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Summary
New biological drugs such as peptide drugs, gene delivery cargos, and vaccines are emerging to fill pharmaceutical voids. Infrared (IR) absorption spectroscopy is a non-invasive measurement that can characterize these complex biomolecules in their original solution condition. However, conventional IR spectroscopy approaches are unsuitable for hydrated proteins due to the strong IR absorption by water. The Biomaterials group has developed a high-sensitivity IR technique based on a quantum cascade laser (QCL) and a solvent absorption compensation (SAC) method. After a series of upgrades, the system can acquire an IR spectrum covering the fingerprint range with a 1000 times higher sensitivity than conventional FT-IR spectroscopy. This breakthrough novel IR spectroscopy can become a standard spectroscopic measurement tool in biopharmaceutical and biological industries and sciences.
Description
Infrared (IR) absorption spectroscopy has been widely used as a non-invasive, label-free characterization method for the chemical identification and structure of complex 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. However, the interference by strong absorption by the solvent, water, keeps FT-IR from characterizing low-concentration samples.
Recently, we developed a new optical technique called solvent absorption compensation (SAC) for quantum cascade laser (QCL)-based mid-IR absorption spectroscopy [1,2]. We further improved the detection sensitivity with a double-beam modulation (DBM) technique [3,4] and expanded the spectral range by a double-pass acousto-optic modulation (DP-AOM) technique [5].
The high-sensitivity IR spectroscopy technique is further developed to become a standard measurement tool for the non-destructive characterization of entirely new biological systems, including new protein drugs and gene therapy.
PUBLICATIONS
[1] B. Chon, S. Xu, Y. J. Lee, Compensation of Strong Water Absorption in Infrared Spectroscopy Reveals the Secondary Structure of Proteins in Dilute Solutions. Anal. Chem. 93, 2215 (2021).
[2] Y. J. Lee, Spectrum Adjuster and Producing a Pure Analyte Spectrum, US Patent Issued, 10,345,226 (2019).
[3] S.-M. Kim, Y.-R. Chang, Y. J. Lee, Single-Detector Double-Beam Modulation for High-Sensitivity Infrared Spectroscopy. Sci. Rep. 13, 18231 (2023).
[4] Y. J. Lee, Single-Detector Double-Path Intensity-Modulation Spectrometer, US Patent Published, US 2024/0167877 A1 (2024).
[5] S.-M. Kim, Y.-R. Chang, Y. J. Lee, Quantum Cascade Laser Infrared Spectroscopy for Glycan Analysis of Glycoproteins (under review).