search
Contact Us
HOME

  • Crossref logo
  • Crossref Similarity Check logo
Journal Search Engine

to

Search Advanced Search Adode Reader(link)
Download PDF Export Citaion korean bibliography PMC previewer
ISSN : 1225-0112(Print)
ISSN : 2288-4505(Online)
Applied Chemistry for Engineering Vol.32 No.3 pp.253-259
DOI : https://doi.org/10.14478/ace.2021.1040

Recent Research Trend of Biosensors for Colorectal Cancer Specific Protein Biomarkers

Jingjing Li, Yunpei Si, Hye Jin Lee†
Department of Chemistry, Kyungpook National University, Daegu 41566, Republic of Korea
†Corresponding Author: Kyungpook National University, Department of Chemistry, Kyungpook National University, Daegu 41566, Republic of Korea Tel: +82-53-950-5336 e-mail: hyejinlee@knu.ac.kr
April 30, 2021 ; May 19, 2021 ; May 20, 2021

Abstract


Colorectal cancer (CRC) is one of the most prevalent diseases in modern society, constituting a serious threat to global health. Currently, routine clinical screening and early removal of precancerous polyps are the most successful methods for reducing CRC incidence and mortality. However, the high cost and invasive detection of sigmoidoscopy and colonoscopy limited the CRC-screening participation and prevention. The emergence of biosensors provides an inexpensive, sensitive, less invasive tool for detecting CRC disease biomarkers. This review highlights some of recent efforts made on developing biosensors with electrochemical and optical techniques targeting CRC specific protein biomarkers for early diagnosis and prognosis, potential applications, and future perspectives.


Colorectal cancer , Protein biomarkers , Biosensors , Electrochemical methods , Optical techniques

대장암 진단용 단백질 바이오마커 측정을 위한 바이오센서 개발의 최신 연구 동향

리 징징, 스윈 페이, 이 혜진†
경북대학교 자연과학대학 화학과

초록

    1. Introduction

    Over the past decades, industrialization and disruptive technology have significantly aided modern civilization and improved the quality of life. However, because of our changing lifestyles, we have developed civilization-wide diseases, such as cancers, cardio-cerebrovascular diseases, and obesity[1]. Cancers remain the second leading cause of death worldwide, with an estimated 9.6 million deaths in 2018, putting a significant strain on global health. Colorectal cancer (CRC) is linked to many factors such as lifestyle, gender, age, and drug use, which is the second and the third most prevalent cancer in females and males, respectively[2,3]. CRC development is a multistep process that begins with genetic alterations and progresses through a series of subsequent changes at the molecule level, such as abnormal transcription, translation, and protein expression, eventually leading to adenomas and metastatic carcinomas at the tissue level[4]. In this process, various CRC related protein biomarkers were reported, such as interleukin-6 (IL-6), interleukin-8 (IL-8), carbohydrate antigen 19-9 (CA19-9), CA11-19, carcinoembryonic antigen (CEA), tumor protein 53 (p53), retinol-binding protein 4 (RBP4), heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1), vascular endothelial growth factor (VEGF), thrombospondin (THBS), and epidermal growth factor receptor (EGFR)[4-6].

    Currently, fecal immunochemical test (FIT), computed tomography colonography (CTC), sigmoidoscopy, and colonoscopy are used as standard clinical screening tests for CRC to reduce the incidence and mortality[7,8] (see Figure 1). FIT is the most widely used cost-effective approach by testing hemoglobin in feces using an antibody, but still suffers from high false positive and negative results as well as limited sensitivity while CTC, sigmoidoscopy, and colonoscopy provide more accurate direct visualization of lesions but require drastic bowel preparation, higher cost, and low participation rate[3,8]. Thus, there is still a high demand for cost-effective, fast, convenient, sensitive, and specific tools in terms of diagnosis and prognosis of CRC.

    Attractively, monitoring of CRC protein biomarker abnormalities using biosensors offers a less invasive way for CRC diagnosis, prognosis, and recurrence due to the simplicity, cost-effectiveness, rapid detection, high selectivity, and sensitivity in addition to the potential for miniaturization[4,9]. Depending on the transducer, recently developed biosensors for CRC protein biomarker include electrochemical, optical, and other signaling devices. The selective detection is based on the biomolecule recognition between the target CRC protein and capture probes such as antibody, aptamer, and receptor immobilized on the transducer surfaces. This mini review will give a quick overview of recent biosensor developments in conjunction with electrochemical and optical methods targeting particularly for CRC protein biomarkers.

