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Nanoscale biopsy measurement characterises tumours

22 October 2012

Ultra-sharp atomic force microscope tip of several nanometers in size is used as a probe to 'feel' cells and extracellular structures within a tumour biopsy.

Using ARTIDIS to feel the tissue structure of a tumour biopsy by a nanometer-sized atomic force microscope tip (image: Martin Oeggerli)
Using ARTIDIS to feel the tissue structure of a tumour biopsy by a nanometer-sized atomic force microscope tip (image: Martin Oeggerli)

Despite major scientific advancements in our understanding of the disease, breast cancer diagnostics remains slow and subjective. Here, the real danger lies in the lack of knowing whether metastasis, the spread of cancer, has already occurred.

Nevertheless, important clues may be hidden in how metastasis is linked to specific structural alterations in both cancer cells and the surrounding extracellular matrix. This forms the motivation behind ARTIDIS (Automated and Reliable Tissue Diagnostics), which was conceived by Dr Marko Loparic, Dr Marija Plodinec and Professor Roderick Lim at the University of Basel to measure the local nanomechanical properties of tissue biopsies.

At the heart of ARTIDIS lies an ultra-sharp atomic force microscope tip of several nanometres in size that is used as a local mechanical probe to “feel” the cells and extracellular structures within a tumour biopsy. In this way, a nano-mechanical “fingerprint” of the tissue is obtained by systematically acquiring tens of thousands of force measurements over an entire biopsy. Subsequent analysis of over one hundred patient biopsies could confirm that the fingerprint of malignant breast tumours is markedly different as compared to healthy tissue and benign tumours.

This was validated by histological analyses carried out by clinicians at the University Hospital Basel, which showed a complete agreement with ARTIDIS. Moreover, the same nanomechanical fingerprints were found in animal studies initiated at the Friedrich Miescher Institute.

Dr Plodinec explains: "This unique fingerprint reflects the heterogeneous make-up of malignant tissue whereas healthy tissue and benign tumours are more homogenous." Strikingly, malignant tissue also featured a marked predominance of 'soft' regions that is a characteristic of cancer cells and the altered micro-environment at the tumour core.

The significance of these findings lies in reconciling the notion that soft cancer cells can more easily deform and 'squeeze' through their surroundings. Indeed, the presence of the same type of 'soft' phenotype in secondary lung tumors of mice reinforces the close correlation between the physical properties of cancer cells and their metastatic potential."

"Resolving such basic scientific aspects of cancer further underscores the use of nanomechanical fingerprints as quantitative markers for cancer diagnostics with the potential to prognose metastasis.", says Dr Loparic.

A complete biopsy analysis by ARTIDIS currently takes four hours in comparison to conventional diagnostics, which can take one week. Based on the potential societal impact of ARTIDIS to revolutionise breast cancer diagnostics, Lim’s team and the Swiss company Nanosurf AG have now been awarded about 1.2 million Swiss francs by the Commission for Technology and Innovation (CTI) to further develop ARTIDIS into a state-of-the-art device for disease diagnostics with further applications in nanomedicine.

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