Team:Bielefeld-CeBiTec/Human Practices
-->
Human practice means to analyze how the world influences our project and how our project influences the world. This is something one can only achieve by establishing a dialogue with the people we identified to be affected by our work and implementing their feedback to improve our project. Scientists in general are often assuming they would know the best way to design and execute a project or product. But staying in the ivory tower does not work if we want to see synthetic biology solving the problems of the future.
But first: Let’s review the situation – a survey on the consumption of contraceptive methods
Our product is intended to be used by a diverse group of people. Therefore, it is important to find out if there is a general interest in our product and if so, what it should look like in detail. For this purpose, we conducted an online survey asking these questions.
Key data of our survey:
-160 participants -ages from 18 to 50 Remarkable data:
-78% of the people have at least minor issues with taking hormones daily
-85% of the people are interested in a new contraception method
-82% of the people would prefer a healthy but uncomfortable method
Read more about our survey and its results here.
The results clarified how many people with a uterus use contraception, which method they use it and whether they are satisfied with it. It turned out that many participants see weak points in the existing contraceptive methods in terms of safety, health, comfort and well-being. Accordingly, in further questions the participants often stated that they were interested in our product WavySense.
We first contacted Mr. Hagemeyer and the research group on the 23th of July via E-Mail. We asked them for advice regarding the developement of a miniturized IC and moreover for a possible measuring setup to test our method.
A lot of new information and approaches have arisen from the first meeting: Mr. Hagemeyer and his team further background information about the functionality of high frequency technology. Furthermore, they made us aware of the limits and, above all, the complexity of our project, which we initially underestimated. Together we established that implementing the measurement method with a single PCB (Printed Circuit Board) was the most effective solution for our mobile device. However, Mr. Hagemeyer pointed out to us that this required a sufficient planning and testing phase, which we could not Fit into our project plan. After working together on other possible realizations, we decided to use an already operating PCB with a DDS (Direct Digital Sythesis) to generate the high frequencies. The phase shift should be detected with a board developed by us.
We realized how demanding this task would be. But Mr. Hagemeyer and his team offered us to take over the creation of the circuit diagrams and the design of the PCB. This was the only way we could develop a miniturized system that would allow us to generate and amplify high frequencies and also measure the phase shift in time. A resulting determination of the concentration would therefore be possible.
We are very grateful for the professional expertise of the entire working group.
First contact: 28th of June 2020, E-Mail
First Zoom Meeting: 6th of July 2020
Another crucial point in our development of a mobile device for concentration determination is data processing and data transfer via Bluetooth. Therefore, we contacted Johannes Fiedler and Berd Froböse, who are working at the Bielefeld University of Applied Science. Both are part of the research group „Textile Technologies “and could give us initial inspiration for the technical implementation of our project. We first contacted Mr. Fiedler on the 28th of June 2020 via email. He recommended Mr. Froböse for the field of electronics and we arranged a joint meeting. Both gave us information regarding the basic requirements for the realization of our project. In addition, they were able to help us decide whether the data processing should be managed directly by the processor of the Arduino or by the mobile device of the users. Mr. Fiedler also offered us his help regarding the implementation of the data processing. Due to the lack of time, we could not make use of it. However, if we continue the project, we can count on his support.
Centre for Biological Signalling Studies,
Freiburg University, Germany
First contact: 27th of May 2020 via Skype
As we came across the paper “A Two-Step Approach for the Design and Generation of Nanobodies” (2018) by Dr Hanna Wagner et al.[3], we immediately established contact with her. In two insightful conversations she gave helpful advice on how to plan and enable our project. Regarding nanobody grafting, she particularly helped us with the in-silico grafting and the selection of the numbering scheme as well as the general procedure. She also recommended us a nanobody scaffold, which we ultimately used for our own nanobodies.
Faculty of Technology /
AG cellular and molecular biotechnology
Bielefeld University, Germany
First contact: 6th of May 2020 via Zoom
First contact: 6th of May 2020 via Zoom Prof. Dr. Kristian Müller continuously supported our project in manifold ways. He gave us insights into the usage of antibodies, nanobodies and the Phage Display technology. Based on his suggestions and information about Phage Display and Antibodies, we chose to opt for a Phagemid Display and decided, which antibodies to use as CDR donors in the graft. He also introduced us to the program ChimeraX, with this so that we could visualize our grafts, which which enabled us to further improve them. In several meetings we discussed in depth the procedure for the Phagemid Display, and how to obtain a strong binder from our graft. Thanks to his (and his PhD candidate Lennard Karsten’s) advice, we were able to improve our approach to the Phagemid Display. In addition to his advice he also supported us with materials. During the course of the project we generously obtained E. coli strains, the phagemid vector, helper phage, specific antibodies for a phage ELISA and other materials from his working group.
