1-s2.0-S0165993612000143-main

Trends in Analytical Chemistry, Vol. 33, 2012 Trends

Mesoporous silica-based materialsfor use in biosensorsMohammad Hasanzadeh, Nasrin Shadjou, Miguel de la Guardia,

Morteza Eskandani, Peyman Sheikhzadeh

There have been great advancements in the development of biosensors capable of characterizing and quantifying biomolecules.

This article gives an overview of the formation, the properties and the electrochemical applications of ordered mesoporous silica-

based materials in electrocatalysis, electrosorption, matrix immobilization, construction of systems for controlled release of

active compounds, sensors, biosensors and immunosensors. We also present a comprehensive overview of current developments

and key issues in the determination of some biological molecules with particular emphasis on the evaluation of models.

ª 2012 Elsevier Ltd. All rights reserved.

Keywords: Biological molecule; Biosensor; Electrocatalysis; Electrochemistry; Electrosorption; Immunosensor; Mesoporous crystalline material

(MCM); Mesoporous silica-based material; SBA; Sensor

Mohammad Hasanzadeh*

Drug Applied Research Center, Tabriz University of Medical Sciences,

Tabriz, Iran

Nasrin Shadjou*

Department of Chemistry, K.N. Toosi University of Technology,

Tehran, Iran

Miguel de la Guardia

Department of Analytical Chemistry, University of Valencia, Dr. Moliner 50, 46100,

Burjassot, Valencia, Spain

Morteza Eskandani,

Department of Chemistry, K.N. Toosi University of Technology, Tehran, Iran

Peyman Sheikhzadeh

Medical Physics Department, Tabriz University of Medical Sciences,

Tabriz, Iran

*Corresponding authors.

E-mail: [email protected], [email protected]

0165-9936/$ - see front matter ª 2012 Elsevier Ltd. All rights reserved. doi:10.1016/j.trac.2011.10.011

1. Introduction

Ordered mesoporous materials (OMMs)have attracted much attention because oftheir potential for advanced applicationsin separation technologies, catalysis andelectronic engineering and nanosciencedue to their well-ordered microstructureand special pore size. Recently, mesopor-ous MCM-41 was used successfully to en-hance the ionic conductivity of PEO-basedpolymer electrolytes [1,2].

The invention of a new family of meso-porous silicate/aluminosilicate molecularsieves has attracted worldwide interest inmany areas of physical, chemical andengineering sciences. This led to the dis-covery of the so-called M41S family ofmesoporous materials of greatest interest.They have been grouped into four maincategories, as depicted in Fig. 1.

Now, ordered mesoporous silica materi-als have attracted more attention in vari-ous branches of materials science andbioscience. So far, several ordered meso-porous silicas [e.g., MCM-41, SBA-15 andmesocellular foam (MCF)], have been syn-thesized and utilized for bioimmobilization.

MCM-41 is an amorphous, mesoporoussilicate material that is principally definedby domains of highly organized hexagonal

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http://dx.doi.org/10.1016/j.trac.2011.10.011

Trends Trends in Analytical Chemistry, Vol. 33, 2012

arrays of one-dimensional, parallel cylindrical channelsthroughout its structure. The effective pore size of thechannels of MCM-41 is tunable through the choice of thetemplating reactant used in its synthesis, with theeffective size controllable from 1.5 nm to 10 nm. More-over, the pore-size distribution can often be made ex-tremely narrow, leading to essentially monosized poresthroughout the material.

One of the best-known newly discovered mesoporoussilicas is SBA-15, which is a structurally well-orderedmesoporous material with a narrow pore-size distribu-tion of 1.5–300 A. It has regular, cylindrical, orderedhexagonal pores, with a narrow pore-size distributionand large surface area. Scanning electron microscopy

Mmat

Synthesis Cha

Chemical Speciation Structural Topological Distribution

Electrosynthesis Modification Functionalization Hybridization

Electrochemistry

Figure 1. Phase formation from c16TMA/SiO2/H2O. Structure of mesoporMCM-48 (cubic, Space group ia3d) and SBA-15.

118 http://www.elsevier.com/locate/trac

(SEM) images of SBA-15 reveal that it comprises manyrope-like domains with relatively uniform sizes.

Electrodes modified with electrochemically-activedyes, metal ions and metal complexes adsorbed into theporous silicate materials (e.g., zeolites and MCM-41)have potential applications in electrochemical sensorsand electrocatalysis [3]. The electrochemistry of transi-tion metal ions incorporated into the pores of micropo-rous and mesoporous silicates have been studied. Detailsof electron transfer in microheterogeneous silicate elec-trodes and modified porous electrodes have shown dif-ferent pathways for the substrates adsorbed on theexternal surface and at the interior channels and voids ofsilicates [4].

esoporous erial science

racterization Application

Transduction and sensing Synthesis Gas storage Energy Production and storage

ous M41S materials: MCM 41 (2D hexagonal, space group p6 mm),

Disordered rods MCM-41

MCM-48 Lamellar Phase

SBA-15

Figure 2. Relationships between electrochemistry and porous materials science.


