\r\n\tAs the subject of adhesives is in constant development, this book's purpose is to get together information about adhesives science and technology, recent advances, and applications that use adhesive technology. Also, to make these contents available to engineering students, engineers, researchers, and the people interested in this topic. The book is expected to present works that aim to contribute to the development of new technologies and the use of non-traditional materials in engineering.
",isbn:"978-1-83880-670-5",printIsbn:"978-1-83880-669-9",pdfIsbn:"978-1-83880-671-2",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,isSalesforceBook:!1,isNomenclature:!1,hash:"c58b7d4c17e2a202af1dc4b906b7becb",bookSignature:"Prof. António Bastos Pereira and Dr. Alexandre Luiz Pereira",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11819.jpg",keywords:"The Technology of the Adhesives, Recent Advances, New Perspectives, Structural Adhesives Bonding, Durability of Structural Adhesives, New Applications, Repair of Composites, Bonding of Composites, Experimental Mechanics Tests, Thermal Analysis, Finite Element Method, Numerical Analysis.",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"April 15th 2022",dateEndSecondStepPublish:"May 13th 2022",dateEndThirdStepPublish:"July 12th 2022",dateEndFourthStepPublish:"September 30th 2022",dateEndFifthStepPublish:"November 29th 2022",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"12 days",secondStepPassed:!0,areRegistrationsClosed:!1,currentStepOfPublishingProcess:3,editedByType:null,kuFlag:!1,biosketch:"Dr. António Pereira is a professor and researcher, who graduated from the University of Porto, and gained experience as an engineer working at Renault, with an h-index of 23, and more than 1500 citations for 70 papers published in SCI journals.",coeditorOneBiosketch:"An active researcher in Solid Mechanics, Dr. Alexandre Luiz Pereira holds a degree in Mathematics from the State University of Rio de Janeiro, and a degree in Mechanical Engineering from the Fluminense Federal University in Brazil.",coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"211131",title:"Prof.",name:"António",middleName:"Bastos",surname:"Pereira",slug:"antonio-pereira",fullName:"António Pereira",profilePictureURL:"https://mts.intechopen.com/storage/users/211131/images/system/211131.png",biography:"Founding shareholder and Director of Martifer Group (ca. 3500 employees) (1990-1999) - was responsible for the planning and production of about 500 steel structures and industrial equipment with a total amount exceeding 100 million euros.\nAssistant Professor at the Department of Mechanical Engineering, University of Aveiro, since 2000. Board Member and Member of the Executive Committee at the Department of Mechanical Engineering, University of Aveiro (2011 – 2015), currently Director of TEMA - Centre for Mechanical Technology and Automation.\nHis main research area has been mechanics of composite materials, with particular emphasis on delamination fracture mechanics. He has published 44 papers in SCI journals and has delivered 30 presentations at international conferences. 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1. Introduction
An ectopic pregnancy (EP) refers to the implantation of a pregnancy outside of the uterus cavity. The overall rate of EP is 1–2% in the general population and 2–5% among patients who have utilized assisted reproductive technology (ART) [1, 2]. Up to 98% of ectopic pregnancies occur in the fallopian tubes. Non-tubal ectopic pregnancies are rare, accounting for 7–10% of all ectopic pregnancies and occurring outside the uterus and tubes [3, 4], yet are associated with higher morbidity due to their late presentation and diagnostic difficulties [5, 6, 7, 8]. There are six main locations for non-tubal ectopic pregnancies that are cervical, interstitial, cornual, ovarian, Cesarean scar, and abdominal. The main risk factors for non-tubal pregnancy include previous ectopic, history of assisted reproduction, pelvic infections, smoking, and the use of the progesterone only pill or intrauterine device [9]. Early diagnosis and treatment of patients are associated with decreased morbidity and mortality in non-tubal pregnancy and, very importantly, preserve the uterus and subsequent fertility.
2. Cervical ectopic pregnancy
Cervical pregnancies are rare accounting for less than 1% of all ectopic pregnancies, and the incidence is 1:2500–18,000 [3, 4, 9]. They result due to the risk of trophoblast penetration through the mucosa of cervical wall into the uterine vessels. Cervical ectopics may arise should the blastocyst pass through the uterine cavity and implant into the mucosa of the endocervical canal [10, 11, 12, 13]. Almost 70% of cases with subsequent cervical EP have a history of dilation and curettage (D&C) in a previous pregnancy [12, 14]. Also in vitro fertilization (IVF) seems as a risk factor but often jointly with D&C and other possible risk factors; anatomic anomalies (myomas, synechiae), intrauterine device (IUD) use, and diethylstilbestrol exposure, although these are not strong associations, are difficult to isolate as an independent contributor to risk [15].
Vaginal bleeding without pain is the most common presenting symptom but in more advanced pregnancies may be coupled with abdominal pain and urinary problems. Examination findings include an enlarged, globular, or distended cervix, which is often associated with dilatation of the external os [12].
Before 1979, cervical pregnancy was almost always associated with hysterectomy because of out-of-control vaginal bleeding, and the primary diagnosis was made by histological analysis of the hysterectomized uterus [16]. Preoperative diagnosis was rarely possible. After the first ultrasound report of cervical pregnancy was published by Raskin in 1978, transvaginal ultrasonography has become the main diagnostic tool [17]. This put forward more conservative approaches that attempt to limit morbidity and preserve fertility. The majority of patients with a cervical pregnancy are women with low parity; thus, preservation of reproductive function is a priority [12].
Cervical pregnancy may appear as a hemorrhagic mass, gestational sac, or presence of a fetus (with or without cardiac activity) on TvUSG [10, 12]. Defined sonographic criteria are shown in Table 1. A cervical EP is identified on ultrasound by a distended cervical canal containing a gestational sac (Figure 1), below a closed internal cervical os [19, 20], misdiagnosed as an intrauterine pregnancy with a low implantation site or a failed pregnancy imminent abortion. The “sliding sign” involves the sliding of the products of conception against the endocervical canal when gentle pressure by the sonographer during transvaginal ultrasound associated with spontaneous abortions in progress and should be absent in a cervical ectopic pregnancy [5, 6, 9].
Table 1.
Sonagraphic criteria for cervical pregnancy.
Figure 1.
Cervical ectopic pregnancy [18].
The treatment for cervical ectopic pregnancy is unclear. İf gestation is <12 weeks, with no fetal heart present and lower-serum hCG values, conservative management is most effective in women wishing to preserve fertility [21, 22].
Single- or multiple-dose systemic methotrexate (MTX) efficacy is 91%, reported in a meta-analysis [21]. MTX is more successful in pregnancies <9 weeks and with beta hCG levels <10,000 mIU/mL, CRL <10 mm, and absent fetal cardiac activity [9, 23]. The folic acid antagonist methotrexate is the most widely used systemic chemotherapy.
In cervical pregnancy with embryonic heart activity, the treatment of choice is local injection of methotrexate or potassium chloride by ultrasound-guided injection [24].
İn the treatment of cervical ectopic pregnancy, uterine artery ligation, uterine artery embolization, balloon tamponade, cervical curettage, cerclage, cervical stay sutures, and injection of prostaglandin F2a can be combined to control hemorrhage [3, 7, 10, 25].
Medical management must only be suggested if the patient is hemodynamically stable; otherwise, surgical treatment should be attempted as dilatation and evacuation, hysteroscopic resection, and hysterectomy.
3. Interstitial ectopic pregnancy
The incidence of interstitial pregnancy is 1–11% of all ectopic pregnancies. It has a high complication and maternal mortality rate, approximately 20% of all deaths caused by ectopic pregnancies [3, 4, 5]. The pregnancy implants at the junction of the interstitial part of the fallopian tube and the uterine myometrium. The main risk factor for interstitial implantation is prior ipsilateral salpingectomy; a residual “stump” of tube may form the focus of ectopic pregnancy development [26]. Symptoms are amenorrhea or spotting with or without abdominal pain.
Diagnostic criteria by ultrasound include:
Myometrial tissue <5 mm thick surrounded by gestational sac [26] (Figure 2).
