little synthetic biology activities that are geared toward a range of audiences: The activities were simple such that they could be enjoyed by kids under the age of 10 (sometimes as young as 5,) but these activities had embedded in them big synthetic biology ideas, ideas that adults could ponder, and even people with a scientific background could enjoy.
Summer Pathways
In much of the same spirit as in our participation in Building With Biology, our team collaborated with the BU foundational research team to host several activities for a group of high school students from areas all over New England. We taught a group of young women interested in STEM fields of study about basic principles of synthetic biology, electric circuits and microprocessors and engaged them in a discussion of engineering ethics.
Blog Collaboration
In one last collaboration with the BU foundational research team, together we published a reference blog to discuss the history and significance of patent practices in relation to synthetic biology.
