Next Generation LCMS Multiplexing Platform for High Throughput Assays with Advanced Analytical Intelligence

Significance of the topic

The demand for high-throughput liquid chromatography–mass spectrometry (LC-MS) workflows is growing in clinical diagnostics, pharmaceutical analysis and forensic testing. Traditional multiplexing platforms often face challenges such as sample carryover, frequent maintenance and downtime that limit productivity. The Nexera QX Multiplexing Platform integrates advanced hardware design with analytical intelligence to address these limitations, enabling robust, continuous analysis with minimal carryover and maintenance interruptions.

Study objectives and overview

This work demonstrates the performance of the Nexera QX system in reducing carryover, maintaining sensitivity and improving throughput. Key objectives include:

• Evaluating novel autosampler and column rinsing strategies for carryover elimination
• Assessing the accuracy and linearity of calibration for challenging analytes like fentanyl
• Verifying system robustness during extended continuous operation

Methodology and instrumentation

Samples and preparation:

• Urine specimens extracted by solid-phase extraction
• Calibration ranges 0.2–500 ng/mL (lower analytes) up to 0.8–2000 ng/mL (higher analytes)

System configuration:

• Nexera QX four-channel multiplexing system: autosampler, column oven, four binary pumps and four single pumps
• Dedicated LPGE pump for needle inner rinsing with up to four solvent selections
• Triple quadrupole mass spectrometer (Shimadzu LCMS-8060NX) with new IonFocus source and Qarray bias

Rinsing methods:

• Internal needle rinse using a mixture of mobile phase A, B and organic solvent at up to 5 mL/min
• Stream and full analytical flow path rinsing to combat column and plumbing carryover
• Automatic triggering of dedicated rinse protocols by AI when high-concentration thresholds are exceeded

Key results and discussion

Carryover reduction:

• Autosampler carryover in blank samples fell below 5% of cutoff following injections at 70,000 ng/mL (acceptance threshold <10%)
• Column carryover drastically reduced using ternary gradient flushing in equilibration steps

Calibration performance:

• Linear calibration achieved for fentanyl and other challenging compounds thanks to improved ionization stability from IonFocus electrodes and reduced ion competition

Robustness and throughput:

• Continuous operation over 30 days with no maintenance required
• Retention time %RSD of 1.7% for norfentanyl and 0.5% for fentanyl
• Peak area %RSD of 9.7% (norfentanyl) and 8.9% (fentanyl)

Benefits and practical applications

The Nexera QX platform offers several practical advantages:

• Significantly reduced carryover minimizes sample re-injections and batch repeats
• Customizable rinse sequences allow laboratories to tailor workflows for diverse assay panels
• Seamless software interface with batch importing simplifies routine or research operations
• Enhanced source and ion optics design ensure stable sensitivity over prolonged use

Future trends and opportunities

Emerging directions for high-throughput LC-MS include:

• Expanded AI-driven diagnostics for predictive maintenance and dynamic method optimization
• Integration with laboratory information management systems (LIMS) for end-to-end automation
• Increased multiplexing channel counts to further boost sample throughput
• Adoption of novel ionization sources and high-resolution detectors to extend method capabilities

Conclusion

The Nexera QX Multiplexing LC-MS platform, combining innovative hardware design with advanced analytical intelligence, delivers robust high-throughput performance with minimal carryover and maintenance. Its flexible rinsing strategies, improved ionization stability and user-friendly software create an efficient solution for clinical, pharmaceutical and forensic laboratories seeking to maximize productivity and data confidence.