Nexera UC and Nexera UC Prep

Significance of the Topic

Supercritical fluid extraction (SFE) and supercritical fluid chromatography (SFC) deliver a greener, faster and more sensitive approach to sample preparation and analysis. By exploiting unique properties of supercritical CO2, such as low viscosity, high diffusivity and liquid-like solvency, analysts can achieve high-resolution separations, simplified workflows and reduced solvent consumption. These capabilities address key challenges in industries from pharmaceuticals to food science, where rapid multi-analyte quantification and preparative purification are increasingly demanded.

Study Objectives and Overview

This review summarizes the development and applications of the Nexera UC series, which integrates SFE, SFC, and preparative purification in automated systems. Objectives include:

• Highlight unified speed, sensitivity and resolution improvements in analytical and preparative tasks.
• Describe method development strategies such as column and modifier scouting for both achiral and chiral analyses.
• Demonstrate small- and large-scale fractionation workflows with high recovery rates.
• Present on-line SFE–SFC automation for direct extraction and separation of solid samples.

Methodology and Instrumentation

SFC employs supercritical CO2 as the primary mobile phase, optionally modified with low percentages of organic co-solvents like methanol to tune polarity. Key features include:

• Rapid elution due to low fluid viscosity and high diffusion coefficient.
• Extended polarity coverage enabling simultaneous analysis of nonpolar fatty acids and polar glycerides.
• Enhanced MS sensitivity via reduced ion suppression.

Automated method scouting leverages up to 12 column chemistries and multiple modifiers to generate and evaluate hundreds of separation conditions. Shim-pack UC column phases such as C18, silanol, diol, and novel polymer-bonded phases support seamless scale-up from analytical (2.1–4.6 mm I.D.) to preparative (10–30 mm I.D.) formats. The LotusStream gas–liquid separator enables precise small-volume fraction collection, and proprietary software (Method Scouting Solution, Prep Solution) controls integrated injection, separation, and fractionation processes.

Main Results and Discussion

• Analytical SFC reduced run times by up to 75% compared to HPLC while improving isomeric resolution (e.g., Rs improved from 1.33 to 1.70 for α-tocopherol).
• Simultaneous analysis of fatty acids and glycerides was achieved in a single 12 min SFC gradient, replacing the need for separate GC and HPLC methods.
• SFC–MS/MS demonstrated up to six-fold higher peak intensities for prostaglandin D2 compared to LC–MS/MS.
• Automated chiral screening of β-indapamide and linalool enantiomers resulted in high selectivity (Rs>2.6) and 96% preparative recovery.
• Stacked injections enabled continuous fractionation of up to nine samples within the time previously required for three injections, boosting throughput three-fold.
• On-line SFE–SFC of tomato paste and dried blood spots completed extraction and analysis in under 10 min, bypassing conventional solvent-based pretreatment.

Benefits and Practical Applications

• Reduced solvent consumption and environmental impact by replacing hexane/chloroform with CO2 and low-toxicity co-solvents.
• Highly automated workflows cut manual sample handling and operator error.
• Scalable solutions from trace analysis to gram-scale preparative purification with high recovery and purity.
• Broad applicability across pharmaceuticals (chiral drug candidates, cleaning validation), natural product research, food quality control, and biomarker analysis.

Future Trends and Opportunities

Anticipated advances include:

• Integration of machine learning for predictive method development and real-time optimization.
• Further miniaturization and modular designs to fit diverse laboratory footprints.
• Expansion of eco-friendly SFC mobile phases and stationary phases tailored to polar analytes.
• Coupling high-resolution mass spectrometry and multidimensional SFC methodologies for complex mixture profiling.
• Continuous, fully online extraction–separation–fractionation platforms for bioprocess monitoring and quality assurance in regulated industries.

Conclusion

The Nexera UC family exemplifies the power of supercritical fluid technology to unify rapid analysis, high sensitivity and preparative capabilities within single automated platforms. By consolidating extraction, separation, detection and fraction collection, laboratories can accelerate method development, improve analytical performance and reduce environmental footprint. Ongoing innovation in column chemistry, software and system integration promises broader adoption of SFE/SFC as a mainstream solution in analytical and preparative chemistry.

Instrumentation Used

• Nexera UC Analytical SFC System with CO2 pump and modifier delivery
• Nexera UC Prep with integrated cooling unit for 10–150 mL/min preparative flows
• Shim-pack UC column series (C18, silanol, diol, polymer-based, chiral phases)
• LotusStream gas–liquid separator for small-volume fractionation
• FRC-40SF and LH-40SF fraction collectors and injectors for stacked and multi-fraction workflows
• LabSolutions software with Method Scouting Solution and Prep Solution modules