",isbn:"978-1-83969-506-3",printIsbn:"978-1-83969-505-6",pdfIsbn:"978-1-83969-507-0",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,hash:"0e5d67464d929fda6d8c83ec20c4138a",bookSignature:"Dr. Endre Zima",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/10704.jpg",keywords:"Anatomy, Physiology, Perioperative, Non-Cardiac Causes, Antiarrhythmic Drugs, Development, SARS-CoV2, Infection, Cardiac Arrest, Resuscitation, PPE, Arrhythmias",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"February 11th 2021",dateEndSecondStepPublish:"March 11th 2021",dateEndThirdStepPublish:"May 10th 2021",dateEndFourthStepPublish:"July 29th 2021",dateEndFifthStepPublish:"September 27th 2021",remainingDaysToSecondStep:"7 days",secondStepPassed:!1,currentStepOfPublishingProcess:2,editedByType:null,kuFlag:!1,biosketch:"Prof. Dr. Endre Zima works as the chief of Cardiac ICU at Semmelweis University Heart and Vascular Center. His fields of interest are intensive cardiac care, CPR, post-cardiac arrest care, device therapy of arrhythmias, defibrillator waveform, and AED development.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"201263",title:"Dr.",name:"Endre",middleName:null,surname:"Zima",slug:"endre-zima",fullName:"Endre Zima",profilePictureURL:"https://mts.intechopen.com/storage/users/201263/images/system/201263.jpg",biography:"Prof. Dr. Endre Zima works as the chief of Cardiac ICU at Semmelweis University Heart and Vascular Center. Dr. Zima is specialized in anesthesiology-intensive care and cardiology. He has authored 13 book chapters and more than 130 journal papers, achieved a Hirsch-index of 14, g-index of 22, and more than 650 independent citations. \nHe has been holding graduate and postraduate lectures and practices in anesthesiology since 2006, and in cardiology since 2008. He is a PhD Lecturer in Semmelweis University since 2010. He obtains an accreditation of EHRA on Cardiac Pacing and Implantable Cardioverter Defibrillators, he is accredited AALS Instructor of European Resuscitation Council. \nHe is a Fellow of the European Society of Cardiology, member of the European Heart Rhythm Association and Acute Cardiovascular Care Association, board member of the Hungarian Society of Cardiology (HSC), president of Working Group (WG) on Cardiac Pacing of HSC , board member of WG of Heart Failure. Dr. Zima is also a member the Hungarian Society of Resuscitation, Hungarian Society of Anesthesiology. 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Venkateswarlu",coverURL:"https://cdn.intechopen.com/books/images_new/371.jpg",editedByType:"Edited by",editors:[{id:"58592",title:"Dr.",name:"Arun",surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"878",title:"Phytochemicals",subtitle:"A Global Perspective of Their Role in Nutrition and Health",isOpenForSubmission:!1,hash:"ec77671f63975ef2d16192897deb6835",slug:"phytochemicals-a-global-perspective-of-their-role-in-nutrition-and-health",bookSignature:"Venketeshwer Rao",coverURL:"https://cdn.intechopen.com/books/images_new/878.jpg",editedByType:"Edited by",editors:[{id:"82663",title:"Dr.",name:"Venketeshwer",surname:"Rao",slug:"venketeshwer-rao",fullName:"Venketeshwer Rao"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"4816",title:"Face Recognition",subtitle:null,isOpenForSubmission:!1,hash:"146063b5359146b7718ea86bad47c8eb",slug:"face_recognition",bookSignature:"Kresimir Delac and Mislav Grgic",coverURL:"https://cdn.intechopen.com/books/images_new/4816.jpg",editedByType:"Edited by",editors:[{id:"528",title:"Dr.",name:"Kresimir",surname:"Delac",slug:"kresimir-delac",fullName:"Kresimir Delac"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"16424",title:"Recent progress in the construction methodology of fluorescent biosensors based on biomolecules",doi:"10.5772/17724",slug:"recent-progress-in-the-construction-methodology-of-fluorescent-biosensors-based-on-biomolecules",body:'\n\t\t
\n\t\t\t
1. Introduction
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The creation of novel molecular tools for detection and monitoring of the transitional concentration and localization changes of biologically important molecules, such as biomacromolecules, signaling small molecules and biologically important ions, is a great challenge in the field of chemical biology. Therefore, much attention has been devoted by chemists and biologists to developsensing tools that allow real-time tracking of the molecules of interests in vivo or in vitro. (Thevenot, D. R. et al., 2001; Jelinek, R. et al., 2004; Borisov, S. M. et al., 2008) Among them, the fluorescent biosensor, which is defined as the sensor that converts a molecular recognition event to a measurable fluorescent signal change, has recently emerged as a powerful tool for the following reasons. (Hellinga, H.W. et al., 1998; Johnsson, N. et al., 2007; Johnsson, K., 2009; Wang, H. et al., 2009; Liu, J. et al., 2009)Biomacromolecular receptors, such as nucleic acids (DNA or RNA) or proteins, have superior characteristics as the recognition platform because they play crucial roles in numerous biological processes to mediate and regulate a range of strict recognition and chemical reactions within cells. As for the tools for the transducer, the fluorescence detection has the superior physical properties, such as high sensitivity, excellent spatial resolution, good tissue penetration and low cost for the detection system, in contrast to the other detection method including optical, electrical, electrochemical, thermal, magnetic detections. Thus, transducing the molecular recognition events with the fluorescence signals is very appealing and has been one of the most widely adapted methods. (Giepmans, B.N. et al., 2006; Rao, J. et al., 2007) The rational design strategies of fluorescent biosensors have not been matured as generally considered by the researchers in the biological field. A simple strategy to construct a biosensor with tailored characteristics would be to conjugate a recognition module with a signal transducer unit, although there is no simple methodology to conjugate the recognition module and the transducer unit to afford a usable fluorescent biosensor. Here we focus to overview the progress in the design strategy of fluorescent biosensors, such as the auto-fluorescent protein-based biosensor, protein-based biosensor covalently modified with synthetic fluorophores and signaling aptamers.
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2. Auto-fluorescent proteins (AFPs) based biosensors
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Auto-fluorescent proteins (AFPs) such as green fluorescent protein (GFP) from jellyfish (Shimomura, O. et al., 1962) are widely used as noninvasive fluorescent markers for gene expression, protein localization, and intracellular protein targeting (Chalfie, M. et al., 1994; Lippincott-Schwartz, J. et al., 2001). The application of AFPs is not limited to the fluorescent markers. Various kinds of AFP-based biosensors have recently been developed by fusion of reporter proteins or mutation of AFPs for imaging and sensing important molecules and key events in living cell. ( Zhang, J. et al. 2002; Zhang, J. et al. 2007; Mank, M. et al., 2008; VanEngelenburg, S. B. et al. 2008; Lawrence, D. S. et al. 2007; Ozawa, T. 2006; Prinz, A. et al. 2008)The advantage of AFP-based biosensor is that it can be endogenously expressed in cells or tissues simply by transfection of the plasmid DNAencoding it. This approach is a noninvasive method and therefore avoids damage to the cell. Because AFPs based biosensor can be produced automatically, the influence of dilution due to vital activity, such as cell growth and division, is minimal. Moreover, it is possible to control the localization of biosensors to the sites of interest within cell by introducing a certain organelle-specific targeting signal. These biosensors have been powerful tool for in vivo applications.
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2.1. Single AFP based biosensor
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In the case of biosensors based on a single AFP, analyte binding events affect directly or indirectly to fluorescent properties or formation, respectively, of the chromophore moiety of AFP. The former is classified as analyte-sensitive sensors and the latter as conformation-sensitive sensors.
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The design of analyte-sensitive sensors utilizes AFP variants, whose fluorescent properties are directly affected by the interaction between a target molecule and a chromophore moiety in AFP. In general, the fluorescence of most of AFP variants is affected reversibly by moderate acidification of the chromophore. To exploitsuch intrinsic properties of AFPs, pH sensitive AFP variants have been developed. (Kneen, M. et al. 1998; Llopis, J. et al. 1998; Miesenbock, G. et al. 1998; Matsuyama, S. et al. 2000) Mutants of YFPs showing pH sensitivity bind to halide ion selectively and the binding of anion leads to fluorescence quenching due to the induced pKa shift. (Wachter, R. M. et al. 1999; Jayaraman, S. et al. 2000; Wachter,R. M. et al. 2000) The fluorescence of AFP becomes sensitive to other signals by the introduction of specific mutation in close proximity to the chromophore or within the barrel structure. In this manner,biosensors specific for Mercury (II) ion (Chapleau, R.R. et al. 2008)and Zinc (II) ion (Barondeau, D. P. et al. 2002) have been created.The receptor function of the sensor was directly integrated into the chromophore by alteration of the chemical nature around the chromophore.
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Another design strategy of a single AFP based biosensor relies on circularly permutated AFP (cpAFP), which is classified as a conformation-sensitive sensor, that is, a conformational change of the receptor associated with the ligand-binding event results a formation of the AFP chromophore. The cpAFP is a regenerated AFP variant, in which the original N- and C termini are connected with a flexible peptide linker toregenerate novel N and C termini at specific positions.(Baird, G. S. et al. 1999) A number of cpAFPs with novel termini retained their fluorescence even when a foreign receptor was inserted at the termini. Indeed, cpAFP variants that detect Ca2+ (Nakai, J. et al. 2001; \n\t\t\t\t\t\tSouslova, E. A. et al. 2007\n\t\t\t\t\t; Baird, G. S. et al. 1999, Nagai, T. et al. 2001), cGMP (Nausch, L. W. et al. 2008), H2O2 (Belousov, V.V. et al. 2006; Dooley, C.T. 2004), Zn2+ (Mizuno, T. et al. 2007) and an inositol phosphate derivative (Sakaguchi, R. et al. 2009), have been developed by inserting appropriate receptor modules.
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Morii and coworkers developed a cpAFP-based sensor for D-myo-inositol-1,3,4,5-tetrakisphosphate, Ins(1,3,4,5)P4, by utilizing a newly designed split PH domain of Bruton’s tyrosine kinase (Btk) and cpGFP (Sakaguchi, R. et al. 2009) (Figure 1). Interestingly, the conjugate Btk-cpGFP realized a ratiometric fluorescence detection of Ins(1,3,4,5)P4 by the excitation of each distinct absorption band, and retained ligand affinity and selectivity of the original PH domain.
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Figure 1.
Schematic illustration shows a fluorescent biosensor for Ins(1,3,4,5)P4 based on the split Btk PH domain-cpGFP conjugate (Sakaguchi, R. et al. 2009). The original N and C termini of GFPwere linked with a short peptide linker (orange), and the novel terminal of cpGFP (purple) was fused to the split Btk PH domain (blue). Theconformational change of the PH domain induced by the ligand-binding event was transduced to the structuralchange of the chromophore of cpGFP, and then resulted in the ratiometric fluorescence change of cpGFP.
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2.2. Split AFP based biosensor
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It is considered that the formation of a AFPs chromophore requires a properly folded and an intact structure. However, many experimental data indicate that slight structural modifications of AFPs, like circular permutation and insertion of recognition domains as described in the previous section, still give fluorescent AFPs constructs. Therefore, AFP sensors in the absence of targets often reveal unavoidable background fluorescence. An excellent strategy to accomplish full suppression of the initial fluorescence utilizes an AFP variant that was split into two non-fluorescent fragments.( Shyu, Y.J. et al. 2008; Kerppola T. K. 2006 ) Regan and co-workers first demonstrated that a split GFP displayed a quite low background fluorescence in the separated state and a fluorescence emission was significantly recovered by the reassembly of the two fragments when they were placed in close proximity by strongly interacting antiparallel leucine zippers.(Ghosh, I. et al. 2000) Based on this strategy, a receptor composed of two subunits that are associated by binding to the analyte can be converted into a fluorescent biosensor by connecting each of the two subunits with each split AFP fragment (Figure 2). Actually, several types of biosensors have been developed for fluorescent detection of specific DNA sequences (Stains, C. I. et al. 2005; Demidov, V. V. et al. 2006), DNA methylation(Stains, C. I. et al. 2006), mRNA(Ozawa, T. et al. 2007; Valencia-Burton, M. et al. 2007) and protein interactions (Nyfeler, B. et al. 2005; Hu, C. -D. et al. 2003; Wilson, C. G. et al, 2004).
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Unlike the above-mentioned split AFP reconstitution, in which split AFP halves reform into a fluorescent structure via noncovalent association, another reconstitution strategy, intein-mediated reconstitution, has been developed by Ozawa and co-workers (Ozawa, T. et al. 2000). In this strategy, split inteins were fused to split EGFPs. Each split intein-EGFP fusion is attached to a protein of interest. The split inteins are brought into close proximity to trigger protein splicing when an analyte induces the association between proteins of interest. As a result, the two EGFP fragments are linked with a covalent bond and emit fluorescence. More comprehensive information on this reconstitution strategy is available in other excellent reviews (Ozawa, T. 2006; Awais, M. et al. 2011).