In this article, we review current research activitiesconcentrating on electrochemical aspects of MCM-41,MCM-48 and SBA for applications in electrocatalysis,biosensors, immunosensors, electroanalytical behaviorand immobilization matrixes.

2. Electrochemical applications

2.1. Sensor, biosensor, immunosensor and electroana-lytical applicationsAll mesoporous materials, in spite of their variety ofphysicochemical and structural properties, can be stud-ied via electrochemical methods and treated as materialsfor electrochemical applications. In most cases, meso-porous materials can be synthesized, modified or func-tionalized via electrochemical methods. Intersection ofelectrochemistry with mesoporous materials science canbe connected to:

(1) electroanalytical methods for gaining composi-tional and structural information on porousmaterials;

(2) electrosynthesis routes for preparing or modifyingporous materials;

(3) design and performance of electrocatalysts forsynthesis and sensing;

(4) characterization of photochemical and magneto-chemical properties;

(5) design and performance of electrochemical, electro-optical and other sensors;

(6) design and performance of porous materials (e.g.,electrode materials and fuel cells); and,

(7) design and performance of capacitors, electro-optical devices and solar cells.

The relationship between electrochemical items andmaterials science can be grouped according to threemain aspects, as shown in Fig. 2. Mesoporous materialscan be modified, functionalized, or hybridized via

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electrochemically-assisted procedures, so resulting in thepreparation of novel materials.

Electrochemical applications of mesoporous materialsinvolve important issues, including:(1) transduction (electro-optical and magneto-optical

devices) and sensing;(2) gas production and storage;(3) electrosynthesis at industrial scale; and,(4) pollutant degradation.

In the analytical domain, mesoporous materials canbe used in electroanalytical techniques (potentiometryand amperometry) for determining a wide variety ofanalytes, from gas composition to pollutants or bioana-lytes, with applications in tissue engineering, DNAsequencing, cell markers, and medical diagnosis. Meso-porous materials find not only applications in biosensorsand immunosensors but also electroanalytical applica-tions for advanced integrated circuits in the microelec-tronics industry.

Interest in biosensor research is driven by theincreasing need for specific sensors to enable fast, routinemeasurements in many fields of analysis. A fairly highnumber of recently developed biosensors can detectseveral hundred analytes (e.g., amino acids, sugars, andenzyme cofactors, which are important for biologicalsystems). There have recently been overviews regardingpharmaceutical applications.

Electrochemical biosensors hold a leading positionamong the bioprobes currently available and hold greatpromise for environmental monitoring. Such devicescomprise two components; a biological entity that rec-ognizes the target analyte and the electrode transducerthat translates the biorecognition event into a usefulelectrical signal.

Affinity electrochemical biosensors, employing naturalbinding molecules as the recognition element, shouldalso play a growing role in future environmental moni-toring. In this case, the recognition process is governedprimarily by the shape and the size of the receptor pocketand the analyte of interest. Particularly promising areelectrochemical immunosensors due to the inherentspecificity of antibody-antigen reactions [5]. Disposableimmunoprobes based on mediated electrochemistry havebeen developed.

In addition to immunosensors, the environmental areamay benefit from the production of electrochemicalimmunoassay-test kits, which commonly rely on labelingthe antigen with an electroactive tag or an enzyme thatacts on a substrate and liberates an electroactive product.

Since the discovery of ordered mesoporous silicamolecular sieves [6], interest in this research field hasexpanded all over the world. With distinctive properties(e.g., specific porous networks, large surface area, nar-row pore-size distribution and tunable pore sizes over awide range), mesoporous silica has attracted muchattention and broad applications in drug delivery [7],


and sorption and separation [8,9]. From the point ofview of electrochemical sensing, these unique propertiesstrongly indicated that mesoporous silica is an excellentsensing material to prepare electrochemical sensors, sodifferent mesoporous silica-based electrochemicalsensors have been developed for heavy-metal ions [10]and bisphenol [11].

SBA-15, one of mesoporous silicas with uniformtubular channels, adjustable pore size (from 5 to 30 nm)and good biocompatibility [12], has been widely used forthe construction of biosensors [13]. So far, SBA-15 hasbeen applied for immobilizing GOD [14], Cyt C [15], andco-immobilizing of GOD [16] and antibody [17]. Thehighly ordered pore structures of SBA-15, its large sur-face areas and huge pore volumes make it an ideal hostfor enzyme immobilization. Recently, ionic liquids havebeen used as modifiers for fabrication of biosensors dueto their high ionic conductivity and good biocompati-bility for enhanced electrochemical response [18,19].Another group [20] has successfully applied ionic liquidsto fabricate electrochemical biosensors and has achievedsatisfactory results.

