selected projects by Anesta Kothari
SMART TOILET PAPER
a simple, paper-based device that can quantify specific elements of the gut microbiome from fecal samples.
MICROBIOME + HEALTH
Although we frequent the bathroom to rid of our bodily wastes, there’s a lot that we can gather about our health from our feces. There are over 39 trillion microbes that live within the human body (most of which reside in the intestinal track). Contrary to common belief, most of these bacteria contribute towards good health – in terms of helping us digest foods, develop our immune system, and help the overall body systems function.
In a more specific case, current research shows how certain microbial communities within the body can inhibit the drug Digoxin and render the initial prescribed dosage to be inaccurate. Digoxin is typically used to treat patients with heart failures, however because of its narrow therapeutic window, it is critical that it is administered at the right dosage.
Although the procedures and instruments used to analyze and measure the microbiome exist, they are complex and expensive and therefore inaccessible for most individuals who need to frequently monitor their microbiome to keep their dosage (of Digoxin) in check. Can we find a simple and low-cost solution that can effectively track the human microbiome? Can healthcare be simplified that it can reside in the confines of a house? Can the bathroom be the new clinic? How can we assess the relevance of the collected data?
how does it work?
The main inspiration for the Smart Toilet Paper came from a paper-based malaria detection device called the Paperfuge, which was developed out of the bioengineering group at Stanford. It consists of a paper disc with a looped string threaded through its center and is capable of replicating the spinning mechanism of a micro centrifuge (spinning at up to 20,000 rpm).
One of the most common methods to extract DNA from their host cells is through the spin-column method, which relies on the positively charge surface of the silica membrane found within the column. DNA strands, which are negatively charged on their surfaces, bind to the silica, while all other cell components pass through this membrane. The DNA strands can later be released from the silica membrane into a separate container using a TE buffer. These processes, which typically require a micro centrifuge to push the solutions across the membrane, can also be done using the same mechanism as demonstrated in the Paperfuge device.
In order to see whether certain bacterial species or genes are present, the DNA fragments are amplified/multiplied using specially-designed primers. By doing so, only the targeted fragments, if present, would be amplified and can be visibly inspected. The conventional method for DNA amplification is known as Polymerase Chain Reaction (PCR), which typically takes about 120 mins and requires a thermocycler (95oC, 50oC, 72oC) to repeatedly split the DNA into single strands and allow for new nucleotides to bind and produce new copies of double-stranded DNA. The amplification method proposed for the Smart Toilet Paper is called Recombinase Polymerase Amplification (RPA). This method uses enzymes, rather than the alternating temperatures, to aid in the splitting and binding processes, therefore can be isothermal (37-42oC) and produce similar amounts of amplification in under 20 minutes. A quantified lateral flow assay system would be used to visualize the results.
THE PROCESS
The development of the Smart Toilet Paper was, by no means, a linear process. As the science was better understood, the design evolved to accommodate both functionality and ease of use. The following board represents the multiple (and often) parallel trajectories of the project (ranging from the design, chemistry, physics, material/fabrication, to user experience).
The current scientific experiments have successfully shown a simplified version of the device able to extract the DNA from E.Coli (strain C) cells and amplify the same DNA sample using two sets of primers (correct/positive and incorrect/negative). The results have been examined using a gel electrophoresis. The paper-based read-outs are still in progress.
PROJECT TRAJECTORY
Although Digoxin is not the most widely prescribed drug, a direct link to the human microbiome has already been established, therefore it is appropriate as a first example of how the Smart Toilet Paper can be applied. The current development of the Smart Toilet Paper is a proof of concept that can be extended to other applications beyond drug modulation.
A few clinicians have already expressed the value of using the Smart Toilet Paper for infectious disease detection, especially in cases where it is time-critical (in which point of care is required) or where resources are limited. The clinicians have also stated that in order for the microbiome research to penetrate into the clinical practice, more robust analytical data would be required. Although the field is fairly young, there is a constant increase in the number of research, publications, clinical trials, as well as funding that goes into microbiome-related research/projects. The project’s long-term goal is to be used as a non-invasive means of detecting chronic diseases that may also be asymptomatic, which also depends on the advancement in microbiome research. The design of the Smart Toilet Paper would also evolve not only to accommodate the varying applications but also to continue to increase its simplicity and efficacy.
