Isolation and Assessment of Blood-Circulating Cancer Exosomes with LSS and SERS Lab on a Chip Optical Spectroscopic Instrument

使用芯片光学光谱仪器上的 LSS 和 SERS 实验室分离和评估血液循环癌症外泌体

• 批准号: 10328506
• 负责人: Lev T Perelman
• 金额: $ 63.73万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-02-01 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10328506
• 关键词: Address; Adopted; Algorithms; Apoptotic; Area; Biochemical; Biogenesis; Biological; Biomedical Engineering; Blood; Blood Circulation; Blood specimen; Cancer Biology; Cancer Center; Cancerous; Cell Culture Techniques; Cells; Cellular biology; Clinical; Clinical Data; Clinical Management; Clinical Research; Collaborations; DNA; Data; Development; Diagnosis; Doctor of Philosophy; Endocytic Vesicle; Endoscopy; Epithelial; Gastroenterologist; Gastrointestinal tract structure; Goals; Human; Imaging Device; Indiana; Industrialization; Lab-On-A-Chips; Laboratories; Light; Light-Scattering Spectroscopy; Liquid substance; Malignant Neoplasms; Malignant neoplasm of pancreas; Mathematics; Measurement; Measures; Medicine; Membrane; Messenger RNA; Methodology; Methods; MicroRNAs; Microfabrication; Microfluidic Microchips; Molecular; Monitor; Nature; Neoplasm Circulating Cells; Neoplasm Metastasis; Normal Cell; Oncogenic; Oncology; Optics; Organ; Organelles; Pathologist; Peripheral; Physiological; Plasma; Primary Neoplasm; Property; Proteins; Raman Spectrum Analysis; Refractive Indices; Research; Sampling; Scientist; Screening for cancer; Shapes; Signal Pathway; Site; Source; Spectrum Analysis; Statistical Data Interpretation; Surface; System; Systems Development; Techniques; Testing; Universities; Vesicle; Vision; algorithm development; angiogenesis; base; cancer cell; cancer genetics; cell free DNA; chemical fingerprinting; clinical application; clinical imaging; decision making algorithm; early detection biomarkers; exosome; experience; improved; insight; instrument; instrumentation; interest; laboratory experiment; light scattering; microvesicles; molecular marker; neoplastic cell; novel; pancreatic cancer patients; physical property; polarized light; predictive marker; response; single molecule; tumor; tumor progression; tumorigenesis; vibration

Project Summary Shed into the peripheral circulation from a primary tumor, circulating tumor cells (CTCs) are limited by their extremely sparse concentrations in blood. In contrast, molecular markers secreted by tumor cells into the vasculature are present in much higher concentrations and could provide important insight on cancer cell biology and predictive biomarkers for early detection, progression and metastasis. These markers, including soluble proteins, cell-free DNA (cfDNA), and circulating microvesicles and exosomes have been shown to contain valuable information on the molecular state of often difficult to access tumor sites. Unfortunately, the source of the soluble proteins found in blood cannot be determined, resulting in the high false-positive rates, while significantly more specific cfDNA often reflect the dying or apoptotic cells. Exosomes, small membrane vesicles of endocytic origin, show the greatest potential as an easily accessible biomarker for early cancer detection and monitoring due to their unique properties, including their stability in biological fluids and their potential to be efficiently isolated. Cancer cells release more exosomes than normal cells and exosomes secreted from tumor cells can promote tumor progression, survival, invasion and angiogenesis. In this application we propose to develop an optical spectroscopic technique, which combines light scattering spectroscopy (LSS) and surface enhanced Raman spectroscopy (SERS) for highly rigorous isolation and assessment of blood-circulating cancer exosomes for early cancer detection in a rapid and inexpensive lab-on-a-chip system. As it is shown in this application, not only LSS can separate exosomes from microvesicles, the capability not available at the moment, but it also can differentiate various types of exosomes originated in different organs of the digestive tract, while SERS is capable of differentiating exosomes secreted by cancerous and normal cells of the same organ.

项目摘要 从原发性肿瘤中脱落到周围循环中，循环肿瘤细胞（CTC）受到限制 他们的血液中极为稀疏的浓度。相反，肿瘤细胞分泌的分子标记物 进入脉管系统以更高的浓度存在，并且可以提供重要的见解 癌细胞生物学和预测性生物标志物，用于早期检测，进展和转移。这些 标记物，包括可溶性蛋白，无细胞DNA（CFDNA）以及循环微泡和外泌体 已显示出有关通常难以进入肿瘤的分子状态的有价值的信息 站点。不幸的是，无法确定血液中发现的可溶性蛋白的来源，从而导致 高阳性速率高，而明显更具体的cfDNA通常反映了垂死或凋亡 细胞。外泌体，小膜囊泡的内吞作用，显示出最大的潜力，很容易 由于其独特特性，包括 它们在生物流体中的稳定性及其有效分离的潜力。癌细胞释放更多 外泌体比正常细胞和从肿瘤细胞分泌的外泌体可以促进肿瘤进展， 生存，侵袭和血管生成。 在此应用程序中，我们建议开发一种相结合的光谱技术 光散射光谱（LSS）和表面增强的拉曼光谱法（SER） 在A 快速且廉价的实验室片系统。正如本应用程序中所示的那样，LSS不仅可以分开 来自微泡的外泌体，目前尚不可用，但也可以区分 各种类型的外泌体起源于消化道的不同器官，而SERS则能够 由同一器官的癌细胞和正常细胞分泌的外泌体区分外泌体。

项目成果

Two-photon polymerization nanofabrication of ultracompact light scattering spectroscopic probe for detection of pre-cancer in pancreatic cyst

双光子聚合纳米加工超小型光散射光谱探针检测胰腺囊肿癌前病变

• DOI: 10.1016/j.optlaseng.2021.106616
• 发表时间: 2021
• 期刊: Optics and Lasers in Engineering
• 影响因子: 4.6
• 作者: Sheil, Conor J.;Khan, Umar;Zakharov, Yuri N.;Coughlan, Mark F.;Pleskow, Douglas K.;Sawhney, Mandeep S.;Berzin, Tyler M.;Cohen, Jonah M.;Glyavina, Maria;Zhang, Lei
• 通讯作者: Zhang, Lei

Rapid detection and identification of bacteria directly from whole blood with light scattering spectroscopy based biosensor

利用基于光散射光谱的生物传感器直接从全血中快速检测和鉴定细菌

• DOI: 10.1016/j.snb.2021.130489
• 发表时间: 2021
• 期刊: Sensors and Actuators B: Chemical
• 作者: Qiu, Le;Zhang, Lei;Horowitz, Gary L.;Turzhitsky, Vladimir;Coughlan, Mark F.;Glyavina, Maria;Khan, Umar;Zakharov, Yuri N.;Vitkin, Edward;Itzkan, Irving
• 通讯作者: Itzkan, Irving