Wildly frugal

Standing at the lectern in a darkened auditorium, Stanford bioengineering professor Manu Prakash told his audience that he was going to demonstrate a few low-cost scientific instruments that had been developed in his lab. He looked more like a graduate student than a professor, with his untamed hair and rumpled down jacket, as he reached into his backpack and pulled out what looked like a colorful paper bookmark.“This is the Foldscope,” he said, “a microscope made from 97 cents of materials.” He pointed to a tiny spherical lens at the center, and told them that they could look through it and see microscopic objects with the naked eye.

To illustrate its magnification power, he played a video clip that had been recorded by attaching a Foldscope to a smartphone camera lens. The image of a gnat laying eggs squirmed across the auditorium’s large movie screen. Its hairy body was translucent, revealing its pulsating organs. It was like a scene from an alien horror film. A few people gasped.

Next, he held up something that looked like a whirligig toy, a loop of twine threaded through two holes in a 3-inch-diameter disc. He grabbed the twisted ends, then rhythmically pulled. As the twine coiled and uncoiled, the disc spun at a dizzying speed. Prakash explained how he could attach a thin tube of blood along the radius of the disc and the spinning forces would separate, say, malaria parasites from blood cells, making it easy to detect the organisms under a microscope. This 20-cent, hand-powered device, called a “paperfuge” because of the prototype’s paper disc, can do the job of a $1,000 commercial centrifuge.

Prakash was presenting at The Sequoias, a brainy retirement community nestled in the wooded foothills west of Stanford University. He had been invited to lecture on this February morning by resident Fabian Pease, PhD, an 80-year-old professor emeritus of electrical engineering at Stanford and a key collaborator on what may be Prakash’s most ambitious project yet: designing a scanning electron microscope that provides the basic functions of a $60,000 model for just $100.

The Foldscope, the simple centrifuge and the SEM all exemplify “frugal science,” designing scientific instruments that are affordable to people in resource-poor regions. Prakash is on a mission to inspire others to create tools that will ignite the curiosity of our next generation of scientists and engineers. And it seems as if he won’t stop until every child on the planet has a backpack full of frugal science tools.

Out of India

Prakash’s love of invention began during his childhood in a small town in northern India. He grew up in a home where his mother, who had a PhD and taught political science at a local college, emphasized learning. Outside of school, he was encouraged to explore and invent. He and his brother loved spending time building rockets, dissecting animals, collecting unoccupied bird nests and assembling large science models.

This informal, curiosity-driven learning time fueled my love of science,” says Prakash.

As an undergraduate at the Indian Institute of Technology in Kanpur, Prakash studied computer science. But he soon found that he disliked sitting in front of a computer all day. So, he began sneaking off to tinker in the robotics lab, where he built an omnidirectional walking spider-robot and a program that simulated the drawing style of children. He wanted to do more of this kind of work, and he heard that MIT was the place for inventors, so he applied and got in.

“I’ve been wanting to talk to you, too. Could you help us design a $100 scanning electron microscope?”

“I just got remarkably lucky. There was no rational reason to accept me. I only had a computer science degree and I hadn’t published any papers,” says Prakash.

At MIT, Prakash thrived. He invented a computer that used logic circuits comprised of microfluidic bubbles traveling along tiny etched canals, rather than electrons moving within metal pathways. And he worked out equations that described how water striders walk on water and how birds feed. He received his PhD in applied physics in 2008, then was awarded a Junior Fellowship at Harvard, which allowed him to pursue scholarship in any discipline for three years.

While Prakash was visiting a health clinic in India in 2010, he saw a photo of Mahatma Gandhi that set his course. In the photo, Gandhi looks through a microscope to observe the bacteria that cause leprosy. Prakash loved the contrasts in the photo. It showed Gandhi in a loincloth, sitting cross-legged on the ground, using an expensive European microscope at a time when India was struggling to shed its dependence on all things European. The instrument was impractical for rural India, where, because of the humid climate, lenses often cloud over with mold. But Gandhi knew he needed this instrument to help fight disease in his country.

