Micro/Nano Robotics for Single Cancer Cells

Project Information

MNR4SCell

Grant agreement ID: 734174

DOI

10.3030/734174

Project closed

EC signature date 28 October 2016

Start date 1 January 2017

End date 31 October 2022

Funded under

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Total cost

€ 1 755 000,00

EU contribution

€ 1 215 000,00

Coordinated by

UNIVERSITY OF WARWICK
United Kingdom

Periodic Reporting for period 2 - MNR4SCell (Micro/Nano Robotics for Single Cancer Cells)

Reporting period: 2019-01-01 to 2022-10-31

Summary of the context and overall objectives of the project

Cancer is considered as the second leading cause of death worldwide. There were an estimated 17 million cancer cases around the world in 2018. The number is expected to increase to 27.5 million by 2040. It is important to develop methodologies that improve understanding of disease condition and progression. Physicochemical forces drive proliferation, differentiation, and migration of cells in live tissue. Significant alteration of these forces or heterogeneity within the tissue implicates a role of nanomechanics in cancer diagnosis. Over the past few years, single cell biology has been performed using micro/nano robotics for exploration of the nanomechanical and electrophysiological properties of cells. However, most of the research so far has been empirical and the understanding of the mechanisms and thus possible for cancer therapy are limited. Therefore, a systematic approach to address this challenge using advanced micro/robotics techniques is timely and important to a wide range of the technologies where micro/nano manipulation and measurement are in demand. The ultimate goal of MNR4SCell is to establish long-term research collaboration between Europe and China in the challenging field of micro/nano robotics for the characterisation, diagnosis and targeted therapy of single cancer cells. The synergistic approach established by MNR4SCell will keep the leading position of the consortium in the world for potential major scientific and technological breakthroughs in micro/nano robotics and biomedical applications. The scientific objectives of the project are given as follows:
• To establish a long-term and lasting research collaboration network through the MNR4SCell programme by exchange of researchers for short periods during the project.
• To exchange ideas and technology concepts for further development of micro/nano robotics for the measurement, diagnosis and targeted therapy of single cancer cells.
• To strengthen research partnerships through staff exchanges and networking activities between European and Chinese organisations.
•To take a synergistic approach to the research areas and explore novel methodologies and applications for potential major scientific and technological breakthroughs.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

Various micro/nano robotic techniques for cell measurement and manipulation robots have been studied, and the applications and user requirements for the proposed MNR4SCell technologies have been defined and implemented. Different micro/nano robotics and automation techniques have been reviewed. The sensing and actuation techniques for cell manipulation and measurement have been developed. The advanced knowledge for measurement and characterisation of single live cells has been studied. AFM-based nanorobotics provide a powerful method for the live cell characterisation, and double probe nanorobot provide more flexibility and manoeuvrability for cell measurement, characterisation and handling. The optical tweezers can also be utilized for the handling of live cells without mechanical contacts, which provides a number of advantages including non-invasion and label free handling. The magnetic nanoparticle manipulation method using magnetic force microscope has also been investigated for the improvement of manipulation success rate. The human-robot interface techniques have also been developed to control the micro/nano robots and automate the operation procedure and thus increase manipulation accuracy and success rate.
The techniques for key components of micro/nano robotics have explored. A number of micro/nano positioning stages and grippers have been developed for the improvement of positioning accuracy, speed and flexibility which are the crucial requirements for the high precision and high efficiency handling and manipulation. Electrodes with several defined patterns have been achieved by laser interference lithography direct writing and electron beam lithography. The broad modular range nanomechanical mapping AFM has been developed for measurement and characterisation of cells and soft materials. This approach can be particularly useful for analysing heterogeneous samples with large elastic modulus variations in multi-environments. In situ monitoring of the nanomechanical properties of cancer cells has been studied using the developed AFM technique. In-situ quantification the complex poisson’s ratio of single cells have been investigated using a magnetic bead probe based nanomechanical spectroscopy. AFM-based nanoindentation for cell mechanical property measurement has also established to explore the influence of different drugs for the cancer cell therapy. Different mobile micro/nano robots driven by magnetic forces have been developed for the drug delivery and treatment. The Scanning Ion Conductance Microscopy has been developed and utilized for the cell topography and electric property measurement.
Micro/nano robotics and their applications in cancer therapy have significant potentials for commercial exploitation. Till now, there are 7 patents applications have been filed. We have put more efforts on the dissemination and exploitation of the project achievements e.g. workshops, seminars, and conferences. Especially, through the industrial partner’s contribution, the further exploitation of the developed techniques has been implemented to benefit the end-users. Based on the research achievement and outcomes, a spin-off company 'Changli Nano-Biology Ltd’ has been establihsed for the production of atomic force microscopy and applications in biology.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

The broad modulus range nanomechanical mapping AFM has been developed for measurement and characterisation of cells and soft materials. This approach not only successfully drives the softest commercial probe for mapping extremely soft samples in liquid but also provides an indentation force of hundreds of nanonewtons for stiff samples with a soft probe for mapping extremely soft samples in liquid but also provides an indentation force of hundreds of nanonewtons for stiff samples with a soft probe. Features of direct measurements of the indentation force and depth can unify the elastic modulus range up to four orders of magnitude using a single probe. This approach can be particularly useful for analysing heterogeneous samples with large elastic modulus variations in multi-environments. In situ monitoring of the nanomechanical properties of cancer cells has been studied using the developed AFM technique. The Scanning Ion Conductance Microscopy has been developed and utilized for the cell topography and electric property measurement.
The physiomechanical characteristics of single cancer cell under different external mechanical and chemical stumuli have been extensively investigated by use of the developed micro/nano robotics and automation technologies. The relationships between the single cell behavior and the external stimuli have been established. These obtained knowledge and techniques have pave the way for drug screen and single cell diagnosis and therapy of cancers, which is one of the leading cause of death. The opportunities for correlative mapping of single cells at the nanoscale are huge and they could lead to a new tool for clinical diagnosis. The achived technical results of this project will be of considerable potential benefit to the nanoscopy, nanorobotics, photonic, sensing and biomedical communities in areas of key strength for EU industry.

MNR4Cell