Citation: Shihui Qiu, Chuanjie Shen, Xiaoyu Jian, Yunxing Lu, Zhaoduo Tong, Zhenhua Wu, Hongju Mao, Jianlong Zhao. Single-cell level point mutation analysis of circulating tumor cells through droplet microfluidics[J]. Chinese Chemical Letters, ;2022, 33(5): 2701-2704. doi: 10.1016/j.cclet.2021.08.128 shu

Single-cell level point mutation analysis of circulating tumor cells through droplet microfluidics

Shihui Qiu ^{a, b} ,
Chuanjie Shen ^{a, b} ,
Xiaoyu Jian ^a ,
Yunxing Lu ^{a, b} ,
Zhaoduo Tong ^{a, b} ,
Zhenhua Wu ^{a, *,} ,
Hongju Mao ^{a, b, *,} ,
Jianlong Zhao ^{a, b}

a.
State Key State Laboratory of Transducer Technology, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai 200050, China
b.
Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing 100049, China

wuzhx@mail.sim.ac.cn

hjmao@mail.sim.ac.cn

Received Date: 10 July 2021
Revised Date: 15 August 2021
Accepted Date: 31 August 2021
Available Online: 6 September 2021

Figures(4)

Tumor heterogeneity plays a critical role in the determination of appropriate anticancer therapy. As circulating tumor cells (CTCs) contain all tumor-related information, the genetic changes on CTCs could help us choose the appropriate treatments for different patients. Single-base mutations are very common in tumor genetic changes which may result in drug resistance. Here, we introduce a single-cell mutation detection platform based on droplet microfluidics. This platform integrates cell capsulation, cell lysis, polymerase chain reaction (PCR) and the observation process. The droplets' generation speed is over 6000 per minute and more than 600 cells could be encapsulated in one second. To verify the performance of our platform in practical use, we performed the mutation analysis of 4 kinds of cells with our platform and noted that the genetic status of each single cell was clearly discriminated. Moreover, these results agreed with those from direct sequencing. Compared with other forms of single-cell mutation detection techniques, our platform has high throughput, short experimental time and less experimental operations.
- Single cell,
- CTCs,
- Point mutation,
- EGFR,
- Microfluidics
1. [1]
  M.G. Krebs, R.L. Metcalf, L. Carter, et al., J. Nat. Rev. Clin. Oncol.11 (2014) 129-144. doi: 10.1038/nrclinonc.2013.253
2. [2]
  A. Tartarone, E. Rossi, R. Lerose, et al., J. Lung Cancer107 (2017) 59-64. doi: 10.1016/j.lungcan.2016.05.027
3. [3]
  T. K. Sundaresan, L.V. Sequist, J.V. Heymach, et al., J. Clin. Cancer Res. 22 (2016) 1103-1110. doi: 10.1158/1078-0432.CCR-15-1031
4. [4]
  S. Maheswaran, L.V. Sequist, S. Nagrath, et al., J. N. Engl. J. Med. 359 (2008) 366-377. doi: 10.1056/NEJMoa0800668
5. [5]
  X. Lu, L. Yu, Z. Zhang, et al., J. Med. Res. Rev. 38 (2018) 1550-1581. doi: 10.1002/med.21488
6. [6]
  B. Zou, V.H.F. Lee, L.J. Chen, et al., Sci. Rep. 7 (2017) 6595. doi: 10.1038/s41598-017-06632-y
7. [7]
  S. Kobayashi, T. J. Boggon, T. Dayara, et al., J. N. Engl. J. Med. 352 (2005) 786-792. doi: 10.1056/NEJMoa044238
8. [8]
  A.M. Sieuwerts, J. Kraan, J. Bolt-de Vries, et al., J. Breast Cancer Res. Treat. 118 (2009) 455-68. doi: 10.1007/s10549-008-0290-0
9. [9]
  S. Shen, C. Ma, L. Zhao, et al., J. Lab Chip14 (2014) 2525-2538. doi: 10.1039/C3LC51384J
10. [10]
  Y. Zhang, Y. Zhang, Y. Tang, et al., Anal. Chem. 87 (2015) 9761-9768. doi: 10.1021/acs.analchem.5b01901
11. [11]
  C.L. Chen, D. Mahalingam, P. Osmulski, et al., J. Prostate73 (2013) 813-826. doi: 10.1002/pros.22625
12. [12]
  J. B. Dahl, J. M. G. Lin, S. J. Muller and S. Kumar, J. Annu. Rev. Chem. Biomol. Eng. 6 (2015) 293-317. doi: 10.1146/annurev-chembioeng-061114-123407
13. [13]
  P. Van Loo and T. Voet, J. Curr. Opin. Genet. Dev. 24 (2014) 82-91. doi: 10.1016/j.gde.2013.12.004
14. [14]
