Journal Home > Volume 11 , Issue 5
Nano Research 2018, 11(5): 2592-2604 https://doi.org/10.1007/s12274-017-1885-8
Research Article | Issue | Published: 12 May 2018

Programmable DNA-responsive microchip for the capture and release of circulating tumor cells by nucleic acid hybridization

Show Author's Information Shan Guo1,§,  Haiyan Huang1,§,  Xujing Deng2,  Yuqi Chen1,  Zhuoran Jiang1,  Min Xie3,  Songmei Liu2,  Weihua Huang3( ),  Xiang Zhou1( )
College of Chemistry and Molecular Sciencesthe Institute for Advanced Studies of Wuhan University, Hubei Province Key Laboratory of Allergy and Immunology, Wuhan UniversityWuhan430072China
Zhongnan HospitalWuhan UniversityWuhan430072China
Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education)College of Chemistry and Molecular Sciences, Wuhan UniversityWuhan430072China

§ Shan Guo and Haiyan Huang contributed equally to this work.

Keywords:
aptamer, DNA-responsive microchip, hierarchical architecture, circulating tumor cells (CTCs), capture, release, nucleic acid hybridization
Cite this article:
Guo S, Huang H, Deng X, et al. Programmable DNA-responsive microchip for the capture and release of circulating tumor cells by nucleic acid hybridization. Nano Research, 2018, 11(5): 2592-2604. https://doi.org/10.1007/s12274-017-1885-8
Download citation
EndNote(RIS)
BibTeX

577

Views

15

Downloads

Citations

34

Crossref

N/A

WoS

34

Scopus

2

CSCD

Abstract Full text Electronic supplementary material About this article

The detection and analysis of circulating tumor cells (CTCs) from patients′ blood is important to assess tumor status; however, it remains a challenge. In the present study, we developed a programmable DNA-responsive microchip for the highly efficient capture and nondestructive release of CTCs via nucleic acid hybridization. Transparent and patternable substrates with hierarchical architectures were integrated into the microchip with herringbone grooves, resulting in greatly enhanced cell-surface interaction via herringbone micromixers, more binding sites, and better matched topographical interactions. In combination with a high-affinity aptamer, target cancer cells were specifically and efficiently captured on the chip. Captured cancer cells were gently released from the chip under physiological conditions using toehold-mediated strand displacement, without any destructive factors for cells or substrates. More importantly, aptamer-containing DNA sequences on the surface of the retrieved cancer cells could be further amplified by polymerase chain reaction (PCR), facilitating the detection of cell surface biomarkers and characterization of the CTCs. Furthermore, this system was extensively applied to the capture and release of CTCs from patients′ blood samples, demonstrating a promising high-performance platform for CTC enrichment, release, and characterization.


menu
Abstract
Full text
Outline
Electronic supplementary material
About this article

Programmable DNA-responsive microchip for the capture and release of circulating tumor cells by nucleic acid hybridization

Show Author's information Shan Guo1,§, Haiyan Huang1,§, Xujing Deng2, Yuqi Chen1, Zhuoran Jiang1, Min Xie3, Songmei Liu2, Weihua Huang3( ), Xiang Zhou1( )
College of Chemistry and Molecular Sciencesthe Institute for Advanced Studies of Wuhan University, Hubei Province Key Laboratory of Allergy and Immunology, Wuhan UniversityWuhan430072China
Zhongnan HospitalWuhan UniversityWuhan430072China
Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education)College of Chemistry and Molecular Sciences, Wuhan UniversityWuhan430072China

§ Shan Guo and Haiyan Huang contributed equally to this work.

Abstract

The detection and analysis of circulating tumor cells (CTCs) from patients′ blood is important to assess tumor status; however, it remains a challenge. In the present study, we developed a programmable DNA-responsive microchip for the highly efficient capture and nondestructive release of CTCs via nucleic acid hybridization. Transparent and patternable substrates with hierarchical architectures were integrated into the microchip with herringbone grooves, resulting in greatly enhanced cell-surface interaction via herringbone micromixers, more binding sites, and better matched topographical interactions. In combination with a high-affinity aptamer, target cancer cells were specifically and efficiently captured on the chip. Captured cancer cells were gently released from the chip under physiological conditions using toehold-mediated strand displacement, without any destructive factors for cells or substrates. More importantly, aptamer-containing DNA sequences on the surface of the retrieved cancer cells could be further amplified by polymerase chain reaction (PCR), facilitating the detection of cell surface biomarkers and characterization of the CTCs. Furthermore, this system was extensively applied to the capture and release of CTCs from patients′ blood samples, demonstrating a promising high-performance platform for CTC enrichment, release, and characterization.

