Confocal Raman spectroscopy

Because the use of colloidal silver or gold as a substrate for single molecule SERS, as observed with confocal microscopy, has met with some criticism (the chemically prepared colloids are exposed to the molecules to be adsorbed and are subsequently deposited onto a substrate, e.g. an ITO-coated glass slide during this 

---

Leopold et al. and Nyholm et al. have investigated this oscillatory system by in situ confocal Raman spectroscopy [43], and in situ electrochemical quartz crystal microbalance [44], and in situ pH measurement [45] with the focus being on darification of the osdllation mechanism. Based on the experimental results, a mechanism for the oscillations was proposed, in which variations in local pH close to the electrode surface play an essential role. Cu is deposited at the lower potentials ofthe oscillation followed by a simultaneous increase in pH close to the surface due to the protonation... 

When investigating opaque or transparent samples, where the laser light can penetrate the surface and be scattered into deeper regions, Raman light from these deeper zones also contributes to the collected signal and is of particular relevance with non-homogeneous samples, e.g., multilayer systems or blends. The above equation is only valid, if the beam is focused on the sample surface. Different considerations apply to confocal Raman spectroscopy, which is a very useful technique to probe (depth profile) samples below their surface. This nondestructive method is appropriate for studies on thin layers, inclusions and impurities buried within a matrix, and will be discussed below. 

Gierlinger, N., Hansmann, C., Roder, T., Sixta, H., Gindl, W. and Wimmer, R. (2005). Comparison of UV and confocal Raman spectroscopy to measure the melamine - formaldehyde resin content within ceU walls of impregnated spruce wood. Holzforschung, 59(2), 210-213. 

Noda, K., Sato, H., Watanabe, S., Yokoyama, S., and Tashiro, H. 2007. Efficient characterization for protein crystals using confocal Raman spectroscopy. Appl. Spectros. 61 11-18. 

Schafer, T., Di Paolo, R. E., Franco R.,and Crespo, J. G., Elucidating interactions of ionic liquids with polymer films using confocal Raman spectroscopy, Chem. Commun., 2594-2596,2005. 

Breitenbach, J., W. Schrof, and J. Neumann. 1999. Confocal Raman spectroscopy Analytical approach to solid dispersion and mapping of drugSiarm ReSl6 1109-1113. 

A clever way to minimize the unwanted background from the cover plate or the environment is combining laser tweezers and confocal Raman spectroscopy (LTRS) [73, 74], While the single cells are levitated well off the surface and held in the focus of the laser beam the Raman spectral patterns of these cells are recorded with high sensitivity. Another appealing fact is the usage of one laser for both Raman excitation and optical trapping to keep the instrumental efforts as low as possible. Additionally the trapped cells can also be micro-manipulated and moved from one place to another, e.g., from the native matrix to a clean collection chamber. 

Caspers, P.J., et al. 2002. Monitoring the penetration enhancer dimethyl sulfoxide in human stratum corneum in vivo by confocal Raman spectroscopy. Pharm Res 19 1577. 

Uniform analyte distribution is often a good assumption for liquid samples such as blood serum or even whole blood if stirring is continuous. For biological tissue, human skin in particular, heterogeneity is a major factor. Detailed morphological structures and molecular constituents of skin have been studied using confocal Raman spectroscopy.9... 

Caspers PJ, Lucassen GW, Puppels GJ. Combined in vivo confocal Raman spectroscopy and confocal microscopy of human skin. Biophysical Journal 2003, 85, 572-580. 

Spectroscopy (spectrometry) — Confocal Raman spectroscopy — Figure... 

The standard method of confocal Raman spectroscopy is presented in Ref. [355] using HOD films grown by the three-step process. The process conditions are listed in Table H.3. The film thickness was approximately 0.8 pm. In the Raman spectra of... 

The internal stress within the diamond film grown on Pt(lll) substrate was characterized by confocal Raman spectroscopy [401, 402]. The film thickness was... 

Figure 6 The CH4 C H symmetric stretch region from confocal Raman spectroscopy for methane in hydrate cages for the product of the reaction of methane and water. The spectra suggest that crystals of both si and sll hydrate form, the latter being metastable. From ref 20...

Creely, C.M., Singh, G.P. and Petrov, D. (2005) Dual wavelength optical tweezers for confocal Raman spectroscopy. Opt. Commun., 245, 465-470. 

Laser-source confocal Raman spectroscopy was used to analyze solid dispersions to evaluate the physical properties and determine the distribution of ibuprofen in extrudates of polyvinylpyrrolidone (PVP). As is shown in Figure 14, a shift in the Raman spectra occurs when the crystalline form of ibuprofen is compared to a solution or a PVP extrudate containing ibuprofen. For comparison purposes, ibuprofen was completely dissolved in dimeric... 

The lack of any further Raman shifts during a stability study indicated that the ibuprofen in the melt extrudate is stable and that there were no crystallization processes that could affect the dissolution and bioavailability. Therefore, one use of confocal Raman spectroscopy could be to optimize various formulations and quickly determine their likely long-term stability. 

The relative signal intensity of the Raman shift was also found to be proportional to HPLC assay results. With the use of confocal Raman spectroscopy, the ibuprofen distribution in the extrudate was mapped therefore, this technique can be used to measure homogeneity (blend uniformity) in a fast and nondestructive manner. 

Breitenbach, J., Schrof, W, and Neumann, J. Confocal Raman spectroscopy analytical approach to solid dispersions and mapping of drugs. Pharm. Res. 16(7) 1109-1113, 1999. 

There are several common configurations for Raman spectrometers. Unlike NIR, Raman can be readily done under a confocal microscope. Confocal Raman spectroscopy allows for the chemical composition of materials to be determined with micron spatial resolution including some depth profiling. Confocal Raman measurements have been shown to be useful quantitative analytical tools for the investigation of drug eluting stents [11]. Raman microscopy has been used to quantify thin... 

---