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Figure 2.
Schematic illustration shows split AFP based fluorescent biosensor. A fluorescent protein such as GFP is split into two halves [GFP(N) and GFP(C)], which connect each of the two binding subunits, are associated by binding to the analyte.
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2.3. FRET based biosensor
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Non-radiative transfer of energy from an excited donor fluorophore to an acceptor chromophore is known as fluorescence resonance energy transfer (FRET). In order to induce FRET, the excitation spectrum of the acceptor must overlap with the emission spectrum of the donor, and the two fluorophores must be close in proximity (< 10 nm) and in a favorable orientation (Sapsford, K.E. et al. 2006). The efficiency of FRET is sensitive to the distance and the orientation between the donor and acceptor groups. To obtain the expected energy transfer efficiency for biological applications, the following two issues in the sensor design should be considered. First, suitable FRET pairs in which the donor emission spectrum overlaps the acceptor absorption spectrum should be chosen. In the AFP-based FRET strategy, CFP and YFP mutants have been favorably utilized as a FRET donor and an acceptor, respectively(Piston, D.W. et al. 2007). Second, the donor and the acceptor fluorophores should be placed at a rational distance which can drastically change the efficiency of FRET before and after the sensing event.(Ohashi, T. et al. 2007) Therefore, a FRET based biosensor can sense the analyte in a ratiometric manner by comparing the donor and acceptor emission intensities that are result from the analyte induced distance and/or conformational changes. Based on the mechanism by which FRET efficiency changes, AFP-based FRET biosensors can be divided into two classes, that is, an intramolecular and an intermolecular FRET systems (Figure 3). In the case of intramolecular FRET biosensors, the two fluorophores are attached at two ends of a peptide sequence in the receptor protein or the concatenation of interacting domains. The feasibility of this strategy strongly depends on the magnitude of the structural change of the receptor. In the case of a receptor that displays a large structural change upon binding to the substrate, this strategy would be the most straightforward way to integrate the signal transduction function into the receptor of interest. Based on this strategy, various FRET biosensor for imaging intracellular events such as enzyme activities [e.g. protease(Mahajan, N. P. et al. 1999; Luo, K. Q. et al. 2001; Rehm, M. et al. 2002; Ai, H. W. et al. 2008), kinase(Sato, M. et al. 2002; Nagai, Y., et al. 2000), phosphatase(Newman, R. H. et al. 2008)] and dynamics of intracellular second messengers [e.g.Ca2+(Miyawaki, A. et al. 1997; Romoser,V. A. et al. 1997), cAMP (Nikolaev,V. et al. 2004), cGMP(Sato, M. et al. 2000), IP3(Sato, M. et al. 2005)] have been developed. It should be noted that careful optimization, such as tuning the position of AFPs relative to the sensing domain by changing the linker between each of protein units, is frequently necessary to realize the satisfactory response of the FRET change. Most importantly, the
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Figure 3.
AFP-fused FRET based biosensors. (a) Intramolecular FRET-based biosensor: The protein domains with a large structural change upon the analyte binding event. (b) Intermolecular FRET-based biosensor: The change of FRET efficiency is induced by the dissociation or association of the subunit upon the analyte-binding event.
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obligatory conformational change in the receptor proteinseverely limits the choice of proteins available for the construction of FRET biosensors by this strategy. Recently,Johnsson and co-workers have demonstrated a new type of FRET biosensor based on their SNAP-tag technique, for which conformational changes upon analyte binding were not required (Brun, M.A. et al. 2009). Intermolecular FRET biosensors have been developed by employing two protein domains separated from each other, to which AFPs of FRET donor and acceptor are attached, respectively. Zaccoro and co-workers constructed FRET biosensor for cAMP by applying this strategyto the regulatory and catalytic subunit of protein kinase A (PKA)(Zaccolo, M. et al. 2000; Zaccolo, M et al. 2002). This biosensor can detect the rise of intracellular cAMP concentration by the decrease in the FRET efficiency induced by dissociation of the catalytic subunit from the regulatory subunit. Although this strategy shows a potential to effect a dynamic FRET change by the analyte-induced association and/or dissociation of protein subunits, the stoichiometry of the FRET donor and acceptor may vary between either cells or intracellular compartments. In these cases, they cause difficulty in analysis of the FRET efficiency changes.More comprehensive information on dual FRET-based biosensors is available in other excellent reviews(Souslova, E. A. et al. 2007; VanDngelenburg, S. B. et al. 2008; Carlson, H. J. et al. 2009).
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3. Protein-based biosensor covalently modified with fluorescent artificial molecules
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Another useful strategy to construct fluorescent biosensors is a structure-based design of a protein covalently modified with a fluorescent dye. Advantages for the use of fluorescent dyes areas follows. First, the relatively smaller size of the synthetic fluorophore is likely to less perturb the property of the original receptor protein. Second, a superior characteristic of dye, that is, the fluorescence changes in intensity and wavelength and the microenvironmental sensitivity such as pH, polarity or molecular recognition, could be introduced to the receptor protein. Not only simple dyes but also functional molecules, such as artificial receptors, can be incorporated. Third, the attachment of dye to the protein framework is more flexible than the use of AFPs. While the attaching positions of AFP are generally limited to the N- and C termini of receptor proteins, the incorporation of small dye to proteins is also possible in the middle of loop regions orat close proximity to the binding pocket. On the other hands, unlike AFPs based biosensor, this type of protein-based biosensor generally require the invasive technique for translocating across the plasma membrane, such as electroporation (Marrero, M.B. et al. 1995; Fenton, M. et al. 1998; Sakaguchi, R. et al. 2010), lipofection (Zelphati, O., et al. 2001; Zheng, X. et al. 2003), microinjection (Abarzua, P. et al. 1995), and tagging cell-permeable peptide sequences(Wadia, J.S. et al 2005; Sugimoto, K. et al 2004). In addition, the central issue for the construction of these types of biosensors is the way to introduce a dye into the receptor protein site-selectively. Here, a variety of fluorescent biosensors that use fluorescent molecules is described according to a classification of the incorporation methodologies of fluorescent dye.
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3.1. Introduction of a thiol reactive fluorophore on a unique cysteine residue of engineered receptor protein
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The most important process to success this methodology is that all of the original cysteine residue of the receptor protein must be initially substituted with other amino acids to avoid the nonspecific labeling of cysteine reactive fluorophores. Following the process, a unique cysteine residue was introduced at specific position.The positionto introduce a fluorophore is most conveniently determined by the three-dimensional structure of the receptor protein.
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As a pioneering work, bPBPs (bacteria periplasmic binding protein), a representative protein scaffold, were converted to fluorophore-modified biosensors by Hellinga et al.(Dwyer, M. A. et al. 2004) or others (Gilardi, G. et al. 1994; Brune, M. et al. 1998;\n\t\t\t\t\tHirshberg, M. et al. 1998). Most of bPBPs consist of two domains connected by a hinge region, with a ligand binding site located at the interface between the two domains, which can permitdynamic conformational changes induced upon ligand binding. Therefore, two distinct approaches are used to establish an efficient signal transduction mechanism that would sense the ligand-binding event. In the first approach, an environmentally sensitive fluorophore is positioned in the binding pocket so that the ligand-induced changes in the fluorescence are produced by the direct fluorophore-ligand interactions. This approach often has a disadvantage that unfavorable steric interactions between the introduced fluorophore and the ligand lower the binding affinity. The second approach introduces environmentally sensitive fluorophore at the regionthat is distant from the ligand-binding site but exhibits dynamic domain movement in response to the ligand binding. This allosteric sensing mechanism shows an advantage that the ligand binding is essentially unaffected by introducing a fluorophore.
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On the other hand, there are number of proteins that do not undergo such a dynamic conformational change upon ligand binding, but they are capable of recognizing the various substances of biological importance. The useful methodology to convert such non-allosteric proteins to fluorescent biosensors is to introduce an environmentally sensitive fluorophore within the proximity of the ligand-binding site, though this strategy might have some drawbacks as mentioned above. But several successful examples demonstrated that such a methodology is applicable for obtaining biosensors (Chan, P. H. et al. 2004; Nalbant,P. et al. 2004; Chan, P. H. 2008). Morii and coworkers constructed novel biosensors for inositol 1,4,5-trisphosphate [Ins(1,4,5)P3]and 1,3,4,5-tetrakisphosphate [Ins(1,3,4,5)P4]by utilizing the pleckstrin homology (PH) domain of phospholipase C (PLC) δ1(Morii, T. et al. 2002) and the general receptor for phosphoinositides 1 (GRP1)(Sakaguchi, R. et al. 2010) (Figure 4), respectively. In these biosensorsa synthetic fluorophore was attached at the proximity of the ligand-binding site based on the three dimensional structures of proteins so that the changes in orientation of the fluorophore induced by the substrate binding lead to a sufficient fluorescence response. This structure-based design of synthetic fluorophore-modified biosensors is a powerful method to produce biosensors with high selectivity and appropriate affinity to target inositol derivatives in living cells(Sakaguchi, R. et al. 2010; Sugimoto, K. et al. 2004; Nishida, M. et al. 2003).
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3.2. Site-specific unnatural amino acid mutagenesis with an expanded genetic code
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As mentioned above, the post-labeling of unique cysteine residues required preliminary preparation that all of the original cysteine residue of the receptor protein must be substituted with other amino acids. The process might cause the instability of the receptor protein mutant. A mutagenesis technique for direct incorporation of synthetic fluorophores as unnatural amino acids into desired positions in proteins can avoid such a problem. A site-specific mutagenesis with an expanded genetic code that employed an amber suppression method(Wang, L. 2005; et al. Xie, J. et al. 2006) or a four-base codon method(Hohsaka, T. et al., 2002) in cell-free translation systems has provided a variety of fluorescently modified
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Figure 4.
A schematic illustration shows a fluorescent biosensor for Ins(1,3,4,5)P4 based on the GRP1 PH domain(Sakaguchi, R. et al. 2010). Firstly, the original cysteine residues (cyan) of GRP PH domain were replaced with other amino acids. Second, a unique cysteine residue (magenta) was introduced to the resultant mutant followed by labeling with thiol reactive fluorescein (green) as an environment sensitive fluorophore to give Ins(1,3,4,5)P4 sensor. The local environmental change of the fluorophore induced by the ligand-binding event was transduced to the fluorescence enhancement.
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proteins(Anderson, R. D. et al. 2002; Taki, M. et al. 2002; Kajihara D. et al. 2006). As an excellent example, Hohsaka and co-workers prepared a series of semisynthetic calmodulins, two different position of which were replaced with unnatural amino acids bearing a FRET pair of BODIPY derivatives by using two sets of four-base codons. Some of the doubly modified calmodulin sensed calmodulin-binding peptide by substantial FRET signal changes. This is a powerful tool for site-specific introduction of unnatural amino acids into protein, though the examples of the construction of fluorescent biosensor based on these methods are still limited.
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3.3. Covalent introduction of fluorescent molecules by chemical modification
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Modification of a protein by using genetic method often causes the lower activity or instability of the mutated protein as mentionedin the previous section. In addition, the method is not appropriate when the three dimensional structure of a receptor protein is not known. In that case, an approach to site-specifically incorporate a signal transducer proximal to the binding pocket of intact receptor protein by using selective chemical modifications is valid.
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As the primary example, Schultz and co-workers constructed an antibody-based fluorescent biosensor by using an affinity-labeling method (Pollack,S. J. et al. 1988). The chemically engineered antibody, of which the proximal antigen-recognition site was modified by fluorescent molecule, can detect antigen binding by fluorescence decrease. Hamachi and co-workers constructed a lectin-based fluorescent biosensor using an improved photo affinity labeling method, termed as P-PALM (post-photoaffinity labeling modification) (Hamachi, I. et al. 2000; Nagase, T. et al. 2001, Nagase, T. et al. 2003). This methodology can introduce artificial molecules (e.g. fluorophore, artificial receptor) proximal to the active site of a target protein without genetically modifying the protein framework. In a proof-of-principle experiment, P-PALM was demonstrated by using concanavalin A (Con A), an extensively studied lectin (saccharide-binding protein).Introduction of a thiol group as a chemoselective modification sitein proximity of the ligand-binding pocket of Con A is conducted by a designed photoaffinity labeling molecule, which is composed of a ligand module, a photoreactive module and a cleavable disulfide module.Depending on the nature of the subsequent modification by a thiol reactive artificial molecule, not only environmental sensitive fluorophore (Koshi, Y. et al. 2005; Nakata, E. et al. 2005; Nakata, E. et al. 2008) but also fluorescent artificial receptor (Nakata, E. et al. 2004) can be introduced to Con A. Intact Con A can be converted to a various type of fluorescent biosensors that successfully sense the saccharide derivatives in different manners. Because the initial P-PALM strategy based on thiol chemistry shows limited bioorthogonality, this method is not applicable to many proteins. To overcome this drawback, Hamachi group adopted the ketone/aldehyde-based hydrazone/oxime exchange reaction (Takaoka, Y. et al. 2006) and the organometallic Suzuki reaction (Wakabayashi, H. 2008) as bioorthogonal chemoselective modifications. Recently, Hamachi and co-workers also developed ligand-directed tosyl (LDT) chemistry-based approach as a more general and simple strategy of target selective chemical modification (Tsukiji, S. 2009). A detailed description of their strategies is described in other review articles(Nakata, E. et al. 2007; Wang. H. et al. 2009).