    2. Electrochemical Biosensing Platforms for CRC Protein Biomarker

    Electrochemical biosensors are most extensively used for CRC protein biomarker detection by converting the electrode surface changes caused by biomolecular interactions to electrochemical measurable signals using amperometric, voltammetric, capacitive in addition to impedometric techniques. While significant research efforts have been conducted to detect CRC biomarkers[4,10], this section will only focus on portable electrochemical biosensors recently developed for CRC protein biomarkers, which are summarized in Table 1.

    Screen-printed carbon electrodes (SPCEs) are one of the most widely used electrochemical device fabrications with portability for CRC protein biomarker detection[11-16]. Butmee et al.[11] reported a label-free sensitive and selective biosensing platform for CEA using anti-CEA antibody immobilized on manganese dioxide decorated graphene nanoplatelets modified SPCE. CEA was detected by monitoring the electrochemical signal of [Fe(CN)6]3-/4- redox probes associated with biosensor surface changes when incubating with different concentrations of CEA. This method could detect CEA from 0.001~100 ng/mL using linear sweep voltammetry, offering a limit of detection (LOD) of 0.10 pg/mL. Paniagua et al.[12] prepared novel Au-SiO2 Janus nanoparticles (NPs) with the functionalization of horseradish peroxidase (HRP) and biotin thiol-modified DNA aptamer, which enabled CEA to bind specifically with aptamer and was captured by avidin-functionalized magnetic NanoCaptors®. The complex was loaded on SPCE surfaces using magnetic deposition. The label enzyme HRP catalyzing hydrogen peroxide substrate enabled quantitative detection of CEA from 1~5,000 ng/mL and an LOD of 210 pg/mL.

    The detection of CRC protein biomarkers was also reported using layer-by-layer (LbL) assembled polyelectrolytes modified SPCE. Ibáñez-Redín et al.[13] described a disposable biosensor for CA19-9 detection from 0.01~40 U/mL and an LOD of 0.07 U/mL. In this work, a multilayer film was constructed on SPCE using LbL assembly of polyacrylic acid (PAA) and polyethylenimine (PEI) coated carbon black (CB) for anti-CA19-9 antibody immobilization. Polyelectrolytes improved not only conductivity but also dispensability of CB. Such an approach was also used to fabricate a sensing platform for p53 protein determination where the authors modified SPCE with LbL assembled PEI and citrate functionalized NiFe2O4 NPs for subsequent immobilization of anti-p53 antibody and p53 antigen binding. This biosensor offered a detection range of 1.0~1,000 pg/mL and an LOD of 5.0 fg/mL[14].

    Meanwhile, an integrated plastic chip electrode (PCE) composed of graphite and polymethylmethacrylate free of exfoliation problem for SPCE printed layers was prepared for RBP4 detection[17]. Gold sputter coating and amino terminated monolayer were used to modify the plastic chip, which enabled the immobilization of anti-RBP4 antibody via glutaraldehyde (GA) crosslinker. The surface resistance caused by the antibody-antigen interaction was monitored by electrochemical impedance spectroscopy using [Fe(CN)6]3-/4- species for RBP4 quantitation ranging from 0.1 to 1,000 pg/mL.

    Another good substrate to fabricate electrochemical biosensors for detecting CRC protein like ILs is the conductive indium tin oxide (ITO) glass-based electrode[18-21]. Aydın[18] demonstrated an impedimetric label-free IL-6 biosensor by immobilizing IL-6 receptor on an ITO glass modified with a conjugated epoxy polypyrrole polymer (Epx-PPyr). This sensor provided a linear detection range from 0.02 to 16 pg/mL with an LOD of 6.0 fg/mL. In another related work, the authors modified ITO electrode with acetylene black (AB) with Epx-PPyr composites to enlarge the surface area and biomolecule-loading capacity, which demonstrated a wider and sensitive detection range for IL-6 from 0.01 to 50 pg/mL with an LOD of 3.2 fg/mL[19]. Besides, both biosensors showed acceptable recovery results for IL-6 analysis in diluted human serum samples.

