Label-free autofluorescence-detected photothermal mid-IR (AF-PTIR) microscopy is demonstrated experimentally and applied to test the distribution of active pharmaceutical ingredients (APIs) in a mixture containing representative pharmaceutical excipients. Two-photon excited UV-fluorescence (TPE-UVF) supports autofluorescence of native aromatic moieties using visible-light optics. Thermal modulation of the fluorescence quantum yield serves to report on infrared absorption, enabling infrared spectroscopy in the fingerprint region with a spatial resolution dictated by fluorescence. AF-PTIR provides high selectivity and sensitivity in image contrast for aromatic APIs, complementing broadly applicable optical photothermal IR (O-PTIR) microscopy based on photothermal modulation of refractive index/scattering. Mapping the API distribution is critical in designing processes for powdered dosage form manufacturing, with high spatial variance potentially producing variability in both delivered dosage and product efficacy. The ubiquity of aromatic moieties within API candidates suggests the viability of AF-PTIR in combination with O-PTIR to improve the confidence of chemical classification in spatially heterogeneous dosage forms.

No abstract

No abstract

The authors present an adaptive algorithm based on a non‐linear regression model for mitigating time‐varying etalon drifts in line‐scanned optical absorption spectrometers. By dynamically varying the etalon spectral background using physically realistic degrees of freedom, the authors’ dynamic etalon fitting‐routine (DEF‐R) significantly increases the spectral baseline recalibration interval as compared to conventional fringe subtraction models. They provide an empirical demonstration of the efficacy of DEF‐R using an on‐chip 10 cm silicon waveguide for near‐infrared methane absorption spectroscopy at 6057 cm−1, which suffers significant etalon spectral noise due to reflections and multi‐path interference from stochastic line‐edge roughness imperfections. They demonstrate the corresponding improvement in both spectral clean‐up and long‐term stability via Allan‐variance analysis. For the sensor presented here, application of DEF‐R enables Gaussian‐noise limited performance for more than 102 s and provides almost an order‐of‐magnitude improvement in stability time with respect to conventional baseline subtraction. Although DEF‐R is applied here to an on‐chip sensor embodiment, they envision their technique to be applicable to any absorption sensor limited by time‐varying etalon drifts.

Faraday rotation spectroscopy (FRS) employs the Faraday effect to detect Zeeman splitting in the presence of a magnetic field. In this article, we present system design and implementation of radical sensing in a photolysis reactor using FRS. High sensitivity (100 ppb) and time resolved in situ HO2 detection is enabled with a digitally balanced acquisition scheme. Specific advantages of employing FRS for sensing in such dynamic environments are examined and rigorously compared to the more established conventional laser absorption spectroscopy (LAS). Experimental results show that FRS enables HO2 detection when LAS is deficient, and FRS compares favorably in terms of precision when LAS is applicable. The immunity of FRS to spectral interferences such as absorption of hydrocarbons and other diamagnetic species absorption and optical fringing are highlighted in comparison to LAS.