Dr. Pletser’s experience includes 30 years of working with the European Space Agency as a Senior Physicist/Engineer and coordinating their parabolic flight campaigns, and he is the Guinness World Record holder for the most number of aircraft flown (12) in parabolas, personally logging more than 7,300 parabolas.
\\n\\n
Seeing the 5,000th book published makes us at the same time proud, happy, humble, and grateful. This is a great opportunity to stop and celebrate what we have done so far, but is also an opportunity to engage even more, grow, and succeed. It wouldn't be possible to get here without the synergy of team members’ hard work and authors and editors who devote time and their expertise into Open Access book publishing with us.
\\n\\n
Over these years, we have gone from pioneering the scientific Open Access book publishing field to being the world’s largest Open Access book publisher. Nonetheless, our vision has remained the same: to meet the challenges of making relevant knowledge available to the worldwide community under the Open Access model.
\\n\\n
We are excited about the present, and we look forward to sharing many more successes in the future.
\\n\\n
Thank you all for being part of the journey. 5,000 times thank you!
\\n\\n
Now with 5,000 titles available Open Access, which one will you read next?
Preparation of Space Experiments edited by international leading expert Dr. Vladimir Pletser, Director of Space Training Operations at Blue Abyss is the 5,000th Open Access book published by IntechOpen and our milestone publication!
\n\n
"This book presents some of the current trends in space microgravity research. The eleven chapters introduce various facets of space research in physical sciences, human physiology and technology developed using the microgravity environment not only to improve our fundamental understanding in these domains but also to adapt this new knowledge for application on earth." says the editor. Listen what else Dr. Pletser has to say...
\n\n\n\n
Dr. Pletser’s experience includes 30 years of working with the European Space Agency as a Senior Physicist/Engineer and coordinating their parabolic flight campaigns, and he is the Guinness World Record holder for the most number of aircraft flown (12) in parabolas, personally logging more than 7,300 parabolas.
\n\n
Seeing the 5,000th book published makes us at the same time proud, happy, humble, and grateful. This is a great opportunity to stop and celebrate what we have done so far, but is also an opportunity to engage even more, grow, and succeed. It wouldn't be possible to get here without the synergy of team members’ hard work and authors and editors who devote time and their expertise into Open Access book publishing with us.
\n\n
Over these years, we have gone from pioneering the scientific Open Access book publishing field to being the world’s largest Open Access book publisher. Nonetheless, our vision has remained the same: to meet the challenges of making relevant knowledge available to the worldwide community under the Open Access model.
\n\n
We are excited about the present, and we look forward to sharing many more successes in the future.
\n\n
Thank you all for being part of the journey. 5,000 times thank you!
\n\n
Now with 5,000 titles available Open Access, which one will you read next?
\n'}],latestNews:[{slug:"stanford-university-identifies-top-2-scientists-over-1-000-are-intechopen-authors-and-editors-20210122",title:"Stanford University Identifies Top 2% Scientists, Over 1,000 are IntechOpen Authors and Editors"},{slug:"intechopen-authors-included-in-the-highly-cited-researchers-list-for-2020-20210121",title:"IntechOpen Authors Included in the Highly Cited Researchers List for 2020"},{slug:"intechopen-maintains-position-as-the-world-s-largest-oa-book-publisher-20201218",title:"IntechOpen Maintains Position as the World’s Largest OA Book Publisher"},{slug:"all-intechopen-books-available-on-perlego-20201215",title:"All IntechOpen Books Available on Perlego"},{slug:"oiv-awards-recognizes-intechopen-s-editors-20201127",title:"OIV Awards Recognizes IntechOpen's Editors"},{slug:"intechopen-joins-crossref-s-initiative-for-open-abstracts-i4oa-to-boost-the-discovery-of-research-20201005",title:"IntechOpen joins Crossref's Initiative for Open Abstracts (I4OA) to Boost the Discovery of Research"},{slug:"intechopen-hits-milestone-5-000-open-access-books-published-20200908",title:"IntechOpen hits milestone: 5,000 Open Access books published!"},{slug:"intechopen-books-hosted-on-the-mathworks-book-program-20200819",title:"IntechOpen Books Hosted on the MathWorks Book Program"}]},book:{item:{type:"book",id:"2529",leadTitle:null,fullTitle:"State of the Art of Therapeutic Endocrinology",title:"State of the Art of Therapeutic Endocrinology",subtitle:null,reviewType:"peer-reviewed",abstract:'During the last two decades, evidence of increasing trends of several endocrine-related disorders has been strengthened. 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He has expertise in shotgun proteomics analysis, reversed-phase chromatography and label-free comparative proteomics\napproaches. Dr. Magdeldin has published outstanding articles on aquaporin research using proteomics technology. He also created the outstanding “All and\nNone” methodology for analyzing large-throughput proteomics data published\nin a highly respected proteomics journal. He currently serves as a guest editor,\nassociate editor and peer reviewer for several international journals. 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He has been recruited as a quality and laboratory expert for seminars and professional laboratory meetings throughout Europe, Africa, and South America.\r\n23+ years of experience in the medical laboratory, having held key scientific leadership roles:\r\n13+ years as a senior researcher\r\n8+ years as a consultant of a metrology laboratory based on ISO/IEC 17025 specifications and related standards\r\n17+ years as a consultant and auditor of quality management systems based on ISO 9001, ISO/IEC 17025, and ISO 15189 standards\r\n16+ years as a quality manager in the Portuguese Institute of Blood and Transplantation, including national coordination over 6+ years\r\n6+ years as a teacher of quality assurance\r\nDr. Pereira is the author of several peer-review scientific articles, indexed book chapters and indexed books' Editor. 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This requires extensive analysis of developing trends in scientific research in order to offer our readers relevant content. Creating the book catalogue is also based on keeping track of the most read, downloaded and highly cited chapters and books and relaunching similar topics. I am also responsible for consulting with our Scientific Advisors on which book topics to add to our catalogue and sending possible book proposal topics to them for evaluation. Once the catalogue is complete, I contact leading researchers in their respective fields and ask them to become possible Academic Editors for each book project. Once an editor is appointed, I prepare all necessary information required for them to begin their work, as well as guide them through the editorship process. I also assist editors in inviting suitable authors to contribute to a specific book project and each year, I identify and invite exceptional editors to join IntechOpen as Scientific Advisors. 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\n
1. Introduction
\n
Nanoindentation [1], relatively simple and effective, has already been used as a standard technique for evaluating mechanical properties of thin films [2, 3, 4, 5, 6, 7]. In the recent years, a number of scientists have focused on thin films with defects through simulations and experiment [8, 9, 10, 11]. Yu has analyzed the effects of nanocavity on nanoindentation, which is one kind of defect [12]. Surface roughness, grouped by the pits and steps, has already been a popular topic, and lots of nanoindentation simulations on a step have been studied [13, 14, 15, 16, 17, 18, 19, 20]. It is well-known that the surface pits are very common in polycrystalline surfaces on microchips or microelectromechanical systems (MEMS). Therefore, it is necessary and significant to observe the nanoindentation on the pitted surface. Ni et al. [21] have compared nanoindentation of Al thin film with and without surface defects by multiscale simulation, and Zhang et al. [22] have probed the delay effect of dislocation nucleation in nanoindentation due to the surface pit defect. However, the distance effect of the pit and the size effect on elastic-plastic transition, which is especially important to thin film performance in microchips and MEMS, have not been taken into account yet. Now, this chapter is further to study and represent the distance effect [23] and the size effect of the pit [24] on nanohardness by quasi-continuum (QC) method [25], which is a relatively effective way to investigate large-scale model, where the molecular dynamics (MD) is mostly limited by the model scale.
