Revisão de Sensores Impedimetricos

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A review on impedimetric biosensors
Article in Artificial Cells · September 2014

DOI: 10.3109/21691401.2014.942456 · Source: PubMed
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Artificial Cells, Nanomedicine, and Biotechnology
An International Journal
ISSN: 2169-1401 (Print) 2169-141X (Online) Journal homepage: http://www.tandfonline.com/loi/ianb20
Elif Burcu Bahadır & Mustafa Kemal Sezgintürk
To cite this article: Elif Burcu Bahadır & Mustafa Kemal Sezgintürk (2016) A review on
impedimetric biosensors, Artificial Cells, Nanomedicine, and Biotechnology, 44:1, 248-262, DOI:
10.3109/21691401.2014.942456
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Artificial Cells, Nanomedicine, and Biotechnology, 2016; 44: 248–262
Copyright © 2014 Informa Healthcare USA, Inc.
ISSN: 2169-1401 print / 2169-141X online
DOI: 10.3109/21691401.2014.942456

Elif Burcu Bahadır1 & Mustafa Kemal Sezgintürk2
1Namık Kemal University, Scientific and Technological Research Center, Tekirdağ, Türkiye, and 2Biochemistry Division,
Chemistry Department, Faculty of Science, Namık Kemal University, Tekirdağ, Türkiye
Abstract Shortly, EIS provides a fingerprint of the interfacial region

