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An Integrated Double-Filtration Microfluidic Device for Detection of Extracellular Vesicles from Urine for Bladder Cancer Diagnosis

  • Li-Guo Liang
  • Ye-Feng Sheng
  • Sherry Zhou
  • Fatih Inci
  • Lanjuan Li
  • Utkan Demirci
  • ShuQi Wang
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 1660)

Abstract

Extracellular vesicles (EVs) are present in a variety of bodily fluids and they play an important role in cellular communications and signal transduction mechanisms. Studies have shown that the number of EVs and EV-associated biomarkers (i.e., proteins, nucleic acids and lipids) can be used to aid clinical diagnosis. Although ultracentrifugation is commonly used for EV isolation, it is not practical for clinical settings. Here, we developed an integrated double-filtration device that isolated and enriched EVs from urine, and subsequently detected/quantified EVs from urine via microchip ELISA. Results showed that the concentration of EVs was significantly elevated compared to healthy controls. Receiver operating characteristic analysis demonstrated that this integrated EV quantification device had a sensitivity of 81.3% at a specificity of 90% (16 bladder cancer patients and eight healthy controls). Thus, this integrated device shows great potential to supplement urine cytology for diagnosis of bladder cancer in point-of-care (POC) settings.

Key words

Filtration Extracellular vesicles (EVs) Microchip ELISA Bladder cancer Diagnostics 

Notes

Acknowledgments

Dr. Wang acknowledges the support from the Ministry of Science and Technology of the People’s Republic of China (2016YFC1101302) from China. Dr. Demirci would like to acknowledge R01 AI093282, R01 GM108584, R01 DE02497101, R01 AI081534, R21 Al113117, R21 Al110277, U54 EB015408, DOD LC150650 11976867, and Canary Center seed grant.

Competing financial interests: Dr. U. Demirci is a founder of, and has an equity interest in: (1) DxNow Inc., a company that is developing microfluidic and imaging technologies for point-of-care diagnostic solutions, and (2) Koek Biotech, a company that is developing microfluidic IVF technologies for clinical solutions. U.D.’s interests were viewed and managed in accordance with the conflict of interest policies.

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Copyright information

© Springer Science+Business Media LLC 2017

Authors and Affiliations

  • Li-Guo Liang
    • 1
    • 2
    • 3
  • Ye-Feng Sheng
    • 1
    • 2
    • 3
  • Sherry Zhou
    • 4
  • Fatih Inci
    • 4
  • Lanjuan Li
    • 1
    • 2
  • Utkan Demirci
    • 4
    • 5
  • ShuQi Wang
    • 1
    • 2
    • 3
    • 4
  1. 1.State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, College of MedicineZhejiang UniversityHangzhouChina
  2. 2.Collaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesHangzhouChina
  3. 3.Institute for Translational MedicineZhejiang UniversityHangzhouChina
  4. 4.Department of Radiology, Bio-Acoustic MEMS in Medicine (BAMM) Laboratory, Canary Center at Stanford for Cancer Early DetectionStanford School of MedicinePalo AltoUSA
  5. 5.Department of Electrical EngineeringStanford UniversityStanfordUSA

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