Aptamer-based biosensors for the diagnosis of sepsis

Lubin Liu1, Zeyu Han1, Fei An1, Xuening Gong1, Chenguang Zhao1, Wei Zheng1, Li Mei2, Qihui Zhou2
1Institute for Translational Medicine, Department of Stomatology, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, 266003, China
2School of Stomatology, Qingdao University, Qingdao 266003, China

Tóm tắt

AbstractSepsis, the syndrome of infection complicated by acute organ dysfunction, is a serious and growing global problem, which not only leads to enormous economic losses but also becomes one of the leading causes of mortality in the intensive care unit. The detection of sepsis-related pathogens and biomarkers in the early stage plays a critical role in selecting appropriate antibiotics or other drugs, thereby preventing the emergence of dangerous phases and saving human lives. There are numerous demerits in conventional detection strategies, such as high cost, low efficiency, as well as lacking of sensitivity and selectivity. Recently, the aptamer-based biosensor is an emerging strategy for reasonable sepsis diagnosis because of its accessibility, rapidity, and stability. In this review, we first introduce the screening of suitable aptamer. Further, recent advances of aptamer-based biosensors in the detection of bacteria and biomarkers for the diagnosis of sepsis are summarized. Finally, the review proposes a brief forecast of challenges and future directions with highly promising aptamer-based biosensors.

Từ khóa


Tài liệu tham khảo

Hotchkiss RS, Karl IE. The pathophysiology and treatment of sepsis. N Engl J Med. 2003;348:138–50.

Cohen J. The immunopathogenesis of sepsis. Nature. 2002;420:885–91.

Bone RC. The pathogenesis of sepsis. Ann Intern Med. 1991;115:457–69.

Kanashiro A, Sônego F, Ferreira RG, Castanheira FVS, Leite CA, Borges VF, et al. Therapeutic potential and limitations of cholinergic anti-inflammatory pathway in sepsis. Pharmacol Res . 2017;117:1–8.

Hotchkiss RS, Moldawer LL, Opal SM, Reinhart K, Turnbull IR, Vincent JL. Sepsis and septic shock. Nat Rev Dis Prim. 2016. https://doi.org/10.1038/nrdp.2016.45.

Thompson BT. Drotrecogin alfa (activated) did not reduce mortality at 28 or 90 days in patients with septic shock. Ann Intern Med. 2012;157:24774.

Opal SM, Garber GE, LaRosa SP, Maki DG, Freebairn RC, Kinasewitz GT, et al. Systemic host responses in severe sepsis analyzed by causative microorganism and treatment effects of drotrecogin alfa (activated). Clin Infect Dis. 2003;37:50–8.

Vincent JL, Rello J, Marshall J, Silva E, Anzueto A, Martin CD, Moreno R, Lipman J, Gomersall C. International study of the prevalence and outcomes of infection in intensive care units. JAMA. 2009;302:2323–9.

Zhang G, Ghosh S. Molecular mechanisms of NF-κB activation induced by bacterial lipopolysaccharide through Toll-like receptors. J Endotoxin Res. 2000;6:453–7.

Lin KH, Wang FL, Wu MS, Jiang BY, Kao WL, Chao HY, et al. Serum procalcitonin and C-reactive protein levels as markers of bacterial infection in patients with liver cirrhosis: A systematic review and meta-analysis. Diagn Microbiol Infect Dis. 2014;80:72–8.

Fleischmann C, Scherag A, Adhikari NKJ, Hartog CS, Tsaganos T, Schlattmann P, et al. Assessment of global incidence and mortality of hospital-treated sepsis current estimates and limitations. Am J Respir Crit Care Med. 2016;193:259–72.

Filbin MR, Lynch J, Gillingham TD, Thorsen JE, Pasakarnis CL, Nepal S, et al. Presenting symptoms independently predict mortality in septic shock: Importance of a previously unmeasured confounder. Crit Care Med. 2018;46:1592–9.

Kumar A, Ellis P, Arabi Y, Roberts D, Light B, Parrillo JE, et al. Initiation of inappropriate antimicrobial therapy results in a fivefold reduction of survival in human septic shock. Chest. 2009;136:1237–48.

Singer M, Deutschman CS, Seymour C, Shankar-Hari M, Annane D, Bauer M, et al. The third international consensus definitions for sepsis and septic shock (sepsis-3). JAMA. 2016;315:801–10.