An echogenic line between the gestational sac in the cornua and endometrial cavity named “interstitial line” has a sensitivity of 80% and specificity of 98% [4, 5, 6, 28] (Figure 3).
Empty uterine cavity and gestational sac located in the interstitial portion of the tube, >1 cm far away from cavity [4, 6, 29].
Figure 2.
Empty uterine cavity and gestational sac located in the interstitial portion of the tube, >1 cm far away from cavity [27].
Figure 3.
“Interstitial line” [27].
Conservative management may be appropriate in patients who are hemodynamically stable without rupture and with a low or falling beta hCG but carries a risk of uterine rupture due to the weakened myometrial wall [4]. Medical management is to use of methotrexate either given systemically or by local injections. Single- or multiple-dose methotrexate regimens have success rates between 66 and 100% [9]. There is risk of failure due to increased vascularity, higher beta hCGs, and larger gestational sacs, so patient selection must be critical. Using systemic methotrexate in combination with gefitinib (oral epidermal growth factor receptor inhibitor) may be an alternative therapy [30].
Surgical treatment is indicated when medical management failure, according to patient preference, or if there is hemodynamic instability, severe hemorrhage, and/or findings concerning rupture, including pain or imaging evidence of hemoperitoneum. Minimally invasive surgeries are cornuostomy, salpingostomy, and cornual resection for earlier diagnosis. Cornuostomy (entails a linear incision, following the injection of dilute vasopressin at the cornua to minimize blood loss), cornual resection, or salpingostomy is being used for smaller interstitial ectopic pregnancies measuring <3.5 cm [31, 32]. Cornual resection has been recommended for advanced management of more interstitial pregnancies >3.5 cm [33, 34]. Laparotomy and hysterectomy are still the first-line treatment in patients with hemodynamic instability and severe hemorrhage. Selective uterine artery embolization can be used in conjunction with methotrexate in order to reduce hemorrhage, but there are concerns about the safety and complications of future pregnancies after this technique [35, 36].
4. Cornual ectopic pregnancy
Cornual pregnancies are one of the rare forms of ectopic pregnancy at 0.2–2% and occur in a cornua of a bicornuate uterus, in an rudimentary horn, in a unicornuate uterus, and/or in a septate uterus [37]. Cornual and interstitial pregnancies are often referred to interchangeably, but the following criteria can be used to diagnose cornual pregnancy on ultrasound examination [38]:
A single interstitial portion of fallopian tube in the main uterine body.
A mobile gestational sac surrounded by myometrium and separate from the uterus.
Gestational sac adjoining to the unicornuate uterus with a vascular pedicle.
Methotrexate is generally ineffective due to late diagnosis. Surgery is the main management for cornual ectopic pregnancies that includes myomectomy for an unruptured ectopic, laparoscopic cornuotomy, cornual resection, or excision of the rudimentary horn [4, 39, 40, 41]. Laparotomy and hysterectomy may prove necessary due to hemorrhage or large cornual ectopics. Elective Cesarean section is widely recommended in subsequent pregnancies because of risk of uterine rupture.
5. Ovarian ectopic pregnancy
Ovarian ectopic pregnancy accounts for 3% of all ectopic pregnancies [42]. Previous pelvic inflammatory disease, endometriosis, and assisted reproductive technologies seem as risk factors [43, 44, 45, 46, 47]. İnterference in the release of the ovum from the ruptured follicle, tubal malfunction, and inflammatory thickening of the tunica albuginea are suggested etiologies [48]; however, ovarian ectopic pregnancies have been reported in patients lacking fallopian tubes [49]. Usually symptoms present with abdominal pain and light vaginal spotting. Diagnosis can be difficult to differentiate from a hemorrhagic or corpus luteal cyst or indeed a tubal ectopic.
Diagnostic criteria described by Spiegelberg [50] (Figure 4):
Completely intact fallopian tubes.
Anatomically gestational sac located in the normal position at the ovary.
Both ovary and gestational sac connected to the uterus by ovarian ligament.
Placental trophoblastic tissue attached to the ovarian cortex.
Figure 4.
Ovarian ectopic pregnancy [51].
Also ovarian EPs may be suspected by ultrasound when a hypoechogenic area is seen with peripheral Doppler flow surrounded by a wide echogenic ring and may be completely surrounded by ovarian cortex, and a fetal pole is rarely present [38, 43].
Management is most commonly surgical, and little data is available on the medical management of this condition with systemic MTX either single- or multiple-dose regimens [2]. Fifty milligrams of MTX injections directly into the ovarian EP with transvaginal or laparoscopically have also been reported as a successful management [52, 53]. MTX may also be used in the treatment of persistent trophoblastic tissue after laparoscopy [45]. Partial or total oophorectomy or ovarian wedge resection with laparoscopic surgery has become the standard for management of hemodynamically stable patients [7, 9]. Conservative resection (wedge resection) is performed in patients who want to preserve their fertility.
6. Abdominal ectopic pregnancy
The rarest form of ectopic pregnancies is at 0.9–1.4% and relates to implantation at sites throughout the abdomen including omentum; organs such as the liver, spleen, and bowel; large vessels; pelvic cul-de-sac; broad ligament; and pelvic side wall [4, 28, 54, 55, 56]. Abdominal ectopic pregnancy can be defined as primary or secondary; when the fimbrial end does not ‘pick up’ the ovulated follicle is primary type, tubal abortion via the fimbria and peritoneal implantation related with secondary abdominal ectopics [4, 28]. Risk factors are similar to tubal ectopic prior history of a medically treated ectopic, previous pelvic inflammatory disease, prior surgery, endometriosis, and assisted conception. Abdominal ectopic pregnancies have been described after ART, specifically after IUI [57], after IVF [58], and after Clomid [59]. Symptoms include abdominal pain, painful fetal movements, vaginal bleeding, nausea, and vomiting. Abdominal X-ray, ultrasound, or diagnostic laparoscopy are used to diagnose, although MRI may be beneficial. İn several case reports, diagnosis is only made at Cesarean section [60].
Diagnostic ultrasound criteria have been suggested by Gerli et al. [61]:
Absence of an intrauterine gestation sac.
Absence of tube and a complex adnexal mass.
Gestational cavity surrounded by loops of bowel and separated by peritoneum.
Wide mobility similar to fluctuation of the sac with pressure of the transvaginal probe toward the posterior cul-de-sac.
Laparotomy and delivery with removal of the fetus with or without placental tissue are the traditional management [62]. The maternal mortality rate is eight times higher than for any other ectopic pregnancies [63, 64]. Expectant management suggested at rare reports orders to attain a live birth. If abdominal pregnancy is diagnosed after the twentieth week of gestation, expectant management can be considered with close follow-up at a tertiary health care facility. Delivery is recommended at 34 weeks if fetus has no congenital malformations, and placenta which implanted away from upper abdomen is often left in place to avoid the risk for hemorrhage [65, 66]. A few case reports have described subsequent methotrexate treatment and ultrasound-guided injection of potassium chloride [4] or radiological artery embolization to minimize blood loss before leaving placental tissue behind [28, 56, 67, 68, 69].
7. Cesarean scar pregnancy
Cesarean scar pregnancies are extremely rare, 1:2226 of all pregnancies and 6% of all ectopic pregnancies in women who have undergone at least one previous Cesarean section [4]. Scar pregnancies may be presented with painless vaginal bleeding and also associated with significant rates of uterine rupture and major hemorrhage, uterine rupture, and hypovolemic shock [50]. Risk factors include previous Cesarean, myomectomy, dilatation and curettage, adenomyosis, IVF, and manual removal of the placenta [28, 70]. The suggested theory of pathogenesis is the blastocyst enters a microscopic tract in the uterine scar and implants in the deficient uterine wall. The impact of the number of previous Cesarean sections, the time interval between Cesarean sections, and the rate of scar implantation are unclear [71, 72, 73]. With increasing rates of Cesarean section and repeated Cesarean sections, the scar surface area is getting bigger and is increasingly deficient due to fibrosis, poor vascularity, and postoperative healing, thereby leading to higher rates of blastocyst implantation [72]. Although it is suggested to use ultrasound with Doppler, hysteroscopy, and MRI to diagnose and differentiate Cesarean scar from cervical ectopic pregnancies, transvaginal ultrasound is the first-line approach [50].