    In addition, photoelectrochemical (PEC) biosensors, a multidisciplinary sensing technique that combines optical and electrochemical approaches, measure electrode photocurrent caused by excitation of photoactive materials exposed to the external light source[25]. The PEC method owes higher sensitivity than the electrochemical and optical ones due to the different energy forms of light excitation source and electrical readout[25,26]. For example, Zhang et al.[22] designed a PEC sensing system for CEA using fluorine-doped tin oxide (FTO) glass photoelectrode which is modified with photosensitive graphitic like carbon nitride and copper indium disulfide hybrids (g-C3N4/CuInS2) and cobalt oxyhydroxide (CoOOH) nanosheets for light blocking. CEA sandwich complexes labelled with alkaline phosphatase (ALP) were then constructed on the surface. ALP catalyzed the substrate of ascorbic acid-2-phosphate to produce an ascorbic acid and break down CoOOH nanosheets allowing g-C3N4/CuInS2 exposure to light. This method could detect CEA concentrations from 0.02 to 40 ng/mL in buffer and showed similar sensing results with those detected by an ELISA kit for serum sample analysis.

    Paper based microfluidic electrochemical biosensors were also used for CRC biomarkers such as EGFR and vascular endothelial growth factor C (VEGF-C) owing to the advantages of low cost and no need for extra equipment for sample flowing[23,24]. For instance, Sun et al. [24] proposed an origami paper-based microfluidic electroanalytical device for real-time sensing of VEGF-C from 0.01 to 100 ng/mL with an LOD of 10 pg/mL (Figure 2). The microfluidic chip was fabricated using wax and screen printing technologies. The modification of working electrodes using new methylene blue (NMB), amino functionalized single- walled carbon nanotubes (NH2-SWCNTs), and gold NPs (AuNPs) nanocomposites enhanced electrical conductivity and provided sufficient surface area for anti-VEGF-C antibody and antigen loading. Such an inexpensive paper-based electrochemical microfluidic chip was applied for VEGF-C analyses in clinical serum samples and the discrepancy with a commercial instrument was less than 9.81%.

    3. Optical Biosensing Platforms for CRC Protein Biomarker

    Apart from electrochemical biosensors, this section will describe some of few recent examples of optical biosensing platforms developed for CRC protein biomarker, including colorimetric and fluorescence-based lateral flow immunoassay (LFIA), surface plasmon resonance (SPR), and surface-enhanced Raman scattering (SERS) shown in Table 2. LFIA is a well-established optical sensing technique mainly composed of a sample pad, conjugate pad, nitrocellulose (NC) detection membrane, and absorbent pad[27]. The principle of LFIA is based on the specific recognition of biomolecules and reflected by the colored or fluorescence changes of signal labels on the detection membrane [28,29]. SPR biosensor measures the refractive index changes on the plasmonic metal (e.g., Au) surface in response to molecule biorecognition[30,31]. It is a highly sensitive label-free technique for real-time detection but still has a limitation, such as nonspecific adsorption[32]. Different from SPR, SERS measures the changes of inelastic scattering on noble metal surfaces induced by biomolecule interaction and used for different malignancy diagnosis[33,34].

    Protein detection using LFIA is based on the optical intensity of colored or fluorescent labels such as dyes, quantum dots, colloidal gold, carbon dots, and magnetic NPs[28,29]. For example, Tang et al.[41] reported a fluorescent LFIA strip for IL-6 detection using CdSe@ZnS quantum dots as labels, which demonstrated a linear range from 10 to 4000 pg/mL with an LOD of 1.995 pg/mL (Figure 3). This LFIA strip was applied to clinical serum sample analyses and comparable to a commercial chemiluminescence immunoassay kit. In another work, europium (III) chelate-doped NPs (EuNPs) were used as labels in LFIA for IL-6 detection[36]. EuNPs have long fluorescence lifetime, narrow and sharp emission peak, offering a dynamic range from 2 to 500 pg/mL and an LOD of 0.37 pg/mL for IL-6 in the buffer. As for clinical human serum sample application, IL-6 LFIA biosensor showed a high correlation with those from a commercial SIEMENS CLIA IL-6 kit.

