O-PTIR Spectroscopy Advances Submicron Chemical Analysis for Pharmaceutical R&D and Quality Control
核心洞察
Optical Photothermal Infrared Spectroscopy (O-PTIR) combines infrared chemical specificity with submicron spatial resolution, overcoming key limitations of conventional IR microscopy.
The technology enables high-resolution mapping of active pharmaceutical ingredients and excipients, plus detection of contaminants, foreign particles, and manufacturing defects.
O-PTIR supports characterization of biologic formulations and protein aggregates while streamlining analytical workflows and regulatory compliance.
The pharmaceutical and biopharmaceutical industries increasingly require rapid, accurate, and high-resolution analytical tools to characterize complex materials, ensure product quality, and accelerate innovation. Optical Photothermal Infrared Spectroscopy (O-PTIR) represents a breakthrough technology that combines the chemical specificity of infrared spectroscopy with submicron spatial resolution, overcoming many limitations of conventional IR microscopy.
Photothermal Spectroscopy Corp (搜索) (PSC), a Santa Barbara, CA-based scientific equipment company, pioneered sub-micron IR microscopy and spectroscopy. The company's vision is to enable the power of sub-micron IR spectroscopy to be applied to high-value problems in both industry and academia through the adoption of O-PTIR and co-located multi-modal techniques.
How O-PTIR Works
O-PTIR overcomes the IR diffraction limit by combining a mid-IR pulsed, tunable laser that heats the sample. When the IR laser is at a wavelength that excites a molecular vibration in the sample, absorption occurs, creating photothermal effects including photothermal expansion. A visible probe laser, focused to a 0.5 µm spot size, measures the photothermal response via the scattered light.
The component of the reflected visible laser signal that is modulated at the IR pump laser repetition rate is directly proportional to the absorption coefficient of the sample at that wavenumber. The IR pump laser can be tuned through the entire fingerprint region in one second or less to obtain an IR spectrum.
By operating in reflection mode, O-PTIR eliminates several longstanding limitations and offers substantial benefits for the IR community, including sub-micron resolution using a non-contact optical method. The sub-micron resolution is demonstrated on a multi-layer packaging film, where reflection mode spectra measured 0.5 µm apart show highly differentiated chemical fingerprints indicating different materials.
Advantages Over Conventional IR Methods
O-PTIR eliminates key limitations of traditional IR spectroscopy by providing sub-micron IR spatial resolution with transmission-like FTIR quality spectra in non-contact reflection mode, with no Mie scattering effects. Measurements are collected quickly and easily without the need for sample contact, unlike ATR spectroscopy. Additionally, O-PTIR provides spectra comparable to FTIR without the dispersive artifacts observed in ATR.
By operating in reflection mode, the need for thin samples is also eliminated, leading to dramatically easier sample preparation and faster turnaround times.
Applications in Pharmaceutical Development and Quality
The technology enables the investigation and identification of submicron particles beyond the spatial resolution limits of conventional IR microscopy, delivering unprecedented spatial resolution, multimodal analytical capabilities, and actionable chemical insights for small-molecule pharmaceuticals, biologics, advanced formulations, and drug delivery systems.
Key applications include high-resolution mapping of active pharmaceutical ingredients (APIs) and excipient distributions, detection and characterization of contaminants, foreign particles, and manufacturing defects, and characterization of biologic formulations and protein aggregates. O-PTIR can also streamline analytical workflows, improve product quality, and support regulatory compliance.
Platform Evolution
With the introduction of the mIRage (搜索)® IR microscope, PSC pioneered the breakthrough sub-micron infrared spectroscopy and microscopy technique known as O-PTIR. The subsequent release of the mIRage-R combined O-PTIR with Raman technologies, introducing the world's first simultaneous sub-micron IR and Raman microscope and spectroscopy system, providing simultaneous IR and Raman data from the exact same spot, at the same time, with the same sub-micron spatial resolution.
The launch of the mIRage (搜索)-LS extended platform capabilities by combining O-PTIR with co-located fluorescence microscopy and further improved IR spatial resolution to sub-500nm. The mIRage-LS allows O-PTIR technology to address high-value life science research problems not able to be addressed by conventional IR microscopy.
Upcoming Webinar
PSC will host a webinar on Thursday, June 25, 2026, with three time zones available, demonstrating how O-PTIR enables the investigation and identification of submicron particles beyond the spatial resolution limits of conventional IR microscopy.
Dr. Mustafa Kansiz, Director of Product Management with more than 25 years of experience in IR and Raman microspectroscopy, will introduce O-PTIR as an innovative technique that provides detailed chemical information while overcoming many limitations of conventional IR methods. Guest speaker Dr. Kevin Dahl, Director of Pharmaceutical Products and Applications with more than 20 years of experience in pharmaceutical product development and investigations, will draw on real-world case studies to discuss how O-PTIR technology is being used across development, manufacturing, and quality assurance to address analytical challenges and enhance product understanding.