Ultrasound diagnostic criteria by Jurkovic et al. [74]:
An empty uterine cavity without contact with the sac.
Gestational sac located anteriorly at the level of the internal os covering the visible or presumed site of the previous lower uterine segment of the prior hysterotomy (Figure 5).
The myometrium must be very thin (1–3 mm) or absent between the bladder and sac (Figure 6).
A negative “sliding organ sign” and the presence of peripheral Doppler flow.
Figure 5.
Caesarean scar pregnancy [75].
Figure 6.
Myometrial thickness of scar pregnancy [76].
There is no definitive consensus of treatment, yet first-trimester termination is recommended to prevent uterine rupture, major hemorrhage, life-threatening complications, and maternal morbidity and preserve future fertility. Term births are associated with hemorrhage and emergent cesarean hysterectomy [74, 77, 78]. Systemic methotrexate can be used in hemodynamically stable patients with an unruptured scar pregnancy, <8 gestation weeks, and a myometrial thickness of <2 mm between the pregnancy and the bladder and more successful if beta hCG level is <5000 IU/L [74]. Local potassium chloride, bilateral uterine artery injection of methotrexate combined with embolization, and combination of gefitinib and systemic methotrexate have been described [4, 30]. Surgical approaches are uterine curettage, resection or excision with hysteroscopy, laparoscopy or laparotomy. Curettage is an accepted treatment under ultrasound guidance following chemotherapy, but it should not be performed as a first-line treatment because of complication with hemorrhage. Resection allows for revision of the lower uterine segment, which theoretically may reduce risk for recurrence [79]. Hysteroscopic resection is not recommended when the residual myometrium is less than 3 mm, given the risk of anterior wall perforation and bladder injury [80, 81]. Hysterectomy may be required for uterine rupture or more advanced pregnancies [4].
8. Conclusion
Non-tubal ectopic pregnancies are rare but can be a life-threatening condition due to late diagnosis. Earlier diagnosis and treatment of patients are associated with decreased morbidity and mortality in non-tubal pregnancy and, very importantly, preserve the uterus and subsequent fertility [28]. Clinicians should have a high index of suspicion in patients presenting with pain and bleeding in pregnancy and take careful note of their previous obstetric and gynecology history to identify key risk factors for ectopic pregnancy. Ultrasound criteria now exist for all non-tubal ectopic pregnancies, facilitating early diagnosis and giving the patient options for management. It seems reasonable therefore to treat these pregnancies with a combination of local or systemic chemotherapy and/or surgical removal. Increased experiences have led to choose the best way to manage non-tubal pregnancies and develop new techniques.
\n',keywords:"non-tubal ectopic pregnancy, methotrexate, cervical, interstitial, cornual, ovarian, caesarean ectopic",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/69498.pdf",chapterXML:"https://mts.intechopen.com/source/xml/69498.xml",downloadPdfUrl:"/chapter/pdf-download/69498",previewPdfUrl:"/chapter/pdf-preview/69498",totalDownloads:1094,totalViews:0,totalCrossrefCites:0,totalDimensionsCites:0,totalAltmetricsMentions:0,impactScore:0,impactScorePercentile:45,impactScoreQuartile:2,hasAltmetrics:0,dateSubmitted:"May 13th 2019",dateReviewed:"June 10th 2019",datePrePublished:"October 11th 2019",datePublished:"March 25th 2020",dateFinished:"October 10th 2019",readingETA:"0",abstract:"Ectopic pregnancies occur at 1–2% of all pregnancies. The most common implantation site is the fallopian tube with 95, and 5% are non-tubal located. The aim of this review is to determine the current state of data about the diagnosis and the treatment of non-tubal ectopic pregnancies. Literature is reviewed concerning cervical, interstitial, cornual, ovarian, Caesarean scar, and abdominal ectopic pregnancies from PubMed databases. Non-tubal ectopic pregnancies are often misdiagnosed and overlooked. Clinical symptoms and ultrasound must be combinated to diagnose. Management may involve medical treatment with methotrexate or surgery or a combination according to patient’s clinical stability and the location of ectopic pregnancy. Non-tubal ectopic pregnancies are rare but can be a life-threatening condition due to late diagnosis. Early diagnosis and treatment of patients are associated with decreased morbidity and mortality in non-tubal pregnancy and, very importantly, preserve the uterus and subsequent fertility. İncreased experiences have led to choose the best way to manage non-tubal pregnancies and develop new techniques.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/69498",risUrl:"/chapter/ris/69498",book:{id:"8484",slug:"non-tubal-ectopic-pregnancy"},signatures:"Aliye Nigar Serin and Özer Birge",authors:[{id:"301412",title:"Dr.",name:"Ozer",middleName:null,surname:"Birge",fullName:"Ozer Birge",slug:"ozer-birge",email:"ozbirge@gmail.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"301413",title:"Dr.",name:"Aliye Nigar",middleName:null,surname:"Serin",fullName:"Aliye Nigar Serin",slug:"aliye-nigar-serin",email:"nserin85@hotmail.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"Osmaniye Korkut Ata University",institutionURL:null,country:{name:"Turkey"}}}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Cervical ectopic pregnancy",level:"1"},{id:"sec_3",title:"3. Interstitial ectopic pregnancy",level:"1"},{id:"sec_4",title:"4. Cornual ectopic pregnancy",level:"1"},{id:"sec_5",title:"5. Ovarian ectopic pregnancy",level:"1"},{id:"sec_6",title:"6. Abdominal ectopic pregnancy",level:"1"},{id:"sec_7",title:"7. Cesarean scar pregnancy",level:"1"},{id:"sec_8",title:"8. Conclusion",level:"1"}],chapterReferences:[{id:"B1",body:'Barnhart K. Ectopic pregnancy. The New England Journal of Medicine. 2009;361:379-387'},{id:"B2",body:'Practice Committee of the American Society for Reproductive Medicine. Medical treatment of ectopic pregnancy: A committee opinion. Fertility and Sterility. 2013;100:638-644'},{id:"B3",body:'Cecchino GN, Junior EA. Methotrexate for ectopic pregnancy: When and how. Archives of Gynecology and Obstetrics. 2014;290:417-423'},{id:"B4",body:'Shen L, Fu J, Huang W, Zhu H, Wang Q , Yang S, et al. Interventions for non-tubal ectopic pregnancy. 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Fertility and Sterility. 2014;101:1501-1507'},{id:"B81",body:'Marotta ML, Donnez J, Squifflet J, Jadoul P, Darii N, Donnez O. Laparoscopic repair of post-cesarean section uterine scar defects diagnosed in nonpregnant women. Journal of Minimally Invasive Gynecology. 2013;20:386-391'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Aliye Nigar Serin",address:"nserin85@hotmail.com",affiliation:'
Department of Gynaecology and Obstetrics, Osmaniye State Hospital, Turkey
Department of Gynaecology and Obstetrics, Akdeniz University Hospital, Turkey
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1. Introduction
Iron oxides are transition metal oxides ubiquitously found in nature, having many implications in various biological and geological processes [1, 2, 3, 4]. They occur naturally as aggregates, mineral nanoparticles, or nanostructured coatings onto other soil grains [5], being an essential biogeochemically-active component of the Earth ecosystem [6]. Moreover, iron oxides are formed in a variety of polymorphs with different stoichiometric and crystalline structures [2, 3, 7], including oxides, e.g., wüstite or ferrous oxide (FeO), magnetite (Fe3O4 or FeO·Fe2O3), maghemite (γ-Fe2O3), ε-Fe2O3, hematite (α-Fe2O3), and β-Fe2O3, hydroxides, e.g., iron(III) hydroxide (bernalite) and iron(II) hydroxide, and oxyhydroxydes, e.g., goethite, feroxyhyte, akaganeite, and lepidocrocite [2, 3, 7, 8, 9, 10, 11, 12, 13]. Among them, magnetite, maghemite, and hematite are crystalline and most commonly used in biomedical and pharmaceutical applications, while other forms, such as goethite, are amorphous and occur at high pressure and temperature conditions [2, 3, 7, 14]. Furthermore, iron oxides can also be categorized based on their electrical properties into insulative, i.e., ferrous oxide, conductive, i.e., magnetite, and semiconductive, i.e., hematite and goethite [1].
