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

摘要 作为一种真正的无标记成像技术，振动显微镜为细胞和组织提供了 化学对比度极高，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聚焦拉曼显微镜， 已经成功商业化的方法(一个不断增长的5亿美元市场)，现在 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 在相互作用方面，红外显微镜在生物学领域具有特别高的潜力，可以产生可测量的影响 和生物医学。与此同时，中红外(MIR)成像技术一直停滞不前，如MIR 技术仍然依赖于低像素密度的冷却摄像头，阻碍了实际应用的高效 绘制培养细胞和组织切片图。该提案旨在引入一种全新的MIR检测 克服了困扰更广泛地实施传统 和平号摄像机。我们提出，直接的片上MIR检测可以通过以下方式在scmos相机中实现 近红外门脉冲使非简并双光子吸收(NTA)的过程。通过 这项拟议的工作用现代的scmos相机取代了低温冷却的和平号阵列探测器。 克服了MIR显微镜的一个关键限制，代表着朝着更实用的方向迈出的重要一步 MIR成像在生物医学科学中的应用。 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，我们初步的 数据强调了NTA方法用于MIR检测的可行性。在提议的工作中，我们推动使用NTA 与现代的scmos相机，确定其对MIR显微镜的效用，并比较其在 已建立的MIR显微光谱学方法在生物医学成像方面的应用。

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.