Averages of the Lactobacilli and Bifidobacteria log numbers, in babies born by cesarean section and vaginally delivery, fed with pasteurized milk from human milk banks (HMB), formula (FM) and breast milk (BM).
\\n\\n
These books synthesize perspectives of renowned scientists from the world’s most prestigious institutions - from Fukushima Renewable Energy Institute in Japan to Stanford University in the United States, including Columbia University (US), University of Sidney (AU), University of Miami (USA), Cardiff University (UK), and many others.
\\n\\nThis collaboration embodied the true essence of Open Access by simplifying the approach to OA publishing for Academic editors and authors who contributed their research and allowed the new research to be made available free and open to anyone anywhere in the world.
\\n\\nTo celebrate the 50 books published, we have gathered them at one location - just one click away, so that you can easily browse the subjects of your interest, download the content directly, share it or read online.
\\n\\n\\n\\n\\n"}]',published:!0,mainMedia:null},components:[{type:"htmlEditorComponent",content:'
IntechOpen and Knowledge Unlatched formed a partnership to support researchers working in engineering sciences by enabling an easier approach to publishing Open Access content. Using the Knowledge Unlatched crowdfunding model to raise the publishing costs through libraries around the world, Open Access Publishing Fee (OAPF) was not required from the authors.
\n\nInitially, the partnership supported engineering research, but it soon grew to include physical and life sciences, attracting more researchers to the advantages of Open Access publishing.
\n\n\n\nThese books synthesize perspectives of renowned scientists from the world’s most prestigious institutions - from Fukushima Renewable Energy Institute in Japan to Stanford University in the United States, including Columbia University (US), University of Sidney (AU), University of Miami (USA), Cardiff University (UK), and many others.
\n\nThis collaboration embodied the true essence of Open Access by simplifying the approach to OA publishing for Academic editors and authors who contributed their research and allowed the new research to be made available free and open to anyone anywhere in the world.
\n\nTo celebrate the 50 books published, we have gathered them at one location - just one click away, so that you can easily browse the subjects of your interest, download the content directly, share it or read online.
\n\n\n\n\n'}],latestNews:[{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"},{slug:"intechopen-identified-as-one-of-the-most-significant-contributor-to-oa-book-growth-in-doab-20210809",title:"IntechOpen Identified as One of the Most Significant Contributors to OA Book Growth in DOAB"}]},book:{item:{type:"book",id:"5099",leadTitle:null,fullTitle:"Advances in Microfluidics - New Applications in Biology, Energy, and Materials Sciences",title:"Advances in Microfluidics",subtitle:"New Applications in Biology, Energy, and Materials Sciences",reviewType:"peer-reviewed",abstract:"Increasing innovations and applications make microfluidics a versatile choice for researchers in many disciplines. This book consists of multiple review chapters that aim to cover recent advances and new applications of microfluidics in biology, electronics, energy, and materials sciences. It provides comprehensive views of various aspects of microfluidics ranging from fundamentals of fabrication, flow control, and droplet manipulation to the most recent exploration in emerging areas such as material synthesis, imaging and novel spectroscopy, and marriage with electronics. The chapters have many illustrations showcasing exciting results. This book should be useful for those who are eager to learn more about microfluidics as well as researchers who want to pick up new concepts and developments in this fast-growing field.",isbn:"978-953-51-2786-4",printIsbn:"978-953-51-2785-7",pdfIsbn:"978-953-51-4147-1",doi:"10.5772/60788",price:139,priceEur:155,priceUsd:179,slug:"advances-in-microfluidics-new-applications-in-biology-energy-and-materials-sciences",numberOfPages:422,isOpenForSubmission:!1,isInWos:1,isInBkci:!0,hash:"bd857fbb862f64969eb6ba55b35f5ff4",bookSignature:"Xiao-Ying Yu",publishedDate:"November 23rd 2016",coverURL:"https://cdn.intechopen.com/books/images_new/5099.jpg",numberOfDownloads:34639,numberOfWosCitations:52,numberOfCrossrefCitations:19,numberOfCrossrefCitationsByBook:2,numberOfDimensionsCitations:51,numberOfDimensionsCitationsByBook:3,hasAltmetrics:1,numberOfTotalCitations:122,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"May 11th 2015",dateEndSecondStepPublish:"June 1st 2015",dateEndThirdStepPublish:"September 5th 2015",dateEndFourthStepPublish:"December 4th 2015",dateEndFifthStepPublish:"January 3rd 2016",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,7,8",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"24996",title:"Dr.",name:"Xiao-Ying",middleName:null,surname:"Yu",slug:"xiao-ying-yu",fullName:"Xiao-Ying Yu",profilePictureURL:"https://mts.intechopen.com/storage/users/24996/images/system/24996.jpg",biography:"Dr. Yu was trained as a physical chemist and kineticist at the University of Michigan, Ann Arbor, Michigan, USA. She did her postdoctoral research at Brookhaven National Laboratory and Colorado State University, USA. She has been a senior scientist at Pacific Northwest National Laboratory since 2006. She has led the development of a novel mesoscale imaging tool based on microfluidics at PNNL since 2009, which has resulted in two issued patents, a prestigious R&D 100 Awards, and a Federal Laboratory Consortium Technology Transfer Excellence Award. Dr. Yu has developed new concepts in aerosol sampling and led and participated in many field studies for in situ measurements of aerosols. Dr. Yu is the chair of the Department of Energy chemical exposure working group and a member of the TEEL Advisory Group for consequence assessment.",institutionString:"Pacific Northwest National Laboratory",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"2",institution:null}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"697",title:"Microfluidics",slug:"microfluidics"}],chapters:[{id:"52333",title:"Advances in Low Volume Sample Analysis Using Microfluidic Separation Techniques",doi:"10.5772/64952",slug:"advances-in-low-volume-sample-analysis-using-microfluidic-separation-techniques",totalDownloads:1733,totalCrossrefCites:3,totalDimensionsCites:3,hasAltmetrics:1,abstract:"During the last decades, a great interest has been shown for miniaturised separation techniques. The use of microfluidic techniques fulfills the constant needs for increasing sample throughput and analysis sensitivity, while reducing costs and sample volume consumption. In this chapter, three microfluidic separation techniques will be addressed: capillary electrophoresis, gas chromatography and liquid chromatography. A special attention will be paid to miniaturised liquid chromatography, with a deep investigation of its advantages compared with classical liquid chromatography. Sample preparation adapted to low volumes (a few µl) will also be discussed.",signatures:"Virginie Houbart and Marianne Fillet",downloadPdfUrl:"/chapter/pdf-download/52333",previewPdfUrl:"/chapter/pdf-preview/52333",authors:[{id:"177056",title:"Prof.",name:"Marianne",surname:"Fillet",slug:"marianne-fillet",fullName:"Marianne Fillet"}],corrections:null},{id:"52462",title:"Molecular Microfluidic Bioanalysis: Recent Progress in Preconcentration, Separation, and Detection",doi:"10.5772/65772",slug:"molecular-microfluidic-bioanalysis-recent-progress-in-preconcentration-separation-and-detection",totalDownloads:1717,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"This chapter reviews the state-of-art of microfluidic devices for molecular bioanalysis with a focus on the key functionalities that have to be successfully integrated, such as preconcentration, separation, signal amplification, and detection. The first part focuses on both passive and electrophoretic separation/sorting methods, whereas the second part is devoted to miniaturized biosensors that are integrated in the last stage of the fluidic device.",signatures:"Emmanuel Roy, Antoine Pallandre, Bacem Zribi, Marie-Charlotte\nHorny, François-Damien Delapierre, Andrea Cattoni, Jean Gamby\nand Anne-Marie Haghiri-Gosnet",downloadPdfUrl:"/chapter/pdf-download/52462",previewPdfUrl:"/chapter/pdf-preview/52462",authors:[{id:"45172",title:"Prof.",name:"Anne-Marie",surname:"Haghiri-Gosnet",slug:"anne-marie-haghiri-gosnet",fullName:"Anne-Marie Haghiri-Gosnet"}],corrections:null},{id:"51878",title:"Application of Microfluidics in Stem Cell Culture",doi:"10.5772/64714",slug:"application-of-microfluidics-in-stem-cell-culture",totalDownloads:2178,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:0,abstract:"In this chapter, we review the recent developments, including our studies on the microfabricated devices applicable to stem cell culture. We will focus on the application of pluripotent stem cells including embryonic stem cells and induced pluripotent stem cells. In the first section, we provide a background on microfluidic devices, including their fabrication technology, characteristics, and the advantages of their application in stem cell culture. The second section outlines the use of micropatterning technology in stem cell culture. The use of microwell array technology in stem cell culture is explored in the third section. In the fourth section, we discuss the use of the microfluidic perfusion culture system for stem cell culture, and the last section is a summary of the current state of the art and perspectives of microfluidic technologies in stem cell culture.",signatures:"Shinji Sugiura, Kohji Nakazawa, Toshiyuki Kanamori and Kiyoshi\nOhnuma",downloadPdfUrl:"/chapter/pdf-download/51878",previewPdfUrl:"/chapter/pdf-preview/51878",authors:[{id:"83549",title:"Dr.",name:"Kiyoshi",surname:"Ohnuma",slug:"kiyoshi-ohnuma",fullName:"Kiyoshi Ohnuma"},{id:"177083",title:"Dr.",name:"Shinji",surname:"Sugiura",slug:"shinji-sugiura",fullName:"Shinji Sugiura"},{id:"177084",title:"Prof.",name:"Kohji",surname:"Nakazawa",slug:"kohji-nakazawa",fullName:"Kohji Nakazawa"},{id:"177085",title:"Dr.",name:"Toshiyuki",surname:"Kanamori",slug:"toshiyuki-kanamori",fullName:"Toshiyuki Kanamori"}],corrections:null},{id:"51261",title:"Advanced Microfluidic Assays for Caenorhabditis elegans",doi:"10.5772/64283",slug:"advanced-microfluidic-assays-for-caenorhabditis-elegans",totalDownloads:2183,totalCrossrefCites:1,totalDimensionsCites:4,hasAltmetrics:1,abstract:"The in vivo analysis of a model organism, such as the nematode Caenorhabditis elegans, enables fundamental biomedical studies, including development, genetics, and neurobiology. In recent years, microfluidics technology has emerged as an attractive and enabling tool for the study of the multicellular organism. Advances in the application of microfluidics to C. elegans assays facilitate the manipulation of nematodes in high-throughput format and allow for the precise spatial and temporal control of their environment. In this chapter, we aim to illustrate the current microfluidic approaches for the investigation of behavior and neurobiology in C. elegans and discuss the trends of future development.",signatures:"Natalia A. Bakhtina, Neil MacKinnon and Jan G. Korvink",downloadPdfUrl:"/chapter/pdf-download/51261",previewPdfUrl:"/chapter/pdf-preview/51261",authors:[{id:"176973",title:"Ph.D. Student",name:"Natalia",surname:"Bakhtina",slug:"natalia-bakhtina",fullName:"Natalia Bakhtina"},{id:"177026",title:"Dr.",name:"Neil",surname:"MacKinnon",slug:"neil-mackinnon",fullName:"Neil MacKinnon"},{id:"177027",title:"Prof.",name:"Jan",surname:"Korvink",slug:"jan-korvink",fullName:"Jan Korvink"}],corrections:null},{id:"51292",title:"Microfluidics for Ultrafast Spectroscopy",doi:"10.5772/64428",slug:"microfluidics-for-ultrafast-spectroscopy",totalDownloads:1861,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Ultrafast laser technologies became one of the essential tool in the characterization of molecular compounds. Being comprised of spectroscopists, laser scientists, chemists and biologists, the “ultrafast community” is often disconnected and consequently unaware of the developments in microfluidic systems. The challenges of studying limited amount of precious liquid sample by means of ultrafast spectroscopy remains silent and, while no commercial systems are available, each research group is developing its own “home-made” options. This chapter will therefore contribute in filling up the gap that exist between the two communities, that of the ultrafast spectroscopy and that of microfluidics by revealing the importance of this analytical tool as well as the advantages of applying microfluidic technics to it. In this goal, the chapter will focus of the recently developed microfluidic flow-cell. With a minimal volume of about 250 µL, the flow-cell enables the study of precious protein complexes that are simply not available in larger quantities. The multiple advantages of the microfluidic flow-cell will be illustrated by the analysis of the cytochrome bc1. In particular, the study will describe how the capabilities of the microfluidic flow-cell enabled the resolution of the ultrafast electronic and nuclear dynamics of specific embedded chromophores.",signatures:"Adrien A. P. Chauvet",downloadPdfUrl:"/chapter/pdf-download/51292",previewPdfUrl:"/chapter/pdf-preview/51292",authors:[{id:"177016",title:"Dr.",name:"Adrien",surname:"Chauvet",slug:"adrien-chauvet",fullName:"Adrien Chauvet"}],corrections:null},{id:"52463",title:"Flow-Scanning Microfluidic Imaging",doi:"10.5772/64707",slug:"flow-scanning-microfluidic-imaging",totalDownloads:1721,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The advantages of microfluidics for fast analysis of microscopic suspensions have led to the commercial development of flow cytometers. In this chapter, we propose new microscopy methods that combine controlled motion of micro-organisms in a laminar microfluidic flow, optics, and computation. We propose three new imaging modalities. We first introduce a flow-based version of structured illumination microscopy, where the necessary phase shifts are