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The body’s chemistry may energize pacemakers or search-and-rescue roaches

CREATURE POWER  Biological fuel cells that generate electricity by harnessing sugars and oxygen in the body may one day power implanted devices in humans and other animals.

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Sometime in the future: A patient leaves the hospital with a new pacemaker implanted next to her heart to steady its beat. Her older brother, who went through the same procedure a few years earlier, will soon need another major surgery to replace his pacemaker’s batteries. But she won’t. Her device can generate its own electricity indefinitely with sugar and oxygen harvested from her bloodstream.

Scientists are racing to perfect the technology that could make this possible. If they succeed, these “biological fuel cells” could usher in a new wave of medical devices smaller and more versatile than today’s batteries allow.

A pacemaker requires a lot of power, so it may not be the first medical device to go battery free. But what about a contact lens that monitors glucose levels in patients with diabetes? Powering it with the chemicals in tears is not so far-fetched. A patient-powered skin patch may one day measure temperature around a surgical wound to signal an infection.

Creative scientists have used snails, clams, rats and rabbits to power fuel cells for weeks at a time. A cluster of lobsters even managed to keep a wristwatch ticking. Someday, plants or half-robot insects wearing biological fuel cells could sniff out pollutants, search for earthquake survivors in collapsed buildings or eavesdrop on secret conversations.

To realize this sci-fi future, scientists first have to solve serious problems with the longevity of biological fuel cells and find ways to squeeze more power out of them. But they’ve shown startling progress in the decade since the first implanted biological fuel cell — in a grape — emitted power.

A constant supply of energy

Biological fuel cells run on some of the same fuels our bodies do, such as glucose. In general, a fuel cell uses chemical reactions to generate electricity. Batteries do the same, but all their fuel is stored inside. When it runs out, the battery dies. Fuel cells require constant input, like an engine.

Most biological fuel cells depend on enzymes, chemicals in our bodies that speed up reactions. These catalysts perform a range of complex and specific tasks inside cells. The enzyme glucose oxidase is a large molecule, hundreds of times bigger than the fuel that it breaks down, glucose. It is a long strand twisted into a lumpy ball with an internal pocket shaped so that only glucose fits into it. In this protected nook, the reaction that splits glucose into molecules that cells can use happens without interference.

What an enzyme can accomplish in one action, a chemist would need dozens of steps to achieve, adding just the right amount of each ingredient at just the right time and carefully controlling temperature, pH and other factors to ensure that the desired transformations — and only those — take place.

At its most basic, a biological fuel cell is two enzyme-coated conductive wires implanted in tissue, a blood vessel or a nerve. Scientists have made these wires as thin as 5 micrometers, small enough to fit inside a nerve cell in the brain. The most common versions work like this: One wire, the anode, is coated with an enzyme, such as glucose oxidase or GOx, that reacts with glucose. The other wire, the cathode, is coated with an oxygen-reacting enzyme, for example, bilirubin oxidase or BOx. When GOx reacts with a glucose molecule, the enzyme takes two electrons from glucose. Meanwhile, BOx adds four electrons to an oxygen molecule. When the anode and cathode are connected, the electrons can flow from GOx to BOx, creating an electrical current. Add a light bulb to the connection and it would glow — at least in theory.

The enzymatic reaction cycle of glucose and oxygen produces about half a volt of electricity. Not much. By contrast, a AA battery carries about 1.5 volts. Medtronic, maker of one common pacemaker, recommends replacing the battery when it can produce no more than 2.6 volts.

In 2003, chemist Adam Heller revived an idea first put forth by artificial heart developers in the 1960s. They saw the potential of using enzymes as highly specific and effective catalysts in biological fuel cells. Heller, of the University of Texas at Austin, made the idea a reality. In a grape, a fruit high in glucose, he devised the first implanted enzyme-based biological fuel cell.

Heller’s tiny power plant was groundbreaking, but it had practical drawbacks. Within 20 hours, its power output fell by half because side reactions with the enzyme caused buildup on the cathode, reducing its conductivity. Publishing his findings in Physical Chemistry Chemical Physics, Heller predicted the lifetime of glucose-oxygen biological fuel cells might eventually reach weeks, far short of the years-long lifetime necessary to compete with batteries.