Keywords: aptamer, DNA-responsive microchip, hierarchical architecture, circulating tumor cells (CTCs), capture, release, nucleic acid hybridization

References(45)

1

Alix-Panabières, C.; Pantel, K. Challenges in circulating tumour cell research. Nat. Rev. Cancer 2014, 14, 623-631.
DOI Google Scholar
2

Paterlini-Brechot, P.; Benali, N. L. Circulating tumor cells (CTC) detection: Clinical impact and future directions. Cancer Lett. 2007, 253, 180-204.
DOI Google Scholar
3

Park, J. M.; Lee, J. Y.; Lee, J. G.; Jeong, H.; Oh, J. M.; Kim, Y. J.; Park, D.; Kim, M. S.; Lee, H. J.; Oh, J. H. et al. Highly efficient assay of circulating tumor cells by selective sedimentation with a density gradient medium and microfiltration from whole blood. Anal. Chem. 2012, 84, 7400-7407.
DOI Google Scholar
4

Seal, S. H. A sieve for the isolation of cancer cells and other large cells from the blood. Cancer 1964, 17, 637-642.
DOI
5

Lee, H. J.; Oh, J. H.; Oh, J. M.; Park, J. M.; Lee, J. G.; Kim, M. S.; Kim, Y. J.; Kang, H. J.; Jeong, J.; Kim, S. I. et al. Efficient isolation and accurate in situ analysis of circulating tumor cells using detachable beads and a high-pore-density filter. Angew. Chem., Int. Ed. 2013, 52, 8337-8340.
DOI Google Scholar
6

Tang, Y. D.; Shi, J.; Li, S. S.; Wang, L.; Cayre, Y. E.; Chen, Y. Microfluidic device with integrated microfilter of conical-shaped holes for high efficiency and high purity capture of circulating tumor cells. Sci. Rep. 2014, 4, 6052.
DOI Google Scholar
7

Cristofanilli, M.; Budd, G. T.; Ellis, M. J.; Stopeck, A.; Matera, J.; Miller, M. C.; Reuben, J. M.; Doyle, G. V.; Allard, W. J.; Terstappen, L. W. et al. Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N. Engl. J. Med. 2004, 351, 781-791.
DOI Google Scholar
8

Wen, C. Y.; Wu, L. L.; Zhang, Z. L.; Liu, Y. L.; Wei, S. Z.; Hu, J.; Tang, M.; Sun, E. Z.; Gong, Y. P.; Yu, J. et al. Quick-response magnetic nanospheres for rapid, efficient capture and sensitive detection of circulating tumor cells. ACS Nano 2014, 8, 941-949.
DOI Google Scholar
9

Xie, M.; Lu, N. N.; Cheng, S. B.; Wang, X. Y.; Wang, M.; Guo, S.; Wen, C. Y.; Hu, J.; Pang, D. W.; Huang, W. H. Engineered decomposable multifunctional nanobioprobes for capture and release of rare cancer cells. Anal. Chem. 2014, 86, 4618-4626.
DOI Google Scholar
10

Wang, S. T.; Wang, H.; Jiao, J.; Chen, K. J.; Owens, G. E.; Kamei, K.; Sun, J.; Sherman, D. J.; Behrenbruch, C. P.; Wu, H. et al. Three-dimensional nanostructured substrates toward efficient capture of circulating tumor cells. Angew. Chem., Int. Ed. 2009, 48, 8970-8973.
DOI Google Scholar
11

Zhang, N. G.; Deng, Y. L.; Tai, Q. D.; Cheng, B. R.; Zhao, L. B.; Shen, Q. L.; He, R. X.; Hong, L. Y.; Liu, W.; Guo, S. S. et al. Electrospun TiO2 nanofiber-based cell capture assay for detecting circulating tumor cells from colorectal and gastric cancer patients. Adv. Mater. 2012, 24, 2756-2760.
DOI Google Scholar
12

Nagrath, S.; Sequist, L. V.; Maheswaran, S.; Bell, D. W.; Irimia, D.; Ulkus, L.; Smith, M. R.; Kwak, E. L.; Digumarthy, S.; Muzikansky, A. et al. Isolation of rare circulating tumour cells in cancer patients by microchip technology. Nature 2007, 450, 1235-1239.
DOI Google Scholar
13

