Stress is re(d)al!

“What time was it again?”It was time to go to the hospital to meet Iris, my best friend who got hospitalized due to a minor case of acute stress syndrome. More than 30 percent of the student population of India report being under extreme stress.

During the COVID-19 lockdown, Indian students faced multiple stressors: Online Learning Difficulties affected 40 %. Isolation took 50. Concern for the pandemic struck 60—uncertainty at 70. I was one of them and so was my best friend. Repetitive stress is considered to be the early onset of depression. For the many, it expresses as minor headaches or increased blood pressure. For the few, it becomes much worse. 

Firstly, to analyze why we need a solution that detects stress much more than one that reduces stress, we must analyze what’s wrong with Indian parents. The debate about whether stress just exists in the minds of amateur young students who want to escape working hard is one with no resolve in the minds of Indian parents. What’s wrong with Indian parents is that they don’t understand stress is a real problem. The naivety of such myths and notions has to be studied because it affects the youth of India. 26 students committed suicide in Kota, Rajasthan in 2023 which is the highest in the past 8 years. “Suicide Mat Karna Bas” or just don't commit suicide is the tagline given to the Kota crisis. Something must change. And with CortisolX,  something will. With CortisolX, detection would become as easy as taking a photo of your bio-fluid sample mixed with cortisol-detecting technology. Yes, that's exactly what CortisolX will do. At the heart of the solution presented in this application is Cortisol, the quantifying hormone for stress in the human body. 

Cortisol boosts glucose in the bloodstream and tissue repair but slows nonessential functions during stress. Long-term stress can cause high blood pressure, atherosclerosis, diabetes, immune suppression, osteolysis, and myolysis in healthy individuals.

That being said, cortisol still has its merits. The emerging concept of “eustress” revolves around notions of the positive impact of stress on productivity and emotional well-being. Its merits and demerits are as hackneyed as they are ambiguous. This flexible dichotomy of cortisol levels and their impact varies from individual to individual. Therefore, a possible benefactor of this argument can be a method through which individuals can easily calculate their stress levels after various activities they do to understand the circumstances where their stress is not great for them. 

If we can create an early detection system- that being a method of cortisol detection with ease and cost effectivity - that can detect the amount of cortisol being produced in the body, then we’ll not only be giving proof to students across the globe that their stress is valid, but we’ll also be giving them an easy-to-use and non-invasive method to detect their stress levels when they do various activities and understand why does their body feel like an opponent in the game of “stress”. 

“For the next time you feel stressed, Stress is  Red!” 

The build-up from the previous prompt of this application allows me to introduce CortisolX in the right light. CortisolX is an easy-to-use stress detection mechanism focused on proving that stress is not just in the head but is out there, more accurately, it's in there.  The mechanism of this technology is based on the detection of cortisol which is present in biofluids. When the body experiences stress, the hypothalamus releases corticotropin-releasing hormone, which prompts the pituitary gland to secrete adrenocorticotropic hormone. This in turn stimulates the adrenal glands to produce cortisol, a key hormone in the stress response. Cortisol circulates in the blood and can diffuse into various tissues, including the apocrine glands located in areas such as the armpits and groin. Moreover, apocrine glands also release small amounts of cortisol through passive diffusion, similar to how cortisol is handled by the salivary glands, indicating a minor but measurable level of cortisol directly from the apocrine glands under stress conditions.

This innovative approach is a leap towards a non-electronic biosensor for quantifying stress in humans. This research utilizes Blue Tetrazolium Chloride and Tetramethylammonium hydroxide to analyze the concentration of corticosteroids present. When hydrocortisone or cortisol is present in sweat or saliva, the Blue Tetrazolium solution changes from pale yellow to magenta red, a shift which is easily quantifiable via spectrophotometry based on Beer-Lambert’s Law. comprises a semipermeable patch with microfluidic networks, saturated with Blue Tetrazolium Solution. During the prototype stage of this project, saliva has been primarily used as the primary biofluid solely due to the ease of obtaining it. The working of the solution has been highlighted in the second part of this application. 

The project aims to develop a rapid, colorimetric cortisol quantification method in sweat for teenagers and young adults. This easy-to-use biosensor allows them to track stress levels, crucial for early stress management and preventing depression. It encourages open discussions about mental health between young people and their parents, enhancing stress biomarker analysis and promoting mental health awareness, fostering a culture of proactive well-being management. The question is why this solution might work. Here’s why:

1) It is proof: Across India and beyond, stress is prevalent, affecting people like my best friend Iris, who was hospitalized due to stress. Yet, we often lack concrete proof of this stress due to outdated methodologies. CortisolX changes this, turning an abstract concept into something tangible—stress as a color, stress as red. 

