More than half of the publishers listed alongside IntechOpen (18 out of 30) are Social Science and Humanities publishers. IntechOpen is an exception to this as a leader in not only Open Access content but Open Access content across all scientific disciplines, including Physical Sciences, Engineering and Technology, Health Sciences, Life Science, and Social Sciences and Humanities.
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Our breakdown of titles published demonstrates this with 47% PET, 31% HS, 18% LS, and 4% SSH books published.
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“Even though ItechOpen has shown the potential of sci-tech books using an OA approach,” other publishers “have shown little interest in OA books.”
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Additionally, each book published by IntechOpen contains original content and research findings.
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We are honored to be among such prestigious publishers and we hope to continue to spearhead that growth in our quest to promote Open Access as a true pioneer in OA book publishing.
Simba Information has released its Open Access Book Publishing 2020 - 2024 report and has again identified IntechOpen as the world’s largest Open Access book publisher by title count.
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Simba Information is a leading provider for market intelligence and forecasts in the media and publishing industry. The report, published every year, provides an overview and financial outlook for the global professional e-book publishing market.
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IntechOpen, De Gruyter, and Frontiers are the largest OA book publishers by title count, with IntechOpen coming in at first place with 5,101 OA books published, a good 1,782 titles ahead of the nearest competitor.
\n\n
Since the first Open Access Book Publishing report published in 2016, IntechOpen has held the top stop each year.
\n\n\n\n
More than half of the publishers listed alongside IntechOpen (18 out of 30) are Social Science and Humanities publishers. IntechOpen is an exception to this as a leader in not only Open Access content but Open Access content across all scientific disciplines, including Physical Sciences, Engineering and Technology, Health Sciences, Life Science, and Social Sciences and Humanities.
\n\n
Our breakdown of titles published demonstrates this with 47% PET, 31% HS, 18% LS, and 4% SSH books published.
\n\n
“Even though ItechOpen has shown the potential of sci-tech books using an OA approach,” other publishers “have shown little interest in OA books.”
\n\n
Additionally, each book published by IntechOpen contains original content and research findings.
\n\n
We are honored to be among such prestigious publishers and we hope to continue to spearhead that growth in our quest to promote Open Access as a true pioneer in OA book publishing.
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\n'}],latestNews:[{slug:"intechopen-expands-to-all-global-amazon-channels-with-full-catalog-of-books-20210308",title:"IntechOpen Expands to All Global Amazon Channels with Full Catalog of Books"},{slug:"stanford-university-identifies-top-2-scientists-over-1-000-are-intechopen-authors-and-editors-20210122",title:"Stanford University Identifies Top 2% Scientists, Over 1,000 are IntechOpen Authors and Editors"},{slug:"intechopen-authors-included-in-the-highly-cited-researchers-list-for-2020-20210121",title:"IntechOpen Authors Included in the Highly Cited Researchers List for 2020"},{slug:"intechopen-maintains-position-as-the-world-s-largest-oa-book-publisher-20201218",title:"IntechOpen Maintains Position as the World’s Largest OA Book Publisher"},{slug:"all-intechopen-books-available-on-perlego-20201215",title:"All IntechOpen Books Available on Perlego"},{slug:"oiv-awards-recognizes-intechopen-s-editors-20201127",title:"OIV Awards Recognizes IntechOpen's Editors"},{slug:"intechopen-joins-crossref-s-initiative-for-open-abstracts-i4oa-to-boost-the-discovery-of-research-20201005",title:"IntechOpen joins Crossref's Initiative for Open Abstracts (I4OA) to Boost the Discovery of Research"},{slug:"intechopen-hits-milestone-5-000-open-access-books-published-20200908",title:"IntechOpen hits milestone: 5,000 Open Access books published!"}]},book:{item:{type:"book",id:"2079",leadTitle:null,fullTitle:"Problems, Perspectives and Challenges of Agricultural Water Management",title:"Problems, Perspectives and Challenges of Agricultural Water Management",subtitle:null,reviewType:"peer-reviewed",abstract:"Food security emerged as an issue in the first decade of the 21st Century, questioning the sustainability of the human race, which is inevitably related directly to the agricultural water management that has multifaceted dimensions and requires interdisciplinary expertise in order to be dealt with. 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1. Introduction
Urinary tract infections (UTIs) are considered the most frequent bacterial infections in humans usually caused by Enterobacteriaceae. Among them, Escherichia coli is a predominant etiological factor of UTI [1]. The pathogenic E. coli strains belong to different pathotypes including enteric E. coli and extraintestinal E. coli (ExPEC). Seven major pathotypes of enteric E. coli cause mainly gastroenteritis but sometimes are responsible for diseases outside the intestinal tract [2]. Three pathotypes of the ExPEC are able to exist in the gut but do not cause diseases in this place. Whereas, colonization by the ExPEC strains of other host niches including the central nervous system, blood, and the urinary tract leads to illness in human [3]. Among ExPEC, uropathogenic E. coli (UPEC) is the most frequently associated with human diseases. UPEC strains cause 80–90% of community-acquired UTIs and more than 30% of hospital-acquired UTIs [4]. Development of UTIs depends on anatomical factors of host, defense mechanisms, and virulence factors of infecting microorganism. Bacterial infections of the urinary tract are important problem, because about 60% of women in the United States will have at least one UTI during their life. About 8 million physician visits per year are related to these often chronic infections, making UTIs a problem of economic and medical significance [5]. UPEC can colonize the bladder and cause cystitis or may ascend into the kidneys, causing pyelonephritis [3]. E. coli may also spread from the urinary tract to the bloodstream causing bacteremia in above 30% of cases and the potential sepsis [6]. The presence of high numbers of E. coli in the urine without the clinical symptoms is referred as asymptomatic bacteriuria (ABU) and such infection in healthy, nonpregnant women is generally not treated [7]. Infections of the urinary tract occur when E. coli enter through the urethra and effectively colonize the bladder. E. coli is the most common pathogen causing cystitis, pyelonephritis with the possibility of causing kidney damage and death. This microorganism can induce acute renal failure and in case of complications after renal transplantation, E. coli is the most common clinical isolate [8]. It is considered that human intestinal tract is a primary reservoir of UPEC strains, although in some cases, clonal group of UPEC strains can be transmitted by contaminated food [9]. Host inflammatory responses on the breach of the sterile urinary tract by UPEC consist of the production of cytokines and chemokines, neutrophil influx, the exfoliation of infected bladder epithelial cells, and the generation of reactive nitrogen and oxygen species [5]. Genomic differences among UPEC and other E. coli show evolutionary adaptations, which enable UPEC to colonize environmental niches within the urinary tract such as epithelia lining the lumenal walls of the urethra, bladder, renal pelvis, and collecting ducts of the kidneys [10].
UPEC strains have different virulence factors that enable the bacteria to adhere and colonize the uroepithelial cells and to establish the UTIs. UPEC harbor more genes encoding adhesins, iron acquisition systems, and toxins than K12 strains and commensal E. coli isolates. These virulence genes are often encoded on mobile genetic elements called pathogenicity islands [11, 12].
This paper describes key virulence factors of UPEC, the role of biofilm formation by UPEC in development of UTIs and in catheter-associated UTIs. The resistance to antibiotics and new therapeutic approaches of treatment and control of UPEC will be also discussed.
2. Virulence factors of UPEC
2.1. Adhesins
Adhesive proteins as the most important determinants of pathogenicity of UPEC strains are arguable [13], but based on many observations of ABU strains, it was found that these strains are nonadherent and nonhemolytic [14]. UPEC adhesins activate host signaling pathways that promote bacterial invasion [15]. Bacterial adherence to urothelium is important in the development of UTI because it allows the bacteria to persist in the urinary tract against flushing by urine flow. Function of type 1 fimbriae as virulence factors in human pathology remains unclear because they are expressed in both commensal and pathogenic E. coli strains [16, 17]. The type 1 fimbriae are heteropolymeric surface organelles that consist of several subunits. These fimbriae bind E. coli cells to the urothelial mannosylated glycoproteins uroplakin by subunit FimH, which is located at the distal tip of the type 1 fimbriae. UPEC commonly expresses FimH that efficiently bind monomannose- and trimannose-containing glycoprotein receptors. Whereas, commensal E. coli strains usually bind to trimannose residues [18]. Binding of FimH to uroplakins that are expressed in the differentiated urothelium of the bladder and urethers causes adhesion and cellular invasion of E. coli and promotes formation of intracellular bacterial communities which leads to the acute stage of infection [19, 20]. FimH adhesin enables UPEC to escape before the immune response by internalization within urothelial cells. Inside infected urothelial cells, E. coli is harbored within vesicles [21, 22]. Blocking of FimH adhesin with antibodies or inactivity of the fimH gene has a negative effect on the ability of UPEC to colonize the bladder epithelium [5]. fimH gene is the most commonly identified virulence gene in the isolates causing UTI [17].
About 80% of UPECs express P fimbriae that are frequently associated with acute pyelonephritis [23]. P fimbriae are encoded by papA-K gene operon which can be localized on one or more pathogenic-associated islands [24]. The P-fimbrial–tip adhesins (PapG adhesins) bind to Gal α (1–4) Gal in glycosphingolipids of the membrane of urothelial cells localized in the kidney. The PapG adhesins are encoded by four classes of papG genes but only two of them are associated with uropathogenicity. Class II adhesin genes are predominant among the isolates from pyelonephritis and from renal transplant patients, while class III genes are found more frequently among cystitis isolates [25–27]. Attachment of P fimbriae to receptors leads to activation of the immune cell response and to the development of inflammation- and pain-associated with UTIs. P fimbriae improve bacterial colonization of the tubular epithelium that can adversely affect renal filtration leading to total obstruction of the nephron and consequently contributes to the full pathophysiology of pyelonephritis [14].
S fimbriae of E. coli bind to sialyl galactosides occurring in the receptors of erythrocytes and renal tubular epithelium cells, and are also involved in UTIs development. S fimbriae show binding to epithelial cells of lower urinary tract and kidney and may facilitate bacterial dissemination within host tissues [15, 28].
E. coli strains harboring operons coding fimbrial Dr and afimbrial Afa adhesins are also associated with UTIs. Dr adhesins bind to decay-accelerating factor (DAF) which is widely distributed along the urinary tract and plays an important role in colonization of urinary tract by Dr adhesin-producing E. coli [29]. UPECs with Afa adhesins have a tropism to renal tissue and have the ability to induce chronic or recurrent infection [30]. The research recently conducted by Muenzner et al. [31] showed that uropathogenic E. coli strains, which express the Dra/AfaE adhesins, bind to CEACAMs (carcinoembryonic antigen-related cell adhesin molecules) present on epithelial cells. The interaction of CEACAMs with Dra/AfaE adhesins causes increase of integrin activity, promote matrix adhesion, and suppress epithelial exfoliation, which promotes host infection.
Curli are highly adhesive extracellular amyloid fibers produced by UPEC and other Enterobacteriaceae [32]. The major subunit of curli is the CsgA [33]. Curli promote adherence to epithelial cells and resistance against the human antimicrobial peptide LL-37, and also cause induction of the proinflammatory cytokine IL-8. They exhibit exclusive role in promoting UPEC biofilms and represent one of the major biofilm components [34]. Curli are produced at limitation of nutrients and salts, at reduced oxygen tension and at temperature below 30°C. However, it is believed that many pathogenic bacteria and commensal strains can also express curli at 37°C during infection in humans [35]. Curli fimbriae interact with serum proteins and this might promote bacterial dissemination in host. UPEC strains-producing curli are more likely to cause urosepticaemia than strains which do not produce curli [36].
2.2. Toxins
Production of toxins by UPEC is an important virulence factor because they may induce an inflammatory response and lead to symptoms of urinary tract infections. The most important virulence factor of UPEC is α-hemolysin (HlyA). This toxin is strongly proinflammatory and leads to secretion of IL-6, IL-8, and chemotaxins that increase clinical severity in UTI patients [27, 37]. HlyA belongs to the family of RTX (repeats in toxin) [38]. HlyA is a lipoprotein of 110 kDa that forms pores in host cells, leading at high concentrations of HlyA to cell lysis, that enable UPEC to defeat mucosal barriers, damage effector immune cells, and gain access to nutrients and iron [39]. At sublytic concentrations, HlyA implicates the inhibition of chemotaxis and bacterial killing by phagocytes and induces apoptosis of neutrophils and renal cells, and also promotes the exfoliation of bladder epithelial cells [40]. Hilbert et al. [41] found that cytotoxicity, cytokine suppression, and HlyA production were tightly linked in clinical strains, and that E. coli utilizes HlyA to inhibit epithelial cytokine production in vitro. HlyA is responsible for about 50% of UTIs cases which leads to renal complications [27].
