Table of Contents

    Topic review

    A Graphene-PEDOT

    View times: 488
    Submitted by: Yi-Kuang Yen


    A graphene and poly (3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) modified conductive paper-based electrochemical impedance spectroscopy (EIS) aptasensor has been successfully fabricated by a simple and continuous coating process. A graphene/PEDOT:PSS modified paper electrode forms the nanocomposite providing a conductive and sensitive substrate for further aptamer functionalization of the biosensor. This low-cost paper-based aptasensor exhibits its sensitivity to carcinoembryonic antigens (CEA) in standard buffer solutions and human serum samples in a linear range of 0.77–14 ng·mL−1. The limit of detection (LOD) is found to be 0.45 ng·mL−1 and 1.06 ng·mL−1 for CEA in both samples, separately. This aptamer-based sensing device was also evaluated and received a good correlation with the immunoassay detection method. The proposed paper-based aptasensor has demonstrated its potential as a rapid simple point-of-care analytical platform for early cancer diagnosis in less developed areas where manufacturing facilities, analytical instruments, and trained specialists are limited.

    1. Introduction

    Developing sensitive and reliable point-of-care (POC) devices for early cancer screening, diagnosis, and treatment monitoring is an important task in both the developing and developed world [[1][2]]. Promising interdisciplinary research grows on this context because POC analytical platforms can reduce cost, decrease the sample amount, achieve an on-site diagnosis and mitigate patient stress [[3][4]]. Additionally, with the discovery of tumor biomarkers, such as alpha-fetoprotein, prostate specific antigen (PSA) and carcinoembryonic antigen (CEA), the feasibility of analysis in oncology has been enhanced [[5]]. CEA is one of the most widely used tumor markers associated with colorectal cancer, pancreatic cancer, gastric cancer, and lung cancer [[6]]. Generally, the normal serum level of CEA in humans should be less than 5 ng/mL which is the cutoff value for the indication of cancer [[7][8]]. In addition, changes in serum CEA levels in patients with colorectal cancer can be used to detect early recurrence after surgery [[9]]. It also has been reported that elevated serum CEA levels might play an important role in predicting a poor prognosis for pancreatic cancer patients [[10]].

    2. A Graphene-PEDOT:PSS Modified Paper-Based Aptasensor for Electrochemical Impedance Spectroscopy Detection of Tumor Marker

    The clinical detection of CEA is mainly based on immunoassays. For example, chemical luminescence microparticle immunoassay (CMIA) and electrochemiluminescence immunoassay (ECLIA) are the two most commonly used immunoassays in hospitals [[11]]. The advantages of these methods are automatic batch inspection, simple operation, and wide detection intervals, but the disadvantage is that the equipment needed is expensive and cumbersome. In addition to conventional immunoassays, a Love Wave surface acoustic wave (SAW) sensor has been reported for the automatic and online detection of CEA in exhaled breath condensate [[12]]. Electrochemical immunosensors have recently been of interest to scientists due to their captivating properties, which include high sensitivity, fast response, short diagnostic time, and miniaturization [[13]]. For example, a new electrochemical immunosensor based on a AuNPs/PEDOT/GR composite was fabricated for enhancing the detection sensitivity of CEA in real human serum [[14]]. Furthermore, a conducting paper-based electrochemical immunosensor was developed for CEA sensing by progressively creating a poly (3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) film directly over the paper substrate [[15]]. This approach demonstrated the advantageous properties of a paper-based sensor including flexibility, lightweight, low cost, easy fabrication, biocompatibility, and biodegradability, which satisfied the demand for developing disposable POC devices for areas with a shortage of medical resources. Besides electrochemical immunosensors, a microfluidic paper-based electrochemical aptasensor was fabricated through wax printing and screen printing for simultaneous detection of CEA and neuron-specific enolase (NSE) in a clinical sample [[16]]. This method provided a great sensitivity of detection and a possible low-cost platform. However, the patterning processes for the devices and the synthesis of nanocomposites for sensing electrodes depend on customized equipment and well-trained personnel. These requirements might be difficult to satisfy in areas with limited resources, or remote or rural communities, where the demand for analytical devices is clearly evident [[17]].

    In this work, a paper-based electrochemical aptasensor for CEA detection was developed using graphene ink and PEDOT:PSS progressively modified on paper substrate to form a conductive composite paper electrode. Graphene has excellent characteristics including ideal mechanical strength, good electrical conductivity and a high surface-to-volume ratio which makes surface transporting electrons highly sensitive to adsorbed molecules [[18][19]]. It also has been reported that the combination of graphene and PEDOT:PSS produces better sensing properties for working electrodes [[20][21]1]. All fabrication steps were at room temperature and required no sophisticated printing techniques. Through the immobilization of aptamers, the newly conductive paper-based device demonstrated its sensitivity and selectivity of electrochemical measurements of CEA in serum samples. This inexpensive and disposable paper-based electrochemical sensor would provide a point-of-care biomarker analytical tool for cancer diagnostics in less industrialized or resource-limited areas where fabrication facilities and skilled personnel are limited.

