Highly Efficient Capture of Circulating Tumor Cells by Using Nanostructured Silicon Substrates with Integrated Chaotic Micromixers

Wang, Shutao; Liu, Kan; Liu, Jian; Yu, Zeta Tak For; Xu, Xiaowen; Zhao, Libo; Lee, Tom; Lee, Eun Kyung; Reiss, Jean; Lee, Yi-Kuen; Chung, Leland W.K.; Huang, Jiaoti; Rettig, Matthew B.; Seligson, David B.; Duraiswamy, Kumaran N.; Shen, Clifton K.‐F.; Tseng, Hsian‐Rong

doi:10.1002/anie.201005853

Cited by 585 publications

(485 citation statements)

References 35 publications

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“…Examples of microfluidic approaches include micropillar arrays [9,16,17], chaotic mixers [18,19], filters [20,21], and devices with other micro-and nanostructured surfaces [22][23][24][25][26]. Of those techniques that are capable of processing whole blood, immunocapture methods have shown the greatest potential for capturing rare cancer cells with high efficiency (62-95%) [16][17][18][19]. Studies that used the epithelial cell-adhesion molecule (EpCAM) to capture lung, prostate, pancreatic, and colorectal CTCs have reported a wide range of capture purities (9-67%) [16,18,19].…”

Section: Introductionmentioning

confidence: 99%

Characterization of a hybrid dielectrophoresis and immunocapture microfluidic system for cancer cell capture

Huang

Santana

et al. 2013

Electrophoresis

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The capture of circulating tumor cells (CTCs) from cancer patient blood enables early clinical assessment as well as genetic and pharmacological evaluation of cancer and metastasis. Although there have been many microfluidic immunocapture and electrokinetic techniques developed for isolating rare cancer cells, these techniques are often limited by a capture performance tradeoff between high efficiency and high purity. We present the characterization of shear-dependent cancer cell capture in a novel hybrid dielectrophoresis (DEP)-immunocapture system consisting of interdigitated electrodes fabricated in a Hele-Shaw flow cell that was functionalized with a monoclonal antibody, J591, which is highly specific to prostate-specific membrane antigen (PSMA)-expressing prostate cancer cells. We measured the positive and negative DEP response of a prostate cancer cell line, LNCaP, as a function of applied electric field frequency, and showed that DEP can control capture performance by promoting or preventing cell interactions with immunocapture surfaces, depending on the sign and magnitude of the applied DEP force, as well as on the local shear stress experienced by cells flowing in the device. This work demonstrates that DEP and immunocapture techniques can work synergistically to improve cell capture performance, and it will aid in the design of future hybrid DEP-immunocapture systems for highefficiency CTC capture with enhanced purity.

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Section: Introductionmentioning

confidence: 99%

Characterization of a hybrid dielectrophoresis and immunocapture microfluidic system for cancer cell capture

Huang

Santana

et al. 2013

Electrophoresis

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“…Microfabrication-assisted technology, using microscale arrays of round or rectangular posts, channels, or other simple patterns, has the potential to solve this problem (17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27). Here, we focused on the mechanical properties of cancer cells in designing a unique cell purification system for the purpose of generating subpopulations enriched in highly deformable cells.…”

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confidence: 99%

Microfluidics separation reveals the stem-cell–like deformability of tumor-initiating cells