Cytotoxic necrotizing factor 1 (CNF1) is produced by approximately one third of UPEC [14]. The toxicity of this protein is linked with its ability to constitutive activation of the Rho GTPases that affect numerous cellular functions such as the formation of actin stress fibers and membrane ruffle formation. The result is the entry of E. coli into urothelial cells [42]. CNF1 promote apoptosis of bladder epithelial cells, probably stimulating their exfoliation and increasing bacterial entry to underlying tissue [43]. Besides, CNF1 inhibits activities of neutrophils, reducing phagocytosis and antimicrobial activity [44].
Secreted autotransporter toxin (Sat) is referred to as serine protease autotransporter and is associated with pyelonephritic E. coli strains. Sat is considered a virulence factor because it has toxic activity against cell lines of bladder or kidney origin. Sat induces elongation of cells and loosening of cellular junctions in cell lines of kidney. Furthermore, Sat triggers vacuolation within the cytoplasm of both human bladder and kidney cell lines [45]. Another secreted toxin called Vat (vacuolating autotransporter toxin), often expressed by UPEC strains, shows the ability to induce a variety of cytopathic effects in target host cells, including swelling and vacuolation. However, the role of Vat in UTI pathogenesis has not been thoroughly studied [46].
2.3. Iron acquisition systems
Limiting iron availability in the urinary tract is an important host defense against bacterial pathogens. For growth and metabolic activity, bacteria require a cytoplasmic iron concentration of about 10−6 M, while free iron concentrations in the mammalian host are extremely low (10−25 M in the blood and lower at other sites of organism) [47]. Consequently, pathogenic bacteria have to be equipped with systems for acquisition of iron from the host. Bacteria produce siderophores, low-molecular-weight molecules that bind and transport iron (Fe3+) through the bacterial membrane into cytosol where the iron is released. Iron bound siderophores are transported through (with) specific receptors at the outer membrane that facilitate carrying of siderophore-iron complexes through the bacterial membrane. Common siderophore system is enterobactin and its receptor FebA, which is expressed by both pathogenic and K12 E. coli strains, although in the context of infection and also other siderophore systems (salmochelin and IroN, aerobactin and IutA, and yersiniabactin and FyuA) have been observed in UPEC [3]. The occurrence of these systems in UPEC strains difficult to identify certain systems as virulence factors of UPEC [48].
3. Biofilm formation by UPEC
Currently biofilm is defined as a structured bacterial community embedded in a self-produced matrix and attached to an abiotic or living surface [49].
The biofilm matrix is composed with exopolysaccharides, which form a hydrated viscous layer and protects enclosed bacterial cells against dehydration, toxic molecules such as antibiotics, and from immune system of host [50]. Bacteria within the biofilm differ in gene expression resulting in a phenotype different from the planktonic bacteria. The slow growth of pathogens in biofilms is the major factor conferring resistance to antibiotics [51]. The ability of bacteria to form biofilm is associated with pathogenesis of numerous diseases. Biofilm formation results in chronic, persistent infections that are difficult to eradicate with antimicrobial treatment. It is believed that biofilms occur in up to 60% of human infections [52]. UPEC can persist within the bladder tissue in underlying epithelial cells or create biofilm-like pods in the recurrent cystitis [53]. Biofilm of E. coli may form on the urothelium and is involved in infections associated with biomaterials such as catheters or prostheses. UPEC strains are frequently isolated from biofilms formed in the lumen of catheters and showing resistance to antibiotic treatment [54]. Catheter-associated urinary tract infection (CAUTI) is the most common nosocomial infection, and approximately 80% of UTIs acquired in the hospital are associated with catheterization [55]. The insertion of indwelling catheter into the bladder increases the susceptibility of patients to UTIs, because these devices are the initiation site of infection by introducing opportunistic organisms into the urinary tract [56]. UPEC strains are capable of colonizing the intestinal and vaginal tracts, and these sites are potential reservoirs of microorganisms for UTIs and CAUTIs [57]. The urinary catheter connects the colonized perineum with the sterile bladder providing a route for bacterial entry along the catheter lumen or the external surface of the catheter [58]. CAUTI is related to the susceptibility of catheter material to microbial colonization. The initial stage of biofilm formation on a urinary catheter includes deposition of conditioning film of host urinary components, such as proteins, electrolytes, and other organic molecules [59]. These molecules on the surface of the urinary catheter may change its surface and neutralize any antiadhesive properties [60]. Planktonic bacteria are attached to the surface of the urinary catheter through hydrophobic and electrostatic interaction [61]. Development of biofilm on surface of the catheter occurs through the division of binding bacterial cells, appending additional planktonic bacteria and secretion of extracellular matrix. Detachment of single cell or group of bacterial cells from the biofilm may result in the passage of pathogens into the urine [51]. For this reason, biofilm formation on the urinary catheters is critical for initiating and maintaining of CAUTIs and is a reservoir of resistant pathogenic bacteria [62]. Several factors contribute to the formation of biofilm by E. coli, e.g. fimbriae, curli, and flagella. Type 1 fimbriae involved in biofilm formation may also support the colonization of urinary catheter surface [15]. The risk of CAUTI depends on the duration of catheterization, the quality of catheter care, and host susceptibility. Prolonged catheterization is the most important risk factor associated with CAUTI [62]. Long-term urinary catheter use (more than 30 days) causes permanent bacterial colonization of the urine in 100% cases [63]. Examination of people in a nursing home showed that long-term catheterization was significantly related with bacteriuria, pyelonephritis, and renal inflammation [58]. Forming of biofilm on the urinary catheters is a public health problem for patients who need these medical devices. It is recommended that patients who are chronically catheterized were treated with 5–10 days of targeted antibiotic therapy [64].
4. Antimicrobial resistance of UPEC
Antimicrobial resistance in UPEC is a clinical problem in patients with UTIs, in particular in women with recurrent UTI. The empirical antimicrobial treatment in case of recurrent UTIs exerts significant resistance pressure on the uropathogens and the fecal flora, which serves as resistance reservoirs for potential uropathogens [65–67]. Antimicrobial resistance among E. coli causing UTI is increasing in many countries around the world and shows considerable variations during different time periods and in different areas [68, 69].
The level of resistance of UPEC strains from hospitalized patients in Poland and Turkey to ampicillin was 56% [70, 71], while above 85% of UPEC strains from patients in India were resistant to this antibiotic [68]. High percentage (67.3%) of E. coli strains resistant to tetracycline was isolated from people with UTI from different parts of India [68].
Sanchez et al. [72] suggested that the increase of resistance of UPEC to ciprofloxacin is a result of widespread use of this antibiotic in the treatment of uncomplicated UTIs in the early 2000s. The most recent published data suggested that the level of resistance to trimethoprim-sulfamethoxazole increased and in different countries was over 21–24.2% [71–73]. This trend has continued for decades and the increasing resistance of E. coli to trimethoprim-sulfamethoxazole can be explained by frequent use of this antimicrobial agent because it is recommended as the second-line drug in treating acute uncomplicated cystitis in women. Authors reported low resistance of E. coli to nitrofurantoin (0.85–1.6%) and no increase in resistance in the last decade was observed [71, 72].
The extended spectrum of β-lactamases (ESBLs) produced by Enterobacteriaceae is responsible for resistance of amino and ureido penicillin, oxyimino cephalosporin, and monobactams, but not to 7-α-substituted β-lactam [74]. The production of ESBLs by UPEC strains complicates treatment because these strains are resistant not only to β-lactam antibiotics but often are also resistant to other classes of antibiotics-like aminoglycosides, quinolones, and cotrimoxazole, such as gentamicin, ciprofloxacin, and trimethoprim-sulfamethoxazole, respectively [75–77]. This reduces the treatment options to a limited number of antibiotics and empirical therapy with cephalosporins and fluoroquinolones often fail in patients with UTI [78]. Hoban et al. [79] found that these resistant microorganisms are more susceptible to the carbapenems, imipenem, and ertapenem, than to other antibiotics. ESBL-producing microorganisms were primarily considered multiresistant organisms originating in hospitals, but in recent years, the number of ESBL producers increased also among outpatients, especially related with UTIs. The authors reported 21 and 21.4% ESBL-producing E. coli found in community-acquired UTIs in Turkey [80] and in North India [81], respectively, while in Mexico, 31% of uropathogenic E. coli isolated from hospitalized patients [77] and 17.6% E. coli from hospitalized European UTI patients [79] were producers of ESBLs. UTIs complicated by ESBL producers tend to lead to uncertain outcomes and prolong hospitalization, especially that these organisms tend to be multidrug resistant [74]. Among ESBLs, the CTX-M enzymes are the most prevalent among isolates of UPE from inpatients and outpatients leading to serious problems for the antimicrobial management of these infections [82, 83]. There is a need for new therapy of UTI caused by multiresistant ESBL-producing UPEC.
5. Treatment and control of UPEC
Currently, the antibiotic therapy is an important part of the therapeutic strategy for UTI. The increased antibiotic resistance in recent years suggests that the choice of antibiotic should be guided by the results of sensitivity assay, although in cases of community-acquired UTI, an empirical therapy is often used [23]. The drugs of first-line choice for empirical treatment of uncomplicated UTI in all European countries are fosfomycin trometamol, pivmecillinam, or nitrofurantoin macrocrystals [84]. Trimethoprim-sulfamethoxazole is also used in countries where resistance to this chemotherapeutic is low. Higher rates of side effects in comparison with other drugs limit the use of quinolones as second-line therapy. Moreover, in many countries in Europe, high resistance rates of E. coli strains to nalidixic acid were observed [85], and thus aminoglycosides and carbapenem are the drugs of choice. In patients with recurrent infections of the urinary tract, the antibiotics may be recommended prophylactically. It is believed that two recurrences of UTI within 6 months after therapy or three episodes per year could be considered an indication to establish prophylaxis after treatment. The drugs for this purpose are nitrofurantoin, trimethoprin-sulfamethoxazole, fosfomycin trometamol, and cotrimoxazole at lower doses than therapeutic [86]. However, repeated antibiotic treatment of UTI and prophylactic use of antibiotics frequently results in a rise in resistance to antibiotics and adversely affects microbiota of patients which may lead to secondary infections posttreatment, such as gastrointestinal infection and vaginal yeast infection [87, 88].
For this reason, alternative or additional prophylactic strategies have been investigated. One of them is improving the management of UTI by the development of preventive vaccines. Effective vaccine for UTI will need to generate a strong mucosal immune response in the urinary tract. Designing a UTI vaccine that would be effective against UPEC is difficult due to heterogeneous nature of the UPEC population. UTI vaccine should be designed based on more than one antigen because not all strains express the exact set of virulence genes during infections. A vaccine based on the multiple virulence factors, such as fimbrial adhesins or iron receptors, could be clinically effective against UTI [89]. The vaccine with whole or lysed fractions of inactivated bacteria can be effective to generate protective immunity. Urovac® is one of such vaccines (Solco Basel AG, Birsfelden, Switzerland, and Protein Express, Cincinnati, OH, USA) containing ten heat-killed uropathogens, including six UPEC strains. The UPEC strains in the Urovac® show different virulence factors, such as hemolysin, type 1, P, and S fimbrial adhesins, CNF-1, siderophores, and the E. coli CFT073 pathogenicity island marker and many different O and H antigens. Evaluating the efficacy of vaginally administrated Urovac® found that the immunization did not ensure significant long-term protection from UTI or an increase in mean levels of UPEC antibodies in serum, vagina, or urine [90]. However, among the women receiving Urovac, 72% were free from UTIs, while only 30% of women given placebo remained free from UTIs caused by E. coli. Moreover, in the Urovac vaccinated group, the number of E. coli caused UTIs was significantly lower compared to the control group [91]. Another vaccine which is used in Switzerland since 1988 and sold in other countries worldwide is OM-89/Uro-Vaxom® (OM Pharma, Myerlin, Switzerland). Uro-Vaxom is an oral capsule containing a lyophilized mix of membrane proteins from 18 UPEC strains. The clinical studies showed that Uro-Vaxom was significantly more effective than placebo in preventing recurrent UTI [92].
Other prophylaxis method is use of different Lactobacillus species in the form of probiotics which reduced the risk of UTI and vaginal infections. Use of Lactobacillus species maintains low pH and produces hydrogen peroxide that inhibits growth of E. coli in urinary tract but also activates Toll-like receptor-2 and therefore leads to reduced inflammatory reaction [93]. Beerepoot et al. [94] conducted study in which postmenopausal women with recurrent UTI prophylactically received trimethoprim-sulfamethoxazole or oral capsules containing L. rhamnosus GR-1 and L. reuteri RC-14. After 12 months of treatment, the reduction in recurrence was more than 50% in both groups. However, in group that received trimethoprim-sulfamethoxazole, the two-fold increase in resistance was observed.
