Raman Microscopy

Method Introduction

Raman microscopy is a powerful technique that delivers bright field images of particles as low as a few micrometers and allows for the identification of individual particles through Raman spectroscopy. The technique can be applied to samples in suspension or after isolation on a filter.

A reservoir is filled with the sample to analyze particles in liquid formulations, and microscopic images of the suspended particles are taken, enabling a morphological analysis. Particles of interest are subsequently illuminated with a laser beam, and the lens collects the electromagnetic radiation from the illuminated particle. The wavelength corresponding to that of the laser light (Rayleigh scattering) is filtered out, while the rest of the collected light is dispersed onto a detector. The recorded Raman scattering information serves as a chemical fingerprint, which is compared to a library or a reference compound to determine the chemical identity or origin of the particle.

Applications

Raman microscopy is typically used during troubleshooting and root-cause analysis. Coriolis offers Raman microscopy as a stand-alone service or as part of a particle identification study or formulation development program.

Raman microscopy has a high spatial resolution and can be applied to particles as small as ca. 5 µm. Depending on the particle properties, long acquisition times might be required, typically allowing only a few particles per sample to be analyzed. Data from Raman microscopy can be combined with flow imaging microscopy (FIM) results. At this moment, the particle morphology information from both instruments is used to link particle identity to quantitative information.

Analyzing particles suspended in liquid presents challenges, especially when formulation components interfere with the scattering signal. In this case, particles inside the sample may be isolated on a filter, preferably a metal-coated membrane or a gold filter. This reduces the influence of water and formulation components on the analysis.

Quality and Biosafety Level

We provide all our analytical services with the highest quality standards. Experienced scientists carry out each project, and a scientific reviewer comprehensively checks every report or data presentation.

We offer this technology with the following quality and biosafety levels:

R&D level

We offer this method under R&D. Our GRP system assures the highest-quality research standards.

Up to biosafety level 2

This method can be applied to nucleic acids, viruses, cells, viral vectors, including lentiviruses and more.

Analytical Method Development, Qualification and Validation

For common sample types, we can often apply standardized methods with little setup effort. However, when needed, our experienced analytical experts create or optimize custom methods tailored to your active pharmaceutical ingredient, product type and development phase.

Method Development

Our method development approach tailors sample preparation, method settings and data analysis to the needs of your project and sample.

We include representative samples and, where available, suitable reference standards and stressed/degraded materials, allowing our analytical scientists to design a highly suitable, stability-indicating, robust and repeatable method. Upon request, we will compile a detailed description of the method for your records.

Method Qualification

Method qualification is the initial assessment of an analytical procedure’s performance to show its suitability for its intended purpose.

During method qualification, our analytical scientists perform documented testing demonstrating that the analytical procedure meets criteria in several categories. Criteria may include factors such as repeatability, specificity and robustness. We compile a qualification plan and report, including all relevant data.

Method Validation

Under GMP conditions, method validation confirms that an analytical procedure’s performance suits its intended purpose. Depending on the method’s scope, a broad range of method characteristics, such as specificity, accuracy, precision, limit of detection/limit of quantification (LOD/LOQ), linearity and range, is considered.

During method validation, our analytical scientists perform documented testing demonstrating that the analytical procedure consistently produces a result that meets the predetermined acceptance criteria. We compile a validation plan and report that includes all relevant data.

Depending on the development phase, a fit-for-purpose validation approach can be offered, adjusting the validation required efforts in a phase-appropriate way to meet the method’s needs.

Method Verification

Compendial method verification confirms that a compendial method (e.g., from Ph. Eur. or USP) is suitable and reliable for its intended purpose under the specific conditions of the laboratory.

Unlike full method validation, compendial method verification is often considered a partial validation since the method has already undergone extensive testing and validation during its inclusion in the compendium. The extent of method verification depends on the type of method.

During method verification, our analytical scientists perform documented testing demonstrating that the developed analytical method performs adequately for the specific product or matrix being tested and within the specific laboratory where the method will be employed.

Talk to Our Experts or Request a Quote

Our expert team is ready to answer your questions and guide you to the services best suited to your program’s modality, stage and challenge. If your needs are well-defined, we’ll begin the quotation process.

Related Services

Fourier transform infrared (FTIR) microscopy Scanning electron microscopy coupled energy-dispersive x-ray spectroscopy (SEM-EDS)

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