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1. Introduction
Natural killer (NK) cells constitute a minor subset of lymphocytes that are crucial components of the innate immune system and play critical roles in host immunity against malignant cells and virus-infected cells but also in bacterial, fungal, and parasite immune responses [1]. NK cells represent 10% of the lymphocytes in human peripheral blood, and they comprise the third largest population of lymphocytes following B and T cells.
Natural killer cells have diverse biological functions including killing pathogen-infected cells and cancer cells as well as an immunoregulatory role [2]. Natural killer cells can discriminate between normal cells and cells that do not express adequate amounts of major histocompatibility complex (MHC) class I molecules.
NK cell cytotoxicity is regulated by a balance between activating and inhibitory signals delivered by receptors expressed at the cell surface. These cells are known to directly recognize and kill malignant cells or induce apoptosis. However, tumor cells have the ability to evade immunosurveillance by using multiple mechanisms. Furthermore, tumors harbor a population of cancer stem cells (CSC), which is responsible of tumor progression and therapeutical resistance.
Therapeutic applications of NK cells in cancer and NK cells targeting cancer stem cells (CSCs) represent a promising strategy for cancer immunotherapy.
2. NK cells’ biology and function
NK cells originate from common lymphoid progenitor cells and further differentiate into immature/mature NK cells in bone marrow. They are then distributed in peripheral lymphoid and nonlymphoid organs and tissues [3–5], including bone marrow, spleen, peripheral blood, placenta, lung, liver, uterus [6], and peritoneal cavity while limited numbers are localized in lymph nodes [7]. Human NK cell turnover in blood is around 2 weeks [8].
NK cells were originally described as large granular lymphocytes with natural cytotoxicity against tumor cells. NK cells were later recognized as a separate lymphocyte lineage, with both cytotoxicity and immunoregulatory role, as they are involved in the production of cytokines [9]. More recently, data revealed that activated NK cells may also influence the outcome of helminth infections. CD4-NK cells increasing early following nematode infection with Brugia pahangi are able to produce IL-4 and then could polarize the immune response toward a Th2 profile [10]. In fact, protection against helminthic infections are usually mediated by Th2 immune response characterized by secretion of IL-4, IL-5, and IL-13, secretion of IgE antibodies, and activation of mast cells [11, 12]. Studies revealed that the clearance of these parasites is more efficient and complete in the presence of NK cells. In the case of Th2 immunity disruption, NK cells may become an important source of IL-13 during murine gastrointestinal nematode infections [13, 14]. Human NK cells can be classified into two major subsets CD56dim and CD56bright depending on their immunophenotype and functions and more recently in terms of their homing properties [15, 16]. CD56dim NK cells are fully mature, make up about 90% of the NK cells in peripheral blood and inflammatory sites, and they express perforin and exhibit a high cytotoxic activity after encountering target cells [17, 18]. These CD56dim NK cells are cytotoxic and produce interferon γ (IFN-γ) upon interaction with tumor cells in vitro [19]. In contrast, CD56bright cells are more immature, make up about 5–15% of total NK cells, and have been considered primarily as cytokine producers, while playing a limited role in cytolytic responses. Approximately, 90% of NK cells in lymph nodes belong to the CD56bright subset and lack perforin [20]. These cells exert immunoregulatory function by producing abundant cytokines such as IFN-γ in response to stimulation with interleukins (IL)-12, IL-15, and IL-18 [21]. In response to nematode infection, CD56bright NK cells can bind with a secreted protein ES from the human hookworm Necator americanus and induce IFN-gamma production [22]. Natural killer cells have diverse biological functions, which include recognizing and killing pathogen-infected and cancer cells. Circulating NK cells are mostly in their resting phase, but after activation by cytokines and chemokines, they are capable of extravasation and recruitment into distinct inflamed or malignant tissues [9, 23]. NK cells also have an immunoregulatory role as their ligand interaction with cell-surface receptors lead to the production of several cytokines.
NK cells mediate two predominant pathways of cell death. The first pathway, a granule exocytosis pathway [24], involves the release of cytotoxic granule, perforin (a membrane-disrupting protein), and granzymes (a family of structurally related serine proteases) responsible for NK cell-mediated killing by inducing apoptosis of the target cell [25–27]. In the second pathway, a caspase-dependent apoptosis involves the association of death receptors such as first apoptosis signal (Fas) cell surface death receptor and tumor-necrosis-factor–related apoptosis inducing ligand receptor (TRAILR) on target cells with their corresponding ligands, members of the tumor necrosis factor (TNF) family of cytokines, expressed by NK cells, and regulated by IFN-γ, such as FASL, and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), resulting in caspase-dependent target cell apoptosis [28–32]. Antibody-dependent cellular cytotoxicity (ADCC) can also be a mechanism of killing of tumor cells by NK cells by triggering the NK CD16 receptor (FcγRIII), which binds to the IgG and antibody-coated targets [33].
Natural killer cells can discriminate between normal cells and those that do not express adequate amounts of MHC class I molecules. They were originally defined by their ability to spontaneously eliminate cells lacking expression of MHC class I molecules. NK cells express receptors that bind to MHC class I molecules including the killer cell immunoglobulin-like receptors (KIRs) that play major roles in regulating the activation thresholds of NK cells in humans [34].
3. NK cell cytotoxicity
NK cell cytotoxicity is tightly regulated by a balance between activating and inhibitory signals [35] delivered by a multitude of receptors expressed at the cell surface [36] (Figure 1). The inhibitory NK cell receptors interact with MHC class I molecules expressed on almost all nucleated cells, preventing NK cell activation against healthy cells (Figure 2a). NK cell activation is blocked through engagement of their KIR receptors [37]. This explains self-tolerance and prevention of host cell killing. NK cells can discriminate between normal host cells and infected or abnormal cells by recognition of MHC class I molecules. It was earlier discovered that NK cells are activated when they encounter cells that lack self-MHC class I molecule. For example, under stress conditions, such as cellular transformation, cells downregulate MHC-I expression causing NK cells to lose inhibitory signaling and be activated in a process called “missing-self recognition” [38]. This model is based on the fact that NK cell activity is normally controlled by self-MHC molecules that interact with a large repertoire of inhibitory NK receptors. In this condition, activation receptors are no longer suppressed and they induce potent stimulatory signals, resulting in NK cell activation including cytokine production and granule release leading to cytotoxicity [39, 40]. Abnormal cells can also upregulate the expression of ligands to activate receptors on the NK cells that can overcome the inhibitory signals.
Figure 1.
Examples of activating and inhibitory NK cell receptors and their respective ligands. AICL: activation-induced C-type lectin; B7-H6: Member of the B7 family of immunoreceptors; DNAM-1: DNAX accessory molecule 1; HLA: human leucocyte antigen; KIR2DL: killer-cell immunoglobulin-like receptor 2DL; KIR3DL: Killer-cell immunoglobulin-like receptor 3DL; KIR2D5: killer-cell immunoglobulin-like receptor 2D5; KIR3D5: killer-cell immunoglobulin-like receptor 3D5; LIR-1: leukocyte inhibitory receptor 1; MICA: MHC class I polypeptide-related sequence A; MICB: MHC class I polypeptide-related sequence B; NKG2A: natural killer group protein 2 family member A; NKG2C: natural killer group protein 2 family member C; NKp30: natural killer Cell P30-related Protein; NKp46: natural killer Cell P46-related Protein; NKp80: Natural killer Cell P80-related Protein; PD1: programmed cell death 1; PD-L1: programmed death-ligand 1; PD-L2: programmed death-ligand 2; PVR: polio virus receptor; TIGIT: T cell immunoreceptor with Ig and ITIM domains.
Figure 2.
NK cell functions. (a) Inhibitory NK cell receptors interact with MHC class I molecules expressed on nucleated cells, preventing NK cell activation and lysis against normal cells. (b) NK cells can eliminate tumors cells that downregulate major histocompatibility complex (MHC) class I molecules causing NK cells to lose inhibitory signaling and be activated in a process called “missing-self recognition.” (c) NK cells can kill tumor cells that retain full expression of MHC class I but overexpress induced stress ligands recognized by activating NK cell receptors, which override the inhibitory signals and elicit target cell lysis.
3.1. Activating NK cell receptors
NK cells require external signals to begin the process of cell activation, which usually occurs via triggering receptors. A number of receptors have been identified that allow NK cells to become activated. The major activating receptors expressed on human NK cells include the natural cytotoxicity receptors (NCRs: NKp30, NKp44, NKp46), the immunoglobulin gamma Fc-region receptor III (FcγRIII/CD16), activating forms of killer cell Ig-like receptors (KIR: KIR2DS and KIR3DS), NKG2D, C-type lectin receptors (CD94/NKG2C, NKG2E/H, and NKG2F), NKp80, and 2B4 [41]. NKG2D and NCRs are particularly important receptors for triggering NK cell responses toward tumor cells [42].