Research on dietary supplementation showed that cranberry juice and its extracts reduced UTI recurrences. The active metabolite of cranberry, proanthocyanidin A prevents bacterial adhesion to the urothelial layer by inhibiting P fimbriae expression [95]. The minimum daily dose of proanthocyanidin A, which is able to reduce significantly the number of urinary E. coli to be 36 mg [96]. The study conducted by Wojnicz et al. [97] showed that cranberry extract Żuravit S.O.S.® reduced motility and adhesion to epithelial cells in E. coli strains isolated from urine of patients with pyelonephritis and also limited the ability of these strains to form biofilm.
Bacteriophages are highly specific and very effective in lysing bacteria. The use of lytic phages that are able to pass through the extracellular matrix against E. coli biofilm causes a reduction of bacteria number in biofilm and also prevents biofilm formation on catheter coated with hydrogel containing bacteriophages [98, 99]. Biofilm-associated UTIs are difficult to treat due to the high level of antimicrobial resistance showed by biofilm structures. Many authors recommend macrolides (erythromycin, clarithromycin, and azithromycin) as the treatment of choice in biofilm-associated infections because these antibiotics inhibit the production of primary component of the matrix, alginate [100, 101]. Ciprofloxacin, norfloxacin, gentamicin, or nitrofurazone are often used as components in coating and impregnating the catheters in the aim to inhibit bacterial attachment and development of biofilm [55, 102]. New therapeutic antibiofilm treatments are studied as alternative to antibiotics in order to inhibit biofilm formation and also to avoid the emergence of resistant bacterial populations. The silver showed antimicrobial activity by interacting with bacterial cell membrane and is used to coat catheters. The study showed a statistically significantly lower frequency of bacterial infection in patients treated with a silver alloy-coated catheter compared to those treated with uncoated catheter. Schaeffer et al. [103] reported that bacteriuria was present in 27% of patients with the silver-coated silicone catheter and in 55% of group with uncoated silicone catheter. It was also demonstrated that silver alloy used in hydrogel-coated urinary catheter reduced of up 45% of CAUTI [104]. However, the study conducted by Desai et al. [105] showed that E. coli adherence was not significantly lower on silver-impregnated silicone or latex catheters compared to adherence of E. coli on catheters without silver.
The new antibiofilm strategy is phage therapy using engineered bacteriophages that have biofilm-degrading enzymatic activity. It was demonstrated that engineered phages that express biofilm-degrading enzymes are more efficient in removing bacterial biofilms than nonenzymatic phage alone. Lu and Collins [106] generated bacteriophage which expressed biofilm-degrading enzyme (DspB) during infection. The DspB showed simultaneous action against both bacterial cells in the biofilm and the biofilm matrix. The engineered enzymatic phage reduced bacterial biofilm cell in 99.9%. One of the new ways of eliminating biofilm is the use of nanoparticles. Water-based synthesis of yttrium fluoride (YF3) nanoparticles that showed antibacterial properties against E. coli was described. The minimal inhibitory concentration was observed at 0.01 mg/mL. In addition, YF3 nanoparticles-coated catheters were able to significantly reduce bacterial colonization compared to the uncoated surface, which provides the potential to develop the concept of utilizing yttrium fluoride nanoparticles as novel antimicrobial and antibiofilm agents [107].
The alternative strategies to decrease UPEC infection include the use of plant-derived antibacterial agents containing different functional groups in their structure and development of resistance in bacteria to these antimicrobials is less frequent [108]. Borges et al. [109] showed that phenolic acids such as gallic and ferulic acid have prevented biofilm formation and show potential to reduce the mass of biofilms formed by the Gram-negative bacteria including E. coli. The antibiofilm effect of trans-cinnamaldehyde (TC) on UPEC was reported by Amalaradjou et al. [110]. These authors showed that TC was effective against UPEC biofilm on polystyrene or latex, and the expression of E. coli genes encoding attachment and invasion of bladder cells was significantly decreased by TC [111]. Phytochemicals as alternative antimicrobials in preventing and inactivating E. coli biofilm on urinary catheters were also assessed. It was demonstrated that TC at the concentration of 0.5% was highly effective for preventing E. coli biofilm formation in the lumen of urinary catheter and after 1 day of completely inhibited biofilm formation. Whereas, completely inactivated biofilm after 1 day was observed at 1.25% and 1.5% TC solution. p-Coumaric and ferulic acids have preventive action on E. coli biofilm formation on urinary catheter but complete inactivation of the biofilm formed at presence of these phytochemicals was not observed [112]. Recently showed that two alkaloids, piperine from black pepper and reserpine from Indian snakeroot, decreased swarming and swimming motilities of the uropathogenic E. coli CFT073. Additionally, piperine increased penetration of ciprofloxacin and azithromycin in to biofilm of E. coli CFT073. Authors suggest that these substances can affect on bacterial colonization by inhibition bacterial motility and also may help in treatment of infection by strengthening the penetration of antibiotic in biofilms [113].
One of the other strategies to prevent colonization, invasion, and biofilm formation by UPEC is inhibition of the assembly of pili by family of bicyclic 2-pyridones, termed pilicides.
The activity of pilicides was evaluated in two different pilus biogenesis systems in UPEC. Hemagglutination mediated by either type 1 or P pili, adherence to bladder cells, and biofilm formation mediated by type 1 pili were all reduced by 90% in laboratory and clinical E. coli strains [114]. Pilicide ec240 was found to disrupt type 1 pili, P pili, S pili, and flagellar motility [115]. Other pilicides also inhibit the production of Dr pili that are important in pyelonephritis [116]. Mannosides are FimH receptor analogues and bind to this pilus with high affinity, which results in blocking FimH binding to mannosylated receptors. The use of mannosides is considered a new strategy in treating and preventing UTIs because they prevent bladder colonization and invasion and are effective against multidrug-resistant UPEC and against established UTIs [117].
6. Conclusions
UTIs belong to the most common bacterial infections. E. coli is the major factor of community-acquired UTIs and a large part of nosocomial UTIs is also caused by this microorganism. UPECs have a wide range of virulence factors and spread of antimicrobial resistance that threaten effective treatment of UTIs using antibiotics. Intensive research that can identify essential virulence mechanisms of UPEC can lead to the development of UTI treatments and prophylactics. The identification of virulence determinants, especially responsible for initial attachment and adhesion of bacterial cells to receptors can be the basis for the development of targeted therapy that prevents the development of UTI. New strategies of UTIs treatment and prevention include chemical compounds such as pilicides and mannosides that block UPEC adhesion or vaccines against siderophores, pili, and UPEC toxins. However, they are still at the preclinical stage of development. These novel antivirulence therapies for treatment of UTIs still require substantial effort associated with future clinical trials.
\n',keywords:"UPEC, UTI, virulence factors, biofilm, antimicrobial resistance, treatment of UPEC, prevention",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/54475.pdf",chapterXML:"https://mts.intechopen.com/source/xml/54475.xml",downloadPdfUrl:"/chapter/pdf-download/54475",previewPdfUrl:"/chapter/pdf-preview/54475",totalDownloads:1178,totalViews:549,totalCrossrefCites:2,totalDimensionsCites:2,hasAltmetrics:0,dateSubmitted:"May 18th 2016",dateReviewed:"February 8th 2017",datePrePublished:null,datePublished:"July 12th 2017",dateFinished:null,readingETA:"0",abstract:"Urinary tract infections (UTIs) are considered to be the most frequent bacterial infections. Escherichia coli is the major factor of community-acquired UTI (80–90%) and a large part of nosocomial UTI (30%), including cystitis, pyelonephritis, prostatitis, and asymptomatic bacteriuria. Uropathogenic E. coli (UPEC) shows a variety of virulence factors that allow their transition from the intestinal tract to the urinary tract and causing infection. The virulence factors responsible for pathogenesis outside the gastrointestinal tract belong to various functional groups. Antimicrobial resistance among E. coli causing UTIs is increasing in many countries around the world. This paper presents key virulence factors of UPEC such as adhesins, toxins, iron acquisition systems, and biofilm formation by UPEC, which are major problems in patients with long-term catheterization. The resistance of UPEC to antibiotics and innovative strategies of treatment and control of UPEC including drug therapy, preventive vaccines, probiotics, cranberry as source of antimicrobial metabolites, bacteriophages, new therapeutic antibiofilm treatment such as engineered phages, nanoparticles, and plant-derived antibacterial agents are also presented.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/54475",risUrl:"/chapter/ris/54475",book:{slug:"-i-escherichia-coli-i-recent-advances-on-physiology-pathogenesis-and-biotechnological-applications"},signatures:"Barbara Kot",authors:[{id:"189685",title:"Associate Prof.",name:"Barbara",middleName:null,surname:"Kot",fullName:"Barbara Kot",slug:"barbara-kot",email:"barbara.kot@uph.edu.pl",position:null,institution:null}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Virulence factors of UPEC",level:"1"},{id:"sec_2_2",title:"2.1. Adhesins",level:"2"},{id:"sec_3_2",title:"2.2. Toxins",level:"2"},{id:"sec_4_2",title:"2.3. Iron acquisition systems",level:"2"},{id:"sec_6",title:"3. Biofilm formation by UPEC",level:"1"},{id:"sec_7",title:"4. Antimicrobial resistance of UPEC",level:"1"},{id:"sec_8",title:"5. Treatment and control of UPEC",level:"1"},{id:"sec_9",title:"6. Conclusions",level:"1"}],chapterReferences:[{id:"B1",body:'Kaper JB, Nataro JP, Mobley HL. Pathogenic Escherichia coli. Nat Rev Microbiol. 2004;2:123-140. DOI:10.1038/nrmicro818'},{id:"B2",body:'Allocati N, Masulli M, Alexeyev MF, Di Ilio C. Escherichia coli in Europe: An overview. Int J Environ Res Public Health. 2013;10:6235-6254. DOI:10.3390/ijerph10126235'},{id:"B3",body:'Wiles TJ, Kulesus RR, Mulvey MA. Origins and virulence mechanisms of uropathogenic Escherichia coli. Exp Mol Pathol. 2008;85:11-19. DOI:10.1016/j.yexmp.2008.03.007'},{id:"B4",body:'Samet M, Ghaemi E, Nejad MH, Jamali A. 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Effect of silver oxide/trichloroisocyanuric acid antimicrobial urinary drainage system on catheter-associated bacteriuria. J Urol. 1988;139:69-73.'},{id:"B104",body:'Rupp ME, Fitzgerald T, Marion N, Helget V, Puumala S, Anderson JR, Fey PD. Effect of silver-coated urinary catheters: Efficacy, cost-effectiveness, and antimicrobial resistance. Am J Infect Control. 