Microtransporter in an artificial blood vessel

A tiny magnetic sphere, loaded with tumour treatment, rolls against the bloodstream, targeted towards cancer cells

Another step has been taken towards the goal of precisely navigating medication through the bloodstream towards diseased tissue. Researchers at the Max Planck Institute for Intelligent Systems in Stuttgart have developed a microrobot that resembles a white blood cell in size, shape and mobility. A microroller was loaded with therapeutic drugs and adhered to diseased tissue cells with the help of antibodies on it, and additionally it was rolled and steered through an artificial blood vessel using external magnetic fields. In further tests, a microtransporter targeted cancer cells and discharged an active substance at the spot.

Going against the flow: As this illustration shows, the new microtransporters developed by Max Planck researchers in Stuttgart can roll along the inner walls of blood vessels, even against the flow of blood.

To reach different tissues and organs in the human body, there is no better access route than the circulatory system. Cells or synthetic drug transporters can most reliably target diseased tissue such as tumours if they can move not only with the bloodstream but also against it. When building their latest microrobot, the team at the Max Planck Institute for Intelligent Systems took their inspiration from white blood cells: the guardians of the immune system and only blood cells able to actively move against the blood flow. When making their way to sites where pathogens have invaded, leucocytes roll along the inner walls of blood vessels. They are only able to do this because the blood flow rate is significantly lower at the vessel walls than in the centre of a blood vessel.

Metin Sitti, Director of the Physical Intelligence Department at the Max Planck Institute for Intelligent Systems, together with researchers in his department, took advantage of this characteristic. They have developed a magnetic microtransporter, which they loaded with a tumour treatment and then steered through an artificial blood vessel using a small magnetic coil. “Our vision is to create the next generation of vehicle for minimally invasive, targeted drug delivery that can travel even further into the body and reach even more inaccessible areas,” says Metin Sitti.

The first microrobots to move against the blood flow

Tumour, it’s got your name on it: When the Stuttgart researchers target microtransporters towards cancerous tumours as illustrated here, specific antibodies attach themselves to the abnormal cells.

Each microroller has a diameter of less than eight micrometres and has a glass core. The researchers coated one side of the tiny sphere with a thin nickel and gold layer, making the tiny ball magnetic. They coated the other hemisphere with an anti-cancer drug, together with antibodies to steer the microroller towards tumour cells.

In a test in an artificial blood vessel, the spherical drug vehicle actively moved along the vessel wall against the flow of fluids such as mouse blood. “No microrobot has so far been able to withstand flows like this,” says Yunus Alapan, postdoctoral researcher at the Intelligent Systems Department and co-author of the publication. “But we’ve managed it! And not only that, our robots can independently recognize the cells of interest, for example, cancer cells.”

A swarm of microtransporters is necessary for drug delivery

However, there are further challenges to overcome before transporters like these can be launched under real-life conditions. In fact, they are still far from ready to be tested in the human body. Although the researchers have succeeded in observing the robots under a microscope, “In clinics, however, the resolution of current imaging techniques is not high enough for imaging individual microrobots in the human body,” says Ugur Bozuyuk, a PhD student at the Max Planck Institute for Intelligent Systems and co-author of the study. Furthermore, the drug cargo transported by a single microrobot would not be sufficient, given the size difference between a microrobot which measures less than ten micrometres and organ tissue thousands of micrometres in size. “It would be necessary to manipulate a large number of microrobots in a swarm to achieve a sufficient effect,” says Ugur Bozuyuk. “But we are still nowhere near that.”

The motivation for the research project goes back to a lecture given by Nobel physics laureate Richard Feynman in 1959 entitled ‘There’s Plenty of Room at the Bottom’. In his talk, he imagined microscopic machines that could move through blood vessels and perform operations from inside the human body, coining the term ‘swallowing the surgeon’.

A new approach to navigating through the circulatory system

Over the past two decades, research on micro-machines has made huge progress thanks to significant advances in manufacturing techniques, materials used, control and imaging techniques. However, current microrobots are still limited to environments such as those found in the eyes, or tissues that are relatively easy to access, such as the gastrointestinal tract. They are also only capable of moving through low-speed fluids. With their new, bio-inspired microrobots, the Max Planck researchers in Stuttgart hope to create a new approach to controlled navigation through the circulatory system. This could one day pave the way for targeted drug delivery to diseased tissue using microrobots.



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