no longer obtained by controlled displacement of the illumination pattern but by flowing the sample itself. Then, we propose a three-dimensional (3D) deconvolution microscopy method with a microfluidic device for continuous acquisition of gradually defocused images. Finally, we introduce a microfluidic device for phase-space image acquisition, and computational methods for the reconstruction of either phase of intensity, in 3D. The imaging modalities we introduce all retain the benefits of fluid systems for noninvasive bioimaging. The proposed devices can easily be integrated on existing microscopes as a modified microscope slide, or on flow cytometers, and aquatic imagers with minor adjustments. Alternative on-chip implementations are also possible, with lens-free devices, and near-field optical and microfluidic elements directly assembled on the surface of a CCD (Charge-Coupled Device) or CMOS (Complementary metal–oxide–semiconductor) chip.",signatures:"Nicolas Pégard, Chien-Hung Lu, Marton Toth, Monica Driscoll and\nJason Fleischer",downloadPdfUrl:"/chapter/pdf-download/52463",previewPdfUrl:"/chapter/pdf-preview/52463",authors:[{id:"177068",title:"Mr.",name:"Jason",surname:"Fleischer",slug:"jason-fleischer",fullName:"Jason Fleischer"},{id:"177174",title:"Dr.",name:"Nicolas",surname:"Pegard",slug:"nicolas-pegard",fullName:"Nicolas Pegard"},{id:"177175",title:"Dr.",name:"Marton",surname:"Toth",slug:"marton-toth",fullName:"Marton Toth"},{id:"177176",title:"Prof.",name:"Monica",surname:"Driscoll",slug:"monica-driscoll",fullName:"Monica Driscoll"},{id:"177177",title:"Mr.",name:"Chien-Hung",surname:"Lu",slug:"chien-hung-lu",fullName:"Chien-Hung Lu"}],corrections:null},{id:"51594",title:"Integrated Control of Microfluidics – Application in Fluid Routing, Sensor Synchronization, and Real-Time Feedback Control",doi:"10.5772/64429",slug:"integrated-control-of-microfluidics-application-in-fluid-routing-sensor-synchronization-and-real-tim",totalDownloads:1923,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:1,abstract:"Microfluidic applications range from combinatorial chemical synthesis to high-throughput screening, with platforms integrating analog perfusion components, digitally controlled microvalves, and a range of sensors that demand a variety of communication protocols. A comprehensive solution for microfluidic control has to support an arbitrary combination of microfluidic components and to meet the demand for easy-to-operate system as it arises from the growing community of unspecialized microfluidics users. It should also be an easy to modify and extendable platform, which offer an adequate computational resources, preferably without a need for a local computer terminal for increased mobility. Here we will describe several implementation of microfluidics control technologies and propose a microprocessor-based unit that unifies them. Integrated control can streamline the generation process of complex perfusion sequences required for sensor-integrated microfluidic platforms that demand iterative operation procedures such as calibration, sensing, data acquisition, and decision making. It also enables the implementation of intricate optimization protocols, which often require significant computational resources. System integration is an imperative developmental milestone for the field of microfluidics, both in terms of the scalability of increasingly complex platforms that still lack standardization, and the incorporation and adoption of emerging technologies in biomedical research. Here we describe a modular integration and synchronization of a complex multicomponent microfluidic platform.",signatures:"Elishai Ezra, Danny Bavli and Yaakov Nahmias",downloadPdfUrl:"/chapter/pdf-download/51594",previewPdfUrl:"/chapter/pdf-preview/51594",authors:[{id:"176924",title:"Prof.",name:"Yaakov",surname:"Nahmias",slug:"yaakov-nahmias",fullName:"Yaakov Nahmias"},{id:"176930",title:"Dr.",name:"Elishai",surname:"Ezra Tsur",slug:"elishai-ezra-tsur",fullName:"Elishai Ezra Tsur"},{id:"176931",title:"Dr.",name:"Danny",surname:"Bavli",slug:"danny-bavli",fullName:"Danny Bavli"}],corrections:null},{id:"51293",title:"Microfluidics for Soft Electronics",doi:"10.5772/63376",slug:"microfluidics-for-soft-electronics",totalDownloads:1860,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Microfluidics- based soft electronic systems have the potential to assist conventional rigid devices and circuits to achieve extreme levels of elasticity in wearable electronics and other applications. The goal of employing microfluidics-based approach among other existing methods is to enhance users comfort through fulfillment of wearable’s mechanical performance requirements such as flexibility, twistability, and stretchability. This chapter presents a brief survey of different solutions for developing elastic electronics and a thorough review of the progress in microfluidics-based approaches. This chapter mainly focuses on the description of the fabrication process, design, and measurement steps of different antennas and complex systems realized using microfluidic interconnects.",signatures:"Babak Taghavi, Jiantong Li, Mikael Östling and Shi Cheng",downloadPdfUrl:"/chapter/pdf-download/51293",previewPdfUrl:"/chapter/pdf-preview/51293",authors:[{id:"176954",title:"Ph.D. Student",name:"Babak",surname:"Taghavi",slug:"babak-taghavi",fullName:"Babak Taghavi"},{id:"177061",title:"Dr.",name:"Jiantong",surname:"Li",slug:"jiantong-li",fullName:"Jiantong Li"},{id:"177062",title:"Prof.",name:"Mikael",surname:"Östling",slug:"mikael-ostling",fullName:"Mikael Östling"},{id:"177063",title:"Dr.",name:"Shi",surname:"Cheng",slug:"shi-cheng",fullName:"Shi Cheng"}],corrections:null},{id:"51462",title:"Microfluidic Sensors and Circuits for Internet of Things Applications",doi:"10.5772/64346",slug:"microfluidic-sensors-and-circuits-for-internet-of-things-applications",totalDownloads:1900,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"As we move into the Internet of Things (IoT) and cloud computing era, the number of sensors deployed which seamlessly integrate themselves into environment is growing rapidly. These sensors should be minimally intrusive, both optically and mechanically, while providing high temporal and spatial contextual awareness of its environment. In this chapter, microfluidic sensors and circuits are presented to better bridge the physical and digital world for healthcare applications. Specifically, a discussion of cardiovascular sensing, glaucoma diagnosis and flexible tactile sensor arrays for smart skin application is presented.",signatures:"John Yan",downloadPdfUrl:"/chapter/pdf-download/51462",previewPdfUrl:"/chapter/pdf-preview/51462",authors:[{id:"177003",title:"Ph.D.",name:"John",surname:"Yan",slug:"john-yan",fullName:"John Yan"}],corrections:null},{id:"51262",title:"Electroosmotic Flow Pump",doi:"10.5772/64601",slug:"electroosmotic-flow-pump",totalDownloads:2494,totalCrossrefCites:0,totalDimensionsCites:4,hasAltmetrics:1,abstract:"Electroosmotic flow (EOF) pumping has been widely used to manipulate fluids such as liquid sample reagents in microfluidic systems. In this chapter, we will introduce the research progress on EOF pumps in the fields of microfluidic science and technology and briefly present their microfluidic applications in recent years. The chapter focuses on pump channel materials, electrodes, and their fabrication techniques in microfluidics.",signatures:"Meng Gao and Lin Gui",downloadPdfUrl:"/chapter/pdf-download/51262",previewPdfUrl:"/chapter/pdf-preview/51262",authors:[{id:"176994",title:"Prof.",name:"Lin",surname:"Gui",slug:"lin-gui",fullName:"Lin Gui"},{id:"177064",title:"Ph.D.",name:"Meng",surname:"Gao",slug:"meng-gao",fullName:"Meng Gao"}],corrections:null},{id:"51712",title:"Laser-Based Fabrication for Microfluidics Devices on Glass for Medical Applications",doi:"10.5772/64324",slug:"laser-based-fabrication-for-microfluidics-devices-on-glass-for-medical-applications",totalDownloads:1646,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:0,abstract:"We report a laser-based process for microstructuring glass materials for microfluidics applications. The hybrid technique is composed of a nanosecond Q-Switch Nd:YVO4 laser for fabricating the initial microfluidic microstructures on soda-lime glass substrates and a thermal treatment for reshaping and improving its morphological and optical qualities. The proposed technique preserves the advantages of the laser direct-write technique in terms of design flexibility, simplicity, fast prototyping, low cost, and so on. The beam spot size, pulse overlapping, ablation threshold, debris deposition, heating temperature, and time are investigated and optimized for fabricating optimal microfluidics structures on glass. The manufactured chips for circulating tumor cells (CTCs) capture were tested with tumor cells (Hec 1A) after being functionalized with an EpCAM antibody coating. Cells were successfully arrested on the pillars after being flown through the device giving our technology a translational application in the field of cancer research.",signatures:"Daniel Nieto García and Gerard O’Connor",downloadPdfUrl:"/chapter/pdf-download/51712",previewPdfUrl:"/chapter/pdf-preview/51712",authors:[{id:"176988",title:"Dr.",name:"Daniel",surname:"Nieto",slug:"daniel-nieto",fullName:"Daniel Nieto"},{id:"177787",title:"Prof.",name:"Gerard",surname:"O'Connor",slug:"gerard-o'connor",fullName:"Gerard O'Connor"}],corrections:null},{id:"52232",title:"Microfluidics in Membraneless Fuel Cells",doi:"10.5772/64448",slug:"microfluidics-in-membraneless-fuel-cells",totalDownloads:2102,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"In the 1990s, the idea of developing miniaturized devices that integrate functions other than what normally are carried out at the laboratory level was conceived, and the so-called “lab-on-a-chip” (LOC) devices emerged as one of the most important research areas. LOC devices exhibit advantages related to the use of microfluidic channels such as small sample and reagent consumption, portability, low-power consumption, laminar flow, and higher surface area/volume ratio that enhances both thermal dissipation and electrochemical kinetics. Fuel cells are electrochemical devices that convert chemical energy to electrical energy. These are considered as one of the greener ways to generate electricity because typical fuel cells produce water and heat as the main reaction byproducts. The technical challenges to develop systems at the microscale and the advantages of microfluidics exhibited an important impact on fuel cells for several reasons, mainly related to avoid inherent problems of gaseous-based fuel cells. As a result, the birth of a new type of fuel cells as microfluidic fuel cells (MFCs) took place. The first microfluidic fuel cell was reported in 2002. This MFC was operated with liquid fuel/oxidant and had the advantage of the low laminar flow generated using a “Y” microfluidic channel to separate the anodic and cathodic streams, resulting in an energy conversion device that did not require a physical barrier to separate both streams. This electrochemical system originated a specific type of MFCs categorized as membraneless also called colaminar microfluidic fuel cells. Since that year, numerous works focused on the nature of fuels, oxidants and anodic/cathodic electrocatalysts, and cell designs have been reported. The limiting parameters of this kind of devices toward their use in portable applications are related to their low cell performances, small mass activity, and partial selectivity/durability of electrocatalysts. On the other hand, it has been observed that the cell design has a high effect on the cell performance due to internal cell resistances and the crossover effect. Furthermore, current technology is growing faster than last centuries and new microfabrication technologies are always emerging, allowing the development of smaller and more powerful microfluidic energy devices. In this chapter, the application of microfluidics in membraneless fuel cells is addressed in terms of evolution of cell designs of miniaturized microfluidic fuel cells as a result of new discoveries in microfabrication technology and the use of several fuels and electrocatalysts for specific and selective applications.",signatures:"Jesus A. Diaz-Real, Minerva Guerra-Balcázar, Noe Arjona, Francisco\nCuevas-Muñiz, Luis Gerardo Arriaga and Janet Ledesma-García",downloadPdfUrl:"/chapter/pdf-download/52232",previewPdfUrl:"/chapter/pdf-preview/52232",authors:[{id:"23083",title:"Dr.",name:"Luis Gerardo",surname:"Arriaga",slug:"luis-gerardo-arriaga",fullName:"Luis Gerardo Arriaga"},{id:"176367",title:"Dr.",name:"Janet",surname:"Ledesma-García",slug:"janet-ledesma-garcia",fullName:"Janet Ledesma-García"},{id:"177828",title:"Dr.",name:"Noe",surname:"Arjona",slug:"noe-arjona",fullName:"Noe Arjona"},{id:"177829",title:"MSc.",name:"Jesus A.",surname:"Díaz-Real",slug:"jesus-a.