A negative control describes a sample that has been treated with the same reagents as your 'unknown' samples but does not contain the analyte of interest. For example, if you were designing an experiment to assess the concentration of protein in a sample, the negative control would be a tube of protein-free buffer. The negative control would be treated in the same manner as the protein samples (i.e. boiled with colorimetric agent). The negative control gives a baseline reading and indicates if there is any matrix interference from the buffer.