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Before a person we use with or in, before a thing we use at, about or by and before a gerund we use at; Keith is very disappointed at not winning the prize. We use that (optional before a new clause): I was disappointed (that) I didn't get an invitation.
We use in when we are referring to the final work: The drawing was done in charcoal. Dora writes her letters in green ink. When we are referring to the instrument used we use with: The children are learning to write with a pen. Helen prefers to paint with a thin brush.