Ottesen EA, Hong JW, Quake SR, Leadbetter JR. Microfluidic digital PCR enables multigene analysis of individual environmental bacteria. Science. 2006;314:1464−67.

Burtscher C, Wuertz S. Evaluation of the use of PCR and reverse transcriptase PCR for detection of pathogenic bacteria in biosolids from anaerobic digestors and aerobic composters. Appl Environ Microbiol. 2003;69:4618–27.

Pechorsky A, Nitzan Y, Lazarovitch T. Identification of pathogenic bacteria in blood cultures: comparison between conventional and PCR methods. J Microbiol Methods. 2009;78:325–30.

Park KS. Nucleic acid aptamer-based methods for diagnosis of infections. Biosens Bioelectron. 2018;102:179–88.

Tuerk C, Gold L. Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase. Science. 1990;249:505–10.

Ad E, Jw S. In vitro selection of RNA molecules that bind specific ligands. Nature. 1990;346:818–22.

Meek KN, Rangel AE, Heemstra JM. Enhancing aptamer function and stability via in vitro selection using modified nucleic acids. Methods. 2016;106:29–36.

Zhou S, Lu C, Li Y, Xue L, Zhao C, Tian G, et al. Gold nanobones enhanced ultrasensitive surface-enhanced raman scattering aptasensor for detecting Escherichia coli O157:H7. ACS Sens. 2020;5:588–96.

Deng B, Lin Y, Wang C, Li F, Wang Z, Zhang H, et al. Aptamer binding assays for proteins: the thrombin example-A review. Anal Chim Acta. 2014;837:1–15.

Sung TC, Chen WY, Shah P, Chen CS. A replaceable liposomal aptamer for the ultrasensitive and rapid detection of biotin. Sci Rep . 2016;6:1–8.

He JL, Wu ZS, Zhou H, Wang HQ, Jiang JH, Shen GL, et al. Fluorescence aptameric sensor for strand displacement amplification detection of cocaine. Anal Chem. 2010;82:1358–64.

Fan Y, Zhang W, Liu Y, Zeng Z, Quan X, Zhao H. Three-dimensional branched crystal carbon nitride with enhanced intrinsic peroxidase-like activity: a hypersensitive platform for colorimetric detection. ACS Appl Mater Interfaces. 2019;11:17467–74.

Li N, Ho CM. Aptamer-based optical probes with separated molecular recognition and signal transduction modules. J Am Chem Soc. 2008;130:2380–1.

Lautner G, Balogh Z, Bardóczy V, Mészáros T, Gyurcsányi RE. Aptamer-based biochips for label-free detection of plant virus coat proteins by SPR imaging. Analyst. 2010;135:918–26.

Simeonov Y, Weber U, Penchev P, Ringbæk TP, Schuy C, Brons S, et al. 3D range-modulator for scanned particle therapy: development, Monte Carlo simulations and experimental evaluation. Phys Med Biol. 2017;62:7075–96.

Beiranvand ZS, Abbasi AR, Dehdashtian S, Karimi Z, Azadbakht A. Aptamer-based electrochemical biosensor by using Au-Pt nanoparticles, carbon nanotubes and acriflavine platform. Anal Biochem Elsevier Ltd. 2017;518:35–45.

Mok W, Li Y. Recent progress in nucleic acid aptamer-based biosensors and bioassays. Sensors. 2008;8:7050–84.

Xu L, Dai Q, Shi Z, Liu X, Gao L, Wang Z, et al. Accurate MRSA identification through dual-functional aptamer and CRISPR-Cas12a assisted rolling circle amplification. J Microbiol Methods. 2020;173:105917.

Zhou J, Bobbin ML, Burnett JC, Rossi JJ. Current progress of RNA aptamer-based therapeutics. Front Genet. 2012;3:1–14.

Yang L, Pijuan-Galito S, Rho HS, Vasilevich AS, Eren AD, Ge L, et al. High-throughput methods in the discovery and study of biomaterials and materiobiology. Chem Rev. 2021. https://doi.org/10.1021/acs.chemrev.0c00752.

Zhou Q, Chen J, Luan Y, Vainikka PA, Thallmair S, Marrink SJ, et al. Unidirectional rotating molecular motors dynamically interact with adsorbed proteins to direct the fate of mesenchymal stem cells. Sci Adv. 2020. https://doi.org/10.1126/sciadv.aay2756.

