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

用于早产生物标志物分析的 3D 打印集成微流体装置

• 批准号: 10250315
• 负责人: Adam Thomas Woolley
• 金额: $ 25.52万
• 依托单位: BRIGHAM YOUNG UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-18 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10250315
• 关键词: 3-Dimensional; 3D Print; Address; Biological Assay; Biological Markers; Birth; Blinded; Blood; Blood specimen; Clinical; Complex; Coupled; Detection; Development; Device or Instrument Development; Devices; Diagnosis; Diagnostic; Evaluation; Fingers; Fluorescence; Future; Goals; Health; Healthcare; Human; Intervention; Label; Lasers; Measurement; Measures; Medical; Methods; Microchip Electrophoresis; Microfluidic Microchips; Microfluidics; Miniaturization; Neonatal; Newborn Infant; Peptides; Performance; Phase; Plant Resins; Play; Pregnancy Complications; Pregnant Women; Premature Birth; Preventive measure; Process; Production; Prospective Studies; Proteins; Pump; Risk; Risk Assessment; Sampling; Scheme; Serum; Severities; Software Design; Solid; Structure; System; Testing; Therapeutic Intervention; Time; United States; Universities; Utah; Work; assay development; base; case control; cost; delivery complications; design; experimental study; improved; manufacturability; microdevice; miniaturize; monomer; neonatal death; operation; prevent; protein biomarkers; prototype; scale up

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.

早产（PTB）是最常见的妊娠并发症，有超过50万例早产 每年在美国。肺结核是造成大多数新生儿死亡和新生儿疾病的原因。 不幸的是，在收缩前评估PTB风险的能力在临床上是不可用的;这种能力 将允许治疗干预，防止或预先交付，潜在地减少PTB和 新生儿并发症的严重程度。该提案的重点是开发3D打印集成 用于血清肽和蛋白质的快速、灵敏和潜在廉价定量的微流体系统 PTB风险生物标志物，收缩发生前几周。因此，这项建议为人类健康提供了一个重要的 潜在的影响，以减少PTB的发生和并发症，伴随着他们。 该提案测试了一个假设，即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的测量， 蛋白质PTB生物标志物。这些设备将允许在提前通知的情况下评估PTB风险， 可以在宫缩开始前采取预防措施。这种方法提供了一个低- 用于PTB生物标志物分析的成本、可扩展和简单的系统，这是非常期望的能力，但不 目前可用于平面微加工装置或常规的基于实验室的分析。 重要的是，拟议的工作还将促进3D打印在制造100微米以下的材料方面的广泛使用。 微流控特性在各种材料中的应用，加速了生物医学微流控分析的发展。 该提案的目标是开发集成微流体系统的3D打印， 简单和低成本的设备制造，提供相关血清生物标志物的快速定量分析， PTB风险将通过三个具体目标实现这一目标。In Aim 1 3D打印微流体 组件（阀门、泵、色谱柱和分离柱等）将被设计，被创造， 小型化和改进。在目标2中，将评价所得器械的PTB生物标志物分析， 并行引导Aim 1组件优化。在Aim 3中，这些3D打印的集成微流体设备将 用于测量血液样本中的PTB生物标志物，以设定用于预测PTB的诊断阈值 在宫缩发生前几周的风险。3D打印微器件制造中的限制过程也将被 以评估这些方法的生产规模扩大潜力。 重要的是，这项工作解决了诊断PTB风险的关键未满足的需求，而医疗干预是 可行;此外，这种低于100微米的3D打印微流体结构制造方法应该具有 广泛的适用性，远远超出了PTB的生物标志物，进一步证明了 这些研究。