Label-free microfluidic enrichment of cancer cells from noncancer cells in ascites fluid

无标记微流体从腹水中的非癌细胞中富集癌细胞

• 批准号: 9251748
• 负责人: John F McDonald
• 金额: $ 18.7万
• 依托单位: GEORGIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-06-01 至 2019-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9251748
• 关键词: Abdomen; Abdominal Cavity; Affect; Antibodies; Ascites; Atomic Force Microscopy; Biological Assay; Biological Process; Biophysics; Cancer Patient; Cancer Science; Cell Line; Cell Separation; Cell Size; Cell Survival; Cells; Centrifugation; Clinic; Collection; Complex; Coulter counter; Data; Detection; Development; Device Designs; Disease; Erythrocytes; Flow Cytometry; Gene Expression; Gene Proteins; Geometry; Human; Image Cytometry; Immunoassay; In Vitro; Knowledge; Label; Laboratory Research; Liquid substance; Lymphocyte; Magnetic nanoparticles; Magnetism; Malignant Neoplasms; Malignant neoplasm of ovary; Mesothelial Cell; Methods; Microfluidic Microchips; Microfluidics; Microscopy; Molecular; Molecular Analysis; Morphology; Neoplasm Metastasis; Pathologist; Patients; Periodicity; Pharmacotherapy; Preparation; Procedures; Proteins; Reagent; Research Proposals; Sampling; Scientist; Series; Serous; Sorting - Cell Movement; Standard Preparations; System; Techniques; Technology; Testing; Variant; base; cancer biomarkers; cancer cell; cancer type; cell type; chemotherapy; clinical Diagnosis; constriction; density; design; drug testing; effusion; improved; macrophage; public health relevance; success; tumorigenesis

 DESCRIPTION (provided by applicant): The examination of cancer cells collected from effusions and ascites is an important step to identify or determine the progress of cancer by pathologists or in preparation of performing analytical techniques by cancer scientists. However this examination is complicated due to the presence of many noncancerous cells, including mesothelial, macrophage, and lymphocyte cells. Standard preparation techniques such as centrifugation can be utilized to increase the density of total cells in the sample, but further purification of the collected sample to highly enrich the cancer cells is troublesome and expensive, typically requiring laborious processing and expensive labeling reagents such as antibodies. As such, enriching cancer cells from ascites is rarely performed in the clinic and infrequently in the research laboratory. The objective of this research proposal is to test a label free microfluidic cell sorting technology that utilizes differences in cell stiffness and cell sizeto enrich cancer cells from noncancerous cells present in ascites fluid. The technology utilizes the observed fact that the cancer cells frequently undergo biophysical and morphological changes to be distinct from other noncancerous cell types. The technology consists of microchannels with periodic constrictions that are designed to direct soft cells along a different path than stif cells. We will examine how variations in channel geometry and other system parameters can be harnessed to provoke cancer cell segregation through inherent biophysical differences. A high throughput and label-free method to purify cancer cells from noncancerous cells will greatly benefit the accuracy and efficiency of both cancer science and clinical diagnoses. Successful completion of this project will create a new enrichment method to facilitate the detection of very low levels of diseased cells in complex fluids or to enhance the purity of cancer cell subpopulations within heterogeneous mixtures, including effusions and ascites fluid.

 描述（由申请人提供）：检查从渗出液和腹水中收集的癌细胞是病理学家识别或确定癌症进展或癌症科学家准备执行分析技术的重要步骤。然而，由于存在许多非癌细胞，包括间皮细胞、巨噬细胞和淋巴细胞，这种检查是复杂的。标准制备技术如离心可用于增加样品中总细胞的密度，但进一步纯化收集的样品以高度富集癌细胞是麻烦且昂贵的，通常需要费力的处理和昂贵的标记试剂如抗体。因此，从腹水中富集癌细胞很少在临床上进行，也很少在研究实验室中进行。本研究提案的目的是测试标签 免费的微流控细胞分选技术，利用细胞硬度和细胞大小的差异，从腹水中的非癌细胞中富集癌细胞。该技术利用观察到的事实，即癌细胞经常经历生物物理和形态学变化，以区别于其他非癌细胞类型。该技术由周期性收缩的微通道组成，旨在引导软细胞沿着与硬细胞不同的路径。我们将研究如何利用通道几何形状和其他系统参数的变化，通过固有的生物物理差异引起癌细胞分离。从非癌细胞中纯化癌细胞的高通量和无标记方法将极大地有利于癌症科学和临床诊断的准确性和效率。该项目的成功完成将创造一种新的富集方法，以便于检测复杂液体中极低水平的病变细胞，或提高异质混合物（包括渗出液和腹水）中癌细胞亚群的纯度。