-diaz-real",fullName:"Jesus A. Díaz-Real"},{id:"177830",title:"Dr.",name:"Francisco",surname:"Cuevas-Muñiz",slug:"francisco-cuevas-muniz",fullName:"Francisco Cuevas-Muñiz"},{id:"177831",title:"Dr.",name:"Minerva",surname:"Guerra-Balcázar",slug:"minerva-guerra-balcazar",fullName:"Minerva Guerra-Balcázar"}],corrections:null},{id:"51264",title:"Microfluidics in CO2 Capture, Sequestration, and Applications",doi:"10.5772/64284",slug:"microfluidics-in-co2-capture-sequestration-and-applications",totalDownloads:1991,totalCrossrefCites:5,totalDimensionsCites:7,hasAltmetrics:0,abstract:"The abnormal climate change has made the reduction of CO2 emission that received worldwide attention. The integration of CO2 capture-sequestration application for enhanced oil recovery (EOR) technology will be the new trend. Several scholars have applied microfluidics in CO2 capture, oil and gas analysis, and CO2 sequestration. The mass transfer process for CO2 capture can be intensified owing to the large specific surface/volume ratio and high contact area in microchannels. The small amount of feeding volumes of oil and gas samples and the quick response for the analysis make the microfluidics a promising tool for the oil and gas analysis. Moreover, microfluidics can reveal the transport mechanism at microscale for multiphase interfacial phenomena in microchannels within porous media during the CO2 flooding process in line with the pressure, temperature, and material properties of the rock within the oil reservoir. This chapter will elaborate the progress of the application of microfluidic technology in the utilization of CO2, including the mechanism of mass transfer for CO2 in microreactors, the advantages of microfluidics in oil and gas analysis, and the fundamentals of microfluidics in CO2 flooding, oil recovery improvement, and CO2 sequestration.",signatures:"Taotao Fu",downloadPdfUrl:"/chapter/pdf-download/51264",previewPdfUrl:"/chapter/pdf-preview/51264",authors:[{id:"177065",title:"Associate Prof.",name:"Taotao",surname:"Fu",slug:"taotao-fu",fullName:"Taotao Fu"}],corrections:null},{id:"52334",title:"Generation and Evaporation of Microsprays",doi:"10.5772/64756",slug:"generation-and-evaporation-of-microsprays",totalDownloads:2099,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"This chapter aims to comprehensively review the techniques and features of micro-sprays for various applications via micro-droplet generators over decades, especially focusing on the past and present microfluidics. It is organized briefly as below. The background of current research and development about the micro-spray techniques is first introduced, followed by the generation and evaporation of spray detailed with the concentrated respects of critical requirements for materials and facilities. Then, we address the critical design issues of micro-sprayers such as the actuators and nozzles required to be satisfactory for generating a number of droplets. Subsequently, we further describe characterization of droplets in form of spray concerning droplet size, speed, rates, and patterns in microfluidics. Moreover, the chapter presents the proof-of-concept and commercial applications of the micro-spraying processes, highlighting their current technical progresses and future challenges, which shall be intimately related to the droplet generation and evaporation including droplet evaporative cooling, direct printing, screen printing, nano-material coating, liquid nebulization, and miscellaneous employment. Finally, we draw a conclusion in the end of the chapter.",signatures:"Chin-Tai Chen",downloadPdfUrl:"/chapter/pdf-download/52334",previewPdfUrl:"/chapter/pdf-preview/52334",authors:[{id:"65914",title:"Prof.",name:"Chin-Tai",surname:"Chen",slug:"chin-tai-chen",fullName:"Chin-Tai Chen"}],corrections:null},{id:"52959",title:"Overview of Materials for Microfluidic Applications",doi:"10.5772/65773",slug:"overview-of-materials-for-microfluidic-applications",totalDownloads:2542,totalCrossrefCites:1,totalDimensionsCites:10,hasAltmetrics:0,abstract:"For each material dedicated to microfluidic applications, inherent microfabrication and specific physico‐chemical properties are key concerns and play a dominating role in further microfluidic operability. From the first generation of inorganic glass, silicon and ceramics microfluidic devices materials, to diversely competitive polymers alternatives such as soft and rigid thermoset and thermoplastics materials, to finally various paper, biodegradable and hydrogel materials; this chapter will review their advantages and drawbacks regarding their microfabrication perspectives at both research and industrial scale. The chapter will also address, the evolution of the materials used for fabricating microfluidic chips, and will discuss the application‐oriented pros and cons regarding especially their critical strategies and properties for devices assembly and biocompatibility, as well their potential for downstream biochemical surface modification are presented.",signatures:"Emmanuel Roy, Antoine Pallandre, Bacem Zribi, Marie‐Charlotte\nHorny, François Damien Delapierre, Andrea Cattoni, Jean Gamby\nand Anne‐Marie Haghiri‐Gosnet",downloadPdfUrl:"/chapter/pdf-download/52959",previewPdfUrl:"/chapter/pdf-preview/52959",authors:[{id:"45172",title:"Prof.",name:"Anne-Marie",surname:"Haghiri-Gosnet",slug:"anne-marie-haghiri-gosnet",fullName:"Anne-Marie Haghiri-Gosnet"}],corrections:null},{id:"51463",title:"Synthesis of Functional Materials by Non-Newtonian Microfluidic Multiphase System",doi:"10.5772/64521",slug:"synthesis-of-functional-materials-by-non-newtonian-microfluidic-multiphase-system",totalDownloads:2068,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"With increasing level of polymer solution involvement in multiphase microdevice for formation of emulsion and fabrication of functional materials, it is of paramount importance to systematically understand the relevant physics of droplet formation in non-Newtonian fluids and how the material formation process may be affected due to the complex rheological effect. The chapter aims to review and discuss the recent advances in technologies that enable fabrication and application of functional materials formed from non-Newtonian microfluidic multiphase system. Rheological behavior of polymer solutions and the mathematical models are reviewed. The influence of microstructure on rheological behavior of polymer solutions and the fundamental physical phenomena driving non-Newtonian microfluidic multiphase system are discussed. Shear thinning and viscoelastic effect on breakup dynamics and droplet formation are presented. 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Their major outcomes, current progress in synthesis of micro and nanostructures by using microfluidics techniques and potential applications for the next future are reviewed throughout three different sections. Emphasis is placed on nanomaterials production basics, nanomaterials production techniques and microfluidic reactors (types, materials, designs). The integration of nanoparticle and microreactor technologies delivers enormous possibilities for the further development of novel materials and reactors. In this chapter, recent achievements in the synthesis of nanoparticles in microfluidic reactors are stated. 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Venkateswarlu",coverURL:"https://cdn.intechopen.com/books/images_new/371.jpg",editedByType:"Edited by",editors:[{id:"58592",title:"Dr.",name:"Arun",surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"72",title:"Ionic Liquids",subtitle:"Theory, Properties, New Approaches",isOpenForSubmission:!1,hash:"d94ffa3cfa10505e3b1d676d46fcd3f5",slug:"ionic-liquids-theory-properties-new-approaches",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/72.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"314",title:"Regenerative Medicine and Tissue Engineering",subtitle:"Cells and Biomaterials",isOpenForSubmission:!1,hash:"bb67e80e480c86bb8315458012d65686",slug:"regenerative-medicine-and-tissue-engineering-cells-and-biomaterials",bookSignature:"Daniel Eberli",coverURL:"https://cdn.intechopen.com/books/images_new/314.jpg",editedByType:"Edited by",editors:[{id:"6495",title:"Dr.",name:"Daniel",surname:"Eberli",slug:"daniel-eberli",fullName:"Daniel Eberli"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"57",title:"Physics and Applications of Graphene",subtitle:"Experiments",isOpenForSubmission:!1,hash:"0e6622a71cf4f02f45bfdd5691e1189a",slug:"physics-and-applications-of-graphene-experiments",bookSignature:"Sergey Mikhailov",coverURL:"https://cdn.intechopen.com/books/images_new/57.jpg",editedByType:"Edited by",editors:[{id:"16042",title:"Dr.",name:"Sergey",surname:"Mikhailov",slug:"sergey-mikhailov",fullName:"Sergey Mikhailov"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1373",title:"Ionic Liquids",subtitle:"Applications and Perspectives",isOpenForSubmission:!1,hash:"5e9ae5ae9167cde4b344e499a792c41c",slug:"ionic-liquids-applications-and-perspectives",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/1373.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"39608",title:"Microbial Interactions in the Gut: The Role of Bioactive Components in Milk and Honey",doi:"10.5772/50122",slug:"microbial-interactions-in-the-gut-the-role-of-bioactive-components-in-milk-and-honey",body:'The fact that living organisms play a key role on health, was put on a scientific basis at the beginning of the last century by Elie Metchinikoff, when working at the Pasteur Institute in Paris. The findings that Bulgarian peasants, who ingested large amounts of soured milks, also lived to a ripe old age led him to conclude about the beneficial effects of fermented milks.
One of the most convincing demonstrations of the role of the gut microbiota in resistance to disease was provided by Collins and Carter [1]. These authors proved that germ-free guinea–pig was killed by 10 cells of
Probiotic was initially defined by Parker [2] as “Organisms and substances which contributes to intestinal microbial balance”. Fuller [3] redefined probiotics as “A live microbial feed supplement which beneficially affects the host animal by improving its intestinal microbial balance”. This definition clarifies the need for a probiotic to be viable.
The term prebiotic was subsequently adopted to define “non-digestible food ingredients that beneficially affect the host by selectively stimulating the growth and/or activity of one or a limited number of bacteria in the colon that improve host health”[4] Modification by prebiotics of the composition of the colonic microbiota leads to the predominance of a few of the potentially health-promoting bacteria, especially, but not exclusively, lactobacilli and bifidobacteria. Much of the work on prebiotics deals with the use of oligosaccharides, although the first demonstration of this type of effect was observed with a disaccharide, lactulose. Gibson and Roberfroid [4] also launched the concept of symbiotic by combining the rationale of pro- and prebiotics, is proposed to characterize some colonic foods with interesting nutritional properties that make these compounds candidates for classification as health-enhancing functional food ingredients.
The bacterial genera most often used as probiotics are lactobacilli and bifidobacteria. At present, probiotics are almost exclusively consumed as fermented dairy products such as yogurt or freeze-dried cultures, but in the future they may also be found in fermented vegetables and meats [5].
The microbial community inhabiting the gastrointestinal tract is characterized by its high population density, wide diversity, and complexity of interactions. Bacteria are predominant but a variety of protozoans, yeasts and bacteriophages are also found. Bacteria are not distributed randomly throughout the gastrointestinal tract but instead are found at population levels and species distributions that are characteristic of specific regions of the tract. The stomach and proximal small intestine contain relatively low numbers of microorganisms. Acid- tolerant lactobacilli and streptocococci predominate in the upper smal intestine. The distal small intestine (ileum) maintains a more diverse microbiota and higher bacterial numbers. The large intestine (colon) is characterized by large numbers of bacteria, low redox potential, and relatively high short-chain fatty acid concentrations. The prominent role played by anaerobic bacteria in this dynamic ecosystem is evident from the finding that more than 99% of the bacteria isolated from human fecal specimens are anaerobic or aerotolerant [6].
The intestinal tract is a dynamic ecosystem that is influenced by host, intrinsic, and environmental factors. Thus, our undestanding of gut microbial interactions and how the gastrointestinal activity is modulated, might help on establishing screening criteria to identify potentially probiotic bacteria suitable for human or animal use.
The nature of the microbial interaction can be predominantly by competition or mutualism [7]. In the gut they can affect either the population level of a given strain or the metabolic activity of that strain. In addition, genetic transfers can occur between strains within the gut. The host and the diet cam modulate the expression of the microbial interactions. These interactions involve multiple mechanisms that are poorly understood. Such mechanisms are involved either in the size of subdominant microbial populations or in the metabolic activities of predominant populations. Diet and perhaps other environmental factors, such as stress, can modify their expression.
The gastrointestinal tract of neonates becomes colonized immediately after birth with environmental microorganisms, mainly from the mother by several processes including sucking, kissing, and caressing. The proximity of the birth canal and the anus, as well as parental expression of neonatal care, are effective methods of ensuring transmission of microbes from one generation to the next [6].The pattern and level of exposure during the neonatal period is likely to influence the microbial succession and colonization in the gastrointestinal tract. Infants from developing countries have an early colonization with enterobacteria whereas those born in countries with good obstetric and hygienic procedures, may result in a delayed development pattern or even the absence of certain groups of intestinal bacteria during succession [8].
After the birth process, neonates are continuously exposed to new microbes that enter the gastrointestinal tract with food. This begins with breast milk, which contains up to 106 microbes/mL in healthy mothers. The most frequently encountered bacterial groups include staphylococci, streptococci, corynebacteria, lactobacilli, micrococci, propionibacteria and bifidobacteria originated from the nipple and surrounding skin as well as the milk ducts in the breast [6, 9, 10].
A pronounced dominance of bifidobacteria was observed over the entire breast-feeding period, with a corresponding reduction in facultative bacteria [11, 12]. There is a strong evidence suggests that the early composition of the microbiota of neonates plays an important role for the postnatal development of the immune system [13, 14].
Both adults and neonates are regularly exposed to microorganisms via the diet, but are affected differently. The microorganisms entering newborns via milk are more likely to colonize than are those entering healthy adults [6, 15].
Bacterial species or strains that will be established in the infant bowel might be capable to utilize the substrates provided by the diet and the particular human host.
