Researchers at Tel Aviv University (TAU) have developed a hybrid micro-robot that can navigate between different cells in a biological sample, distinguish between different types of cells, identify whether they are healthy or dying, and then transport the desired cell for further study, such as genetic analysis. The micro-robot can also transfer a drug and/or gene into the captured targeted single cell.

The micro-robot, the size of a single biological cell (about 10 microns across), is controlled and navigated using two both electric and magnetic mechanisms. According to the researchers, the development may help promote research in the important field of “single cell analysis” as well as find uses in medical diagnosis, drug transport and screening, surgery, and environmental protection.

The innovative technology was developed by Professor Gilad Yossifon of TAU’s School of Mechanical Engineering and Department of Biomedical Engineering. His collaborators included post-doctoral researcher Dr. Yue Wu and student Sivan Yakov, as well as Dr. Afu Fu, a post-doctoral researcher from the Technion — Israel Institute of Technology. The research was published on March 15, 2023, in Advanced Science.

Professor Yossifon explains that micro-robots, sometimes called micro-motors or active particles, are tiny synthetic particles the size of a biological cell that can move from place to place and perform various actions (for example, the collection of synthetic or biological cargo) autonomously or through external control by an operator. According to Professor Yossifon, “Developing the micro-robot’s ability to move autonomously was inspired by biological micro-swimmers, such as bacteria and sperm cells. This is an innovative area of research that is developing rapidly, with a wide variety of uses in fields such as medicine and the environment, as well as a research tool.”

As a demonstration of the capabilities of the micro-robot, the researchers used it to capture single blood and cancer cells and a single bacterium, and showed that it is able to distinguish between cells with different levels of viability, such as a healthy cell, a cell damaged by a drug, or a cell that is dying or dying in a natural “suicide” process, a distinction that may be significant, for example, when developing anti-cancer drugs. After identifying the desired cell, the micro-robot captured it and moved the cell to where it could be further analyzed.

Another important innovation is the ability of the micro-robot to identify target cells that are not labeled. The micro-robot identifies the type of cell and its condition (such as its degree of health) using a built-in sensing mechanism based on the cell’s unique electrical properties.

“Our new development significantly advances the technology in two main aspects: hybrid propulsion and navigation by two different mechanisms, electric and magnetic,” Professor Yossifon says. “In addition, the micro-robot has an improved ability to identify and capture a single cell, without the need for tagging, for local testing or retrieval and transport to an external instrument.

“This research was carried out on biological samples in the laboratory for in vitro assays, but the intention is to develop future micro-robots that will also work inside the body, as effective drug carriers that can be precisely guided to the target, for example.”

The researchers explain that the hybrid propulsion mechanism of the micro-robot is of particular importance in physiological environments, such as found in liquid biopsies. “The electrically-based micro-robots that have operated until now were not effective in certain environments characterized by relatively high electrical conductivity, such as physiological environments, where the electric drive is less effective,” Professor Yossifon says. “This is where the complementary magnetic mechanism comes into play, which is very effective regardless of the electrical conductivity of the environment.

“The capabilities of the micro-robot are relevant for a wide variety of applications as well as for research,” Professor Yossifon concludes. “Among other things, the technology will support the  medical diagnosis at the single cell level, the introduction of drugs or genes into cells, genetic editing, directing drugs to their destination inside the body, cleaning the environment from polluting particles, drug development, and creating a ‘laboratory on a particle,’ a microscopic laboratory designed to carry out diagnostics in places accessible only to micro-particles.”