Electrochemical impedance spectroscopy (EIS) is a sensitive (Maalouf et al. 2007).
technique for the analysis of the interfacial properties Electrochemical reactions, known as electron transfers at
related to biorecognition events such as reactions catalyzed the electrode surface, involve electrolyte resistance, adsorp-
by enzymes, biomolecular recognition events of specific tion of electroactive species, charge transfer at the electrode
binding proteins, lectins, receptors, nucleic acids, whole cells, surface, and mass transfer from the bulk solution to the
antibodies or antibody-related substances, occurring at the electrode surface. Each reaction process is represented by
modified surface. Many studies on impedimetric biosensors are an electrical circuit that consists of resistance, capacitors, or
focused on immunosensors and aptasensors. In impedimetric constant phase elements combined in parallel or in series.
immunosensors, antibodies and antigens are bound each The most favorite model of electrical circuit for a simple
other and thus immunocomplex is formed and the electrode electrochemical reaction is the Randles–Ershler electrical
is coated with a blocking layer. As a result of that electron equivalent circuit model, consisting of electrolyte resistance
transfer resistance increases. In impedimetric aptasensors, (Rs), charge-transfer resistance (Rct) at the electrode/elec-
impedance changes following the binding of target sequences, trolyte interface, double-layer capacitance (Cdl), and mass
conformational changes, or DNA damages. Impedimetric transfer resistance (Rmt), also Warburg impedance (W). The
biosensors allow direct detection of biomolecular recognition solution resistance is determined by the solution conductiv-
events without using enzyme labels. In this paper, impedimetric ity and the geometry of the reaction cell, namely the distance
biosensors are reviewed and the most interesting ones are between the electrodes and the cross-sectional area of solu-
discussed. tion linking the electrodes. The double layer capacitance dis-
Keywords: biosensor, electrochemical impedance spectroscopy, plays the electrostatic interplay between the electrode and
impedance-based biosensor the electrolyte and depends on the electrode area, nature,
the electrolyte ionic strength, and permittivity. Together,
Rct and W make up the faradaic impedance. Rct reflects the
charge transfer kinetics and can be thought of as the ratio of
Introduction
overpotential to current in absence of mass transfer limita-
The pioneering study of Clark and Lyons, more than four tion. Equivalent circuit models can be partially or completely
decades ago, shed light on some analytical researches in empirical, each circuit component comes from a physical
designing of biosensors, which perform as economical process in the electrochemical cell and has a characteristic
and fast tools for clinical, chemical, environmental, and impedance behavior (Yuan et al. 2010).
pharmaceutical studies. Because of its simple use and por- The impedance spectrum of an electrochemical sys-
tability in relatively complex samples, biosensors offer a tem which is a function of frequency can be displayed in
potential alternative to advanced bioanalytical systems (Jin Nyquist or Bode plots. Nyquist plots usually include a semi-
et al. 2011). circle region lying on the axis followed by a straight line. The
Electrochemical impedance spectroscopy (EIS) appears semicircle portion (at higher frequencies) corresponds to
to be an excellent technique for the investigation of both the electron-transfer-limited process, and the straight line
bulk and interfacial electrical properties of electrode systems (at low-frequency range) represents the diffusion-limited
which can be used to determine quantitative parameters of process. This spectrum can be used to extract the electron
electrochemical processes. If biorecognition events occur transfer kinetics and diffusional characteristics. In very
at the modified surfaces, the interfacial properties change. fast electron transfer processes the impedance spectrum
Correspondence: Mustafa Kemal Sezgintürk, Namık Kemal University, Scientific and Technological Research Center, Tekirdağ-, Türkiye. Tel: 90-282-250-
26-05. E-mail: [email protected], [email protected]
(Received 10 April 2014; revised 27 June 2014; accepted 3 July 2014)
248
A review on impedimetric biosensors 249
includes only the linear part, while very slow electron Antibody-antigen based impedimetric immunosensors
transfer processes are characterized by a large semicircular Impedimetric immunosensor is a sensitive technique
region (Yuan et al. 2010, Wang 2006). The diameter of the for simultaneous, label-free detection of antigen–antibody
semicircle equals to the electron transfer resistance (Wang binding. In impedimetric immunosensors antibodies are
2006). Bode plot is logarithm of the absolute value of imped- immobilized on the electrodes, optical fiber, or semicon-
ance (Z) and the phase (F) are plotted against the logarithm ductor chips, and they have attracted great interest in recent
of frequency (f ). years because of their promising applications in various
EIS is a powerful tool for investigating the interfacial areas. Antibodies and antigens are bound to each other
properties related to bio-recognition events occurring at and thus immunocomplex is formed and the electrode is
the modified surfaces. One of the advantages of EIS is the coated with a blocking layer. As a result of that, electron
small amplitude perturbation from steady state, which transfer changes. After antigens binding to the antibodies,
makes it a non-destructive technique. The impedance the access of the redox probes is hindered to a higher degree
can be measured in the presence or absence of a redox than in the absence of antigens. Since the Faradic reaction
couple, which is referred to faradic and non-faradic imped- of a redox couple hinders increasingly, the electron transfer
ance measurement, respectively. The faradic biosensors resistance will increase and the capacitance will decrease
detect biorecognition events which occur at the modified (Hou et al. 2013).
electrode by measuring the change in the faradaic current The most important step in the preparation of impedi-
(interfacial electron transfer resistance) owing to steric metric immunosensors is immobilization of biomolecules
hindrance caused by the biomolecular interaction and/or on the electrode surface, because it is essential to generate
by the electrostatic repulsion between the free charges of stable, reproducible, and selective biosensors. For example,
the target molecules and the electroactive species in the antibodies are physically adsorbed on the gold surface; but
supporting electrolyte. Redox probe selection depends on the adsorption of antibodies directly onto the bulk metal
various parameters such as the charge, hydrophobicity/ surface leads to the denaturation and the reduction of their
hydrophilicity, size of the redox couple, and the chemical bioaffinity. When antibodies are adsorbed on the surface of
and physical properties of the modified electrodes (Elshafey noble metal nanoparticles can retain their activity due to
et al. 2013a). the biocompatibility of these nanoparticles mainly AuNPs
The limitations of the EIS technique are the several (Chullasat et al. 2011). Table I summarizes the impedimetric
requirements to obtain a valid impedance spectrum. immunosensors in literature.
Theoretically, there are three basic requirements for AC Antibody-binding proteins such as protein A and pro-
impedance measurements: linearity, stability, and causality. tein G are generally used to immobilize oriented antibod-
The accuracy of EIS measurement depends not only on ies. Elshafey et al. (2013a) developed an electrochemical
the technical precision of the instrumentation but also impedance immunosensor based on the detection of cancer
on the operating procedures (Yuan et al. 2010). marker epidermal growth factor receptor (EGFR) in brain
plasma. Anti EGFR antibodies bind to protein G modified
electrode via their nonantigenic Fc regions.
Biosensors based on impedance
Canbaz et al. (2014) quantified HER-3 for the first time by
Biosensors are designed for monitoring a biological reaction using anti-HER-3 antibody as biorecognition element. Self-
at the surface of transducers (Helali et al. 2006). A variety of assembly of hexandithiol on a gold electrode was success-
biomolecules such as enzymes, antibodies, cells, and micro- fully performed and then gold nanoparticles immobilized
organisms are the basic detection elements. For the develop- on SAMs to enhance the surface area. Cysteamine mono-
ment of an electrochemical biosensor, the key requirement layers were self assembled on the gold nanoparticles. After
is reproducibly immobilizing these biomolecules on to the performing SAMs, glutaraldehyde was used as crosslinking
sensor surface with keeping their biological activity (Rezaei agent to anti-HER-3 immobilization. By using BSA, active
et al. 2014). According to literature, various strategies have ends of the electrode surface are blocked. Finally, artificial
been used to design impedimetric biosensors. Among serum samples were spiked with HER-3 and detected by
these strategies are formation of surface functional groups the biosensor. They used the single impedance technique,
(carboxyl, amino, etc.) through various chemistries such as which is firstly used to characterize the binding between
silane on glass or indium tin oxide, and alkanethiol mono- HER-3 and anti-HER-3.
layers on Au to covalently link biomolecules to surfaces; Hou et al. (2014) constructed a sandwich immunosensor
the physical entrapment of biomolecules by various elec- for PSA detection. The signal was amplified based on the Ab2–-
trochemically formed polymers (i.e., polypyrrole and poly- AuPd–DNA toward the catalytic precipitation of 4-choloro-1-
