Department of Biomedical Engineering, University of Michigan, 1101 Beal Ave, Ann Arbor, MI 48109, USA.
Lab Chip. 2018 Mar 27;18(7):1057-1065. doi: 10.1039/c8lc00084k.
Laser emission-based detection and imaging technology has attracted significant interest in biomedical research due to its high sensitivity, narrow linewidth, and superior spectral and spatial resolution. Recent advances have further revealed the potential to use laser emission to investigate chromatin dynamics, as well as to diagnose cancer tissues based on nuclear biomarkers. To move the laser emission based detection technology a step further towards practical use, in this work, we developed a highly robust tissue laser platform by microfabricating an SU8 spacer with a fixed height on the top mirror of the Fabry-Pérot (FP) cavity, which allows generation of reproducible and stable lasing results regardless of tissue thickness. Then we applied this platform to achieve lasing emission from formalin-fixed, paraffin-embedded (FFPE) lung tissues, which account for an overwhelming fraction of tissues collected for research and clinical use worldwide. We further showed that the cancer and normal FFPE lung tissues can be distinguished by their respective lasing thresholds. Two different tissue thicknesses (10 μm and 5 μm) commonly used in pathological labs were explored. Finally, we tested three additional types of tissues (colon, stomach, and breast) that were prepared independently by lab technicians in a pathology lab in China and shipped to the US in order to validate the general applicability and practicality of the laser emission-based technology as well as the corresponding sample preparation protocol and the tissue laser platform. Our work will not only vastly broaden the applications of laser emission-based detection/imaging technology but also help translate it from the laboratory to an automated system for clinical practice that may eventually benefit biomedicine and biological research.
基于激光发射的检测和成像技术由于其高灵敏度、窄线宽以及优越的光谱和空间分辨率，在生物医学研究中引起了极大的兴趣。最近的进展进一步揭示了利用激光发射来研究染色质动力学的潜力，以及基于核生物标志物诊断癌症组织的潜力。为了将基于激光发射的检测技术进一步推向实际应用，在这项工作中，我们通过在 Fabry-Pérot（FP）腔的上镜面上微制造具有固定高度的 SU8 间隔物，开发了一种高度稳健的组织激光平台，无论组织厚度如何，都可以产生可重复和稳定的激光发射结果。然后，我们应用该平台实现了从福尔马林固定、石蜡包埋（FFPE）肺组织中产生激光发射，这些组织占全球用于研究和临床使用的组织的绝大多数。我们进一步表明，癌症和正常的 FFPE 肺组织可以通过各自的激光发射阈值来区分。探索了病理实验室中常用的两种不同的组织厚度（10 μm 和 5 μm）。最后，我们测试了另外三种类型的组织（结肠、胃和乳腺），这些组织由中国病理实验室的实验室技术人员独立制备，并运到美国，以验证基于激光发射的技术以及相应的样本制备方案和组织激光平台的普遍适用性和实用性。我们的工作不仅将极大地拓宽基于激光发射的检测/成像技术的应用范围，还有助于将其从实验室转化为临床实践的自动化系统，最终可能使生物医学和生物学研究受益。