2) It is early detection: Repetitive and excessive stress can lead to depression. CortisolX allows for early cortisol detection, serving as a proxy for stress levels. This detection technology enables individuals to monitor their stress over various activities, understanding their physiological responses better.

3) It is equitable access: The affordability of producing CortisolX enables widespread distribution without significant financial strain. Priced at just a dollar, it can be economically viable and accessible, promoting widespread implementation by governments and organizations at a minimal cost.

Help us make stress red.

CortisolX is designed to serve a diverse group of individuals, each with unique needs concerning stress management and wellness. Our primary target audiences include students, stressed faculty members, and individuals interested in monitoring how different activities affect their cortisol levels, enabling them to harness the benefits of eustress effectively.

Students often face significant academic pressures that can lead to chronic stress, impacting their mental and physical health. By using CortisolX, students can monitor their stress levels in real-time, allowing for timely interventions such as counseling or lifestyle adjustments. This proactive approach can significantly reduce the risk of stress-related disorders and improve their overall academic performance and well-being.

Stressed Faculty in educational institutions also stand to benefit greatly from our solution. The demands of teaching, research, and administrative responsibilities can accumulate, leading to burnout. CortisolX offers faculty members a tool to manage their stress more effectively, promoting a healthier work-life balance and enhancing job satisfaction and productivity.

Individuals analyzing activity-based cortisol variations will find CortisolX especially useful. This group comprises people who want to optimize their daily routines by understanding how specific activities impact their stress levels. Whether it's exercise, meditation, or work-related tasks, CortisolX can help them identify what increases or decreases their cortisol, enabling them to make informed decisions to maximize the positive aspects of stress and improve their overall quality of life.

By providing these groups with accurate, real-time data on cortisol levels, CortisolX empowers them to take control of their stress management, leading to healthier, more fulfilled lives.

 From ideating to penning the idea down; from spending days reading papers to spending nights executing experiments; from presenting the idea in Chennai and Delhi as a concept to conducting mass testing on the students of our school, CortisolX has come far.  These reasons allow Lakshya and Manvy to be capable of making this work. Here’s a detailed look at how these efforts collectively empower them to bring this innovative stress-detection tool to the forefront:

Ideation:  Originating from a personal connection to the issue at hand, Lakshya and Manvy gave countless hours to the ideation process for CortisolX which was deeply influenced by their own experiences as students grappling with stress. This connection provided the initial spark and continuous fuel for their project. Understanding stress not as a distant concept but as a personal challenge allowed us to identify and address gaps in existing stress management tools, leading to the development of a solution that is both effective and empathetic.

In-Depth Chemical Research: The cornerstone of CortisolX lies in its complex biochemical design, meticulously refined through extensive research. Our team lead, Lakshya Mutha,  invested countless hours in labs, studying the reaction kinetics by Graham et al. This foundational research was expanded through numerous trials, adjusting variables like temperature, concentration, and exposure times with substances such as blue tetrazolium and tetramethylammonium hydroxide (TMAOH). These rigorous scientific endeavors have ensured that CortisolX operates reliably across diverse conditions, optimizing its efficacy and user experience.

Attached above is a look at Lakshya’s desk: 

3 falcon tubes filled with different concentrations of the chemicals that he has used to test his stress levels. The red colored vial indicates my cortisol levels just before my English exam. He and Manvy will see this project to completion solely because they care - not only about their stress levels but the stress levels of their community. 

Personal Motivation: Each team member has directly encountered the debilitating effects of stress, making this project a personal mission beyond academic pursuits. Their intimate experiences drive them to create CortisolX, a product we deeply believe in and relate to. This personal connection ensures that every aspect of CortisolX is crafted with genuine care, aiming to deliver a transformative tool for stress management.

Community Validation and Engagement: CortisolX was emphatically endorsed at the Iris National Fair—India’s largest national science fair with a selection rate of less than 1%. Positive feedback from students and teachers across Delhi, Gurgaon, Mumbai, and Jaipur confirmed the urgent market need for such a product. This endorsement validated our approach and highlighted CortisolX's broad applicability and potential for widespread implementation.

These points summarise our case for why we are best suited to take forward this solution. It’s personal, as it should be. This approach enhances our chances of succeeding and making CortisolX available to people in our community; and then across India and other youth-driven nations. 

CortisolX is presently in the prototype phase of development. It has garnered significant traction as a concept after being advertised at ProjectX in Chennai and the Iris National Fair in Delhi NCR. These platforms not only provided exposure but also facilitated initial feedback that was crucial for further development. This traction indicates a positive initial response from the community, yet CortisolX remains a prototype due to several factors that underscore its early stage.