Protection against colonization of the intestinal tract by potentially pathogenic microorganisms, due to the gut microbiota, was called competitive exclusion [17], whose pioneering evidence had been obtained by Nurmi and Rantala [18], with birds. When these, soon after birth, were inoculated with cecal material of an adult bird, the frequency of Salmonella infections was significantly reduced.
Undoubtedly the main benefit attributed to probiotics is the competitive exclusion of pathogens that occurs by different mechanisms including: a) competition for receptors in the intestinal epithelium as occurs with lactobacilli that directly inhibits the binding of
Constituents of the normal microbiota and some pathogenic bacteria have the ability to colonize the mucosal surfaces [21] Some microorganisms seem to be able to securely attach to the intestinal epithelium [22], and is thought to be this an important prerequisite for probiotics in a long-term survival during competition against other microorganisms for specific niches and subsequent multiplication. However, no consensus among researchers exists about the fact that a probiotic should or should not adhere to mucosal surfaces, colonize and then exert a probiotic effect, being an alternative its regular consumption to maintain the levels needed to promote the effect, forming a transient microbiota [23].
Another desired effect of a probiotic includes altered metabolism of the intestinal microbiota as the reduction in the synthesis of toxins or carcinogenic substances or an increased production of short-chain fatty acids or other substances that improve the condition of the mucosa. Prebiotics may also be given to augment immune reaction, preferably those that have a protective effect without causing overt inflammation. The ability of lactic bacteria to inactivate mutagenic compounds, such as dyes and N-nitrosamines, has been attributed to cell wall components, such as peptidoglycan and polysaccharides [24].. The lactic acid bacteria also may mediate anticarcinogenic activities by reducing the activity of fecal bacterial enzymes such as nitroredutases, azoredutases and glucuronidase (EC 3.2.1.31) that convert procarcinogenic to carcinogenic compounds in the colon [14]
The ability to sense other bacteria may have important consequences for competitive and nutritional strategies controlling for example, entry into stationary phase, dispersal and the production of antimicrobial compounds. The ability to interfere with the signalling of bacteria will determine the fitness of the given organism to survive in the gut and may also have therapeutic potential. The study of cell-to-cell communication in gastrointestinal(GI) tract bacteria is not as advanced as it is for bacteria from other ecosystems. In Gram-negative bacteria the best-characterized systems involve
Probiotics may play an active role inflammatory bowel diseases by enhancing the intestinal barrier at the mucosal surface. Caballero-Franco et al. [26] investigated whether the clinically tested VSL#3 probiotic formula and/or its secreted components could augment the protective mucus layer in vivo and in vitro. For in vivo studies, Wistar rats were orally administered the probiotic mixture VSL#3 on a daily basis for seven days. After treatment, basal luminal mucin content increased by 60%. In contrast to the animal studies, cultured cells incubated with VSL#3 bacteria did not exhibit increased mucin secretion. However, the bacterial secreted products contained in the conditioned media stimulated a remarkable mucin secretion effect. Among the three bacterial groups (
The competitive exclusion of pathogens mediated by lactobacilli is usually performed by two mechanisms: (i) production of antimicrobial substances such as lactic acid and bacteriocins, and (ii) adhesion to the mucosa and coaggregation which can form a barrier which prevents colonization by pathogenic microorganisms [27].
Three mechanisms of aggregation have been reported so far. The first is related to the interaction between the components of the cell surface, as in the oral cavity with
Autoaggregation has been correlated with adhesion, which is known to be a prerequisite for colonization and infection of the gastrointestinal tract by many pathogens. Adherence to the epithelium is therefore a prerequisite for enterotoxigenic
Coaggregation is a process by which genetically distinct bacteria become attached to one another via specific molecules. Cumulative evidence suggests that such adhesion influences the development of complex multi-species biofilms. The coaggregation properties of probiotic strains with pathogens as well as their ability to displace pathogens are of importance for therapeutic manipulation of the aberrant intestinal microbiota. Aggregation abilities of a probiotic with the pathogen strains were strain-specific and dependent on time and incubation conditions [31]
Recently, the complement protein mannose-binding lectin (MBL) has been shown to play a role in the first line of defense against
In other cases, the adhesins are not lectins, such as in the case of
The second mechanism, described in lactobacilli, is dependent upon secretion of a protein of 32 kDa that promotes aggregation and a high frequency of conjugation [35] According to Collado, Meriluoto and Salminen [31] the ability to autoaggregate, together with cell-surface hydrophobicity and coaggregation abilities with pathogen strains can be used for preliminary screening in order to identify potentially probiotic bacteria suitable for human or animal use.
Finally, inMany components of human milk are multifunctional, providing antimicrobial, antiinflammatory, antioxidant effect besides being growth factors [40].
Breast milk not only provides a range of substrates for bacterial growth, but it also appears to be a reservoir for some of the bacteria we inherit, including Lactobacillus sp. and
Although it is likely that antimicrobial components in human milk inhibit the growth of pathogenic bacteria, it is also likely that some substances stimulate the growth of beneficial bacteria,
The gut microbiota of breastfed infants is different from that of formula-fed infants. According to Penders [43], exclusively formula-fed infants were more often colonized with
Oliveira [12] studied the influence of diet and type of delivery in 68 neonates aged between seven and 21 days on both composition and evolution of the gut
Oliveira [12] also found that bifidobacteria numbers in infants born vaginally and fed with breast milk (BM) were higher than the others, while those who received pasteurized human milk from milk banks (HMB) showed a significant lower number of
The same negative pasteurization effect was observed by Oliveira [12] on the growth of lactobacilli (Table 1). Although breast-milk contains viable lactobacilli and bifidobacteria that might contribute to the initial establishment of the microbiota in the newborn, the negative effect of human milk pasteurization on the lactobacilli and bifidobacteria gut population, cannot be explained solely on the destruction of those bacteria by the pasteurization process. Milk formulas do not contain these bacteria, but favored the development of bifidobacteria and lactobacilli in the intestine reaching a number significantly higher, as compared to the gut microbiota of pasteurized human milk fed infants.
Indeed, the health-promoting effects of breast-milk have been linked partly to the presence of lactobacilli and bifidobacteria in breast-milk [10, 47], but clearly also to different milk bifidogenic components.
Both lactotobacilli and bifidobacteria benefit in environments with low redox potential and the presence of antioxidant compounds present in human milk. Anti-oxidants such as lactoferrin, α-tocopherol, β carotene, cysteine, ascorbic acid, uric acid, catalase and glutathione peroxidase are present in human milk [40]. Most of these compounds are thermo-labile and might have been destroyed during milk pasteurization process. Whey protein is rich in
Cesarean | Vaginally | |
HMB | 2,4 a A | 3,3 b A |
FM | 2,8 a B | 5,7 a A |
BM | 3,8 a B | 5,6 a A |
HMB | 5,6 a A | 3,7 b A |
FM | 5,7 a A | 6,5 ab A |
BM | 6,2 a A | 7,4 a A |
Averages of the Lactobacilli and Bifidobacteria log numbers, in babies born by cesarean section and vaginally delivery, fed with pasteurized milk from human milk banks (HMB), formula (FM) and breast milk (BM).
For many years, the oligosaccharides were considered for his role in the modulation of intestinal microbiota of infants. Currently, there is strong evidence that free oligosaccharides as well as glycoproteins are potent inhibitors of bacterial adhesion on the surface of the epithelium in the early stages of the infectious process. Therefore, the milk oligosaccharides have two important functions. The first as a source prebiotic stimulating the growth of probiotic bacteria and a second, operating in a non-specific defense mechanism inhibiting pathogens from adhering to the gastrointestinal mucosa. Although the exact pathophysiological mechanism of diarrhea is not yet fully elucidated, it seems that the ability of microorganisms to adhere to the mucosal surface is essential for spreading diarrheagenic bacteria in the duodenum [50].
Concentrations of total oligosaccharides in human milk (HMO) is 5,0-8,0 g per liter whereas just traces are found in cow’s milk. In cow’s milk, only small amounts of oligosaccharides are detectable, with sialyllactose being the major component [51].
Differences in the qualitative or quantitative aspects of term and preterm milk have not been observed, but compositional changes of oligosaccharides in term milk occurs during lactation with the largest amounts being found at early stages. The highest concentrations of HMOs can be found in colostrum (20 g/L), but even mature milk contains oligosaccharides in concentrations up to 13 g/L [52]. Coppa [11] reported that lactose concentration (±SD) in human milk increased from 56 ± 6.06 g/L on day 4 to 68.9 ± 8.16 g/L on day 120. Oligosaccharide level decreased from 20.9 ± 4.81 g/L to 12.9 ± 3.30 gIL, respectively. Monosaccharides represented only 1.2% of total carbohydrates.
Although intact HMOs may be absorbed, ENGFER et al. [52] postulate that a majority of HOs reach the large intestine, where they serve as substrates for bacterial metabolism. Therefore, HMOs might be considered the soluble fiber fraction of human milk
Human milk compared with other milk species, is considered unique in terms of its complex oligosaccharides content. With few exceptions, HMOs have a core structure consisting of a lactose unit at the reducing end linked to
Within human milk oligosaccharides at least 10 containing GlcNAc are known as growth factors for a so-called bifidus biota in breastfed infants. Dietary modulation of the intestinal microflora is today one of the main topics of interest in the nutritional sciences. Fructo-oligosaccharides (FOS) and galacto-oligosaccharides (GOS) are prebiotics whose bifidogenic activity has been proven in adults. Moro and Arslanoglu [19] demonstrated that supplementation of infant formulas with a mixture of GOS and FOS modified the fecal flora of term and preterm infants, stimulating the growth of Bifidobacteria. In the trial with term infants, the bifidogenic effect of the prebiotic mixture was dose dependent and there was also a significant increase in the number of Lactobacilli in the supplemented group.
The similarities between epithelial cell surface carbohydrates and oligosaccharides in human milk strengthen the idea that specific interactions of those oligosaccharides with pathogenic microorganisms do occur preventing the attachment of microbes to epithelial cells. HMOs may act as soluble receptors for different pathogens, thus increasing the resistance of breast-fed infants. Some of the best-characterized adhesins of bacteria are those of
Rockova et al. [53] reported that two strains of
Whey proteins constitute about 60-80% of the total protein content of human milk, but only 18% of bovine milk. Furthermore, the composition of whey proteins is different for each of the milks: beta-lactoglobulin, that is not found in human milk, predominates in bovine milk, while alfalactalbumin and lactoferrin predominate in human milk. The alfalactalbumin is necessary for the synthesis of lactose in the mammary gland, through the action of the lactose synthetase enzyme, their concentration in human milk ranges from 0.22 to 0.46 g/dl. The betalactoglobulin has been blamed for allergies to bovine milk [54].
Undenatured whey protein is rich in
Whey proteins present in human milk, such as secretory IgA, lactoferrin and lysozyme are very stable in acid medium, and reasonably resistant the action of proteolytic enzymes, it is believed, therefore, that over three quarters of these proteins appear intact in the feces of infants. Approximately 6-10% of lactoferrin is not digested by the intestinal tract, assuming that it can reach the colon and play prebiotic activities [56]
Lactoferrin, a glyco-protein, is a major protein in human milk (1.3-2.8 g/L) while it is present only in traces in cow´s milk. Lactoferrin inhibits the growth of bacteria and fungi due to its ability to bind iron, a function known as
In addition, lactoferrin also promotes the growth of beneficial bacteria such as
Lysozyme is an antimicrobial enzyme (EC 3.2.1.17) found in tears, saliva, human milk whey, mucus, neutrophil granules and egg- white. It hydrolyses b (1,4) linkage between N acetylglucosamine and N-acetylmuramic acid in bacterial cell wall. Gram positive bacteria are more susceptible to lysozyme than Gram negative. The enzyme synergistically interacts with other immunoprotective components like IgA, C3 complement components and lactoferin. Human milk contains up to 400 mg/mL of lysozyme, which is a concentration approx. 3000 times higher than in bovine milk.[58]
Resistance to lysozyme and the ability to utilize human milk oligosaccharides (HMOs) were identified as the most important factors affecting the growth of bifidobacteria in human milk. Four out of 5 strains of human origin were resistant to lysozyme and utilized HMOs. In contrast,
According to Rockova et al. [58] the lysozyme-resistant
Lactoperoxidase makes up approximately 0.5% of the whey protein. In the presence of hydrogen peroxide (formed in small quantities by cells), catalyzes the oxidation of thiocyanate (part of saliva), forming hypothiocyanate, which can kill both gram-positive and gram-negative bacteria. Thus, lactoperoxidase in human milk may contribute to the defense against infection already in the mouth and upper gastrointestinal tract. Human milk contains active lactoperoxidase, but its physiologic significance is not yet known.[42]
κ-Casein, a minor casein subunit in human milk, is a glycoprotein with charged sialic acid residues. The heavily glycosylated k-casein molecule has been shown to inhibit the adhesion of
Glycomacropeptide is resultant from the tryptic hydrolysis of human k-casein, containing sugars glucosamine and galactosamine. The molecular weight of intact human
Glycomacropeptide helps control appetite and inhibit the formation of dental plaque and dental cavities. It is a growth factor for bifidobacteria (bifidogenic factor 1) Levels of glycomacropeptide may range from 1% to 18% [40]
The main fatty acids present in human milk are restricted to those with 12-18 carbon atoms chains,namely lauric, myristic, palmitic, palmitoleic, stearic, oleic, linoleic and linolenic. Some of the long chain polyunsaturated acids such as arachidonic and others are derived from essential fatty acids linoleic and linolenic acids, totaling together with their precursors, about 15% of fat of human milk. This percentage is much higher than that found in bovine milk. Palmitic, oleic and linoleic add up together about 70% of total fatty acids of colostrum and 74% of that of mature milk [54]
Corcoran et al. [60] studied the effect of inclusion of various C18 fatty acids with 0–2 double bonds in either
Rosberg-Cody et al. [61] isolate different strains of the genus
Most of the honey in the world is produced by bees from the nectar. Nectar is a sugar solution and water, may contain pure sucrose, a mixture of sucrose, glucose and fructose, or glucose and fructose only. The nectar is transported to the combs of the hive, where they will undergo physical and chemical changes responsible for their maturation (Crane, 1983). The chemical composition of honey, as well as aroma, color and medicinal properties, are directly related to the nectar source that originated with the bee species that produced it, with their geographic and climatic conditions. All these factors contribute to the wide variation found in honey [62].