By contrast, iron oxides can be processed into nanoparticles with magnetic properties, which further allow for their manipulation by external magnetic fields [7, 15]. Among them, magnetite nanoparticles are, by far, the most intensively studied, as they have demonstrated considerable potential in a myriad of applications, including drug delivery, magnetofection, hyperthermia, photoablation therapy, magnetic resonance imaging as contrast enhancement agents, theranostics, biosensing, bioanalysis through biological labeling, tracking, and detection, bioseparation, antimicrobial therapies, tissue engineering and regeneration, wound healing, catalysis, nanorobots, ferrofluids, microelectronics and ultrahigh density magnetic storage media, magnetic paints, pollutant removal sorbents, and batteries [7, 16, 17, 18, 19, 20, 21, 22]. Additionally, recent studies have shown an intrinsic peroxidase activity of iron oxide nanoparticles, which could be further exploited in applications such as biocatalysis, wastewater treatment, detection tools, magnetic enzyme-linked immunosorbent assay kits, or artificial enzymes [23, 24, 25, 26, 27, 28, 29].
Evidently, each of the previously mentioned applications require specific nanoparticle properties [30]. In this context, it has been confirmed that the physico-chemical properties of magnetite nanoparticles, namely, size, shape, stability, crystal structure and crystallinity, chemical composition, and surface area, energy, and roughness, significantly determine their magnetic properties and, consequently, their biological behavior, drug concentration, toxicity, and efficacy [19, 31, 32, 33]. Moreover, studies have shown that the synthesis route of magnetite nanoparticles greatly impacts their physico-chemical properties, thus highlighting the necessity to improve synthesis performance by enhancing standardization, automation, monitoring, and mass production [17, 19, 33].
Presently, the most ubiquitous synthesis method for magnetite nanoparticles is the co-precipitation of ferrous and ferric ions through the addition of an alkaline solution [34]. Although it is a simple and cost-efficient method characterized by considerably high productivity [32], its reproducibility is still limited due to the presence of the intermediate phases within the final product. Additionally, it does not allow for the precise control of nanoparticle size and shape, which further leads to significant variations in the physico-chemical properties of the final product [32, 34, 35, 36]. Therefore, there is a fundamental need for the exploration of novel synthesis processes that could further ensure optimal, controllable, and scalable properties. In this context, iron oxide nanoparticles obtained from natural, green sources are continuously gaining the interest of the scientific community as they provide a potential alternative to overcome the limitations of conventional nanoparticles [37]. Consequently, characterization techniques should also be advanced to ensure a reliable assessment of nanoparticle properties. In this manner, the variety of magnetic nanoparticle applications, ranging from biomedicine and pharmaceutical industry to data storage, could greatly benefit from such improvements.
Therefore, this chapter aims to provide an updated overview of the most recent developments within the field of magnetite nanoparticle synthesis and processing, as well as the most advanced characterization techniques utilized for evaluating their properties and potential.
2. Novel iron oxide nanoparticles synthesis methods
There are two well-established approaches involved in the synthesis of nanoparticles, namely, top-down and bottom-up approaches. Generally, top-down methods involve the crushing, breaking, or fractioning of bulk materials into smaller parts to produce nanoparticles through mechanical action [38, 39]. Such methods include mechanical crushing, milling, or grinding, laser ablation, sputtering, etching, or electron beam deposition, offering an alternative eco-friendly route despite the required high time and power consumption [40, 41, 42]. By contrast, bottom-up approaches are based on chemical reactions among specific atoms, ions, or molecules necessary for the formation of nanoparticles. Considering these principles, synthesis routes can be further divided based on the nature of the involved process into physical, that can be associated to the top-down methods, chemical (e.g., co-precipitation, sol-gel, thermal decomposition, emulsion and microemulsion, hydrothermal, and microwave-assisted methods), and biological (which utilize plants or microorganisms for the generation of nanoparticles), the latter two being attributed to bottom-up approaches (Figure 1) [38, 39, 43, 44].
Figure 1.
The main types of magnetite nanoparticle synthesis methods. Reprinted from an open-access source [43].
Figure 2 depicts a comparison between the most commonly used methods for the synthesis of magnetite nanoparticles. It can be observed that chemical methods comprise the majority of the investigated routes, the co-precipitation method accounting for the highest percentage. Specifically, the co-precipitation process involves two possible pathways, either partial oxidation of iron(II) salts or the aging of a stoichiometric mixture of iron(III) and iron(II) salts through the addition of an alkaline solution that leads to nucleation and growth mechanisms and finally to the generation of Fe3O4 nanoparticles. The chemical reaction principle involved in the production of magnetite nanoparticles is shown in Eq. (1):
Figure 2.
The prevalence of the most commonly utilized magnetite nanoparticle synthesis methods. Reprinted from an open-access source [45].
Fe2++2Fe3++8OH−↔FeOH2+2FeOH3→Fe3O4+4H2O.E1
Although it is the easiest to implement, time-efficient, and safe method, involving limited use of harmful solvents, the co-precipitation process is considerably disadvantageous in terms of reproducibility and possibility to control the outcome properties of the obtained nanoparticles [46, 47].
Thus, there is a fundamental need for the investigation of novel synthesis routes that could improve the features of magnetite nanoparticles. In this context, recent years have witnessed a shift toward the implementation of previously non-conventional methods that could potentially provide a plethora of alternatives in terms of modulating physico-chemical properties. Thus, the following sections will describe the most recent advancements within the production of magnetite nanoparticles through microwave-assisted, microfluidic, and green synthesis methods.
2.1 Microwave-assisted method
Owing to its numerous advantages, microwave-assisted synthesis has become a particularly attractive method for various synthetic chemistry reactions. Specifically, this technique has provided the means for the easy production of nanoparticles in a considerably time- and cost-efficient manner, with reduced energy consumption and increased environmental friendliness [48, 49, 50, 51] through the use of 50% less power than electric furnaces with similar capacities [52]. Besides the associated economic aspects, the microwave-assisted method has received increased scientific interest due to the possibility of tuning the parameters to obtain the desired size and shape of magnetite nanoparticles with significantly narrow distributions and high reproducibility, phase purity, and yield [49, 50, 51]. This is possible due to the characteristic uniform heating and nucleation, rapid kinetics and crystallization, and phase selectivity [50, 51].
The basic principle involved in this method is based on the activation and subsequent alignment of dipoles (i.e., mechanism of dipolar polarization) and/or ions (i.e., mechanism of ionic conduction) present within a material through the interactions with microwave electromagnetic radiations. Consequently, internal heating will occur in a highly homogenous manner, thus, leading to a rapid temperature rise that is responsible for reducing the reaction time and the necessary energy [48, 49, 50, 51, 52]. In the case of magnetite nanoparticles, it has been demonstrated that the microwave-assisted method offers the possibility to control their magnetic properties by adjusting the experimental parameters [49].
Generally, the microwave-assisted method is combined with other synthesis processes, such as co-precipitation. Thus, the synthesis involves the co-precipitation of iron oxide nanoparticles through the classical method, followed by the microwave treatment that enables the control over the properties of the nanoparticles. Several studies have demonstrated the possibility to obtain monodisperse iron oxide nanoparticles with well-controlled sizes and high crystallinity, saturation magnetizations, and stability, as compared to the co-precipitation counterparts [53, 54, 55, 56]. Additionally, the possibility of developing uniform polyethylene glycol [53], humate polyanion [54], and silica [55] coatings was also demonstrated.