We embarked on mass testing in a school environment, where the prototype's effectiveness in detecting stress through cortisol levels was directly compared with results from stress-related questionnaires. These tests yielded promising results, confirming a reliable correlation between the biosensor’s readings and the students’ reported stress levels. Despite these positive outcomes, the transition from a prototype to a commercial product has been hindered by stringent regulatory guidelines in India, which are necessary for approval and patenting.

Currently, CortisolX is still a prototype because it has not yet moved beyond the testing phase to consistent market availability. The project's journey from concept to prototype involved engaging directly with potential users and collecting data that proved its efficacy. However, achieving commercial viability involves navigating a plethora of guidelines that ensure the product is safe and effective for public use. My next steps involve refining CortisolX based on the feedback received, enhancing its accuracy, and preparing for the regulatory challenges ahead.

The prototype phase is vital as it allows us to fine-tune the technology and prepare it for broader use. By continuing to test and adapt CortisolX, we aim to transition from a promising prototype to a reliable, market-ready product that offers a non-invasive, easy-to-use method for stress detection, potentially transforming how stress is managed and understood.

We strive to reach a wider audience, not only to advertise CortisolX but to educate more people about stress being a hormone in our veins, not a misconception in our brains. We want to network with research communities and gain mentorship from domain experts, mainly because we are working in a field closely related to pharmaceuticals. What further pushed us to apply to MIT Solve was the opportunity to receive funding to support the low-cost production of stress patches, allowing us to organize workshops and distribute them to students cost-free.

More importantly, we want to introduce the idea of cheap cortisol detection to the world.If students and parents will get more aware about their stress levels, they'll be able to diagnose repetitive stress more easily. 

By the time this reaches the respected researchers of academia at MITSOLVE, thousands of applications targeting equity health from a holistic point of view will be under review. A majority of them would be focused on utilizing AI to provide a direct or indirect service to different communities, and maybe one of them will get selected. A minority of them might involve technology that could cease the dynamic of a specific dichotomy, becoming the winner of the Global Health Equity challenge. Albeit, there might be 4, maybe 5 applications targeting a problem that seems to have normalized in the Indian community - the lack of understanding when it comes to mental health.   What’s interesting is that, during this process, CortisolX will be tackling a problem affecting a majority, tackled by a minority yet solved by no one. 

What makes CortisolX innovative is that it makes cortisol detection as accessible as it can be. It gives validation to students who have been neglected due to ancient notions of allegedly non-existing mental health problems. It allows people from across the world to analyze their stress levels during different activities of the day, easily accessing the powers of eustress. It also is an early detection system that can be used by hospitals to detect hypercortisolism and hypocortisolism.Moreover, the Cortisol website will tell users about the concentration of cortisol present and activities that can help them reduce stress. These are the main reasons why CortisolX is efficient and innovative. 

CortisolX also uses electrospun technology where the Blue tetrazolium, TMAOH and Polyvinyl solution have  been used to make an electrospun patch that can change color upon contact with cortisol. This has been highlighted in the posters attached

What truly sets CortisolX apart is that it’s both a community specific and a world based approach on mental health. Imagine the difference it could create, the suicides it could prevent and the hope it could give to not just my people but our people. 

1.8 billion students people.

3.5 billion employed people.

For them, it's the following 

It is proof: Across India and beyond, stress is prevalent, affecting people like my best friend Iris, who was hospitalized due to stress. Yet, we often lack concrete proof of this stress due to outdated methodologies. CortisolX changes this, turning an abstract concept into something tangible—stress as a color, stress as red. 

It is early detection: Repetitive and excessive stress can lead to depression. CortisolX allows for early cortisol detection, serving as a proxy for stress levels. This detection technology enables individuals to monitor their stress over various activities, understanding their physiological responses better.

It is equitable access: The affordability of producing CortisolX enables widespread distribution without significant financial strain. Priced at just a dollar, it can be economically viable and accessible, promoting widespread implementation by governments and organizations at a minimal cost.

To systematically progress CortisolX from a prototype to a widely available product, we have outlined strategic goals over the next six months, one year, and five years.

Six-Month Goals:

In the immediate six months, our focus is on advancing the prototype through rigorous testing with students at coaching institutes. This phase will provide critical data to support our application for a patent, facilitating the commercialization of CortisolX. Concurrently, we aim to conduct a pilot study and publish the results to substantiate the biosensor’s efficacy on a larger scale.We also plan to conduct cortisol testing with students studying in coaching centres of Kota so that we can validate their stress levels and maybe prevent it from getting worse. 