aniline) or gel coatings; immobilizing biomolecules within naphthol (4-CN). DNAzyme catalyzed the oxidation of 4-CN,
Langmuir–Blodgett (LB) films based on amphiphilic poly- while AuPd hybrid nanostructures not only provided a large
electrolytes; and the layer-by-layer assembly of alternately surface coverage for immobilization of biomolecules but
charged polyions. also promoted 4-CN oxidation to some extent. The produced
Nanostructured materials, which are very attractive owing insoluble benzo-4-chlorohexadienone via 4-CN was coated
to their unique optical, electrical, catalytical, and magnetic on the electrode surface, and hindered the electron transfer
properties, have been used in the field of biosensors and between the solution and the electrode, thus increasing the
nanoelectronic devices. Faradaic impedance of the base electrode.
Table I. Impedimetric immunosensors.
Target molecule Immobilization step Assay principle Limit of detection References
Sulfate reducing Foam Ni/AuNPs/11 mercaptoundecanoicacid (MPA)/Ab/BSA/SRB Antibody–bacteria 2.1  101–2.1  107 cfu/ml Wan et al. (2010)
bacteria (SRB) interaction
Aflatoxin M1 (AFM1) Ag wire/11-mercaptoundecanoic acid (MPA)/primary monoclonal antibody Antibody–antigen 1 pg/ml Bacher et al. (2012)
(anti-AFM1 mAb)/EDC/NHS/AFM1 interaction
Pathogenic bacteria Anodized alümina membrane/(3-glycidyloxypropyl)-trimethoxysilane/ Antibody–pathogen 83.7 cfu/ml Joung et al. (2013)
(GPTMS)/hyaluronic acid (HA)/EDC/sulfo-NHS/anti-E.coli O157:H7 interaction
antibodies/E.coli O157:H7
Semicarbazide (SEM) GCE/chitosan-cystein(chi-cys)/EDC/NHS/AuNPs/SEM-MCAb/BSA/SEM Antibody–antigen 1 ng/ml Jin et al. (2013)
interaction
Doxorubicin Au/3-(trimethoxysilyl)-1-propanethiol (MPTs)AuNPs/doxorubicin monoclonal Antibody–antigen 10.09 pg/ml Rezaei et al. (2014)
antibody/BSA/doxorubicin interaction
Interleukin-6-antigen SiO2/Si/SWCNTs/AuNPs/mercaptoacetic acid/EDC/NHS/anti-IL-6-antibody- Antibody–antigen 0.01 pg/ml Yang et al. (2013c)
BSA/IL-6 antigen interaction
250 E. B. Bahadır & M. K. Sezgintürk
Campylobacter (CJ) GCE/o-carboxymethylchitosan Fe3O4 nanoparticles/anti-Fla A monoclonal Antibody–bacteria 1  103 cfu/ml Huang et al. (2010)
antibodies 2D12(2D12 McAbs)/BSA/CJ interaction
Ketamine Au/3-mercaptopropionic acid(3-MPA)/EDC/NHS/ketamine antibody/ketamine Antibody–antigen 0.41 pmol/L Chen et al. (2013b)
interaction
Hemoglobin Silicon/Au/1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N- Antibody–antigen 20 ng/ml Hleli et al. (2006a)
biotinyl(biotinyl–PE and 6-mercaptohexadecanoic acid (MHDA)/ interaction
neutravidin/biotinylated anti-hemoglobin/hemoglobin
Bisphenol A (BPA) GCE/5i2:5′2″-terthiophene-3′-carboxylic acid (TTCA)/EDC/polyclonal (PAb) Antibody–antigen 0.3 ng/ml Rahman et al. (2007)
antibody/PBSTG/BSA/BPA interaction
VEGF Au/cysteamine/PAMAM/glutaraldehyde/VEGFR1/BSA/VEGF Receptor–factor 5 pg/ml Sezgintürk and Uygun (2012)
interaction
C-reactive protein (CRP) Au/polyethylene glycol (PEG)/EDC/NHS/anti CRP/BSA/CRP Antibody–antigen 176 pM Bryan et al. (2013)
interaction
Troponin specific Au/cys/synthetic peptide (epitope cTnC-89–98 of troponin C) C-antibody Antibody–peptide – Mantzila et al. (2007)
antibody interaction
Atrazine Gold deposited silicon/biotinyl-PE/MDHA/IgG/neutravidin/biotinylated-Fab Antibody–antigen 20 ng/ml Hleli et al. (2006b)
fragment K47 antibody/atrazin interaction
Ochratoxin A (OTA) Indium tin oxide (ITO)/chitosan(CS)-polyaniline(PANI)/IgG/BSA/OTA/OTA Protein–antigen 1 ng/ml Khan and Dhayal (2009)
interaction
5-Morpholino-3-amino- Au/1,4-benzendithiol/AuNPs/AMOZ-McAb/BSA/AMOZ Antibody–antigen 1 ng/ml Jın et al. (2011)
2-oxalidone (AMOZ) interaction
Penicillin G Thioctic acid/EDC/NHS/anti-penicillin/1-dodecanethiol/penicillin Antibody–protein 3  10-15 Thavarungkul et al. (2007)
interaction
Anti-avidin Ti/TiO2 electrode/avidin/BSA/anti-avidin Antibody–antigen – Mantzila and Prodromidis (2006)
interaction
Salmonella Au/tyramine/glu/anti-Salmonella antibodies (SA)/BSA/S.typhimurium Antibody–bacteria 10 cfu/ml Pournaras et al. (2008)
typhimurium interaction
TREM-1 Gold screen printed electrode/thiolated antibody (MCH-Ab)DL-dithiothreitol Antibody–antigen 3.3 pM Ciani et al. (2012)
MMP9 (DTT) interaction 1.1 nM
HSL 1.4 nM
HCCR-1 Au/Prolinker B/MCH/anti-HCCR-1/HCCR-1 Antibody–antigen – Chen et al. (2013a)
interaction
Anti-hemogglutinin GCE/EDC/NHS/ethanolamine/anti-His IgG monoclonal antibody/recombinant Antibody–antigen 2.1 pg/ml Jarocka et al. (2014)
antibodies His tagged hemogglutinin (His6-H5HA)/BSA/Anti-hemoggutinin antibodies interaction
EGFR Au/AuNPs/Cys/1,4-phenylene diisothiocynate (PDITC)/protein G/ Antibody–antigen 0.34 pg/ml in PBS; 0.88 Elshafey et al. (2013a)
ethanolamine/anti-EGFRantibody/EGFR interaction pg/ml in human plasma
IGF-1 Au/AuNPs/1,6-hexandithiol (HDT)/monoclonal anti IGF-1/BSA/IGF-1 Antibody–antigen 0.15 pg/ml Rezaei et al. (2011)
interaction
(Continued)
Table I. (Continued)
Okaidaic acid (OA) Screen printed electrode (SPE)/4-carboxyphenyl film/NHS/EDC/anti-okaidaic Antibody–antigen 0.3 mg/L Hayat et al. (2012)
acid monoclonal antibody (anti-OA-mAb)/ethanolamine/OA interaction
Atrazine Niobium/niobium oxide(Nb/NbOxHy)/APTES/Fb fragment K47/atrazine Protein–antigen 50 mg/ml Helali et al. (2008)
interaction
E.coli AuSPEs/crosslinker 3,3′-dithiobis (sulfosuccinimidyl propionate) (DTSSP)/anti Antibody–cell 104 CFU/ml Escamilla-Gómez et al. (2009)
E.coli antibody/cell culture/ethanolamine interaction 3.3 CFU/ml
AuSPEs/2-pyridyl disulfide activated E.coli antibody/cell culture
CEA GCE/AuNP/Ab1/CEA/HRP-GO-Ab2 Sandwich type 0.64 pg/ml Hou et al. (2013)
a-fetoprotein (AFP) GCE/Au-Gra/anti-AFP(Ab1)/BSA/AFP/SWCNHs-HRP-GOD-Ab2 Sandwich type 0.33 pg/ml Yang et al. (2013a)
Aflatoxin M1 (AFM1) SPE/BSA  AFM1/gold labelled anti-AFM1 antibody/AFM1 Sandwich type 15 ng/ml Vig et al. (2009)
Chagas’ disease Au/anti-CRA  anti-FRA/CRA/FRA Antibody–antigen – Diniz et al. (2003)
interaction
E.coli O157:H7 Graphene oxide paper(rGOPE)/AuNPs/streptavidin/biotinylated anti E.coli Antibody–cell 1.5  102 cfu/ml Wang et al. (2013b)
O157:H7 antibody/BSA/E.coli O157:H7 interaction
SRB GCE/reduced graphene sheets(RGSs)/anti-SRB antibody/BSA/SRB cell Antibody–cell 102 cfu/ml Wan et al. (2011)
interaction
Low density lipoprotein Au/polyvinylformal(PVF)/AuNPs/anti-LDL—Mab/BSA/LDL Antibody–antigen 3.50 mg/ml Oliveira et al. (2011a)
(LDL) interaction
Human serum albümin Silicon nitride (SiN4)/SiO2/aldehyde functionalized Si-P/triethoxysilane Antibody–antigen 10-14 M Caballero et al. (2012)
(HSA) aldehyde(TEA)/monoclonal anti-HSA/BSA/HSA interaction
CD 14 or CD 16 Au/MUA/MCH/EDC/NHS/protein G/BSA/CD 14 or CD 16 antibody/monocytes Protein–cell 1000 cells Montrose et al. (2013)
interaction
Hapten/herbicide SPE/AuNPs/anti-diuron antibody/hapten/herbicide Antibody–antigen 5.46 ng/ml Bhalla et al. (2012)
interaction
CRP H-terminated nanocrystalline diamond (NCD)/anti-CRP antibodies/BSA/CRP Antibody–antigen 10 nm Vermeeren et al. (2011)
interaction
Ciproflaxin Au/pyrrole-NHS/anticiproflaxin antibody/BSA/ciproflaxin Antibody–antigen 10 pg/ml Ionescu et al. (2007)
interaction
Digoxin SPE/aniline/biotin-sulfo-NHS/neutravidin/biotinylated anti-digoxin antibody/ Antibody–antigen 0.1 ng/ml Barton et al. (2009)
BSA HSA/digoxin or BSA interaction 1.5 ng/ml
atrazine Au/polypyrolle film/nitrilotriacetic acid (NTA) Cu  2/histidine-tagged IgG Antibody–antigen 10 pg/ml Ionescu et al. (2010)
atrazine antibody/BSA/atrazine interaction
OTA Au/4-carboxyphenyl (4-CP)/EDC/NHS/OTA antibody/ethanolamine/OTA Antibody–antigen 0.5 ng/ml Radi et al. (2009)
interaction
Fenvalerate GCE/CS/glu/fenvalerate monoclonal antibody/rabbit ovalbumin/fenvalerate Antibody–antigen 0.8 mg/L Wang et al. (2013a)
interaction
Murine double minute 2 Polycrystalline Au/cys/PDITC/MDM2 antibody/ethanolamine/MDM2 Antibody–antigen 1.3 pg/ml Elshafey et al. (2013b)
(MDM2) interaction
Human chorionic Screen printed carbon ink electrode/polypyrrole-pyrole-2-carboxylic acid Antibody–antigen 2.3 pg/ml Holford et al. (2013)
gonadotropin (hCG) copolymer/NHS/EDC/hCG antibody/ethanolamine/hCG interaction
Psoriasin SPE/polyaniline/biotin-sulpho-NHS/neutravidin/biotinylated anti-psoriasin/ Antibody–antigen 250 pg/ml Truong et al. (2011)
BSA/psoriasin interaction
Cardiac troponin (cTnI), Au/MHDA  biotin caproyl-DPPE neutravidin/biotinylated anti-sLOX-1 or anti- Antibody–antigen 1013 M Billah et al. (2012)
Soluble lectin like cTnI/cTnI or sLOX-1 interaction
oxidized LDL
receptor-1 (sLOX-1)
Anti-myelin basic Pt/gelatin-titanium dioxide TiO2/MBP/BSA/anti-MBP Antibody–antigen 0.1495 ng/ml Derkus et al. (2013)
protein (anti-MBP) Pt/gelatin/MBP/BSA/anti-MBP interaction 0.1528 ng/ml
OTA ITO/TiO2/CS/IgG/BSA/OTA Antibody–antigen 10 ng/ml Khan and Dhayal (2008)
interaction
OTA ITO/nano-ZnO/rabbit-immunoglobulin antibodies (r-IgGs)/BSA/OTA Antibody–antigen 0.006 ng/dm3 Ansari et al. (2010)
interaction
(Continued)
Adenovirus (Ads) Au/PANI  2-mercaptoethylamine(2-ABA)/sulfosuccinimidyl 4-(N- Antibody–adenovirus 1000 virus particles/ml Caygill et al. (2012)
maleimidomethyl)cyclohexane-1-carboxylate (sulfo-SMCC)/reduced IgG/ interaction
Ads
Atrazine İnterdigitated m-electrode (IDmE)/antigen/atrazine antibody Antibody–antigen 5.76 ppb Rodríguez et al. (2008)
interaction
Doxorubicin Stainless stell(SS)/APTES/AuNPs/doxorubicin-specific monoclonal antibody/ Antibody–antigen 1.7 pg/ml Rezaei et al. (2013)
BSA/doxorubicin interaction
Chloramphenical (cap) Au/SATUM/AuNPs/MSA/EDC/NHS/anti-cap antibody/ethanolamine/cap Antibody–antigen 1016 M Chullasat et al. (2011)
interaction
E.coli O157:H7 Au/11-mercapto-1-undecanol/epichlorohydrin/HA/EDC/NHS/anti E.coli Antibody–bacteria 7 cfu/ml Joung et al. (2012)
O157:H7/E.coli O157:H7 interaction
Stress-induced- Nanowell (NWA)/11-mercaptoundecanoic acid/EDC/NHS/streptavidin/ Antibody–bacteria 10 pg/ml Lee et al. (2013)
phosphoprotein-1 ethanolamine/biotinylated anti-STIP-1 antibody/STIP-1 interaction