More than half of the sensors described in the litera-ture are electrochemical and can be classified as poten-tiometric, amperometric or conductometric.

In potentiometric biosensors, an antibody is immobi-lized on the surface of SBA-15. The sensor allows mini-aturization, an advantage that has led to hundreds ofvariations being developed in recent years.

Cai et al. [21] reported application of a new biosensorbased on SBA-15 for breast cancer. This group designeda new label and fabricated a novel sandwich-type elec-trochemical immunoassay for the ultrasensitive detec-tion of breast cancer (BRCA). Horseradish peroxidase(HRP) was entrapped in the pores of amino-group-functionalized SBA-15 and the secondary antibody (Ab2)combined with SBA-15 by covalent bonds. Ionic liquid(IL) was added into the mixed solution of SBA-15/HRP/Ab2 and the IL increased the electrochemical activity ofHRP and promoted electron transport. Fig. 3a and bshow the immobilization and fabrication procedures,respectively. The sandwich immunoassay protocol basedon the amino-group-functionalized SBA-15 as label andHRP as enhancer was improved the performance of theimmunoassay in this study.

In amperometric biosensors, a bioenzyme is typicallyimmobilized on the surface of SBA-15. In this ampero-metric electrode, bioenzyme reacts with the substrate(e.g., a sugar or a phenolic compound) and a current isproduced that depends on the concentration of theanalyte. Recently, Dai et al. [16] proposed a novelbienzyme-channeling sensor that was constructed byentrapping GOD and HRP in well-ordered hexagonalmesoporous silica structures (SBA-15). The proposedbiosensor shows excellent performance and good stabil-ity for flow-injection analysis of the glucose level of

Figure 3. Fabrication of an immunosensor.


serum. In conclusion, these enzyme-based sensors areusually specific for one class of substances, so they canbe used for screening compounds or mixtures of com-pounds, for which a specific biological effect is known.

Enzyme-based sensors can also be used for thescreening of enzyme-inhibiting agents. These effects areoften related to a broad variety of substances and are notrestricted to one class of compounds.

One well-investigated biosensor system for pharma-ceutical applications is the tannic-acid biosensor, whichis based on mesoporous materials. Xu et al. [22] pre-pared an electrochemical sensor for determination oftannic acid by anodic stripping voltammetry using anSBA-15-modified carbon-paste electrode (SBA-MCPE).They compared the sensitivity of this sensor with those ofa porous pseudo CPE (PPCPE) and a polypyrrole-modi-fied CPE (PCPE) under the same conditions. The resultsshowed that the sensitivity of PPCPE was the highest.The limit of detection (LOD) of the PPCPE is 0.01 lM,which is about 10 times lower than that of CPE and isabout 5 times lower than that of PCPE or SBA-MCPE.The procedure is shown in Fig. 4. A major limitation ofthe pharmaceutical biosensors is that they are sensitiveto pH-active components of the sample and have to beoperated at low buffer concentrations. The latter demandis often in conflict with the stability of the SBA-CPE used.

Conductometric biosensors belong to the third andleast exploited category of the electrochemical sensors.In this category, mesoporous silicates have been used tomodify electrodes for the detection of cations by anodicstripping voltammetry (also referred to as adsorptionstripping voltammetry, ASV). This technique involves

immersion of the working electrode in a solution ofanalyte at open circuit for accumulation (or precon-centration). After rinsing, the electrode is placed in astripping medium, typically containing acid, and a neg-ative potential is applied to reduce the metal cation. Thepotential is swept towards positive to redoxidize themetal and to regenerate the electrode. The peak-currentresponse is measured for sensing purposes. Mesoporoussilicas and hybrid organosilicas allow easy access tomany active sites, will not swell (as polymers can), andcan be formulated to retain their function despite abra-sive wear.

While an unmodified silicate material can accumulatemetal cations through interactions with anionic silanolgroups, most electrochemical applications rely on sur-face modifications within the silicate to provide bindingaffinity. Walcarius et al. [23] reported an electrochemi-cal sensor based on MCM-41-modified CPE (MMCPE) forin-situ investigation of the sorption properties of themesoporous material towards some heavy metal cations[e.g., copper (II) and mercury (II)]. The effect of poten-tially competing cations (e.g., alkali and alkaline-earthelements) was found to be low, so that MMCPE could beused as a new sensor for these species, with improvedselectivity compared to electrodes modified with com-mon ion exchangers.

