Label-free Detection of PD-1 Antibody and Antigen Immunoreaction Using Nano-Sensors

doi:10.6023/A18110472

Acta Chim. Sinica ›› 2019, Vol. 77 ›› Issue (3): 287-292.DOI: 10.6023/A18110472 Previous Articles

Article

纳米孔技术对PD-1抗原抗体结合检测的实验研究

傅方舟^a,b, 张志诚^a,b, 孙倩怡^a,b, 徐冰^a,b, 沙菁㛃^a,b

a 东南大学江苏省微纳生物医疗器械设计与制造重点实验室南京 211189;
b 东南大学机械工程学院南京 211189

投稿日期:2018-11-22 发布日期:2019-01-18
通讯作者: 沙菁? E-mail:major212@seu.edu.cn
基金资助:
项目受国家自然科学基金（Nos.51675101，51435003，51375092）和江苏省研究生科研创新计划项目（SJCX18_0019）资助.

Label-free Detection of PD-1 Antibody and Antigen Immunoreaction Using Nano-Sensors

Fu Fangzhou^a,b, Zhang Zhicheng^a,b, Sun Qianyi^a,b, Xu Bing^a,b, Sha Jingjie^a,b

a Jiangsu Key Laboratory for Design and Manufacture of Micro-Nano Biomedical Instruments, Southeast University, Nanjing 211189;
b School of Mechanical Engineering, Southeast University, Nanjing 211189

Received:2018-11-22 Published:2019-01-18
Supported by:
Project supported by the National Natural Science Foundation of China (Nos. 51675101, 51435003, 51375092) and the Postgraduate Research & Practice In-novation Program of Jiangsu Province (SJCX18_0019).

Immunotherapy for cancer is a method to treat cancer by using the body's own immune system. Programmed death receptor 1 (PD-1) is one of the checkpoints in the immunotherapy. The signal pathway PD-1 (programmed death receptor 1)/PD-L1 (ligand of PD-1) is closely related to the immune escape of the cancer cells. The inhibitor drugs for PD-1 checkpoint, essentially the monoclonal antibodies of PD-1 or PD-L1 which is essentially the immune checkpoints inhibitors could block the PD-1/PD-L1 pathway and reactivate T-cells to kill cancer cells, and as a result, the immunotherapy for cancer is realized. In order to study the binding process of PD-1 drugs and PD-1 antigen in vivo, in this work, solid-state nanopore as a single molecule method is used to detect the binding of PD-1 antibody and antigen. The PD-1 antibody as well as antigen is driven though the same nanopore under the same experimental condition by the external electric field. Since the antibody's block is about 0.01297 while the antigen's block is 0.00404, the PD-1 antibody is distinguished with the PD-1 antigen according to the theoretical formula. Driving the PD-1 antigen though the nanopore modified by PD-1 antibody (a series of experiments are conducted for characterization) under the same temperature and buffer concentration, the antibody-antigen complexes are detected and distinguished with PD-1 protein and its antibody through the relative current drop analysis and the current drop achieved before. The results suggest that the antibody and antigen have a specific binding (the smaller peak represents the free PD-1 antibody and antigen) and the binding process can be detected by nano-sensors. So the nanopore is able to distinguish the antibody, the antigen and the complexes without any labling. And in the future, the nanopore technology may be a rapid and label-free way for patients and doctors to evaluate the drugs' efficiency.

Key words: nanopore, programmed death receptor 1 (PD-1), antibody, antigen, label-free

Cite this article

Fu Fangzhou, Zhang Zhicheng, Sun Qianyi, Xu Bing, Sha Jingjie. Label-free Detection of PD-1 Antibody and Antigen Immunoreaction Using Nano-Sensors[J]. Acta Chim. Sinica, 2019, 77(3): 287-292.

