3D-Printed Integrated Microfluidic Devices for Preterm Birth Biomarker Analysis

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Preterm birth (PTB) is the most common complication of pregnancy, with over 500,000 early births annually in the United States. PTB is responsible for the majority of neonatal deaths and newborn illnesses. Unfortunately, the ability to assess PTB risk prior to contractions is not available clinically; this capability would allow therapeutic interventions that prevent or forestall delivery, potentially decreasing PTBs and the severity of neonatal complications. This proposal focuses on the development of 3D-printed integrated microfluidic systems for rapid, sensitive and potentially inexpensive quantitation of serum peptide and protein PTB risk biomarkers, weeks before contractions occur. This proposal thus offers a major human health impact in potential to decrease the occurrence of PTBs and the complications that accompany them. This proposal tests the hypothesis that the development of 3D printing for rapid design, fabrication, testing and improvement of integrated microfluidic systems will facilitate the measurement of serum peptide and protein PTB biomarkers. These devices will allow assessment of PTB risk with advance notice so preventative measures can be implemented before contractions commence. This approach provides a low- cost, scalable and simple system for PTB biomarker analysis, a capability that is highly desirable, yet not presently available either with planar microfabricated devices or conventional lab-based analyses. Importantly, the proposed work will also facilitate the broad usage of 3D printing in making sub-100 µm microfluidic features in various materials, accelerating the development of biomedical microfluidic assays. The goal of this proposal is the development of 3D printing of integrated microfluidic systems to allow simple and low-cost device fabrication, providing rapid quantitative analysis of serum biomarkers correlated with PTB risk. This objective will be met through three specific aims. In Aim 1 3D-printed microfluidic components (valves, pumps, chromatographic and separation columns, etc.) will be designed, created, miniaturized and improved. In Aim 2 the resulting devices will be evaluated for PTB biomarker analysis in parallel to guide Aim 1 component optimization. In Aim 3 these 3D-printed integrated microfluidic devices will be used to measure PTB biomarkers in blood samples to set diagnostic thresholds for use in predicting PTB risk weeks before contractions occur. Limiting processes in 3D printed microdevice fabrication will also be identified to assess production scale-up potential for these methods. Importantly, this work addresses the key unmet need to diagnose PTB risk while medical intervention is feasible; additionally, this sub-100-µm 3D-printed microfluidic structure fabrication approach should have broad applicability, well beyond biomarkers for PTB, further demonstrating the major human health impact of these studies.