바이오엔지니어링개론1 INTRODUCTION - melab.snu.ac.krmelab.snu.ac.kr/melab/lib/exe/fetch.php?media=data:chapter1and2.pdf · TEXTBOOK • “Introduction to Biomedical Engineering”

바이오엔지니어링개론 1INTRODUCTION

September 1, 2011Hee Chan Kim

TEXTBOOK

• “Introduction to Biomedical Engineering” 2nd Edition by John Enderle, Susan Blanchard, Joseph Bronzino

• Purpose of the textbook : to serve as an introduction to and overview of the field of biomedical engineering

• Coverage : major fields of activity in which biomedical engineers are engaged

• 1000 page-thick

Class Schedule순번 화요일 주제 담당교수 목요일 주제 담당교수

1 09월 01일 Ch. 1&2 Introduction 김희찬

2 09월 06일 Ch. 8 Biomedical Instrumentation 김희찬 09월 08일 Ch. 9 Biomedical Sensors 김희찬

3 09월 13일 추석 09월 15일 Ch. 3 Physiology & Anatomy 최진욱

4 09월 20일 Ch. 3 Physiology & Anatomy 최진욱 09월 22일 Ch. 13 Genomics & Bioinformatics 윤형진

5 09월 27일 Ch. 14 Genomics & Bioinformatics 윤형진 09월 29일Ch. 9 In vitro Diagnostics

Technology김영수

6 10월 04일Ch. 9 In vitro Diagnostics

Technology김영수 10월 06일 Ch. 10Biomedical Signal Processing 박광석

7 10월 11일Ch. 10Biomedical Signal

Processing박광석 10월 13일 Ch.11Biomedical Signal Processing 박광석

8 10월 18일 Ch.11Biomedical Signal Processing 박광석 10월 20일 Mid term Exam

9 10월 25일Ch. 6 Biomaterial & Tissue Engineering

최영빈 10월 27일Ch. 6 Biomaterial &Tissue Engineering

최영빈

10 11월 01일Ch.7 Biomaterial &Tissue Engineering

최영빈 11월 03일Ch. 7 Biomaterial &Tissue Engineering

최영빈

11 11월 08일 Ch. 4 Biomechanics 이정찬 11월 10일 Ch. 4 Biomechanics 이정찬

12 11월 15일 Ch. 5 Biomechanics 이정찬 11월 17일Ch.12 Modeling, Simulation &

Control김성완

13 11월 22일Ch. 12 Modeling, Simulation &

Control김성완 11월 24일 Ch. 15 Medical Imaging 김희찬

14 11월 29일 Ch. 16 Medical Imaging 김희찬 12월 01일 Ch. 16 Medical Imaging 김희찬

15 12월 06일 Ch. 17 Medical Imaging 김희찬 12월 08일 Final Exam

Class Introduction

• 1 chapter per 1 week• Homepage : http://melab.snu.ac.kr

Lecture 2011-2학기 ‘바이오엔지니어링개론 I’

• Overview and Introduction : shallow and wide knowledge

1 BIOMEDICAL ENGINEERING: A HISTORICAL PERSPECTIVE

Lecture Contents

• What is ‘Engineering’ ?– Difference between ‘Science’ and

‘Engineering’

• What is ‘Biomedical Engineering’?– Distinction from other conventional

engineering disciplines

• Contributions of ‘Biomedical Engineering’ to Modern Healthcare System

What is ‘Engineering’?

• “Engineering is the creation, maintenance, and development of things that have not existed in the natural world and that satisfy some human desire or need.”

• “Science studies what is; Engineering creates what never was.” - Theodore van Karman -

What is ‘Engineering’?

• Scientists make knowledge with money. Engineers make money with knowledge.

• Scientists pursue 1% of possibility, Engineers try to eliminate 1% of uncertainty.