Eventually, many tests and screenings will extend into the house, which would not only add convenience for the users, alleviate the clinics for more urgent matters, but also increase data collection for the purposes of clinical research. In speaking with clinicians, they are also onboard with the at-home health screenings, as long as the data has been verified for the devices (through clinical trials) and can be understood and interpreted by healthcare providers. The development of the Smart Toilet Paper will involve not only users, but also healthcare providers and other stakeholders to ensure its adoption meets certain key criteria.
PROJECT ADVISERS
Martin Bechthold, Director of the Doctor of Design Studies and Master in Design Engineering Program (GSD)
Rachel Carmody, Principal Investigator, Assistant Professor (HEB)
Curtis Huttenhower, Professor of Computational Biology and Bioinformatics (HSPH), Human Microbiome Project I &II
Peter Stark, Professor of Applied Physics (SEAS)biophysics, microfluidics, microfabrication
Mary Tolikas, Director, Wyss Center for Bio and Neuroengineering
ADDITIONAL SUPPORT
Melissa Hancock, Biological/Environmental Lab Engineer (SEAS)
Richard Novak, Senior Staff Engineer (Wyss)
Elaine Kristant, Senior Mechanical And Systems Lab Engineer (SEAS)
Steve Cortesa, Mechanical Engineer for Active Learning (SEAS)
Madeline Hickman, Design Specialist In Mechanical Engineering (SEAS)
Katia Chadaideh, Graduate Student (HEB)
Xiao Tan, Research Fellow in Medicine (MGH)
Jock Herron, Instructor in Architecture (GSD)
Michael Super, Lead Senior Staff Scientist (Wyss)
Douglas Kwon, Principal Investigator (Ragon Institute)
Alex Kostic, Assistant Professor of Microbiology and Immunobiology, Joslin Diabetes Center (Harvard)
Joshua Korzenik, Director of Crohn’s and Colitis Center (Brigham and Women’s Hospital)
Michael Springer, Associate Professor of Systems Biology (HMS)
Thomas Gililand, Clinical Fellow in Medicine - Cardiology (MGH)
Woodward Yang, Gordon McKay Professor of Electrical Engineering and Computer Science (SEAS)
Andrew Witt, Assistant Professor in Practice of Architecture (GSD)
Jonathan Grinham, Lecturer in Architecture and Research Associate (GSD)
Emily Venable, Research Assistant I Lab (SEAS)
Emma Accorsi, PhD Student (HSPH)
Jennifer Price, Assistant Professor (UCSF)
Jeremy Wilkinson, Director at Harvard Microbiome Analysis Core
Alesso Fasano, Division Chief, Pediatric Gastroenterology and Nutrition (MGH)
Ma Somsouk, Associate Professor (UCSF)
Suzanne Sharpton, Clinical Fellow (UCSF)
Kathy Yang, Professor at Department of Clinical Pharmacy (UCSF)
Victor Valcour, Professor of Medicine (UCSF)
Nicholas Vogt, PhD Student (UW)
award
“Outstanding Independent Design Engineering Project” (thesis) award (2019)
PHARMA 2100
AN ANALYSIS ON THE U.S. PHARMACEUTICAL FUNDING
Is our country focused more on fixing our problems or on preventing our problems?
Inspired by the way the U.S. healthcare is portrayed in Matthew Heineman and Susan Froemke’s documentary Escape Fire, the purpose of this study is to analyze the global pharmaceutical industry and gauge where the emphasis on funding lies between therapeutic and preventive methods in our health. The intended audience is a mix of governmental leaders, related R & D start-ups, and curious global citizens who care about the trajectory of their healthcare system.
The following data is based on a small sampling of the currently(2017) active pharmaceutical companies around the world. About a 10% random sample were taken from each bucket of different sized companies (measured by the number of employees). This data was obtained in 2017 through the Orbis Database, the World Bank Data, and the Bloomberg Global Health Index.
The categorization (therapeutic, preventive, or neutral) was determined using a text-based analysis on the companies’ trade and product descriptions. The data were then organized by countries, population counts, health index scores, and amounts of funding to see if there were any evident patterns. By sorting the companies in the order of their funding amounts, a pattern emerges to show a greater density of companies pursuing more preventative methods/care in the higher end of the funding spectrum, while a greater density of companies working toward reactionary care reside in the lower end of the spectrum. This means our healthcare system is currently putting more financial emphasis on preventive care. A possible extension of this study would be to do a similar spread across different years and see if the ratio has changed throughout the years or not.
