Table of Contents

COVER

TITLE PAGE

COPYRIGHT
CONTRIBUTORS
FOREWORD

CHAPTER 1: OVERVIEW

1.1 INTRODUCTION
1.2 NEED FOR MEDICAL DEVICES
1.3 TECHNOLOGY CONTRIBUTION TO MEDICAL DEVICES
1.4 CHALLENGES IN THE MEDICAL DEVICE INDUSTRY
REFERENCES

CHAPTER 2: DESIGN ISSUES IN MEDICAL DEVICES

2.1 MEDICAL DEVICE DEVELOPMENT (MDD)
2.2 CASE STUDY
2.3 CONCLUSIONS
REFERENCES

CHAPTER 3: FORMING APPLICATIONS

3.1 FORMING
3.2 TYPICAL PROCESS PARAMETERS
3.3 MANUFACTURING PROCESS CHAIN
3.4 IMPLANTABLE DEVICES
3.5 BONE IMPLANTS
3.6 OTHER BIOMEDICAL APPLICATIONS
REFERENCES

CHAPTER 4: LASER PROCESSING APPLICATIONS

4.1 INTRODUCTION
4.2 MICROSCALE MEDICAL DEVICE APPLICATIONS
4.3 PROCESSING METHODS FOR MEDICAL DEVICE FABRICATION
4.4 BIOMATERIALS USED IN MEDICAL DEVICES
4.5 MICROJOINING OF SIMILAR AND DISSIMILAR MATERIALS
4.6 LASER MICROMACHINING FOR MICROFLUIDICS
4.7 LASER MICROMACHINING FOR METALLIC CORONARY STENTS
REFERENCES

CHAPTER 5: MACHINING APPLICATIONS

5.1 INTRODUCTION
5.2 MACHINABILITY OF BIOCOMPATIBLE METAL ALLOYS
5.3 SURFACES ENGINEERING OF METAL IMPLANTS
5.4 WEAR AND FAILURE OF METAL IMPLANTS
5.5 MICROMILLING-BASED FABRICATION OF METALLIC MICROCHANNELS FOR MEDICAL DEVICES
5.6 MACHINING-BASED FABRICATION OF POLYMERIC MICRONEEDLE DEVICES
5.7 A CASE STUDY: MILLING-BASED FABRICATION OF SPINAL SPACER CAGE
REFERENCES

CHAPTER 6: INKJET- AND EXTRUSION-BASED TECHNOLOGIES

6.1 INTRODUCTION
6.2 INKJET TECHNOLOGY
6.3 MATERIAL EXTRUSION TECHNOLOGY
REFERENCES

CHAPTER 7: CERTIFICATION FOR MEDICAL DEVICES

7.1 INTRODUCTION
7.2 THE MEDICAL DEVICES APPROVAL, REGISTRATION, OR CERTIFICATION
7.3 THE PREMARKET KEY ACTIVITY: THE DEMONSTRATION OF THE CONFORMITY TO THE SAFETY AND PERFORMANCE REQUIREMENTS
7.4 THE POSTMARKET KEY ACTIVITY: THE SURVEILLANCE
7.5 THE ROLE OF THE QUALITY MANAGEMENT SYSTEMS
7.6 THE VERIFICATION AND THE AUDITING
7.7 THE ROLE OF THE STANDARDS
7.8 EXAMPLES OF APPROBATION/CERTIFICATION ROADS IN SOME WORLD AREAS
7.9 IN-DEPTH STUDIES
REFERENCES

INDEX

END USER LICENSE AGREEMENT

List of Illustrations

Chapter 2: DESIGN ISSUES IN MEDICAL DEVICES

Figure 2.1 Total medical device life cycle (according to Center for Devices and Radiological Health (CDRH), US FDA).
Figure 2.2 Linear life cycle model of medical device according to El-Haik and Mekki [7].
Figure 2.3 Simplified schema of the linear medical device development model according to Pietzsch et al. [9].
Figure 2.4 Schema of waterfall model [16].
Figure 2.5 Schema of design for validation model (DFV-V model) according to Alexander and Bishop [15].
Figure 2.6 Design and manufacturing activities for developing a medical device.
Figure 2.7 Functional analysis of the prosthesis to replace the scapholunate interosseous ligament (SLIL).
Figure 2.8 Synthesis of the morphological matrix.
Figure 2.9 Conceptual design: compact system (concept 1) and ball-and socket-ball system (concept 2) and wired system (concept 3).
Figure 2.10 Evolution of the compact system.
Figure 2.11 Final scapholunate prosthesis (a) and its insertion in the bones (b).
Figure 2.12 Manufacturing steps.
Figure 2.13 (a) Display of WHATs and HOWs in QFD and (b) QFD competitive analysis.
Figure 2.14 (a) QFD physical contradictions and (b) TRIZ contradiction matrix.
Figure 2.15 Geometry solutions using TRIZ principles.
Figure 2.16 Customization parameters of final stent design.
Figure 2.17 Stent (a) directly manufactured using fab@home (b), a fused deposition modeling machine.

