I have 4 .sff files (each about 250 MB, with a total of about 350000 sequences). When I merge them using the merge.files command, and subsequently subject them to trim.flows(), it just keeps going, with the scrap file-size just increasing with no apparant limit (tens of GB, until I shut down mothur).
When I process the flow files separately, this works just fine, and quits at the expected sizes.
Unfortunately, you can’t merge sff files. Especially since you may use the same barcodes in different sff files for different samples. We suggest merging data before running unique.seqs.