2.2 Microfluidic approaches
Microfluidics is a relatively new field that has brought together fluid dynamics, chemistry, and material science principles for allowing the precise and accurate manipulation of small fluid volumes within microchannels [57, 58]. In this context, microfluidic technology-based methods for the synthesis of nanomaterials have emerged as an alternative to conventional routes that could provide possible solutions to the currently existing limitations. Specifically, microfluidic devices represent synthesis platforms with outstanding features for the fabrication of nanoparticles, including small capillary dimensions and consequent large surface/volume ratios and reduced reagent volume use, rapid and uniform mass and heat transfer, ease of automation, reduced residence time, and precise control of mixing [38, 57, 58, 59]. In this manner, by increasing the control of the implicated reaction parameters (e.g., device geometry, flow rate, reagent concentration, reaction time, temperature) [59, 60], nanoparticles with superior uniformity, stability, and encapsulation efficiency and narrow particle size distributions can be obtained in a highly reproducible and controllable manner [38, 57, 58, 59, 60].
Based on their geometry, microfluidic devices can be classified into tubular reactors, which generally involve circular channels that are either in-house produced or purchased (most common commercially available reactors have T and Y type junctions), and chip reactors, which involve more complex geometries and are usually in-house manufactured using various fabrication techniques [38]. The working principle of microfluidic approaches for the synthesis of nanoparticles resides on the movement of fluids within microchannels and microchambers with unique geometries to integrate the preparation, reaction, and separation steps. In this context, there are two main types of microfluidic reactors that involve different synthesis strategies, namely, single-phase or continuous-flow microfluidics and multi-phase or droplet-based microfluidics, which can be further divided according to the carrier fluid into gas–liquid and liquid–liquid segmented flows [38, 59].
Microfluidics is currently evolving as a promising alternative for the synthesis of magnetite nanoparticles with controlled size, shape, and surface chemistry that can be modulated according to the application requirements [57, 58]. Since it involves a relatively simple reaction, it can be obtained through both types of synthesis strategies. Continuous-flow microreactors that contain one inlet for the iron precursor solution and one inlet for the alkaline solution will ensure the formation of the nanoparticles at the interface between the two fluid layers if the pH value is high enough for nucleation. While this is usually the preferred route owing to its increased homogeneity and versatility, some applications require faster interactions. Therefore, the multiphase microfluidics involving cross-flow designs are receiving increasing attention. In this approach, the channels containing the precursor solutions, i.e., the dispersed phase, will intersect the channels containing the alkaline solution, i.e., the continuous phase, where the nanoparticles will form and be further transported within the continuous phase [38, 60]. Furthermore, the microfluidic platforms used for the synthesis of magnetite nanoparticles can be made of various materials, such as glass, metals, silicon, or polymers, that must be resistant to the fluids introduced within the microchannels [38].
Although the number of studies is still limited, the results are promising, thus paving the way toward the future of nanoparticle synthesis. In this context, the synthesis of magnetite nanoparticles was investigated through the use of a single-flow polydimethylsiloxane microfluidic reactor [61] and a T-junction polymethylmethacrylate microchip fabricated by a laser cutting machine [57]. Furthermore, another study fabricated magnetite nanoparticles using a 3D flow microfluidic device focused by two basic sheath streams, that were subjected to a postsynthesis surface functionalization step outside the microreactor [62]. Moreover, other studies demonstrated the possibility of developing in situ chitosan-coated magnetite nanoparticles using two types of microchip configurations fabricated through 3D printing [63] and by the soft lithography process [64].
2.3 Green synthesis methods
The merge between nanotechnology and biology has led to the rise of a new and highly advanced field of nanomaterial synthesis using living microorganisms of both prokaryotic and eukaryotic origins, such as algae, bacteria, fungi, yeasts, viruses, and plants [65]. Within this framework, the synthesis of nanoparticles via green technologies utilizing microorganisms and plant extracts is continuously emerging as a safe, cost-efficient, renewable, and environmentally friendly alternative [65, 66, 67, 68] which does not implicate complex protocols [69] or the use of intermediary base groups [70]. Additionally, green synthesis methods lead to the formation of nanoparticles with higher stability as they do not involve the use of chemicals that increase particle reactivity, enhanced biocompatibility, non-toxicity, and antimicrobial and anticancer properties [66, 67, 68, 69]. Such methods are possible due to the resistance mechanisms developed by microorganisms and plants to endure the highly toxic environments generated by high metal concentrations. Specifically, the intrinsic chemical processes of these living entities can remodel inorganic metal ions into nanoparticles to reduce or eliminate the toxic effects. There are two main processes involved in the biogenic synthesis of nanoparticles, namely, through bioreduction, i.e., the reduction of metal ions by intrinsic biological processes, and biosorption, involving the assimilation of metal ions within the cell wall and the consequent formation of stable nanoparticulate structures through the assembly with the present macromolecules [65].
Generally, plant-based synthesis of nanoparticles is more advantageous in terms of higher kinetics, increased reduction and stabilization yield, and easier large-scale production [66, 68, 70]. The plant-mediated formation of nanoparticles can occur intracellularly or inside the plant, through the presence of specific biomolecules (e.g., aldehydes, ketones, flavones, phenols, amino acids, proteins, polysaccharides, tannins, terpenoids, saponins, vitamins), extracellularly, using plant extracts, or through individual phytochemicals. The mechanism involves the linkage between the atmospheric or phytochemical-generated oxygen that reduces the metal ions, followed by the electrostatic interactions between the newly formed metal oxides that will lead to the formation of the nanoparticles. The nature of the phytochemicals is responsible for their size, shape, stability, and reactivity variations [67, 68, 71]. Based on their produced phytochemicals, various plant parts have been investigated, including root, leaf, flower, petal, fruit, stem, peel, or seed [70].
Although green synthesis methods have been mostly applied for obtaining silver, gold, and copper nanoparticles, the synthesis of iron oxide nanoparticles through the use of plants or microorganisms has become an intensively studied field owing to the biocompatible, non-toxic, and stable nature of the final products [72]. Thus, there are many protocols available in the literature for the green synthesis of iron oxide nanoparticles, which generally follow a similar methodology. Briefly, the procedure begins with the starting material preparation and extraction, by collecting, washing, drying, weighing, grinding into a fine powder, boiling in water or methanol/ethanol under continuous stirring, centrifugation, and filtration. Subsequently, the extract is mixed with the precursor salt solutions, such as FeSO4·7H2O, FeCl3·6H2O, (FeNO3)3·9H2O, FeSO4, FeCl3, FeCl2·4H2O, FeCl2, or FeSO4·5H2O, of varying molarities. Finally, the mixture is heated and vigorously stirred until the color of the solution changes and intensifies according to the type of iron salts utilized. The obtained iron oxide nanoparticle pellets are further washed and dried [73].
The available literature studies reported the synthesis of iron oxide nanoparticles using Bauhinia tomentosa [74], pomegranate seeds [75], Hibiscus rosa-sinensis [76], Mimosa pudica root [77], Carica papaya leaf extract [78], Cymbopogon citratus [79], Ficus carica leaf extract [80], and Platanus orientalis leaf extract [81].
3. Advanced iron oxide nanoparticles characterization techniques
As previously emphasized, the physico-chemical properties of iron oxide nanoparticles often dictate their applications [82]. Since the characterization of nanoparticles is significantly challenging due to the increased interdisciplinarity of the field, it is fundamentally important to characterize nanoparticles to the maximum extent to ensure a more rapid implementation in commercial applications [83]. Generally, the physicochemical properties of iron oxide nanoparticles are evaluated through a variety of different techniques, depending on the parameter that must be determined [35, 73, 82]. Table 1 depicts the most important characteristics of iron oxide nanoparticles and the suitable characterization techniques for determining them.
Nanoparticle property
Characterization techniques
Size
TEM, XRD, DLS, NTA, HRTEM, SAXS, SEM, AFM
Size distribution
DLS, NTA, SAXS
Shape
TEM, HRTEM, SEM, AFM, STEM
Crystal structure
XRD, HRTEM, SAED, STEM
Elemental/chemical composition
XRD, SEM-EDX, ICP-MS, XPS, EELS
Surface area/specific surface area
BET analysis, NMR
Surface charge
Zeta potential
Magnetic properties
VSM, SQUID, Mössbauer spectroscopy, MFM
Table 1.
