High throughput screening of biosensors directly in mammalian cells enables live cell imaging and drug screening

by Longwei Liu

Fluorescent biosensors based on fluorescence resonance energy transfer (FRET), a microscope imaging technology that uses fluorescent color changes to measure active molecular actions, have revolutionized biomedical science by enabling the direct measurement of signaling activities in living cells.

However, scientists face a big challenge when developing FRET biosensors—they are largely developed by trial and error, making it cumbersome for scientists to identify high-performance FRET biosensors. Now, bioengineers at the University of California San Diego developed a technology that can identify such biosensors with ease.

The technology, called FRET-Seq platform, is the first to accomplish this feat. It couples FRET signals to next-generation sequencing techniques that are capable of screening large-scale libraries directly in mammalian cells. The FRET readings from single cells expressing the biosensors are then used to screen and sort cells into different groups. The sorted cells then get analyzed by next-generation sequencing, which helps scientists to identify the biosensor sequences.

The UC San Diego team, led by postdoctoral researcher Longwei Liu and former Ph.D. student Praopim Limsakul from the lab of bioengineering professor Peter Yingxiao Wang, detailed their work in a paper published Aug 19 in Nature Communications.

FRET-Seq also uses a new self-activating FRET (saFRET) design, in which a kinase domain is linked to the conventional biosensor and causes the activation. This design can overcome difficulties in mammalian-cell library screening caused by the heterogenic kinase activities from individual cells. Counter-sorting strategy associated with this design further improves both sensitivity and specificity of biosensors during the screening process.

The biosensors developed through this platform have better sensitivity when applied in live-cell imaging, which allows applications evaluating immune T cell functions and screening drugs. In fact, ZAP70 is a critical kinase involved in many diseases, including autoimmunity, organ transplant rejection, graft-versus-host disease, or B cell CLL. Using the ZAP70 biosensor designed in this work, Liu and colleagues have screened a kinase inhibitor library and identified several inhibitors, including FDA-approved cancer drugs, that can be repurposed to inhibit ZAP70 activity and hence, related autoimmune diseases.

Looking into the future, the team is extending this FRET-seq technology as a general platform for the development of other high-performance and ultrasensitive biosensors for single cell imaging. The team is also integrating the high content screening platforms equipped with fully automated cellular imaging apparatus and analysis algorithms to screen large-scale compound libraries for drug discovery.

Other contributors of this work include: Yan Huang, Reed E. S. Harrison, Tse-Shun Huang, Yiwen Shi, Yiyan Yu, Krit Charupanit, Sheng Zhong, Shaoying Lu, Jin Zhang, and Shu Chien as well as the team of Xianhui Meng and Jie Sun from Zhejiang University.

Digitizing the genome

by Cam Lamoureux, UC San Diego bioengineering PhD candidate 

The genome has historically been known as life’s instruction manual. Indeed, the genome sequence of any organism contains all of the information needed to specify its form and function, from the simplest single-celled bacterium to complex organisms such as humans. But with rapidly developing sequencing technology, the genome is taking the stage as a new type of hard drive, nature’s way of storing information.

Understanding exactly how the genome represents an organism’s information remains a challenge for scientists. Any given DNA base (A, T, C or G) in the genome sequence can be involved in multiple different functions. As part of a gene, for example, a DNA base codes for a particular building block, known as an amino acid, of the protein that the gene specifies. That amino acid, in turn, may be part of a particular shape in the final protein. The DNA base may also be part of a sequence on the opposite side of the DNA double helix that is involved in controlling another gene’s activity. With so many different functions, information encoded by the genome sequence is convoluted and overlapping, yet it is critical to understanding an organism’s behavior.

Our work in bioengineering professor Bernhard Palsson’s Systems Biology Research Group at UC San Diego addresses this challenge. We introduce a completely new way of representing this information. For every DNA base, we can answer a simple yes/no question about every type of information the sequence can encode: does this DNA base encode that information? Borrowing from computer science, we realized that the answer to this question can be thought of as a “bit,” a binary digit. By doing so, we can scan across the entire genome of any organism, ask this question, and tabulate the answer as 1 for “yes” and 0 for “no.”

