Detection of asymptomatic early-stage disease is critical for effective treatment of most cancer types. For instance, when detected at Stage I, the 5-year survival rate for ovarian cancer patients is greater than 90%, versus 20% for advanced-stage disease. However, currently most cancers are diagnosed at late stages, which underscore the pressing need of novel biomarkers, strategies and technologies. Probing circulating exosomes is emerging as a new paradigm for non-invasive cancer diagnosis and monitoring of treatment response, because of growing evidences of their biological functions and clinical implications in tumorigenesis and progression. Tumor-derived exosomes accumulate in human blood and are enriched in a selective repertoire of biomolecules, including signaling proteins, enzymes, tumor antigens, miRNAs, and mRNAs. The constitutive release and exosome enrichment of certain tumor markers present distinctive opportunities for early cancer diagnosis. Despite the potential for cancer diagnosis, biology and clinical value of exosomes remain largely unknown, due to the challenges in efficient isolation, molecular classification and comprehensive characterization of exosomes. Here we propose to tackle this major roadblock by developing an innovative microfluidic technology that enables selective isolation, subpopulation classification by surface protein topography, and in situ multiplexed barcode protein profiling of exosomes, all streamlined in a """"""""sample-in-answer-out"""""""" system. The project consists of two specific aims: 1) Develop an integrated Microfluidic Exosome Profiling Assay (MEPA) for molecular analysis of circulating exosomes in microliter volumes of plasma;and 2) Characterize and validate MEPA for potential use in early detection of cancer using ovarian cancer as the disease model. This research, if successful, will yield a transformative technology that can substantially improve the analytical performance for molecular characterization of tumor-derived exosomes while overcoming the constraints of exosome loss/damage during isolation, analysis throughput, and sample consumption in conventional protocols. Thus the technology should offer an unprecedented ability to accelerate the exosome research, opening new opportunities to probing the biology of a tumor noninvasively and to developing novel reliable biomarkers for screening and early detection of cancer.

Public Health Relevance

Blood-based assays of cancer biomarkers hold a great promise for early diagnosis of cancers. In comparison to other screening methods, such tests may demonstrate superior sensitivity and specificity to detect cancer at pre-symptomatic early stages when this deadly disease is curable. Our studies aim to develop an innovative, transformative biomedical technology that can greatly promote biological and clinical investigation of blood- borne tumor-released exosomes as a new class of markers for non-invasive early detection of cancer. The technology is also adaptable for potential use as a clinical diagnostic platform for disease staging and monitoring of response to therapy.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Exploratory/Developmental Grants (R21)
Project #
Application #
Study Section
Special Emphasis Panel (ZCA1)
Program Officer
Patriotis, Christos F
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Kansas Lawrence
Schools of Arts and Sciences
United States
Zip Code
Zhang, Peng; Crow, Jennifer; Lella, Divya et al. (2018) Ultrasensitive quantification of tumor mRNAs in extracellular vesicles with an integrated microfluidic digital analysis chip. Lab Chip 18:3790-3801
Zhang, Peng; Samuel, Glenson; Crow, Jennifer et al. (2018) Molecular assessment of circulating exosomes toward liquid biopsy diagnosis of Ewing sarcoma family of tumors. Transl Res 201:136-153
Li, Kang; Rodosthenous, Rodosthenis S; Kashanchi, Fatah et al. (2018) Advances, challenges, and opportunities in extracellular RNA biology: insights from the NIH exRNA Strategic Workshop. JCI Insight 3:
Yang, Yang; Zeng, Yong (2018) Microfluidic communicating vessel chip for expedited and automated immunomagnetic assays. Lab Chip 18:3830-3839
Wang, Yazhen; Southard, Kristopher M; Zeng, Yong (2016) Digital PCR using micropatterned superporous absorbent array chips. Analyst 141:3821-31
He, Mei; Zeng, Yong (2016) Microfluidic Exosome Analysis toward Liquid Biopsy for Cancer. J Lab Autom 21:599-608
Zhang, Peng; He, Mei; Zeng, Yong (2016) Ultrasensitive microfluidic analysis of circulating exosomes using a nanostructured graphene oxide/polydopamine coating. Lab Chip 16:3033-42
Zhao, Zheng; Yang, Yang; Zeng, Yong et al. (2016) A microfluidic ExoSearch chip for multiplexed exosome detection towards blood-based ovarian cancer diagnosis. Lab Chip 16:489-96
Alturkmani, Hani J; Pessetto, Ziyan Y; Godwin, Andrew K (2015) Beyond standard therapy: drugs under investigation for the treatment of gastrointestinal stromal tumor. Expert Opin Investig Drugs 24:1045-58
Bucur, Octavian; Almasan, Alex; Zubarev, Roman et al. (2015) An updated h-index measures both the primary and total scientific output of a researcher. Discoveries (Craiova) 3: