TROPHY: ulTRafast hOlograPHic FTIR microscopY

许多人类的病理，如癌症，是由于复杂的生化变化，这些变化始于亚细胞水平，并导致渐进性变化，从而导致肿瘤成分的异质性。肿瘤细胞的多克隆性阻碍了诊断和治疗，导致肿瘤克隆的产生，从而导致治疗抵抗和促进转移。准确的肿瘤活检诊断以识别这些特定的细胞克隆对于提供针对肿瘤特征的靶向治疗、改善患者预后和提高生存率至关重要。为了实现这一愿景，我们引入了超快全息FT-IR显微镜，作为振动显微镜的一种范式转变，融合了光热红外(PT-IR)、傅立叶变换(FT)-IR和数字全息显微镜(DHM)的元素。奖杯将这些技术带入了前所未有的超快时间尺度，在热弛豫之前的峰值处探测到了由相干红外振动引起的折射率变化。从PT-IR借鉴了红外振动激发与可见光探测相结合的高空间分辨率，从FT-IR借鉴了使用时域干涉测量从宽带激发获得高光谱分辨率，从DHM高灵敏度和定量检测折射率(相)变化。与人工智能算法相结合，这项技术将使分子生物标志物能够以高空间分辨率、高化学选择性和高速进行定量浓度成像，对医学研究和临床产生革命性的影响。在肿瘤学方面，它将应用于肿瘤活检的术中诊断，提供肿瘤分级、分期和亚型，并支持肿瘤完全切除。它还将允许确定为患者量身定做的最佳治疗方法，并在靶向治疗下识别耐药肿瘤克隆，为癌症的精确医学铺平道路。

Many human pathologies such as cancer are due to complex biochemical alterations that start at a sub-cellular level and lead to progressive changes that result in a heterogeneous tumor composition. The polyclonality of tumor cells hampers the diagnosis and the therapy giving rise to tumor clones that lead to therapy resistance and promote metastases. An accurate diagnosis of tumor biopsies to identify these particular cell clones is crucial to provide targeted therapy tailored to the tumor characteristics, to improve the patient outcomes and increase survival rates. For this vision to come true, we introduce ulTRafast hOlograPHic FT-IR microscopY (TROPHY) as a paradigm shift in vibrational microscopy, blending elements of photo-thermal infrared (PT-IR), Fourier transform (FT)-IR, and Digital Holography Microscopy (DHM). TROPHY brings these techniques to the unprecedented ultrafast timescale, where the refractive index change induced by coherent IR vibrations is probed at its peak value before thermal relaxation. TROPHY borrows from PT-IR the combination of IR vibrational excitation with visible probing for high spatial resolution, from FT-IR the use of time-domain interferometry to obtain a high spectral resolution from broadband excitation, from DHM highly sensitive and quantitative detection of the refractive index (phase) change. Combined with artificial intelligence algorithms, this technology will enable quantitative concentration imaging of molecular biomarkers with high spatial resolution, high chemical selectivity and high speed, with a transformative impact on medical research and clinics. In oncology, it will be applied to intraoperative diagnosis of tumor biopsies, providing tumor grading, staging and subtyping, and supporting complete tumor resection. It will also allow to determine the best therapeutic approach tailored to the patient and identify resistant tumor clones under targeted therapy, paving the way for precision medicine in cancer.