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Principles and Applications of RF/Microwave in Healthcare and Biosensing Principles and Applications of RF/Microwave in Healthcare and Biosensing Edited by Changzhi Li Mohammad-Reza Tofighi Dominique Schreurs Tzyy-Sheng Jason Horng AMSTERDAM(cid:129)BOSTON(cid:129)HEIDELBERG(cid:129)LONDON NEWYORK(cid:129)OXFORD(cid:129)PARIS(cid:129)SANDIEGO SANFRANCISCO(cid:129)SINGAPORE(cid:129)SYDNEY(cid:129)TOKYO AcademicPressisanimprintofElsevier AcademicPressisanimprintofElsevier 125LondonWall,LondonEC2Y5AS,UnitedKingdom 525BStreet,Suite1800,SanDiego,CA92101-4495,UnitedStates 50HampshireStreet,5thFloor,Cambridge,MA02139,UnitedStates TheBoulevard,LangfordLane,Kidlington,OxfordOX51GB,UnitedKingdom Copyright©2017ElsevierInc.Allrightsreserved. Nopartofthispublicationmaybereproducedortransmittedinanyformorbyanymeans,electronicor mechanical,includingphotocopying,recording,oranyinformationstorageandretrievalsystem,without permissioninwritingfromthepublisher.Detailsonhowtoseekpermission,furtherinformationaboutthe Publisher’spermissionspoliciesandourarrangementswithorganizationssuchastheCopyrightClearance CenterandtheCopyrightLicensingAgency,canbefoundatourwebsite:www.elsevier.com/permissions. ThisbookandtheindividualcontributionscontainedinitareprotectedundercopyrightbythePublisher (otherthanasmaybenotedherein). Notices Knowledgeandbestpracticeinthisfieldareconstantlychanging.Asnewresearchandexperiencebroaden ourunderstanding,changesinresearchmethods,professionalpractices,ormedicaltreatmentmaybecome necessary. Practitionersandresearchersmustalwaysrelyontheirownexperienceandknowledgeinevaluating andusinganyinformation,methods,compounds,orexperimentsdescribedherein.Inusingsuchinformation ormethodstheyshouldbemindfuloftheirownsafetyandthesafetyofothers,includingpartiesfor whomtheyhaveaprofessionalresponsibility. Tothefullestextentofthelaw,neitherthePublishernortheauthors,contributors,oreditors,assume anyliabilityforanyinjuryand/ordamagetopersonsorpropertyasamatterofproductsliability,negligence orotherwise,orfromanyuseoroperationofanymethods,products,instructions,orideascontained inthematerialherein. BritishLibraryCataloguing-in-PublicationData AcataloguerecordforthisbookisavailablefromtheBritishLibrary LibraryofCongressCataloging-in-PublicationData AcatalogrecordforthisbookisavailablefromtheLibraryofCongress ISBN:978-0-12-802903-9 ForInformationonallAcademicPresspublications visitourwebsiteathttps://www.elsevier.com Publisher:JoeHayton AcquisitionEditor:TimPitts EditorialProjectManager:CharlotteKent ProductionProjectManager:MelissaRead Designer:GregHarris TypesetbyMPSLimited,Chennai,India List of Contributors M. Baboli ColumbiaUniversity,NY, United States O. Boric´-Lubecke University ofHawaii, Manoa, HI, United States J.-C. Chiao University ofTexas atArlington,Arlington,TX, United States R. Go´mez-Garcı´a University ofAlcala´,Madrid, Spain T.-S.J. Horng NationalSun Yat-Sen University,Kaohsiung, Taiwan C. Li Texas Tech University, Lubbock, TX,UnitedStates V. Lubecke University ofHawaii, Manoa, HI, United States M. Mercuri Holst Centre,IMEC,Eindhoven, Netherlands J.-M.Mun˜oz-Ferreras University ofAlcala´,Madrid, Spain J. Oberhammer KTH Royal InstituteofTechnology,Stockholm, Sweden A. Rahman University ofHawaii, Manoa, HI, United States D.M.M.-P. Schreurs KU Leuven, Leuven,Belgium M.-R. Tofighi PennsylvaniaStateUniversity,Harrisburg, PA,UnitedStates F. To¨pfer KTH Royal InstituteofTechnology,Stockholm, Sweden F.-K. Wang NationalSun Yat-Sen University,Kaohsiung, Taiwan xi Introduction BACKGROUND Healthcare is a top global challenge due to the ever-increasing demand for higher quality of life, the aging population, and the various social, cultural, political, and economic impacts. While the productivity and stability of society are dependent on the outcomes of healthcare, the rising costs of medical care are impacting almost everyone in the world. Due to the aging of populations and the prevalence of chronic diseases, there is a strong demand to use advanced technologies to shoulder the burdens of individuals and healthcare systems in both developing and developed countries. In recent years, a significant growth of research that uses engineering innova- tions to improve the efficacy while reducing the cost of health provision has been taking place. Among these efforts, radio frequency (RF) and microwave technolo- gies play a critical role in disease diagnosis, care delivery, and telemedicine. Researchers have devoted a lot of efforts to the monitoring and imaging applica- tions of RF/microwave technologies, some of which have entered or are being tested for clinical use. They also apply wireless sensing and communication over or through body tissues to transmit physiological or biochemical information. In addition, based on the biological effects caused by