1.3 What is ‘Biomedical Engineering’?

• Biomedical Engineering is one of engineering disciplines

• Biomedical Engineering involves;– applying the concepts, knowledge, and

approaches of virtually all engineering disciplines (e.g., electrical, mechanical, and chemical engineering) to solve specific healthcare related problems

– the application of principles in bio-systems to solve engineering problems

“For the diseased & the disabled”

“For the healthier life”

&

BiomedicalEngineering

Biology Medicine

Biomedical Science

EngineeringM

ETHO

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the application of engineering concepts and technologies to solve biological and medical problems

the application of principles in bio-systems to solve

engineering problems

Biomedical Engineering

• Opportunities for interaction between engineers and healthcare professionals are many and varied.

• Effective communication skill is essential– Terminologies & Attitude


• Biomedical Engineering– from being concerned primarily with the

development of medical devices in the 1950s and 1960s to include a more wide-ranging set of activities (Fig. 1.9)

• Bioengineering : – the broad umbrella term used to

describe this entire field– a basic-research-oriented activity closely

related to biotechnology and genetic engineering


• Biological Engineering• Clinical (or medical) Engineer

– Biomedical engineers working within a hospital or clinic (Fig. 1.10)

– first encouraged to enter the clinical scene during the late 1960s in response to concerns about the electrical safety of hospital patients.

1.4 Roles Played by Biomedical Engineers

• Biomedical Engineering involves training essentially three types of individuals:(1) the clinical engineer in health care : the ‘‘problem

solver.’’ This biomedical engineer (most likely the clinical engineer or biomedical design engineer) maintains the traditional service relationship with the life scientists who originate a problem that can be solved by applying the specific expertise of the engineer.

(2) the biomedical design engineer for industry : ‘‘technological entrepreneur’’ (most likely a biomedical design engineer in industry). This individual assumes that the gap between the technological education of the life scientist or physician and present technological capability has become so great that the life scientist cannot pose a problem that will incorporate the application of existing technology.

(3) the research scientist : the ‘‘engineer–scientist’’ (most likely found in academic institutions and industrial research labs), is primarily interested in applying engineering concepts and techniques to the investigation and exploration of biological processes.

1.5 Professional Status of Biomedical Engineering

• Biomedical engineers are professionals.– Serve clients (society)– Licensing– Code of ethics

• the status of professionalization by the occurrence of six crucial events: – (1) the first training school; – (2) the first university school; – (3) the first local professional association;– (4) the first national professional association;– (5) the first state license law; and – (6) the first formal code of ethics.

• The field of biomedical engineering,– all six of these critical steps have been taken– originated as a professional group interested primarily in

medical electronics in the late 1950s,

1.6 Professional Societies• The American Institute for Medical and Biological

Engineering (AIMBE, 1992) to serve as an umbrella organization in the United States for the purpose of unifying the bioengineering community,– the American College of Clinical Engineering– the American Institute of Chemical Engineers– the American Medical Informatics Association– the American Society of Agricultural Engineers– the American Society for Artificial Internal Organs– the American Society of Mechanical Engineers– the Association for the Advancement of Medical

Instrumentation– the Biomedical Engineering Society (BMES)– the IEEE Engineering in Medicine and Biology Society– an interdisciplinary Association for the Advancement of

Rehabilitation and Assistive Technologies– the Society for Biomaterials.

Preference of BME

1.1 Evolution of the Modern Health Care System

• Using instrument :

– Skulls with holes by trephiners for treatment of extreme pain

(migraine) or attacks of falling to the ground (epilepsy)

• Interrelationships between the supernatural and

one’s health :

LEFT TO RIGHT: The Eye of Horus(symbol of recovery), the symbol for Jupiter, and the Rx symbol share similar elements.


• B.C. 3000 : Egyptian doctor, Imhotep• B.C. 1000 : medicine was already a highly respected

profession in Greece– Asclepius : the god of medicine and healing in ancient Greek

mythology.– First hospitals : sanatorium with religious overtones

Figure 1.1 Illustration of a sick child brought into the Temple of Aesculapius (Courtesy of http://www.nouveaunet.com/images/ art/84.jpg).