    Furthermore, Huang et al.[37] established a magnetic colorimetric LFIA for CA19-9 detection in whole blood using CNTs decorated with Fe3O4 magnetic NPs as labels (CNTs-Fe3O4). The CNTs-Fe3O4 conjugated anti-CA19-9 could recognize CA19-9 antigen and magnetically separated from the blood matrix. The CA19-9/anti-CA19-9/CNTs-Fe3O4 complexes were captured by the probe at test line showing visualized brown band for protein quantitation by measuring the color intensity. This LFIA biosensor showed a linearity ranging from 2 to 200 U/mL with an LOD of 1.75 U/mL in buffer solutions and 30 U/mL in human blood. Remarkably, the magnetic separation of CA19-9/anti-CA19-9/ CNTs-Fe3O4 complexes from the complex matrix could reduce biofouling and improve the selectivity, which was demonstrated by negligible interfering effects from biomolecules such as CEA and mammaglobin.

    Whereas utilizing SPR, Lee et al.[6] recently reported a biosensor for detecting hnRNP A1 in human plasma samples of CRC patients (see Figure 4). The DNA aptamers specific to hnRNP A1 were crosslinked on a carboxylic acid-terminated SPR gold chip via (1-ethyl-3- (3-dimethylaminopropyl)carbodiimide hydrochloride/N-hydroxysulfosuccinimide (EDC/Sulfo-NHS) followed by successive specific binding of protein and detection probe to form sandwich complexes. In this work, hnRNP A1 DNA aptamer was used as a capture probe for biosensor fabrication because of its higher binding affinity and robustness compared to the antibody. This biosensor exhibited an LOD of 0.22 nM and was successfully applied to the direct analysis of hnRNP A1 concentrations in both human normal and CRC patient plasma solutions. Also, Ermini et al.[39] demonstrated a four-channel SPR immunosensor composed of AuNPs/streptavidin/biotin-anti-CEA Ab2/CEA/anti-CEA Ab1 on a glass chip coated with a thin Au layer, which could detect CEA as low as 17.8 pg/mL. In this work, the authors found that high ligand doses per NP (LDPN) for AuNPs/streptavidin complexes enhanced the absolute zeta potential value as well as the stability, reproducibility, specific sensing response and reduced nonspecific binding. In contrast, the AuNPs/streptavidin biofunctionalization strategy for biotin-Ab2 binding showed lower nonspecific and similar specific responses versus the one using AuNPs-Ab2 via EDC/Sulfo-NHS crosslinking at high LDPN in both buffer and plasma. Overall, both SPR biosensors discussed here showed a diminished response in human plasma samples compared to those from the buffer, which could be attributed to the reduced specific and enhanced nonspecific interactions caused by strong steric problems or energy barriers in the complex matrix[6,39].

    There are two types of SERS biosensing methods including direct detection using label-free and indirectly using SERS tags; the label-free one offers molecular information but could suffer from the low signal and interference in the matrix while the SERS tags using different Raman reporters could show stable signal and provide more diversity in biosensor fabrication[42]. For example, Medetalibeyoglu et al.[40] reported a SERS-based sandwich assay using 4-mercaptobenzoic acid as Raman reporter for CEA detection in plasma samples. In this work, the composites of d-Ti3C2TX MXene with self-assembled Fe3O4@AuNPs were used as magnetic supporting substrate for CEA capture antibody immobilization due to the excellent mechanical strength and large surface area. For the SERS tag, 4-mercaptobenzoic acid conjugated MoS2 nanoflowers@AuNPs hybrids were used for CEA detection antibody immobilization to form a sandwich assay for CEA biosensing. Thus, CEA quantitation was performed by transferring CEA sandwich complexes on a glass slide, resulting in a linear range from 0.1 pg/mL to 100 ng/mL. In addition, this sensor could detect a standard CEA added in plasma samples with high accuracy.

