System for Performing Cleavage, Deprotection, Ultrafiltration, and Diafiltration Operations

A common system for performing cleavage, deprotection, ultrafiltration, and diafiltration operations for producing an oligo product, comprising:

• an oligo column configured to configured for solid-phase synthesis of the oligo product;
• a single process vessel downstream of the oligo column and configured for receiving and/or performing post-synthesis processing of the oligo product;
• a supply of nitrogen, glycol, a cleavage solution, a deprotection solution, a quenching buffer, and a buffer solution;
• a feed pump;
• a deprotection pump;
• a recirculation loop comprising a recirculation pump and an inline heat exchanger;
• an ultrafiltration/diafiltration cartridge (“UF/DF cartridge”) comprising a ultrafiltration/diafiltration membrane (“UF/DF membrane”)
• wherein the deprotection pump is configured to pump the cleavage solution from the supply thereof, through the oligo column, and into the process vessel, thereby flushing the oligo product from the oligo column into the process vessel;
• wherein the feed pump is further configured to pump the deprotection solution from the supply thereof, through the deprotection pump, and into the process vessel, thereby mixing the deprotection solution into the oligo product;
• wherein the recirculation pump is configured to pump a product solution comprising the oligo product from the process vessel through a recirculation loop and back into the process vessel;
• wherein the feed pump is configured to pump the quenching buffer from the supply thereof and into the process vessel, thereby combining the oligo product with the quenching buffer to form a combined product solution;
• wherein the recirculation pump is configured to pump the combined product solution and the quenching buffer from the process vessel through the recirculation loop and to the UF/DF cartridge, such that the combined product solution and the quenching buffer are exposed to the UF/DF membrane, thereby producing a first permeate that is directed to waste and a first retentate comprising the oligo product that flows back into the process vessel;
• and
• wherein the recirculation pump is configured to pump the first retentate from the process vessel and the buffer solution from the supply thereof through the recirculation loop and to the UF/DF cartridge, such that the first retentate and the buffer solution are exposed to the UF/DF membrane, thereby undergoing diafiltration and producing a second permeate that is directed to waste and a second retentate comprising the oligo product that flows back into the process vessel.

A method of synthesizing an oligo product, comprising:

• performing a solid-phase synthesis step using an oligo column to produce an oligo product;
• performing a cleavage step to detach the oligo product from a solid support within the oligo column;
• optionally performing a deprotection step to process the oligo product post solid-phase-synthesis;
• performing an ultrafiltration step to separate the oligo product from waste products of the solid-phase synthesis;
• and
• performing a diafiltration step to carry out one or more buffer exchanges,
• wherein the solid-phase synthesis step, cleavage step, deprotection step, ultrafiltration step, and diafiltration step are performed using a common system.