There is an increased need for Technology that could perform simultaneous multi-factored disease detection simply, accurately, cheaply, and quickly. Rising incidences of multifactorial diseases like microbial Infections like Schizopernia, diabetes, Alzheimer's, obesity, and cardiac diseases in recent year is concerning, and so is a lack of Diagnostics that could do so.
Microscopy, Spectroscopy, and various other detection techniques face a fundamental issue of information loss or “Cell to pixel loss problem” - information gets lost when biological entities are converted to human interpretable signals.
The iGEM Team IISER Mohali believes that an excellent solution to an existing problem can only be defined with the help of its well-informed users. Over the season, our team worked to talk to every possible stakeholder associated with the problem we were working on. We tried to design a solution that could fulfill the needs of its stakeholders. Our every conversation helped us delve deeper and develop a better solution that can create an impact.
In the end, we wanted to ensure that NeuraSyn is just the beginning which could solve the Global issue of lack of Technology for simultaneous multi-factored disease and help us take a massive leap in the development of a simple, cheaper, faster, and quicker detection system.
In our region and the country, the most low-income population is exposed to less-than-ideal sanitary conditions, contaminated food, and poor-quality potable water. According to WHO, 110 billion USD is lost yearly in productivity and medical expenses resulting from unsafe food in low- and middle-income countries like India. Our location in Punjab, an agricultural, dairy, and food industry hub, gives us first-hand exposure to these problems. Thus, we have chosen the bacteria E.coli and S. typhi and the fungus Penicillium chrysogenum, all of which commonly contaminate food and water. The conditions above result in an overwhelming number of bacterial and fungal infections.
Septicemia (sepsis) is a fatal organ dysfunction in response to bacterial infection in the blood that currently has a 17% mortality rate, which jumps to 26% in severe cases in our country. In addition, due to antimicrobial resistance, there is an ever-increasing trend of patients getting infected by multi-drug-resistant bacteria. The tropical climate, malnutrition, and unhygienic living situations also cause an alarming number of lethal fungal infections. The detection of fungi is complex, and research concerning new antifungals is slow, resulting in 32.75 out of 1000 patients being sent to the Intensive Care Unit with fungal infections in the national capital.
Although there are other methods to detect microbes, one of the fundamental problems with microscopy, spectroscopy, or other detection methods is the “cell-to-pixel loss” problem - information gets lost when biological entities/events are converted to human interpretable signals.
Also, the growing population strains the resources and personnel in healthcare and quality testing fields. Complicated, time-consuming methods like culturing and PCR to detect bacteria or fungi are becoming impractical in many scenarios.
So, when offered the chance to concentrate on one issue this year, we had no choice but to consider what was happening in our neighborhood.
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Dr. Archana Angrup
PGIMER Chandigarh
We met Dr. Archana Angrup, Department of medical microbiology PGIMER, to understand the existing situations of bacterial infection in Chandigarh, India. We also wanted to learn about the current technology, efficiency, and accuracy.
She highlighted that mostly blood culture is the gold standard that is often performed in most hospitals to detect microbial infections. It takes three days to yield results, and by that time, the patient’s situation becomes in peril if affected by a microbe carrying antibiotic-resistance genes. She also pointed out that the problem with ELISA and RT-PCR is that they have to wait for a batch of samples to perform the test, making it even worse for patients.
Meeting Dr. Archana helped us reflect on our project. She gave us positive feedback. She believed our project could significantly impact society. We decided to look over the possibility of developing a device to detect antibiotic-resistant microbes.
Our dry lab team looked over the possibility of mutations affecting the specificity and binding ability of the aptamers. They concluded that although it might be possible for it to happen, the possibility is relatively low.
Quality control Microbiologist at Verka Milk Plant, Chandigarh
We visited Verka Milk Plant, Chandigarh, to learn about the existing methods to detect microbes and the limitations they face. There they introduced us to Madhuri Sharma, a quality control Microbiologist with 12 years of experience. We asked about the losses they often face and how long it generally takes them to analyze the quality of their products.
The engaging conversation with Madhuri Sharma helped us understand that primarily traditional cultural methods are used during the quality control testing of the product and explained to us the preventive measures they follow up at each step of processing their products, ensuring that the product doesn't get contaminated. Hence it's rare for their products to fail quality testing. However, it does take time for them to perform culturing, and around 24 to 48 hours later, they get the results. They also informed us that they don't get to know the strain of the microbes as their method doesn't determine it, and having a device could be advantageous.
We reflected on the discussion we had with Madhuri Sharma and others at Verka. One of the parameters they suggested we look over was the accuracy of our envisioned technology. Hence, our dry lab and wet lab team decided to ensure that our design would be more accurate, simple, quicker, and cheaper than the current devices.