• Hippocrates (B.C. 460-370)– father of medicine– taught disease as a natural process– founder of the rational art of medicine

• Roman Empire (BC 27-AD476)– contribution to public health– “first aid” in battle field and “base hospital”– sewer systems and aqueduct– Galen (Greek) : greatest physician in the history of Rome


• Dark ages (AD476 – AD1000) – teaching of the Catholic church made medical research

stagnated– Christianity : charity for sick and poor, monastic medicine,

evolution of modern hospital[ from Latin ‘hospes’ meaning “host” or “guest”]

• Renaissance (14c – 17c)– significant progress in the science of medicine– study of human anatomy in painting : Michelangelo, Raphael,

Durer, and Leonardo da Vinci– new medical schools embraced the Hippocratic doctrine : the

patient was human, disease was a natural process, and commonsense therapies


• Renaissance (14c – 17c)– The age of examination and measurement– In 1592, Galileo lectured on mathematics to medical

students (in Pauda, Italy), demonstrated thermoscope, pendulum, and telescopic lens, encouraged physicians the use of scientific tools

– Sanctorius (Galileo’s student): comparative studies of human temperature and pulse

– William Harvey (graduate of Pauda) : applied Galileo’s laws of motion and mechanics to the problem of blood circulation

– In England, Henry VIII (1491-1547) : the oldest medical institution, “the College of Physicians”, doctors and medical students replaced the nursing sisters and monk physicians


• 18C in France and American colonies :– humanitarian and democratic movements in

concerned equal rights and welfare of people

– hospital remained a place to avoid : high death rate (25% patients, 6~12% attendants)

– First American hospital was delayed: the Pennsylvania Hospital (1751), Massachusetts General (1821)

– Florence Nightingale (1820-1910) : improved nursing practices


• American hospitals a century ago– 324 charity and 24 pay beds (Johns Hopkins Hospital in

1870s)

– not admit contagious diseases or incurables

– surgery admissions only 5%

– simple provisions of cooking and washing facilities

1.2 The Modern Health Care System• 20C : explosion in scientific knowledge

and technology– technological innovation gave physicians

enormous power– 1895 Wilhelm Conrad Röntgen : x-ray (the first

Nobel Prize in Physics in 1901)– 1903 William Einthoven : first

electrocardiograph– mid-1930s sulfanilamide : inhibit the growth of

streptococci in mice– early 1940 penicillin

1.2 The Modern Health Care System

• 20C : explosion in scientific knowledge & technology– blood type 1900, sodium citrate 1913– blood bank 1930s with adequate refrigeration technology

• American Nobel Prize winner in physiology and medicine : possible by the technology available to clinical scientists– 1900~1929 : 0 mostly from Europe– 1930~1944 : 7– 1945~1975 : 37– 1975~2003 : 40

• Development of complex surgical procedures– Drinker respirator 1927

– Heart-lung machine 1939

– Cardiac catheterization 1940s


Iron lung ward filled with Polio patients, Rancho Los Amigos Hospital, California. 1953

A Heart-Lung Machine (upper right) in a coronary artery bypass surgery.


• Development of complex surgical procedures– Electron microscope 1950s

– Atomic age : nuclear medicine

• Medicine began to change to accommodate the new technology

Electron microscope constructed by Ernst Ruska in 1933


• World War II– Military technology for peaceful application– Science and technology : cause and effect

• Gunnery – Ballistics• Steam Engine – Thermodynamics• Powered Flight – Aerodynamics

• The realm of electronics– Pursuit of knowledge that was undertaken with technical

uses in mind.– Telemetry, Computer (Apollo Project, 1969)– complex calculations, keeping records (via artificial

intelligence) and even controlling the very instrumentation


• Electronics - Medical Imaging– CT, PET, US, MRI

A Multislice CT Scanner: Philips 'Brilliance' 64-channel thin-slice

Modern 3 tesla clinical MRI scanner.

Image of a typical positron emission tomography (PET)

facility Medical sonographic instrument


• Spare part surgery– Kidney transplantation 1954– artificial heart valves– artificial blood vessels– Artificial heart– Liver transplantation– Surgery plays a prominent role

• Hospital became the central institution– Role of the Emergency ward– This evolutionary process became inevitable as technology

produced increasingly sophisticated equipment

• In 21C, technology has struck medicine like a thunderbolt.– Human genome project (1990~2003)

• Some of the engineering products vital to the effort included automatic sequencers, robotic liquid handling devices, and software for databasing and sequence assembly.