With this approach, we can construct a clean, quantitative record of the bits of information that an entire genome encodes. We call this method of genome annotation the “Bitome.”

We envision that the Bitome will serve as a key foundational tool for genome engineering, with applications in the sustainable production of industrial and medical compounds. For example, bioprocess engineers who reprogram bacterial genomes to sustainably produce chemical compounds can use our method to quickly assess which parts of an organism’s genome sequence are important for their application, and which are less important. They can make predictions about how proposed changes to the genome sequence will affect the organism.

While the Bitome’s capability mirrors traditional genome browsers, our approach provides far more utility and flexibility. Because we have digitized genome information, we can perform computations on those bits of information.

As a test case, we studied the E. coli genome and showed that DNA bases that contain fewer bits of information are more likely to be mutated during adaptive evolution. Because this observation is based on information that can be encoded by any genome sequence—not just E. coli—it could be used to predict genes that are more likely to mutate in cancerous tissues, for example.

The Bitome’s digitized representation facilitates prediction with machine learning. In part of our study, we applied machine learning to pinpoint the use of a particular stop codon as a predictor of mutability. This result is significant because it provides a deeper understanding of how genes mutated during adaptive evolution, a key tool for genome engineering. We also used machine learning to predict gene essentiality directly from the genome, another key capability for engineering genomes.

We are excited by the potential future applications of the Bitome as a way of analyzing genome sequences. This concept is inherently extensible to any organism’s genome and will undoubtedly serve useful both for deeply understanding the information encoded in a genome and for predicting behavior based on that information. With this work, we hope to further bridge the gap between the genome sequence information and the complex, critical functions that it encodes.

Publication: Lamoureux, C. et al (2020) The Bitome: digitized genomic features reveal fundamental genome organization. Nucleic Acids Res. https://doi.org/10.1093/nar/gkaa774

Metabolic and genetic basis for auxotrophies in Gram-negative species

By Yara Seif

While some bacteria survive independently, others reduce their metabolic expenditures by utilizing the nutrients available to them in their environment. These bacteria choose to adapt the concept of simple living or “less is more,” meaning one can survive on minimal requirements (we could definitely learn from them). Auxotrophy, a.k.a nutritional dependencies, are a characteristic of host adaptation. They are hard to characterize experimentally because there are too many nutrients to choose from, and also because they differ from one strain to another.

In a study published Mar. 5 in PNAS, we develop a computational workflow that uses both flux balance analysis and comparative genomics to predict nutrient requirements de novo and from sequences alone.

In our workflow, we compare the gene content across several strains of bacteria, and build metabolic networks tailored to each genetic background. Next, we simulate for growth on a minimal medium, and when that cannot be achieved, we run our algorithm called AuxoFind, to search for possible nutrients that would restore growth in silico.

Metabolic networks were tailored to the gene content of different bacteria and nutrient dependencies were predicted and validated experimentally. Image courtesy of Systems Biology Research Group

We find that when the same gene is missing, the nutrient requirements change across species, because they have different metabolic networks and combinations of alternative pathways. We also observed that the absences are manifested as a result of a large range of genetic modifications going from simple and small mutations (like single nucleotide polymorphisms) to large and complex genetic changes (whole genome rearrangements and multi-gene deletions).

The significance of this work is as follows:

Patients with certain diseases (such as Crohn’s disease or cystic fibrosis) tend to be chronically infected with bacteria. Over time, these bugs become more vicious because they slowly adapt to the in vivo environment. Understanding how these adaptations occur is a first step towards devising therapeutic solutions.

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Yara Seif is a UC San Diego bioengineering Ph.D. student. As a member of Bernhard Palsson's Systems Biology Research Group, she studies the metabolism of bacterial strains as well as the evolution of metabolic traits across strains especially in relation to their lifestyle. Her research so far has included multi-strain genomic and metabolic analysis of gram-negative strains using a combination of constraint-based metabolic modeling, comparative genomics and machine learning.