So far, Heller has been right. No research group has done much better than weeks, but researchers continue to push for more, tweaking and adapting Heller’s prototype.

Progress came in 2009, when Serge Cosnier and his team at Joseph Fourier University in Grenoble, France, demonstrated the first enzymatic biological fuel cell implanted in an animal.

Cosnier’s fuel cell functioned for 40 days in a rat’s abdomen. Although it produced only 0.13 volts, about one-quarter the voltage of Heller’s grape, the experiment showed that animals can tolerate long-term implantation.

Like Heller’s, Cosnier’s biological fuel cell lost power quickly, as the cells consumed the available oxygen and glucose in their vicinity, his team reported in PLOS ONE. In animals with complex circulatory systems, it takes time to move blood around to replenish these fuels, and because oxygen is less plentiful than sugar, it usually runs out first. A Japanese group led by Matsuhiko Nishizawa solved this problem with a fuel cell open to the air. After demonstrating the principle in a grape, his group at Tohoku University is now adapting the idea into a power-generating patch. This flexible biological fuel cell would have the oxygen-fueled cathode on top, exposed to the air, while an array of tiny needles on the underside would reach sugars in the skin or tissue beneath.

Bugs as spies

Clams, insects and lobsters offer a neat way around the fuel delivery problem. Invertebrates don’t have the system of blood vessels most vertebrates do. The difference is like comparing a go-kart track to bumper cars. Rather than having to follow a closed course, the glucose and other molecules can travel more freely around invertebrates’ bodies. This greater fuel availability makes organisms with open circulatory systems attractive targets for enzymatic biological fuel cells.

Chemist Daniel Scherson at Case Western Reserve University in Cleveland prefers to work with insects. “It’s a nuisance to get permission to deal with animals,” he says. “NIH doesn’t regard insects as animals, so you don’t need an ethics review of insect trials.” In a 2012 report in the Journal of the American Chemical Society, Scherson and colleagues explain how they devised an air-breathing enzymatic biological fuel cell using cockroaches.

He sees cockroaches as the next generation of first responders. “There is a real problem in creating a self-powered drone that can, for example, crawl under rubble,” Scherson says. Better than a robot, he thinks, would be a roboticized insect. Biological fuel cells could power communications between the bug and a remote operator who controls its movements.

The idea’s not that far out. Researchers at North Carolina State University, in Raleigh, have demonstrated that they can control some movements in both cockroaches and moths. Scherson envisions adding a biological fuel cell that would provide power for the electronics controlling a roboticized insect or for sensors that could tell first responders if an area is safe for humans. He has already demonstrated a basic version of this: a living, mobile cockroach that generates its own power to broadcast a signal to a receiver.

He also thinks the design could be adapted with microphones or cameras to recruit bugs as spies. “If a fly was flying in a room or stuck to a wall, nobody would think that was anything special,” he says. “Unless the bug had a self-powered recording device.” He says the CIA has already been in touch.

Three creatures better than one?

Two years ago, Evgeny Katz decided to push the boundaries further, looking for new approaches and collaborations to speed progress toward field-ready devices. With a thick Russian accent and a burst of white hair and mustache, Katz’s optimism is infectious.

He began with a snail. Like others before him, Katz saw electrical output in his fuel cell drop off quickly, falling by three-quarters in the first half hour. However, his team at Clarkson University in Potsdam, N.Y., found that the original levels could be reached again and again if the snail was given food and allowed to rest.

To get more power, Katz began wiring animals together. Three clams with biological fuel cells turned a small electric motor in an experiment reported in the September 2012 Energy & Environmental Science. The following year, his team used two lobsters to power a digital watch. Katz then came as close as anyone to realizing one of the technology’s longest-sought goals: Using laboratory equipment to mimic the conditions in a human circulatory system, Katz ran a pacemaker using five connected biological fuel cells.

