Cameras Help Accelerate Human Cell Analysis Process from Days to Minutes

Heart-shaped flow lines are formed, which are shown here by inverted superimposition of multiple individual images (Source: Zellmechanik Dresden)

Scientists at the Dresden University of Technology in Dresden, Germany, have developed an analytical procedure that allows the mechanical properties of 100,000 cells to be assessed in less than two minutes, or ten thousand times faster than conventional methods. Using advanced camera technology from Mikrotron, the research team was able to reach unprecedented cell analysis speeds.

First, to understand cell analysis, consider a piece of fruit. How does one know that a fruit, say an avocado is ripe and ready to eat? Simply by squeezing it in order to check its firmness. The softer the fruit is, the higher is the degree of ripeness. This same principle can be applied in a laboratory, since biological cells behave in a much similar way. Their mechanical properties allow various conclusions to be drawn. Certain white blood cells, for instance, are softer during the starting period of an infection. Also, many types of cancer cells can be deformed more easily than healthy cells and the status of the cell cycle can be determined based on how firm a cell is.

Using conventional technologies for cell analysis has been slow with a maximum of one hundred cells being sampled per hour. To provide perspective, one single drop of blood contains roughly ten thousand white blood cells. Consequently, measurements had to be performed around the clock in order to analyze a meaningful quantity. Obviously, this form of analysis is simply too slow for routine, efficient applications in the laboratory.

RT-DC is used to examine the mechanical fingerprint of blood samples in just a few minutes. To do so, cells flow at a speed of 10 cm/s through a microfluidic channel structure from right to left. The image detail width is 1.5 mm. For measuring purposes, the cells are focused in the narrowest part of the channel by the additional flow coming from the right, from above and below. (Source: Zellmechanik Dresden)

At Dresden University of Technology, the scientists have developed a method that speeds up this assessment process by a factor of 10,000 using real-time deformability cytometry (RT-DC). They have coined the phrase AcCellerator for the new system and started a new company, Zellmechanik Dresden to further push the limits of cell analysis.

During the process a stream of deformed cells flows into the setup at a speed of 10 cm/s and passes the field of view of a microscope with 400× magnification. In principle, the system permits any inverse microscope to be connected; however, it is most frequently used with an AxioObserver from Zeiss. An EoSens CL high-speed camera from Mikrotron is connected to the microscope and captures each individual cell, with up to four thousand frames per second. The camera also controls the 1 μs short LED light impulse sent out for each image acquisition. The standard resolution of 250 × 80 pixels is automatically adjusted to the channel width. All images are transferred in real time to the computer unit via a Camera Link interface. A specifically designed program based on National Instruments LabVIEW then analyzes the deformation of each particular cell. Analyzing a single image takes less than 250 μs.

“This process enables us to measure the mechanical properties of several hundred cells per second. In one minute, this permits us to carry out analysis that would take a week in the technologies we used before,” says Dr. Oliver Otto, CEO of Zellmechanik Dresden. Within just fifteen minutes, a precise characterization of all blood cell types, including cell activation status, is analyzed. Due to the high throughput of cells, only one single drop of blood is needed for the analysis.”

The Mikrotron EoSens CL is connected to the microscope by means of a rotary adapter. This enables it to rotate in case the measuring area in the chip is not lying parallel to the camera chip. (Source: Zellmechanik Dresden)

Integration of the High-Speed Camera

The AcCellerator achieves its amazing measuring speed thanks to the combination of Mikrotron high-speed camera technology and high processing power. Several reasons led the scientists to opt for the EoSens CL.

“The Mikrotron camera is both a great value and easy to operate,” explains Dr. Daniel Klaue, Dr. Otto’s counterpart in the management team at Zellmechanik Dresden. “It was also important to the team of developers that the camera could be controlled with LabVIEW and that it had open interfaces. The integration into the system was simple and uncomplicated. Superior imaging quality was complimented by exemplary customer support by Mikrotron.”

Thanks to the AcCellerator, cell mechanic evaluation for the first time has become usable in clinical applications. In the future, mechanical fingerprinting of cells could be used for fast diagnosis as well as for monitoring infections. Blood count changes or metastasizing cells can be detected in a matter of minutes. The technology is also opening up many new areas of application in research by enabling scientists to examine all processes in which cytoskeleton changes are responsible for the mechanical stabilization of the cell, including migration or cell division. (Source: Mikrotron)

Links: Biotechnology Center (BIOTEC), Technische Universität Dresden, Dresden, GermanyZELLMECHANIK DRESDEN GmbH, Dresden, GermanyHigh-Speed Recording Cameras, Mikrotron GmbH, Unterschleissheim, Germany

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