First Day of School Instagram Takeover

Yesterday was the first day of the new school year. Bioengineering junior Julie Yip took over the Jacobs School of Engineering Instagram. Check out her day going around campus to classes, browsing Library Walk, and meeting with her friends!

My name is Julie and I'm a third year Bioengineering: Biotechnology major here at the #jacobsschoolofengineering. I'm taking over Instagram (again) for this first day of classes. Best of luck to my fellow Tritons! ❤️ #instagramtakeover #firstdayofschool

A photo posted by UC San Diego Engineering (@ucsandiegoengineering) on Sep 22, 2016 at 12:11pm PDT

Visited the ECE Open House and had some free coffee and pastries. Yum! #ucsdece #instagramtakeover #firstdayofschool

A photo posted by UC San Diego Engineering (@ucsandiegoengineering) on Sep 22, 2016 at 12:12pm PDT

Caught a few of my favorite people on Library Walk today! The Biomedical Engineering Society has been a family to me ever since I joined as a freshman. They are an amazing group of driven individuals who can always make you laugh 💞 #bmesucsd #instagramtakeover #firstdayofschool

A photo posted by UC San Diego Engineering (@ucsandiegoengineering) on Sep 22, 2016 at 12:24pm PDT

Met these lovely girls from @phisigmarhoatucsd today. If you're an engineering or science major and thinking if going Greek, this sorority may be a perfect fit! #instagramtakeover #firstdayofschool

A photo posted by UC San Diego Engineering (@ucsandiegoengineering) on Sep 22, 2016 at 12:27pm PDT

I love the @ucsdguardian! Some of the most brilliant, creative people ever. I actually have a news article in today's issue. Grab a paper and read! #instagramtakeover #firstdayofschool

A photo posted by UC San Diego Engineering (@ucsandiegoengineering) on Sep 22, 2016 at 12:34pm PDT

Medical, Educational Missions and Outreach (MEMO) had the cutest bear! Love them! @memo_ucsd #instagramtakeover #firstdayofschool

A photo posted by UC San Diego Engineering (@ucsandiegoengineering) on Sep 22, 2016 at 12:40pm PDT

Grabbing lunch with friends! #instagramtakeover #firstdayofschool

A photo posted by UC San Diego Engineering (@ucsandiegoengineering) on Sep 22, 2016 at 1:15pm PDT

Pikachu says to go to First Friday. Save the date! #instagramtakeover #firstdayofschool

A photo posted by UC San Diego Engineering (@ucsandiegoengineering) on Sep 22, 2016 at 1:49pm PDT

Curbing the HIV Epidemic: UC San Diego Students Design Low-Cost HIV Viral Load Monitoring System for Tijuana, Mexico

A group of students from the Jacobs School of Engineering at the University of California San Diego will spend the summer trying to curb the HIV epidemic in Tijuana, Mexico. 

Two teams from UC San Diego’s Engineering World Health (EWH) student organization and Global TIES program are combining forces this summer to bring a device they created to monitor viral load in HIV patients to a clinical setting in Tijuana, Mexico for testing. 

The teams were tasked with building a low-cost HIV monitoring device for a hospital in Mozambique. UC San Diego Health doctors Matt Strain and Davey Smith are advising both of the teams. 

“Patients in the United States on HIV therapy are tested every three to six months to make sure their treatment is still effective,” said Yajur Maker, Co-President of Engineering World Health and bioengineering undergraduate student at the Jacobs School. “This enables doctors to change the patient’s therapy if the virus has become resistant to the drugs being given.”

To establish when the virus has become resistant, the patient’s viral load or the amount of virus present in the blood, must be assessed.

“If a therapy is working, the viral load goes down,” said Maker. “If the virus has become resistant, it goes up.”

Viral load test equipment costs roughly $80,000, and $65 per test. The students from the Global TIES Open Viral Load (OVL) Team and EWH have each developed prototype viral load testing devices that cost under $2,000.  The projected cost per test is $5. 

The two teams are combining forces to take their completed devices to a clinic in Tijuana, Mexico for testing, with the help of their advisors.