2004;32:445-450. DOI:10.1016/S0196655304004742'},{id:"B105",body:'Desai DG, Liao KS, Cevallos ME, Trautner BW. Silver or nitrofurazone impregnation of urinary catheters has a minimal effect on uropathogen adherence. J Urol. 2010;184:2565-2571. DOI: 10.1016/j.juro.2010.07.036'},{id:"B106",body:'Lu TK, Collins JJ. Dispersing biofilms with engineered enzymatic bacteriophage. Proc Natl Acad Sci U S A. 2007;104:11197-11202. DOI: 10.1073/pnas.0704624104'},{id:"B107",body:'Lellouche J, Friedman A, Gedanken A, Banin E. Antibacterial and antibiofilm properties of yttrium fluoride nanoparticles. Int J Nanomed. 2012;7:5611-5624. DOI: 10.2147/IJN.S37075'},{id:"B108",body:'Domadia P, Swarup S, Bhunia A, Sivaraman J, Dasgupta D. Inhibition of bacterial cell division protein FtsZ by cinnamaldehyde. Biochem Pharmacol. 2007;832:831-840. DOI: 10.1016/j.bcp.2007.06.029'},{id:"B109",body:'Borges A, Saavedra MJ, Simões M. The activity of ferulic and gallic acids in biofilm prevention and control of pathogenic bacteria. Biofouling 2012;28:755-767. DOI: 10.1080/08927014.2012.706751'},{id:"B110",body:'Amalaradjou MAR, Narayanan A, Baskaran SA, Venkitanarayanan K. Antibiofilm effect of trans-cinnamaldehyde on uropathogenic Escherichia coli. J Urol. 2010;184:358-363. DOI: 10.1016/j.juro.2010.03.006'},{id:"B111",body:'Amalaradjou MAR, Narayanan A, Venkitanarayanan K. Trans-cinnamaldehyde decreases attachment and invasion of uropathogenic Escherichia coli in urinary tract epithelial cells by modulating virulence gene exptression. J Urol. 2011;185:1526-1531. DOI: 10.1016/j.juro.2010.11.078'},{id:"B112",body:'Kot B, Wicha J, Piechota M, Wolska K, Grużewska A. Antibiofilm activity of trans-cinnamaldehyde, p-coumaric, and ferulic acids on uropathogenic Escherichia coli. Turk J Med Sci. 2015;45:919-924. DOI:10.3906/sag-1406-112'},{id:"B113",body:'Dusane DH, Hosseinidoust Z, Asadishad B, Tufenkji N. Alkaloids modulate motility, biofilm formation and antibiotic susceptibility of uropathogenic Escherichia coli. PLoS One. 2014;9:e112093. DOI: 10.1371/journal.pone.0112093'},{id:"B114",body:'Pinkner JS, Remaut H, Buelens F, Miller E, Aberg V, Pemberton N, Hedenström M, Larsson A, Seed P, Waksman G, Hultgren SJ, Almqvist F. Rationally designed small compounds inhibit pilus biogenesis in uropathogenic bacteria. Proc Natl Acad Sci U S A. 2006;103:17897-17902. DOI: 10.1073/pnas.0606795103'},{id:"B115",body:'Greene SE, Pinkner JS, Chorell E, Dodson KW, Shaffer CL, Conover MS, Livny J, Hadjifrangiskou M, Almqvist F, Hultgrenet SJ. Pilicide ec240 disrupts virulence circuits in uropathogenic Escherichia coli. mBio. 2014;5:e02038-14. DOI:10.1128/mBio.02038-14'},{id:"B116",body:'Piatek R, Zalewska-Piatek B, Dzierzbicka K, Makowiec S, Pilipczuk J, Szemiako K, Cyranka-Czaja A, Wojciechowski M. Pilicides inhibit the FGL chaperone/usher assisted biogenesis of the Dr fimbrial polyadhesin from uropathogenic Escherichia coli. BMC Microbiol. 2013 Jun 12;13:131. DOI: 10.1186/1471-2180-13-131.'},{id:"B117",body:'Totsika M, Kostakioti M, Hannan TJ, Upton M, Beatson SA, Janetka JW, Hultgren SJ, Schembri MA. A FimH inhibitor prevents acute bladder infection and treats chronic cystitis caused by multidrug-resistant uropathogenic Escherichia coli ST131. J Infect Dis. 2013;15; 208: 921-928. DOI: 10.1093/infdis/jit245'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Barbara Kot",address:"barbara.kot@uph.edu.pl",affiliation:'
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Lanzaro",slug:"gregory-c.-lanzaro"},{id:"169011",title:"Dr.",name:"Yoosook",middleName:null,surname:"Lee",fullName:"Yoosook Lee",slug:"yoosook-lee"}]},{id:"43973",title:"Advances and Perspectives in the Study of the Malaria Mosquito Anopheles funestus",slug:"advances-and-perspectives-in-the-study-of-the-malaria-mosquito-anopheles-funestus",signatures:"Ibrahima Dia, Moussa Wamdaogo Guelbeogo and Diego Ayala",authors:[{id:"154416",title:"Dr.",name:"Diego",middleName:null,surname:"Ayala",fullName:"Diego Ayala",slug:"diego-ayala"},{id:"167122",title:"Dr.",name:"Ibrahima",middleName:null,surname:"Dia",fullName:"Ibrahima Dia",slug:"ibrahima-dia"},{id:"169020",title:"Dr.",name:"Moussa",middleName:"Wamdaogo",surname:"Guelbeogo",fullName:"Moussa Guelbeogo",slug:"moussa-guelbeogo"}]},{id:"43614",title:"Highlights on Anopheles nili and Anopheles moucheti, Malaria Vectors in Africa",slug:"highlights-on-anopheles-nili-and-anopheles-moucheti-malaria-vectors-in-africa",signatures:"Christophe Antonio-Nkondjio and Frédéric Simard",authors:[{id:"153999",title:"Dr.",name:"Christophe",middleName:null,surname:"Antonio Nkondjio",fullName:"Christophe Antonio Nkondjio",slug:"christophe-antonio-nkondjio"},{id:"154272",title:"Dr.",name:"Frédéric",middleName:null,surname:"Simard",fullName:"Frédéric Simard",slug:"frederic-simard"}]},{id:"43975",title:"The Dominant Mosquito Vectors of Human Malaria in India",slug:"the-dominant-mosquito-vectors-of-human-malaria-in-india",signatures:"Vas Dev and Vinod P. Sharma",authors:[{id:"151166",title:"Dr.",name:"Vas",middleName:null,surname:"Dev",fullName:"Vas Dev",slug:"vas-dev"},{id:"169007",title:"Dr.",name:"Vinod",middleName:null,surname:"P. Sharma",fullName:"Vinod P. Sharma",slug:"vinod-p.-sharma"}]},{id:"45385",title:"Vector Biology and Malaria Transmission in Southeast Asia",slug:"vector-biology-and-malaria-transmission-in-southeast-asia",signatures:"Wannapa Suwonkerd, Wanapa Ritthison, Chung Thuy Ngo, Krajana\nTainchum, Michael J. Bangs and Theeraphap Chareonviriyaphap",authors:[{id:"151663",title:"PhD.",name:"Wannapa",middleName:null,surname:"Suwonkerd",fullName:"Wannapa Suwonkerd",slug:"wannapa-suwonkerd"},{id:"151737",title:"Dr.",name:"Michael",middleName:null,surname:"J. Bangs",fullName:"Michael J. Bangs",slug:"michael-j.-bangs"},{id:"169010",title:"Dr.",name:"Wanapa",middleName:null,surname:"Ritthison",fullName:"Wanapa Ritthison",slug:"wanapa-ritthison"}]},{id:"43254",title:"Understanding Anopheles Diversity in Southeast Asia and Its Applications for Malaria Control",slug:"understanding-anopheles-diversity-in-southeast-asia-and-its-applications-for-malaria-control",signatures:"Katy Morgan, Pradya Somboon and Catherine Walton",authors:[{id:"154092",title:"Dr.",name:"Catherine",middleName:null,surname:"Walton",fullName:"Catherine Walton",slug:"catherine-walton"},{id:"154867",title:"Dr.",name:"Katy",middleName:null,surname:"Morgan",fullName:"Katy Morgan",slug:"katy-morgan"},{id:"169019",title:"Dr.",name:"Pradya",middleName:null,surname:"Somboon",fullName:"Pradya Somboon",slug:"pradya-somboon"}]},{id:"44155",title:"The Systematics and Bionomics of Malaria Vectors in the Southwest Pacific",slug:"the-systematics-and-bionomics-of-malaria-vectors-in-the-southwest-pacific",signatures:"Nigel W. Beebe, Tanya L. Russell, Thomas R. Burkot, Neil F. Lobo and\nRobert D. Cooper",authors:[{id:"152080",title:"Dr.",name:"Nigel",middleName:null,surname:"Beebe",fullName:"Nigel Beebe",slug:"nigel-beebe"},{id:"169012",title:"Dr.",name:"Tanya",middleName:null,surname:"L. Russell",fullName:"Tanya L. Russell",slug:"tanya-l.-russell"},{id:"169013",title:"Dr.",name:"Thomas",middleName:null,surname:"R. Burkot",fullName:"Thomas R. Burkot",slug:"thomas-r.-burkot"},{id:"169014",title:"Dr.",name:"Neil",middleName:null,surname:"F. Lobo",fullName:"Neil F. Lobo",slug:"neil-f.-lobo"},{id:"169015",title:"Dr.",name:"Robert",middleName:null,surname:"D. Cooper",fullName:"Robert D. Cooper",slug:"robert-d.-cooper"}]},{id:"43671",title:"Ecology of Larval Habitats",slug:"ecology-of-larval-habitats",signatures:"Eliška Rejmánková, John Grieco, Nicole Achee and Donald R.\nRoberts",authors:[{id:"151632",title:"Prof.",name:"Nicole",middleName:null,surname:"Achee",fullName:"Nicole Achee",slug:"nicole-achee"},{id:"152601",title:"Prof.",name:"Eliska",middleName:null,surname:"Rejmankova",fullName:"Eliska Rejmankova",slug:"eliska-rejmankova"},{id:"169016",title:"Dr.",name:"John",middleName:null,surname:"Grieco",fullName:"John Grieco",slug:"john-grieco"}]},{id:"43954",title:"From Anopheles to Spatial Surveillance: A Roadmap Through a Multidisciplinary Challenge",slug:"from-anopheles-to-spatial-surveillance-a-roadmap-through-a-multidisciplinary-challenge",signatures:"Valérie Obsomer, Nicolas Titeux, Christelle Vancustem, Grégory\nDuveiller, Jean-François Pekel, Steve Connor, Pietro Ceccato and\nMarc Coosemans",authors:[{id:"131417",title:"Dr.",name:"Valérie",middleName:null,surname:"Obsomer",fullName:"Valérie Obsomer",slug:"valerie-obsomer"},{id:"152754",title:"Prof.",name:"Marc",middleName:null,surname:"Coosemans",fullName:"Marc Coosemans",slug:"marc-coosemans"},{id:"153949",title:"Dr.",name:"Pietro",middleName:null,surname:"Ceccato",fullName:"Pietro Ceccato",slug:"pietro-ceccato"},{id:"153950",title:"Dr.",name:"Gregory",middleName:null,surname:"Duveiller",fullName:"Gregory Duveiller",slug:"gregory-duveiller"},{id:"153952",title:"Dr.",name:"Christelle",middleName:null,surname:"Vancutsem",fullName:"Christelle Vancutsem",slug:"christelle-vancutsem"},{id:"153980",title:"Dr.",name:"Nicolas",middleName:null,surname:"Titeux",fullName:"Nicolas Titeux",slug:"nicolas-titeux"},{id:"154158",title:"Dr.",name:"Steve J",middleName:null,surname:"Connor",fullName:"Steve J Connor",slug:"steve-j-connor"},{id:"167685",title:"MSc.",name:"Jean-Francois",middleName:null,surname:"Pekel",fullName:"Jean-Francois Pekel",slug:"jean-francois-pekel"}]},{id:"43960",title:"Simian Malaria Parasites: Special Emphasis on Plasmodium knowlesi and Their Anopheles Vectors in Southeast Asia",slug:"simian-malaria-parasites-special-emphasis-on-plasmodium-knowlesi-and-their-anopheles-vectors-in-sout",signatures:"Indra Vythilingam and Jeffery Hii",authors:[{id:"151116",title:"Dr.",name:"Indra",middleName:null,surname:"Vythilingam",fullName:"Indra Vythilingam",slug:"indra-vythilingam"},{id:"169006",title:"Dr.",name:"Jeffery",middleName:null,surname:"Hii",fullName:"Jeffery Hii",slug:"jeffery-hii"}]},{id:"44039",title:"Thermal Stress and Thermoregulation During Feeding in Mosquitoes",slug:"thermal-stress-and-thermoregulation-during-feeding-in-mosquitoes",signatures:"Chloé Lahondère and Claudio R. Lazzari",authors:[{id:"151619",title:"Prof.",name:"Claudio",middleName:null,surname:"R. Lazzari",fullName:"Claudio R. Lazzari",slug:"claudio-r.-lazzari"},{id:"151620",title:"Ms.",name:"Chloé",middleName:null,surname:"Lahondère",fullName:"Chloé Lahondère",slug:"chloe-lahondere"}]},{id:"43955",title:"The Anopheles Mosquito Microbiota and Their Impact on Pathogen Transmission",slug:"the-anopheles-mosquito-microbiota-and-their-impact-on-pathogen-transmission",signatures:"Mathilde Gendrin and George K. Christophides",authors:[{id:"154007",title:"Dr.",name:"Mathilde",middleName:null,surname:"Gendrin",fullName:"Mathilde Gendrin",slug:"mathilde-gendrin"},{id:"154008",title:"Prof.",name:"George",middleName:"K",surname:"Christophides",fullName:"George Christophides",slug:"george-christophides"}]},{id:"43829",title:"Bacterial Biodiversity in Midguts of Anopheles Mosquitoes, Malaria Vectors in Southeast Asia",slug:"bacterial-biodiversity-in-midguts-of-anopheles-mosquitoes-malaria-vectors-in-southeast-asia",signatures:"Sylvie Manguin, Chung Thuy Ngo, Krajana Tainchum, Waraporn\nJuntarajumnong, Theeraphap Chareonviriyaphap, Anne-Laure\nMichon and Estelle Jumas-Bilak",authors:[{id:"50017",title:"Prof.",name:"Sylvie",middleName:null,surname:"Manguin",fullName:"Sylvie Manguin",slug:"sylvie-manguin"},{id:"75315",title:"Prof.",name:"Theeraphap",middleName:null,surname:"Chareonviriyaphap",fullName:"Theeraphap Chareonviriyaphap",slug:"theeraphap-chareonviriyaphap"},{id:"88985",title:"Prof.",name:"Anne-Laure",middleName:null,surname:"Michon",fullName:"Anne-Laure Michon",slug:"anne-laure-michon"},{id:"88986",title:"Prof.",name:"Estelle",middleName:null,surname:"Jumas-Bilak",fullName:"Estelle Jumas-Bilak",slug:"estelle-jumas-bilak"},{id:"156016",title:"MSc.",name:"Chung Thuy",middleName:null,surname:"Ngo",fullName:"Chung Thuy Ngo",slug:"chung-thuy-ngo"},{id:"156018",title:"MSc.",name:"Krajana",middleName:null,surname:"Tainchum",fullName:"Krajana Tainchum",slug:"krajana-tainchum"},{id:"156019",title:"Dr.",name:"Waraporn",middleName:null,surname:"Juntarajumnong",fullName:"Waraporn Juntarajumnong",slug:"waraporn-juntarajumnong"}]},{id:"43899",title:"Distribution, Mechanisms, Impact and Management of Insecticide Resistance in Malaria Vectors: A Pragmatic Review",slug:"distribution-mechanisms-impact-and-management-of-insecticide-resistance-in-malaria-vectors-a-pragmat",signatures:"Vincent Corbel and Raphael N’Guessan",authors:[{id:"152666",title:"Dr.",name:"Vincent",middleName:null,surname:"Corbel",fullName:"Vincent Corbel",slug:"vincent-corbel"},{id:"169017",title:"Dr.",name:"Raphael",middleName:null,surname:"N'Guessan",fullName:"Raphael N'Guessan",slug:"raphael-n'guessan"}]},{id:"43851",title:"Perspectives on Barriers to Control of Anopheles Mosquitoes and Malaria",slug:"perspectives-on-barriers-to-control-of-anopheles-mosquitoes-and-malaria",signatures:"Donald R. Roberts, Richard Tren and Kimberly Hess",authors:[{id:"151439",title:"Prof.",name:"Donald",middleName:null,surname:"R. Roberts",fullName:"Donald R. Roberts",slug:"donald-r.