    We have developed an electrochemical paper-based aptasensor for CEA detection, based on a straightforward and continuous graphene/PEDOT:PSS modification process. The conductive paper electrode was further chemically functionalized in a specially designed reactor for the immobilization of CEA aptamer. The proposed aptasensor was applied for sensing CEA with EIS analysis. These results displayed a good linearity in the range of 0.76–14 ng·mL−1 and a low limit of detection for CEA. In addition, this sensing system was successfully applied for the determination of CEA in human serum and compared with the immunoassay method. This method does not require complicated fabrication techniques, costly substrates, or nanomaterials demanding specialized synthetic techniques. This new and sensitive paper-based aptasensor might be an alternative POC tool for cancer markers screening in less developed countries or resource limited areas.

    The entry is from 10.3390/s20051372


    1. Steven A. Soper; Kathlynn Brown; Andrew Ellington; Bruno Frazier; Guillermo Garcia-Manero; Vincent Gau; Steven I. Gutman; Daniel F. Hayes; Brenda Korte; James L. Landers; et al. Point-of-care biosensor systems for cancer diagnostics/prognostics. Biosensors and Bioelectronics 2006, 21, 1932-1942, 10.1016/j.bios.2006.01.006.
    2. Mickey Urdea; Laura A. Penny; Stuart S. Olmsted; Maria Y. Giovanni; Peter Kaspar; Andrew Shepherd; Penny Wilson; Carol A. Dahl; Steven Buchsbaum; Gerry Moeller; et al. Requirements for high impact diagnostics in the developing world. Nature 2006, 444, 73-79, 10.1038/nature05448.
    3. Yu Shen; Thien-Toan Tran; Sidharth Modha; Hideaki Tsutsui; Ashok Mulchandani; A paper-based chemiresistive biosensor employing single-walled carbon nanotubes for low-cost, point-of-care detection. Biosensors and Bioelectronics 2019, 130, 367-373, 10.1016/j.bios.2018.09.041.
    4. Thien Hoang; Bao-Han Ly; Thanh-Xuan Le; Thanh-Thao Huynh; Hoang-Tuan Nguyen; Toi Van Vo; Thi Thu Hien Pham; Khon Huynh; Minimal microfabrication required digital microfluidic system toward point-of-care nucleic acid amplification test application for developing countries. Microsystem Technologies 2020, , 1-11, 10.1007/s00542-019-04733-4.
    5. Leila Farzin; Mojtaba Shamsipur; Recent advances in design of electrochemical affinity biosensors for low level detection of cancer protein biomarkers using nanomaterial-assisted signal enhancement strategies. Journal of Pharmaceutical and Biomedical Analysis 2018, 147, 185-210, 10.1016/j.jpba.2017.07.042.
    6. Jing-Yi Huang; Lang Zhao; Wan Lei; Wei Wen; Yi-Jia Wang; Ting Bao; Huayu Xiong; Xiuhua Zhang; Sheng-Fu Wang; A high-sensitivity electrochemical aptasensor of carcinoembryonic antigen based on graphene quantum dots-ionic liquid-nafion nanomatrix and DNAzyme-assisted signal amplification strategy. Biosensors and Bioelectronics 2018, 99, 28-33, 10.1016/j.bios.2017.07.036.
    7. Gota Saito; Sotaro Sadahiro; Hiroko Kamata; Hiroshi Miyakita; Kazutake Okada; Akira Tanaka; Toshiyuki Suzuki; Monitoring of Serum Carcinoembryonic Antigen Levels after Curative Resection of Colon Cancer: Cutoff Values Determined according to Preoperative Levels Enhance the Diagnostic Accuracy for Recurrence.. Oncology 2017, 92, 276-282, 10.1159/000456075.
    8. Jian Han; Yueyun Li; Jinhui Feng; Mingdang Li; Ping Wang; Zhiwei Chen; Yunhui Dong; A novel sandwich-type immunosensor for detection of carcino-embryonic antigen using silver hybrid multiwalled carbon nanotubes/manganese dioxide. Journal of Electroanalytical Chemistry 2017, 786, 112-119, 10.1016/j.jelechem.2017.01.021.