electromagnetic waves inter- acting with tissues, microwave diagnosis and treatment of diseases in living sys- tems are under rapid development, generating significant impacts in fields such as biosensing andhyperthermia. Although RF/microwave engineering is a well-established discipline with many applications such as wireless communication and wireless power transfer, using RF/microwave technology for healthcare and biosensing involves special grand challenges. Most conventional RF/microwave systems rely on electro- magnetic waves that propagate in homogeneous and isotropic media. However, when applying the same discipline to biomedical applications, tremendous puz- zles are presented due to the anatomical, physiological, and biochemical varia- tions in human bodies. Moreover, the problems are compounded by realistic issues such as the lack of simulation models and experimental data, difficulty in conducting tests because studies strongly depend on human subjects, unmeasur- able effects in biological systems, difficulty unifying protocols and conducting experiments, safety issues in human studies, as well as practical constraints in clinical implementation. In addition, another barrier that is difficult to break is the large gap between the languages and mindsets of engineers and healthcare practitioners. xiii xiv Introduction Therefore, there is a strong demand for both engineering and clinical research- ers to understand the achievements and future directions in the development of microwave technologies for the fast-growing biomedical fields. It is believed that more clinical, pharmaceutical, and biochemical aspects can be addressed if researchersandpractitionersfromdifferentfieldsaremadeawareofthemultitude of possibilities, potential new applications, and challenges in future innovative healthcare solutions. RECENT PROGRESS ON RF/MICROWAVE BIOMEDICAL RESEARCH Important recent progress on RF/microwave biomedical research can be roughly dividedintotwocategories. Oneis thebiological interaction andeffects;the other is RF systemsand instrumentation for healthcare applications. Researchers have been intensively studying the mechanisms, effects, and applications of the interaction of electromagnetic waves with biological materials at molecular, cellular, and tissue levels. On one hand, a large number of devices and components on circuit-board and integrated-chip levels have been developed for microwave characterization of biological materials and living systems. Based on these devices, therapeutic and diagnostic applications have been proposed and some of them are being clinically tested. Examples of typical applications include the diagnosis of malignant tumors and lab on chip for real-time complex body fluid analysis. On the other hand, RF/microwave energy is used to treat diseases intherapeuticandsurgicalapplications. Examplesinclude hyperthermia andmini- mally invasive natural orifice transluminal endoscopic surgery, which in general can improve treatment efficiency, reduce pain, and shorten the recovery time for patients. In the meantime, there are abundant systems and instrumentations for health- care applications developed based on RF/microwave technologies. Prime examples are magnetic resonance imaging (MRI) and microwave imaging. MRI, whose invention has been honored by several Nobel Prizes, has been widely adopted in clinical practice to benefit the well-being of human society. Microwave and millimeter-wave imaging have shown their advantages and daily uses not only in health applications, but also in security systems. Another area that has caught the attention of many researchers and practitioners is that of wire- less sensors and systems for health monitoring and telemedicine. For example, wireless signals are utilized to noninvasively measure physiological signals and biological signals at doctors’ offices, in health-care facilities, or even at home; they can also transmit signals between sensors and stimulators implanted in the human body and external wearable controllers for further transmission, proces- sing, and control, forming a closed-loop system for continuous and autonomous management of disease symptoms. Introduction xv ABOUT THIS BOOK This book aims to help authors learn the multiple directions in which RF/micro- wave technologies are heading toward healthcare and biosensing applications, the achievements that have been made so far, and the challenges for researchers to solve in the near future. Chapter 1 by Li and Schreurs reviews the fundamentals of microwave engineering, which will be used in the other chapters of this book. Since microwave engineering is a discipline that has gone through many years of development, Chapter 1 only illustrates basic knowledge and is aimed at helping readers from other disciplines to understand the basic principles relevant to this