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

早产(PTB)是最常见的妊娠并发症，有超过50万人早产 每年在美国。肺结核是新生儿死亡和新生儿疾病的主要原因。 不幸的是，在收缩前评估肺结核风险的能力在临床上是不可用的；这种能力 将允许进行治疗干预，以防止或预先阻止分娩，潜在地减少PTB和 新生儿并发症的严重程度。本提案重点发展了3D打印一体化 快速、灵敏、廉价的血清多肽和蛋白质微流控定量系统 PTB风险生物标志物，在宫缩发生前几周。因此，这项建议提供了一个重要的人类健康 潜在的影响，以减少肺结核的发生和伴随的并发症。 这一提议验证了3D打印的发展对快速设计、制造、测试 集成微流控系统的改进将有助于血清肽和 蛋白PTB生物标志物。这些设备将允许在提前通知的情况下评估肺结核风险 可以在宫缩开始之前实施预防措施。这种方法提供了一种低成本- 用于结核分枝杆菌生物标志物分析的成本、可扩展和简单的系统，这是非常可取的能力，但不是 目前可用于平面微制造设备或传统的基于实验室的分析。 重要的是，拟议的工作还将促进3D打印在100微米以下的制造中的广泛使用 各种材料中的微流控特性，加速了生物医学微流控检测的发展。 这项提议的目标是开发集成微流控系统的3D打印，以允许 制造简单且低成本的装置，提供相关血清生物标志物的快速定量分析 有肺结核的风险。这一目标将通过三个具体目标来实现。AIM 1 3D打印微流控 组件(阀门、泵、色谱柱和分离柱等)将被设计，创造， 小型化和改进型。在目标2中，将对所产生的装置进行评估，以进行PTB生物标志物分析 并行指导目标1组件优化。在AIM 3中，这些3D打印集成微流控设备将 用于检测血液样本中的肺结核生物标志物，以设定诊断阈值，用于预测肺结核 宫缩发生前几周的风险。3D打印微器件制造中的限制工艺也将是 确定评估这些方法的生产放大潜力。 重要的是，这项工作解决了诊断肺结核风险的关键需求，而医疗干预是 可行；此外，这种亚100微米3D打印微流控结构制造方法应该具有 广泛的适用性，远远超出结核病的生物标志物，进一步表明了 这些研究。

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.