Stott, S. L.; Hsu, C. H.; Tsukrov, D. I.; Yu, M.; Miyamoto, D. T.; Waltman, B. A.; Rothenberg, S. M.; Shah, A. M.; Smas, M. E.; Korir, G. K. et al. Isolation of Circulating tumor cells using a microvortex-generating herringbone-chip. Proc. Natl. Acad. Sci. USA 2010, 107, 18392-18397.
DOI Google Scholar
14

Wang, S. T.; Liu, K.; Liu, J.; Yu, Z. T. F.; Xu, X. W.; Zhao, L. B.; Lee, T.; Lee, E. K.; Reiss, J.; Lee, Y. K. et al. Highly efficient capture of circulating tumor cells by using nanostructured silicon substrates with integrated chaotic micromixers. Angew. Chem., Int. Ed. 2011, 50, 3084-3088.
DOI Google Scholar
15

Yoon, H. J.; Kim, T. H.; Zhang, Z.; Azizi, E.; Pham, T. M.; Paoletti, C.; Lin, J.; Ramnath, N.; Wicha, M. S.; Hayes, D. F. et al. Sensitive capture of circulating tumour cells by functionalized graphene oxide nanosheets. Nat. Nanotechnol. 2013, 8, 735-741.
DOI Google Scholar
16

Shen, Q. L.; Xu, L.; Zhao, L. B.; Wu, D. X.; Fan, Y. S.; Zhou, Y. L.; Ouyang, W. H.; Xu, X. C.; Zhang, Z.; Song, M. et al. Specific capture and release of circulating tumor cells using aptamer-modified nanosubstrates. Adv. Mater. 2013, 25, 2368-2373.
DOI Google Scholar
17

Sheng, W. A.; Chen, T.; Tan, W. H.; Fan, Z. H. Multivalent DNA nanospheres for enhanced capture of cancer cells in microfluidic devices. ACS Nano 2013, 7, 7067-7076.
DOI Google Scholar
18

Park, M. H.; Reátegui, E.; Li, W.; Tessier, S. N.; Wong, K. H. K.; Jensen, A. E.; Thapar, V.; Ting, D.; Toner, M.; Stott, S. L. et al. Enhanced isolation and release of circulating tumor cells using nanoparticle binding and ligand exchange in a microfluidic chip. J. Am. Chem. Soc. 2017, 139, 2741-2749.
DOI Google Scholar
19

Cheng, S. B.; Xie, M.; Xu, J. Q.; Wang, J.; Lv, S. W.; Guo, S.; Shu, Y.; Wang, M.; Dong, W. G.; Huang. W. H. High-efficiency capture of individual and cluster of circulating tumor cells by a microchip embedded with three-dimensional poly(dimethylsiloxane) scaffold. Anal. Chem. 2016, 88, 6773-6780.
DOI Google Scholar
20

Adams, A. A.; Okagbare, P. I.; Feng, J.; Hupert, M. L.; Patterson, D.; Göttert, J.; McCarley, R. L.; Nikitopoulos, D.; Murphy, M. C.; Soper, S. A. Highly efficient circulating tumor cell isolation from whole blood and label-free enumeration using polymer-based microfluidics with an integrated conductivity sensor. J. Am. Chem. Soc. 2008, 130, 8633-8641.
DOI Google Scholar
21

Labib, M.; Green, B.; Mohamadi, R. M.; Mepham, A.; Ahmed, S. U.; Mahmoudian, L.; Chang, I. H.; Sargent, E. H.; Kelley S. O. Aptamer and antisense-mediated two-dimensional isolation of specific cancer cell subpopulations. J. Am. Chem. Soc. 2016, 138, 2476-2479.
DOI Google Scholar
22

Song, Y. L.; Zhu, Z.; An, Y.; Zhang, W. T.; Zhang, H. M.; Liu, D.; Yu, C. D.; Duan, W.; Yang, C. J. Selection of DNA aptamers against epithelial cell adhesion molecule for cancer cell imaging and circulating tumor cell capture. Anal. Chem. 2013, 85, 4141-4149.
DOI Google Scholar
23

Wan, Y.; Liu, Y. L.; Allen, P. B.; Asghar, W.; Mahmood, M. A. I.; Tan, J. F.; Duhon, H.; Kim, Y. T.; Ellingtone A. D.; Iqbal, S. M. Capture, isolation and release of cancer cells with aptamer-functionalized glass bead array. Lab Chip 2012, 12, 4693-4701.
DOI Google Scholar
24

