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

基本信息

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
项目类别：
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

项目摘要

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，早产人数超过 500,000 在美国，PTB 每年造成大部分新生儿死亡和新生儿疾病。不幸的是，临床上尚无法在宫缩前评估 PTB 风险。将允许预防或阻止分娩的治疗干预，有可能减少 PTB 和该提案重点关注 3D 打印集成的开发。用于快速、灵敏且可能廉价地定量血清肽和蛋白质的微流体系统因此，该建议为宫缩发生前几周提供了 PTB 风险生物标志物。减少 PTB 发生及其伴随并发症的潜力。该提案测试了以下假设：3D 打印的发展可用于快速设计、制造、测试集成微流体系统的改进将有助于血清肽和这些设备将允许在提前通知的情况下评估 PTB 风险。可以在宫缩开始之前实施预防措施。成本低、可扩展且简单的 PTB 生物标志物分析系统，这是一种非常理想的功能，但目前还没有目前可用于平面微加工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 打印在制造 100 µm 以下的材料中的广泛应用各种材料的微流控特性，加速了生物医学微流控检测的发展。该提案的目标是开发集成微流体系统的 3D 打印，以允许简单且低成本的设备制造，提供相关血清生物标志物的快速定量分析该目标将通过 In Aim 1 3D 打印微流体来实现。组件（阀门、泵、色谱和分离柱等）将被设计、创建、在目标 2 中，将评估所得设备的 PTB 生物标志物分析。与目标 1 组件优化并行，在目标 3 中，这些 3D 打印集成微流体设备将。用于测量血液样本中的 PTB 生物标志物，以设置用于预测 PTB 的诊断阈值收缩发生前几周的风险也将受到影响。确定以评估这些方法的生产规模扩大潜力。重要的是，这项工作解决了在医疗干预尚未实现的情况下诊断 PTB 风险的关键未满足需求。此外，这种亚 100 µm 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，进一步证明了其对人类健康的重大影响这些研究。