Perspective: Patching My Patch-Clamping
The first time I worked in a neuroscience lab was in 2014 when I joined a fundamental research group in Amsterdam and got trained in the “patch-clamp” method.
It was my first time doing wet lab work, so I had various opportunities to mess up. I fully took advantage of each one of them.
The patch-clamp technique is used to study the electrical properties of neurons and works as follows: A glass tube much smaller than the eye of a needle in diameter, known as a micropipette, is used to remove a tiny “patch” of the cell membrane in order to access intracellular space. The micropipette is filled with an electrolyte solution and there is a thin electrode that records the electrical current in the nerve cell. This electrode is connected to an amplifier that amplifies the signal, which, in turn, is connected to a digitizer that digitises the signal.
If all this sounds too complicated to understand, it certainly is: it took me about six months to start having a remote idea of what I was doing. Nevertheless, I was very excited. An entire new microworld was unfolding in front of my surprised eyes.
People’s voices were filled with fear and respect when they talked about the micropipette machine. They warned new students, multiple times a day, that they should not, under any circumstances and by no means, ever, until the end of times, touch the rest of the settings except the temperature.
On my first day at the lab, Victor, another student who was one year ahead of me, taught me how to make my micropipettes. He led me to the room where the micropipette-making machine was and explained that the only thing that I had to do was put a piece of glass inside the machine, program it to the right temperature, and then the machine would heat up, melt the glass and then pull it apart from the two sides, creating micropipettes with invisibly thin tips.
This sounded straightforward, but there was something sacred about it. People’s voices were filled with fear and respect when they talked about the micropipette machine. They warned new students, multiple times a day, that they should not, under any circumstances and by no means, ever, until the end of times, touch the rest of the settings except the temperature. This would cause a great lab catastrophe and it might even break the machine, which was very expensive to fix. This terrified me, so I listened obediently and never deviated from the exact instructions that I was given: pick up a glass, put it inside, set up the temperature, and let the machine do the rest. This way nothing bad will ever happen.
Victor had his set-up right across mine, as both of us were based at the corner of the patch-clamp lab, and we shared a long desk. He was tall, skinny, and perhaps slightly awkward in his movements. His eyes were wide and blue and if you looked carefully into them, you could find hints of kindness and sadness, well-hidden behind the serious look. In the beginning, we thought that we would not get along. I thought that he was a bit too shy, maybe even arrogant. He thought that I was a bit intrusive, and certainly too loud. We would definitely not get along.
The next step, when you already had your micropipettes, was getting used to moving them towards the cells using joystick-like micromanipulators that allowed the execution of very fine and delicate movements, which are essential for the success of the operation. Neurons are apparently very easy to kill – I learned this the hard way.
Moving the micropipette towards the cells in a delicate manner is a tough task. Most students spend the first couple of days or even weeks breaking one pipette after the other, hitting them with force on the cell plates, killing several cells each time, until they finally get it. I was not an exception. I broke all my pipettes into pieces with admirable speed, then went to the machine to make some more and quickly came back to break those as well. Every broken pipette was a blow to my self-esteem. Every dead cell planted a doubt regarding whether this internship had really been a good idea, whether this master’s program had really been a good idea, whether every single life decision so far had really been a good idea. Victor tried to comfort me, saying that it happens to everyone, and I should not take it personally. This was already difficult for my impatient nature and detecting a tone of amusement in his comforting words was not very helpful.
Every broken pipette was a blow to my self-esteem. Every dead cell planted a doubt regarding whether this internship had really been a good idea, whether this master’s program had really been a good idea, whether every single life decision so far had really been a good idea.