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4. Signaling aptamers
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Protein based biosensors are generally constructed by using native or slightly modified proteins as the scaffold. Therefore, the function of the constructed biosensor, such as the specificity and the affinity toward the substrate, depends on that of the native receptor. Unlike receptor proteins, DNA or RNA based receptors (aptamers) which have appropriate affinity and specificity for various targets ranging from small molecules to proteins can be generated by using in vitro selection, also known as SELEX (systematic evolution of ligands by exponential enrichment)(Ellington, A.D. 1994; Ellington, A.D. et al. 1990; Gold, L. et al. 1995; Osborne, S. E. et al. 1997; Wilson, D. S. et al. 1999). That is, aptamers that bind to the substrate of interest with tailor made functions, such as the specificity and the affinity, can potentially be generated through in vitro selection. Previous work indicated that most of the structurally characterized aptamers underwent induced-fit type of conformational change upon ligand binding [Westhof, E. et al. 1997]. Introduction of the signal transduction module such as a fluorophore at an appropriate site of the aptamer enables a read out of the ligand-binding event as a local environmental change of the fluorophore. Thus, the design of aptamer-based fluorescent sensors represents an attractive and promising alternative to the protein-based sensors. Some excellent reviews of aptamer sensors have already covered the selection and evolution techniques and sophisticated applications of the aptamer sensors [Liu, J. et al 2009; Mok, W. et al. 2008]. Here we focus on unique modular strategies to construct aptamer sensors, which would avoid the cumbersome trial-and-error process to construct a sensor with an optimized function.
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4.1. Modular strategies for tailoring aptamer sensors
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Sophisticated design strategies have successfully provided fluorescent biosensors based on biomoleculessuch as DNA, RNA or proteins, but these strategies usually require the redundant optimization of sensor functions. For example, introduction of the fluorophore often impairs the original receptor function and does not always ensure the fluorophore-labelled receptor to act as an expected sensor. It is quite difficult to empirically apply the obtained findings from the previously constructed biosensor to the other one, because the communication between the substrate binding and the signal-transduction is not so simple and is unique to the individualbiosensor. On the other hand, a modular strategy that permitsfacile preparation of biosensors with tailored characteristics by a simple combination of a receptor and a signal transducer has recently emerged as a new paradigm for a versatile design of fluorescent biosensors. Stojanovic and co-workers have proposed a modular design of signaling aptamers based on the allosteric regulation of binding events (Stojanovic, M. N. et al. 2004).The target binding aptamers were fused with the reporter dye binding aptamers, which can drastically increase the fluorescent intensity of reporter dye, and the reporter dye binding was significantly enhanced upon target binding. Fluorescent sensors for adenosine triphosphate(ATP), flavin mononucleotide (FMN) and theophylline have been demonstrated based on this design, showing the generality of the approach. Later, several groups reported various allosteric aptamer sensors based on the methodology(Kolpashchikov, D. M. 2005; Xu, W. et al. 2010;Furutani, C. et al. 2010).
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The application of the selection and evolution technique is not limited to obtain functional macromolecules solely composed of RNA or DNA. Morii and co-workers have recently developed a conceptually new strategy for preparation of fluorescent biosensors with diverse functions based on a framework of ribonucleopeptide (RNP), such as the structurally well characterized complex of the Rev Responsive Element (RRE)-HIV Rev peptide (Rev peptide) and RRE RNA (Figure 5) (Tainaka, K. et al. 2010). In the first step to construct the fluorescent RNP sensor, a randomized nucleotide sequence was introduced into the RNA subunit of RNP to construct RNP library. In vitro selection method was applied to the RNP library to afford a series of RNP receptors for a given target (Morii, T. et al. 2002). In the second step, the Rev peptide was modified with a fluorophore as the transducer of binding event without greatly disturbing the affinity and specificity of the RNP receptor. The constructed fluorescent RNP sensor showed the fluorescent intensity changing upon binding to the target molecule as the result of the conformational change of RNA subunit by inducing target binding. In similar to RNA aptamers, the RNPreceptors, which obtained by in vitro selection, are considered as a RNP receptor library, because a variety of RNA structures and reveal different affinity to the target molecule were included. The combined peptide subunit is also easily converted to functionalized Rev peptide libraries, such as various fluorophore modified Rev peptide libraries with a variety of excitation and emission wavelengths. By taking the advantage of such the noncovalent nature of the RNP complex, RNP sensors with desired affinity, selectivity and optical sensing properties could be selected in a high-throughput manner by combining a series of RNA subunits derived from each of the library. Actually, a variety of fluorescent biosensors for targeting ATP (Hagihara, M. et al. 2006), GTP (Hagihara, M. et al. 2006), histamine(Fukuda, M. et al. 2009), phosphotyrosine (Hasegawa, T. et al. 2005), and phosphotyrosine-containing peptide fragment (Hasegawa, T. et al. 2008) have been produced by the group, showing the generality of the approach. Recently, the group showed that ATP-binding RNP sensor was rationally converted to GTP-binding RNP sensor to have realized the detail of the recognition mechanism (Nakano, S. et al. 2011). Though the noncovalent configuration conveniently provides fluorescent RNP sensors in the selection stage, ithave a possibility to becomes a disadvantage for the practical measurements after optimization of the sensor function, for instance, the RNP complex would dissociate to each component under reducing condition such as the nanomolar range. Acovalently linking of RNA and peptidesubunits without sacrificing the sensing function wouldovercome such disadvantages.
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Figure 5.
Screening methodology of a tailor-made RNP fluorescent sensor[Hagihara, M. et al. 2006]. Combination between the RNA subunit library and several dye-labeled Rev peptide subunits generates combinatorial fluorescent RNP receptor libraries, from which RNP sensors with desiredfunction, such as optical property, affinity and selectivity, are selected.
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5. Perspective
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Here we overviewed construction methodologies of fluorescent biosensor based on biomolecules, that is, protein-based biosensor and aptamer-based biosensor. The systematic developments of these technologies have expanded the applicability of fluorescent biosensors. In the case of the protein based biosensor, there is no doubt that these sensors represent the most practical and reliable tools for the real-time measurements of various biologically important molecules in living cells. Actually, the function of second messengers, for example, in the cell has been progressively clarified owing to significant contribution of these new biosensors. However, the wide varieties of the construction strategies, which have both the advantages and drawbacks as mentioned above, strongly indicated the lack of general approach to conjugatea recognition modulewith a signal transducer unit. Further effort in the fields for establishing a general and simple strategy to construct usable biosensors will realize tailor-made fluorescent biosensors.
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Aptamer-based biosensorshave potential to realize the tailor-made biosensor with finely tuneable affinity and selectivity based on in vitro selection technique, and to visualize intracellular molecules. However, this type of sensor ispractically passive with challenges in cell application owing to the inherent liability of RNA molecules in the intracellular condition. Such the drawbackswill be overcome by the improved selection and evolution technique to construct theaptamers thatresist to the cellular degradation activity.
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\n\t\n',keywords:null,chapterPDFUrl:"https://cdn.intechopen.com/pdfs/16424.pdf",chapterXML:"https://mts.intechopen.com/source/xml/16424.xml",downloadPdfUrl:"/chapter/pdf-download/16424",previewPdfUrl:"/chapter/pdf-preview/16424",totalDownloads:2437,totalViews:248,totalCrossrefCites:0,totalDimensionsCites:2,hasAltmetrics:0,dateSubmitted:"October 22nd 2010",dateReviewed:"March 4th 2011",datePrePublished:null,datePublished:"July 18th 2011",dateFinished:null,readingETA:"0",abstract:null,reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/16424",risUrl:"/chapter/ris/16424",book:{slug:"biosensors-emerging-materials-and-applications"},signatures:"Eiji Nakata, FongFong Liew, Shun Nakano and Takashi Morii",authors:[{id:"29264",title:"Prof.",name:"Takashi",middleName:null,surname:"Morii",fullName:"Takashi Morii",slug:"takashi-morii",email:"t-morii@iae.kyoto-u.ac.jp",position:null,institution:null}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Auto-fluorescent proteins (AFPs) based biosensors",level:"1"},{id:"sec_2_2",title:"2.1. Single AFP based biosensor",level:"2"},{id:"sec_3_2",title:"2.2. Split AFP based biosensor",level:"2"},{id:"sec_4_2",title:"2.3. FRET based biosensor",level:"2"},{id:"sec_6",title:"3. Protein-based biosensor covalently modified with fluorescent artificial molecules",level:"1"},{id:"sec_6_2",title:"3.1. Introduction of a thiol reactive fluorophore on a unique cysteine residue of engineered receptor protein",level:"2"},{id:"sec_7_2",title:"3.2. Site-specific unnatural amino acid mutagenesis with an expanded genetic code",level:"2"},{id:"sec_8_2",title:"3.3. Covalent introduction of fluorescent molecules by chemical modification",level:"2"},{id:"sec_10",title:"4. Signaling aptamers",level:"1"},{id:"sec_10_2",title:"4.1. Modular strategies for tailoring aptamer sensors",level:"2"},{id:"sec_12",title:"5. 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Institute of Advanced Energy, Kyoto University, Kyoto, Japan
Institute of Advanced Energy, Kyoto University, Kyoto, Japan
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Ansari, M. Alhoshan, M.S. Alsalhi and A.S. 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Hashim, S. Fatimah Abd Rahman and M. E. A. 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Novikova, Kirill A. Afonin and Neocles B. Leontis",authors:[{id:"6596",title:"Professor",name:"Neocles",middleName:null,surname:"Leontis",fullName:"Neocles Leontis",slug:"neocles-leontis"},{id:"134005",title:"Prof.",name:"Irina",middleName:null,surname:"Novikova",fullName:"Irina Novikova",slug:"irina-novikova"},{id:"134006",title:"Prof.",name:"Kirill",middleName:null,surname:"Afonin",fullName:"Kirill Afonin",slug:"kirill-afonin"}]},{id:"6919",title:"Surface Plasmon Resonance Biosensors for Highly Sensitive Detection of Small Biomolecules",slug:"surface-plasmon-resonance-biosensors-for-highly-sensitive-detection-of-small-biomolecules",signatures:"John S. Mitchell and Yinqiu Wu",authors:[{id:"6591",title:"Dr.",name:"John",middleName:null,surname:"Mitchell",fullName:"John Mitchell",slug:"john-mitchell"},{id:"133989",title:"Dr.",name:"Yinqiu",middleName:null,surname:"Wu",fullName:"Yinqiu Wu",slug:"yinqiu-wu"}]},{id:"6920",title:"Detection of SARS-CoV Antigen via SPR Analytical Systems with Reference",slug:"detection-of-sars-cov-antigen-via-spr-analytical-systems-with-reference",signatures:"Dafu Cui, Xing Chen and Yujie Wang",authors:[{id:"6951",title:"Prof.",name:"Dafu",middleName:null,surname:"Cui",fullName:"Dafu Cui",slug:"dafu-cui"},{id:"82019",title:"Dr.",name:"Xing",middleName:null,surname:"Chen",fullName:"Xing Chen",slug:"xing-chen"},{id:"104753",title:"Dr.",name:"Yujie",middleName:null,surname:"Wang",fullName:"Yujie Wang",slug:"yujie-wang"}]},{id:"6921",title:"Bacterial Bioluminescent Biosensor Characterisation for On-line Monitoring of Heavy Metals Pollutions in Waste Water Treatment Plant Effluents",slug:"bacterial-bioluminescent-biosensor-characterisation-for-on-line-monitoring-of-heavy-metals-pollution",signatures:"Thomas Charrier, Marie José Durand, Mahmoud Affi, Sulivan Jouanneau, Hélène Gezekel and Gérald Thouand",authors:[{id:"5875",title:"Professor",name:"Gerald",middleName:null,surname:"Thouand",fullName:"Gerald Thouand",slug:"gerald-thouand"},{id:"134028",title:"Prof.",name:"Marie José",middleName:null,surname:"Durand",fullName:"Marie José Durand",slug:"marie-jose-durand"},{id:"134030",title:"Prof.",name:"Mahmoud",middleName:null,surname:"Affi",fullName:"Mahmoud Affi",slug:"mahmoud-affi"},{id:"134031",title:"Prof.",name:"Sulivan",middleName:null,surname:"Jouanneau",fullName:"Sulivan Jouanneau",slug:"sulivan-jouanneau"},{id:"134032",title:"Prof.",name:"Hélène",middleName:null,surname:"Gezekel",fullName:"Hélène Gezekel",slug:"helene-gezekel"}]},{id:"6922",title:"Integrated Biosensor and Interfacing Circuits",slug:"integrated-biosensor-and-interfacing-circuits",signatures:"Lei Zhang, Zhiping Yu and Xiangqing He",authors:[{id:"6943",title:"Prof.",name:"Lei",middleName:null,surname:"Zhang",fullName:"Lei Zhang",slug:"lei-zhang"},{id:"134001",title:"PhD.",name:"Zhiping",middleName:null,surname:"Yu",fullName:"Zhiping Yu",slug:"zhiping-yu"}]},{id:"6923",title:"Intelligent Communication Module for Wireless Biosensor Networks",slug:"intelligent-communication-module-for-wireless-biosensor-networks",signatures:"R. Naik, J. Singh and