Millimeter-Sized Feats Of Engineering Could Enable Smart Drug Delivery

July 5, 2022

By Deborah Borfitz 

July 5, 2022 | Fingertip-sized robots never fail to fascinate visitors to the lab of Renee Zhao, assistant professor of mechanical engineering at Stanford University. Her latest origami millirobot with spinning-enabled propulsion can be seen swimming in water and moving untethered over slick, uneven surfaces. 

The clinical vision here is precisely targeted drug delivery using wireless micromachines that can navigate the rugged terrain of the human body, including the slippery surface of organs and vessels where blood flow may be impeded by hypertension and arterial plaques, says Zhao. Excitement stems from a groundbreaking, all-in-one amphibious robot whose locomotion is controlled by the strength and orientation of a three-dimensional magnetic field.  

As suggested by experiments in ex vivo animal organs, the robot could sail across the body in a single leap at distances 10 times its length, she adds. Resistance from fluids can be overcome by changing the magnitude and frequency of the magnetic field.  

The technology is designed not for one disease but many—including cardiovascular conditions, kidney disease, and cancer, Zhao says. She is currently working with Stanford medical doctors to plan for in vivo testing of the latest millirobot model in pigs and rabbits. 

As recently described in an article appearing in Nature Communications (DOI: 10.1038/s41467-022-30802-w), the robust, easy-to-use multifunctional device zips to its intended destination and there releases its high-concentration drug cargo. It doesn’t just use origami’s folding/unfolding capability to navigate, as other origami robotic systems have done, but is also shaped like a sphere to make it easier to change direction whether moving in or out of water. 

In-water propulsion of the robot is aided by the propeller-like geometric feature of the origami to extend radially and rotate to exert linear thrust, Zhao says. Other unique design aspects include a longitudinal hole in the robot’s center and lateral slits angled up the sides to reduce water resistance and induce negative pressure in the origami cavity for fast swimming and suction for cargo pickup and transportation. 

Design Inspiration 

Zhao has been designing her millimeter-scale origami robots for close to three years now for specific assignments, for example to crawl through confined spaces such as those in the gastrointestinal tract and abdomen. In this instance, the device was inspired by the earthworm's abdominal contractions during locomotion and constructed of soft materials but structured in a way to give it sufficient stiffness to overcome external load in the lateral direction, as discussed in an article that Science Advances (DOI: 10.1126/sciadv.abm7834) published in March. 

Last year, in PNAS (DOI: 10.1073/pnas.2110023118), Zhao and her colleagues reported on an octopus-inspired stretchable origami robotic arm that might be used in conjunction with endoscopy, intubation, and catheterization procedures to steer tubes and catheters into position. Here, a remote magnetic field control allows distributed actuation of the system for omnidirectional bending and twisting. 

The newest origami device, unlike previous ones, is structurally a single unit rather than an amalgamation of separate geometrical components for locomotion and functions, she says. Its foldability can be used as a pumping mechanism for liquid medicines, based on increases and decreases in the volume of its internal cavity. 

A pill or capsule could likewise be target-delivered through the bloodstream by spinning the robot, using the suction generated because of the very low pressure in its chamber, Zhao continues. “The robot can suck in a solid pill, take it to wherever we need it to be, and release it.”  

Multifunctional Unit 

The robotic devices Zhao has had a hand in designing have been shrinking in size and currently are running between two and three millimeters—small enough to swim in a blood vessel of average diameter with some degree of plaque buildup, she says. Origami is the constant, owing to its “shape-morphing capability under external loading... [with] magnetic actuation to minimize the size of the device.” 

Electromagnetic fields are generated by a system much like a magnetic resonance imaging (MRI) machine, Zhao says, although far weaker fields are needed for targeted drug delivery than to take pictures of the anatomy. Patients might one day go into a precision medicine room for treatment as they would an MRI room for a scan. 

In parallel to animal testing of the latest millirobot, the research team will be working on automation of the device and assessing its compatibility with various clinical tubes and catheters, says Zhao. “Eventually, we want to test the potential of this technology... in clinical trials.”  

The one unit could be engineered to function in multiple ways to solve different medical problems, she says. In addition to the millirobot’s ability to navigate blood vessels to dispense medicines and carry instruments or cameras, the Zhao lab is also working on using ultrasound imaging to track where the robots go.