",isbn:"978-1-83881-111-2",printIsbn:"978-1-83880-992-8",pdfIsbn:"978-1-83881-112-9",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,isSalesforceBook:!1,hash:"acb2875b3bfc189c9881a9b44b6a5184",bookSignature:"Dr. Abdo Abou Jaoudé",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11865.jpg",keywords:"Linear Operators, Normal Operators, Spectral Theorem, Applications, Differential Operators, Integral Operators, Functional Calculus, Complex Variables, Complex Analysis, Theory, Recent Advances, Latest Trends",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"April 13th 2022",dateEndSecondStepPublish:"May 11th 2022",dateEndThirdStepPublish:"July 10th 2022",dateEndFourthStepPublish:"September 28th 2022",dateEndFifthStepPublish:"November 27th 2022",remainingDaysToSecondStep:"11 days",secondStepPassed:!0,currentStepOfPublishingProcess:3,editedByType:null,kuFlag:!1,biosketch:"Abdo Abou Jaoudé is a pioneering Associate Professor of Mathematics and Statistics at Notre Dame University-Louaizé. 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1. Introduction
Within the human body, there is a vast array of uniquely arranged biologic structures. The elegance of these geometries is only matched by their equally varied functional sophistication. The harmony at which all components operate is truly awe-inspiring and from an engineering perspective, daunting to replicate. Yet in depth analysis of body tissues reveals a unique story. Many complex hierarchal structures can be deconstructed into simple recurring forms. Two ubiquitous geometries native to soft tissue are fibrillar networks and thin walled tubules. For instance, much of the extracellular matrix (ECM) that lends mechanical support to cells and tissues are fibrillar in nature. Vessels involved in either fluid transport or filtration are also high aspect ratio tubes of varying diameters. Furthermore, fibrillar and tubular themes are even found in hard tissues such as bone and cartilage.
In this chapter, we describe how researchers are synthetically recreating three-dimensional matrix analogs for regenerative medicine. We first highlight the complexities and nuances of real tissue and discuss the challenges in designing, fabricating and implementing biomimetic scaffolds for implantation. Applications of state of the art research pertaining to soft tissues and stem cell work will also be examined. We finally address current technological shortcomings and provide strategies for recreating function-specific tissue/organ systems with appropriate biophysical parameters
1.1. Structure-Function Relationships
The unique architectures found in biology have been evolutionarily shaped to perform particular tasks and this marriage between form and function is well manifested in the human body. For example, the layout of the nervous system is closely tied to cellular specialization. Neurons that perform signal integration are endowed with complex, multi-dendritic processes, while transmission neurons have axons that span several meters in length in some mammals. A similar undercurrent is observed in the circulatory system, where the biconcave geometry of red blood cells is optimized to facilitate oxygen exchange, mobility in a fluid medium and clotting (Wang, Pan et al. 2009; Wang, Gao et al. 2009). Injury or pathology can affect cell morphology, inducing problematic physiologic abnormalities. In the discussion of blood, conditions such as sickle cell anemia can alter flow dynamics and cause unwanted blood clots.
The forces at work that determine cell shape are also evident in the extracellular matrix (Figure 1). Mechanically mediated adaptation occurs frequently in the musculoskeletal system. For instance, bone undergoes a structural remodeling process in the presence or absence of loading (Wolffe’s law). Recent studies into bone’s nanostructure also reveal heterogeneous patterns that may impart load dispersal properties (Ortiz 2009). The axial hierarchal organization of supporting ligaments and tendons also reflect their functional role. Much like cables, these aligned elastic tissues are well suited to bearing tensile loads (Frank 2004). We emphasize that biologic structure-function relationships exist at all length scales- even down to the nanometer level of DNA and proteins.
Figure 1.
A) Many body tissues depict fibrillar and tubular thematic elements. Muscle and skin cross sections reprinted with permission (Singelyn, DeQuach et al. 2009) and (Chen, Ho et al. 2004), respectively. Bone micrograph courtesy of O. Akkus. (B) Tissue engineering aims to restore function by repair, replacement or regeneration of damaged tissue. Cellular therapies involve harvesting healthy cells (adult or stem cells), culturing in a matrix and subsequent reimplantation into the damaged site. Alternatively, acellular (cell free) biomatrices may also be used to promote endogenous healing and remodelling.
1.2. The Role of Architecture in Tissue Engineering
Like most machines, components of the body eventually fail. Disease states, mechanical insult or normal wear may initiate the process of tissue degradation. The goal of tissue engineering is the restoration of lost function. Recently, cellular therapies have drawn significant interest, with stem cell research at the forefront of biomedical innovation. The pluripotent nature of stem cells makes them attractive candidates for regenerating all organ types. In contrast, acellular treatments designed to promote endogenous wound healing are also tenable strategies. However, regardless of the therapeutic regime it has become evident that matrix architecture plays an active role in tissue remodeling. The matrix contributes to how a cell transduces input from the external physical environment into biochemical signals that dictate cell response. A wealth of evidence has shown that cells grown in 3-D culture systems demonstrate altered morphologies and gene expression compared to traditional 2-D platforms. Affecting the cell’s physical environment may be used to ultimately control cell behavior and fate (Sands and Mooney 2007; Ingber 2008). Thus, the structure-function relationships that govern normal physiology are equally instrumental during the repair process. This dogma underpins tissue engineered replacements: restorative devices should emulate the natural order of the body.
Interestingly, while there are countless architectural schemes in vivo, two elements found in high frequency are fibrils and tubules. Most body tissues are hierarchal fibrillar or tubular arrangements. It is the variation in size, organization and composition of these simple building blocks that dictates the wide range of observed mechanical and biophysical properties (Figure 2). Replicating these diverse structures from the macroscopic to the nanoscale level is a significant scientific undertaking. However, advancements in micro and nanofabrication have paved the path for constructing biologic analogs beginning at the molecular level. In the following sections, we discuss unique manufacturing methods capable of producing ECM-like architectures. Specifically, we emphasize emergent manufacturing techniques such as electrospinning, phase separation and nanoscale self-assembly. These methods provide invaluable tools for developing the next generation of biointegrative implants.
Figure 2.
The role of length scales on cellular behavior. As geometric features become smaller, changes in cell morphology and fate can be observed. Micrometer based lengths induce more 2-D (planar) geometries, while cells are more spatially interactive on 3-D nanoscaled meshes. Adapted from (Stevens and George 2005).
1.3. Emulating Nature: Fabrication of Micro and Nanoscale Architectures
1.3.1. Electrospinning
Electrospinning is a fabrication technique that utilizes electrostatic forces to draw continuous fibers from a viscoelastic medium. The process of electrospinning is quite archaic, dating back to 1902. However, in the mid 1990’s electrospinning was resurrected in the laboratory as many researchers recognized its utility in the growing nanoengineering discipline (Doshi and Reneker 1995). Since then, a multitude of materials ranging from synthetic and natural polymers, ceramics, semiconductors, biomacromolecules and even cell suspensions have been electrostatically spun (Pham, Sharma et al. 2006; Jayasinghe, Irvine et al. 2007). Resultant fibers can be as large as 10m or as small as 5nm. The material versatility, ease of manufacture, combined with fibers within biologically relevant length scales makes electrospinning a highly attractive method for scaffold production.
The fundamental principle guiding electrospinning is uniaxial stretching of a fluid. Figure 3 describes a typical laboratory configuration for electrospinning. A high voltage (5-30kV) is applied to a dissolved polymer solution. The repulsive force in the fluid accumulates until at a critical point, the electrostatic repulsion overcomes surface tension and a bead erupts from the spinneret (tip). The exiting jet soon enters a dynamic instability phase, which is marked by a chaotic swirling motion. Continued elongation of the jet coincides with solvent evaporation and the fluid stream eventually lands on the grounded collector plate. At this point, the charges dissipate and the fiber solidifies/cures.
The dynamics of the spray jet is a well studied phenomenon and computational models have been made to describe the thinning event. Variables such as viscosity, conductivity, voltage, tip to collector distance and humidity can have an effect on fiber morphology. Details for these can be found elsewhere (Rutledge and Fridrikh 2007). Since electrospinning generates shear stresses within the thinning jet, large scale alignment at the molecular level can be achieved (Stephens, Fahnestock et al. 2005).
One of the primary challenges facing electrospinning is the control of architecture. Since the spinning process is predominately chaotic, the final mat of fiber is unwoven and randomly oriented. However, multiple strategies have been devised to fabricate hierarchal or oriented fibrils. These include focusing of the falling jet with external electric fields or modifications to the collecting plate. For example, one technique used for obtaining aligned fibers is the placement of a rotating disc/drum as the collector (Figure 3). Electrospun fibers are deposited on the edge of the disc, with alignment being parallel to the edge width. Electrospinning may also be used to coat various shapes such as tubes for cardiovascular applications. Alternatively, Xia and co-workers developed a unique split plate collector system to create aligned fibers over a span of several centimeters (Li, Wang et al. 2004). If alternating split plates are used, the ground can be cycled between each electrode pair, creating layer by layer stacked mats of orthogonal alignment (Xie, Macewan et al. 2009).
Others have also used field assisted approaches to create braided fibers (Theron, Zussman et al. 2001). These particular structures have promise in use for axially loaded tissue such as ligaments and tendons. Coaxial spinning with two concentric spinnerets has also shown potential for creating composite fibers (Jiang, Hu et al. 2005; McCann, Marquez et al. 2006). In this process a hybrid fiber with a different core material can be produced. The core can be retained or selectively dissolved to fashion microtubular entities.
Figure 3.
A) Schematic depiction of the electrospinning process. A charged solution is drawn from the tip and the residual random fibers collect on a grounded plate. (B) A spinning disc technique commonly employed to create aligned electrospun fibers. Fibers aggregate on the disc edge. Corresponding random and aligned fibers produced from shown setup. Reproduced with permission from (Prabhakaran, Venugopal et al. 2009) and (Lee, Bashur et al. 2009).
1.3.2. Phase Separation and Selective Dissolution
Phase separation is a unique process that has the capacity to form both fibrillar and tubular constructs. There are multiple variations to phase separation, but a common modality is solid-liquid phase extraction. One novel strategy involves creating a thermal gradient to separate two constituent phases. For example, Ma and Zhang used this method to manufacture nanofibrous foams and networks (Ma and Zhang 1999). In this process, the parent polymer was first dissolved in a solvent. The solution was then placed in a refrigerator to gel. Solvent exchange was carried out with distilled water and the subsequent compound frozen and freeze dried. Resultant fibrillar architectures showed fibril diameters between 50-500nm. Local porosity was high, reaching 98% in some cases. Fiber matrix properties were controlled primarily by the gelation temperature. The same group also manipulated this technique to form microtubular arrays. In this case, a dissolved polymer solution was laterally insulated and placed on a cold source. The uniaxial thermal gradient induced a directional precipitation of the dissolved polymer (Figure 4). The solid-liquid separated solution was subsequently freeze dried. Stokols and Tuszynski also used a uniaxial thermal gradient with agarose to form linear channels (Stokols and Tuszynski 2004). These channels were continuous for up to 1cm and had pore sizes (channel diameter) on the order of 30-100m. These structures swelled in the presence of water due to hydrophilicity and resembled endogenous myotubes and endoneurial tubes.
Recently, Li et al. devised an inexpensive method to form single and aggregate high aspect ratio tubules with sacrificial sugar (Li, Rickett et al. 2009). Initially, sugar filaments formed from melt spinning were coated with a degradable polymer (PLLA). After polymer curing, the sugar core was dissolved with water, leaving a thin continuous tubular membrane. The final tubules also showed nanoscopic pores which are desirable for nutrient and waste diffusion. Multiple tube aggregates were made by fusion. The use of “cotton candy” as a core template was also employed by Bellan et al. for simulated microvasculature (Bellan, Singh et al. 2009). In this case, PDMS polymer was poured around long sugar filaments. The sugar was dissolved with water, leaving a solid PDMS block with embedded microtubes. The winding tubes were capable of supporting fluid media at physiologic flow rates.
Figure 4.