Liu et al. [7] applied layer-by-layer (LBL) assembly toprepare a new modified electrode for determination ofnitroaromatic compounds. LBL assembly is a polymerthin-film-deposition technique developed by Decher andHong [24]. Lijian et al. [25] reported successful constructionof {SBA/PSS (poly (sodium 4-styrene-sulfonate))} n/PDDA


Anodic Striping

Copper Wire

Calcium Carbonate microsphere

graphite Powder and Pyrrole

FeCl3 Solution

Polimerizing

Hydrocoloric Acid Extraction

Accumulation Tannic Acid

Prous Pseuduo-Carbon Paset Electrode

Figure 4. Electrochemical detection of tannic acid at MCM 41/carbon-paste electrode.


(poly (diallyldimethylammonium chloride))-modifiedglassy-carbon electrode (GCE) with controllable layers. Bymeans of the LBL technique, an {SBA/PSS}n/PDDA GCEfor the NAC determination was prepared by assemblingnm-sized SBA-15 and PDDA, PSS on the surface of theGCE.

Also, Lin et al. [17] proposed a novel immunoassay-channeling sensor by incorporating alkaline phospha-tase (ALP)-labeled antibody into the larger mesopores(15 nm) of SBA-15 with IL-Ch hybrid film. Thisresearch group concluded that the immunosensors de-signed were suitable to be used as platforms in the sen-sitive determination of other antigens or bioactivemolecules.

Interestingly, Zeng et al. [26] suggested a mesoporousAl-MCM-41-modified electrode for determination of epi-nephrine. The electrochemical responses of epinephrineundoubtedly suggest that the mesoporous Al-MCM-41-modified electrode not only possesses a larger surfacearea but also exhibits strong catalytic ability.


Recently, Zhang et al. [27] investigated the electro-chemical behavior of dihydroxybenzenes in detail at theNH2-SBA15/CPE, which significantly enhanced elec-tron-transfer kinetics.

At the end of this sub-section, it is worth mentioningthat functionalized mesoporous silica can be usedas a quantitative analytical tool for electrochemicalbiosensing. The functionalized mesoporous silica iscompetitive with other electrochemical biosensors.

While reported results are exciting and exhibit greatpotential for future applications, new breakthroughs arestill required for meso-electrochemical systems. Forexample, many of the new nanodevices built have notyet been investigated in vivo, so important informationregarding circulation properties in blood and accumu-lation in liver or other tissues needs to be acquired, andeventual problems emerging from those studies will needto be addressed.

Although the fast advancement of mesoporous-basedbiosensors highlights their future applications in diverse


scientific fields, the major impacts of such technologiesappear to be in early detection of diseases, pathogens,genetic mutations and bio-targets. Of these applications,early detection of cancer seems to provide an interestingapproach for the development of novel target-basedtherapies (e.g., using mesoporous-electrochemical probesfor detection and targeting). Also, nanobiosensor-basedsilica materials provide fast, simple, sensitive detectionsystems for pathogens and toxins that may providerobust tools for forensic medicine and bio-defenseresearch. Nevertheless, some electrochemical andpiezoelectric platforms have already been commercial-ized.

2.2. Immobilization matrix, electrochemical sorptionand electrocatalytical applications2.2.1. Immobilization matrix. According to previouspapers [28,29], mesoporous silica sieve MCM-41 canprovide a suitable immobilization of larger biomoleculematrixes due to their large pore size, ordered, uniformpore structure, huge surface area, high loading capacity,good biocompatibility and fine environment for electrontransfer. Moreover, enzymes can be firmly incorporatedinto the matrix without the aid of other cross-linkingreagents. But conductivity of only MCM-41 cannotproperly satisfy its application for enzyme support in thebiosensors. Methylene Blue (MB) is a conductive dye andcan improve electron-transfer process in the enzyme-catalyzed reactions, when it is adsorbed on MCM-41 orembedded in the surfactant-silica hybrid MCM-41mesophase [30].

Recently, Xu et al. [22] introduced a novel immobili-zation enzyme method, which uses MCM-41 containingMB/polyvinyl alcohol (PVA) composite film immobilizedlaccase by absorption to fabricate a perfect laccase-mobilized Au electrode to improve some disadvantages ofthe amperometric laccase biosensor.

Xian et al. [13] reported encapsulation of hemoglobin(Hb) on mesoporous silicas SBA-15 and Au-doped SBA-15 (Au-SBA-15). The influences of solution pH and thestructure of the mesoporous silicas on the adsorptioncapacity of Hb were studied in detail. In this study, thedirect electrochemistry of Hb was observed when Hb wasimmobilized with mesoporous silicas (SBA-15 or Au-SBA-15). Compared with pure SBA-15, incorporation ofgold nanoparticles into SBA-15 could enhance theelectron-transfer rate of Hb. Moreover, Hb-loaded mes-oporous material is likely to be applied in biosensingbecause it exhibits high peroxidase-like activity towardelectrocatalytic reduction of hydrogen peroxide. Thework provides an efficient strategy to create nanobio-composites with active components by assembling pro-teins with great adsorption capacity. It also provides apromising platform to study the direct electron transferof immobilized proteins with an underlying electrode.Similar work was conducted by Li et al. [31] using

MCM-41. The major disadvantage of the mesoporoussensors based on Au-SBA-15 for the detection of smallmolecules or proteins in solution is interference from theother similar molecules, resulting in a decrease indetection sensitivity of the sensors.