Export EndNote|Reference Manager|ProCite|BibTeX|RefWorks

share this article

References

[1] Chen, M. J.; Novaes, P. E.; Gadia, R. Rev. Assoc. Med. Bras. 2017, 63, 729.
[2] Meyer, L. A.; Cronin, A. M.; Sun, C. C. J. Clin. Oncol. 2016, 34.
[3] Salto, S.; Shimozuma, K.; Ohashi, Y. Value Health 2007, 10, A340.
[4] Riaz, S. P.; Lüchtenborg, M.; Jack, R. H. Eur. J. Cancer 2012, 48, 54.
[5] Matsuzawa, F.; Ohki, S. Y.; Aikawa, S. I. Sci. Adv. Mater. 2005, 6, 463.
[6] Saleh, O. A.; Sohn, L. L. Proc. Natl. Acad. Sci. U. S. A. 2003, 100, 820.
[7] Schibel, A. E. P.; Ervin, E. N. Langmuir 2014, 30, 11248.
[8] Wang, S.; Haque, F.; Rychahou, P. G. ACS Nano 2013, 7, 9814.
[9] Stephen, W. H.; Eric, M.; Iftekhar, A. BMC Bioinformatics 2007, 8, S20.
[10] Wu, H. J.; Li, Y.; Fan, J. Anal. Chem. 2014, 86, 1988.
[11] Brower, V. JNCI, J. Natl. Cancer Inst. 2015, 107, djv069.
[12] Li, Q.; Quan, L.; Lyu, J. Oncotarget 2016, 7, 64967.
[13] Miller, K. D.; Siegel, R. L.; Lin, C. C. CA-Cancer J. Clin. 2016, 66, 271.
[14] Muqbil, I.; Azmi, A. S.; Mohammad, R. M. Cancers 2018, 10, 138.
[15] Barbee, M. S.; Ogunniyi, A.; Horvat, T. Z. Ann. Pharmacother. 2015, 49, 907.
[16] Cao, C.; Liao, D.-F.; Ying, Y.-L.; Long, Y.-T. Acta Chim. Sinica 2016, 74, 734. (曹婵, 廖冬芳, 应佚伦, 龙亿涛, 化学学报, 2016, 74, 734.)
[17] Sha, J. J.; Xu, B.; Chen, Y. F.; Yang, Y. J. Acta Chim. Sinica 2017, 75, 11. (沙菁?, 徐冰, 陈云飞, 杨颜菁, 化学学报, 2017, 75, 11.)
[18] Liao, D. F.; Cao, C.; Ying, Y. L. Small 2018, 14, 1704520.
[19] Kasianowicz, J. J.; Bezrukov, S. M. Nat. Biotechnol. 2016, 34, 481.
[20] Feng, Y.; Zhang, Y.; Ying, C. Genom. Proteom. Bioinf. 2015, 13, 4.
[21] Howorka, S.; Cheley, S.; Bayley, H. Nat. Biotechnol. 2001, 19, 636.
[22] Wanunu, M. Phys. Life Rev. 2012, 9, 125.
[23] Liu, N. N.; Yang, Z. K.; Ou, X. W. Mikrochim. Acta 2016, 183, 955.
[24] Venkatesan, B. M.; Bashir, R. Nat. Nanotechnol. 2011, 6, 615.
[25] Ying, Y.-L.; Zhang, X.; Liu, Y.; Xue, M.-Z.; Li, H.-L.; Long, Y.-T. Acta Chim. Sinica 2013, 71, 44. (应佚伦, 张星, 刘钰, 薛梦竹, 李洪林, 龙亿涛, 化学学报, 2013, 71, 44.)
[26] Nguyen, B. H.; Nguyen, V. H. Adv. Nat. Sci.-Nanosci. 2016, 7, 023002.
[27] Stoloff, D. H.; Wanunu, M. Curr. Opin. Biotechnol. 2013, 24, 699.
[28] Han, A.; Creus, M.; Schürmann, G. Anal. Chem. 2008, 80, 4651.
[29] Freedman, K. J.; Bastian, A. R.; Chaiken, I.; Kim, M. J. Small 2013, 9, 750.
[30] Kwak, D.; Chae, H.; Lee, M. Angew. Chem., Int. Ed. 2016, 128, 5807.
[31] Ying, Y. L.; Yu, R. J.; Hu, Y. X. Chem. Commun. 2017, 53, 8620.
[32] Wang, H. F.; Huang, F.; Gu, Z. Chin. J. Anal. Chem. 2018, 46, 50. (王慧锋, 黄飞, 顾震, 分析化学, 2018, 46, 50.)
[33] Lin, Y.; Ying, Y. L.; Gao, R. Acta Chim. Sinica 2017, 75, 675. (林瑶, 应佚伦, 高瑞, 王慧峰, 龙亿涛, 化学学报, 2017, 75, 675.)
[34] Li, Q.; Lin, Y.; Ying, Y. L.; Liu, S. C.; Long, Y. T. Sci. Sin.:Chim. 2017, 47, 1445. (李巧, 林瑶, 应佚伦, 刘少创, 龙亿涛, 中国科学:化学, 2017, 47, 1445.)
[35] Deblois, R. W.; Bean, C. P. Rev. Sci. Instrum. 1970, 41, 909.
[36] Han, A. P.; Schurmann, G.; Mondin, G.; Bitterli, R. A.; Hegelbach, N. G.; de Rooij, N. F.; Staufer, U. Appl. Phys. Lett. 2006, 88, 350.
[37] Larkin, J.; Henley, R. Y.; Muthukumar, M.; Rosenstein, J. K.; Wanunu, M. Biophys. J. 2014, 106, 696.
[38] Kowalczyk, S. W.; Grosberg, A. Y.; Rabin, Y. Nanotechnology 2011, 22, 315101.
[39] Dekker, C. Nat. Nanotechnol. 2007, 2, 209.
[40] Gierak, J.; Madouri, A.; Biance, A. L. Microelectron. Eng. 2007, 84, 779.
[41] Ma, J.; Qiu, Y.; Yuan, Z. Phys. Rev. E 2015, 92, 022719.

