Biomedical Devices and Sensors E-Book

Jérome Molimard

• Herausgeber: John Wiley & Sons
• Kategorie: Fachliteratur
• Sprache: Englisch

Veröffentlichungsjahr: 2024

Beschreibung

Monitoring the human body is a key element of digital health science. Low-cost sensors derived from smartphones or smartwatches may give the impression that sensors are readily available; however, to date, very few of them are actually medical devices.

Designing medical devices requires us to undertake a specific approach demanding special skills, as it concerns the integrity of the human body. The process is tightly framed by state regulations in order to ensure compliance with quality assessment, risk management and medical ethics requirements.

This book aims to give biomedical students an overview on medical devices design. It firstly gives a historical and economical approach, then develops key elements in medical device design with reference to EU and US regulations, and finally describes sensors for the human body. The clinical approach is presented as the central element in medical device qualification and this offers a perspective on the use of numerical simulation, particularly since its continued growth in the USA; despite the fact that the approach is strictly limited by regulations.

Leseprobe

Technological Prospects and Social Applications Set

coordinated byBruno Salgues

Volume 8

Biomedical Devices and Sensors

Jérôme Molimard

First published 2024 in Great Britain and the United States by ISTE Ltd and John Wiley & Sons, Inc.

Apart from any fair dealing for the purposes of research or private study, or criticism or review, as permitted under the Copyright, Designs and Patents Act 1988, this publication may only be reproduced, stored or transmitted, in any form or by any means, with the prior permission in writing of the publishers, or in the case of reprographic reproduction in accordance with the terms and licenses issued by the CLA. Enquiries concerning reproduction outside these terms should be sent to the publishers at the undermentioned address:

ISTE Ltd27-37 St George’s RoadLondon SW19 4EUUK

www.iste.co.uk

John Wiley & Sons, Inc.111 River StreetHoboken, NJ 07030USA

www.wiley.com

© ISTE Ltd 2024The rights of Jérôme Molimard to be identified as the author of this work have been asserted by him in accordance with the Copyright, Designs and Patents Act 1988.

Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s), contributor(s) or editor(s) and do not necessarily reflect the views of ISTE Group.

Library of Congress Control Number: 2024936647

British Library Cataloguing-in-Publication DataA CIP record for this book is available from the British LibraryISBN 978-1-78630-946-4

Foreword

Medical devices have a long history. It was in Egypt that the first traces of prostheses and orthoses were found. These major discoveries highlight the Egyptians’ mastery of textile manufacturing techniques, metallurgy and woodworking. These discoveries also show their medical knowledge, as well as their understanding of anatomical, morphological and aesthetic issues, the latter two being essential to help with the treatment.

The treatises by Galen and Amboise Paré demonstrate the constant progress of medical devices over the centuries, mainly concerning the development of war medicine.

It was especially from the 19th century, following on from the Industrial Revolution, that their development accelerated. The first implantable hip was invented in the late 19th century, and the first textile-based cardiovascular implants were created in the 1950s, as was the first pacemaker.

Medical devices are now fully fledged means of treatment and diagnosis. They are used in many pathological situations. Among them, there are products as varied as surgical masks, glasses, compression stockings, lumbar belts, orthopedic implants, X-ray machines, blood glucose measuring devices and, more recently, smartphone applications allowing for a more precise support of the patient in their daily life.

Scientific progress, in a more detailed understanding of pathologies, but also progress in engineering sciences such as materials, mechanics, electronics, numerical modeling and artificial intelligence, has made it possible to bring more complex and innovative medical devices to the market.

We are entering a new era in the 21st century. The growth of the population, which is expected to reach 10 billion by the end of the 21st century, its unprecedented ageing, and its growing sedentarization are all factors leading to an increase in chronic pathologies (diabetes, cardiovascular problems, musculoskeletal disorders, etc.) for which medical devices are the treatments of choice.

The availability of medical devices for healthcare professionals and patients has become an important issue. The increasing complexity of the products means that their components are produced and assembled in various locations across the world. Any geopolitical issues can have a direct impact on their availability and quality.

