Isolating clinically important cells from large fluid volumes with microfluidics

摘要 微流体技术通过创造研究单细胞的新方法，彻底改变了医学世界 并且正在稳步成为多年来梦寐以求的变革领域。临床试验依赖于 大体积（即，1升）的生物流体是微流体中还有待面对的一个挑战。那里 是许多重要的样品，例如腹膜灌洗液或尿液，其中必须 为了收集足够的细胞进行正确的诊断。当前的批处理过程是有损的，同时- 繁琐且因用户而异。这项工作将开发一种新的微流体技术，以显着地控制， 从大量流体中离心和分离细胞。我们的目标是开发一个自动化的，高度敏感的 和极高的通量技术，以减少这些样品的体积， 容易获得临床相关材料，改进当前的检测技术， 在诊断和治疗方面的未来发展。处理大量体液的能力 并提取稀有和稀释的细胞，将使多种诊断和预后测试，以监测和 早期诊断癌症对患者有重要的益处。 这项技术将依赖于一种被称为惯性聚焦的基本流体动力学现象。 可以利用被动现象来将细胞定位和集中在细胞内的特定位置。 流体通道，其允许容易地去除无细胞流体。虽然惯性聚焦是已知的， 自20世纪60年代以来，它并没有完全被很好地理解，特别是对于复杂装置中的生物样品， 几何这项工作将使用工程原理和详细的模拟，通过实验验证 与模型细胞，以优化器件性能。最终的装置将由多个微- crofluidic阶段，这使得最终的设计空间复杂。参数数量太大， 只通过实验来探索。 具体的目的是设计和实验验证微流控惯性聚焦装置capa， 能够将1升液体减少到1毫升，同时保留所有感兴趣的细胞。

Abstract Microfluidics has revolutionized the world of medicine by creating new ways of investigating single cells and is steadily becoming the transformative field dreamed of for many years. Clinical tests relying on large volumes (i.e. 1 liter) of biological fluid is one challenge yet to be confronted in microfluidics. There are a number of important samples such as peritoneal lavages or urine where large fluid volumes must be processed in order to collect enough cells for proper diagnoses. Current batch processes are lossy, cum- bersome and vary by user. This work will develop a novel microfluidic technology to significantly con- centrate and isolate cells from large fluid volumes. The goal is to develop an automated, highly sensitive and extremely high throughput technology for reducing the volume of these samples to allow scientists easy access the clinically relevant material, improving the current detection techniques and providing for future advancements in diagnostics and treatments. The ability to process large volumes of bodily fluids and extract rare and dilute cells, will enable multiple diagnostics and prognostic tests to monitor and early diagnose cancer with important benefits to patients. The technology will rely upon a fundamental fluid dynamics phenomena known as inertial focusing. The passive phenomena can be exploited to locate and concentrate cells in particular locations within a fluid channel, which allow for easy removal of cell free fluid. While inertial focusing has been known since the 1960s it is not completely well understood, especially with biological samples in complex device geometry. The work will use engineering principles and detailed simulations, validated by experiments with model cells, in order to optimize device performance. The final device will consist of multiple mi- crofluidic stages which makes the final design space complex. The number of parameters is too large to explore by experiment alone. The specific aim is to design and experimentally validate a microfluidic inertial focusing device capa- ble of reducing 1 liter of fluid to 1 milliliter while retaining all cells of interest.