Highly efficient capture of circulating tumor cells by using nanostructured silicon substrates with integrated chaotic micromixers.
Highly efficient capture of circulating tumor cells by using nanostructured silicon substrates with integrated chaotic micromixers.
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DOI：
10.1002/anie.201005853
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发表时间：
2011-03-21
影响因子：
16.6
通讯作者：
Tseng, Hsian-Rong
中科院分区：
文献类型：
--
作者：
Wang, Shutao;Liu, Kan;Liu, Jian;Yu, Zeta T. -F.;Xu, Xiaowen;Zhao, Libo;Lee, Tom;Lee, Eun Kyung;Reiss, Jean;Lee, Yi-Kuen;Chung, Leland W. K.;Huang, Jiaoti;Rettig, Matthew;Seligson, David;Duraiswamy, Kumaran N.;Shen, Clifton K. -F.;Tseng, Hsian-Rong
转移是实体瘤患者癌症相关死亡的最常见原因。[1-4]大量证据表明，在恶性进展的早期阶段，肿瘤细胞从原发肿瘤块脱落。[5-7]这些“脱离”循环肿瘤细胞（ctc）[8-11]进入血液并进入身体的不同组织，是癌症转移的关键途径。目前确定肿瘤状态的金标准需要侵入性活检和随后的活检样本的遗传和蛋白质组学分析。另外，CTC的测量和分析可以被视为肿瘤的“液体活检”，在关键窗口提供对肿瘤生物学的深入了解，干预实际上可以产生影响。然而，由于血液中ctc的数量极低，ctc的检测和表征在技术上一直具有挑战性。ctc通常存在于转移性癌症患者的血液中，最多只有数百个cellsmLÀ1，而普通血细胞则大量存在（bbb109个细胞mLÀ1）。在过去的十年中，各种各样的技术[8,12 - 17]不断发展，以应对从患者血液样本中计数和分离ctc的挑战。许多方法采用不同的富集机制，如基于捕集剂标记磁珠的免疫磁分离[8,16]，基于微流体的技术[12,14,17]，增强细胞表面接触，以及基于尺寸差异分离ctc的微过滤装置[13]。这些新兴技术的敏感性依赖于ctc的富集程度，这对于检测早期癌症进展（如肿瘤侵犯血管系统）的临床应用至关重要。最近，我们发现一种涂有癌细胞捕获剂（即上皮细胞粘附分子抗体，抗epcam）的3d纳米结构底物[18]，由于其增强了硅纳米柱（SiNP）底物与纳米级细胞表面成分（如微绒毛和丝状足）之间的局部地形相互作用[21]，其细胞捕获效率显著提高[19,20]。这种高亲和力的细胞测定可用于在固定设备设置中从加标的全血样本中恢复癌细胞，细胞捕获效率从40%到70%不等。在这种固定细胞捕获实验的基础上，我们预计通过增加细胞-底物接触频率可以进一步提高细胞捕获性能。通过将一个简单但功能强大的流体处理系统，即混沌混合通道[22]与有图案的纳米结构衬底相结合，可以通过增强细胞-衬底接触频率和亲和力的协同效应来实现高效的CTC捕获。虽然有几种微流控平台[12,14,17]能够提高ctc捕获效率，但基于微柱的ctc捕获技术[12,17]存在景深问题，因此需要多次横截面成像扫描，以避免由于设备固定的ctc的垂直深度而导致图像失焦或重叠
Metastases are the most common cause of cancer-related death in patients with solid tumors.[1–4] A considerable body of evidence indicates that tumor cells are shed from a primary tumor mass at the earliest stages of malignant progression.[5–7] These “break-away” circulating tumor cells (CTCs)[8–11] enter the blood stream and travel to different tissues of the body, as a critical route for cancer metastasis. The current gold standard for determining tumor status requires invasive biopsy and subsequent genetic and proteomic analysis of biopsy samples. Alternatively, CTC measurement and analysis can be regarded as a “liquid biopsy” of the tumor, providing insight into tumor biology in the critical window where intervention could actually make a difference. However, detection and characterization of CTCs has been technically challenging owing to their extremely low number in the bloodstream. CTCs are often found in the blood of patients with metastatic cancer, in only up to hundreds of cellsmLÀ1, whereas common blood cells exist in high numbers (> 109 cells mLÀ1). Over the past decade, a diverse suite of technologies [8, 12–17] have been evolving to meet the challenge of counting and isolating CTCs from patient blood samples. Many employ different enrichment mechanisms, such as immunomagnetic separation based on captureagent-labeled magnetic beads,[8, 16] microfluidics-based technologies [12, 14, 17] that enhance cell-surface contacts, and microfilter devices [13] that isolate CTCs based on size difference. The sensitivity of these emerging technologies, which is critical to their clinical utility for detecting early cancer progression (eg, tumor invasion of vascular systems), relies on the degree of enrichment of CTCs. Recently, we discovered that a 3D-nanostructured substrate [18] coated with cancer-cell capture agents [19, 20](ie, epithelial cell adhesion molecule antibody, anti-EpCAM) exhibits significantly improved cell-capture efficiency owing to its enhanced local topographic interactions [21] between the silicon nanopillar (SiNP) substrates and nanoscale cellular surface components (eg, microvilli and filopodia). Such a high-affinity cell assay can be employed to recover cancer cells from spiked whole-blood samples, in a stationary device setting,[18] with cell-capture efficiency ranging from 40 to 70%. On the basis of this stationary cell-capture assay, we anticipated that further improvement of cell-capture performance can be achieved by increasing cell–substrate contact frequency. By integrating a simple but powerful fluidic handling system, namely a chaotic mixing channel,[22] with a patterned nanostructured substrate, highly efficient CTC capture can be realized by the synergistic effects of enhanced cell–substrate contact frequency as well as affinity. Although there are several microfluidic platforms [12, 14, 17] capable of achieving improved CTC-capture efficiency, the micropillarbased CTC-capture technologies [12, 17] suffer from depth of field issues thus requiring multiple cross-sectional imaging scans to avoid out-of-focus or superimposed images of deviceimmobilized CTCs because of to the vertical depth of the
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影响因子：
158.5
作者：
Cristofanilli, M;Budd, GT;Hayes, DF
通讯作者：
Hayes, DF
影响因子：
16.6
作者：
Liu, Jian;Williams, Brian A.;Quake, Stephen
通讯作者：
Quake, Stephen
影响因子：
10.8
作者：
Fischer KE;Alemán BJ;Tao SL;Hugh Daniels R;Li EM;Bünger MD;Nagaraj G;Singh P;Zettl A;Desai TA
通讯作者：
Desai TA
影响因子：
15
作者：
Adams, Andre A.;Okagbare, Paul I.;Soper, Steven A.
通讯作者：
Soper, Steven A.
影响因子：
3.9
作者：
Murthy, SK;Sin, A;Toner, M
通讯作者：
Toner, M