Characterization of particulate matter (PM) has been, and remains, a considerable challenge for scientists working in a range of industries. Small-molecule pharmaceuticals1, biopharmacueticals2, semiconductors, and microplastics3 all present contamination, chemistry, and instability problems for particulates below 20μm in size, where collection of high-quality spectroscopic data can be very challenging. Access to chemically-specific information on this size scale has potential to improve understanding of kinetic, process, product formulation stability and safety/efficacy and environmental outcomes. Novel tools are needed to push modern laboratory capabilities to higher sensitivity and smaller particulate size.
Optical Photothermal Infrared Spectroscopy (O-PTIR)4 is a novel technique for chemically characterizing PM at size scales down to submicron, even sub-500 nm – previously difficult to interrogate. O-PTIR is a pump-probe spectroscopic technique, where an infrared pump laser thermally excites a sample, which is then probed by a visible probe laser. Absorption of the IR laser, corresponding to vibrational transitions in the sample material, result in a subtle change in the temperature of the sample. This change in temperature results in a concomitant change in the refractive index of the material and sample expansion, changing the probe beam intensity. Measurement of the probe beam intensity as a function of IR wavelength tuning thus provides essentially pure IR absorbance spectrum comparable and compatible with existing FTIR transmission or ATR spectra. The net effect is measuring an IR spectrum that is free of optical effects such as density or the wavelength dependence of IR techniques such as ATR. Additionally, Raman scatter may be concurrently collected from the sample, providing an orthogonal vibrational spectroscopic fingerprint of the sample.
Optically, the resolution of O-PTIR is determined by the visible probe beam, which can be focused tightly relative to the IR pump beam. This results in spatial resolution capabilities of ~500nm, a massive 30x improvement over the 10-15 μm spatial resolution of FTIR systems, opening an experimental window in the subvisible extending into the submicron. The following examples prove O-PTIR capable of providing valuable information for biologic samples, where low signal strength has hobbled traditional dispersive Raman.
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Please click on ‘Request Application Note’ and download the application note ‘O-PTIR of biopharmaceutical particulates’.