Developing a low cost, highly compact holographic imaging based microfluidic cell sorting system using 3D printing

使用 3D 打印开发低成本、高度紧凑的基于全息成像的微流体细胞分选系统

• 批准号: 10575747
• 负责人: Jiarong Hong
• 金额: $ 38.98万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10575747
• 关键词: 3-Dimensional; 3D Print; Automation; Automobile Driving; Biological Assay; Blood Cells; Cancer Diagnostics; Cancer cell line; Cell Separation; Cells; Cellular Morphology; Clinical; Clinical Treatment; Computer software; Detection; Devices; Diagnosis; Erythrocytes; Flow Cytometry; Hematological Disease; Holography; Hour; Image; Lab On A Chip; Leukocytes; Literature; Malignant Neoplasms; Medical; Medical Research; Methods; Microfluidic Microchips; Microfluidics; Microspheres; Mission; National Human Genome Research Institute; Neoplasm Circulating Cells; Optics; Organ; Pattern; Performance; Point-of-Care Systems; Public Health; Reaction Time; Research; Resolution; Sampling; Sickle Cell; Sickle Cell Anemia; Sorting; Specificity; Speed; System; Techniques; Technology; Testing; Three-Dimensional Imaging; Time; bioprinting; clinical application; clinical diagnostics; cost; deep learning; density; design; disease diagnostic; efficacy evaluation; fabrication; image processing; imaging capabilities; improved; liquid biopsy; machine vision; meter; microscopic imaging; miniaturize; new technology; operation; performance tests; personalized cancer therapy; point-of-care diagnostics; prototype; sensor; single cell analysis

SUMMARY With advancement in machine vision and deep learning, imaging-based microfluidics have demonstrated their potential to serve as precise single cell analysis and sorting devices for various challenging medical applications including bioprinting and cell patterning, sorting rare cells (e.g., circulating tumor cells, sickle cells) from blood for disease (e.g., cancer, sickle diseases) diagnosis, etc. However, current imaging-based microfluidic cell sorting systems suffer from the issues of low throughput and world-to-chip interfacing. These issues are largely related to the shallow depth of field of conventional microscopic imaging, which significantly restricts the number of cells that can be analyzed per image and increases the complexity and cost involved in fabricating cell sorting chips integrated with imaging and valve actuation capabilities. These issues limit the implementation of such microfluidic systems in clinical diagnostics and treatment, particularly in which target cells are extremely rare in samples. Although different types of high throughput cell sorting microfluidic systems have been developed, they either have insufficient sorting precision or require the integration of different sorting methods, which further increases the system complexity and lowers its reliability. This exploratory R21 project aims to develop a high throughput, low cost and compact solution for imaging- based cell sorting microfluidic devices to improve their appeal for critical clinical applications. Our solution utilizes 3D holographic imaging to overcome the depth of field issue of conventional microscopic imaging, increase the specificity of cell detection, and enables high throughput and high precision cell sorting using microfluidics. We will use multi-material 3D printing technique to generate fast responsive sorting valves and miniaturized holographic imaging sensors with performance that exceeds the ones in the literature. Our approach will not only substantially reduce the cost, time, and enhance the degree of automation for fabricating these microfluidic devices, but also enable sleek and compact microfluidic design, contamination-free fabrication, and superior and consistent imaging quality during hours of operation that is essential for many clinical operations. The 3D printing approach developed in this project can provide the basis for low cost and high efficiency fabrication of a broad range of microfluidic devices used in medical research and clinical applications (e.g., lab-on-a-chip diagnostics, point-of-care systems, organ replication-on-a-chip, and bioassays). The integration of 3D imaging capability with 3D printing will enable new designs of high throughput, high precision, and high specificity microfluidic systems with versatile functionalities that are not available in conventional microfluidics used in medical field. In particular, the cell sorting devices fabricated in this proposed project can significantly speed up the cell-based liquid biopsy for cancer diagnostics and personalized cancer treatment.

概括 随着机器视觉和深度学习的进步，基于成像的微流控技术已经证明了它们的优势 具有作为精确单细胞分析和分选设备用于各种具有挑战性的医疗应用的潜力 包括生物打印和细胞图案化、从血液中分选稀有细胞（例如循环肿瘤细胞、镰状细胞） 用于疾病（例如癌症、镰状病）诊断等。然而，目前基于成像的微流控细胞 分拣系统面临吞吐量低和世界与芯片接口的问题。这些问题很大程度上是 与传统显微成像的浅景深有关，这极大地限制了 可以对每个图像进行分析的细胞数量，并增加了制造细胞分选所涉及的复杂性和成本 集成成像和阀门驱动功能的芯片。这些问题限制了此类措施的实施 临床诊断和治疗中的微流体系统，特别是在靶细胞极其罕见的情况下 样品。尽管已经开发了不同类型的高通量细胞分选微流体系统，但它们 要么分拣精度不够，要么需要不同分拣方法的融合，这进一步 增加了系统的复杂性并降低了其可靠性。 这个探索性的 R21 项目旨在开发一种高通量、低成本和紧凑的成像解决方案 基于细胞分选的微流体装置，以提高其对关键临床应用的吸引力。我们的解决方案利用 3D全息成像克服了传统显微成像的景深问题，增加了 细胞检测的特异性，并利用微流控技术实现高通量和高精度细胞分选。我们 将使用多材料3D打印技术来生成快速响应的分选阀和小型化 全息成像传感器的性能超过文献中的传感器。我们的方法不会 仅大幅降低制造这些微流体的成本、时间并提高自动化程度 设备，而且还实现了时尚紧凑的微流体设计、无污染制造以及卓越和 手术期间一致的成像质量对于许多临床手术至关重要。 3D打印 该项目开发的方法可以为广泛的低成本和高效率制造提供基础 用于医学研究和临床应用的一系列微流体设备（例如，芯片实验室诊断、 护理点系统、芯片上的器官复制和生物测定）。 3D 成像能力与 3D打印将实现高通量、高精度和高特异性微流体系统的新设计 具有医疗领域使用的传统微流体所不具备的多功能功能。尤其， 该项目中制造的细胞分选设备可以显着加速基于细胞的液体活检 用于癌症诊断和个性化癌症治疗。