EWH Team

“We’ll adopt the best components from each team’s design and incorporate them into a system that’s ready for field implementation,” said Maker.

The teams have won over $31,000 in funding this year, including the Open Viral Load and Engineering World Health systems winning first and second place respectively in the Big Ideas at Berkeley Global Health track and receiving $2,000 each from the UCSD Social Innovation Fund. 

"The Open Viral Load Team was one of two [Global TIES] teams selected for this year's Clinton Global Initiative University, said Mandy Bratton, the Executive Director for Global TIES at UC San Diego.  “We are very proud of the work these students are doing and the impact it promises to have for HIV patients in low resource areas.”

Low-Cost HIV Monitoring

The key is determining the viral load, or the copies of HIV present in the body. After a certain threshold, or above a certain number of copies, the virus is determined to be resistant to HIV therapy, and patients must start new therapies. However, in low resource settings and without the necessary equipment, changing therapies is nearly impossible for doctors to justify.

The OVL and EWH teams are approaching the problem differently. In EWH’s case, the device consists of a low-cost centrifuge, PCR thermocycler, and a gel electrophoresis box.

The centrifuge, part of the Open Viral Load HIV-Monitoring device, processes blood.

“The centrifuge processes the blood so that we can get to the viral RNA,” said Maker. “After we extract the RNA, we amplify a gene specific to HIV using the thermocycler. Finally, we run it through the gel box to see whether viral RNA is present in large quantities. This helps doctors make the call on whether the patient’s HIV medication is not working. This process isn’t novel, but we’re making it accessible to hospitals and clinics in low-resource areas, such as Tijuana, which is so close to home.”

The difference between EWH’s device and the device the Global TIES team has built is the output.

“The difference is a qualitative versus a quantitative output. EWH’s device has a qualitative yes or no output, identifying for the doctor when a viral load threshold has been reached,” said Maker. “On the other hand, the OVL Team has built a device that quantifies the amount of virus present.”

Hayley Chong and Kirk Hutchison are part of the OVL Team. 

Chong is a third year bioengineering major. “I chose Global TIES as a freshman because every student I met that was in the program was passionate about their project,” said Chong.

Hutchison, a second year biology major, chose to participate in Global TIES after hearing a talk by a Global TIES member at an event.

“Global TIES is the reason I came to UC San Diego,” said Hutchison.

The two joined the OVL Team at the same time, after taking the introductory course  in the Global TIES program. 

“We decided to come up with a way to quantify the viral load,” said Chong. “We started with a microwell chip – once we extract the RNA, we can deposit it on the microwell chip and use a fluorescent probe to detect the number of copies in each sample. If five wells on the chip light up, there are five copies of the virus.”

The device is also advantageous because its components can be used separately to identify other diseases. Students will also be working with Dr. Davey Smith this summer to adapt the device as a rapid response test for the Zika virus.

Impact

Over the course of the summer, groups of students from the two teams now look to clinically validate the designs and begin field implementation. Lab testing will continue under Drs. Strain and Smith here in the U.S. and with their new partner Dr. Jose Roman Chavez Mendez at the Universidad Autónoma de Baja California (UABC) in Tijuana. With the teams collaborating and working together this summer, the future looks bright as they look to make an impact on the first of many low-resource settings.

High school student researchers develop early detection test for ovarian cancer

Two students in a UC San Diego bioengineering lab are on the verge of a medical breakthrough -- and they're only in high school. Meet Gitanjali and Priyanka Multani, inventors of a new test for early detection of ovarian cancer.

"We've created a blood test essentially, so it's non-invasive, easier and more cost effective," Gitanjali said. Gitanjali and Priyanka are identical twins who will be seniors at Torrey Pines High School starting this fall. They developed the technology under the tutelage of UC San Diego bioengineering professor Ratnesh Lal. Their project tied for a first place ACS Science Award at the 62nd Annual Greater San Diego Science and Engineering Fair on March 16, 2016.

Their story was featured on CW6 San Diego. Watch the interview and read the story here.

Update (7/13): the Multani twins and their work were also featured in the Del Mar Times.

