When I last spoke to John Rogers from the University of Illinois, we talked about his new “electronic skin” – a patch that can be applied like a temporary tattoo, that monitor heartbeats and brain activity, and that flexes and bends without breaking. We talked about his curved camera, inspired by the human eye. We spoke about his flexible medical sensors that can mould to the contours of a beating heart or the fissures of a human brain. We chatted about the $500,000 MIT-Lemelson prize that he had won for his inventions.
I tell you all this because I want you to understand that when John Rogers says his team’s new invention is “some of our best stuff ever”, he’s not speaking lightly.
Rogers has now created a line of “transient electronics”, which last for a specified amount of time before completely dissolving away. Having made his name by taking rigid and brittle electronics and making them flexible and bendy, he has now flipped durability on its head too. Electronics are typically engineered to last as long as possible, but Rogers wants to create machines that will disintegrate after a given time. And his team have already shown how this disappearing tech could be used to make medical implants that are absorbed by the body after their work is done.
Medical implants are an obvious application, and the one that led them down this road in the first place. They have already been working on flexible sensors that can be implanted into the brain and heart, to monitor for signs of epilepsy or heart attacks. “The thing you bump up against is how to get these things to survive in the body for a long time without adverse effects,” says Rogers. “One way to deal with that problem is to move around it. A lot of these implants don’t need to last forever.”
None of our machines can do what a cuttlefish or octopus can do with its skin: change its pattern, colour, and texture to perfectly blend into its surroundings, in matter of milliseconds. Take a look at this classic video of an octopus revealing itself.
But Stephen Morin from Harvard University has been trying to duplicate this natural quick-change ability with a soft-bodied, colour-changing robot. For the moment, it comes nowhere near its natural counterparts – its camouflage is far from perfect, it is permanently tethered to cumbersome wires, and its changing colours have to be controlled by an operator. But it’s certainly a cool (and squishy) step in the right direction.
The camo-bot is an upgraded version of a soft-bodied machine that strode out of George Whitesides’ laboratory at Harvard University last year. That white, translucent machine ambled about on four legs, swapping hard motors and hydraulics for inflatable pockets of air. Now, Morin has fitted the robot’s back with a sheet of silicone containing a network of tiny tubes, each less than half a millimetre wide. By pumping coloured liquids through these “microfluidic” channels, he can change the robot’s colour in about 30 seconds.
Sticking to surfaces and walking up walls are so commonplace among insects that they risk becoming boring. But the green dock beetle has a fresh twist on this tired trick: it can stick to surfaces underwater. The secret to its aquatic stride is a set of small bubbles trapped beneath its feet. This insect can plod along underwater by literally walking on air.
The green dock beetle (Gastrophysa viridula) is a gorgeous European resident with a metallic green shell, occasionally streaked with rainbow hues. It can walk on flat surfaces thanks to thousands of hairs on the claws of their feet, which fit into the microscopic nooks and crannies of whatever’s underfoot. Most beetles have the same ability, and some boost the adhesive power of their hairs by secreting a sticky oil onto them.
These adaptations work well enough in dry conditions, but they ought to fail on wet surfaces. Water molecules should interfere with the hairs’ close contact, and disrupt the adhesive power of the oil. “People believed that beetles have no ability to walk under water,” says Naoe Hosoda from the National Institute for Material Science in Tuskuba, Japan.
They were clearly wrong. Together with Stanislav Gorb from the Zoological Institute at the University of Kiel, Germany, she clearly showed that the green dock beetle has no problems walking underwater. The duo captured 29 wild beetles, and allowed them to walk off a stick onto the bottom of a water bath. Once there, they kept on walking. Read More
When bacteria start building cities, we’re in trouble. The normally free-floating cells can gather in large numbers and secrete a slimy matrix that they live within. These communities are called biofilms, and they grow wherever there is a surface to support them. Hospital catheters are prime real estate, but they’ll settle on everything from plumbing to oil refineries to ship hulls.
