27-May-2020 - Max-Planck-Institut für die Physik des Lichts

"Ultimate cell sorter" developed: combining imaging of deformed cells and AI

High-speed method for identifying and sorting cells requires no external cell labeling

In medicine and biology, there is great interest in efficient and inexpensive methods for identifying and separating different cell types, for example for medical diagnostics or for regenerative therapies using stem cells. Up to this point, the method of choice has been the so-called flow cytometry, in which cells are labeled with fluorescent antibodies and then identified as they flow through a channel. However, this method has its weak points: Not only is it relatively expensive and time-consuming, but also the antibodies themselves can be problematic. As they are exogenous, they can change the properties of the cells they dock onto and can cause difficulties, for example, when they are injected into the body. Besides, the identification of cells is not always error-free in flow cytometry.

To help address these points, the physical properties of the cells can be used as an additional distinguishing feature: Due to the cytoskeleton, a fine network of filaments within the cell structure, each cell type has characteristic mechanical properties such as shape, size and, in particular, deformability. The team headed by Jochen Guck, Director at the Max Planck Institute for the Science of Light, had developed a new technique based on this a few years ago: Real-time deformability cytometry (RT-DC). In this technique, a cell suspension is pressed through a transparent channel thinner than hair in diameter. The cells are then stretched without damage and the degree of deformation allows an assignment to a specific cell type.

The cell types are assigned with the help of a high-speed camera that records the deformed cells in the channel at 2,000 to 4,000 images per second. This is comparable with videos in which you can watch a balloon pop in slow motion. The images are evaluated with special software that evaluates certain previously defined cell properties in real time. This real-time evaluation, in which every cell is identified immediately as it flows through the channel, is now the basis for the first innovation: it allows the cells to be deflected into a collection channel after identification. For the first time, cells can now be sorted based on their deformability.

Another novelty is to combine RT-DC with artificial intelligence: Hundreds of thousands of images of individual cells are an ideal basis for training a neural network to recognize different cell types. The AI-algorithm can then identify cells at previously unreached speed and also sort them in real time as wished.

Guck compares this approach to the strength of Google: "If cat owners post millions of cat photos on the Internet and write something like 'my cat', the search algorithm is trained on the image and the comment to recognize the characteristics that make a cat. If someone then googles for 'cat', the algorithm can train the neural network to identify the pictures with cat properties and filter them out of all other pet photos. "

With Guck's new method, the situation is similar: Since the fluorescent molecules are selected in such a way that they only dock onto certain cells, the lighting up of a fluorescent molecule corresponds to the comment "my cat". The photo of the cell with all its properties corresponds to the cat picture. In this way, the neural network learns that lighting up is connected to a specific cell type and can establish a connection to the associated photo of the cell. If the neural network has been trained sufficiently for a cell type by the fluorescence marker, the marker can finally be omitted entirely and the cell type is also recognized without fluorescence, just as the Google algorithm has learned to recognize cats without additional comments.

This new method has many advantages: After training the neural network, the time-consuming and cost-intensive fluorescence marking for identification is no longer necessary and the cells are no longer changed by foreign molecules. At this point, the images shot by the high-speed camera are sufficient to identify the cells. This procedure is very gentle on the cells, does not change the cell properties and can analyze up to 1,000 cells per second. The application of artificial intelligence to RT-DC also offers the advantage that the parameters, on the basis of which the cell recognition or a cell change through disease can be determined, do not have to be defined beforehand. You can let the AI decide which image information is best to differentiate cells.

Guck calls the newly developed method, which has now been published in the journal Nature Methods, an "ultimate cell sorter": it combines the accuracy of the established detection via fluorescence with the sensitivity of inherent mechanical cell properties and has the potential to become a future standard method to be used in all biological and biomedical laboratories. In the future, it will be possible, for example, to quickly recover blood-forming stem cells from a sample, which can then be injected into a chemotherapy patient to rebuild the immune system, or to sort out particularly suitable photoreceptor cells from human organoids in order to avert certain forms of blindness by transplantation.

Facts, background information, dossiers
  • artificial intelligence
More about MPI für die Physik des Lichts
  • News

    Sensitive detection of molecules

    To observe molecules, one has to use sensitive tools. Such measurements would be important for determining the concentration of minute particles in blood samples or during neuronal information transfer in the brain. A team of Max Planck scientists has taken a decisive step in this direction ... more

    A molecule in an optical whispering gallery

    Being able to track individual biomolecules and observe them at work is every biochemist’s dream. This would enable the scientists to research in detail and better understand the workings of the nanomachines of life, such as ribosomes and DNA polymerases. Researchers at the Max Planck Insti ... more

    The shadow of a disease

    In future, some diseases might be diagnosed earlier and treated more effectively. Researchers at the Max Planck Institute for the Science of Light in Erlangen have developed an optical method that makes individual proteins, such as the proteins characteristic of some cancers, visible. Other ... more

  • Research Institutes

    Max-Planck-Institut für die Physik des Lichts

    more

More about Max-Planck-Gesellschaft
  • News

    Circular RNA makes fruit flies live longer

    Ribonucleic acid, or RNA, is part of our genetic code and present in every cell of our body. The best known form of RNA is a single linear strand, of which the function is well known and characterized. But there is also another type of RNA, so-called “circular RNA”, or circRNA, which forms ... more

    Neandertal genes in the petri dish

    Protocols that allow the transformation of human induced pluripotent stem cell (iPSC) lines into organoids have changed the way scientists can study developmental processes and enable them to decipher the interplay between genes and tissue formation, particularly for organs where primary ti ... more

    The relationship of proteins

    Proteins control life as one of the most important biomolecules - as enzymes, receptors, signal or structural building blocks. Researchers at the Max Planck Institute (MPI) of Biochemistry have for the first time uncovered the proteomes of 100 different organisms. The selected specimens com ... more

  • Videos

    Epigenetics - packaging artists in the cell

    Methyl attachments to histone proteins determine the degree of packing of the DNA molecule. They thereby determine whether a gene can be read or not. In this way, environment can influence the traits of an organism over generations. more

    Biomaterials - patent solutions from nature

    Animals and plants can produce amazing materials such as spider webs, wood or bone using only a few raw materials available. How do they achieve this? And what can engineers learn from them? more

    Chaperones - folding helpers in the cell

    Nothing works without the correct form: For most proteins, there are millions of ways in which these molecules, composed of long chains of amino acids, can be folded - but only one way is the right one. Researchers in the department "Cellular Biochemistry" at the Max Planck Institute for Bi ... more

  • Research Institutes

    Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V.

    The research institutes of the Max Planck Society perform basic research in the interest of the general public in the natural sciences, life sciences, social sciences, and the humanities. In particular, the Max Planck Society takes up new and innovative research areas that German universiti ... more