Turning Engineers into Change Makers

Drive innovation from concept to commercialization – that’s the goal of one of the first initiatives – a four-course management training program for engineering students - of the new Institute of the Global Entrepreneur at the University of California San Diego. We sat down with a few of the students in program to get their thoughts on how they see it helping them translate their technology to the marketplace.

Nick Forsch, Bioengineering, Ph.D. Grad Year ‘19

“I caught the startup bug when I participated in a biomedical design competition - I love the innovation that comes out of small groups of people working towards a common goal with limited resources,” said Nick Forsch, a bioengineering PhD student at UC San Diego. “The nature of startups forces product design to focus on the essential components for meeting the needs of the target market.”

Upon arriving at UC San Diego after his undergraduate education at Washington University in St. Louis, Forsch joined bioengineering professor Andrew McCulloch’s cardiac mechanics lab. McCulloch’s research focuses on understanding the development of heart failure using models of cardiac electromechanics. When he’s not in class or the lab, Forsch is on of the vice presidents of the Bioengineering Graduate Society and enjoys playing soccer.

Read more about Nick

Originally from Huntington Beach, California, Karcher Morris came to UC San Diego to complete an undergraduate degree, and eventually a Ph.D. in mechanical engineering. When he’s not in class or doing research in Professor Frank Talke’s mechanics lab, Morris can be found in the EnVision Arts and Engineering Maker Studio where he TAs a number of experiential learning courses, or learning about business.

Karcher Morris, Mechanical and Aerospace Engineering Ph.D. Grad Year ‘18

“About a year and a half into my Masters, I decided to switch into a Ph.D. program because I had a great lab and a great PI,” said Morris. “At that point, I wondered about an MBA program. With undergraduate degrees in both aerospace engineering and management science, I was always looking for that well-rounded experience.”

According to Morris, it was one or the other when it came to graduate school. “I could either further my technical skillset or switch to business.”

Morris is part of the first course in the new program.

“This class has given me a new perspective because I’m working with a diverse group of motivated engineers.”

Read more about Karcher

Somayeh Imani found her niche in circuit design of wearable sensors – and it opened her eyes to the world of startups.

Group photo of Patrick Mercier's Energy-Efficient Microsystem lab. Imani is second from the left in the back row.

“There is so much opportunity in the field of wearables to commercialize technology,” said Imani, who is a graduate student in the Energy-Efficient Microsystem lab of Patrick Mercier, the Co-Director of the Center for Wearable Sensors at the University of California San Diego. “But commercialization is hard – you need a business plan and marketing skills –things that engineers don’t usually learn much about during their degree.”

Imani is part of the new pilot course – the first of four in the Technology Management and Entrepreneurism Fellowship Program – that aims to turn engineers into change makers through exposing them to the lab to market commercialization process. Participants earn a certificate at the end of four quarters.

Read more about Somayeh

  

Engineer demonstrates technique for targeting RNA inside living cells

Dave Nelles

When he’s not surfing in Mexico or listening to electronic music, Dave Nelles is busy tinkering – inside living cells!

Growing up, Nelles always knew he wanted to develop technology, but was intrigued by the complexity and diversity of processes in biology.

“Biology is on the verge of becoming a predictive and quantitative pursuit,” says Nelles. “Compared to fields like physics where we have many good models of natural phenomena, biology in general is less mature. One reason for this is a lack of tools to measure and alter specific components of living cells.”

Motivated by this gap, Nelles focused his graduate work in materials science and engineering on technologies to measure and alter a fundamental biological molecule: RNA. Inside cells, DNA is transcribed into messenger RNA (mRNA), which is subsequently translated into protein.

Proteins are the building blocks of life – many functions that take place inside of a cell are made possible by proteins.

“In many diseases, the processing of mRNA is dysfunctional, meaning that the protein that is encoded for by that RNA will not be made correctly, or at all,” said Nelles.

In molecular biology, there’s a technique called CRISPR-Cas9 that is used to modify DNA and has the potential to cure a range of genetic diseases. Nelles and his collaborators have been able to demonstrate that CRISPR-Cas9 can not only bind to DNA, but also to RNA.  This approach is described in a paper published on March 17^th in the journal Cell.