\n
\n
\n
2. Distance effect of surface pit defect
\n
\n
2.1 Methodology
\n
The quasi-continuum (QC) method [26] is an effective mixed continuum and atomistic approach for simulating the mechanical response, especially in large-scale materials. The Ercolessi-Adams potential, which is one of the EAM potentials [27, 28, 29, 30], is used in this QC method, in order to describe the atomistic behavior. The parameters for Al in this potential are as shown in Table 1.
\n
\n
\n
\n\n
\n
Content
\n
Value
\n
\n\n\n
\n
Crystallographic lattice (a1)
\n
0.4032 nm
\n
\n
\n
Atomic lattice spacing in [1 1 1] direction (d0)
\n
0.2328 nm
\n
\n
\n
Atomic spacing in \n\n\n\n\n1\n¯\n\n1\n\n0\n\n\n\n direction (h0)
(1 1 1) surface energy γ111 is 0.869 J/m2, which is comparable with the experimental values of 1.14–1.20 J/m2 [31].
The experimental values extrapolated to T = 0 K are C11 = 118.0 GPa, C12 = 62.4 GPa, and C44 = 32.5 GPa [27].
\n
The schematic illustration of nanoindentation model with a pit defect and its unit cell model of Al in the selected directions is as shown in Figure 1, where the width of the rigid rectangular indenter is 0.932 nm (four times the lattice constant of Al in [1 1 1] direction (d0)). Such indenter width is chosen based on the simulation example “Nano-Indentation by a Square Punch” in QC tutorial document [32] and others’ works [21, 22]. It is convenient to simulate and analyze that if the indenter shape is set rectangular, result from that the boundary of energy field (displacement field) and the distance between the pit and the indenter will not changed during the indenter being driven down into the \n\n\n\n\n1\n¯\n\n10\n\n\n\n surface in this simulation, and that is exactly necessary to probe the distance effect of the pit. The width D and depth H of the pit in the model are 0.688 and 0.730 nm, respectively. Such pit size is chosen relatively moderate and proper, more sensitive to the distance effect based on our previous works [21, 22] and some pre-simulations. The thickness of this model in the out-of-plane direction is 0.4938 nm, which equals to the minimal repeat size applying the periodic boundary condition. Fifteen different d (defined as the adjacent distance between the pit and indenter) have been calculated in this chapter, respectively, 1d0, 2d0, 3d0, 4d0, 5d0, 6d0, 7d0, 8d0, 9d0, 10d0, 11d0, 12d0, 13d0, 17d0, and 21d0, in order to make a more comprehensive investigation.
\n
Figure 1.
The schematic illustration of nanoindentation model with a pit defect and its unit cell model of Al in the selected directions, where the unusual shapes in local region are not finite elements, they are just the schematic of its specific region that one corresponding representative atom belongs to.
\n
The parameter “PROXFACT” in QC method is applied to judge the range of nonlocal effects. The repatom is made nonlocal when any element is in its range of PROXFACT*rcut, where rcut is defined as the atomistic potential cutoff radius. Nonlocality is triggered if \n\n\nmax\n\na\n,\nb\n;\nk\n\n\n\n\n\nλ\nk\na\n\n−\n\nλ\nk\nb\n\n\n\n>\nepscr\n\n (k = 1, 2, 3), where \n\n\nλ\nk\na\n\n\n and \n\n\nλ\nk\nb\n\n\n are the eigenvalues of right Cauchy-Green deformation tensor C in two elements a and b, and the factor “epscr” is applied to judge whether a repatom has to be made nonlocal because of the significant variations in the deformation gradients around the repatom.
\n
For normal atomistic modeling standards, the dimensions of this simulation thin film is quite large with approximately 1.3 million atoms or 4 million degrees of freedom (as shown 0.1 μm in height and 0.2 μm in width in Figure 1). Fortunately, QC method applies the molecular dynamics model at the intense deformation region and a finite element model elsewhere in order to reduce the degrees of freedom without losing atomistic details, where only 4000 atoms or 12,000 degrees of freedom have to be treated in this model by comparison, and can be easily finished in a few days through personal computer.
\n
\n
\n
2.2 Results
\n
\n
2.2.1 Nanoindentation without defect
\n
Nanoindentation without defect is necessary to be studied for comparison, and the load-displacement curve of the nanoindentation on a defect-free surface is shown in Figure 2, where load (N/m) is presented as per unit length of indenter in the out-of-plane direction. It can be easily found out that the load curve gradually increases in the loading process (OA segment), indicating the elastic stage of thin films. The load first reaches the maximum value of 15.14 N/m at the load step 0.48 nm (point A) and then suddenly drops to the minimum value of 7.67 N/m at point B.
\n
Figure 2.
Load-displacement curves for nanoindentation on Al film without surface pit.
\n
To find out the reason of such abrupt load decline in AB segment, the atoms structure and out-of-plane displacements have been probed and shown in Figure 3, where the step of 0.48 and 0.50 nm is, respectively, corresponding to the point A and point B in Figure 2.
\n
Figure 3.
Snapshot of atoms under indenter and corresponding out-of-plane displacement plot, where UZ is atom displacement at out-of-plane. (1) point A in Figure 2 (dislocation nucleation); (2) point B in Figure 2 (dislocation emission).
\n
Through Figure 3, we can make a conclusion here that the load reaches the critical value for dislocation emission at point A, which indicates the onset of the plastic stage. After that two Shockley partial dislocations are emitted at point B. Therefore the nanohardness of Al thin film without defect is 16.24 GPa, calculated by equation [33]: \n\nH\n=\n\n\nP\nmax\n\nA\n\n\n, where Pmax is the maximum value of load and A is the contact area of the indenter.
\n
Due to the indenter width 0.932 nm in this simulation, the yield load is obtained approximately 15.14 N/m, which is smaller than 24.7 N/m acquired by Tadmor and Miller [31] with the indenter width 2.5 nm. It is reasonable that the paper [34] shows that as the indenter width decreases, the yield load would decline because of the requirement decline of the necessary strain energy.
\n
\n
\n
2.2.2 Distance effect of the surface pit
\n
Figure 4 shows the nanohardness with various distances cases of the surface pit defects. Compared to the defect-free situation shown as a red horizontal, it indicates that the nanohardness of pitted surface has been declined. That is because a discontinuity at the boundary and the structure may lead to the reduction of stain energy storage when indenting. Additionally, when the adjacent distance between the pit and indenter (d) increases, the nanohardness increases in a wave that goes up in a period of three atoms (donated by circle in Figure 4) and finally tends to the case of nanoindentation on a defect-free surface.
\n
Figure 4.
Nanohardness vs. distance of adjacent boundary between the pit and indenter.
\n
To make a further probe, it is well-known that many physical properties mostly depend on the stacking patterns of atoms, such as cleavage, electronic band structure, and optical transparency [35]. Based on this simulation, the periodic arrangement of atoms “ABCABC” on {1 1 1} atomic close-packed planes of face-centered cubic metal (the illustration as shown in Figure 4) is exactly corresponding to increasing distances d on [1 1 1] direction. That is to say, when the pit moves each atom in the [1 1 1] direction away from the indenter, the strain energy at the pit surface on the {1 1 1} stacking fault energies (SFE) changes because of the proximity of the pit [36]. Consequently, such wave pattern associated with a cycle of three atoms is closely related to the crystal structure of periodic atom arrangement on {1 1 1} atomic close-packed planes of FCC metal.
\n
A further discussion has been made in order to figure out the spatial extent of surface pit influence on nanohardness. It can be found out from Figure 4 that when the distance between the pit and indenter increases, the nanohardness gradually close to the nanohardness of defect-free case (16.24 GPa). If we set 1.5% to determine whether the nanohardness influence exists, it can be found out that when the adjacent distance (d) goes 16 atomic spacing far away from the indenter, there is almost no effect on nanohardness (as shown in Figure 4). Moreover, it can be predicted that each material has its critical value of such spatial extent of surface pit influence on nanohardness, which might have great significance to the size design of thin film in microchips without obvious reduction of the hardness.
