Intelligent System Emulation Technology (ISET)

Significance of the Topic

High‐performance liquid chromatography (HPLC) method transfer between different instruments is a routine yet challenging task in regulated analytical laboratories. Variations in dwell volume, gradient mixing behavior, extra‐column volume and data acquisition settings can lead to differences in retention times, resolution and sensitivity. Addressing these challenges is essential to ensure reproducible results, reduce method redevelopment efforts and maintain compliance with regulatory guidelines.

Objectives and Study Overview

This whitepaper introduces Agilent’s Intelligent System Emulation Technology (ISET) integrated into the 1290 Infinity LC platform. The goals are to:

• Identify key parameters affecting instrument‐to‐instrument method transfer.
• Review current workarounds for dwell‐volume mismatch.
• Explain the ISET approach and its algorithmic emulation of other Agilent LC systems.
• Demonstrate performance through practical examples.

Methodology and Instrumentation

ISET combines the ultra‐low dwell volume, wide pressure range and high sensitivity of the 1290 Infinity LC with a software‐based emulation algorithm. Key steps include:

• Full characterization of target systems (1100, 1200, 1220, 1260 Series).
• Extraction of system functions—delay volume, gradient mixing profile, extra‐column dispersion.
• Real‐time adjustment of pump and gradient programs to reproduce the behavior of the selected system.

Main Results and Discussion

Using ISET, retention times and peak resolutions observed on legacy instruments can be reproduced on the 1290 Infinity LC without hardware modifications or method edits. Examples include:

• Pesticide separation on a 3×50 mm Poroshell column: Rs values matched between emulated 1200 Series and native 1290 runs.
• Impurity profiling on a 4.6×50 mm, 1.8 µm column: identical chromatographic profiles and resolution metrics across systems.

These case studies illustrate that ISET corrects for dwell‐volume induced retention shifts and mixing discrepancies, achieving one‐to‐one method transfer.

Benefits and Practical Applications

Implementation of ISET offers:

• Effortless system emulation via a single mouse click.
• Elimination of manual dwell‐volume measurements and method adjustments.
• Compatibility with regulated workflows—no need for method revalidation under USP <621>.
• Enhanced laboratory productivity by unifying method development on a single UHPLC platform.

Future Trends and Applications

Looking forward, system emulation technology can expand to multi‐vendor integration, AI‐driven method optimization and dynamic adaptation to complex sample matrices. Enhanced data analytics may further refine emulation accuracy and support predictive maintenance of chromatographic systems.

Conclusion

Agilent’s ISET feature within the 1290 Infinity LC represents a breakthrough in HPLC method transfer. By embedding accurate system emulation into the instrument control software, laboratories can consolidate methods, accelerate transfers and leverage UHPLC performance without sacrificing reproducibility or regulatory compliance.

Instrumental Setup

• Agilent 1290 Infinity LC with ISET
• Agilent 1260 Infinity LC
• Agilent 1200 Series LC
• Agilent 1100 Series LC
• Agilent 1220 Infinity LC