    9. Gota Saito; Sotaro Sadahiro; Hiroko Kamata; Hiroshi Miyakita; Kazutake Okada; Akira Tanaka; Toshiyuki Suzuki; Monitoring of Serum Carcinoembryonic Antigen Levels after Curative Resection of Colon Cancer: Cutoff Values Determined according to Preoperative Levels Enhance the Diagnostic Accuracy for Recurrence.. Oncology 2017, 92, 276-282, 10.1159/000456075.
    10. Qingcai Meng; Si Shi; Chen Liang; Dingkong Liang; Wenyan Xu; Shunrong Ji; Bo Zhang; Quanxing Ni; Jin Xu; Xianjun Yu; et al. Diagnostic and prognostic value of carcinoembryonic antigen in pancreatic cancer: a systematic review and meta-analysis. OncoTargets and Therapy 2017, 10, 4591-4598, 10.2147/OTT.S145708.
    11. Nafija Serdarevic; Jasmina Smajic; Comparison of chemiluminescent microparticle immunoassay (CMIA) with electrochemiluminescence immunoassay (ECLIA) for Carcinoembryonic antigen (CEA). Journal of Health Sciences 2018, 8, 94-100, 10.17532/jhsci.2018.520.
    12. Xi Zhang; Yingchang Zou; Chao An; Kejing Ying; Xing Chen; Ping Wang; A miniaturized immunosensor platform for automatic detection of carcinoembryonic antigen in EBC. Sensors and Actuators B: Chemical 2014, 205, 94-101, 10.1016/j.snb.2014.08.011.
    13. Il-Hoon Cho; Jongsung Lee; Jiyeon Kim; Min-Soo Kang; Jean Kyung Paik; Seockmo Ku; Hyun Mo Cho; Joseph Irudayaraj; Dong Hyung Kim; Current Technologies of Electrochemical Immunosensors: Perspective on Signal Amplification. Sensors 2018, 18, 207, 10.3390/s18010207.
    14. Yan-Sha Gao; Tao-Tao Yang; Yong-Fang Yu; Jingkun Xu; Limin Lu; Xiao-Fei Zhu; Wen-Min Wang; Kaixin Zhang; A label-free electrochemical immunosensor for carcinoembryonic antigen detection on a graphene platform doped with poly(3,4-ethylenedioxythiophene)/Au nanoparticles. RSC Advances 2015, 5, 86910-86918, 10.1039/C5RA16618G.
    15. Saurabh Kumar; Suveen Kumar; Chandra Mouli Pandey; B. D. Malhotra; Conducting paper based sensor for cancer biomarker detection. Journal of Physics: Conference Series 2016, 704, 12010, 10.1088/1742-6596/704/1/012010.
    16. Yang Wang; Jinping Luo; Juntao Liu; Shuai Sun; Ying Xiong; Yuanyuan Ma; Shi Yan; Yue Yang; Huabing Yin; XinXia Cai; et al. Label-free microfluidic paper-based electrochemical aptasensor for ultrasensitive and simultaneous multiplexed detection of cancer biomarkers.. Biosensors and Bioelectronics 2019, 136, 84-90, 10.1016/j.bios.2019.04.032.
    17. Yanyan Xia; Jin Si; Zhiyang Li; Fabrication techniques for microfluidic paper-based analytical devices and their applications for biological testing: A review. Biosensors and Bioelectronics 2016, 77, 774-789, 10.1016/j.bios.2015.10.032.
    18. Niti Garg; Ashok Mohanty; Nathan Lazarus; Lawrence Schultz; Tony R Rozzi; Suresh Santhanam; Lee Weiss; Jay L Snyder; Gary K. Fedder; Rongchao Jin; et al. Robust gold nanoparticles stabilized by trithiol for application in chemiresistive sensors. Nanotechnology 2010, 21, 405501, 10.1088/0957-4484/21/40/405501.
    19. Krishnendu Saha; Sarit S. Agasti; Chaekyu Kim; Xiaoning Li; Vincent Rotello; Gold Nanoparticles in Chemical and Biological Sensing. Chemical Reviews 2012, 112, 2739-2779, 10.1021/cr2001178.
    20. Tran Thanh Tung; Mickael Castro; Tae Young Kim; Kwang S. Suh; Jean-Francois Feller; Graphene quantum resistive sensing skin for the detection of alteration biomarkers. Journal of Materials Chemistry 2012, 22, 21754-21766, 10.1039/c2jm34806c.
    21. Chakrit Sriprachuabwong; Chanpen Karuwan; Anurat Wisitsorrat; Ditsayut Phokharatkul; Tanom Lomas; Pornpimol Sritongkham; Adisorn Tuantranont; Inkjet-printed graphene-PEDOT:PSS modified screen printed carbon electrode for biochemical sensing. Journal of Materials Chemistry 2012, 22, 5478, 10.1039/c2jm14005e.