Label-Free Autofluorescence-Detected Mid-Infrared Photothermal Microscopy of Pharmaceutical Materials

Razumtcev, Aleksandr; Li, Minghe; Rong, Jiayue; Teng, Chu C.; Pflüegl, Christian; Taylor, Lynne S.; Simpson, Garth J.

doi:10.1021/acs.analchem.1c05504

Cited by 11 publications

(15 citation statements)

References 47 publications

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“…Strong SHG was observed from all crystals within an FoV for the sample containing only α-indomethacin (Figure ). Moreover, both crystal forms exhibited strong TPE-UVF, consistent with a previous report indicating bright TPE-UVF activity per unit volume for indomethacin …”

Section: Resultssupporting

confidence: 91%

“…Moreover, both crystal forms exhibited strong TPE-UVF, consistent with a previous report indicating bright TPE-UVF activity per unit volume for indomethacin. 29 Qualitative and Quantitative Characterization of the Mixtures of Two Crystal Forms. A concentration series of solid mixtures of αand γindomethacin was prepared to investigate the LoD of the AF-PTIR microscopy for comparison with routine commercially available methods.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

“…The instrumentation supporting AF-PTIR, TPE-UVF, and SHG imaging was described in detail previously. 29 In brief, the microscope system was based on a counter-propagating probe and mid-infrared pump sources (Figure 1). A 1064 nm near-IR femtosecond laser (Fianium FemtoPower; 150 fs pulses at 50 MHz repetition rate and up to 1 W average power at 1064 nm emission) was used for nonlinear imaging.…”

Section: ■ Experimental Methodsmentioning

confidence: 99%

“…The instrumentation supporting AF-PTIR, TPE-UVF, and SHG imaging was described in detail previously . In brief, the microscope system was based on a counter-propagating probe and mid-infrared pump sources (Figure ).…”

Section: Experimental Methodsmentioning

confidence: 99%

“…F-PTIR was applied to characterize the chemical composition of phase-separated domains in a ritonavir ASD and to perform chemically selective microscopy of living cells. In follow-up work related to pharmaceutical formulations, Simpson and co-workers used native two-photon excited UV-fluorescence (TPE-UVF) of indomethacin API crystals to perform label-free autofluorescence-detected mid-IR photothermal microscopy (AF-PTIR) . AF-PTIR was shown to enable chemical mapping of the indomethacin API crystals within a commercial solid dosage form.…”

Section: Introductionmentioning

confidence: 99%

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Parts-per-Million Detection of Trace Crystal Forms Using AF-PTIR Microscopy

Razumtcev

Simpson

2022

Anal. Chem.

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Autofluorescence-detected photothermal mid-infrared (AF-PTIR) microscopy was shown to enable parts-per-million detection of α-indomethacin impurity in γ-indomethacin samples. Subtle differences in the photothermal response of the UV-autofluorescence of two indomethacin crystal polymorphs were used for sub-micron chemical discrimination based on fingerprint region mid-IR spectroscopy. The AF-PTIR assignment was independently confirmed by second harmonic generation (SHG) microscopy, which was shown to reduce the total analysis time by rapidly identifying the suitable fields of view. AF-PTIR microscopy has the potential to assist in the early identification of crystal form impurities in the solid dosage forms development pipeline.

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Section: Resultssupporting

confidence: 91%

Section: ■ Results and Discussionmentioning

confidence: 99%

Section: ■ Experimental Methodsmentioning

confidence: 99%

Section: Experimental Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Parts-per-Million Detection of Trace Crystal Forms Using AF-PTIR Microscopy

Razumtcev

Simpson

2022

Anal. Chem.

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Mid-Infrared Photothermal Microscopy: Principle, Instrumentation, and Applications

et al. 2022

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Midinfrared photothermal (MIP) microscopy, also called optical photothermal infrared (O-PTIR) microscopy, is an emerging tool for bond-selective chemical imaging of living biological and material samples. In MIP microscopy, a visible probe beam detects the photothermal-based contrast induced by a vibrational absorption. With submicron spatial resolution, high spectral fidelity, and reduced water absorption background, MIP microscopy has overcome the limitations in infrared chemical imaging methods. In this review, we summarize the basic principle of MIP microscopy, the different origins of MIP contrasts, and recent technology development that pushed the resolution, speed, and sensitivity of MIP imaging to a new stage. We further emphasize its broad applications in life science and material characterization, and provide a perspective of future technical advances.

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Hyperspectral and Nanosecond Temporal Resolution Widefield Infrared Photothermal Heterodyne Imaging

et al. 2023

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Label-free, bond-selective imaging offers new opportunities for fundamental and applied studies in chemistry, biology, and materials science. Preventing its broader application to investigating spatially-congested specimens are issues related to low sensitivity as well as low spatial and temporal resolution. Here, we demonstrate a widefield, mid-infrared (MIR) photothermal imaging technique, called widefield Infrared Photothermal Heterodyne imaging (wIR-PHI), that massively parallelizes acquisition of MIR absorption data through use of a high-speed complementary metal-oxide-semiconductor camera. wIR-PHI possesses notable features that include: spatial resolution significantly below the MIR diffraction limit, hyperspectral imaging capabilities, high sensitivity, and ∼100 ns temporal resolution. The first two features are highlighted by hyperspectral imaging of proximally close poly(methyl methacrylate) (PMMA) and polystyrene (PS) nanoparticles where clear, bond-specific imaging of nanoparticles, separated by less than the MIR diffraction limit, is demonstrated. Sensitivity is highlighted by imaging individual PMMA and PS nanoparticles with radii between r = 97−556 nm. This leads to a current, peak absorption cross-section limit-of-detection of σ abs = 1.9 × 10 −16 cm 2 . wIR-PHI's 100 ns temporal resolution is simultaneously demonstrated by observing the decay of photothermal contrast on individual nanoparticles on a ∼200−6200 ns timescale. In whole, wIR-PHI's dramatic increase in acquisition speed opens opportunities for future MIR kinetic imaging and spectroscopic studies of important chemical, biological, and material processes.

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Label-Free Autofluorescence-Detected Mid-Infrared Photothermal Microscopy of Pharmaceutical Materials

Cited by 11 publications

References 47 publications

Parts-per-Million Detection of Trace Crystal Forms Using AF-PTIR Microscopy

Parts-per-Million Detection of Trace Crystal Forms Using AF-PTIR Microscopy

Mid-Infrared Photothermal Microscopy: Principle, Instrumentation, and Applications

Hyperspectral and Nanosecond Temporal Resolution Widefield Infrared Photothermal Heterodyne Imaging

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