\n
However, it can be easily found out that the first three distances cases, respectively, d = 1d0, d = 2d0, and d = 3d0, do not match such wave pattern well. Atomic structure and corresponding strain distribution of these three cases have been further carried out to explain such unusual phenomenon.
\n
Von Mises strain distribution and a strain comparison before and after the notch propagation in the distance cases of, respectively, 1d0, 2d0, and 3d0, are shown in Figure 5. It can be easily found out that a notch formed at the left side of surface pit in the distance cases of 1d0 and 2d0, which actually induces serious damage to the structure of materials and severe strain concentration (as shown in Figure 5A–D), while it does not if the distance d equals 3d0 (as shown in Figure 5E and F). That is to say, due to the great reduction of the nanohardness in the cases of 1d0 and 2d0, the first three distance cases in nanohardness curve as shown in Figure 4 will not match the wave pattern that goes up in a period of three atoms.
\n
Figure 5.
Von Mises strain distribution of notch propagation. (A) d = 1d0 at the load step of the indenter 0.38 nm; (B) d = 1d0 at the load step of the indenter 0.4 nm; (C) d = 2d0 at the load step of the indenter 0.44 nm; (D) d = 2d0 at the load step of the indenter 0.46 nm; (E) d = 3d0 at the load step of the indenter 0.46 nm; (F) d = 3d0 at the load step of the indenter 0.48 nm.
\n
\n
\n
2.2.3 Critical load for dislocation emission with initial surface pit
\n
As is known to all that the pit influences the nanohardness is actually through the way of affecting nucleation and emission of the dislocation. It is necessary and significant to make a further probe on the critical load for elastic-to-plastic transition in the case of nanoindentation on the pitted surface according to the formula of defect-free model, where the formula to calculate the critical load for dislocation emission is carried out by Tadmor [31], shown as Eq. (1):
where Pcr is the critical load of dislocation emission, h is the depth of dislocation dipole emitted down beneath the indenter, a is the half width of indenter, γ111 is the (1 1 1) surface energy of Al single crystal, and k is the slope of the load-displacement curve during the elastic section.
\n
The critical load calculated by the simulation results of QC method and by Eq. (1) of dislocation theory has been displayed, respectively, as “QC data” and “theory load” in Table 2. It is necessary to note that the simulation data in the case of 1d0 and 2d0 is not suitable to be taken into account because of the notch propagation. The differential of the critical data between QC method and dislocation theory is fluctuant as the distance (d) changes. Based on the result that the nanohardness goes up in a period of three atoms, the critical load for elastic-to-plastic is also in such periodicity. Thus, the correction form (set as Δ) might be reasonably defined as the following:
\n
\n\nΔ\n=\nA\n\nd\n\n+\nB\n⋅\nSin\n\nd\n\n\nE2
\n
\n
\n
\n
\n
\n\n
\n
Distance (d0)
\n
QC data (N/m)
\n
Theory load (N/m)
\n
Data difference (N/m)
\n
\n\n\n
\n
3
\n
14.28
\n
18.02
\n
3.75
\n
\n
\n
4
\n
14.46
\n
17.29
\n
2.83
\n
\n
\n
5
\n
14.48
\n
17.88
\n
3.39
\n
\n
\n
6
\n
14.24
\n
17.41
\n
3.15
\n
\n
\n
7
\n
14.86
\n
17.96
\n
3.14
\n
\n
\n
8
\n
14.85
\n
17.65
\n
2.83
\n
\n
\n
9
\n
14.38
\n
17.92
\n
3.07
\n
\n
\n
10
\n
14.87
\n
17.87
\n
3.49
\n
\n
\n
11
\n
14.86
\n
18.03
\n
3.16
\n
\n
\n
12
\n
14.49
\n
17.56
\n
2.70
\n
\n
\n
13
\n
14.70
\n
17.99
\n
3.50
\n
\n
\n
17
\n
15.06
\n
18.04
\n
3.34
\n
\n
\n
21
\n
15.09
\n
18.17
\n
3.11
\n
\n\n
Table 2.
The comparison of critical load between QC method and dislocation theory.
\n
where A(d) is the hardness reduction due to the surface pit and B·Sin(d) is specially set for the periodic arrangement of atoms. It is well recognized that the critical load of elastic-to-plastic transition will decrease [37], when the pit size (D, H as shown in Figure 1) increases. We use a dimensionless factor \n\n\nD\n\na\n1\n\n\n⋅\n\nH\n\na\n1\n\n\n\n (dividing by the crystallographic lattice constant) to express the size influence of the pit, which has already been demonstrated reasonable in published article [24]. If the distance between the indenter and the pit is infinitely large, the influence on nanohardness can be almost ignored, and if the pit size increases, the rate of nanohardness change decreases with the distance variation. According to the function property and calculation formula designed by Tadmor [31], we take the form of \n\nln\n\n\n1\n+\n\n\n\n\nd\n0\n\nd\n\n\n\n\n\nd\n0\n\nD\n\n⋅\n\n\nh\n0\n\nH\n\n\n\n\n\n\n to express the distance effect of surface pit, considering that it is relevantly reasonable. Moreover, the affection of surface pit is closely due to the material property such as Burgers vector \n\n\nb\n→\n\n\n, shear modulus μ, and Poisson ν. It is reasonable to apply \n\n\nμb\n\n4\nπ\n\n\n1\n−\nν\n\n\n\n\n\n to express the influence of material property based on Eq. (1). In addition, the atomic periodical arrangement is actually three atoms “ABCABC” on {1 1 1} atomic close-packed planes of FCC metal. Namely, a form of \n\nSin\n\n\n\n\n2\nπ\n\n\n3\n\nd\n0\n\n\n\n⋅\nd\n+\nφ\n\n\n\n is proper to express the periodicity of atom arrangement. Besides, we know that the unit of correction term (Δ) is exactly N/m. So, the correction can be defined as the following based on the discussion above:
where \n\nα\n\n, \n\nβ\n\n, and \n\nφ\n\n are three constants that need to be matched and fitted. Based on the simulation data in Table 2, these three constants \n\nα\n\n, \n\nβ\n\n, and \n\nφ\n\n can be acquired by calculation approximately \n\n\n3\n2\n\n\n, \n\n\n2\n15\n\n\n, and \n\n−\n\nπ\n3\n\n\n, respectively. So the critical load for the first dislocation emission of Al film has been revised with initial surface pit as follows:
Figure 6 shows the comparison of the critical load for dislocation emission of Al thin film in different distance cases calculated by the theoretical formula before and after modification. Though there is no parameter d in Eq. (1), the curves with blocks are calculated by depth h corresponding each distance case in this simulation. The simulation QC data is closer to the theoretical results which are calculated by Eq. (4) after modification. That is to say, such modification to the theoretical formula is justified as the pit size and the distance between the pit and indenter have both been taken into account.
\n
Figure 6.
The comparison of the necessary load for elastic-to-plastic transition of Al thin film with various distances between the pit and the indenter calculated by the theoretical formula before and after modification.
\n
The modified formula displays the decreasing trend of nanohardness as the distance between the pit and indenter increases, which quite agrees with the experimental results of nanoindentation on the surface step with different distances [14]. Further, such study might be referential to the research of material properties with defects, especially in microchips and MEMS.
\n
\n
\n
\n
\n
3. Size effect of surface pit defect
\n
\n
3.1 Method and model
\n
The quasi-continuum method is adopted in this simulation, which is one of the multiscale approaches that keeps an atomistic description at highly deformed regions, whereas a linear elastic continuum method is implemented far away from this dislocation core. In this simulation, the Ercolessi-Adams potential (EAM) [38] is also applied to describe the atomistic behavior of the system.
