Clinical Application of a Graphene Oxide-Based Surface Plasmon Resonance Biosensor to Measure First-Trimester Serum Pregnancy-Associated Plasma Protein-A/A2 Ratio to Predict Preeclampsia

Abstract

Chen-Yu Chen,1,2 Ying-Hao Wang,1 Chie-Pein Chen,1 Fang-Ju Sun,3 Yi-Yung Chen,1 Yu-Jun Huang,1 Nan-Fu Chiu4,5 1Department of Obstetrics and Gynecology, MacKay Memorial Hospital, Taipei, 10449, Taiwan; 2Department of Medicine, MacKay Medical College, New Taipei City, 252005, Taiwan; 3Department of Medical Research, MacKay Memorial Hospital, Taipei, 10449, Taiwan; 4Laboratory of Nano-Photonics and Biosensors, Institute of Electro-Optical Engineering, National Taiwan Normal University, Taipei, 11677, Taiwan; 5Department of Life Science, National Taiwan Normal University, Taipei, 11677, TaiwanCorrespondence: Chen-Yu Chen, Department of Obstetrics and Gynecology, MacKay Memorial Hospital, No. 92, Section 2, Zhong-Shan North Road, Taipei, 10449, Taiwan, Tel [phone], Fax [phone], Email [email protected] Nan-Fu Chiu, Laboratory of Nano-Photonics and Biosensors, Institute of Electro-Optical Engineering, National Taiwan Normal University, No. 88, Section 4, Ting-Chou Road, Taipei, 11677, Taiwan, Tel [phone], Fax [phone], Email [email protected]: Preeclampsia, a major cause of adverse pregnancy outcomes, involves metalloproteinases pregnancy-associated plasma protein (PAPP)-A and PAPP-A2 from placental trophoblasts. The graphene oxide (GO)-based surface plasmon resonance (SPR) biosensor has higher sensitivity, affinity, and selective ability than the traditional SPR biosensor. The aim of this study was to explore the feasibility of measuring first-trimester serum PAPP-A/PAPP-A2 ratio as a novel predictor of preeclampsia using the GO-SPR biosensor.Methods: This prospective case-control study of pregnant women was conducted at MacKay Memorial Hospital, Taipei, Taiwan between January 2018 and June 2020. The SPR angle shifts of first-trimester serum PAPP-A, PAPP-A2, and PAPP-A/PAPP-A2 ratio measured using the GO-SPR biosensor were compared between preeclampsia and control groups.Results: Serum samples from 185 pregnant women were collected, of whom 30 had preeclampsia (5 early-onset; 25 late-onset). The response time between the antibody-antigen association and dissociation only took about 200 seconds. The SPR angle shift of PAPP-A in the preeclampsia group was significantly smaller than that in the control group (median (interquartile range): 5.33 (4.55) versus 6.89 (4.10) millidegrees (mDeg), P = 0.008). Conversely, the SPR angle shift of PAPP-A2 in the preeclampsia group was significantly larger than that in the control group (5.70 (3.81) versus 3.63 (2.38) mDeg, P < 0.001). Receiver operating characteristic (ROC) curve analysis revealed a cut-off PAPP-A/PAPP-A2 ratio to predict all preeclampsia of ≤ 0.76, with an area under the ROC curve (AUC) of 0.79 (95% CI 0.73– 0.85, P < 0.001). Sub-group analysis revealed a cut-off PAPP-A/PAPP-A2 ratio to predict early-onset preeclampsia of ≤ 0.53 (AUC 0.99, 95% CI 0.96– 1.00, P < 0.001), and ≤ 0.73 to predict late-onset preeclampsia (AUC 0.75, 95% CI 0.68– 0.81, P < 0.001).Conclusion: Measuring first-trimester serum PAPP-A/PAPP-A2 ratio using the GO-SPR biosensor could be a valuable method for early prediction of preeclampsia. Keywords: graphene oxide, surface plasmon resonance, biosensor, preeclampsia, PAPP-A/PAPP-A2 ratio

Keywords

• graphene oxide
• surface plasmon resonance
• biosensor
• preeclampsia
• papp-a/papp-a2 ratio