H. P. Le",authors:[{id:"6622",title:"Mr.",name:"Rohit",middleName:null,surname:"Naik",fullName:"Rohit Naik",slug:"rohit-naik"},{id:"134015",title:"Prof.",name:"Shakti",middleName:null,surname:"Singh",fullName:"Shakti Singh",slug:"shakti-singh"}]},{id:"6924",title:"Design and Construction of a Distributed Sensor NET for Biotelemetric Monitoring of Brain Energetic Metabolism Using Microsensors and Biosensors",slug:"design-and-construction-of-a-distributed-sensor-net-for-biotelemetric-monitoring-of-brain-energetic-",signatures:"Pier Andrea Serra, Giulia Puggioni, Gianfranco Bazzu, Giammario Calia, Rossana Migheli and Gaia Rocchitta",authors:[{id:"6091",title:"Prof.",name:"Pier Andrea",middleName:null,surname:"Serra",fullName:"Pier Andrea Serra",slug:"pier-andrea-serra"},{id:"134017",title:"Prof.",name:"Giulia",middleName:null,surname:"Puggioni",fullName:"Giulia Puggioni",slug:"giulia-puggioni"},{id:"134018",title:"Prof.",name:"Gianfranco",middleName:null,surname:"Bazzu",fullName:"Gianfranco Bazzu",slug:"gianfranco-bazzu"},{id:"134020",title:"Prof.",name:"Giammario",middleName:null,surname:"Calia",fullName:"Giammario Calia",slug:"giammario-calia"},{id:"134021",title:"Prof.",name:"Rossana",middleName:null,surname:"Migheli",fullName:"Rossana Migheli",slug:"rossana-migheli"},{id:"134022",title:"Prof.",name:"Gaia",middleName:null,surname:"Rocchitta",fullName:"Gaia Rocchitta",slug:"gaia-rocchitta"}]},{id:"6925",title:"Information Assurance Protocols for Body Sensors Using Physiological Data",slug:"information-assurance-protocols-for-body-sensors-using-physiological-data",signatures:"Kalvinder Singh and Vallipuram Muthukkumarasamy",authors:[{id:"5907",title:"Dr.",name:"Kalvinder",middleName:null,surname:"Singh",fullName:"Kalvinder Singh",slug:"kalvinder-singh"},{id:"22410",title:"Prof.",name:"Vallipuram",middleName:null,surname:"Muthukkumarasamy",fullName:"Vallipuram Muthukkumarasamy",slug:"vallipuram-muthukkumarasamy"}]},{id:"6926",title:"Symbolic Modelling of Dynamic Human Motions",slug:"symbolic-modelling-of-dynamic-human-motions",signatures:"David Stirling, Amir Hesami, Christian Ritz, Kevin Adistambha and Fazel Naghdy",authors:[{id:"108937",title:"Mr.",name:"Kevin",middleName:null,surname:"Adistambha",fullName:"Kevin Adistambha",slug:"kevin-adistambha"},{id:"114019",title:"Dr.",name:"David",middleName:null,surname:"Stirling",fullName:"David Stirling",slug:"david-stirling"},{id:"134024",title:"Prof.",name:"Amir",middleName:null,surname:"Hesami",fullName:"Amir Hesami",slug:"amir-hesami"}]}]}]},onlineFirst:{chapter:{type:"chapter",id:"63269",title:"Microemulsions as Nanoreactors to Obtain Bimetallic Nanoparticles",doi:"10.5772/intechopen.80549",slug:"microemulsions-as-nanoreactors-to-obtain-bimetallic-nanoparticles",body:'\n
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1. Introduction
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From the pioneering work of Boutonnet et al. [1], the synthesis of nanoparticles in microemulsions has been widely investigated with a variety of technical applications in catalysis [2, 3, 4], photonics [5], and energy conversion and storage devices [6, 7, 8]. The microemulsion route allows to control the size and composition of nanoparticles. A microemulsion consists of nanometer-sized water droplets dispersed in the oil phase and stabilized by a surfactant film. Reactants can be dissolved in the nano-sized water droplets or reverse micelles and can be exchanged between them by direct material transfer during an interdroplet collision [9]. The intermicellar exchange allows the reactants to be carried by the same droplet, so the chemical reaction can proceed inside the nanoreactor. Due to the space limitation inside the micelle, nucleation and growth of the particle are restricted, so it can result in the formation of size-controlled particles. In spite of the complexity of the reaction medium, microemulsion route has several advantages when compared to traditional methods. The first one is that nanoparticle size is directly controlled by the water/surfactant ratio, so narrow size distributions can be obtained. Another advantage is that surfactants around the nanoparticles can be removed with ease and nanoparticles can be prepared at room temperature. In addition, the confinement of reactants inside micelles induces important changes in reactant concentrations, which strongly affect the reaction rates. Finally, in relation to catalysis, nanoparticles obtained by the microemulsion route present an improved catalytic behavior than particles with the same composition which are synthesized by traditional procedures [10, 11].
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A variety of nanomaterials, ranging from metals [12, 13, 14], bimetallic structures [15, 16, 17], other inorganic nanoparticles [18, 19, 20], and organic compounds [21, 22], has been prepared by this approach. In the field of catalysis, microemulsion approach was successfully used to prepare different nanostructured catalytic materials [2, 10, 17, 23, 24, 25].
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Nevertheless, microemulsion route present a challenge due to the difficulty in managing the material intermicellar exchange. As mentioned above, reactants are distributed in separate nanoreactors, so the whole process (chemical reaction, nucleation, and subsequent growth to build up final particles) is conditioned by the material exchange between them. This exchange is mainly dictated by the surfactant, which is located on the interface between water and oil phases. The hydrophilic portion of the surfactant is anchored into water and the lipophilic one into oil, forming a film which surrounds the micelle surface. It is believed that, when a micelle-micelle collision is violent enough, the surfactant film breaks up, allowing the material exchange. As a consequence, the rate of intermicellar exchange controls the reactants encounter and therefore plays a key role in chemical kinetics in microemulsions. The ease with which intermicellar channels are established as well as their size and stability are determined by the microemulsion composition, which in turn has been shown to affect final nanoparticle properties [26, 27, 28].
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In the paper at hand, we are focused on the study of Pt/M (M = Au, Rh) nanoparticles synthesized in microemulsions. Platinum-based nanoparticles (NPs) exhibit remarkable electrocatalytic activity in many important chemical and electrochemical reactions including oxygen reduction reaction (ORR) and direct methanol oxidation [29]. Apart from the inherent chemical and physical properties of the constitutive metals, the catalytic activity, which is one of the more relevant applications of bimetallic nanoparticles, relies notably on the metal distribution, that is, on the intraparticle nanoarrangement [30]. Bimetallic nanoparticles can show four main mixing patterns: (a) core-shell structures, in which one metal forms the core and the second metal covers the first one forming the surrounding shell; (b) mixed structures, which are often called alloys; (c) multilayer structures [31]; and (d) sub-cluster segregated structures, characterized by a small number of heteroatomic bonds [12]. So, the control of bimetallic intrastructure, mainly within the first atomic layers from the surface [25, 32], is key for performance enhancement of bimetallic catalysts. Furthermore, the optimal metal distribution depends on the particular chemical reaction. Au-core/Pt-shell nanocatalyst exhibits an improved activity to catalyze formic acid electro-oxidation [33] or oxygen reduction reaction [34, 35]. On the contrary, an alloyed Pt-Au is better for electro-oxidation of methanol [36]. Therefore, an in-depth study aimed at tailoring well-defined structures will be of great interest.
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Although the simultaneous reduction of the two metals by the microemulsion route is one of the most common procedures to control the size and composition of bimetallic nanoparticles [24, 37], the prediction of the resulting metal arrangement is complicated, as far as the current state-of-the-art is concerned. As a matter of fact, many studies designed to produce new nanoarrangements via microemulsions come from trial-and-error experiments, mainly due to the high number of involved synthetic variables and to their interaction with the inherent complexity of the reaction media. A robust tool for elucidating the interplay between the different factors concerning final bimetallic nanoarrangements is computer simulation. With the aim of understanding the different factors affecting final nanostructures, we perform a comprehensive kinetic analysis of coreduction of different couple of metals in the light of the interplay between three kinetic parameters: intermicellar exchange rate, chemical reduction rates of the two metals, and reactants concentration. The particular combination of these factors determines the reaction rate of each metal, which in turn defines the final metal arrangement.
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2. The model
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A model was developed to simulate the kinetic course of the two chemical reductions (see Ref. [38] for details). The reaction medium is a microemulsion, which is described as a set of micelles. The one-pot method is reproduced by mixing equal volumes of three microemulsions, each of which contains one of the three reactants (two metal precursors and the reducing agent R). This pattern of mixing reactants recreates the one-pot method, by which the two metal salts are simultaneously reduced.
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2.1 Initial reactants concentration
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Reactants are initially distributed throughout micelles using a Poisson distribution, that is, the occupation of all micelles is not similar. In this study, we present results using different values of metal precursors concentration, but keeping a proportion 1:1 of the two metals: 〈cAuCl4−〉 = 〈cPtCl62−〉 = 〈c〉 = 2, 16, 32, and 64 metal precursors in each micelle, which corresponds to 0.01, 0.08, 0.16, and 0.40 M, respectively, in a micelle with a radius of 4 nm. Au and Rh precursors (AuCl4− and RhCl63−) are represented by M+. Calculations have been made under isolation conditions, that is, reducing agent R is in excess: (〈cR〉 = 10〈cPtCl62−〉).
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2.2 Microemulsion dynamics and time unit
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Micelles move and collide with each other. The intermicellar collision is a key feature in kinetics in microemulsions, because upon collision micelles are able to establish a water channel, which allows the exchange of their contents (metal precursors, reducing agent, metallic atoms, and/or growing particles). The material intermicellar exchange makes possible the reactant encounter inside micelles and, as a consequence, it is determinant of chemical reactions to occur. The intermicellar collision is simulated by choosing a 10% of micelles at random. These selected micelles collide, fuse (allowing material intermicellar exchange), and then redisperse. One Monte Carlo step begins in each intermicellar collision and ends when the quantity of species carried by colliding micelles is revised in agreement to the exchange criteria described below.
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2.3 Metal characterization: reduction rate ratio
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The reduction rate of a metal A (vA) can be related to the standard potential (ε0A) by means of the Volmer equation:
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where jA is the current density, nA is the number of electrons, F is the Faraday constant, kred,A is the chemical rate constant, βA is the transfer coefficient, cO,A is the concentration of oxidized A, R is the gas constant, and T is temperature. When two metals A and B, initially at the same concentration (cO,A = cO,B), are reduced simultaneously to synthesize an A/B bimetallic nanoparticle, this equation can be simplified by assuming the following approximations: the number of electrons (nA = nB = n), the transfer coefficients (βA =βA = β), and the chemical rate constants (kred,A = kred,B = kred) are equal. (One must keep in mind that main factor governing reduction rates is by electrochemical potential.) Under this condition, a simple relation between the rates of electron transfer of two species A and B and their standard potentials can be deduced.
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This equation supports the rule according to which the higher the difference between the standard potentials of the two metals, the higher the ratio between both reduction rates is.
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2.3.1 Au/Pt nanoparticles
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On the basis of Eq. (2), to simulate the reduction rate of Au/Pt nanoparticles, the standard reduction potential must be taken into account. When the Au precursor is AuCl4−, the standard reduction potential is ε0(AuCl4−) = 0.926 V, which is higher than that of Pt precursor ε0(PtCl62− = 0.742 V). This results in a faster formation rate of Au particles. In fact, Au is reduced so quickly that kinetics cannot be studied by conventional methods, so stopped flow techniques were needed [39]. The color change occurs instantaneously, so Au reduction was simulated as fast as possible, that is, 100% of Au precursors located in colliding micelles react to produce Au atoms, whenever the amount of reducing agent was enough. The reduction rate parameter of a metal A (vA) is the percentage of reactants inside colliding micelles which are reduced during a collision to give rise to products (A atoms). Regarding to Pt, its reduction rate was successfully simulated by using vPt = 10%, that is, only a 10% of Pt precursor reacts in each collision (vPt = 10%) [40]. In this way, Au/Pt nanoparticle formation is simulated by a reduction rate ratio vAu/vPt = 100/10 = 10, that is, Au reduction is 10 times faster than Pt.
