Applications of Raman Spectroscopy in Medical Diagnostics, Incoming Inspection and Silicon Wafer Testing

Raman spectroscopy uses inelastic scattering of protons from molecules that are covalently bound in order to identify functional groups, stresses, strains and crystallinity.

It is a tool that is widely used within the spectroscopy community for both qualitative and quantitative molecular analysis and has applications ranging from airport security scanning to high-end university research.

It can often be confusing to determine which spectrometer is best suited for any given application due to the broad range of applications available for Raman spectroscopy. This article will provide an overview of three common applications to help alleviate this challenge: incoming material verification, silicon wafer stress monitoring and biomedical diagnostics. It will also suggest a preferred spectrometer for each application.

Medical Diagnostics

Raman spectroscopy has repeatedly been shown to have a huge potential for point-of-care monitoring and diagnostics because it can provide a non-destructive, non-contact molecular fingerprint of many common physiological biomarkers.

There have been thousands of publications within the field of cancer detection alone, which range from applications such as urine testing for monitoring lung cancer response to treatment to interoperative cancer boundary detection during brain, oral, and breast tumor removal.

Most common biomolecules, such as proteins, nucleic acids, fats and lipids, are highly Raman active because of their nonpolar molecular structure. Additionally, and perhaps more importantly, due to the extreme polarity of water molecules, the large amounts of water in these samples does not interfere with the spectra.

Raman can be used in both tissue and bodily fluids to identify blood disorders, pathogens, cancers and other abnormalities. This is because of the dichotomy between the scattering cross-sections of biological macromolecules and water.

Biological molecules are complex and therefore tend to produce much broader spectral features than most other Raman active molecules. This means that the spectral range and resolution requirements of the device are often relatively relaxed and also lends itself to a reduction in overall signal efficiency requiring longer integration times.

In fit-for-purpose instrumentation, which is designed to look only at a few select spectra, this is particularly evident. For this application, a good choice is a spectrometer such as the AvaSpec-Hero, model number AvaSpec-1024X58-HSC-EVO because of its higher-sensitivity back-thinned CCD detector and deep cooling.

Furthermore, the AvaSpec Hero has an extremely wide dynamic range of 40,000:1 and this makes it much easier to detect subtle variations which can often mark the difference between healthy and diseased tissue.

Silicon Wafer Testing

Another application that is up and coming, particularly in the photovoltaics’ industry, is the monitoring of both crystallinity and stresses in silicon wafers. Pure crystalline is utilized in the production of over 85% of the commercially available solar cells on the market today because it is much more effective at converting light into electricity than its amorphous counterpart.

Amorphous silicon solar cells offer less than 10% efficiencies whilst crystalline silicon is capable of producing conversion efficiencies of approximately 20%. Therefore, quality control of these devices at the wafer level is critical to ensure peak performance. Raman spectroscopy is ideally suited for the job because, since the effect is polarization sensitive, the orientation of the silicon molecular structure will affect scattered Raman spectra. In the case of pure crystalline silicon, there is only one allowed molecular vibration which results in a single narrow spectral peak at 521cm-1.

Conversely, for amorphous silicon, where the molecules are randomly orientated, the band shifts and broadens which results in a very wide peak centered at 480 cm-1. However, even if the wafer is made of pure crystalline silicon, if it undergoes stresses or strains during the manufacturing process it will reduce the efficiency and lifetime of the solar cell.

This is because the stress results in the molecular bonds becoming dampened which causes slight changes in the vibrational frequency and these can be detected by looking at the shift in the Raman peak.

Sensitivity is not usually a concern in either of these applications due to the large Raman cross-section of silicon, however, high resolution is critical in order to detect the small shifts in the 521cm-1 peak from stresses and strains. Importantly, silicon is unique for having a photoluminescence peak in the near infrared and this means it is preferable to use visible wavelength excitation lasers to further increase the Raman scattering efficiency of the system.

Therefore, the AvaSpec-ULS2048X64-TEC, high resolution TE cooled spectrometer (capable of 3 cm-1 resolution in the visible range of the spectrum), is recommended. Avantes’ proprietary data transfer rates, analogue digital I/O capabilities and high-speed electronic triggering additionally help this unit’s ability to integrate seamlessly into a high-speed wafer inspection system.

Incoming Inspection

The final application to be explored is incoming material inspection for nutraceutical and pharmaceutical manufacturing. This utilizes the same fingerprinting ability of Raman spectroscopy described in the biomedical section above. Over the past ten years this application has led, in part, to the handheld Raman systems which can be seen on the market today. This is due to its rapid material verification process which allows raw materials to pass quickly from the quarantine area to the production floor.

Typically this is accomplished by integrating the spectrometer, data processing unit and laser into a single handheld device which has embedded chemometrics for verifying the identity of excipients, API’s and other pharmaceutical ingredients. The Rama laser can be focused through optically transparent packaging which means the contents can be analyzed without opening the produce and exposing its contents to the environment and this makes it ideally suited for this application.

Size is one of the most critical design considerations for integration into a handheld device and for that reason, the AvaSpec-Mini-2048CL is the spectrometer of choice for many handheld instrumentation manufacturers. It weighs only 175 grams and is compact (95 mm x 68 mm x 20 mm – roughly the size of a pack of playing cards).

Due to the highly efficient 2048-pixel CMOS linear array detector, the AvaSpec-Mini uses less than 2.5 watts of power. It is produced with the latest in automated production technology which provides excellent temperature stability and unit-to-unit reproducibility and this is critical for customers who want to transfer methods from one handheld instrument to another.

Final Thoughts

The three applications discussed, whilst far from the only Raman spectroscopy applications, should provide a framework that can be used by a systems integrator when deciding which spectrometer would be best for their specific application.

This information has been sourced, reviewed and adapted from materials provided by Avantes BV.

For more information on this source, please visit Avantes BV.


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