Simultaneous real-time detection of pregnancy-associated plasma protein-a and-a2 using a graphene oxide-based surface plasmon resonance biosensor

Shi Yuan Fan, Nan Fu Chiu, Chie Pein Chen, Chia Chen Chang, Chen Yu Chen

    Research output: Contribution to journalReview articlepeer-review

    Abstract

    Background: Pregnancy-associated plasma protein-A and-A2 (PAPP-A and-A2) are principally expressed in placental trophoblasts and play a critical role in the regulation of fetal and placental growth. PAPP-A2 shares 45% amino acid similarity with PAPP-A. This study aimed to investigate the efficacy of real-time detection of PAPP-A and PAPP-A2 using a novel surface plasmon resonance (SPR) biosensor based on graphene oxide (GO). Methods: Traditional SPR and GO-based SPR chips were fabricated to measure PAPP-A and PAPP-A2 concentrations. We compared SPR response curves of PAPP-A and PAPP-A2 between traditional SPR and GO-SPR biosensors. We also performed interference tests and specificity analyses among PAPP-A, PAPP-A2, and mixed interference proteins. Results: The time to detect PAPP-A and PAPP-A2 was about 150 seconds with both traditional SPR and GO-SPR biosensors. Approximately double SPR angle shifts were noted with the GO-SPR biosensor compared to the traditional SPR biosensor at a PAPP-A and PAPP-A2 concentration of 5 μg/mL. The limit of detection of the GO-SPR biosensor was as low as 0.5 ng/mL for both PAPP-A and PAPP-A2. Interference testing revealed that almost all of the protein bonded on the GO-SPR biosensor with anti-PAPP-A from the mixture of proteins was PAPP-A, and that almost no other proteins were captured except for PAPP-A2. However, the SPR signal of PAPP-A2 (5.75 mdeg) was much smaller than that of PAPP-A (13.76 mdeg). Similar results were noted with anti-PAPP-A2, where almost all of the protein bonded on the GO-SPR biosensor was PAPP-A2. The SPR signal of PAPP-A (5.17 mdeg) was much smaller than that of PAPP-A2 (13.94 mdeg). Conclusion: The GO-SPR biosensor could distinguish PAPP-A and PAPP-A2 from various mixed interference proteins with high sensitivity and specificity. It could potentially be used to measure PAPP-A and PAPP-A2 in clinical blood samples during pregnancy.

    Original languageEnglish
    Pages (from-to)2085-2094
    Number of pages10
    JournalInternational Journal of Nanomedicine
    Volume15
    DOIs
    Publication statusPublished - 2020

    Keywords

    • Biosensor
    • Graphene oxide
    • Pregnancy-associated plasma protein-A
    • Pregnancy-associated plasma protein-A2
    • Surface plasmon resonance

    ASJC Scopus subject areas

    • Biophysics
    • Bioengineering
    • Biomaterials
    • Pharmaceutical Science
    • Drug Discovery
    • Organic Chemistry

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