-roberts"},{id:"151656",title:"Mr.",name:"Richard",middleName:null,surname:"Tren",fullName:"Richard Tren",slug:"richard-tren"},{id:"154152",title:"Ms.",name:"Kimberly",middleName:null,surname:"Hess",fullName:"Kimberly Hess",slug:"kimberly-hess"}]},{id:"43874",title:"Residual Transmission of Malaria: An Old Issue for New Approaches",slug:"residual-transmission-of-malaria-an-old-issue-for-new-approaches",signatures:"Lies Durnez and Marc Coosemans",authors:[{id:"152754",title:"Prof.",name:"Marc",middleName:null,surname:"Coosemans",fullName:"Marc Coosemans",slug:"marc-coosemans"},{id:"169018",title:"Dr.",name:"Lies",middleName:null,surname:"Durnez",fullName:"Lies Durnez",slug:"lies-durnez"}]},{id:"44330",title:"Vector Control: Some New Paradigms and Approaches",slug:"vector-control-some-new-paradigms-and-approaches",signatures:"Claire Duchet, Richard Allan and Pierre Carnevale",authors:[{id:"151662",title:"Dr.",name:"Pierre",middleName:null,surname:"Carnevale",fullName:"Pierre Carnevale",slug:"pierre-carnevale"},{id:"169000",title:"Dr.",name:"Richard",middleName:null,surname:"Allan",fullName:"Richard Allan",slug:"richard-allan"},{id:"169008",title:"Dr.",name:"Claire",middleName:null,surname:"Duchet",fullName:"Claire Duchet",slug:"claire-duchet"}]},{id:"43870",title:"New Salivary Biomarkers of Human Exposure to Malaria Vector Bites",slug:"new-salivary-biomarkers-of-human-exposure-to-malaria-vector-bites",signatures:"Papa M. Drame, Anne Poinsignon, Alexandra Marie, Herbert\nNoukpo, Souleymane Doucoure, Sylvie Cornelie and Franck\nRemoue",authors:[{id:"151515",title:"Dr.",name:"Papa Makhtar",middleName:null,surname:"Drame",fullName:"Papa Makhtar Drame",slug:"papa-makhtar-drame"},{id:"151648",title:"Dr.",name:"Franck",middleName:null,surname:"Remoué",fullName:"Franck Remoué",slug:"franck-remoue"},{id:"154034",title:"Dr.",name:"Anne",middleName:null,surname:"Poinsignon",fullName:"Anne Poinsignon",slug:"anne-poinsignon"},{id:"154035",title:"MSc.",name:"Alexandra",middleName:null,surname:"Marie",fullName:"Alexandra Marie",slug:"alexandra-marie"},{id:"154037",title:"Dr.",name:"Souleymane",middleName:null,surname:"Doucoure",fullName:"Souleymane Doucoure",slug:"souleymane-doucoure"},{id:"154038",title:"MSc.",name:"Herbert",middleName:null,surname:"Noukpo",fullName:"Herbert Noukpo",slug:"herbert-noukpo"},{id:"154039",title:"Dr.",name:"Sylvie",middleName:null,surname:"Cornélie",fullName:"Sylvie Cornélie",slug:"sylvie-cornelie"}]},{id:"44149",title:"Transgenic Mosquitoes for Malaria Control: From the Bench to the Public Opinion Survey",slug:"transgenic-mosquitoes-for-malaria-control-from-the-bench-to-the-public-opinion-survey",signatures:"Christophe Boëte and Uli Beisel",authors:[{id:"98400",title:"Dr.",name:"Christophe",middleName:null,surname:"Boëte",fullName:"Christophe Boëte",slug:"christophe-boete"},{id:"167749",title:"Dr.",name:"Uli",middleName:null,surname:"Beisel",fullName:"Uli Beisel",slug:"uli-beisel"}]}]}]},onlineFirst:{chapter:{type:"chapter",id:"65089",title:"High Purity Germanium: From Gamma-Ray Detection to Dark Matter Subterranean Detectors",doi:"10.5772/intechopen.82864",slug:"high-purity-germanium-from-gamma-ray-detection-to-dark-matter-subterranean-detectors",body:'\n
\n
1. Introduction
\n
This chapter provides a technical overview of HPGe detectors and their applications, both in science and day-to-day life. This overview covers the applications of HPGe as a material for γ-ray detection and its other more recent use in particle physics. It represents an introduction rather than a complete and exhaustive description of possible detector applications of HPGe.
\n
Since the 1970s, photon detectors (γ and X) have been developed from high purity germanium [1]. The reason why HPGe has remained in use for such a long time as high-resolution γ- and X-ray detector material is mainly because it contains a very low concentration of electrically active defects [2, 3] which may be lower than 109 cm−3. Such value is difficult to reach in compound semiconductors. Even for detector-grade silicon, the doping level is slightly higher. High electron density (Z = 32), together with low average energy, is needed for e-h pair generation. Above 1 keV of initial particle energy, germanium is a good choice for the detection of photon or ionizing particles. See \nTable 1\n and Refs. [4, 5, 6, 7, 8, 9, 10] for studies, both theoretical and experimental, on ionization in semiconductors. In the early days of germanium γ-ray detection, less purified material was used. The compensation method for net doping density reduction was based on the lithium drifting technique [11]. With an applied voltage bias, the drift of the interstitial Li+ ions through the detector is made possible leading to the neutralization of acceptors by the creation of Li+ acceptor pairs. However, progress in Ge purification led to the obsolescence of compensation techniques. Lithium is still used as a doping ion for the creation of n+ contacts, even though ion-implantation is now a mainstream technique for this purpose. Room-temperature γ-ray detection is still a challenge as the best candidate material exhibits higher defect concentrations and/or is difficult to grow into large crystals. Cadmium telluride is a material of choice for photo-detection, and gallium arsenide is another option. However, considerable progress would be necessary to match the easiness of use of HPGe in its present-day applications, despite the need for cryogenic apparatus.
\n
Table 1.
Semiconductors that may be used for the direct detection of γ rays and their average energy for electron hole creation Ehn and other quantities, the linear energy transfer is indicated for high-energy charged-particle detection (at Minimum Ionization).
\n
The main contributions to the development of high-purity germanium have been made already in the 1970s by the LBNL [1] and other US laboratories as well as industrial companies. There are presently a few corporations in Europe which supply such materials, without mentioning those from Eastern Europe. High-purity single crystals are usually grown in hydrogen atmosphere in a silica crucible [9, 12]. This prevents the introduction of oxygen and other electrically active impurities. However, this process introduces substitutional silicon, which is electrically inactive, similar to carbon. These crystals exhibit high levels of interstitial hydrogen, which may form complexes with some metallic impurities such as copper [13]. Good quality crystals (despite being small) may be fabricated in University labs [11, 14] which show that nowadays the availability of such crystals is better than ever. Gamma-ray detector manufacturers usually use commercially available crystals, which are subsequently processed, or in some cases fabricate the material itself. It should be noted that except for isotopically enriched crystals (for physics experiments), most crystals are made of natural germanium with a proportion of isotopes indicated in \nTable 2\n.
\n
Table 2.
Stable isotopes found in natural germanium with the nuclear moments and abundance.
\n
\n
\n
2. Gamma-ray detection and spectroscopy
\n
In this chapter, we introduce the principle of γ-ray detection and spectroscopy. Most high-energy photons (100 keV–10 MeV) interact with the electrons in the HPGe material [15]. As the density of electrons is proportional to Z, Ge is a material close to the optimum among well-characterized semiconductors, together with CdTe and GaAs. As the absorption coefficient increases along with Z, this results in a good detection efficiency for a given detector volume compared for instance with silicon. Here are the three main processes by which gamma rays lose energy in the detecting media: the photoelectric effect, Compton scattering, and e+e− pair creation. The photoelectric process [16] is dominant at low energies (<100 keV approximately) and is related to emission of electrons from the atomic shells. This process depends on the energy of the photons and the atomic number of the detecting media. The energy of a photon is absorbed by an inner-shell electron and leads to its emission from the atom. Subsequently, the photoelectrons lose their kinetic energy in the semiconductor by electron-hole pair generation. This first term is the photoelectron energy (Ephotoelectron), and the second is the difference between the gamma energy (Eγ) and the electron binding energy (Ebindingenergy).
The electron binding energy for K-shell valence electrons is of the order of 11 keV in Ge, compared to around 1.8 keV in silicon. Other, shallower shells may also be excited, contributing to the signal, which means that as the photon energy increases, inner shells can be excited gradually and the absorption will exhibit abrupt increase. This does not have a direct influence on the average number of electron-hole pairs generated per unit of energy deposited; we will discuss this in the following paragraph [8]. The absorption coefficient is proportional to:
\n
\n\n\n\nZ\n4\n\n\nE\n3\n\n\n\nE2
\n
This means that the contribution of the photoelectric effect vanishes at high energies (E), when the other two processes of interaction of gamma rays with matter become dominant. In the intermediate energy range, Compton effect dominates, hence the absorption of the photon becomes a multistep process with Compton electrons (<1 MeV) being absorbed after traveling a short distance, while Compton photons are created and absorbed in subsequent steps. One should note that some photons can escape the detecting medium and consequently do not contribute to a full-energy peak. These induce a signal background (Compton background) that is particularly large in low volume detectors. Techniques exist to mitigate this drawback using a secondary detector surrounding the primary one. This secondary detector is referred to as a Compton shield [17]. This anticoincidence scheme with these two detectors eliminates the un-absorbed photon events. This shows that for high detection efficiency, a relatively large volume of the detector is necessary for γ-ray spectroscopy. This is much different for γ-ray tracking is, when detector granularity is required. Time coincidence between events in neighboring detectors is the way to proceed to identify the particles. The probability of interaction with the electrons of the solid through Compton effect increases when the density of electrons n increases, being roughly proportional to it. If ρ is the mass density of the solid and A the mass number, the average electron density is proportional to ρ/A, which is the atomic density, multiplied by Z, the number of electrons per atom [16].