Zhou Q, Zhao Z, Zhou Z, Zhang G, Chiechi RC, van Rijn P. Directing mesenchymal stem cells with gold nanowire arrays. Adv Mater Interfaces. 2018;5:1–8.

Ji Y, Han Z, Ding H, Xu X, Wang D, Zhu Y, et al. Enhanced eradication of bacterial/fungi biofilms by glucose oxidase-modified magnetic nanoparticles as a potential treatment for persistent endodontic infections. ACS Appl Mater Interfaces. 2021. https://doi.org/10.1021/acsami.1c01748.

Fan Y, Liu Y, Zhou Q, Du H, Zhao X, Ye F, et al. Catalytic hairpin assembly indirectly covalent on Fe3O4@C nanoparticles with signal amplification for intracellular detection of miRNA. Talanta. 2021;223:121675.

Yu Z, Li Q, Wang J, Yu Y, Wang Y, Zhou Q, et al. Reactive oxygen species-related nanoparticle toxicity in the biomedical field. Nanoscale Res Lett. 2020;15:1–14.

Yao J, Yang M, Duan Y. Chemistry, biology, and medicine of fluorescent nanomaterials and related systems: New insights into biosensing, bioimaging, genomics, diagnostics, and therapy. Chem Rev. 2014;114:6130–78.

Biju V. Chemical modifications and bioconjugate reactions of nanomaterials for sensing, imaging, drug delivery and therapy. Chem Soc Rev. 2014;43:744–64.

Smith BR, Gambhir SS. Nanomaterials for in vivo imaging. Chem Rev . 2017;117:901–86.

Zu G, Cao Y, Dong J, Zhou Q, van Rijn P, Liu M, et al. Development of an Aptamer-Conjugated Polyrotaxane-Based Biodegradable Magnetic Resonance Contrast Agent for Tumor-Targeted Imaging. ACS Appl Bio Mater. 2019;2:406–16.

Chang YC, Yang CY, Sun RL, Cheng YF, Kao WC, Yang PC. Rapid single cell detection of Staphylococcus aureus by aptamer-conjugated gold nanoparticles. Sci Rep. 2013;3:1–7.

Shen H, Wang J, Liu H, Li Z, Jiang F, Wang FB, et al. Rapid and Selective Detection of Pathogenic Bacteria in Bloodstream Infections with Aptamer-Based Recognition. ACS Appl Mater Interfaces. 2016;8:19371–8.

Song JH, Lee SM, Park IH, Yong D, Lee KS, Shin JS, et al. Vertical capacitance aptasensors for real-time monitoring of bacterial growth and antibiotic susceptibility in blood. Biosens Bioelectron. 2019;143:111623.

Lee KS, Lee SM, Oh J, Park IH, Song JH, Han M, et al. Electrical antimicrobial susceptibility testing based on aptamer-functionalized capacitance sensor array for clinical isolates. Sci Rep . 2020;10:1–9.

Graziani AC, Stets MI, Lopes ALK, Schluga PHC, Marton S, Ferreira IM, et al. High efficiency binding aptamers for a wide range of bacterial sepsis agents. J Microbiol Biotechnol. 2017;27:838–43.

Shin HS, Gedi V, Kim JK, Lee DK. Detection of Gram-negative bacterial outer membrane vesicles using DNA aptamers. Sci Rep. 2019;9:1–8.

Kim SE, Su W, Cho M, Lee Y, Choe WS. Harnessing aptamers for electrochemical detection of endotoxin. Anal Biochem. 2012;424:12–20.

Bai L, Chai Y, Pu X, Yuan R. A signal-on electrochemical aptasensor for ultrasensitive detection of endotoxin using three-way DNA junction-aided enzymatic recycling and graphene nanohybrid for amplification. Nanoscale. 2014;6:2902–8.

Posha B, Nambiar SR, Sandhyarani N. Gold atomic cluster mediated electrochemical aptasensor for the detection of lipopolysaccharide. Biosens Bioelectron. 2018;101:199–205.

Pourmadadi M, Shayeh JS, Omidi M, Yazdian F, Alebouyeh M, Tayebi L. A glassy carbon electrode modified with reduced graphene oxide and gold nanoparticles for electrochemical aptasensing of lipopolysaccharides from Escherichia coli bacteria. Microchim Acta Microchimica Acta. 2019;186:2–9.