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The two reductions can take place simultaneously within the same micelle. The metal precursors and/or reducing agent that did not react remain behind in the micelle and will be exchanged or react later.
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2.3.2 Pt/Rh nanoparticles
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In order to research the influence of another metal in the pair Pt/M on Pt reduction, a metal whose reduction rate would be 10 times slower than Pt was chosen. In this manner, the reduction rate ratio is the same as used to simulate Au/Pt nanoparticles, so the possible differences in the kinetic behavior and the final metal distributions cannot be supported by the difference between the standard potentials. Therefore, the reduction rate of Pt is the same as that of Au/Pt pair (vPt = 10%), but now Pt is the faster metal. Taking into account the standard reduction potential of RhCl63−, ε0(RhCl63−) = 0.44 V, this Rh precursor is a good candidate to be simulated as vRh = 1% (only a 1% of RhCl63− located in the colliding micelles will be reduced (vPt/vRh = 10/1 = 10)).
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The number of each species located within each micelle is adjusted at each step in agreement with the possibility of chemical reduction and the intermicellar exchange criteria (see below). As the metallic atoms are produced in each micelle, they are assumed to be deposited on nanoparticle seed. That is, unlike for reactants, which are isolated within the micelle, all metal atoms inside a micelle are aggregated forming a growing nanoparticle. In order to calculate the metal distribution in the final bimetallic nanoparticle, the sequence of metals which are reduced is monitored in each micelle as a function of time.
Two different intermicellar exchange criteria are implemented depending on the nature of exchanged species. Metal precursor, reducing agent, and free metal atoms are isolated species, which will be redistributed between two colliding micelles in accordance with the concentration gradient principle: they are transferred from the more to the less occupied micelle. The exchange parameter kex quantifies the maximum amount of isolated species that can be exchanged during an intermicellar collision. As a result of this redistribution, the metal salts (PtCl62− and/or M+) and the reducing agent R can be located within the same micelle. At this stage, chemical reduction can occur at a rate which depends on the nature of the metal.
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As the reductions take place, metal atoms are produced within micelles. It is assumed that metal atoms are deposited on nanoparticle seed, so all metal atoms inside a micelle are considered to be aggregated forming a growing nanoparticle. The larger size of a growing nanoparticle leads to a second interdroplet exchange protocol. It is assumed that the exchange of growing particles is restricted by the size of the channel connecting colliding micelles. The ease with which this channel can be established as well as the channel size is mainly determined by the flexibility of the surfactant film. The flexibility parameter (f) specifies the maximum particle size for transfer between micelles. The exchange criterium of growing particles also takes into account Ostwald ripening, which assumes that larger particles grow by condensation of material, coming from the smaller ones that solubilize more readily than larger ones. This feature is included in the model by considering that if both colliding micelles carry a growing particle, the smaller one is exchanged towards the micelle carrying the larger one, whenever the channel size would be large enough.
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As the synthesis advances, micelles can contain simultaneously reactants and growing particles. In this situation, autocatalysis can take place. Thus, if one of the colliding micelles is carrying a growing particle, the reaction always proceeds on it. If both colliding micelles contain particles, reaction takes place in the micelle containing the larger one, because it has a larger surface, so a higher probability of playing as catalyst.
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Based on these simple criteria for material interdroplet exchange, surfactant film flexibility can be characterized as follows. There are two main requirements for material intermicellar exchange to occur: the size of the channel connecting colliding micelles must be large enough and the dimer formed by colliding micelles must be stable, that is, they must remain together long enough. Isolated species (reactants and free metals) traverse the intermicellar channel one by one, so one can assume that the key factor determining their exchange is the dimer stability. That is, when the two micelles stay together longer (higher dimer stability), a larger quantity of species can be exchanged. Channel size would not be relevant in this case. Based on this, kex, which quantifies how many units of isolated species can be exchanged during a collision, is related to the dimer stability. Conversely, when the transferred material is a particle constituted by aggregation of metal atoms, which travels through the channel as a whole, channel size becomes decisive. This kind of material exchange will be restricted by the intermicellar channel size (f parameter). From this picture, the flexibility of the surfactant film is simulated by means of these two parameters, kex (dimer stability) and f (intermicellar channel size).
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A rigid film, such as AOT/n-heptane/water microemulsion, was successfully reproduced considering a channel size f = 5, associated to kex = 1 free atoms exchanged during a collision [26]. In case of flexible film, both factors rise together, because a more flexible film produces more stable dimer and larger channel size, allowing a quicker exchange of isolated species as well as an exchange of larger particles [41]. That is, a flexible film is associated to a faster material intermicellar exchange rate. A more flexible microemulsion, such as 75% Isooctane/20% Tergitol/5% water microemulsion, was successful compared to simulation data using the values f = 30, kex = 5 [42].
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2.5 Description of the metal distribution in the bimetallic nanoparticle
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The composition of each nanoparticle is revised at each step and monitored as a function of time. When all metal precursors were reduced and the content of all micelles remains constant over time, nanoparticle synthesis is considered to be finished. At this stage, the sequence of metal deposition of each particle (which is stored as a function of time) is stabilized. One simulation run produces a set of micelles, each one of them can carry one particle with different composition or be empty. At the end of each run, the averaged nanoparticle is calculated. Finally, results are averaged over 1000 runs.
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The intrastructure of each particle is calculated by analyzing the sequence in which the two metals are deposited on the nanoparticle surface. So that, each sequence is arranged in 10 concentric layers, assuming that final nanoparticle is spherical. Then, the averaged percentage of each metal is calculated layer by layer. The final bimetallic distribution is represented by histograms, in which the layer composition is described by a color grading, as stated in the following pattern: Au, Pt, and Rh are represented by red, blue, and green, respectively. As the proportion of pure metal in the layer is higher, the color becomes lighter. In order to illustrate the heterogeneity of nanoparticle composition, the number of particles with a given percentage of the faster reduction metal (Au in Au/Pt and Pt in Pt/Rh nanoparticles) in each of 10 layers is also represented in the histograms. This analysis is reproduced layer by layer, from the beginning of the synthesis (inner layer or core) to the end (outer layer or surface). To simplify, the metal distribution is also shown by means of concentric spheres, whose thickness is proportional to the number of layers with the same composition, keeping the same color pattern.
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3. Results and discussion
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3.1 Factors affecting metal distribution: initial reactants concentration
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The simulation model was successfully validated by comparison with experimental results. Au/Pt nanoparticles were synthesized in a 75% Isooctane/20% Tergitol/5% water microemulsion [42] (which can be characterized as flexible microemulsion)using different precursor concentrations. (〈cAuCl4−〉 = 〈cPtCl62−〉 = 〈c〉 = 0.01, 0.08, 0.16, and 0.40 M. The resulting Au/Pt particles were studied by HR-STEM and their structures were revealed by cross sections scanned with EDX analysis. The studied conditions were reproduced by simulation, using concentrations 〈cAuCl4−〉 = 〈cPtCl62−〉 = 〈c〉 = 2, 16, 32, and 64 metal precursors in each micelle, which corresponds to 0.01, 0.08, 0.16, and 0.40 M, respectively, in a micelle with a radius of 4 nm. As mentioned above, Au/Pt pair was characterized as vAu/vPt = 10 reduction rate ratio, and the 75% Isooctane/20% Tergitol/5% water microemulsion was simulated as a flexible surfactant film (f = 30, kex = 5).
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The left column in Figure 1 shows the simulated nanostructures obtained at each concentration. In order to compare the experimental and simulated nanostructures, the quantity of each metal crossed by a beam of 2 Å (approximate EDX beam size) was computed from each simulated final nanoparticle, and the theoretical STEM profiles were calculated. The STEM profiles of the average particle for each concentration are shown in center (theoretical) and right (experimental) columns of Figure 1. For a better comparison, experimental x-axis was changed from nm to counts, and the two kind of profiles were normalized to 1. Both profiles show the expected behavior: the surface (outer layers) is enriched in Pt, because of its slower reduction rate, and Au, which is reduced faster, accumulates in the core (inner layers). As concentration increases (see Figure 1 from the top to the bottom), deeper Pt profiles are obtained. This means that the final nanostructure shows an improved metal segregation as concentration is higher. It is clearly observed in the histograms, which evolve from Au core covered by a mixed shell obtained at a low concentration to a more mixed Au core covered by a pure Pt shell as concentration increases (see decreasing red bar on the left and increasing blue bar on the right in histograms of Figure 1). This means that the nanostructure can be fine-tuned with sub-nanometer resolution, just by changing concentration.
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Figure 1.
Left column: simulated histograms for different initial concentrations (Au:Pt = 1:1). The proportion of pure metal in the layer is higher as the color becomes lighter (red: 100% Au, blue: 100% Pt, gray: 50% Au-Pt). Centre column: calculated STEM profiles for the average nanoparticle. Right column: measured STEM profiles for Au/Pt nanoparticles synthesized in a water/tergitol/isooctane microemulsion. Simulation parameters: flexible film (kex = 5, f = 30); reduction rate ratio (vAu/vPt = 100/10); and reducing agent concentration 〈cR〉 = 10〈M+〉. Adapted with permission from Ref. [42]. Copyright (2015) American Chemical Society.
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A good agreement between experimental and theoretical results was attained, upholding the validity of the simulation model to predict the atomic structure of bimetallic nanoparticles. On this basis, the model becomes a strong tool to further enhance our knowledge of the complex mechanisms governing reactions in microemulsions and the impact of compartmentalization on final nanostructures.
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The better metal segregation obtained as concentration increases is also observed when the two reductions are slowing down, as shown in Figure 2. This figure shows the final nanostructures obtained for the pair Pt/Rh (vPt/vRh = 10/1 = 10), under the same synthetic conditions as used in Figure 1 to prepare Au/Pt nanoparticles. The better metal separation cannot be attributed to a larger reduction rate ratio, because in both cases the faster metal is 10 times faster than the slower one (vAu/vPt = 100/10 = 10). The better metal separation obtained for Pt/Rh pair is more evident at low concentration, where an alloy is obtained for Au/Pt and a core-shell structure for Pt/Rh (compare histograms when <c>= 2 in Figures 1 and 2). This means that, although the reduction rate ratio is similar, when the reduction rate of the faster metal slows down as in Pt, the other metal (Rh) is delayed even more. As a consequence, both reactions take place at different stages of the synthesis, resulting in better segregated structures.
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Figure 2.
Histograms show the number of particles with a given percentage of the faster reduction metal (Pt) in each layer at different concentrations. In all cases, 〈cR〉 = 10〈cPtCl62−〉, and cPtCl62−:RhCl63− is in 1:1 proportion. Reduction rates: vPt = 10%, vRh = 1% (vPt/vRh = 10); flexible film (f = 30, kex = 5). Scheme color: Pt and Rh are represented by blue and green bars, respectively. Lighter colors mean less mixture. The nanostructure is also shown by colored concentric spheres, keeping the same color pattern.
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3.2 Factors affecting metal distribution: reduction rate ratio
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The difference between the standard potentials of the two metal precursors is believed to be the most relevant factor to determine the kinetics and the resulting bimetallic arrangement [43]. As established in Eq. (2), the higher the difference between the standard potentials of the two metals, the higher the ratio between both reduction rates is. It results in the earlier reduction of the faster reduction metal, which builds up the core and becomes the seed for the subsequent deposition of the slower metal, which forms the surrounding shell. On the contrary, when the two reduction rates are almost similar, a mixed nanoalloy is expected. In spite of this argumentation was initially proposed for reactions in homogeneous media, and it does not take into account the confinement of reactants within micelles, it is frequently applied to explain results in microemulsion. As a rule, it is observed a tendency from nanoalloy to core-shell structure as difference in reduction potential is increased (see Table 1 in Ref. [44]). Previous simulation studies allow to clearly observe a better separation of the two metals as reduction rate ratio is larger (for a deeper discussion, see Ref. [28]).
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3.3 Factors affecting metal distribution: microemulsion composition
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To isolate the effect of microemulsion composition on nanoparticle structure, a particular pair of metals must be chosen and analyze if a change in the microemulsion composition leads to a different metal segregation. For example, Pt/Ru nanoparticles were obtained as nanoalloy, both for rigid (water/Brij-30/n-heptane [45]) and flexible films (water/Berol 050/isooctane 80 [46] or water/NP5-NP9/cyclohexane [47]). But in this couple, the small difference in reduction potentials leads to quite similar reduction rates, which hinder metal segregation, even with a slow intermicellar exchange rate. As a matter of fact, when couples with higher reduction rate ratio are studied (such as Au/Ag, Au/Pt, and Au/Pd), an increase in surfactant flexibility results in the expected transition from a core-shell to a nanoalloy. As an example, alloyed Au/Pt nanoparticles were prepared using a flexible film such as water/Tergitol 15-S-5/isooctane [17] or water/TritonX-100/cyclohexane [48]. On the contrary, rigid films (water/AOT/isooctane [39] and water/Brij 30/n-heptane [49]) lead to segregated structures. The simulation model also predicts this result, as shown in Figure 3, in which different Au/Pt (vAu/vPt = 10) arrangements were obtained by employing different values of surfactant film flexibilities. The ability of the microemulsion to minimize the difference between the reduction rates is clearly reflected in the progressive mixture of Au and Pt as increasing the intermicellar exchange rate (for a deeper discussion, see the following sections).
