Verifying the Performance of the Integrating Sphere Module on the Thermo Scientific Antaris FT-NIR Analyzer

Verifying the Performance of the Integrating Sphere Module on the Thermo Scientific Antaris FT-NIR Analyzer — Summary

Importance of the topic

Fourier transform near-infrared (FT-NIR) diffuse reflectance spectroscopy enables rapid analysis of solids and powders with minimal sample preparation, making it highly valuable for quality control, raw material identification and process monitoring in pharmaceutical, chemical and materials industries. The integrating sphere is a central element for collecting diffuse reflectance from heterogeneous samples; its optical design, reference handling and stability determine the reliability and reproducibility of analytical results. Verifying the performance of such a module is therefore essential to ensure accurate spectral data, robust chemometric models and confidence in routine production or research workflows.

Objectives and overview of the study

The study aimed to evaluate four key performance aspects of the Antaris FT-NIR integrating sphere module: instrument sensitivity (noise and signal-to-noise ratio), wavelength accuracy, spectral resolution behavior, and instrument stability/precision over time. Tests were designed to mimic common diffuse reflectance use cases — spectra collected from powders and solids in vials — and used standard materials and procedures to quantify each performance metric.

Methodology

Test strategy and sample handling:

• Spectra were collected directly through sample vials placed on the integrating sphere window; the internal gold-coated reference flag served as the background.
• Sensitivity testing: single 30-second sample acquisition at 8 cm-1 resolution (background collected with gold flag in place and not moved).
• Wavelength accuracy: moist air (water vapor) introduced into the instrument; peak positions compared to HITRAN database values.
• Resolution testing: spectra of the NIST SRM 1920a reflectance standard (powdered heavy metal oxides) recorded at resolutions ranging from 2 to 32 cm-1 to assess peak shape and resolving power.
• Stability/precision: a talc-in-lactose powder mixture (nominal ~10% talc) was repeatedly measured using a TQ Analyst classical least squares (CLS) calibration and an automated RESULT software workflow acquiring spectra every 15 minutes over 24 hours; only a single background was used to emphasize instrument stability effects.

Measurement parameters:

• Spectral resolutions tested: 2, 4, 8, 16, 32 cm-1 (resolution-dependent noise and peak definition studied).
• Sensitivity spectra recorded at 8 cm-1; precision tests at 4 cm-1.

Instrumentation used

• Thermo Scientific Antaris FT-NIR analyzer with internal gold-coated integrating sphere module and protective sapphire window.
• Automated internal gold diffuse reference flag for background acquisition.
• NIST SRM 1920a reflectance standard for resolution verification.
• HITRAN database (1996 reference) for water vapor line positions to assess wavelength accuracy.
• Thermo Scientific TQ Analyst software for CLS calibration development.
• Thermo Scientific RESULT software for automated workflow and repeated measurement acquisition.

Main results and discussion

Sensitivity and noise:

• RMS noise in the 8 cm-1 spectrum was better than 10 micro-absorbance units in the 4500 cm-1 and 6000 cm-1 regions, corresponding to an effective signal-to-noise ratio on the order of 100,000:1 for strong diffuse reflectance features (near log(1/R) ≈ 1).

Wavelength accuracy:

• Using water vapor lines and HITRAN reference values, peak position deviations were below 0.3 cm-1 (approximately 0.1 nm) at 4 cm-1 resolution, indicating excellent wavelength calibration suitable for spectrally specific applications.

Spectral resolution behavior:

• Spectra of NIST SRM 1920a recorded at 2–32 cm-1 demonstrated the expected sharpening of features at higher resolution. While higher resolution improves spectral specificity for sharp bands (e.g., some pharmaceutical actives), it also increases noise.
• For many diffuse reflectance applications a practical compromise is 4 or 8 cm-1 resolution to balance sensitivity and specificity.

Stability and precision:

• Repeated measurements (100 repeats) on a ~10% talc in lactose mixture over 24 hours (laboratory environment without special temperature control) showed negligible drift. The mean calculated talc content was 9.997% with a standard deviation of 0.029%.
• The use of a single background across the entire run highlighted the intrinsic instrumental stability of the integrating sphere module and detection chain.

Application example:

• Talc in lactose provides a representative case where a sharp talc band near 7200 cm-1 requires adequate resolution for specificity; the Antaris module performed well for this use case when using appropriate resolution settings.

Benefits and practical applications of the method

• High sensitivity and excellent wavelength accuracy make the integrating sphere-equipped Antaris FT-NIR suitable for quantitative diffuse reflectance analyses of solids and powders with minimal sample prep.
• Stable performance over extended runs supports repetitive QC workflows, routine assay monitoring and PAT-style implementations.
• The open sample area and automated internal reference reduce sample handling and potential reference damage, facilitating measurements of larger or irregular samples and improving throughput.
• Combined with chemometric software (TQ Analyst, RESULT), the system enables automated, scheduled acquisition and inline-style monitoring of sample composition.

Future trends and potential uses

• Integration with more advanced chemometric and machine-learning models to improve robustness across diverse matrices and to better compensate for sample heterogeneity.
• Increased automation and connectivity for real-time process analytical technology (PAT) and continuous manufacturing environments.
• Improved detector technologies and noise-reduction strategies to allow higher effective resolution without prohibitive SNR penalties.
• Development of tailored integrating sphere geometries, coatings and reference strategies to optimize collection for highly scattering or layered samples.
• Expanded use for non-destructive screening in pharmaceuticals (raw materials, tablet coatings, blend uniformity), food and agricultural products, polymers and minerals.

Conclusions

The integrating sphere module on the Thermo Scientific Antaris FT-NIR analyzer demonstrates high sensitivity (RMS noise <10 µA at tested regions), excellent wavelength accuracy (<0.3 cm-1 at 4 cm-1), controllable resolution from 2–32 cm-1 and outstanding short-term stability (24 h repeatability with SD 0.029% for talc content). These characteristics support reliable diffuse reflectance analyses of powders and solids for quantitative and qualitative applications in pharmaceutical and industrial settings. The instrument design — including the internal gold reference flag and open measurement area — simplifies routine measurements while preserving performance needed for demanding NIR applications.

References

• NIST Standard Reference Material (SRM) 1920a — Reflectance standard (powdered heavy metal oxides).
• HITRAN molecular spectroscopic database (1996 Edition) — reference water vapor line positions used for wavelength accuracy assessment.
• Thermo Fisher Scientific — Antaris FT-NIR Analyzer technical note and software: TQ Analyst, RESULT (Technical Note 51669).