1. Depression - Our story started with the team coming across the increasing number of suicides amongst college students in India. After one such incident, a team member opened up to us about their struggle with MDD. Their story was characterized by lack of understanding and awareness about the condition, and little support from people around them. Their diagnosis process was time-consuming and effort-intensive, including multiple inconclusive doctor visits and prescriptions of antidepressant medication with awful side effects. We found that about 208 million people are depressed globally. Moreover, the global prevalence of anxiety and depression increased by a massive 25%, according to a scientific brief released by the World Health Organization (WHO) during the COVID-19 pandemic. Sadly, this isn’t just a global issue, it is also very prominent in our locality, Vithura in Kerala, India. In 2017, the prevalence of mental disorders was reported to be 12.43%, and the number of individuals with mental health illnesses in the state increased by a whopping 54% from 2002 to 2018. We found that misdiagnoses among mental illnesses are common, with a global average of 33% for MDD misdiagnosis. We learnt about the long, frustrating and exhausting process of depression diagnosis. 


2. Antidepressant tracking - we found that once a person is diagnosed with moderate to severe MDD, they are prescribed antidepressants. There are mainly one kind of antidepressants prescribed - Serotonin and norepinephrine reuptake inhibitors. These are given to patients through a trial and error process, which can be time-consuming, and even cause harm if met with awful side effects. clinicians usually rely on the symptom-based delayed behavioural changes to check for the effect of the antidepressants. 


3. Lack of biomarker reliability - as we started interacting with various stakeholders, we were met with a lot of skepticism about the blood biomarkers. We were told right off the bat that our biomarkers won't work and that our tool can't be used for diagnosis. They informed us that biomarkers in psychiatry are very new and they're not reliable at all, especially for diagnosis. 

To gain a better understanding of the scale of the issue, we decided to initiate our study within our institute. We mediated a panel discussion to know the opinions of our peers and faculty members regarding mental health, its illnesses, and ways in which current healthcare facilities could be improved. Our findings revealed that many students experience feelings of isolation, misunderstanding, and are grappling with issues that are often not recognized as diseases by the general population. Particularly in Indian academia, mental health has not received adequate attention for a considerable period, with changes in this regard only slowly unfolding. Stigma and ignorance surrounding mental health persist, creating hesitancy among individuals to seek help when needed. Check out our Education page for more details!

Although the panel discussion aimed to shine a spotlight on mental health issues, we recognized the need to reach out to individuals diagnosed with mental illnesses—the patients themselves. To address this, we developed a survey that provided an open and anonymous platform for anyone to safely share their experiences and opinions. We received 25 responses , all of which were crucial in enhancing our understanding of the problem. 

Through these conversations, we came to realize that clinical depression is much more prevalent than commonly perceived and can significantly impact various aspects of an individual’s personal, social, academic, and professional domains of life. Our interviews featured a diverse group of individuals, each sharing their unique experiences. This diversity only underscores the urgent need for an improved and more accessible diagnostic process, as well as heightened awareness about mental illnesses.

After our visit to NIMHANS, we started to realize that the tool might not be very successful as a diagnostic tool, and that we can’t entirely rely on blood biomarkers for a final diagnosis. Upon inspection, we realized that the actual problem with a blood biomarker-based approach is the fact that there is a severe lack of data and research,on how biomarkers affect psychiatric illnesses. The selected biomarkers are not established for their correlation with psychiatric disorders and hence the initial hesitation from the clinicians on the applications of the tool. Apart from this, another problem is that clinical studies are hard and mental health being a sensitive and stigmatised topic in today’s society, research has been slow compared to that for other diseases. The specificity of the biomarkers are a huge problem too. Studies show that single biomarker tests for clinical depression are not specific at all and that they can never be used for diagnosis of MDD. 

We also learnt that currently, there exist no protocol to predict prescription of antidepressant medication to patients. The suitable treatment is chosen through trial-and-error processes, which waits for behavioral changes to show up. This method is usually very time-consuming, and may even be harmful for the patient.

Talking to the people around us made us realize that MDD diagnosis is as much of a local problem as it is a global one. Interacting with caretakers in nearby primary health care centers, the panel discussion conducted on our campus, even the old age home visits conducted by the IIT Roorkee team in Madhya Pradesh , the increase in the number of suicides of mentally ill students of prestigious institutes in India, all point towards the prevailing stigma and misconceptions surrounding mental health illnesses still lurking in our society. 

