Advances in Biochemical Engineering/Biotechnology 133 Series Editor: T. Scheper Harald Seitz Sarah Schumacher Editors Molecular Diagnostics 133 Advances in Biochemical Engineering/Biotechnology Series Editor T. Scheper, Hannover, Germany Editorial Board S. Belkin, Jerusalem, Israel P. Doran, Hawthorn, Australia I. Endo, Saitama, Japan M. B. Gu, Seoul, Korea W.-S. Hu, Minneapolis, MN, USA B. Mattiasson, Lund, Sweden J. Nielsen, Göteborg, Sweden G. Stephanopoulos, Cambridge, MA, USA R. Ulber, Kaiserslautern, Germany A.-P. Zeng, Hamburg-Harburg, Germany J.-J. Zhong, Shanghai, China W. Zhou, Framingham, MA, USA For furthervolumes: http://www.springer.com/series/10 Aims and Scope Thisbookseriesreviewscurrenttrendsinmodernbiotechnologyandbiochemical engineering. Its aim is to cover all aspects of these interdisciplinary disciplines, whereknowledge,methodsandexpertisearerequiredfromchemistry,biochemistry, microbiology,molecularbiology,chemicalengineeringandcomputerscience. Volumes are organized topically and provide a comprehensive discussion of developments in the field over the past 3–5 years. The series also discusses new discoveries and applications. Special volumes are dedicated to selected topics which focus on new biotechnological products and new processes for their synthesis and purification. In general, volumes are edited by well-known guest editors. The series editor and publisher will, however, always be pleased to receive suggestions and supplementary information. Manuscripts are accepted in English. Inreferences,AdvancesinBiochemicalEngineering/Biotechnologyisabbreviated as Adv. Biochem. Engin./Biotechnol. and cited as a journal. Harald Seitz Sarah Schumacher • Editors Molecular Diagnostics With contributions by I. Berger (cid:2) F. F. Bier (cid:2) A. Böhm (cid:2) P. S. Dittrich E. Ehrentreich-Förster (cid:2) H. Eickhof (cid:2) U. Frömmel F. J. Gruhl (cid:2) A. Kühn (cid:2) K. Länge (cid:2) W. Lehman H. Lehrach (cid:2) C. Lüdecke (cid:2) A. Malik (cid:2) J. Nitschke B. E. Rapp (cid:2) B. Regierer (cid:2) T. Robinson (cid:2) S. Rödiger D. Roggenbuck (cid:2) M. Ruhland (cid:2) P. Schierack (cid:2) I. Schimke C. Schmidt (cid:2) C. Schröder (cid:2) S. Schumacher R. Sudbrak (cid:2) V. Zazzu 123 Editors HaraldSeitz SarahSchumacher Fraunhofer InstituteforBiomedical Engineering Potsdam Germany ISSN 0724-6145 ISSN 1616-8542 (electronic) ISBN 978-3-642-37690-0 ISBN 978-3-642-37691-7 (eBook) DOI 10.1007/978-3-642-37691-7 SpringerHeidelbergNewYorkDordrechtLondon LibraryofCongressControlNumber:2013935488 (cid:2)Springer-VerlagBerlinHeidelberg2013 Thisworkissubjecttocopyright.AllrightsarereservedbythePublisher,whetherthewholeorpartof the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation,broadcasting,reproductiononmicrofilmsorinanyotherphysicalway,andtransmissionor informationstorageandretrieval,electronicadaptation,computersoftware,orbysimilarordissimilar methodology now known or hereafter developed. Exempted from this legal reservation are brief excerpts in connection with reviews or scholarly analysis or material supplied specifically for the purposeofbeingenteredandexecutedonacomputersystem,forexclusiveusebythepurchaserofthe work. Duplication of this publication or parts thereof is permitted only under the provisions of theCopyright Law of the Publisher’s location, in its current version, and permission for use must always be obtained from Springer. Permissions for use may be obtained through RightsLink at the CopyrightClearanceCenter.ViolationsareliabletoprosecutionundertherespectiveCopyrightLaw. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publicationdoesnotimply,evenintheabsenceofaspecificstatement,thatsuchnamesareexempt fromtherelevantprotectivelawsandregulationsandthereforefreeforgeneraluse. While the advice and information in this book are believed to be true and accurate at the date of publication,neithertheauthorsnortheeditorsnorthepublishercanacceptanylegalresponsibilityfor anyerrorsoromissionsthatmaybemade.Thepublishermakesnowarranty,expressorimplied,with respecttothematerialcontainedherein. Printedonacid-freepaper SpringerispartofSpringerScience+BusinessMedia(www.springer.com) Preface Nearly20yearsagotheconceptofmoleculardiagnosticsmovedintothefocusof academicandindustrialresearch.Thisshiftwasmainlydrivenbynewtechniques like DNA Microarrays which often result in miniaturization of assays and the automatization of processes. Since, then the field of molecular diagnostics has been expanded and clinical diagnostic laboratories function as a playing field for this expansion. Vast and dynamic changes in the test menus, instrumentation and clinicalapplicationshavebeensomeoftheimpactsmoleculardiagnosticshashad. Nevertheless, so far only a few promising techniques have become standard routine. Human beings differ in their level of health. Even individuals with the same disease can have specific differences in their clinical picture. Therefore it is importanttoadjusttherapyandmedicamentsindividually.Todaythisapproach is known as ‘‘personalized medicine’’. Molecular Diagnostics covers current molecularbiologicaltechniquesusednotonlytoidentifytheunderlyingmolecular defects in inherited disease, but also to monitor therapies. Multiple studies in modern science have shown that changes on a molecular level are often directly linked to the origin of diseases. Consequently, new targets have been recognized and often used as potential biomarkers for intervention. These targets are able to act on different levels, like proteomics, genomics, or metabolomics. Theaimistodevelopdisease-specificbiomarkers,whichcanbeappliedinvivo inthepatientorinvitrobyanalyzinghumansampleslikeblood,tissues,orurine. Ideally, these markers allow not only