Wang et al. [32] suggested that GOD can be immo-bilized on SBA-15 and Nafion matrices, and the immo-bilization of GOD provides excellent stability. GODimmobilized on SBA-15 and Nafion matrices can un-dergo a direct, nearly reversible electrochemical reac-tion, involving exchange of two electrons and twoprotons. GOD immobilized on SBA-15 and Nafionmatrices possesses excellent bioelectrocatalytic activityfor the reduction of O2. Thus, in the future, orderedmesoporous silica-SBA-15 may be used as a matrix forthe cathodic biocatalyst in a biofuel cell. In short, or-dered mesoporous silica-SBA-15 provides an efficientmatrix for immobilization of GOD and facilitates theelectron exchange between GOD and the electrode. As amatrix material of modified electrode, it is thereforehoped that SBA-15 may be applied in biosensors andbiofuel cells in the future.

To complete our discussion in this sub-section, Table 1summarizes recent reports on the electrochemicalapplication of MCM and SBA for determination some ofbiological molecules [33–41].

From SEM and tunneling electron microscopy (TEM)images, as shown in Table 2, it is learned that theaverage diameters of the MCM and SBA are in the range10–100 nm. Also, the diameter of the modified meso-porous material discussed is in the range 8–20 nm.

2.2.2. Electrochemical sorption. Adsorption selectivity isimportant for recovery and re-use of captured pollutants.The enormous surface area, easily accessible porechannels and simple pore chemistry make mesoporoussilica materials ideal for design and preparation ofselective adsorbents. Adsorption selectivity was achievedby judicious grafting of organic functional moieties withgood affinity for the target adsorbate. Recently, Kumarand Natarajan [41] reported the electrochemicalbehavior of phenosafranine (PS+) adsorbed on themodified electrodes using microporous and mesoporousmaterials (MCM-41). These researchers indicated thatthe one-dimensional channel of the mesoporous materialprovided an easier micro-environment for phenosafra-nine for the electron-transfer reaction, compared to themicroporous silicate materials.

In another work, Vinu et al. [42] studied the adsorp-tion of Cyt C on to SBA-15 (Santa Barbara amorphous)and found that the amount of Cyt C adsorbed on differentadsorbents can be significantly changed by adjusting thesolution pH. The maximum loading of Cyt C wasachieved near the isoelectric point of Cyt C (pI 9.8).When the surface charges of the protein and the MPS arecomplementary, adsorption occurs easily [43].


Table 1. Recent reports on the electrochemical application of MCM and SBA

Electrochemical sensor basedon mesoporous materials

Application Limit of detection (LOD) Linear range Ref.

MCM-41 Bisphenol A 0.038 lM 0.22–8.8 lM [11]Hb/Au-SBA-15 Electrocatalytic reduction of

hydrogen1.0 lM 0.01–5 lM [13]

Au/GNPs-SBA-15/IO4-xidized-GOD Glucose 15 lM 0.02–14 mM [14]Au/H2N-SBA-15/IO4-oxidized-GOD 45 lM 0.06–3 mMCo-entrapping GOD and HRP inthe mesopores of SBA-15

Glucose 0.027 lM 0.003–34 mM [16]

(ALP)-labeled antibody/SBA-15 Determination of a-fetoprotein(AFP)

1.0 to 150 ng/mL 0.8 ng/mL�1 [17]

BMIM.BF4-coatedSBA-15

Detection of Breast cancersusceptibility gene (BRCAl)

4.86 pg/mL 0.01–15 ng/mL [18]

SBA-15 modified CPE (SBA-MCPE) Detection of tannic acid 0.05 lM 0.02–1 lM [22]composite film of MCM-41 containingMB/PVA modified Au electrode

Determination of Laccase 0.331 lM 4.0–87.98 lM [23]

{SBA/PSS}n/PDDA modified electrode TNT 0.002 lM – [25]TNB 0.002 lMDNT 0.0015 lMDNB 0.002 lM

(NH2-SBA15/CPE) Dihydroxybenzene isomers [27]Hydroquinone, 0.3 lM 0.8–160 lMCatechol 0.5 lM 1.0–140 lMResorcinol 0.8 lM 2.0–160 lM

