近日馬薩諸塞州總醫(yī)院（MGH）的研究人員在《美國科學院院刊》（PNAS）上發(fā)表文章稱他們開發(fā)出了第二代的CTC芯片（CTC-Chip）,，并將其命名為HB芯片。第一代的CTC芯片是一種用于捕獲罕見循環(huán)腫瘤細胞（CTCs）的設備,。與第一代CTC芯片相比,，第二代的HB芯片制作更為簡單，且可更高效地捕獲腫瘤細胞,，提供全面且易于獲取的數(shù)據(jù),。
馬薩諸塞州總醫(yī)院醫(yī)學工程學中心的Shannon Stott博士說：“第一代的CTC芯片僅適用于小規(guī)模的實驗室研究，而不能運用于較大的臨床研究,。第二代的BH芯片在保留第一代CTC-Chip性能的基礎上,，又增添了一些新的特征。第一代CTC芯片及過去一些最前沿的技術都無法捕捉的小循環(huán)腫瘤細胞群,，如今BH芯片可以對其進行捕獲,。這對于我們研究的開展具有重要的意義。”
循環(huán)腫瘤細胞（CTCs）是指在血液中以極低水平存在的活實體瘤細胞,。2007年馬薩諸塞州總醫(yī)院癌癥中心和醫(yī)學工程學中心開發(fā)出了第一代CTC芯片,，可從血流中捕獲循環(huán)腫瘤細胞，為臨床決策提供了重要信息,。
第一代的CTC芯片是一種基于微流體學的CTC檢測技術,。它在一張與標準載玻片尺寸相同的硅片上面覆蓋8萬個顯微位點，每一個位點都包被上能夠捕獲CTC的抗體,。當血液樣品通過微流芯片時,，這些位點叢確保CTC在流過芯片前捕獲它們,。這種設計不僅制造相對困難，成本昂貴,，且顯微位點周圍的血流通暢性限制了與抗體覆蓋位點接觸的CTC數(shù)量,。為了提高CTC的捕獲數(shù)量，研究人員設計了一種小室流動槽,，可使樣品流體快速混合,，顯著提高捕獲細胞的數(shù)量。
HB芯片在增加血液樣本處理量的同時,，提高了捕獲罕見循環(huán)腫瘤細胞的能力,。HB芯片將微芯片安裝在標準載玻片上，利用標準的病理檢測方法對癌細胞進行鑒別,。新設備易于開啟,，捕獲的循環(huán)腫瘤細胞還可用于其他檢測或用于培育。研究人員對癌癥患者血液樣品進行檢測證實HB芯片在CTC芯片的基礎上提高了25%的癌細胞捕獲率,，可捕捉血液樣本中超過90%的癌細胞,。
HB芯片從幾個患者的血液樣本中捕捉出4到12個循環(huán)腫瘤細胞群，而過去捕捉的循環(huán)腫瘤細胞中從未發(fā)現(xiàn)此類的腫瘤細胞群,。“這些細胞群有可能是從原發(fā)腫瘤處分離出來進入血液的,，但也有可能是循環(huán)腫瘤細胞在循環(huán)血流中發(fā)生增殖形成的，”論文的資深作者,、馬薩諸塞州總醫(yī)院醫(yī)學工程中心BioMicroElectroMechanical系統(tǒng)資源中心的負責人Mehmet Toner博士說：“對這些細胞群進行進一步的研究將有助于我們深入了解腫瘤的轉(zhuǎn)移過程,。”
論文的共同作者、馬薩諸塞州總醫(yī)院癌癥中心的Daniel Haber博士說：“這項新技術為我們提供了一個有力的平臺對癌癥轉(zhuǎn)移進行更精密的研究,，并可支持我們進一步地開展靶向性癌癥治療的臨床研究,。”（生物谷 Bioon.com）
生物谷推薦原文出處：
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.