    4. Conclusions and Future Perspectives

    This review exhibited some of recent biosensing devices developed for common CRC protein biomarkers and potential applications using electrochemical, LFIA, SPR and SERS techniques. While electrochemical strategies provide inexpensive way of fabricating sensors with facile introduction of different surface modification, LFIA methods generally formed on NC membranes become the most encouraging diagnostic device for point-of-care testing with the advantages of relatively low cost and fast sensing[43,44]. On the other hand, SPR and SERS are capable of label-free and sensitive detection of target protein biomarkers but still requiring expensive plasmonic metal (e.g. Au) materials. Overall, the use of biosensors provides a cost-effective, highly sensitive, less invasive, and user-friendly detection strategy for CRC monitoring compared to some clinically visualizable screening techniques. However, there is no single ideal biomarker for CRC diagnosis making it difficult to identify CRC based on the result of a single biomarker detection. Furthermore, CRC is related to multiple abnormal biomarkers, some of which are multifunctional biomarkers for different diseases, for example, IL-6 for prostate cancer, cardiovascular disease, and diabetes[ 18]. From our perspective, multiplexed biosensors for CRC biomarkers are needed, as they improve sensing accuracy and reduce cost. However, the application of multiplexed biosensors for CRC diagnosis and analysis in patient samples is still in its infancy. Thus, many efforts are still required to facilitate the transition of CRC biosensors to clinical applications and homecare devices. Multiplexed sensing devices, such as electrode arrays and barcode configurations-based electrochemical biosensors, microfluidic devices, and multiplexed LFIA have made a significant progress on biomarker detection[45-49]. The combined use of multichannel electrodes and multiplexed LFIA for simultaneous detection of different CRC biomarkers could be a promising strategy for improving accuracy and precision of CRC diagnosis. We also envision that the widespread availability of convenient and affordable CRC biosensors could encourage screening participation and reduce the global cancer burden.

    Acknowledgement

    This research was supported by Kyungpook National University Development Project Research Fund, 2018.

    Figures

    ACE-32-3-253_F1.gif
    An overview of CRC-screening strategies highlighting different biosensing techniques for CRC protein biomarkers.
    ACE-32-3-253_F2.gif
    Schematic showing the (a) fabrication process of an origami paper based electrochemical biosensor and (b) modification of the working electrode for VEGF-C detection using SWCNTs, NMB, and AuNPs composites. Reproduced with permission from ref. [24] (Open access under the Creative Commons CC BY license, 2021 Springer Nature).
    ACE-32-3-253_F3.gif
    Schematic showing the components of an LFIA strip for CEA detection. Reprinted with permission from ref. [41] (Open access under the Creative Commons CC-BY-NC-ND license, 2021 Wiley Periodicals).
    ACE-32-3-253_F4.gif
    Schematic showing (a) the formation of the sandwich complex on an SPR gold chip for hnRNP A1 detection with an aptamer and anti-hnRNP A1 and (b) real-time analyses in CRC plasma samples. Reproduced with permission from ref. [6]. Copyright, 2020 Elsevier.

    Tables

    Electrochemical Biosensors Developed for CRC Protein Biomarkers
    Some Examples of Optical Biosensors Developed for CRC Protein Biomarkers