Shin and Ustunol [63] defines honey as natural syrup containing mainly fructose (38.5%) and glucose (31.3%). Other sugars in honey include maltose (7.2%), sucrose (1,5%) and a variety of oligosaccharides (4.2%). In addition to the complex mixture of carbohydrates, are enzymes, minerals, pigments, waxes and pollen. More than one hundred eighty substances have been found in different honey types.
Honey is a complex product of easy digestion and assimilation, constituting a source of energy that contributes to the balance of biological processes in that it contains suitable proportions, enzymes, vitamins, fatty acids, amino acids, phenolic and aromatic substances [64]. In addition contains oligosaccharides which stimulates the growth of probiotic bacteria in the gut [65, 66].
Leite et al. [65], found in various di-and trisaccharides in Brazilian honeys. Maltose showed up in higher levels in honeys surveyed followed by other five disaccharides, turanose, nigerose, melibiose, sucrose, isomaltose and four trisaccharides, maltotriose, panose, melezitose and raffinose..
Cellobiose, gentiobiose, isomaltose, kojibiose, laminaribiose, maltose, maltulose, melibiose, nigerose, palatinose, trehalose, trehalulose, turanose, and sucrose are the main disaccharides found in honey [66, 67]. However, it would be rather difficult to identify the predominant disaccharide or certain combinations in the previously studied honey types. For example, maltulose and turanose were found in many honey samples, however their concentrations varied to a wide extent. Thus, Sanz and others [66] found the highest amounts of maltulose and turanose (0.66 to 3.52 and 0.72 to 2.87 g/100 g of honey, respectively) in 10 samples of honey from different regions of Spain and commercially available nectar and honeydew honeys.
Carbohydrate degradation has been extensively studied in a variety of different
Pokusaeva et al. [68] describe the identification of two genes,
Proline is the main amino acid present in honey; it is added by the bee and its amount varies depending on the floral source.[67].
Macedo et al. [69] studied the effect of the
It is well stablished the role of several oligosaccharides as prebiotic substances. The prebiotic effect of human milk, however, is not related to a single growth-promoting substance, but rather to a complex of interacting factors. In particular the prebiotic effect has been ascribed to several oligosaccharides, that is clearly proved. The role and the way milk fat and proteins such as lactoferrin, lysozyme stimulate the growth of probiotic bacteria is not yet clearly defined.
Nanomaterials (NMs) are engineered chemical substances or materials with a particle size of 1–100 nm in diameter. Today NMs are extensively explored and engaged for commercial purposes in different fields, and many sophisticated NMs have shown great promise in biotechnology and biomedicine [1]. NMs display inimitable physicochemical attributes due to their size range in nanometers, high surface area, tunable surface charge, unique composition, various morphologies, and surface composition. Due to their remarkable physicochemical attributes, NMs are significantly different from their bulk materials of a similar symphony, allowing them to perform remarkably well with improved functionality, sensitivity, competence, and selectivity towards developing biomedicines. Various NMs are evaluated to get desired biomedical efficacy for nanomedicine-related applications, including different metal nanoparticles, liposomes, quantum dots, polymeric micelles, dendrimers, and carbon-based nanoparticles. Two critical mechanisms for delivering drug-loaded NMs to the diseased sites are passive targeting and active targeting. A passive targeting mechanism happens via enhanced permeability and retention (EPR) [2]. Inactive targeting mechanism relies on surface functionalized NMs with various biomarkers that bind with receptors over-expressed at the pathological tissue [3].
The importance of cell culture advances in the medical sector has long been recognized. Mammalian cell culture (MCC) entails first isolating cells from a specific organ tissue and then creating a culture in a suitable artificial setting. Disaggregation using different methods may be used to obtain preliminary separation of cells from the identified organ tissues. The isolated primary cells are typically obtained from an
Nutritional necessities comprise an adherent substrate or growing medium that offers conditions like essential amino acids, sugars, vitamins, minerals, growth factors, hormones, and gases (O2, CO2). All these features regulate physicochemical factors such as pH, osmotic pressure, and temperature. Many cell lines need solid or semi-solid support in the form of a substrate, while others can be grown in a suspension culture medium. These technologies have evolved as a means of assessing the efficacy and side effects of novel active pharmaceutical ingredients (APIs), immunotherapeutic, and biopharmaceuticals [5]. Animal, plant, and bacterial cells are regularly cultured in fixed culture medium under precise laboratory circumstances; among this, animal-based cell cultures are more complex than others due to their genetic complexity. Directed differentiation of adult stem cells and pluripotent stem cell culture is another challenging aspect. Recent advances in stem cell culture technology have provided significant input for the successful culture of tissue-mimicking 3D organoids [4, 6].
In recent years, nanotechnology (NT) and associated disciplines have gained rapid escalation in biomedical implementations such as diagnosis, testing, tracking, drug delivery, nanomedicine, medical implants, and electronics due to their camaraderie with biological entities. Biomedicine embraces the design and synthesis of NMs, along with other nanoparticles (NPs) and nano-devices [7]. Once properly formulated, NMs show their natural aptitude to traverse with the blood flow via various routes based on their attributes and eventually get access to all the organs. Due to their intrinsic biocompatible interactions, the NPs exhibit unique physicochemical attributes associated with lesser immunogenicity and non-toxicity. There are numerous advantages of using NMs for various biological applications: i) it increases the concentration of drug in the pathological tissues and control the slow release of the drug; ii) it solves issues connected to the low solubility and bioavailability of the drug; and iii) enhanced biodegradability and biocompatibility iv) drugs/genes/imaging agents can be easily loaded due to their tunable surface functionalities [1, 7, 8]. Imaging agents could endow
NMs attract considerable interest due to their unique, tunable, versatile physicochemical properties, easy preparation methods, biocompatibility, and surface functionalization [1]. Nonetheless, the compatibility of the nanoparticles with biological entities constitutes the most fundamental phenomenon and highlights the importance of basic research [9]. Most bio-applications, including drug delivery, bioimaging, and treatment, start from the attachment of nanoparticles onto the target cells. The biocompatibility of nanoparticles depends on the physical and chemical attributes like diameter, shape, composition, concentration, functionalized moieties, and surface potential (Figure 1) [10]. Among the various NMs, Quantum dots have risen as an innovative bio-imaging tool due to their unique tunable physicochemical attributes. Existing research has guided the development of versatile quantum dots that are highly fluorescent and stable under diverse biological circumstances. Moreover, quantum dots with enclosed amphipathic polymers have been developed and surface-functionalized with receptor targeting ligands for bio-imaging and drug-delivery in animal models. Fascinatingly, these materials were found to be compatible with the cells. However, their complete chronic
Precision of targeted drug delivery using nanocarriers and bio-compatibility. Nanoparticle based drug delivery platform depends on surface functionality, size and shape and surface charge and composition.
Polymeric nanoparticles have drawn considerable attention in drug and gene delivery, tissue engineering, and many biomedical applications due to their non-toxic nature and high compatibility to biological systems. They are colloidal in nature and composed of natural or synthetic, or semi-synthetic polymers. In this perspective, biodegradable nanoparticles of the highly compatible triblock copolymer are used for non-viral gene transfections [3].
Liposomes are another popular nanomaterial drug delivery system that is best documented and adapted owing to their bio-congenial physicochemical properties [12]. Liposomes consist of unilamellar/ multilamellar lipid bilayers having an aqueous core inside. The nanoscale carrier system offers substantial advantages such as biodegradability, biocompatibility, ease of synthesis, less toxicity, sustained drug release, and the ability to incorporate hydrophilic and hydrophobic drugs. Liposomal-surface modification is a crucial strategy for targeted therapy and especially for cancer treatment [13]. Seventeen liposomal formulations are clinically approved for cancer, inflammation, infectious diseases, antibiotic drugs, and anesthetics, while several liposomal formulations are under various phases of clinical trials [12, 13].
Despite several encouraging biomedical implementations of nanoparticles, the biocompatible assessments including, complete acute and chronic toxicological evaluation of NMs, are inadequately comprehended. Additionally, the toxicity of the nanoparticle design aims to find out favorable physicochemical attributes of different materials. Hence, the active bio-molecule with biological entities must be highly allied to the nanoparticles approaching direct contact with biological objects rather than its transient initial distribution. Much to our intrigue, various nanoparticles - liposomes, lipoplexes, polymeric nanoparticles, polyplexes, metal nanoparticles, metal oxides, dendrimers, and quantum dots are wisely engineered for their medical application like diagnosis, drug and gene delivery, tissue engineering, and biosensing [8, 13, 14]. Moreover, it is unavoidable to thoroughly assess and investigate compatibility/unwanted toxicity with nanoparticles to bring clinical success. The subsequent section will relate to how the physicochemical properties of engineered nanoparticles can be persuaded towards accomplishing the desired biological aspiration lacking any toxicological impact.
Nanoparticles exhibit outstanding physicochemical attributes which can be manipulated to harness the best possible benefits out of them - their tunable diameter, high surface area, various morphologies, different concentrations and compositions, surface functionalization, etc. [15] (Figure 1). Interactions of NMs to the cell surface, their internalization, and subcellular localization, communication with the cells eventually contribute to therapeutic or adverse effects. Understanding the physicochemical attributes of NMs and their interactions with biological entities can help design superior NMs for further applications. We are jotting down the relevant physicochemical attributes of nanoparticles, which may modulate their function in therapeutic or toxicity aspects; thus, they need to be engineered wisely [16].
For engineered nanoparticles, the primary crucial feature is their dimensions/size, which partially governs other physicochemical characteristics. The reduced diameter of the nanoparticles, provide possibilities for high cellular localization making them interact with cellular tissues, especially pathological tissue to a greater extent to attain specific biological outcome for the remedial purpose. Size-dependent bio-distribution studies were performed using three different sizes containing (20, 50, and 200 nm) drug conjugated silica nanoparticles. It revealed that nanoparticles having 50 nm diameter had the highest tumor localization, enhanced cancer tissue retention, and slower clearance [16]. Moreover, nano-sized particles preside over their pharmacokinetics, are predictable to traverse biological barriers, which is not possible for bulk particles. Besides, ~50 nm diameter particles showed higher efficacy because of active engagement to the biological tissues, modulating pathways, and cellular activities [17].
The surface charge is a unique character of NMs to manage its therapeutic and toxicological effects and plays a significant role in electrostatic interactions of NMs and living entities (Figure 1) [10]. Besides, the cellular localization pathways and tissue interactions are regulated by the surface charge of the nanoparticles, thus playing a significant role in the compatibility and cellular toxicity. Several reports suggest that nanoparticles with a positive charge highly interact with the negatively charged cell membranes and provoke genotoxicity [18]. Positively charged cationic liposomal drug and gene delivery systems have been extensively studied for the last decade. It was recently shown that cationic lipoplexes are not showing any genotoxicological aberrations in the Swiss albino mice. Typically, cell membranes are anionic in nature; thus, negatively charged NMs have very slow cellular internalization compared to neutral and positive nanoparticles [14]. Surface potentials of metal particles in regulating different tumorous and non-tumorous tissue types are also established. Several studies have suggested the role of the surface potential of different nanoparticles and their interactions with the biological entities and how surface charge modulates their biological functions, which shed light to design and engineer nanoparticles for a selective cellular target for various diseases with minimal toxicity [16, 18].