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Figure 3.
Number of particles with a given percentage of the faster reduction metal (Au) in each layer using three different microemulsion compositions (different f and kex parameters). 〈cAuCl4−〉 = 〈cPtCl62−〉 = 4; 〈cR〉 = 10〈cPtCl62−〉 reduction rates: vAu = 100%, vPt = 10%. Scheme color: Au and Pt are represented by red and blue bars, respectively. Lighter colors mean less mixture. Adapted with permission from Ref. [44].
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3.4 Kinetic study
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The results shown in previous figures were obtained under isolation conditions, that is, the reducing agent concentration is much higher than stoichiometry, so the change in R concentration during the course of the reaction is negligible. As a result, the metal reduction, which is a bimolecular reaction, appears to be first order, when the reaction media is homogeneous. In order to study how the confinement of reactants inside micelles would affect chemical kinetics, the depletion of the number of metal precursors M+ (M+ = AuCl4−, PtCl6−2−, RhCl63−) was monitored as the synthesis advances. The logarithmic plot of M+ concentration versus time is shown in Figure 4 using different initial reactant concentrations. Left and right columns show results for Au/Pt and Pt/Rh couples, respectively. Au, Pt, and Rh are represented by dashed, solid, and dashed-dotted lines, respectively. Figure 4A and B was obtained by simulating a flexible film and C and D a rigid one. At first sight, metal reductions obey first-order kinetics in both Au/Pt and Pt/Rh synthesis, as expected. Nevertheless, it is important to note that, with the exception of Rh, a time lag is required to reach the linear regime. Two points must be highlighted: First, the higher the concentration, the longer the time lag between the beginning of the synthesis and the achievement of the linear behavior. On the second hand, the time lag strongly depends on the intermicellar exchange rate, being longer as the exchange rate is slower (rigid film). Both factors (concentration and film flexibility) suggest that the rate-determining step is the intermicellar exchange rate at earlier reaction times, as explained as follows. The synthesis starts when the microemulsions containing the reactants are mixed. In order to be able to react, reactants must be located inside the same micelle. The reactants redistribution between micelles is dictated by the rate with which reactants can go through the channels communicating colliding micelles, that is, the intermicellar exchange rate. So, a slow exchange rate only allows the exchange of few reactants in each collision, which implies that more collisions are required to redistribute reactants and allow the reactants encounter. Therefore, a rigid film requires much longer lag times than a flexible one (compare Figure 4AwithB and CwithD, for any value of concentration). Apart from that, reactants redistribution is also affected by concentration, because the number of reactants which can traverse the intermicellar channel during an effective collision is restricted. Therefore, if concentration within micelle is large, more collisions (i.e., more time) are needed to make possible reactants redistribution. Finally, it is interesting to point out that this delay in reaching linear behavior disappears when a very slow chemical reduction takes place, as shown by Rh kinetics in right column of Figure 4 (see dashed-dotted lines), which is linear from the beginning, at any concentration value. This behavior can be taken as indication that the reduction rate is so slow (only a 1% of reactants give rise to products) that the limiting step is the reduction itself.
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Figure 4.
Plot of ln M+ (number of metal salt) against time (in Monte Carlo step, mcs) using different initial concentration c (metal salts/micelle). Solid, dashed, and dashed-dotted represent Au, Pt, and Rh, respectively. A and B shows results for a flexible surfactant film (kex = 5, f = 30) and C and D for a rigid one (kex = 1, f = 5). Au/Pt pair (vAu/vPt = 100/10 = 10) is represented in A and C and Pt/Rh pair (vPt/vRh = 10/1 = 10) in B and D. Stars indicate the half-life (red, blue, and green means Au, Pt and Rh, respectively).
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Summarizing, the time lag required to achieve linear behavior in Figure 4 reflects the time it takes for reactants to encounter. This time lag can be determinant of final metal segregation, because the inner layers of nanoparticle are building up during this stage.
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Pseudo-first-order rate constants, kobs, can be calculated from linear regime of the logarithmic plot as shown in Figure 4. The values of the pseudo-first-order rate constants are represented in Figure 5 as a function of concentration. One can observe that the slopes of Au reduction are always higher than the slopes of Pt, which in turn is faster that Rh, as expected. Classical chemical kinetics in a homogeneous reaction medium establishes that kobs in bimolecular reactions does not depend on precursors concentrations. This is the case for Pt and Rh, whose kobs values did not depend neither on the concentration nor on the intermicellar exchange rate. In contrast, kobs values of Au are strongly influenced by both factors. To explain this behavior, one have to take into account that the limiting step in Au chemical reduction is the intermicellar exchange [38, 50], because of the extremely fast Au reduction rate. One can observe that the dependence of kobs on concentration decreases as intermicellar exchange rate is faster, until reaching an almost constant value at very fast intermicellar exchange rate (see gray line in Figure 5), as expected. In comparison, Pt and Rh reductions are so slow that their rates are not limited by the exchange rate.
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Figure 5.
kobs (slopes of the linear parts from the plots in Figure 3) as a function of concentration for different microemulsion compositions and different metals. vAu = 100, vPt = 10, vRh = 1. Lines are only a guide to the eye.
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One can conclude from Figure 5 that intermicellar exchange rate exerts a different degree of influence depending on the reduction rate of the metal in comparison to the intermicellar exchange rate. This means that the compartmentalization of reaction medium takes part in chemical kinetics more or less depending on the metal nature. This different interplay between exchange rate and reduction rate has to be reflected in the metal segregation of final nanoparticle. It was proposed that if the intermicellar exchange rate can only modify the rate of metals whose reduction is very fast [38], such as Au, only bimetallic nanoparticle including Au could be prepared with different metal distributions as a function of microemulsion composition (intermicellar exchange rate) by a one-pot method (see Table 1 in Ref. [44]). To the best of our knowledge, only Au/Pt, Au/Ag, and Au/Pd have been synthesized in a different intrastructure by different authors. Thus, when a rigid film (such as provided by AOT) is used, Au-Pt nanoparticles are arranged in a core-shell distribution [39]. On the contrary, more flexible surfactants such as Brij30 [49], tergitol [17], or TritonX-100 [48] give rise to alloyed nanoparticles. In relation to Au/Ag, alloys were obtained with TritonX-100 [51] and C11E3 and C11E5 [52], but an enriched in Ag surface was observed when microemulsion contains AOT [53]. Finally, AOT was also used to obtain core-shell Au-Pd nanoparticles [54] and alloys with Pd-rich surface [55]. In contrast, true Au-Pd alloys [4] have been obtained with Brij30 and TritonX-100. With that in mind, it could be suggested that metal segregation in the nanoparticle can be modified by a change in the microemulsion composition only when one of the metals is Au or another very fast reduction rate metal. Nevertheless, in spite of the agreement between theoretical and experimental data, this assumption is based on the kinetic constants, which were calculated from the linear plot shown in Figure 4. It must be emphasized that the linear regime is not fulfilled at initial stages of the reaction, when the core is been building up. With the aim of studying the relevance of the non-linear behavior at the beginning of the synthesis, the half-life, defined as the time that it takes for the reactant concentration to decay to half of its initial value, was calculated for each case. Stars in Figure 4 show half-life under different synthesis conditions (Au, Pt, and Rh are represented by red, blue, and green stars, respectively). With the exception of Rh and Pt at very low concentration, half-life is usually smaller than the time needed to achieve the linear regime. As observed in Figure 4C and D, Au and Pt reductions in a rigid microemulsion and at high concentration have a half-life much earlier than linear plot. This means that not only the initial layers but also the middle ones are formed under a nonlinear regime. So, chemical reductions are still not a first-order process during the formation of a large part of the particle (for a deeper discussion on life time, see Ref. [38]).
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4. Conclusions
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The generalized belief according to which the difference in the reduction potentials determines the intrastructure in a bimetallic nanoparticle should be improved. We propose that there are three potentially limiting factors which restrict chemical kinetics of bimetallic nanoparticles prepared from microemulsions: chemical reduction rate itself, exchange rate of reactants between micelles, and reactants concentration. The specific combination of these three factors determines the reaction rate of each metal, which in turn determines the sequence of metals deposition and the resulting bimetallic arrangement.
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The kinetic study of Pt/M nanoparticles prepared via microemulsions under isolation conditions shows that chemical reductions are pseudo-first-order reactions, but not from the initial stages. At the beginning of the synthesis, the reactants encounter is dictated by the redistribution of reactants between micelles, which is controlled by the intermicellar exchange rate. As a result, the limiting step of faster reduction metals, such as Au, is the intermicellar exchange. On the contrary, microemulsion dynamics has a little effect if reduction rates are very slow (i.e., Rh). This means that compartmentalization of the reaction media has a different impact depending on the reduction rate of the particular metal. We are not referring only to the reduction rate of a metal in relation to the another metal in the pair but also how fast the reduction takes place in relation to the intermicellar exchange rate. Specifically, for a given reduction rates ratio and keeping fixed microemulsion composition and concentration, the fact that the two reactions were slow (as in Pt/Rh) leads to a better metal segregation than if both reactions are faster (as in Au/Pt). Therefore, with the exception of very slow metal reduction as Rh, intermicellar exchange rate drastically impacts on chemical kinetics, particularly at the beginning of the synthesis. This is not a minor matter, because it will be reflected in the composition of the core and middle layers of the resulting nanoparticle. So, the ability of microemulsion to manipulate the sequence of metal deposition, when the metal reductions are quite fast in relation to the intermicellar exchange rate, can be used to design the experiments to synthesize bimetallic particles with ad hoc nanoarrangements. This ability disappears when the two chemical reductions are slow, because of chemically controlled kinetics.
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In this paper, computer simulation has proved to be very useful tool to identify suitable synthesis parameters, which control metal segregation in a bimetallic nanoparticle. Further insights into the interplay between metal nature, exchange rate, and final bimetallic structure can be gained from kinetics studies.
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Acknowledgments
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This work was supported by MINECO, Spain (MAT2015-67458-P, co-financed with FERDER Funds), from the European Union’s H2020 research and innovation programme under grant agreement No. 646155 (INSPIRED) and from Xunta de Galicia (Programa REDES ED431D-2017/18). D.B. thanks for the postdoc grant from Xunta de Galicia, Spain (POS-A/2013/018).
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Conflict of interest
The authors declare no conflict of interest.
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Notes/thanks/other declarations
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This research is dedicated to Prof. Julio Casado Linarejos, who teached us the fundamentals of chemical kinetics.
