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For such material a vacuum bed would probably be the best solution. The Meteor MDF top can be removed an a torsion box/vacuum box could be hung inside the frame.
For the little experience I have cutting acrylic on a CNC I used t-track clamps around the perimeter, and tabs to keep the parts in place as they were cut.
You could just pre-drill and screw your acrylic sheets down to the MDF bed. Be sure and not put a screw anywhere the bit may run.

I'm going to recommend you intentionally try many strategies. That's the only guarantee you'll figure out what works best for your specific needs.

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