The processes for marketing authorization as well as for reimbursements have also been strengthened, as has the case for medicines. Marketing authorizations (CE marking in Europe, FDA approval in the United States, CFDA approvals in China, etc.), and even more so the conditions of access to reimbursement, differ between each major region of the world, and usually between each state. Often based on the compliance of medical devices with technical guidelines or standards, the marketing authorization and reimbursement require more and more. Due to the increasing complexity of the products, they use clinical trials in order to demonstrate their therapeutic efficacy.

The unique nature of medical devices makes it difficult to use the same clinical trial methodologies as for medicines. A placebo for a medical device is often impossible. This peculiarity means that different clinical trial techniques are used, and more recently the use of numerical models, or sensors, has emerged.

In this book, Professor Jérôme Molimard offers an extraordinary perspective on medical devices from their design to their launch on the market. The author describes in detail aspects that are very rarely addressed at the same time. This pedagogical approach first addresses the elements necessary for the implementation of the market, the conformity of which must be demonstrated from the design stage. The use of sensors and numerical models is then described in detail. These two types of tools are essential for the R&D phases, allowing considerable savings in terms of time to bring products to market. In the final part, the book discusses in more detail the methods used in clinical research and biostatistics necessary to demonstrate the efficacy of medical devices.

I am sure this book will be of interest to all students, engineers, health professionals and scientists wishing to better understand medical devices. It is a reference work for understanding their different aspects.

Reynald CONVERT

Technology and Intelligence Director

Thuasne

France

1Medical Device: Definition, History and Economic Background

1.1. Definition

Everyday life in hospitals can provide as many examples of medical devices as necessary to convince someone of the diversity and the significant importance of this sector in modern medicine: hip prostheses, insulin pumps, pacemakers, magnetic resonance imaging (MRI) devices, as well as syringes, crutches, wheelchairs or dressings. Despite their diversity, they all belong to the category of medical devices. A definition can be extracted from the Regulation (EU) 2017/745 of the European Parliament and of the Council of April 5, 2017.

“Medical device” means any instrument, apparatus, appliance, software, implant, reagent, material or other article intended by the manufacturer to be used, alone or in combination, for human beings for one or more of the following specific medical purposes:

diagnosis, prevention, monitoring, prediction, prognosis, treatment or alleviation of disease;

diagnosis, monitoring, treatment and alleviation of, or compensation for, an injury or disability;

investigation, replacement or modification of the anatomy or of a physiological or pathological process or state;

providing information by means of in vitro examination of specimens derived from the human body, including organ, blood and tissue donations, and which does not achieve its principal intended action by pharmacological, immunological or metabolic means, in or on the human body, but which may be assisted in its function by such means

.

The following products shall also be deemed to be medical devices:

devices for the control or support of conception;

products specifically intended for the cleaning, disinfection or sterilization of devices as referred to in Article 1(4) and in the first paragraph of this chapter.

As can be seen, the category of medical device is defined by its claim (human care, in a medical meaning) and by the means used (all means except pharmacological). It is interesting to see that software is mentioned in this definition, and thus, a piece of software that influences the medical process in some way is considered a medical device.

There is indeed a gray area between medical devices and other common devices. In this gray area lie most of the healthcare Internet of Things (IoT) gadgets or smartphone applications (e.g. cardiac monitoring, physical activity monitoring and brain sensing headbands). Most of these are not registered as medical devices and pretend to be sports or well-being applications, even if they target those who are anxious about their health and may suffer from chronic diseases. The quality of such measurement and/or processing, their influence on the customer’s health and the use of such amounts of personal data both by medical professionals or even private companies must be put into question by regulatory authorities as well as by the consumer themselves.

1.2. Examples of medical devices

The history of medical devices is directly related to that of techniques. It borrows from mechanics, optics, electronics and computer sciences and applies these to medicine. Surgeons in the Neolithic period performed brain surgery; copper dilators for urethral stenosis from the ancient Egyptians have been found; we could also refer to Mayan glasses. Should all of these be considered medical devices?

