YOU鈥橰E making such a racket it鈥檚 a wonder you can hear yourself think. Noisy bacteria are carousing in your gut. The mitochondria in your cells are humming like power stations in overdrive, and replicating DNA strands are unzipping with a noise like tearing metal. Every bit of you drums out a unique acoustic signature. Up close, your body sounds like a badly tuned orchestra playing Times Square at rush hour.
Now imagine that somewhere in all that biological commotion, cancer cells have started to divide. As they spread, they play a melody that to a trained ear is as distinctive as the strains of Elgar鈥檚 cello concerto. No artificial ear, however well trained, is sharp enough to penetrate the cellular caterwauling to pick out the distinctive sounds made by those cancer cells. But Flavio Noca hopes to change all that.
Noca, a physicist and engineer at the Jet Propulsion Laboratory in Pasadena, California, is part of a team that has built a prototype of the ultimate in microscopic ears. They hope these ears will eventually, be so small and so keen they will be able to tell apart two kinds of cell simply from the racket they make. By injecting them into your bloodstream, the nano-ears could be used to eavesdrop on your metabolism like miniature stethoscopes, spotting diseased or cancerous cells before they get a chance to spread. If they are keen enough, Noca鈥檚 nano-ears might even be sent to other planets to listen for creatures or identify chemical reactions in alien oceans, using nothing more than the symphony of clicks, shrieks and bangs they produce.
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It鈥檚 not as bonkers as it sounds. Talk to any bird watcher and they鈥檒l tell you how easy it can be to identify creatures from their calls. So why shouldn鈥檛 the same apply on a smaller scale? 鈥淎s microorganisms crawl around and do biochemistry, they make noise in the same way that a steam reactor makes noise,鈥� says Kenneth Nealson, director of JPL鈥檚 Center for Life Detection. The movement of flagella and cilia, and even cell division and respiration, may make distinctive sounds. 鈥淭hink of the sound a Volkswagen makes compared to the noise of a truck. The pitch and pattern of sound are very different and the same could well be true for different kinds of organisms. But no one鈥檚 thought much about the significance of those noises because we haven鈥檛 been able to hear them very well.鈥�
Things began to change in 1999, when Noca and a team at JPL decided to give planetary explorers a new tool: a robotic probe with super-sensitive hearing. Land it on a planet鈥檚 surface and the probe could put its 鈥渆ar鈥� to the ground and listen out for tiny life forms going about their business.
This is far easier said than done. Today鈥檚 state-of-the-art microphones use a flexible membrane that vibrates in response to sound waves. This motion is picked up electrically and amplified. But if you want to listen out for the faint whispers of minute creatures, membranes simply don鈥檛 cut the mustard. Large ones are relatively heavy, so quiet sounds don鈥檛 have enough energy to set them wobbling. Making them smaller and lighter doesn鈥檛 help either, since the tinier a membrane gets, the stiffer it becomes. In other words, its sensitivity plummets. Noca did the maths and realised that membrane mini-microphones were a dead end.
The answer, he decided, was to steal a trick from nature. In the human ear, for example, sounds picked up by the eardrum are passed, via three bones, to the cochlea, a fluid-filled organ about the size of a pea. Inside the cochlea are rows of hair cells-about 15,000 in all-topped with tufts of fine filaments called stereocilia. Acoustic vibrations move the fluid in the cochlea and waft these stereocilia in much the way that gusts of wind shiver the branches of willow trees. Each time they move, the stereocilia trigger electrical impulses that the brain interprets as sound. Stereocilia are so sensitive that we can distinguish among up to half a million sounds.
Noca and his group decided that carbon nanotubes-a cylindrical form of the buckyball structure-would make perfect synthetic stereocilia. Nanotubes are more durable than diamond, yet flex as easily as human hairs.
However, at the time, it was almost impossible to make these tubes in the huge quantities that artificial ears would require. The only manufacturing technique available was lithography-using electron beams to build the tubes up slowly layer by layer. But then Noca got to know Jingming 鈥淛immy鈥� Xu.