After we first introduced Prof. Dr. Müller to our project he told us that grafting can be problematic. However, he recommended alternative approaches based on scFv (single chain fragment variable) or Fab fragments (fragment, antigen binding). As an alternative, we could have used an anti metatype antibody against an estradiol antibody, which in theory is very promising for our project in comparison to the SAW technique. However, generating anti metatype antibodies is beyond our capacities. If we could obtain the sequences, this method would have been suitable for the project.
In case of grafting, it can also be very challenging as estradiol and progesterone are very small antigens. Therefore, scFv provides a better method due to its structure, so both methods should be tested and compared. Because the framework residues are structurally important, the grafted sequences have to be checked visually with Chimera X for steric obstacles.
Next we had a meeting with Prof. Dr. Kristian Müller about the phage display. To prepare the library for the phage display we will have to perform an error prone PCR (epPCR). Prof. Dr. Müller has provided us with various protocols for the phage display method.
According to the information he already provided, the task was to concertize the phage display, since different approaches would be possible. For our project, the application of a phagemid display is suitable, in which a phagemid vector and a helper phage operate together. Furthermore, it is useful to change the conditions from panning round to panning round. To be more precise, gradually imitate the natural conditions of the urine to be tested. For subsequent purification, an intein should be used.
During our meetings with Prof. Dr. Müller we got a deeper introduction into the program ChimeraX and –step by step- learned to profecionally check the grafted sequences.
Next, we were able to deepen our knowledge about the phagemid display, more precisely, about the specifications of the phagemid vector. For panning, the use of biotinylated antigens and streptavidin-coated immunotubes has been shown to be the most suitable.
During our last meeting with with Prof. Dr. Müller and PhD student Lennard Karsten we discussed the process in detail. The cloning should be done by means of restriction digestion and the transformation by electroshock. The necessary materials for the phage display were provided to us.
Lastly, we were advised to check the binding capacity by phage ELISA. For this purpose, Prof. Dr. Müller provided us with HRP conjugated antibodies against the phage M13 protein 8.
AppPilots GMbH&Co.KG.
First contact: 1th September 2020
For the development of our app, we talked to Daniel Torlop, who is the head of android development at AppPilots GMbH & Co. KG. He told us how we can make the app accessible to as many users as possible, for example by taking color-blind people into account when choosing colors and using appropriate symbols. In this context, he also referred to the Google guidelines (https://material.io/design/). We were told to think about what content we want and need in the app and how we can best present it in a uniform manner. Additionally we discussed the question how to best best implement communication between the app and the chip. He referred to Bluetooth Low Energy, commonly used standard that also enables the connection with IOS devices. Finally, we talked about data security. The result was that we will only save the data locally on the user's device and may enable the data to be encrypted on the device itself. After finishing a prototype of our app, we showed it to some potential users and asked them for feedback. We learned that it would be a nice option, to let the user choose which graphs are presented to him/her. Also, minor changes in the Interface were inspired by the feedback.
anesthesia
First contact: 1st of September 2020
Fabio Gancitano gave us some input on our project from a doctors point of view. With him we discussed how our hormone-biochip could be used in the future. Furthermore, he recommended studies and other experiments/studies how hormone concentration varies from human to human. We learned that factors like age, weight or other circumstances have an impact on hormone concentration.
University Bielefeld, Germany
First contact: 21st of October 2020
Based on her expertise in gender studies at our university, she has supported us in our questions about gender. During our zoom meeting we talked to her about important terms of gender studies, where we can inform ourselves, the current opinion of the general public on gender issues, and what to look for in gender sensitive language. Additionally, she supported us by proofreading our wiki text about gender equality and taught us to use gender correct language.
[1] https://cit-ec.de/en/ks
[2] Turbé, Valérian; Gray, Eleanor R.; Lawson, Victoria E.; Nastouli, Eleni; Brookes, Jennifer C.; Weiss, Robin A. et al. (2017): Towards an ultra-rapid smartphone- connected test for infectious diseases. In: Scientific reports 7 (1), S. 11971. DOI: 10.1038/s41598-017-11887-6.
[3] Wagner, Hanna J.; Wehrle, Sarah; Weiss, Etienne; Cavallari, Marco; Weber, Wilfried (2018): A Two-Step Approach for the Design and Generation of Nanobodies. In: International journal of molecular sciences 19 (11). DOI: 10.3390/ijms19113444.