Nanoparticles play a vital role in promoting intracellular delivery of encapsulated therapeutic agents and increase their retention in pathological tissues compared to healthy tissues [1]. Surface functionalization with suitable receptor-targeted ligands using different methods results in the formation of targeted nanoparticles with improved therapeutic response and minimized off-target side effects by prolonging their circulation time in blood, increasing target specificity, cellular uptake, and drug accumulation in the tumors (escaping lysosomal degradation and enhancing stimuli-responsive drug release) (Figure 1) [17, 19]. Depending on their application, nanoparticles are functionalized with different targeting ligands either by directly conjugating ligands to PEGylated nanoparticles through post-insertion technique or by covalent grafting on the surface of the nanoparticles. In this context, surface functionalization of nanoparticles with antibodies, peptides, folic acid, aptamers has been extensively studied. This prompts scientists to design and engineer nanoparticles for selective targeting and high retention in the tumor tissue rendering minimal toxicity to the vital organs [19, 20].
Nanoparticles play a vital role in promoting intracellular delivery of enclosed therapeutic agents and increase their retention in the different pathological tissues compared to other therapies [21]. Like normal tissues, tumors need nourishments by means of food and oxygen and a capacity to remove metabolic excretes and carbon dioxide. Diverse patterns of tumor-associated neovascularization, obtained by angiogenesis, cope with these demands. Primary conservative treatment modalities involved in cancer treatment are surgery, radiotherapy, and chemotherapy, while additional therapies such as immune therapy, targeted therapy, and hormone therapy are chosen depending on the type of tumor [22]. On the other hand, the failure of chemotherapeutic drugs to specifically target cancer tissue hinders many treatment modalities. It is habitually faster and economically cheaper to design an existing drug to encapsulate in a delivery system a more effective way to superior targeting of tissues than to invent a completely new one. The drug delivery mechanism can be classified into passive and active, respectively.
Passive targeted drug delivery mainly depends on the physicochemical attributes of the NMs, such as shape, diameter, surface potentials, and pathophysiological conditions of the disease microenvironment. Intravenously injected drug encapsulated NMs tend to disperse throughout the body evenly [23]. However, unlike normal tissues, tumor cells tend to take up particles of a definite diameter to a greater extent than healthy cells due to the arrangement of capillary endothelial cells, accumulating extravasated molecules in the interstitial spaces poor lymphatic drainage increases the permeation and accumulation of drug-mediated NMs. This type of NMs accumulation in the tumor region is known as the EPR effect [1, 2]. The EPR effect is influenced by physicochemical attributes of NM including particle diameter, shape, and surface potentials greatly influence the circulation time, penetration speed, tumor localization, and intracellular internalization.
Particle diameter plays a critical role in achieving effective drug delivery as it enhances permeation and circulation time and reduces renal clearance. For example, phagocyte cells facilitate larger particle uptake, while non-phagocytic cells favor the uptake of smaller particles. PEGylated NPs reduced plasma protein adsorption on their surface and reduced hepatic filtration when their size is smaller than 100 nm [24]. Particle diameter with 20–200 nm effectively enhances the permeation in both hyper-permeable and poorly permeable tumors, and particles with less than 6 nm avoid renal clearance. The NPs surface potentials could play a vital role in circulation and cellular localization [24, 25]. NPs with positive surface potentials such as cationic liposomes induce non-specific interactions with blood components and aggregation of liposomes results in a reduction of EPR effect and increased renal clearance. However, positively charged NPs are more readily taken up by cancer cells. Whereas anionic and neutral surface potential-bearing NPs circulate longer in the blood circulation [1, 2, 24].
Besides, Polyethylene glycol (PEG) polymer is used as a stabilizer (stealth liposomes) that increases the circulation time in blood up to 24–48 hours and improves
An ideal nanoparticle delivery system should be proficient at reaching, recognizing, and delivering its payload to determined morbid tissues and avoid drug-induced toxicity to healthy tissues [7]. Therefore, functionalizing specific targeting moieties on the surface of nanoparticles is the most usual plan. Nanoparticles are functionalized on their outer surface by targeting moieties such as small molecule ligands, monoclonal antibodies, aptamers, cell-penetrating peptides, and proteins that are internalized into morbid cells by interacting with cell surface receptors like folate receptors, transferrin receptors, tyrosine kinases like EGFR, and so on [28] (Figure 1). Cell surface receptors that are significantly overexpressed in diseased cells, compared to normal healthy cells, provide a potential target for the design and development of actively targeted drug delivery and help to reduce off-target effects [7, 17]. These ligand moieties can interact with target-specific diseased cells and protect nanoparticles from enzymatic demolition.
Targeted drug delivery significantly minimizes the toxicity and induces patient compliance with less frequent dosing. Active targeting depends on ligands bound to the NP surface to improve their uptake selectivity and protect NPS from enzymatic destruction. The main principle of active targeting involves functionalizing an NP with a ligand that binds to a molecule overexpressed on cells. Ligands with a high binding affinity to a specific cell type exhibit higher delivery efficiency. One important thing to consider is that healthy cells still express the same molecule, and as healthy cells greatly outnumber, the chances of NPs missing their target will also increase. An intelligent selection and functionalization with multiple ligands can effectively mitigate the problem. Apart from this, active targeting mainly determined the kind of nanoparticle carrier, ligand targeting specific receptors, functional agents used for linking a ligand to the nanoparticles, hydrophilic polymers, and encapsulated active ingredients [28, 29].
Targeting tumor cell surface receptors is a common approach in active targeting. Nanoparticles were linked with targeted ligands for targeting specific cell receptors and thus upregulated the intracellular localization and therapeutic efficiency. Liposomes are conjugated with antibodies, a Y-shaped glycoprotein, or its fragments often termed as immunoliposomes, increasing the specificity of liposomes by targeting antigen-presenting cancer cells, which undergo endocytosis and destroy cancer cells followed by immune system clearance [28]. Folate receptors are membrane proteins overexpressed by various tumor cells. Folic acid is a ligand for targeting folate receptors, which pose high affinity, stability, and conjugation capacity [30]. It is conjugated with nanoparticles and a PEG spacer that inhibits steric hindrance between the cells and liposomes, which helps to increase cellular uptake and drug delivery of folate-targeted anticancer drugs. Targeting folate receptors with folic acid ligands helps deliver therapeutic and imaging agents effectively to the requisite site. Endothelial growth factor receptors (EGFR) overexpressed in solid tumors like non-small cell lung cancer, colorectal, squamous cell carcinoma of the ovary, kidney, head, neck, pancreas, prostate, and breast cancers can help in designing EGFR targeted drug delivery system. Antibody fragments used for targeting EGFR are functionalized on nanoparticle surfaces in order to acquire high targeting specificity [31]. Fibroblast growth factor receptors are overexpressed in cancers like lung, prostate, bladder, etc. Several groups have reported remarkable interaction of FGFs conjugated liposome with FGFR and discussed in detail [32, 33]. Overexpression of CD44 is observed in cancers like leukemia, ovarian, colon, gastric, pancreatic, and epithelial cancers. Hyaluronic acid acts as a ligand for CD44 and is used to deliver gemcitabine and DOX encapsulated within the liposomes [34].
Targeting the tumor microenvironment is another approach in active targeting, and one aspect is targeting the tumor vasculature instead of the tumor. This approach helps in the targeted destruction of neo-angiogenic blood vessels essential for tumor growth and metastasis [29, 35]. Vascular endothelial growth factor receptors (VEGFR) play a significant role in tumor angiogenesis and vascular permeability and regulate other aspects of tumorigenesis. Bevacizumab, a monoclonal antibody approved by USFDA, is used as an anti-human VEGF for targeting VEGFRs and FGFRs tyrosine receptors for active targeting [29]. Vascular cell adhesion molecules (VCAM-1) are cell adhesion molecules (CAMs) present on the endothelial cells responsible for inflammation. VCAM-1 is overexpressed in cancers like non-small cell lung cancer and tumor vasculature. Anti-VCAM and Fab-conjugated liposomes have high cellular uptake into Human Umbilical Vein and Endothelial Cells (HUVEC) compared to conventional liposomes [36].
Matrix metalloproteases (MMPs) are calcium-dependent endopeptidases involved in remodeling extracellular matrix, tumor invasiveness, and metastasis by modulating the formation of new blood vessels [37]. Conjugating MMP-2 cleavable peptides to liposomes loaded with cell-penetrating peptides increase the tumor selectivity. αβ-integrins are the heterodimeric transmembrane glycoproteins that facilitate the adhesion of endothelial cells with adjacent tissue and blood vessels. A tripeptide Arg-Gly-Asp (RGD) exhibited high specificity for αvβ3 integrin helps in developing integrin targeted liposomes, which inhibits adhesion and angiogenesis in the tumor microenvironment (TME) [38]. Active targeting amends the intuitive patterns of a nanocarrier, directing to the specificity of the pathological tissue. In contrast, passive targeting delivery depends on the natural distribution of the therapeutic motifs and the EPR effect. Both the targeting mechanisms depend on blood circulation and the location of initial drug delivery. However, rare commercial advances are made using actively targeted NPs [39].
Early detection and diagnosis can play a pivotal role in the battle against many diseases. Scientists harness the unique attributes of nanomaterials to generate novel molecular contrast agents for
The main lacunae in cancer treatment are a late diagnosis. The resolution of current imaging methods is low and can detect cancers at the late/ advanced stage or metastasized. A tissue biopsy can only help physicians to ascertain the tumor type and characteristics. Detection becomes even more challenging when metastatic modules and micrometastasis need to be identified.
By virtue of their unique properties, NPs make them ideal for their use for nano bio-sensing applications with enhanced sensitivity. Nanoparticles are widely used for detecting cells and pathogens, separating pathogens, recognize different biological substances, and detecting molecular and cellular functions [41, 42]. Accurate and professional separation of desired cells from the composite of various cell mixtures is essential for numerous biological applications. Nanoparticles have been investigated as a promising and very sensitive tool for the specific identification of cells. Identification and incarceration of metastatic cancer cells in the circulation can help understand and a strong analytical biomarker for various metastatic cancers, which can change the patient’s prognosis. Nanoparticle-based methods are more frequently used for the identification and capture of metastatic circulating cancer cells. In this technique, magnetic nanoparticles were used to specifically track and separate the cells by using a ligand-receptor-based mechanism [42]. These techniques can also be used for the white blood cells with an anti-CD45-APC as a nanoparticle targeting ligand [44].
Additionally, various nanoparticle-based technologies have been investigated as a sensor for the identification and selection of various pathogens. The most frequently used method for finding bacteria is magnetic biosensors that involve immunological mechanisms using magnetic nanoparticles functionalized with antibodies against surface antigens. Many researchers have been utilizing small molecule tethered nanoparticles to analyze the bacteria successfully. Magnetic glyco-nanoparticles mediated particles could detect bacteria within 5 minutes, including subtraction from the sample by the bacterial interaction with carbohydrates on mammalian cell surfaces [41].
Nanoparticles have been investigated as imaging agents due to their exceptional physicochemical attributes for various biomedical applications such as cancers and cardiovascular diseases. Fluorescent labels can be easily conjugated to the surfaces of the nanoparticles by various chemical methods to design a wide range of imaging agents for dynamic
RGD peptide conjugated self-emitting quantum dots can be used for specific integrins highly expressed in tumors. The targeted nanoparticle has been examined for complex imaging competence, like imaging various molecular targets using different spectral emissions specific nanoparticles. Recently, nanotechnology has been used for imaging metastatic tumor cells in circulation, tumor cells, and their vasculature, stem cells, and lymph nodes [48]. Che et al. designed shortwave infrared window (SWIR)-responsive QDs for bone-specific real-time
Theranostic NMs are designed by the consolidation of diagnostic and therapeutic abilities in one biodegradable nanoparticle [50]. Novel theranostic materials should have the following properties; i) highly compatible with biological entities, ii) proficiently and precisely accumulate in desired morbid tissue, iii) describe the biochemical and morphological attributes of maladies, iv) exhibit minimal toxicological effects, v) and deliver a sufficient amount of therapeutic agent. Several techniques have been used to functionalize the surface of nanoparticles for theranostics use. Surface functionalization may include imaging agents, drugs, therapeutic cargo, nucleic acid, and contrast agents by either chemical functionalization or by biofunctionalization. Chemical functionalization depends on chemical cross-linking, while biofunctionalization of nanoparticles relies on bioinspired ligands obtained from natural phytochemicals). The use of nanotechnology offers a promising alternative for the diagnosis of various cancers. Various investigations convey that nanoparticles could be engineered for advanced diagnostic agents to detect cancers [51]. Double drug encapsulated liposomes can be functionalized to enhance theranostic efficacy [51, 52]. Multifunctional Metal nanoparticles can serve as a unique platform for cancer theranostics. The range of use of metal nanoparticles includes MRI imaging, biological catalysis, magnetic hyperthermia, magnetic drug delivery, photo-responsive drug delivery, and cell separation. Metal nanoparticles, including, Polymer-NP constructs containing Gd3+ complexes, Fe3 + − terpyridine complexes, and polymeric shell-based contrast agents, are widely studied for their theranostic use as MRI contrast. Magnetic particle imaging (MPI), a novel imaging technique, is based on the analysis of iron oxide NPs in response to a magnetic field.