Nelles explains, “Just as CRISPR-Cas9 is making genetic engineering accessible to any scientist with access to basic equipment, RNA-targeted Cas9 may support countless other efforts for studying the role of RNA processing in disease or for identifying drugs that reverse defects in RNA processing.”

In collaboration with Mitchell O’Connell in the lab of Jennifer Doudna at the University of California, Berkeley, Nelles tagged Cas9 with a fluorescent protein and targeted various RNAs to track their movement inside living cells.

“This work is the first example, to our knowledge, of targeting RNA in living cells with CRISPR-Cas9,” said senior author Gene Yeo, PhD, associate professor of Cellular and Molecular Medicine. “Our current work focuses on tracking the movement of RNA inside the cell, but future developments could enable researchers to measure other RNA features or advance therapeutic approaches to correct disease-causing RNA behaviors.”

“For many experiments involving RNA tracking, the cells need to be dead or the targeted RNA must be genetically modified in order for the RNA to be detectable,” said Nelles. “Our experiments were done inside living cells with unmodified RNAs, which has many advantages – for example, we were able to observe RNA being transported to stress granules over time.“

Stress granules are accumulations of RNA and protein in a cell and their formation has been linked to neurodegenerative diseases. Nelles and his team hope that providing a way to track these RNAs will assist with new drug development.

After graduating this Spring, Nelles will be continuing his work as a postdoc at UC San Diego.

Want to learn more about other projects at the Jacobs School? Register to attend Research Expo on April 14, 2016.

#ILookLikeAnEngineer: Christopher Yin

Meet Chris, the next student of our campaign and VP Project Team for Engineering World Health. With a passion for improved global health, he hopes to impact entire populations through engineering - all while listening to The Velvet Underground and doing some creative writing. 

Name: Christopher Yin

Major: Bioengineering

Graduation Date: 2018

Why did you choose engineering at UC San Diego?

When I was applying to schools, I wasn’t even really considering UC San Diego. I was set on attending a private university, and if that didn’t work out and I had to choose a UC, then, of course, it would have to be Berkeley. The only reason I included UC San Diego was because I saw that its bioengineering program was ranked second in the nation. I attended Triton Day and  realized that it’s a great school for engineering. There are a ton of resources available for research and a number of engineering organizations on campus - those were primarily what drew me here.

What are your career goals?

I want to pursue either a Ph.D. or an M.D./Ph.D. program. I like being in school, and I like learning. Ultimately, I want to be involved in research that has an impact on global health. I love the science and I want to understand as much as I can, but I also really appreciate the part of engineering where you actually build your solutions. It’s pretty satisfying to make something tangible, and especially to have that something matter to other people. Engineering represents the opportunity to affect not just individuals, but entire populations.

Do you have a favorite quote or mantra?

From David Foster Wallace’s Infinite Jest: “I do things like get in a taxi and say, ‘The library, and step on it.’”

What are three things that are unique about you?

(1) Along with being a bioengineer, I would also like to write stories and novels. (2) I love brussel sprouts. (3) I listen to old and weird music, like The Velvet Underground, King Khan and BBQ Show.

What does this campaign mean to you?

The only way I can think to answer this question is with something platitudinous like, “It’s important for people’s awareness of engineering to encompass the full breadth and diversity of the people who do the engineering.” But just because it sounds cliché doesn’t mean it’s not true. I still think there needs to be a greater push early-on in education for all students, regardless of race, gender, religion, sexuality, etc., to explore STEM fields and figure out for themselves if it’s something they want to pursue. From my experience, any demographic disparities are due not so much to a lack of ability or opportunity, but a lack of awareness of ability and opportunity. If campaigns like this could change that, then that would be pretty great.

Freshman bioengineering students 3D print bones in hands-on class

UC San Diego bioengineering undergraduates are close to wrapping up the winter quarter of a new hands-on bioengineering course designed to expose freshmen to central topics and tools of bioengineering work on three hands-on projects. The class meets in the new EnVision Maker Studio at UC San Diego and is part of the Jacobs School's Experience Engineering Initiative.