A new family of receptors that recognize nectin and nectin-like molecules has recently emerged as a critical regulator of NK cell functions — DNAX accessory molecule 1 (DNAM-1, CD226) is an adhesion molecule that controls NK cell cytotoxicity and interferon-γ production against a wide range of cancer and infected cells [43].
The B7 family member B7-H6 is a tumor cell ligand for the activating natural killer cell receptor NKp30 in humans [44]. Activating KIR receptor recognizes classical MHC-I molecules [45], whereas NKG2D recognizes the nonclassical MHC-I molecules, MICA/MICB, retinoic acid early transcript 1E protein (RAET1E), RAET1G, RAET1H, RAET1I, RAET1L, and RAET1N (also known as ULBP1–ULBP6) [46, 47]. These ligands are not present on the cell surface of most normal cells, but are upregulated at the cell surface after cellular stress, on rapidly proliferating cells, infected cells, transformed cells, and tumor cells [48], further increasing the NK cell activity [49]. CD16 binds the Fc portion of IgG antibodies to initiate antibody-dependent cellular cytotoxicity (ADCC) and provides NK cells with the ability to recognize and kill target cells coated with antibodies [50]. DNAM-1 ligands CD112 and CD155 have been described in different pathological conditions, and recent evidence indicates that their expression is regulated by cellular stress.
All of these activating receptors promote cytotoxicity and cytokine production responses through stimulating intracellular protein tyrosine kinase cascades.
3.2. Inhibitory NK cell receptors
Inhibitory receptors are able to prevent the activation of NK cells and have been thought of as fail-safe mechanisms to prevent attack on normal cells and tissues. In general, these receptors express one or more immunoreceptor tyrosine-based inhibition motifs (ITIM), and they recruit SH2-containing phosphatase-1 (SHP1), SH2-containing phosphatase-2 (SHP2), and/or SH2-containing inositol phosphatase (SHIP) proteins upon binding to their ligands [51]. These phosphatases prevent the activation of cellular signaling cascades by inhibiting phosphorylation of proteins.
The inhibitory receptors encompass two distinct classes: the monomeric type I glycoprotein of the immunoglobulin superfamilies KIR2DL and KIR3DL [51], leukocyte immunoglobulin-like receptors (ILT2), and the hetero-dimeric C-type lectin-like receptor (CTLR) called CD94/NKG2A (natural killer group protein 2 family member A) [52, 53].
4. NK cells in tumor immunosurveillance and cancer
NK cells are innate cellular components that regulate adaptive immune responses in the immune surveillance of cancer. Primary immunodeficiencies affecting NK cells were associated with higher rates of malignancy and a higher risk of developing various types of cancer [54, 55]. NK cells have been shown to control the growth and metastasis of transplantable tumors in numerous mouse models by antibody depletion of NK cells [56].
NK cells can eliminate tumors that downregulate expression of MHC class I (Figure 2b), possibly in response to selective pressure exerted by CD8+ T cells. Furthermore, NK cells can kill tumor cells that retain full expression of MHC class I if they have upregulated ligands that engage activating NK cell receptors, thus overriding the inhibitory signals (Figure 2c).
For example, NKG2D ligand expression on tumor cells induces NK cell activation and is sufficient to overcome inhibitory signals delivered by MHC class I receptors, thereby enabling NK cells to eliminate tumors expressing normal levels of MHC class I [48, 57]. Mice deficient of NKG2D (Klrk1−/−) are more susceptible to tumorigenesis [58] confirming the crucial role of NKG2D in tumor immunosurveillance.
However, tumor cells are able to evade immunosurveillance by using multiple mechanisms. Tumor cells can secrete inhibitory cytokines such as transforming growth factor-β (TGFβ) that suppresses the activity of NK cells. Furthermore, tumor cells can express inhibitory receptor-specific ligands such as glucocorticoid-induced TNFR-related protein (GITR) that can downmodulate activating receptors NKG2D on NK cells. To escape to NK cell immunosurveillance, tumor cells can also secrete immunomodulatory molecules such as prostaglandin E2 (PGE2), indoleamine 2,3-dioxygenase (IDO), adenosine, TGFβ, and interleukin-10 (IL-10). Tumor cells can proteolytically shed NKG2D ligands (NKG2DLs) leading to a decreased amount of NKG2DL and to the production of soluble ligands that downmodulate NKG2D receptor on NK cells [59, 60]. Finally, secretion of immunosuppressive molecules or expression of NKG2DLs by cells of the tumor microenvironment can downmodulate NKG2D receptor on NK cells.
Soluble NKG2DLs have been detected at high levels in the serum of cancer patients [61] and might be used as a diagnostic marker [62]. Tumor cells can escape immunosurveillance by the secretion of soluble factors such as lactate dehydrogenase, leading to NKG2DLs expression on healthy host myeloid cells [63]. NKG2D Downregulation could be the result of its chronic exposure to NKG2D ligand on tumor cells [64]. Recent work in a mouse model suggests that a shed NKG2D ligand, MULT1, stabilizes expression of NKG2D on NK cells and increase their antitumor activity [65]. Controlling NKG2DL expression level on tumors provides an attractive therapeutic strategy for immunotherapy.
In patients and animal models, impaired NK cells or NK cell deficiency have been associated not only with recurring viral infections, but also with an increased incidence of various types of cancer [55]. Tumor cells often acquire the ability to escape NK cell-mediated immune surveillance. In fact, during tumor development and progression, many malignant cells acquire the ability either to evade from NK cell recognition or to impair NK cell function.
Cells undergoing malignant transformation often downregulate their expression of MHC class I molecules, and the absence of inhibitory signaling on NK cells permits their function. A defective immunity has been well established in different types of cancer. The imbalance of immune status is inclined to immunosuppression in cancer patients, which results in tumor immune evasion. Such immunosuppression is characterized by a decrease in NK cell numbers in peripheral blood and a decreased tumor infiltrate as compared to normal tissues. Moreover, in many types of cancer, a defective expression of activating receptors and overexpression of inhibitory receptors is observed [66].
The role of NK cells against parasites that may promote or impede carcinogens is poorly understood. Chronic inflammation is a key feature in carcinogenesis associated with helminth infections. For example, Strongyloides stercoralis infection was associated with an increased occurrence of lymphoid cancers [67]. An association of colorectal cancer with chronic S. stercoralis infection has also been reported in a Columbian patient [68]. This nematode is not only a cofactor for the development of lymphoid cancers induced by HTLV-1 [69] but is also associated with the development of colon adenocarcinoma by activating the host immune response. A study reports a case of Strongyloides infection in a 72-year-old man presenting a large population of cells (NK-LGL) with a natural killer phenotype abnormally activated and diagnosed with NK-LGL leukemia [70]. The role of NK cells in the immune response to Strongyloides is not defined, but it is possible that an abnormal or clonal expansion of NK cells could suppress antihelminth immunity. Activated NK cells, perhaps producing interferon, suppressed the T-helper 2 response that previously controlled the Strongyloides infection.
5. NK cell in cancer immunotherapy
Cancer immunotherapy is the targeted therapy designed to induce antitumor response against malignancies by harnessing the power of the immune system [71]. The ability to recognize and lyse transformed cells without prior immunization, the ease of isolation and expansion ex vivo, and the shorter life span make NK cells a good alternate to immunotherapy. Furthermore, NK cell can kill cancer cells without damaging healthy tissues or risking the T cell–driven inflammatory cytokine storm that can accompany other immunotherapies. The NK cells derived from peripheral or umbilical cord cells, embryonic or induced pluripotent stem cells, and NK cell lines were being tested for treating various malignancies. Several promising clinical therapies have been used to exploit NK cell functions in treating cancer patients.
5.1. Adoptive NK cell transfer therapy
Adoptive NK cell transfer therapy is a strategy aimed at enhancing the biological function of the immune system by means of autologous or allogeneic NK cells. NK cells for adoptive NK cell transfer therapy (autologous or allogeneic) are usually obtained from the peripheral blood of the patient or from a donor. They can also be derived from the bone marrow, umbilical-cord blood, human embryonic stem cells, or induced pluripotent stem cells and are now considered as alternative sources of therapeutic NK cells [72].
Various approaches exist for the therapy with the adoptive transfer of NK cells. In autologous transfer, NK cells from the patient are activated and expanded in vitro in the presence of cytokines. IL-2 has been used for this purpose, but recently, the combination of IL-12, IL-15, and IL-18 might generate NK cells that are more functional and have memory properties. The expanded and activated NK cells are then transferred back into the patient. To sustain the expansion and function of the infused NK cells, patient receives IL2 cytokine administration. Although autologous NK cells might recognize activating signals such as stress molecules on cancer cells, their anti-tumor activity is limited by the inhibitory signal transmitted by self-HLA molecules.