A) Diagram of thermal phase separation technique. A solution of dissolved polymer is placed on a cold source. The induced thermal gradient causes precipitation of the solute in a unixial fashion. Reprinted and adapted from (Stokols and Tuszynski 2004). (B) Corresponding microstructure of microchannels from phase separation (Stokols and Tuszynski 2004). (C) Depiction of selective dissolution for fabricating microchannels. Sucrose templates are coated with a polymer. The core is preferentially dissolved with another solvent. (D) Cross sectional images of microtubular geometries created by sacrificial templating. Reprinted with permission from (Li, Rickett et al. 2009).
One of the primary advantages of using phase separation approaches is the simplicity of the process. Phase separation generally requires minimal equipment, resources and the gamut of structures can range from nanoscale fibrils to micrometer tubes capable of sustaining fluid flow. In addition to the basic underlying structure, additional pores or discontinuities may be imparted via particulate leaching. Thus, scaffolds with several orders of architectural complexity may be realized.
1.3.3. Self Assembly
Self assembly is a process that describes the spontaneous formation of material patterns or structures without external influence. The forces that govern the aggregation phenomenon are local molecular interactions such as electrostatic forces, hydrophobic interactions and hydrogen bonding (Tu and Tirrell 2004). Self assembly is a key concept in “bottoms up” nanofabrication, where structures are constructed from individual molecular units. Self assembly is a fundamental theme in nature and is responsible for simple or complex hierarchal shapes including lipid bilayers (micelles), DNA, proteins and viral capsids. Consequently, understanding the basic tenants of self assembly has given researchers insight into forming biocompatible supramolecular structures. The key in self-assembled structures is design of base units that have two distinguishing components: a segment for directing the aggregation process and a biologically active moiety that encodes cell-specific instruction (Tu and Tirrell 2004).
Figure 5.
In situ hydrogel polymerization for instances where significant soft tissue damage occurs. Inset shows the nanofibrillar arrangement of RADA-16 peptide amphiphiles. Reprinted with permission (Nagai, Unsworth et al. 2006).
Peptide amphiphiles (PA) are common building blocks for use in self assembly. This approach was first used to fabricate membranes composed of nanofibrillar meshes based on repeating amino acid ((Ala-Glu-Ala-Glu-Ala-Lys-Ala-Lys)2) sequences (Zhang, Holmes et al. 1993). Recently, the same group developed an arginine, alanine, aspartate, and alanine (RADA-16) sequence that assembled into three-dimensional hydrogels composed of nanofibrils (Figure 5). The primary base sequences were additionally functionalized with an osteogenic growth peptide and two other cell adhesion motifs via direct solid phase extension of the C-termini (Horii, Wang et al. 2007).
Similarly, Silva et al. incorporated a pentapeptide amino acid sequence (isolucinelysine-valine-alanine-valine, IKVAV onto a hydrocarbon tail (Silva, Czeisler et al. 2004). The IKVAV epitope is found in laminin protein and enhances neural cell adhesion and growth (Chen 2003). A special glutamine residue was added to give the amphiphile a net negative charge at physiologic pH. Exposure to positive charges, such as from the cell medium or body fluid would trigger the polymerization event, causing the amphiphile to form a network of nanofibers. Other attributes of individual nanorods include high aspect ratios (micrometer length vs 5-8 nanometer diameter) and high IKVAV epitope density for cell interaction. Other designer hydrogels based on peptide amphiphile self assembly have also been created. Unique characteristics of hydrogels include high water content (99%), compatibility with in situ application and resemblance to natural ECM.
1.4. Application of Biomimetic Architectures
1.4.1. Vasculature
Blood vessels are a major constituent of the human cardiovascular system and function as a vehicle for metabolic and gaseous transport. In arteries, three layers exist. The outmost wall consists of fibroblasts embedded within a randomly aligned collagen type I matrix for structural support. Smooth muscle cells (SMC) surrounded by elastin fibers and collagen types I and III compose the elastic medial zone. Finally, the innermost layer is an endothelial (EC) monolayer rich in collagen type IV and elastin that provides a smooth surface for blood flow.
Atherosclerosis is a common cardiovascular disease characterized by the pathological reduction in arterial elasticity and narrowing of the arteries. Decreased diameter of the interior lumen subsequently leads to loss of circulation. Once blood flow is compromised, the preferred treatment option is vascular bypass surgery. Autologous replacement of damaged arteries frequently involves the internal mammary artery or the saphenous vein. However, such treatments yield donor site morbidity and are often unable to bridge large diameter vessels (Conte 1998). Alternative options using traditional synthetic grafts, including expanded polytetrafluoroethylene (e-PTFE) and woven polyethylene terephthalate (PET) fibers are suitable for medium (6-10mm) and large (>10 mm) vascular substitutes, but are not successful as small diameter prosthetics (Ma, Kotaki et al. 2005). Development of a small-diameter vascular graft capable of withstanding the immense environmental pressures of the circulatory system presents a significant challenge. Conquering this remaining obstacle is often seen as the Holy Grail of tissue engineering (Conte 1998).
Figure 6.
Tissue engineered vascular grafts. (A) Gross overview of an electrospun composite scaffold composed of collagen type I and poly(ε-caprolactone) (PCL). (B) SEM image of the circumferential morphology (x4.0K) and (C) Exterior surface (x6.0K) (Lee, Liu et al. 2008).
New advancements in nanofiber-based scaffold production (i.e. electrospinning, phase separation and self-assembly) allow for the creation of grafts that imitate the molecular and structural properties of the vasculature ECM. For instance, Ramakrishna et al. developed a synthetic biodegradable aligned poly(L-lactide-co-ε-caprolactone) [PLLA-CL] nanofibrous scaffold(Mo, Xu et al. 2004; Xu, Inai et al. 2004; Xu, Inai et al. 2004). Aligned fibers produced a scaffold topography that mimicked the circumferential orientation of cells and fibrils found in the medial layer of arteries. When cultured with SMC and ECs, the scaffold promoted cell attachment and migration along the axis of the aligned nanofibers and demonstrated increased levels of cell proliferation when compared to an inert control. Integration of cells within the nanofibers formed a three-dimensional cellular network while maintaining phenotypic shape (Mo, Xu et al. 2004; Xu, Inai et al. 2004; Xu, Inai et al. 2004). Alternatively, Boland et al. produced a natural, three-layered vascular construct composed of collagen and elastin. Outer layers of the construct were seeded with SMC and FB with the interior lumen seeded with ECs. This cell seeded scaffold allows for natural tissue development in the injured site by promoting cell motility, proliferation and matrix deposition/remodeling (Matthews, Wnek et al. 2002). Figure 6 demonstrates a composite vascular system composed of poly(ε-caprolactone) (PCL) and collagen. The composite scaffolds exhibited adequate tensile strength (4±0.4 MPa), and elasticity (2.7±1.2MPa) for appropriate physiological performance. Composite scaffolds aided the formation of a confluent outer layer and interior lumen when seeded with smooth muscle cells and endothelial cells, respectively (Lee, Liu et al. 2008).
Similar tri-laminate vascular constructs were developed using cell self-assembly as reported by L’Heureux et. Al (L\'Heureux, Paquet et al. 1998; L\'Heureux, McAllister et al. 2007). Intact layers of human vascular cells were cultured past confluency to form a uniform cell sheet with a naturally produced randomly aligned ECM. The sheet was then rolled over a support mandrel to create a tubular arrangement. An outermost layer was constructed in the same fashion by placing a sheet of fibroblasts on top of the previous SMC layer. Further maturation of the tube allowed for prolific ECM production before the interior lumen was seeded with ECs (L\'Heureux, Paquet et al. 1998; L\'Heureux, McAllister et al. 2007).
1.4.2. Ligament and Tendon Tissue Engineering
Ligaments are comprised of dense, parallel collagen (types I and III) bundles that serve as load bearing tissues. Fibroblasts preferentially aligned along the longitudinal axis of the crosslinked bundles regulate mechanical attributes through matrix remodeling. The high tensile strength of this configuration and elastic properties of the collagen fibrils allow for controlled movement and joint stability.
Mechanical trauma disrupting the integrity of the ligament produces significant joint dysfunction resulting in abnormal kinematics and potentially long term degenerative joint diseases (Lin, Lee et al. 1999). Conventional reconstructive surgical procedures using autografts have had limited success (Arnoczky, Tarvin et al. 1982). Major shortfalls include donor site morbidity, stress shielding and tendonitis (Lee, Shin et al. 2005).
Ligament tissue engineering is a viable alternative to surgical approaches. However, several challenges remain in the realization of scaffolds capable of withstanding the large cyclic loads. Nanofiber manipulation techniques provide promising solutions by replicating the natural orientation and spatial distribution of molecules and cells within an engineered construct.
Figure 7.
Ligament Engineering (A) Ligament schema showing parallel fibers with adhered fibroblasts (Doroski, Brink et al. 2007). (B) SEM micrograph of aligned PU fibers (500 to 800 nm) (C) cultured with fibroblasts (FB) indicating the direction of alignment (DA) along aligned fibers (Lee, Shin et al. 2005).
For example, using a modified electrospinning process, Lee et al. collected polyurethane (PU) nanofibers on a rotating collecting target to produce a uniformly aligned matrix as shown in Figure 7. Fibers were then seeded with human ligament fibroblasts (HLFs) to investigate the affects of fiber alignment on cell behavior. Results demonstrated cellular alignment with fiber orientation and increased matrix deposition under longitudinal load compared to HLFs seeded on randomly oriented fibers (Lee, Shin et al. 2005).
An alternative method for controlled collagen assembly was proposed by Akkus and collaborators. The novel electrochemical technique passed electric current through a dialyzed collagen solution placed between two parallel electrodes to promote molecular migration. This process allowed for the generation of highly oriented and densely packed elongated collagen bundles ranging between 50-400μm in diameter and 3-7cm in length. Polarized imaging was used to assess collagen orientation and fibrillar assembly as shown in Figure 8. Electrochemically oriented collagen bundles showed color patterning similar to natural tendon fibers, indicating a comparable degree of fiber orientation. Furthermore, the synthetically aligned fibers exhibited a 30-fold increase in mechanical strength compared to randomly oriented collagen fibers. Mechanically robust and highly oriented bundles formed using this method highlight a promising tissue engineering approach for tendon and ligament repair (Cheng, Gurkan et al. 2008).
Figure 8.
Synthetic alignment of collagen fibers using an electrochemical technique. (A) Electrochemical cell with collagen solution between two parallel electrodes and color coded pH gradient required for rotational alignment. (B) SEM image of an intentionally split collagen bundle, indicating uniform orientation and alignment along the longitudinal axis (C) Polarized image of bleached native tendon and electrochemically aligned collagen construct. Both tissues depict the blue retardation coloring, indicating comparable fiber orientation (Cheng, Gurkan et al. 2008).
1.4.3. Skin
Skin is the largest organ in the body and consists of two main layers: dermis and epidermis. The keratinized stratified epidermis is the primary cell layer while the dermal zone provides structural support and nutrient renewal. Skin engineering has a history spanning 100 years yet autografts remain the gold standard for treating full thickness skin injuries. A design goal for therapeutic skin substitutes resides in emulating the skin’s stratified composition. Since the dermal layer is a dense network of collagen and elastin, porous fibrillar constructs make excellent candidates as a substrate for skin reconstruction. Indeed, this approach has been used since the 1970’s as the basis for artificial skin (Yannas and Burke 1980). The first skin constructs used a scaffold composed of a collagen base with added glycosaminoglycans to promote wound healing (Schulz, Tompkins et al. 2000). An additional silicone membrane (“pseudo-epidermis”) was overlaid on the collagen layer to function as a heat and moisture barrier. Variations in this bilayered theme are presently employed in skin graft products (Falanga and Sabolinski 1999).
However, a significant drawback in artificial skin is the lack of vasculature, pigmentation and anti-bacterial properties. To circumvent these deficiencies, scientists are using either stem cells or genetically modified cells in combination with biomatrices. The goal is to develop artificial skin fragments that are vascularised and have the ability to ward off infection, sweat and protect against UV radiation. In one report, researchers transfected keratinocytes to secrete an antimicrobial protein (Smiley, Gardner et al. 2007). Bacterial growth was suppressed on these skin cultures, which suggests genetic manipulation to be a viable method for reducing post-operative infection. Alternatively, Katti et al. employed electrospinning to produce nanofibrous poly(lactide-coglycolide) membranes incorporating a broad spectrum antibiotic (Katti, Robinson et al. 2004).