Fang, S.; Wang, C.; Xiang, J.; Cheng, L.; Song, X. J.; Xu, L. G.; Peng, R.; Liu, Z. Aptamer-conjugated upconversion nanoprobes assisted by magnetic separation for effective isolation and sensitive detection of circulating tumor cells. Nano Res. 2014, 7, 1327-1336.
DOI Google Scholar
25

Qiu, J. C.; Zhao, K.; Li, L. L.; Yu, X.; Guo, W. B.; Wang, S.; Zhang, X. D.; Pan, C. F.; Wang, Z. L.; Liu, H. A titanium dioxide nanorod array as a high-affinity nano-bio interface of a microfluidic device for efficient capture of circulating tumor cells. Nano Res. 2017, 10, 776-784.
DOI Google Scholar
26

Wu, L.; Ji, H. W.; Guan, Y. J.; Ran, X.; Ren, J. S.; Qu, X. G. A graphene-based chemical nose/tongue approach for the identification of normal, cancerous and circulating tumor cells. NPG Asia Mater. 2017, 9, e356.
DOI Google Scholar
27

Wang, Z. L.; Sun, N.; Liu, M.; Cao, Y.; Wang, K. W.; Wang, J. E.; Pei, R. J. Multifunctional nanofibers for specific purification and release of CTCs. ACS Sens. 2017, 2, 547-552.
DOI Google Scholar
28

Zhang, P. C.; Chen, L.; Xu, T. L.; Liu, H. L.; Liu, X. L.; Meng, J. X.; Yang, G.; Jiang, L.; Wang, S. T. Programmable fractal nanostructured interfaces for specific recognition and electrochemical release of cancer cells. Adv. Mater. 2013, 25, 3566-3570.
DOI Google Scholar
29

Zhang, F. L.; Jiang, Y.; Liu, X. L.; Meng, J. X.; Zhang, P. C.; Liu, H. L.; Yang, G.; Li, G. N.; Jiang, L.; Wan, L. J. et al. Hierarchical nanowire arrays as three-dimensional fractal nanobiointerfaces for high efficient capture of cancer cells. Nano Lett. 2016, 16, 766-772.
DOI Google Scholar
30

Meng, J. X.; Zhang, P. C.; Zhang, F. L.; Liu, H. L.; Fan, J. B.; Liu, X. L.; Yang, G.; Jiang, L.; Wang, S. T. A Self-cleaning TiO2 nanosisal-like coating toward disposing nanobiochips of cancer detection. ACS Nano 2015, 9, 9284-9291.
DOI Google Scholar
31

Guo, S.; Xu, J. Q.; Xie, M.; Huang, W.; Yuan, E. F.; Liu, Y.; Fan, L. P.; Cheng, S. B.; Liu, S. M.; Wang, F. B. et al. Degradable zinc-phosphate-based hierarchical nanosubstrates for capture and release of circulating tumor cells. ACS Appl. Mater. Interfaces 2016, 8, 15917-15925.
DOI Google Scholar
32

Zhang, L. Q.; Wan, S.; Jiang, Y.; Wang, Y. Y.; Fu, T.; Liu, Q. L.; Cao, Z. J.; Qiu, L. P.; Tan, W. H. Molecular elucidation of disease biomarkers at the interface of chemistry and biology. J. Am. Chem. Soc. 2017, 139, 2532-2540.
DOI Google Scholar
33

Lv, S. W.; Wang, J.; Xie, M.; Lu, N. N.; Li, Z.; Yan, X. W.; Cai, S. L.; Zhang, P. A.; Dong, W. G.; Huang, W. H. Photoresponsive immunomagnetic nanocarrier for capture and release of rare circulating tumor cells. Chem. Sci. 2015, 6, 6432-6438.
DOI Google Scholar
34

Li, W.; Wang, J. S.; Ren, J. S.; Qu, X. G. Near-infrared upconversion controls photocaged cell adhesion. J. Am. Chem. Soc. 2014, 136, 2248-2251.
DOI Google Scholar
35

Jeon, S.; Moon, J. M.; Lee, E. S.; Kim, Y. H.; Cho, Y. An electroactive biotin-doped polypyrrole substrate that immobilizes and releases EpCAM-positive cancer cells. Angew. Chem., Int. Ed. 2014, 53, 4597-4602.
DOI Google Scholar
36