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\n',keywords:"bimetallic nanoparticles, microemulsions, reduction rate, intermicellar exchange rate, nanocatalysts",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/63269.pdf",chapterXML:"https://mts.intechopen.com/source/xml/63269.xml",downloadPdfUrl:"/chapter/pdf-download/63269",previewPdfUrl:"/chapter/pdf-preview/63269",totalDownloads:377,totalViews:0,totalCrossrefCites:0,dateSubmitted:"May 10th 2018",dateReviewed:"July 27th 2018",datePrePublished:"November 5th 2018",datePublished:null,dateFinished:null,readingETA:"0",abstract:"Microemulsions are frequently used as nanoreactors for the synthesis of bimetallic nanoparticles. The ability to manipulate the metal distribution in bimetallic nanoparticles is essential for optimizing applications, and it requires a deeper understanding of how compartmentalization of reaction medium affects nanoparticle synthesis. A simulation model was developed to predict the atomic structure of bimetallic nanoparticles prepared via microemulsion in terms of metals employed and microemulsion composition. The model was successfully proved by comparing theoretical and experimental Au/Pt STEM profiles. On this basis, the model becomes a strong tool to further enhance our knowledge of the complex mechanisms governing reactions in microemulsions and its impact on final nanostructures. The purpose of this study is to perform a comprehensive kinetic analysis of coreduction of different couple of metals in the light of the interplay between three kinetic parameters: intermicellar exchange rate, chemical reduction rates of the two metals, and reactants concentration. The particular combination of these factors determines the reaction rate of each metal, which in turn determines the final metal arrangement.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/63269",risUrl:"/chapter/ris/63269",signatures:"Concha Tojo, David Buceta and M. Arturo López-Quintela",book:{id:"6830",title:"Microemulsion",subtitle:"a Chemical Nanoreactor",fullTitle:"Microemulsion - a Chemical Nanoreactor",slug:"microemulsion-a-chemical-nanoreactor",publishedDate:"September 18th 2019",bookSignature:"Juan C. Mejuto",coverURL:"https://cdn.intechopen.com/books/images_new/6830.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"192394",title:"Prof.",name:"Juan",middleName:"C.",surname:"Mejuto",slug:"juan-mejuto",fullName:"Juan Mejuto"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:null,sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. The model",level:"1"},{id:"sec_2_2",title:"2.1 Initial reactants concentration",level:"2"},{id:"sec_3_2",title:"2.2 Microemulsion dynamics and time unit",level:"2"},{id:"sec_4_2",title:"2.3 Metal characterization: reduction rate ratio",level:"2"},{id:"sec_4_3",title:"2.3.1 Au/Pt nanoparticles",level:"3"},{id:"sec_5_3",title:"2.3.2 Pt/Rh nanoparticles",level:"3"},{id:"sec_7_2",title:"2.4 Microemulsion characterization: intermicellar exchange criteria",level:"2"},{id:"sec_8_2",title:"2.5 Description of the metal distribution in the bimetallic nanoparticle",level:"2"},{id:"sec_10",title:"3. Results and discussion",level:"1"},{id:"sec_10_2",title:"3.1 Factors affecting metal distribution: initial reactants concentration",level:"2"},{id:"sec_11_2",title:"3.2 Factors affecting metal distribution: reduction rate ratio",level:"2"},{id:"sec_12_2",title:"3.3 Factors affecting metal distribution: microemulsion composition",level:"2"},{id:"sec_13_2",title:"3.4 Kinetic study",level:"2"},{id:"sec_15",title:"4. Conclusions",level:"1"},{id:"sec_16",title:"Acknowledgments",level:"1"},{id:"sec_19",title:"Conflict of interest",level:"1"},{id:"sec_16",title:"Notes/thanks/other declarations",level:"1"}],chapterReferences:[{id:"B1",body:'Boutonnet M, Kizling J, Stenius P, Maire G. The preparation of monodisperse colloidal metal particles from microemulsions. Colloids and Surfaces. 1982;5:209-225\n'},{id:"B2",body:'Sánchez-Dominguez M, Boutonnet M. Synthesis of nanostructured catalytic materials from microemulsions. Catalysts. 2016;6:4-8\n'},{id:"B3",body:'Heshmatpour F, Abazari R. 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Particle shape optimization by changing from an isotropic to an anisotropic nanostructure: Preparation of highly active and stable supported Pt catalysts in microemulsions. Nanoscale Research Letters. 2013;5:796-805\n'},{id:"B24",body:'Parapat RY, Parwoto V, Schwarze M, Zhang B, Su D-S, Schomäcker R. A new method to synthesize very active and stable supported metal Pt catalysts: Thermo-destabilization of microemulsions. Journal of Materials Chemistry. 2012;22:11605-11614\n'},{id:"B25",body:'König RYG, Schwarze M, Schomäcker R, Stubenrauch C. Catalytic activity of mono- and bi-metallic nanoparticles synthesized via microemulsions. Catalysts. 2014;4:256-275\n'},{id:"B26",body:'Tojo C, Blanco MC, López-Quintela MA. Preparation of nanoparticles in microemulsions: A Monte Carlo study of the influence of the synthesis variables. Langmuir. 1997;13:4527-4534\n'},{id:"B27",body:'Magno LM, Sigle W, Aken PAV, Angelescu DG, Stubenrauch C. Microemulsions as reaction media for the synthesis of bimetallic nanoparticles: Size and composition of particles. Chemistry of Materials. 2010;22:6263-6271\n'},{id:"B28",body:'Tojo C, de Dios M, López-Quintela MA. On the structure of bimetallic nanoparticles synthesized in microemulsions. Journal of Physical Chemistry C. 2009;113:19145-19154\n'},{id:"B29",body:'Stamenkovic VR, Mun BS, Arenz M, Mayrhofer KJ, Lucas CA, et al. Trends in electrocatalysis on extended and nanoscale Pt-bimetallic alloy surfaces. Nature Materials. 2007;6:241-247\n'},{id:"B30",body:'Shi J. On the synergetic catalytic effect in heterogeneous nanocomposite catalysts. Chemical Reviews. 2013;113:2139-2181\n'},{id:"B31",body:'Ferrando R, Jellinek J, Johnston RL. Nanoalloys: From theory to applications of alloy clusters and nanoparticles. Chemical Reviews. 2008;108:845-910\n'},{id:"B32",body:'Spanos I, Dideriksen K, Kirkensgaard JJK, Jelavic S, Arenz M. Structural disordering of de-alloyed Pt bimetallic nanocatalysts: The effect on oxygen reduction reaction activity and stability. Physical Chemistry Chemical Physics. 2015;17:28044-28053\n'},{id:"B33",body:'Zhang G-R, Zhao D, Feng Y-Y, Zhang B, Su DS, et al. Catalytic Pt-on-au nanostructures: Why Pt becomes more active on smaller au particles. ACS Nano. 2012;6:2226-2236\n'},{id:"B34",body:'Shao M, Peles A, Shoemaker K, Gummalla M, Njoki PN, et al. Enhanced oxygen reduction activity of platinum monolayer on gold nanoparticles. Journal of Physical Chemistry Letters. 2011;2:67-72\n'},{id:"B35",body:'Notar Francesco I, Fontaine-Vive F, Antoniotti S. Synergy in the catalytic activity of bimetallic nanoparticles and new synthetic methods for the preparation of fine chemicals. ChemCatChem. 2014;6:2784-2791\n'},{id:"B36",body:'Zhao L, Thomas JP, Heinig NF, Abd-Ellah M, Wang X, Leung KT. Au-Pt alloy nanocatalysts for electro-oxidation of methanol and their application for fast-response non-enzymatic alcohol sensing. Journal of Materials Chemistry C. 2014;2:2707-2714\n'},{id:"B37",body:'Yin Z, Ma D, Bao X. Emulsion-assisted synthesis of monodisperse binary metal nanoparticles. Chemical Communications. 2010;46:1344-1346\n'},{id:"B38",body:'Tojo C, Buceta D, López-Quintela MA. Bimetallic nanoparticles synthesized in microemulsions: A computer simulation study on relationship between kinetics and metal segregation. Journal of Colloid and Interface Science. 2018;510:152-161\n'},{id:"B39",body:'Wu M, Chen D, Huang T. Preparation of Au/Pt bimetallic nanoparticles in water-in-oil microemulsions. Chemistry of Materials. 2001;13:599-606\n'},{id:"B40",body:'Tojo C, Buceta D, López-Quintela MA. Understanding the metal distribution in core-shell nanoparticles prepared in micellar media. Nanoscale Research Letters. 2015;10:339-349\n'},{id:"B41",body:'Quintillán S, Tojo C, Blanco MC, López-Quintela MA. Effects of the intermicellar exchange on the size control of nanoparticles synthesized in microemulsions. Langmuir. 2001;17:7251-7254\n'},{id:"B42",body:'Buceta D, Tojo C, Vukmirovik M, Deepak FL, López-Quintela MA. Controlling bimetallic nanostructures by the microemulsion method with sub-nanometer resolution using a prediction model. Langmuir. 2015;31:7435-7439\n'},{id:"B43",body:'Feng J, Zhang C. Preparation of Cu-Ni alloy nanocrystallites in water-in-oil microemulsions. Journal of Colloid and Interface Science. 2006;293:414-420\n'},{id:"B44",body:'Tojo C, Buceta D, López-Quintela MA. On metal segregation of bimetallic nanocatalysts prepared by a one-pot method in microemulsions. Catalysts. 2017;7:1-17\n'},{id:"B45",body:'Solla-Gullón J, Vidal-Iglesias FJ, Montiel V, Aldaz A. Electrochemical characterization of platinum-ruthenium nanoparticles prepared by water-in-oil microemulsion. Electrochimica Acta. 2004;49:5079-5088\n'},{id:"B46",body:'Rojas S, García-García FJ, Jaeras S, Martínez-Huerta MV, García Fierro JL, Boutonnet M. Preparation of carbon supported Pt and PtRu nanoparticles from microemulsion. Applied Catalysis, A: General. 2005;285:24-35\n'},{id:"B47",body:'Liu Z, Lee JY, Han M, Chen W, Gan LM. Synthesis and characterization of PtRu/C catalysts from microemulsions and emulsions. Journal of Materials Chemistry. 2002;12:2453-2458\n'},{id:"B48",body:'Pal A. Gold–platinum alloy nanoparticles through water-in-oil microemulsion. Journal of Nanostructure in Chemistry. 2015;5:65-69\n'},{id:"B49",body:'Habrioux A, Vogel W, Guinel M, Guetaz L, Servat K, et al. Structural and electrochemical studies of Au-Pt nanoalloys. Physical Chemistry Chemical Physics. 2009;11:3573-3579\n'},{id:"B50",body:'Tojo C, de Dios M, Buceta D, López-Quintela MA. Cage-like effect in Au-Pt nanoparticle synthesis in microemulsions: A simulation study. Physical Chemistry Chemical Physics. 2014;16:19720-19731\n'},{id:"B51",body:'Pal A, Shah S, Devi S. Preparation of silver, gold and silver-gold bimetallic nanoparticles in w/o microemulsion containing triton X-100. Colloids and Surfaces, A: Physicochemical and Engineering Aspects. 2007;302:483-487\n'},{id:"B52",body:'Cheng J, Bordes R, Olsson E, Holmberg K. One-pot synthesis of porous gold nanoparticles by preparation of Ag/Au nanoparticles followed by dealloying. Colloids and Surfaces, A: Physicochemical and Engineering Aspects. 2013;436:823-829\n'},{id:"B53",body:'Chen D, Chen C. Formation and characterization of Au-Ag bimetallic nanoparticles in water-in-oil microemulsions. Journal of Materials Chemistry. 2002;12:1557-1562\n'},{id:"B54",body:'Wu M, Chen D, Huang T. Synthesis of au/Pd bimetallic nanoparticles in reverse micelles. Langmuir. 2001;17:3877-3883\n'},{id:"B55",body:'Simoes M, Baranton S, Coutanceau C. Electrooxidation of sodium borohydride at Pd, au, and PdxAu1−x carbon-supported nanocatalysts. Journal of Physical Chemistry C. 2009;113:13369-13376\n'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Concha Tojo",address:"ctojo@uvigo.es",affiliation:'
Physical Chemistry Department, University of Vigo, Spain
Laboratorio de Magnetismo y Nanotecnología, University of Santiago de Compostela, Spain
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IntechOpen books are indexed by the following abstracting and indexing services:
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BKCI is a part of Web of Science Core Collection (WoSCC) and the world’s leading citation index with multidisciplinary content from the top tier international and regional journals, conference proceedings, and books. The Book Citation Index includes over 104,500 editorially selected books, with 10,000 new books added each year. Containing more than 53.2 million cited references, coverage dates back from 2005 to present. The Book Citation Index is multidisciplinary, covering disciplines across the sciences, social sciences, and arts & humanities.
Produced by the Web Of Science group, BIOSIS Previews research database provides researchers with the most current sources of life sciences information, including journals, conferences, patents, books, review articles, and more. Researchers can also access multidisciplinary coverage via specialized indexing such as MeSH disease terms, CAS registry numbers, Sequence Databank Numbers and Major Concepts.
Produced by the Web Of Science group, Zoological Record is the world’s oldest continuing database of animal biology. It is considered the world’s leading taxonomic reference, and with coverage back to 1864, has long acted as the world’s unofficial register of animal names. The broad scope of coverage ranges from biodiversity and the environment to taxonomy and veterinary sciences.
Provides a simple way to search broadly for scholarly literature. Includes peer-reviewed papers, theses, books, abstracts and articles, from academic publishers, professsional societies, preprint repositories, universities and other scholarly organizations. Google Scholar sorts articles by weighing the full text of each article, the author, the publication in which the article appears, and how often the article has been cited in other scholarly literature, so that the most relevant results are returned on the first page.
Microsoft Academic is a project exploring how to assist human conducting scientific research by leveraging machine’s cognitive power in memory, computation, sensing, attention, and endurance. Re-launched in 2016, the tool features an entirely new data structure and search engine using semantic search technologies. The Academic Knowledge API offers information retrieval from the underlying database using REST endpoints for advanced research purposes.
The national library of the United Kingdom includes 150 million manuscripts, maps, newspapers, magazines, prints and drawings, music scores, and patents. Online catalogues, information and exhibitions can be found on its website. The library operates the world's largest document delivery service, providing millions of items a year to national and international customers.
The digital NSK portal is the central gathering place for the digital collections of the National and University Library (NSK) in Croatia. It was established in 2016 to provide access to the Library’s digital and digitized material collections regardless of storage location. The digital NSK portal enables a unified search of digitized material from the NSK Special Collections - books, visual material, maps and music material. From the end of 2019, all thematic portals are available independently: Digital Books, Digitized Manuscripts, Digitized Visual Materials, Digital Music Materials and Digitized Cartographic Materials (established in 2017). Currently available only in Croatian.
The official DOI (digital object identifier) link registration agency for scholarly and professional publications. Crossref operates a cross-publisher citation linking system that allows a researcher to click on a reference citation on one publisher’s platform and link directly to the cited content on another publisher’s platform, subject to the target publisher’s access control practices. This citation-linking network covers millions of articles and other content items from several hundred scholarly and professional publishers.