Figure 9.
Schematic showing the presence of endothelial progenitor cells in a mouse model of skin trauma (Kim, Han et al. 2009). Empty (cell free) scaffolds showed some endogenous remodeling and blood vessel formation. Injection of EPCs improved the degree of vascularization while pre-seeded scaffolds provided the best results. Reprinted with permission.
To recreate other salient features of skin, research groups have suggested using bulb stem cells residing in hair follicles to reproduce epidermis (Larouche, Tong et al. 2008). Similarly, Kim et al harvested endothelial progenitor cells (EPCs) for use in a mouse skin excision injury model (Figure 9). Experimental data showed EPC seeded scaffolds promoted angiogenesis and microvasculature at the wound site (Kim, Han et al. 2009). Newer developments in skin technology have added combinations of fibroblasts, keratinocytes or epithelial cells into biodegradable scaffolds (Priya, Jungvid et al. 2008; Schulz, Tompkins et al. 2000). After a designated culture time, the cells populate and remodel the matrix, creating a rudimentary living skin. Other studies on substrate architecture shed light on optimum fibril diameters and packing density for enhancing collagen expression (Kumbar, Nukavarapu et al. 2008) microbial infiltration (Powell and Boyce 2008).
The collective cellular and scaffolding data suggests a promising future for patients with severe skin damage. The combination of appropriately modified physical substrates coupled with cell seeding may lead to skin products that provide necessary protection while simultaneously reducing the appearance of scar (Metcalfe and Ferguson 2007).
1.4.4. Nervous system
Neurons are highly ordered cells specializing in a variety of integrative and signal transmission functions. When damaged, neurons have the intrinsic ability to regenerate, although the degree of regeneration is heavily dependent upon the local microenvironment. In the central nervous system (CNS) damaged neurons undergo a form of abortive regeneration. Multiple avenues are being pursued to coax adult neurons to recapitulate developmental processes (Rossignol, Schwab et al. 2007; Ruff, McKerracher et al. 2008). In contrast, peripheral nervous system (PNS) axons readily sprout and extend after injury. However, the quality of regeneration is lacking due to insufficient guidance cues (Lundborg 2000). It has been postulated that in addition to biochemical signals, physical guidance may further aid and direct the regeneration process.
For treating brain and spinal cord injuries hydrogels have been proposed. Hydrogels form a loose network of fibers representative of the endogenous CNS matrix. For example, Silva et al. (Silva, Czeisler et al. 2004), used a pentapeptide IKVAV sequence mounted onto a hydrophobic tail to create self assembling peptide amphiphiles. These amphiphiles directed differentiation of neural progenitor cells while inhibiting astrocyte differentiation in vitro. Additional investigation using a spinal cord compression model showed IKVAV nanofibers reduced glial scar formation, cell death and encouraged migration of oligodendrocytes into the implant region (Tysseling-Mattiace, Sahni et al. 2008).
In another study, peptide amphiphiles consisting of RADA16 were used to successfully restore vision in an optic nerve guinea pig animal model (Ellis-Behnke, Liang et al. 2006). In this case, the peptide hydrogel created a permissive environment that promoted neural tissue bridging of severed tracts. Other studies with hydrogels have shown promising outcomes. Stokols et al. reported a unique agarose guidance scaffold consisting of long linear channels (Stokols and Tuszynski 2004). These constructs had pore diameters (channels) of 119±26m and were capable of sustained growth factor release. Follow-up assessment of the scaffolds in a spinal cord injury paradigm showed organized axonal regeneration through the agarose channels (Stokols and Tuszynski 2006).
In contrast to the brain, nerves within the PNS have a unique global structural arrangement. Peripheral nerve axons are longitudinally oriented, with individual axons ensheathed in collagen based tubes (endoneurial tube). Following axotomy, these continuous tubes facilitate the regeneration process by providing a physical template that directs axon extension. Imitating this structural feature is therefore vital for encouraging outgrowth and reducing fiber misdirection (Sumner 1990).
Figure 10.
A)-(D) Fluorescent longitudinal sections of rat sciatic nerve and the structural arrangement. Reprinted from (Ribeiro-Resende, Koenig et al. 2009). (E) Microtubular polymeric arrays which mimic the oriented nature of peripheral nerves. (F) Dorsal root ganglia neurons and Schwann cells co-cultures align on tubules depicted in (E). Reprinted with permission from (Li, Rickett et al. 2009). (G) Dorsal root ganglia neurons extend along electrospun nanofibers (Kim, Haftel et al. 2008).
Conduits containing aligned electrospun fibers have been used to mimic the function of endoneurial tubes (Figure 10). For instance, Kim et al. created a 17mm gap defect in rat sciatic nerve and used an artificial conduit to bridge the damage site (Kim, Haftel et al. 2008). Acrylonitrile-co-methylacrylate (PAN-MA) polymer was spun into aligned or unaligned configurations. Both types of conduits were implanted and after 16 weeks, animals were sacrificed for analysis. Histological and functional data showed superior axonal regeneration in animals receiving the aligned fiber conduits. This study showed that for the PNS, aligned fiber morphology can be used to facilitate the regeneration process. Moreover, Li et al. used microtubular arrays to emphasize oriented Schwann cell and neurite alignment in vitro (Li, Rickett et al. 2009). The microtubes supported cell growth on the exterior surface and within the lumen. Other investigations have demonstrated improved regeneration on polymer filaments in long gap injuries with rats (Cai, Peng et al. 2005).
1.5. Future Directions and Conclusion
Bioengineering has evolved from the simple notion of biocompatibility to an age which values intelligent materials for providing cell-specific instructional cues. One of these signaling mechanisms is physical and is intimately tied to cell mechanotransduction. Indeed, the local spatial arrangement of the extracellular environment plays a pivotal role in governing morphogenesis, migration and differentiation. Thus, understanding how nano and microscale architectures influence cell response and the subsequent macroscopic properties is fundamental in developing restorative constructs.
Recent manufacturing innovations have yielded tissue analogs approximating the natural ECM at multiple length scales. However, significant challenges remain. In terms of the three-dimensional aspect, most artificial scaffolds are relatively homogeneous and do not represent the stratified or graded physiochemical properties found in vivo. Therefore, a design challenge for future 3-D structures lies in implementation of zonal transitions. Such scaffolds would encourage heterotypic cell interactions essential to the constructive remodeling process. Additionally, we now recognize that the ECM is more than a framework for cell residence. Natural ECM contains multiple support proteins and biochemical factors that maintain local dynamic homeostasis, reinforce mechanical properties and direct wound healing (Badylak 2007). Incorporating such compounds synergistically within the material architecture is critical for optimum success.
Finally, stem cells and biomolecular delivery are inevitably going to play a larger role in regenerative medicine. Current investigations with stem cells have already demonstrated promise in various experimental injury models. New insights into controlling stem cell fate are necessary in realizing safe and effective therapies. Nonetheless, the confluence of cellular methods with biomimetic architectures bodes well for functional restoration of damaged or diseased tissues.
Acknowledgments
We would like to thank Michel Schweinsberg for his contributions in artwork.
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Emulating Nature: Fabrication of Micro and Nanoscale Architectures",level:"2"},{id:"sec_3_3",title:"1.3.1. Electrospinning",level:"3"},{id:"sec_4_3",title:"1.3.2. Phase Separation and Selective Dissolution",level:"3"},{id:"sec_5_3",title:"1.3.3. Self Assembly",level:"3"},{id:"sec_7_2",title:"1.4. Application of Biomimetic Architectures",level:"2"},{id:"sec_7_3",title:"1.4.1. Vasculature",level:"3"},{id:"sec_8_3",title:"1.4.2. Ligament and Tendon Tissue Engineering",level:"3"},{id:"sec_9_3",title:"1.4.3. Skin",level:"3"},{id:"sec_10_3",title:"1.4.4. Nervous system",level:"3"},{id:"sec_12_2",title:"1.5. Future Directions and Conclusion",level:"2"},{id:"sec_14",title:"Acknowledgments",level:"1"}],chapterReferences:[{id:"B1",body:'ArnoczkyS. P.TarvinG. B.MarshallJ. L.1982 Anterior Cruciate Ligament Replacement Using Patellar Tendon- an Evaluation of Graft Revascularization in the Dog. Journal of Bone and Joint Surgery-American 64 (2): 217-224.'},{id:"B2",body:'BadylakS. 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1. Introduction
The problem of X-ray beam formation with a minimal size cross section and a small angular divergence is the central problem of all X-ray diagnostical methods. The first real step for the solution of this problem was connected with the names of P. Hirsch and J. Keller suggested to form X-ray microbeams by employing the glass capillary [1]. More recently, the planar thin film waveguides have been offered for X-ray microbeam formation [2]. Authors of the work showed that the waveguide with a material media core for X-ray beam transportation can form small size beams, but the beam intensity attenuation was very great. In the direction, development similar investigations were carried out in a number of experimental works [3, 4, 5]. Authors of these investigations have managed to obtain X-ray beams with a width of 100 nm, a height of some millimeters, and the total intensity near 5 × 107 photon/s in condition of the resonant synchrotron radiation coupling. The significant progress in these research works was achieved by switching over a study from coupling mechanism of the emergent beam preparation to the ones based on the radiation transportation by the core layer from input of the waveguide to its outlet. In result of the flux mode structure analysis, the phenomenon of an X-ray standing wave arising was mentioned [4]. The properties of X-ray beams formed by polycapillary optics systems have been intensively studied, too [6, 7, 8, 9, 10]. The optics of systems is based on the phenomenon of X-ray beam multiple total external reflections on the inner surface of a quartz capillary. Mono and polycapillary optics are the beautiful facilities for the formation of microsize beams. At the same time, the polycapillary optics is characterized by significant losses of X-ray beam intensity in the transportation process. The problem of X-ray flux intensity losses was the subject of a specific investigation [11]. Authors of the work studied the effect of capillary damages in result of X-ray beam influence. They demonstrated the linear worsening of X-ray beam transmission ability for the glass capillary with an increase of radiation dose. This effect is not significant for the quartz guides of X-ray fluxes.
In parallel with the traditional approaches to micron and submicron X-ray beam formation mentioned above, it has been discovered the specific technique of a superfine beam preparation by using the so-called “slitless” collimator [12, 13, 14] formed by two quartz plane polished plates mated together. Its device lets to form X-ray emergent beam with the visible magnitude of a radiation intensity compared with the incident beam intensity value [12]. Unfortunately, the study of this phenomenon and attempts of its practical application have been undertaken in recent years only [15, 16]. In fact, the slitless X-ray collimator represents the planar waveguide with a minimum size of an air slit. Width of the slit is defined by roughness and waviness levels of the collimator reflector plane surfaces. At the same time, the air core between guide claddings is the ideal waveguide channel from standpoint of the radiation flux intensity preservation. Similar waveguides with fixed and tunable air gaps have begun to find the practical application in the works of Zwanenburg group [17, 18]. Their waveguides with Cr claddings and air core can produce the emergent beam with a width of d = 500 nm, a height of h = 0.1 mm, and a total intensity of J = 2.4 × 107 photon/s [17]. Great omission of these works consisted in the ignoration of X-ray standing wave arising in air core of their radiation guides.
The original glance on the problem of X-ray flux transportation by a planar extended slit clearance was presented in the works of Kawai group [19]. As opposite to the standing wave conception, authors included the specific notion about X-ray traveling waves or Yoneda wing. This approach has some grounding in theory [20, 21]. But these works left behind bracket the interference interaction between falling and reflecting fluxes.
Very strange approach was suggested by Dabagov for the description of X-ray flux transportation by a hollow quartz capillary [22]. Instead of the conventional conception connected with the multiple total external reflection mechanisms, author advanced the idea of “X-ray quantum subsurface channeling.” We believe that the approach is not pragmatic since the channeling phenomenon offers a photon motion in the periodic potential, but the surface of amorphous quartz cannot produce the correct periodic field.
