It depends on what type of experiment we are talking about and what type of particles we are trying to measure. Also, this isn’t really ELI5 but I’m not sure it can be… apologies…
Let’s take, for example, cosmic rays. If we want to isolate out neutrinos or dark matter, we begin by putting our experiment underground. The cosmic rays that travel through the atmosphere will have some particles that interact with the atoms in the atmosphere. This blocks these types of particles from hitting our detector. Most particles that make it through the atmosphere will then interact with the atoms in the ground before we get to our detector. Sometimes at this point, we will wrap our detector with some dense material like lead so the final remaining particles will get blocked out.
The stuff that ends up hitting our detector is the stuff that interacts weakly. This means it travels long distances without running into other particles or atoms which are allowed to interact with it. For the example given, the only stuff leftover is neutrinos and dark matter.
A lot of times in particle physics experiments, it isn’t about blocking out stuff we don’t want to “isolate” particles. Instead it is about measuring all the stuff we get and then sorting it to figure out what is what. We then keep the measurements of the stuff we were “looking for”.
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