Reátegui, E.; Aceto, N.; Lim, E. J.; Sullivan, J. P.; Jensen, A. E.; Zeinali, M.; Martel, J. M.; Aranyosi, A. J.; Li, W.; Castleberry, S. et al. Tunable nanostructured coating for the capture and selective release of viable circulating tumor cells. Adv. Mater. 2015, 27, 1593-1599.
DOI Google Scholar
37

Hou, S.; Zhao, H. C.; Zhao, L. B.; Shen, Q. L.; Wei, K. S.; Suh, D. Y.; Nakao, A.; Garcia, M. A.; Song, M.; Lee, T. et al. Capture and stimulated release of circulating tumor cells on polymer-grafted silicon nanostructures. Adv. Mater. 2013, 25, 1547-1551.
DOI Google Scholar
38

Lv, S. W.; Liu, Y.; Xie, M.; Wang, J.; Yan, X. W.; Li, Z.; Dong, W. G.; Huang, W. H. Near-infrared light-responsive hydrogel for specific recognition and photothermal site-release of circulating tumor cells. ACS Nano 2016, 10, 6201-6210.
DOI Google Scholar
39

Huang, Q. Q.; Chen, B. L.; He, R. X.; He, Z. B.; Cai, B.; Xu, J. H.; Qian, W. Y.; Chan, H. L.; Liu, W.; Guo, S. S. et al. Capture and release of cancer cells based on sacrificeable transparent MnO2 nanospheres thin film. Adv. Healthcare Mater. 2014, 3, 1420-1425.
DOI Google Scholar
40

Liu, H. L.; Li, Y. Y.; Sun, K.; Fan, J. B.; Zhang, P. C.; Meng, J. X.; Wang, S. T.; Jiang, L. Dual-responsive surfaces modified with phenylboronic acid-containing polymer brush to reversibly capture and release cancer cells. J. Am. Chem. Soc. 2013, 135, 7603-7609.
DOI Google Scholar
41

Zhang, Z. Y.; Chen, N. C.; Li, S. H.; Battig, M. R.; Wang, Y. Programmable hydrogels for controlled cell catch and release using hybridized aptamers and complementary sequences. J. Am. Chem. Soc. 2012, 134, 15716-15719.
DOI Google Scholar
42

Delport, F.; Pollet, J.; Janssen, K.; Verbruggen, B.; Knez, K.; Spasic, D.; Lammertyn, J. Real-time monitoring of DNA hybridization and melting processes using a fiber optic sensor. Nanotechnology 2012, 23, 065503.
DOI Google Scholar
43

Kwong, G. A.; Radu, C. G.; Hwang, K.; Shu, C. J.; Ma, C.; Koya, R. C.; Comin-Anduix, B.; Hadrup, S. R.; Bailey, R. C.; Witte, O. N. et al. Modular nucleic acid assembled p/MHC microarrays for multiplexed sorting of antigen-specific T cells. J. Am. Chem. Soc. 2009, 131, 9695-9703.
DOI Google Scholar
44

Vermesh, U.; Vermesh, O.; Wang, J.; Kwong, G. A.; Ma, C.; Hwang, K.; Heath, J. R. High-density, multiplexed patterning of cells at single-cell resolution for tissue engineering and other applications. Angew. Chem., Int. Ed. 2011, 50, 7378-7380.
DOI Google Scholar
45

Deng, Y. L.; Zhang, Y.; Sun, S.; Wang, Z. H.; Wang, M. J.; Yu, B. Q.; Czajkowsky, D. M.; Liu, B. Y.; Li, Y.; Wei, W. et al. An integrated microfluidic chip system for single-cell secretion profiling of rare circulating tumor cells. Sci. Rep. 2014, 4, 7499.
DOI Google Scholar
File
12274_2017_1885_MOESM1_ESM.pdf (2.2 MB)
Publication history
Copyright
Acknowledgements

Publication history

Received: 16 March 2017
Revised: 11 October 2017
Accepted: 13 October 2017
Published: 12 May 2018
Issue date: May 2018

Copyright

© Tsinghua University Press and Springer-Verlag GmbH Germany 2017

Acknowledgements

Acknowledgements

This work was supported by the National Natural Science Foundation of China (NSFC) (Nos. 21432008, 91413109 and 21575110). China Postdoctoral Innovative Talent Support Program of China (No. BX201700176).

Return