A number of publications with model description attempts of X-ray flux propagation through a narrow extended slit are presented in the literature [23, 24, 25, 26]. These models are built on the working hypothesis that X-ray radiation is the planar monochromatic electromagnetic wave. But it is universally known that the realistic X-ray sources produce the quasimonochromatic radiation fluxes with λ0 average wavelength and Δλ monochromatism degree.
Materials with information about Δλ magnitudes featured for X-ray characteristic radiation produced by X-ray laboratory sources are presented in Handbook editions [27, 28]. But the main shortage at interpretation of X-ray flux transportation by different waveguide structures including slitless collimator devices was the statement that X-ray flux propagation takes place accordingly to the multiple total external reflection mechanisms as sole possible one. We were skeptical of this point of view and decided to produce the systematic investigation of the planar extended slit clearance width influence on its X-ray emergent beam parameters. For similar investigations, we selected construction presented in Figure 1. It is the air planar extended X-ray waveguide (PXW).
Figure 1.
Scheme of X-ray initial flux capture area and the emergent beam formation by the planar extended slit clearance formed by two quartz reflectors (a) and real construction of the device for the study of the spatial intensity distribution dependence in X-ray beams on the slit clearance width (b). 1: aligning handles; 2: installation plate; 3: spring pawls; 4: fine tuning screws; 5: radiation guide holder; 6: quartz reflectors with length 100 mm; h and s: height and width of slit clearance (φ1 = φ2).
2. Technological features of PXW fabrication
The main components of the PXW structure are planar polished dielectric reflectors forming its radiation-transporting air slit clearance. In preparation of reflector working surfaces, it is necessary to fulfill a number of technological requirements guaranteeing the desired surface quality. The technical parameters that determine the surface quality are first of all the roughness and waviness and, moreover, a specific factor associated with local work hardening arising from nonuniform surface heating during polishing.
Modern polishing methods are capable of ensuring a surface roughness level of about 0.5 nm. Such a high degree of polishing can be controlled via direct testing with the help of atomic-force microscopy. The aforementioned roughness level is quite comparable with the range within which the potential on the condensed material surface varies from the value typical of its entire volume to that corresponding to vacuum [29, 30]. At the same time, the atomic-force microscopy technique makes it impossible to estimate the surface waviness and, moreover, the level and degree of surface distortions caused by the appearance of local work hardening. To a certain extent, the influence of these parameters on the surface quality can be estimated with the help of an optical method based on violated total internal reflection [31], which enables us to discard reflectors with appreciable contributions to the deterioration of the reflector surface quality.
In preparation of waveguide resonators, the most critical technological stage is thin film metallic strip deposition on the edges of one of the quartz reflectors constituting a pair used to create a waveguide-resonance channel. The deposited materials are titanium or chromium with a high degree of adhesion to the quartz surface. During the deposition process, the surface of the future waveguide-resonance channel was coated with aluminum foil. Thin film metallic strips were primarily deposited in the vacuum chamber of a Leybord LG L-560 setup via the electron beam evaporation method. The film coating growth rate was 0.1 nm/s. During the deposition process, the chamber pressure was maintained at a level of 10−4 Pa. However, in spite of relatively high vacuum, the metallic-strip material contained a certain number of oxygen atoms (up to 10 at%). When the films were deposited, some reflectors were heated up to 80°C. As a result, the density of coating adhesion to the quartz glass surface increased appreciably. A simplified diagram of the mutual arrangement of assemblies in the chamber used to the deposit coatings in vacuum is depicted in Figure 2. The position of the reflector intended for coating deposition is symmetric with respect to the point source of metal atoms.
Figure 2.
Simplified diagram of the chamber used to deposit titanium strips on quartz reflectors: (1) electron gun, (2) focusing system, (3) titanium target, (4) quartz reflector, (5) vacuum volume, h = 200 mm, l = 100 mm; and A and B are the positions of blank samples during deposition.
The basic requirement to the quality of the prepared strip coatings is thickness homogeneity along the entire length of the PXW reflector. Let us consider the geometry of the diagram, as shown in Figure 2. Then, under the assumption of angular homogeneity of the metal atom flux excited by the electron beam, it can be expected that the deposited strips will be characterized by a nonuniform coating thickness and its largest value will be at the reflector center. For coating deposition condition optimization, it is necessary to employ the thickness control methods. At the center (t2) and edges (t1) of the reflector (Figure 3), the deposited strip thicknesses were determined via the Rutherford backscattering (RBS) of Не+ ions with the help of “blank samples.” Single-crystal silicon samples located on aluminum foil, which covered the surface during deposition, were used as these blank samples. Thus, each reflector with deposited metallic coatings can be characterized by at least two Ti/Si blank samples. Their experimental investigations were performed by means of the Sokol-3 ion beam analytical complex situated at the Institute of Microelectronics Technology and High Purity Materials, Russian Academy of Sciences [32]. The results of these measurements are depicted in Figure 4.
Figure 3.
Waveguide-resonator reflector with thin film strips on the edges: t1 and are the coating thicknesses on its edges, and t2 is the thickness in the central part.
Figure 4.
Typical spectra of the RBS of Не+ ions (Е0 = 1 MeV). Data were obtained for Ti/Si blank samples located at the positions А and В (Figure 2) corresponding to the (a) edge and (b) center of the strip coatings of the quartz reflectors.
Using the spectra of the RBS of Не+ ions (E0 = 1 MeV) (Figure 4), it is possible to perform accurate determination of the thicknesses of the strips deposited on reflectors in their central part (Figure 4a) and on the edges (Figure 4b). These thicknesses are determined by approximating peaks with almost flat tops, which correspond to Не+ ion scattering from the coating atoms. (The low energy steps observed in the RBS spectra of the tested targets correspond to Не+ ion scattering from substrate atoms.) The presented spectra were mathematically processed using RUMPP, the modified version of the famous RUMP approximation program [33]. Approximation of the aforementioned spectra indicates that the film strip thicknesses are t2 = 114 ± 0.5 nm in the central part and t1 = 107.5 ± 0.5 nm on the edges. Thus, the inhomogeneity in the thickness of the strips deposited onto the given reflector is 6%. This result completely coincides with the estimate based on geometric considerations. The above data correspond to the reflector whose coatings were deposited at a distance of h = 200 mm between the source of the evaporated atoms and its surface (Figure 2). The reflector length is l = 100 mm. Under the assumption that the deposition rate is proportional to the squared distance from the source, the expected difference turns out to be 6.1%. For the coating thickness difference decreasing, we increased the h-distance up to 1000 mm. In that case, the thickness difference accordingly to RBS data achieved to 1%. Experiments showed that the similar conditions are acceptable for X-ray waveguide assemblage.
Specific attention has been given to the direct determination of the effective slit width in different waveguides and in a slitless collimator because the data presented in early works about slitless devices [12, 13, 14] were not clear with respect to the width. The width was evaluated by very effective optical method connected with the attenuated total internal reflection effect [31]. In our investigation, we used the laser source with λ0 = 680 nm. Figure 5 presents the measurement geometry. The studied waveguide was situated in a specific cartridge equipped by black light absorber. The light beam introduced into the waveguide by using the quartz prism fixed on the waveguide reflector by specific oil (n = 1.45). The prism could change its position on the reflector surface. Emergent light beam in the measurement process registered by standard photodiode equipped by circular aperture with a diameter of d = 0.5 mm. In the measurements process, the light beam in transit through the prism incidented on the waveguide, underwent the attenuated total internal reflection on the waveguide slit clearance and a lux meter recorded the reflection intensity. The normalization measurement was executed by using the waveguide with a width slit of s = 0.12 mm. Specific details of investigations are described elsewhere [34]. The measured data for several waveguides with different slit widths are presented in Figure 6.
Figure 5.
Principle scheme for direct measurements of a waveguide slit width by methods of the attenuated internal total reflection (AITR). I and II are quartz reflectors of a waveguide. Scheme was published, in first, in Ref. [34].
Figure 6.
Experimental data presented the relationship between the waveguide slit width and the reflectivity magnitude are obtained by AITR method. The point characterized the slitless collimator has a specific design.
Standard least square method was used for the experimental data fitting allowed to get a relationship between the light beam reflectivity factor and the width of waveguide slit clearance. In process of the slitless collimator study, we registered the gap width variation in interval 0–60 nm at the prism translation along the slitless unit. In result, we concluded that the slitless collimator is characterized by effective width of the gap s = 30 ± 30 nm.
3. Experimental setup for the radiation intensity distribution study
The main device to study the X-ray intensity distribution was the HZG-4 diffractometer manufactured by Carl Zeiss Jena Firm. We produced some modification of the device by its detector circle radius increasing up to 500 mm. In the modification result, the measurement space resolution improved in three times. The measurement spectroscopic circuit was completed by NIM standard units produced by Ortec firm. The shaping time of amplifier unit was selected as 0.5 μs. Such selection allowed to get the pulse registration count rate up to 100 kHz. The design of our registration setup is presented in Figure 7. X-ray diffractometer used as the setup background is characterized by scanning regimes in nonstop function and start-stop moving with a minimum step of δ(2θ) = 0.001°. X-ray detector was equipped by slit-cut arrester with a width of s = 0.1 mm and a height of h = 10 mm and Soller slit system limiting the registered flux vertical divergence by value near 2°. X-ray flux take-off angle was selected near 6°. Main volume of experimental investigations was executed by X-ray tube BSW-24 (Cu) in regime U = 20 keV and I = 10 mA. Similar tube with Fe anode was exploited in some selective measurements. The X-ray space intensity distribution data collection was produced with the use of Cu filter attenuator characterized by the CuKα radiation decreasing factor K = 200. For the energy spectrum characterization, our facility setup was equipped by a pulse multichannel analyzer ACCUSPEC Canberra Packard in the form of PC computer board. In measurements of PXW parameters, we used the characteristic part of initial X-ray spectra only.
Figure 7.
Instrumental facility for the spatial distribution study of a quasimonochromatic radiation intensity in X-ray beams formed by quartz planar waveguides.
4. Angular radiation intensity distribution in X-ray beams
In the course of our measurements, the waveguide position in experimental setup in experimental process was not changed. In the experimental process, the distance between the waveguide inlet and the X-ray tube focal position was 75 mm, and the distance between the waveguide outlet and the X-ray detector slit was 460 mm. X-ray flux capture angle calculated on the basis of geometric approach was equal to 0.08° owing to the size of tube focus projection evaluated as 0.1 mm. In experiments, the diffractometer angular step Δ(2θ) was 0.02°. At the same time, the detector slit angular acceptance was 0.01°. The single channel analyzer during experiments transmitted only pulses connected with the Cu characteristic radiation. Scheme of experimental measurement is presented in top position of Figure 8. Experimental results are shown in bottom of Figure 8.
Figure 8.
Experimental scheme for the spatial distribution study of X-ray beam intensity formed by PXWs (1) patterns of CuKαβ intensity spatial distribution in beams formed by PXWs with slit sizes 43 nm, 800 nm, and 35 μm (2), and the experimental dependence of CuKαβ total intensity in beams formed by PXWs on its slit width (3).
The slit clearance size interval 0 ≤ s ≤ 2 μm was characterized by the absence of the intensity distribution profile transformations for waveguide emergent X-ray beams. Profiles of these distributions were beautifully described by the Gaussian function. It showed some differences in FWHM values and total intensity magnitudes. The intensity magnitude scattering is likely due to our polishing technology wretchedness, but its increasing at s > 200 nm is higher as the experimental error. The distribution FWHM was not exceeded the radiation capture angle. At the same time, when the slit clearance width had exceeded 3 μm, the space intensity distribution found new form, which could be interpreted as a set of lines. Experimental data of the waveguide emergent beam total integral intensity dependence on the slit clearance width are presented in Figure 8. These dependence can be described by three typical size interval: s ≤ 200 nm (a), 200 ≤ s ≤ 3000 nm (b), and s ≥ 3 μm (c) with different characters of the dependence.
