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The importance of being frugal

Frugal science inventions like a paper microscope for less than €1 and a range of other inexpensive diagnostic tools could play a revolutionary role in diagnosing diseases and in facilitating medical education and research around the world.

That’s the hope of leading pioneers of the science, Prof Manu Prakash and Dr Saad Bhamla, who are working together at Stanford University, California, US, on a number of innovative and inexpensive diagnostic devices that often involve leveraging the complex physics of a simple toy for global health applications.

“Frugal science has global potential,” Dr Bhamla tells the Medical Independent (MI) in a telephone interview from the lab.

Foldscope

The folding microscope, known as a Foldscope, suggests that the potential is very real. The groundbreaking device was co-invented by Prof Prakash, Assistant Professor of Bioengineering at Stanford, and Mr Jim Cybulski, who was a PhD student in mechanical engineering in Prof Prakash’s laboratory.

Their inspiration came from field visits around the world, when they frequently encountered bulky, broken microscopes, or a complete lack of the instrument, Dr Bhamla recalls.

The pilot programme began in the lab in 2014 and 50,000 Foldscopes were delivered to 155 countries for feedback. The reaction was overwhelmingly positive and the Foldscopes were successfully used for many purposes, including identifying the microscopic eggs of agricultural pests in India and detecting bacteria in water samples, as well as fake medicine.

A year later, Foldscope Instruments was founded to scale-up production of the device and pave the way for other low-cost tools. Their goal now is to distribute one million Foldscopes to medical, scientific and educational institutions around the world by the end of 2017, says Dr Bhamla.

In a world where nearly half a million people are killed by malaria each year – mostly children under five-years-old and mainly in Africa, and billions more are at risk of the disease – the value of having access to a diagnostic tool like the low-cost and easily portable Foldscope is obvious.

The poorer regions of the world suffer most from malaria, as outlined in latest estimates from the World Health Organisation (WHO). The African region accounts for most global cases of malaria (88 per cent), followed by South-East Asia (10 per cent) and the Eastern Mediterranean (2 per cent). However, in order to treat malaria and other diseases, health professionals must first be able to make a diagnosis. One problem in doing so is that there are not enough microscopes available or that they are too expensive to buy and maintain.

However, the Foldscope is made up almost entirely of paper, with the lens and battery also built in to the sheet. It is small enough to fit in one’s pocket. The higher resolution version magnifies up to 2,100 times and costs around $1, while the lower resolution device costs around 50 cents.

Remote areas

Dr Bhamla stresses that remote areas in developed nations could also benefit from the Foldscope and similar diagnostic devices. “Even in the United States there are extremely remote places where there is little electricity or infrastructure and places like that can definitely benefit,” he says.

“That’s the mindset we have when we think about developing these tools. They are, of course, for diagnostics – diagnosing diseases, especially infectious diseases – but we also focus on the design of the tools and their mobility, as well as the fact that they should be low cost,” he tells MI.

“It means we should be able to build tools keeping in mind the environment and the setting in which they’ll be used, usually in resource-limited settings like remote places in India and Africa where we do our field work. You can carry them around in your pocket and they can work in extremely rugged conditions.”

Education is also a major area that would benefit from the availability of such tools, he says. “Having access to low-cost scientific tools for biology or physics or field ecology means you’ve suddenly opened up a new opportunity because you now have access to tools that are extremely low-cost. The potential is enormous in the developing world, but I would also argue it’s wider than that when it comes to the educational potential.

“How often do kids have access to microscopes and centrifuges in their school or homes? So imagine if you could give some of these devices to people who could be inspired by them and get them involved in exploring science and in thinking about health issues. How many of us have seen our own blood through a microscope or seen separated plasma and blood?”

Dr Bhamla cited the development of the centrifuge as another milestone. The paperfuge, as they’ve dubbed it, can spin a blood sample very quickly, causing different types of cells to separate from each other. Most centrifuges are bulky, require electricity and are expensive, therefore many field hospitals in developing nations don’t have easy access to the technology.

“We’ve just published our work so far on the centrifuge (in Nature Biomedical Engineering) and I’m continuing to work on it right now. It’s a 20 cent device.” A conventional centrifuge can cost thousands of euro.

“It’s an ultra-low-cost (20 cents), lightweight (2g), human-powered paper centrifuge, designed on the basis of a theoretical model inspired by the mechanics of an ancient whirligig (or spinning toy).”

It comprises a circular disc with a loop of twine threaded through it and as the string loop is pulled and relaxed, it triggers rapid winding and unwinding phases with alternate clockwise and anticlockwise spinning of the disc, resulting in spin-rates of many thousands of revolutions per minute (rpm). The paperfuge is essentially based on the same idea.

“The paperfuge achieves speeds of 125,000rpm (and equivalent centrifugal forces of 30,000g), with theoretical limits predicting 1,000,000rpm,” Dr Bhamla explains. “We’ve demonstrated that the paperfuge can separate pure plasma from whole blood in less than 1.5 minutes and isolate malaria parasites in 15 minutes. By spinning the sample in a capillary pre-coated with acridine orange dye, glowing malaria parasites can be identified by simply placing the capillary under a microscope. Such ultra-cheap, power-free centrifuges should open up opportunities for point-of-care diagnostics in resource-poor settings and for applications in science education and field ecology.”

