Rapid and high-sensitivity screening of pregnancy complications by profiling circulating placental extracellular vesicles
Herein, we developed a specific, rapid sensor to quantify placental extracellular vesicle (EV) protein biomarkers of early pregnancy complications. A distinct tetraspanin CD9 and placental alkaline phosphatase (PLAP) expression pattern was observed via targeted multiple reaction monitoring of EVs from maternal plasma collected before 18 weeks of gestation. A classification model was developed using training and validation patient sets, distinguishing between individuals at high risk of developing complications from those with normal pregnancies, achieving 80% sensitivity, 90% specificity, 89% positive predictive value (PPV), and 82% negative predictive value (NPV). Superparamagnetic nanoflowers that captured target EVs (CD9<sup>+</sup>/PLAP<sup>+</sup>) were used to construct a 4-flex glass strip nanozymatic readout system. The sensor analyzes plasma for EVs, identifying gestational diabetes mellitus risk with a 95% combined sensitivity, 100% specificity, 100% PPV, and 96% NPV. This nanoplatform identifies individuals at risk of developing pregnancy complications with a >90% classification accuracy, exhibiting potential for clinical applications.
Authors
- Angela Nakahara
- Dominic Guanzon (ORCID: https://orcid.org/0000-0001-7913-5749)
- Soumyalekshmi Nair (ORCID: https://orcid.org/0000-0001-6733-6164)
- Aase Handberg (ORCID: https://orcid.org/0000-0001-5719-203X)
- Sherri Longo (ORCID: https://orcid.org/0000-0003-4781-7037)
- Alexis Salas-Burgos (ORCID: https://orcid.org/0000-0002-6577-9970)
- Md. Shahriar A. Hossain (ORCID: https://orcid.org/0000-0002-7291-9281)
- Melissa Razo-Azamar
- Andrew Lai (ORCID: https://orcid.org/0000-0002-4424-8767)
- Carlos Palma (ORCID: https://orcid.org/0000-0001-6182-7501)
- Greg Duncombe (ORCID: https://orcid.org/0000-0002-2757-5213)
- Carlos Salomón (ORCID: https://orcid.org/0000-0003-4474-0046)
- David McIntyre (ORCID: https://orcid.org/0000-0001-8819-5794)
- Mostafa Kamal Masud (ORCID: https://orcid.org/0000-0002-5346-3135)
- Flavio Carrión (ORCID: https://orcid.org/0000-0002-4086-6867)
- Yusuke Yamauchi
Institutions
- Universidad de Santiago de Chile (CL)
- Mater Health Services (AU)
- Queensland University of Technology (AU)
- The University of Queensland (AU)
- University of Concepción (CL)
- Royal Brisbane and Women's Hospital (AU)
- Ochsner Medical Center (US)
- Aalborg University Hospital (DK)
- Mater Research (AU)
- Nagoya University (JP)
Publication Details
- Journal
- Science Advances
- Published
- 2025-02-26
- DOI
- https://doi.org/10.1126/sciadv.adr4074
- Citations
- 7
- Primary Topic
- Extracellular vesicles in disease
- Type
- article
- Field-Weighted Citation Impact
- 5.64