3D printed microfluidic devices for integrated solid-phase extraction and microchip electrophoresis of preterm birth biomarkers

Abstract

Background: Preterm birth (PTB) is a leading cause of neonatal mortality, such that the need for a rapid and accurate assessment for PTB risk is critical. Here, we developed a 3D printed microfluidic system that integrated solid-phase extraction (SPE) and microchip electrophoresis (μCE) of PTB biomarkers, enabling the combination of biomarker enrichment and labeling with μCE separation and fluorescence detection.

Results: Reversed-phase SPE monoliths were photopolymerized in 3D printed devices. Microvalves in the device directed sample between the SPE monolith and the injection cross-channel in the serpentine μCE channel. Successful on-chip preconcentration, labeling and μCE separation of four PTB-related polypeptides were demonstrated in these integrated microfluidic devices. We further show the ability of these devices to handle complex sample matrices through the successful analysis of labeled PTB biomarkers spiked into maternal blood serum. The detection limit was 7 nM for the PTB biomarker, corticotropin releasing factor, in 3D printed SPE-μCE integrated devices.

Significance: This work represents the first successful demonstration of integration of SPE and μCE separation of disease-linked biomarkers in 3D printed microfluidic devices. These studies open up promising possibilities for rapid bioanalysis of medically relevant analytes.

Keywords: 3D printing; Microchip electrophoresis; Microfluidics; Preterm birth biomarkers; Sample preparation; Solid-phase extraction.