Biobanks

Concept

The biobank of the Medical University of Graz is specifically designed to support the needs of systems biology approaches to human diseases, drug discovery, and public health. It is a research core facility of the Medical University of Graz, which mainly builds on one of the world's largest collection of diseased human tissues of the Institute of Pathology. In the context of the Austrian Genome Program GEN-AU I www.gen-au.at the tissue collection has been developed into a biobank by establishing the logistics and technologies for coordinated and standardized collection of various human biological samples, medical and experimental data as well as human disease-associated animal models. Furthermore high throughput genomics (cDNA-arrays) and proteomics (tissue microarrays) analysis platforms, and an IT-infrastructure, which enables proper access und usage of biological samples as well as associated data have been established. In the course of the GATiB (Genome Austria Tissue Bank) project http://www.univie.ac.at/LSG/gatib/ in the second phase of the GEN-AU programme (GEN-AU 2) the biobank will be further developed into a biological resource centre putting specific emphasis on standardization, international networking and the ethical, legal and societal issues (ELSI) of biobanking.

Applications

The advancement of modern biomedical research, aiming at improved therapeutic and diagnostic methods and strategies, culminating eventually in personalized medicine requires an integrated infrastructure which links biobanks with the required IT-infrastructure, analysis platforms, systems biology and other biological resources.

Research projects, focusing on specific aspects of a disease, greatly benefit from extensive collections of tissues. Biomarkers and potential therapeutic targets discovered by comparative analysis of normal and diseased tissue can be studied in detail in corresponding animal models. The results of this research can then be validated again in human tissue.

Modern concepts for the elucidation of disease processes necessarily rely on the wealth of information contained in diseased tissue, and on the comparison with healthy specimens. Technologies, such as gene expression analysis, proteomics and metabolomics directly fuel systems biology which promises to understand the disease process on the level of an organism. Certainly such efforts are presently just beginning. However, they will be futile if the demands for biological data cannot be met. Biobanks are in a unique position to meet these demands.

Providing knowledge of the molecular basis of disease, biobanks play a key role in the development of new drugs and diagnostic tools by the pharmaceutical industry. The trend towards personalized medicine and the increasing global operation of companies indicate that biobanks will need to provide samples and data from populations of different ethnic origin, which can reasonably only be achieved within an international network of biobanks. These trends and developments have far-reaching social, ethical, and political-legal implications that need to be considered to warrant smooth interaction between science and society on national and global levels (Webster et al., 2004; Cambon-Thomsen, 2004).

Types of biobanks

There are several types of biobanks, each format serving particular purposes:

  • Population-based biobanks
  • Disease-based biobanks
  • Biomolecular resource centres (antibodies etc.)
  • Repositories for cells and model organisms
  • Centres for biomolecular technologies

Organisation Chart of the Biobank of the Medical University of Graz

 

 

 

Analysis platforms

Tissue Microarray (TMA)

Tissue microarray (TMA) technology has miniaturized conventional procedures for tissue analysis by combining hundreds of different tissues in a single array.
Major advantages are:

  • TMA format enables high throughput analysis under uniform experimental conditions
  • TMAs significantly reduced tissue consumption preserving limited tissue samples
  • TMAs allow automatic readout of experiments and the data storage in data bases
The principle of TMA
 

 Recognizing the importance of the TMA platform for the extraction of key information from annotated human diseased tissue, Oridis Biomed and the Institute of Pathology have co-developed a proprietary TMA construction process. At the heart of this process is a proprietary automated tissue arrayer.

 

 TMA robot 

 

Automation / Standardisation

The TMA construction process is designed to ensure the efficient production of arrays of consistent quality and to automatically provide digital documentation of the production process, eliminating this task from array construction and enabling a review of the construction process by third party array users. SOPs for each task in the process play an important role in this. The most important part of the process however is a patent-protected TMA robot that performs barcode-driven block handling and tissue core transfer. Up to 20 replicate arrays can be constructed in a single production process.

Tissue core selection

The selection of representative cores from cancer tissue samples is a critical step in TMA construction as these tissues are often highly heterogeneous. The robotic system performs this task with great accuracy using digital images of block and marked section since a detailed image of the area of interest is provided. This digital core selection procedure also records the position from which each core was removed allowing future selection of adjacent cores as well as quality control of the process.

 

 Key manufacturing steps for original tissue (donor block) to TMA section.

 

Quality control

TMA sections contain variable numbers of evaluable cores principally because of variable tissue thickness and loss of or damage to cores during sectioning. Novel methods are being developed for rapid assessment of the number of evaluable cores on all sections which do not interfere with subsequent use for expression studies. This quality information will be particularly valuable in the context of automated analysis of stained TMA sections, for instance in projects aiming to screen large number of gene products for disease-relevance (Haedicke et al., 2003).

 

 Details of a TMA with immunohistochemical reactions using keratin and vimentin antibodies on consecutive TMA sections showing complemintary reaction patterns.