(STIP-1)
PSA GCE/b-cyclodextrin (CD)/anti-mouse antibody PSA (Ab1)/PSA/Ab2-AuPD- Sandwich type 0.73 pg/ml Hou et al. (2014)
DNA/4-CN  H2O2
Histidine tagged Au/HDT/gold nanorods/anti-his (C-term) mouse monoclonal antibody (AH- Antibody–antigen 5 pg 7ml Wasowicz et al. (2008)
proteins IgG)/BSA/rSPR-His6 interaction
Multiple Sclerosis Disposable printed circuit board (PCB) electrodes/16-MHDA/EDC/sulfo-NHS/ Antibody–antigen  100 fM Bhavsar et al. (2009 )
anti-IL-12-IgG/etanolamin/.interleukin-12 (IL-12) interaction
Multiple Sclerosis Gold-coated silver ribbon electrode/16-MHDA/EDC/NHS/anti-IL-12-IgG/ Antibody–antigen  100 fM La Belle et al. (2007)
etanolamin/.interleukin-12 (IL-12) interaction
Salmonella GCE/MWCNT/PAMAM/AuNPs/MACA/NHS/EDC/anti Salmonella Antibody–cell 5  102 CFU ml 1 Dong et al. (2013)
typhimurium typhimurium antibodies/BSA/Salmonella typhimurium interaction
Hepatitis B Pt/polyvinylbutyral(PVB)-Au-hepatitis B surface antibody(HBsAb)/HBsAg Antibody–antigen 7.8 ng/ml Tang et al. (2004)
interaction
Insulin Au/polyethylene glycol/EDC/NHs/anti-insulin/BSA/insulin Antibody–antigen 1.2 pM Xu et al. (2013b)
interaction
Atrazine Au/magnetic beads coated with streptavidin/biotinyl-FAB fragment K47 Antibody–antigen 10 ng/ml Helali et al. (2006)
antibody/atrazine interaction
Tumor necrosis factor Silicon wafer/Ti-Au layer/dithiobis-succinimidyl-propionate (DSP)/anti-TNF- Antibody–antigen ∼57 fM Pui et al. (2013)
(TNF-a) a/ethanolamine/TNF-a interaction
HSA Au/APTES/anti-HSA/%5 milk powders/HSA Antibody–antigen ∼2  104 mg/ml Chuang et al. (2011)
interaction
E.coli O157:H7 Au/MHDA/EDC  AFP DIEA/anti-E.coli/2-(2-amino etohxy)ethanol (AEE)/ Antibody-cell 2 CFU/mL Barreiros dos Santos et al. (2013)
E.coli O157:H7 interaction
MCF-7 cells GCE/polypyrrole-NHS film/anti c-erbB-2/BSA/MCF-7 cells Antibody–cell 100 cell/mL Seven et al. (2013)
interaction
Deep venous Silicon wafers/Ti/Au/11-amino-1-undecanethiol (amino thiol)/SWCNT-COOH/ Antibody–antigen 0.1 pg/ml Bourigua et al. (2010)
thrombosis biomarker NHS/EDC/anti-D-dimer/D-dimer interaction
(D-dimer)
S-100 protein Au/12-mercaptododecanoic acid (12-MCA)/5′-(mercaptomethyl)- Antibody–antigen 10 ng/ml Chen et al. (2011)
2,2′bithiophene-5-carbaldehyde (S2TA)/antiS100/ethanolamine interaction
hydrochloride (ETA-HCl)/S100
17b-estradiol Au/3-mercaptopropionic acid (3-MPA)/EDC/NHS/esterogen Receptor–factor 1013 M Kim et al. (2012)
receptor-a/BSA/17b-estradiol interaction
E.coli Au/PANI/Glu/anti-E.coli antibody/E.coli Antibody–antigen 102 CFU/mL Chowdhury et al. (2012)
interaction
HER-3 Carbon nanotube modified screen printed electrode/EDC/NHS/anti-HER-3/ Antibody–antigen 2 fg/ml Asav and Sezgintürk (2014)
BSA/HER-3 interaction
Cancer-associated sialyl- SPE/Au/MHDA/EDC/NHS/Sambucus nigra agglutinin type I (SNA-I)/ Antibody–antigen 20 ng Silva et al. (2014)
Tn (STn) antigen ethanolamine/STn antigen interaction
(Continued)
Xi et al. (2011) developed a label free electrochemical

