Microchip ELISA Coupled with Cell Phone to Detect Ovarian Cancer HE4 Biomarker in Urine

  • ShuQi Wang
  • Ragip Akbas
  • Utkan DemirciEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 1256)


Ovarian cancer is a leading cause of death from gynecologic cancers in the USA, and early diagnosis can potentially increase 5-year survival rate. Detection of biomarkers derived from hyperplasia of epithelial tissue by enzyme-linked immunosorbent assay (ELISA) proves to be a practical way of early diagnosis of ovarian cancer. However, ELISA is commonly performed in a laboratory setting, and it cannot be used in a clinical setting for on-site consultation. We have shown a microchip ELISA that detects HE4, an ovarian cancer biomarker, from urine using a cell phone integrated with a mobile application for imaging and data analysis. In microchip ELISA, HE4 from urine was first absorbed on the surface; the primary and secondary antibodies were subsequently anchored on the surface via immuno-reaction; and addition of substrate led to color development because of enzymatic labeling. The microchip after color development was imaged using a cell phone, and the color intensity was analyzed by an integrated mobile application. By comparing with an ELISA standard curve, the concentration of HE4 was reported on the cell phone screen. The presented microchip ELISA coupled with a cell phone is portable as opposed to traditional ELISA, and this method can facilitate the detection of ovarian cancer at the point-of-care (POC).

Key words

Microchip ELISA Mobile application Diagnostics HE4 biomarker 



We would like to acknowledge the W.H. Coulter Foundation Young Investigator Award, RO1 A1081534, R21 AI087107. This work was supported by the Center for Integration of Medicine and Innovative Technology (CIMIT) under US Army Medical Research Acquisition Activity Cooperative Agreements DAMD17-02-2-0006, W81XWH-07-2-0011, and W81XWH-09-2-0001. And this work was made possible by a research grant that was awarded and administered by the US Army Medical Research & Materiel Command (USAMRMC) and the Telemedicine & Advanced Technology Research Center (TATRC), at Fort Detrick, MD. We also acknowledge NIH U01 HL065899-08.

Utkan Demirci (UD) is a founder of, and has an equity interest in, DXNow, a company that is developing microfluidic and imaging technologies for point-of-care diagnostic solutions. UD’s interests were reviewed and are managed by the Brigham and Women’s Hospital and Partners HealthCare in accordance with their conflict of interest policies.


  1. 1.
    Clarke-Pearson DL (2009) Clinical practice. Screening for ovarian cancer. N Engl J Med 361(2):170–177CrossRefGoogle Scholar
  2. 2.
    Visintin I et al (2008) Diagnostic markers for early detection of ovarian cancer. Clin Cancer Res 14(4):1065–1072CrossRefGoogle Scholar
  3. 3.
    Wang S, Xu F, Demirci U (2010) Advances in developing HIV-1 viral load assays for resource-limited settings. Biotechnol Adv 28(6):770–781CrossRefGoogle Scholar
  4. 4.
    Wang S et al (2013) Point-of-care assays for tuberculosis: role of nanotechnology/microfluidics. Biotechnol Adv 31(4):438–449CrossRefGoogle Scholar
  5. 5.
    Wang S et al (2011) Integration of cell phone imaging with microchip ELISA to detect ovarian cancer HE4 biomarker in urine at the point-of-care. Lab Chip 11(20):3411–3418CrossRefGoogle Scholar
  6. 6.
    Kim YG et al (2009) Quantum dot-based HIV capture and imaging in a microfluidic channel. Biosens Bioelectron 25(1):253–258CrossRefGoogle Scholar
  7. 7.
    Moon S et al (2009) Integrating microfluidics and lensless imaging for point-of-care testing. Biosens Bioelectron 24(11):3208–3214CrossRefGoogle Scholar
  8. 8.
    Hellstrom I et al (2010) Detection of the HE4 protein in urine as a biomarker for ovarian neoplasms. Cancer Lett 296(1):43–48CrossRefGoogle Scholar
  9. 9.
    Wang S et al (2014) Micro-a-fluidics ELISA for rapid CD4 cell count at the point-of-care. Sci Rep 4:3796Google Scholar
  10. 10.
    Cramer DW et al (2011) Ovarian cancer biomarker performance in prostate, lung, colorectal, and ovarian cancer screening trial specimens. Cancer Prev Res (Phila) 4(3):365–374CrossRefGoogle Scholar
  11. 11.
    Zhu CS et al (2011) A framework for evaluating biomarkers for early detection: validation of biomarker panels for ovarian cancer. Cancer Prev Res (Phila) 4(3):375–383CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  1. 1.Demirci Bio-Acoustic-MEMS in Medicine (BAMM) LaboratoryCanary Center at Stanford for Early Cancer Detection, School of Medicine, Stanford UniversityPalo AltoUSA
  2. 2.Civil Engineering DepartmentÖzyeğin UniversityIstanbulTurkey

Personalised recommendations