Point-of-Care Photonic Devices for Cancer Detection

生物光子学是关于产生和利用光来理解细胞和组织的功能。由于光的优点，如无创渗透到组织，非电离，实时和高分辨率的光学成像，它被用于医学，以改善诊断，治疗和随访护理，设置趋势的护理点（POC）和个性化医疗。2015年，全球生物光子学市场价值342.9亿美元，预计到2024年将达到913.1亿美元。这一强劲增长归因于人口老龄化加剧和对医疗保健改善的需求。新型癌症检测装置是生物光子学研究的重要领域之一。***目前的癌症诊断标准是对可疑肿瘤进行组织活检，并在集中实验室进行组织病理学分析。新的POC设备可以将诊断转移到医生办公室，这将大大提高癌症的早期发现。本研究项目将设计并实现下一代用于癌症检测的光子器件，重点是检测血管内的循环肿瘤细胞（CTCs）。ctc是源自实体瘤的癌细胞，脱落到血液中。CTC是转移的直接指示，占所有癌症相关死亡的90%。CTC也发生在局部癌症患者和肿瘤发展的早期阶段。ctc的数量是预测生存或预测对特定治疗反应的关键指标。因此，检测CTCs对于个体化医疗中癌症的检测和治疗效果的监测具有基础性的意义。***大多数肿瘤生长不明显，没有症状，直到它们达到显著的大小或晚期。由于血液循环会将CTC从全身带到外周血管，我们可以通过在血液中发现CTC来检测不同类型的癌症。有从全血样本中枚举ctc的离体方法。我们设想下一代方法应该是在体内检测ctc，不需要抽血，整个血容量可以采样以发现罕见的ctc，并且该技术可以重复应用。我们将通过设计新的体内流式细胞仪（IVFC）来实现我们的目标。IVFC通过对血管照射光来检测CTC，检测出CTC特有的信号。在目前用于动物的IVFC中，ctc是由有毒的外源染料或转基因荧光蛋白标记的。我们将利用内在对比，特别是利用光学相干断层扫描通过散射检测CTC的形态特征，并利用双光子激发荧光通过自身荧光检测CTC中的内源性物质来发展IVFC。它将开辟无标签检测ctc的新领域，并引领下一代POC设备，以改善癌症检测。

Biophotonics is about generating and harnessing light for comprehending the functioning of cells and tissues. Due to the advantage of light such as noninvasive penetration into tissue, nonionizing, and real-time and high-resolution optical imaging, it is used in medicine to improve diagnosis, therapy and follow-up care, setting the trend towards point-of-care (POC) and personalized medicine. The global biophotonics market was valued at $34.29 billion in 2015, and estimated to reach $91.31 billion by 2024. This robust growth is attributed to the increasing aging population and demand for health care improvements. New device for cancer detection is one of the most important areas of biophotonics.***The current standard of cancer diagnosis is to take tissue biopsies from suspicious tumors and perform histopathology analysis in a centralized lab. New POC devices that can shift the diagnostics to the doctor's office will significantly improve the early detection of cancer. This research program will design and realize the next generation photonic devices for cancer detection, focusing on detecting circulating tumor cells (CTCs) in vivo inside blood vessels. ***CTCs are cancer cells of solid tumor origin shed into the bloodstream. CTC is a direct indication of metastasis which accounts for 90% of all cancer-related deaths. CTC also happens in patients with localized cancers and in earlier stage during tumor development. The numbers of CTCs is a critical measure of prognostic for survival or predictive of response to a specific therapy. Therefore, detecting CTCs has the fundamental importance for cancer detection and monitoring treatment outcome in personalized medicine.***Most tumors grow unnoticeably without symptoms until they have reached a significant size or a late stage. As blood circulation will bring CTC to the peripheral vessels from over the entire body, we can potentially detect different types of cancers by finding CTCs in the bloodstream. There are ex vivo approaches to enumerate CTCs from whole blood sample. We envision that the next generation method should detect CTCs in vivo, where no blood needs to be drawn and the entire blood volume could be sampled to find rare CTCs, and the technique could be applied repeatedly.***We will achieve our objective by designing novel in vivo flow cytometry (IVFC). IVFC can detect CTCs by shining light on blood vessel and detect signal that is specific to CTC. In the current IVFC used for animals, CTCs are labeled by toxic exogenous dyes or genetically modified fluorescent proteins. We will develop IVFC by utilizing the intrinsic contrast, particularly using optical coherence tomography to detect the morphological features of CTC by scattering, and using two-photon excited fluorescence to detect endogenous substances in CTC by autofluorescence. It will open a new area of detecting CTCs label-free and lead to next generation POC devices for improving cancer detection.