– Nanotechnology



• New Technologies– Laser Surgery

– Tele/Ubiquitous Healthcare

– EMR

– Tissue Engineering, stem cell treatment, regenerative medicine

2 MORAL AND ETHICAL ISSUES

Lecture Contents

• 3 “Things” in Medicine – Medical Device, Drug, Biological Subjects

• Medical Devices– Definition and Law/Regulations– Characteristics and Development

• Clinical Trial – moral and ethical issues

의사의 도구

약 의료기기

생물학적제재

지식과 수기

Medical Devices : the things that

Biomedical Engineers provide

의료기기법“의료기기”라 함은 사람 또는 동물에게 단독 또는조합하여 사용되는 기구ㆍ기계ㆍ장치ㆍ재료 또는 이와유사한 제품으로서 다음 각호의 1에 해당하는 제품을말한다. (다만, 약사법에 의한 의약품과 의약외품 및 장애인복지법 제55조의 규정에 의한 재활보조기구 중 의지(義肢)ㆍ보조기(補助器)를 제외한다.)

1. 질병의 진단ㆍ치료ㆍ경감ㆍ처치 또는

예방의 목적으로 사용되는 제품

2. 상해 또는 장애의 진단ㆍ치료ㆍ경감 또는

보정의 목적으로 사용되는 제품

3. 구조 또는 기능의 검사ㆍ대체 또는

변형의 목적으로 사용되는 제품

4. 임신조절의 목적으로 사용되는 제품

"an instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article, including a component part, or accessory which is:

• recognized in the official National Formulary, or the United States Pharmacopoeia, or any supplement to them,

• intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease, in man or other animals, or

• intended to affect the structure or any function of the body of man or other animals, and which does not achieve any of it's primary intended purposes through chemical actionwithin or on the body of man or other animals and which is not dependent upon being metabolized for the achievement of any of its primary intended purposes."

Medical Device Definition

의료기기의 등급분류

• 1등급 : 인체에 직접 접촉되지 아니하거나 접촉되더라도 잠재적 위험성이 거의 없고, 고장이나 이상으로 인하여 인체에 미치는 영향이 경미한 의료기기

• 2등급 : 사용 중 고장이나 이상으로 인한 인체에 대한위험성은 있으나 생명의 위험 또는 중대한 기능장애에직면할 가능성이 적어 잠재적 위험성이 낮은 의료기기

• 3등급 : 인체 내에 일정기간 삽입되어 사용되거나, 잠재적 위험성이 높은 의료기기

• 4등급 : 인체 내에 영구적으로 이식되는 의료기기, 심장ᆞ중추 신경계ᆞ중앙혈관계 등에 직접 접촉되어 사용되는 의료기기, 동물의 조직 또는 추출물을 이용하거나 안전성 등의 검증을 위한 정보가 불충분한 원자재를 사용한 의료기기

의료기기의 등급분류

• 1등급 : 검안경(Ophthalmoscope)

• 2등급 : 심전계(ECG)

• 3등급 : 인공신장기(Hemodialyzer)

• 4등급 : 인공심장 박동기(pacemaker)

1. 의료용 영상을 저장, 확대, 축소, 조회 등 하는 장치2. 의료용 영상을 저장, 확대, 축소, 조회와 함께 분석, 전송

처리하는 장치 및 출력하는 장치3. 의료용 영상을 획득하여 모의치료, 모의시술 등에 사용하

는 장치4. 의료용 영상을 전산진단기능(CAD) 등 상기 목적 이외에

사용하는 기구

Regulatory Categories of Medical Devices

• Class I general controls. Manufacturers are required to perform registration, premarketing notification, record keeping, labeling, reporting of adverse experiences, and good manufacturing practices(GMP). These controls apply to all three classes.

