Delivery of Reactants From a Batch Reactor Using the Agilent InfinityLab Online LC Solutions

Importance of the Topic

Online monitoring of homogeneous chemical and biological transformations is critical for process optimization, quality control, and timely decision making. Effective sample delivery from batch reactors to liquid chromatography (LC) systems enables near real-time analysis, reducing time lags and improving data reliability.

Objectives and Study Overview

This study demonstrates the integration of generic third-party pumps with the Agilent InfinityLab Online LC Solutions and Online LC Monitoring Software. Using an aldol condensation model reaction, four sample delivery devices—inclusive of an Agilent isocratic pump, a piston pump, a peristaltic pump, and a programmable syringe pump—were evaluated for near real-time sample transfer and data consistency.

Methodology and Instrumentation

Instrumentation

• Agilent 1290 Infinity II High-Speed Pump, 1260 Infinity II Online Sample Manager, multicolumn thermostat, diode array detector, isocratic pump, Poroshell EC-C18 column
• Watson-Marlow peristaltic pump, Masterflex Ismatec digital piston pump, New Era NE-1000 syringe pump

Analytical Conditions

• Solvents: water + 0.1% formic acid and ACN + 0.1% formic acid
• Gradient 40 to 90% ACN in 0.85 min at 1.3 mL/min, column at 45 °C
• Injection volume 1 µL, DAD detection at 290 nm

Sampling Protocol

• Deep-well plate sealing, 600 µL target with 100× dilution (6 µL sample)
• Draw speed 100 µL/min, dispense speed 130 µL/min, dilution eject 10 000 µL/min
• Sample interval 4 min over 120 min reaction in EasyMax reactor (p-anisaldehyde and NaOH in acetone/water)

Connectivity

• ERI cables for TTL control of external pumps (custom wiring per device)
• Sample delivery orchestrated entirely by Online LC Monitoring Software

Main Results and Discussion

All four pump types produced nearly identical chromatographic trends for educt depletion and product formation, with the crossover point at ~8.5 min. Area percentages at early, mid, and late sampling times showed deviations of less than 1%, confirming that heterogeneous pump principles do not compromise analytical consistency.

Benefits and Practical Applications

• Cost-effective selection of pumps tailored to chemical or biological media
• Seamless orchestration of diverse devices via a single software interface
• Enhanced real-time reaction monitoring for process development and QA/QC

Future Trends and Opportunities

• Automated feedback loops with machine learning for adaptive sampling
• Broader compatibility standards for third-party device integration
• Miniaturized and high-throughput sampling modules for continuous flow systems
• Integration with cloud-based analytics and digital twins for process intensification

Conclusion

Generic sample delivery pumps and devices, when controlled by Agilent Online LC Monitoring Software, deliver consistent and reliable online LC data across different working principles. This flexibility allows users to adapt sampling hardware to specific reaction needs without compromising analytical performance.

Reference

1. Viviano M. et al. A Scalable Two Step Continuous Flow Synthesis of Nabumetone and Related 4-Aryl-2-butanones. Org. Process Res. Dev. 2011, 15, 858–870.
2. Lautz C. et al. Agilent Technologies application note, no. 5994-3980EN, 2021.
3. Agilent 1260 Infinity II Isocratic Pump User Manual, accessed August 2022.
4. Watson-Marlow 120U/DV Peristaltic Pump User Manual, accessed August 2022.
5. Ismatec Masterflex Digital Piston Pump User Manual, accessed August 2022.
6. New Era NE-1000 Programmable Syringe Pump Manual, accessed August 2022.