Chapter 3: FORMING APPLICATIONS

Figure 3.1 (a) Open-die forging; (b) closed-die forming; and (c) sheet stamping. Source: Schuler 1998 [2]. Reproduced with permission of Springer Berlin Heidelberg.
Figure 3.2 Typical sequence for T-shaped tube hydroforming process: (a) the tube in the hydroforming dies; (b) the produced part after hydroforming. Reproduced with permissions of Antonio Fiorentino.
Figure 3.3 Examples of biomedical devices used in orthopedics. Source: Figure courtesy of Chris Martin.
Figure 3.4 Examples of types of joints present in the human body. Source: Tortora and Derrickson 2009 [12]. Reproduced with permission of John Wiley & Sons.
Figure 3.5 (a) Elbow joint scheme. Source: Tortora and Derrickson 2009 [12]. Reproduced with permission of John Wiley & Sons. (b) Elbow prosthesis. Source: Sanchez-Sotelo, 2011 [13]. Reproduced with permission of The Open Orthopaedics Journal.
Figure 3.6 (a) Human knee joint scheme. Source: Tortora and Derrickson 2009 [12]. Reproduced with permission of John Wiley & Sons. (b) Knee prosthesis. Source: Culjat et al., 2012 [16]. Reproduced with permission of John Wiley & Sons.
Figure 3.7 (a) Lateral view of human ankle. Source: Figure courtesy of Philip Chalmers. (b) Example of X-ray images of artificial joint inserted on ankle. Source: Barg et al., 2010 [19]. Reproduced with permission of Springer International Publishing.
Figure 3.8 Scheme of human hand bones. Source: Figure courtesy of Mariana Ruiz Villarreal.
Figure 3.9 (a) Examples of finger joints; (b) example of X-ray images of artificial joint inserted on shoulder. Source: Gibson 2005 [21]. Reproduced with permission of John Wiley & Sons.
Figure 3.10 (a) Shoulder scheme. Source: Tortora and Derrickson 2009 [12]. Reproduced with permission of John Wiley & Sons. (b) Shoulder prosthesis. Source: Ekelund 2009 [22]. Reproduced with permission of Journal of Orthopaedic & Sports Physical Therapy. (c) Example of X-ray images of artificial joint inserted on shoulder. Source: Ekelund 2009 [22]. Reproduced with permission of Journal of Orthopaedic & Sports Physical Therapy.
Figure 3.11 (a) Human hip scheme. Source: Tortora and Derrickson 2009 [12]. Reproduced with permission of John Wiley & Sons. (b) From left to right: Frontal plane cross-section of a femur; press fit implant; the original Chamley femoral stem and polyethylene cup; noncemented stem with a porous ingrowth surface. Source: Culjat et al., 2012 [16]. Reproduced with permission of John Wiley & Sons.
Figure 3.12 (a) Human wrist scheme. Source: Tortora and Derrickson 2009 [12]. Reproduced with permission of John Wiley & Sons. (b) X-ray images of wrist prosthesis positioning. Source: Facca et al., 2010 [24]. Reproduced with permission of John Wiley and Sons.
Figure 3.13 Vertebral column scheme. Source: Tortora and Derrickson 2009 [12]. Reproduced with permission of John Wiley & Sons.
Figure 3.14 (a) Spine anatomy. Source: Kojić et al., 2008 [25]. Reproduced with permission of John Wiley & Sons. (b) Spinal vertebrae without spinal device and with spinal device. Source: Culjat et al., 2012 [16]. Reproduced with permission of John Wiley & Sons.
Figure 3.15 Skull and cranial bones. Source: Hollins 2012 [27]. Reproduced with permission of John Wiley & Sons.
Figure 3.16 Manufacturing process of cranial prosthesis. Source: Fiorentino et al., 2012 [34]. Reproduced with permission of John Wiley & Sons.
Figure 3.17 Pre-bent of a plate over AMT model. Source: Wilde et al., 2012 [38]. Reproduced with permission of Springer-Verlag.
Figure 3.18 From left to right: dentition scheme; titanium screw dental implant (resembling a tooth root). Source: Wingrove 2013 [44]. Reproduced with permission of John Wiley & Sons.

