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Teaser, summary, work performed and final results

Periodic Reporting for period 1 - MNR4SCell (Micro/Nano Robotics for Single Cancer Cells)

Teaser

Cancer is considered as the second leading cause of death worldwide. There were an estimated 14.1 million cancer cases around the world in 2012. The number is expected to increase to 24 million by 2035. It is important to develop methodologies that improve understanding of...

Summary

Cancer is considered as the second leading cause of death worldwide. There were an estimated 14.1 million cancer cases around the world in 2012. The number is expected to increase to 24 million by 2035. 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. At least three new research proposals for both the EU and Chinese funding programmes will be prepared, and visits between partners will be arranged during and after the project period. As the research work is fully supported by partners’ existing projects and their own resources, in such a case, a long-term research cooperation platform MNR4SCell will be firmly established, and will be in function even after the project period.
• To exchange ideas and technology concepts for further development of micro/nano robotics for the measurement, diagnosis and targeted therapy of single cancer cells. All the consortium partners have been actively working on international, national and regional research projects in micro/nano mechanisms and robotics, metrology and characterisation, and nano-biomechanics for many years. The advanced knowledge and expertise will significantly contribute to the development of new technologies on MNR4SCell.
• To strengthen research partnerships through staff exchanges and networking activities between European and Chinese organisations. Partners can learn from each other the new science and technology developments of micro/nano robotics assisted manipulation and measurement technologies and benchmark them against their own developments.
•To take a synergistic approach to the research areas and explore novel methodologies and applications for potential major scientific and technological breakthroughs by the optimal combination of the different backgrounds and disciplines from the partners.

Work performed

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. 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 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 (MFM) 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 to 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 (HIT, AU). 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 (SICM) has been developed and utilized for the cell topography and electric property measurement.

Final results

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 (6 pN nm-1) 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, from 1 kPa to 10 MPa (in liquid) and 1 MPa to 20 GPa (in air or liquid) 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 (SICM) has been developed and utilized for the cell topography and electric property measurement.

Website & more info

More info: https://warwick.ac.uk/fac/sci/eng/research/grouplist/measurement/mnr4scell.