Registered experimental data and common sense allowed to assume that the X-ray waveguide emergent beam consists of some independent deposits. One can suppose by using the geometrical optics concept that one of them is connected with the X-ray beam direct propagation through the waveguide slit clearance without waveguide reflector surface interaction. It is clear that at any width of the slit clearance, the direct beam will form its own partial peak and will show the linear dependence of its integral intensity variation on the slit clearance width. Its intensity will be equal to zero for the case of the slit clearance zero magnitude. Experimental data showed that the direct beam propagation mechanism was not able to describe the integral beam intensity variation dependence on the slit clearance width, especially, for the nanosize slit interval (a). In this region, the emergent beam total intensity maintains constant magnitude, which is more higher than zero. Calculations showed that the direct beam deposit into the experimental data magnitude for this region is less that 1%. Second region (b) is characterized by the monotonous integral intensity increasing at growth of the slit clearance width. This effect can be connected with a deposit increasing the direct beam in the total X-ray beam intensity. Third region (c) defined as s > 3 μm demonstrates sharp intensity growth at the width increasing. This area is characterized by an addition deposit appearing connected with X-ray beam multiple total external reflections on waveguide reflector surfaces. The slit clearance width increasing in this region leads to linear growth of intensity deposits defined by mechanisms of X-ray beam direct and multiple external total reflection propagations. The total integral intensity growth of the waveguide emergent beam break off when the slit clearance width exceeds size of the radiation source focus projection.
The experimental data comparison featured for different regions of the slit clearance width and peculiarities discussion of different mechanisms of radiation fluxes propagation insist us on conclusion that the nanosize region (a) is characterized by the specific waveguide-resonance manner of X-ray flux propagation [35]. Devices functioned in frame of the resonance manner we called the planar X-ray waveguide resonators (PXWRs) [29]. PXWR forms the X-ray quasimonochromatic flux as the indivisible ensemble with parameters, which are not depended from the slit clearance width and the initial distribution in radiation flux captured by the device. The waveguide mechanism of the X-ray quasimonochromatic flux propagation featured for the narrow extended slit clearance demonstrates the X-ray radiation density increasing and decreasing the irreversible losses. Angular divergence of PXWR emergent beam is equal to its radiation capture angle, and they cannot exceed twice value of the total reflection critical angle featured for the reflector material.
The slit clearance width intermediate interval (region b) is connected with two independent deposits into integral intensity defined by direct and quasiresonance beam propagation mechanisms. The increase of slit clearance ensures small growth of the beam integral intensity, but its radiation density diminishes. Spatial intensity distribution featured for this region shows a single-component form owing to small influence of the multiple total external effects on the emergent beam integral intensity. This effect deposit into the intensity becomes decisive factor when the slit clearance width exceeds critical value s = 3 μm (c). In this case, emergent beam divergence arrives its maximum Δθ = 2θc independently from the device input aperture magnitude. The intensity distribution demonstrates multicomponent structure.
With practical point of view, it is very interesting to compare the radiation density parameter featured for PXWR and waveguides corresponding to “b” and “c” regions with similar parameter featured for X-ray beams formed by a conventional slit-cut device. The beam integral intensity on the slit-cut former output is more higher than one formed by different PXWs. But in the radiation density parameter, the planar extended waveguide structures are more effective. Direct comparison of the slit width is presented in Figure 9. Enhanced radiation density peculiar to X-ray beams formed by PXW is connected with width difference of the waveguide slit clearance and the radiation source focus projection. Waveguides capture X-ray radiation fluxes in the angular aperture Δφ ≤ 2θc from radiation source focus projection with width P ∼ 0.1 mm into the slit clearance with more smaller width. In result, waveguide devices concentrate radiation. According to the data presented in Figure 9, PXWR is able to increase X-ray radiation density on three orders in its emergent beam in comparison with beams formed by slit-cut system. It is interesting that the maximum radiation density is expected for the slitless collimator. But the practical use of X-ray slitless system is troubled owing to the absence of the intensity stationary in its emergent beams.
Figure 9.
Experimental dependences of CuKαβ flux radiation densities on slit width for X-ray beams formed by PXWs (a) and by the single slit-cut system (b).
5. Waveguide-resonance model for X-ray flux propagation
Figure 10a presents the idealizing scheme of X-ray flux total external reflection, which takes into account the degree of a radiation monochromatization Δλ along with the average wavelength λ0. Owing to this principal limitation, the size of radiation standing wave area in the space over reflector will be bounded. Δλ through the coherence length parameter characterizes the length of an electromagnetic radiation train or the photon longitudinal size. The interference phenomenon is possible if the path difference between the incident and the reflected fluxes does not exceed the magnitude of this parameter. But in any case, the longitudinal size of the interference area cannot exceed of the value. By this, it means that the coherence length of quasimonochromatic radiation is responsible for the longitudinal magnitude evaluation of X-ray standing wave area. In this framework of the phenomenological model, we accepted that the transverse size of the area is approximately equal to the longitudinal one. This premise is absolutely right so far as the real interference effect is connected with the spatial coherence of the quasimonochromatic flux radiation [36].
Figure 10.
Scheme of the interference field of X-ray standing wave arising from the external total reflection phenomenon in case of the quasimonochromatic flux interaction with material interface (a). Δw is the source focus projection, R is the distance between X-ray source and target position, φ is the angular flux divergence, Δz is the penetration depth, and D is the standing wave period. Standing wave intensities in the air area and in the reflector volume (b).
The next model postulate says that the description of the total X-ray reflection phenomenon must take into account the fundamental principle of a field continuity [37]. According to this principle, the interference field of X-ray standing wave cannot abruptly terminate on the material-vacuum (air) interface. The conventional model of X-ray beam total external reflection suggests that the radiation electromagnetic field amplitude undergoes exponential attenuation in the reflector material [38]. But the principle of electromagnetic field continually demands the exponential low multiplication on the interference term. Visualization of the modification is presented in Figure 10b and can be defined by the expression [39]:
E→Tzxt=2θθ+a+ibe2πiza+ibλ0eiω0t−2πpxxE→0E1
where θ is the incident angle; λ0 and ω0 are the wavelength and the angular frequency of the radiation, respectively; px is the x-component of the photon momentum; and a and b are presented by the specific expressions [38]:
a2=12θ2−2δ2+4β2−θ2−2δb2=12θ2−2δ2+4β2−θ2−2δE2
where δ and β factors are the formal parameters incoming into the conventional expression for the material refractive index [38]:
n=1−δ−iβE3
The δ-factor is connected with the volume material polarization effect, and β-factor characterizes the attenuation degree of X-ray radiation flux in the material. But we would like to notice that the refractive index introduction in form presented by expression (3) is not correct, in principle. It suggests that the X-ray beam propagation velocity in material volume is higher than the velocity of the electromagnetic wave propagation in vacuum. Professor L.D. Landau at first pointed on this collision [40].
Figure 10a and b displays the principle model for an electromagnetic field distribution in the reflection area over and under the interface. The size of the interference area appeared over the interface is limited by the coherence radiation condition. But the interference area size under the interface is not limited. The entire volume of the reflector will be excited as a result of a flux total reflection on its local spot.
The external total reflection phenomenon is accompanied by an additional phase shift Δψ [41]. This parameter is the function of the flux incident angle φ. At the critical total reflection angle (φ ≅ θc), the additional phase shift strives to zero, but at the sliding incidence (φ ≅ 0), Δψ value approximates to “π.” The variation of the additional phase shift magnitude influences on the interference area size. Therefore, in framework of the waveguide-resonance model, the solution was accepted that the size of X-ray standing wave interference area is approximately conformed to half magnitude of the coherence length for the radiation flux undergoing the total reflection on the material interface [39].
If we place two planar dielectric polished reflectors on some distance, we can get the air planar extended slit clearance, which can be used for the realization of X-ray flux multiple external total reflection effects (Figure 11a). The consecutive multiple external total reflection phenomena are characterized by appearing the local interference area set. Since every elementary act of X-ray flux total reflection excites material volume of reflector, the next second reflection in the slit clearance on the reflector surface will lead to the material volume excitation. One can find specific X-ray flux incident angles, which will show the phasing of consecutive total reflection on every reflector (magic angles). Peculiarities of X-ray beam propagation through the air slit clearance are depended from the existence or absence of the phasing. The presence of phasing effect allows to transport the X-ray quasimonochromatic flux by PXW with small attenuation. The magic angle existence defines the discrete mode structure featured for the multiple total external reflection mechanisms. This picture is inherent for the X-ray polycapillary optics.
Figure 11.
Visualizating schemes of X-ray flux propagation through the planar extended slit clearance by the multiple total reflection mechanisms (a) and by the waveguide-resonance one (b). P is the parameter of the interference field protrusion from PXWR slit.
The mechanism of X-ray flux multiple total reflections is very efficient for the description of its propagation through planar wide slit clearances. But this mechanism is not able to characterize peculiarities of the radiation flux transportation by the super narrow planar extended slits. X-ray flux propagation through similar slits can be described on the basis of waveguide-resonance idea.
The conception of X-ray flux waveguide-resonance propagation is accompanied by appearing the X-ray standing wave uniform interference field in all narrow extended slit clearance spaces owing to the mutual overlap of local interference areas (Figure 11b). Overlay of these areas will be realized for any magnitudes of incident angles when it does not exceed the value of total reflection critical angle θc for the reflector material. The mode structure conception for PXWR is not existed. Moreover, we can confirm that the radiation coherence length magnitude is the critical parameter for the X-ray flux mechanism propagation change from the multiple external total reflections to the waveguide-resonance proceeding.
The narrow extended slit clearance radiation transport properties discussed above were investigated in the geometry when the projection of X-ray source focus was deposited in the symmetry plane of PXWR [39]. In this measurement geometry, the axis of X-ray incidence flux coincides with the axis of waveguide resonator. But in common case, the radiation flux can incident on the PXWR inlet at off-axis conditions. Measures in conditions of an initial X-ray flux off-axis incidence allow to differ the discrete mode structure from one with the continuous character, if the flux divergence is not great. The waveguide-resonance concept predicts that the off-axis incidence of X-ray flux will lead to the appearance of the emergent beam in the form of the double peak for a radiation spatial distribution (Figure 11b). The angular distance between the maximum of peaks must be equal to a double magnitude of the incidence angle. It is expected that the intensity of peaks must be approximately equivalent, and its divergences will be correlated with the radiation capture angle. Moreover, the integral intensity of the double-peak structure must be the monotonous function on the incidence angle for the angular interval –θc ≤ θ ≤ θc. The reliable confirmation of all predictions following from the model of X-ray flux waveguide-resonance propagation was obtained in the course of our experimental investigations [36].
The integral intensity of PXWR emergent beam is insignificantly differed from the intensity of X-ray initial beam. Its magnitude can be described by the expression [39]:
Wx=W0e−αμxE4
where W0 is the initial beam intensity, μ is the linear absorption factor of reflector material for the radiation transported by PXWR, and α is the composite function defined by set factors of physical and geometrical nature. α magnitude is very small, and the attenuation of X-ray flux transported by PXWR is not significant. The experimental measurements showed that the attenuation factor for CuKα radiation transported by the quartz PXWR with a length of l ∼ 100 mm can be near some per cents. The intensity losses for PXWR are smaller as the calculated values characterized for the multiple total reflection mechanisms. High radiation transportation efficiency of the planar X-ray waveguide-resonator is the result of the mode structure continuity for the flux propagating through its narrow extended slit clearance.
It is very important to notice that X-ray flux transportation by the waveguide-resonance mechanism is the result of the spatial coherence of quasimonochromatic radiation irradiated by X-ray tube. Owing to the fundamental physical reasons, a single X-ray photon in conditions of the total external reflection on the material interface cannot undergo interference with itself. The reflection process for X-ray and for other nature waves is accompanied by the Goos-Hanchen wave front displacement of the beam reflection position about the point of the beam incoming place, which is presented by the expression [42, 43, 44]:
Δx=λ0π1θc2−θ2+2iβ1θc2+2iβE5
where θc is the magnitude of the total reflection critical angle. Minimum and maximum magnitudes of the displacement are arrived at θ = 0 and θ = θc, correspondingly. The expressions for these values have forms:
Δxmin=λ0πθc2;Δxmax=λ0πθc12βE6
Calculation of these factors shows that its magnitudes do not exceed the radiation coherence length and interference takes place.
