One day, a visit to the hospital with a serious illness could end not with surgery or bottles of pills, but with an injection of medical microrobots. In the broadest sense, microrobots are simply microscopic-scale automated machines designed to perform selected movements in response to specific stimuli—but their tiny size means that they could travel through the body to perform tasks that no conventional robot could do. For example, they might clean out arteries that are blocked with plaque, perform highly targeted tissue biopsies, or treat cancerous tumors from the inside.
Similar in size to living human cells, microrobots are far less likely to cause tissue damage than conventional medical interventions, such as surgical incisions and catheter insertions. By aiming for specific destinations in the body, microrobots could drastically reduce the side effects of pharmaceuticals. Looking further ahead, once they can be manipulated accurately and repeatedly at the subcellular size range, microrobots could enable tissue engineering and regenerative medicine, whereby damaged tissue and organs could be repaired or entirely rebuilt.
Medical engineers have been working toward these goals for more than three decades, but recent advances in semiconductor fabrication techniques have spurred a surge in microscale and nanoscale research that is making viable medical microrobots look increasingly attainable. These advances are natural extensions of technologies developed for building microelectromechanical system (MEMS) devices. The applications of MEMS devices have exploded since they were first commercially introduced in the 1990s. They can now be found in settings as varied as automotive airbags, inkjet printers, optical switches, and blood-pressure sensors.
Current research is also making progress in the delivery of therapeutic payloads, including drugs and imaging agents. Compared to the problems of fabrication and locomotion, drug delivery is relatively straightforward: A microrobotic agent simply triggers a payload-release mechanism after being guided to a target location in the body. Successful tests have been demonstrated in vivo for small animals. For example, autonomous microrobots propelled by hydrogen microbubbles have been used in live mice to treat gastric bacterial infections. These microrobots improved payload-retention rates by pressing the drug directly against the stomach wall.
Compared to traditional drug delivery methods, which often rely on passive diffusion to reach a desired area, actively guided microrobots offer a way to deliver on-demand payloads much closer to the target location. This precision delivery means that a higher concentration of the drug will arrive at the most beneficial site, and that the risk of potential side effects is minimized because the drug is much less likely to diffuse to the surrounding tissue.
The greatest challenges to practical medical microrobotics now lie in the areas of locomotion and control. Inside the human body, the microrobots must be able to move reliably through wet areas as well as traverse through pockets of air found in places such as the stomach, intestines, and lungs. Researchers are exploring a variety of microrobot designs that, much like an all-terrain tire or a monster truck, could tackle a variety of conditions and surfaces. Our group sees special promise in microrobots that move about with a tumbling motion—devices that we call microscale tumbling magnetic robots (μTUMs), or microtumblers. If we can make these little tumblers cheap, safe, and versatile enough, we could be a lot closer to a revolution in the delivery of therapeutic treatments.
Challenges of Going Small
Broadly speaking, the greatest difference between microrobots and conventional robotic systems is their extremely small size, which imposes some severe constraints. The most significant is that microrobots are too small to easily incorporate any on-board power source, sensors, or computer circuitry. Features such as motors, electronic sensors, and self-contained intelligence—all commonly used in large robots—are generally infeasible for microrobots. Creative new methods and designs need to be developed to account for this critical limitation, and contemporary knowledge of macroscale robots cannot be directly transferred to the microscale.
Biodegradability and biocompatibility are concerns for injectable microrobots because tiny foreign objects should not stay in the body permanently, and they must not cause any disruptive immunogenic reactions. Toxic structural materials or chemical propellants that could be acceptable in a factory setting are strictly off-limits for objects that will be injected into the body.
Microtumblers use friction to grip a surface and move forward. They can tumble off ledges and into valleys several times their size and use local adhesive forces to climb steep inclines.
The small size of microrobots makes it difficult to generate real-time, noninvasive images of them inside the body. A camera is sufficient for investigating living tissue analyzed in a controlled environment outside of the body; however, it is more difficult to visually capture small objects in vivo, let alone capture the complex three-dimensional nature of their surroundings. Endoscopy, ultrasonic imaging, and fluoroscopic imaging are among the solutions under exploration, but current visualization technology is still far from perfect.