    References

    1. A. J. M. Watson and P. D. Collins, Colon cancer: A civilization disorder, Dig. Dis., 29, 222-228 (2011).
    2. Cancer, https://www.who.int/health-topics/cancer#tab=tab_1 (Access on April 23, 2021).
    3. E. Ferlizza, R. Solmi, M. Sgarzi, L. Ricciardiello, and M. Lauriola, The roadmap of colorectal cancer screening, Cancers, 13, 1101 (2021).
    4. J. Quinchia, D. Echeverri, A. F. Cruz-Pacheco, M. E. Maldonado, and J. Orozco, Electrochemical biosensors for determination of colorectal tumor biomarkers, Micromachines, 11, 411 (2020).
    5. W. Fei, L. Chen, J. Chen, Q. Shi, L. Zhang, S. Liu, L. Li, L. Zheng, and X. Hu, RBP4 and THBS2 are serum biomarkers for diagnosis of colorectal cancer, Oncotarget, 8, 92254-92264 (2017).
    6. S. H. Lee, Y. E. Park, J. E. Lee, and H. J. Lee, A surface plasmon resonance biosensor in conjunction with a DNA aptamer-antibody bioreceptor pair for heterogeneous nuclear ribonucleoprotein A1 concentrations in colorectal cancer plasma solutions, Biosens. Bio- electron., 154, 112065 (2020).
    7. U. Ladabaum, J. A. Dominitz, C. Kahi, and R. E. Schoen, Strategies for colorectal cancer screening, Gastroenterology, 158, 418-432 (2020).
    8. M. F. Kaminski, D. J. Robertson, C. Senore, and D. K. Rex, Optimizing the quality of colorectal cancer screening worldwide, Gastroenterology, 158, 404-417 (2020).
    9. P. Kuppusamy, N. Govindan, M. M. Yusoff, and S. J. A. Ichwan, Proteins are potent biomarkers to detect colon cancer progression, Saudi J. Biol. Sci., 24, 1212-1221 (2017).
    10. M. Barani, M. Bilal, A. Rahdar, R. Arshad, A. Kumar, H. Hamishekar, and G. Z. Kyzas, Nanodiagnosis and nanotreatment of colorectal cancer: An overview, J. Nanopart. Res., 23, 18 (2021).
    11. P. Butmee, G. Tumcharern, G. Thouand, K. Kalcher, and A. Samphao, An ultrasensitive immunosensor based on manganese dioxide- graphene nanoplatelets and core shell Fe3O4@Au nanoparticles for label-free detection of carcinoembryonic antigen, Bioelectrochemistry, 132, 107452 (2020).
    12. G. Paniagua, A. Villalonga, M. Eguílaz, B. Vegas, C. Parrado, G. Rivas, P. Díez, and R. Villalonga, Amperometric aptasensor for carcinoembryonic antigen based on the use of bifunctionalized Janus nanoparticles as biorecognition-signaling element, Anal. Chim. Acta, 1061, 84-91 (2019).
    13. G. Ibáñez-Redín, E. M. Materon, R. H. M. Furuta, D. Wilson, G. F. do Nascimento, M. E. Melendez, A. L. Carvalho, R. M. Reis, O. N. Oliveira, Jr., and D. Gonçalves, Screen-printed electrodes modified with carbon black and polyelectrolyte films for determination of cancer marker carbohydrate antigen 19-9, Microchim. Acta, 187, 417 (2020).
    14. G. Ibáñez-Redín, N. Joshi, G. F. do Nascimento, D. Wilson, M. E. Melendez, A. L. Carvalho, R. M. Reis, D. Gonçalves, and O. N. Oliveira, Jr., Determination of p53 biomarker using an electrochemical immunoassay based on layer-by-layer films with NiFe2O4 nanoparticles, Microchim. Acta, 187, 619 (2020).
    15. R. Elshafey, P. Brisebois, H. Abdulkarim, R. Izquierdo, A. C. Tavares, and M. Siaj, Effect of graphene oxide sheet size on the response of a label‐free voltammetric immunosensor for cancer marker VEGF, Electroanalysis, 32, 2205-2212 (2020).
    16. G. Ibáñez-Redín, R. H. M. Furuta, D. Wilson, F. M. Shimizu, E. M. Materon, L. Arantes, M. E. Melendez, A. L. Carvalho, R. M. Reis, M. N. Chaur, D. Gonçalves, and O. N. Oliveira, Jr., Screen-printed interdigitated electrodes modified with nanostructured carbon nano-onion films for detecting the cancer biomarker CA19-9, Mater. Sci. Eng. C, 99, 1502-1508 (2019).
    17. A. Paul, C. M. S., E. Primiceri, D. N. Srivastava, and G. Maruccio, Picomolar detection of retinol binding protein 4 for early management of type II diabetes, Biosens. Bioelectron., 128, 122-128 (2019).