In allogenic transfer, NK cells can be obtained from HLA-matched or haploidentical (partially matched) donors. The best responses are obtained when haploidentical donors do not express KIRs that recognize the patient’s HLA molecules, because donor NK cells do not receive an inhibitory signal from the patient’s cancer cells. NK cells are expanded through processes similar to those used for autologous transfer except that T cells should be removed.
5.1.1. CAR-engineered NK cells
NK cells can be transduced with activating chimeric antigen receptors (CARs) that specifically bind to antigens overexpressed by tumor cells. CARs are designed by the fusion of an antigen binding with a hinge region, a transmembrane domain and one or more stimulatory molecules. CARs can be engineered in autologous or allogeneic NK cells or in NK cell lines such as NK-92. Each CAR has the CD3ζ chain (or sometimes the FcRγ chain) as its main signaling domain. To increase persistence and superior functionality, co-stimulatory domains, usually from CD28 or CD137, can be added to the CAR construct. CARs from the first generation have no stimulatory domain, whereas CARs from the second generation and third generation have one co-stimulatory domain or two co-stimulatory domains, respectively. CAR engineering endows NK cells with antigen specificity. The binding of a CAR to the tumor antigen delivers a potent activating signal that triggers NK cell cytotoxicity, which results in the elimination of cancer cells. Several recent studies have documented a success using NK cells engineered to express activating chimeric antigen receptors (CARs) specific to tumor antigens [73]. Many B-cell acute and chronic leukemia can escape killing by natural killer cells. The introduction of chimeric antigen receptors (CAR) into T cells or NK cells could potentially overcome this resistance [74]. NK-92 leukemia cell lines were transduced to express CARs specific for CD19 [75] and CD20 [76] expressed on B cell malignancies and also for disialoganglioside GD2, a glycolipid expressed on neuroblastoma and various other cancer types [77].
In glioblastoma, the most aggressive primary brain malignancy, intracranial administration of NK-92-EGFR-CAR cells represents a promising therapy [78]. In human multiple myeloma (MM), CS1-specific (a surface protein highly expressed on MM cells) chimeric antigen receptor (CAR)-engineered natural killer cells [79] enhance responses to tumor cells in vitro and suppressed tumor growth when tested in vivo in xenograft models [65, 78, 80]. Autologous or allogeneic transplantation of CS1-specific CAR NK cells may be a promising strategy to treat multiple myeloma.
5.2. Cytokine-induced NK cell activation
To promote NK cell expansion, the use of IL-2 has demonstrated the effectiveness on NK cell activation and anti-tumor responses [81]. It was reported that NK cells from lung cancer patients could regain the cytotoxicity against targets after activation by IL-2 [82]. However, NK cells activation using high-dose IL-2 has some side effects because of severe capillary leaky syndrome. To improve the therapeutic efficacy and safety, a different strategy combining IL-2 with other NK cell activators was used. Hellstrand et al. [83] administered IL-2 together with histamine to 22 acute myeloid leukemia (AML) patients and showed a good clinical outcome. IL-2 diphtheria toxin (IL2DT), a recombinant cytotoxic fusion protein has been used in order to increase the depletion of regulatory T cells (Treg) and therefore improving in vivo donor NK cell expansion and remission induction [84].
5.3. NK cells targeting cancer stem cells
Tumor harbors a population of cancer cells with “stem-cell” like properties including self-renewal and the ability to produce differentiated progeny [85]. These cells termed cancer stem cells (CSCs) can drive tumor progression and therapeutic resistance to standard cancer therapy. In fact, cancer stem cells have been proposed as an important mechanism of tumor initiation and/or repopulation after tumor debulking by chemotherapy and/or by radiotherapy.
In addition, CSCs have been associated with tumor relapse and metastasis, even in cases of apparent complete response to systemic therapy [86]. Then, targeting CSCs is a promising strategy for cancer therapy. Natural killer cells have the ability to reject allogeneic hematopoietic stem cells, and there are increasing data demonstrating that NK cells can selectively identify and lyse CSCs. Tallerico et al. [87], for example, demonstrated that metastatic colorectal cancer, which contains a high proportion of CSCs, showed increased susceptibility to NK cytotoxicity. Similarly, Castriconi et al. [88] reported that glioblastoma-derived CSCs were susceptible to NK cell cytotoxicity. Human cancer cells with stem cell-like phenotype exhibit enhanced sensitivity to the cytotoxicity of IL-2 and IL-15 activated natural killer cells [89]. IL-2- and IL-15-activated NK cells were found to be cytotoxic against human breast cancer stem cells and CD 133+ melanoma CSCs [90]. Recently, Ames et al. [91] showed that NK cells kill CSCs from different kinds of tumors, through the interaction of the NKG2D activating receptor with its ligand (MICA/B).
6. Conclusions
NK cells have a crucial role in immunosurveillance against tumor development. However, when both the innate and adaptive immune systems fail and tumors develop, NK cells and their receptors can still be targeted in many therapeutic approaches. NK cells are more effective in treating hematologic malignancies than in treating solid tumors. This might result from inefficient homing of NK cells to the site of tumor. Therefore, NK cell-based immunotherapy can be successfully exploited in the hematopoietic stem cell transplantation for the treatment of hematological malignancies, but efforts have to be made to improve the homing and in vivo persistence of NK cells. Targeting CSCs with NK cell-based immunotherapy represents an attractive strategy for cancer therapy.
NK cells clearly have a role in future immunotherapies of the treatment of cancer and should continue to be evaluated in clinical trials.
\n',keywords:"NK cells, cancer-immunotherapy, cancer stem cells",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/57230.pdf",chapterXML:"https://mts.intechopen.com/source/xml/57230.xml",downloadPdfUrl:"/chapter/pdf-download/57230",previewPdfUrl:"/chapter/pdf-preview/57230",totalDownloads:1271,totalViews:562,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,dateSubmitted:"December 2nd 2016",dateReviewed:"September 25th 2017",datePrePublished:null,datePublished:"December 13th 2017",dateFinished:null,readingETA:"0",abstract:"Natural killer (NK) cells are crucial components of the innate immune system and play critical roles in host immunity against viral infections and cancer. NK cells’ activity is controlled by the interaction of a wide range of receptors expressed on their surfaces with cell surface ligands. Opposite signals delivered by inhibitory and activating receptors tightly regulate NK cells’ cytotoxicity. Natural killer cells can discriminate between normal and cancer cells. NK cells are known to directly recognize and kill malignant cells or induce apoptosis. However, tumor cells have the ability to evade those attacks. The main mechanisms involve the lack of expression or downregulation of the expression of major histocompatibility complex (MHC) class I molecules and secretion of soluble NKG2D ligands by tumor cells. Furthermore, tumors harbor a population of cancer stem cells (CSCs), which can drive tumor progression and therapeutical resistance. This chapter highlights the roles of NK cells in tumor immunosurveillance and their applications for cancer immunotherapy. NK cell biology and function as well as the role of their receptor interactions will be described. We will discuss the therapeutic applications of NK cells in cancer and NK cells targeting CSCs as a promising strategy for cancer therapy.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/57230",risUrl:"/chapter/ris/57230",book:{slug:"natural-killer-cells"},signatures:"Lynda Addou-Klouche",authors:[{id:"203178",title:"Dr.",name:"Lynda",middleName:null,surname:"Addou-Klouche",fullName:"Lynda Addou-Klouche",slug:"lynda-addou-klouche",email:"alsoyana@yahoo.fr",position:null,institution:{name:"Université Djillali Liabes",institutionURL:null,country:{name:"Algeria"}}}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. NK cells’ biology and function",level:"1"},{id:"sec_3",title:"3. NK cell cytotoxicity",level:"1"},{id:"sec_3_2",title:"3.1. Activating NK cell receptors",level:"2"},{id:"sec_4_2",title:"3.2. Inhibitory NK cell receptors",level:"2"},{id:"sec_6",title:"4. NK cells in tumor immunosurveillance and cancer",level:"1"},{id:"sec_7",title:"5. NK cell in cancer immunotherapy",level:"1"},{id:"sec_7_2",title:"5.1. Adoptive NK cell transfer therapy",level:"2"},{id:"sec_7_3",title:"5.1.1. CAR-engineered NK cells",level:"3"},{id:"sec_9_2",title:"5.2. Cytokine-induced NK cell activation",level:"2"},{id:"sec_10_2",title:"5.3. NK cells targeting cancer stem cells",level:"2"},{id:"sec_12",title:"6. Conclusions",level:"1"}],chapterReferences:[{id:"B1",body:'Bouzani M, Ok M, McCormick A, Ebel F, Kurzai O, Morton CO, Einsele H, Loeffler J. Human NK cells display important antifungal activity against Aspergillus fumigatus, which is directly mediated by IFN-gamma release. Journal of Immunology. 2011;187(3):1369-1376'},{id:"B2",body:'Glas R, Franksson L, Une C, Eloranta ML, Ohlén C, Orn A, et al. Recruitment and activation of natural killer (NK) cells in vivo determined by the target cell phenotype. An adaptive component of NK cell-mediated responses. 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International Immunology. 2009;21(7):793-801'},{id:"B91",body:'Ames E, Canter RJ, Grossenbacher SK, Mac S, Chen M, Smith RC, Hagino T, Perez-Cunningham J, Sckisel GD, Urayama S, Monjazeb AM, Fragoso RC, Sayers TJ, Murphy WJ. NK cells preferentially target tumor cells with a cancer stem cell phenotype. Journal of Immunology. 2015;195(8):4010-4019'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Lynda Addou-Klouche",address:"addouklouche.lynda@yahoo.fr",affiliation:'
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1. Introduction
Low-and medium-power electric drives based on brushless electric machines are widely used both in industrial applications and in special-purpose products (space, medicine, robotics). Traditionally, brushless electric machines with a radial magnetic flux are used for this purpose. This is due to the good specific energy indicators of these electric machines, well-established technology of their production [1, 2, 3, 4, 5, 6, 7].