Curiosity

Prof Prakash saw the need for such a device during a trip to Uganda, recalls Dr Bhamla. They were in a health centre talking to healthcare workers when they found a centrifuge used as a doorstop because there was no electricity. The workers said they needed a powerful centrifuge that they could use anywhere and it had to be cheap.

Prof Prakash began brainstorming design ideas with Dr Bhamla. After weeks of exploring ways to convert human energy into spinning forces, they began focusing on toys invented before the industrial age, like yo-yos, tops and whirligigs.

“One night I was playing with a button and string and out of curiosity, I set up a high-speed camera to see how fast a button whirligig would spin. I couldn’t believe my eyes,” Dr Bhamla recalls. He discovered that the whirring button was rotating at 10,000 to 15,000rpms. He then recruited three undergraduate engineering students from the Massachusetts Institute of Technology (MIT) and Stanford to build a mathematical model showing how the device operates.

More work followed in the lab and in the field. Ultimately they were able to create a prototype with rotational speeds of up to 125,000rpm. Their lab now has a low-cost centrifuge that doesn’t require any electricity – just strings and a piece of paper. Much work remains to be done, but the end is now in sight.  Dr Bhamla tells MI the device could become available within two years.

Another innovation from the lab was the development of a $5 programmable chemistry set that was inspired by hand-crank music boxes. Like the music box, the prototype includes a hand-cranked wheel and paper tape with periodic holes. When a pin encounters a hole in the tape, it flips and activates a pump that releases a single drop from a channel. In the simplest design, 15 independent pumps, valves and droplet generators can all be controlled simultaneously. The portable, programmable chemistry kit that evolved can be used in modern labs to carry out experiments on a very small scale and its education potential – something close to Dr Bhamla’s heart – lies in the fact that children in the classroom, as well as health workers in the field, can carry a complete laboratory in a backpack.

Dr Bhamla is also enthusiastic about the ongoing development of a water-droplet-based computer that operates using the unique physics of moving water droplets.

The droplet computer, on which work began a decade ago, can theoretically perform any operation that a conventional electronic computer can accomplish, although at significantly slower rates. But the point in this computer is not to process information but to exploit the fact that droplets, even small ones, can carry chemicals or biological materials.

Those properties could help turn the computer into a precision, high-speed laboratory. Instead of running reactions in bulk test tubes, each droplet can carry some chemicals and become its own test tube. The idea is that the computer can precisely control and manipulate physical matter.

Promising

As to other developments in the pipeline, Dr Bhamla cited promising work by Prof Prakash and Stanford graduate student Ms Haripriya Mukundarajan, which involves using mobile phones to help track a species of mosquitoes connected with the spread of malaria. This could assist with environmental controls, such as removing breeding habitats or working with locals to avoid mosquito-dense areas. It is based on the phones detecting and recognising the presence and identity of different species.

Some species sound quite similar, however, so researchers would need information on the location and time of day to help them decipher the insect’s identity. The phone also has to be just five centimetres from the insect. But Dr Bhamla says he is optimistic about the project.

Could the devices that emerge from frugal science be potentially revolutionary for medicine, particularly in the developing world? “Absolutely,” says Dr Bhamla. “That’s why we are so excited about these and why we spend time thinking about building them. Another way we look at this is that we have specific problems or challenges that we want to address and the only constraint for us in designing these tools to meet these challenges is that they should be extremely affordable and low-cost. That allows us to be as creative as possible in choosing our inspiration from other fields and other technologies.

“Diagnostics is our focus with these devices and we have to do multiple rounds of field work in testing and in validating them and working with local community health workers on feedback. We think of the community health workers as our customers. Some of the work is done in our lab and some in the field.”

In fact, shortly before he spoke with MI, Dr Bhamla had returned from field work with local healthcare workers testing the paperfuge in Madagascar, a country in which malaria is endemic.

Both Prof Prakash and Dr Bhamla are from India, which has played a central role in inspiring their work. “I grew up in Mumbai and Manu (Prof Prakash) is from Rampur, so the inspiration for this work comes from seeing the challenges and the lack of infrastructure and diagnostic devices there.

“The impact that can have on the health and wellbeing of people is very apparent when you grow up in these places. Then when you have an engineering mindset you think about what can you do to help. So I would say that having seen these challenges growing up is where our inspiration comes from.”

Dr Bhamla suggests that the extent of their work and the number and nature of the devices they produce is limited only by their imagination. “When you think about a tool that is accessible it tends to open up the world much more than you imagined. If it’s accessible, it’s then left to the creativity of the individual using it for its possibilities. Imagination has no bounds and you can use the device in different ways to solve a problem and build on it. It’s all about having a collection of tools. To solve big problems, you don’t need just one tool. You need a lot of tools to address different parts of the problem.”

And what’s next? “Stay tuned,” Dr Bhamla says.

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