6. Verification of the waveguide-resonance mechanism
The direct verification of the waveguide-resonance mechanism manifestation for the X-ray beam propagation can be found in the work of Japanese scientists [45]. The work was devoted to the transport property study of the angular structure as shown in Figure 12a. Japanese authors measured the MoKα flux intensity dependence on magnitude of the taper angle between two Si planar reflectors forming the radiation transportation structure. Figure 12b demonstrates the results of the measurements. The diffuse extremum I (near 0.1°) corresponds to reaching the critical total reflection angle for the molybdenum radiation on the silicon surface. The second extremum appearing near 0.007° cannot be explained without using the waveguide-resonance concept. The growth of X-ray radiation transport efficiency connected with this maximum reflects the transformation effect from the multiple total reflection propagations to the mechanism of the waveguide-resonance flux stream. The increase of an emergent beam intensity connects with a decrease in the flux attenuation featured for the waveguide-resonance propagation mechanism. The intensity of the second extremum is half of the first one, and the width of it is smaller than the first one on approximately one order. In result, the beam corresponding to the second radiation maximum will be characterized by the enhanced radiation density. The discussed results can be conceded as the independent confirmation of the waveguide-resonance mechanism objective reality for the quasimonochromatic X-ray flux propagation through the extended nanosize slit clearances.
Figure 12.
Experimental scheme for the study of the radiation flux transporting peculiarities featured for the angular structure built on the basis of two Si reflectors under the variation of the taper angle between them (a), and the experimental diagram reflecting the emergent beam intensity dependence on the taper angle magnitude (b) [45].
7. Specific properties of PXWR
The waveguide-resonance mechanism is characterized by some specific properties of the quasimonochromatic radiation flux propagation through narrow extended slits, and the coherence length parameter is the limiting factor for the mechanism realization. The white radiation generated by X-ray tube is not characterized by parameter of the coherence length owing to the nature of this radiation arising [46]. But the experimental data presented in Figure 13 show that the white radiation is transported by PXWR. At the same time, its related deposit at the total intensity of X-ray beam formed by PXWR is smaller than one in the beam formed by slit-cut system. So, one can expect that the spatial coherence degree for the white radiation generated by X-ray tube is smaller than this parameter featured for X-ray quasimonochromatic lines. Figure 13 shows that the white component intensity falls down approximately two times in all spectral ranges investigated in the experiments. Thus, a planar X-ray waveguide resonator cannot be considered as a restrictive filter for the hard white radiation. But PXWR application for X-ray beam formation decreases the white radiation deposit in the total beam intensity. This effect will be greatest for the smallest slit clearance width. The specific feature of PXWR is the impossibility to use it for β-filtration of X-ray tube initial radiation. The β-filtration procedure for X-ray diffractometry is well known [47]. This procedure is based on the use of the thin film absorber manufactured from the material, which is characterized by the energy absorption edge intervened between EKα and EKβ of the tube characteristic radiation. Similar β-filter can be built on the basis of planar monocapillar prepared by using the dielectric reflectors containing a significant concentration of atoms characterized by a suitable value of the energy absorption edge. Our direct experiments showed that the similar approach is not right for PXWR. β-Radiation flux excites the uniform interference field of X-ray standing wave in all space of PXWR air slit clearance, and the intensity attenuation is not observed.
Figure 13.
Experimental diffraction patterns for SiO2 (101) monocrystal specimen collected in conditions of a standard Bragg-Brentano geometry (a) and a waveguide-resonator application for the initial beam formation (b). The pattern normalization was carried out on the basis of equivalence of characteristic line intensities. Pattern (a) was registered at BSW-24 (Fe) X-ray tube regime U = 25 keV, I = 3 mA and pattern (b) U = 25 keV, I = 9 mA. Geometrical sizes at the measurements were (a) l0 = 235 mm, l1 = 50 mm, l2 = 235 mm, S1 = S2 = 0.1 mm and (b) l0 = 235 mm, l1 = 50 mm, l2 = 155 mm, l3 = 85 mm, S1 = 0.1 mm, sPXWR = 0.1 μm. The collection was carried out without a pulse discrimination.
Specific properties of PXWR are not exhausted by the peculiarities discussed above. For example, the beam formed by the waveguide resonator has the nanosize width and the enhanced radiation density. The beam is not accompanied by diffraction satellites and can be modulated by an external influence. But the planar X-ray waveguide resonator is characterized by two serious lacks. The angular divergence of the beam formed by PXWR of the simplest design is usually near 0.1°, and its real integral intensity is smaller than the integral intensities of beams formed by the slit-cut systems and the polycapillary optic devices on 1–2 orders [39]. The angular divergence of PXWR emergent beam can be decreased without influence on its integral intensity by application of PXWR with specific design, which has name as the composite planar X-ray waveguide resonator (CPXWR) [48].
Figure 14 presents the results of comparative investigations of X-ray characteristic beam formation by PXWR with the simplest construction (a) and CPXWR (b). Left part of the figure presents the measurement schemes. Spatial distributions of X-ray intensities in beams formed by these devices are shown in the right part of the figure. Radiation capture angle is the same and is equal to Δφ1 = 0.11°. Composite waveguide resonator differs from PXWR with the simplest construction by gap existence ΔL ∼ 0.1 mm between two PXWRs with the simplest construction built on the basis of short reflectors. The divergence of the waveguide emergent beams was studied by the method of the step-by-step detector scanning. The angular size of the detector slit S1 was near 0.01°. The scanning step was Δ(2θ) = 0.02°.
Figure 14.
Experimental schemes and flux intensity spatial distributions for CuKαβ beams formed by PXWR (a) and CPXWR (b) [48]. SPXWR = SCPXWR = 88 nm, LPXWR = LCPXWR = 100 mm, l1 = 75 mm, l2 = 60 mm, l3 = 400 mm, S1 = 0.1 mm, L1 = L2 = 50 mm, ΔL = 0.1 mm. Source regimes of BSW-24 (Cu) for both measurements U = 20 keV, I = 10 mA, A – filter attenuation factor K = 200.
Experimental intensity distributions for the beams formed by the conventional and the composite PXWRs demonstrate the Gauss form of distributions. FWHM of the peak distinguished for PXWR is Δφ2 = 0.11°. At the same time, the magnitude of this parameter for CPXWR emergent beam is Δφ2 = 0.05° only. Total intensities of the peaks are approximately the same. Data presented show that the gap existence leads to the beam angular constriction without intensity losses. Such result is very alike on existence of the tunneling effect in the gap space. The increasing of ΔL distance up to 10 mm has led to an abrupt decrease of the peak total intensity and its FWHM.
Using the modified reflectors for the waveguide-resonator building allows to solve the second PXWR problem – low integral intensity of its emergent beam. Standard quartz glass plates modified by 30 mm polished tapers with an angle of ψ = 0.5° were used for building the specific waveguide resonator (Figure 15b). For further radiation gathering power enhancement, the tapers were coated by HfO2 thin film. Then, Ti strips with 90 nm thickness were deposited onto one plate edges, and the waveguide-resonance structure with a slit channel width of 90 nm and a height of 4 mm was assembled. In result, we received the skewed input concentrator with an angular aperture near 1°. Next, the comparative measurements of the conventional PXWR and the modified waveguide resonator were executed. The geometric parameters of the measuring schemes are given in Figure 15. Intensity spatial distributions for beams formed by the tested devices are shown in the same figure. In addition, the values of the total intensity (with and without the use of attenuator A) and the angular divergence of the beams are also quoted therein. The distributions were obtained at radiation source operation conditions [BSW-24 (Fe), U = 20 keV, I = 10 mA].
Figure 15.
Experimental schemes for the study of the intensity spatial distributions in X-ray beams formed by the waveguide resonator of a conventional construction (a) and PXWR with specific design (b) and real intensity distributions in its emergent beams. I* is the measurement magnitude, and I** is the intensity corrected by taking into account the attenuator (A).
The data show that the envelope shape and FWHM of the intensity spatial distribution for a quasimonochromatic component of the beams formed by the conventional and the modified PXWR are nearly the same. On the other hand, the total intensity of the beam formed by the modified waveguide resonator is substantially higher than the beam intensity formed by the conventional PXWR. The data show a fivefold increase in the radiation gathering power of the waveguide resonator due to the application of the input skewed radiation concentrator. Experimental value of the radiation gathering power enhancement obtained in our measurements was somewhat less than the rating. It is presumably explained by the nonoptimal length and form of the tapers. Nevertheless, the above result allows to state that the application of the input skewed concentrator is a powerful tool for the radiation gathering power enhancement of the waveguide-resonance structures, which provides the system modification without a significant loss in other parameters of the emergent beam.
In principle, there are other methods for the improvement of waveguide-resonator parameters. The most drastic method of PXWR parameter modification is the building of the multi-slit waveguide-resonance structures. According to our opinion, this way is very perspective, but it entails serious problems connected with the interference effect between the individual beams [49].
8. Practical application of the phenomenon
Experiments showed that the phenomenon of X-ray flux waveguide resonance increases the efficiency of X-ray fluorescence material analysis in conditions of exciting beam total reflection on studied surface (TXRF) [50]. This method modification by PXWR including the setup of TXRF spectrometer allowed to decrease the pollution detection limits in comparison with the convention of 1–2 orders. PXWR uses in experimental scheme of the particle induced X-ray emission (PIXE) allowed to elaborate the new experimental method for surface material element diagnostic [51]. Moreover, in some specific geometries, the method can provide element surface analysis being free from matrix effects.
The waveguide-resonance propagation of X-ray characteristic radiation fluxes can be achieved not only in frame of the external total reflection phenomenon but also at the use of the Bragg reflection. By using the Bragg-Laue waveguide-resonance cell (BLWRC), it is possible to build the pulsed X-ray laser on table, which will be useful for the study of kinetic processes [52]. Based on the use of phenomenon consequences, it is possible to realize the reactions of cold nuclear fusion [53]. But the more important result of waveguide-resonance radiation propagation phenomenon discovery, we regard the possibility appearing to elaborate the function correct model for optical fibers and waveguides of light beams. Conventional model of its function is based on the light flux notion as the infinite plane wave and on the light flux transportation mechanism by planar symmetrical waveguide as the multiple internal total reflections in frame of the geometrical paradigm [54, 55, 56, 57, 58, 59, 60, 61, 62, 63]. Similar approach is not right, in principle. It is well known that any radiation source generates quasimonochromatic beams with λ0 mean wavelength and Δλ monochromatization degree. So, any quasimonochromatic beam is characterized by the coherence length parameter. Up-to-date optical lasers generate the beams with several tens of meters of coherence length. Owing to the core size of planar symmetrical optical waveguides varies from some micrometers to some millimeters, we can conclude that all optical waveguides and fibers are functioned in frame of the waveguide-resonance phenomenon manifestation, and instead of mode structure, it is a need to discuss the properties of uniform interference field of optical radiation standing wave.
9. Conclusion
The paper presented some experimental results allowed to consider that the waveguide-resonance conception is right. We described the features of the waveguide-resonance mechanism discussed its principle model and fixed the critical parameter being responsible for mechanism change of the radiation flux propagation. References presented allowed to understand some practical application of the phenomenon and its consequences. The paper contains the short description of X-ray device functioned on the basis of mechanism – the planar X-ray waveguide resonator, the discussion of PXWR properties, and the ways of its construction perfection.
Acknowledgments
The authors would like to thank Prof. J. Kawai and Prof. R. Van Grieken for the great attention to the waveguide-resonance direction of X-ray optics and Dr. M.S. Afanas’ev for help.