Chapter 4: LASER PROCESSING APPLICATIONS

Figure 4.1 Microscale medical device applications.
Figure 4.2 Various microchannel geometries fabricated with laser micromachining.
Figure 4.3 PDMS microchannel schematic.
Figure 4.4 Silicon-to-glass bonding with Nd:YAG laser.
Figure 4.5 Microchannels fabricated on PMMA and PDMS with laser micromachining in NIR and UV wavelengths.
Figure 4.6 Laser micromachining based PMMA and PDMS microchannel profiles.

Chapter 5: MACHINING APPLICATIONS

Figure 5.1 (a) Titanium alloy Ti-6Al-4V spinal fixation plate and (b) SS316L stainless steel bone crusher as produced with micromilling.
Figure 5.2 Burr formation in micromilling of channels in Ti-6Al-4V titanium alloy.
Figure 5.3 Micromilling of PMMA polymer to produce microneedle arrays.
Figure 5.4 Microneedle array-based patch prototypes produced with micromilling.
Figure 5.5 Examples of common disc problems.
Figure 5.6 Spinal spacer cage designs (Rutgers Manufacturing Automation Laboratory).
Figure 5.7 Two design models used in finite element analysis.
Figure 5.8 Boundary conditions and loads for the two designs.
Figure 5.9 Finite element mesh for the two designs (Rutgers Manufacturing Automation Laboratory).
Figure 5.10 (a) Design A with 160 N load on 59 teeth cage and (b) Design B with 100 N load on 59 teeth cage (Rutgers Manufacturing Automation Laboratory).
Figure 5.11 Surface obtained from the tool path strategy (Rutgers Manufacturing Automation Laboratory).
Figure 5.12 Steps in automated milling process (Rutgers Manufacturing Automation Laboratory).
Figure 5.13 (a) Designed and (b) prototype spinal spacer cage fabricated with milling process (Rutgers Manufacturing Automation Laboratory).

Chapter 6: INKJET- AND EXTRUSION-BASED TECHNOLOGIES

Figure 6.1 Binder jetting process overview.
Figure 6.2 Material jetting working principle.
Figure 6.3 Overview based material extrusion principles (a) filament-based extrusion, (b) syringe-based extrusion, (c) screw based.
Figure 6.4 Filament extrusion: problems caused by the (a) filament, (b) improper diameter filament, and (c) buckling.
Figure 6.5 Schematic of extrusion-based systems.
Figure 6.6 Fused deposition modeling process.
Figure 6.7 Working principle of multiphase jet solidification (MJS).

List of Tables

Chapter 2: DESIGN ISSUES IN MEDICAL DEVICES

Table 2.1 Identification of Functional Requirements (FRs) and Design Constraints (Cs) for New Prosthesis
Table 2.2 Attribute List of Stent

Chapter 4: LASER PROCESSING APPLICATIONS

Table 4.1 Comparison between Continuous Wave and Pulsed Lasers
Table 4.2 Manufacturing Process Comparison for Key Characteristics
Table 4.3 Process Parameters for Laser Processing of Polymers

Chapter 5: MACHINING APPLICATIONS

Table 5.1 Medical Implants and Alloy Materials Used
Table 5.2 Mechanical Properties of Alloys Used in Joint Replacements
Table 5.3 Biocompatibility of Biomaterials Including Metal Alloys
Table 5.4 Spinal Spacer Cage Design Methods
Table 5.5 Tools Utilized in Milling Process

Chapter 6: INKJET- AND EXTRUSION-BASED TECHNOLOGIES

Table 6.1 Additive Manufacturing Categories as Classifies by ASTM
Table 6.2 FDM Modeling Materials

Chapter 7: CERTIFICATION FOR MEDICAL DEVICES

Table 7.1 Checklist for Documenting the Premarket Conformity to the Safety and Performance Principles

