Curved Tube Online Sampling for Pharmaceutical Mobile Phase
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Solution Overview
Problem
The challenge in pharmaceutical and chemical manufacturing is scaling up biotechnological processes from small-scale models to production scale, where process solutions like buffers and chromatography columns do not trivially translate, leading to sub-optimal performance and difficulties in obtaining representative samples for quality assurance, especially in GMP-compliant environments.
Innovation Solution
A method for online sampling an aliquot from a mobile phase using an apparatus with a tube and a sample device featuring a needle and pump, allowing for sterile, continuous, and representative sampling without compromising process integrity, utilizing a curved tube geometry to minimize turbulence and ensure unidirectional flow, and optionally including a check valve for contamination prevention.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If a sampling system is introduced to extract representative samples from the mobile phase, then measurement precision and process knowledge are improved, but the system complexity and risk of contamination increase
Solution Approach 1:
The needle is nested within the curved tube structure, with the needle tip positioned inside the tube lumen. This nested configuration allows the sampling system to be integrated into the existing chromatography apparatus without adding external complexity, while still enabling representative sample extraction from the mobile phase flow
Solution Approach 2:
The curved tube acts as an intermediary element between the mobile phase and the sampling needle. It provides a controlled interface that directs mobile phase flow toward the needle tip, ensuring representative sampling while preventing direct contact between the sampling system and the main process stream, thereby reducing contamination risk
2Loss of information
If sampling is performed during production process, then real-time process knowledge is obtained, but process time and yield may be compromised
Solution Approach 1:
The sampling system operates continuously during the chromatography process without interrupting the mobile phase flow or requiring process shutdown. The needle remains in position within the curved tube, continuously extracting samples as the mobile phase passes by, thereby maintaining productivity while providing real-time process information
Solution Approach 2:
Only a small aliquot of the mobile phase is diverted for sampling rather than stopping the entire process. The sampling needle extracts a partial volume of the flowing mobile phase, providing sufficient process knowledge without significantly impacting overall process time or yield
3Measurement precision
If a needle is positioned to face the flow direction, then sample representativeness is improved, but turbulence and contamination risk increase
Solution Approach 1:
The tube is designed with a curved geometry rather than a straight configuration. This curvature redirects the mobile phase flow to follow the tube contour and gently approach the needle tip from the side, minimizing direct impingement and reducing turbulence generation while still ensuring representative sample extraction
Solution Approach 2:
The curved tube creates localized flow patterns with different characteristics at different positions. Near the needle tip, the flow is directed smoothly to ensure representative sampling, while elsewhere in the tube the flow maintains laminar characteristics, minimizing overall turbulence and contamination risk
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
Enables safe and efficient GMP-compliant sample extraction and analysis at production scales, providing representative data and real-time process knowledge while maintaining system integrity, allowing for higher resolution analysis and adaptable sampling for various analytical needs.
Implementation Method 1
operating the pump so as to draw an aliquot out of the mobile phase
Implementation Method 2
utilizing a curved tube geometry to minimize turbulence and ensure unidirectional flow
Data Source
AI summary
Methods and systems for online sampling an aliquot from a mobile phase comprising an analyte for producing a pharmaceutical or chemical product, wherein the apparatus comprises an analytical device and a tube between an inlet and an outlet, wherein the outlet is in fluid communication with the analytical device, the method comprising: providing a sample device comprising a needle with a needle tip, a septum pierceable by the needle and a pump, wherein the needle is moveable between an extended position in which the septum is pierced by the needle, and a retracted position, in which the septum is not pierced, disposing the sample device at the curved portion of the tube, moving the needle to the extended position such that the needle tip faces the flow direction, and drawing out an aliquot out of the mobile phase.