For Prakash, this image embodies the idea that a single person embracing science during a tumultuous time can make a difference. “This is the picture that started me on my path of frugal science,” he says. He decided to spend at least half of his time as a professor developing low-cost science tools for everyone, everywhere.

It’s a small world

Pease, a lanky, British-born microscope lover with a full head of silver hair, first heard about Prakash at a June 2014 scientific conference in Washington, D.C. His former Stanford student Alireza Nojeh, PhD, told him over dinner about an extraordinary presentation he’d seen earlier in the day: A Stanford bioengineering professor had designed a working paper microscope that cost about a dollar. It was Prakash, who had joined Stanford’s faculty in 2011.

Pease had to have one, so as soon as he returned to Stanford, he phoned Prakash, who happened to work in the building next door.

“I’ve been wanting to talk to you, too,” said Prakash. “Could you help us design a $100 scanning electron microscope?”

“It’s been tried and it can’t be done. The vacuum pumps are too expensive,” said Pease, who in 1964 wrote his PhD thesis on a high-resolution scanning electron microscope he had designed and built.

Electrons are small, fast and difficult to control, since they obey the strange rules of quantum mechanics. Prakash knew that Pease’s expertise in harnessing electron beams would be invaluable in his pursuit of a low-cost SEM. Pease was a pioneer in developing electron beam lithography tools used to build large-scale integrated circuits. He also helped Tom Newman, his graduate student, win Nobelist Richard Feynman’s most famous physics challenge — to inscribe text small enough to fit all the pages of Encyclopedia Britannica’s 24 volumes on the head of a pin. (They did it by using electron-​beam lithography.)

Undaunted, Prakash appealed to Pease’s love of audacious challenges: “What if we shot the electrons through a very small distance in air, so that we didn’t need vacuum pumps?”

An SEM works on the same principle as a document scanner: by firing a precisely controlled beam back and forth across an object, measuring the intensity of the reflected beam and turning the beam into an image by layering dots on a screen. (It’s a beam of light in a scanner and of electrons in an SEM.) But SEMs work on a much, much smaller scale, which drives up costs. Generating detailed images of microscopic bacteria and viruses requires a very fine electron beam. And to keep the beam from hitting air molecules and scattering, it is fired inside an airless chamber attached to a pump and power supply.

But instead of this costly set-up, they could shoot the beam through a sealed vacuum tube like those used in old television sets. Or they could shoot it through a very thin glass window, positioned extremely close to the desired object. If they didn’t need a 40,000-volt power supply to drive the vacuum pumps, the other microscope subsystems could be run on a trickle charge from batteries.

For battery advice, they turned to Yi Cui, PhD, a Stanford professor of materials science and engineering. He suggested that such a battery could be made for several dollars by using conductive ink to print about 1,000 battery cells on an 8-inch-long, flexible circuit board.

The next challenge was to figure out how to create a tight beam of electrons without using an expensive, power-hungry laser. Pease called in Nojeh, who after Stanford went on to teach engineering at the University of British Columbia. Nojeh proposed that they focus an office-supply laser pointer on an array of carbon nanotubes to create such a beam.

At a certain point, Pease forgot how impossible the goal had seemed at first.

“It took me back to my childhood,” says Pease. He had pulled out his old textbooks and started thinking about how to simplify everything.

Now Pease is a regular fixture in Prakash’s lab, joining three generations of scholars dedicated to squeezing cost out of the microscope subsystems. They currently have a working test prototype.

The primordial soup

Many of the Prakash lab’s best ideas originate at the Friday meetings where Prakash and his 13 students brainstorm and solve problems. They are primarily biologists, physicists and engineers, but past members have included a circus performer, a music technologist and several high school students. Today, roughly half of the students are developing frugal science tools. The other half study how biological organisms function.

Take Halteria grandinella. Prakash brought this organism into the lab accidentally, from water collected during a Foldscope testing field trip at Lake Tahoe. At a recent lab meeting, Deepak Krishnamurthy, a tall, bearded graduate student wearing nerdy black glasses, led a discussion of the single-celled creature.