Within a biofilm, bacteria are extraordinarily durable. Antibacterial chemicals have a tough time reaching them within their slimy fortress. Even if they do, there’s always a batch of dormant cells that can persist through a chemical onslaught and restart the community. They’re involved in the majority of persistent hospital infections, and it’s easy to see why. You could bleach a biofilm for an hour and still fail to kill it. They’ve survived in pipes that are flushed with toxic chemicals for a week.
Since killing biofilms is a Sisyphean task, some scientists are trying to prevent them from forming at all. They’ve tried textured surfaces, chemical coats, and antibiotic-releasing layers. But Joanna Aizenberg has developed a new solution that goes well beyond what the competitors can do. Inspired by the flesh-eating pitcher plant, she created a material so slippery that biofilms simply cannot form upon it.
Kit Parker has built an artificial jellyfish out of silicone and muscle cells from a rat heart. When it’s immersed in an electric field, it pulses and swims exactly like a real jellyfish. The unusual creature is part of Parker’s efforts to understand the ways in which muscles work, so that he can better engineer heart tissue. And it has a bizarre intended purpose: Parker wants to use it to test heart drugs. I wrote about his work for Nature, so head over there for the main story. Meanwhile, here’s my full interview with Parker about the jellyfish. He’s a fantastic interviewee – you’ve got to imagine him almost shouting this stuff.
Building a jellyfish using rat tissue isn’t exactly a typical everyday idea. Where did it come from?
My group does cardiovascular research and I spend a lot of time thinking about building tools for early-stage drug discovery. We’re known for making actuators and things you can measure contractility with, and using micro-scale tissue engineering to build tissues on chips. Several years ago, I got really frustrated with the field. Drug companies are screaming because their drug pipelines are running dry. We don’t have good ways of treating a lot of these heart diseases in the clinic. It dawned on me that probably the reason why is that we’re failing to understand the fundamental laws of muscular pumps.
I started looking around for inspiration in a simpler system. This was late 2007, and I was visiting the New England aquarium. I saw the jellyfish display and it hit me like a thunderbolt I thought: I know I can build that.
That spring, we had a visitor: John Dabiri from CalTech, a famous fluid mechanician. He does a variety of propulsion studies on various species. He was walking down the hall and I grabbed him and said: John, I think I can build a jellyfish. He didn’t know who I was. He looked at me like I had a horn growing out of my head but I was pretty excited and waving my arms, and I think he was afraid to say no. So, he said yeah. He sent a graduate student Janna Nawroth to my lab for four years. Three of my postdocs who are on that paper are now professors – this is the best of the best that we put on that project.
And what did you actually do?
We took a jellyfish, and did a bunch of studies to understand how it activates its muscles. We studied its propulsion and we made a map of where every single cell was. We used a software programme that we had developed a few years ago, borrowed from law enforcement agencies for doing quantitative analysis of fingerprints, and we used it to analyse the protein networks inside the cells.
We found something very interesting right away: the electrical signals that the jellyfish uses to coordinate its pumping are exactly like that of the heart. In the heart, the action potential [electrical signal that travels along nerves – Ed] propagates as a wave through cardiac muscle. That’s how you get this nice, smooth contraction. The activation has to spread like when you drop a pebble in water. The same thing happens in the jellyfish, and I don’t think that’s by accident. My bet is that to get a muscular pump, the electrical activity has got to spread as a wavefront
After we had the map of where every cell was, we took a rat apart and rebuilt it as a jellyfish.
Why study jellyfish?
The one that we used is a juvenile – it’s like a thin monolayer of cells. It’s a very simple structure to build.
The great thing about this is that most tissue engineering is just arts and crafts. We throw cells together and we say, ‘It looks like a liver; there’s a bunch of cells’. Or we throw heart cells together and hope that we build bits of heart. But if I’m building an aircraft or bridge, we don’t just throw concrete and aluminium and alloys together. We do mechanical testing on the substrates. We have mathematical models and computer simulations to understand the flight of the aircraft. We know how the bridge is going to work. Some engineers build out of copper or concrete or steel. I build things out of cells. If I’m going to be an engineer rather than an artist, I’m going to need to build quality control methods into what I’m doing.
