Smart Technologies for Tumor Therapy

Nanorobots for targeted delivery in deep tissues

Current members: Dr. Haoying Wang, Dr. Yue Gao, Yunfei Zhang

Key collaborator: Prof. Alexander M Leshansky, Technion, Israel

In our previous research, we developed the world's smallest nanorobot that can penetrate real biological tissues [ref]. The nanopropellers mimic the corkscrew propulsion of bacteria and have a spherical head and a helical tail with a diameter of ~500 nm, which perfectly matches the nano-sized pores of the targeted biological tissue. The propellers exhibit a finite magnetic moment in the diametric direction and when actuated under a rotating magnetic field, the rotation is coupled to translation due to its helical shape. Our experimental results show that a swarm of nanopropellers can be controlled to navigate over centimeter distance in the eye and reach the targeted region (optic disc) of ~6 mm in diameter on the retina. One key research question is whether the active nanoparticles can be wirelessly guided to penetrate solid tumor tissues and more efficiently deliver cancer drugs.

Ref.: https://doi.org/10.1126/sciadv.aat4388

Human-scale magnetic control systems

Current members: Moonkwang Jeong, Ann-Sophia Mueller

Traditional electromagnetic actuation systems often have limited accessible volume, which restricts the controllable working space of the robots for in vivo medical applications at human scale. In this project, we develop a new 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. The permanent magnetic actuation set-up 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. The project was presented at IEEE MARSS 2023 [ref], and won the award nomination of "The Best Student Paper". 

The group is developing new machine learning methods to accurately localize and precisely control the micro-robots in complex biological environments.

Ref.: https://doi.org/10.1109/MARSS58567.2023.10294119 

SMOL – magnetic localization of wireless devices

Current members: Felix Fischer, Dr. Liyuan Tan, Dr. Haoying Wang

Former member: Dr. Christian Gletter

One common challenge of current minimally-invasive medical instrument and implants is the reliable and wireless tracking of their positions deep in the human body. State-of-the-art imaging methods, such as ultrasound, MRI, and fluoroscopy/CT, have difficulties to continuously, wirelessly, safely and accurately monitor the three-dimensional position and orientation of microdevices. We developed small-scale magneto oscillatory localization (SMOL), which utilizes a miniature magnet attached to a cantilever to form a mechanically resonant system.Thanks to the passive design, no batteries or wires are required, and the device can be miniaturized to millimeter-scale, with large tracking depth up to 12 cm and very high accuracy and precision below 1 mm.It offers real-time spatial tracking for micro-robots as well as minimally-invasive surgical tools and medical implants.

Ref.: https://doi.org/10.1038/s44182-024-00008-x

On-demand wireless drug implants

Current members: Dr. Jiyuan Tian
Former member: Dr. Yangchao Zhou

On-demand controlled drug delivery is essential for the treatment of chronic diseases. The drug is released at the time when required, thus its efficacy is boosted and the side effects are minimized. However, most state-of-the-art drug delivery methods rely on slow and uncontrollable passive diffusion. Active drug delivery methods, such as thermopneumatic pumps and electromagnetic valves were recently developed, however, they still suffer from slow response and large device size. We developed a miniaturized microfluidic device for wirelessly controlled ultrafast active drug delivery, driven by a radio-frequency oscillating solid-liquid interface. The oscillation generates acoustic streaming in the drug reservoir, which opens an elastic valve to emit the drug with very fast response of the delivery on the order of 1 ms, more than three orders of magnitude faster than the start-of-the-art. 

Ref.: https://doi.org/10.1002/adem.202302253

Acoustic hologram for contactless cell manipulation

Current members: Dr. Meng Zhang

Key collaborator: Prof. Zhichao Ma, Shanghai Jiaotong University, China

We developed a radically new approach that enables the generation of complex 3D ultrasound fields with much higher complexity. This work has been published in Nature. We used a 3D-printed highly-structured phase plate – the acoustic hologram – to achieve arbitrary shaped acoustic pressure fields. A plane wave coming from a single transducer that passes through the acoustic hologram element experiences a phase modulation across its wavefront. The 3D-printed acoustic hologram can be finely structured and can thus give rise to diffraction-limited arbitrary shaped acoustic pressure fields with unparalleled complexity. Recently, we also develop a new MEMS device for the dynamic modulation of an acoustic hologram, and demonstrated the capability of using ultrasound field to wirelessly manipulate soft microparticles and pattern cells.

Ref.: https://www.nature.com/articles/nature19755

Ref.: https://www.nature.com/articles/s41467-020-18347-2

3D printing in vitro tumor models

Current members: Moonkwang Jeong, Ann-Sophia Müller
Former members: Dr. med. Xiangzhou Tan, Dr. Eunjin Choi, Nurcemal Atmaca, Dandan Li                                                                                                                                                                                                                                                                                                                     Key Collaborator: Prof. Arkadiusz Miernik, Department of Urology, University Hospital Freiburg

Additive manufacturing enables the design and fabrication of objects with complex three-dimensional shapes that cannot be obtained from standard subtractive machining approaches. The research project aims to develop the process to 3D print a soft printing material that simultaneously has high spatial resolution and high resemblance of real biological tissues. We demonstrate the range of potential applications by fabricating in vitro organ models with a resolution of tens of micrometers, including hollow branched networks that represent blood vessels, using materials, such as gels, that are soft and biocompatible. The method can generate realistic 3D complex environment with cells and extracellular matrices, which can be widely applied for in vitro experiments to test new biomedical devices and robots.

Ref.: https://doi.org/10.1007/s10439-021-02793-0

Cyber-physical organ models for surgical simulation

Current members: Ann-Sophia Müller, Moonkwang Jeong
Former member: Do Yeon Kim

Artificial Intelligence (AI) has revolutionized many fields, such as computer vision and natural language processing. These beneficial areas share the common features that the available data are abundant, standardized, accessible and relatively cheap to acquire. However, when similar machine learning approaches are applied to biomedical problems, one major challenge is how to obtain a large amount of data under realistic conditions. 

We develop the digital twin of human organs that combines the advantages of physical and cyber models, to facilitate the sensing of hard-to-acquire biomedical data under realistic surgical conditions. We created a fully-automated pipeline for the quantitative outcome assessment in surgical trainings. For example, with a focus on the transurethral resection of the prostate (TURP) and the transurethral removal of bladder tumor (TURBT). A customized organ scanner and machine-learning algorithms are developed to measure the organ phantoms and pin-point mistakes, providing quantitative data to accelerate the training of surgeons and surgical robots.

Ref.: https://doi.org/10.3390/jfb13040301