Yazdian F, Rashedi H. Applying reduced graphene oxide-gold nanoparticles for the electrochemical detection of endotoxin. In: Proceedings of the 7th international conference on innovation in science and technology. 2020. p. 280–94.

Yuan Y, Li L, Zhao M, Zhou J, Bai L. An aptamer based voltammetric biosensor for endotoxins using a functionalized graphene and molybdenum disulfide composite as a new nanocarrier. Anal R Soc Chem. 2018;144:1253–9.

An Z, Jang CH. Simple and label-free liquid crystal-based optical sensor for highly sensitive and selective endotoxin detection by aptamer binding and separation. ChemistrySelect. 2019;4:1416–22.

Ji J, Pang Y, Li D, Huang Z, Zhang Z, Xue N, et al. An aptamer-based shear horizontal surface acoustic wave biosensor with a CVD-grown single-layered graphene film for high-sensitivity detection of a label-free endotoxin. Microsyst Nanoeng. 2020. https://doi.org/10.1038/s41378-019-0118-6.

Zhang Z, Yang J, Pang W, Yan G. An aptamer-based fluorescence probe for facile detection of lipopolysaccharide in drinks. RSC Adv R Soc Chem. 2017;7:54920–6.

Niu J, Hu X, Ouyang W, Chen Y, Liu S, Han J, et al. Femtomolar detection of lipopolysaccharide in injectables and serum samples using aptamer-coupled reduced graphene oxide in a continuous injection-electrostacking biochip. Anal Chem. 2019;91:2360–7.

Giorgi-Coll S, Marín MJ, Sule O, Hutchinson PJ, Carpenter KLH. Aptamer-modified gold nanoparticles for rapid aggregation-based detection of inflammation: an optical assay for interleukin-6. Microchim Acta Microchimica Acta. 2020;187:1–11.

Tertis M, Leva PI, Bogdan D, Suciu M, Graur F, Cristea C. Impedimetric aptasensor for the label-free and selective detection of Interleukin-6 for colorectal cancer screening. Biosens Bioelectron. 2019;137:123–32.

Khosravi F, Loeian SM, Panchapakesan B. Ultrasensitive label-free sensing of IL-6 based on PASE functionalized carbon nanotube micro-arrays with RNA-aptamers as molecular recognition elements. Biosensors. 2017;7:1–13.

Hao Z, Pan Y, Huang C, Wang Z, Zhao X. Sensitive detection of lung cancer biomarkers using an aptameric graphene-based nanosensor with enhanced stability. Biomed Microdevices . 2019;21:1–9.

Hao Z, Pan Y, Huang C, Wang Z, Lin Q, Zhao X, et al. Modulating the linker immobilization density on aptameric graphene field effect transistors using an electric field. ACS Sensors. 2020;5:2503–13.

Zamarreño CR, Ardaiz I, Ruete L, Muñoz FJ, Matias IR, Arregui FJ. C-reactive protein aptasensor for early sepsis diagnosis by means of an optical fiber device. Proc IEEE Sensors 2013. 2013; p. 4–7.

Bernard ED, Nguyen KC, DeRosa MC, Tayabali AF, Aranda-Rodriguez R. Development of a bead-based aptamer/antibody detection system for C-reactive protein. Anal Biochem. 2015;472:67–74.

Ghosh S, Metlushko A, Chaudhry S, Dutta M, Stroscio MA. Detection of c-reactive protein using network-deployable DNA aptamer based optical nanosensor. In: 2019 IEEE EMBS International Conference on Biomedical & Health Informatics (BHI). 2019. p. 1–4.

Wang J, Wu H, Yang Y, Yan R, Zhao Y, Wang Y, et al. Bacterial species-identifiable magnetic nanosystems for early sepsis diagnosis and extracorporeal photodynamic blood disinfection. Nanoscale. 2018;10:132–41.

Saito S. SELEX-based DNA aptamer selection: a perspective from the advancement of separation techniques. Anal Sci. 2021;37:17–26.

Zhuo Z, Yu Y, Wang M, Li J, Zhang Z, Liu J, et al. Recent advances in SELEX technology and aptamer applications in biomedicine. Int J Mol Sci. 2017;18:1–19.