Biomedical Devices

Design, Prototyping, and Manufacturing

Edited by

Tuğrul Özel

Paolo Jorge Bártolo

Elisabetta Ceretti

Joaquim De Ciurana Gay

Ciro Angel Rodriguez

Jorge Vicente Lopes Da Silva

No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, scanning, or otherwise, except as permitted under Section 107 or 108 of the 1976 United States Copyright Act, without either the prior written permission of the Publisher, or authorization through payment of the appropriate per-copy fee to the Copyright Clearance Center, Inc., 222 Rosewood Drive, Danvers, MA 01923, (978) 750-8400, fax (978) 750-4470, or on the web at www.copyright.com. Requests to the Publisher for permission should be addressed to the Permissions Department, John Wiley & Sons, Inc., 111 River Street, Hoboken, NJ 07030, (201) 748-6011, fax (201) 748-6008, or online at http://www.wiley.com/go/permission.

Limit of Liability/Disclaimer of Warranty: While the publisher and author have used their best efforts in preparing this book, they make no representations or warranties with respect to the accuracy or completeness of the contents of this book and specifically disclaim any implied warranties of merchantability or fitness for a particular purpose. No warranty may be created or extended by sales representatives or written sales materials. The advice and strategies contained herein may not be suitable for your situation. You should consult with a professional where appropriate. Neither the publisher nor author shall be liable for any loss of profit or any other commercial damages, including but not limited to special, incidental, consequential, or other damages.

For general information on our other products and services or for technical support, please contact our Customer Care Department within the United States at (800) 762-2974, outside the United States at (317) 572-3993 or fax (317) 572-4002.

Wiley also publishes its books in a variety of electronic formats. Some content that appears in print may not be available in electronic formats. For more information about Wiley products, visit our web site at www.wiley.com.

Title: Biomedical devices : design, prototyping, and manufacturing / edited by Tuğrul Özel, Paolo Jorge Bártolo, Elisabetta Ceretti, Joaquim De Ciurana Gay,

Description: Hoboken, New Jersey : John Wiley & Sons, 2016. | Includes bibliographical references and index.

Identifiers: LCCN 2016018375| ISBN 9781118478929 (cloth) | ISBN 9781119267041 (epub)

Classification: LCC R856 .B487 2016 | DDC 610.28/4--dc23 LC record available at https://lccn.loc.gov/2016018375

CONTRIBUTORS

Aldo Attanasio, Department of Mechanical Engineering and Industrial Engineering, University of Brescia, Brescia, Lombardy, Italy
Paulo Jorge Bártolo, School of Mechanical, Aerospace and Civil Engineering, Manchester Institute of Biotechnology, University of Manchester, Manchester, UK
Karen Baylón, Department of Mechanical Engineering, Instituto Tecnológico y de Estudios Superiores de Monterrey, Campus Monterrey, Monterrey, Nuevo León, Mexico
Marino Bindi, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, Brescia, Lombardy, Italy
Elisabetta Ceretti, Department of Mechanical and Industrial Engineering, University of Brescia, Brescia, Lombardy, Italy
Luis Criales, Department of Industrial and Systems Engineering, School of Engineering, Rutgers University, Piscataway, NJ, USA
Jorge Vicente Lopes Da Silva, Technological Center Renato Archer, Centro de Tecnologia da Informação Renato Archer, Brazilian Ministry of Science and Technology, Campinas, São Paulo, Brazil
Domenico Dalessandri, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, Brescia, Lombardy, Italy
Joaquim De Ciurana Gay, Department of Mechanical Engineering and Industrial Construction, University of Girona, Girona, Catalonia, Spain
Marco Domingos, School of Mechanical, Aerospace and Civil Engineering, Manchester Institute of Biotechnology, University of Manchester, Manchester, UK
Alex Elias-Zuñiga, Department of Mechanical Engineering, Instituto Tecnológico y de Estudios Superiores de Monterrey, Campus Monterrey, Monterrey, Nuevo León, Mexico
Inés Ferrer, Department of Mechanical Engineering and Industrial Construction, University of Girona, Girona, Catalonia, Spain
Antonio Fiorentino, Department of Mechanical and Industrial Engineering, University of Brescia, Brescia, Lombardy, Italy
Maria Luisa Garcia-Romeu, Department of Mechanical Engineering and Industrial Construction, University of Girona, Girona, Catalonia, Spain
Claudio Giardini, Department of Mechanical and Industrial Engineering, University of Brescia, Brescia, Lombardy, Italy
Jordi Grabalosa, Department of Mechanical Engineering and Industrial Construction, University of Girona, Girona, Catalonia, Spain
Arne Hensten, Faculty of Health Sciences, UiT The Arctic University of Norway, Tromsø, Norway
Laura Laffranchi, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, Brescia, Lombardy, Italy
Karla Monroy, Department of Mechanical Engineering and Industrial Construction, University of Girona, Girona, Catalonia, Spain
Tuğrul Özel, Department of Industrial and Systems Engineering, School of Engineering, Rutgers University, Piscataway, NJ, USA
Corrado Paganelli, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, Brescia, Lombardy, Italy
Ciro Angel Rodriguez, Department of Mechanical Engineering, Instituto Tecnológico y de Estudios Superiores de Monterrey, Campus Monterrey, Monterrey, Nuevo León, Mexico
Stefano Salgarello, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, Brescia, Lombardy, Italy
Lidia Serenó, Department of Mechanical Engineering and Industrial Construction, University of Girona, Girona, Catalonia, Spain
Daniel Teixidor Ezpeleta, Department of Mechanical Engineering and Industrial Construction, University of Girona, Girona, Catalonia, Spain
Thanongsak Thepsonthi, Department of Industrial Engineering, Burapha University, Chon Buri, Thailand
Giuseppe Vatri, Major Prodotti Dentari Spa, Moncalieri, TO, Italy