Cheng et al. used GE11, a novel peptide with EGFR binding affinity and complexed with doxorubicin-loaded liposomes, and observed higher liposomal uptake and accumulation than, unconjugated liposomes using NIRF [53]. In another study Song et al. designed a multifunctional targeting liposome for targeting lung cancer. Octreotide (OCT), a synthetic 8-peptide analog of somatostatin, was used to surface coat the liposome for enhanced binding with the somatostatin receptors overexpressed in a subset of tumors. Double anti-cancer drug (Honokiol and epirubicin) co-encapsulated liposomes showed enhanced OCT- somatostatin receptor binding and
Biosafety is a notion that requires protecting human health and the surroundings of pathogenic and genetically modified mammalian cells or organisms used in the research. Mammalian cell culture is identified as a shelter for infectious etiologic substances, and it should change the compliance with containment measures recommended for the etiologic agent itself. The utility of cell cultures comes under the preview of a range of regulatory provisions that consider the estimation of biological risks. Genetically modified mammalian cell cultures were used in different continents; in that case, a bio-safety assessment should be regulated. The major guidelines issued to mitigate the biological risks for the users and environment are mainly by the World Health Organization; the Centers for Disease Control and Prevention, and the Swiss Expert Committee for Biosafety. Several countries or geographical zones have different directives; for example, in Europe, genetically modified research was brought into the regulatory provision (Directive 2009/41/EC). Mammalian cell culturing activities focusing on developing pharmaceutical drugs are covered by the Regulation (EC) No 726/2004 and its amendment laying down actions for the authorization and direction of medicinal goods for human and animal use. 3D cultures, especially organoid culture systems, are regularly used for disease modeling and studying nanomaterial-based physiological effects. Human Pluripotent stem cell-derived organoids are being generated from various human cell types and need better bio-safety and bioethics assessment. It must be ascertained that rules focusing on extenuating the biological risks for laboratory researchers, public health, and the environment falls under the preview one or several regulatory provisions based on biological risk assessment. Here, we are going to address the bio-safety issues involving mammalian cell cultures.
Biosafety refers to the way of protecting scientists, the health of other humans, and the environment from the probable side effects of microorganism, pathogenic, and genetically modified organisms and cells from human and mouse backgrounds. Laboratory biosafety uses safety principles and techniques to minimize the health hazard from accidental exposure or unplanned spillage while using infectious agents, toxins and other biological hazards in the laboratory setting. The bio-safety assessments applied to mammalian cells depend on a systematic assessment of the intrinsic attributes of the mammalian cultures like genetically modified cells and contaminated or intentionally infected with pathogens. Figure 2 shows a summary of the biosafety assessment and management process that is followed while handling cell culture-based experiments. This also considers an exposure analysis, which means that type of exploitation carried out with the cultures should be considered. The risk analysis of cell cultures that carry the pathogens follows the same methods for analyzing pathogens themselves. Primarily, the inclusive depiction of major pathogens is measured by the subsequent guidelines (i) pathogenicity and the infectious dose (ii) mode of transmission, (iii) host range, (iv) the epidemiology, potential reservoir and vectors, and the ability to zoonosis (v) the stability and the resilience of the pathogens in the surroundings.
Flow diagram illustrating the summarizing the biosafety assessment and management process while handling cell culture-based experiments. Flow chart is inspired by reference [
Moreover, information related to the physicochemical properties of the pathogenic organism is considered, such as (i) susceptibility to disinfectants, (ii) physical inactivation, and (iii) drug susceptibility (e.g., sensitivity and known resistance to antibiotics or antiviral compounds). Lastly, aspects related to the disease caused by the pathogen are also to be taken into consideration. This includes (i) the availability of effective prophylaxis, (ii) the availability of efficient therapy, and (iii) any reported case of laboratory-acquired infections (LAIs). Even though underemphasized, several LAIs of mammalian cell cultures (or having virus suspension) has appeared. Among all, the exposure to vaccinia viruses amplified in mammalian cell cultures causes infections to laboratory researchers. Guidelines have been developed recently to work cautiously with vaccinia viruses and take a count of LAIs relating to this virus [55].
Understanding and having a complete analysis of the intrinsic infections of cell cultures help to perform well and safe mammalian cell culture. To assess biological risks connected with the mammalian cell cultures, three intrinsic properties related to cell cultures should be considered: the species of origin, the cell type or type of tissue (the organ of origin of the cell line), and the status of the culture. Correspondingly, mammalian cells other than human cells render less risk; still, some infectious agents are proficient at crossing one species to another species, leading to zoonosis. Highly reported infections of viruses comprise hantavirus, hemorrhagic fever viruses, bird Influenza virus, and severe acute respiratory syndrome (SARS) associated virus. Primary cell cultures are created from organ tissues. Highly characterized mammalian cells give the lowest risks compared to primary cultures or less characterized cell lines. Mammalian cells originating from different laboratories without having any proof of identity may cause cross-contamination and pathogen spreading problems, and thereby proper risk assessment and cell characterization are warranted [55, 56]. Several techniques are available for the bio-safety assessment, like RT-PCR, flow cytometry, cytogenetic analysis, DNA fingerprinting, and iso-enzyme analysis. Adventitious contagions of mammalian cell cultures are a vital problem for any activity that involves cell culturing. Contamination agents for cell cultures are bacteria, fungi, mycoplasms, parasites, viruses, prions, and even other animal cells. Modulated experimental results suggest that they spoil the cell cultures. Bio-safety point of view modified mammalian cell cultures for laboratory research, production purposes, or diagnosis purposes they may give support for contaminating materials that cause harm to human health.
The futuristic technologies in bio-medicine are changing the current concepts and opening up new dimensions. Interestingly as new optimistic channels are opening and expanding, the issues of bioethics are becoming accurate and pertinent. Bioethics is the use of ethical principles in the field of medicine and healthcare. The rational application of ethics in evaluating mammalian cell culture-based experiments is highly warranted, especially during the emerging waves of change in biomedicine. Increased International cross-connection to facilitate open discussion in bioethics and related fields across cross-cultural aspects in bioethics is vital [57]. Several relevant questions arise regarding the private and sensitive use of source data for cells, moral concerns regarding the uses of embryonic and fetal tissue, genetic manipulation, gene therapy, mixing of animal and human cells, tissue banking, legal and intellectual properties associated with
Regarding the humane use of animals, the National Institutes of Health has issued policies as mentioned in the Public Health Service Policy on Humane Care and Use of Laboratory Animals. FDA Human Tissue Task Force and the Center for Biologics Evaluation and Research (CBER) regulates the use of human cells or tissue for implantation, transplantation, infusion, or transfer into a human recipient. The International Society for Stem Cell Research (ISSCR) has also released guidelines for stem cell research and clinical translation. The United States Congress and state legislatures are instrumental in creating laws concerning bioethics. Several professional bioethics organizations, including the American Society for Bioethics and Humanities, American Society for Law, Medicine, and Ethics, Canadian Bioethics Society, provide a platform for discussion over bioethics [57]. Several public institutions supported by academicians and researcher-based initiative for propagating public dialog plays a vital role in educating the masses.
Intellectual property rights (IPR) prevail in any primitive design of the human brain, such as methodical design. IPR mentions the lawful rights agreed to the designer for guarding his innovation for a definite period. These lawful rights grant special rights to the originator or his lender to exploit his idea for a specific period. It is well established that IPR participates in the financial system. It is furthermore overwhelmingly recognized that the intellectualism linked with the originality must be agreed due to value so that products come out of intelligence. The importance of the producer of the technology has turn into lofty and consequently guard the information against unauthorized persons, the use has become a measure, at least sometimes, that would make sure revitalization of the research, investments in developing the technology. IPR helps to look after funds, time, capital, endeavor invested by the producer of an intellectual idea; as a result, IPR, in this way, encourages the profitable encouragement of a realm by encouraging positive competition and heartening trade and industry [58].
The industries have reputations in discussions about IPR strategies, and they are in the face line for controversies about the association among IPRs, R&D incentives, cost, and right to use to supplies [59]. Although, some discussions on the critical issue are relatively little practical proof to support developing IPR policy. This experimental evidence on IP and products inspect practical issues are the primary sources of the data. The industrial sector is composite and much synchronized in the majority of economies. Looking cross-nationally, the contrast among the countries in their perspective on these essential policy affairs generates some additional provocations. In a cosmopolitan industry having control over research and development conveniences in many countries, anticipating a successful transnational technology, goods are raised and developed internationally and are commercialized worldwide. Still, retails are nationalized, with no considerable uniformity across the nations in IPR authorities and various public health care organizations. IPRs may shore up significant discrepancies to price across the nations in returns and demand to prices. These discrepancies in the prices may potentially develop new local and global disagreements. Prominently, for any nation, the essential exchange in IPR regulation options is incredibly dependent on the organizations and function of its health care system.
While having a commendable collaboration, the complete fulfillment of a patent portfolio is to give equal rights for industry and academic institutions. In many countries, research organizations pursuing research in academic institutions, despite their most important work in society as a generator of the intellectual idea, the main concern is to be to deal with IP in a proficient mode. All academic institutions must become accustomed to this development to successfully fulfill the responsibility entrusted to a national or regional innovation ecosystem.
On the supply side, goods safety, supervision of manufacturing, and legal frameworks leading technology transfer among public-funded academic institutions and money-making industries playing an equal role in determining competition. Providing IPR policy to academic institutions has a favorable outcome and various settlements for shareholders. The most significant overarching advantage of these IPR policies was pronounced increases involvement in improving the global innovation performance, i.e., ultimately leading to improving the marketable products and processes. The development of spin-out companies from universities is also growing at a faster rate. The critical part is that the university should own the background IP. Then a resource of external financial support is necessary to finance the start-up company. IPR affairs at academic institutions glow enormous meandering return impending for the national economy. Publishing articles regarding innovations play an essential role in the profession of academic scientists. Participating in knowledge transfer from academia to manufacturing industries can promote academic entrepreneurship. Moreover, these patents have precious information than other publishing articles. Thus, utilizing and increasing patent writing might be beneficial in scientific research. Appropriate IPR policies and tractable technology transfer professionals play a pivotal role in streamlining the necessary work-frame. Published patents improve the economy and reputation of the academic institutions as well as the researchers.
Nanomaterials, due to their nano-size and unique physicochemical properties, have contributed significantly to the advance of biomedicine. The scope of nanomedicine also relies on the intelligent engineering of different nanoparticles with tunable attributes to modulate their nano-bio communications for biomedical applications. Elucidation of nanoparticle interactions with biological systems will help find favorable physicochemical properties to enhance biocompatibility and therapeutic efficacy with no adverse effects. A complete toxicological evaluation of engineered nanomaterials is still inadequately understood, restraining the successful translation of nanomedicine. Nanoparticle surface functionalization with specific targeting moieties can effectively develop ideal nanoparticle delivery systems for various biomedical applications and targeted therapeutics. Hence,
In conclusion, MCC is an essential tool in modern-day biomedicine, and its applications are countless in the diagnosis and therapy of human diseases. Cell culture procedures are reliable, reproducible, and unbiased, but culturing the cells is complex at times. The vast opportunities to employ MCC procedures to address rudimentary and translational research queries have elucidated the essential attentions for setting up a cell culture laboratory. Especially 3D organoid culture methods have created a cellular environment that mimics the
Genome sequencing, mapping, and annotating its genetic code have become a priority in biotechnology, especially intending to understand the interaction of nanoparticles and mammalian cells. Reporting and cataloging the identified gene sequences can be critical for the progress of science and also for disease-specific therapeutics. Nanotechnology-based research has contributed significantly to many scientific fields and associated industries. Hence nanotechnology, combined with the mammalian cell culture system, can result in a research solution and can deliver considerable benefits to society at large. Hence the importance of intellectual property rights for protecting the innovator’s right over the discovery. A good understanding of the IPR policies and technology transfer protocol is vital. Academic institutions and government organizations can assist in creating a congenial platform for efficient policy management. A deeper understanding of nanoparticle-cell interaction and the design of futuristic nanocarriers can open up an era of next-generation therapeutics and theranostics.
M.K.P. acknowledges Professors S. Dubinett, B. Gomperts, and V. Hartenstein from UCLA for providing constant support and mentoring.
The authors declare no conflict of interest. The authors have no other pertinent affiliations or financial connection with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
Conceptualization - MKP; writing original draft preparation - HR, AM, MKP; Review and editing - MKP.
No funds available.