纳米孔技术对PD-1抗原抗体结合检测的实验研究

Label-free Detection of PD-1 Antibody and Antigen Immunoreaction Using Nano-Sensors

PDF

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 15

Recommended Articles

Metrics

Comments

[1]	Xue Ni, Kaili Xin, Zhengli Hu, Cuiling Jiang, Yongjing Wan, Yi-Lun Ying, Yi-Tao Long. A Time-Series Signal Classification Algorithm and Its Application to Nanopore Ionic Current Signal Identification^★ [J]. Acta Chimica Sinica, 2023, 81(8): 912-919.
[2]	Chaofan Ma, Wei Xu, Wei Liu, Changhui Xu, Jingjie Sha. Proactive Manipulation Techniques for Protein Transport at Confined Nanoscale [J]. Acta Chimica Sinica, 2023, 81(7): 857-868.
[3]	Ma Qiulin, Feng Nan, Ju Huangxian. Advances in Analytical Methodology of Prostate Cancer Markers [J]. Acta Chimica Sinica, 2020, 78(11): 1213-1222.
[4]	Feng Tingting, Gao Shouqin, Wang Kun. Colorimetric Sensing of Prostate Specific Membrane Antigen Based on Gold Nanoparticles [J]. Acta Chim. Sinica, 2019, 77(5): 422-426.
[5]	Li, Mengyin, Ying, Yilun, Long, Yi-Tao. Unveiling the Synergistic Effect from Key Sensing Regions in Aerolysin-Based Single Oligonucleotide Detection [J]. Acta Chimica Sinica, 2019, 77(10): 984-988.
[6]	Niu, Hongyan, Hu, Zhengli, Ying, Yilun, Long, Yi-Tao. Detection of Single c-di-AMP by an Aerolysin Nanopore [J]. Acta Chimica Sinica, 2019, 77(10): 989-992.
[7]	Lin Yao, Ying Yilun, Gao Rui, Wang Huifeng, Long Yitao. Analysis of Single-entity Anisotropy with a Solid-state Nanopore [J]. Acta Chim. Sinica, 2017, 75(7): 675-678.
[8]	Sha Jingjie, Xu Bing, Chen Yunfei, Yang Yanjing. Experimental Research of Protein Translocation Using Solid-state Nanopore [J]. Acta Chim. Sinica, 2017, 75(11): 1121-1125.
[9]	Hu Zhengli, Du Jihui, Ying Yilun, Peng Yueyi, Cao Chan, Long Yi-Tao. Single-Molecule Analysis of Colorectal Cancer-associated MicroRNAs via a Biological Nanopore [J]. Acta Chim. Sinica, 2017, 75(11): 1087-1090.
[10]	Cao Chan, Liao Dongfang, Ying Yilun, Long Yitao. Detection of Single Oligonucleotide by an Aerolysin Nanopore [J]. Acta Chim. Sinica, 2016, 74(9): 734-737.
[11]	Wang Yue, Yu Xufeng, Liu Yunyun, Xie Xiao, Cheng Xiulan, Huang Shaoming, Wang Zhimin. Fabrication of Graphene Nanopores and a Preliminary Study on λ-DNA Translocation [J]. Acta Chimica Sinica, 2014, 72(3): 378-381.
[12]	Lin Jiehua, Zhang Huihui, Shao Meijia. A Label-free Immunosensor based on Ionic Liquids Modified Mesoporous Silica for Simultaneous Determination of Two Tumor Markers [J]. Acta Chimica Sinica, 2014, 72(2): 241-245.
[13]	Feng Shilei, Hu Shu, Liu Bing, Liu Wei . QM/MM Molecular Dynamics Simulation for the MHC class I Molecule Interacting with Antigen Peptide [J]. Acta Chimica Sinica, 2013, 71(9): 1313-1320.
[14]	Yu Changyu, Liu Wei, Liu Tao, Song Zhe, Zhu Minghua. Prediction of Th Cell Epitopes Based on ISC-SVR Method [J]. Acta Chimica Sinica, 2013, 71(04): 670-678.
[15]	Ying Yilun, Zhang Xing, Liu Yu, Xue Mengzhu, Li Honglin, Long Yitao. Single Molecule Study of the Weak Biological Interactions Between P53 and DNA [J]. Acta Chimica Sinica, 2013, 71(01): 44-50.