\n',keywords:"X-ray flux, external total reflection, X-ray standing wave, coherence length, X-ray nanophotonics, planar X-ray waveguide resonator, waveguide-resonance propagation phenomenon, spatial coherence, angular divergence, partial angular tunneling effect",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/72815.pdf",chapterXML:"https://mts.intechopen.com/source/xml/72815.xml",downloadPdfUrl:"/chapter/pdf-download/72815",previewPdfUrl:"/chapter/pdf-preview/72815",totalDownloads:395,totalViews:0,totalCrossrefCites:0,dateSubmitted:"February 9th 2020",dateReviewed:"June 12th 2020",datePrePublished:"July 15th 2020",datePublished:"October 21st 2020",dateFinished:"July 15th 2020",readingETA:"0",abstract:"The work discussed shortly the experimental results, which was the waveguide-resonance mechanism relevation forerunner of characteristic X-ray radiation flux propagation. Technology of the planar air extended slit clearance preparation is presented. The methodology of X-ray beam parameter study formed by these slit clearances, which allowed to find the critical parameter answering for the radiation flux propagation mechanism change from the multiple external total reflections to the waveguide-resonance one, is described. Main features of the X-ray flux waveguide-resonance propagation mechanism were revealed. The self-consistent model of the mechanism is displayed with details. It is shown that the waveguide-resonance effect has universal character, and it reflects the fundamental nature phenomenon. The peculiarities of X-ray device functioned in frame of the phenomenon manifestation planar X-ray waveguide resonator (PXWR) and the increasing methods of its practical efficiency are discussed. The phenomenon practical application is presented concisely.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/72815",risUrl:"/chapter/ris/72815",signatures:"Egorov Evgenii Vladimirovich and Egorov Vladimir Konstantinovich",book:{id:"10093",type:"book",title:"Electromagnetic Propagation and Waveguides in Photonics and Microwave Engineering",subtitle:null,fullTitle:"Electromagnetic Propagation and Waveguides in Photonics and Microwave Engineering",slug:"electromagnetic-propagation-and-waveguides-in-photonics-and-microwave-engineering",publishedDate:"October 21st 2020",bookSignature:"Patrick Steglich",coverURL:"https://cdn.intechopen.com/books/images_new/10093.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",isbn:"978-1-83968-189-9",printIsbn:"978-1-83968-188-2",pdfIsbn:"978-1-83968-190-5",isAvailableForWebshopOrdering:!0,editors:[{id:"223128",title:"Dr.",name:"Patrick",middleName:null,surname:"Steglich",slug:"patrick-steglich",fullName:"Patrick Steglich"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"232472",title:"Dr.",name:"Vladimir",middleName:null,surname:"Egorov",fullName:"Vladimir Egorov",slug:"vladimir-egorov",email:"egorov@iptm.ru",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"Institute of Microelectronics Technology and High Purity Materials",institutionURL:null,country:{name:"Russia"}}},{id:"247324",title:"Mr.",name:"Evgeniy",middleName:null,surname:"Egorov",fullName:"Evgeniy Egorov",slug:"evgeniy-egorov",email:"hed1317@mail.ru",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Technological features of PXW fabrication",level:"1"},{id:"sec_3",title:"3. Experimental setup for the radiation intensity distribution study",level:"1"},{id:"sec_4",title:"4. Angular radiation intensity distribution in X-ray beams",level:"1"},{id:"sec_5",title:"5. Waveguide-resonance model for X-ray flux propagation",level:"1"},{id:"sec_6",title:"6. Verification of the waveguide-resonance mechanism",level:"1"},{id:"sec_7",title:"7. Specific properties of PXWR",level:"1"},{id:"sec_8",title:"8. Practical application of the phenomenon",level:"1"},{id:"sec_9",title:"9. Conclusion",level:"1"},{id:"sec_10",title:"Acknowledgments",level:"1"}],chapterReferences:[{id:"B1",body:'Hirsch P, Kellar J. An X-ray micro-beam technique: I-collimation. Proceedings of the Physical Society of London Series B. 1951;64:369-374'},{id:"B2",body:'Spiller E, Segmuller A. Propagation of X-rays in waveguide. 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Institute of Microelectronics Technology Russian Academy of Science, Russia
Institute of Radio Engineering and Electronics Russian Academy of Science, Russia
Financial University under the Government of Russian Federation, Russia
'},{corresp:null,contributorFullName:"Egorov Vladimir Konstantinovich",address:null,affiliation:'
Institute of Microelectronics Technology Russian Academy of Science, Russia
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He has written ninety-three scientific papers and edited/co-edited eight books and seven book chapters.",institutionString:"Pantai Hospital Kuala Lumpur",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"6",totalChapterViews:"0",totalEditedBooks:"4",institution:null},equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7844",title:"Voice and Swallowing Disorders",subtitle:null,isOpenForSubmission:!1,hash:"9a81e27eb29c12553e9524f20a93b57d",slug:"voice-and-swallowing-disorders",bookSignature:"Monjur Ahmed",coverURL:"https://cdn.intechopen.com/books/images_new/7844.jpg",editedByType:"Edited by",editors:[{id:"206355",title:"Associate Prof.",name:"Monjur",middleName:null,surname:"Ahmed",slug:"monjur-ahmed",fullName:"Monjur Ahmed"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1758",title:"Otolaryngology",subtitle:null,isOpenForSubmission:!1,hash:"8b845def701f65d6ae3487686581983f",slug:"otolaryngology",bookSignature:"Balwant Singh Gendeh",coverURL:"https://cdn.intechopen.com/books/images_new/1758.jpg",editedByType:"Edited by",editors:[{id:"67669",title:null,name:"Balwant Singh",middleName:null,surname:"Gendeh",slug:"balwant-singh-gendeh",fullName:"Balwant Singh Gendeh"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],booksByTopicTotal:3,seriesByTopicCollection:[],seriesByTopicTotal:0,mostCitedChapters:[{id:"37024",doi:"10.5772/38247",title:"Proteins Involved in Otoconia Formation and Maintenance",slug:"proteins-involved-in-otoconia-formation-and-maintenance",totalDownloads:2672,totalCrossrefCites:0,totalDimensionsCites:3,abstract:null,book:{id:"1758",slug:"otolaryngology",title:"Otolaryngology",fullTitle:"Otolaryngology"},signatures:"Yunxia Wang Lundberg and Yinfang Xu",authors:[{id:"117097",title:"Dr.",name:"Yinfang",middleName:null,surname:"Xu",slug:"yinfang-xu",fullName:"Yinfang Xu"},{id:"117202",title:"Dr.",name:"Yesha",middleName:null,surname:"Lundberg",slug:"yesha-lundberg",fullName:"Yesha Lundberg"}]},{id:"37027",doi:"10.5772/37764",title:"Endoscopic Dacryocystorhinostomy",slug:"endoscopic-dacryocystorhinostomy",totalDownloads:5354,totalCrossrefCites:0,totalDimensionsCites:2,abstract:null,book:{id:"1758",slug:"otolaryngology",title:"Otolaryngology",fullTitle:"Otolaryngology"},signatures:"Farhad Farahani",authors:[{id:"114231",title:"Prof.",name:"Farhad",middleName:null,surname:"Farahani",slug:"farhad-farahani",fullName:"Farhad Farahani"}]},{id:"37031",doi:"10.5772/38325",title:"Comparison Among Phonation of the Sustained Vowel /ε/, Lip Trills, and Tongue Trills: The Amplitude of Vocal Fold Vibration and the Closed Quotient",slug:"comparative-analysis-of-the-amplitude-of-vibraition-of-the-vocal-folds-and-the-coefficient-of-contac",totalDownloads:3560,totalCrossrefCites:0,totalDimensionsCites:2,abstract:null,book:{id:"1758",slug:"otolaryngology",title:"Otolaryngology",fullTitle:"Otolaryngology"},signatures:"Gislaine Ferro Cordeiro, Arlindo Neto Montagnoli\r\nand Domingos Hiroshi Tsuji",authors:[{id:"116654",title:"MSc.",name:"Gislaine",middleName:null,surname:"Cordeiro",slug:"gislaine-cordeiro",fullName:"Gislaine Cordeiro"},{id:"116666",title:"Dr.",name:"Arlindo Neto",middleName:null,surname:"Montagnoli",slug:"arlindo-neto-montagnoli",fullName:"Arlindo Neto Montagnoli"},{id:"116667",title:"Dr.",name:"Domingos Hiroshi",middleName:null,surname:"Tsuji",slug:"domingos-hiroshi-tsuji",fullName:"Domingos Hiroshi Tsuji"}]},{id:"37033",doi:"10.5772/36074",title:"A Review of Tonsillectomy Techniques and Technologies",slug:"a-review-of-tonsillectomy-techniques-and-technologies",totalDownloads:6683,totalCrossrefCites:0,totalDimensionsCites:2,abstract:null,book:{id:"1758",slug:"otolaryngology",title:"Otolaryngology",fullTitle:"Otolaryngology"},signatures:"S. K. Aremu",authors:[{id:"106996",title:"Dr.",name:"Shuaib",middleName:"Kayode",surname:"Aremu",slug:"shuaib-aremu",fullName:"Shuaib Aremu"}]},{id:"70727",doi:"10.5772/intechopen.90768",title:"Neuro-Olfactory Regulation and Salivary Actions: A Coordinated Event for Successful Blood-Feeding Behavior of Mosquitoes",slug:"neuro-olfactory-regulation-and-salivary-actions-a-coordinated-event-for-successful-blood-feeding-beh",totalDownloads:751,totalCrossrefCites:0,totalDimensionsCites:2,abstract:"The synergistic actions of the nongenetic and genetic factors are crucial to shape mosquitoes’ feeding behavior. Unlike males, adult female mosquitoes are evolved with unique ability to take blood meals from a vertebrate host for reproductive success which eventually makes them a potential vector. Processing and integration of chemical information in the neuro-olfactory system followed by salivary actions facilitate blood meal uptake process. Thus, deciphering the underlying molecular mechanism of odor sensing through the detection machinery (olfactory system), odor processing and decision-making by decision machinery (brain), and regulation of saliva secretion by the action machinery (salivary gland) is likely to reveal molecular pathways which can be targeted to disrupt mosquitoes’ feeding behavior. Here we summarize how smart actions of highly specialized neurosensory systems guide and manage feeding behavior associated complex events of (i) successful navigation to find a suitable host, (ii) making food choice decisions, and (iii) regulation of the salivary gland actions in mosquitoes.",book:{id:"8732",slug:"sino-nasal-and-olfactory-system-disorders",title:"Sino-Nasal and Olfactory System Disorders",fullTitle:"Sino-Nasal and Olfactory System Disorders"},signatures:"Tanwee Das De and Rajnikant Dixit",authors:[{id:"309585",title:"Dr.",name:"Tanwee",middleName:null,surname:"Das De",slug:"tanwee-das-de",fullName:"Tanwee Das De"}]}],mostDownloadedChaptersLast30Days:[{id:"70060",title:"Maxillofacial and Oral Aspects of Dysphagia",slug:"maxillofacial-and-oral-aspects-of-dysphagia",totalDownloads:971,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Oral cavity/mouth is first recipient of food. Food is broken down and prepared for initial phases of digestion. The oral preparatory phase is voluntary. In this phase, food is manipulated by the tongue and teeth. A bolus which is ready to swallow is prepared. Any disruption of oral cavity functions commonly due to oral infections, space infections, facial trauma, congenital-cleft lip and palate, temporo-mandibular joint disorders, salivary gland pathology, oral cancers, radiation therapy, etc., can cause dysphagia. In this chapter, we would explain the maxillofacial and oral aspects of dysphagia along with diagnosis and treatment aspects.",book:{id:"7844",slug:"voice-and-swallowing-disorders",title:"Voice and Swallowing Disorders",fullTitle:"Voice and Swallowing Disorders"},signatures:"Mohammed Basha",authors:null},{id:"70716",title:"Imaging in Sinonasal Disorders",slug:"imaging-in-sinonasal-disorders",totalDownloads:858,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Computed tomography (CT) is the “working horse” in sinonasal imaging and should always be the first choice. Magnetic resonance imaging (MRI) is complementary to CT when complications to rhinosinusitis or neoplasm are suspected. Imaging of the paranasal sinuses is common due to stuffy nose. In order to correct interpretation, proper imaging technique as well as knowledge of bony anatomy and variants and mucosal incidental findings are of outmost importance. Acute rhinosinusitis is very common and does not need imaging unless complications are suspected. In chronic rhinosinusitis, a CT examination is needed to find the cause and site of the mucociliary obstruction and to rule out other causes as odontogenic and fungal sinusitis and neoplasms.",book:{id:"8732",slug:"sino-nasal-and-olfactory-system-disorders",title:"Sino-Nasal and Olfactory System Disorders",fullTitle:"Sino-Nasal and Olfactory System Disorders"},signatures:"Heidi Beate Eggesbø",authors:[{id:"65505",title:"Dr.",name:"Heidi Beate",middleName:null,surname:"Eggesbø",slug:"heidi-beate-eggesbo",fullName:"Heidi Beate Eggesbø"}]},{id:"70261",title:"Sinusitis, Asthma and Headache",slug:"sinusitis-asthma-and-headache",totalDownloads:627,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Sinusitis is the infection of sinuses. Sinuses are four hollow cavities in face which are