a distinction between healthy and diseased people, but also, e.g., the classification of different types of cancer. Moreover, multiplexing multiparameter analyses often have a higher sensitivity, wide dynamic range, and need shorter incubation time. So the quite new field of ‘‘MolecularDiagnostics’’isabletoopennewwaysfordetectingdiseases,evenat anearlystage.Thispreventssevereharmforapatient,reducescostsandtheeffort ofmedicalexaminations,givesaccesstonewmethodsinmodernmedicine,andis well-suited for point-of-care diagnostics. v vi Preface Newlydevelopedassays,devicesforinvitrodiagnosticsandthecorresponding imaging technologies should not only be available in specialized institutes or laboratories. Even common hospitals and surgeries, as well as general medicine, should gain access to these techniques. The development of molecular diagnostic tools is an interdisciplinary task of clinicians, experimental and theoretical groups in universities, research institutes and industrial facilities. This multidisciplinarity gives the opportunity to use knowledge and resources of diverse institutes and researchers in an ideal way. Contributorsofthechaptersarewell-knownexpertsintheirfield,andcomefroma variety of disciplines, to ensure breadth and depth of coverage. Therefore this volume contains contributions from scientists working in different fields and institutes. We want to thank Springer-Verlag for giving us the opportunity to edit this volume. Furthermore for the constant help and support during the preparation of thisvolume,especiallyMs.KarinBartsch,ProjectCoordinator,andMs.Elizabeth Hawkins, Chemistry Editor. We also want to acknowledge the authors for distributing their chapters and spending their time preparing interesting articles. Finally, we want to thank all colleagues who made this volume possible. Inconclusion,wehopethatinthisvolumeyouwillfindinspiringliteratureand useful information about molecular diagnostics. Sarah Schumacher Harald Seitz Contents Integration in Bioanalysis: Technologies for Point-of-Care Testing . . . 1 Frank F. Bier and Soeren Schumacher Future of Medicine: Models in Predictive Diagnostics and Personalized Medicine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15 Babette Regierer, Valeria Zazzu, Ralf Sudbrak, Alexander Kühn and Hans Lehrach A Highly Versatile Microscope Imaging Technology Platform for the Multiplex Real-Time Detection of Biomolecules and Autoimmune Antibodies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35 Stefan Rödiger, Peter Schierack, Alexander Böhm, Jörg Nitschke, Ingo Berger, Ulrike Frömmel, Carsten Schmidt, Mirko Ruhland, Ingolf Schimke, Dirk Roggenbuck, Werner Lehmann and Christian Schröder Platform Technologies for Molecular Diagnostics Near the Patient’s Bedside. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75 Soeren Schumacher, Christine Lüdecke, Eva Ehrentreich-Förster and Frank F. Bier Microfluidic Technology for Molecular Diagnostics . . . . . . . . . . . . . . 89 Tom Robinson and Petra S. Dittrich Biosensors for Diagnostic Applications. . . . . . . . . . . . . . . . . . . . . . . . 115 Friederike J. Gruhl, Bastian E. Rapp and Kerstin Länge vii viii Contents Planar Protein Arrays in Microtiter Plates: Development of a New Format Towards Accurate, Automation-Friendly and Affordable (A3) Diagnostics. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 149 Holger Eickhoff and Arif Malik Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 167 AdvBiochemEngBiotechnol(2013)133:1–14 DOI:10.1007/10_2012_164 (cid:2)Springer-VerlagBerlinHeidelberg2013 PublishedOnline:24January2013 Integration in Bioanalysis: Technologies for Point-of-Care Testing Frank F. Bier and Soeren Schumacher Abstract Biosensors, Lab-on-Chip technologies, and sensor-actor molecules are steps towards the integration of bioanalysis into small devices that will help in providing analysis where it is needed: the point-of-care. This article gives a brief overview of recent achievements and future prospects. Contents 1 Introduction.......................................................................................................................... 2 1.1 TheConceptofMolecularBiomarkers..................................................................... 2 1.2 SocietalNeeds............................................................................................................ 3 1.3 IntegrationasaKeyParameter.................................................................................. 4 2 IntegrationSteps.................................................................................................................. 5 2.1 BiosensorsandBiochips............................................................................................. 6 2.2 Lab-on-ChipSystems................................................................................................. 9 2.3 IntegrationontheChip:‘‘ActiveArrays’’................................................................. 10 2.4 AutonomousBiosensors............................................................................................. 11 2.5 Sensor-ActorMolecules:MolecularIntegration....................................................... 12 3 TheGoal:SystemsIntegration........................................................................................... 12 References.................................................................................................................................. 13 F.F.Bier(&)(cid:2)S.Schumacher FraunhoferInstituteforBiomedicalEngineering(IBMT), BranchPotsdam,AmMühlenberg13,14476Potsdam,Germany e-mail:[email protected] URL:www.ibmt.fraunhofer.de;www.taschentuchlabor.de; www.theradiagnostik.de;www.ivd-plattform.de