Nobody is going to get into an airplane unless they’ve done computer simulations and assumed that they’ve manufactured this within allowable tolerance. It’s not just guesswork. No one’s going to want a tissue-engineered heart or other organ put into their body unless they’ve got some manufacturers’ specification. The great thing about the jellyfish is that you can do all these highly quantitative propulsion studies. That’s why I had to have John Dabiri’s team with this – they’re the best in the world at biological propulsion. And we were able to match quantitatively match the exact same propulsion characteristics in our medusoid – our engineered jellyfish – as the real one.
The most interesting thing is that the mouth of the jellyfish is inside the bell. In order to feed itself, it creates a vortex on the power stroke that throws particulate matter up towards its mouth. We thought if we’re good, if we’re really good at this, we’re going to recreate that vortex, and we did. We found that it depended on some very precise organisation of the protein networks inside the cells.
The whole idea was to bring engineering design methodology with tissue engineering, with a very rigorous set of parameters to show that our tissue-engineered jellyfish is very much a jellyfish. Morphologically, we’ve built a jellyfish. Functionally, we’ve built a jellyfish. Genetically, this thing is a rat.
So, the jellyfish isn’t the endpoint. The point of building it, and getting it to behave exactly like a normal jellyfish, is to show how much you understand about how the cells work. Is that it?
That’s right, but it depends on the lens through which you do this. For the marine biologist who’s interested in how jellyfish swim, we’ve demonstrated how important the muscular structure is and the protein alignment inside these cells for the jellyfish to survive and feed itself. The jellyfish scientist looks at this different rather than someone who’s trying to mimic biological propulsion. They look at this as how do you build something that can propel itself with this peristaltic pumping. The tissue engineer looks at this as applying the tissue engineering methodology to the highest possible standard to tissue engineering, which hadn’t been done before.
If you’re a cardiovascular physiologist or a company doing discovery, you look at this and say: wow, for years, all we’ve measure in a dish is contractility. But there’s a big difference between that and pumping. Now we’ve shown that we can build a muscular pump in a dish. You’ve got a heart drug? You let me put it on my jellyfish, and I’ll tell you if it can improve the pumping.
The first two or three years of any drug’s lifetime is always spent in a dish. We filed a patent on this to use this and variations on it as a drug discovery assay. The next stage is to see if we can build this out of human cells. And we’ll probably build a variation on the jellyfish for actual drug-testing.
In your paper, you describe the jellyfish as a synthetic organism.
Usually when we talk about synthetic life forms, somebody will take an existing living cell and put new genes into the cell so that it behaves in a different manner. That’s synthetic biology but I think it’s overstating what you did. We built an animal. I think we’re taking synthetic biology to a new level. It’s not just about genes. It’s about morphology and function.
So has this study got you further towards understanding the “fundamental laws of muscular pumps”?
Yeah it has. The heart and your guts both have action potential wavefronts that propagate through the tissue. We’re going to try this in an octopus and squid, but my bet is that to get a muscular pump, you have to organise the electrical activity in the same way. You have this clean wavefront, not a single pulse down a one-dimensional nerve fibre. It’s got to spread as a wavefront.
We also found that the muscle cells in a jellyfish are shaped freakishly differently to a cardiac muscle cell. But if you strip away the outer part of the cells, the protein networks within that cell are universally built in the same way and aligned among cellular aggregates in the same way. We think structure begets function. What I’m really pleased about is that everything that my group has learned about the heart in terms of structure and function equally applies to the jellyfish. I feel like we’re learning some fundamental biology here. Some people do basic biology by deconstructing stuff. Engineers do basic science in a different way. What we’ve done is learned something about the basic science by building it de novo.
Bait. Tissue-engineered bait. I want to go fishing and have a much better form of bait. That’s the only thing that’s going to impress my family. They could care less about this high-order science. They want to know if they can win a bass tournament.
Seriously, there are lots of different things. We’re going to develop this into assays for drug discovery. That’s pretty important to use. We’re working on that. We’re looking to reverse-engineer other marine life-forms too; we’ve got a whole tank of stuff in there, and an octopus on order. We’re trying to build larger and smaller versions of the jellyfish so we can look at drug effects.