• Class II premarket notification. Most medical devices are cleared for commercial distribution in the U.S. (after May 8, 1976) by the premarket notification [510(k)] process. The purpose of a 510(k) is to demonstrate that the medical device to be marketed is substantially equivalent (SE) to a legally marketed device that was or is currently on the U.S. market.

• Class III premarketing approval. PreMarket Approval(PMA) is required for devices used in supporting or sustaining human life and preventing impairment of human health. The FDA has extensively regulated these devices by requiring manufacturers to prove their safety and effectiveness prior to market release.

의료기기 취급자의 의무

• 의료법에 의한 의료기관개설자(의사) 및 수의사법에 의한 동물병원개설자, 의료기기제조업자, 의료기기수입업자, 의료기기수리업자, 의료기기판매업자, 의료기기임대업자

• (부작용 관리) 의료기기취급자는 의료기기를 사용하는 도중에 사망 또는 인체에 심각한 부작용이 발생하였거나 발생할 우려가 있음을 인지한 경우에는 이를 식품의약품안전청장에게 즉시 보고하고 그 기록을 유지하여야 한다.

제조품목허가 및 신고의 대상

• 허가대상 :

- 지정된 등급이 2등급ᆞ3등급 또는 4등급인 품목

- 지정된 등급이 1등급인 품목 중 이미 허가를 받거나 신고한 품목과 구조ᆞ원리ᆞ성능ᆞ사용목적또는 사용방법 등이 본질적으로 동등하지 아니한품목

• 신고대상 :

- 지정된 등급이 1등급인 품목 중 이미 허가를 받거나 신고한 품목과 구조ᆞ원리ᆞ성능ᆞ사용목적및 사용방법 등이 본질적으로 동등한 품목

2.9 REGULATION OF MEDICAL DEVICE INNOVATION

• Food and drugs have been regulated by the FDA since 1906, medical devices first became subject to FDA regulation in 1938 to ensure that legitimate medical devices were in the marketplace and were truthfully labeled, not misbranded

• The first substantive legislative attempt to address the premarket review of all medical devices occurred with the Medical Device Amendment of 1976 which requires approval from the FDA before new devices are marketed and impose requirements for the clinical investigation of new medical devices on human subjects.

• 5 major program centers of FDA : Center for Devices and Radiological Health (CDRH)

• 6 distinct offices located within the CDRH : Office of Device Evaluation (ODE)

2.10 MARKETING MEDICAL DEVICES• 510(k) notification • Premarket Approval (PMA)• Investigational Device Exemption (IDE) – solely intended

for investigational use on human subjects• Product Development Protocol (PDP) – alternative to

IDE and PMA• With respect to clinical research on humans, the FDA

divides devices into two categories: devices that pose significant risk and those that involve insignificant risk.

• Clinical research involving a significant risk device can not begin until an Institutional Review Board (IRB) has approved both the protocol and the informed consent form, and the FDA itself has given permission.

• The FDA allows unapproved medical devices to be used without an IDE in three types of situations: feasibility studies, emergency use, and treatment use.

ClinicalUse

Idea

Commercialization Process of Medical Instruments

Prototype

BenchTest

AnimalTest

ClinicalTest

Approval

Production

HIRA

SampleTest(PMS)인증

Death Valley

개 발 평 가의료기기 R&D

의료기기 R&D

기술개발 생체내 평가

Idea/Technology Safety/Efficacy

Short-term Long-term

Deterministic Statistics/Ethics

Engineering Biomedicine

Interwound

개발 평가

의료기기 R&D

Idea

Design

Simulation

Prototype

Test

Proposal

IACUC

Animal Model

Animal Test

Analysis

Proposal(P.I.확보)

IRB

GMP/기술문서(제조사확보)

KFDA

Subject Recruit

Clinical Test

Analysis

의료기기의 임상시험

• 임상시험(Clinical Investigation) : 의료기기의 안전성과 유효성을 증명하기 위하여사람을 대상으로 실시하는 시험 또는 연구

• 대 상:– 식품의약품안전청 지정 : 3,4등급

– 제조, 판매업자 요청 : 전등급

• 절 차:– 서울대학교병원 의료기기 IRB(Institutional

Review Board)

– 식품의약품안전청장

2.6 HUMAN EXPERIMENTATION

(Clinical Trial)• To determine their effectiveness and value,

the new drugs and medical devices eventually are used on humans

• The issue is not only whether humans should be involved in clinical studies designed to benefit themselves or their fellow humans but also clarifying or defining more precisely the conditions under which such studies are to be permitted.

