近日马萨诸塞州总医院（MGH）的研究人员在《美国科学院院刊》（PNAS）上发表文章称他们开发出了第二代的CTC芯片（CTC-Chip），并将其命名为HB芯片。第一代的CTC芯片是一种用于捕获罕见循环肿瘤细胞（CTCs）的设备。与第一代CTC芯片相比，第二代的HB芯片制作更为简单，且可更高效地捕获肿瘤细胞，提供全面且易于获取的数据。
马萨诸塞州总医院医学工程学中心的Shannon Stott博士说：“第一代的CTC芯片仅适用于小规模的实验室研究，而不能运用于较大的临床研究。第二代的BH芯片在保留第一代CTC-Chip性能的基础上，又增添了一些新的特征。第一代CTC芯片及过去一些最前沿的技术都无法捕捉的小循环肿瘤细胞群，如今BH芯片可以对其进行捕获。这对于我们研究的开展具有重要的意义。”
循环肿瘤细胞（CTCs）是指在血液中以极低水平存在的活实体瘤细胞。2007年马萨诸塞州总医院癌症中心和医学工程学中心开发出了第一代CTC芯片，可从血流中捕获循环肿瘤细胞，为临床决策提供了重要信息。
第一代的CTC芯片是一种基于微流体学的CTC检测技术。它在一张与标准载玻片尺寸相同的硅片上面覆盖8万个显微位点，每一个位点都包被上能够捕获CTC的抗体。当血液样品通过微流芯片时，这些位点丛确保CTC在流过芯片前捕获它们。这种设计不仅制造相对困难，成本昂贵，且显微位点周围的血流通畅性限制了与抗体覆盖位点接触的CTC数量。为了提高CTC的捕获数量，研究人员设计了一种小室流动槽，可使样品流体快速混合，显著提高捕获细胞的数量。
HB芯片在增加血液样本处理量的同时，提高了捕获罕见循环肿瘤细胞的能力。HB芯片将微芯片安装在标准载玻片上，利用标准的病理检测方法对癌细胞进行鉴别。新设备易于开启，捕获的循环肿瘤细胞还可用于其他检测或用于培育。研究人员对癌症患者血液样品进行检测证实HB芯片在CTC芯片的基础上提高了25%的癌细胞捕获率，可捕捉血液样本中超过90%的癌细胞。
HB芯片从几个患者的血液样本中捕捉出4到12个循环肿瘤细胞群，而过去捕捉的循环肿瘤细胞中从未发现此类的肿瘤细胞群。“这些细胞群有可能是从原发肿瘤处分离出来进入血液的，但也有可能是循环肿瘤细胞在循环血流中发生增殖形成的，”论文的资深作者、马萨诸塞州总医院医学工程中心BioMicroElectroMechanical系统资源中心的负责人Mehmet Toner博士说：“对这些细胞群进行进一步的研究将有助于我们深入了解肿瘤的转移过程。”
论文的共同作者、马萨诸塞州总医院癌症中心的Daniel Haber博士说：“这项新技术为我们提供了一个有力的平台对癌症转移进行更精密的研究，并可支持我们进一步地开展靶向性癌症治疗的临床研究。”（生物谷 Bioon.com）
生物谷推荐原文出处：
PNAS doi: 10.1073/pnas.1012539107
Isolation of circulating tumor cells using a microvortex-generating herringbone-chip
Shannon L. Stott a,b,c,1, Chia-Hsien Hsua,b,c,1,3, Dina I. Tsukrova, Min Yud, David T. Miyamotod,e, Belinda A. Waltmand, S. Michael Rothenbergd,f, Ajay M. Shaha, Malgorzata E. Smasd, George K. Korira, Frederick P. Floyd, Jr.a, Anna J. Gilmand, Jenna B. Lordd, Daniel Winokurd, Simeon Springerd, Daniel Irimiaa,b,c, Sunitha Nagratha,b,c, Lecia V. Sequistd,g, Richard J. Leed,g, Kurt J. Isselbacherd,2, Shyamala Maheswaranc,d, Daniel A. Haberd,f,g, and Mehmet Tonera,b,c
- Author Affiliations
aCenter for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114;
bShriners Hospital for Children, Harvard Medical School, Boston, MA 02114;
cDepartment of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114;
dMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114;
eDepartment of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114;
gDepartment of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114; and
fHoward Hughes Medical Institute, Chevy Chase, MD 20815
?3Present address: Division of Medical Engineering Research, National Health Research Institutes, No. 35, Keyan Road, Zhunan Town, Miaoli County, 35053, Taiwan.
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 microfluidic 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 microvortices 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-conjugated 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.