impedimetric biosensor based on lectin–bacteria interac-
Canbaz and Sezgintürk (2014)
Sonuç and Sezgintürk (2014)

tion. S. cerevisiae was captured by concanavalin A (Con A)
interface through the interaction of Con A with the glycosyl
Gholivand et al. (2014)

References
Da Silva et al. (2014)

complexes on cellular surface. In the presence of mannose
Canbaz et al. (2014)
Jacobs et al. (2014)
Zhou et al. (2014)

Arya et al. (2014)
(Man) on the electrode surface or in the reaction solution,
Xi et al. (2011)
the Rct was decreased. The resulting electrode also showed a
major decrease of the Rct, indicating the decreased amount
of bound S. cerevisiae and efficient competition between
Man and S. cerevisiae.
Aptamer-based impedimetric biosensors

10 fg/ml in PBS, 100 fg/ml
Aptamers are artificial single-stranded DNA or RNA oligonu-

Limit of detection
cleotides (typically smaller than 100 mer). They are selected

from large randomized oligonucleotide libraries by SELEX
–
(systematic evolution of ligands by exponential enrichment).
in serum
0.28 pg/ml
103 cfu/ml
0.2 pg/ml
0.1 pg/ml
Different types of target molecules including proteins, small

40 fg/ml
1 pg/ml
1.5 nM
molecules, cells, viruses and bacteria, and amino acids can

be bound specifically to aptamers with high affinity. Aptam-
ers have presented some superior features such as high
specificity of binding affinity, better stabilization, and longer
Assay principle
Con A lectin–toxin
cells interaction
shelf life when compared to antibodies (Erdem et al. 2014).

Lectin–bacteria or
Antibody–antigen
Antibody–antigen
Antibody–antigen
Antibody–antigen
Antibody–antigen
Antibody–antigen
Antibody–antigen
Electrochemical nucleic acid sensors (genosensors)

interaction
interaction
interaction
interaction
interaction
interaction
interaction
interaction
provide sensitive and inexpensive nucleic acid detection

in complex samples, and they require a reduced number of
PCR-based amplification steps without the need for target
purification (Regan et al. 2014).
In impedimetric techniques, changes in current,
Au/1,6-haxandithiol (HDT)/Staphylococcal protein A (SPA)/anti-CEA/BSA/CEA
(PSS)/PAH/concanavalin A (Con A) or ricinus agglutinin (RCA)/BSA/bacteria
resistance or impedance following the binding of target

Printed circuit boards (PCB)/zinc oxide thin films (ZO)/dithiobis succinimidyl
Au/3-mercapto-1-propanesulfonic acid (MPS)/polycation (PAH)/polyanion

propionate (DSP)/anti-troponin T capture antibody/Superblock/protein
sequences (hybridization), conformational changes or DNA

Au (MACS)/coiled-coil peptide (CCP) modified microelectrode array/HA-
damages can be monitored. After target binding a measur-

able change occurs with these modes (1) direct detection of
hybridization (label-free), (2) labeling of the target nucleic
acid sequences with redox active substances/nanoparticles
or (3) signal probes (indirect labels) that intercalate within
the stacked base pairs, electrostatically bind to the phos-
Au/4-aminothiophenol/glu/anti-HER3/BSA/HER3
phate backbone or sit within the grooves of the double helix

Immobilization step
Au/HDT/AuNPs/Cys/glu/anti-HER-3/BSA/HER-3
(Regan et al. 2014). Table II summarizes the impedimetric

aptamer-based biosensors in literature.
Steel electrode/PANI/glu Con A/BSA/LPS
Steel electrode/PANI/glu Con A/BSA/LTA
ITO/APTES/glu/anti-HER-3/BSA/HER-3
Various materials such as gold nanoparticles, quantum

dots, carbon nanotubes (Bonanni and Del Valle 2010), ZnO
(Yumak et al. 2011), FePt/ZnS nanocore–Shell (Chang and
Wu 2010), a mercaptoacetic acid-modified cadmium sulfide
(Sun et al. 2007) and carbon-nanotubes/nano zirconium
GCE/MWCNTs/BSA/BN
dioxide/chitosan (Yang et al. 2007), graphene oxide/gold

or mammalian cells
nanoplatform (Gupta et al. 2013) have demonstrated that

they amplify the changes in charge transfer resistance (Rct)
antibody/HA
troponin-T
and increase the sensitivity of DNA hybridization detection.

Zhang et al. (2013b) used an adjunct probe for signal ampli-
fication. An adjunct probe, thiol-modified DNA sequence
with 14 bases, functioned as a fixer to immobilize the dis-
sociative element of reporter probe to form loop structure. It
blocked charge transfer and amplified EIS signal. An increase
Lipoteichoic acid (LTA)
Human cervical cancer
Human influenza virus
hemagglutinin (HA)
hydrochloride (BN)
of Rct in the presence of the adjunct probe was more than ten
Lipopolysaccharide
Carcinoembriyonic
Protein troponin T
Gram 2 bacteria
Gram  bacteria
times that of Rct without adjunct probe. Bonanni et al. (2009)

antigen (CEA)
Target molecule
Buprenorphine
used streptavidin modified gold nanoparticles for signal

amplification of impedimetric detection of DNA hybridiza-
(LPS)
Fungus
cells
HER-3
HER-3
tion. It permitted rapid formation of an easily detected con-