book. Therefore, readers with good microwave engineering background can skip that chapter. In Chapter 2, Interaction between electromagnetic waves and biolog- ical materials, by Tofighi, the modeling and measurement procedure for electro- magnetic properties of biological materials, namely complex permittivity, is described, which serves as the foundation for the interaction between RF/micro- wave and biological materials. The chapter also covers issues related to interfac- ing with tissue through sensing probes, such as coaxial, microstrip, and coplanar waveguide transmission lines, providing a useful perspective that is beneficial to some other medical and biological applications discussed in this book. Chapter 3, Microwave cancer diagnosis, by To¨pfer and Oberhammer, focuses on microwave diagnosis of malignant tumors, based on the fact that a special microwave signa- ture has been observed for many malignant tumors. A multitude of techniques, including free-space quasi-optical techniques, near-field probes, microwave tomography, ultra-wideband radar, and passive microwave imaging, some of which have already entered clinical trials, are presentedfor the diagnosisofbreast cancer,skincancer,andbraintumors.Chapter 4,Wireless closed-loopstimulation systems for symptom management, by Chiao, presents closed-loop systems for autonomous management ofdisease symptoms, using examplesofneural andgas- tric electrical stimulation applications that target the management of neurological and gastric disorders. Wireless signal transduction and wireless power transfer mechanisms across tissues make it possible to eliminate batteries in the implants for long-term use and to reduce the implant size for endoscopic implementation. As a result, these systems can provide better care for patients who have chronic illness and improve the healthcare system with personalized medicine and lower costs. Starting from Chapter 5, Human-aware localization using linear-frequency- modulated continuous-wave radars, the rest of the book discusses biomedical radars for various healthcare applications. In Chapter 5, Human-aware localiza- tion using linear-frequency-modulated continuous-wave radars, Mun˜oz Ferreras, Go´mez Garc´ıa and Li present coherent linear-frequency-modulated continuous- wave radars. With a relatively simple hardware front-end, the solution is capable of both relative displacement and absolute range measurements, thus enabling versatile health care applications based on physiological motion sensing and human-aware localization. Chapter 6, Biomedical radars for monitoring health, by xvi Introduction Wang, Mercuri, Horng, and Schreurs. discusses in more depth specific applica- tions, such as vital signs monitoring, exercise assistance, and fall detection, show- ing the wide applicability of injection-locked radar and step-frequency continuous-wave radar. Finally, Chapter 7, RF/wireless indoor activity classifica- tion, by Rahman, Boric´-Lubecke, Lubecke and Baboli, applies biomedical radar to indoor activityclassification. We hope that this book will inspire the readers to develop their own ideas to leverage advanced RF/microwave technologies and devise innovative solutions in the highlyimportant field to benefit the well-beingof allhuman beings. We dedicate our respects to pioneers who started to apply RF/microwave technologies to healthcare and biosensing. We would also like to sincerely acknowledge the important supports provided by funding agencies, including the Belgian National Fund for Scientific Research (FWO), the European Institute of Innovation & Technology (EIT)—Health, the Ministry of Science and Technology (MOST) ofTaiwan, and the USNational Science Foundation(NSF). CHAPTER 1 Fundamentals of microwave engineering C.Li1and D.M.M.-P. Schreurs2 1TexasTechUniversity,Lubbock,TX,UnitedStates2KULeuven,Leuven,Belgium CHAPTER OUTLINE 1.1 Introduction.........................................................................................................2 1.2 TransmissionLinesTheory...................................................................................3 1.2.1 ASimpleModelofTransmissionLines.................................................3 1.2.2 ImpedanceandReflectionCoefficient..................................................5 1.2.3 SpecialCasesofTransmissionLines....................................................6 1.2.4 VoltageStandingWaveRatio...............................................................8 1.3 RFMatrices.........................................................................................................9 1.3.1 MatricesforCircuitAnalysis................................................................9 1.3.2 S-Parameters...................................................................................10 1.3.3 ConversionAmongtheMatrices.........................................................13 