The aspect that most interests him is the organism’s ability to jump at speeds unheard of in the world of microbes. While he was trying to take a picture of the microbe, it disappeared from the microscope’s field of view and reappeared elsewhere, almost as if by teleportation. The organism, which lives in pond scum, is spherical with a floppy tuft of hairlike projections, called cilia. It looked like it was wearing a bad toupee.

Prakash kicked off the discussion: “OK, let’s get this out of the way. Yes, the cilia on top look like President Trump’s hair.”

Everyone laughed, then Krishnamurthy launched into his slide deck. Someone asked how the organism propels itself backward so quickly. Krishnamurthy waved his arms in a breast-stroke motion to show how the cilia propel the microbe slowly forward, then spun his arms like a frenzied egg-beater to show how the cilia generate explosive backward thrust. He pulled up a graph that showed velocity over time. Then he shared a dance-step diagram that traced the microbe’s pattern of motion. People argued about the purpose of the hyperspeed jumps. And for an hour, there was nothing more important than this little pond dweller.

A million points of light

Toward the end of his lecture at the Sequoias, Prakash pulled up a world map with pins showing where his team had shipped Foldscopes. So far, they’ve delivered 50,000 microscopes to 135 countries, beginning in 2013 with a grant from the Gordon and Betty Moore Foundation. The prototypes were funded by a Spectrum-Stanford Clinical and Translational Science Award from the National Institutes of Health.

Prakash added, “When we ship a kit, it comes with two Foldscopes, one for you and a second one for someone who has never looked through a microscope.”

A man in the audience asked, “Is there a temptation when you invent these things to make a lot of money?”

“This is a philosophical question I think about,” said Prakash. “We do file patents, but we decided that we wouldn’t evaluate our success by money, but by how many people are carrying these tools in their hands.”

To move the Foldscope from a lab-based project to a self-sustaining initiative, Prakash and Jim Cybulski, its co-​inventor​ and Prakash’s first graduate student, created a for-profit business, Foldscope Instruments, with a nonprofit subsidiary, thus enabling people with resources to subsidize those without. Their next goal is to ship 1 million Foldscopes around the world by the end of 2017. Foldscope Instruments will also commercialize other innovations from Prakash’s lab, such as the paperfuge, which was announced in January 2017, and a $5 chemistry set, announced in April 2014.

Navi Radjou, an innovation strategist and a coauthor of the book Frugal Innovation: How to Do More with Less, says Prakash is onto something but it could take a while for people to catch on. “The Foldscope’s first benefit is in education; it’s a great way to get kids to learn by doing,” he says. “But when I talk about the Foldscope to large medical device companies, I don’t feel enthusiasm from the audience. The idea of affordable tools is a threat to their core business models.”

Radjou adds that in the United States, there’s a perception that if something is low-cost, it’s shoddy. “It may be that the developing world will leapfrog the West in frugal innovation, because of the West’s attachment to a ‘more is better’ mentality,” he says. “The challenge is, how can Manu inspire the whole science community to embrace this concept?”

Prakash and Cybulski have learned that it’s important to have partners in each country who can help train new users and promote the adoption of frugal science tools. To that end, Foldscope Instruments is partnering with a variety of industry, nonprofit and community groups.

Through the Sigma-Aldrich Curiosity Labs initiative, they will provide students in 47 cities worldwide with Foldscopes and mentoring. To begin integrating the microscopes into Indian schools, clinics and everyday life, the Foldscope team is working with the Indian government to couple micro-research grants with free Foldscopes. They recently announced a call for proposals from Indian kids, teachers and tinkerers alike.

“This was a special moment for me, since I deeply understand what a program like this might have meant for me as a kid growing up in a small town in India,” says Prakash.

Near the end of his lecture at the senior center, Prakash offered to launch a Foldscope club there. He and Pease would teach the seniors how to build microscopes; then they, in turn, could teach their children and grandchildren.

“Tell the children that everything that you touch, every experience that you have, everything that you hold, has a microscopic component,” Prakash urged them. “Every living thing is made of these living cells. And just like with astronomy, when you look through a microscope lens, there are galaxies of things crawling around.”

As the lights in the auditorium went on, a crowd of seniors rushed the stage, each clamoring for a Foldscope.