(GOD/MCM-41/Nafion/GCE) Bioelectrocatalytic oxidation ofglucose

0.18 mM – [32]

Nafion/GOD-SBA-15/GC Bioelectrocatalytic oxidation ofglucose

0.6 mM 0.20–1.0 mM [32]

Hb/MCM-CILE Determination of H2O2 0.05 lM 5–310 lM [33]Ferricyanide/MCM-41 Electrocatalytic reduction of

H2O2

– – [34]

70:30[Co-3a-(MCM-41) and Co-3a-(ITQ-2)]

Electroreduction of oxygen toH2O2

– – [35]

Mb/HMS/GCE Determination of H2O2 0.06.2 lM 4.0–124 lM [36]Determination of NO2 0.8 lM 8.0–216 lM

GC/Ag- MPS Reduction of NO�2 – 10.0–40.0 mM [37]GC/Ag-MPS-ZnPc – 10.0–50.0 mMFePcS/functionalized MCM-48 Oxidation of styrene – – [38]FePcS/functionalized MCM-41 – –ordered mesoporous carbons (OMC) Determination of dopamine – 0.04–1.0 mM [39]GOD-HRP Bienzyme Channelingin SBA-15 Mesoporous

Glucose 0.27 lM 0.003–3.4 mM [40]

bicontinuous gyroidal mesoporous carbon (BGMC) (NADH) 1.0 lM 0.003–1.4 mM [41]GOx/MCM Glucose 10 lM – [42]MCM-41 Simultaneous detection of ascorbic acid, uric acid and, xanthine [43]

Ascorbic acid 3 lM 0.04–4.0 mMUric acid 0.1 lM 0.5–7.5 lMXanthine 0.75 lM 4.5–1000 lM

Polyporous C@WC1-x/MCM-41 composite p-Nitrophenol reduction – – [50]


In a similar study, Zhu et al. [44] investigated thedirect electrochemistry behavior of Cyt C on themodified GCE by SBA-15 with a high-redox potential.They reported a dramatically high cathodic redox po-tential was first observed from the Cyt C/SBA-15 sys-tem, in which the Cyt C kept its biological activity. Astable, quasi-reversible direct electrochemistry behaviorof a surface-controlled electrode process with asingle proton transfer was obtained on the SBA-15-modified GCE, which could provide a novel way to


understand electron transfer between protein andporous materials.

Mesoporous materials have gained and will continueto attract global interest for applications in adsorption,separation and storage. Significant progress in pollutioncontrol, gas storage and bioadsorption has been made inthe past decade. Due to their high specific surface areas,large pore volumes, and regular and tunable pore sizes,mesoporous materials have shown unprecedentedadsorption performance towards a wide range of

Table 2. Recent reports on the SEM/TEM/BET images of MCM and SBA

Electrochemical sensor based onmesoporous materials

SEM/TEM/BET images Technique/pore size Ref.

MCM-41 SEM/100 nm [11]

Hb/Au-SBA-15 TEM/20 nm [13]

Au/GNPs- SBA-15/IO4-oxidized-GOD

TEM/30 nm [14]

Au/H2N-SBA-15/IO4-oxidized-GOD TEM/40 nm

Co-entrapping GOD and HRP in themesopores of SBA-15

Brunauer–Emmett–Teller (BET)/8 nm [16]

(ALP)-labeled antibody/SBA-15 A(SEM/1 lm) B(TEM/10 nm) [17]

BMIM.BF4-coatedSBA-15

A(TEM/SBA-15)/60 nm)

B(TEM/SBA-15/HRP/Ab2/BMIM.BF4 30 nm)

C(SEM/700 nm) [18]

SBA-15-modified CPE (SBA-MCPE) SEM/10 lm [22]

(continued on next page)



Table 2. (continued)

Electrochemical sensor based onmesoporous materials

SEM/TEM/BET images Technique/pore size Ref.

{SBA/PSS}n/PDDA-modifiedelectrode

A(SEM/500 nm) [25]

B(TEM/50 nm)Composite film of MCM-41containing MB/PVA modified Auelectrode

SEM/5 lm [23]

Hb/MCM-CILE SEM/10 lm [33]

Nafion/GOD-SBA-15/GC TEM/20 nm [32]GC/Ag-MPS-ZnPc TEM/10–20 nm

(4Ag-12Ag)[37]

Ordered mesoporous carbons (OMC) TEM/100 nm [39]

GOD-HRP Bienzyme Channeling inSBA-15 Mesoporous

TEM/50 nm [40]


inorganic and organic guests with fast adsorptionkinetics, high capacity and good stability. Moreover,theoretically, their active surfaces provide the possibilityof creating specific binding sites for any guest.

