AWARDEES: Manu Prakash and Jim Cybulski
FEDERAL FUNDING AGENCIES: National Science Foundation, National Institutes of Health
Picture a microscope. You are likely imagining a heavy metal base, a viewfinder tube to squint through, and knobs on the side to bring a tiny specimen into focus. An essential tool for science for over 400 years, microscopes have identified disease-causing bacteria, revealed the building blocks of living organisms, and introduced children to the joys of science. But in certain areas of the world, barriers to transport, training, and maintenance can make even standard microscopes inaccessible.
Foldscope (Foldscope Instruments, Inc.)
Manu Prakash and Jim Cybulski’s response to the problem is the Foldscope, a paper microscope that can achieve powerful magnification and costs less than $1 in parts. It has been a little over a decade since the Foldscope’s inception, but 1.8 million have already been distributed in over 160 countries, dramatically increasing accessibility to science. Foldscopes have been used for everything from identifying agricultural pests to STEM education in refugee camps. But how was a several-thousand-dollar scientific instrument reimagined in paper form? Prakash and Cybulski found the answer through curiosity and play.
The Journey Begins
Manu Prakash grew up in the northern Indian village of Rampur. Aside from time spent on rigid, exam-focused schoolwork, where students rarely (if ever) got hands-on experience with scientific instruments, Prakash remembers spending hours upon hours tinkering in nature. “No one told me, ‘This is science,’” says Prakash. He thought constructing a “microscope” from his older brother’s glasses lens was just play. Today, Prakash still traces his predilection for curiosity-driven scientific exploration to informal learning outside of the classroom.
Manu Prakash, Stanford University (Manu Prakash)
Cut to 2011; after years of studying science and engineering, culminating in a Ph.D. in Applied Physics, Prakash was hired as a professor at Stanford University. While he waited for his physical lab to be set up, Prakash decided to get a jump on fieldwork; he traveled to Thailand and India to study infectious disease diagnostics.
The World Health Organization estimates that 241 million people were diagnosed with malaria in 2020. However, there are far more suspected cases each year, so more testing capacity is sorely needed. Early malaria diagnosis is crucial; it allows doctors to intervene and stop disease progression, reduces deaths, and limits transmission, so increasing malaria diagnosis accessibility saves lives.
Prakash found one potential key to the lack of diagnostic capacity in an unexpected place: a lab in the middle of a Thai rainforest where a $50,000 microscope was locked away in a room. Out of the tests for malaria, examination of blood samples under a microscope is considered the most reliable. So why was this essential instrument sitting unused? The problem had multiple dimensions. First, microscopes are bulky and difficult to transport to remote locations. Second, even when a microscope is available, access to training, repairs, or maintenance may be out of reach. And third, microscopes are expensive and delicate, so trained lab technicians may still feel anxious about using them in areas where budgets are tight.
Prakash began wondering, what would a cheap, hardy microscope that could be widely distributed look like? A self-proclaimed doodler, Prakash sketched in his journal the concept of a microscope that could be printed like a newspaper.
Impact-Oriented Scientists
Jim Cybulski, Foldscope Instruments (Jim Cybulski)
Back at Stanford University, graduate student Jim Cybulski was looking for a Ph.D. project that was impactful outside the lab. He had a background in engineering but hadn’t quite found the balance between innovation and impact within the world of academia and industry. That all changed when he met with Prakash, newly returned from field work travels. Cybulski recalls feeling an immediate resonance with Prakash. They had both grown up in non-wealthy, rural households (Cybulski grew up in Northeastern Pennsylvania), and they both liked tinkering.
When Prakash told Cybulski about his vision of an inexpensive, accessible microscope, Cybulski immediately understood the potential; he saw the opportunity to create something with great utility.
How to Make a Microscope
At their most basic, microscopes have an eyepiece (the tube you look through), a lens (the magnification), a component that holds a specimen for viewing (which pans from side to side to explore different areas of the specimen), a mechanism to bring a specimen into focus (usually by moving it physically closer or farther from the lens), and a light source (to illuminate the specimen).
Cybulski explains that scientific tool developers usually choose one of two supposedly non-compatible priorities: the need to make the tool cheap and just good enough to get the job done, or the need to make a high performing tool regardless of cost. Cybulski and Prakash rejected that binary. They wanted their microscope to be low-cost (made for less than $1), high performing (able to “see” a malaria parasite), and accessible (capable of large-scale worldwide distribution).