  G. Du, Q. Fang and J. M. den Toonder, J. Anal. Chim. Acta903 (2016) 36-50. doi: 10.1016/j.aca.2015.11.023
15. [15]
  C.M. Earhart, C.E. Hughes, R.S. Gaster, et al., J. Lab Chip14 (2014) 78-88. doi: 10.1039/C3LC50580D
16. [16]
  L. Du, H. Liu, J. Zhou, et al., J. Microsyst. Nanoeng. 6 (2020) 33. doi: 10.1038/s41378-020-0138-2
17. [17]
  S. M. Park, D. J. Wong, C. C. Ooi, et al., J. P. Natl. Acad. Sci. USA. 113 (2016) 8379-8386.
18. [18]
  R. Novak, Y. Zeng, J. Shuga, et al., Angew. Chem. Int. Ed. 50 (2011) 390-395. doi: 10.1002/anie.201006089
19. [19]
  E. Brouzes, M. Medkova, N. Savenelli, et al., J. P. Natl. Acad. Sci. USA. 106 (2009) 14195-14200. doi: 10.1073/pnas.0903542106
20. [20]
  T.K. Chiu, K.F. Lei, C.H. Hsieh, et al., J. Sensors. 15 (2015) 6789-6806. doi: 10.3390/s150306789
21. [21]
  F. Del Ben, M. Turetta, G. Celetti, et al., Angew. Chem. Int. Ed. Engl. 55 (2016) 8581-8584. doi: 10.1002/anie.201602328
22. [22]
  V. Trivedi, A. Doshi, G.K. Kurup, et al., J. Lab Chip10 (2010) 2433-2442. doi: 10.1039/c004768f
23. [23]
  E.Z. Macosko, A. Basu, R. Satija, et al., J. Cell161 (2015) 1202-1214. doi: 10.1016/j.cell.2015.05.002
24. [24]
  A.M. Klein, L. Mazutis, I. Akartuna, et al., J. Cell161 (2015) 1187-1201. doi: 10.1016/j.cell.2015.04.044
25. [25]
  A.I. Phipps, D.D. Buchanan, K. Makar, et al., J. Cancer Epidemiol. Biomarkers Prev. 21 (2012) 1792-1798. doi: 10.1158/1055-9965.EPI-12-0674
26. [26]
  Z.H. Wu, T.L. Ma, J.L. Coll, et al., J. Biosens. Bioelectron. 80 (2016) 175-181. doi: 10.1007/978-981-10-2857-1_15
27. [27]
  X.J. Bian, Jing, F. X., Li, G. et al., J. Biosens. Bioelectron. 74 (2015) 770-777. doi: 10.1016/j.bios.2015.07.016
28. [28]
  W.L. Gao, X.F. Zhang, H.J. Yuan, et al., J. Biosens. Bioelectron. 139 (2019) 111326. doi: 10.1016/j.bios.2019.111326
1. [1]
  Feng Wu , Xuemin Kong , Yixuan Liu , Shuli Wang , Zhong Chen , Xu Hou . Microfluidic-based isolation of circulating tumor cells with high-efficiency and high-purity. Chinese Chemical Letters, 2024, 35(8): 109754-. doi: 10.1016/j.cclet.2024.109754
2. [2]
  Shiyu Hou , Maolin Sun , Liming Cao , Chaoming Liang , Jiaxin Yang , Xinggui Zhou , Jinxing Ye , Ruihua Cheng . Computational fluid dynamics simulation and experimental study on mixing performance of a three-dimensional circular cyclone-type microreactor. Chinese Chemical Letters, 2024, 35(4): 108761-. doi: 10.1016/j.cclet.2023.108761
3. [3]
  Jun Lu , Jinrui Yan , Yaohao Guo , Junjie Qiu , Shuangliang Zhao , Bo Bao . Controlling solid form and crystal habit of triphenylmethanol by antisolvent crystallization in a microfluidic device. Chinese Chemical Letters, 2024, 35(4): 108876-. doi: 10.1016/j.cclet.2023.108876
4. [4]
  Cheng Wang , Ji Wang , Dong Liu , Zhi-Ling Zhang . Advances in virus-host interaction research based on microfluidic platforms. Chinese Chemical Letters, 2024, 35(12): 110302-. doi: 10.1016/j.cclet.2024.110302
5. [5]
  Guifeng Wen , Zheyuan Zhong , Yue Fan , Xuelin Tian , Shilin Huang . Multidimensional droplet manipulation on superhydrophobic surfaces using acoustic tweezers. Chinese Chemical Letters, 2025, 36(5): 110672-. doi: 10.1016/j.cclet.2024.110672
6. [6]
  Zhaorui Song , Qiulian Hao , Bing Li , Yuwei Yuan , Shanshan Zhang , Yongkuan Suo , Hai-Hao Han , Zhen Cheng . NIR-Ⅱ fluorescence lateral flow immunosensor based on efficient energy transfer probe for point-of-care testing of tumor biomarkers. Chinese Chemical Letters, 2025, 36(1): 109834-. doi: 10.1016/j.cclet.2024.109834
7. [7]
  Yunan Yuan , Zhimin Luo , Jie Chen , Chaoliang He , Kai Hao , Huayu Tian . Constructing thermoresponsive PNIPAM-based microcarriers for cell culture and enzyme-free cell harvesting. Chinese Chemical Letters, 2024, 35(7): 109549-. doi: 10.1016/j.cclet.2024.109549
8. [8]
