EN / DA
Disease and treatment

Micromotors can ferry living cells

Researchers have invented real-time hydrogel-producing micromotors that can entrap and move cells. This discovery presents significant pharmaceutical opportunities and the potential to improve how tissue can be designed both outside and inside the human body.

Researchers from the Technical University of Denmark have done something no one else has.

For the first time, they have succeeded in designing micromotors (autonomously propelled bots) that can entrap small particles such as living cells or microparticles and move them around. Much like a spider weaving a web, these microbots spew thread-like gel to trap and transport cells.

The discovery presents significant pharmaceutical opportunities because the microbots potentially can very accurately deliver drugs to the target tissue in the body and move cells around either in the body or in the laboratory.

“Our study is the first to show real‐time local hydrogel polymerization via an artificial microswimmer, which can entrap cells and other microobjects and move them around. Within frontline pharmaceutical research fields from targeted drug delivery to biomimetics, this is the first step towards bringing these fields a big step further” explains the first author, Sarvesh Kumar Srivastava, Postdoctoral Fellow, Department of Health Technology, Technical University of Denmark, Lyngby.

The new study was published recently in Advanced Materials.

Controlling microbots with magnets

These microbots are constructed in the shape of a small hollow cylinder and made of a resin called SU-8, which the researchers then fill out with a hydrogel reaction mixture.

A hydrogel is a network of polymer chains that can absorb large amounts of water without being dissolved or deformed. Hydrogel is used as scaffolding in constructing tissue in the laboratory. Most people are probably familiar with hydrogel through diapers, with the hydrogel absorbing urine.

When the researchers take the microbots and place them in a liquid, the microbots activate to form elongated thread-like hydrogel tails that propel them forward. Using the tail, a microbot can entrap both cells and other particles, and by making the microbots magnetic, the researchers can very accurately control where they move and which cells or particles are entrapped.

“We can control a microbot magnetically and position it near a cell that it needs to entrap, or it can simply scoop up a cell with its hydrogel tail. In addition, our microbots are biocompatible, which means that the cells we entrap with the microbots behave as these cells should. This means that we may be able to use microbots inside living systems in the near future,” explains Sarvesh Kumar Srivastava.

Delivering chemotherapy directly to a tumour or creating organs in a lab?

Although there is a long way to go before these researchers’ TRAP technology (thread-like radical polymerization via autonomously propelled bots) can revolutionize the pharmaceutical industry, we can still examine the opportunities the technology could bring.

This technology can deliver drugs where they are needed in the body. The microbots are covered with a thin layer of metal, and this means doctors can use magnetism to gather the microbots at the exact location in the body where they want them to deliver the drugs – such as delivering chemotherapy to the centre of a tumour.

Second, the microbots may conceivably be used to design tissue in the laboratory. Researchers and doctors may be able to use microbots to move stem cells around, for example, and get them develop into exactly the required types of cells. The researchers may want to use nerve cells in an organ and can use the microbots to move the nerve cells into the organ where they are needed.

“Forming real-time hydrogels, cell entrapment and magnetic control give us effective alternatives to the current methods of forming complex microsystems,” explains another author, Fatemeh Ajalloueia, Postdoctoral Fellow, Technical University of Denmark.

Can they also be used inside people?

Microbots might even be used to design tissues and organs in cell cultures, and even within humans.

Some forms of tissue damage such as brain injuries are currently irreversible, but in the future microbots might be able to transport new brain cells to the places in the brain where some have been lost.

In biomimetics, the microbots might be used to make smooth transitions between humans and, for example, an artificial leg or a pacemaker, thereby making the artificial part a “natural” part of a person.

“In the future, we envision creating healthy tissues and organs by moving cells and making them develop into different types of cells in certain specific places,” says Sarvesh Kumar Srivastava about an idea that seems like science-fiction but holds great promise for organ transplantation and medical technologies.

Thread-like radical-polymerization via autonomously propelled (TRAP) bots” has been published in Advanced Materials. In 2017, the Novo Nordisk Foundation awarded a grant to co-author Anja Boisen for the project MIMIO – Microstructures, Microbiota and Oral Delivery.

Sarvesh Kumar Srivastava
Postdoc
Drug delivery and Sensing In the IDUN section, we are working on micro- and nano sensor development and microdevices for drug delivery. The sensor projects are focusing on micro- and nanosensors as resonating strings, surface enhanced Raman scattering, electrochemistry on a disc and Raman spectroscopy. With these we can for example measure resonance frequency shifts of nanograms of material, perform rapid diagnostics and studies of molecular action of drugs and obtain finger-print spectra to identify unknown compounds. Furthermore, we are focusing on micrometer sized containers as an oral drug delivery system. The microcontainers are fabricated in polymeric material. Following the fabrication, the microcontainers are loaded with drug using methods such as embossing, inkjet printing and supercritical impregnation. The drug-loaded microcontainers are then coated with a polymeric lid, and the microcontainers are tested in vitro and in vivo for oral drug delivery of for example insulin, antibiotics and vaccines.