\n
\n\n\n\nn\n=\nZ\n×\n\nρ\nA\n\n\n\n\nE3
\n
This shows that as the Z/A ratio is constant, it is reasonable to use very dense media. Hence, it proves that germanium is a better choice than silicon for this purpose, as would be CdTe or GaAs, if the defect concentration could be reduced to an acceptable level. We will discuss the problem of defects in the following paragraph. Present-day experiments benefit from simulation codes such as GEANT4 or others [18] for their design. HPGe γ-ray detectors are no exception. The other process that becomes important at higher photon energy is the electron-positron pair creation, which may appear at energies above 1022 keV. This kind of interaction is related to γ-nuclear coupling, where the γ-photon interacts with the nucleus resulting in a creation of a e−/e+ pair with a total kinetic energy equal to Ek = Eγ − 1.022 MeV (Ek is the kinetic energy of the e = e− pair, and Eγ is the energy of the incident gamma photon). Subsequently, the positron may annihilate with an electron in the material, which leads to the production of two γ-rays of 511 keV that may (but not have to) be absorbed in the detecting material through Compton or photoelectric effect processes. As one or both 511-keV photons may escape from the detector with no energy deposition, satellite peaks appear in the measured energy spectrum, called escape peaks and separated from the total absorption peak by a 511 keV energy difference (or 1022 keV for double escape). Again, some discrimination is possible to avoid this effect, although one should be interested in visualizing the different peaks to investigate how the incident particle has interacted with the detector medium. The e + e- pair creation is most important at energies above 10 MeV [16], which shows that HPGe is not a good choice for very energetic photons such as cosmic radiation or those generated by high-energy accelerators (~1 GeV) since huge monocrystals would be required to provide a significant detection efficiency. This is hardly possible, with the largest commercially available HPGe crystals weighing 1–2 kg (larger crystals have been grown for specific applications) and having a diameter of a few centimeters. If we consider photofission [19], it has been reported that it occurs in natural lead for 10 MeV range photons. However, as the dependence on the fissility parameter is sublinear in logarithmic scale, it should be considered as being very weak for a germanium nucleus. Let us compare with lead, the fissility parameters read:
Hence, according to these figures, photofission should be much lower for natural Ge than for natural Pb. We therefore can consider this contribution as negligible in the energy range a few tens of MeV for the photons that are usually analyzed using HPGe spectrometers. This is the case in nuclear sciences for radioisotope identification and monitoring. Hence, for nuclear physics, HPGe is an adequate choice and widely used for detection of low energy and medium energy photons. In high-energy physics experiments, electromagnetic calorimeters are mostly based on dense liquids or solids and exhibit some granularity [20], while the energy resolution at high energy is not as good as for HPGe at low energies. Up to now, no high energy physics experiment has ever introduced HPGe as a semiconductor detector in calorimeters. Instead, silicon cells with absorbers are used in calorimeters and are proposed for several future detectors with the advantage of operation at room temperature, which is possible with semiconductors exhibiting a larger band gap, such as silicon.
\n
\n
\n
3. Technology, material, geometry, and performance of HPGe gamma-ray detectors
\n
Focusing on photon energy resolution criterion, HPGe still provides one of the best results. With a good quality material, the energy resolution is very close to the Fano limit [21, 22]. To obtain this, the readout electronics must be low noise. Historically, the front-end transistor was a JFET cooled to the temperature of the detector (77 K, liquid nitrogen temperature) [9, 23]. This reduced the energy resolution to less than 1 keV for 1 MeV photons. It would now be possible to use very low-noise room temperature CMOS μ electronic circuits [24] to match the low-noise specifications required for γ-ray spectrometry. The front-end readout electronics for these detectors is usually a charge-sensitive device, which is necessary for spectrometric measurements for which the generated charge is proportional to the energy deposited in the detectors. These CSA (charge-sensitive amplifiers) have an integrating pole followed by filtering stage (usually based on derivation-integration schemes for optimal filtering). This is done by a so-called shaper in order to optimize the signal/noise ratio and to reduce event pile up through fast operation. This channel is however slow (a few μs), so it may be supplemented by a fast current-sensitive channel, for coincidence, veto (anticoincidence) or timing purposes.
\n
Because a typical size of a HPGe detector is not optimum for timing measurements, the resolution obtained with a CFD (Constant Fraction Discriminator) is close to 400 ps [25], which is a high value compared with other fast detectors (PM or APD). In fact, this value was measured for a planar germanium detector of a volume of a few cubic centimeters, and it would be even higher for standard coaxial HPGe detectors.
\n
\n
3.1 Starting material
\n
In order to reach optimum resolution of semiconductor detectors, the crystal defect density should be decreased, in particular for those that are electrically active. This has become possible when defect and impurity control in the process of crystal growth has reached a sufficient level of reliability. In addition to point defects and impurities, dislocations play a major role as they behave like a sink for impurities [1, 9, 12]. They can currently be revealed by chemical crystal etching. The pits observed using optical microscopes are related to dislocations, which allows determining the etch-pit density. These dislocations induce a broad DLTS signal in n-type high purity material [3]. These are moderately deep donor states with carrier capture cross section of the order of 10−13 cm−2 or more. The peak is at 50–60 K for a large emission rate window (56 s−1) [3]. This means that at 77 K, the emission rate is large enough to have no marked effect on carrier trapping as the electrons are released with a time constant that is low compared with the drift time. With σn higher than 10−13 cm−2, which is the case with a filling pulse shorter than 1 ms in duration (with a 1010 cm−3 carrier concentration, and 106 cm s−1 of thermal velocity at 50 K, in our DLTS measurements), the emission rate at 77 K exceeds the capture rate for an activation energy of 100 meV. The other fact is that the DLTS signal fades away above 65 K, so the contribution of the dislocation band should be low as long as the concentration remains at a reasonable level. This gives a rule of thumb [2] for the dislocation density that should not exceed 104 cm−2 and should be above 102 cm−2 for detector-grade material, at least for the material used in the 1980s–1990s. If the dislocation density is too low, the deep impurities such as those related with copper (substitutional or bound with hydrogen) will be higher, as they cannot precipitate onto the dislocation lines and have a higher density than isolated impurities. They give rise to deep hole traps that affect greatly the hole transport even at 77 K. These traps have an activation energy higher than 0.160 eV and capture cross sections above 10−13 cm−2, (similar to coulombic/attractive centers) with concentrations reaching 109 cm−3.
\n
\n
\n
3.2 Geometry and process
\n
The structures that have been used from the early days of Ge detectors are p+n−n+ and p+p−n+, usually with a Li-diffused n+ contact and a boron-implanted p+ contact, and a thin metallization of sputtered aluminum or electrolytically plated gold in old detectors. Following an appropriate surface treatment (etching with CP4 mixture after cleaning with solvents such as acetone) and rinsing with a slightly oxidizing mixture, the detectors are placed in secondary vacuum, and after surface desorbing, the leakage current can be stabilized at low values. The leakage dark current at 77 K with a reverse bias of 1 kV or more for large coaxial detectors can be reduced to the order of a few pA or less. Usually a thermal treatment above room temperature will allow surface desorbing, and consequently impurities on the surface will be eliminated. The question of passivation is still open, as germanium does not have the self-passivation properties of silicon, for which oxygen creates a stable oxide layer of a few nm at room temperature. Germanium oxides are not stable [26, 27, 28, 29] and react with water. More recent passivation methods are based on amorphous layer deposition such as a-Ge-H (amorphous hydrogenated germanium). These constitute a coating, rather than standard passivating layers. In spite of this, their effect is to stabilize leakage currents at 77 K at reasonable values. However, these values are higher than those for bare Ge material in vacuum.
\n
As the presence of defects mainly alters the transport of holes, efforts were made to reduce the mean-drift length of holes by an adequate electrode configuration [30]. For coaxial detectors, the hole-collecting electrode can be placed at the outer surface of the detectors. This is usually a p+ outside implant, which is shallower than the n+ electrode, which is placed on the axis of the detector. Holes have a shorter drift distance than the electrons, the p+ electrode being negatively biased. This configuration is less sensitive to cumulative nonionizing radiation effects. N-type material is used contrary to p-type material with opposite electrode configuration in the conventional detectors. The same is true for planar detectors, for which the collecting length is reduced to values well below 1 cm. The cumulative radiation effects are mainly deep defects introduced by irradiation by nonionizing particles, such as hadrons (particularly neutrons and protons), but also energetic electrons. These particles, particularly at energies in the MeV range, induce displacement cascades in the detecting crystalline material and therefore produce defects of various nature, point-like or clusters. The temperature of operation and irradiation has a great influence on the outcome [25]. The result is a degradation of the energy resolution, which can be observed as a broadening of the photo-peaks, with a tail at low energy giving them an asymmetric aspect. As the detector can be compared to an ionization chamber with two electrodes polarized at different potentials, the current integrated by the readout electronics is a displacement current. The total charge collection is achieved when all holes and electrons are collected by the n+ (positively biased) and p+ (negatively biased) electrodes (cathode and anode). If carriers become trapped during the transport process, a loss of charge occurs leading to a peak tail at low energy. The collected charge is lower than the photo generated charge. Statistically, there is a certain charge deficit in the signal corresponding to one event, so the high-energy side of the peaks is not much affected [30], contrary to the low energy side. This leads to a loss of energy resolution. The charge loss is often followed by charge reemission with a large time constant, which has no real influence of the spectrum. An analytical model of radiation-induced defects has been proposed in Ref. [25] and developed in later papers.
\n
\n
\n
3.3 Defects
\n
The radiation-induced effects have been widely studied in HPGe detectors [30, 25, 31], and, in the beginning, without a quantitative relation to crystalline defects introduced by irradiation in HPGe. Since these effects result in resolution degradation, their characterization is of utmost importance. We can cite a few extensive works on this subject, mostly using electrical measurements [12, 13]. A powerful characterization technique called photoelectric spectroscopy [32] or alternatively photo-thermal ionization spectroscopy (PTIS) has been successfully applied to HPGe, but this technique is limited to shallow hydrogenoid levels with low concentration and not operation-detrimental deep levels. It applies a two-step process, phonon + photon (far infrared) and requires low temperature operation (LHe) below the ionization temperature of impurities and dopants. No overlapping of the bound electron wavefunction is required, so it can only be used when the impurities have a low concentration. For deep-defects, deep level transient spectroscopy (DLTS) became the technique of choice. In particular, it helped to establish that deep traps that are created by a temperature increase above 77 K are more detrimental to detector operation than the primary defects that are created by irradiation at low temperature [3]. Neutron-induced defects are thought to be vacancy and interstitial related at 77 K. After annealing above this temperature, divacancies and impurity-vacancy defects are the most numerous centers observed that are electrically active. They give rise to numerous deep hole-traps with capture cross sections of the order of 10−13 cm−2. They only anneal out above 420–470 K, where less electrically active defects are created. The stable defects at 100 K and less are disordered regions containing a large concentration of vacancies and interstitials. These act as hole-traps but are less effective in degrading resolution than secondary defects observed at room temperature. Numerous studies have been devoted to the degradation of the resolution, and most of them identify the causes as being related to the defects with capture cross sections of the order of 10−11 cm−2 [2]. We know from experiments and simulations that these are due to zones with a high local defect density, which enhances capture probability [33] through an electrostatic effect.
\n
Street [34] has found that the presence of disorders in amorphous silicon enhances the cross section for the capture of carriers by the defects. Later, an analytical model has been developed that clearly explains this effect using simple assumptions [33]. This mitigates the direct role of disordered regions as being the sole origin of carrier capture at 77 K. The sizes of these disordered regions areof the order of the range of primary recoil atoms (\nFigure 1\n). Isolated defects should contribute greatly to the trapping process. The recoil of an atom is induced by the collision with the impinging particle. SRIM simulations show that its range is of the order of 10 nm at 10–30 keV, with around a few hundred vacancies being created on its trajectory. The recoil energy has been computed for neutrons in the MeV energy range, see \nFigure 1\n. In most cases, a thermal treatment above room temperature is used to remove radiation damage. In Ref. [31], recombination-enhanced annealing using minority-carrier injection was applied but with no significant results, at least at room temperature. At low temperature, when the defects are not stable, no improvement could be observed with this method. However, a strong dependence of the annealing stages on the material type (p or n) was observed in Refs. [3, 25] and other detector studies.
\n
Figure 1.
SRIM simulation showing the vacancy distribution for a Ge recoil of 30 keV.
\n
\n
\n
3.4 Alternatives to HPGe
\n
For a long time, materials alternative to HPGe have been proposed, and corresponding detectors were fabricated. GaAs is one example (mostly for X-ray detection), and, more importantly, CdTe. The goal was to eliminate the need for cryogenic operation by the use of large band gap semi-insulating material (diamond is also considered). Many difficulties still exist, mostly related to the defect density that is much higher in binary materials [9]. The other drawback is the possibility to grow large crystals, which proves to be more difficult for alternative materials. Large diamond single crystals with a low nitrogen content are difficult to grow as they need high-pressure processing. However, some CdTe photon detectors using segmented crystals for photon identification have been successfully implemented on space missions (INTEGRAL) [24]. Segmentation allows reducing drift length and therefore trapping, so that the resolution can be maintained at an acceptable level.
\n
\n
\n
3.5 Particle identification
\n
Particle identification through pulse shape discrimination is one of the developments that are used mainly in nuclear physics [35]. These techniques can be adequately used to determine the region of the detector where the interaction took place. There have been early reports for methods of particle identification in germanium and silicon detectors [36, 37]. The detection of photons is basically through ionization, and there is no important interaction with the nucleus, which could transfer momentum to the nucleus. If we consider other particles with a significant mass, their interaction with the nucleus may induce the recoil, which in turn is slowed down in the detector material. The slowing-down process results in ionization (electron-hole pair generation), defect creation (vacancies and interstitials), and phonon creation. One should note that according to SRIM simulations, in the typical energy range for the recoil (20–30 keV), the most important contribution (73%) is from phonon emission. The energy used for vacancy creation is of the order of 3%, which indicates that defect monitoring [38] could provide an alternative way to estimate the total integrated flux of interacting particles, since when stable defects are created, their concentration is proportional to the total number of interacting particles in a given time interval, which can be very long. The rest of the energy is used for ionization (25%). This result is close to the experimental result obtained for cryogenic detectors, as it will be discussed in the paragraph on dark matter detection.
