Quantitative Measurements and Improved Spectral Precision

The Zero X Plus microscope objective incorporates "Collimated Laser with Backscatter Collection" to provide "Representative Sampling" and "Real-Time Raman Calibration" to provide Improved Spectral Precision allowing for improved qualitative and quantitative analysis of complex solid samples using a traditional research Raman microscope.

• Closely related to the PhAT Probe and Transmission Raman techniques as both rely on diffuse scattering and photon migration within the sample to enhance the Raman signal and provide representative sampling.
• Unwanted Raman signals from surface coatings are significantly reduced making it ideal for coated tablets and capsules.
• Extended Wavenumber Range: The Zero X Plus optic enables the collection of representative spectra over the complete Raman spectral range (5 to 3425 cm^-1)
• "Real-Time Raman Calibration" can correct for unwanted wavenumber shifts observed in Raman spectra from the laser or spectrograph due to thermal drifting or instability.

Reduced Unwanted Signal from Surface Coatings

The Raman spectra below collected from a generic Excedrin tablet using a research Raman microscope with a focusing 20X objective. The surface coating generates a strong unwanted background signal

The Raman spectra below was collected from the same generic tablet using "Collimated Laser with Backscatter Collection" on the same Raman microscope. The collimated laser is transmitted through the surface coating and the Raman spectra from the bulk of the sample dominates the combined Raman spectra as per Transmission Raman.

Representative Sampling

The Zero X Plus on a Raman microscope will enable representative sampling from the "Collimated Laser with Backscatter Collection" design over the full Raman spectral range (5 to 3425 cm^-1) and not just the limited wavenumber ranges of the PhAT probe and Transmission Raman. Below RIO 50 Plus (Blue Spectra) and PhAT Probe (Red Spectra)

Real-Time Calibration

The Raman spectral plot below is of an Aspirin tablet with the reference Raman band from the CaF² standard superimposed onto the spectral plot. The Raman spectra plot from the CaF² optic is shown in the lower right corner.

Unwanted wavenumber shifts observed in Raman spectra from the laser or spectrograph due to thermal drifting or instability can be corrected for by using the CaF² Raman reference band.

Features

• Representative Sampling: Simply switch from traditional focused point measurements to Zero X Plus large spot measurements to enable representative sampling using "Collimated Laser with Backscatter Collection" generating reproducible measurements and representative sampling.
• Extended Wavenumber Range: The Zero X Plus optic enables the collection of representative spectra over the complete Raman spectral range (5 to 3425 cm^-1)
• Long Working Distance: The Zero X Plus optic enables the non-contact collection of Raman spectra from samples inside deep wellplates.
• Large Spot Size: The Zero X Plus optic enables signal averaging over SERS surfaces.
• Real-Time Calibration: An integrated CaF² optic generates a reference Raman band at 321.0 wavenumbers superimposed onto each collected Raman spectra.
• Improved Spectral Precision: Will allow for spectral separation of each component compared to the traditional spatial separation of individual components.
• Upgrade Option: The Zero X Plus microscope objective can be used on most Raman microscopes.

Applications

Qualitative analysis by spectral separation of individual components and chemometric modeling for concentration predictions.

• Coated tablets
• Uncoated Tablets
• Capsules
• Powders
• Blends
• Microplastics
• SERS substrates

References

RAMAN IMMERSION PROBE SYSTEMS AND METHODS
U.S. Patent – 10,976,259 B2
REAL-TIME RAMAN CALIBRATION
US Patent Application Serial No. 17/386,723

Collimated Laser with Backscatter Collection

The technique uses diffuse scattering and photon migration within the bulk of the sample to enhance the Raman signal and generate representative Raman spectra enabling the Quantitative Analysis of Solids and Powders. This technique relates closely to the approach used by a PhAT Probe and Transmission Raman instrument.

Features

• The RIO 50 Plus optic can enable the collection of representative spectra over the complete Raman spectral range (5 to 3425 cm^-1)
• The RIO 50 Plus optic has a long working distance and depth of field making it ideal for both Non-contact or Immersible applications.
• The RIO 50 Plus optic is a retrofit option for use with most existing Raman instruments.

RIO 50 Plus Probe Optic

Applications

Qualitative and Quantitative measurements on:

• Complex Mixtures
• Powders
• Blends
• Granules
• Slurries

Probe Comparison

RIO 50 plus (Blue Spectra) versus PhAT Probe (Red Spectra)

Real-Time Raman Calibration

Unwanted wavenumber shifts observed in Raman spectra from the laser or spectrograph due to thermal drifting or instability can be corrected for by using the Raman reference band at 321.0 cm^-1 superimposed onto each collected Raman spectra.

Features

• Improved spectral precision will improve the sensitivity and robustness of chemical models and calibration transfer between different probes and instruments.
• The 321.0 cm^-1 reference Raman band lies between the 5-200 cm^-1 Terahertz region and the 400-1800 cm^-1 chemical fingerprint region.
• The overall flat spectral response avoids unwanted Raman bands generated by sapphire windows or lenses

RIO 50 Plus Probe Optic

Applications

Qualitative and Quantitative measurements on:

• Complex Mixtures
• Powders
• Blends
• Granules
• Slurries

Raman Reference Band

The 321.0 w avenumber Raman band in the plot below is from the integrated CaF₂ optic

Probe Optic Light Shield

The RIO 100 is an immersion optic that collects enhanced Raman spectra using diffuse scattering from particles and photon migration within turbid liquids. The gold-plated RIO 100 Probe Optic Light Shield with retroreflector enhances the Raman signal by extending the laser pathlength by diffuse scattering from particles within the turbid liquid sample.

Features

The inner and outer slots on the surface of the probe optic light shield are offset to allow for liquid flow and to provide:

• Improved laser safety
• Reduced interference from unwanted outside lighting
• Reduced laser induced fluorescence from glass reactors

RIO 100 Probe Optic

Applications

Potential applications are:

• Nucleation processes
• Crystallization processes
• Upstream fermentation
• Downstream fermentation
• Nanoparticles
• Micro-plastics

Gold-Plated Probe Optic Light Shield