A small, rectangular microrobot robot, as tiny as a few human hairs, can travel throughout a colon by doing ‘back’ and ‘side’ flips.

The microrobot system, which includes an untethered tumbling magnetic microrobot, a two-degree-of-freedom rotating permanent magnet, and an ultrasound imaging system, was specifically developed for in vitro and in vivo biomedical applications.

In developing this microrobot sysytem, engineers at Purdue University have developed a new tool to diagnose and transport drugs in humans, whose colons and other organs have ‘rough terrain.’

Live ultrasound footage shows a microrobot tumbling through a colon in vivo. Image courtesy: © 2020 Purdue University video/Elizabeth Niedert and Chenghao Bi. Used with permission. Click on the image to enlarge.

The tiny robot  tumbles end-over-end in a ‘net forward motion’ due to applied magnetic torque from the rotating magnet. By turning the rotational axis of the magnet, two-dimensional directional control is possible and the microrobot was steered along various trajectories, including a circular path and P-shaped path.[1]

‘Back’ and ‘Side’ Flips
According to the developers, the ‘back flip’ and ‘side flip’ motion helps to get the right diagnoisis or transport a therapeutic agent directly to its target site. This could remove side effects, such as hair loss or stomach bleeding, that the drug may otherwise cause by interacting with other organs along the way to the the intended target site.

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The study, published in the journal Micromachines and supported by the National Science Foundation and the National Cancer Institute at the National Institutes of Health, was condicted by the Purdue Center for Cancer Research and aligns with Purdue Engineering Initiatives in Autonomous and Connected Systems and Engineering-Medicine.[1]

In the study, the engeneers, for the first time, demonstrate how a microrobot tumbles through a biological system in vivo. But because the micriroibot system is too small to carry a battery, it is powered and wirelessly controlled from the outside by a magnetic field.

“When we apply a rotating external magnetic field to these robots, they rotate just like a car tire would to go over rough terrain,” said David Cappelleri, a Purdue associate professor of mechanical engineering.

“The magnetic field also safely penetrates different types of mediums, which is important for using these robots in the human body.”

The researchers chose the colon for in vivo experiments because it has an easy point of entry – and it’s very messy.

“Moving a robot around the colon is like using the people-walker at an airport to get to a terminal faster. Not only is the floor moving, but also the people around you,” said Luis Solorio, Ph.D., an assistant professor in Purdue’s Weldon School of Biomedical Engineering.

The microrobot can be seen just to the right of the “U” in United States on this U.S. penny. Photo Courtesy: © 2020 Purdue University image/Georges Adam. Used with permission.

“In the colon, you have all these fluids and materials that are following along the path, but the robot is moving in the opposite direction. It’s just not an easy voyage,” Solorio added, who’s work centers on the development of novel microenvironments to provide specific cues to cancer cells, e.g., environmental factors that drive phenotypic changes in cancer, how cues within the cellular microenvironment influence those changes, and how those changes affect the response of cancer to therapeutic treatments.

‘Rough Conditions’
The magnetic microrobot can successfully tumble throughout the colon despite these rough conditions, the researchers’ experiments showed.

The team conducted the in vivo experiments in the colons of live mice under anesthesia, inserting the microrobot in a saline solution through the rectum. They used ultrasound equipment to observe in real time how well the microrobot moved around.

The microrobots could also tumble in colons excised from pigs, the researchers found, which have similar guts to humans.

“Moving up to large animals or humans may require dozens of robots, but that also means you can target multiple sites with multiple drug payloads,” said Craig Goergen, Ph.D., Purdue’s Leslie A. Geddes Associate Professor of Biomedical Engineering, whose research group led work on imaging the microrobot through various kinds of tissue.

Delivering drugs
Solorio’s lab tested the microrobot’s ability to carry and release a drug payload in a vial of phosphate-buffered saline. The researchers coated the microrobot with a fluorescent mock drug, which the microrobot successfully carried throughout the solution in a tumbling motion before the payload slowly diffused from its body an hour later.

A schematic of the microrobot system developed by researchers at Purdue University. The tiny robot tumbles in two modes. Image courtesy: © 2018 – 2020 Purdue University image/ Chenghao Bi, Maria Guix. Used with permission. Click on the image to enlarge.

“We were able to get a nice, controlled release of the drug payload. This means that we could potentially steer the microrobot to a location in the body, leave it there, and then allow the drug to slowly come out. And because the microrobot has a polymer coating, the drug wouldn’t fall off before reaching a target location,” Solorio said.

In addition, cytotoxicity tests conducted by the research team demonstrated that the materials used ro make the microrobot, SU-8 and polydimethylsiloxane (PDMS), did not show a statistically significant difference in toxicity to murine fibroblasts from the negative control, even when the materials were doped with magnetic neodymium microparticles.[1]

The magnetic microrobots, cheaply made of polymer and metal, are nontoxic and biocompatible, the study showed. Cappelleri’s research group designed and built each of these robots using facilities at the Birck Nanotechnology Center in Purdue’s Discovery Park.

“Commonly-used roll-to-roll manufacturing machinery could potentially produce hundreds of these microrobots at once,” Cappelleri noted.

The researchers believe that the microrobots could act as diagnostic tools in addition to drug delivery vehicles.

“From a diagnostic perspective, these microrobots might prevent the need for minimally invasive colonoscopies by helping to collect tissue. Or they could deliver payloads without having to do the prep work that’s needed for traditional colonoscopies,” Goergen concluded.

[1] Niedert EE, Bi C, Adam G, Lambert E, Solorio L, Goergen CJ, Cappelleri DJ. A Tumbling Magnetic Microrobot System for Biomedical Applications. Micromachines 2020, 11, 861. DOI: 10.3390/mi11090861

Featured image: A microrobot tumbling through a colon in vivo. Image courtesy: © 2020 Purdue University video/Elizabeth Niedert and Chenghao Bi. Used with permission.

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