Preparative Chromatography Flow Paths for Low Hold-Up Volume
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Solution Overview
Problem
Chromatography systems with small volume chromatography devices face significant hold-up volume issues, particularly in preparative chromatography processes, leading to poor peak resolution, increased waste of buffers, and inefficient use of process liquids due to the high number of cycles.
Innovation Solution
A preparative chromatography system with separate and individual flow paths for process liquids, utilizing pumps and valves to minimize hold-up volume by priming and mixing liquids downstream of the chromatography device, allowing for efficient cycling and reduced mixing during transitions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Speed
If conventional packed bed chromatography systems are used, then binding capacity is sufficient, but flow rates are limited due to diffusion limitations
Solution Approach 1:
The patent employs porous bead-based chromatography media with optimized pore structures that enable both high flow rates and sufficient binding capacity. The porous architecture allows convective flow through the beads while maintaining adequate surface area for analyte binding, resolving the contradiction between flow rate and productivity.
2Loss of substance
If small volume chromatography devices are used, then buffer consumption is reduced, but hold-up volume becomes significant compared to device volume
Solution Approach 1:
The system segments the flow path into distinct zones: a small chromatography device for separation and larger external flow paths for buffer delivery. By separating these functions and using efficient valve switching to minimize the volume of connecting tubing, the system reduces hold-up volume effects while maintaining small device size and low buffer consumption.
Solution Approach 2:
The patent introduces low-dead-volume valves and connectors as intermediaries between the small chromatography device and buffer reservoirs. These components are specifically selected to minimize hold-up volume while enabling efficient buffer delivery, thus resolving the contradiction between small device size and peak resolution.
3Productivity
If preparative chromatography processes cycle many times, then productivity increases, but hold-up volume effects are amplified leading to poor peak resolution
Solution Approach 1:
The system maintains continuous buffer flow through the chromatography device during cycle transitions, eliminating dead time between cycles. The optimized flow path design ensures that buffer continuously sweeps through the device, preventing analyte diffusion and maintaining sharp peaks even during repetitive cycling operations.
Solution Approach 2:
The patent employs dynamic valve switching and flow rate modulation to adapt the system performance to different cycling conditions. During rapid cycling, higher flow rates are maintained to compensate for hold-up volume effects, while during slower operations, flow rates are optimized for resolution, thus maintaining both productivity and peak resolution across varying cycle frequencies.
4Productivity
If high flow rates are used, then system throughput increases, but diffusion-limited separation processes become less effective
Solution Approach 1:
The patent uses porous chromatography media with optimized pore size distributions that enable convective flow dominance at high linear velocities. The porous structure is designed so that at high flow rates, flow occurs primarily through the pores rather than around the beads, maintaining separation efficiency while achieving high throughput.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The system significantly reduces hold-up volume, enhancing peak resolution, reducing processing time and liquid consumption, and maintaining flexibility in process sequences while supporting high flow rates and multiple chromatography devices.
Implementation Method 1
a first pump provided in the first upper flow path and arranged to provide the first process liquid to the chromatography device, a second pump provided in the second upper flow path and arranged to provide the second process liquid to the chromatography device
Implementation Method 2
Chromatography is today the dominant industrial scale method to provide high purity substances
Implementation Method 3
separation and purification has been achieved primarily with conventional packed bed chromatography utilizing columns of porous beads
Data Source
AI summary
The present invention relates to a preparative chromatography system (200, 500, 800) and a chromatography process (400, 700) adapted to repetitive cycling of chromatography volumes. The system (200, 500, 800) comprises at least two upstream pumps (203a, 803a, 203b, 803b) and separate flow paths (220) from process liquid sources to the chromatography device (200, 500, 800). The system (200, 500, 800) is arranged to prime one flow path (220) with one process liquid while providing another process liquid to the chromatography device and thereby minimizing the hold-up volume of the system (200, 500, 800).