...
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Isolation of circulating tumor cells using a microvortex-generating herringbone-chip
【24h】

Isolation of circulating tumor cells using a microvortex-generating herringbone-chip

机译:使用产生微涡旋的人字形芯片分离循环肿瘤细胞

获取原文
获取原文并翻译 | 示例
           

摘要

Rare circulating tumor cells (CTCs) present in the bloodstream of patients with cancer provide a potentially accessible source for detection, characterization, and monitoring of nonhematological cancers. We previously demonstrated the effectiveness of a micro-fluidic device, the CTC-Chip, in capturing these epithelial cell adhesion molecule (EpCAM)-expressing cells using antibody-coated microposts. Here, we describe a high-throughput microfluidic mixing device, the herringbone-chip, or "HB-Chip," which provides an enhanced platform for CTC isolation. The HB-Chip design applies passive mixing of blood cells through the generation of microvor-tices to significantly increase the number of interactions between target CTCs and the antibody-coated chip surface. Efficient cell capture was validated using defined numbers of cancer cells spiked into control blood, and clinical utility was demonstrated in specimens from patients with prostate cancer. CTCs were detected in 14 of 15 (93%) patients with metastatic disease (median= 63 CTCs/mL, mean = 386 ± 238 CTCs/mL), and the tumor-specific TMPRSS2-ERG translocation was readily identified following RNA isolation and RT-PCR analysis. The use of transparent materials allowed for imaging of the captured CTCs using standard clinical histopathological stains, in addition to immunofluorescence-conju-gated antibodies. In a subset of patient samples, the low shear design of the HB-Chip revealed microclusters of CTCs, previously unappreciated tumor cell aggregates that may contribute to the hematogenous dissemination of cancer.
机译:存在于癌症患者血液中的稀有循环肿瘤细胞(CTC)为非血液学癌症的检测,表征和监测提供了潜在的可利用来源。我们以前证明了微流体设备CTC-Chip在使用抗体包被的微柱捕获这些表达上皮细胞粘附分子(EpCAM)的细胞中的有效性。在这里,我们描述了一种高通量的微流体混合装置,人字形芯片或“ HB-Chip”,它为CTC分离提供了增强的平台。 HB-Chip设计通过微漩涡的产生将血细胞被动混合,以显着增加靶CTC与抗体包被的芯片表面之间相互作用的数量。使用限定数量的掺入对照血液中的癌细胞来验证有效的细胞捕获,并在前列腺癌患者的标本中证明其临床实用性。 15例转移疾病患者中有14例(93%)检测到CTC(中位数= 63 CTCs / mL,平均值= 386±238 CTCs / mL),并且通过RNA分离和RT可以容易地鉴定出肿瘤特异性TMPRSS2-ERG易位-PCR分析。除了免疫荧光结合抗体之外,使用透明材料还可以使用标准的临床组织病理学染色剂对捕获的四氯化碳进行成像。在一部分患者样品中,HB-Chip的低剪切设计显示了CTC的微簇,这些簇是先前未被发现的肿瘤细胞聚集体,可能有助于癌症的血源性传播。

著录项

  • 来源
  • 作者单位

    Center for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114 Shriners Hospital for Children, Harvard Medical School, Boston, MA 02114 Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114;

    rnDivision of Medical Engineering Research, National Health Research Institutes, No. 35, Keyan Road, Zhunan Town, Miaoli County, 35053, Taiwan;

    rnCenter for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114;

    rnDepartment of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114;

    rnDepartment of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114 Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114;

    rnDepartment of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114;

    rnDepartment of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114 Howard Hughes Medical Institute, Chevy Chase, MD 20815;

    rnCenter for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114;

    rnDepartment of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114;

    rnCenter for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114;

    rnCenter for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114;

    rnDepartment of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114;

    rnDepartment of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114;

    rnDepartment of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114;

    rnDepartment of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114;

    rnCenter for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114 Shriners Hospital for Children, Harvard Medical School, Boston, MA 02114 Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114;

    rnCenter for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114 Shriners Hospital for Children, Harvard Medical School, Boston, MA 02114 Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114;

    rnDepartment of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114 Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114;

    rnDepartment of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114 Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114;

    rnDepartment of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114;

    rnDepartment of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114 Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114;

    rnDepartment of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114 Howard Hughes Medical Institute, Chevy Chase, MD 20815 Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114;

    rnCenter for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114 Shriners Hospital for Children, Harvard Medical School, Boston, MA 02114 Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    microfluidics; ctcs; prostate cancer; clusters; point-of-care;

    机译:微流体ctcs;前列腺癌;集群即时护理;

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号