As mentioned in the previous sections, interacting with psychiatrists and background research also shed light on the fact that Depression is a spectrum as a disease in itself, in addition to consisting of a plethora of symptoms.

At this point, it dawned on us that the problem is just as complex as the solution. Thus we set our trajectories on to learning more about this problem; as well as communicating this it to a larger audience since it was becoming clear that large sections of the society are still ignorant of the concept of mental healthcare. We realized the importance of presenting and communicating the problem first, before presenting any solutions.

Who better to talk about these challenges than the very people who have gone through them? This was our line of thought as we collaborated with Into Their Minds and Dancing Neuron to provide platforms for the survivors and patients of mental health disorders to talk about their experiences. 

One of our valuable team members, Aabha Shams shared her experiences with misdiagnosis of her depression spanning over 7 years in a Purple Science podcast interview with Srushti Chipde from The Dancing Neuron. Podcasts have emerged as a powerful and versatile medium for science communication in today's world. They play a significant role in bridging the gap between the reading and non-reading community.

Thе еpisodе, titlеd "Unlocking Hopе: An attеmpt at advancing dеprеssion diagnosis for a bеttеr tomorrow", providеd an еxtеnsivе discussion of our projеct's primary focus: Major Dеprеssivе Disordеr and its frеquеntly hеartbrеaking misdiagnosis.  You can find the podcast here!

In order to really uncover the variability of the experiences related to mental health challenges we collaborated with Into Their Minds, a science communication initiative for an open call to anyone who has faced these and is willing to share their experiences. This led to a series of stories documented in the form of Instagram posts, where we explored the struggles related to ADHD, Schizophrenia, and OCD; all co-existing with depression as well as experiences with diagnosis (and misdiagnosis) of a trans person. These interviews can be found on our instagram page.  

For an expert's opinion, we interviewed Dr Samir Parikh, the Director of Fortis Mental Healthcare programme. Getting a psychiatrist's perspective of the disease and diagnostic experience was very insightful for us. He also talked about the importance of establishing the neurological basis of depression, and treating MDD like any other disease with somatic symptoms. 

The interview was uploaded on YouTube and reached over 500 people. 

Our 2 month long ideation phase was followed by extensive literature review. We proposed 'OASYS' - an objective tool that can act as a diagnostic aid for MDD through the quantification and analysis of blood biomarkers. However we found a disappointingly low amount of research centered around biomarkers and MDD. After a month of reading papers and talking to PhDs, we chose a comprehensive panel of blood biomarkers co-related to MDD.

Serotonin, the neurotransmitter and the GsAlpha protein, a protein complex associated with the cell membrane receptor were found to be downregulated in patients of MDD while miR-124 and miR-132 were found to show upregulated levels in blood.

We presented our project to several academicians and mental health professionals in order to collect inputs. Talking to Dr. Bhavana Muralidharan from InStem gave us confidence in our decision of going ahead with cortisol, serotonin and gs alpha. At the same time, many psychiatrists were doubtful about microRNAs. We talked to Prof. Lekha Dinesh Kumar, a cancer research scientist from CCMB who gave us all the validation we needed for proceeding with miRNAs. We greatly valued her words, especially because they came from someone who has worked on microRNAs for over 10 years.

We happened to visit the Government Medical college in June in order to meet psychiatrists and learn about the current diagnostic procedures. That is where we talked to Dr Arun B Nair and a few psychiatry students who both individually suggested that we consider Cortisol as a blood biomarker for MDD. This was an extremely valuable insight since upon further literature review we found that a comparatively greater amount of research has been done to study correlations of Cortisol and MDD. Additionally, studies have shown the cortisol levels in blood can be analyzed to measure the severity of MDD as well. Thus we added a fifth biomarker into our array of putative biomarkers

Parallely, we were also working on our quantifiers.

Initially, we had decided to harness the power of click chemistry and combine it with specific aptamers to build clickmers that can quantify Gs alpha, cortisol and serotonin. Click chemistry refers to a set of chemical reactions that are highly efficient, specific, and give high yields under mild reaction conditions. We approached our Director Prof. JN Moorthy and Dr. Reji Varghese from the School of Chemistry in our institute regarding this - who pointed out that using click chemistry for quantification might be inefficient, considering minute quantities in the blood involved in microfluidics and its time consuming nature.