Human Practices
Summary
Facing a problem: only a few contraception methods but many different consumers
In our project we started with an issue several team members faced – insufficient choice of contraception methods-, and our first step was to find out wether this is a problem for the broader public. So, we decided to design a questionnaire. We conducted a survey about common contraception methods and how necessary it would be to look for alternatives. This survey encouraged us in our goal to revolutionize contraception and finally deliver a method that is safe and healthy. Furthermore, results inspired us to change our design andbuild a device perfectly adjusted to the end-users needs.
Our product is intended to be used by a diverse group of people. Therefore, it is important to find out if there is a general interest in our product and if so, what it should look like in detail. For this purpose, we conducted an online survey asking these questions.
Key data of our survey:
-160 participants -ages from 18 to 50 Remarkable data:
-78% of the people have at least minor issues with taking hormones daily
-85% of the people are interested in a new contraception method
-82% of the people would prefer a healthy but uncomfortable method
Read more about our survey and its results here.
The results clarified how many people with a uterus use contraception, which method they use it and whether they are satisfied with it. It turned out that many participants see weak points in the existing contraceptive methods in terms of safety, health, comfort and well-being. Accordingly, in further questions the participants often stated that they were interested in our product WavySense.
WavySense: a product developed from a continuous dialogue between experts and end-users
But we did not only had help from our end-users. Regarding the scientific implementation of our project, our team is extremely grateful and happy for all the help we got from outstanding persons and science groups who supported us evolving our idea and concept. The following people continuously helped us out and the two-way dialogue improved the science behind our project.
Since most of us are biology students we needed to deepen our knowledge in electronics to construct a (small) device with the desired functionality. Therefore, we got a lot of advice from the sensorics team in the CiTec in Bielefeld, who helped us in terms of designing and engineering our biochip. Furthermore, COVID-19 complicated using other facilities then our lab but Dr. Martina Viefhues suggested to helped us by modifying our chip with techniques only available in the physics faculty.
Furthermore, got a lot of input and material for the biological part of our project. For example, Prof. Dr. Kristian Müller gave us insights into the use of antibodies, nanobodies and Phage Display technology. He helped us not only with his suggestions and his advice, but also with materials.
Experts for Microelectronics and Hardware
Jens Hagemeyer and the research group "Cognitorics and Sensor Systems"
In the field of microelectronics and the developement of a functional circuit for the digital measurement of the phase shift, we made contact with Jens
Hagemeyer, who is the research leader of the Team „Reconfigurable Systems“ of the research group „Cognitorics and Sensor Systems“. With his team, he works in the Citec
(Center for Excellence Cognitive Interactive Technology), which is part of the Bielefeld University. The research
group focuses on nanoelectronics, cognitronics and reconfigurable systems [1].
Bernd Froböse and Johannes Fiedler
Graduate engineer and Graduate mathematicianFirst contact: 28th of June 2020, E-Mail
First Zoom Meeting: 6th of July 2020
Another crucial point in our development of a mobile device for concentration determination is data processing and data transfer via Bluetooth. Therefore, we contacted Johannes Fiedler and Berd Froböse, who are working at the Bielefeld University of Applied Science. Both are part of the research group „Textile Technologies “and could give us initial inspiration for the technical implementation of our project. We first contacted Mr. Fiedler on the 28th of June 2020 via email. He recommended Mr. Froböse for the field of electronics and we arranged a joint meeting. Both gave us information regarding the basic requirements for the realization of our project. In addition, they were able to help us decide whether the data processing should be managed directly by the processor of the Arduino or by the mobile device of the users. Mr. Fiedler also offered us his help regarding the implementation of the data processing. Due to the lack of time, we could not make use of it. However, if we continue the project, we can count on his support.
Dale Athey
MBA, PhD
Biosensor expert,
Newcastle University
First contact: 12th of May 2020, E-Mail
We contacted Dale Athey after we read one of his very interesting publications about using a SAW-Biochip to detect HIV in a blood sample within ten seconds [2]. At the very beginning of our project, he advised us how we could measure small molecules and what to consider when producing specific antibodies. Additionally, he confirmed that we could follow our approach to use the SAW technique for our biosensor. Furthermore, he established our contact to Dr. Hiromi Yatsuda.
Biosensor expert,
Newcastle University
First contact: 12th of May 2020, E-Mail
We contacted Dale Athey after we read one of his very interesting publications about using a SAW-Biochip to detect HIV in a blood sample within ten seconds [2]. At the very beginning of our project, he advised us how we could measure small molecules and what to consider when producing specific antibodies. Additionally, he confirmed that we could follow our approach to use the SAW technique for our biosensor. Furthermore, he established our contact to Dr. Hiromi Yatsuda.
Dr. Hiromi Yatsuda
Biosensor Project Leader,
Research and Development
Japan Radio Co., Ltd.
