Rapid infrared biomedical imaging at high pixel density with a sCMOS camera

摘要 振动显微镜是一种真正的无标记成像技术，可提供细胞和组织的图谱， 特别高的化学对比度，因为它直接探测样品的基本振动模式。 振动成像方法包括红外吸收显微光谱和共焦拉曼显微镜， 已经成功商业化的方法（一个不断增长的5亿美元的市场）， 分析和生物实验室中常见的调查工具。考虑到更强的红外光物质 红外显微镜具有特别高的潜力，在生物学领域产生可衡量的影响， 和生物医学。与此同时，中红外（MIR）成像技术仍然停滞不前， 技术仍然依赖于低像素密度的冷却相机，这阻碍了高效的实际应用。 绘制培养细胞和组织切片。该提案旨在引入一种全新的MIR检测 这种方法克服了困扰更广泛地实施传统方法的根本障碍， MIR摄像头我们建议，直接，片上MIR检测可以在sCMOS相机中实现，通过 非简并双光子吸收（NTA）的过程，使近红外门脉冲。通过 用现代sCMOS相机取代低温冷却的MIR阵列探测器， 克服了MIR显微镜的关键限制，代表了朝着更实用的方向迈出的重要一步。 在生物医学科学中实现MIR成像。 我们的团队包括生物医学振动成像和非线性光学方面的专家， 数据强调了NTA方法用于MIR检测的可行性。在建议的工作中，我们推动使用NTA 使用现代sCMOS相机，确定其用于MIR显微镜的实用性，并比较其性能， 生物医学成像应用与建立中红外显微光谱方法。

ABSTRACT A genuine label-free imaging technology, vibrational microscopy provides maps of cells and tissues with exceptionally high chemical contrast as it directly probes the fundamental vibrationals modes of samples. Vibrational imaging approaches include IR-absorption micro-spectroscopy and confocal Raman microscopy, methods that have been successfully commercialized (a growing 500 million dollar market) and are now common tools of inquiry found in analytical and biological laboratories. Given the much stronger IR light-matter interaction, IR microscopy has a particularly high potential to make a measurable impact in the fields of biology and biomedicine. At the same time, the mid-IR (MIR) imaging technology has remained stagnant, as MIR technology still relies on cooled cameras with low pixel density, preventing practical applications in efficient mapping of cultured cells and tissue sections. This proposal aims to introduce a radically new MIR detection approach that overcomes the fundamental hurdles that have plagued a broader implementation of traditional MIR cameras. We propose that direct, on-chip MIR detection can be achieved in an sCMOS camera through the process of non-degenerate two-photon absorption (NTA) enabled by a near-infrared gate pulse. By replacing cryogenically cooled MIR arrayed detectors with a modern sCMOS camera, the proposed work overcomes a key limitation in MIR microscopy and represents an important step toward a more practical implementation of MIR imaging in the biomedical sciences. Our team includes experts in biomedical vibrational imaging and nonlinear optics, and our preliminary data underlines the feasibility of the NTA method for MIR detection. In the proposed work we push NTA for use with modern sCMOS cameras, determine its utility for MIR microscopy and compare its performance for biomedical imaging applications with established MIR microspectroscopy methods.