\n
The nanoindentation model used in the simulation has been shown in Figure 7, where the x-axis direction is [1 1 1] direction, the y-axis direction is [\n\n\n1\n¯\n\n\n 1 0], and the outer-of-plane z direction is [\n\n\n1\n¯\n\n\n\n\n\n1\n¯\n\n\n 2] direction. And its schematic of local and nonlocal representative atoms with initial surface pit defect has been shown in Figure 8. Such orientation is selected to facilitate dislocation emission. The model size is 200 nm in width and 100 nm in height, which is about 10 times of the usual MD size. The width of the rigid indenter is 4d0, where d0 is one atomic lattice spacing in [1 1 1] direction 0.2328 nm. The adjacent distance between the indenter and the pit in this model is chosen to be 4d0 (as shown in Figure 7), which is proved to be reasonable referring to the research on nanoindentation on a stepped surface [14], where the spatial extent of the step’s influence has been figured out to be approximately three times the contact radius. Therefore, the contact radius of this simulation is 2d0 (half of the indenter width), and the distance between the left side of surface pit defect and the center of the indenter is exactly 6d0 (4d0+4d0/2 = 6d0), which quite agrees with this reference [14] (6d0/2d0 = 3). Although the indentation tip shape is different between this simulation and the nanoindentation experiment, where it is square and round-like, respectively, actually, the nanohardness are both calculated by the real contact radius. That is to say, the change of the nanohardness in these two cases is quite similar if considering the ratio of defect distance to the real contact radius (as well as the experiment discussion). The simulation models of the width effect and height effect of surface pit defect are shown as Figure 7, and relevant parameter values are shown in Table 3 in order to make a more comprehensive investigation. Besides, the comparison model of nanoindentation on the stepped surface step with the height of the step 10h0 has also been carried out as shown in Figure 7(d). Further, this model keeps the boundary condition rigid at the bottom and free at the sides, and the thickness is equal to the minimal repeat distance. The displacement-imposed boundary condition forces the atoms under the indenter to move into the material gradually. Each load step of indentation has set 0.02 nm in order to be more proper and effective to catch the dislocation nucleation and mission. Moreover, the final depth is 1.2 nm, which ensures that the behavior in the vicinity of the indenter will not be affected by the far-field boundary conditions.
\n
Figure 7.
Schematic representation of the nanoindentation model of size effect: (a) width (D) changing from 1d0 to 10d0 of surface pit defect with the fixed height = 5h0; (b) the comparison model of surface step with height = 5h0; (c) height (H) changing from 1h0 to 10h0 of surface pit defect with the fixed width = 5d0; (d) the comparison model of surface step with height = 10h0.
\n
Figure 8.
Schematic representation of local and non-local representative atoms with initial surface pit defect.
\n
\n
\n
\n
\n
\n\n
\n
Width effect
\n
Height effect
\n
\n
\n
Width of pit (d0)
\n
Height of pit (h0)
\n
Width of pit (d0)
\n
Height of pit (h0)
\n
\n\n\n
\n
1
\n
5
\n
5
\n
1
\n
\n
\n
2
\n
2
\n
\n
\n
3
\n
3
\n
\n
\n
4
\n
4
\n
\n
\n
5
\n
5
\n
\n
\n
6
\n
6
\n
\n
\n
7
\n
7
\n
\n
\n
8
\n
8
\n
\n
\n
9
\n
9
\n
\n
\n
10
\n
10
\n
\n\n
Table 3.
The models parameters of the width effect and height effect.
\n
\n
\n
3.2 Results and discussion
\n
\n
3.2.1 Width effect on the yield load due to the pit defect
\n
As is known to all that the yield load of materials is one of the most important factors of the material properties, however it can be obviously affected by defects such as surface pit defect. Normally, the yield load can be easily obtained from the first peak load in the load-displacement curve, which suggests onset of the elastic-to-plastic transition. In this chapter, we have taken 10 different widths of the pit from D = 1d0 to 10d0 with a fixed height H = 5h0, in order to investigate the width effect of surface pit defect on the yield load. The change of the yield load curve as pit width has been revealed in Figure 9. Generally, a reduction tendency of the yield load of Al thin film with the pit defect displays result from more and more serious destruction to the atomic structure by the increase of the pit width. Further, the yield load experiences an extremely slow reduction when the pit width increases from D = 1d0 to 7d0; after that it obviously drops from 14.8 to 14.24 N/m when the pit width reaches 7d0. Then, the yield load decreases slowly again.
\n
Figure 9.
The yield load of thin film as the width changing of surface pit defect (with a standard deviation of 0.01 N/m). QC—quasicontinuum method.
\n
It is necessary and significant to compare the nanoindentation on a stepped surface with H = 5h0 as shown in Figure 7(b), where the pit width can be treated as infinitely large. The result is approximately 14.23 N/m, very close to the yield load in the case of D = 10d0 (the red point in Figure 9). This implies that the yield load of Al thin film nearly equals the yield load value in the case of stepped surface when the pit width increases to 10d0.
\n
\n
\n
3.2.2 Height effect on the yield load due to the pit defect
\n
We have taken 10 different heights of the pit from H = 1h0 to 10h0, with a fixed width D = 5d0, in order to investigate the height effect of surface pit defect on the yield load as shown in Figure 7(c). The change of the yield load curve as pit height has been revealed in Figure 10. Similarly, the yield load experiences an extremely slow reduction when the pit height increases from H = 1h0 to 5h0; after that it obviously drops from 14.79 to 14.14 N/m when the pit width reaches 6d0. Then, the yield load decreases slowly again.
\n
Figure 10.
The yield load of thin film as the height changing of surface pit defect (with a standard deviation of 0.01 N/m).
\n
In the same way, it is also necessary and significant to compare the nanoindentation on a stepped surface with H = 10h0 as shown in Figure 7(d). The result is approximately 13.75 N/m (the red point in Figure 10), which is quite near the yield load 13.93 N/m in the case of H = 10h0.
\n
\n
\n
3.2.3 The investigation of dislocation nucleation and the estimation of Peierls stress
\n
We have carried out a further probe of atomic snapshot and corresponding out-of-plane displacement plot, in order to explain the obvious drops of yield load (D = 7d0 to 8d0 segment in Figure 9, H = 5h0 to 6h0 segment in Figure 10). Taking the cases of D = 1d0 in width effect simulation and H = 1h0 in height effect simulation, for example, it can be easily found out from nucleated dislocations and UZ contours displayed in Figure 11 that two dissociated <1 1 0> edge dislocations are emitted beneath the indenter after nucleation during the thin film yielding. Moreover, the dislocated structure along with the out-of-plane displacements experienced by the atoms has also been displayed in Figure 11, with the dimension 0.1 nm, where a fingerprint of the dislocations has been clearly shown between the partials in the stacking fault regions. According to the structure of FCC metal, it can be easily found out that the dislocations are composed of 1/6 <1 1 2> Shockley partials. On the left,
Snapshot of atoms under the indenter and corresponding out-of-plane displacement plot, where UZ is atom displacement at out-of-plane: (a) width changing D = 1d0 at the yield of thin film; (b) height changing H = 1h0 at the yield of thin film.
Comparing all these width and height effect cases in this simulation, we find that emission depth of dislocations changes due to the size of the pit. Take Figure 11(a) and (b), for example, the dislocation dipole similarly travels into bulk after nucleation at the load step of 0.5 nm; however, its center of the emission depth settles, respectively, at the depth of 5.2 and 6.08 nm. It might be predicted that the yield load of thin film in macroscopy corresponds to the emission depth of dislocation in microscopy.
\n
Considering that Peierls stress is exactly the resisting force during the dislocation movement due to the lattice structure, all these emission depths of dislocations have been adopted as an equilibrium distance to further calculate the Peierls stress predicted by the EAM potential [38]. Except the lattice friction, there are two forces acting on the dislocation: (i) the Peach-Koehler force (FPK) due to the indenter stress field driving the dislocation into bulk and (ii) the image force (FI) pulling the dislocation up to the surface. The dislocation, which is forced by the sum of these two forces, escapes the attractive region and propagates into the bulk and is finally stopped by lattice friction. Consequently, the force on the dislocation will be balanced at the equilibrium depth by the lattice friction force that is due to the Peierls stress (\n\n\nσ\np\n\n\n) [31].
