You can configure your fans however you like, use as many dust filters as you can, and make sure your PC is well away from carpets and floor-bound fluff, but at some point, the inside of your case is going to get dusty. You can't escape it, and it's a good idea to clean your PC now and then if you want to keep your components' temperatures manageable. Here are the methods we use to safely and thoroughly clean out our computers.
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The most important thing to consider when cleaning your case is that we want to make it possible for cool, fresh air to get into the case and hot air to get out. If dust filters are clogged or there's excess dust collected around the heat sinks, that's not going to be possible and your system could overheat.
To counter that, you want to do everything you can to eliminate dust and leave your system fresh and clean.
Note: Whenever cleaning your PC or its components, you need to take extra special care about static damage. Using an anti-static wristband is ideal, but if you don't have one to hand, make sure to regularly ground yourself by touching your case or PSU housing.
Once you've knocked all the dust loose, use a vacuum cleaner to clean up any dust that ends up on the floor. However,don't use the vacuum directly on the interiorof your case, as there is a real risk of static damage. (You could use one as a blower in a pinch, which Jarred regularly does, but don't get the tip close to sensitive components.)
If your PC hasn't been cleaned in a while, there's a good chance you have dust caked onto the fans, vents, and heat sinks. In this case, a quick dusting won't get you much further than the below picture, and you'll need to do a deep clean.
If you display your PC like a work of art as much as a functional tool or gaming machine, then you'll want to do more than just give it a light dusting. For that, we'd recommend removing everything from the case. That means redoing all of your cable management, draining the water-cooling loop, and unhooking all your drive caddies. The end result, though, is worth it.
Note: We still recommend an anti-static wrist band when handling any components. If you don't have one to hand, periodically touch your PC case to ground yourself.
There are certain components, like the interior of your PSU, that you aren't going to be able to clean effectively without taking it apart and voiding your warranty. Doing so can be dangerous, too. Instead, we'd recommend using a can of compressed air with a long straw attached to give it a little blast to dislodge any stubborn dust. When you next turn it on, its own fan and natural airflow should blow any loosened dust out of the rear.
When you're finished cleaning, put everything back together. Take this opportunity to do a little cable management as it can help avoid dust build up by making for a cleaner passage of air through your system.
To maintain a healthy system, we recommend a light dusting at least every three to six months, or more often if you have pets or live in an especially dusty environment. For deep cleanings, every six months to a year is recommended if you want to maintain peak performance, or every couple of years at the very least to avoid any potential overheating issues.