* Electrophysiology
* Glucose monitoring for the blind
* 3-D bone printing

Rachel Daniels, a student in the class, says she learned a lot about the human spine from the bone printing project.

"By analyzing real life CT scans we were able to pull important data, allowing us to print a replica of the T10 vertebrae using plastic printing material," she said. "Once several prints were made we tested the correlation between load and displacement in the inter-vertebral disks by simply placing varying forces upon the vertebrae and measuring displacement. We concluded the heavier the load, the larger the total displacement until a plateau was reached."

We wrote about the very first iteration of this experiential bioengineering course in Pulse magazine last summer.

Below are images from the course.

Tools used include BioRadios, MATLAB, CAD software, 3D printers, foam cutters, hand tools.

Engineering World Health Hosts HealthHack 2016

The UC San Diego chapter of Engineering World Health held its second annual HealthHack February 27-28, garnering over 110 students of varied engineering and health science majors to produce a prototype or design to solve a serious global health problem.

The teams, comprised of up to four people, were given the following challenge: “To diagnose, limit, prevent, or treat a mental condition and its associated problems. Empower a patient to curb dependence on inaccessible resources, specifically in a low-resource setting.”

Neel Parekh, President Project Team for EWH, described what generated the prompt for HealthHack was what he sees as a significant need.

“I guess the simple answer is that mental health solutions are just not represented well in the engineering community,” Parekh said. “Engineers often focus on infectious and chronic diseases, but tend to give up when it comes to mental health. I also researched the [statistics] and felt bad myself for kind of not contributing to that realm enough, and [I] decided to pursue it further until I realized that there could be some really interesting engineering solutions to these mental health issues.”

According to the World Health Organization, countries with low and lower middle incomes carry almost three-quarters of neuropsychiatric disorders worldwide. Almost one-third of countries do not have a defined budget for mental health. Even more so, roughly 21 percent of countries that do have specific mental health budgets provide less than 1 percent of their total health budget on mental health.

The competition consisted of 27 hours of hacking, with the aid of graduate student, faculty, and industry mentors. Additionally, all participants had Arduinos and access to the MAE Design Studio at their disposal, in addition to workshops on 3D Printing and Hardware. Teams had to submit a written proposal, outlining the current need for the prototype or device, explanation of the solution, process for implementation, and any limitations and potential collaborations.

The first round of judging was a project expo, in which the 23 teams that submitted final proposals delivered 3-minute pitches to judges from academia and industry. Six finalists were selected for the last round. After a keynote speech from Illumina representative Adrian Fawcett, each team gave an 8-minute presentation before a panel of judges, including representatives from ResMed, the von Liebig Entrepreneurism Center and UC San Diego. 

Prototypes and designs included:

• Hidden watch for anxiety and epilepsy
• Wearable headband to aid narcolepsy patients 
• Mobile game for individuals affected by autism spectrum disorder
• Whole cell biosensor for a holistic approach to depression, bipolar disorder, anxiety and ADHD
• Stuffed animals to comfort those suffering from depression 
• Mobile app that tracks diet and physical health to improve awareness and self-diagnosis of depression, schizophrenia, obsessive compulsive and bipolar disorders
• Aid for refugees suffering from PTSD
• Focus on maternal stress and cortisol levels 
• Isolation prevention for the mentally distressed  
• Game that improves independence for the depressed, without having the affected realize the game is for treatment
• Application of radio frequency to provide diagnostic information for PTSD patients 
• Aid for the chronically homeless affected by mental and behavioral disorders
• Game for young adults suffering from depression 

Finalists

Third Place: PEN

Rodolfo Flores, Applied Mathematics, ‘18

Alfredo Lucas, Bioengineering: Bioengineering ‘18

Gustavo Umbelino, Computer Science, ’18

Focused on ADHD, in particular students who easily fall under in-class distractions, the team developed a Stimulating Pen that sends constant reminders to the users through vibrations and visual cues. The device also has a component for anxiety relief that allows the user to continuously press the button on the pen’s top, similarly to clicking a pen nonstop. The incidence of ADHD is higher amongst impoverished individuals, correlating income with the disease’s prevalence.