Our dry and wet lab team reviewed the existing literature to understand most detection methods' accuracy. We understood that although culturing takes time, its accuracy is undoubted, so we decided to work on ensuring the accuracy of our device.
Madhuri Sharma
Visit to PBTI
Punjab BioTechnology Incubator
Punjab Biotechnology incubator, established under the Department of Science, Technology and environmental, Punjab, is well known in our city Chandigarh as a Centre to get water, food, and Agri products tested out for the presence of contamination. Hence, we went on a journey to the Punjab biotechnology incubator and met Ms. Harmeet there. We wanted to understand the time taken by the detection systems used by them and their accuracy.
Ms. Harmeet highlighted that they often use conventional techniques like culturing to detect pathogens as users don't want to spend more on molecular Diagnostic methods like ELISA, PCR, etc. She advised us to focus on developing an affordable detection system because, from their experience, many consumers don't want to go for expensive tests.
We thought over the suggestions we received at PBTI, Chandigarh. One of the key takeaways from the visit was to look over the options to develop an affordable, accurate, quick, and cheap technology so that users don’t hinder away because of the cost aspect.
Initially, we were going to use thiol-modified aptamers attached over gold electrodes to develop the aptasensor, one of the most robust methods to detect electrochemical changes. However, we performed GO/PANI modification to the Glassy carbon electrode and then attached our aptamers over it. The method turned out to be a success which helped us make this technology more viable.
Krishi Vigyan Kendra (Farm Science Center), Mohali
Our location in Punjab is one of India's agriculture and animal husbandry hubs. Thus, we were apt to meet scientists, veterinarians, and agriculture experts from Krishi Vigyan Kendra (Farmers Science Center), Mohali, to understand the method of detection widely used in agriculture and animal husbandry to detect pathogenic diseases and evaluate our project's guiding values.
Dr. Balbir from KVK, Mohali informed us that agriculture experts usually don’t even need to perform any molecular diagnostic methods to tell whether a crop is affected by a pathogenic disease. He also told us that our device is meant to take liquid samples for detection, so every time we want to use it, we would need a way to prepare liquid samples of the crops, which is not a feasible option.
Dr. Balbir‘s suggestions helped us delve deeper into understanding the user needs and made us realize some flaws in our proposed implementation. It also reminded us that although agriculture might not be the sector, we can greatly impact animal husbandry.
We analyzed our proposed implementation plan and reviewed making the technology more user-friendly and hassle-free. We started looking over its implementation in poultry, cattle, and bee-keeping as Dr. Balbir and his team suggested.
Visit to KVK
Prof. Indranil Banerjee
IISER Mohali
Prof. Indranil Banerjee worked with MEA60 neural chips during his post-doc days. We met him to discuss “NeuraSyn,” its implications, and our proposed implementation.
Prof. Indranil was concerned about handling and developing a neural chip as he worked on one of the versions, MEA60, which is an inspiration for our proposed chip. He told us that even though the neural chip might be entirely accurate and quicker than RT-PCR, and ELISA, the development method is complicated and requires efficient handling.
We reflected on his suggestions and decided to redesign our chip design which might solve the issues he was concerned with. Also, we pondered the questions raised over its feasibility and decided to analyze our proposed implementation again.
Our neural chip development team tested several other designs that could solve his concerns and connected with experts from BlackRock Neurotech and Cortical Labs, some of the leading companies engaged in bio-computation.
We also acknowledge that science advances human welfare. A human-centered design, however, entails much more than merely addressing people. It involves comprehending the social environment. It involves knowing the right questions to ask. At this point, our inquiry focused on the intersection of people and science: how could scientists better respond to societal issues and consider their beliefs while formulating a solution?
Opening up discussions with ethicists and social scientists had a significant impact on the early development of our project because they showed us how to frame the issue within the frequently challenging conversations that society and synthetic biology have already had about these issues. These discussions helped us listen to and involve people in creating our initiative in a thoughtful and meaningful way.
To ensure that our project, "NeuraSyn", originated from this careful consideration, we spoke to social scientists, bio-ethicist, and environmentalists.
Prof. Anu Sabhlok
Social Scientist and member of the Bio-ethics committee, IISER Mohali
Prof. Anu Sabhlok helped us understand what values our project should prioritize over the others and also guided us to learn the comprises we might be making while doing so. She gave us crucial suggestions about the project.
Prof. Anu told us to meet other researchers to design our proposed implementation. She helped us understand the values our project should prioritize and if any conflict might arise.
We pondered her suggestions and decided to consult more researchers associated with developing point-of-care diagnostics.