\n
\n\n\nF\nPK\n\n+\n\nF\nΙ\n\n=\nb\n\nσ\np\n\n\nE7
\n
Shear stress beneath the indenter is necessary to be further obtained to calculate the Peach-Koehler force. In this simulation, the rectangular indenter is frictionless, applying to an elastic thin film occupying the lower half-plane. When y < 0, the shear stress in bipolar coordinates is [39]
where P is the indentation load. According to the coordinate system of 2a indentation contact (the width of indenter is 2a), as shown in Figure 12, at a depth h beneath the right indenter tip, there is \n\nr\n=\n\n\n\na\n2\n\n+\n\nh\n2\n\n\n\n\n, \n\n\nr\n1\n\n=\nh\n\n, \n\n\nr\n2\n\n=\n\n\n4\n\na\n2\n\n+\n\nh\n2\n\n\n\n\n, \n\nθ\n=\n−\n\ntan\n\n−\n1\n\n\nh\n/\na\n\n, \n\n\nθ\n1\n\n=\n−\nπ\n/\n2\n\n, and \n\n\nθ\n2\n\n=\n−\n\ntan\n\n−\n1\n\n\n\n\nh\n/\n2\na\n\n\n\n. The Peach-Koehler force is
Peierls stress of all these cases of pit size has been calculated and plotted based on the discussion above, where Figures 13 and 14, respectively, show Peierls stress of width effect and height effect. In the case of width effect, Peierls stress maintains around the value of 100 MPa with tiny fluctuation from D = 1d0 to 7d0; after that the Peierls stress displays a sudden obvious dropdown to about 70 MPa, which is quite similar compared with yield load curve in Figure 9. In the case of height effect, Peierls stress maintains around the value of 70 MPa with tiny fluctuation from H = 1h0 to 5h0; after that the Peierls stress displays a sudden obvious dropdown to about 50 MPa, which is also greatly in accordance with the yield load curve in Figure 10. The conclusion can be drawn that such obvious decline of yield load (D = 7d0 to 8d0 segment in Figure 9, H = 5h0 to 6h0 segment in Figure 10) is closely related to the severe reduction of the Peierls stress, suggesting that it is reasonable and effective to explain the variation of yield load through the Peierls stress.
\n
Figure 13.
The variation of Peierls stress in the simulation of width effect (with a standard deviation of 0.2 MPa).
\n
Figure 14.
The variation of Peierls stress in the simulation of height effect (with a standard deviation of 0.1 MPa).
\n
\n
\n
3.2.4 Size coefficient
\n
We make a further probe on the difference of turning point between width effect and height effect, corresponding to D = 7d0 in the width effect simulation and H = 5h0 in the height effect simulation. It can be predicted that the influence degree of width factor is different from the height factor. It is necessary to quantify the size effect of surface pit defect to explain the reason of these differences. It can also be easily recognized that if the distance between the pit and the indenter decreases, the influence would be much more severe on the hardness and yield load. Namely, controlling the same influence of the pit on the nanohardness, the larger size of the pit is required when the pit goes far away from the indenter. Therefore, we defined a size coefficient α as the following, which is dimensionless in order to explain the size effect of surface pit defect:
\n
\n\nα\n=\n\n\nL\n∗\n\n\nd\n∗\n\n\n\nE11
\n
where “L*” is the characteristic length of the pit, such as D in the width effect simulation or H in the height effect simulation and “d*” is the distance between the center of the indenter and the left boundary of the pit, namely, 6d0 in this simulation.
\n
According to the simulation result of width effect, the critical width value to make a sudden obvious drop of yield load is 7d0 (as shown the point D = 7d0 in Figure 9). Consequently, the size coefficient α is approximately 1.17 (\n\n\n\nL\n∗\n\n\nd\n∗\n\n\n=\n\nD\n\nd\n∗\n\n\n=\n\n\n7\n\nd\n0\n\n\n\n6\n\nd\n0\n\n\n\n=\n\n7\n6\n\n\n). When α reaches approximately 2 (\n\n\n\nL\n∗\n\n\nd\n∗\n\n\n=\n\nD\n\nd\n∗\n\n\n=\n\n\n10\n\nd\n0\n\n\n\n6\n\nd\n0\n\n\n\n=\n1.7\n\n), as shown in the point D = 10d0 in Figure 9, the yield load of thin film with surface pit defect nearly equals the one of nanoindentation with surface step as shown in the red point in Figure 9.
\n
According to the simulation result of height effect, the critical height value to make a sudden obvious drop of yield load is 5h0 (as shown the point H = 5h0 in Figure 10). Consequently, the size coefficient α is approximately 0.51 (\n\n\n\nL\n∗\n\n\nd\n∗\n\n\n=\n\nH\n\nd\n∗\n\n\n=\n\n\n5\n\nh\n0\n\n\n\n6\n\nd\n0\n\n\n\n=\n0.51\n\n). When α reaches approximately 1 (\n\n\n\nL\n∗\n\n\nd\n∗\n\n\n=\n\nH\n\nd\n∗\n\n\n=\n\n\n10\n\nh\n0\n\n\n\n6\n\nd\n0\n\n\n\n=\n1.02\n\n), as shown in the point H = 10h0 in Figure 10, the yield load of thin film with surface pit defect nearly equals the one of nanoindentation with surface step as shown in the red point in Figure 10.
\n
By contrast, the size coefficient of height is approximately half of the one of width to boost the sudden decline of yield load, implying that the height of the pit has a greater influence on the yield load than the width.
\n
Moreover, the change of yield load of thin film as the pit area has been plotted and shown in Figure 15, where we can easily find out that the slope of yield load curve by height increasing is larger than the one by width increasing. That is to say, the height increasing makes the yield load decrease faster. Besides, the yield load by width increasing is smaller than the one by height increasing during 5h0d0 to 25h0d0 segment of the pit area, which results from the height of the pit in width increase curve (as shown red curve in Figure 15) is larger than the other one (black curve). If the area increases over than 25h0d0, the yield load by height increase is smaller than the one by the width increase. It can be well explained that the height of the pit in the curve of height increase goes up over 6h0, while the one in the curve of width increase still maintains 5h0, suggesting that the height of the pit has played a more important role on yield load.
\n
Figure 15.
The yield load of thin film as the area changing of surface pit defect.
\n
\n
\n
\n
\n
4. Conclusions
\n
Through this whole chapter, we apply the QC method to study the influence of surface pit defect in nanoindentation. Fifteen distances of adjacent boundaries between the pit and indenter have been taken into account to study the distance effect, compared with the nanoindentation on defect-free surfaces, while various sizes of the pit have been taken into account to study the size effect, compared with the nanoindentation on the stepped surfaces. Based on the discussion, we can make some conclusions as the following:
Compared with the nanoindentation on the defect-free surface, the pit defect plays a significant role in the elastic-to-plastic transition that leads to the decrease of the nanohardness.
The nanohardness increases in a wave that goes up in a period of three atoms when the pit moves far away from the indenter atom by atom, which is strongly linked to the crystal structure of periodic atom arrangement on {1 1 1} atomic close-packed planes of FCC metal. Moreover, it can be nearly considered as no influence on the nanohardness if the adjacent distance between the pit and indenter increases over than 16 atomic spacing.
The formula for critical load of dislocation emission of Al thin film has been effectively revised with initial pit defect, where the reduction trend of nanohardness, as the increasing distance between the pit and the indenter, is in great accordance with the experimental results of nanoindentation on the stepped surface with various distances. Such study might be referential to the research of material properties with defects, especially in microchips and MEMS.
When the size coefficient of width (of height) equals about one unit (half unit), the yield load experiences an obvious drop. When it reaches about two units (one unit), the yield load is nearly close to that of the nanoindentation on a stepped surface.