Second Place: Calm Cap

Neha Chhugani, Bioengineering: Biosystems, ‘19

Anokhi Saklecha, Biochemistry and Cell Biology, ‘19

Renu Singh, Bioengineering: Bioinformatics, ‘18

Vaish Sridharan, Bioengineering: Bioengineering, ‘19

These four girls were awarded $500 in prize money for their $5 wearable head device that alleviates anxiety, the most prevalent neuropsychiatric disorder worldwide. The device utilizes acupressure beads at acupressure points GV 24.5 and GV 20, cerebral regions that the International Anesethesia Research Study reports to correlate with stress relief. In addition, the device includes a battery-operated sound chip that plays calming music or meditation instructions and a microprocessor that records frequencies and durations of panic attacks. Calm Cap is worn at patient’s discretions, such that they may put on the device when they feel a panic attack approaching, and they may do so without any additional aid.

First Place: Amniotic Wrap

Niranjanaa Jeeva, Bioengineering: Bioengineering, ‘19

Ella Stimson, Bioengineering: Bioengineering, ‘19

Julie Yip, Bioengineering: Biotechnology, ’18

                                   

With the prize money of $1000, the team looks forward to collaborating with the von Liebig Entrepreneurism Center to further develop their prototype. The team was focused on Postpartum Depression, a disorder that affects 15 percent of mothers after giving birth, and this condition affects almost twice as many women in underdeveloped countries in comparison to industrialized countries.

One of the symptoms of PPD is difficulty bonding with the infant, thus, the team created a blanket that connects mother to child. The baby has a small sock with Lilypad Arduinos and infrared sensors, which detect the baby’s pulse and therefore its heart rate. This heart rate is sent via Bluetooth the mother’s blanket, which has Lilypad Arduinos and vibrational motors that mimic the baby’s heart beat. A study at the Eindhoven University of Technology revealed that biosignals of an individual’s heart beat can form an intimate connection and interpersonal distance with another person. In addition, the changes in the infant’s heart rate will be analyzed to gently awaken and notify the mother, before hearing the cries of her child. Estimated at $12 in cost, the design strengthens the mother-infant bond and has potential to relieve other symptoms of PPD, allowing the mother to independently improve her health in the comfort of her home.

First year Bioengineering student Niranjanaa Jeeva expressed her surprise, noting her attendance was derived in her hope to develop more engineering skills, and she noted how competing was a humbling experience.

“HealthHack was definitely an exciting experience!” Jeeva told the Jacobs School. “I went into it hoping to learn a few engineering skills, maybe create a viable idea to present at the end of the weekend. As a first year, I believed that there was really no way that I could win. Luckily, I was part of a great team. Together, we worked hard through many frustrating hours to come up with our idea and had a great time doing it. Maybe it was because I was so exhausted by the end of the second day, but I was so surprised when we won. All the other teams who competed had such amazing ideas. I am so grateful for the chance to have met and competed with such creative and innovative people!”

Ella Stimson, also a first year Bioengineering student of Amniotic Wrap, described how the event has encouraged her to further pursue engineering for improved quality of life and global health.

“Initially, I joined for the experience and not so much for the competition itself,” Stimson said. “This mindset continued until our group found a topic and design idea that all of us were passionate about,” Stimson said. “I’m thrilled that our enthusiasm was reflected in our product and supported by others. This competition made me realize that there are so many areas of our world’s health that is lacking resources and help and it amazes me that just 24 hours of designing and hacking can make an impact in that - whether it’s our group or any of the other groups’ idea. Now, I really want to make sure that our idea gets out there in the world and makes some kind of difference.”

As for the future of HealthHack competition, Parekh said to the Jacobs School, “I just want the idea that engineers can contribute to global health to continue to prosper and…have the UCSD community of engineering, including professors, entrepreneurship, and administration, to understand that they should be conducive to students that can come up with really amazing things.”