Here is an unfortunate clash of circumstance. Vaccines and antibiotics become useless in heat, but the countries where they are most needed – poor ones where infectious diseases are a major cause of death – are really hot. Because of this, millions of dollars are spent on keeping vaccines cold and millions of lives are affected when they can’t be.
The factory that makes a vaccine can be continents away from the arm of the child who will receive it. Those distant points are separated by the “cold chain” – a network of refrigerators, freezers, insulated vehicles, cold boxes, specially equipped depots, and trained personnel. If the chain fails, and vaccines are allowed to heat up, they rapidly and permanently degrade. This happens even in developed countries, but it’s a huge problem for developing ones, where electricity and refrigeration can be sparse luxuries.
If there was a way of stabilising vaccines so they can withstand high temperatures, it could save millions of both lives and dollars. And Jeney Zhang, a graduate student from Tufts University, has developed one possible method: wrapping vaccines and antibiotics in molecular cages of silk.
Within these prisons, the MMR vaccine and two common antibiotics were still viable after months at high temperature. Matt Cottingham, a vaccine specialist from the University of Oxford, says, “The stability is amazing. No one’s even come close to that. It’s certainly better than anything else that’s currently being used.”
Silk is no stranger to medical applications. Spewed from the salivary glands of silkworm caterpillars, this natural fibre is strong, flexible and biodegradable. It has been used to make surgical sutures, medical implants, and replacement tissues. It can also be used to imprison small molecules. Individual silk molecules come together to form a structure with tightly organised regions, interspersed with looser “pockets”. In these pockets, molecules can be shielded from the elements.
Zhang, working in the lab of silk maestro David Kaplan, showed that silk can stabilise two antibiotics – penicillin and tetracycline – as well as the measles, mumps and rubella (MMR) vaccine.
Wrapped in silk, penicillin spent a month at 60 degrees Celsius with no loss of activity. Normally, it breaks down after a few weeks at room temperature (25C), or just a day at human body temperature (37C) – a month at 60 is unheard of. Tetracycline is even more delicate. In silk, it lost 20 per cent of its activity after a month at 60C, and was unharmed at lower temperatures.
The MMR vaccine fared similarly well. The vaccine consists of weakened versions of the viruses behind the three diseases. They are shipped as a freeze-dried powder, which has to be dissolved in a special solvent before being injected.
If the powders are kept at 45C, they become completely useless within 20 weeks. If the viruses are wrapped in silk before being freeze-dried, they stay almost good as new, keeping at least 85 per cent of their original potency after 6 months, no matter the temperature. Put it another way: at 37C, it would normally take 9 weeks for the viruses to lose half their original potency, but it takes 94 weeks if they are encased in silk.
How does the silk protect its payload? It’s not clear. The silk may protect the viruses in the vaccines from enzymes that would otherwise destroy the proteins on their outer shells. Without those proteins, the immune system has no way of recognising what the virus looks like, or preparing itself for future infections. The silk might also act as a physical barrier that constrains the viral proteins and stops them from deforming at warmer temperatures. And it could keep water away from the vaccines.
There’s clearly still a lot of basic questions left to answer, not least, as Cottingham asks: “Would this be compatible with being injected into babies?” Kaplan expects so. “Silk has been used in medical devices, such as sutures, for decades and the FDA approved it for new medical products more recently,” he says. It’s a promising first step towards making the cold chain a little less brittle.
Reference: Zhang, Pritchard, Hu, Valentin, Panilatitis, Omenetto & Kaplan. 2012. Stabilization of vaccines and antibiotics in silk and eliminating the cold chain. PNAS http://dx.doi.org/10.1073/pnas.1206210109
Image by GiveWell
For engineers looking to create the next generation of armour, the ocean is the place to look. Animals from snails to crabs protect themselves with hard shells whose microscopic structures imbue them with exceptional durability, surpassing even those of most man-made materials. They are extreme defences.