Recently, brushless electric machines with axial magnetic flux (BMAMF) have been increasingly used for these purposes. These electric machines are actively developing, and we can talk about the formation of a new class of brushless electric drives that are competitive with traditional brushless electric drives. There is a process of transition from the design of individual products to the development of an industrial range of electric machines of this type. International and domestic practice confirms this trend [8, 9, 10, 11, 12].
The following reasons can explain the active introduction of electric machines of this class into production:
at present, the industrial production of powerful magnets with high values of residual induction and coercive force has been intensively developed, which allowed to concentrate the energy of the magnetic field in small volumes and reduce the size of electric machines;
modern development of computing tools and special software allows you to optimize the geometry of BMAMF for efficient use of the volume occupied by them. At the same time, optimally designed BMAMF under conditions of limited size can have better specific weight size and energy indicators compared to radial electric machines;
modern technologies allow to create BMAMF more economical to manufacture and reliable in operation.
It should be noted that, despite the urgent need for practical implementation, theoretical research on the analysis and synthesis of electric machines of this class is episodic and scattered. As a rule, developers analyze one design for a special drive. The results of these studies are quite difficult to transform into another constructive type. The influence of the electronic switch on the engine characteristics has not been fully studied.
Recently, there has been a tendency to increase the number of phases to improve reliability [13]. At the same time, the switching theory for multiphase BMAMF execution is not sufficiently covered in scientific publications and requires further improvement and development.
There is no unified theory for calculating electric machines of this class that would link electromagnetic power with electromagnetic loads and basic dimensions, taking into account design features.
Thus, the existing contradiction between the practical need for implementation and the insufficiently developed theory of analysis and synthesis is the main source of further development of electric machines of this class, which determines the relevance of scientific research in this area.
2. Analysis of the effect of commutation on the electromagnetic moment for any number of phases of the anchor winding for BMAMF
The winding of the brushless electric machine is connected to the power source via a commutator. Its principle of operation is as follows: when the rotor is turned, those sections of the armature winding are connected to the source, which are most profitable to pass current through from the point of view of creating an electromagnetic moment.
Switching the valve machine should be understood as connecting and disconnecting the phases of the armature winding with electronic keys to the power source. The main characteristics of the electric machine depend on the choice of switching method: moment, power consumption and useful power, efficiency, current.
The classification of the main types of switching of brushless machines is shown in Figure 1. Analog switching implements vector control of the brushless machine. Vector control is a control method that generates harmonic phase currents and controls the magnetic flux of the rotor. Currently, vector control systems are well developed in theory and implemented in practice. They have a wide range of applications, due to the development of power electronics, which allows you to create reliable and relatively cheap converters, as well as the development of high-speed microelectronics that can implement control algorithms of almost any complexity. However, it is necessary to recognize the great complexity of implementing this type of switching. For this reason, it is not considered in the work.
Figure 1.
The classification of the main types of switching of BMAMF.
In contrast to analog switching, in discrete switching, electronic keys on the inter-switching interval have only two States: on and off. Discrete switching by the nature of the current is divided into one-half-period switching, when the current in the phase sections flows in only one direction, and two-half-period switching, when the current flows in both directions.
Single-half-period switching is simple enough to implement, since it requires only one key per switched phase. However, the armature phase is connected to the source only in the zone of polarizing which creates a positive electromagnetic moment. After that, the phase is in the disconnected state without generating electromagnetic torque. To maintain the required torque, it is necessary to increase the linear load on the connected phases, which leads to increased losses and reduced efficiency. Due to the worst energy performance, Single-half-period switching is also excluded from further analysis.
Types of two-half-period switching are distinguished by the time the phase is connected in the inter-switching interval. A distinction should be made between 180-degree switching and 180-(180/m) degree switching.
In the future, we will consider 180-degree switching and 180-(180/m)-degree switching.
At present, there is a steady trend towards an increase in the number of phases of the anchor winding. This is due to the following factors:
improved energy performance, in particular efficiency;
indicators that characterize the quality of output parameters are improved, in particular, the pulsation of the electromagnetic moment is reduced;
increased reliability in case of failures of one or more phases.
Increased reliability is a determining factor when the number of phases increases.
According to the method of connecting multiphase windings to each other, three options are possible: in the “star”, in the “ring”, with independent connection (galvanically isolated phases).
If the number of phases is more than three, when connected to a “star”, the current flows only through the phases that have the highest and lowest potential on the switched keys. This reduces the power of the multiphase BMAMF.
The connection of the winding to the ring is rarely used due to the increased current through the keys. When connecting in a “star” and “ring”, it is difficult to ensure high reliability in case of phase failures.
Galvanically isolated phases require a large number of power keys (four keys per phase), but they provide the greatest reliability in case of open and short circuit failures. Taking into account the development trends of power electronics for the production of hybrid assemblies, we choose to focus on the study of this type of connection of multiphase BMAMF windings.
Thus, two-half-period (180-(180/m)-degree switching and two-half-period 180-degree switching with galvanically isolated phases are selected for further analysis.
For the selected switching types, we will carry out the further analysis.
2.1 Analysis of 180-(180/m) - degree commutation for BMAMF with any phases
To analyze the commutation, we determine the interaction of amperes-turns with the magnetic field of permanent magnets at different positions of the armature and inductor relative to each other. In this case, a trapezoidal one with an equivalent amplitude replaces the actual distribution of induction in the air gap [13].
By the pole overlap coefficient, we mean the ratio:
α=bmτ,E1
where bm- width of the pole;
τ - distance between of the neutrals.
The linear load of the phase conductors is represented as rectangles, equal in width to the phase zone, and equal in amplitude to the average linear load of the phase (Figure 2). The analysis is carried out for relative values, taking the base value of the induction amplitude and the average linear load on the average diameter of the axial machine. This representation of an electric machine for analysis should be recognized as traditional.
Figure 2.
Representation of air gap induction and linear load.
Figure 3 shows a diagram of the positions of the amperes of the turns in the inter-switching interval for the two pole divisions and the moments of connection and disconnection of the corresponding phases.
Figure 3.
The diagram for the (180–180/m)-degree commutation.
We derive the equation of the electromagnetic moment for a generalized axial machine, which is a disk with a distributed current layer that is permeated by a magnetic flux (Figure 4).
Figure 4.
Model for axial gap machine.
The equation of an elementary electromagnetic force acting on an infinitesimal section of a generalized axial machine can be written in the following form based on Ampere’s law.
dF=BdidrE2
where B – elementary section induction;
di – elementary section current;
dr – length of an elementary section.
For an elementary moment, we can write the equation
dM=rdF=Brdidr,E3
where r – radius of the elementary section location.
Imagine the induction as the product of a base value equal to the amplitude of the induction in the air gap and the relative function of the change in the induction within the pole division.
B=BδBαel,E4
where αel – angular coordinate in electrical degrees.
By analogy with induction, we express the linear load function on the average radius of the disk of a generalized axial machine depending on the pole division
Ax=AsrAiαelx,E5
where Asr - the amplitude of the linear load on the average radius of the disk.
Aiαelx – relative function of the linear load change for the i-th phase within the pole division in electrical degrees;
x– offset of the beginning of the first phase relative to the neutral.
Given that there is a relationship between geometric and electrical degrees
α=2pαel,E6
where 2p – the number of poles of a generalized axial machine.
The expression for the current of an elementary section can be written as follows
whereDsr – average ring diameter of a generalized axial machine,
Lring – ring thickness of the generalized axial machine (Figure 4).
For the basic moment value, we take the expression
Mb=p2AsrBδDsr2Lring.E10
Then the dependence of the relative moment on the displacement of the armature relative to the inductor for the i-th phase will have the form.