2.8 INFORMED CONSENT• It is the principal condition that must be satisfied for

human experimentation to be considered both lawful and ethical.

• An attempt to preserve the rights of individuals by giving them the opportunity for self-determination, that is, to determine for themselves whether they wish to participate in any experimental effort.

• In 1964 the World Medical Association(WMA) in Finland endorsed a code of ethics for human experimentation as an attempt to provide some guidelines in this area.

• In October 2000 the 52nd WMA General Aasembly in Edinburgh, Scotland revised these guidelines.

의료기기임상시험계획승인

임상시험계획승인신청(Clinical Investigational

Medical Device Application) : 해당 의료기기를 사용하

여 인체를 대상으로 안전성•유효성자료 수집을 목적으로 임상

시험을 실시하고자 하는 자가 식품의약품안전청장(이하 ”청

장“이라 한다)의 승인을 신청하는 것을 말한다.

임상시험용 의료기기의 치료적 사용(Treatment Use of

an Investigational Device): 생명을 위협하는 중대한 질

환 등을 가진 환자를 치료하기 위하여 임상시험용 의료기기를

인도적 차원에서 사용하는 것을 말한다.

응급사용(Emergency Use): 임상시험계획을 승인하기

전, 응급한 경우에 임상시험용 의료기기를 사용할 수 있도록

한 것을 말한다.

의료기기 임상시험 절차도

IRB

• IRB(Institutional Review Board)– 임상시험심사위원회– 의학연구윤리심의위원회– 임상연구를 위한 연구계획서 심사

IRB의 설립

• 1974년 터스키기 실험이후 연구윤리 심의를의무화함

• 정부의 허가를 받아야하는 약, 의료기기, 생물학적 제재(백신, 유전자등) 연구의 심의

• 기타 정부가 지원하는 인체관련 모든 연구• 정부 감독기관이 대학등 연구기관과 맺고,

연구자 윤리 교육 및 윤리 심의를 받도록 함

IRB의 구성

• 임상시험의 윤리적, 과학적, 의학적 측면을 검토, 평가할 수 있는 경험과 자격을 갖춘 위원– 5인이상– 1인 이상의 의학, 치의학, 한의학, 또는 간호학 외

의 전공을 가진자 (nonscientific area, 우리나라는주로 종교계 인사가 많음)

– 1인 이상의 해당 시험기관과 관련이 없는자

• 연구자 및 직접 관련이 있는 위원은 결정과정에 참여하거나 의견을 제시하지 못함

IRB의 임무

• 피험자의 권리, 안전, 복지를 보호• 특별히 취약한 피험자들의 안전 보호

– 수감자, 어린이, 정신질환자,시설아동, 군인, 죄수, 학생 등

• 특별히 윤리적 측면에서의 고려 검토– 비치료적 임상시험을 대리인 동의하에 실시하는 경우– 사전동의가 불가능한 경우 (응급상황에서의 연구)

• 연구책임자의 적합성 여부 검토• 적어도 1년 1회 이상 지속적 검토

2.14 THE ROLE OF BIOMEDICAL ENGINEER IN THE FDA PROCESS

• Biomedical engineers need to be aware of FDA regulations and the process for FDA approval of the use of medical devices and systems.

• These regulatory polices are, in effect, society’s mechanism for controlling the improper use of these devices.

Documents

바이오엔지니어링개론1 INTRODUCTION - melab.snu.ac.krmelab.snu.ac.kr/melab/lib/exe/fetch.php?media=data:chapter1and2.pdf · TEXTBOOK • “Introduction to Biomedical Engineering”