Trimer modification requires a highly custom synthesis protocol in which multiple additional factors are taken into account. Each trimer mix job is individually analyzed in order to provide the most cost effective pricing in terms of synthesis cost and trimer amidite usage. If a small number of trimer mix incorporations are needed then it is more cost effective to manually couple the trimer mix rather than machine couple. While manual coupling adds increased labor to the quote, the amidite usage is decreased since there is no need to prime the machine. Also, manual coupling eliminates the need for a machine validation requiring an additional charge.