Mfi∗=∫0πelBαelAiαelxdαelE11
Decompose the function of induction and linear load into a harmonic series. We take into account the symmetry of the curves relative to the coordinate axes.
i – the number of the phase; m – number of phases.
The total torque of the anchor winding will be created as a sum of the phases torques (one phase is switched of)
M180−180m∗x=∑i=1m−1Mfi∗x.E17
The medium torque for this type of commutation may be described by the following formula
Msr180−180/m∗=∫0πelmM180−180/m∗xdxπelm.E18
It is possible to see from diagram 3 that different wires conductors create different torque because they take place in different magnet field conditions. The factor below can estimate the efficiency of anchor wire:
Kef180−180mαm=Msr180−180/m∗πel.E19
Let us name this factor as the efficiency factor of the anchor for (180–180/m)-degree commutation, This factor depends from pole factor and number of the phases. The curves for (180–180/m)-degree commutation (Eq. 19)) are presented in Figure 5. The curves analysis shows that it is necessary to increase pole factor and number of the phases for increasing the electromagnetic torque.
Figure 5.
The dependences of the efficiency factor of the anchor wire for (180–180/m)-degree commutation from pole factor and number of phases.
The absolute moment may be defined by the following formula
Msr180−180/m=π2AsrBδDsr2LringKef180−180m.E20
The curves analysis shows that it is necessary to increase pole factor and number of the phases for increasing the electromagnetic torque.
2.2 Analysis of 180-degree commutation for BMAMF with any phases
We will use the same harmonic analysis method for 180-degree commutation.
The diagram of the 180-degree commutation is presented in Figure 6.
Figure 6.
The diagram for the 180-degree commutation.
We may use the same formulas (Eq. (9), Eq. (12), Eq. (14)) for induction in the air gap, current load, and torque for the one phase.
For the total relative torque, we may write the following formula (all phases are switched on).
M180∗x=∑i=1mMfi∗x.E21
The medium torque
Msr180∗=∫−πel2mπel2mM180∗xdxπelm.E22
The efficiency factor of the anchor for 180-degree commutation
Kef180αm=Msr180∗πel.E23
The curves for this factor (Eq.(23)) are presented in the Figure 7.
Figure 7.
The dependences of the efficiency factor of the anchor for 180-degree commutation from pole factor and number of phases.
The absolute moment may be defined by the following formula
Msr180=π2AsrBδDsr2LringKef180.E24
We can create the same conclusion for this type of the commutation. It is necessary to increase the pole factor and number of the phases for increasing the electromagnetic torque.
Let us compere the efficiency of this type commutation. The electromagnetic torque will be the criteria for this analysis.
2.3 The compare of the (180–180/m)-degree commutation and 180- degree commutation for BMAMF with any phases
We will use the same sizes and the same current load for both types of commutation.
The ratio of the total electromagnetic torques is
Msr180Msr180−180/m=Kef180Kef180−180m.E25
Let us compere both commutations for pole factor 0.8. It is typical pole factor for brushless machine. The curve of this analysis is shown in the Figure 8.
Figure 8.
The compere of the (180–180/m)-degree commutation with the 180-degree commutation for pole factor 0.8.
The curve shows that 180-degree commutation has the advantage but for big numbers of phases this advantage is decreasing. It is possible to do this compere for another type of the pole factors and we will have the same conclusion.
We show the advantage of the 180-degree commutation with using the electromagnetic torque.
The studies have shown that to increase the efficiency of the system it is necessary to increase the number of phases and use the180-degree commutation but it is necessary to say that the cost of electronic control system will be increasing with increasing the number of phases. Therefore, the researcher has to take a mind this information when he will create the real equipment.
It should be noted that as the number of phases increase, the difference in efficiency of these type of commutation decreases too. Since the (180–180/m)-degree commutation is simpler to implement, so it can be chosen for practice.
The study can define the following results:
The electromagnetic torque will be increasing for both type commutations with increasing the number of phases.
180-degree commutation has the advantage with different phases and different pole factors if compare it with the (180–180/m)-degree commutation.
These conclusions determine the trend of increasing efficiency, but in practice, it is necessary to calculate the price for choosing the best type of commutation.
3. Analysis of electromagnetic power of various designs of the BMAMF
BMAMF have a large number of designs. Different designs in the same dimensions develop different torque and power. To compare the effectiveness of various designs, we will classify them.
3.1 Classification of various BMAMF designs
The shape of active elements that create an electromagnetic moment can classify a large number of design modifications of BMAMF. The shape of permanent magnets may be cylindrical, prismatic and segmental magnets. BMAMF phase coils can have ring, trapezoidal, wave, and toroid shapes. The combination of various permanent magnet shapes with armature winding shapes creates a variety of BMAMF designs [14, 15]. The classification of BMAMF structures is shown in Figure 9.
Figure 9.
Classification of BMAMF.
The main design versions of BMAMF active parts with various forms of magnets and coils are shown below. On their basis, it is possible to build various design modifications. Let us call these models basic. Figure 10 shows a BMAMF with cylindrical magnets and ring coils. Figure 11 shows a BMAMF with segment magnets and trapezoidal coils. Figure 12 shows a BMAMF with segment magnets and toroid coils.
Figure 10.
BMAMF with cylindrical magnets and a smooth anchor with ring coils.
Figure 11.
BMAMF with segment magnets and a smooth anchor with trapezoidal.
Figure 12.
BMAMF with segment magnets and a smooth armature with toroidal coils.
The development of computational models for the above structures has its own peculiarities. Let us output the values of the electromagnetic moment and electromagnetic power for the basic versions shown in Figure 10–13.
Figure 13.
BMAMF with segment magnets and toothed anchor.
3.2 Electromagnetic torque and electromagnetic power for BMAMF with cylindrical magnets and smooth armature with ring coils
Let us define the electromagnetic moment of the phase in the position at which it has the maximum value. This is the position at which the axis of the ring coil coincides with the geometric neutral. A sketch of the magnetic system and the armature winding is shown in Figure 14. To facilitate reference to the dependencies given below, we denote this design as model 1.
Figure 14.
Sketch of the magnetic system and armature windings BMAMF with ring armature windings.
The real value of the magnetic induction in the gap is replaced by its average value, assuming that it does not change within the pole division.
The ratio between the maximum induction and the average induction is determined by the formula
Bsr=BδSpoleSτ,E26
where Spole– surface of the pole,
Sτ– area of the pole division/.
Let us choose an arbitrary j turn with an anchor current ia. On this turn, we select an elementary conductor with length dl on the left and right sides. These elementary conductors will be affected by elementary forces, like conductors in a magnetic field, which will be directed to the center of the anchor coil. These forces can be decomposed into components on the X-axis and on the y-axis. The forces on the Y-axis will compensate for each other as equal in magnitude and opposite in direction.
The electromagnetic moment will only be created by forces directed along the x-axis. Elementary moment of the j-th turn:
where Kmod1180 – efficiency coefficient of model 1 on the number of phases for 180- degree commutation
Kmod1180=∑i=1mcos−π2+π2m+πmi−12m.E36
The graphical dependence of this coefficient on the number of phases for 180-degree switching (Eq.(36)) is shown in Figure 16.
Figure 16.
Dependence of the efficiency coefficient of model 1 on the number of phases for 180 - degree commutation.
Physical meaning of the efficiency coefficients of the model is to determine the share that the phases invest in creating the maximum moment.
Let us determine the average electromagnetic moment and electromagnetic power for the model1 BMAMF for various switching options, taking into account the efficiency coefficients derived above.
It is of theoretical interest to choose the most efficient type of switching for model 1 with the same electromagnetic loads and in the same dimensions. For quantitative evaluation, we introduce the commutation comparison coefficient as the ratio of electromagnetic powers (180–180/m) - degree commutation and 180-degree commutation:
The graphical dependence of this coefficient on the number of phases is shown in Figure 17.
Figure 17.
Dependence of the commutations comparison coefficient for model 1.
The dependence analysis shows that for model 1, 180-degree commutation has an advantage with a small number of phases. As the number of phases increases, this advantage decreases.
3.3 Electromagnetic moment and electromagnetic power for BMAMF with segment magnets and trapezoidal coils
A sketch of the magnetic system and the BAMF armature winding of this design is shown in Figure 18. Let us refer to this design as model 2.
Figure 18.
Sketch of the magnetic system and armature winding BMAMF with segment magnets and trapezoidal armature windings.
Let us select elementary conductors of length dr on an arbitrary j-turn of the winding and define elementary moments for them. They will be a function of the angular position and radius of the elementary section.
dMαr1j=dMαr2j=iaBαrdr,E42
where r – radius, where the elementary conductor is located.
