Scientists at the TU Dresden have developed an analysis method that allows the mechanical properties of 100,000 cells to be evaluated in just two minutes. This is 10,000 times faster than conventional methods. The research team achieved the high speed with the EoSens® CL high-speed camera from Mikrotron.

 

How can you tell when an avocado is ripe? You test its firmness by squeezing it. The softer it is, the more ripe it is. It's similar with biological cells. Their mechanical properties allow many conclusions to be drawn. For example, certain white blood cells become softer at the beginning of an infection. Many types of cancer cells are more easily deformable than healthy cells and the strength of a cell can be used to determine the status of the cell cycle.

With conventional technologies, it has so far been possible to scan a maximum of 100 cells within one hour. However, one drop of blood already contains 10,000 white blood cells. In order to analyse a meaningful quantity of these, one would have to measure continuously for 24 hours. These technologies are too complicated and too slow for routine, economical application in the life sciences or medicine.

The principle of Real-Time Deformability Cytometry

Scientists at the Technical University of Dresden have therefore developed a procedure that accelerates the evaluation by a factor of 10,000. The award-winning method is called "Real-Time Deformability Cytometry" (RT-DC) and is used in the AcCellerator. In this setup, deformed cells flow at a speed of 10 cm/s through the field of view of a microscope with 400x magnification. In principle, the system can be connected to any inverted microscope, but is most often used with a Zeiss AxioObserver. An EoSens® CL high-speed camera from Mikrotron captures each individual cell at up to 4,000 images per second and controls the 1 μs short LED light pulses. The images are transferred to the computer in real time via a Camera Link® interface. The resolution is automatically adjusted to the channel width. The standard size is 250 x 80 px. A specially developed program based on LabVIEW from National Instruments then evaluates the deformation of each individual cell.

The advantage of high speed

The analysis of an image takes 250 μs. "This allows us to measure the mechanical properties of several hundred cells per second. This allows us to perform analyses in one minute for which comparable technologies require a week," explains Dr. Oliver Otto, Managing Director of Zellmechanik Dresden. Within only 15 minutes an exact characterization of all blood cell types including the activation status of the cells is available. Due to the high throughput of cells, one drop of blood is sufficient.

The integration of the high-speed camera

The AcCellerator achieves this unique measuring speed through the combination of high-speed camera technology and high computing power. Special attention was therefore paid to the selection of the camera. The company chose the EoSens® CL from Mikrotron for several reasons. "The price/performance ratio is very good and it is easy to use", Dr. Daniel Klaue, who is also the managing director of Zellmechanik Dresden along with Dr. Otto, explains the decision. It was also important to the development team that the camera can be controlled with LabVIEW and has open interfaces. The integration into the system was easy and uncomplicated. "The support from Mikrotron is also great", Dr. Klaue continues. "There is always someone to contact and problems are solved very quickly."

The application possibilities

With the AcCellerator, the evaluation of cell mechanics becomes available for clinical applications for the first time. The mechanical fingerprint of cells could in future be used for the rapid diagnosis and monitoring of infections. Changes in the blood count or metastasising cells can be recorded in a few minutes.

The technology also opens up a wide range of new applications in research. It makes it possible to investigate all processes in which the cytoskeleton changes, such as migration or cell division.