Dimensions is a next-generation linked research information system that makes it easier to find and access the most relevant information, analyze the academic and broader outcomes of research, and gather insights to inform future strategy. Dimensions delivers an array of search and discovery, analytical, and research management tools, all in a single platform. Developed in collaboration with over 100 leading research organizations around the world, it brings together over 128 million publications, grants, policy, data and metrics for the first time, enabling users to explore over 4 billion connections between them.
The primary aim of DOAB (Directory of Open Access Books) is to increase discoverability of Open Access books. Metadata will be harvestable in order to maximize dissemination, visibility and impact. Aggregators can integrate the records in their commercial services and libraries can integrate the directory into their online catalogues, helping scholars and students to discover the books.
OAPEN is dedicated to open access, peer-reviewed books. OAPEN operates two platforms, the OAPEN Library (www.oapen.org), a central repository for hosting and disseminating OA books, and the Directory of Open Access Books (DOAB, www.doabooks.org), a discovery service for OA books.
OpenAIRE aims at promoting and implementing the directives of the European Commission (EC) and the European Research Council on the promotion and funding of science and research. OpenAIRE supports the Open Access Mandate and the Open Research Data Pilot developed as part of the Horizon 2020 projects.
An integrated information service combining reference databases, subscription management, online journals, books and linking services. Widely used by libraries, schools, government institutions, medical institutions, corporations and others.
SFX® link resolver gives patrons and librarians a wealth of features that optimize management of and access to resources. It provides patrons with a direct route to electronic full-text records through OpenURL linking, delivers alternative links for further resource discovery, access to journals, and more. Released in 2001 as the first OpenURL resolver, SFX is continuously enhanced to support the newest industry developments and meet the evolving needs of customers. The records include a mix of scholarly material – primarily articles and e-books – but also conference proceedings, newspaper articles, and more.
A non-profit, membership, computer library service and research organization dedicated to the public purposes of furthering access to the world's information and reducing information costs. More than 41,555 libraries in 112 countries and territories around the world use OCLC services to locate, acquire, catalogue, lend and preserve library materials.
The world’s largest collection of open access research papers. CORE's mission is to aggregate all open access research outputs from repositories and journals worldwide and make them available to the public. In this way CORE facilitates free unrestricted access to research for all.
Perlego is a digital online library focusing on the delivery of academic, professional and non-fiction eBooks. It is a subscription-based service that offers users unlimited access to these texts for the duration of their subscription, however IntechOpen content integrated on the platform will always be available for free. They have been billed as “the Spotify for Textbooks” by the Evening Standard. Perlego is based in London but is available to users worldwide.
MyScienceWork provides a suite of data-driven solutions for research institutions, scientific publishers and private-sector R&D companies. MyScienceWork's comprehensive database includes more than 90 million scientific publications and 12 million patents.
CNKI (China National Knowledge Infrastructure) is a key national information construction project under the lead of Tsinghua University, and supported by PRC Ministry of Education, PRC Ministry of Science, Propaganda Department of the Communist Party of China and PRC General Administration of Press and Publication. CNKI has built a comprehensive China Integrated Knowledge Resources System, including journals, doctoral dissertations, masters' theses, proceedings, newspapers, yearbooks, statistical yearbooks, ebooks, patents, standards and so on. CNKI keeps integrating new contents and developing new products in 2 aspects: full-text academic resources, software on digitization and knowledge management. Began with academic journals, CNKI has become the largest and mostly-used academic online library in China.
As one of the largest digital content platform in China,independently developed by CNPIEC, CNPeReading positions herself as “One Platform,Vast Content, Global Services”. Through their new cooperation model and service philosophy, CNPeReading provides integrated promotion and marketing solutionsfor upstream publishers, one-stop, triune, recommendation, online reading and management servicesfor downstream institutions & libraries.
ERIC (Education Resources Information Center), sponsored by the Institute of Education Sciences (IES) of the U.S. Department of Education, provides access to education literature to support the use of educational research and information to improve practice in learning, teaching, educational decision-making, and research. The ERIC website is available to the public for searching more than one million citations going back to 1966.
The ACM Digital Library is a research, discovery and networking platform containing: The Full-Text Collection of all ACM publications, including journals, conference proceedings, technical magazines, newsletters and books. A collection of curated and hosted full-text publications from select publishers.
BASE (Bielefeld Academic Search Engine) is one of the world's most voluminous search sengines especially for academic web resources, e.g. journal articles, preprints, digital collections, images / videos or research data. BASE facilitates effective and targeted searches and retrieves high quality, academically relevant results. Other than search engines like Google or Bing BASE searches the deep web as well. The sources which are included in BASE are intellectually selected (by people from the BASE team) and reviewed. That's why data garbage and spam do not occur.
Zentralblatt MATH (zbMATH) is the world’s most comprehensive and longest-running abstracting and reviewing service in pure and applied mathematics. It is edited by the European Mathematical Society (EMS), the Heidelberg Academy of Sciences and Humanities and FIZ Karlsruhe. zbMATH provides easy access to bibliographic data, reviews and abstracts from all areas of pure mathematics as well as applications, in particular to natural sciences, computer science, economics and engineering. It also covers history and philosophy of mathematics and university education. All entries are classified according to the Mathematics Subject Classification Scheme (MSC 2020) and are equipped with keywords in order to characterize their particular content.
IDEAS is the largest bibliographic database dedicated to Economics and available freely on the Internet. Based on RePEc, it indexes over 3,100,000 items of research, including over 2,900,000 that can be downloaded in full text. RePEc (Research Papers in Economics) is a large volunteer effort to enhance the free dissemination of research in Economics which includes bibliographic metadata from over 2,000 participating archives, including all the major publishers and research outlets. IDEAS is just one of several services that use RePEc data.
As the authoritative source for chemical names, structures and CAS Registry Numbers®, the CAS substance collection, CAS REGISTRY®, serves as a universal standard for chemists worldwide. Covering advances in chemistry and related sciences over the last 150 years, the CAS content collection empowers researchers, business leaders, and information professionals around the world with immediate access to the reliable information they need to fuel innovation.
BKCI is a part of Web of Science Core Collection (WoSCC) and the world’s leading citation index with multidisciplinary content from the top tier international and regional journals, conference proceedings, and books. The Book Citation Index includes over 104,500 editorially selected books, with 10,000 new books added each year. Containing more than 53.2 million cited references, coverage dates back from 2005 to present. The Book Citation Index is multidisciplinary, covering disciplines across the sciences, social sciences, and arts & humanities.
Produced by the Web Of Science group, BIOSIS Previews research database provides researchers with the most current sources of life sciences information, including journals, conferences, patents, books, review articles, and more. Researchers can also access multidisciplinary coverage via specialized indexing such as MeSH disease terms, CAS registry numbers, Sequence Databank Numbers and Major Concepts.
Produced by the Web Of Science group, Zoological Record is the world’s oldest continuing database of animal biology. It is considered the world’s leading taxonomic reference, and with coverage back to 1864, has long acted as the world’s unofficial register of animal names. The broad scope of coverage ranges from biodiversity and the environment to taxonomy and veterinary sciences.
Provides a simple way to search broadly for scholarly literature. Includes peer-reviewed papers, theses, books, abstracts and articles, from academic publishers, professsional societies, preprint repositories, universities and other scholarly organizations. Google Scholar sorts articles by weighing the full text of each article, the author, the publication in which the article appears, and how often the article has been cited in other scholarly literature, so that the most relevant results are returned on the first page.
Microsoft Academic is a project exploring how to assist human conducting scientific research by leveraging machine’s cognitive power in memory, computation, sensing, attention, and endurance. Re-launched in 2016, the tool features an entirely new data structure and search engine using semantic search technologies. The Academic Knowledge API offers information retrieval from the underlying database using REST endpoints for advanced research purposes.
The national library of the United Kingdom includes 150 million manuscripts, maps, newspapers, magazines, prints and drawings, music scores, and patents. Online catalogues, information and exhibitions can be found on its website. The library operates the world's largest document delivery service, providing millions of items a year to national and international customers.
The digital NSK portal is the central gathering place for the digital collections of the National and University Library (NSK) in Croatia. It was established in 2016 to provide access to the Library’s digital and digitized material collections regardless of storage location. The digital NSK portal enables a unified search of digitized material from the NSK Special Collections - books, visual material, maps and music material. From the end of 2019, all thematic portals are available independently: Digital Books, Digitized Manuscripts, Digitized Visual Materials, Digital Music Materials and Digitized Cartographic Materials (established in 2017). Currently available only in Croatian.
The official DOI (digital object identifier) link registration agency for scholarly and professional publications. Crossref operates a cross-publisher citation linking system that allows a researcher to click on a reference citation on one publisher’s platform and link directly to the cited content on another publisher’s platform, subject to the target publisher’s access control practices. This citation-linking network covers millions of articles and other content items from several hundred scholarly and professional publishers.
Dimensions is a next-generation linked research information system that makes it easier to find and access the most relevant information, analyze the academic and broader outcomes of research, and gather insights to inform future strategy. Dimensions delivers an array of search and discovery, analytical, and research management tools, all in a single platform. Developed in collaboration with over 100 leading research organizations around the world, it brings together over 128 million publications, grants, policy, data and metrics for the first time, enabling users to explore over 4 billion connections between them.
The primary aim of DOAB (Directory of Open Access Books) is to increase discoverability of Open Access books. Metadata will be harvestable in order to maximize dissemination, visibility and impact. Aggregators can integrate the records in their commercial services and libraries can integrate the directory into their online catalogues, helping scholars and students to discover the books.
OAPEN is dedicated to open access, peer-reviewed books. OAPEN operates two platforms, the OAPEN Library (www.oapen.org), a central repository for hosting and disseminating OA books, and the Directory of Open Access Books (DOAB, www.doabooks.org), a discovery service for OA books.
OpenAIRE aims at promoting and implementing the directives of the European Commission (EC) and the European Research Council on the promotion and funding of science and research. OpenAIRE supports the Open Access Mandate and the Open Research Data Pilot developed as part of the Horizon 2020 projects.
An integrated information service combining reference databases, subscription management, online journals, books and linking services. Widely used by libraries, schools, government institutions, medical institutions, corporations and others.
SFX® link resolver gives patrons and librarians a wealth of features that optimize management of and access to resources. It provides patrons with a direct route to electronic full-text records through OpenURL linking, delivers alternative links for further resource discovery, access to journals, and more. Released in 2001 as the first OpenURL resolver, SFX is continuously enhanced to support the newest industry developments and meet the evolving needs of customers. The records include a mix of scholarly material – primarily articles and e-books – but also conference proceedings, newspaper articles, and more.
A non-profit, membership, computer library service and research organization dedicated to the public purposes of furthering access to the world's information and reducing information costs. More than 41,555 libraries in 112 countries and territories around the world use OCLC services to locate, acquire, catalogue, lend and preserve library materials.
The world’s largest collection of open access research papers. CORE's mission is to aggregate all open access research outputs from repositories and journals worldwide and make them available to the public. In this way CORE facilitates free unrestricted access to research for all.
Perlego is a digital online library focusing on the delivery of academic, professional and non-fiction eBooks. It is a subscription-based service that offers users unlimited access to these texts for the duration of their subscription, however IntechOpen content integrated on the platform will always be available for free. They have been billed as “the Spotify for Textbooks” by the Evening Standard. Perlego is based in London but is available to users worldwide.
MyScienceWork provides a suite of data-driven solutions for research institutions, scientific publishers and private-sector R&D companies. MyScienceWork's comprehensive database includes more than 90 million scientific publications and 12 million patents.
CNKI (China National Knowledge Infrastructure) is a key national information construction project under the lead of Tsinghua University, and supported by PRC Ministry of Education, PRC Ministry of Science, Propaganda Department of the Communist Party of China and PRC General Administration of Press and Publication. CNKI has built a comprehensive China Integrated Knowledge Resources System, including journals, doctoral dissertations, masters' theses, proceedings, newspapers, yearbooks, statistical yearbooks, ebooks, patents, standards and so on. CNKI keeps integrating new contents and developing new products in 2 aspects: full-text academic resources, software on digitization and knowledge management. Began with academic journals, CNKI has become the largest and mostly-used academic online library in China.
As one of the largest digital content platform in China,independently developed by CNPIEC, CNPeReading positions herself as “One Platform,Vast Content, Global Services”. Through their new cooperation model and service philosophy, CNPeReading provides integrated promotion and marketing solutionsfor upstream publishers, one-stop, triune, recommendation, online reading and management servicesfor downstream institutions & libraries.
ERIC (Education Resources Information Center), sponsored by the Institute of Education Sciences (IES) of the U.S. Department of Education, provides access to education literature to support the use of educational research and information to improve practice in learning, teaching, educational decision-making, and research. The ERIC website is available to the public for searching more than one million citations going back to 1966.
The ACM Digital Library is a research, discovery and networking platform containing: The Full-Text Collection of all ACM publications, including journals, conference proceedings, technical magazines, newsletters and books. A collection of curated and hosted full-text publications from select publishers.
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