\n
\n
\n
3.6 Simulation
\n
Simulations of the interaction of photons with matter have been given a certain attention. Monte Carlo codes have been developed. Recently, the NWEGRIM code [18] from Pacific Northwest laboratories has been used to simulate the interaction of photons in silicon, but these simulations could also be applied to germanium. GEANT4 has been used for simulation of charged particles interacting with germanium [39].
\n
\n
\n
\n
4. Gamma-ray tracking arrays
\n
High-purity germanium γ-ray tracking arrays, such as AGATA (Advanced GAmma Tracking Array) [40] and GRETINA/GRETA (Gamma Ray Energy Tracking Array) [41] represent the state-of-the-art in high-resolution γ-ray spectroscopy for nuclear physics experiments. These spectrometers are composed of highly segmented large-volume HPGe crystals. Pulse-shape analysis, applied to the recorded signals from the segments, yields three-dimensional interaction positions with a typical precision of about 2 mm [40, 41]. Subsequently, a γ-ray tracking algorithm is applied to the determined interaction points in order to group and order them in sequences corresponding to individual γ-rays. In this procedure, the geometrical criteria and the Compton scattering formula are used, and the full energy of a γ-ray is determined as the sum of the energies of the interactions ascribed to the same trajectory.
\n
The γ-ray tracking arrays provide improved energy resolution for in-beam nuclear physics studies, thanks to much reduced Doppler broadening as compared to standard γ-ray spectrometers. The use of γ-ray tracking also eliminates the need for Compton-suppression shields, commonly used with HPGe crystals in order to improve the peak-to-total ratio. Consequently, the entire 4π solid angle can be surrounded with Ge crystals, which leads to significantly increased detection efficiency. The resolving power of a 4π γ-ray tracking array is estimated to be up to two orders of magnitude better than that of the existing conventional γ-ray spectrometers, depending on the physics case [41]. This is particularly important for studies of very exotic nuclei far from stability, employing weak radioactive-ion beams at intermediate energies (up to several hundred MeV/u), which leads to recoil velocities that may exceed 30% of the speed of light [42].
\n
\n
\n
5. Dark matter direct detection and related studies
\n
The last two decades have seen an important effort devoted to search for dark matter, using underground direct detection apparatus [36, 37, 43, 44, 45, 46, 47]. The first stage was to design a detector that is able to discriminate between particles in order to identify the so-called weakly interacting massive particles that are thought to be a constituent of dark matter. The developed detectors include two channels: a “thermal” channel which is based on the thermalization of phonons and a ionization channel which is proportional to the number of carriers collected. In reality, the so-called Luke-Neganov effect [48, 49] affects the properties of the detector. The Luke-Neganov effect consists in the amplification of the phonon signal by the electron (carrier) drift [50].
\n
The charge signal may be expressed as:
\n
\n\n\n\n\ns\nc\n\n=\n\nE\nε\n\nq\n,\n\n\n\nE5
\n
where E is the average energy for electron-hole pair creation, and
\n
\n\n\n\n\ns\nT\n\n=\n\nE\nε\n\nqV\n+\nE\n\n\n\nE6
\n
The ST term is proportional to the charge multiplied by the voltage drop, so we can write that if t is the time necessary for the charge to be collected,
\n
\n\n\n\nI\n=\nSc\n/\nt\n\n\n\nE7
\n
First term: \n\nItV\n\n, which is a Joule-like term. Energy = power × time = current × voltage × time = charge × voltage.
\n
These relations indicate the need to operate at weak field to achieve a reduction in the contribution of the phonon signal. At high fields, the phonon signal tends to grow linearly with the applied voltage. Of course, the heat signal can only be detected if the calorific capacity is low enough, and so the operating temperature should be very low. Germanium detectors are also good cryogenic (mK range) bolometers. Another reason for the choice germanium is that its nucleus is nucleon rich (for instance compared with silicon). This should enhance interaction cross sections of WIMPS with the detecting medium. If we consider the interaction of fast neutrons with germanium (in the MeV range) as an example, the elastic-scattering cross section is much higher than the inelastic cross section [31] and is of the order of 3 barns [5]. Hence, the mean free path of these fast neutrons is close to a few centimeters. The recoil nucleus with an energy of a few tens of keV dissipates 25% of its energy into ionization, which amounts to a few keV (5 keV). The ionization channel monitors this fraction of energy. A similar phenomenon was observed, but not published, in planar HPGe 77 K detectors, exposed to neutrons, in the MeV range [51]. The heat channel monitors almost entire energy deposited by the recoils, except for the fraction needed for vacancy-interstitial (defect) creation. If a neutron is fully absorbed in the bolometer following multiple scattering, the total energy of all recoils matches the initial energy of the impinging neutron, and therefore the heat channel signal reflects the total energy deposited.
\n
The calibration runs yielded the ratio of the ionization signal to the phonon energy equal to 30%. This is very close to the value of 25%/73% = 0.35 determined in a SRIM simulation. When the particle interacts with matter purely via ionization, as it is the case for photons, the ratio of ionizing energy to the total energy is close to one, if no Luke-Neganov amplifying occurs. Therefore, this configuration can be used for particle discrimination [46]. For the WIMPS experiments, if we consider that these particles interact with the nuclei of the detecting media, this provides a way of discriminating the photons from other events. At this cryogenic energy (a few mK), the shallow and deep levels may disturb the charge transport through the detector (\nFigure 2\n). This is the reason why the detector is saturated with photo-generated carriers prior to data acquisition. In spite of this, more detailed defect studies on the starting material should be made [52]. In particular, as very shallow levels may have an impact, the nonthermal carrier emission or capture should be studied. Additionally, a method using alternately biased electrodes on each surface of the detectors, including the sides, has enabled the measurement of volume-only events, eliminating near-surface events related to low-energy particles strongly interacting with the medium [46]. Other techniques have been developed [53] to solve this problem.
\n
Figure 2.
Diagram showing the energy of the trapping level in Ge band gap versus temperature, using a simple Boltzmann factor. This is valid at high temperature for thermal emission with a time constant Tau. The region investigated by DLTS is delimited by the upper square on the right. The purple arrow shows the operation of DM cryogenic experiments such as EDELWEISS.
\n
\n
\n
6. Applications in industry and daily life
\n
As many particle detectors, HPGe detectors are now also used for other purposes than fundamental research. HPGe detectors can now be found in different industries such as environment control, medical imaging, and of course radioactive material control.
\n
One of the most common uses of HPGe is the monitoring of atmospheric radiations. Stations around the world check the air quality and collect air content samples or solid samples, such as rocks, water, or plants. The samples are then analyzed in a laboratory. Thanks to their excellent resolution and low background once placed in a suitable environment, and the radio-elements contained in the samples can be determined. It is, for example, possible to detect radio-elements with concentrations down to 0.1–1 Bq/kg in solids and 0.1 Bq/L in water. The system can be improved by adding scintillator array around the germanium detectors to eliminate signals from cosmic rays. Such system is, for example, used to obtain a sensitivity of millibecquerels per cubic meter of an air sample.
\n
Another practical example of use of HPGe to study radioactivity of liquids can be found in the study of old wines. Take a 1928 vintage bottle of Bordeaux wine; its cost can approach $10,000. However, how sure is the buyer that this bottle is really from 1928? To check this, the bottle was placed in an array of germanium detectors. The analysis immediately showed that the bottle contained traces of Cs137. Cs137 is a radioactive element presents in the atmosphere due to nuclear bombs…, which means that it cannot be found in a bottle of 1928. The quantification of Cs137 is now used to date wine produced after 1950 without opening the bottle.
\n
So far, HPGe detectors for medical purposes were mainly used for nuclear waste control produced by hospital. Here, the procedure is the same than for any nuclear waste collected from a nuclear power plant for example. The contaminated volume is placed near the detector. The analysis of the spectrum will reveal radioactive elements present and their quantity. The cost and mechanical constraints related to the use of liquid nitrogen limited the deployment of HPGe in hospitals for medical imaging. However, novel imaging methods, combining HPGe and silicon detectors are envisioned for future scanners such as ProSPECTus. Such system could reduce the dose to the patient, improve image quality, and be faster to acquire.
\n
The list of industrial applications of HPGe will become longer as we progress toward more reliable, easier to use, and cheaper detectors. Originally only pushed by fundamental research, the development of new HPGe is now also driven by the needs of companies using them. New applications, not yet considered, will then emerge.
\n
\n
\n
7. Conclusions
\n
The future of HPGe detectors depends on the availability of other materials that would match the resolution performance of HPGe at 77 K, while operating at room temperature. Segmentation of the detectors provides a way to reduce carrier collection lengths and hence to mitigate the effects of electrically active deep defects. With integrated microelectronics, the noise can be as low as a few tens of electrons. With on detectors CMOS chips and low capacitance detectors, the electronic noise can be reduced to less than 100 e-h pairs. With ε equal to 4.5 eV (GaAs, CdTe), this corresponds to a resolution of the order of 450 eV. This could also be applied to HPGe detectors that are being used for double beta decay or dark matter experiments. The multielectrode scheme that is implemented in EDELWEISS III [46] is a first step toward a time-projection chamber HPGe detector, allowing an improved discrimination ability. Each electrode could be a separate channel, which would be easy for the detector operated at low field and low voltage. It seems clear that the use in more routine applications such as, for instance, high-precision radioactive material characterization and radioactive material tracing to avoid nuclear dissemination will remain a field where HPGe is the most competitive despite the need for LN2 cryogenic installations. Development of cryogenic cooling fridges will eliminate this specific constraint. In scientific applications, HPGe, being one of the chemically purest materials ever fabricated, will remain needed.
\n
\n
Acknowledgments
\n
The contribution of researchers from IRFU and other institutions, with whom the first author had fruitful discussions while working on dark matter instrumentation, is gratefully acknowledged.
\n
Conflict of interest
The authors declare having no conflict of interest.
