WHAT INFORMATION LIES IN CELL MECHANICS?

How would you determine the ripe kiwi fruit?

Problem: Which of the two kiwis is to your liking?
Two kiwis - one hidden property.

Sometimes it is difficult to see  a difference. But it might be really easy to feel  it.

Solution: Applying the appropriate force and sensing the mechanical properties of the fruit will clearly show you the difference between the ripe and the overripe kiwi.

Is this also valid for smaller tissue fragments of the fruit? What if we go down to the single cell level?

The mechanical properties of cells are governed by functionally important cell components, e.g. the cytoskeleton. They constitute an emerging label-free biomarker and allow for direct insights into cellular function or dysfunction.  Thereby, mechanical properties contribute to the understanding and evaluation of drug treatment effects, immune cell activation, stem cell differentiation, cancer prognosis, or the assessment of state and quality of cultured cells.

  • Cell deformability correlates with a cell's condition and function.
  • Cell deformability can be assessed without labeling.
  • The potential for applications is tremendous.

How to squeeze a single cell?

To generate defined forces, isolated cells are pumped through a micro-channel with a cross section slightly larger than that of the cells'. The pressure gradient of the surrounding fluid creates a flow profile and deforms the cells hydrodynamically. The flow velocity and the viscosity of the fluid control the forces acting on the cells.

  • Cells can be deformed by hydrodynamic forces.
  • Forces are controlled by flow velocity and viscosity.
  • Softer cells display greater deformations.

How to measure deformability Fast?

REAL-TIME DEFORMABILITY CYTOMETRY

Cells flow at velocities of several cm/s from right to left, focused centrally in the micro-channel by a sheath flow from the upper and lower right corners. The flow cytometry arrangement in combination with the real-time analysis of the cell shape allows for a non-destructive, continuous measurement at high rates of up to 1000 cells per second - an 10.000 fold improvement over other methods addressing cellular mechanics. The high throughput facilitates the application as a standard analytical method in cell biology and clinical research with statistically meaningful numbers of single cell measurements in only a few minutes. By gating for cell size or deformability, it is possible to detect low number sub-populations of cells. In the picture above, the only white blood cell (colored red) can be pinpointed within the background noise of hundreds of red blood cells.

EXAMPLE APPLICATION

Label-free analysis of whole blood

The mechanical hemogram, as shown on the left, is a break through application made possible by RT-DC. Unlike other available methods, we can analyze the mechanical fingerprint of white blood cells - responsible for the immune response - without the employment of cell purification methods that alter the mechanical properties. We obtain a readout portraying the in vivo situation within 15 minutes which carries an immense potential for future diagnostic applications.

  • Mechanical hemogram in 15 min
  • No isolation or purification necessary
  • Real-time analysis for simultaneous data review

Strong benefits for scientific and medical applications

Any question, suggestion or criticism?
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