1.2.1. Surgery equipment

Audry and Ghislain (2009) consider that the history of modern medical devices begins in 1894 with E. Fournier, who commercialized the first syringe presenting industrial features, normalization and large diffusion. A few years later, in 1904, the “Dräger-Roth” inhalator, set-up in Germany, opened the way to modern anesthesia.

The hip prosthesis is a good example of advances in materials and material processing in a health application. At the beginning of the 20th century, surgeons tried to insert materials into the body to replace lost cartilage. But this created bio-compatibility or structure mechanics problems. The solution was found in the UK: totally replacing the joint. After an attempt with ivory, the first functional prosthesis using Chromium-Cobalt-Molybdenum alloy was proposed in 1936 by Dr. Bohlman, but there was a high friction coefficient, with a lot of wear particles diffused in the body. Polytetrafluoroethylene (PTFE) appeared in 1959 and in the 1970s Prof. Boutin proposed a total hip replacement with a ceramic head. In the same period, Prof. G. Bousquet improved mobility by adding a second degree of freedom to hip prosthesis with the concept of double mobility prosthesis, reducing the risk of dislocation.

The fight against strokes was one of the biggest adventures for humans in the second half of the 20th century and medical devices were the weapons of cardiac surgeons forged by engineers. In 1950, J. Hoops developed the first prototype of the pacemaker. This model was cumbersome and not easy to live with because it was external and required a power supply. The first internal pacemaker was developed and implanted a few years later, in 1958, by Drs. R. Elmqvist and A. Senning in Sweden. In fact, during the 1950s, many independent projects came out in Europe and North America.

This period saw many advances in bio-materials, and some of these resulted in important applications in cardiology. For example, Prof. A. Carpentier developed the first bio-prosthesis: the human mitral valve was replaced by a bio-prosthesis based on a valve from a pig. The original system wore off after few years; now, the third generation lifespan is 25 years. During the 1970s and the 1980s, electronic engineering allowed for the miniaturization of all of the systems. In 2008, after many years of research, Carpentier started the Carmat company, which developed a totally artificial heart, taking advantage of the previous developments in cardiac regulation for pacemakers, but also bio-materials, in particular animal-based materials. The first implantation of a totally artificial heart succeeded in 2013.

Miniaturization of medical devices totally changed the way in which surgeons practiced operations. In 1973, Profs. Bruhat and Manhes achieved the first endoscopic surgery of an extra-uterine pregnancy in Clermont-Ferrand (France). Since then, the advances in microelectronics, medical imaging and augmented reality have made endoscopic surgery possible in many fields: general surgery, urology or even cardiac surgery, with endoscopic placement of stents or cardiac valves. This new paradigm in surgery strongly decreases the invasiveness of surgery and thus increases the chance of the patient’s recovery, limits the side effects of the surgery and finally decreases the overall medical cost.

Finally, insulin pumps are another interesting example of a medical device, which have become the gold standard for chronic diseases. The innovation came from Germany, with glycemia measurement units proposed in 1969, and 10 years later, we saw the first pump. The technical problem that lay behind this is the insulin regulation that controls the patient’s diabetes. Now, both the measurement unit and pump are miniaturized enough to be implanted into the human body. The last step is to connect the measurement to the pump controller, but this raises more than just technical questions: what would happen in the case of a problem? Who is ultimately responsible for the care?

1.2.2. Medical imaging

Perhaps the biggest change in medical practices over the 50 past years is medical imaging.