connected to nasal pathways to help moisten, warm and filter the air which we breathe in. Sinuses get irritated due to bacteria, virus and allergens. It is often associated with asthma and headache. Pressure in the sinuses is built by over production of mucous and leads to sinus headache. Asthma gets severe with the sinusitis as both are related to sino-nasal pathway. Treatment includes steroids, nasal decongestants, antibiotics and to avoid allergens which not only reduce the symptoms of asthma but also sinusitis. Acute sinusitis may turn into chronic sinusitis including narrowing of nasal passages, deviated septum and lumps in the nose (polyp). It can be treated with surgical procedures. The only way to prevent sinusitis is by precaution and medication. Post nasal drip may also associate with asthma causing bronchial constriction.",book:{id:"8732",slug:"sino-nasal-and-olfactory-system-disorders",title:"Sino-Nasal and Olfactory System Disorders",fullTitle:"Sino-Nasal and Olfactory System Disorders"},signatures:"Fozia Masood",authors:[{id:"302764",title:"Dr.",name:"Fozia",middleName:null,surname:"Masood",slug:"fozia-masood",fullName:"Fozia Masood"}]},{id:"71245",title:"Septoplasty: Endoscopic and Open Techniques",slug:"septoplasty-endoscopic-and-open-techniques",totalDownloads:955,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Septoplasty is one of the most commonly performed procedures by rhinologists. This article will provide a brief review of the surgical anatomy and the operative techniques of this procedure. Both endoscopic and open septoplasty procedures will be addressed. However, more than 15% of patients undergoing septoplasty fail to achieve symptomatic relief. Incomplete separation of the bony-cartilaginous junction and inadequate correction of the caudal septal deviation are the main reasons for persistent septal deviation after primary septoplasty. In revised septoplasty, correction of the caudal septal deviation can be done by proper correction of the cartilaginous curvature and strengthening of the structure using a batten graft.",book:{id:"8732",slug:"sino-nasal-and-olfactory-system-disorders",title:"Sino-Nasal and Olfactory System Disorders",fullTitle:"Sino-Nasal and Olfactory System Disorders"},signatures:"Yi-Tsen Lin",authors:[{id:"311313",title:"Dr.",name:"Yi-Tsen",middleName:null,surname:"Lin",slug:"yi-tsen-lin",fullName:"Yi-Tsen Lin"}]},{id:"70540",title:"Swallowing Disorders in Cervical Facial Tumors",slug:"swallowing-disorders-in-cervical-facial-tumors",totalDownloads:722,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"We review current state of the art protocols on swallowing disorders associated to cervical facial tumors. The clinician needs to translate physiology notions to bedside diagnosis. Facing such a case the ENT surgeon must follow several key steps: thorough history taking, barium transit, endoscopy evaluation of swallowing, high resolution diagnosis imaging. Afterwards surgical treatment plan should take into consideration the need to careful dissection of vascular and nervous structures. Dysphagia may present from initial diagnosis or after surgical resection of the tumor or during radiation and chemotherapy. We discuss the use of various staging scales or questionnaires for assessing quality of life. We illustrate the importance of swallowing disorders management with various cases of tumors at the level of skull base, pharynx, salivary glands, larynx, esophagus, etc. There are various solutions for dysphagia ranging from nasogastric feeding tube placement to percutaneous endoscopic gastrostomy to specially designed exercises. Sometimes the surgeon neglects these disorders and focuses on airway management. However, the rule should be to encourage swallowing as soon as possible after surgery. A good nutritional status is necessary for a positive prognosis in swallowing disorders. Team effort in tertiary oncology units is the key in supporting such complex cases.",book:{id:"7844",slug:"voice-and-swallowing-disorders",title:"Voice and Swallowing Disorders",fullTitle:"Voice and Swallowing Disorders"},signatures:"Daniela Vrinceanu and Mihai Dumitru",authors:null}],onlineFirstChaptersFilter:{topicId:"1098",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:87,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:98,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:27,numberOfPublishedChapters:287,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:9,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:139,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:0,numberOfUpcomingTopics:2,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!1},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:107,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:10,numberOfPublishedChapters:103,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:0,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!1},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:10,numberOfOpenTopics:4,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}}]},series:{item:{id:"11",title:"Biochemistry",doi:"10.5772/intechopen.72877",issn:"2632-0983",scope:"Biochemistry, the study of chemical transformations occurring within living organisms, impacts all areas of life sciences, from molecular crystallography and genetics to ecology, medicine, and population biology. Biochemistry examines macromolecules - proteins, nucleic acids, carbohydrates, and lipids – and their building blocks, structures, functions, and interactions. Much of biochemistry is devoted to enzymes, proteins that catalyze chemical reactions, enzyme structures, mechanisms of action and their roles within cells. Biochemistry also studies small signaling molecules, coenzymes, inhibitors, vitamins, and hormones, which play roles in life processes. Biochemical experimentation, besides coopting classical chemistry methods, e.g., chromatography, adopted new techniques, e.g., X-ray diffraction, electron microscopy, NMR, radioisotopes, and developed sophisticated microbial genetic tools, e.g., auxotroph mutants and their revertants, fermentation, etc. More recently, biochemistry embraced the ‘big data’ omics systems. Initial biochemical studies have been exclusively analytic: dissecting, purifying, and examining individual components of a biological system; in the apt words of Efraim Racker (1913 –1991), “Don’t waste clean thinking on dirty enzymes.” Today, however, biochemistry is becoming more agglomerative and comprehensive, setting out to integrate and describe entirely particular biological systems. The ‘big data’ metabolomics can define the complement of small molecules, e.g., in a soil or biofilm sample; proteomics can distinguish all the comprising proteins, e.g., serum; metagenomics can identify all the genes in a complex environment, e.g., the bovine rumen. 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Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. He has published more than 100 peer-reviewed research articles and graduated numerous Ph.D. and postdoctoral students.",institutionString:null,institution:{name:"New York University Langone Medical Center",institutionURL:null,country:{name:"United States of America"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:3,paginationItems:[{id:"7",title:"Bioinformatics and Medical Informatics",coverUrl:"https://cdn.intechopen.com/series_topics/covers/7.jpg",isOpenForSubmission:!0,editor:{id:"351533",title:"Dr.",name:"Slawomir",middleName:null,surname:"Wilczynski",slug:"slawomir-wilczynski",fullName:"Slawomir Wilczynski",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035U1loQAC/Profile_Picture_1630074514792",biography:"Professor Sławomir Wilczyński, Head of the Chair of Department of Basic Biomedical Sciences, Faculty of Pharmaceutical Sciences, Medical University of Silesia in Katowice, Poland. His research interests are focused on modern imaging methods used in medicine and pharmacy, including in particular hyperspectral imaging, dynamic thermovision analysis, high-resolution ultrasound, as well as other techniques such as EPR, NMR and hemispheric directional reflectance. Author of over 100 scientific works, patents and industrial designs. Expert of the Polish National Center for Research and Development, Member of the Investment Committee in the Bridge Alfa NCBiR program, expert of the Polish Ministry of Funds and Regional Policy, Polish Medical Research Agency. Editor-in-chief of the journal in the field of aesthetic medicine and dermatology - Aesthetica.",institutionString:null,institution:{name:"Medical University of Silesia",institutionURL:null,country:{name:"Poland"}}},editorTwo:null,editorThree:null},{id:"8",title:"Bioinspired Technology and Biomechanics",coverUrl:"https://cdn.intechopen.com/series_topics/covers/8.jpg",isOpenForSubmission:!0,editor:{id:"144937",title:"Prof.",name:"Adriano",middleName:"De Oliveira",surname:"Andrade",slug:"adriano-andrade",fullName:"Adriano Andrade",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRC8QQAW/Profile_Picture_1625219101815",biography:"Dr. Adriano de Oliveira Andrade graduated in Electrical Engineering at the Federal University of Goiás (Brazil) in 1997. He received his MSc and PhD in Biomedical Engineering respectively from the Federal University of Uberlândia (UFU, Brazil) in 2000 and from the University of Reading (UK) in 2005. He completed a one-year Post-Doctoral Fellowship awarded by the DFAIT (Foreign Affairs and International Trade Canada) at the Institute of Biomedical Engineering of the University of New Brunswick (Canada) in 2010. Currently, he is Professor in the Faculty of Electrical Engineering (UFU). He has authored and co-authored more than 200 peer-reviewed publications in Biomedical Engineering. He has been a researcher of The National Council for Scientific and Technological Development (CNPq-Brazil) since 2009. He has served as an ad-hoc consultant for CNPq, CAPES (Coordination for the Improvement of Higher Education Personnel), FINEP (Brazilian Innovation Agency), and other funding bodies on several occasions. He was the Secretary of the Brazilian Society of Biomedical Engineering (SBEB) from 2015 to 2016, President of SBEB (2017-2018) and Vice-President of SBEB (2019-2020). He was the head of the undergraduate program in Biomedical Engineering of the Federal University of Uberlândia (2015 - June/2019) and the head of the Centre for Innovation and Technology Assessment in Health (NIATS/UFU) since 2010. He is the head of the Postgraduate Program in Biomedical Engineering (UFU, July/2019 - to date). He was the secretary of the Parkinson's Disease Association of Uberlândia (2018-2019). Dr. Andrade's primary area of research is focused towards getting information from the neuromuscular system to understand its strategies of organization, adaptation and controlling in the context of motor neuron diseases. His research interests include Biomedical Signal Processing and Modelling, Assistive Technology, Rehabilitation Engineering, Neuroengineering and Parkinson's Disease.",institutionString:null,institution:{name:"Federal University of Uberlândia",institutionURL:null,country:{name:"Brazil"}}},editorTwo:null,editorThree:null},{id:"9",title:"Biotechnology - Biosensors, Biomaterials and Tissue Engineering",coverUrl:"https://cdn.intechopen.com/series_topics/covers/9.jpg",isOpenForSubmission:!0,editor:{id:"126286",title:"Dr.",name:"Luis",middleName:"Jesús",surname:"Villarreal-Gómez",slug:"luis-villarreal-gomez",fullName:"Luis Villarreal-Gómez",profilePictureURL:"https://mts.intechopen.com/storage/users/126286/images/system/126286.jpg",biography:"Dr. Luis Villarreal is a research professor from the Facultad de Ciencias de la Ingeniería y Tecnología, Universidad Autónoma de Baja California, Tijuana, Baja California, México. Dr. Villarreal is the editor in chief and founder of the Revista de Ciencias Tecnológicas (RECIT) (https://recit.uabc.mx/) and is a member of several editorial and reviewer boards for numerous international journals. He has published more than thirty international papers and reviewed more than ninety-two manuscripts. His research interests include biomaterials, nanomaterials, bioengineering, biosensors, drug delivery systems, and tissue engineering.",institutionString:null,institution:{name:"Autonomous University of Baja California",institutionURL:null,country:{name:"Mexico"}}},editorTwo:null,editorThree:null}]},overviewPageOFChapters:{paginationCount:17,paginationItems:[{id:"81751",title:"NanoBioSensors: From Electrochemical Sensors Improvement to Theranostic Applications",doi:"10.5772/intechopen.102552",signatures:"Anielle C.A. Silva, Eliete A. Alvin, Lais S. de Jesus, Caio C.L. de França, Marílya P.G. da Silva, Samaysa L. Lins, Diógenes Meneses, Marcela R. Lemes, Rhanoica O. 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