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）是怀孕最常见的并发症，有超过500,000个早期出生 在美国遇到。 PTB负责大多数新生儿死亡和新生儿疾病。 不幸的是，在临床上无法获得收缩之前评估PTB风险的能力；这个功能 将允许治疗干预措施，以防止或阻止分娩，可能会减少PTB和 新生儿并发症的严重程度。该提案重点是开发3D打印的集成 微流体系统，用于快速，敏感且潜在的血清胡椒和蛋白质的廉价定量 PTB风险生物标志物，在收缩发生前几周。因此，该建议提供了主要的人类健康 潜在减少PTB的发生及其伴随并发症的影响。 该提案测试了以下假设：快速设计，制造，测试的3D打印的开发 改进集成的微流体系统将促进血清胡椒和 蛋白质PTB生物标志物。这些设备将允许通过提前通知评估PTB风险，因此 可以在合同开始之前实施预防措施。这种方法提供了低 - 成本，可扩展和简单的PTB生物标志物分析的系统，这是高度可取的功能，但不是 目前可配备平面微观制造设备或常规实验室的分析。 重要的是，拟议的工作还将促进3D打印的广泛使用，以使100 µm低于100 µm 各种材料中的微流体特征，加速了生物医学微流体测定的发展。 该提案的目的是开发集成微流体系统的3D打印以允许 简单和低成本的装置制造，提供血清生物标志物相关的快速定量分析 有PTB风险。这个目标将通过三个具体目标实现。在AIM 1 3D打印微流体 组件（阀，泵，色谱和分离柱等）将设计，创建， 小型和改进。在AIM 2中，将评估所得的设备以进行PTB生物标志物分析 平行于指导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，以设置用于预测PTB的诊断阈值 发生收缩前几周的风险。 3D印刷微电位制造中的限制过程也将是 确定以评估这些方法的生产规模潜力。 重要的是，这项工作解决了诊断PTB风险的关键需求，而医疗干预是 可行的;此外，这种低于10​​0-µm 3D打印的微流体结构制造方法应具有 广泛的适用性，远远超出了PTB的生物标志物，进一步证明了人类健康的主要影响 这些研究。