THEIA: fast super-resolution TeraHErtz mIcroscopy for nAtural sciences

太赫兹显微镜位于物理和电气工程的交界处，它为生物、化学、物理和工程领域的前沿研究和发展提供了一个平台。通过探测与红外辐射和光相比根本不同的生物分子结构和功能动力学信息，太赫兹辐射有望为生命科学的光谱学和成像技术带来革命性的变化。此外，太赫兹辐射具有非电离和对水等极性物质非常敏感的优势，提供了无标签的皮肤病诊断和比危险的X射线或光学成像技术更好的软组织图像对比度。因此，太赫兹技术的广泛采用，更不用说太赫兹显微镜了，已经落后于微波、红外和光学。阻碍太赫兹显微镜发展的另一个障碍是，它未能在接近实时的情况下实现低于衍射极限的分辨率，这是它的光学同行几十年前通过荧光团实现的一个特征。这种超分辨率和快速采集时间的特性对于生命科学来说尤其重要，因为生命科学的标本(例如细胞)具有微米尺寸，并且通常在其生物环境中连续运动。这项研究计划中提出的变革性太赫兹显微镜将明确解决这一问题，并将通过结合来自完全不同领域的两种技术：逝去波照明(用于光学显微镜和光纤传感器)和合成孔径收集(用于星载遥感)，在太赫兹频率实现前所未有的快速无标签超分辨率成像。为了成功实施太赫兹显微镜，该项目将必须：(I)设计和制造基于超表面的新的高性能光学元件，因为传统透镜在太赫兹频率下有损耗，而且体积大。(2)开发专门针对显微镜系统的有效信号分析和处理算法，以便以能够研究生物样本的时间演变的速度生成分辨率更高的图像。(3)设计系统，集成硬件(太赫兹光源、高性能光学器件和太赫兹相机)和软件(控制和图像重建算法)，并对显微镜进行校准，以创建交钥匙系统。项目还将(4)将0.3太赫兹显微镜与其他频率和成像方式进行比较，以量化其在生命科学显微镜领域的附加值。这些信息对生命科学界的参与至关重要，因为太赫兹技术在工程和物理科学界之外基本上是未开发的。

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.