Multimodal Sub-Visible Vibrational Micro-spectroscopy of Biopharma and Environmental Particulates

Particulates are a significant concern in both pharmaceuticals and environmental research due to their potential health and safety risks. In biopharmaceuticals, sub-visible particles can trigger immunogenic responses and compromise drug safety and efficacy. In the environment, microplastics (1 µm to 1 mm) and nanoplastics (<1 µm) have become pervasive contaminants, capable of penetrating biological barriers and transporting toxic compounds, posing serious ecological and health hazards.
Traditional methods for particulate characterization, such as Raman microscopy and infrared spectroscopy, face limitations. While Raman microscopy can identify particles as small as 300–500 nm, it often suffers from fluorescence interference and slow measurement speeds due to poor sensitivity. FTIR spectroscopy, effective for particles larger than ~10 µm, lacks the spatial resolution required for smaller particulates and often suffers from spectral distortions due to dispersive scattering.
Optical Photothermal Infrared (O-PTIR) spectroscopy overcomes these challenges by combining submicron spatial resolution with the chemical specificity of infrared spectroscopy. Key advantages of O-PTIR include its ability to deliver sub-micron, even sub-500nm IR spatial resolution with the ability to perform simultaneous Raman spectroscopy and requires minimal sample preparation. Recent advancements further enhance its utility by integrating widefield epi-fluorescence imaging, enabling co-located fluorescence and chemical analysis for fluorescently labeled samples or for samples with distinctive autofluorescence.
These features make submicron O-PTIR particularly effective for the detailed characterization of sub-visible particulates in pharmaceuticals, such as protein aggregates and contaminants, and environmental samples like microplastics and aerosols. This tri-modality technique represents a significant step forward in particle characterization to address critical challenges in these fields.