  Weiyu Chen , Zenghui Li , Chenguang Zhao , Lisha Zha , Junfeng Shi , Dan Yuan . Enzyme-modulate conformational changes in amphiphile peptide for selectively cell delivery. Chinese Chemical Letters, 2024, 35(12): 109628-. doi: 10.1016/j.cclet.2024.109628
9. [9]
  Yukai Tong , Zhijun Wu , Bo Zhou , Min Hu , Anpei Ye . Surface tension of single suspended aerosol microdroplets. Chinese Chemical Letters, 2024, 35(4): 109062-. doi: 10.1016/j.cclet.2023.109062
10. [10]
  Kun Tang , Yu-Wu Zhong . Water reduction by an organic single-chromophore photocatalyst. Chinese Journal of Structural Chemistry, 2024, 43(8): 100376-100376. doi: 10.1016/j.cjsc.2024.100376
11. [11]
  Kun-Heng Li , Hong-Yang Zhao , Dan-Dan Wang , Ming-Hui Qi , Zi-Jian Xu , Jia-Mi Li , Zhi-Li Zhang , Shi-Wen Huang . Mitochondria-targeted nano-AIEgens as a powerful inducer for evoking immunogenic cell death. Chinese Chemical Letters, 2024, 35(5): 108882-. doi: 10.1016/j.cclet.2023.108882
12. [12]
  Yang Liu , Yan Liu , Kaiyin Yang , Zhiruo Zhang , Wenbo Zhang , Bingyou Yang , Hua Li , Lixia Chen . A selective HK2 degrader suppresses SW480 cancer cell growth by degrading HK2. Chinese Chemical Letters, 2024, 35(8): 109264-. doi: 10.1016/j.cclet.2023.109264
13. [13]
  Boran Cheng , Lei Cao , Chen Li , Fang-Yi Huo , Qian-Fang Meng , Ganglin Tong , Xuan Wu , Lin-Lin Bu , Lang Rao , Shubin Wang . Fluorine-doped carbon quantum dots with deep-red emission for hypochlorite determination and cancer cell imaging. Chinese Chemical Letters, 2024, 35(6): 108969-. doi: 10.1016/j.cclet.2023.108969
14. [14]
  Jing Chen , Peisi Xie , Pengfei Wu , Yu He , Zian Lin , Zongwei Cai . MALDI coupled with laser-postionization and trapped ion mobility spectrometry contribute to the enhanced detection of lipids in cancer cell spheroids. Chinese Chemical Letters, 2024, 35(4): 108895-. doi: 10.1016/j.cclet.2023.108895
15. [15]
  Yanjing Li , Jiayin Li , Yuqi Chang , Yunfeng Lin , Lei Sui . Tetrahedral framework nucleic acids promote the proliferation and differentiation potential of diabetic bone marrow mesenchymal stem cell. Chinese Chemical Letters, 2024, 35(9): 109414-. doi: 10.1016/j.cclet.2023.109414
16. [16]
  Zhixue Liu , Haiqi Chen , Lijuan Guo , Xinyao Sun , Zhi-Yuan Zhang , Junyi Chen , Ming Dong , Chunju Li . Luminescent terphen[3]arene sulfate-activated FRET assemblies for cell imaging. Chinese Chemical Letters, 2024, 35(9): 109666-. doi: 10.1016/j.cclet.2024.109666
17. [17]
  Ying Gao , Rong Zhou , Qiwen Wang , Shaolong Qi , Yuanyuan Lv , Shuang Liu , Jie Shen , Guocan Yu . Natural killer cell membrane doped supramolecular nanoplatform with immuno-modulatory functions for immuno-enhanced tumor phototherapy. Chinese Chemical Letters, 2024, 35(10): 109521-. doi: 10.1016/j.cclet.2024.109521
18. [18]
  Yuanzheng Wang , Chen Zhang , Shuyan Han , Xiaoli Kong , Changyun Quan , Jun Wu , Wei Zhang . Cancer cell membrane camouflaged biomimetic gelatin-based nanogel for tumor inhibition. Chinese Chemical Letters, 2024, 35(11): 109578-. doi: 10.1016/j.cclet.2024.109578
19. [19]
  Zheyi Li , Xiaoyang Liang , Zitong Qiu , Zimeng Liu , Siyu Wang , Yue Zhou , Nan Li . Ion-interferential cell cycle arrest for melanoma treatment based on magnetocaloric bimetallic-ion sustained release hydrogel. Chinese Chemical Letters, 2024, 35(11): 109592-. doi: 10.1016/j.cclet.2024.109592
20. [20]
  Qian Ren , Xue Dai , Ran Cen , Yang Luo , Mingyang Li , Ziyun Zhang , Qinghong Bai , Zhu Tao , Xin Xiao . A cucurbit[8]uril-based supramolecular phosphorescent assembly: Cell imaging and sensing of amino acids in aqueous solution. Chinese Chemical Letters, 2024, 35(12): 110022-. doi: 10.1016/j.cclet.2024.110022

Get Citation

PDF

XML

Metrics

PDF Downloads(8)
Abstract views(957)
HTML views(48)

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142