W. Röntgen discovered X-ray radiations in 1895 in Germany. Although he was following some pioneers’ works, he was the first to publish material on it. He discovered that X-rays pass through solids. After making an image of a woman’s hand, he understood the great interest of X-rays in medicine. The technique spread very quickly: the first surgery under X-rays was performed by J. Hall-Edwards only 1 year later in the UK, and in 1896 a Georgian physician I. Tarkhanishvili discovered that X-rays affect metabolism. Soon after, side effects were reported: hair loss, burns, etc. An early researcher developed a type of cancer due to the radiation produced by X-rays and died in 1904. Advances in X-ray generation and detection saw a perambulation in the history of modern physics, with names such as M. von Laue, W.L. Bragg or W.E. Bragg. We ended up with W. Coolidge who invented X-ray tubes with a continuous emission in 1913 and M. Skłodowska-Curie, who, in 1914, developed mobile radiography units for soldiers in World War I (Figure 1.1). Medical imaging using X-rays is based on the absorption properties of high atomic numbers such as calcium, which provokes a contrast. Bone or dental imaging is straightforward; what is more, after calibration, the bone density can be directly deduced from image intensity maps. Cardiovascular imaging is possible using contrast agents. In this 2D projection form, X-rays are used for dental applications, detection of skeleton problems, but also in the diagnosis of various diseases (pneumonia, lung cancer, pulmonary edema, bowel obstruction, gallstones, kidney stones, etc.), or for implant follow-ups. One image only is a conical projection; by taking various images at different points of view, it is possible to back-project the X-rays (Radon transform) and to reconstruct the whole volume. Of course, the cost for that is higher irradiation and some very recent advances could reduce this irradiation level. In 1968, G. Charpak developed a new detector in France, the “multi-wire detection chamber” that divides the irradiation received by the patient by a factor of ten. In 2008, this detector was implanted by EOS Imaging (Paris, France) in an integrated X-rays system that reconstructs 3D images by using two images of the patient and a knowledge basis.

Compared to X-rays, MRI is a relatively new technology that first began in 1946 with the discovery of the magnetic resonance phenomenon independently by F. Bloch and E. Purcell (USA). Magnetic resonance is a physical phenomenon that occurs on atoms when they are subjected to a high magnetic field: they reorient and relax into their original position if the magnetic field stops, emitting radio signals. MRI imaging is based on the different relaxation times (named T1, T2). It was used first for chemical and physical analysis, and only in 1971 was it used for medical applications by R. Damadian, P. Lauterbur and P. Mansfield. It was necessary to speed-up the mathematical processing to make it useful in medicine. Then, studying different kinds of tissues outlined differences, specifically for cancerous tissues. As already introduced for X-ray imaging, MRI took advantage of multiple image exposure to perform 3D reconstructions. Developments in MRI are strongly related to the generation of magnetic fields. With the progress of superconductors, MRI systems have increased the magnetic field from 0.5 T to 1.5 T or 3.0 T which is common in clinical practice nowadays, and up to 7 T for research applications1. Besides this orientation, which uses more power and more expensive equipment, other orientations consist of decreasing the magnetic field by the optimization of the signal-to-noise ratio with numerical processing and MRI sequence optimization. The MRI sequence can enhance tissue visibility and MRI suppliers compete for the quality of the sequences they propose. The last major innovation – but again in the engineering field rather than in the scientific one – in 1996, Fonar (New York, USA) proposed an open MRI where the patient is not in a supine position but in a standing one. This gives better representativity and comfort for the patient and opens the way to functional MRI with patients in movement. Innovations, still in the research field, are now being driven by molecules heavier than water, that can give information on the biochemical state of the patient, for example, their inflammation level.

Figure 1.1.Photograph of the second Solvay conference. Among the participants, W.L. Bragg, M. Curie and M. von Laue (public domain)