The characteristics of iron oxide nanoparticles and the associated characterization techniques. Adapted from an open-access source [35, 73, 83].
TEM—transmission electron microscopy, XRD—X-ray diffraction, DLS—dynamic light scattering, NTA—nanoparticle tracking analysis, HRTEM—high-resolution TEM, SAXS—small-angle X-ray scattering, SEM—scanning electron microscopy, AFM—atomic force microscopy, STEM—scanning transmission electron microscope, SAED—selected area electron diffraction, EDX—energy-dispersive X-ray spectroscopy, ICP-MS—inductively coupled plasma mass spectrometry, XPS—X-ray photoelectron spectroscopy, EELS—electron energy loss spectroscopy, BET—Brunauer–Emmett–Teller, NMR—nuclear magnetic resonance, VSM—vibrating sample magnetometry, SQUID—superconducting quantum interference device, MFM—magnetic force microscopy.
The most important parameter to be evaluated is the size and consequently the size distribution of the nanoparticles, as it can affect other properties and determine the behavior of the final product within the envisaged application [35, 83]. Although size measurements within the macroscale might appear trivial, size determinations within the nanoregime might lead to different interpretations depending on the characterization technique employed. When referring to nanoparticles, size can be correlated to the atomic structure-defined physical dimension, the diffusion/sedimentation-dependent effective size of the nanoparticle within a matrix or solvent, or the effective size weighted by the mass/electron distribution [84, 85]. Furthermore, size distribution represents an estimation of the quality of the synthesis process, as the general aim is to obtain close to monodisperse nanoparticles [82, 83, 84].
The shape also plays a fundamental role upon the behavior of iron oxide nanoparticles, as it can further lead to toxic effects due to cell harming. Therefore, the employed synthesis routes must allow for the control of nanoparticle shape as a crucial parameter [86, 87]. Commonly, electron microscopy techniques are utilized for the precise evaluation of the morphology and consequently the shape of the nanoparticles [83, 88].
Moreover, crystal structure and chemical composition also represent essential characterization steps in the process of iron oxide nanoparticle development [83]. Although X-ray diffraction represents the most common technique for crystal structure, crystallinity, and phases evaluation [89], studies have shown that in the case of nanoparticles with sizes below 5 nm, the diffractogram patterns are influenced [90]. Thus, other, more reliable methods should be developed. Selected area electron diffraction represents an alternative that better depicts the crystal structure of nanoparticles [84]. Chemical and elemental composition determination provides an estimation of the purity of the nanoparticles. Additionally, the chemical composition is a key parameter that can influence the electrochemical activity of the nanoparticles [91]. Moreover, another interesting characterization possibility involves the precise distinction between iron(II) and iron(III) to differentiate the iron oxide phases present within the nanoparticles, which could be possible through the electron energy loss spectroscopy method [92].
Although it might result in high agglomeration degrees, high surface areas of iron oxide nanoparticles are essential for ensuring the desired application [83, 87]. For example, in waste or pollutant removal applications, iron oxide nanoparticles must possess high surface areas to increase capture and immobilization efficiency [93]. Surface area is determined through straightforward gas sorption techniques, such as the BET analysis [84].
The surface charge can be correlated with the colloidal stability and interactions of the nanoparticles. Specifically, the interactions of iron oxide nanoparticles within the biological fluids will determine the formation of the protein corona on their surface and, thus, the probability of cellular uptake [84]. Generally, the surface charge of nanoparticles is measured through a zeta potentiometer by applying a voltage to the samples. The results are given in terms of zeta potential ζ, which refers to the difference in the electric potential between the particle surrounding stationary charge layers and the potential of the solution [94, 95, 96, 97]. Zeta potential values higher than +15 mV and lower than −15 mV are usually attributed to colloidally stable suspensions, as they generate electrostatic repulsions that are strong enough to counteract aggregation of the nanoparticles [82, 84, 85]. However, there are several parameters that could influence the zeta potential, such as the pH and ionic strength of the solvent or the presence of charged/uncharged molecules that can be adsorbed onto the surface of the nanoparticles [84].
Considering the extensive studies performed toward hyperthermia applications for controlled drug delivery and cancer therapy, an essential characteristic of iron oxide nanoparticles is their magnetic behavior. The magnetic properties of iron oxide nanoparticles directly depend upon the synthesis route and the size and shape of the obtained nanostructures [35]. Similar to other properties, the magnetic behavior of nanostructured materials is significantly different than those of the bulk materials, since the size decrease leads to changes from the multidomain to the single domain and, finally, to the superparamagnetic state [83]. Specifically, nanoparticles with superparamagnetic properties are characterized by negligible remanent magnetization and coercive field. Thus, when the external magnetic field is removed, the nanoparticles exhibit no magnetism. By contrast, ferro- and ferrimagnetic nanoparticles feature a magnetic hysteresis, associated with a remanent magnetization, thus requiring a coercive field for reverting the magnetization to zero [35, 98]. Furthermore, the magnetic behavior can also be influenced by the agglomeration and aggregation processes, which further favor dipole-dipole or exchange interactions [99]. There are several methods that can be utilized for the analysis of iron oxide nanoparticle magnetism, each associated with specific sensitivities [35].
4. Conclusions
Iron oxide nanoparticles have been intensively studied for a variety of applications within numerous fields, ranging from medicine and pharmaceutics to microelectronics and analytical chemistry. Since their utilization is continuously rising, the need for improving the currently available synthesis methods is fundamental. In this context, novel preparation routes must be explored to develop uniform and standardized iron oxide nanoparticles. Among the recently implemented strategies, microwave-assisted, microfluidics, and green synthesis methods have demonstrated an undoubted potential toward reaching this goal. Specifically, nanoparticles obtained through these methods were characterized by superior properties as compared to the co-precipitation counterparts. Furthermore, the advancements within the characterization techniques could further lead to new insights and potential improvements within this area. In this context, the most important techniques often include size, shape, structure, crystallinity, and magnetic behavior determinations. Therefore, the intensive research work investigating the synthesis of iron oxide nanoparticles must further continue.
Acknowledgments
We acknowledge the support of the research grant from the Romanian National Authority for Scientific Research and Innovation, UEFISCDI, project number TE 103, code: PN-III-P1-1.1-TE-2019-1450, entitled multifunctional lab-on-a-chip microfluidic platform for the fabrication of nanoparticles.
Conflict of interest
The authors declare no conflict of interest.
Notes/thanks/other declarations
We thank the esteemed group of researchers that have created the National Research Center for Micro and Nanomaterials from the University Politehnica of Bucharest and have considerably contributed to the development of numerous research studies.
