Atomic Force Microscope Infrared Spectroscopy of Griseofulvin Nanocrystals

Abstract

The goal of this work was to evaluate the ability of photothermal induced resonance (PTIR) to measure the local infrared absorption spectra of crystalline organic drug nanoparticles embedded within solid matrices. Herein, the first reports of the chemical characterization of sub-100 nm organic crystals are described; infrared spectra of 90 nm griseofulvin particles were obtained, confirming the chemical resolution of PTIR beyond the diffraction limit. Additionally, particle size distributions via dynamic light scattering and PTIR image analysis were found to be similar, suggesting that the PTIR measurements are not significantly affected by inhomogeneous infrared absorptivity of this system. Thus as medical applications increasingly emphasize localized drug delivery via micro/nano-engineered structures, PTIR can be used to unambiguously chemically characterize drug formulations at these length scales.

Infrared Imaging and Spectroscopy Beyond the Diffraction Limit

“…PTIR characterization has been applied to investigate a wide array of samples including bacteria (28,29,(103)(104)(105)(106), cells (107)(108)(109)(110), lipids (111), proteins (112), polymers (30,(113)(114)(115)(116)(117)(118)(119)(120)(121), drugs (122,123), quantum dots (124), plasmonic nanostructures (97,(125)(126)(127), metal-organic frameworks (128), and organo-trihalide perovskites (129). PTIR setups require a pulsed, spectrally narrow, wavelength-tunable laser source; an AFM tip operating in contact mode; and far-field optics to focus light under the tip.…”

“…The application of PTIR in biology and polymer science was reviewed recently (85,137) and is not discussed here extensively. A short list of those applications include the localization of viruses inside bacteria and the identification of viral infection stages (103), the localization and quantification of biopolymer (105) and biofuel (106) production in bacteria cultures, the imaging of phase-separated drug-polymer blends (122), and the characterization of drug nanocrystals in solid matrixes (123). A few examples of PTIR characterization in materials science are reported below.…”

Recent advances in hybrid measurement methods based on atomic force microscopy and surface sensitive measurement techniques

“…Here, the obtained amplitudes are related to the strength of the cantilever oscillation. Studies utilizing PTIR have analyzed the chemical information of biological samples, such as proteins, 279,280 lipids and lipid vesicles, 281,282 cells, 283,284 bacteria, 48,279,285 polymer samples and thin lms, 49,286-288 medical devices, 289 drugs, 290,291 nanostructures, [292][293][294] metal-organic frameworks (MOFs), 295 organo-halide perovskites, 296,297 and nano-patterned metals 298 at a resolution up to 50 nm. Here the improved resolution of the PTIR serves to analyze nanoscale regions of relatively thin samples.…”

Metal-dielectric-metal resonators with deep subwavelength dielectric layers increase the near-field SEIRA enhancement

“…Because of the broad applicability of IR spectroscopy and its chemical specificity, PTIR has enabled the characterization of diverse samples including: polymers [49,50], metal-organic frameworks [51], tri-halide perovskites [52,53], bacteria [43,54], cells [55,56], proteins [57] and drugs nanocrystals [58]. Recently our group applied the PTIR technique to measure high resolution absorption spectra and maps in the near-field surrounding PMMA coated of gold ASRRs which enabled the quantification of the SEIRA absorption enhancement with ≈ 100 nm resolution [3].…”