Darmostuk M, Rimpelova S, Gbelcova H, Ruml T. Current approaches in SELEX: an update to aptamer selection technology. Biotechnol Adv. 2014;33:1141–61.

Kaur H. Recent developments in cell-SELEX technology for aptamer selection. Biochim Biophys Acta Gen Subj. 2018;1862(10):2323–9.

Khilnani P. Severe sepsis and septic shock. In: Chawla R, Todi S, editors. ICU Protoc A stepwise approach. India: Springer; 2012. p. 703–7.

Cross AS, Zierdt CH, Roup B, Almazan R, Swan JC. A hospital-wide outbreak of septicemia due to a few strains of Staphylococcus aureus. Am J Clin Pathol. 1983;79:598–603.

Vollmer W, Blanot D, De Pedro MA. Peptidoglycan structure and architecture. FEMS Microbiol Rev. 2008;32:149–67.

Schumann P. Peptidoglycan structure. Methods Microbiol. Elsevier Ltd. 2011;38:101–29.

Ferreira IM, de Souza Lacerda CM, de Faria LS, Corrêa CR, de Andrade ASR. Selection of peptidoglycan-specific aptamers for bacterial cells identification. Appl Biochem Biotechnol. 2014;174:2548–56.

Beveridge TJ. Structures of gram-negative cell walls and their derived membrane vesicles. J Bacteriol. 1999;181:4725–33.

Jan AT. Outer Membrane Vesicles (OMVs) of gram-negative bacteria: a perspective update. Front Microbiol. 2017;8:1–11.

Khan ZA, Siddiqui MF, Park S. Current and emerging methods of antibiotic susceptibility testing. Diagnostics. 2019. https://doi.org/10.3390/diagnostics9020049.

Syal K, Mo M, Yu H, Iriya R, Jing W, Guodong S, et al. Current and emerging techniques for antibiotic susceptibility tests. Theranostics. 2017;7:1795–805.

Behera B, Anil Vishnu GK, Chatterjee S, Sitaramgupta VVSN, Sreekumar N, Nagabhushan A, et al. Emerging technologies for antibiotic susceptibility testing. Biosens Bioelectron. 2019;142:111552.

Kumar A, Roberts D, Wood KE, Light B, Parrillo JE, Sharma S, et al. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock*. Crit Care Med. 2006;34:1589–96.

Song J, Moon S, Park DW, Cho H, Kim JY, Park J, et al. Biomarker combination and SOFA score for the prediction of mortality in sepsis and septic shock. Medicine (Baltimore). 2020. https://doi.org/10.1097/MD.0000000000020495.

Bauer M, Strom M, Hammond DS. Anything You Can Do, I Can Do Better : can aptamers replace antibodies in clinical diagnostic applications? Molecules. 2019;24:1–13.

Alizadeh N, Yousef M, Reza S. Aptamer-assisted novel technologies for detecting bacterial pathogens. ScienceDirect. 2017;93:737–45.

Gold L, Ayers D, Bertino J, Bock C, Bock A, Brody EN, et al. Aptamer-based multiplexed proteomic technology for biomarker discovery. Nat Preced. 2010. https://doi.org/10.1371/journal.pone.0015004.

Liu Y, Hou J, Li Q, Chen K, Wang SN, Wang J. Biomarkers for diagnosis of sepsis in patients with systemic inflammatory response syndrome : a systematic review and meta—analysis. Springerplus. 2016. https://doi.org/10.1186/s40064-016-3591-5.

Preston A, Mandrell RE, Gibson BW, Apicella MA. The lipooligosaccharides of pathogenic gram-negative bacteria. Crit Rev Microbiol. 1996;22:139–80.

Rosadini CV, Kagan JC. Early innate immune responses to bacterial LPS. Curr Opin Immunol . 2017;44:14–9.

Welch H. Herbert 0. Calvery WTM and CWP, The Method of Preparation and Test for Bacterial Pyrogen. J Am Pharm Assoc. 1949;71:2955–7.

Iwanaga S, Miyata T, Tokunaga F, Muta T. Molecular mechanism of hemolymph clotting system in Limulus. Thromb Res. 1992;68(1):1–32.

Franco E, Garcia-Recio V, Jiménez P, Garrosa M, Girbés T, Cordoba-Diaz M, et al. Endotoxins from a pharmacopoeial point of view. Toxins (Basel). 2018;10:1–9.