The mantis shrimp smashes them apart with its fists.
That’s the animal that David Kisailus from the University of California, Riverside is studying. “People have been studying molluscs for decades because they’re thought to be very impact-resistant,” he says. “The mantis shrimp eats these guys for dinner.”
One minute, a cockroach is running headfirst off a ledge. The next minute, it’s gone, apparently having plummeted to its doom. But wait! It’s actually clinging to the underside of the ledge! This cockroach has watched one too many action movies.
The roach executes its death-defying manoeuvre by turning its hind legs into grappling hooks and its body into a pendulum. Just as it is about to fall, it grabs the edge of the ledge with the claws of its hind legs, swings onto the underneath the ledge and hangs upside-down. In the wild, this disappearing act allows it to avoid falls and escape from predators. And in Robert Full’s lab at University of California, Berkeley, the roach’s trick is inspiring the design of agile robots.
Full studies how animals move, but his team discovered the cockroach’s behaviour by accident. “We were testing the animal’s athleticism in crossing gaps using their antennae, and were surprised to find the insect gone,” says Full. “After searching, we discovered it upside-down under the ledge. To our knowledge, this is a new behavior, and certainly the first time it has been quantified.”
Anyone who has tried to pull a razor clam from a sandy beach knows that they can dig fast. These edible animals can bury themselves at around one centimetre per second, and they go deep. A clam the length of a hand can create a burrow up to 70 centimetres down.
Like all molluscs, the clam has a muscular foot, but it’s not that muscular. Based on measurements of the foot’s strength, Amos Winter from Massachussetts Institute of Technology calculated that it should only be able to dig a couple of centimetres into the mud. It shouldn’t be able to submerge its body, much less create a burrow five times longer.
But Winter knows the razor clam’s secret: it doesn’t just rely on raw power. The clam adds water to the soil just below it, making it softer and easier to penetrate. It digs by turning part of a beach into quicksand.
The clam’s digging equipment couldn’t be simpler: a pair of long valves that run the length of its body and open or close its shell; and a foot that sits beneath the them. It extends the foot downwards and pushes against it to lift the shell up slightly. Then, it contracts the valves, sending blood into the foot and inflating it. This foot becomes an anchor. By pulling against it, the clam can drag its shell downwards.
To understand how these motions create a burrow despite the foot’s weedy nature, Winter had to capture several clams. And to do that, he had to become a licensed clam digger. Back in the lab, studying the clams wasn’t easy. As Winter writes in a wonderfully deadpan academic way: “The adage ‘clear as mud’ is used to describe the difficulty of visually investigating burrowing animals.” He finally saw what the clams were doing when he created a homemade “visualiser”— a repurposed ant farm. The animal was trapped between two transparent plates, filmed with high-speed cameras, and surrounded by a ‘beach’ of glass beads.
Winter’s videos revealed that when the clam contracts its valves, it does more than just pump the foot with blood. The contraction closes its shell, which relieves the pressure on the surrounding soil. The soil starts to crumble, and mixes with water pulled into the gap from above. The water “fluidises” the soil, making it soft and loose like quicksand. It offers far less resistance, and the clam can move through it with around ten times less energy. It does so quickly, before the soil has a chance to solidify again.
Winter isn’t just studying clams for the sake of it. The list of sponsors for his study is telling: Battelle Memorial Institute, a science and technology development company; Bluefin Robotics; and the Chevron Corporation, an energy company that explores for oil and gas.
Winter used his newfound knowledge to create RoboClam: a robot that duplicates the clam’s burrowing technique. It’s about the size of a lighter, but it comes with a much larger supportive frame of pistons and regulating elements. After further development, RoboClam could act as a lightweight anchor that could be easily set and unset. It could tether small robotic submarines for studying the ocean floor; help to install undersea cables or deep-water oil rigs; or even detonate buried underwater mines.
Reference: Winter, Deits & Hosoi. 2012. Localized fluidization burrowing mechanics of Ensis directus. Journal of Experimental Biology http://dx.doi.org/10.1242/jeb.058172
Photo by Arne Huckelheim