We prioritized the values we wanted and met Prof. Indranil and others to discuss the implications of the neural chip.
T.V Ramachandra
Associate Professor at Centre of Ecological Science, IISc Bengaluru
Prof. TVR is an environmentalist who could help us understand the sustainability aspect associated with the project. Hence, we met him and asked for his opinion.
Prof. TVR suggested that we focus on ensuring that our device is suitable for use beyond bio-containment. He also told us to have a proper plan for discarding the kit after use.
We reflected upon his suggestions and decided to devise a guideline for the disposal of our device so that it doesn’t cause harm to the user and the environment.
We decided to include a dismantling guide for each device component after its use so that it could be partly recycled, reused, and biodegradable.
We could only conclude that the issue of late microbial detection was severe and complex based on our research and discussions with those who deal with it. Thus, our goal was to develop a multifaceted solution to this problem by adding stakeholder voices.
We came back from listening to stakeholders' experiences and worries with various requirements and ideals to include in our project.
We realized that a good solution would be a
We placed a high priority on including these requirements and principles in our project. Time and money were both constrained, though. We understood that it was not realistic for us to meet all of the project's requirements this year. The values and needs we would prioritize this year had to be ranked in order of importance as a result.
Although each stakeholder stated their specific concerns, the need for a quicker and more comprehensive microbe detection system served as the unifying theme and element everyone felt was most important. The lack of such technology puts every individual, group, and industry at risk of suffering losses.
Therefore, our top aim was to develop a method that would be quicker, more precise, and capable of simultaneously detecting a microbe from a cohort in a sample. We initially wanted to have a solution to apply them toward so that we could plan for safety and optimize for financial feasibility.
The development of a Neural chip and an aptasensor in the wet lab and dry lab settings to achieve this prioritization can be understood from these efforts.
Can empower Quicker Detection
The neural chip and aptasensor solve this issue by directly detecting the impedance change (without any third-party converter) and amplifying the signal. It is quick - giving results in minutes, unlike culturing, which takes days, and is simple - it can be operated by meagrely trained personnel.
Is Sustainable
Digitization drives have introduced electronics and computers in every country over the past few decades. While this helps increase productivity and efficiency, it has resulted in a massive increase in carbon footprint and the generation of toxic waste. The neural chip provides a non-toxic and sustainable computing alternative that is accurate, fast, and can quickly “learn” to solve new problems.
Is more accurate
One of the fundamental problems with microscopy, spectroscopy, or other detection methods is the “cell-to-pixel loss” problem - information gets lost when biological entities/events are converted to human interpretable signals. The neural chip solves this issue as it directly detects the impedance change (without any third-party converter and can amplify the signal. Thus, our platform aims to be accurate - aptamers being highly sensitive, specific, and independent of immunogenicity.
Is User-friendly
The growing population strains the resources and personnel in healthcare and quality testing fields. Complicated, time-consuming methods like culturing and PCR to detect bacteria or fungi are becoming impractical in many scenarios. Hospitals use cultures (2-3 days) to determine bacterial and fungal species in infections, which takes time, is cumbersome, and needs trained professionals. Hence, our system envisions being User-friendly as it requires special training.
Can detect multi-cohorts of microbes
We plan to address this problem by developing a detection system to detect microbes. The neural chip design contains neuroblast (Neuro 2A) cells in a culture in the center and metal electrodes to carry electrical signals. The neural chip will be trained to detect electrical currents and make decisions based on a certain threshold (this can be a variable). The aptamers (short DNA fragments) bind to bacteria or fungi/fungal components, which causes a change in a measurable quantity, such as an increase in impedance/resistance. The presence of any target organisms causes the respective aptamer to bind to it. The binding increases the system's impedance, which is “sensed” by the trained neural chip. The neural circuit then “decides” based on the threshold and sends output to a microcontroller stating whether bacteria or fungi are present and, if so, which ones. Hence, it enables us to perform detection in multi-cohort of microbes.
A revolutionary tool in our scientific toolkit, synthetic biology, has enormous promise to improve the planet. Engineering a Neural chip to detect the impedance change and amplify the signals once the microbe binds to the aptamer can; very likely help in achieving our goals. Furthermore, The neural chip design contains neuroblast (Neuro 2A) cells in a culture in the center and metal electrodes to carry electrical signals. The neural chip will be trained to detect electrical currents and make decisions based on a certain threshold (this can be a variable). The aptamers (short DNA fragments) bind to bacteria or fungi/fungal components, which causes a change in a measurable quantity, such as an increase in impedance/resistance. The test strip contains three aptamers attached to an electrode, placed in three wells - one for each target organism. The sample is deposited onto the strip. The presence of any target organisms causes the respective aptamer to bind to it. The binding increases the system's impedance, which is “sensed” by the trained neural chip. The neural circuit then “decides” based on the threshold and sends output to a microcontroller stating whether bacteria or fungi are present and, if so, which ones.
