Evolution of the Single-use FlexiPro Chrom System
05 May 25
By:
“Be flexible so you can change with change”
— Bruce Lee
Adapt. Evolve. Overcome.
When the MiniPro™ Chrom system was introduced in 2009, the flow rate ranged up to 120 L/hr (2 L/min) and helped to bridge the gap between laboratory scale development and pilot scale manufacturing. The MiniPro Chrom system was one of the first GMP systems for protein purification that could fit on a benchtop.
So a few years later when developing a single-use system, the VERDOT design team used the compact footprint of the MiniPro Chrom in order to conserve valuable cleanroom floorspace.
The “Flash” system, as it was initially called, was designed to minimize operator downtime with rapid flow kit changeover and to maximize instrument flexibility with two different flow kit sizes in a single unit. This time, though, the system featured flow rates up to 600 L/hr (10 L/min).
The original design consisted of three parts (Figure 1):
- A central unit housing the PLC controller, instrument transmitters, and solenoids
- A pump drive unit containing the pump motors and VFD that could accommodate two sizes of pump heads for the two different flow kits.
- A fluidic panel that could be changed out between the “Low Flow” kit (5-150 L/hr) and the “High Flow” kit (20-600 L/hr).
Figure 1. Original system design comprised of three modular units.
In planning to build the prototype, it quickly became obvious that the three-unit design was not practical, and the units could be consolidated into a single cabinet. The central unit and pump drive unit were already designed to be used with multiple flow kits and needed no modification.
The fluidic panel unit, however, needed some consideration for the change to a single cabinet design. It consists of three integral parts, each with their own innovative features:
- 1) the panel itself with directional grooves that outline the mounting of the flow path
- 2) the pneumatic pinch valves
- 3) the transparent door
The directional grooves of the fluidic panel promote easy and intuitive flow kit installation. With the single cabinet design, the grooves needed to accommodate differences in tubing thickness of the two flow kits. For the High Flow Kit, the tubing fits snugly in the directional grooves but for the Low Flow Kit, the pinch valves help to keep the tubing properly aligned in the grooves.
This brings us to another VERDOT innovation – the pneumatic pinch valves. On the surface, they appear quite simple. It’s just a metal bar that compresses the flexible tubing in the closed position and removes the compression in order to open the tubing. In reality, these valves are quite unique compared to pinch valves of other systems.
Most types of commercially available pinch valves are designed for safety to prevent accidental pinching of hands / fingers and require two hands to open the valve. Additionally, their “V-shape” design is often restricted to only one or two sizes of tubing for each size valve.
The FlexiPro Chrom valves close against a flat surface rather than using a “V-shape”. This is possible because of their position in the fluidic panel – that is, they are protected from accidental pinch points by the grooves + the transparent door. The simple design allows for more than just closing and opening the tubing – the valve is compatible with a wide range of tubing sizes and can be easily rotated out of its groove (Figures 2 and 3) for fast flow kit installation with only one person.
Thus, the VERDOT design meant that the pinch valves didn’t need modification to be able to accommodate two different flow kit sizes and enabled fast and efficient flow kit changeovers without a safety hazard.
Figure 2. Pinch valve in open position.
Figure 3. Pinch valve in closed position.
A transparent door was designed with cutouts to prevent the door from closing unless the flow kit and pinch valves are in their correct position. The door is secured with an interlocking sensor that confirms to the control software that the door is closed before processing can begin, further reducing operator errors.
The transparent door design also makes the entire fluid path visible to the operator from the front of the system.
The final system design was named FlexiPro™ Chrom and was launched in 2014 (Figure 4).
Figure 4. The compact FlexiPro Chrom system.
Ongoing Improvements
A few years after the FlexiPro Chrom system was introduced, we heard from a customer working in gene therapy that they needed lower flow ranges for their GMP application. They noted that at that time, no GMP chromatography systems on the market could operate in their required flow range.
VERDOT engineers investigated the possibility of designing an entirely new system, but with a little innovation, they found that they could adapt the existing FlexiPro Chrom system to expand the flow range down to 10 mL/min.
The first hurdle was to find pumps and pump heads that 1) worked in the established flow range, 2) used single-use components, and 3) could be modified to fit the pump drive installed on the FlexiPro Chrom system. You can read all about the FlexiPro Chrom pumps here.
The tubing for the smaller kits (now dubbed Very Low Flow Kit and Ultra Low Flow Kit) is platinum-cured silicone, which is quite a bit smaller and more flexible than the braided silicone that is used for the Low Flow and High Flow kits. These differences meant that the fluidic panel could not be used “as is” and would need additional modification.
Installing a different fluidic panel when changing the flow kit size would be a difficult task, especially in a cleanroom.
How could the smaller flow kits be used on the same fluidic panel?
As discussed above, the pneumatic pinch valve design is ideal for multiple tubing diameters, so it was no problem to use the smaller tubing. Still, the tubing was very loose in the fluidic panel grooves and would not stay in place easily.
With a little VERDOT innovation, a small adapter clip was devised to fit in the grooves of the fluidic panel and hold the VLFK and ULFK tubing. The clips are reversible and can be used for either tubing size, as shown in Figure 5.
Figure 5. Reversible flow kit adapter clip to hold the VLFK and ULFK tubing within the grooves of the fluidic panel.
Seems like a small thing, but that little clip is like a linchpin that allows the FlexiPro Chrom to have the widest range of flow rates in a single compact system. Even many years later, the VERDOT FlexiPro Chrom is the only system available using 1/16” ID GMP flow kits for advanced therapies like cell & gene therapy, mRNA, DNA, etc.
The current version of the FlexiPro Chrom with all four flow kit sizes was introduced in 2018.
About the Author
Kim Brisack is the Global Applications Support Manager for VERDOT and in that role, she has worked with companies all over the world. She has extensive experience in GMP downstream operations for almost thirty years, including roles in PD and MSAT at Bayer Healthcare in Berkeley CA as well as R&D Applications and Marketing for Process Chromatography at Bio-Rad in Hercules CA. Based in San Francisco CA, she spends her free time at her ranch near Yosemite National Park with her partner and five dogs, two cats, and three horses.
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