HER 3
jugate with biotinylated DNA through a streptavidin–biotin

Table II. The impedimetric antibody-antigen biosensors.
Limit of
Target Molecule Immobilization step Assay principle detection References
DNA Au/DNA MCH/complementary DNA/[Co(GA)2(aqphen)]Cl hybridization – Regan et al. (2014)
Target DNA GCE/GO EDC/p-aminothiophenol (ATP)/AuNPs/ssDNA/target DNA hybridization 1.1  1014 M Gupta et al. (2013)
Target DNA Au/capture prob adjunct probe/6-mercapto-1-hexanol/reporter probe/target DNA hybridization 6.3 pM Zhang et al. (2013b)
Thrombin Au/aptamer 15 mers/mercaptopropanol/Thrombin Aptamer–thrombin complex 3.1 ng/ml Meini (2012)
Au/aptamer 29 mers/mercaptopropanol/Thrombin
Thrombin Au/cysteamine hydrochlorise (CH)/PAMAM/amino modified thrombin aptamer(15-mer single Aptamer–thrombin interaction 0.1 nM Zhang et al. (2009)
stranded DNA) (TBA)/Thrombin
Poly-G Cocarbon nanotube microelectrode arrays/EDC/sulfo-NHS/poly-C-NH2 oligonücleotide/ hybridization 100 pM Pacios et al. (2012)
SDS hydroxylamine/poly(ethylene glycol complementary strand (Poly-G)
Thrombin Au/thiolated thrombin-binding aptamers (TBA)/thrombin/TBA and rhodamin 6G (R6G) hybridization 0.02 nM Li et al. (2008)
functionalized AuNPs
PML/RARA fusion GCE/FePt/CNTs/ssDNA/target DNA (cDNA) hybridization 2.1  1013 M Zhang et al. (2013a)
gene
Dengue serotype Au/AuNpPANI with SH-terminal group/specific primer/complementary target hybridization 7 pM Nascimento et al. (2011)
catechol Pencil graphite electrode (PGE)/MWCNT/DNA/catechol (CA) hybridization – Ensafi and Rezaei (2014)
Target DNA Au/probe DNA/dithiothireitol (DTT)/MCH/target DNA/reporter DNA-AuNPs hybridization 30 aM Wang et al. (2012)
Lysozyme PGE/CHIT-GO/amino linked DNA aptamer (APT)/lysozyme Aptamer–protein interaction 0.38 mg/ml Erdem et al. (2014)
Aflatoxin M1 Au/cys/AuNPs/ss-HSDNA/aflatoxin M1 Aptamer–mycotoxin interaction 0.36 ng/ml Dinçkaya et al. (2011)
80 bases long ss DNA SiO2/S4N4/LDH/ODN/20 bases-DNA probe/100-bases long DNA/complementary 80 base long hybridization 1.8 ng/ml Baccar et al. (2012)
DNA
Lysozyme GCE/graphene/Fe2O3/lysozyme-binding aptamer (LBA)/lysozyme Aptamer–protein interaction 0.16 ng/ml Du et al. (2013)
Target DNA GCE/polyaniline/ERGNO probe DNA/t-DNA hybridization 2.5  1016 M Yang et al. (2013b)
PML/RARA fusion Carbon ionic liquid electrode (CILE)/TiO2/probe ss DNA/PML/RARA fusion gene hybridization 2.8  1014 M Zhang (2013)
gene
Target DNA SPCE/MWCNT/aminated DNA probe/biotinylated target DNA/strept-AuNPs/silver Streptavidin–biotin interaction 22 fmol Bonanni et al. (2009)
Immunoglobulin E GCE/MWCNT/ionic liquid (IL)/chitosan nanocomposite (CHIT)/IGE-specific 5′-amino Aptamer–protein interaction 37 nm Khezrian et al. (2013)
terminated aptamer/BSA/methylene blue (MB)/IGE
Cytochrome c (cyt c) Graphite-epoxy composite electrode (GEC)/aptamer/PEG/cyt c Aptamer–protein interaction 69.2 pM Ocaña et al. (2014)
lysozyme SPE/MWCNT/amino-linked DNA aptamer/lysozyme Aptamer–protein interaction 12.09 mg/ml Rohrbach et al. (2012)
Thrombin Pt/poly(pyrrole-nitrilotriacetic acid)(pyrrole-NTA)/Cu 2/histidine tagged thrombin-binding Aptamer–protein interaction 4.4  1012 mol/L Xu et al. (2013b)
aptamer (His TBA)/thrombin
Ig E Nanocrystalline diamond (NCD) film/EDC/amino (NH2)-terminated IgE aptamer/BSA/IgE Aptamer–protein interaction 0.03 mg/ml Tran et al. (2011)
Thrombin Au/DTT/thiol modified anti-thrombin binding aptamer (TBA)/MCH/thrombin Aptamer–protein interaction 0.3 ng/ml Qi et al. (2013a)
Target DNA GCE/MWNT/G2-PAMAM/probe DNA (ssDNA)/target DNA hybridization 0.1 pM Zhu et al. (2010)
Thrombin (Thr) Avidin-graphite epoxy composite electrode (AV-GEC)/biotinylated aptamer of thrombin Sandwich type 0.2 pM Ocaña and Valle (2014)
(AptThrBio1)/Thr/AptThrBio2/gold-streptavidin nanoparticles (strep-AuNPs)/silver
Target DNA Au/MUA/MCH/3’SH-prob ss DNA-NH2-5′/AuNPs/DDT/target DNA hybridization 0.3 fM Wang et al. (2013c)
H5 target DNA Complementary metal oxide semiconductor (CMOS) silicon dioxide thin film/APTES/ hybridization 1 fM Lai et al. (2012)
glutaraldehyde/H5 amino modified capture DNA probe/H5 target DNA
Hepatit B virüs PEGs/AuNRs (gold nanorods)/thiol linked DNA probe ss ODNs/target ssODNs hybridization 0.5 mg/ml Congur et al. (2013)
(HBV) DNA
Tombramycin Polycrystalline gold electrode/MPA/EDC/NHS/tombramycin/ethanolamin/anti-tombramycin Aptamer–protein interaction 0.7 mM González-Fernández
aptamer et al. (2011)
E.coli outer Au/E.coli DNA aptamer I (ECAI) functionalized with a thiol group/MCH/OMPs Aptamer–protein interaction 107 M Queirós et al. (2013)
membrane Au/E.coli DNA aptamer II (ECAII) functionalized with a thiol group/MCH/OMPs
proteins (OMPs)
(Continued)
interaction, thus avoiding the need of synthesizing DNA

modified with nanoparticles, which is a more time consum-
Wun and Yang (2013)
Erdem and Congur
Erdem and Congur
Sheng et al. (2014)

References ing procedure. Due to signal amplification it was possible to
Mese et al. (2014)

Patel et al. (2013)
Fan et al. (2013)
increase the sensitivity of the method, obtaining a compa-
rable signal with a DNA amount 40 times lower.
(2013)
(2014)
The charge transfer resistance (Rct) of the electrode
increased with the concentration of the target DNA hybrid-
ized with the target ss-DNA (Gupta et al. 2013, Zhang 2013).
The single-base mismatched DNA sequence and double-
base mismatched DNA sequence were recognized via
detection
Limit of
∼21.7 ng/mL
1.63 mg/ml
1.81 mg/ml
8.9 mg/ml comparing the increase of their Rct values. The results dem-
0.21 nM
onstrated that this DNA biosensor displayed high selectivity

10 aM
1 nM
for the hybridization detection (Zhang 2013).

Thrombin was selected as target molecules for several
studies in literature, because it is a major stimulus of both
Aptamer–antigen interaction
Aptamer–antigen interaction
Aptamer–protein interaction
Aptamer–protein interaction
procoagulant and anticoagulant reactions, and thus is a

key element in various pathogenesis, including leukemia,
Assay principle
arterial thrombosis, and liver disease (Xu et al. 2013a). The

most extensively investigated prototype thrombin-binding
hybridization
hybridization
hybridization
aptamer (TBA) is a 15-mer single-stranded DNA. After bind-

ing to thrombin, TBA forms an intermolecular quadruplex
structure and restricts the activity of thrombin. The assembly
of the TBA monolayer film onto the electrode surface led to
a further increase in the Rct value, owing to the abundance of
Pencil graphite electrode (PeGE)/ds DNA/bleomycin (BLM) cis-platin (Cis-DPP) mitomycin C
negative charges on TBA sugar-phosphate backbone. After

GCE/ITO/nanostructured magnesium oxide (nMgO)-cMWCNTs/NHS/EDC/NH2-ssDNA/target
incubation in thrombin, the formation of TBA–thrombin

Pencil graphite electrode (PGE)/G4-PAMAM/EDC/HBV-DNA probe/complementary DNA
complex on the electrode surface contributed to a significant

increase in the Rct value. Also, TBA–thrombin complex insu-
lates the electron transfer between the electrode surface and
electrode solution (Zhang et al. 2009).
Another strategy for DNA detection involves a three-
component “sandwich” assay, in which the redox label is
ITO/Au film/complementary DNA (cDNA)/MCH/selected DNA/dt DNA
attached to a synthetic sequence specifically designed to

Au/Triangular Pyramid Frustum Nanostructure (TPFDNA)/cocaine
bind an overhang portion of the probe and target DNA.

