Chemical Imaging of Pharmaceutical Materials: Fabrication of Micropatterned Resolution Targets

Abstract

Resolution targets composed of thick poly(ethylene glycol) (PEG) lines on silicon substrates have been fabricated using the method of micromolding in capillaries (MiMIC). Patterns of three parallel lines with equal width and spacing have been prepared, with widths between 5 and 25 microm. Raman chemical images of the PEG-on-silicon devices as well as the metal-on-glass masks used to prepare the devices were measured. The Raman images were used to determine the impulse response of the instrument by comparing the measured images to model functions prepared by convolution of a test impulse function with the object functions of the devices. Impulse widths for PEG-on-silicon targets were approximately two times greater than impulse widths for metal-on-glass targets. The results provide a quantitative measure of the influence of light-matter interactions on the spatial resolution achievable with chemical imaging instruments. This work shows that microfluidic channels can be used to produce robust patterns of PEG on silicon, and these patterns are realistic resolution targets for spectroscopic chemical imaging of pharmaceutical materials.

Confocal Raman Microscopy: Performance, Pitfalls, and Best Practice

“…Both the objects and the surrounding matrix should have strong and distinct Raman spectra. Such samples are not currently available (although progress is being made in that direction using microfluidic techniques to produce polymer resolution targets 25 ), so most work to date has been performed with much simpler systems.…”

2-D Image Localization in Hyperspectral Image Analysis of Pharmaceutical Materials

“…With more attention being paid to the potential of chemical imaging, researchers are realizing the importance of photon diffusion and its corresponding spatial dispersion in chemical images. These phenomena have been reported in both nearinfrared (NIR) [1] and Raman chemical images [2]. Because of the photon diffusion along both the depth and radial directions, spatial information existing outside of an observed pixel is detected within the pixel.…”

Raman Imaging Instrumentation

“…As part of ASTM E13.10, a Raman imaging task force was formed that focused on method and standard development for assessing Raman imaging performance. Such standards [98] and methods would be used to characterize dayto-day system performance, which could be used to alert the user of the need for maintenance and/or calibration and to determine the suitability of equipment for a specific analysis. …”