Along with MRI, computer tomography (CT) scans are expensive techniques whose effects on the body are questionable. The last system presented here – even if this short-list is still somewhat incomplete – is ultrasound imaging. L. Spallanzani in Italy discovered that bats were using sounds he could not hear to orient themselves (echolocation) and he was the first to describe these sounds from 1000 to 200,000 Hz. Thanks to P. Langevin (France), humans have been able to reproduce what bats can do since 1915: he invented a device that could detect objects at the bottom of the sea, the hydrophone. This is considered to be the “first transducer”. The real history of ultrasound imaging began in 1942 in Austria: K. Dussik transmitted an ultrasound beam through the human skull to detect brain tumors. The piezoelectric crystal (PZT) first emits ultrasound and then receives the echo. The first equipment came out in 1948 to detect gallstones (G.D. Ludwig, USA). It was a simple unidirectional system (A-mode ultrasound), but very soon (1949–1951) D. Howry and J. Holmes (USA) pioneered 2D imaging, known as B-mode ultrasound equipment. The most well-known applications are in obstetrics and the detection of tumors – in particular breast tumors, and those in pneumology or urology. In 1966, pulse-Doppler ultrasound imaging came out (D. Baker, D. Watkins and J. Reid) leading to blood flow imaging and angiology applications. Applications of ultrasounds concern any soft tissue that can transmit a mechanical vibration. The idea of coupling medical imaging and mechanical loading came out in 1991 thanks to J. Ophir (USA). A simple analysis shows that such a technique gives an image of the tissue elasticity, and due to this, it has been called elastography. The principal characteristic of ultrasound elastography – compared to MRI – is that the transducer itself can generate the load. In 2004 J.L. Genisson (France) proposed the ultrasonic shear wave elastography that could propagate a wave inside the body. Because it enhances the differences in tissue stiffness, elastography is more efficient in the detection of tumors than the classical B-mode. Now, modern ultrasound systems have a frequency range from 1 to 18 MHz depending on the penetration sought (acoustic absorption varies with the square of the frequency) and a sensor arrangement gathers 128–960 transducers, even 3,000 in specific cases.

Now, ultrasound techniques are developing in a very novel direction. Because ultrasounds are transmitting energy, it is possible to increase and to concentrate this energy in small areas, provoking local heat, and as a consequence cell apoptosis. This new technique, known as high-intensity focused ultrasound (HIFU), is therefore a local noninvasive ablation technique. It can be easily image guided by decreasing the power. HIFU was ideated in the 1950s by W. Fry and F. Fry in Cincinnati (USA), but the first medical developments came out in Europe. In 2006, F. Murat (France) demonstrated its efficiency on prostate cancer, and this approach has been approved by the EU.

1.3. Medical device industry

1.3.1. The industrial sector

The sector of medical devices is one which is not very old. One of the main characteristics of this sector is the diversity of the actors: physicians, engineers, pharmacologists, lawyers, etc. This diversity is also valid inside each profession; among physicians for example, medical device innovation may come from cardiologists, physical medicine or orthopedists. Of course, this is the same for engineers, with biomechanics, electronics, automation or artificial intelligence. Teams that contain an entrepreneur, an engineer and a physician will always be a boost to success for any start-up project.

The youth of the sector, and the dynamism of the actors of the medical field, explains that 95%2 of the activity is performed by small- (B Braun, Carmat, Supersonic Imaging, EOS Imaging, etc.) and medium-sized companies (Thuasne, Sigvaris, Ossür, L&R, etc.). Of course, some of the classical optics companies are present (Philips, Zeiss, Seimens, etc.). Even some pure players are big enough to count as multinationals (Abbott, Medtronics, etc.). Now, the European Union wants fewer bigger-sized companies.

Because of this dispersion of the players, quantification cannot be accurate, but it is admitted that the medical devices represent one-third of the pharmacological market (187 €bn in 2005). The medical device market has a 4.8% growth each year, whereas the pharmacological market growth is 5.8% (EU) or 5.6% (USA). Another important difference is the lifecycle of the products: all of the regulation processes for medical devices is copy-pasted from drugs, but the development lasts for 5–6 years, whereas that of drugs is around 12 years. The time on the market for a medical device is also half of that of a drug (5 years instead of 8 years).

The U.S. market is the largest, with 239 €bn (∼43.5%); the European market represents 150 €bn (27.3%) followed by Asia (with China, 7.2%). Following this trend, the United States is the major supplier, followed by the European Union. Within Europe, Germany covers 31% of European production, France 16%, followed by the UK and Italy (11% each).

Notes

1

Note that such an electromagnetic field constrains what is inside the field to strictly nonmagnetic materials.

2

Economic figures for this paragraph come from the following: MedTechEurope (2002). MedTech Europe’s facts & figures 2022 [Online]. Available at:

https://www.medtecheurope.org/resource-library/medtech-europes-facts-and-figures-2022/

.EFPIA (2002). The pharmaceutical industry in figures – Key data [Online]. Available at:

https://www.efpia.eu/media/637143/the-pharmaceutical-industry-in-figures-2022.pdf

.PIPAME Report (2011).