The maximum moment of all phases in the intercommutation interval will depend on the pole overlap coefficient of the magnetic system, determined by equation (Eq. (1)), the number of phases, and the type of switching. Let us determine the influence of these factors on model 2. By analogy with model 1, we introduce the efficiency coefficient of model 2, which is the ratio of the maximum moment of the armature winding at the real pole overlap coefficient to the maximum moment at the theoretical pole overlap coefficient equal to 1.0. As a rule, the distance between the side faces of permanent magnets is the same on the inner and outer diameters. In this case, the pole overlap coefficient changes linearly when moving from the inner diameter to the outer one. Therefore, analytical expressions can be derived for the average diameter of a ring with magnets and further use this linear relationship.
For (180–180/m)-degree commutation, the efficiency coefficient of the model is defined by the following expression
where αsr – real coefficient of pole overlap on the average ring diameter of the magnetic system;
Mαsrm180−180mmax– maximum moment of the armature winding at the real coefficient of pole overlap;
Mαsr=1m180−180mmax– the maximum moment of the armature winding with a pole overlap coefficient equal to 1, which is only theoretically possible;
Mαsrm180−180mmax∗– relative value of the maximum moment of the armature winding at the real coefficient of pole overlap.
The relative value of the maximum moment of the armature winding can be determined from the expression (Eq. (17)) for the offset of the armature from the neutral by x=π2m (see Figure 19)
Figure 19.
Position of multiphase armature winding sections at the maximum electromagnetic moment for (180–180/m)-degree commutation.
The physical meaning of the efficiency coefficient of model 2 is similar to the coefficient for model 1. The graphical dependence of the coefficient for (180–180/m) - degree switching (Eq.(46)) is shown in Figure 20.
Figure 20.
Efficiency coefficient of model 2 for (180–180/m) - degree switching at different values of the number of phases and the coefficient of pole overlap on the average diameter of the ring of the magnetic system.
Taking into account the introduced efficiency coefficient of the model, we can write the following expression of the maximum electromagnetic moment for (180–180/m) - degree commutation
where Mαsrm180max – maximum moment of the armature winding at the real coefficient of pole overlap;
Mαsr=1m180max– maximum moment of the armature winding with a pole overlap coefficient equal to 1, which is only theoretically possible;
Mαsrm180max∗– relative value of the maximum moment of the armature winding at the real coefficient of pole overlap.
Efficiency coefficient of model 2 for 180 - degree switching at different the coefficient of pole overlap on the average diameter of the ring of the magnetic system (Eq. (51)) is shown at Figure 22. We can see that this coefficient does not depend on the number of phases.
The relative value of the maximum moment of the armature winding can be determined from the expression (Eq.(21)) for the zero offset of the armature from the neutral (see Figure 21)
Figure 21.
Position of multiphase armature winding sections at the maximum electromagnetic moment for 180-degree commutation.
Figure 22.
The efficiency coefficient of model 2 for 180-degree commutation at different values of the pole overlap coefficient on the average diameter of the ring of the magnetic system.
Mαsrm180max∗=M180max∗0=∑i=1mMfi∗0.E52
Maximum electromagnetic torque for 180-degree commutation
By analogy with the previous analysis, for quantitative evaluation, we introduce the switching comparison coefficient, as the ratio of electromagnetic powers (180–180/m) - degree commutation and 180-degree commutation:
The graphical dependence of this coefficient on the number of phases and the coefficient of the pole arc (Eq.(56)) is shown in Figure 23.
Figure 23.
Dependence of the comparison coefficient (180–180/m) - degree commutation and 180-degree commutation for model 2.
It should be noted that such a comparative analysis makes sense only for the same electromagnetic loads: induction in the air gap and linear load on the average diameter of the disk of the magnetic system.
These dependencies are of great practical importance. Their analysis shows that for the same electromagnetic loads, magnetic systems with a high value of the pole overlap coefficient have an advantage for any number of phases. Graphic dependences of the switching comparison coefficient are below 1.0. However, for magnetic systems with a pole overlap coefficient of 0.7–0.5, which is very typical for practice, the advantage is (180–180/m) - degree commutation for the number of phases starting from 3 and higher.
Given that (180–180/m) - degree commutation has a simpler and cheaper technical implementation, this theoretical conclusion is of great practical importance.
3.4 Electromagnetic moment and electromagnetic power for BMAMF with segment magnets and toroidal coils
The analysis will be carried out by analogy with the previous models. A sketch of the magnetic system and armature winding BMAMF of this design is shown in Figure 24. Let us designate this design as model 3.
Figure 24.
Sketch of the magnetic system and armature windings BMAMF with segment magnets toroidal armature windings.
Let us select an elementary conductor of length dr on an arbitrary j-th turn of the winding and determine the elementary moment for it.
dMαrj=iaBαrdr.E57
Electromagnetic moment j-th of the turn
Mαrj=∫rinroutdMαrj=2iaBαrout2−rin22.E58
Electromagnetic moment of the phase section
MαrWS=∑j=1WSdMαrj=2iaBαrout2−rin22WS.E59
Maximum value of the electromagnetic moment of an arbitrary i-th phase
Mαrfimod3=MαrWSp=2iaBαrout2−rin22WS2p.E60
By analogy with model 2, we introduce the efficiency coefficient of model 3, which is the ratio of the maximum moment of the armature winding at the real pole overlap coefficient to the maximum moment at the theoretical pole overlap coefficient equal to 1.0. It should be noted that the electromagnetic moment for model 3 is 2 times higher than the electromagnetic moment of model 1. This can be seen from the comparison of equation (Eq. (47)) and equation (Eq. (61)). From a physical point of view, this is because with the same external and internal diameters of the magnetic system, the electromagnetic moment in model 3 is created from 2 sides. We will consider this in the following equations.
For (180–180/m)-degree communication the efficiency coefficient of the model is defined by the following expression
The relative value of the maximum moment of the armature winding, which is created on one side of the working air gap, can be determined from the expression (Eq. (17)), for the displacement of the armature from the neutral poles by an amount x=π2m .
The graphical dependence of the coefficient for (180–180/m) - degree commutation is shown in Figure 25.
Figure 25.
The efficiency coefficient of model 3 for (180–180/m) - degree commutation at different values of the number of phases and the coefficient of pole overlap on the average diameter of the ring of the magnetic system.
Maximum electromagnetic torque for (180–180/m)-degree commutation
The relative value of the maximum moment of the armature winding can be determined from the expression (1.16) for the zero offset of the armature from the neutral (see Figure 21).
By analogy with model 2, the efficiency coefficient of model 3 for this type of switching will not depend on the number of phases and will be determined only by the value of the overlap coefficient on the average ring diameter of the magnetic system. The graphical dependence of this coefficient is shown in Figure 26.
Figure 26.
Model 3 efficiency coefficient for 180-degree commutation with different values of the pole overlap coefficient on the average ring diameter of the magnetic system.
Maximum electromagnetic torque for 180-degree commutation
By analogy with the previous analysis, for quantitative evaluation, we introduce the switching comparison coefficient for model 3 as the ratio of electromagnetic powers (180–180/m) - degree communication and 180-degree commutation:
Since the analytical dependences of the efficiency coefficient for model 2 and model 3 are multiples of 2, the graphical dependence of this coefficient on the number of phases for different values of the pole overlap coefficient completely coincides with the curves shown in Figure 23 for model 3, we can draw conclusions similar to those for model 2 regarding the advantages of commutations types when changing the number of phases and the pole overlap coefficient.
3.5 Electromagnetic moment and electromagnetic power for BMAMF with segment magnets and toothed anchor
The armature winding for this design can be made by analogy with a radial design (wave or loop) or toroidal. It should be noted that the windings for these three options would differ only in the shape of the frontal parts, which will only affect the calculation of active and inductive resistances. The active zone with copper (the groove-tooth zone) will be identical for all variants. Consequently, the electromagnetic processes of mutual conversion of electromagnetic and mechanical energy will also be identical. This allows you to combine all design types with a toothed anchor into one basic model. We denote it as model 4.to analyze the tooth structure, we apply a well-known technique: we place all the ampere-conductors in a uniform layer on the armature surface in the working air gap with an equivalent linear current load. The value of the induction in the gap for this model will be considered equivalent to the real induction. If this assumption is accepted, all analytical expressions, including the electromagnetic moment, electromagnetic power, and model efficiency coefficients, will be similar to the expressions for model 3.
The average electromagnetic torque and electromagnetic power for (180–180/m)-degree commutation on the basis of the above
where Kmod4180 – the efficiency coefficient of the model, determined by Figure 26.
It should be noted that, despite the analogy with model 3, the value of the average electromagnetic power and electromagnetic moment for model 4 would be approximately 4–6 times higher due to higher values of electromagnetic loads (induction in the gap and linear current load on the average armature diameter).
