Marie,
I do not understand your situation, so I have some questions/comments:
1. I do not understand what you mean by "best" DOE. First, how do you define best? It is unlikely anyone can do this, so my advice is to create multiple designs and compare and contrast them (precision, resolution, inference space, efficiency, etc.). Predict what information/knowledge is possible from each experiment and weigh his against the resources required.
2. I completely agree with Phil that using categorical response variables can be very inefficient. You will lack discrimination especially with less than 5 categories. This usually results in needing large sample sizes to evaluate. It would be helpful to know what the responses are as we may provide thoughts on how to modify them, but understand this may be proprietary.
3. I am confused by some of your statements. They seem to be contradictory:
"I need to include negative control for that..." and "negative control is not an option" ?
and then "this design doesn't use the value 0 for my continuous factor."
So do you want 0 as a level in the experiment or not for the continuous factor?
"All models are wrong, some are useful" G.E.P. Box