1.4 SmithChart........................................................................................................13 1.4.1 ReflectionCoefficientontheSmithChart...........................................14 1.4.2 RelationshipBetweenReflectionCoefficientandImpedance................15 1.4.3 AdmittanceontheSmithChart..........................................................16 1.4.4 UsefulRulesofSmithChartandImpedance/AdmittanceCalculation....16 1.5 ImpedanceMatching..........................................................................................18 1.5.1 MatchingWithLumpedElements......................................................19 1.5.2 MatchingbyTransmissionLines........................................................20 1.5.3 MatchingbyaQuarter-WaveTransformer............................................21 1.6 MicrowavePassiveComponents.........................................................................22 1.6.1 Three-PortPowerCouplers................................................................22 1.6.2 Four-PortPowerCouplers..................................................................27 1.7 MicrowaveActiveCircuits..................................................................................28 1.7.1 Amplifiers:Gain,NoiseFigure,Linearity,Stability,andEfficiency........28 1.7.2 Mixers:ActiveVersusPassive,NoiseFigure,Linearity..........................40 1.7.3 Oscillators:OscillatorStructures,PhaseNoise....................................43 C.Li,M.Tofighi,D.SchreursandT-Z.J.Horng(Eds):PrinciplesandApplicationsofRF/Microwave 1 inHealthcareandBiosensing. ©2017ElsevierInc.Allrightsreserved. 2 CHAPTER 1 Fundamentals of microwave engineering 1.8 SystemArchitectures.........................................................................................47 1.8.1 HeterodyneArchitecture....................................................................47 1.8.2 HomodyneArchitecture.....................................................................48 1.8.3 DoubleSidebandArchitecture...........................................................48 1.8.4 DirectIFSamplingArchitectures.......................................................49 1.8.5 OtherArchitectures...........................................................................50 Acknowledgments.....................................................................................................50 References...............................................................................................................50 1.1 INTRODUCTION The principles and applications of radio frequency (RF)/microwave in health- care and biosensing are strongly based on the analysis, design, and use of microwave components, circuits, and systems. “Microwave” refers to electro- magnetic waves from 1 to 300GHz, while RF is normally defined as the elec- tromagnetic wave frequencies from about 3kHz to 300GHz [1,2]. Therefore, RF and microwave combined cover a very large range of the electromagnetic spectrum and have many potential applications that interact with our daily life from the cell level to the human body level. To help readers better understand the analysis and the engineering techniques used in other chapters of this book, fundamentals of microwave engineering are presented in this chapter. The discussion starts from transmission lines, which are used in almost any RF/microwave circuit to carry high-frequency signals. It will then review S-parameters, which are the basic “language” for microwave measurements. Based on that, the Smith Chart and impedance matching will be introduced as important microwave circuits and systems design tools. With the help of these tools, microwave passive components (e.g., power dividers, combiners, and hybrids) and active building blocks (e.g., amplifiers, mixers, and oscillators) will be discussed. Finally, some fundamental RF/microwave system architec- tures will be presented. If a reader has been trained with microwave knowledge, she/he can skip this chapter. On the other hand, if the reader is from another discipline such as a healthcare profession, reading this chapter would help her/him to understand the technologies involved in various applications covered by the other chap- ters. However, it should be noted that microwave engineering and systems is based on a large engineering discipline that has gone through many years of development. Therefore, the contents of this chapter only illustrate the basic knowledge sets and principles. As readers go further into specific healthcare and biosensing topics in other chapters, they are encouraged to use the refer- ences or contact the chapter authors to get relevant information and sugges- tions on self-learning methods for the corresponding microwave theory and techniques topics.

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