CHÚ
a simple + comfortable air filter that fits in your nose
AIR POLLUTION
Given that air pollution causes about 11.2% of all deaths per year or 6.5 million deaths (split roughly 50/50 between indoor and outdoor air pollution). According to the EPA’s Air Quality Index, Beijing alone suffers at the ‘unhealthy’ level for at least 80% of the year.
CHÚ can help.
The typical face mask does not filter out a lot of the harmful particulates that exist in cooking fumes and smog. The unsealed condition between the face and the mask also contributes to the issue.
DESIGN PROCESS
We went through three phases in the design of the CHÚ: (1) form, (2) material, and (3) simplicity. The first designs focus on how the CHÚ fits on the head/face. In the second round, we experimented with different materials ranging in rigidness and flexibility to allow for ease of wear. We then optimized the design in both form and material to come to a simple final prototype.
The CHÚ consists of two main components: (1) tusks and (2) filter. The filter filament is housed in a cartridge that also serves as the link between the two tusks. Air is then delivered through the tusks and into the nostril. We have incorporated a silicone seal at the tips to seal and accommodate different sized nostrils.
HOW IT WORKS
Sizing and flexibility is key for CHÚ to fit properly on the head/ face. The aft filter allows for the tusks to flex for different head sizes and eases the process of donning and doffing the CHÚ. The soft silicone tips allow for a tight fit/seal in nostrils of different sizes. When idle, CHÚ can be draped around the neck and remain as an accessory.
The air intake, located at the back, allows atmospheric air to enter into a series of torturous path filters and continue through the tusks directly into the nostrils. Silicone gel ring seals the perimeter space between the nostril and the CHÚ, preventing unfiltered air from entering the nose directly. Exhaled air exits the CHÚ nostril opening and purges through the one-way gill valves. The filter can be “tuned” to various geographic locations based on local pollutant types and levels.
The business of CHÚ is through the subscription model. The CHÚ device can be registered upon purchase, which would allow the makers of CHÚ to curate the right CHÚ filter for your unique experience. We would recommend when new filters should be ordered and provide travel packages geared toward your destinations.
Team (MDE Collaborative Studio)
Katherine Spies and Anesta Kothari
award
Semi Finalist at the AlphaLab Gear Hardware Cup (2018)
ATELIÉR
personalized therapy that unlocks your creative state
WHAT IS CREATIVITY?
Creativity can be defined as the ability to associate concepts and abstract thoughts to generate new and unique ideas. Scientifically speaking, humans have 5 brainwaves (delta, theta, alpha, beta, gamma) --each corresponding to a different state of mind.
TECHNOLOGY + DESIGN
Atelier combines VR technology with two technologies into one powerful mechanism. An electroencephalography (EEG) is a monitoring device which uses electrodes (placed along the scalp) to measure the brainwaves of the user. An electrooculography (EOG) is a recent technology that also uses electrodes (placed on the face around the eyes) to track the position of the eye based on a voltage difference from the cornea. Both EEG and EOG are used to track specific visual stimuli that effect the changes in brainwaves (especially the alpha waves).
The design of Atelier Thinking Cap consists of two main components: (1) the ‘brain’, which houses the sensing and computing mechanisms, and (2) the stimuli, which holds the mobile VR headset. Atelier is catered to the individual, portable, and scalable as a manufactured product.
Team (MDE Collaborative Studio)
Vivek HV, Julian Seigelmann, Kenneth So, and Anesta Kothari
CREATIVE THERAPY
The goal of Atelier is to induce alpha waves through three phases. In the (1) Diagnostic phase, the individual is exposed to a variety of imagery. Atelier tracks and catalogs what the eye is seeing when the individual’s alpha peaks. Given this catalog of imagery, in the (2) Optimal Alpha State, Atelier composes an environment based upon the patterns and common characteristics of the cataloged images. And finally in (3) Transition to Reality, the individual is slowly transitioned back to his/her real surrounding and the therapy session ends.
Because we are often unaware of the triggers that spark our creativity, by approaching this issue through an objective lens, we can better identify that unique creative environment for each person. We hope that through multiple sessions, an individual can reach that peak alpha level state much quicker, hence increasing creative productivity.
