Suhasa Kodandaramaiah was one of about 30 people on Earth who could perform something called whole-cell patch-clamping, a technique for studying the inside of a cell developed back in 1981. By hand, it is a painstaking process that, on a good day, lets a researcher examine around three or four individual cells.
Craig Forest, an assistant professor at the George W. Woodruff School of Mechanical Engineering at Georgia Tech, wanted to improve on that number. He, Kodandaramaiah and Ed Boyden, associate professor of biological engineering and brain and cognitive sciences at MIT, decided to try and build a machine that would democratize a technique previously available only to a talented few.
Their first attempt failed. The team initially wanted a robot that could take multiple samples at the same time; after that didn’t work, they concentrated on a robot that could measure electrical activity inside of a single neuron.
What they developed could change how we test drugs forever, not to mention provide a kind of periodic table for neurons in the brain — a detailed map of which neurons do what and how they all interact. We can already measure how sections of the brain work with metal electrodes. That, however, only gives scientists part of the picture.
“Extra-cellular recording with a metal wire is like just hearing the drumbeat of an orchestra,” says Forest. “Inter-cellular measurement with a glass pipette is like hearing every single instrument in an orchestra.”
The machine — tentatively named an auto-patcher — uses a robot arm to move a glass pipette around in three dimensions. The pipette’s point comes down to a micro-needle, which is smaller than a single cell.
As the robot inserts the micro-needle into the brain, it emits little electrical test pulses, which, if blocked, indicate the presence of a cell. The micro-needle then touches down gently on a cell membrane without breaking it; after a suction seal is formed, an electrode breaks through the membrane.
“It lets you discover all the aspects of what a neuron is doing,” says Forest. “Not only an electrical signal, but also the genes that are being expressed and the shape of it. It gives you a complete identification of that neuron.”
Nobody knows how many different kinds of neurons are in the brain — estimates run anywhere from hundreds to tens of thousands. Get this technology in the hands of multiple researchers and you could start identifying every single neuron that exists, a cause supported by none other than Microsoft co-founder Paul Allen and his Allen Institute for Brain Science. The task would be made even easier if the team can make good on its goal of creating a robot that can measure multiple neurons at the same time, thus getting a better picture of how they interact.
The technology has more immediate implications as well. Forest, Boyden and Kodandaramaiah recently started a company called Neuromatic Devices, which could help get the robot in the hands of pharmaceutical companies.
“Being able to look at the programming of a cell is a very powerful way of learning what makes a cell what it is, how it changes and how it responds to a treatment,” says Boyden. The idea is that you could discover how old drugs work and develop new ones to fight brain disorders such as Parkinson’s disease, schizophrenia and epilepsy.
Even beyond the brain, the robot has plenty of uses. The team sells the machine through its company, but it also gives away detailed instructions on how to build and program it through the website autopatcher.org. The idea is to create a community that would trade code and modify and improve the original computer algorithm for other uses.
For example, the robot can do more than just measure electrical activity. Once that seal is formed with the membrane, it could infuse the cell with a chemical or extract messenger RNA and figure out what makes the cell tick. Researchers could also go beyond neurons to study things like tumors and stem cells.
The guys who developed the old hands-on approach to patch-clamping won a Nobel Prize in 1991; if Forest, Boyden and Kodandaramaiah can scale this technology up, they might have a few awards coming their way as well.