One-Year Goals:

Within the next year, our ambition is to expand CortisolX's reach across various states in India. This expansion will involve scaling our operations and growing our team to support increased demand and production. We plan to launch the product through specialized testing centers initially, ensuring controlled dissemination and feedback collection. Additionally, we will complete a provisional patent during this period, securing our innovation while exploring and promoting various stress remedies alongside cortisol testing.

Five-Year Goals:

Looking ahead to the next five years, our vision is to establish CortisolX commercially not only in India but also in other regions with emerging youth populations such as Hong Kong and Singapore. By this stage, we aim to secure a utility patent, ensuring comprehensive protection and recognition of our technological innovation. Our long-term strategy includes making cortisol testing a standard practice in assessing and managing stress, thereby influencing broader health and wellness standards globally.

This roadmap guides our efforts in transforming CortisolX from an innovative concept into a fundamental tool for stress management, enhancing the well-being of the youth across multiple geographies.

The blue tetrazolium reaction, utilized for quantitatively determining corticosteroids, involves the oxidation of the α-carbonyl moiety of the corticosteroid by blue tetrazolium, resulting in the formation of a highly colored formazan compound. 

This reaction is widely employed in pharmaceutical analysis and is based on a mechanism proposed by Oteiza et al. The proposed mechanism suggests that the reaction proceeds through the transfer of an electron pair and a proton from the anion formed by the action of tetramethylammonium hydroxide (TMAOH) on the α-carbonyl moiety of the corticosteroid to blue tetrazolium. This mechanism was supported by experimental data, including kinetics studies and observations of the reaction rate's dependence on the molecular structure of corticosteroids.

 The proposed mechanism involves the formation of a complex between the enolate ion of the corticosteroid and blue tetrazolium, followed by the transfer of an electron pair and a proton to produce a glyoxal derivative and a formazan compound. The intermediate complex formed during the reaction is consistent with the observed experimental data and supports the proposed mechanism.

the transfer of an electron pair and a proton to blue tetrazolium. Overall, the blue tetrazolium reaction provides a reliable method for quantitatively determining corticosteroids in pharmaceutical analysis, with the proposed mechanism offering insights into the underlying chemical processes involved.

There are 2 Co-founders in this project - Lakshya Mutha and Manvy Devraj. 

We have 20 volunteers from our school who have helped us with testing. 

The solution has been in work for the past 6 months. The volunteers were enrolled in March, when we conducted mass testing for our school students.

Even as co-founders, both of us come from different socio-economic backgrounds. The problem we are tackling revolves around the people who have been labeled as "crazy" or have not been validated due to their mental health problems. That is why we have adopted an inclusive approach to stress and mental health. Since both of us have seen our loved ones suffer from repetitive stress levels, we care - not only about our mission -  but about our approach to achieving this mission. Our organization is open to new members who wish to join us in making stress a "real" problem. Scratch real, a red problem. Our approach to inclusivity allows us to understand different perspectives of different backgrounds and we wish to not only empathise but be a voice for these people.  

CortisolX's financial strategy encompasses three integrated revenue models to establish a strong and diverse economic foundation while making our stress management solutions broadly accessible. The fee-for-service model involves selling CortisolX kits directly to individuals eager to monitor and manage their stress, creating a direct revenue stream through competitive pricing. The subscription model is designed to offer regular updates and replenishments, catering to users needing ongoing stress management support, and ensuring they continuously have the necessary tools. The partnership model aims to embed CortisolX within educational and corporate wellness programs, leveraging these relationships for regular demand and sustained engagement. These strategies are poised to not only secure financial sustainability but also expand the reach and efficacy of our stress management solutions. Currently, these plans remain in the strategic phase, with our immediate efforts focused on refining our prototype and conducting essential market research to align our offerings perfectly with market demands.

Using our carefully devised business model, CortisolX plans to achieve financial stability by leveraging a mix of revenue streams that include fee-for-service, subscriptions, and strategic partnerships. This approach is designed to establish a robust and diversified financial foundation. The fee-for-service model will directly sell CortisolX kits to individuals actively seeking to manage their stress, generating a steady income through competitive pricing. Our subscription model is aimed at ensuring long-term user engagement by providing regular updates and replenishments of the kits, which will contribute to recurring revenue. Additionally, through our partnership model, we intend to embed CortisolX within educational and corporate wellness programs, securing regular demand and fostering sustained relationships.

Moreover, we have successfully secured approximately $1000 from angel investors in Rajasthan. This funding is crucial as it supports our initial research and development efforts and helps establish partnerships with educational institutions for comprehensive testing. This investment not only aids in refining our product but also validates our confidence in our business strategy and potential for growth. These combined efforts and financial backing are pivotal as we move forward with our plan to become financially stable and expand the reach of our stress management solutions.