We made sure to consult specialists during the brainstorming and design phases of our solution. This was done to ensure that our solution incorporated their suggestions and reflected the stakeholders' values.
Prof. Anand Bachchawat
Associate Professor at DBS, IISER Mohali
We initially discussed our project with Prof. Anand, a microbiologist, to seek feedback and discuss its viability.
He advised us to develop NeuraSyn as a two-phase project. And told us to make a Proof of concept of our technology.
We took his suggestion into consideration and decided to expand our project in two-phase and develop a proof of concept of our technology this year.
We exhibited a proof of concept of the project to detect commonly found microbes as part of this year’s project and decided to expand the idea and exhibit simultaneous multi-factored disease detection.
Anca Frasineau
Wet Lab lead Team - iGEM 2021, University of Rochester
iGEM 2021 team from Rochester used unmodified aptamers and attached them over rGO, making their aptasensor affordable and feasible for users. We wanted to discuss the aptamer immobilization techniques
Anca explained their method and informed us that although they tested their aptasensor successfully. She isn’t sure about its reusability. She told us to look over electrophoretic deposition methods to modify our electrodes in case we wish to work with unmodified aptamers.
We decided to go through the literature to learn about electrophoretic detection techniques and also met our mentor Prof. Ramendra Sunder Dey, regarding this.
We acted on her suggestions and performed electrophoretic depostion of GO/PANI over a Glassy carbon electrode and fortunately it worked for our aptasensors.
Dr. Richa Sharma
Post-Doc at the University of Edinburgh
We met with Dr. Richa to discuss the electrochemical sensing method of aptamers. We also wanted to understand about successful immobilization of unmodified aptamers and their reusability.
Dr. Richa informed us that the electrochemical method, although robust is indeed expensive so the idea of exploring the modified screen-printed carbon electrodes and attaching aptamers using rGO over it could be helpful.
We thought about her suggestions and discussed them with our mentor regarding this and also went through the literature to understand them well.
Although we ended up working with GO/PANI-modified glassy carbon electrodes, her suggestions helped us to do so.
Issac Sokol
Software Engineer at Blackrock Neurotech
Our team wanted to discuss their new design for neural chips with software experts working in the field of bio-computation which prompted us to meet Isaac.
Issac gave us insights into the nature of data processing in neural chips and discussed the hardware requirements for measuring electrical data from neurons.
Issac‘s suggestions made us understand the need for increased sensitivity of detection systems and helped us in redesigning our neural chip.
Based upon his suggestion and approval of our new chip design, our team worked to get the new design tested.
Hon Weng C
CEO and Founder at Cortical Labs
Our neural chip being inspired by chips developed by Cortical lab made it important for us to seek feedback from its founder over our project.
Hon looked over our training process and verified that backpropagation doesn’t work for a system like ours. He also gave us some suggestions for our new neural chip design.
Hon told us to design the output electrodes bigger for neurons to connect and to reduce the noise.
His suggestions were implemented in the chip’s design which could help in the reduction of noise.
After coming up with a concept and designing a solution based on the counsel and expertise of wet and dry lab professionals and the values of our stakeholders, our team considered the proposed implementation. The proposed implementation is the scientific method that is the most readily apparent. Synthetic biology solutions are required due to the effects of late microbial discovery and concurrent multi-factored disorders.
However, some issues need to be resolved before a synthetic biology-based solution is suggested. Our team placed a high value on considering all technological, safety, ethical, and sociocultural considerations. Our team has chosen to carry out a two-phase project to ensure that a meaningful and thoughtful approach was taken. Our IHP journey was one that was steadfastly committed to a human-centered strategy from the start. The people we contacted and the discussions that resulted from our meetings have significantly impacted our research, from social scientists to stakeholders.
We knew the proposed implementation—a pivotal step in the scientific process and the one with the greatest public exposure—would not be any different. We had to return to the people who had initiated the initiative and whose ideals had given it purpose as we approached the proposed implementation. These discussions influenced the ethical, technical, safety, and communication choices at this project stage. It assisted us in closing the loop and making sure our final answer was ethical and beneficial to everyone.
We analyzed our project in light of the values we chose to prioritize at each level of its development to close the loop and ensure that our solution aligns with stakeholder needs.
The iGEM 2022 team from IISER, Mohali, has enjoyed this year's opportunity to observe, analyze, and interact with this intricate relationship between science and society. We have discovered via our human-centered design that absolute good and responsible things can be accomplished when people and science work together.
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