\n',keywords:"high purity germanium, traps and defects, gamma-ray detection, dark matter, nuclear spectroscopy, nuclear material monitoring",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/65089.pdf",chapterXML:"https://mts.intechopen.com/source/xml/65089.xml",downloadPdfUrl:"/chapter/pdf-download/65089",previewPdfUrl:"/chapter/pdf-preview/65089",totalDownloads:775,totalViews:0,totalCrossrefCites:1,dateSubmitted:"September 6th 2018",dateReviewed:"December 3rd 2018",datePrePublished:"February 15th 2019",datePublished:null,dateFinished:null,readingETA:"0",abstract:"High purity germanium remains the material of choice for the detection of photons in the range of MeV or higher, down to the hard X-ray range. Since the operation of HPGe-based detectors is possible only at or below the liquid nitrogen temperature, their advantage is mainly the resolution, which matches the Fano factor if appropriate cooled electronic readout is used. We focus here on present-day applications of HPGe detectors, which are now broader than ever despite the recent development of room-temperature photon detectors based on binary compounds. We present in particular dark matter detectors and γ-ray trackers as examples of the recent applications of HPGe as a detecting medium. More generally, we discuss the future of γ-ray detectors and the role that the semiconductor detectors will keep with respect to alternative detection materials. This chapter is an introduction to this general topic, and the reader is encouraged to refer to research and review articles on this subject published in the past or recently.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/65089",risUrl:"/chapter/ris/65089",signatures:"Nicolas Fourches, Magdalena Zielińska and Gabriel Charles",book:{id:"8352",title:"Use of Gamma Radiation Techniques in Peaceful Applications",subtitle:null,fullTitle:"Use of Gamma Radiation Techniques in Peaceful Applications",slug:"use-of-gamma-radiation-techniques-in-peaceful-applications",publishedDate:"October 2nd 2019",bookSignature:"Basim A. Almayah",coverURL:"https://cdn.intechopen.com/books/images_new/8352.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"178830",title:"Prof.",name:"Basim",middleName:"A.",surname:"Almayahi",slug:"basim-almayahi",fullName:"Basim Almayahi"}],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. Gamma-ray detection and spectroscopy",level:"1"},{id:"sec_3",title:"3. Technology, material, geometry, and performance of HPGe gamma-ray detectors",level:"1"},{id:"sec_3_2",title:"3.1 Starting material",level:"2"},{id:"sec_4_2",title:"3.2 Geometry and process",level:"2"},{id:"sec_5_2",title:"3.3 Defects",level:"2"},{id:"sec_6_2",title:"3.4 Alternatives to HPGe",level:"2"},{id:"sec_7_2",title:"3.5 Particle identification",level:"2"},{id:"sec_8_2",title:"3.6 Simulation",level:"2"},{id:"sec_10",title:"4. Gamma-ray tracking arrays",level:"1"},{id:"sec_11",title:"5. Dark matter direct detection and related studies",level:"1"},{id:"sec_12",title:"6. Applications in industry and daily life",level:"1"},{id:"sec_13",title:"7. Conclusions",level:"1"},{id:"sec_14",title:"Acknowledgments",level:"1"},{id:"sec_17",title:"Conflict of interest",level:"1"}],chapterReferences:[{id:"B1",body:'\nBaertsch RD, Hall RN. Gamma ray detectors made from high purity germanium. IEEE Transactions on Nuclear Science. 1970;17:235-240\n'},{id:"B2",body:'\nHaller EE, Hansen WL, Goulding FS. Physics of ultra-pure germanium. Advances in Physics. 1981;30:93-138\n'},{id:"B3",body:'\nFourches N, Walter G, Bourgoin JC. Neutron-induced defects in high-purity germanium. Journal of Applied Physics. 1991;69:2033-2043\n'},{id:"B4",body:'\nAlig RC, Bloom S. Electron-hole-pair creation energies in semiconductors. Physical Review Letters. 1975;35(22):1522-1525\n'},{id:"B5",body:'\nAlig RC, Bloom S, Struck CW. 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Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment. 2007;579:454-457\n'},{id:"B11",body:'\nMiller GL, Pate BD, Wagner S. Production of thick semiconductor radiation detectors by lithium drifting. IEEE Transactions on Nuclear Science. 1963;10:220-229\n'},{id:"B12",body:'\nHall RN. Characterization of pure germanium for detector fabrication. IEEE Transactions on Nuclear Science. 1972;19:266-270\n'},{id:"B13",body:'\nPearton SJ. Hydrogen passivation of copper-related defects in germanium. Applied Physics Letters. 1982;40:253-255\n'},{id:"B14",body:'\nWang G, Mei H, Mei D, Guan Y, Yang G. High purity germanium crystal growth at the University of South Dakota. Journal of Physics: Conference Series. 2015\n'},{id:"B15",body:'\nOlive KA et al. Review of particle physics. Chinese Physics C. 2014;38:090001\n'},{id:"B16",body:'\nNelson G, Reilly D. Gamma-ray interactions with matter. 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On the theory of ionization yield of radiations in different substances. Physical Review. 1946;70:44\n'},{id:"B23",body:'\nUpp DL, Keyser RM, Twomey TR. New cooling methods for HPGE detectors and associated electronics. Journal of Radioanalytical and Nuclear Chemistry. 2005;264:121-126\n'},{id:"B24",body:'\nLebrun F, Leray JP, Lavocat P, Crétolle J, Arques M, Blondel CE, et al. ISGRI: The INTEGRAL soft gamma-ray imager. Astronomy & Astrophysics. 2003;411:L141-L148\n'},{id:"B25",body:'\nFourches N, Huck A, Walter G. The role of secondary defects in the loss of energy resolution of fast-neutron-irradiated HPGe gamma-ray detectors. IEEE Transactions on Nuclear Science. 1991;38:1728-1735\n'},{id:"B26",body:'\nBernstein RB, Cubicciotti D. The kinetics of the reaction of germanium and oxygen. Journal of the American Chemical Society. 1951;73:4112-4114\n'},{id:"B27",body:'\nOnsia B, Conard T, De Gendt S, Heyns M, Hoflijk I, Mertens P, et al. A study of the influence of typical wet chemical treatments on the germanium wafer surface. Solid State Phenomena. 2005;103:27-30\n'},{id:"B28",body:'\nKobayashi M, Thareja G, Ishibashi M, Sun Y, Griffin P, McVittie J, et al. Radical oxidation of germanium for interface gate dielectric GeO2 formation in metal-insulator-semiconductor gate stack. Journal of Applied Physics. 2009;106:104117\n'},{id:"B29",body:'\nDelabie A, Bellenger F, Houssa M, Conard T, Van Elshocht S, Caymax M, et al. Effective electrical passivation of Ge(100) for high-k gate dielectric layers using germanium oxide. Applied Physics Letters. 2007;91:082904\n'},{id:"B30",body:'\nPehl RH, Madden NW, Elliott JH, Raudorf TW, Trammell RC, Darken LS. Radiation damage resistance of reverse electrode GE coaxial detectors. IEEE Transactions on Nuclear Science. 1979;26:321-323\n'},{id:"B31",body:'\nFourches N. Etude des defauts dus a l\'irradiation aux neutrons rapides dans le germanium de haute purete. 1989\n'},{id:"B32",body:'\nKogan SM, Lifshits TM. Photoelectric spectroscopy—A new method of analysis of impurities in semiconductors. Physica Status Solidi (a). 1977;39:11-39\n'},{id:"B33",body:'\nFourches N. High defect density regions in neutron irradiated high-purity germanium: Characteristics and formation mechanisms. Journal of Applied Physics. 1995;77:3684-3689\n'},{id:"B34",body:'\nStreet RA. Disorder effects on deep trapping in amorphous semiconductors. Philosophical Magazine B. 1984;49:L15-L20\n'},{id:"B35",body:'\nPullia A, Pascovici G, Cahan B, Weisshaar D, Boiano C, Bassini R, et al. The AGATA charge-sensitive preamplifiers with built-in active-reset device and pulser. In: 2004 IEEE Nuclear Science Symposium Conference Record; 2004\n'},{id:"B36",body:'\nShutt T, Ellman B, Barnes PD Jr, Cummings A, Da Silva A, Emes J, et al. Measurement of ionization and phonon production by nuclear recoils in a 60 g crystal of germanium at 25 mK. Physical Review Letters. 1992;69:3425\n'},{id:"B37",body:'\nGerbier G, Lesquoy E, Rich J, Spiro M, Tao C, Yvon D, et al. Measurement of the ionization of slow silicon nuclei in silicon for the calibration of a silicon dark-matter detector. Physical Review D. 1990;42:3211\n'},{id:"B38",body:'\nBudnik R, Cheshnovsky O, Slone O, Volansky T. Direct detection of light dark matter and solar neutrinos via color center production in crystals. Physics Letters B. 2018;782:242-250\n'},{id:"B39",body:'\nFourches NT, Chipaux R. Electrical-modelling, design and simulation of cumulative radiation effects in semiconductor pixels detectors: Prospects and limits. Journal of Instrumentation. 2015;10:C01036\n'},{id:"B40",body:'\nAkkoyun S, Algora A, Alikhani B, Ameil F, De Angelis G, Arnold L, et al. Agata—Advanced gamma tracking array. Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment. 2012;668:26-58\n'},{id:"B41",body:'\nPaschalis S, Lee IY, Macchiavelli AO, Campbell CM, Cromaz M, Gros S, et al. The performance of the gamma-ray energy tracking in-beam nuclear array GRETINA. Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment. 2013;709:44-55\n'},{id:"B42",body:'\nWeisshaar D, Bazin D, Bender PC, Campbell CM, Recchia F, Bader V, et al. The performance of the γ-ray tracking array GRETINA for γ-ray spectroscopy with fast beams of rare isotopes. Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment. 2017;847:187-198\n'},{id:"B43",body:'\nCreswick RJ, Avignone III FT, Farach HA, Collar JI, Gattone AO, Nussinov S, et al. Theory for the direct detection of solar axions by coherent primakoff conversion in germanium detectors. Physics Letters B. 1998;427:235-240\n'},{id:"B44",body:'\nEssig R, Mardon J, Slone O, Volansky T. Detection of sub-GeV dark matter and solar neutrinos via chemical-bond breaking. Physical Review D. 2017;95:056011\n'},{id:"B45",body:'\nAbt I, Caldwell A, Gutknecht D, Kröninger K, Lampert M, Liu X, et al. Characterization of the first true coaxial 18-fold segmented n-type prototype HPGe detector for the gerda project. Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment. 2007;577:574-584\n'},{id:"B46",body:'\nArmengaud E, Arnaud Q, Augier C, Benoît A, Bergé L, Bergmann T, et al. Performance of the EDELWEISS-III experiment for direct dark matter searches. Journal of Instrumentation. 2017;12:P08010\n'},{id:"B47",body:'\nArmengaud E, Augier C, Benoit A, Bergé L, Bergmann T, Blümer J, et al. Search for low-mass WIMPs with EDELWEISS-II heat-and-ionization detectors. Physical Review D. 2012;86:051701\n'},{id:"B48",body:'\nLuke PN. Voltage-assisted calorimetric ionization detector. Journal of Applied Physics. 1988;64:6858-6860\n'},{id:"B49",body:'\nNeganov BS, Trofimov VN. USSR Patent No 1037771; 1985\n'},{id:"B50",body:'\nDi Stefano P. Recherche de matière sombre non-baryonique au moyen d\'un bolomètre à ionisation dans le cadre de l\'expérience EDELWEISS; 1998\n'},{id:"B51",body:'\nHuck A. CRN, Strasbourg, Private Communication (Nicolas Fourches); 1989\n'},{id:"B52",body:'\nDomange J, Olivieri E, Fourches N, Broniatowski A. Thermally-stimulated current investigation of dopant-related D- and A+ trap centers in germanium for cryogenic detector applications. Journal of Low Temperature Physics. 2012;167:1131-1136\n'},{id:"B53",body:'\nYang LT, Li HB, Wong HT, Agartioglu M, Chen JH, Jia LP, et al. Bulk and surface event identification in p-type germanium detectors. Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment. 2018;886:13-23\n'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Nicolas Fourches",address:"nicolas.fourches@cea.fr",affiliation:'
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EDITED VOLUME
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IntechOpen Edited Volumes are integrated collections of chapters about particular topics that present new areas of research or novel syntheses of existing research and, as such, represent perspectives from various authors.
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Edited Volumes can be comprised of different types of chapters:
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RESEARCH CHAPTER – A research chapter reports the results of original research thus contributing to the body of knowledge in a particular area of study.
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REVIEW CHAPTER – A review chapter analyzes or examines research previously published by other scientists, rather than reporting new findings thus summarizing the current state of understanding on a topic.
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CASE STUDY – A case study involves an in-depth, and detailed examination of a particular topic.
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PERSPECTIVE CHAPTER – A perspective chapter offers a new point of view on existing problems, fundamental concepts, or common opinions on a specific topic. Perspective chapters can propose or support new hypotheses, or discuss the significance of newly achieved innovations. Perspective chapters can focus on current advances and future directions on a topic and include both original data and personal opinion.
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INTRODUCTORY CHAPTER – An introductory chapter states the purpose and goals of the book. The introductory chapter is written by the Academic Editor.
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MONOGRAPHS
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Monographs is a self-contained work on a particular subject, or an aspect of it, written by one or more authors. Monographs usually have between 130 and 500 pages.
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Single or multiple author manuscript
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COMPACTS
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Compacts provide a mid-length publishing format that bridges the gap between journal articles, book chapters, and monographs, and cover content across all scientific disciplines.
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Compacts are the preferred publishing option for brief research reports on new topics, in-depth case studies, dissertations, or essays exploring new ideas, issues, or broader topics on the research subject. Compacts usually have between 50 and 130 pages.
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CONFERENCE PROCEEDINGS
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Collection of papers presented at conferences, workshops, symposiums, or scientific courses, published in book format
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Edited Volumes can be comprised of different types of chapters:
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RESEARCH CHAPTER – A research chapter reports the results of original research thus contributing to the body of knowledge in a particular area of study.
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REVIEW CHAPTER – A review chapter analyzes or examines research previously published by other scientists, rather than reporting new findings thus summarizing the current state of understanding on a topic.
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CASE STUDY – A case study involves an in-depth, and detailed examination of a particular topic.
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PERSPECTIVE CHAPTER – A perspective chapter offers a new point of view on existing problems, fundamental concepts, or common opinions on a specific topic. Perspective chapters can propose or support new hypotheses, or discuss the significance of newly achieved innovations. Perspective chapters can focus on current advances and future directions on a topic and include both original data and personal opinion.
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MONOGRAPHS
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Monographs is a self-contained work on a particular subject, or an aspect of it, written by one or more authors. Monographs usually have between 130 and 500 pages.
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TYPES OF MONOGRAPHS:
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Single or multiple author manuscript
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COMPACTS
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Compacts provide a mid-length publishing format that bridges the gap between journal articles, book chapters, and monographs, and cover content across all scientific disciplines.
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Compacts are the preferred publishing option for brief research reports on new topics, in-depth case studies, dissertations, or essays exploring new ideas, issues, or broader topics on the research subject. Compacts usually have between 50 and 130 pages.
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CONFERENCE PROCEEDINGS
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Collection of papers presented at conferences, workshops, symposiums, or scientific courses, published in book format
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