\n',keywords:"iron oxide nanoparticles, synthesis processes, green synthesis processes, characterization techniques, physico-chemical properties",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/79916.pdf",chapterXML:"https://mts.intechopen.com/source/xml/79916.xml",downloadPdfUrl:"/chapter/pdf-download/79916",previewPdfUrl:"/chapter/pdf-preview/79916",totalDownloads:188,totalViews:0,totalCrossrefCites:1,dateSubmitted:"November 20th 2021",dateReviewed:"November 26th 2021",datePrePublished:"January 5th 2022",datePublished:null,dateFinished:"January 5th 2022",readingETA:"0",abstract:"Recent years have witnessed an extensive application of iron oxide nanoparticles within a wide variety of fields, including drug delivery, hyperthermia, biosensing, theranostics, and cell and molecular separation. Consequently, synthesis and characterization methods have continuously evolved to provide the possibility for controlling the physico-chemical and biological properties of the nanoparticles to better suit the envisaged applications. In this manner, this chapter aims to provide an extensive overview of the most recent progress made within the processes of iron oxide nanoparticle synthesis and characterization. Thus, the chapter will focus on novel and advanced approaches reported in the literature for obtaining standardized nanoparticles with controllable properties and effects. Specifically, it will emphasize the most recent progress made within the microwave-assisted, microfluidics, and green synthesis methods, as they have shown higher capacities of controlling the outcome nanoparticle properties.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/79916",risUrl:"/chapter/ris/79916",signatures:"Cristina Chircov and Bogdan Stefan Vasile",book:{id:"10824",type:"book",title:"Iron Oxide Nanoparticles",subtitle:null,fullTitle:"Iron Oxide Nanoparticles",slug:null,publishedDate:null,bookSignature:"Dr. Xiao-Lan Huang",coverURL:"https://cdn.intechopen.com/books/images_new/10824.jpg",licenceType:"CC BY 3.0",editedByType:null,isbn:"978-1-80355-175-3",printIsbn:"978-1-80355-174-6",pdfIsbn:"978-1-80355-176-0",isAvailableForWebshopOrdering:!0,editors:[{id:"259542",title:"Dr.",name:"Xiao-Lan",middleName:null,surname:"Huang",slug:"xiao-lan-huang",fullName:"Xiao-Lan Huang"}],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. Novel iron oxide nanoparticles synthesis methods",level:"1"},{id:"sec_2_2",title:"2.1 Microwave-assisted method",level:"2"},{id:"sec_3_2",title:"2.2 Microfluidic approaches",level:"2"},{id:"sec_4_2",title:"2.3 Green synthesis methods",level:"2"},{id:"sec_6",title:"3. Advanced iron oxide nanoparticles characterization techniques",level:"1"},{id:"sec_7",title:"4. Conclusions",level:"1"},{id:"sec_8",title:"Acknowledgments",level:"1"},{id:"sec_11",title:"Conflict of interest",level:"1"},{id:"sec_8",title:"Notes/thanks/other declarations",level:"1"}],chapterReferences:[{id:"B1",body:'Gahlot P, Aboudi K, Ahmed B, Tawfik A, Khan AA, Khursheed A, et al. Chapter 9—Direct interspecies electron transfer (DIET) via conductive materials in anaerobic digestion of organic wastes. In: Tyagi V, Aboudi K, editors. Clean Energy and Resources Recovery. 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DOI: 10.1002/adma.201901556'},{id:"B85",body:'Bélteky P, Rónavári A, Zakupszky D, Boka E, Igaz N, Szerencsés B, et al. Are smaller nanoparticles always better? understanding the biological effect of size-dependent silver nanoparticle aggregation under biorelevant conditions. International Journal of Nanomedicine. 2021;16:3021'},{id:"B86",body:'Arno MC, Inam M, Weems AC, Li Z, Binch ALA, Platt CI, et al. Exploiting the role of nanoparticle shape in enhancing hydrogel adhesive and mechanical properties. Nature Communications. 2020;11(1):1420. DOI: 10.1038/s41467-020-15206-y'},{id:"B87",body:'Gomathi T, Rajeshwari K, Kanchana V, Sudha PN, Parthasarathy K. Impact of nanoparticle shape, size, and properties of the sustainable nanocomposites. In: Inamuddin, Thomas S, Kumar Mishra R, Asiri AM, editors. Sustainable Polymer Composites and Nanocomposites. Cham: Springer International Publishing; 2019. pp. 313-336'},{id:"B88",body:'Boselli L, Lopez H, Zhang W, Cai Q, Giannone VA, Li J, et al. Classification and biological identity of complex nano shapes. Communications Materials. 2020;1(1):35. DOI: 10.1038/s43246-020-0033-2'},{id:"B89",body:'Khan I, Saeed K, Khan I. Nanoparticles: Properties, applications and toxicities. Arabian Journal of Chemistry. 2019;12(7):908-931. DOI: 10.1016/j.arabjc.2017.05.011'},{id:"B90",body:'Vorontsov AV, Tsybulya SV. Influence of nanoparticles size on XRD patterns for small monodisperse nanoparticles of Cu0 and TiO2 anatase. Industrial and Engineering Chemistry Research. 2018;57(7):2526-2536. DOI: 10.1021/acs.iecr.7b04480'},{id:"B91",body:'Mukundan V, Shan S, Zhong C-J, Malis O. Effect of chemical composition on the nanoscale ordering transformations of physical mixtures of Pd and Cu nanoparticles. Journal of Nanomaterials. 2018;2018:9087320. DOI: 10.1155/2018/9087320'},{id:"B92",body:'Cavé L, Al T, Loomer D, Cogswell S, Weaver L. A STEM/EELS method for mapping iron valence ratios in oxide minerals. Micron. 2006;37(4):301-309. DOI: 10.1016/j.micron.2005.10.006'},{id:"B93",body:'Koopmans GF, Hiemstra T, Vaseur C, Chardon WJ, Voegelin A, Groenenberg JE. Use of iron oxide nanoparticles for immobilizing phosphorus in-situ: Increase in soil reactive surface area and effect on soluble phosphorus. Science of the Total Environment. 2020;711:135220. DOI: 10.1016/j.scitotenv.2019.135220'},{id:"B94",body:'Ismail AF, Khulbe KC, Matsuura T. Chapter 3—RO membrane characterization. In: Ismail AF, Khulbe KC, Matsuura T, editors. Reverse Osmosis. Amsterdam, The Netherlands: Elsevier; 2019. pp. 57-90'},{id:"B95",body:'Kumar CV, Pattammattel A. Chapter 8—Graphene composites with proteins and biologics. In: Kumar CV, Pattammattel A, editors. Introduction to Graphene. Amsterdam, The Netherlands: Elsevier; 2017. pp. 155-186'},{id:"B96",body:'Yamashita Y, Sakamoto K. Chapter 38—Structural analysis of formulations. In: Sakamoto K, Lochhead RY, Maibach HI, Yamashita Y, editors. Cosmetic Science and Technology. Amsterdam: Elsevier; 2017. pp. 635-655'},{id:"B97",body:'Nasrollahzadeh M, Shafiei N, Soleimani F, Nezafat Z, Soheili Bidgoli NS. Chapter 10—Physicochemical characterization of biopolymer-based metal nanoparticles. In: Nasrollahzadeh M, editor. Biopolymer-Based Metal Nanoparticle Chemistry for Sustainable Applications. Amsterdam, The Netherlands: Elsevier; 2021. pp. 317-478'},{id:"B98",body:'Maldonado-Camargo L, Unni M, Rinaldi C. Magnetic characterization of iron oxide nanoparticles for biomedical applications. Methods in Molecular Biology. 2017;1570:47-71. DOI: 10.1007/978-1-4939-6840-4_4'},{id:"B99",body:'Gutiérrez L, de la Cueva L, Moros M, Mazarío E, de Bernardo S, de la Fuente JM, et al. Aggregation effects on the magnetic properties of iron oxide colloids. Nanotechnology. 2019;30(11):112001. DOI: 10.1088/1361-6528/aafbff'}],footnotes:[],contributors:[{corresp:null,contributorFullName:"Cristina Chircov",address:null,affiliation:'
Department of Science and Engineering of Oxide Materials and Nanomaterials, University Politehnica of Bucharest, Romania
National Research Center for Micro and Nanomaterials, University Politehnica of Bucharest, Romania
'},{corresp:"yes",contributorFullName:"Bogdan Stefan Vasile",address:"bogdan.vasile@upb.ro",affiliation:'
Department of Science and Engineering of Oxide Materials and Nanomaterials, University Politehnica of Bucharest, Romania
National Research Center for Micro and Nanomaterials, University Politehnica of Bucharest, Romania
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The Open Access Publishing Fee (OAPF) is payable only after your book chapter, monograph or journal article is accepted for publication.
