Infrared (IR) absorption spectroscopy has been used widely as a non-invasive, label-free characterization method for chemical identification and structure of biomolecules. Fourier-transform IR (FT-IR) technology is commonly used to characterize proteins and other biological molecules produced during biopharmaceutical processes. FT-IR is advantageous because it does not require additional sample preparation steps, such as buffer exchange and dilution, which are needed for other techniques like far-ultraviolet (UV) circular dichroism (CD) spectroscopy.
Extensive studies on IR spectroscopy of proteins have shown that the amide bands can be used to semi-quantitatively characterize the secondary structure (e.g., a-helix and b-sheet) of the protein backbone conformation. However, the interference by strong water absorption keeps FT-IR from characterizing low concentration samples of <10 mg/mL and prevents the usage of a long-pathlength optical cell. Non-invasive optical characterization of low-concentration protein samples is critical for new types of drugs, such as peptide drugs (typically ≈1 mg/mL) and vaccines (0.1 mg/mL to 10 mg/mL).
Recently, we have developed a new mid-IR absorption spectroscopy using a quantum cascade laser (QCL) technology that can detect the amide I band of a protein solution with 100 times better chemical sensitivity compared to traditional mid-IR. The technology was recently awarded a patent .
 Y. J. Lee, Spectrum Adjuster and Producing a Pure Analyte Spectrum. US Patent Appl. No. 16,164,859. (2018).