To quantify our micro RNAs we had decided on a GFP- tagged Toehold switches.Toehold switches are synthetic RNAs that mimic messenger RNAs. They contain a recognition sequence for a specific stimulus in the form of a specific “input” RNA and a recognition sequence that the protein-synthesizing machinery (ribosome) needs to bind to initiate the translation of a fused protein-coding sequence into its encoded protein product. In the absence of the “input” RNA, the toehold switch is kept in its OFF state by forming a hairpin structure that uses part of the “input” recognition sequence and the ribosome recognition sequence, which is kept inaccessible.

We met Prof. Prashant Kodgire from IIT Indore at the Frontier Symposium conducted in our campus. He made us realize the difficulties in working with in-vitro translation of a protein, especially on a microfluidic chip, and the instability of RNA-RNA interactions. These points were reiterated by Tanvi Kale, a PhD from IISER Pune who works on toehold switches. Prof. Kodgire also introduced us to the idea of FRET, or Fluorescence Resonance Energy Transfer, which is a method of quick and easy detection for biosensing. 

Hence we started looking into FRET, which is a method of non radiative energy transfer between two molecules, a fluorophore and a quencher. Magnetic nanoprobes specific to miR-124 and miR-132 presented as an ideal quantifier since it allows for real time monitoring of microRNAs with great sensitivity. This latter feature is particulary relevant since the amount of microRNAs in the blood serum are relatively lower with respect to the other biomarkers. Dr. Amaresh Sahoo, an associate professor from IIIT Allahabad who works on nanoparticles and therapeutics guided us in the designing of our DNA nanoprobes.

The principle of FRET can be applied in versatile quantifications and hence we started looking for similar methods to quantify the other biomarkers as well. This would ensure that the final readouts fall in the same scale, having some degree of uniformity; providing we use the same fluorophore and quencher.

Dr. Tarun Kumar Sharma, an associate professor from Gujarat Biotechnological University who works on aptamer technology, helped us with combine the principles of FRET into the concept of aptamers. He verified our cDNA designs and aptamer modification.

Amidst hospital visits and wetlab experiments, the drylab team was working on creating a prototype for microfluidics. We wanted the diagnostic device to be based on microfluidics from the very beginning considering the many advantages it brings to the table. In addition to miniaturization of the assays and subsequesnt scaling down of quantities of sample, reagents, and enzymes, it also ensures minimal contamination and high throughout - making microfluidics an ideal PoCT (Point of Care testing) device to measure multiple blood biomarkers. 

We started out by using a software developed by previous iGEM hardware team of Boston University -2016 called Neptune. This is when we found an error in their software which prompted us to contact the ex-iGEM team. The team's instructor Dr. Radhakrishnan got in touch with us to clear our queries and offered us an updated version of their software. Subsequently we ended up talking about OASYS and stumbled upon a gold mine of information in return. Not only did he provide us with numerous resources, he also helped come up with a systematic plan of action for our Microfluidics. Further we met Dr. Lightson from Rajiv Gandhi Centre for Biotechnology to discuss about the material of the chip since he has worked on with multiple materials like paper microfluidics. Finally the design of our PDMS (Polydimethylsiloxane) chip was finalized at C-CAMP Bangalore where Dr. Naseer Ashraf guided us. He advised us against relying on capillary flows for the assays owing to the time taken for incubation. Hence we switched to using pumps in the micro channels, completing the final iteration in our microfluidic design. The prototype of the chip containing two channel was printed at the C-CAMP, Bangalore.

Our visit to NIMHANS, Bangalore and GMC, Trivandrum in the month of June was an important milestone in our project. Following a lot of discussion and reflecting on the meetings we had in these respective institutions, we realized that our project focus needs to shift from the biomarkers because it gives the wrong impression that their correlation to MDD is established. Dr. Indu made us realize the importance of pitching OASYS as a diagnostic aid instead of a diagnostic kit, while Dr. Srikumar prompted us to look back at the problem we faced initially during the ideation phase of our project - lack of data. We recognised the importance of building data for biomarker research and how it needs to catch up in the field of psychiatry, in the words of Dr. Varsha Singh, a cognitive neuroscientist from IIT Delhi. . 