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OAPF Publishing Options
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1,400 GBP Chapter - Edited Volume
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850 GBP Chapter - Book Series Topic (Annual Volume)
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10,000 GBP Monograph - Long Form
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850 GBP Journal Article (Across Portfolio)
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He has published seven patents in the Spanish Patent and Trademark Office. He has been a supervisor on 8 Ph.D. theses (11 more are under supervision), and 130 master theses. He is the founder of The IEEE IWOBI conference series and the president of its Steering Committee, as well as the founder of both the InnoEducaTIC and APPIS conference series. He is an evaluator of project proposals for the European Union (H2020), Medical Research Council (MRC, UK), Spanish Government (ANECA, Spain), Research National Agency (ANR, France), DAAD (Germany), Argentinian Government, and the Colombian Institutions. He has been a reviewer in different indexed international journals (<70) and conferences (<250) since 2001. He has been a member of the IASTED Technical Committee on Image Processing from 2007 and a member of the IASTED Technical Committee on Artificial Intelligence and Expert Systems from 2011. \n\nHe has held the general chair position for the following: ACM-APPIS (2020, 2021), IEEE-IWOBI (2019, 2020 and 2020), A PPIS (2018, 2019), IEEE-IWOBI (2014, 2015, 2017, 2018), InnoEducaTIC (2014, 2017), IEEE-INES (2013), NoLISP (2011), JRBP (2012), and IEEE-ICCST (2005)\n\nHe is an associate editor of the Computational Intelligence and Neuroscience Journal (Hindawi – Q2 JCR-ISI). He was vice dean from 2004 to 2010 in the Higher Technical School of Telecommunication Engineers at ULPGC and the vice dean of Graduate and Postgraduate Studies from March 2013 to November 2017. He won the “Catedra Telefonica” Awards in Modality of Knowledge Transfer, 2017, 2018, and 2019 editions, and awards in Modality of COVID Research in 2020.\n\nPublic References:\nResearcher ID http://www.researcherid.com/rid/N-5967-2014\nORCID https://orcid.org/0000-0002-4621-2768 \nScopus Author ID https://www.scopus.com/authid/detail.uri?authorId=6602376272\nScholar Google https://scholar.google.es/citations?user=G1ks9nIAAAAJ&hl=en \nResearchGate https://www.researchgate.net/profile/Carlos_Travieso",institutionString:null,institution:{name:"University of Las Palmas de Gran Canaria",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"23",title:"Computational Neuroscience",coverUrl:"https://cdn.intechopen.com/series_topics/covers/23.jpg",isOpenForSubmission:!0,editor:{id:"14004",title:"Dr.",name:"Magnus",middleName:null,surname:"Johnsson",slug:"magnus-johnsson",fullName:"Magnus Johnsson",profilePictureURL:"https://mts.intechopen.com/storage/users/14004/images/system/14004.png",biography:"Dr Magnus Johnsson is a cross-disciplinary scientist, lecturer, scientific editor and AI/machine learning consultant from Sweden. \n\nHe is currently at Malmö University in Sweden, but also held positions at Lund University in Sweden and at Moscow Engineering Physics Institute. \nHe holds editorial positions at several international scientific journals and has served as a scientific editor for books and special journal issues. \nHis research interests are wide and include, but are not limited to, autonomous systems, computer modeling, artificial neural networks, artificial intelligence, cognitive neuroscience, cognitive robotics, cognitive architectures, cognitive aids and the philosophy of mind. \n\nDr. Johnsson has experience from working in the industry and he has a keen interest in the application of neural networks and artificial intelligence to fields like industry, finance, and medicine. \n\nWeb page: www.magnusjohnsson.se",institutionString:null,institution:{name:"Malmö University",institutionURL:null,country:{name:"Sweden"}}},editorTwo:null,editorThree:null},{id:"24",title:"Computer Vision",coverUrl:"https://cdn.intechopen.com/series_topics/covers/24.jpg",isOpenForSubmission:!0,editor:{id:"294154",title:"Prof.",name:"George",middleName:null,surname:"Papakostas",slug:"george-papakostas",fullName:"George Papakostas",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002hYaGbQAK/Profile_Picture_1624519712088",biography:"George A. 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He has (co)authored more than 150 publications in indexed journals, international conferences and book chapters, 1 book (in Greek), 3 edited books, and 5 journal special issues. His publications have more than 2100 citations with h-index 27 (GoogleScholar). His research interests include computer/machine vision, machine learning, pattern recognition, computational intelligence. \nDr. Papakostas served as a reviewer in numerous journals, as a program\ncommittee member in international conferences and he is a member of the IAENG, MIR Labs, EUCogIII, INSTICC and the Technical Chamber of Greece (TEE).",institutionString:null,institution:{name:"International Hellenic University",institutionURL:null,country:{name:"Greece"}}},editorTwo:null,editorThree:null},{id:"25",title:"Evolutionary Computation",coverUrl:"https://cdn.intechopen.com/series_topics/covers/25.jpg",isOpenForSubmission:!0,editor:{id:"136112",title:"Dr.",name:"Sebastian",middleName:null,surname:"Ventura Soto",slug:"sebastian-ventura-soto",fullName:"Sebastian Ventura Soto",profilePictureURL:"https://mts.intechopen.com/storage/users/136112/images/system/136112.png",biography:"Sebastian Ventura is a Spanish researcher, a full professor with the Department of Computer Science and Numerical Analysis, University of Córdoba. Dr Ventura also holds the positions of Affiliated Professor at Virginia Commonwealth University (Richmond, USA) and Distinguished Adjunct Professor at King Abdulaziz University (Jeddah, Saudi Arabia). Additionally, he is deputy director of the Andalusian Research Institute in Data Science and Computational Intelligence (DaSCI) and heads the Knowledge Discovery and Intelligent Systems Research Laboratory. He has published more than ten books and over 300 articles in journals and scientific conferences. Currently, his work has received over 18,000 citations according to Google Scholar, including more than 2200 citations in 2020. In the last five years, he has published more than 60 papers in international journals indexed in the JCR (around 70% of them belonging to first quartile journals) and he has edited some Springer books “Supervised Descriptive Pattern Mining” (2018), “Multiple Instance Learning - Foundations and Algorithms” (2016), and “Pattern Mining with Evolutionary Algorithms” (2016). He has also been involved in more than 20 research projects supported by the Spanish and Andalusian governments and the European Union. He currently belongs to the editorial board of PeerJ Computer Science, Information Fusion and Engineering Applications of Artificial Intelligence journals, being also associate editor of Applied Computational Intelligence and Soft Computing and IEEE Transactions on Cybernetics. Finally, he is editor-in-chief of Progress in Artificial Intelligence. He is a Senior Member of the IEEE Computer, the IEEE Computational Intelligence, and the IEEE Systems, Man, and Cybernetics Societies, and the Association of Computing Machinery (ACM). Finally, his main research interests include data science, computational intelligence, and their applications.",institutionString:null,institution:{name:"University of Córdoba",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"26",title:"Machine Learning and Data Mining",coverUrl:"https://cdn.intechopen.com/series_topics/covers/26.jpg",isOpenForSubmission:!0,editor:{id:"24555",title:"Dr.",name:"Marco Antonio",middleName:null,surname:"Aceves Fernandez",slug:"marco-antonio-aceves-fernandez",fullName:"Marco Antonio Aceves Fernandez",profilePictureURL:"https://mts.intechopen.com/storage/users/24555/images/system/24555.jpg",biography:"Dr. Marco Antonio Aceves Fernandez obtained his B.Sc. (Eng.) in Telematics from the Universidad de Colima, Mexico. 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He is currently a principal researcher in data analytics and optimisation at TECNALIA (Spain), a visiting fellow at the Basque Center for Applied Mathematics (BCAM) and a part-time lecturer at the University of the Basque Country (UPV/EHU). His research interests gravitate on the use of descriptive, prescriptive and predictive algorithms for data mining and optimization in a diverse range of application fields such as Energy, Transport, Telecommunications, Health and Industry, among others. In these fields he has published more than 240 articles, co-supervised 8 Ph.D. theses, edited 6 books, coauthored 7 patents and participated/led more than 40 research projects. 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He is currently a full professor in\nthe Department of Automation and Applied Informatics at the\nsame university. Dr. Voloşencu is the author of ten books, seven\nbook chapters, and more than 160 papers published in journals\nand conference proceedings. He has also edited twelve books and\nhas twenty-seven patents to his name. He is a manager of research grants, editor in\nchief and member of international journal editorial boards, a former plenary speaker, a member of scientific committees, and chair at international conferences. His\nresearch is in the fields of control systems, control of electric drives, fuzzy control\nsystems, neural network applications, fault detection and diagnosis, sensor network\napplications, monitoring of distributed parameter systems, and power ultrasound\napplications. 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