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In-flow cyto-tomography on liquid samples identifies foreign and rare tumor cells circulating in the blood stream (2017-02-12)

A research, led by team of young researchers at the Institute of Applied Science and Intelligent Systems of the National Council of Research in Pozzuoli, Napoli, in collaboration with the Ceinge-Advanced Biotechnologies, which involves University Federico II, reveals an innovative technique for the identification of 'foreign' and rare cells circulating in the blood stream, the so called Ctc (Circulating Tumor Cells).

Microfluidic channel used for experiments.

The research has been published in Light: Science and Applications, a Nature Publishing Group Review.

Blood is composed of millions of cells as red blood cells, white cells, platelets, lymphoid cells.
At present, the diagnosis of a blood disease is performed by the blood count, which furnishes statistical parameters on examined cells as the cellular volume, haemoglobin, etc.

In order to obtain morphological information, however, is necessary to study at the microscope the blood smear, which limits the analysis to a little fraction of cells and, also, is subjective, depending on the physician’s interpretation of the image analyzed.

The results demonstrate that is possible to perform an in-flow cyto-tomography on liquid samples using a microfluidic technology, or as it is known 'Lab-on-a-Chip'.

“This new interferometric technique, based on digital holography, allows us to analyze millions of cells while flowing in a microfluidic channel, furnishing parameters as haemoglobin, as same as the traditional blood count.
Moreover, it is able to analyze every single cell almost in real time, reconstructing the three-dimensional image with incredible accuracy”, illustrate the authors Francesco Merola, Lisa Miccio, Pasquale Memmolo and Martina Mugnano by Isasi-Cnr.

“ By the very same approach, it would be possible to identify rare cells, early symptom of potential pathologies, unseen by a classic analysis. The key of the technique is to exploit the 360° rotation of the cells while flowing in the channel, and this allows us to retrieve the 3D structure of each cell with dimensions up to one thousandth of millimeter.”

This study has allowed to obtain a tomography of red blood cells by patients affected with different types of anemias, identifying them with absolute accuracy.
“Thanks to the particular sensitivity of this optical imaging technique, even the smallest morphological variation compared to the healthy red blood cell can be revealed, discerning very quickly and in an objective way the possible related disease: a sort of liquid biopsy”, says Achille Iolascon by Ceinge, Full Professor of Medical Genetics at the Federico II University of Naples.

“Thanks to this technique it will be possible to study every category of cells, not only the blood ones”, ends Pietro Ferraro, Director of Isasi-Cnr (www.isasi.cnr.it) “In fact, thanks also to the contribution of the colleagues of the Institute of Biomolecular Chemistry of the Cnr, the validity has been confirmed also with diatoms - a class of algae producing more than 20% of the oxygen in the entire earth - the presence of which in the oceans is a fundamental signal of the ecosystems health.

Chloroplasts, diatoms’ elements responsible of photosynthesis, are extremely sensitive to contaminants in marine water, and this technique permits to obtain their complete 3D shape, giving information on a potential contamination”.

The interdisciplinary team of investigators made of physicists, engineers, biologists and chemists, has obtained a result that will strongly influence the oncological diagnosis. This first continuous-flow complete tomography opens the way to the possibility of finding the 'needle in a haystack', that is, the circulating tumor cells, early signal of metastasis so far elusive.

For more information
Tomographic Flow Cytometry by Digital Holography.
Francesco Merola, Pasquale Memmolo, Lisa Miccio, Roberto Savoia, Martina Mugnano, Angelo Fontana, Giuliana D’Ippolito, Angela Sardo, Achille Iolascon, Antonella Gambale and Pietro Ferraro
Light: Science & Applications (2017) 6, e16241; doi: 10.1038/lsa.2016.241.