Raman spectroscopy as process analytical tool in downstream processing of biotechnology

Downstream processing or product recovery plays a vital role in the development of bioprocesses. To improve the bioprocess efficiency, some unconventional methods are much required. The continuous manufacturing in downstream processing makes the Process Analytical Technologies (PATs) as an important tool. Monitoring and controlling bioprocess are an essential factor for the principles of PAT and quality by design. Spectroscopic methods can apply to monitor multiple analytes in real-time with less sample processing with significant advancements. Raman spectroscopy is an extensively used technique as an analytical and research tool owing to its modest process form, non-destructive, non-invasive optical molecular spectroscopic imaging with computer-based analysis. Generally, its application is essential for the analysis and characterization of biological samples, and it is easy to operate with minimal sample. The innovation on various types of enhanced Raman spectroscopy was designed to enhance the Raman analytical technique. Raman spectroscopy could couple with chemometrics to provide reliable alternative analysis method of downstream process analysis. Thus, this review aims to provide useful insight on the application of Raman spectroscopy for PAT in downstream processing of biotechnology and Raman data analysis in biological fields.