To date, grafting mesoporous materials with func-tional groups is a basic strategy to get advancedadsorbents, but there are some common disadvantages.Post-grafting is accompanied by an obvious decrease inporosity and uneven distribution of functional groups,resulting in a loss of capacity and probably blockage ofmesopores. Co-condensation gives hybrid materials


carrying evenly distributed functional groups, but part ofthese hybrid materials may be inaccessible. Thus, futuredevelopments may emphasize higher-density, fully-accessible functional groups sacrificing less porosity,thus facilitating molecular diffusion and adsorptionkinetics. In this regard, mesoporous materials, especiallythose obtained from organic-organic assembly, may bethe next generation of adsorbents. However, higherselectivity and molecular recognition would be anotherimportant issue for further research. Moreover, orderedmesoporous composites possessing dual or multifunction


capabilities of detection, adsorption, separation and easyregeneration are likely to trigger new advances. Fromthe aspect of practical implementation, spherical ormonolithic adsorbents may be more applicable becausethey are easier to operate, and, more importantly, theyexhibit better adsorption kinetics than powders.

Finally, mesoporous material adsorbents with long-term cyclic stability are still very limited. For example,the uptake of Hg2+ on thio-OMS normally decreases by30–50% after single regeneration. Thus, adsorbents withbetter cyclic stability are yet to be deployed.

2.2.3. Electrocatalytic applications. Electrocatalytic pro-cesses have received considerable attention because oftheir applications in synthesis and sensing. The term‘‘catalysis’’ is used to describe the modification in thereaction rate of a given chemical reaction by adding acatalyst species (e.g., a mesoporous material). Twoessential conditions have to be met by catalytic pro-cesses:(1) the thermodynamics of the reaction is unaltered;

and,(2) the catalyst stays unchanged.

Also, a common demand is that the catalytic processrequires only small concentrations of the catalyst. In themost general view, the rate of the reaction can be eitherincreased (positive catalysis) or decreased (negativecatalysis), although positive catalysis is preferred.

Designing chemically-modified electrodes for electro-catalysis [45,46] was extensively developed because itprovided an elegant way to facilitate (accelerate)charge-transfer processes. This contributed to decreas-ing the overpotentials often required to perform elec-trochemical transformations, as well as to increasingthe intensity of the corresponding voltammetric re-sponses. So far, exploration of electrocatalytic studieswith mesoporous silica-based materials is only begin-ning [47,48]. Li et al. [47] encapsulated 1:12phosphomolybdic acid in the mesoporous channels ofMCM 41 materials grafted with amine groups. Afterincorporation into CPEs, these materials were found tobe efficient catalysts for the reduction of ClO�3 andBrO�3 species. The electrocatalytic properties of4,4 0-bipyridinium units covalently attached to MCM-41 silica walls were also described with respect to theoxidation of 1,4-dihydrobenzoquinone.

Hydrogen-peroxide detection is often accomplishedusing electrochemical techniques. The silicate materialsprovide large surface areas and facilitate electron ex-change between the iron of the hemo component ofthese proteins and the electrode. Amine functionaliza-tion of the silica provides sites for covalent immobiliza-tion of the proteins. Depending on the size of the proteinand the pore structure of the silicate material, it is pos-sible to bind the protein to the surface of the silica orwithin the pores.

In addition to H2O2 sensing, materials bearinghemoglobin and myoglobin have been applied to thedetection of NO2. Tyrosinase and horseradish peroxidasehave also been immobilized onto MCM-41 to provide amaterial for application to the detection of phenol.

Ojani et al. [34] used aminated MCM-41 for encap-sulation of ferricyanide, and used this material for elec-trocatalytic reduction of H2O2. In this study, CPEmodified with animated MCM-41 was prepared and usedfor immobilization of K3 [Fe(CN)6] in acidic medium.This modified electrode had many advantages (e.g., fastresponse, good chemical and mechanical stability, andclean determination of H2O2 without leaching of ferri-cyanide to the analyte solution).

The large specific surface area and the presence ofredox-active centers make MCM/SBA interesting meso-porous materials for electrochemical sensing and elect-rocatalysis. By the first token, size selectivity can becombined with the coordinating ability of redox-activecenters. An example of the possibility of selective elec-trochemical sensing using MCM-41 was presented byLiao et al. [48]. Interestingly, Liao�s group applied itwhere the reduction of methyl viologen, MVþ2 , by S2 wascatalyzed within the MCM-41 pores without the pres-ence of metal ions, and where sulfide ions could beprovided by way of sulfide salts or as coordinativeunsaturated surface-sulfide ions of occluded sulfidenanoparticles.

