An Interview with... Dr. Olaf Hollricher, Co-founder and Managing Director of Research and Development, WITec GmbH

Dr. Olaf Hollricher, Co-founder and Managing Director of Research and Development, WITec GmbH

Which of your products generates the most interest among those in the pharmaceutical industry?

Any variant in our line of confocal Raman microscopes can be used in pharmaceutical research. Our systems are modular, so the wavelength and number of laser sources, the number and type of spectrometers, the degree of automation and the size of the sample stage, to name just a few of the options, can be chosen by the user. This modularity helps to build exactly the system that is best suited to the customer’s needs.

Our line of alpha300 microscopes can chemically characterize the components in a sample down to about 200-300 nanometers resolution, depending on excitation wavelength, and their high confocality also allows 3D depth profiles to be compiled from 2D scans, which is quite useful for analyzing thin films and coatings.

An additional module, the TrueSurface option, enables topographic Raman imaging, in which a 3D surface can be traced to guide a Raman measurement and keep it perfectly in focus, all in one pass. That option has been very well received by the pharmaceutical industry. They can just put a tablet under the microscope and look at its entire curved surface and identify the molecules in a quick, straightforward process. Coarse powders and inclined samples are the same way. A sample that is rough can be imaged as if it were flat, as the microscope always keeps the point of interest in focus.

What current hardware developments do you regard as important for pharma-related scientific instruments?

Further automation is clearly an important factor going forward. Systems that automate most setup processes are not only easier to use on a day to day basis, but they’re also more consistent because they’ll be calibrated more often and they’ll reduce the potential for operator error. We have something called the TruePower module that reads out the laser power going into the microscope objective, records that value along with the measurement, and allows the operator to set the laser power with 0.1mW precision using a built-in attenuator. That’s fantastic for reproducing measurements exactly at different times.

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Automated wavelength selection, remotely-operated polarization dependent measurement capabilities, aperture alignment, and whitelight/dark-field illumination switching are also really convenient for experiments involving remote operation such as those with environmental enclosures and glove boxes.

What unique capabilities does your company have to offer pharmaceutical development?

We are a leading manufacturer of confocal Raman microscopes. These microscopes use the Raman effect to determine the chemical composition of a sample with sub-micrometer resolution. This ability to visualize distributions and the fact that Raman imaging is a nondestructive method that does not require dyeing or other specialized sample preparation makes it very useful in pharmaceutical laboratories.

A confocal Raman imaging microscope can be used to characterize the homogeneity of pharmaceutical samples, to determine the states of drug substances and excipients and to characterize contaminants and foreign particulates. For drug design, it is useful in the development of solid and liquid formulations, as a tool for process analytics, and can assist in patent infringement and counterfeit analysis.

What are some examples of software developments pertinent to pharmaceutical research?

This year we introduced the WITec ParticleScout software tool for the alpha300 series to greatly accelerate the process of microparticle analysis. It surveys particulate samples using dark- or bright-field illumination and locates all the particles. Focus stacking makes sure the edges of the particles are clearly defined, regardless of size, and image stitching assembles many survey areas into a larger image, which provides large area scanning at high resolution. The researcher can then specify the ones they’re looking for in terms of size, aspect ratio, Feret diameter and many other criteria. A mask is then generated to mark the locations of only the selected particles, which guides the measurement to each selected particle in rapid succession, skipping over the empty space and irrelevant particles to save a huge amount of time. A Raman spectrum is automatically acquired from each one before they are identified individually, or by using the WITec TrueMatch Raman database management software, and a report is generated that comprehensively and quantitatively describes the sample.

TrueMatch can search existing spectral databases of common materials or substrates to identify the contents of a sample. It is fully integrated with the WITec Suite FIVE software environment. Multispectral searches can identify several spectra simultaneously using hit rates that describe the probability of matches and demix searches use the database to describe acquired spectra in terms of pure substances. It can also enable researchers to create their own catalog of spectra related to their individual experiments.

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