THEIA: fast super-resolution TeraHErtz mIcroscopy for nAtural sciences

THz microscopy lies at the interface between physics and electrical engineering, and it provides a platform for cutting-edge research and development in biology, chemistry, physics and engineering. By probing fundamentally different information about biomolecular structure and functional dynamics compared to infrared radiation and light, THz radiation promises to revolutionize spectroscopy and imaging for the life sciences. In addition, THz radiation has the advantage of being non-ionizing and very sensitive to polar substances, such as water, and provides label-free skin disease diagnosis and better image contrast for soft tissues than hazardous X-rays or optical imaging techniques.

Until recently though, THz sources and detectors were very cumbersome. Hence, the widespread adoption of THz technology, let alone THz microscopy, has lagged behind microwaves, infrared and optics. Another hurdle that has held THz microscopy back is its failure to accomplish resolution below the diffraction limit with near-real-time operation, which is a feature that its optical counterpart achieved few decades ago with fluorophores. Such super-resolution and fast acquisition time features are especially critical for the life sciences whose specimens (e.g., cells) have micrometer-dimensions and are typically in continuous motion in their biological environment.

The transformative THz microscope proposed in this research programme will explicitly address this problem and will achieve fast label-free super-resolution imaging not seen before at THz frequencies by combining two techniques from completely different realms: evanescent-wave illumination (used in optical microscopy and in optical fibre sensors) and synthetic-aperture collection (used in spaceborne remote sensing). To succeed in the implementation of the THz microscope, the project will have to:
(i) design and fabricate new high-performance optics based on metasurfaces since conventional lenses are lossy at THz frequencies, as well as being bulky.
(ii) develop efficient signal analysis and processing algorithms specific to the microscopy system to generate images with enhanced resolution at a rate that enables one to study the temporal evolution of biological samples.
(iii) design the system, integrate the hardware (THz source, high-performance optics, and THz camera) and software (control and image reconstruction algorithm) and calibrate the microscope to create a turn-key system.

The project will also (iv) benchmark the 0.3 THz microscope against other frequencies and imaging modalities to quantify its added value to the field of life sciences microscopy. This information will be crucial to engage with the life sciences community since THz technology is largely untapped outside the engineering and physical science communities.

Economy
THz science and engineering are widely recognised as being on the rise. The global market for THz technology is estimated to show a compound annual growth in excess of 30% between 2017 and 2022, with THz imaging devices being the largest device segment (ReportLinker, Mordor Intelligence, and Markets and MarketsTM). Meanwhile, the UK's medical technology sector, including its service and supply chain, consists of more than 3,500 small and medium-sized enterprises (SMEs) alongside few global manufactures that generate an annual turnover in excess of £20bn; this sector employs 120,000 people in the UK (HM Government, Office for Life Sciences, Department for International Trade). By revenue, medical imaging is the faster growing segment with 10% annual growth rate.
THz waves enables a direct probing of biomolecules and biomolecular binding events as well as label-free cancer diagnosis. With this in mind, this research programme is designed to deliver economic impact in the medium term by developing a new near-real-time super-resolution microscopy system that will provide a new effective and efficient diagnosis and monitoring modality for the medical and biomolecule sectors. In the short term, the direct beneficiary of this programme will be the industrial partner (MediWise Ltd.), who will gain additional knowledge and potentially a competitive advantage through product leadership.
The THz microscope will also have an important part to play in the future growth of industrial non-destructive testing. Non-destructive testing is pivotal for health and safety from the manufacturing (e.g., automobile, semiconductor, etc.) to the retail sector. Indeed, non-destructive industrial testing is a sector targeted by the leading UK-based THz instrumentation company TeraView Ltd., which has been commercializing the TeraCota - Terahertz Coating Thickness Analysis product suitable for the automobile and wind power industry.

Society
The THz microscope proposed can speed up and reduce the cost of cancer diagnosis since it does not require any type of labelling. This has a twofold impact in society. On the one hand, it optimises treatment and reduces the risk to patients, resulting in improved patient experience, and quality of life. On the other hand, improvement in the operational performance of the NHS (the UK public health service) will reduce costs, leading to a desirable knock-on effect on the UK taxpayers.

Knowledge
This research programme will generate a new paradigm in high-throughput THz super-resolution imaging. This will be achieved by a disruptive approach combining the synthetic-aperture concept well developed by the radar community with evanescent-wave illumination widely used in optics for imaging and sensing. To merge them effectively, I will use the key enabling technology of metasurfaces (i.e., two-dimensional artificial structures with engineered electromagnetic properties). The bottom-up approach from element (metasurface) to system (microscope) will generate a comprehensive body of knowledge that will contribute to the THz imaging and metamaterials communities alike.
Beyond the lifetime of this research programme, when the THz microscope will be fully operational, the inspection of evolving biological samples at an unprecedented level of detail will open new avenues for research in the life sciences.

People
The THz community is divided broadly speaking into THz electronics and THz photonics. Given that this research programme will leverage knowledge from both disciplines, it will foster interdisciplinary links and benefit researchers from both THz communities, which collectively are represented by more than 20 research groups of engineers, physicists and chemists in the UK. The researchers directly trained on this programme will develop a unique set of skills that will be of direct benefit to their future careers in academia and industry.