Detection of human disease conditions by single-cell morpho-rheological phenotyping of blood

When you are sick and go to the doctor, it is often not obvious what exactly is wrong — what is causing fever, nausea, shortness of breath or other symptoms. It is important to find this out quickly so that the right action can be taken. One of the first steps is to obtain a blood sample and to count how many of the different blood cells are present in it. This is called a complete blood count, and the information it provides has turned out to be surprisingly useful. A large number of certain white blood cells, for example, can show that the body is fighting an infection. But there might be several reasons why the number of white blood cells has increased, so this information alone is often not enough for a specific diagnosis. There are many hundreds of possible tests that can supplement the results of a complete blood count. These might identify bacteria or measure the concentrations of certain molecules in the blood, for example. But which test will give the important clue that reveals the source of the illness? This can be difficult to predict. Although each test helps to narrow down the final diagnosis they become increasingly expensive and time-consuming to perform, and rapid action is often important when treating a disease. Can we get more decisive information from the initial blood test by measuring other properties of the blood cells? Toepfner et al. now show that this is possible using a technique called real-time deformability cytometry. This method forces the blood cells in a small drop of blood to flow extremely rapidly through a narrow microfluidic channel while they are imaged by a fast camera. A computer algorithm can then analyze the size and stiffness of the blood cells in real-time. Toepfner et al. show that this approach can detect characteristic changes that affect blood cells as a result of malaria, spherocytosis, bacterial and viral infections, and leukemia. Furthermore, many thousands of blood cells can be measured in a few minutes — fast enough to be suitable as a diagnostic test. These proof-of-concept findings can now be used to develop actual diagnostic tests for a wide range of blood-related diseases. The approach could also be used to test which of several drugs is working to treat a certain medical condition, and to monitor whether the treatment is progressing as planned.