Following @davis2018simp, we use the term internal contamination as a synonymously with cross-contamination to refer to contamination that occurs between samples, as opposed to External contamination. Internal contamination can arise through various mechanisms and at various steps in the measurement workflow. As @eisenhofer2019cont writes,

Cross-contamination is another challenge during microbiome sample processing, and includes the transfer of primary sample DNA, barcodes, or amplicons from neighboring wells or tubes to create ‘batch effects’ [40]. Cross-contamination can occur at multiple steps throughout sample processing: sample DNA can be accidentally transferred during initial sample processing and placement into tubes or plates [41], and from aerosolization during pipetting or during plate cover removal [42]. Barcode cross-contamination may also occur when incorrect neighboring barcodes ‘jump’ into sample wells or tubes – a phenomenon known as ‘tag switching’ [43]. Finally, cross- contamination can also occur on the sequencing instrument from barcode sequencing errors, residual amplicons from past sequencing runs, or ‘index hopping’, where some sequencing platforms mismatch indexing reads to sequencing reads [44]. Overall, both contaminant DNA and cross-contamination are dynamic and need to be consistently and routinely monitored.

References

[davis2018simp] Davis NM, Proctor DM, Holmes SP, Relman DA, Callahan BJ. 2018. Simple statistical identification and removal of contaminant sequences in marker-gene and metagenomics data. Microbiome 6:226. doi:10.1186/s40168-018-0605-2

[eisenhofer2019cont] Eisenhofer R, Minich JJ, Marotz C, Cooper A, Knight R, Weyrich LS. 2019. Contamination in Low Microbial Biomass Microbiome Studies: Issues and Recommendations. Trends Microbiol 27:105–117. doi:10.1016/j.tim.2018.11.003