Abstract: The disclosure provides methods and compositions for reducing nucleotide impurities in reagents and reaction mixtures. Generally, the methods of the invention involve the inclusion of so-called “scrubbing oligonucleotides” (or “scrubbers”) that preferentially incorporate nucleotide impurities, thereby reducing available free impurities. The disclosure further provides methods of sequencing a target nucleic acid by synthesis that utilize “live” scrubbing. Scrubbing oligonucleotides of various structures are disclosed, including hairpin scrubbers and homopolymeric scrubbers.