Considering all challenges that were brought up by multiple experts, we decided to focus on the technology. Thus our project tagline evolved from being “A blood biomarker -based diagnostic kit for MDD” to “A novel FRET-based microfluidic device to diagnose MDD”. Establishing blood biomarkers for MDD shifted from being the focus of our project to a future goal. Until then OASYS has great potential to be research tool that can be used to collect data for the said putative biomarkers as well as for clinical drug trials. Once this data is analyzed and fluctuations in blood levels are standardized, then, like a self-fulfilling dream, OASYS can be a functional diagnostic aid for Major Depressive Disorder.

Coming to implementation, what had started out as a novel diagnostic device has now transformed into a design of versatile microfluidic technology, modified with the tools of synthetic biology. 

The inspiration for blood-biomarker-based diagnostics came from the work done by previous iGEM teams like Team Moscow 2021 (miPression) and Team IISER-Tirpati 2022 (Aptastelles). This was also validated by the words of Dr. Gokula Krishna, a neurochemist from NIMHANS

However, the application of OASYS in mental healthcare extends beyond what we thought it was. Dr. Manoj K Therayan shed light on the device's capability to track antidepressant effectiveness. It facilitates the study of the impact of a prescribed antidepressant dosage by conducting periodic blood assays throughout the prescription duration. 

Similarly, Dr. Srikumar from NIMHANS highlighted the prognostic potential of the device. 

Combined, both these applications open the door to personalized therapeutics in the field of mental healthcare.

The prospective and importance of OASYS in R&D were pointed out to us by Dr.Varsha Singh and Dr.Aravind Nattu, Director of BoG of IISERs and Professor at IISER Pune. The latter liked our approach of looking at multiple biomolecules that work on multiple levels and physiological pathways, not failing to highlight this as a much-needed novelty in the field of mental healthcare,

For further information, visit our implementation page of OASYS. 

Close-the-loop meetings refer to periodic sessions or discussions held with stakeholders of our project team to review progress, address challenges, and ensure the alignment of project objectives with the overall goals of iGEM. We ensured that we kept in constant contact with our most important stakeholders and followed through with them after each important milestone. Psychologists and academicians we met at the beginning of our project had different (and more positive!) things to say about our new pitch. The focus shifting from the biomarkers to the technology we’re developing greatly increases the applicability of our tool and reduces the complete reliance on biomarkers, which are yet to be validated by clinical studies. Additionally, we made sure to validate our wet lab results by Dr. Bhavana, Dr. Ashwani and Dr. Poonam Thakur. Clinicians like Dr. Saswati and Dr. Biju validated our technology approach, discussing its varied applications and admiring our efforts in advancing research in the area of psychiatric illnesses. Our microfluidic designs were closely monitored by Dr. Radhakrishnan and validated by Dr. Lightson to ensure the most optimized design possible.

This is when we realized that we can and MUST do much more than just try to develop a device that objectively diagnose a mental illness. Rather, we needed to really reach out and normalize conversations around mental health. Thus began our journey of destigmatization. 

Starting with our first attempt to shed light on the mental health scenario by stirring up a discussion between students and faculties on depression and the facilities available on campus. We’ve had a long journey of interacting with people from different walks of life spreading the word of mental health importance. The depression discussion panel saw healthy participation, invoked thoughtful conversations, and highlighted the students’ needs in mental healthcare.

As we moved forward, we conducted numerous awareness sessions for different audiences of different age groups and social and financial backgrounds. These include our following outreach events:

• Orphanage Visit:  Mental health awareness talk for pre teens, teenagers and young adults at Paadhai orphanage in Chennai proved to be very instrumental in spreading awareness among pre teens, teenagers and young adults.

• Kudumbashree talk: The Kudumbashree units represent the soul of a neighbourhood. With their extensive network and efficient management structure, reaching out to one of their units is the best way to convey and spread a message in the community. We are excited to have interacted with them and spread awareness about mental health among them.

• Street play:  Street plays are a powerful tool for mental health awareness because they engage audiences, challenge stereotypes, educate the public, and create a sense of community and advocacy. 

• Awareness talk by Dr. Krishnan: The talk served as a powerful platform to challenge the stigma associated with mental health, educating and encouraging open conversations about mental well-being.

We also conducted a mental health awareness survey and distributed informative pamphlets intending to reach as many people as possible. We were able to reach out to many people, more than we could ever have imagined, with the help of these pamphlets. We didn't just spread awareness about mental health disorders; we also equipped them with the necessary resources to seek help. Our social media handles also served as valuable platforms for spreading awareness. We frequently interacted with our followers on these platforms with our project updates and awareness content. Find more information on our Education page!