CBER | Centre for Biologics Evaluation and Research |
CT | Computed Tomography |
EGFR | Epidermal Growth Factor Receptor |
EPR | Enhanced Permeability and Retention |
FGFR | Fibroblast Growth Factor Receptor |
HUVEC | Human Umbilical Vein Endothelial Cells |
IgM | Immunoglobulin M |
IPR | Intellectual Property Rights |
ISSCR | International Society for Stem Cell Research |
LAIs | Laboratory-Acquired Infections |
MMPs | Matrix Metalloproteases |
MPI | Magnetic Particle imaging |
MRI | Magnetic Resonance Imaging |
NIH | National Institutes of Health |
NMs | Nanomaterials |
NPs | Nanoparticles |
NRIF | Near-infrared Fluorescence |
NT | Nanotechnology |
OCT | Octreotide |
PEG | Polyethylene glycol |
PET | Positron Emission Tomography |
QD | Quantum Dots |
SARS | Severe Acute Respiratory Syndrome |
SPECT | Single-photon Emission Computed Tomography |
SRA | Sequence Read Archive |
SWIR | Shortwave Infrared |
TME | Tumor Microenvironment |
US | Ultrasonography |
USFDA | United States Food and Drug Administration |
VCAM-1 | Vascular Cell Adhesion Molecules-1 |
VEGFR | Vascular Endothelial Growth Factor Receptors |
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\n\n\n\nFormats
\n\nBased on your preferences and the stage of your scientific projects, you have multiple options for publishing your scientific research with IntechOpen:
\n\nPeer Review Policies
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\n\n\n\nCosts
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The area covers many techniques that offer solutions to emerging problems in robotics and enterprise-level software systems. Collaborative intelligence is highly and effectively achieved with multi-agent systems. Areas of application include swarms of robots, flocks of UAVs, collaborative software management. Given the level of technological enhancements, the popularity of machine learning in use has opened a new chapter in multi-agent studies alongside the practical challenges and long-lasting collaboration issues in the field. It has increased the urgency and the need for further studies in this field. We welcome chapters presenting research on the many applications of multi-agent studies including, but not limited to, the following key areas: machine learning for multi-agent systems; modeling swarms robots and flocks of UAVs with multi-agent systems; decision science and multi-agent systems; software engineering for and with multi-agent systems; tools and technologies of multi-agent systems.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/27.jpg",keywords:"Collaborative Intelligence, Learning, Distributed Control System, Swarm Robotics, Decision Science, Software Engineering"}],annualVolumeBook:{},thematicCollection:[],selectedSeries:{title:"Artificial Intelligence",id:"14"},selectedSubseries:null},seriesLanding:{item:{id:"7",title:"Biomedical Engineering",doi:"10.5772/intechopen.71985",issn:"2631-5343",scope:"Biomedical Engineering is one of the fastest-growing interdisciplinary branches of science and industry. The combination of electronics and computer science with biology and medicine has improved patient diagnosis, reduced rehabilitation time, and helped to facilitate a better quality of life. Nowadays, all medical imaging devices, medical instruments, or new laboratory techniques result from the cooperation of specialists in various fields. The series of Biomedical Engineering books covers such areas of knowledge as chemistry, physics, electronics, medicine, and biology. This series is intended for doctors, engineers, and scientists involved in biomedical engineering or those wanting to start working in this field.",coverUrl:"https://cdn.intechopen.com/series/covers/7.jpg",latestPublicationDate:"May 7th, 2022",hasOnlineFirst:!0,numberOfOpenTopics:3,numberOfPublishedChapters:96,numberOfPublishedBooks:12,editor:{id:"50150",title:"Prof.",name:"Robert",middleName:null,surname:"Koprowski",fullName:"Robert Koprowski",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYTYNQA4/Profile_Picture_1630478535317",biography:"Robert Koprowski, MD (1997), PhD (2003), Habilitation (2015), is an employee of the University of Silesia, Poland, Institute of Computer Science, Department of Biomedical Computer Systems. For 20 years, he has studied the analysis and processing of biomedical images, emphasizing the full automation of measurement for a large inter-individual variability of patients. Dr. Koprowski has authored more than a hundred research papers with dozens in impact factor (IF) journals and has authored or co-authored six books. Additionally, he is the author of several national and international patents in the field of biomedical devices and imaging. Since 2011, he has been a reviewer of grants and projects (including EU projects) in biomedical engineering.",institutionString:null,institution:{name:"University of Silesia",institutionURL:null,country:{name:"Poland"}}},subseries:[{id:"7",title:"Bioinformatics and Medical Informatics",keywords:"Biomedical Data, Drug Discovery, Clinical Diagnostics, Decoding Human Genome, AI in Personalized Medicine, Disease-prevention Strategies, Big Data Analysis in Medicine",scope:"Bioinformatics aims to help understand the functioning of the mechanisms of living organisms through the construction and use of quantitative tools. The applications of this research cover many related fields, such as biotechnology and medicine, where, for example, Bioinformatics contributes to faster drug design, DNA analysis in forensics, and DNA sequence analysis in the field of personalized medicine. Personalized medicine is a type of medical care in which treatment is customized individually for each patient. Personalized medicine enables more effective therapy, reduces the costs of therapy and clinical trials, and also minimizes the risk of side effects. Nevertheless, advances in personalized medicine would not have been possible without bioinformatics, which can analyze the human genome and other vast amounts of biomedical data, especially in genetics. The rapid growth of information technology enabled the development of new tools to decode human genomes, large-scale studies of genetic variations and medical informatics. The considerable development of technology, including the computing power of computers, is also conducive to the development of bioinformatics, including personalized medicine. In an era of rapidly growing data volumes and ever lower costs of generating, storing and computing data, personalized medicine holds great promises. Modern computational methods used as bioinformatics tools can integrate multi-scale, multi-modal and longitudinal patient data to create even more effective and safer therapy and disease prevention methods. Main aspects of the topic are: Applying bioinformatics in drug discovery and development; Bioinformatics in clinical diagnostics (genetic variants that act as markers for a condition or a disease); Blockchain and Artificial Intelligence/Machine Learning in personalized medicine; Customize disease-prevention strategies in personalized medicine; Big data analysis in personalized medicine; Translating stratification algorithms into clinical practice of personalized medicine.",annualVolume:11403,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/7.jpg",editor:{id:"351533",title:"Dr.",name:"Slawomir",middleName:null,surname:"Wilczynski",fullName:"Slawomir Wilczynski",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035U1loQAC/Profile_Picture_1630074514792",institutionString:null,institution:{name:"Medical University of Silesia",institutionURL:null,country:{name:"Poland"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"5886",title:"Dr.",name:"Alexandros",middleName:"T.",surname:"Tzallas",fullName:"Alexandros Tzallas",profilePictureURL:"https://mts.intechopen.com/storage/users/5886/images/system/5886.png",institutionString:"University of Ioannina, Greece & Imperial College London",institution:{name:"University of Ioannina",institutionURL:null,country:{name:"Greece"}}},{id:"257388",title:"Distinguished Prof.",name:"Lulu",middleName:null,surname:"Wang",fullName:"Lulu Wang",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRX6kQAG/Profile_Picture_1630329584194",institutionString:null,institution:{name:"Shenzhen Technology University",institutionURL:null,country:{name:"China"}}},{id:"225387",title:"Prof.",name:"Reda",middleName:"R.",surname:"Gharieb",fullName:"Reda Gharieb",profilePictureURL:"https://mts.intechopen.com/storage/users/225387/images/system/225387.jpg",institutionString:"Assiut University",institution:{name:"Assiut University",institutionURL:null,country:{name:"Egypt"}}}]},{id:"8",title:"Bioinspired Technology and Biomechanics",keywords:"Bioinspired Systems, Biomechanics, Assistive Technology, Rehabilitation",scope:'Bioinspired technologies take advantage of understanding the actual biological system to provide solutions to problems in several areas. Recently, bioinspired systems have been successfully employing biomechanics to develop and improve assistive technology and rehabilitation devices. The research topic "Bioinspired Technology and Biomechanics" welcomes studies reporting recent advances in bioinspired technologies that contribute to individuals\' health, inclusion, and rehabilitation. Possible contributions can address (but are not limited to) the following research topics: Bioinspired design and control of exoskeletons, orthoses, and prostheses; Experimental evaluation of the effect of assistive devices (e.g., influence on gait, balance, and neuromuscular system); Bioinspired technologies for rehabilitation, including clinical studies reporting evaluations; Application of neuromuscular and biomechanical models to the development of bioinspired technology.',annualVolume:11404,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/8.jpg",editor:{id:"144937",title:"Prof.",name:"Adriano",middleName:"De Oliveira",surname:"Andrade",fullName:"Adriano Andrade",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRC8QQAW/Profile_Picture_1625219101815",institutionString:null,institution:{name:"Federal University of Uberlândia",institutionURL:null,country:{name:"Brazil"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"49517",title:"Prof.",name:"Hitoshi",middleName:null,surname:"Tsunashima",fullName:"Hitoshi Tsunashima",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYTP4QAO/Profile_Picture_1625819726528",institutionString:null,institution:{name:"Nihon University",institutionURL:null,country:{name:"Japan"}}},{id:"425354",title:"Dr.",name:"Marcus",middleName:"Fraga",surname:"Vieira",fullName:"Marcus Vieira",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003BJSgIQAX/Profile_Picture_1627904687309",institutionString:null,institution:{name:"Universidade Federal de Goiás",institutionURL:null,country:{name:"Brazil"}}},{id:"196746",title:"Dr.",name:"Ramana",middleName:null,surname:"Vinjamuri",fullName:"Ramana Vinjamuri",profilePictureURL:"https://mts.intechopen.com/storage/users/196746/images/system/196746.jpeg",institutionString:"University of Maryland, Baltimore County",institution:{name:"University of Maryland, Baltimore County",institutionURL:null,country:{name:"United States of America"}}}]},{id:"9",title:"Biotechnology - Biosensors, Biomaterials and Tissue Engineering",keywords:"Biotechnology, Biosensors, Biomaterials, Tissue Engineering",scope:"The Biotechnology - Biosensors, Biomaterials and Tissue Engineering topic within the Biomedical Engineering Series aims to rapidly publish contributions on all aspects of biotechnology, biosensors, biomaterial and tissue engineering. We encourage the submission of manuscripts that provide novel and mechanistic insights that report significant advances in the fields. Topics can include but are not limited to: Biotechnology such as biotechnological products and process engineering; Biotechnologically relevant enzymes and proteins; Bioenergy and biofuels; Applied genetics and molecular biotechnology; Genomics, transcriptomics, proteomics; Applied microbial and cell physiology; Environmental biotechnology; Methods and protocols. Moreover, topics in biosensor technology, like sensors that incorporate enzymes, antibodies, nucleic acids, whole cells, tissues and organelles, and other biological or biologically inspired components will be considered, and topics exploring transducers, including those based on electrochemical and optical piezoelectric, thermal, magnetic, and micromechanical elements. Chapters exploring biomaterial approaches such as polymer synthesis and characterization, drug and gene vector design, biocompatibility, immunology and toxicology, and self-assembly at the nanoscale, are welcome. Finally, the tissue engineering subcategory will support topics such as the fundamentals of stem cells and progenitor cells and their proliferation, differentiation, bioreactors for three-dimensional culture and studies of phenotypic changes, stem and progenitor cells, both short and long term, ex vivo and in vivo implantation both in preclinical models and also in clinical trials.",annualVolume:11405,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/9.jpg",editor:{id:"126286",title:"Dr.",name:"Luis",middleName:"Jesús",surname:"Villarreal-Gómez",fullName:"Luis Villarreal-Gómez",profilePictureURL:"https://mts.intechopen.com/storage/users/126286/images/system/126286.jpg",institutionString:null,institution:{name:"Autonomous University of Baja California",institutionURL:null,country:{name:"Mexico"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"35539",title:"Dr.",name:"Cecilia",middleName:null,surname:"Cristea",fullName:"Cecilia Cristea",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYQ65QAG/Profile_Picture_1621007741527",institutionString:null,institution:{name:"Iuliu Hațieganu University of Medicine and Pharmacy",institutionURL:null,country:{name:"Romania"}}},{id:"40735",title:"Dr.",name:"Gil",middleName:"Alberto Batista",surname:"Gonçalves",fullName:"Gil Gonçalves",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYRLGQA4/Profile_Picture_1628492612759",institutionString:null,institution:{name:"University of Aveiro",institutionURL:null,country:{name:"Portugal"}}},{id:"211725",title:"Associate Prof.",name:"Johann F.",middleName:null,surname:"Osma",fullName:"Johann F. Osma",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSDv7QAG/Profile_Picture_1626602531691",institutionString:null,institution:{name:"Universidad de Los Andes",institutionURL:null,country:{name:"Colombia"}}},{id:"69697",title:"Dr.",name:"Mani T.",middleName:null,surname:"Valarmathi",fullName:"Mani T. Valarmathi",profilePictureURL:"https://mts.intechopen.com/storage/users/69697/images/system/69697.jpg",institutionString:"Religen Inc. | A Life Science Company, United States of America",institution:null},{id:"205081",title:"Dr.",name:"Marco",middleName:"Vinícius",surname:"Chaud",fullName:"Marco Chaud",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSDGeQAO/Profile_Picture_1622624307737",institutionString:null,institution:{name:"Universidade de Sorocaba",institutionURL:null,country:{name:"Brazil"}}}]}]}},libraryRecommendation:{success:null,errors:{},institutions:[]},route:{name:"profile.detail",path:"/profiles/18356",hash:"",query:{},params:{id:"18356"},fullPath:"/profiles/18356",meta:{},from:{name:null,path:"/",hash:"",query:{},params:{},fullPath:"/",meta:{}}}},function(){var e;(e=document.currentScript||document.scripts[document.scripts.length-1]).parentNode.removeChild(e)}()