Inoue KY, Ino K, Shiku H, Matsue T. Electrochemical detection of endotoxin using recombinant factor C zymogen. Electrochem commun. 2010;12:1066–9.

Demertzis N. Development of a multiplex sensing platform for the accurate and rapid diagnosis of Sepsis. (Doctoral dissertation, Cardiff University) 2020.

Lee BR, Kim JW, Kang D, Lee DW, Ko SJ, Lee HJ, et al. Highly efficient polymer light-emitting diodes using graphene oxide as a hole transport layer. ACS Nano. 2012;6:2984–91.

Meyer C, Eydeler K, Magbanua E, Zivkovic T, Piganeau N, Lorenzen I, et al. Interleukin-6 receptor specific RNA aptamers for cargo delivery into target cells. RNA Biol. 2012;9:67–80.

Pfäfflin A, Schleicher E. Inflammation markers in point-of-care testing (POCT). Anal Bioanal Chem. 2009;393:1473–80.

Clinical C, Unit T, Hospital QE. Interleukin 6 is a prognostic indicator of outcome in severe intra-abdominal sepsis. Br J Surg. 1994;81:1306–8.

Hunter CA, Jones SA. IL-6 as a keystone cytokine in health and disease. Nat Immunol . 2015;16:448–57.

Kumar S, Tripathy S, Jyoti A, Singh SG. Recent advances in biosensors for diagnosis and detection of sepsis: a comprehensive review. Biosens Bioelectron. 2019;124–125:205–15.

Hencst JM. The role of C-Reaction protein in the evaluation and management of infants with suspected sepsis. Adv Neonatal Care. 2003;3:3–13.

Pierrakos C, Vincent JL. Sepsis biomarkers: a review. Crit Care. 2010;14:1–18.

Yang AP, Liu J, Yue LH, Wang HQ, Yang WJ, Yang GH. Neutrophil CD64 combined with PCT, CRP and WBC improves the sensitivity for the early diagnosis of neonatal sepsis. Clin Chem Lab Med. 2016;54:345–51.

Meyer MHF, Hartmann M, Keusgen M. SPR-based immunosensor for the CRP detection—a new method to detect a well known protein. Biosens Bioelectron. 2006;21:1987–90.

Dominici R, Luraschi P, Franzini C. Measurement of C-reactive protein: two high sensitivity methods compared. J Clin Lab Anal. 2004;18:280–4.

Zubiate P, Zamarreño CR, Sánchez P, Matias IR, Arregui FJ. High sensitive and selective C-reactive protein detection by means of lossy mode resonance based optical fiber devices. Biosens Bioelectron . 2017;93:176–81.

Correia R, James S, Lee SW, Morgan SP, Korposh S. Biomedical application of optical fibre sensors. J Opt. 2018. https://doi.org/10.1088/2040-8986/aac68d.

Shao LY, Yin MJ, Tam HY, Albert J. Fiber optic pH sensor with self-assembled polymer multilayer nanocoatings. Sensors (Switzerland). 2013;13:1425–34.

Fajkus M, Nedoma J, Martinek R, Vasinek V, Nazeran H, Siska P. A non-invasive multichannel hybrid fiber-optic sensor system for vital sign monitoring. Sensors (Switzerland). 2017;17:1–17.

Wendt M, Cappuccilli G. Generating conformation and complex-specific synthetic antibodies. Methods Mol Biol. 2017;1575:303–22.

Porschewski P, Grättinger MAM, Klenzke K, Erpenbach A, Blind MR, Schäfer F. Using aptamers as capture reagents in bead-based assay systems for diagnostics and hit identification. J Biomol Screen. 2006;11:773–81.

Wu B, Jiang R, Wang Q, Huang J, Yang X, Wang K, et al. Detection of C-reactive protein using nanoparticle-enhanced surface plasmon resonance using an aptamer-antibody sandwich assay. Chem Commun. 2016;52:3568–71.

Jarczewska M, Rębiś J, Górski Ł, Malinowska E. Development of DNA aptamer-based sensor for electrochemical detection of C-reactive protein. Talanta. 2018;189:45–54.

Zhang X, Chi KN, Li DL, Deng Y, Ma YC, Xu QQ, et al. 2D-porphrinic covalent organic framework-based aptasensor with enhanced photoelectrochemical response for the detection of C-reactive protein. Biosens Bioelectron. 2019;129:64–71.