    18. E. B. Aydın, Highly sensitive impedimetric immunosensor for determination of interleukin 6 as a cancer biomarker by using conjugated polymer containing epoxy side groups modified disposable ITO electrode, Talanta, 215, 120909 (2020).
    19. E. B. Aydın, M. Aydın, and M. K. Sezgintürk, A novel electrochemical immunosensor based on acetylene black/epoxy-substituted- polypyrrole polymer composite for the highly sensitive and selective detection of interleukin 6, Talanta, 222, 121596 (2021).
    20. S. Verma, A. Singh, A. Shukla, J. Kaswan, K. Arora, J. Ramirez-Vick, P. Singh, and S. P. Singh, Anti-IL8/AuNPs-rGO/ITO as an immunosensing platform for noninvasive electrochemical detection of oral cancer, ACS Appl. Mater. Interfaces, 9, 27462-27474 (2017).
    21. N. Pachauri, G. Lakshmi, S. Sri, P. K. Gupta, and P. R. Solanki, Silver molybdate nanoparticles based immunosensor for the non-invasive detection of Interleukin-8 biomarker, Mater. Sci. Eng. C, 113, 110911 (2020).
    22. K. Zhang, S. Lv, Q. Zhou, and D. Tang, CoOOH nanosheets-coated g-C3N4/CuInS2 nanohybrids for photoelectrochemical biosensor of carcinoembryonic antigen coupling hybridization chain reaction with etching reaction, Sens. Actuators B Chem., 307, 127631 (2020).
    23. Y. Wang, S. Sun, J. Luo, Y. Xiong, T. Ming, J. Liu, Y. Ma, S. Yan, Y. Yang, Z. Yang, J. Reboud, H. Yin, J. M. Cooper, and X. Cai, Low sample volume origami-paper-based graphene-modified aptasensors for label-free electrochemical detection of cancer biomarker- EGFR, Microsyst. Nanoeng., 6, 1-9 (2020).
    24. S. Sun, Y. Wang, T. Ming, J. Luo, Y. Xing, J. Liu, Y. Xiong, Y. Ma, S. Yan, Y. Yang, and X. Cai, An origami paper-based nanoformulated immunosensor detects picograms of VEGF-C per milliliter of blood, Commun. Biol., 4, 121 (2021).
    25. J. Shu and D. Tang, Recent advances in photoelectrochemical sensing: From engineered photoactive materials to sensing devices and detection modes, Anal. Chem., 92, 363-377 (2020).
    26. A. Devadoss, P. Sudhagar, C. Terashima, K. Nakata, and A. Fujishima, Photoelectrochemical biosensors: new insights into promising photoelectrodes and signal amplification strategies, J. Photochem. Photobiol. C, 24, 43-63 (2015).
    27. S. Lee and H. J. Lee, Recent research trend in lateral flow immunoassay strip (LFIA) with colorimetric method for detection of cancer biomarkers, Appl. Chem. Eng., 31, 585-590 (2020).
    28. L. Anfossi, F. Di Nardo, S. Cavalera, C. Giovannoli, and C. Baggiani, Multiplex lateral flow immunoassay: An overview of strategies towards high-throughput point-of-need testing, Biosensors, 9, 1-14 (2019).
    29. M. Sajid, A.-N. Kawde, and M. Daud, Designs, formats and applications of lateral flow assay: A literature review, J. Saudi Chem. Soc., 19, 689-705 (2015).
    30. S. Kim, A. W. Wark, and H. J. Lee, Femtomolar detection of Tau proteins in undiluted plasma using surface plasmon resonance, Anal. Chem., 88, 7793-7799 (2016).
    31. S. H. Baek, H. W. Song, S. Lee, J.-E. Kim, Y. H. Kim, J. S. Wi, J. G. Ok, J. S. Park, S. Hong, M. K. Kwak, H. J. Lee, and S.-W. Nam, Gold nanoparticle-enhanced and roll-to-roll nanoimprinted LSPR platform for detecting interleukin-10, Front. Chem., 8, 285 (2020).
    32. B. Shao, and Z. Xiao, Recent achievements in exosomal biomarkers detection by nanomaterials-based optical biosensors – A review, Anal. Chim. Acta, 1114, 74-84 (2020).
    33. K.-H. Chen, M.-J. Pan, Z. Jargalsaikhan, T.-O. Ishdorj, and F.-G. Tseng, Development of surface-enhanced raman scattering (SERS)- based surface-corrugated nanopillars for biomolecular detection of colorectal cancer, Biosensors, 10, 163 (2020).
