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，如非侵入性渗透到组织中，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，建立了护理点（POC）和个性化医疗的趋势。2015年，全球生物光子市场价值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的加剧和对医疗保健改善的需求。用于癌症检测的新设备是生物光子学最重要的领域之一。目前的癌症诊断标准是从可疑肿瘤中进行组织活检，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的办公室，这将大大提高癌症的早期检测。该研究计划将设计和实现用于癌症检测的下一代光子器件，重点是检测血管内的循环肿瘤细胞（CTC）。* CTC是脱落到血流中的实体瘤来源的癌细胞。CTC是转移的直接指示，其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的数量是预后生存或预测对特定疗法的反应的关键量度。因此，检测CTC对于癌症检测和监测个性化医疗中的治疗结果具有根本重要性。大多数肿瘤生长不明显，没有症状，直到他们已经达到一个显着的大小或晚期。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。存在从全血样品计数CTC的离体方法。我们设想下一代方法应该在体内检测CTC，其中不需要抽取血液，并且可以对整个血液体积进行采样以发现罕见的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术（IVFC）来实现我们的目标。IVFC可以通过照射在血管上的光来检测CTC，并检测CTC特异性的信号。在目前用于动物的IVFC中，CTC被有毒的外源性染料或遗传修饰的荧光蛋白标记。我们将通过利用固有的对比度，特别是使用光学相干断层扫描通过散射检测CTC的形态特征，并使用双光子激发荧光通过自发荧光检测CTC中的内源性物质来开发IVFC。它将开辟一个检测CTC的新领域，并导致下一代POC设备用于改善癌症检测。

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.