LC-MS Medical Devices for Laboratory Developed Tests

Significance of the topic

Liquid chromatography–mass spectrometry (LC–MS) has emerged as a powerful complementary technology to conventional chemistry and immunoassays in clinical diagnostics. By delivering high specificity, rapid analysis and extended analyte coverage while reducing cost per sample and sample volume, LC–MS enables laboratories to develop in-house assays (LDTs) with improved confidence and operational efficiency.

Objectives and study overview

This document presents a comprehensive portfolio of in vitro diagnostic (IVD)-compliant LC–MS medical devices and software solutions by Thermo Scientific designed for laboratory-developed tests. The goals are to replace expensive random-access immunoassays with cost-effective batch LC–MS workflows, meet varying sensitivity and throughput requirements, and integrate seamlessly with laboratory information systems (LIS).

Methodology

A batch testing approach is employed using high-pressure liquid chromatography coupled to tandem mass spectrometry (LC–MS/MS). Quantitative assays rely on targeted selected reaction monitoring (SRM) to measure clinically relevant analytes. Data acquisition and processing are managed via dedicated software that automates method setup, sample queueing, data review and reporting.

Instrumentation

• Vanquish MD HPLC system: dual solvent channels, ultra-precise flow control for robust separation
• TSQ Quantis MD Series mass spectrometer: triple-stage quadrupole with Active Ion Management (AIM+) for routine quantitation
• TSQ Altis MD Series mass spectrometer: enhanced sensitivity variant with optimized ion optics and high-capacity transfer tube
• OptaMax NG atmospheric pressure ionization source: automated gas/voltage connection for ESI or APCI operation
• TraceFinder LDT software: integrated quantitation, batch processing, user permissions and audit trails
• TSQ Series II Altis MD and Quantis MD Software: tuning, calibration and method development environment
• B-Link Universal LIS/LIMS Connector: middleware for bidirectional communication using ASTM-1394-91 and ASTM-1381-95 standards

Key results and discussion

Analytical demonstrations included steroid hormones (e.g., estrone, testosterone) and immunosuppressants (e.g., cyclosporin A, tacrolimus) at low nanogram levels. Mass spectra exhibited clear quantifier and qualifier transitions with high relative abundances and excellent mass resolution. The systems delivered fast SRM cycle times, stable performance over extended runs and reproducible results across instruments.

Benefits and practical applications

• Superior specificity and selectivity reduce false positives/negatives compared to immunoassays
• High throughput and fast turnaround meet clinical laboratory demands
• Multiplexed detection of multiple analytes in a single run enhances flexibility
• Lower operational costs through batch testing and reduced consumables
• IVD compliance with ISO 13485 and FDA 21 CFR 820 standards
• Risk control via validated workflows, certified service engineers and audit-ready software
• Seamless LIS integration minimizes manual data entry and accelerates result reporting

Future trends and applications

Continued adoption of LC–MS for routine clinical assays will drive further automation, higher throughput and expanded analyte coverage. Integration with digital laboratory ecosystems and advanced data analytics will enable personalized medicine, real-time monitoring and more robust decision support. Regulatory frameworks are also evolving to streamline IVD-compliant LC–MS assay deployment.

Conclusion

The Thermo Scientific portfolio provides a fully integrated solution for in-house clinical testing by LC–MS. It combines sensitive instrumentation, dedicated software and robust connectivity to enable laboratories to develop and validate reliable, cost-effective LDTs that meet stringent IVD requirements and support a wide range of clinical applications.

References

• ASTM E1394-91: Standard Specification for Clinical Laboratory Data Interchange
• ASTM E1381-95: Standard Practice for Clinical Laboratory Information Systems