@joshdonn your calculation is in the right direction, the focal length should be longer for a larger sensor. If I have read it correctly, you are still using a 50mm focal length lens? This is the lens required for a small sensor and will give a nice image at the distances used in the standard Openflexure optics. To fill a larger sensor you need a longer focal length lens - from your calculations a 100 or 150mm lens. Then you will also calculate that the camera also needs to be quite a bit further away from the lens than for the smaller sensor. If you have a 160mm tube length objective, then it will be about 60mm. With an infinity corrected objective you still need the longer focal length lens, but the sensor is one focal length away. Once you are up to a 100 or 150mm tube lens on an infinity corrected objective that is almost the same distance as using non-infinity lens without a tube lens.
There is a thread using the Pi High-Q camera, which is the same IMX477 sensor, from when it was first out, showing the length of the optics module with no tube lens.
The alternative approach is to crop. The resolution of a typical microscope objective over its field of view does not usually correspond to anywhere near 12MP. The Pi camera V2 oversamples the image a lot, so my opinion is that the best solution is to keep the optical system the same and crop the image on the larger sensor. You gain all of the advantages of the sensor with better colour saturation at the edges, better noise etc, and you don’t actually lose any useful information. You actually gain a bit because you can crop to a nearly square frame which will use more of the image circle of the lens than you would have for a 4:3 or widescreen sensor. This is discussed a little in the thread on the camera module 3.
None of these alternative cameras are supported in the Openflexure software version 2.X, so lens shading correction and autofocus will not work. It should be possible to implement more cameras once the Openflexure server software version 3 is released.