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Microfluidic Device for Isolating Rare Blood Cells

用于分离稀有血细胞的微流体装置

基本信息

批准号：
7487026
负责人：
LANCE L MUNN
金额：
$ 15.75万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-09-01 至 2010-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7487026
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

项目摘要

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（由申请人提供）：从外周血中分离稀有细胞是癌症诊断和治疗中困难且繁琐的步骤。实例包括在白血病中感兴趣的白细胞、可用作实体瘤治疗的替代标志物的循环内皮细胞和可提供诊断和预后工具的循环癌细胞。在大多数患者中，这些细胞类型中的每一种都被红细胞超过至少1000倍。因此，从全血样品中分离这些细胞是许多临床和基础研究测定所需的第一步。我们最近描述了一种微流体装置，其利用血浆撇除和白细胞边集-微循环中血流的固有特征-直接从全血中富集有核细胞如白细胞。它由一个简单的矩形微通道网络组成，使用标准的光刻和硅树脂成型技术制造，只需要压力驱动的流动来操作。它的初始通道被设计成增强球形细胞的侧向迁移，一旦接近壁，就很容易通过小的提取通道提取。在我们的初步设计中，单次通过该装置产生白细胞与红细胞比率的34倍富集。我们建议进一步开发微流体技术，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。将其集成到需要稀有细胞富集的微量分析设备中，将提供更便宜、更可靠的临床测定，这些测定对于即时检测也是方便和便携的。具体而言，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。当完全开发时，该技术将成为任何微流体设备的必要组成部分，通过消除对初步血液处理步骤的需要来分析有核血细胞群。