Zhang

Kai

Choi

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

192

172

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Here we report a microfluidics method to enrich physically deformable cells by mechanical manipulation through artificial microbarriers. Driven by hydrodynamic forces, flexible cells or cells with high metastatic propensity change shape to pass through the microbarriers and exit the separation device, whereas stiff cells remain trapped. We demonstrate the separation of (i) a mixture of two breast cancer cell types (MDA-MB-436 and MCF-7) with distinct deformabilities and metastatic potentials, and (ii) a heterogeneous breast cancer cell line (SUM149), into enriched flexible and stiff subpopulations. We show that the flexible phenotype is associated with overexpression of multiple genes involved in cancer cell motility and metastasis, and greater mammosphere formation efficiency. Our observations support the relationship between tumor-initiating capacity and cell deformability, and demonstrate that tumor-initiating cells are less differentiated in terms of cell biomechanics.cell mechanics | cytoskeleton | genomic profiling C ell deformability is commonly measured using magnetic twisting cytometry, particle tracking rheometry, optical tweezers, micropipette aspiration, atomic force microscope, and other derivative cell stretching or poking methods (1-4). Applications of these methods to stem cells have revealed the greater deformability of the cytoskeleton and nucleoskeleton in less differentiated cells, whereby deformability generally decreases during differentiation to mature cells (5-8). Research on cancer cell deformability has also consistently revealed that increased deformability is correlated with increased metastatic potential (9-15).Despite the success achieved using cell deformability measurements, isolation of cells with differential deformabilities remains a great challenge (10, 16). Microfabrication-assisted technology, using microscale arrays of round or rectangular posts, channels, or other simple patterns, has the potential to solve this problem (17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27). Here, we focused on the mechanical properties of cancer cells in designing a unique cell purification system for the purpose of generating subpopulations enriched in highly deformable cells. We used microfabrication technology and obtained a subpopulation of SUM149 breast cancer cells with stem-cell-like deformability and mammosphere formation capability.The separation device, a mechanical separation chip (MS-chip), employs artificial microbarriers in combination with hydrodynamic force to separate deformable from stiff cells (Fig. 1A). Both the microbarrier structures and the fluidic parameters are essential to the cell-enrichment process. The most notable feature of the device is the precise placement of the microbarriers to impede the passage of stiff cells. Published in vivo observations suggest that the minimum crossable barrier for cancer cells is ∼8 μm or less (28,29). Here, we took those barrier dimensions into account in designing the MSchip to separate cells based on perfusion through constrictions. As...

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“…Poly(amidoamine) dendrimers and silicon nanowires have previously given a nanostructured surface enhancing cancer cell capture (39,40). Polymeric "tentacles" of DNA aptamers also showed promise for rare cell isolation (41).…”

Section: Discussionmentioning

confidence: 99%

SpyLigase peptide–peptide ligation polymerizes affibodies to enhance magnetic cancer cell capture

Fierer

Veggiani

Howarth

2014

Proc. Natl. Acad. Sci. U.S.A.

156

162

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Individual proteins can now often be modified with atomic precision, but there are still major obstacles to connecting proteins into larger assemblies. To direct protein assembly, ideally, peptide tags would be used, providing the minimal perturbation to protein function. However, binding to peptides is generally weak, so assemblies are unstable over time and disassemble with force or harsh conditions. We have recently developed an irreversible protein-peptide interaction (SpyTag/SpyCatcher), based on a protein domain from Streptococcus pyogenes, that locks itself together via spontaneous isopeptide bond formation. Here we develop irreversible peptide-peptide interaction, through redesign of this domain and genetic dissection into three parts: a protein domain termed SpyLigase, which now ligates two peptide tags to each other. All components expressed efficiently in Escherichia coli and peptide tags were reactive at the N terminus, at the C terminus, or at internal sites. Peptide-peptide ligation enabled covalent and site-specific polymerization of affibodies or antibodies against the tumor markers epidermal growth factor receptor (EGFR) and HER2. Magnetic capture of circulating tumor cells (CTCs) is one of the most promising approaches to improve cancer prognosis and management, but CTC capture is limited by inefficient recovery of cells expressing low levels of tumor antigen. SpyLigase-assembled protein polymers made possible the isolation of cancerous cells expressing lower levels of tumor antigen and should have general application in enhancing molecular capture.bionanotechnology | synthetic biology | metastasis | antibody | nanobiotechnology

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Highly Efficient Capture of Circulating Tumor Cells by Using Nanostructured Silicon Substrates with Integrated Chaotic Micromixers

Cited by 585 publications

References 35 publications

Characterization of a hybrid dielectrophoresis and immunocapture microfluidic system for cancer cell capture

Characterization of a hybrid dielectrophoresis and immunocapture microfluidic system for cancer cell capture

Microfluidics separation reveals the stem-cell–like deformability of tumor-initiating cells

SpyLigase peptide–peptide ligation polymerizes affibodies to enhance magnetic cancer cell capture

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