3.6 Comparative analysis of structures at (180–180/m) - degree commutation and 180-degree commutation
This analysis allows us to make a qualitative assessment of the effectiveness of models in terms of the development of the electromagnetic moment in the same volumes. Prong models are more efficient than models with a smooth anchor due to the large values of electromagnetic loads. For a BMAMF with a smooth anchor, due to different values of the model coefficient, we can conclude: model 2 is more efficient than model 1 and model 3 is more efficient than model 2 and, accordingly, model 1. A quantitative analysis of this efficiency is of Practical interest.
We perform this analysis using the following method: for a fixed number of phases, we determine the ratio of electromagnetic powers for different models and different switching options. For a BMAMF with a smooth armature, the value of the electromagnetic loads will be considered the same. The air gap induction value for the toothed armature is approximately 1.6 times higher than the gap induction value for the model 3 smooth armature (80% of the residual permanent magnet induction for the toothed armature and 50% for the smooth armature). Approximately the same ratio can be assumed for linear loads. These relations are confirmed by practical tests. Therefore, for a comparative analysis for model 4, you can enter an increasing coefficient of 2.56 compared to model 3. The Results are summarized in the table.
Table 1 shows a comparison of models for the variant: pole arc coefficient 0.8, number of phases 3,120-degree commutation.
Table 1.
Comparison of the efficiency of models based on the developed electromagnetic moment for 120-degree switching.
Table 2 shows a comparison of models for the variant: pole arc coefficient 0.8, number of phases 3,180-degree commutation.
Table 2.
A similar comparison for 180-degree commutation.
Tables 1 and 2 show that model 4 is the most efficient in terms of the electromagnetic moment and electromagnetic power.
These tables are convenient to use in practice for choosing the design and type of switching depending on the project.
4. Conclusion
BMAMP is a new class of electric machines. Their use is expanding for electric drives for General industrial applications and special applications in medicine, space and robotics. The theory of their analysis is not fully developed. These studies expand the possibilities of this analysis. The following main conclusions can be drawn from the presented research.
Classification of the main types of commutations is carried out. For a BMAMP with an arbitrary number of phases the discrete (180–180/m)-degree commutation and 180-degree commutation with galvanically isolated phase supply are selected.
The efficiency factor of the armature winding for various types of commutations is given. It is convenient to use this factor to compare the efficiency of commutation types.
The influence of the number of phases on the developed electromagnetic moment for (180–180/m)-degree switching and 180-degree switching is analyzed. It is proved that to increase the electromagnetic moment in the same dimensions and with the same electromagnetic loads, it is necessary to increase the number of phases and the pole arc coefficient for both types of commutation.
Classification of BMAMF designs based on the shape of permanent magnets and armature winding sections is carried out. Basic models for analysis are defined.
The resulting equation of the electromagnetic torque and electromagnetic power for base structures is given. The equations determine the dependence of energy indicators on the main dimensions, electromagnetic loads, design features, and type of commutation. Model efficiency factors are derived for all basic models.
The comparative analysis of the effectiveness of the basic models for electromagnetic power for the same dimensions and the same electromagnetic loads is carried out. The results of the analysis are summarized in tables for different types of switching and the number of phases, quantitatively showing the advantages of one design over another. Tables are convenient to use in engineering practice to select the best option depending on the project situation.
Further research will be aimed at developing methods for computer-aided design of machines of this class.
\n',keywords:"brushless electric machine, axial gap electric machine, discrete commutation, multiphase electric machine, electromagnetic moment, electromagnetic power, permanent magnet, cylindrical magnet, segment magnet, diamagnetic anchor",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/75236.pdf",chapterXML:"https://mts.intechopen.com/source/xml/75236.xml",downloadPdfUrl:"/chapter/pdf-download/75236",previewPdfUrl:"/chapter/pdf-preview/75236",totalDownloads:19,totalViews:0,totalCrossrefCites:0,dateSubmitted:"September 22nd 2020",dateReviewed:"January 11th 2021",datePrePublished:"February 14th 2021",datePublished:null,dateFinished:"February 12th 2021",readingETA:"0",abstract:"An analysis of electric machines with axial magnetic flux is given. First, the effect of commutation on the electromagnetic moment and electromagnetic power is analyzed. Two types of discrete switching are considered. The analysis is performed for an arbitrary number of phases. The first type of switching involves disabling one phase for the duration of switching. The second type of switching involves the operation of all phases in the switching interval. The influence of the pole arc and the number of phases on the electromagnetic moment and electromagnetic power is investigated. The conclusion is made about the advantage of the second type of switching. It is recommended to increase the number of phases. Next, the classification of the main structures of the axial machine is carried out. Four main versions are defined. For each variant, the equation of the electromagnetic moment and electromagnetic power is derived. This takes into account the type of commutation. The efficiency of the selected structures is analyzed. The comparative analysis is tabulated for choosing the best option. The table is convenient for engineering practice. This chapter forms the basis for computer-aided design of this class of machines.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/75236",risUrl:"/chapter/ris/75236",signatures:"Sergey Gandzha and Dmitry Gandzha",book:{id:"7658",title:"Emerging Electric Machines - Advances, Perspectives and Applications",subtitle:null,fullTitle:"Emerging Electric Machines - Advances, Perspectives and Applications",slug:null,publishedDate:null,bookSignature:"Dr. Ahmed F. Zobaa and Dr. Shady H.E. Abdel Aleem",coverURL:"https://cdn.intechopen.com/books/images_new/7658.jpg",licenceType:"CC BY 3.0",editedByType:null,editors:[{id:"39249",title:"Dr.",name:"Ahmed F.",middleName:null,surname:"Zobaa",slug:"ahmed-f.-zobaa",fullName:"Ahmed F. Zobaa"}],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. Analysis of the effect of commutation on the electromagnetic moment for any number of phases of the anchor winding for BMAMF",level:"1"},{id:"sec_2_2",title:"2.1 Analysis of 180-(180/m) - degree commutation for BMAMF with any phases",level:"2"},{id:"sec_3_2",title:"2.2 Analysis of 180-degree commutation for BMAMF with any phases",level:"2"},{id:"sec_4_2",title:"2.3 The compare of the (180–180/m)-degree commutation and 180- degree commutation for BMAMF with any phases",level:"2"},{id:"sec_6",title:"3. Analysis of electromagnetic power of various designs of the BMAMF",level:"1"},{id:"sec_6_2",title:"3.1 Classification of various BMAMF designs",level:"2"},{id:"sec_7_2",title:"3.2 Electromagnetic torque and electromagnetic power for BMAMF with cylindrical magnets and smooth armature with ring coils",level:"2"},{id:"sec_8_2",title:"3.3 Electromagnetic moment and electromagnetic power for BMAMF with segment magnets and trapezoidal coils",level:"2"},{id:"sec_9_2",title:"3.4 Electromagnetic moment and electromagnetic power for BMAMF with segment magnets and toroidal coils",level:"2"},{id:"sec_10_2",title:"3.5 Electromagnetic moment and electromagnetic power for BMAMF with segment magnets and toothed anchor",level:"2"},{id:"sec_11_2",title:"3.6 Comparative analysis of structures at (180–180/m) - degree commutation and 180-degree commutation",level:"2"},{id:"sec_13",title:"4. Conclusion",level:"1"}],chapterReferences:[{id:"B1",body:'Gandzha, S.A Application of the Ansys Electronics Desktop Software Package for Analysis of Claw-Pole Synchronous Motor / S.A. Gandzha, B.I. Kosimov, D.S. Aminov //Machines.–2019.–Vol. 7 No. 4 https://ieeexplore.ieee.org/document/8570132 DOI:10.1109/GloSIC.2018.8570132'},{id:"B2",body:'Gandzha, S. Selecting Optimal Design of Electric Motor of Pilgrim Mill Drive for Manufacturing Techniques Seamless Pipe / S.. Gandzha, B.. Kosimov, D.. Aminov //2019 International Conference on Industrial Engineering, Applications and Manufacturing, ICIEAM 2019.–2019 https://ieeexplore.ieee.org/document/8742941 DOI: 10.1109/ICIEAM.2019.8742941'},{id:"B3",body:'I.E. Kiessh, S.A. Gandzha, “Application of Brushless Machines with Combine Excitation for a Small and Medium Power Windmills”, Procedia Engineering.– 2016.–Vol. 129.– P.191–194, DOI: 10.1016/j.proeng.2016.12.031 https://www.sciencedirect.com/science/article/pii/S1877705815039156?via%3Dihub'},{id:"B4",body:'Gandzha, S., Andrey, S., Andrey, M., Kiessh, I. The design of the low-speed brushless motor for the winch which operates in see-water . International Multidisciplinary Scientific GeoConference Surveying Geology and Mining Ecology Management, SGEM'},{id:"B5",body:'Gandzha, S. The application of the double-fed alternator for the solving of the wind power problems . International Multidisciplinary Scientific GeoConference Surveying Geology and Mining Ecology Management, SGEM'},{id:"B6",body:'Gandzha S.A., Sogrin A.I.,Kiessh I.E. The Comparative Analysis of Permanent Magnet Electric Machines with Integer and Fractional Number of Slots per Pole and Phase. Procedia Engineering 129:408–414, December 2015.'},{id:"B7",body:'Gandzha S., Aminov D., Bakhtiyor K. Application of the combined excitation submersible hydrogenerator as an alternative energy source for small and medium rivers. IEEE Russian Workshop on Power Engineering and Automation of Metallurgy Industry. 4–5 Oct. 2019 Magnitogorsk, Russia. DOI: 10.1109/PEAMI.2019.8915294'},{id:"B8",body:'Aydin, M. S. Huang and T. A. Lipo. “Axial Flux Permanent Magnet Disc Machines: A Review”, In Conf. Record of SPEEDAM, , May 2004, pp. 61–71'},{id:"B9",body:'Akatsu K. and Wakui S. “A comparison between axial and radial flux PM motor by optimum design method from the required NTcharacteristics", Conference Proceeding of ICEM2004, No. 361, Cracow-Poland, 2004.'