Recently, Pal and Ganesan [49] prepared a new elec-trode based on MCM-41 for electrocatalytic reduction ofNO�2 . They reported that Ag nanoparticles anchored onmesoporous silica materials with and without zincphthalocyanine (ZnPc) were prepared (Ag-MPS and Ag-MPS-ZnPc, respectively). This approach to preparationand incorporation of AgNPs (with and without ZnPc) onthe ordered MCM-41-type materials offered distinctadvantages, as was demonstrated in the electroreductionof nitrite in this work.

Recently, Zheng et al. [50] prepared a new polyporouscomposite based on MCM-41 for electrocatalytic reduc-tion of p-nitrophenol.

In conclusion of this section, it is worth mentioningthat the choice of electrode configuration is of criticalimportance regarding the target application of meso-porous materials. Indeed, film-based materials will re-quire mass and/or charge transfer reactions to occuracross the material layer from the solution to the elec-trode surface, while bulky composites will have bothmodifier and conductive part of the electrode in directcontact with the solution. The first configuration wouldthus be of interest for perm-selective detection, whereasthe second would be more appropriate for electrocatal-ysis or voltammetric detection subsequent to analyteaccumulation.

There are several studies that report characteristicphenomena attributed to the regular mesoporous



system, which seem to influence the catalytic activity[51–54]. Detailed studies of these phenomena are inprogress in many laboratories, as, in most cases, thereare still no satisfactory explanations of why the orderedmesoporous materials are superior to less ordered cata-lysts. If, in future, the effects of the pore system areunderstood and rationalized, the way to improve controlof the catalytic activity of complex catalyst systems willbe more clearly visible and catalyst improvements bydesign on different length scales will become accessible.

3. Conclusion and outlook

This review addresses recent advances in MCM- andSBA-based electrochemical biosensors. The electro-chemical properties of MCM and SBA have paved theway to new, improved sensing devices, in general, andelectrochemical biosensors, in particular. MCM- andSBA-based electrochemical transducers offer substantialimprovements in the performance of amperometric en-zyme electrodes, immunosensors and sensing devices.

We featured some recent advances in mesoporousmaterial applications in electrochemical biosensors.Mesoporous materials offer superior ways to maintainbiological activity and improve the sensitivity of bio-sensors. With the development of nanoscience andnanotechnology, the combination of various nm-scalemesoporous materials with enzymes could lead to thedevelopment of multi-functional nano-assembly systemswith simultaneous novel electronic properties. Suchcoupling of high-sensitivity and high-stability capabili-ties allows electrochemical biosensors to rival the mostadvanced electrochemical and optical protocols in bio-assays.

Considering the significance of biological molecules,this review in electrochemical biosensors can be conve-niently applied to evaluate the effects of mesoporousmaterials on the environment. We can anticipate satis-fying many requirements for analyzing different biolog-ical systems and providing a useful reference forassessing the toxic and biological effects of nanomateri-als. The electrochemical method for the investigation ofmetal and semiconductor nanomaterials illustrates theextraordinary sensitivity achievable by these materials.The integration of the technologies will, without doubt,bring significant input to ultra-sensitive biosensors rele-vant to diagnostics, therapy and controlled drug deliveryof interest for human health.

In future, thin films of mesoporous silica will attractextensive attention due to their electrochemical appli-cations as molecular sieves, catalysts, adsorbents, andoptical and sensor devices. Silica can be an excellent,biocompatible candidate for drug delivery and carrydifferent therapeutics to different tissues and cells, par-ticularly cancer cells. Biosilica materials show some


advantage compared with the other nanomaterials (e.g.,large surface area, nanoscale porosity, biocompatibility,biodegradability and high payload ability, which makethem advanced materials for targeting drug-deliveryapplications). However, it should be emphasized that, foraccurate detection of diseases, in spite of the great pro-gress in nanobiosensors, additional efforts are needed toadvance robust nanobiosensing tools that are currentlyat an early stage of development.

Developing a reliable, scalable electrochemical-fabri-cation technique for producing uniform, well-alignedmesoporous materials and integrating individual MCM/SBA into functional devices with high yields are some ofthe technical issues to be addressed in future. Also, novelsignal-transduction mechanisms (e.g., a hybrid trans-duction mode, combining the fieldeffect with eitheramplification/catalysis features of the biological systemsor electrochemical doping processes) could offer newopportunities for the silica-based mesoporous materialsin ultrasensitive detection of biological species.

Also, silica-based mesoporous materials provide aplatform for development and advancement of electro-chemical nanobiosensors, which are increasingly beingimplemented as robust tools for detection in biomedicalsciences. In addition, biochip technologies could offer aunique combination of performance capabilities andanalytical features of mesoporous materials.

AcknowledgementsWe gratefully acknowledge the support of this work byDrug Applied Research Center, Tabriz University ofMedical Sciences, Tabriz, Iran and would like to thankDr. Abolghasem Jouyban and Dr. Jafar Ezzati NazhadDolatabadi for their valuable comments.

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