Mid-infrared molecular tags: a new palette for IR microscopy

该项目开发了一系列分子标签，当受到中红外（MIR）光的刺激时，这些标签会发出强烈的信号。这些分子MIR标签被设计成在用MIR显微镜照射时照亮细胞中选定的部分。研究人员开发的MIR标签能够可视化分子扩散和化学转化，包括细胞和组织中的许多代谢过程，这些过程迄今为止仍然是MIR显微镜无法达到的。这一发展将MIR显微镜从检查细胞和组织的静态图像的仪器转变为研究动态过程的技术，如细胞胆固醇摄取，蛋白质合成和脂肪生成。这种能力为研究难以用标准光学显微镜方法研究的细胞过程开辟了新的机会。研究人员致力于通过“工程与科学领域的就业机会”（ACES）项目向hbcu学生提供暑期研究培训，以扩大不同学生群体的参与。MIR成像，通常以傅里叶变换红外（FTIR）显微镜的形式，是一种基于分子振动对比的无标记成像工具。MIR标签或标记可以显著提高MIR成像的特异性，但MIR标签迄今尚未用于成像目的。MIR标记的使用将扩大红外显微镜的互补振动调色板，开辟了基于红外跃迁的双正交分子探针的新目录，并为超多重成像提供了策略。在这个项目中，PI和co-PI开发了一系列化学基序，这些基序表现出异常强烈的红外响应。他们将使用这些基序作为小分子的振动标签，包括胆固醇、葡萄糖、核酸、氨基酸和其他代谢物。此外，该团队将设计适合荧光编码红外（FEIR）激发和检测的探针，使MIR显微镜下的多重标记研究具有达到单分子极限的灵敏度。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

This project develops a portfolio of molecular tags that emit strong signals when stimulated by mid-infrared (MIR) light. These molecular MIR tags are designed to light up selected parts in the cell when illuminated with an MIR microscope. The MIR tags developed by the investigators enable the visualization of molecular diffusion and chemical conversion, including numerous metabolic processes in cells and tissues, processes that have hitherto remained out of reach for MIR microscopy. This development transforms the MIR microscope from an instrument for inspecting static images of cells and tissue to a technology for studying dynamic processes such as cellular cholesterol uptake, protein synthesis and lipogenesis. This capability opens up new opportunities for investigating cellular processes that are difficult to study with standard optical microscopy methods. The investigators are committed to broaden the participation of a diverse pool of students by providing summer research training to students from HBCUs through the Access to Careers in Engineering and Sciences (ACES) program. MIR imaging, typically in the form of Fourier transform infrared (FTIR) microscopy, is a label-free imaging tool based on molecular vibrational contrast. MIR labels or tags can significantly improve the specificity of MIR imaging, yet MIR labels have so far not been used for imaging purposes. The use of MIR labels would expand the complementary vibrational palette in IR microscopy, opening up a new catalogue of biorthogonal molecular probes based on IR transitions, and offering strategies for super-multiplex imaging. In this project, the PI and co-PI develop a portfolio of chemical motifs that exhibit an exceptionally strong IR-response. They will use these motifs as vibrational tags of small molecules, including cholesterol, glucose, nucleic acids, amino acids and other metabolites. In addition, the team will design probes suitable for fluorescence encoded infrared (FEIR) excitation and detection, enabling multiplex labeling studies in the MIR microscope with sensitivities that reach the single molecule limit.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.