If you are really into closeup territory,the tripod is ,sadly (?) your best friend. You can take the pain out of the equation by adding a "Focusing rail" to the mix.
In 1:1,1:2 territory,you are dealing in depth-of-fields in the millimeter range.
Most find the placement of the tripod so fussy that they give up on it : the rail gives you micrometer adjustment in the to-and-fro,front-and back axis.
Either that,or add a motordrive,handhold,and hope you will get a sharp frame.