Compared to the width, the height of surface pit defect shows a greater influence on the yield load of thin film, implying that the height of the pit is a leading factor on the influence of yield load, which might have great significance to the defect design and applications in artificial materials.
\n
\n
Acknowledgments
\n
The authors would like to thank Professor Tadmor E. B along with his cooperative partners for their open source QC code. Besides, this work is supported by the National Natural Science Foundation of China (Grant No. 11572090).
\n
Conflict of interest
The authors declare that the founding sponsors had no contributions in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; and in the decision to publish the results. So, there is no conflict of interest.
\n',keywords:"surface pit defect, multiscale simulation, size effect, distance effect, quasi-continuum method",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/65671.pdf",chapterXML:"https://mts.intechopen.com/source/xml/65671.xml",downloadPdfUrl:"/chapter/pdf-download/65671",previewPdfUrl:"/chapter/pdf-preview/65671",totalDownloads:404,totalViews:0,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,dateSubmitted:"September 20th 2018",dateReviewed:"January 8th 2019",datePrePublished:"February 14th 2019",datePublished:"November 20th 2019",dateFinished:null,readingETA:"0",abstract:"Microscopic properties of crystal aluminum thin film have been investigated using the quasi-continuum method in order to study the influence of surface defects in nanoindentation. Various distances between the surface pit defect and indenter and various sizes of the pit have been calculated. In this simulation, as the distance between the pit and indenter increases, the nanohardness increases in a wave that goes up in a period of three atoms, and it is found closely related to the crystal structure of periodic atom arrangement on {1 1 1} atomic close-packed planes of FCC metal; there is almost no influence on the nanohardness when the adjacent distance between the pit and indenter is more than 16 atomic spacing. We have modified the theoretical equation of the necessary load for elastic-to-plastic transition of Al film with the initial surface defect size. Furthermore, when the size coefficient of width (of height) equals about one unit (half unit), the yield load experiences an obvious drop. When it reaches about two units (one unit), the yield load is nearly close to that of the nanoindentation on a stepped surface. Additionally, compared to the width, the height of surface pit defect displays a greater influence on the yield load of thin film.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/65671",risUrl:"/chapter/ris/65671",book:{slug:"micromachining"},signatures:"Zhongli Zhang, Yushan Ni, Jinming Zhang, Can Wang and Xuedi Ren",authors:[{id:"276367",title:"Ph.D. Student",name:"Zhongli",middleName:null,surname:"Zhang",fullName:"Zhongli Zhang",slug:"zhongli-zhang",email:"zhangzl@simt.com.cn",position:null,institution:null},{id:"281408",title:"Prof.",name:"Yushan",middleName:null,surname:"Ni",fullName:"Yushan Ni",slug:"yushan-ni",email:"niyushan@fudan.edu.cn",position:null,institution:null},{id:"281414",title:"Mr.",name:"Jinming",middleName:null,surname:"Zhang",fullName:"Jinming Zhang",slug:"jinming-zhang",email:"zhangjm@simt.com.cn",position:null,institution:null},{id:"281415",title:"Mrs.",name:"Can",middleName:null,surname:"Wang",fullName:"Can Wang",slug:"can-wang",email:"wangc@simt.com.cn",position:null,institution:null},{id:"281416",title:"Prof.",name:"Xuedi",middleName:null,surname:"Ren",fullName:"Xuedi Ren",slug:"xuedi-ren",email:"renxd@simt.com.cn",position:null,institution:null}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Distance effect of surface pit defect",level:"1"},{id:"sec_2_2",title:"2.1 Methodology",level:"2"},{id:"sec_3_2",title:"2.2 Results",level:"2"},{id:"sec_3_3",title:"2.2.1 Nanoindentation without defect",level:"3"},{id:"sec_4_3",title:"2.2.2 Distance effect of the surface pit",level:"3"},{id:"sec_5_3",title:"Table 2.",level:"3"},{id:"sec_8",title:"3. Size effect of surface pit defect",level:"1"},{id:"sec_8_2",title:"3.1 Method and model",level:"2"},{id:"sec_9_2",title:"3.2 Results and discussion",level:"2"},{id:"sec_9_3",title:"3.2.1 Width effect on the yield load due to the pit defect",level:"3"},{id:"sec_10_3",title:"3.2.2 Height effect on the yield load due to the pit defect",level:"3"},{id:"sec_11_3",title:"3.2.3 The investigation of dislocation nucleation and the estimation of Peierls stress",level:"3"},{id:"sec_12_3",title:"3.2.4 Size coefficient",level:"3"},{id:"sec_15",title:"4. Conclusions",level:"1"},{id:"sec_16",title:"Acknowledgments",level:"1"},{id:"sec_19",title:"Conflict of interest",level:"1"}],chapterReferences:[{id:"B1",body:'Oliver WC, Pharr GM. An improved technique for determining hardness and elastic modulus using load and displacement sensing indentation experiments. Journal of Materials Research and Technology. 1992;7:1564-1583\n'},{id:"B2",body:'Li XD, Bhushan B. A review of nanoindentation continuous stiffness measurement technique and its applications. Materials Characterization. 2002;48:11-36\n'},{id:"B3",body:'Bamber MJ, Cooke KE, Mann AB, Derby B. Accurate determination of Young’s modulus and Poisson’s ratio of thin films by a combination of acoustic microscopy and nanoindentation. Thin Solid Films. 2001;399:299-305\n'},{id:"B4",body:'Zhu PZ, Hu YZ, Fang FZ, Wang H. Multiscale simulations of nanoindentation and nanoscratch of single crystal copper. Applied Surface Science. 2012;258:4624-4631\n'},{id:"B5",body:'Chen J, Bull SJ. 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Department of Aeronautics and Astronautics, Fudan University, China
Shanghai Institute of Measurement and Testing Technology, China
Shanghai Institute of Measurement and Testing Technology, China
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1. Introduction
Foot-and-mouth disease (FMD) is a contagious viral infection [1] which is caused by foot-and-mouth disease virus (FMDV). The disease appears in cloven-footed animals. Symptoms of the disease are abrupt manifestation of sores on the mouth, nose, feet, etc. [2]. These symptoms can appear within 2–3 days postexposure and can take up to 7–10 days. FMDV belongs to genus Aphthovirus and family Picornaviridae and has seven species. In the year 2001, about 57 zones were previously influenced by dangerous FMD at the detection of FMDV for the first time in Britain. Later on about 43 animals were encountered with FMD just in a day. So estimate regarding the onset of FMD among animals may be biased [3].
For the prevention and elimination of FMDV, two methods could be adopted, that is, massacre and immunization [4]. The virus can last for an extended period of time especially in cool environment and neutral pH.
The foot-and-mouth disease virus (FMDV) belongs to genus Aphthovirus and family Picornaviridae [5]. FMDV has seven diverse serotypes O, A, C, SAT-1, SAT-2, SAT-3, and Asia-1. Serotype O is the most familiar in the world among all the serotypes. More than 60 strains are found among these serotypes. These serotypes differ with each other in different topographic areas. Serotype O was accountable for that Asian epidemic which occurred in the year 1990 and influenced all over the world [1]. FMDV is a single-stranded RNA virus. It contains a protein coat comprising of four capsid proteins designated as VP1, VP2, VP3, and VP4 [4].
Foot and mouth disease (FMD) affects cloven-footed animals. The disease is very fast-growing and transmissible which usually affects pigs, cattle, goats, and sheep. The symptoms include vesicles/blisters on the hoofs, mouth, nose, feet, teats, etc. Ultimately these blisters result in skin erosions. Animals become unable to take food and thus become weak. Other symptoms include salivation, decrease in milk production, and weight loss. This viral problem occurs around the whole globe. FMDV epidemic occurred in different countries of the world like Europe, the United States, and Canada. In the year 1967, FMDV epidemic resulted in mortality of 400,000 pigs in the United Kingdom. Epidemic of FMDV in the United Kingdom causes death of about 70,000 pigs, cattle, and sheep in 70 areas [2].
