Real-Time Peak Integration for Chromatographic Elution Yield

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Solution Overview

Problem

Conventional chromatography elution techniques are inconsistent, leading to inefficient collection of desired products and the inclusion of product-related impurities, which affects product quality, titer, and purity, and results in unnecessary resource expenditure due to inconsistent and inefficient processes.

Innovation Solution

A computing system with a peak area estimation model that analyzes real-time data to determine precise collection points during the elution process, optimizing the collection of desired products while avoiding impurities by controlling process automation systems to begin and cease collection based on area under the curve criteria.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If conventional chromatography elution techniques are used, then the elution process is simple to operate, but the collection consistency and product purity are poor due to inclusion of impurities

Engineering Contradiction:
Improvecollection consistencyVSAvoidsystem complexity
Core Design Contradiction:
Manufacturing precisionVSDevice complexity

Solution Approach 1:

The system continuously monitors UV absorbance data in real-time during elution and uses this feedback to dynamically adjust collection decisions. The peak integration algorithm processes ongoing chromatographic data to identify peak boundaries and calculate area under the curve, enabling the system to respond to actual elution behavior rather than relying on predetermined fixed parameters, thus achieving consistent collection while maintaining operational simplicity

Inventive Principle:
Principle #23Feedback

Solution Approach 2:

The patent replaces manual visual inspection and subjective judgment of chromatograms with an automated computational system that uses algorithms to integrate peak areas and determine collection points. This substitution of mechanical/manual operations with computational automation eliminates human variability and achieves repeatable, consistent results without significantly increasing operational complexity

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

2Productivity

If collection window is widened to capture more desired product, then yield increases, but impurity inclusion increases

Engineering Contradiction:
Improveproduct yieldVSAvoidproduct purity
Core Design Contradiction:
ProductivityVSManufacturing precision

Solution Approach 1:

The automated peak integration algorithm objectively determines peak boundaries by calculating area under the curve based on UV absorbance data, replacing subjective visual estimation. This enables precise identification of where desired product elutes versus where impurities begin, allowing the system to maximize collection of target product while automatically stopping before significant impurity inclusion occurs

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The system dynamically adjusts collection parameters based on real-time analysis of the chromatogram shape and area under the curve calculations. Rather than using fixed collection windows, the algorithm adapts to the actual elution profile, identifying optimal collection start and stop points that maximize product yield while maintaining purity by excluding regions where impurities elute

Inventive Principle:
Principle #35Parameter changes

3Manufacturing precision

If collection window is narrowed to avoid impurities, then product purity improves, but desired product collection decreases

Engineering Contradiction:
Improveproduct purityVSAvoidproduct yield
Core Design Contradiction:
Manufacturing precisionVSProductivity

Solution Approach 1:

The computational peak integration system accurately delineates the boundary between desired product and impurities by calculating area under the UV absorbance curve. This objective mathematical approach identifies the precise point where impurity elution begins, allowing the system to collect essentially all desired product (maximizing yield) while automatically excluding impurity-containing regions (maintaining purity), resolving the trade-off between these two parameters

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

4Measurement precision

If manual visual inspection of chromatograms is used to determine collection points, then system complexity is low, but measurement precision and repeatability are poor

Engineering Contradiction:
Improvecollection point accuracyVSAvoidautomation system complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent implements an automated algorithm that performs numerical integration of UV absorbance data to calculate peak area and determine collection points. This replaces manual visual inspection with an objective computational method that consistently applies the same mathematical criteria to every chromatogram, eliminating human variability and achieving high measurement precision and repeatability

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The system processes real-time UV absorbance data through the peak integration algorithm, which continuously calculates area under the curve and compares it against threshold criteria to automatically determine collection start and stop points. This closed-loop feedback mechanism ensures accurate and repeatable measurement without requiring complex manual intervention or subjective judgment

Inventive Principle:
Principle #23Feedback

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

This approach ensures consistent and repeatable product collection, maximizing yield and minimizing impurities, thereby improving product quality and reducing resource waste by enabling granular control over the elution process.

Implementation Method 1

conventional elution techniques that rely on chromatography elution processes

Methodology Applied
Scientific EffectChromatography: Chromatography

Implementation Method 2

real-time UV absorbance data

Methodology Applied
Scientific EffectAbsorption Spectroscopy: Absorption Spectroscopy

Data Source

PatentUS20240316478A1Real time peak integration for pool collection criteria via chromatographic area under the curve
Publication Date: 2024.09.26 AMGEN INC
  • US20240316478A1 patent drawing
  • US20240316478A1 patent drawing
  • US20240316478A1 patent drawing

AI summary

A elution product yield improvement system includes a processor, an estimation model and an elution controller application including instructions configured, when executed by the processors, to receive initialization data; instantiate a communication link to a remote process/automation system; determine collection criteria; initiate collection; read data values; computing an area ratio via the estimation model; and cease collection. A computer-implemented method for improving elution yield and purity includes receiving initialization data; instantiating a communication link to a remote process/automation system; determining collection criteria; initiating collection; reading data values; computing an area ratio; and ceasing collection. A non-transitory computer readable medium includes program instructions that when executed, cause a computer to receive initialization data; instantiate a communication link to a remote process/automation system; determine collection criteria; initiate collection; read data values; computing an area ratio via the estimation model; and cease collection.