Noca鈥檚 colleague Brian Hunt was a friend of Xu, then professor of emerging technologies at the University of Toronto. In 2000, they met up and Xu told Hunt about his novel way of growing carbon nanotubes the way a turf farm grows grass: you sow the seeds, give them everything they need to germinate and let nature do the rest.
Sowing the seeds
Xu, now at Brown University in Providence, Rhode Island, begins by passing a current through a sheet of aluminium. This dimples it with thousands of tiny pores that vary in size from 4 to 200 nanometres across and up to several thousand nanometres deep. Xu then uses each pore as a miniature plant pot into which he drops a seed or catalyst- typically ions of cobalt, nickel or iron.
To start his nanotubes growing, Xu bakes the seeded pots in a furnace at about 700 掳C. He then pumps acetylene gas across them. At this temperature, the acetylene molecules split apart and any free carbon atoms that come into contact with the seeds stick and start to form into a regular lattice structure. The nanotubes begin to grow.
Xu鈥檚 carbon cilia are just what Noca鈥檚 team needed. About 10 billion can be grown on a patch just one centimetre square. Xu鈥檚 equipment costs about $200,000, compared with $1 billion or more for lithographic gear, so his carbon nanoturf is relatively cheap. Best of all, Xu鈥檚 nanotubes have the potential to be vastly more sensitive than the human variety. 鈥淐ilia in the ear have a diameter of around 100 nanometres and are one or two micrometres long,鈥� Noca says. 鈥淲e can make nanotubes just a few nanometres in diameter and up to 60 micrometres long.鈥� A longer and skinnier hair means greater flexibility, which translates into far greater sensitivity.
With the first hurdle cleared, Noca鈥檚 team still had to find a way to collect the electrical signals that would tell them what the filaments were hearing. 鈥淚t鈥檚 hard to make electrical contact with nanotubes,鈥� Noca points out. 鈥淲e don鈥檛 have precise control over how these things grow. Sometimes we get a good [electrical] contact-sometimes we don鈥檛.鈥�
And how do you make connections to each tube, or even collate and interpret the ocean of signals they produce. 鈥淵ou could do that for an individual nanotube using existing instruments, but the challenges of instrumentation and interpretation for 10 billion is too huge,鈥� Xu says.
Light, rather than voltage, may be the answer. 鈥淲e鈥檙e looking at ways to read the signals optically,鈥� Xu says. Optical microscopes aren鈥檛 sensitive enough to see individual tubes move. But you could shine a laser beam over the whole lot and watch the nanotubes waving in the acoustic wind like a field of corn, Noca suggests. 鈥淭he patterns [of scattered laser light] would tell you which trees are moving, how much, and in which direction.鈥� They鈥檝e already done some preliminary tests and, eventually, Noca hopes to build a computerised library of the light patterns from different sounds. By comparing a pattern of scattered light with patterns held on file, a computer should be able tell just what frequencies the nano-ears are hearing, and even which direction the sounds are coming from. The target sound-for example the rumblings of a mitochondrion-will have a distinctive frequency spectrum. This signature will allow it to be distinguished from the overall din, in the same way the absorption spectrum of a particular molecule can be used to single it out in a test tube of pond water.
Sounds spaced-out
These devices could really come into their own in space. On a quiet planet we might easily be able to hear new and exciting sounds, Nealson says. Just as fish use rows of stereocilia along their sides to detect their prey, perhaps we could listen out for tiny creatures swimming in the oceans that are believed to exist beneath Europa鈥檚 icy crust. Nano-ears may be useful for detecting life on Mars, too. 鈥淐ould we tell the difference between a bacterium growing on glucose and one growing on glycerol? Or between one using oxygen and one doing fermentation? I wouldn鈥檛 be at all surprised,鈥� says Nealson. 鈥淲e have these organisms in culture, ready to test, and I鈥檓 standing in line to do the experiments when Flavio鈥檚 team has devices ready.鈥�
If the ears work in space, why not closer to home? 鈥淲e might someday be able to make an artificial cochlea,鈥� he suggests, 鈥渙r test water quality by listening for the rhythms of swimming microbial life.鈥� The devices could even open up new ways to monitor and analyse human health. Imagine a free-floating nanostethoscope that circulates in your bloodstream, says Noca, tuned to listen out for particular cellular malfunctions.