Foot and mouth disease is a very dangerous communicable disease. It has affected different domestic animals in different areas with very lethal symptoms. Its breakthrough is especially notable in the United Kingdom. In the year 2001, about 57 zones were previously influenced by dangerous FMD at the detection of FMDV for the first time in Britain. Later on about 43 animals were encountered by this FMD just in a day. So estimate regarding the onset of foot and mouth disease among animals may be biased [3].
2. Plants for treatment of FMDV
Different plants were evaluated to prevent or eradicate FMDV. An experiment evaluated two parts of ginseng plant, stem and leaves, regarding susceptibility of mice to immunization to vaccine against serotype Asia-1 of FMDV. Ginseng along with its oil was also used to assess collective outcome regarding immunization against FMDV. This research showed that considerable high titer of various antibodies resulted when ginseng along with oil is given in combination. Important antibodies which were evaluated included IgG1, IgG2a, IgG2b, and IgG3.
In a study forty two plants were used to prepare 47 ethanolic extracts which were evaluated for their antiviral potential against KPS/005/2545 strain of type “O” FMDV. BHK-21 cell line was used in the experimental study. The virus was used at the rate of 106.37 TCID50. Transgenic plant (Arabidopsis thaliana) was used to synthesize VP1 with 135–160 amino acid residues. These antigens were found to provide immunization against viral disease [6]. Some plants showed significant antiviral activity against FMDV which included Morinda elliptica and Morinda citrifolia. Other plants failed to exhibit antiviral activity against FMDV [7]. This indicates that plants have antiviral potential and they can be used as antiviral agents against FMDV.
In another reported study, it was mentioned that FMD is a transmissible ailment of animals. Effective control of this disease needs sensitive, specific, and quick diagnostic tools at each tier of control strategy. Various pen-side tests, namely, lateral flow, RT-LAMP, immunostrip tests, and so forth, were also developed for the detection of the virus in field condition [8].
FMDV is transmissible, and to maintain protection against this virus, a study was conducted on guinea pigs and rabbits. The study suggested that immunization of animals with synthetic peptide 141–160 produces neutralizing antibodies that provide protection against FMDV [9]. Similarly, different synthetic peptide residues 141–158 and 200–213 of VP1 were synthesized from 01 Kaufbeuren strain of FMDV. These peptides were proved to provide protection against FMDV via acting on VP1 carboxyl terminal [10].
In the 1930s, the first vaccine was developed against FMDV. The vaccine was developed from live FMDV with formalin in combination with aluminum hydroxide gel. Treatment of animals with this vaccine reduced the outbreak of viral disease [11]. Later on, vaccines have been developed based on the virus capsid structure. These vaccines were synthesized from purified or recombinant DNA techniques, derived or chemically synthesized VP1 peptides, inoculation with DNA expressing VP1 epitopes or interleukin, and plant expressing VP1 [12]. Moreover, a vaccine was developed by deleting RGD receptor site on VP1, which resisted virus binding to the cell [13]. Similarly, a live attenuated vaccine was prepared that lack the L-coding in A-type A12 virus. The vaccine resulted in replication of cells but decreased the virulent factor of disease in cattle [14]. On the other hand, a swine inoculated with wild-type A12 in combination with oil led to neutralization of FMDV [15].
Different studies have been reported on targeted immunogens that lack infectious nucleic acid. In a reported study, mice were inoculated with active virus 3Cpro in empty capsules. This vaccine produced neutralizing response by producing antibodies [16]. Another study showed improved FMDV antibody response after coadministration of viral capsid along with porcine granulocyte-macrophage colony-stimulating factor [17].
Meanwhile some studies illustrated the recombinant and replication of vaccinia virus containing capsid-coding region of FMDV C1Oberbayern or C3Argentina85 [18]. To prevent the outbreak, Ad5-vectored vaccine was prepared that reduced viral growth. Furthermore, porcine interferon omegas 7 and 8 have also been reported to reduce FMDV in vitro production in swine kidney cells [19, 20].
Nowadays the control and treatment of FMDV have become a worldwide economic problem and a challenge for the society. It not only affects the animals, but humans who eat these animals are also affected. Currently, there is no any particular treatment existing regarding the cure of FMDV. The conventional method involved the use of antibiotics, flunixin, meglumine, and mild disinfectants for treating infected animals. Traditionally for washing the lesions of infected animals, natural soda ash solution, honey, and finger millet flour are used [21].
Vaccination of animals is the first-line treatment for the control of the virus. However, vaccines take several days to elicit its response, and sometimes, a booster dose is required with repeated vaccination. There is no vaccine available which meets the ideal conditions like broad antigenic spectrum, high efficacy, low risk of FMDV release, and low production cost. Inactivated (traditional) and live attenuated (conventional) vaccines are used normally. Inactivated vaccines contain one or more cell culture-derived inactivated virus mixed with the suitable excipients. Inactivated vaccines may be categorized into standard or higher potency vaccines. Standard vaccines provide broad-spectrum coverage against the virus strains, while high-potency vaccine has rapid onset of action and wider range of protection. Live attenuated vaccines are not recommended for use as it reverts the chance of infection and also prevents the recognition of infection in vaccinated animals [22].
Azadirachta indica (AI), known commonly as neem, belongs to family Meliaceae and has possessed antiviral activity against different viruses [23, 24]. There is a study that reported the use of different concentrations (200, 100, 50, 25, 12, 6, and 1 μg/ml) of aqueous and ethanolic leaves extract of Azadirachta indica for evaluating antiviral activity against FMDV in farming animals on BHK-21 (baby hamster kidney) cell culture. Aqueous extract of the said plant showed considerable anti-FMDV activity between the concentration ranges of 12.5–50 and 50–100 μg/ml, whereas ethanolic leaves extract demonstrated strong antiviral activity at concentrations between 6 and 25 μg/ml. Antiviral activity was evaluated by examining cytopathic effects and determining cell survival percentages [25].
Moringa oleifera, local name is Sonjna, belongs to family Moringaceae and is an effective antiviral agent used against Epstein-Barr virus (EBV), herpes simplex virus (HSV), HIV/AIDS, and hepatitis B virus [26]. The anti-FMDV activity of ethanolic leaves extract of Moringa oleifera was evaluated at different concentrations, respectively (200, 100, 50, 25, 12, 6, and 1 μg/ml), on BHK-21 cell culture. Ethanolic leaf extracts of plant showed potent anti-FMDV activity between the concentration ranges of 12–100 and 50–300 μg/ml. However, in another study ethanol leaf extracts of plant showed significant antiviral activity at the concentration ranges from 1 up to 100 μg/ml with 50% cell survival rate [27].
Alhagi maurorum is a member of family Fabaceae, known by local name camel thorn and camelthorn-bush. The successful in vitro anti-FMDV activity of ethanolic, methanolic, and aqueous-acetic acid extracts of A. maurorum was reported at different stages of viral replication cycle, with the main compound found to be 1,2-benzenedicarboxylic acid, diisooctyl ester. Reduction in cytopathic effects (CPEs) and tissue culture infective dose (TCID50) values help in the evaluation of antiviral activity of FMDV on Razi bovine kidney (RBK) cells [28].
The Withania somnifera (WS), or Ashwagandha locally known as “Indian winter cherry” or “Indian ginseng,” belongs to the family Solanaceae. Ashwagandha is a well-known South African herb used in the treatment of herpes simplex virus [29] and infectious bursal disease [30]. In literature in vitro activity of aqueous extract of Ashwagandha roots and leaves was reported against FMDV of livestock on BHK-21 cell line. Ashwagandha roots and leaves demonstrated effective anti-FMDV activity. The antiviral activity of the plant was confirmed by observing reduction in cytopathic effects when treated with Ashwagandha root and leaf extracts [31].