FOREWORD

There has been an increasing demand for biomedical devices including various instruments, apparatuses, implants, in vitro reagents, and similar articles to diagnose, prevent, or treat diseases, improve human health, prolong human life, and recover from serious injuries. Biomedical devices that we utilize are not only continuously getting smaller and more effective but are also designed with more customized functionalities. In response to that demand, new design innovations, new materials, and prototypes of novel medical devices have been introduced on a regular basis. Design, prototyping, and manufacturing techniques for these materials and designs have also been continuously developing in parallel to the needs in biomedical device demands. There have been a large number of books written about design and manufacturing of various products but biomedical device manufacturing remains less covered than other well-known microelectronics and consumer products.

This book brings authors from institutions around the world, perhaps one of the few wide-ranging books on manufacturing processes for medical devices with coverage of various materials including metals and polymers. The book aims to reach audiences such as practicing engineers who are working in medical device industry, students in the biomedical device manufacturing courses, and faculty/researchers who are conducting research in medical device design, prototyping, and manufacturing.

Chapter 1, written by Joaquim De Ciurana, Tuğrul Özel, and Lidia Serenó, provides an introduction with classification and regulation specification about medical devices with sample manufacturing processes and applications. Chapter 2, prepared by Inés Ferrer Real, Jordi Grabalosa, Alex Elias-Zuniga, and Ciro Rodriguez, summarizes design issues and methodologies applicable to well-known medical device prototypes. Chapter 3, prepared by Karen Baylón, Elisabetta Ceretti, Claudio Giardini, and M. Luisa Garcia-Romeu, describes the issues in modeling and analysis for forming processes along with the comparison of different modeling approaches. Chapter 4, prepared by Tuğrul Özel, Joaquim De Ciurana, Daniel Teixidor, and Luis Criales, describes some of the manufacturing processes based on laser processing with several examples for medical devices. Chapter 5, prepared by Tuğrul Özel, Elisabetta Ceretti, Thanongsak Thepsonthi, and Aldo Attanasio, discusses machining applications and manufacturing processes to be used for medical devices made out of metals and plastics. Extrusion- and inkjet-based processes and applications are presented in Chapter 6, which was prepared by Karla Monroy, Lidia Serenó, Joaquim De Ciurana, Paulo Jorge Bártolo, Jorge Da Silva, Marco Domingos, Corrado Paganelli, Marino Bindi, Laura Laffranchi, Domenico Dalessandri, Stefano Salgarello, Antonio Fiorentino, Giuseppe Vatri, and Arne Hensten prepared the Chapter 7 on certification of medical devices.

We thank all the authors who contributed to this book. We also extend our thanks to Ms Anita Lekhwani and Ms Sumathi Elangovan of John Wiley who assisted us in all stages of preparing this book for the publication.

T. Özel, P. Bártolo, E. Ceretti, J. Ciurana Gay, C. A. Rodríguez, J. V. Lopes Da Silva
June 2016