Goal 1: Make it Low Cost
Early sketch of the Foldscope (Foldscope Instruments, Inc.)
True to their doodling and tinkering roots, Prakash and Cybulski sketched designs on paper taken from the printer in the corner of the lab and fiddled with a matchbook. The matchbook had what they were looking for, a cheap but sturdy structure, but it was too small. When Cybulski held up the prototype, he poked himself in the eye with his thumbs. The next iteration was slightly wider and made of file folders they found in the lab. To keep costs low, Prakash and Cybulski decided their microscope should accommodate standard microscope slides — 3-inches by 1-inch thin glass rectangles upon which a specimen is placed for viewing — which scientists typically have on hand.
Foldscope layout scheme (Foldscope Instruments, Inc.)
The other big consideration was the material they should use to construct the microscope. The more Prakash and Cybulski considered it, the more it became clear — what about the material they had been using all along? Paper was cheap and could be folded and cut incredibly precisely, a fact long since established by origami, the Japanese art of folding paper.
With a design finally in sight, they decided on an appropriate name: the Foldscope.
Despite their enthusiasm, the concept was tough to convey, especially when funding was on the line. Prakash remembers stapling a Foldscope to a grant application to help explain the invention. That made their existing funding all the more vital — Prakash’s lab received support from the National Institutes of Health (NIH), and Cybulski received the NIH Fogarty Institute Global Health Equity Scholars Fellowship. Both sources were foundational to the early research that went into the Foldscope’s creation.
Goal 2: Make it High Performing
Over time, Prakash and Cybulski graduated from X-ACTO knives to laser cutters. They wanted to make this tool applicable for scientific data collection. Unlike traditional microscopes which often have multiple lenses and mirrors that enhance magnification, the Foldscope’s only source of magnification is a ball lens, a cheap, tiny glass sphere. Prakash and Cybulski set out to determine the theoretical limit to the resolution achievable by the Foldscope.
In a Foldscope, a piece of black plastic carrier tape holds the lens and serves as the optical aperture, the hole light shines through to illuminate and resolve an image of the specimen. Cybulski and Prakash found that the placement and size of that aperture are crucial. Since a ball lens is a sphere, the light gets distorted around the edges, so to avoid a fuzzy image, the best path for light is straight through the middle. The aperture needs to block all light except through the center path. On the other hand, you can only make that aperture hole so small before no light gets through at all.
Malaria in red blood cells, projection of Foldscope image (Foldscope Instruments, Inc.)
Cybulski and Prakash mathematically calculated the very best theoretical aperture size and built Foldscopes using those calculations. Those Foldscopes achieved vastly improved image quality and resolution compared to other ball lens microscopes with sub-optimal apertures. The final magnification was about 140x, the magnification necessary to see a malaria parasite in a cell.
Goal 3: Make it Globally Accessible
Today, Prakash and Cybulski describe their approach as “frugal science,” a philosophy that has grown out of a simple but formidable goal — science should be made accessible to all. Even after the Foldscope had proved its utility in the lab, Prakash and Cybulski did not consider their work complete. They needed feedback. Input from a wide variety of communities would transform the Foldscope from an instrument that worked in theory to one that people would actually use. To get Foldscopes out into the world, Prakash and Cybulski needed to scale up manufacturing.
The team decided to make 10,000 Foldscopes and distribute the instruments for free to anyone who wanted one. Cybulski says this seemed like a big goal at the time, but the demand surpassed anything they had imagined; somehow, the number grew to 50,000 Foldscopes, then 75,000. A new NSF grant supported them along the way — Prakash emphasizes the importance of funding at that stage; without it, he says, they might never have gotten the Foldscope into the world.
The researchers sent out the first batch of free Foldscopes and started the iterative process of feedback and improvements. The Foldscopes traveled across the globe to people with all kinds of backgrounds. One surprising demographic of Foldscope requesters? Grandparents who wanted the instrument for their grandkids. Prakash and Cybulski were delighted.
