Vibrational Micro-robots in Viscoelastic Biological Tissues

Informations projet

VIBEBOT

N° de convention de subvention: 101041975

DOI

10.3030/101041975

Date de signature de la CE 4 Août 2022

Date de début 1 Janvier 2023

Date de fin 31 Decembre 2027

Financé au titre de

• European Research Council (ERC)

Coût total

€ 1 499 728,00

Contribution de l’UE

€ 1 499 728,00

Coordonné par

DEUTSCHES KREBSFORSCHUNGSZENTRUM HEIDELBERG
Germany

Periodic Reporting for period 1 - VIBEBOT (Vibrational Micro-robots in Viscoelastic Biological Tissues)

Période du rapport: 2023-01-01 au 2025-06-30

Résumé du contexte et des objectifs généraux du projet

Wireless micro-robots hold great potential for minimally-invasive medicine. They may lead to new medical procedures, such as targeted drug delivery, in vivo bio-sensing and stimulation. However, the biggest challenge for real biomedical applications is the penetration of viscoelastic biological media, for instance, mucus, blood clots and solid tumor tissues. Most current micro-/nano-robots can propel in water, however, the same propulsion mechanisms do not readily transfer to viscoelastic biological media. One major bottleneck is the limited propulsion force of the microdevice in a system that could one day also accommodate a human. The overall objective of the project is to develop micro-sized robots that can actively penetrate and navigate in viscoelastic biological tissues; and also wirelessly sense physical signals, such as location and orientation, temperature, magnetic field, and the chemical signals, such as glucose level, pH, oxygen concentration. The actuated motion and the robot’s shape are optimized to facilitate an easier penetration of the biological soft tissues. The proposed work will, on the one hand, generate new scientific knowledge about the micromechanics of viscoelastic tissues; and on the other hand, advance useful wireless technologies that can be applied to current surgical tools, such as a clinical endoscope. Our research will lead to a new class of micro-robots – the VIBEBOTS that will be able to actively penetrate biological soft tissues, and open up entirely new opportunities for numerous biomedical applications.

Travail effectué depuis le début du projet jusqu’à la fin de la période considérée dans le rapport et principaux résultats atteints jusqu’à présent

Major scientific achievements have been made in the following sub-projects during the first two years of the project.

Micro-robots for effective tissue penetration
The micro-robot is fabricated by two-photon lithography 3D printing in a helical shape that is sub-millimeter in diameter and millimeters in length. It exhibits a diametric magnetic moment and rotates under the actuation of a rotating magnetic field. The rotational motion is converted to a forward propulsion by the optimized helical structure, and the propulsion direction is controlled by the applied magnetic field. Imaged by fluoroscopy and ultrasound, the robot demonstrates successful propulsion in ex vivo animal tissues. Histological analysis along the entire trajectory reveals minimal tissue damage, highlighting the potential of micro-robots as a promising minimally-invasive surgical tool. Various medical applications will be further investigated in this project, such as targeted drug delivery, tissue biopsy and biosensing.

Human-scale magnetic system for micro-robot actuation
Traditional electromagnetic actuation systems have limited accessible volume, which restricts the controllable working space of the micro-robots for in vivo medical applications at human scale. We developed a new permanent magnetic actuation set-up comprised of a pair of static magnets and a rotating magnet, which generates a rotational magnetic field vector on a virtual conical surface in a large accessible volume. A mini-robot with sharp spikes to anchor on biological soft tissues is developed. We demonstrate its ability to crawl on biological tissues with full controllability to follow complicated trajectories. The permanent magnetic actuation set-up, which requires neither an expensive power amplifier nor a coil cooling system, has a large enough accessible volume that can in future accommodate a human patient. This project was published as a journal paper, and presented as a talk at the IEEE MARSS conference, where it received the nomination of “The Best Student Paper Award” (Fig. 1).

Wirelessly controlled drug delivery implantable device
We developed a novel self-contained implantable device driven by an oscillatory resonator for on-demand and ultrafast-response drug delivery. The gigahertz acoustic resonator generates an ultra-high frequency vibration. The vibration generates acoustic streaming in the drug reservoir, which opens an elastic valve to deliver the drug. The fast response of the microfluidic device is on the order of magnitude of 1 millisecond, which is more than three orders of magnitude faster than the start-of-the-art methods. By the integration of an on-board magnetic sensor, wirelessly-controlled drug delivery is also realized. Controlled release of drug in the long term was achieved for two weeks continuously with full functionality. The project was highlighted as a cover image in Advanced Engineering Materials (Fig. 2).

Progrès au-delà de l’état des connaissances et impact potentiel prévu (y compris l’impact socio-économique et les conséquences sociétales plus larges du projet jusqu’à présent)

New magnetic localization method for biomedical microdevices
State-of-the-art magnetic localization methods utilize static magnetic fields. However, they suffer from a large required magnetic volume and are not sensitive due to the magnetic noise in the surroundings. We developed a novel Small-scale Magneto-Oscillatory Localization (SMOL) method, which is capable of wirelessly localizing a millimeter-scale tracker with full six degrees of freedom in deep biological tissues. It achieves sub-millimeter accuracy over a large distance of up to 12 cm. The SMOL method requires simple instrumentation and exploits a unique frequency response of the microdevice to maintain high signal-to-noise ratio in unshielded environments, thus it will open up promising opportunities to localize medical micro-robots as well as to sense biological signals deep in the human body for clinical applications (Fig. 3). We use the method to successfully localized the tip of an endoscope in a kidney phantom, without any radiation. The same sensor can also be applied as a Magneto-Oscillatory Wireless Sensor (MOWS) to measure tissue properties, which will be further developed in the project. A journal paper and several conference papers were published and two patents are pending. The technology transfer routes of the developed technology is being investigated.

A team of mini-robots to perform endoscopic electrocauterization surgery
A single micro-robot often lacks the necessary force to carry medical instruments, such as catheters or electrical wires, across slippery biological surfaces. In this study, for the first time, a team of robots is introduced to generate approximately twice the actuating force of a single unit by forming a convoy that collaboratively transports long and heavy cargos. The feet of each unit are optimized to increase propulsive force by about three times, enabling efficient movement on slippery biological surfaces. Another advantage of the TrainBot comes from collaborative motion that individual robots help each other overcome obstacles. TrainBot can transport heavy, extended loads through narrow biological lumens, such as the intestine and bile duct. It successfully performs the first electrocauterization, relieving a biliary obstruction and creating a tunnel for fluid drainage and drug delivery. This collaborative work of multiple small-scale robots opens new way for future minimally-invasive medical procedures. This sub-project was published in Advanced Science (Fig. 4) and the medical applications will be further explored in collaboration with the surgeons at the University Hospital Dresden.

Figures 1-4