Surface area presents additional complications at the microscopic scale. At small scales, volumetric effects become insignificant compared to surface-area effects. This trend is seen in insects, whose small size allows them to safely fall from surfaces many times their own height. Air resistance is far greater than their weight, so their terminal velocity while falling is greatly reduced. Some can even walk on water because their weight is balanced by the water’s surface tension. At the microscale, familiar macroscale volumetric effects, such as weight and inertia, play similarly smaller roles, because effects proportional to surface area and distance (such as electrostatic attraction, adhesion, and drag) dominate.
These factors explain why microrobot mobility poses such a challenge. A fishlike swimming motion, for example, will not work on the microscale because the inertia generated from the reciprocating action is too small to overcome drag. The commonplace forces that cause water to form droplets and balloons charged with static electricity to stick to our heads can cause microrobots to be trapped and stuck.
Engineers have come up with a dizzying number of approaches to mobile microrobot actuation. One approach is acoustic actuation, in which microrobots move toward sound-generated pressure points driven by oscillating sound waves that are applied to the fluid surrounding them. Chemical actuation methods include propulsive chemical motors that expel microbubbles or use local chemical gradients to generate thrust forces.
There are also biohybrid designs that take advantage of the self-contained energy and mobility of living cells, typically by coupling bacteria, sperm, or muscle cells to artificial structures and controlling them remotely by varying the surrounding temperature, acidity, lighting conditions, or magnetic fields. Optical actuation can generate crawling locomotion on elastomer materials, which contract when directly heated by lasers. The problem with many of these methods is that they can be used only in controlled environments and require fine-tuning for applications in vivo.
Therefore, the most popular form of microrobot actuation is magnetism, which is well-suited for use in vivo. By embedding magnetic material inside or around its form, we can manipulate a microrobot with external magnetic fields. To generate these fields, we use electromagnetic coils or movable permanent magnets in a separate system that would be located outside of the body. The magnetic fields can harmlessly penetrate through living tissue and do not require a specialized environment to function.
Changing the orientation and gradient of the external magnetic field imposes torque and force, respectively, on the microrobot that cause it to move along a desired trajectory. How these two field parameters vary over time, in addition to the field’s magnetic strength, determine exactly how the microrobot moves. Magnetic actuation does not require any kind of tether, and it can be used to direct a microrobot in a variety of reconfigurable locomotion styles, applicable in many different working environments.
Perhaps most important, magnetic actuation is safe and robust within the human body. With modifications, the same equipment used in magnetic resonance imaging (MRI) machines can be used to actuate microrobots.
The Tumbling Solution
In addition to their activation methods, experimental microrobots differ according to their locomotion styles. Microswimmer robot designs are appealing for in-vivo applications due to their ability to maneuver three-dimensionally in fluid environments. Recognizing that reciprocating motion does not work well at the microscale, researchers looked to nature for solutions and noticed that all microorganisms moving under their own power propel themselves using the nonreciprocating motion of threadlike appendages known as flagella.
Mimicking the biological world, flagella-based microswimmer designs use microhelices, tiny whips that move with a screwlike motion. Typically, the motion of the flagella is driven by rotating magnetic fields, although some research groups have demonstrated thermal-driven versions. Microswimmers are quite capable in fluid environments, but they have major constraints: They cannot move through pockets of air such as those found inside the human body, and they are unable to make their way through the body’s many rough, sticky surfaces. Indeed, few existing microrobots of any design can negotiate this difficult biological terrain.
Experimental research for driving microrobots across two-dimensional surfaces has largely focused on using magnetic-force gradients, which pull magnetic objects toward areas where the field is stronger. Because of their predictability and precision, force gradients are effective for microassembly applications in controlled environments, but their performance falls short outside of this setting. The sliding action of force gradients is difficult on rough terrain and constantly acts against frictional force. In other words, they are great in laboratory experiments but are ill-suited to the complicated demands of navigating a microrobot through the human body.
After considering the limitations of all the existing forms of locomotion, our team came up with a new approach. In laboratory experiments, we found that rolling or tumbling a microrobot using magnetic torque is more effective than pulling it along a magnetic gradient. Much as a rotating magnetic field can be applied to spin artificial flagella, it can be used to rotate blocklike surface tumblers. This is how we came up with the concept of our microscale tumbling magnetic robots—our µTUMs or microtumblers.
