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。由于光具有无创穿透组织、非电离、实时和高分辨率光学成像等优点，它在医学上被用于改善诊断、治疗和后续护理，并引领了护理点(POC)和个性化医学的趋势。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日益老龄化的人口和对改善医疗保健的需求。新的癌症检测设备是生物光子学最重要的领域之一。*目前癌症诊断的标准是从可疑肿瘤中提取组织活检，并在中央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的办公室，这将显著提高癌症的早期发现。这项研究计划将设计和实现用于癌症检测的下一代光子设备，重点是检测体内血管内循环的肿瘤细胞(CTCs)。*CTC是实体肿瘤来源的癌细胞，流入血液中。CTC是转移的直接指标，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的数量是判断生存预后或预测特定治疗反应的重要指标。因此，在个性化医学中，检测CTC对于癌症检测和监测治疗结果具有重要意义。*大多数肿瘤在达到显著大小或进入晚期后才会在没有症状的情况下生长。由于血液循环会将CTC从全身带到周围血管，我们可能会通过在血液中发现CTC来检测不同类型的癌症。有一些体外方法可以从全血样本中计数CTCs。我们设想，下一代方法将在体内检测CTCs，不需要抽血，可以采集整个血液体积来寻找罕见的CTCs，并且该技术可以重复应用。*我们将通过设计新颖的在体流式细胞术(IVFC)来实现我们的目标。IVFC可以通过照射血管来检测CTC，并检测CTC特有的信号。在目前用于动物的IVFC中，CTCs是由有毒的外源染料或转基因荧光蛋白标记的。我们将利用固有的对比度来发展体外循环功能，特别是利用光学相干层析技术通过散射检测CTC的形态特征，利用双光子激发荧光技术通过自体荧光检测CTC中的内源物质。它将开辟无标签检测CTCs的新领域，并带来用于改进癌症检测的下一代POC设备。

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.