To figure out how your brain works, researchers need to be able to measure the electrical activity of neurons. But now, a new method allows robots to perform the task instead.
Your brain and nervous systems are made up of neurons, sending and receiving the electrical signals that let us breathe, move, think, remember, and generally function. So knowing how individual neurons work, their patterns of electrical activity, and which of their genes are activated at any given time also will also give us insight into how the brain functions as a whole.
But how exactly do you crack open a neuron to analyze its activity? The current method of doing so is a highly specialized technique called whole-cell patch-clamp electrophysiology. In this method, you touch a hollow micro-pipette to the cell membrane of an individual neuron, as in the illustration. Gently, suck a tiny section, or "patch," of membrane into the tip of the pipette without rupturing the cell. Now, you can study the ion channels in that particular patch of membrane.
But let's be even more ambitious. The next step is to apply stronger suction, displacing your patch and leaving the pipette tip sealed to the outside of the cell. Through the open pore in the cell membrane, instruments can record the entire neuron's activity.
As you might imagine, patch-clamp is a fussy and difficult technique that requires months of training, limiting its practice to few laboratories. But what if you could automate the process? Instead of training humans to perform patch-clamp, labs could just order a robot programmed to do the job.
Researchers at MIT and the Georgia Institute of Technology have delegated whole-cell patch-clamp electrophysiology to a robot arm equipped with a cell-detection algorithm. The arm lowers the patch-clamp pipette into the brain of an unconscious mouse while measuring how easy it is for electricity to move out of the pipette. With no cells nearby, electricity flows easily, but when the pipette runs up near a neuron, the flow is impeded, allowing the arm to detect a cell. Under the guidance of an algorithm, the pipette moves along in two-micron increments, measuring the electrical impedance ten times every second and stopping as soon as the impedance shoots up, indicating the presence of a cell. Once it senses the cell, the robot arm can perform the patch-clamp procedure on it.
So far, the automated robot arm is great at detecting the cells, finding neurons 90 percent of the time, but it's not as good at performing the patch-clamp technique, only creating the connection about 40 percent of the time. Still, considering that humans can't get it right all the time either, the robot arm is pretty good at this technique, and it doesn't require a lengthy training process.
Based on their results, the researchers suggest that even more neuroscience could become automated:
"We have developed a robot that automatically performs patch clamping in vivo and demonstrated its use in the cortex and hippocampus of live mice. We anticipate that other applications of robotics to the automation of in vivo neuroscience experiments, and to other in vivo assays in bioengineering and medicine, will be possible. The ability to automatically make micropipettes… and to install them automatically, might eliminate some of the few remaining steps requiring human intervention. The use of automated respiratory and temperature monitoring could enable a single human operator to control many rigs at once, further increasing throughput."
While having robots examine brains for us would certainly be convenient, time-saving, and possibly more precise than human operators, I have to ask: Would you trust a bot with your own open skull? True, humans can make devastating mistakes without machine intervention, but the idea of one of our robot brethren cracking my head open still makes me a wee bit nervous.
Via Nature Methods