Development of a Magnetic Bead-Based Electrochemical Sandwich Assay to Investigate Inflammatory Cytokines in an Instrumented Fetal Membrane on-a-Chip

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The instrumented fetal membrane on-a-chip (IFMOC) is a 3D microfluidic device that mimics the human fetal membranes and functions as a physiologically relevant model to investigate bacterial infections and the preterm premature rupture of the fetal membranes (PPROM) in-vitro. The magnetic bead-based electrochemical sandwich assay (MBESA) serves as an alternative to traditional enzyme-linked immunosorbent assays (ELISAs) to quantify inflammatory cytokines elevated during preterm birth (PTB), such as interleukin-1β (IL-1β). In this work, a MBESA is developed to detect IL-1β levels present within IFMOC cell cultures infected with lipopolysaccharides (LPS) and Group B Streptococcus (GBS). We present the design and application of the MBESA, highlighting the high sensitivity of an electrochemical technique in a biological platform. We discuss the fabrication and implementation of the IFMOC with the MBESA in reproductive research. The electrochemical assay was able to reproducibly detect IL-1β levels up to 600 pg/mL in RPMI 1640 with 10% FBS media. The MBESA is a promising technique to detect multiple inflammatory cytokines present in infected fetal membrane organ on-a-chip cultures. Future work includes optimizing the electrochemical performance of the MBESA, examining the inflammatory cytokine TNF-α to further elucidate PPROM mechanisms, and subsequently investigating therapeutic methods to prevent the onset of PTB. Figure 1