Some of the groundwork has already been done. Physicist Josef Kas at the University of Texas鈥檚 Center for Nonlinear Dynamics studies the elasticity of benign and malignant cells and has demonstrated that normal and cancerous cells have different elastic properties. So they should have different resonant frequencies, says Noca.
If the nanostethoscope hears the characteristic frequencies of tumour cells, for example, it could send a radio signal to doctors who could then use it like an electronic tracking device to pinpoint the location of the malfunctioning cells. 鈥淲e could send these devices throughout your body, interrogate them with an acoustic signal or radio waves, and find the location of the ones that were vibrating. This could allow you to detect cancer at the earliest stage, when only a few cells are malignant.鈥�
It won鈥檛 be easy. 鈥淐ancer cells do have a different elasticity than normal cells, and elasticity is related to sound,鈥� Kas acknowledges. But a cell is like a highly viscous polymer gel with a lot of different components, he says. A cancerous cell wouldn鈥檛 produce a single resonant frequency-more probably it would ring with a broad but unique spectrum of sounds. But, he adds, 鈥淚 don鈥檛 see any reason why Noca鈥檚 idea can鈥檛 work. The worst way to detect cancer is to look for molecular changes in cells. Looking at material properties of cells is definitely the way to go.鈥�
Carbon nanotubes are not toxic and they could also be coated with substances such as polyethylene glycol to help render them almost invisible to the human immune system. Then they could be bundled with a microscopic package of electronics and injected to roam the body鈥檚 byways. It shouldn鈥檛 be too difficult to wire up and collect electrical signals from a simple nano-ear with just a few tubes, says Noca. NASA鈥檚 Ames Research Center in Moffett Field, California, has already created a 鈥減ill鈥� loaded with electronic sensors to monitor the body from within.
We might not have to wait long to see whether Noca鈥檚 device will work. Although it will be a decade or more before doctors keep nanostethoscopes in their medical bags, he expects to have prototypes within three years. To that end, his team is testing different sizes of nanotubes, substrates and ways to pick up the data, and recording their performance in air, water and body fluids such as blood. 鈥淲e can make single-walled tubes thinner-with a diameter of just a few nanometres-and thus more sensitive to vibration,鈥� he says.
So how about listening out for dangerous bacteria? 鈥淲e鈥檙e probably years away from being able to listen to a single bacterium, but bacteria don鈥檛 grow by themselves,鈥� says Nealson. 鈥淭hey grow in colonies of a billion or more.鈥� Multiply the sound of a single bug by a factor of one billion, and there鈥檚 a good chance we鈥檒l hear something, he says.
鈥淢y guess is that within the next year we鈥檒l know whether we鈥檙e able to distinguish bacterial colonies by the fundamental acoustic differences between them. If the approach doesn鈥檛 work, we鈥檒l know soon. If it does, it鈥檒l stimulate a lot of new work.鈥�
Some applications in other fields could be mind-boggling. At the University of Cambridge, for instance, chemist David Klenerman is already exploring novel ways to 鈥渓isten鈥� to the sounds of chemistry (see 鈥淢olecular popcorn鈥�). However, Noca鈥檚 nano-ears could offer a level of sensitivity that Klenerman can only dream of. Eventually, nano-ears may be able to identify chemicals or particular types of reaction, or even decode DNA from the sounds it makes as it unzips. 鈥淎coustics at the molecular level is uncharted territory,鈥� says Klenerman. 鈥淣oca has a lot of work left to do, but there鈥檚 no physical barrier suggesting it isn鈥檛 possible.鈥� Noca can鈥檛 wait to get started. 鈥淭here鈥檚 a whole world buzzing down there and many questions are looking for answers,鈥� he says. 鈥淥ur stereocilia will begin to provide them.鈥�
