The lower maximum labelling achieved through 15N innevitablly leads to smaller density addition to labelled DNA and RNA and hence to a smaller separation of labelled  from unlablled nucleic acids during density centrifugation. For DNA-based SIP this creates a major challange since double-stranded DNA is known to migrate in a density gradient not only as a function of its mass but also as a function of its hydration state, which is ultimately determined by the G+C content (REF). Already in the first attempts to develop 15N-SIP it s has been noticed that due to the relatively small migration of 15N-lablled DNA, unlablled DNA with high-G+C content could overlap even with fully labelled DNA with lower G+C content, and lead to false detection of labelling.