Blood-based indicators for pregnancy disorders: Advanced biophysical approaches

Pregnancy disorders, including preeclampsia, gestational diabetes mellitus, and intrauterine growth restriction, represent a significant global burden of maternal and neonatal morbidity and mortality. Early and accurate detection of these conditions remains a critical clinical challenge, as conventional diagnostic methods often lack the sensitivity and specificity required for timely intervention. Blood-based biomarkers have emerged as a promising avenue for non-invasive surveillance; however, their full diagnostic potential is only now being realized through the application of advanced biophysical analytical techniques. This review examines three advanced methodological approaches - differential scanning calorimetry (DSC), atomic force microscopy (AFM), and microfluidic analysis - as applied to the characterization of blood-based indicators in pregnancy-related disorders. DSC enables thermodynamic profiling of plasma proteomes, revealing disorder-specific denaturation signatures that reflect systemic pathophysiological alterations. AFM provides nanoscale structural and mechanical interrogation of red blood cells, platelets, and plasma proteins, uncovering morphological and viscoelastic changes associated with hemostatic dysregulation and endothelial dysfunction. Microfluidic platforms offer high-throughput, minimally invasive analysis of whole blood rheology, cellular deformability, and biomarker concentrations under physiologically relevant flow conditions. Collectively, these approaches provide complementary and multi-dimensional characterization of the maternal blood milieu that transcends the limitations of conventional biochemical assays. We discuss the current state of evidence, methodological advances, translational barriers, and future directions for integrating these biophysical strategies into point-of-care diagnostic frameworks. The convergence of these technologies holds considerable promise for transforming prenatal screening and enabling precision management of high-risk pregnancies.