FRANCISCO SEPULVEDA’S body has communication issues. His brain doesn’t exchange signals with the rest of his nervous system terribly well, meaning that messages don’t always reach his limbs. During bad phases he has to use a wheelchair.
He has heard all the platitudes about the coming age of brain-computer interfaces, and how advanced neurotechnology will soon upgrade his ailing neural circuits. But Sepulveda is qualified to dismiss the hype, this being his area of research at the University of Essex in Colchester, UK. “Neural engineering will probably not have a solution for this any time soon,” he says.
His longstanding misgivings took a hit late last year, however, when an invention suddenly brought the transhumanist fantasy a step closer to reality. It wasn’t much to look at – just a small switch – but it is a fundamental shift that breaks down the language barrier that has always existed between electronics and biology. Implants based on the technology may one day restore lost senses and mobility, or detect the cellular damage that leads to diseases like Alzheimer’s – and possibly even fix it.
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“These implants may one day restore lost senses and mobility, and detect and cure disease”
Whenever we have tried to interface our technology with biology, whether to eavesdrop on brain cells or use their output to drive a wheelchair, it has been with standard electronics, which are based on negatively charged electrons.
But the native language of biology is positive: its building blocks are protons and positively charged ions such as potassium, sodium and calcium. Without calcium ions, you couldn’t move a muscle. And your ability to taste the sour notes in a packet of Haribo sweets involves proton channels. Indeed, a cell’s response to any event – be it light hitting the retina or food on the tongue – involves a channel opening in the cell wall and ions rushing through, setting up a chain of events resulting in sensation or action.
It is possible to eavesdrop on these signals by translating them into electrons by way of complicated signal processing algorithms. But a lot of subtlety is lost in translation, and you certainly can’t communicate with cells on their own terms. “The interface is the biggest issue,” says , who researches bionanoelectronics at the University of California, Merced.
The ideal interface would be a biologically compatible mechanism that can control the flow of positive charges in and out of a cell. A template already exists for the device we want: the transistor, the on-off switch at the heart of all modern electronics. Every microchip in your laptop contains several hundred million such switches, which control the flow of electricity by stopping and starting the movement of electrons when an external electric field is applied – an effect rather like stepping on a hosepipe.
We have tried for decades to make a transistor that both controls positive charges and is compatible with the body. Since the 1990s, engineers have built various devices that push sodium, potassium and calcium ions into cells (Sensors and Actuators A: Physical, vol 93, p 8). But these have proved hard to build from polymers that are biocompatible (). Efforts to send electrons through biological materials also fared badly: biology simply doesn’t conduct well ().
Then, two years ago, Marco Rolandi and his colleagues at the University of Washington, Seattle, stumbled across maleic chitosan, a sugar molecule found in squid pens and crab shells. They noticed that when it was kept in a humid atmosphere, hydrogen bonds developed between the material’s fibres, which allowed protons to hop along the fibres. To convince them to hop, all Rolandi’s team had to do was apply an external electric field, or voltage (). “It works by the exchange of bonds,” he says, rather than the mechanisms that lead to electron flow. They had found a way to push positive charges around at will.
Best of all, chitosan is soft and pliable. Use it to replace today’s metal-based electronic implants, such as brain stimulators, and it should cause less trauma and less scarring.
In the near term, Rolandi thinks the proton transistor will be useful for listening in on the chatter between neurons without losing anything in translation. Noy sees great potential in this. “In the next decade, I think we should see something very interesting in the field of diagnostics,” he says, such as implants that monitor cell activity. “If we can read the state of a single cell, we might be able to see when the cell is in trouble.”
It is early days, and as yet, Rolandi’s device struggles to even fully qualify as a transistor – it is little more than a few nanofibres that can be opened or closed to the flow of protons. The “off” switch on electronic transistors cuts electron flow by a factor of 10,000; Rolandi’s cuts proton flow by a factor of around 10.
Still, it is worth remembering that, for the proton transistor, it is 1947. That was when scientists at Bell Labs produced the first electronic transistor. It was about a centimetre high, while today Intel routinely squeezes 4 billion of them onto a single microchip.
Since proton and electron transistors are so similar, Rolandi thinks it is feasible to use the latter as a guide. For example, one of the many variables that control the on-off ratio is the “gate” electrode that applies the external electric field (see diagram). “If we make the gate thinner, that will lead to better performance,” he says. He is also trying to improve the conductivity of the material: there might be a polymer with a higher proton concentration than chitosan, and the team is now working to find it. Eventually, Rolandi thinks the proton transistor could lead to a way to control the flow of ions.
That is where the far-reaching applications are. Ion control would make it possible to go beyond listening to cells, and start talking back. This is what intrigues Ravi Bellamkonda, who works on neural interfaces at the Georgia Institute of Technology in Atlanta.
Bellamkonda says that controlling the flow of ions and protons across cell walls – sometimes pushing them in, sometimes sucking them out – might offer a novel path to curing disease. A huge roster of afflictions, including Alzheimer’s and Parkinson’s disease, are associated with the presence of reactive oxygen molecules whose unpaired electrons create what is known as “oxidative stress”. To mitigate this, cells use proton currents. If you could mimic these by pumping protons into cells, you could mop up the oxygen radicals. Similarly, an ion-pumping transistor could inject charge into a cell to change its state. That raises the possibility of reversing the damage done by oxidative stress and perhaps even controlling the process of degeneration and fine-tuning, say, kidney function.
Research on ion transistors is in full swing elsewhere. In May, researchers at Linköping University, in Norrköping, Sweden, reported a promising new approach (Nature Communications, vol 3, p 871). Regardless of who cracks the puzzle first, one thing is clear: the era of bioelectronics is at hand.
Right now, Sepulveda has hearing aids on both ears, but he reckons these devices will be a thing of the past within his lifetime. “I am hopeful that within the next 30 to 40 years we will have implants that will fully restore lost vision and hearing,” he says. The proton transistor, he says, “opens the door to amazing possibilities”.
