Microarrays

Within a short time frame, SCHOTT has installed a new biological laboratory and developed coated substrate glass for DNA chips. Next to research activities, application tests can also be carried out in the new labs.
Dr. Rolf Froboese,
Wasserburg, Germany


Increasing Efficiency

With “SCHOTT Slide A” SCHOTT has developed a coated substrate for microarrays that makes it possible to carry out a more reliable analysis of DNA activity.

Analyses of DNA chips play a key role in pharmaceutical research and development. They make it possible to carry out gene expression analyses of healthy and diseased tissue samples at high throughput rates. The more reliable these initial results are, the more accurate the development of appropriate drugs.

Facing new challenges

The pharmaceutical industry’s search for new drugs still involves pursuing a long-drawn-out and often difficult process. Rather like the old gold diggers, who once had to wash tons of sand to stumble across a few grains of gold, chemists and biologists have to test myriads of combinations of DNA to track down one potential candidate for an active ingredient.

Currently, the heavily research-oriented industry finds itself at the beginning of a new era: the costs of developing new drugs are exploding, as are expectations that functional genomic research will reduce both the time and cost factor involved in the technological process. The objective is not only to identify a large number of potential new active ingredients, but also to speed up and rationalize the pre-clinical research process. Today, it still takes on average twelve to fifteen years from the identification of a potential active ingredient to the finished drug.

A quicker route to new pharmaceutical active ingredients

SCHOTT “Slide A” glass substrates are subjected to a strict quality control in order to ensure reliability and top product quality. Above, the slides are undergoing a visual inspection.
New coated substrate glasses for the immobilization of biomolecules are also available with bar codes which allow customers to trace a DNA chip from its final analysis back to the production batch.
What are the possibilities of reducing these development times which would be totally unacceptable in other key technologies? In the clinical testing phase, the possibilities are quite limited due to considerations regarding patient safety. The focus has been shifted to the earliest possible stage of active ingredient research. One promising approach lies in identifying the genes responsible for the emergence of the disease in the first place.

In pharmaceutical research, one way to identify disease-relevant genes is the use of DNA microarrays. In this process, which is derived from semiconductor engineering, a specially coated glass substrate material is printed with genetic material known as the probe DNA. There are several alternative technologies available for this: e.g. contact printing, adapted inkjet printing and photolithography. Because several hundred thousand gene fragments are located on the substrate, hybridization experiments can be carried out in parallel at high throughput rates. This involves placing fluorescence marked DNA target molecules taken from cells or tissue onto the substrate. If the probe DNA immobilized on the substrate matches the target DNA originating from the sample material, the two complementary single sequences hybridize to form a DNA double sequence. The fluorescence marking makes it possible for specially developed scanners to verify the hybridized DNA molecules.

Double innovation

With the market launch of “SCHOTT Slide A,” SCHOTT has succeeded in offering a coated substrate which makes the evaluation of gene expression experiments safer and at the same time leads to reproducible results for use in pharmaceutical research. The core of the innovation is a multi-amino-silane coating on a special SCHOTT borosilicate glass.

In contrast to conventional products the multi-amino-silane coating achieves a stronger binding of DNA probes across a higher number of “docking points,” which amounts to greater sensitivity. “In the evaluation of gene expression experiments the excellent material properties of the borosilicate glass used show up very positively,” adds Dr. Dirk van den Broek, Executive Vice President of SCHOTT’s “Health” Business Segment. The glass has a very low inherent fluorescence which results in an excellent signal to noise ratio. Together with the extremely flat surface of the glass, which largely puts a stop to irregularities in printing and detection, the results of DNA microarray applications can be evaluated more reliably than before.

People involved in pharmaceutical drug discovery research are looking to increase the reproducibility of the results from all the technologies used. The reliability of the initial data is of major economic importance for the pharmaceutical industry, in order to select those active ingredient candidates with the best prospects. The early sorting out of possible “flops” will lead to more efficient drug disovery research and ultimately to cost savings running into the millions.