It was a big achievement, but it doesn’t translate well to live animals. When he tried implanting two biological fuel cells in a single lobster, he was surprised to find they made only slightly more power than one cell on its own. The lobster, with its conductive fluid and tissue, was short-circuiting. Instead of completing a circuit through all four electrodes, the current skipped from one cell’s cathode to the other’s anode, leaving half of the electrons — and their electrical energy — stranded.

Even worse, Katz realized, the enzymes were woefully inefficient. He calculated that during his snail experiment only 6 percent of the enzymes were generating electricity. The chemical reactions with glucose were happening, but the enzymes weren’t making a good connection with the electrode. “Inside the pretty big enzyme there is a small protected piece responsible for reactions sitting somewhere in the middle,” says Katz. Good for enzyme selectivity; bad for generating power when the electrical connection can’t reach deep inside the enzyme.

One solution is to embed the enzymes within a conductive substance that coats the electrode and can offer a bridge to the electrode for electrons. It’s worked for Heller, Cosnier and Scherson, but the conductive mediator adds bulk to the biological fuel cell. Katz experimented with buckypaper electrodes to offer more connecting surface area for the enzymes. Buckypaper is made of tangled carbon nanotubes compressed into a sheet. Unfortunately, some of the tangles leave big holes between fibers. Enzymes can float in these holes without touching the conductive carbon.

“The distances between the nanowires are approximately 100 or 200 nanometers,” Katz says. “The size of the enzyme is much smaller, about 5 nanometers.” He thinks only better nanotechnology can solve that problem, by adding conductive gold nanoparticles to fill space in the buckypaper or finding a way to compress the nanotubes more tightly.

Better electronics

Limited by the energy in a glucose molecule, research groups have struggled to produce the kind of power needed for implantable medical devices. Heller’s grape made a little more than half a volt. Lobsters and clams don’t do much better.

To break through these fundamental limitations, Katz has partnered with Patrick Mercier, an electrical engineer at the University of California, San Diego, to improve the electronics of biological fuel cells. Mercier is building circuits and transmitters that could operate within the capabilities of enzymatic biological fuel cells.

“I can design electronics that will try to optimize the amount of energy that we can extract from the biological fuel source,” Mercier says. This could include regulating the enzyme reactions to limit fuel consumption so the cell doesn’t run through all the available sugar or oxygen so quickly. He is designing converters that can step up the voltage that biological fuel cells produce to a level better suited for electronics. He and Katz have also tested capacitors, which store and quickly discharge small amounts of electricity. In a video available online, Katz’s team uses a lobster to charge a capacitor, which he gleefully uses to power a small fan — briefly.

These advances may yet lead to battery-free pacemakers. But the advantages of air-breathing cathodes like Nishizawa’s mean that biological fuel cells on patches or other external arrangements will probably appear before truly implantable fuel cells.

Contact lenses, for example, could carry sensors to monitor health, or come equipped with miniaturized displays, cameras and other electronics. Google announced in January a design for a contact lens that could help diabetics monitor their blood glucose levels. The company designed its lens to be powered wirelessly. Although it hasn’t released the full details, almost all wireless power systems waste large amounts of energy in transit. Sergey Shleev of Malmö University in Sweden says biological fuel cell power may be a better option.

Shleev has designed a similar lens that runs on human tears, which contain many of the same compounds as blood and other fluids. In lab tests described last year in Analytical Chemistry, he demonstrated a biological fuel cell that runs on vitamin C, or ascorbate, from tears collected from volunteers. “I can provide a biological fuel cell making a small amount of power,” Shleev says. “Can we incorporate useful electronics into the lens with those power requirements?” Google seems to have shown that it can, and Shleev says he is testing his own prototype for a competing human-powered lens.

In 10 years, enzymatic biological fuel cell researchers have shown small but measurable progress. “The power density is there and if we can get these to work over a long period of time, absolutely we can use these to power pacemakers, possibly cochlear implants,” Mercier says, optimistic that the limits that Heller ran up against may some day be surpassed.

Scherson recalls the moment he powered up his latest cockroach: “Now, we have constructed a cyborg.” Reality seems more like science fiction every day. But any sentient computers out there, please note: It will probably be a few more years before you can wire us up as living batteries to power your Matrix dreams.

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