In literature in vivo anti-FMDV activity of Chinese herbal kombucha is reported against FMDV of swine on baby hamster kidney (BHK-21) cells. Chinese herbal kombucha is a combination of different herbal plants, i.e., Radix Glycyrrhizae, Momordica grosvenorii, Dendranthema morifolium, and Camellia sinensis. Study showed that Chinese herbal kombucha inhibited the replication of FMDV analyzed by using real-time quantitative reverse transcription-PCR (Q-RT-PCR) technique [32].
The ethanolic extract of Spirulina platensis demonstrated the presence of antiviral activity against different isolates of FMDV in baby hamster kidney (BHK) cell culture and in baby mice. The results of this study showed that at 50 μg/ml, S. platensis extract revealed 28.5, 31, and 35.7% reductions in FMDV titers type A, SAT-2, and O, respectively. At the same dose, 50% inhibition in FMDV was observed in infected baby mice [33].
Glycyrrhiza uralensis or Chinese liquorice is used to treat enterovirus 71 (EV71) and Coxsackie virus A16 (CVA16) of FMD. The essential antiviral component in plant is found to be glycyrrhizic acid, as the antiviral activity is directly dependent on the concentration of glycyrrhizic acid. At 1000 μg/ml concentration of plant extract, 1.0 log reduction in EV71 replication and 1.5 log reduction in CVA16 replication were observed. However, at concentration of 200 μg/ml, 1.7 and 2.2 log inhibition in EV71 and CVA16 replication is examined, respectively. Cytopathic effects were observed for determining antiviral activity [34].
Ocimum tenuiflorum (tulsi) of family Lamiaceae and Curcuma longa (turmeric) of family Zingiberaceae also possess potential antiviral activity for FMD. Aqueous extracts of both plants showed effective in vitro antiviral activity against FMDV of livestock on BHK-21 cell line at 1:2 and 1:1 dilutions [31].
Various plant crude extracts were studied for their in vitro antiviral activity against bovine FMDV on BHK-21. The immature fruit extract of Morinda elliptica L. showed FMDV inhibition at concentration of 0.39 μg/μl with TCID50 value of 1 × 103.65. The Morinda citrifolia L. extract also showed FMDV inhibition at 0.19 μg/μl, and TCID50 value was reported to be 1 × 103.35. Extract from leaves and stem of Amaranthus viridis L. has lowest FMDV inhibition at 0.024 μg/μl concentration (1 × 102.44 TCID50). Extracts obtained from the rhizomes of Boesenbergia rotunda L., flowers of Carthamus tinctorius, and fruits of Citrus reticulata and Elaeocarpus hygrophilus showed inhibition of FMDV at concentration of 0.012 μg/μl of all extracts with 1 × 102.14 TCID50 [7].
3. Conclusion
Recently there is no particular treatment available for the treatment of FMDV, and the limitations and disadvantages in the use of vaccines divert the focus of researchers toward natural sources like plant extracts which possess potential antiviral activity. The various research works documented in the literature demonstrated various plant extracts with antiviral potency against FMDV.
4. Future prospects
The successful in vivo and in vitro anti-FMDV activities of plant extracts showed that they have the potential to be used to control the virus growth inside the body and also help in managing the lesions associated with these infections. In plant extracts, different chemical constituents are present which could be further isolated and effectively used in the development of powerful and potent antiviral drug against FMDV.
\n',keywords:"FMDV, treatment, plant extracts",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/67293.pdf",chapterXML:"https://mts.intechopen.com/source/xml/67293.xml",downloadPdfUrl:"/chapter/pdf-download/67293",previewPdfUrl:"/chapter/pdf-preview/67293",totalDownloads:513,totalViews:0,totalCrossrefCites:0,dateSubmitted:"January 4th 2019",dateReviewed:"February 4th 2019",datePrePublished:"June 12th 2019",datePublished:"March 11th 2020",dateFinished:null,readingETA:"0",abstract:"Foot-and-mouth disease (FMD) is a contagious viral infection which is caused by foot-and-mouth disease virus (FMDV). The disease appears in cloven-footed animals. Symptoms of the disease are abrupt manifestation of sores on the mouth, nose, feet, etc. Nowadays the control and treatment of FMDVare becoming a worldwide economic problem and challenge for the society. Currently, there is no particular treatment available for FMDV, as well as the limitations and disadvantages in the use of vaccines divert the focus of researchers toward natural sources like plant extracts which possess potential antiviral activity. Various researches documented in the literature demonstrated various plant extracts with antiviral potency against FMDV. In the current chapter, we discussed about FMDV and its possible treatment with plant extracts.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/67293",risUrl:"/chapter/ris/67293",signatures:"Ishrat Younus, Sidra Maqbool, Sarah Jameel Khan, Humera Sarwar, Shagufta Nesar, Rida Fatima, Sidra Siddique and Moona Baig",book:{id:"8634",title:"Veterinary Medicine and Pharmaceuticals",subtitle:null,fullTitle:"Veterinary Medicine and Pharmaceuticals",slug:"veterinary-medicine-and-pharmaceuticals",publishedDate:"March 11th 2020",bookSignature:"Samuel Oppong Bekoe, Mani Saravanan, Reimmel Kwame Adosraku and P K Ramkumar",coverURL:"https://cdn.intechopen.com/books/images_new/8634.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"186990",title:"Dr.",name:"Samuel Oppong",middleName:null,surname:"Bekoe",slug:"samuel-oppong-bekoe",fullName:"Samuel Oppong Bekoe"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"243372",title:"Dr.",name:"Ishart",middleName:null,surname:"Younus",fullName:"Ishart Younus",slug:"ishart-younus",email:"ishratyounas@gmail.com",position:null,institution:null}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Plants for treatment of FMDV",level:"1"},{id:"sec_3",title:"3. Conclusion",level:"1"},{id:"sec_4",title:"4. Future prospects",level:"1"}],chapterReferences:[{id:"B1",body:'Aftosa F. Foot and Mouth Disease. Ames, Iowa: College of Veterinary Medicine, Iowa State University; 2007'},{id:"B2",body:'Kirk JH. Review of Clinical Signs of Foreign Animal Diseases Which a Mixed Veterinary Practitioner Might Encounter on a Dairy. Veterinary Medicine Extension University of California. CA: Davis Veterinary Medical Teaching and Research Center Tulare; 1992'},{id:"B3",body:'Gibbens JC, Wilesmith JW. Temporal and geographical distribution of cases of foot and mouth diseases during the early weeks of the 2001 epidemic in great Britian. The Veterinary Record. 2002;2002:151-212'},{id:"B4",body:'Davies G. Foot and mouth disease. Research in Veterinary Science. 2002;73(3):195-199'},{id:"B5",body:'ICTV. 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Medicinal Chemistry. 2016;6:578-582'},{id:"B27",body:'Younus I, Siddiq A, Assad T, Baddar S, Jameel S, Ashraf M. Screening antiviral activity of Moringa oleifera L. leaves against foot and mouth disease virus. Global Veterinaria. 2015;15(4):409-413'},{id:"B28",body:'Shakiba Y, Rezatofighi SE, Seyyednejad SM, RoayaeiArdakani M. Inhibition of foot-and-mouth disease virus replication by hydro-alcoholic and aqueous-acetic acid extracts of Alhagi maurorum. Iranian Journal of Pharmaceutical Sciences. 2018;14(1):85-96'},{id:"B29",body:'Kambizi L, Goosen BM, Taylor MB, Afolayan AJ. Anti-viral effects of aqueous extracts of Aloe ferox and Withania somnifera on herpes simplex virus type 1 in cell culture. South African Journal of Science. 2007;103:359-360'},{id:"B30",body:'Pant M, Ambwani T, Umapathi V. Antiviral activity of Ashwagandha extract on infectious bursal disease virus replication. 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