Cells in the speed trap – diagnosis in a matter of seconds

A drop of blood provides a lot of valuable information. However, it takes several hours to analyze the blood of a patient and make a diagnosis. This takes away a lot of time that's crucial for treatment. A new method intends to considerably speed up this process by testing the cells in the blood in terms of their deformability and immune response.

In this MEDICA-tradefair.com interview, Dr. Daniel Klaue and Dr. Christoph Herold explain real-time deformability cytometry, a technology they both developed, describe the new possibilities this could open up for medical science and reveal what ripe fruits have to do with all this.

Dr. Klaue and Dr. Herold, what happens in real-time deformability cytometry?

Dr. Daniel Klaue: We like to explain the technology with an example taken from everyday life: You go to the supermarket with the intent to buy a very ripe fruit. You can only determine how soft or firm the fruit is by picking it up and squeezing it in your hand. After all, all fruits look the same with the naked eye. That's also the case with cells. The stiffness of a cell lets us draw conclusions about its condition – for example, whether an immune cell or leukocyte is flexible enough to migrate from the bloodstream into much denser tissue to destroy pathogens. We are unable to determine this just by looking at the cell. Needless to say, unlike a fruit, we are also unable to simply take a tiny cell into our hand. That's one issue. Another issue is that we don't want to squeeze ten fruits but rather millions of cells in one drop of blood for instance. Together with Professor Jochen Guck of the TU Dresden, we have developed a technology that enables us to scan many cells within a very short amount of time. In this instance, the cells are moved through a narrow channel – thanks to a certain flow profile in the frame. The cells in the middle flow faster than those on the edges, similar to how things work in a river. A softer cell deforms more than a stiffer cell. Simultaneously, we take a picture of each cell and use it to calculate its deformation, providing us with more information. Our device does this at a rate of up to a thousand cells per second. In essence, our technology works sort of like a speed trap: many cells flash by in the channel and we constantly take pictures to analyze them afterward.

How did you come up with this technology?

Klaue: This method is based on exerting pressure on cells and making assertions pertaining to their deformability and has been around for a few decades. However, it was previously carried out in a different and much slower manner. In collaboration with Professor Guck's task force, we were able to develop a research prototype where cells flow through a channel, as mentioned earlier. As it turned out, many researchers were also interested in our technology, prompting us to create a spinoff and develop a commercial device – the AcCellerator – based on the prototype that we can sell to scientists.

What is the advantage over other blood tests?

Klaue: Needless to say, erythrocyte deformability is a crude parameter. We don't detect specific molecules or messengers but solely study the immune cell itself and the body's own response. The advantage over other blood tests is simply that we look at another aspect. Our device will never replace all other equipment or tests at a hospital, though it is designed to complement them. It is intended to assist physicians in choosing the next treatment steps and speed up this process, thus making it more effective and more efficient on the whole.

Dr. Christoph Herold: Our method is basically an assessment of the immune system. We are unable to test for the exact bacterium in the blood. However, we can determine that something is actually out there that prompts the immune system to fight. One major advantage is that we only need a very small amount of blood. It should be noted that this test should be done quite promptly. For example, for our research purposes, we only measured blood that was less than two hours old. We do this because we want to draw conclusions about cells that are still in a living state. Otherwise, information might get lost after several days of storage. Having said that, the test should primarily be used in case of severe infections where lab results normally need to be on hand as quickly as possible. This fact alone ensures that a blood test is done very promptly.

What are the potential medical applications?

Herold: Our technology is designed to determine both the severity and the type of infection we are dealing with – meaning whether this is a bacterial or even viral infection. Our hope is that this method will allow us to determine whether certain immune cells in the blood are in an activation status. Cells change their mechanical properties – stiffness or size –, which allows us to determine the patient's immune status. For example, we could see if he/she is close to sepsis where the immune system creates an overwhelming response to an infection. Another potential application includes the monitoring of treatment pertaining to leukemia cases for example.

Klaue: So far, we are still talking about a pure research device. However, our goal is to take the basic research and develop a medical device. We envision a blood test that enables an extended blood count – we also call it a test of mechanical properties of cells. One application could be a test to determine whether a specific antibiotic achieves the desired outcome and would allow the physician to adapt the treatment until the pathogen has been substantiated. Right now, this often takes up to three days, which means patients have to be treated with a broad-spectrum antibiotic in the interim. In other words, this method is not just intended for diagnostic but also for monitoring purposes.

What potential do you see for your technology?

Klaue: We are still years away from our vision becoming a reality and a point where our AcCellerator can be used on a daily basis at a hospital. It still requires lots of research, clinical trials, the fulfillment of medical device regulatory requirements and extensive negotiations with health insurance companies as it pertains to the reimbursements of costs. As a developer, our next step is to embed a sorting mechanism into our device. After the mechanical measurement, the idea is to separate soft and stiff cells. If one type of cell is better suited for blood cell transplantation, a sorting mechanism is obviously very helpful. Undoubtedly, there are many other feasible applications for users – perhaps far more than we could ever imagine today.