We define three different types of spanning surfaces for knots in thickened surfaces. We use these to introduce new Seifert matrices, Alexander-type polynomials, genera, and a signature invariant. One of these Alexander polynomials extends to virtual knots and can obstruct a virtual knot from being classical. Furthermore, it can distinguish a knot in a thickened surface from its mirror up to isotopy. We also propose several constructions of Heegaard Floer homology for knots in thickened surfaces, and give examples why they are not stabilization invariant. However, we can define Floer homology for virtual knots by taking a minimal genus representative. Finally, we use the Behrens-Golla -invariant to obstruct a knot from being a stabilization of another.

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