These strategies need an extra chemical labeling step
Immobilization step
either in the target DNA or in the synthetic oligonucleotide

which makes the process more expensive and effortful
(Drummond et al. 2003).
Cell-based impedimetric biosensors

In cell-based biosensors, bacterial or prokaryotic cells have
Multi-SPE8/G2-PS/DNA-APT/BSA/APC
Au/AuNPs/aptamer/MCH/acetamiprid
been used for detection systems. Higher eukaryotic and

mammalian cells are higher detection systems. Using cell for
biorecognition events have advantages. They are capable of
external stimuli in situ analysis, most tissue types of cell lines
and a wide range of growth media are commercially available
and they provide more comprehensive and complex func-
tional information than nucleic acid and immunochemical
methods (Banerjee and Bhunia 2009).
(target)
Biological cells have very different electrical proper-

(MC)
DNA
ties because of the cell membranes which consist of a lipid

bilayer containing many proteins, where the lipid molecules
are oriented with their polar groups facing outward into the
Table II. (Continued)
aqueous environment, and their hydrophobic hydrocarbon

Activated protein C
Bleomycin (BLM)
Hepatitis B virus
chains pointing inward to form the membrane interior. In

Target Molecule
Vibrio cholerate
the inside of a cell is present membrane covered particulates,

Acetamiprid
such as mitochondria, vacuoles and a nucleus, and many

(HBV)
Cocaine
dt DNA
dissolved charged molecules. While the cell membrane is

highly insulating, the interior of the cell is highly conductive.
The conductivity of the cell membrane is around 10  7 S/m, covalent attachment, entrapment, cross-linking, or affin-
whereas the conductivity of the interior of a cell can be as ity have been used. Each immobilization method presents
high as 1 S/m (Pethig and Kell 1997, Yang and Bashir 2008). advantages and disadvantages. The choice of the most
Bacterial biosensors coupled to impedimetric detection appropriate technique also depends on the enzyme nature,
can be classified into two types, depending on the location the transducer, and the associated detection mode. The best
of the bacterial cells in the experimental set up. One type method of enzyme immobilization is related to biosensor
deals with measuring the impedance change caused by application which requires maximum sensitivity or stabil-
the interaction between the analyte and bacteria-modified ity. If immobilization method causes enzyme denaturation
electrodes. Another type deals with measuring metabolites or conformational change or if the enzyme on its active site
produced by bacterial cells as a result of growth in the pres- modifies, sensitivity decreases. Enzyme denaturation and
ence of the analyte. Table III summarizes the impedimetric blocking of active sites cause loss of activity. The solution
biosensors based on cells in literature. of this drawback is using spacer arm between the enzyme
Qi et al. (2013b) constructed a biosensor, in which bac- and the support under covalent binding. Techniques based
teria mediated bioimprinted films were used for selective on affinity interactions between enzymes and (strept)avidin
bacterial detection. Chitosan (CS) doped with reduced molecules, lectins, or sugars allow to immobilize enzymes in
graphene sheets (RGSs) was electrodeposited on an indium an ordered and site-specific manner, thus developing effi-
tin oxide electrode, and the resulting RGSs–CS hybrid film cient biosensors. Likewise, self-assembled monolayer-based
served as a platform for bacterial attachment. After deposit- immobilization reduces the number of random orientations,
ing RGSs–CS nanocomposite film onto the ITO electrode, generates uniform, reproducible and stable structures with
the Rct decreased when compared with the result obtained high coverage (Sassolas et al. 2011).
with bare ITO electrode. As a result of graphene facilitat- Table IV summarizes the impedimetric biosensors based
ing the charge transfer process of [Fe(CN)6]4/3. A much on enzymes and proteins in literature.
larger resistance was observed when sulfate reducing bac- Oliveira et al. (2011a) constructed a biosensor for bacte-
teria (SRB) attached onto the conductive films—because rial lipopolysaccharide determination. The deposition of
the bacteria hindered the charge transfer process. After poly(vinyl chloride-vinyl acetate maleic acid) (PVM) on the
the nonconductive CS film was formed to embed the bac- electrode surface formed a film with a large surface area
teria, the Rct increased again. Subsequently, fluorine silane for the assembly of cysteine-coated gold nanoparticles
coupling agent was coated on the functionalized ITO elec- (AuNpCys) and further immobilization of CramoLL lectin. As
trode and the SRB were washed away by acetone to leave a result of the AuNpCys inorganic–organic composite con-
bioimprinted cavities. Consequently, the charge transfer taining an amine group with a positive charge was adsorbed
resistance decreased sharply. on a negatively-charged PVM-modified gold electrode.
Finally, negatively charged CramoLL was immobilized on
Enzyme-based impedimetric biosensors the AuNpCys–PVM composite film based on an electrostatic
Effective immobilization of enzyme onto electrode surface interaction between oppositely charged species.
is one of the key steps in the fabrication of biosensors. Vari- Cortina et al. (2006) developed a urea impedimetric bio-
ous immobilization strategies such as physical adsorption, sensor using Röhm Pharma Eudragit S-100 ehteric polymer,
Table III. The impedimetric biosensors based on cells.