First contact: 28th of May 2020, E-Mail
Dr. Hiromi Yatsuda worked together with Dale Athey PhD on the SAW-Biochip for HIV detection [2]. He transmitted us data, dimensions and materials, from a SAW biosensor he invented. He also recommended various literature to help our project.
Research and Development
Japan Radio Co., Ltd.
First contact: 28th of May 2020, E-Mail
Dr. Hiromi Yatsuda worked together with Dale Athey PhD on the SAW-Biochip for HIV detection [2]. He transmitted us data, dimensions and materials, from a SAW biosensor he invented. He also recommended various literature to help our project.
Experts for Antibodies
Dr. Hanna Wagner
BIOSS,Centre for Biological Signalling Studies,
Freiburg University, Germany
First contact: 27th of May 2020 via Skype
As we came across the paper “A Two-Step Approach for the Design and Generation of Nanobodies” (2018) by Dr Hanna Wagner et al.[3], we immediately established contact with her. In two insightful conversations she gave helpful advice on how to plan and enable our project. Regarding nanobody grafting, she particularly helped us with the in-silico grafting and the selection of the numbering scheme as well as the general procedure. She also recommended us a nanobody scaffold, which we ultimately used for our own nanobodies.
Prof. Dr. Kristian Müller
AG cellular and molecular biotechnology
Bielefeld University, Germany
First contact: 6th of May 2020 via Zoom
First contact: 6th of May 2020 via Zoom Prof. Dr. Kristian Müller continuously supported our project in manifold ways. He gave us insights into the usage of antibodies, nanobodies and the Phage Display technology. Based on his suggestions and information about Phage Display and Antibodies, we chose to opt for a Phagemid Display and decided, which antibodies to use as CDR donors in the graft. He also introduced us to the program ChimeraX, with this so that we could visualize our grafts, which which enabled us to further improve them. In several meetings we discussed in depth the procedure for the Phagemid Display, and how to obtain a strong binder from our graft. Thanks to his (and his PhD candidate Lennard Karsten’s) advice, we were able to improve our approach to the Phagemid Display. In addition to his advice he also supported us with materials. During the course of the project we generously obtained E. coli strains, the phagemid vector, helper phage, specific antibodies for a phage ELISA and other materials from his working group.
Experts for App Development
Daniel Torlop
Head of Android developmentAppPilots GMbH&Co.KG.
First contact: 1th September 2020
For the development of our app, we talked to Daniel Torlop, who is the head of android development at AppPilots GMbH & Co. KG. He told us how we can make the app accessible to as many users as possible, for example by taking color-blind people into account when choosing colors and using appropriate symbols. In this context, he also referred to the Google guidelines (https://material.io/design/). We were told to think about what content we want and need in the app and how we can best present it in a uniform manner. Additionally we discussed the question how to best best implement communication between the app and the chip. He referred to Bluetooth Low Energy, commonly used standard that also enables the connection with IOS devices. Finally, we talked about data security. The result was that we will only save the data locally on the user's device and may enable the data to be encrypted on the device itself. After finishing a prototype of our app, we showed it to some potential users and asked them for feedback. We learned that it would be a nice option, to let the user choose which graphs are presented to him/her. Also, minor changes in the Interface were inspired by the feedback.
Medical Experts
Fabio Gancitano
Evangelisches Klinikum Bethel Bielefeld,anesthesia
First contact: 1st of September 2020
Fabio Gancitano gave us some input on our project from a doctors point of view. With him we discussed how our hormone-biochip could be used in the future. Furthermore, he recommended studies and other experiments/studies how hormone concentration varies from human to human. We learned that factors like age, weight or other circumstances have an impact on hormone concentration.
Gender Experts
Annika Spill
Master Student Gender StudiesUniversity Bielefeld, Germany
First contact: 21st of October 2020
Based on her expertise in gender studies at our university, she has supported us in our questions about gender. During our zoom meeting we talked to her about important terms of gender studies, where we can inform ourselves, the current opinion of the general public on gender issues, and what to look for in gender sensitive language. Additionally, she supported us by proofreading our wiki text about gender equality and taught us to use gender correct language.
References
[2] Turbé, Valérian; Gray, Eleanor R.; Lawson, Victoria E.; Nastouli, Eleni; Brookes, Jennifer C.; Weiss, Robin A. et al. (2017): Towards an ultra-rapid smartphone- connected test for infectious diseases. In: Scientific reports 7 (1), S. 11971. DOI: 10.1038/s41598-017-11887-6.
[3] Wagner, Hanna J.; Wehrle, Sarah; Weiss, Etienne; Cavallari, Marco; Weber, Wilfried (2018): A Two-Step Approach for the Design and Generation of Nanobodies. In: International journal of molecular sciences 19 (11). DOI: 10.3390/ijms19113444.