},{id:"B10",body:'Gandzha, S., Kiessh, I. The high-speed axial gap electric alternator is the best solution for a gas turbine engine . The high-speed axial gap electric alternator is the best solution for a gas turbine engine . International Multidisciplinary Scientific GeoConference Surveying Geology and Mining Ecology Management, SGEM .'},{id:"B11",body:'Gandzha, S. Development of engineering technique for calculating magnet systems with permanent magnets / S.. Gandzha, .E. Kiessh, D.S. Aminov //Proceedings - 2018 International Conference on Industrial Engineering, Applications and Manufacturing, ICIEAM 2018.–2018 No. 10.15593/2224-9397/2019.1.04 https://ieeexplore.ieee.org/document/8728650 DOI:10.1109/ICIEAM.2018.8728650'},{id:"B12",body:'Gandzha S., Bakhtiyor K., Aminov D. Development of a system of multi-level optimization for Brushless Direct Current Electric Machines. International Ural Conference on Electrical Power Engineering (Ural Con) 2019. 1–3 Oct. 2019 Chelyabinsk, Russia. DOI: 10.1109/URALCON.2019.8877650'},{id:"B13",body:'Gandzha, S., Kiessh, I. Selection of winding commutation for axial gap machines with any phases . Proceedings - 2018 International Conference on Industrial Engineering, Applications and Manufacturing, ICIEAM 2018'},{id:"B14",body:'Gandzha S.A. Application of Digital Twins Technology for Analysis of Brushless Electric Machines with Axial Magnetic Flux / Gandzha, S. //Proceedings - 2018 Global Smart Industry Conference, GloSIC 2018.–2018 https://ieeexplore.ieee.org/document/8570132 DOI:10.1109/GloSIC.2018.8570132'},{id:"B15",body:'Gandzha, S. Design of Brushless Electric Machine with Axial Magnetic Flux Based on the Use of Nomograms / S.. Gandzha, D.. Aminov, B.. Kosimov //Proceedings - 2018 International Ural Conference on Green Energy, UralCon 2018.–2018.– P.282–287 https://ieeexplore.ieee.org/document/8544320 DOI: 10.1109/URALCON.2018.8544320'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Sergey Gandzha",address:"gandzhasa@susu.ru",affiliation:'
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The Open Access model is applied to all of our publications and is designed to eliminate subscriptions and pay-per-view fees. This approach ensures free, immediate access to full text versions of your research.
As a gold Open Access publisher, an Open Access Publishing Fee is payable on acceptance following peer review of the manuscript. In return, we provide high quality publishing services and exclusive benefits for all contributors. IntechOpen is the trusted publishing partner of over 118,000 international scientists and researchers.
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*These prices do not include Value-Added Tax (VAT). Residents of European Union countries need to add VAT based on the specific rate in their country of residence. Institutions and companies registered as VAT taxable entities in their own EU member state will not pay VAT as long as provision of the VAT registration number is made during the application process. This is made possible by the EU reverse charge method.
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Services included are:
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English language copyediting and proofreading, including the correction of grammatical, spelling, and other common errors
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XML Typesetting and pagination - web (PDF, HTML) and print files preparation
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Discoverability - electronic citation and linking via DOI
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Permanent and unrestricted online access to your work
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\\n\\t
Exceeds 20 pages (for chapters in Edited Volumes), an additional fee of 40 GBP per page will be required
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If a manuscript requires Heavy Editing or Language Polishing, this will incur additional fees.
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Your Author Service Manager will inform you of any items not covered by the OAPF and provide exact information regarding those additional costs before proceeding.
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Open Access Funding
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To explore funding opportunities and learn more about how you can finance your IntechOpen publication, go to our Open Access Funding page. IntechOpen offers expert assistance to all of its Authors. We can support you in approaching funding bodies and institutions in relation to publishing fees by providing information about compliance with the Open Access policies of your funder or institution. We can also assist with communicating the benefits of Open Access in order to support and strengthen your funding request and provide personal guidance through your application process. You can contact us at oapf@intechopen.com for further details or assistance.
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For Authors who are still unable to obtain funding from their institutions or research funding bodies for individual projects, IntechOpen does offer the possibility of applying for a Waiver to offset some or all processing feed. Details regarding our Waiver Policy can be found here.
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Added Value of Publishing with IntechOpen
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Indexing and listing across major repositories, see details ...
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Long-term archiving
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Dissemination and Promotion
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Benefits of Publishing with IntechOpen
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Proven world leader in Open Access book publishing with over 10 years experience
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+146,150 citations in Web of Science databases
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Currently strongest OA platform with over 130 million downloads
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The Open Access Publishing Fee (OAPF) is payable only after your full chapter, monograph or Compacts monograph is accepted for publication.
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OAPF Publishing Options
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1,400 GBP Chapter - Edited Volume
\n\t
10,000 GBP Monograph - Long Form
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4,000 GBP Compacts Monograph - Short Form
\n
\n\n
*These prices do not include Value-Added Tax (VAT). Residents of European Union countries need to add VAT based on the specific rate in their country of residence. Institutions and companies registered as VAT taxable entities in their own EU member state will not pay VAT as long as provision of the VAT registration number is made during the application process. This is made possible by the EU reverse charge method.
\n\n
Services included are:
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An online manuscript tracking system to facilitate your work
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Personal contact and support throughout the publishing process from your dedicated Author Service Manager
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Assurance that your manuscript meets the highest publishing standards
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English language copyediting and proofreading, including the correction of grammatical, spelling, and other common errors
\n\t
XML Typesetting and pagination - web (PDF, HTML) and print files preparation
\n\t
Discoverability - electronic citation and linking via DOI
\n\t
Permanent and unrestricted online access to your work
What isn't covered by the Open Access Publishing Fee?
\n\n
If your manuscript:
\n\n
\n\t
Exceeds 20 pages (for chapters in Edited Volumes), an additional fee of 40 GBP per page will be required
\n\t
If a manuscript requires Heavy Editing or Language Polishing, this will incur additional fees.
\n
\n\n
Your Author Service Manager will inform you of any items not covered by the OAPF and provide exact information regarding those additional costs before proceeding.
\n\n
Open Access Funding
\n\n
To explore funding opportunities and learn more about how you can finance your IntechOpen publication, go to our Open Access Funding page. IntechOpen offers expert assistance to all of its Authors. We can support you in approaching funding bodies and institutions in relation to publishing fees by providing information about compliance with the Open Access policies of your funder or institution. We can also assist with communicating the benefits of Open Access in order to support and strengthen your funding request and provide personal guidance through your application process. You can contact us at oapf@intechopen.com for further details or assistance.
\n\n
For Authors who are still unable to obtain funding from their institutions or research funding bodies for individual projects, IntechOpen does offer the possibility of applying for a Waiver to offset some or all processing feed. Details regarding our Waiver Policy can be found here.
\n\n
Added Value of Publishing with IntechOpen
\n\n
Choosing to publish with IntechOpen ensures the following benefits:
\n\n
\n\t
Indexing and listing across major repositories, see details ...
\n\t
Long-term archiving
\n\t
Visibility on the world's strongest OA platform
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Live Performance Metrics to track readership and the impact of your chapter
\n\t
Dissemination and Promotion
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Benefits of Publishing with IntechOpen
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Proven world leader in Open Access book publishing with over 10 years experience
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+4,800 OA books published
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Most competitive prices in the market
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Fully compliant with OA funding requirements
\n\t
Optimized processes, enabling publication between 8 and 12 months
\n\t
Personal support during every step of the publication process
\n\t
+146,150 citations in Web of Science databases
\n\t
Currently strongest OA platform with over 130 million downloads
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