Instead of fighting against friction, the µTUMs use it to their advantage to grip the surface and move forward. They can tumble off ledges and into valleys several times their size and use adhesion to climb steep inclines. They can also move through liquids and tumble across many different surface textures. Although μTUMs are not as controllable as their sliding counterparts, they are still steerable and move in predictable, repeatable trajectories.
Furthermore, magnetic torque propulsion from tumbling is more energy efficient than magnet force propulsion. The greater efficiency is important because the input energy from external magnetic fields loses strength over distance, and the human body can absorb only so much magnetic energy before the tissue heats up and suffers damage. By minimizing the amount of input energy required to move the microrobot, tumbling locomotion offers a solution that is both versatile and efficient for negotiating multiple complex terrains.
Once we were convinced that μTUMs could tackle the locomotion challenges, we wanted to make sure they could also be built cheaply and precisely—essential considerations if they are ever to become commonplace medical tools. We designed a fabrication process for the μTUMs that uses photolithography, a standard technique that uses light to transfer 2D geometric patterns onto light-sensitive material, which then cures and solidifies so that the remainder can be removed. Our process is easily reconfigurable and open to experimentation.
Some companies and laboratories are starting to introduce the kind of microscale 3D printing techniques needed to build the μTUM robots we have in mind, but additional advancements are required to produce the microscale magnets needed for them. For now, we created our test versions by embedding magnetic nanoparticles into photoresist (light-sensitive material) and aligning them in a desired direction before the material cures. Once the photoresist has hardened, the magnetic particles are permanently aligned into place.
This method has allowed us to tweak the magnetization polarization of our microrobots so that we could study variations of tumbling locomotion. We have found that sideways tumbling requires less energy to initialize motion than lengthwise tumbling. Lengthwise tumbling, on the other hand, moves the μTUM more quickly because each tumble covers more distance.
Inspirations for Better Mobility
Insects and microbes provided the inspiration for our μTUMs, and we are now looking to nature for further inspiration in developing all-terrain medical microrobots. Many soft-bodied organisms have evolved clever ways of moving through complex natural environments; for example, a snake can slither on the ground or swim in water. To achieve the ultimate goal of adaptive locomotion in many modes, suitable for many environments, we are interested in flexible, stimuli-responsive materials. Recent developments in 3D microprinting and other innovations in fabrication technology have made it easier to incorporate these pliant materials into the structure of a microrobot. A team at the Max Planck Institute for Intelligent Systems in Stuttgart, Germany, just demonstrated a magnetoelastic, millimeter-scale robot that can crawl, swim, climb, roll, and jump in several environments.
To bring mobile microrobots even closer to their biological counterparts, we want to be able to make a group or swarm of robots work together, like ants in a colony. Multiple microrobots could collaborate to carry more of a drug, for example, or one individual might help another to do a task. The problem here is that most magnetic systems cannot direct the movement of one robot independently from another, because they are all tied to the same global field. Preliminary experimental research is under way to develop miniaturized electromagnets that produce local actuation fields and robots designed to respond only to individualized frequencies. These two techniques have shown promising results for independently controlling a small number of microrobots, but swarm control remains a significant challenge.
Once we have mastered the basics of locomotion and control, the next stage will be to enable microrobots to perform complex tasks by physically manipulating their surrounding environment. At the moment, the mechanical end-effectors available to perform such manipulations are fairly modest: They can push, grasp, and, using small fluid vortices, trap objects. To perform the complex medical tasks we envision, microrobots will need expanded and refined capabilities, closer to those of the human hand. The last step would be to take natural inspiration to its highest level, developing smart microrobots that have some onboard computing and decision-making power.
Even the near-term objective of using microrobots to perform targeted drug delivery could have sizable benefits for cancer treatment and many other medical applications. As miniaturization technology advances, in a not-too-distant future we envision teams of tiny robots swimming through blood vessels and exploring far-flung corners of the body, repairing cells and delivering therapeutic agents as they go. A world where human ailments can be cured from inside the body without need for cutting, invasive procedures, or risking potential side effects from drug use remains a more distant vision—for now.
Our preliminary research in actuation and tumbling locomotion in microrobots moves us a step closer to this vision by demonstrating that it is feasible to operate microrobots in multiple complex environments. Our focus so far has largely been on hardware, but it is only a matter of time before advances in computer vision and sensing catch up and lead to truly smart microscopic robots that can heal us from within.
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