Microfluidic Device for Isolating Rare Blood Cells

用于分离稀有血细胞的微流体装置

• 批准号: 7238941
• 负责人: LANCE L MUNN
• 金额: $ 21.19万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-01 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7238941
• 关键词: Affect; Basic Science; Bedside Testings; Biological Assay; Biological Models; Biomimetics; Blood; Blood Cells; Blood Volume; Blood flow; Blood specimen; Caliber; Cancer Patient; Cell Separation; Cells; Centrifugation; Clinic; Clinical; Coagulation Process; Collection; Colon Adenocarcinoma; Count; Cytolysis; Depth; Developing Countries; Devices; Diagnosis; Dimensions; Endothelial Cells; Equipment; Erythroblasts; Erythrocytes; Exhibits; Flow Cytometry; Glioblastoma; Green Fluorescent Proteins; Home environment; Human; Image; Individual; Lateral; Length; Leukocytes; Liquid substance; Methods; Microcirculation; Microfabrication; Microfluidic Microchips; Microfluidics; Molds; Operative Surgical Procedures; Output; Patients; Performance; Plasma; Population; Process; Property; Range; Research; Research Personnel; Resistance; Sampling; Series; Shapes; Side; Silicones; Solid Neoplasm; Sorting - Cell Movement; Staging; Standards of Weights and Measures; Stem cells; Stream; Surrogate Markers; Techniques; Technology; Umbilical vein; Variant; Whole Blood; Width; base; cancer cell; cancer therapy; cell type; circulating cancer cell; design; improved; interest; leukemia; micro-total analysis system; migration; natural flow; outcome forecast; peripheral blood; pressure; programs; prototype; simulation; size; tool

DESCRIPTION (provided by applicant): Isolation of rare cells from peripheral blood is a difficult and tedious step in the diagnosis and treatment of cancer. Examples include leukocytes, which are of interest in leukemia, circulating endothelial cells, which can serve as a surrogate marker for solid tumor treatment, and circulating cancer cells, which may provide a tool for diagnosis and prognosis. In most patients, each of these cell types is outnumbered by red blood cells by a factor of at least 1000. Therefore, isolation of these cells from a sample of whole blood is the required first step of many clinical and basic research assays. We recently described a microfluidic device that takes advantage of plasma skimming and leukocyte margination - intrinsic features of blood flow in the microcirculation - to enrich nucleated cells such as leukocytes directly from whole blood. It consists of a simple network of rectangular microchannels manufactured using standard photolithography and silicone molding techniques, and requires only pressure-driven flow to operate. Its initial channel is designed to enhance lateral migration of spherical cells, which, once near the wall are easily extracted through small extraction channels. In our preliminary design, a single pass through the device produces 34-fold enrichment of the leukocyte-to-erythrocyte ratio. We propose to further develop the microfluidics to provide simple, efficient and inexpensive technology for use as an initial stage in lab-on-a-chip analyses. Its integration into microanalytical devices that require rare cell enrichment will provide less expensive, more reliable, clinical assays that are also convenient and portable for point-of-care testing. Specifically, we will maximize the purity and efficiency of nucleated blood cell isolation and compare the performance with traditional separation techniques. When fully-developed, this technology will be a necessary and integral component of any microfluidic device analyzing nucleated blood cell populations by eliminating the need for preliminary blood processing steps.

描述(申请人提供)：在癌症的诊断和治疗中，从外周血中分离稀有细胞是一个困难和繁琐的步骤。例如，与白血病有关的白细胞、可作为实体瘤治疗替代标记物的循环内皮细胞，以及可能为诊断和预后提供工具的循环癌细胞。在大多数患者中，这些细胞类型中的每一种都是红细胞数量的至少1000倍。因此，从全血样本中分离这些细胞是许多临床和基础研究分析所必需的第一步。我们最近描述了一种微流控设备，它利用血浆撇脂和白细胞边际-微循环中血液流动的内在特征-直接从全血中浓缩有核细胞，如白细胞。它由使用标准光刻和硅胶成型技术制造的矩形微通道组成的简单网络组成，只需压力驱动流即可运行。其初始通道旨在增强球形细胞的横向迁移，一旦靠近壁面，这些细胞很容易通过小的提取通道提取。在我们的初步设计中，一次通过该装置就可以使白细胞与红细胞的比率增加34倍。我们建议进一步开发微流控技术，以提供简单、高效和廉价的技术，作为芯片实验室分析的初始阶段。它集成到需要稀有细胞浓缩的微量分析设备中，将提供更便宜、更可靠的临床分析，也是方便和便携的护理点检测。具体地说，我们将最大限度地提高有核血细胞分离的纯度和效率，并将其性能与传统分离技术进行比较。全面开发后，这项技术将成为任何微流控设备分析有核血细胞群体的必要和不可或缺的组件，因为它消除了初步血液处理步骤的需要。