Transmission Raman spectroscopy (TRS) is a variant of

Raman spectroscopy Raman spectroscopy () (named after Indian physicist C. V. Raman) is a spectroscopic technique typically used to determine vibrational modes of molecules, although rotational and other low-frequency modes of systems may also be observed. Raman sp ...

which is advantageous in probing bulk content of diffusely scattering samples. Although it was demonstrated in the early days of Raman spectroscopy it was not exploited in practical settings until much later, probably due to limitations of technology at the time. It was rediscovered in 2006, where the authors showed that it was capable of allowing Raman spectroscopy through many millimetres of tabletted or powdered samples. In addition, this research has also identified several highly beneficial analytical properties of this approach, including the ability to probe bulk content of powders and tissue in the absence of subsampling and to reject Raman and fluorescence components originating from the surface of the sample.

Theory

Transmission Raman is possible because light scatters through

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materials that do not significantly absorb or block the light. By a similar mechanism to spatially offset Raman spectroscopy, the light in a diffusely scattering sample spreads through the object

randomly In common usage, randomness is the apparent or actual lack of pattern or predictability in events. A random sequence of events, symbols or steps often has no :wikt:order, order and does not follow an intelligible pattern or combination. Ind ...

(Transmission Raman can be regarded as an extreme example of SORS). As Raman photons can be created at all points that the light passes through the total scrambled Raman signal measured on the opposite face of the object is highly representative of the bulk of the material. This desirable property removes a problem with conventional, widely used back-scattering Raman spectroscopy where the signal tends to be representative of the surface and near-surface composition. Because Raman spectroscopy does not rely on absorption and the light spreads throughout the sample, a large thickness can be measured in the absence of photon absorption. This produces an analysis representative of the entire mixture and is typically insensitive to coatings, or thin containers.

Pharmaceutical applications

Transmission Raman lends itself to rapid, non-invasive and non-destructive analysis of

pharmaceutical A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy (pharmacotherapy) is an important part of the medical field and re ...

dosage forms Dosage forms (also called unit doses) are pharmaceutical drug products in the form in which they are marketed for use, with a specific mixture of active ingredients and inactive components (excipients), in a particular configuration (such as a cap ...

such as capsules and tablets. This addresses several limitations of traditional pharmaceutical

assay An assay is an investigative (analytic) procedure in laboratory medicine, mining, pharmacology, environmental biology and molecular biology for qualitatively assessing or quantitatively measuring the presence, amount, or functional activity of a ...

techniques including limitations due to surface sensitivity (e.g.,

reflectance The reflectance of the surface of a material is its effectiveness in reflecting radiant energy. It is the fraction of incident electromagnetic power that is reflected at the boundary. Reflectance is a component of the response of the electronic ...

NIR), the presence of phase changes due to sample preparation (

liquid chromatography In chemical analysis, chromatography is a laboratory technique for the Separation process, separation of a mixture into its components. The mixture is dissolved in a fluid solvent (gas or liquid) called the ''mobile phase'', which carries it ...

) or sub-sampling (conventional Raman, NIR). Transmission Raman is largely insensitive to surface, requires no sample preparation, involves no phase change and is rapid. Transmission Raman spectroscopy of pharmaceutical tablets and capsules was first demonstrated by Matousek and Parker. Subsequent research established the technique’s accuracy and applicability to quantifying tablet and production-style capsule formulations. Pharmaceutical tablets and capsules are typically composed of a combination of

API An application programming interface (API) is a way for two or more computer programs to communicate with each other. It is a type of software Interface (computing), interface, offering a service to other pieces of software. A document or standa ...

s and

excipients An excipient is a substance formulated alongside the active ingredient of a medication, included for the purpose of long-term stabilization, bulking up solid formulations that contain potent active ingredients in small amounts (thus often referred ...

, each of which will produce a Raman spectral component with a relative intensity proportional to the ingredient concentrations. Analysing Raman spectra to produce assay results requires a method to separate the individual spectral components and correlate their intensity contributions with a relative concentration measure. This is typically facilitated using chemometric analysis methods. Transmission Raman spectroscopy can be used as a

process analytical technology Process analytical technology (PAT) has been defined by the United States Food and Drug Administration (FDA) as a mechanism to design, analyze, and control pharmaceutical manufacturing processes through the measurement of critical process paramete ...

(PAT) tool for the detection of physical state of the

and for obtaining qualitative and quantitative information about the composition.

Medical applications

The use of Raman spectroscopy in medical applications has been limited to depths of hundreds of

micrometres The micrometre (American and British English spelling differences#-re, -er, international spelling as used by the International Bureau of Weights and Measures; SI symbol: μm) or micrometer (American and British English spelling differences# ...

( confocal Raman). Transmission Raman has been demonstrated as a potential diagnostic tool for lesions in breast tissue.

References

{{Raman spectroscopy Raman scattering Raman spectroscopy