近日馬薩諸塞州總醫(yī)院（MGH）的研究人員在《美國(guó)科學(xué)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(xì)胞（CTCs）的設(shè)備,。與第一代CTC芯片相比,，第二代的HB芯片制作更為簡(jiǎn)單,，且可更高效地捕獲腫瘤細(xì)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(xué)工程學(xué)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(shí)驗(yàn)室研究,，而不能運(yùn)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(chǔ)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(shù)都無法捕捉的小循環(huán)腫瘤細(xì)胞群,，如今BH芯片可以對(duì)其進(jìn)行捕獲,。這對(duì)于我們研究的開展具有重要的意義。”
循環(huán)腫瘤細(xì)胞（CTCs）是指在血液中以極低水平存在的活實(shí)體瘤細(xì)胞,。2007年馬薩諸塞州總醫(yī)院癌癥中心和醫(yī)學(xué)工程學(xué)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(xì)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(xué)的CTC檢測(cè)技術(shù),。它在一張與標(biāo)準(zhǔn)載玻片尺寸相同的硅片上面覆蓋8萬個(gè)顯微位點(diǎn)，每一個(gè)位點(diǎn)都包被上能夠捕獲CTC的抗體,。當(dāng)血液樣品通過微流芯片時(shí),，這些位點(diǎn)叢確保CTC在流過芯片前捕獲它們。這種設(shè)計(jì)不僅制造相對(duì)困難,，成本昂貴,，且顯微位點(diǎn)周圍的血流通暢性限制了與抗體覆蓋位點(diǎn)接觸的CTC數(shù)量。為了提高CTC的捕獲數(shù)量,，研究人員設(shè)計(jì)了一種小室流動(dòng)槽,，可使樣品流體快速混合，顯著提高捕獲細(xì)胞的數(shù)量,。
HB芯片在增加血液樣本處理量的同時(shí),，提高了捕獲罕見循環(huán)腫瘤細(xì)胞的能力。HB芯片將微芯片安裝在標(biāo)準(zhǔn)載玻片上,，利用標(biāo)準(zhǔn)的病理檢測(cè)方法對(duì)癌細(xì)胞進(jìn)行鑒別,。新設(shè)備易于開啟，捕獲的循環(huán)腫瘤細(xì)胞還可用于其他檢測(cè)或用于培育,。研究人員對(duì)癌癥患者血液樣品進(jìn)行檢測(cè)證實(shí)HB芯片在CTC芯片的基礎(chǔ)上提高了25%的癌細(xì)胞捕獲率,，可捕捉血液樣本中超過90%的癌細(xì)胞。
HB芯片從幾個(gè)患者的血液樣本中捕捉出4到12個(gè)循環(huán)腫瘤細(xì)胞群,，而過去捕捉的循環(huán)腫瘤細(xì)胞中從未發(fā)現(xiàn)此類的腫瘤細(xì)胞群,。“這些細(xì)胞群有可能是從原發(fā)腫瘤處分離出來進(jìn)入血液的，但也有可能是循環(huán)腫瘤細(xì)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(xué)工程中心BioMicroElectroMechanical系統(tǒng)資源中心的負(fù)責(zé)人Mehmet Toner博士說：“對(duì)這些細(xì)胞群進(jìn)行進(jìn)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(xiàng)新技術(shù)為我們提供了一個(gè)有力的平臺(tái)對(duì)癌癥轉(zhuǎn)移進(jìn)行更精密的研究,，并可支持我們進(jìn)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.