Limit of
Target molecule Immobilization step Assay principle detection References
Exogenous agents Au/cys/laminin/EDC/NHS/PC 12 Calcium exocytosis and ion – Slaughter and
cells/exogenous agents modulation Hobson (2009)
E.coli Nitride silicon wafer/gold layer/E.coli E.coli and its metabolites – Kim et al. (2009)
Acetylcholin (ACh) Electrode/bactoagar gel and Conductivity – Valero et al. (2009)
neuroblatoma (N2a)cells/ACh
E.coli Platinum surface/E.coli Conductivity 10 CFU/ml Muñoz-Berbel et al.
(2008)
Sulfate reducing bacteria ITO/reduced graphene sheets (RGSs)- Binding SRB change impedance 0.7  104 CFU/ml Qi et al. (2013b)
(SRB) CHIT film/CS/fluorinated silane of biosensor
coupling solution/SRB
Trichloroethylene (TCE) Gold micro electrode/aminothiol/ Toulenedioxygenase of PpF1 20 mg/L Hnaien et al. (2011)
SWCNT/anti-pseudomonas degraded TCE
antibody/casein/P.putida FI (PpF1)/
TCE
Non-lytic M13 Au/mercaptoacetic acid (MACA)/ Pathogen-cell interaction – Cheng et al. (2013)
bacteriophage infection EDC/NHS/anti-E.coli antibody
(IgG)/E.coli/M13 phage
Bacteriophage PhiX174 Platinum disc electrode/E. Coli WG5 Bacterial infection caused lysis of – García-Aljaro et al.
host strain (2009)
m.o. Silicon wafer/Au/agar Bacterial growth – Choi et al. (2009)
Organochlorine pesticides Steel/starch-casein-agar (SCA)/ Chloride ion release – Rodriguez et al.
(OCPs) streptomyces strain M7 (SM7)/OCP (2014)
ZD6474 Au/RPMI 1640/T47D/ZD6474 Cytotoxic effect of anticancer – Pradhan et al.
drug (2014)
Table IV. The impedimetric biosensors based on enzymes and proteins.
Limit of
Target molecule Immobilization step Assay principle detection References
H2O2 GCE/MWCNTs/1-butyl-3-methylimidazolium hexafluorophosphate ([bmim] Enzymatic degradation 0.025 nM Shamsipur et al. (2012)
[PF6]/catalase (CAT)
Glucose Au/MPA/glucose oxidase (GOx) SAMs Enzymatic degradation 15.6 mM Shervedani et al. (2006)
Urea Pt/ppy (polypyrole) Concentration of urea 50 mM Mondal and
Sangaranarayanan
(2013)
Amyloid-beta oligomers Au SPE/polytramine/3-(4-hydroxyphenyl) propionic acid (POPA)/NHS-biotin/ Concentration of AbO 0.5 pM Rushworth et al. (2013)
(AbO) neutrAvidin/biotin-LC-PrPc (95–110)/amyloid-beta oligomers (AbO)
Glutamate GCE/methyl viologen/nafion/glutamate oxidase (GLOD)/L-glutamate Enzymatic degradation 20 mM Maalouf et al. (2007)
Creatinine (Cre) Creatinine (Cre)-methylacrylate (MA)-molecular imprinted polymer (MIP) Concentration of creatinine 20 ng/ml Reddy and Gobi (2013)
based CPE/creatinin
PCR products Au/MCH/immobilized probe DNA-SH/streptavidin–alkaline phosphate İnteraction between DNA-SH and 1.2 pmol/L Lucarelli et al. (2005)
conjugate/enzymatic substrate solution target oligo
Cyanide Silicon wafers/gold top layer/BSA  glycerol catalase/poly(vinyl alcohol)- Enzymatic inhibition 4 mM Bouyahia et al. (2011)
photopolymerizable styrylpyridinium groups (PVA-SbQ)/cyanide
H2O2 Pt disc/a-COOH-PPy/Cyt-C Reaction between Cyt C and H2O2 0.25 mM Shamsipur et al. (2008)
Dopamine GCE/PEGlated arginine magnetic functionalized Fe3O4 nanoparticles/dopamine Slow electron transfer kinetic 14.1 mM Chandra et al. (2012)
Bacterial Au/poly(vinyl chloride-vinyl acetate maleic acid (PVM)/L-cysteine-gold CramoLL-LPS – Oliveira et al. (2011b)
lipopolysaccharide nanoparticle (AuNpCys)/CramoLL/BSA/LPS
(LPS)
Dopamine Skeleton Nickel/poly(aniline boranic acid) (PABA)/dopamine Dopamine–boronic acid interaction – Plesu et al. (2013)
Urea Carbon and silver SPE/Eudragit S-100 solution Enzymatic degradation 0.02 M Cortina et al. (2006)
(Eudrogit NaCl urease carbodiimide)/urea
Rennet Au/Dithiobis-N-succinimidyl propionate (DTSP)/k-casein/rennet (in imidazole) Between para-k casein and – Panagopoulou et al.
chymosin interaction (2012)
Alcohol Gold coated microscope slides/polydiaminobenzene film/aniline alcohol Enzymatic degradation – Myler et al. (2005)
oxidase/alcohol
which is a copolymer of methyl methacrylate and meth- changes, or DNA damages lead to change in the imped-
acrylic acid that undergo a breakdown process at pH values ance. High specificity of binding affinity, better stability,
higher than 7. In this enzymatic biosensor, urea hydrolysis by and larger shelf life are advantages of aptamer-based bio-
urease, which causes an increase of pH, triggers the degra- sensors. Cell-based impedimetric biosensors are useful in
dation of polymer and generates an increase in capacitance, external in situ analysis. Bacterial, procaryotic, and mam-
which is followed by EIS. malian cells have been used to monitor the amount and
activity of microorganisms. Few studies on enzyme-based
impedimetric biosensors have been reported. These bio-
Conclusion
sensors act based on detection of substrate or product of an
According to IUPAC, biosensor is defined as a self-contained enzyme reaction.
integrated device which is capable of providing specific
quantitative or semi-quantitative analytical information Declaration of interest
using a biological recognition element (biochemical recep-
tor) which is in direct spatial contact with a transducer ele- The authors report no declarations of interest. The authors
ment. A biosensor should be clearly distinguished from a alone are responsible for the content and writing of the
bioanalytical system, which requires additional processing paper.
steps, such as reagent addition. Furthermore, a biosensor
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A review on impedimetric biosensors

Article in Artificial Cells · September 2014

Elif burcu bahadır

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ISSN: 2169-1401 (Print) 2169-141X (Online) Journal homepage: http://www.tandfonline.com/loi/ianb20

A review on impedimetric biosensors

Elif Burcu Bahadır & Mustafa Kemal Sezgintürk

To link to this article: http://dx.doi.org/10.3109/21691401.2014.942456

Published online: 11 Sep 2014.

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A review on impedimetric biosensors

Chemistry Department, Faculty of Science, Namık Kemal University, Tekirdağ, Türkiye

Abstract Shortly, EIS provides a fingerprint of the interfacial region

phosphoprotein-1 ethanolamine/biotinylated anti-STIP-1 antibody/STIP-1 interaction

Xi et al. (2011) developed a label free electrochemical

Canbaz and Sezgintürk (2014)

Sonuç and Sezgintürk (2014)

Gholivand et al. (2014)

Da Silva et al. (2014)

Jacobs et al. (2014)

Zhou et al. (2014)

Aptamer-based impedimetric biosensors

Aptamers are artificial single-stranded DNA or RNA oligonu-

cleotides (typically smaller than 100 mer). They are selected

Different types of target molecules including proteins, small

molecules, cells, viruses and bacteria, and amino acids can

shelf life when compared to antibodies (Erdem et al. 2014).

Electrochemical nucleic acid sensors (genosensors)

provide sensitive and inexpensive nucleic acid detection

(PSS)/PAH/concanavalin A (Con A) or ricinus agglutinin (RCA)/BSA/bacteria

resistance or impedance following the binding of target

Au/3-mercapto-1-propanesulfonic acid (MPS)/polycation (PAH)/polyanion

sequences (hybridization), conformational changes or DNA

damages can be monitored. After target binding a measur-

phate backbone or sit within the grooves of the double helix

(Regan et al. 2014). Table II summarizes the impedimetric

Various materials such as gold nanoparticles, quantum

dioxide/chitosan (Yang et al. 2007), graphene oxide/gold

nanoplatform (Gupta et al. 2013) have demonstrated that

and increase the sensitivity of DNA hybridization detection.

times that of Rct without adjunct probe. Bonanni et al. (2009)

used streptavidin modified gold nanoparticles for signal

tion. It permitted rapid formation of an easily detected con-

jugate with biotinylated DNA through a streptavidin–biotin

interaction, thus avoiding the need of synthesizing DNA

Wun and Yang (2013)

Erdem and Congur

Erdem and Congur

Sheng et al. (2014)

Mese et al. (2014)

onstrated that this DNA biosensor displayed high selectivity

for the hybridization detection (Zhang 2013).