Faces of Foldscopes
Giant moth scales as seen through a Foldscope (Manu Prakash)
Over the next several years, thousands more Foldscopes traveled around the world. True to the instrument’s initial conception, the Foldscope has been used to diagnose malaria, but the sheer range of subsequent applications could never have been foreseen. Foldscope users have explored the microscopic diversity of the Amazon rainforest, monitored agricultural pests, identified animal pathogens, surveilled mosquito populations, and mapped plankton for fisheries management. Over 400 scientific papers have been published using data collected with Foldscopes, including the discovery of two new species.
Cybulski recalls a project in Nigeria that used Foldscopes to detect fake drugs. In some parts of sub-Saharan Africa, over half of the drugs sold in pharmacies are substandard or counterfeit. By crushing a pill into powder and viewing it under a Foldscope, real drugs appear as uniform particles, a signature of the manufacturing process, but fake drugs look like powder. Having access to a Foldscope has empowered people to check the safety of their medications.
Students look through Foldscopes at a workshop (Foldscope Instruments, Inc.)
A key goal of Foldscopes is to impart a sense of agency. Like a pencil, notes Prakash, anyone can pick it up and use it, even if they do not know how to write. The colorful designs on the Foldscope are not accidental; the instrument is designed to feel approachable, like an arts and crafts project. Only after some tinkering do users realize they have stumbled onto something powerful. That is the key to the power of a scientific tool, says Prakash. It has nothing to do with cost or complexity; it is about being accessible at the right moment. Then, someone can work on a problem where they see urgency.
However, in science, we often attribute a higher value to shiny, complex instruments, and Cybulski remembers many encounters with people hesitant to interact with the Foldscope because of the perception that microscopes are expensive and delicate. Cybulski recounts meeting a doctor in India, who, when handed the Foldscope, reached out with shaking hands, worried that he would break it. To combat that perception, Prakash and Cybulski have built infrastructure for training and public engagement workshops around the globe. The programs have multiplied; today, 1,200 projects are in progress in India alone. In the United States, Foldscope programs have been implemented in public libraries and STEM education for juvenile incarcerated populations.
Prakash demonstrates the Foldscope for President Obama (Foldscope Instruments, Inc.)
The community of Foldscope users is not limited by country. On Microcosmos, an online forum set up by Prakash and Cybulski, users from around the world post images captured by hooking their Foldscopes up to a phone camera. Rafikh Shaikh, a Foldscope workshop leader and PhD student in India, says that it is clear Prakash and Cybulski thought about building community since the Foldscope’s inception. NIH staff scientist Lakshminarayan Iyer has been a part of the Microcosmos community for years. He says the greatest impact comes from connecting with others outside of his typical circles. Iyer can share his work with scientists around the world (who use free online translators to transcend language barriers) or advise a child in the U.S. trying to look at the crystals in ice cream.
Muhamed Abbas, an Iraqi Foldscope community member who leads public science engagement projects, explains, “Foldscope is not just a tool for me … and it’s beyond a community of people trying something new. I see myself as part of a global mission to make science more accessible and inspire the next generation to … maintain their curiosity to use science as a tool to find solutions for challenges our communities face all around the world.”
Eyes on the Future
Even after distributing over 1.8 million Foldscopes in 160 countries, Prakash and Cybulski still see work to be done. There are two billion children around the globe that could benefit from a Foldscope. To Prakash and Cybulski, it is a mistake to assume that cutting-edge tools can only be available to a few; rather, access is a choice we make. The key is starting with accessibility in mind from the start.
The two designers have not stopped imagining and innovating, either. As the head of what is now the company Foldscope Instruments, Inc., Cybulski is designing and manufacturing a new generation of more capable Foldscopes, as well as an app that can help Foldscope users get better images and identify specimens. Prakash’s research team at Stanford has developed even more frugal science instruments. The Paperfuge, a paper centrifuge, can spin at high speeds and separate pure plasma from a sample of blood in a minute and a half. Another tool, the Octopi, is a low-cost autonomous microscope that can identify malaria in blood samples.
Despite the immense success and wide-ranging impact of their work, Prakash and Cybulski speak candidly about how tough it was initially to find support for such a silly-sounding idea. They weren’t just thinking outside the box — they cut up the box and used it as construction material. And that is why federal funding for early-stage research is crucial, even if (and especially if) the ideas are odd-sounding. Future impact is magnified when innovative research ideas are supported early on.
Students look through Foldscopes at a workshop (Foldscope Instruments, Inc.)
By Gwendolyn Bogard