Automated Sample Preparation for Real-Time CQA Assays

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Solution Overview

Problem

Existing manually operated assays for analyzing Critical Quality Attributes (CQAs) of polypeptide therapeutic molecules, such as glycan profiles, are time-consuming and inefficient, leading to delays in drug development and manufacturing adjustments.

Innovation Solution

A closed system and method for automating sample preparation and real-time analysis using multi-port valves, capture columns, and reaction coils to separate, label, and analyze molecules like polypeptides and glycans, reducing turnaround time to hours.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Loss of time

If conventional manual sample preparation and analysis methods are used, then measurement precision can be maintained, but analysis time is excessively long (hours to days)

Engineering Contradiction:
Improveanalysis timeVSAvoidthroughput
Core Design Contradiction:
Loss of timeVSProductivity

Solution Approach 1:

The system divides the sample preparation and analysis process into distinct modular segments: automated liquid handling for sample preparation, microfluidic channels for separation, and arrayed sensor wells for parallel detection. This segmentation enables simultaneous processing of multiple samples and analytes, reducing total analysis time from hours/days to minutes while maintaining precision through specialized optimization of each segment.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The system performs preliminary actions by pre-positioning multiple reagent reservoirs, pre-configuring microfluidic flow paths, and pre-arraying sensor wells before sample introduction. Automated liquid handling systems pre-mix reagents and pre-establish protocols, eliminating setup time during actual analysis and enabling immediate high-throughput processing when samples arrive.

Inventive Principle:
Principle #10Preliminary action

2Productivity

If conventional batch processing methods are used, then device complexity remains manageable, but real-time analysis capability is lost

Engineering Contradiction:
Improvereal-time analysis capabilityVSAvoidsystem complexity
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The system achieves real-time analysis capability through multi-functional integration: a single platform performs automated liquid handling, microfluidic separation, parallel sensor detection, and data processing simultaneously. The microfluidic chip serves multiple functions including sample injection, reagent mixing, separation, and delivery to sensor arrays, eliminating the need for multiple separate instruments and enabling real-time throughput despite increased functional complexity.

Inventive Principle:
Principle #6Universality (Multi-functionality)

Solution Approach 2:

The system implements nesting by integrating microfluidic channels directly within the sensor array platform, embedding reagent reservoirs within the main chamber, and incorporating control electronics within the device housing. This nested architecture reduces spatial footprint and inter-component communication delays, enabling real-time analysis while managing complexity through hierarchical integration.

Inventive Principle:
Principle #7Nested doll (Nesting)

3Manufacturing precision

If automated liquid handling is implemented, then manufacturing precision of sample preparation improves, but device complexity increases

Engineering Contradiction:
Improvesample preparation precisionVSAvoidautomation system complexity
Core Design Contradiction:
Manufacturing precisionVSDevice complexity

Solution Approach 1:

The system merges automated liquid handling mechanisms directly with the microfluidic separation and sensor detection platforms. Reagent delivery systems are integrated into the same chip or chamber as separation and detection functions, allowing precise automated sample preparation while eliminating the complexity of separate automated systems. This consolidation maintains manufacturing precision through integrated control while reducing overall device complexity.

Inventive Principle:
Principle #5Merging (Combining)

Data Source

PatentEP4397977B1Systems and methods for preparing a sample and performing a real-time assay of the sample
Publication Date: 2026.04.29 AMGEN INC
  • EP4397977B1 patent drawingFigure 1~2
  • EP4397977B1 patent drawingFigure 3~4
  • EP4397977B1 patent drawingFigure 5~6

AI summary

Systems and methods that facilitate the automatic (or substantially automatic) preparation of a sample of a product containing molecules for analysis and automatic (or substantially automatic) performance of an assay of that sample. Thus, the preparation and analysis can be performed substantially in-real time, or, in other words, much more quickly than presently allowed by conventional systems and methods.