Technology
Continuous Countercurrent Tangential Chromatography (CCTC)
Overview
CCTC purification can be described as the typical process steps found in column chromatography happening simultaneously, with the notable exception of sanitization due to it’s closed-loop nature. In the pipe diagram above an initial capture step is modeled. Each step represents a new buffer condition and the stage inside those steps is comparable to an individual column volume of buffer loaded on to a column. The washout of buffer from one step to another is dictated by the number of stages in the step and gamma the ratio of flow between the retentate and permeate of the step. To ensure complete washout of each step, 3 – 5 stages are used in each non-binding step.
A rendering of our new CCTC Mini is pictured in a “full” configuration with 5 stages installed on each step for maximum washout and recovery.
Steady-State Process Enables Higher Recovery and Process Robustness
The continuous nature of CCTC produces consistent product concentration (peak free!) avoiding aggregation and long exposure of the product to unfavorable buffer conditions.
The steady-state solution enables very short residence times and simple process control leading to a more robust and easy-to-deploy process.
Precise micro-mixing conditions enable the user to precisely model and control all the chemistry in the process (no gradients!).
CCTC Flowpath
Each stage of the CCTC flowpath consists of a membrane connected in series by retentate and permeate tubing. We use a variety of membranes from Repligen with pore sizes ranging 1 – 4 um and in areas that scale as small as 10 cm2 to as large as 10.4 m2, which provide both excellent sizing for process development and manufacturing purifications.
ChromaTan has been hard at work developing 3D printed devices that use the fluid dynamic effect Dean’s Vortex Separation (DVS) to supplement membranes used on the CCTC. DVS devices can be cleaned and reused more easily than membranes making them a great tool for process development purification.
Dramatic Increase in Resin Productivity
With short cycle times and a dilute resin slurry the grams of product produced per volume of per hour is typically >10x the productivity of standard column chromatography.
CCTC Software Control
All CCTC systems ship with a comprehensive application suite which streamlines the entire chromatography process, from recipe design all the way through data analysis. Our guided recipe design software suggest configurations to hit your washout targets while minimizing buffer consumption, and seamlessly feeds into the chemical process modelling utility which you can use to design buffer recipes optimized for the CCTC platform. Recipes can be loaded in the system control software directly from the recipe editor, allowing an operator to step through the process sequence without opportunities to deviate from your process development team’s run plans. Online sensor data is collected in a SQL database where it can be visualized wih high performance, interactive dashboards during and after your runs.
All of these components are provided as web services available on your equipment, without any additional servers or workstations to administer. Simply connect your new CCTC machine to your network and connect to the system with any modern web browser. For customers who prefer a native application, we provide a custom desktop client for easy, straightforward access to all of your equipment’s functionality.
Efficiently Cycle Resin
Cycle times between 20-50 minutes mean that the CCTC can be scaled to reach maximum cycling of the resin once the campaign is completed.
CCTC Resin Selection
The CCTC is a flexible platform that can use many off-the-shelf resins such as MabSelect® and POROS® resin beads to provide direct comparison of performance to standard column chromatography. We have also partnered with Purolite® to develop custom resin for CCTC applications. For standard columns small beads with low cross-linking cannot be used due to pressurization problems that would arise from the resin over-packing. With the CCTC, the resin is suspended allowing the structure of the resin bead to be small, increasing the proportional surface area of each bead, and reducing the need for dense cross-linking, which increases the perfusability of the resin beads. These advantages can lead to shorter binding times and increased binding capacity.
See a comparison of offerings from Purolite Resins.