    34. V. Moisoiu, A. Stefancu, D. Gulei, R. Boitor, L. Magdo, L. Raduly, S. Pasca, P. Kubelac, N. Mehterov, V. Chis, M. Simon, M. Muresan, A. I. Irimie, M. Baciut, R. Stiufiuc, I. E. Pavel, P. Achimas-Cadariu, C. Ionescu, V. Lazar, V. Sarafian, I. Notingher, N. Leopold, and I. Berindan-Neagoe, SERS-based differential diagnosis between multiple solid malignancies: Breast, colorectal, lung, ovarian and oral cancer, Int. J. Nanomedicine, 14, 6165-6178 (2019).
    35. T. Mahmoudi, B. Shirdel, B. Mansoori, and B. Baradaran, Dual sensitivity enhancement in gold nanoparticle‐based lateral flow immunoassay for visual detection of carcinoembryonic antigen, Anal. Sci. Adv., 1, 161-172 (2020).
    36. D. Huang, H. Ying, D. Jiang, F. Liu, Y. Tian, C. Du, L. Zhang, and X. Pu, Rapid and sensitive detection of interleukin-6 in serum via time-resolved lateral flow immunoassay, Anal. Biochem., 588, 113468 (2020).
    37. Y. Huang, Y. Wen, K. Baryeh, S. Takalkar, M. Lund, X. Zhang, and G. Liu, Lateral flow assay for carbohydrate antigen 19-9 in whole blood by using magnetized carbon nanotubes, Microchim. Acta, 184, 4287-4294 (2017).
    38. V. Ranganathan, S. Srinivasan, A. Singh, and M. C. DeRosa, An aptamer-based colorimetric lateral flow assay for the detection of human epidermal growth factor receptor 2 (HER2), Anal. Biochem., 588, 113471 (2020).
    39. M. L. Ermini, X. Chadtova Song, T. Špringer, and J. Homola, Peptide functionalization of gold nanoparticles for the detection of carcinoembryonic antigen in blood plasma via SPR-based biosensor, Front. Chem., 7, 40 (2019).
    40. H. Medetalibeyoglu, G. Kotan, N. Atar, and M. L. Yola, A novel sandwich-type SERS immunosensor for selective and sensitive carcinoembryonic antigen (CEA) detection, Anal. Chim. Acta, 1139, 100-110 (2020).
    41. J. Tang, L. Wu, J. Lin, E. Zhang, and Y. Luo, Development of quantum dot-based fluorescence lateral flow immunoassay strip for rapid and quantitative detection of serum interleukin-6, J. Clin. Lab. Anal., 35, e23752 (2021).
    42. P. Li, F. Long, W. Chen, J. Chen, P. K. Chu, and H. Wang, Fundamentals and applications of surface-enhanced Raman spectroscopy- based biosensors, Curr. Opin. Biomed. Eng., 13, 51-59 (2020).
    43. A. Roointan, T. Ahmad Mir, S. Ibrahim Wani, R. Mati Ur, K. K. Hussain, B. Ahmed, S. Abrahim, A. Savardashtaki, G. Gandomani, M. Gandomani, R. Chinnappan, and M. H. Akhtar, Early detection of lung cancer biomarkers through biosensor technology: A review, J. Pharm. Biomed. Anal., 164, 93-103 (2019).
    44. G. Luka, A. Ahmadi, H. Najjaran, E. Alocilja, M. DeRosa, K. Wolthers, A. Malki, H. Aziz, A. Althani, and M. Hoorfar, Microfluidics integrated biosensors: A leading technology towards lab-on-a-chip and sensing applications, Sensors, 15, 30011-30031 (2015).
    45. P. Yáñez-Sedeño, S. Campuzano, and J. M. Pingarrón, Multiplexed electrochemical immunosensors for clinical biomarkers, Sensors, 17, 965 (2017).
    46. L. Huang, S. Tian, W. Zhao, K. Liu, X. Ma, and J. Guo, Multiplexed detection of biomarkers in lateral-flow immunoassays, Analyst, 145, 2828-2840 (2020).
    47. Y. Gao, W. Huo, L. Zhang, J. Lian, W. Tao, C. Song, J. Tang, S. Shi, and Y. Gao, Multiplex measurement of twelve tumor markers using a GMR multi-biomarker immunoassay biosensor, Biosens. Bioelectron., 123, 204-210 (2019).
    48. M. Johari-Ahar, P. Karami, M. Ghanei, A. Afkhami, and H. Bagheri, Development of a molecularly imprinted polymer tailored on disposable screen-printed electrodes for dual detection of EGFR and VEGF using nano-liposomal amplification strategy, Biosens. Bioelectron., 107, 26-33 (2018).
    49. R.-I. Stefan-van Staden, R.-M. Ilie-Mihai, and S. Gurzu, Simultaneous determination of carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), and serum protein p53 in biological samples with protoporphyrin IX (PIX) used for recognition by stochastic microsensors, Anal. Lett., 53, 2545-2558 (2020).
    Copyright © The Korean Society of Industrial and Engineering Chemistry. All rights reserved.