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Wednesday, 21 August, 2013

Highly efficient hydrodynamic cell sorting


In an article published in the journal “Biomicrofluidics,” biophysicists from Augsburg University demonstrate how tumor cells can be sorted from a blood sample in minimum time.

The sorting of cells in miniature laboratories is a milestone in the quest for new diagnostic methods in medicine and research. With their recent publication in the journal “Biomicrofluidics,” Prof. Thomas Franke and his team of biophysicists at Augsburg University make an important contribution to this rapidly developing field of “Micro Total Analysis Systems.” They present a new method of sorting cells called “Non-Inertial Lift Induced Cell Sorting (NILICS)." It allows cells to be separated from each other in a microscopic channel based on different behaviors without the cells being specially marked for this purpose. The scientists at the Chair of Experimental Physics I at Augsburg University demonstrate the effectiveness of this technique by sorting circulating tumor cells from a suspension of red blood cells.


Disturbances in the fluid flow

On a scale of only a few micrometers, particles in fluids behave differently to what you would expect based on common experience. This is because turbulent flows fo not occur in microscale capillaries. Rather, they show a highly symmetrical flow profile: the individual layers of fluid flow parallel to each other, with no disruption between the layers and no mixing. If this symmetry is disturbed by a deformable object, such as a cell in close proximity to a wall, the system tries to restore its balance. The resulting repelling force pushes the cell away from the wall and towards the center of the channel. Because of the physical properties of the environment in which this effect occurs, it is called “non-inertial lift effect." If one cell is larger or more deformable than another, it causes a greater disturbance of the flow field, thus experiencing a stronger force. These differences allow different types of cells to be separated from each other. The Augsburg-based scientists were already able to prove this for red blood cells and blood platelets in an earlier publication.


Separation of blood and tumor cells

In its current project, the group now investigates the possibility of using the NILICS method to separate circulating tumor cells from red blood cells. Circulating tumor cells are cancer cells that have shed from the primary tumor and circulate through the body in the bloodstream. Their number allows conclusions to be drawn about the seriousness of the disease or the response to a treatment. However, only 1 to 10 tumor cells are found in one milliliter of blood – a minute number compared to the approximately 6 million endogenous blood cells! “This is why we have to separate the tumor cells from this bulk of cells prior to further analysis. And this is where we come into play,” explains Thomas Geislinger.


Sorting accuracy of up to 100 percent

For sorting, the blood sample is diluted and injected into the channel. A second flow focuses the sample to the wall of the microchannel before it flows into the actual sorting area. In the 20-mm-long channel with a diameter of approximately 60 x 60 micrometers, the different types of cells then migrate away from the wall at different speeds. The widened section at the end of the channel increases the distance between the cell populations even further before they are directed to the collection containers through two separate exits. This setup allows up to 100 percent of the tumor cells to be separated from the sample. The sorted cells are still fully viable and can be propagated for subsequent experiments.


Precise, fast and cost-efficient

As part of a Micro Total Analysis System, microfluidic cell separation yields results which are much more precise than would have been achievable with conventional methods. In addition, it is highly cost- and time-efficient. No laboratory tests for days on end are required; instead, results are ready in only a few minutes. As these miniature laboratories are also inexpensive and applicable almost everywhere, their further development is of enormous importance for medical care, particularly in structurally weak regions.



Thomas M. Geislinger and Thomas Franke, Sorting of circulating tumor cells (MV3-melanoma) and red blood cells using non-inertial lift, Biomicrofluidics 7, 044120 (2013); dx.doi.org/10.1063/1.4818907 (9 pages)



Prof. Thomas Franke
Soft Matter and Biological Physics
Chair of Experimental Physics I
Augsburg University

Tel: +49 (0)821 598-3312


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