Table Of ContentSpringer Theses
Recognizing Outstanding Ph.D. Research
For furthervolumes:
http://www.springer.com/series/8790
Aims and Scope
The series ‘‘Springer Theses’’ brings together a selection of the very best Ph.D.
theses from around the world and across the physical sciences. Nominated and
endorsed by two recognized specialists, each published volume has been selected
for its scientific excellence and the high impact of its contents for the pertinent
fieldofresearch.Forgreateraccessibilitytonon-specialists,thepublishedversions
includeanextendedintroduction,aswellasaforewordbythestudent’ssupervisor
explaining the special relevance of the work for the field. As a whole, the series
will provide a valuable resource both for newcomers to the research fields
described, and for other scientists seeking detailed background information on
specialquestions.Finally,itprovidesanaccrediteddocumentationofthevaluable
contributions made by today’s younger generation of scientists.
Theses are accepted into the series by invited nomination only
and must fulfill all of the following criteria
• They must be written in good English.
• ThetopicshouldfallwithintheconfinesofChemistry,Physics,EarthSciences,
Engineering andrelatedinterdisciplinaryfieldssuchasMaterials, Nanoscience,
Chemical Engineering, Complex Systems and Biophysics.
• The work reported in the thesis must represent a significant scientific advance.
• Ifthethesisincludespreviouslypublishedmaterial,permissiontoreproducethis
must be gained from the respective copyright holder.
• They must have been examined and passed during the 12 months prior to
nomination.
• Each thesis should include a foreword by the supervisor outlining the signifi-
cance of its content.
• The theses should have a clearly defined structure including an introduction
accessible to scientists not expert in that particular field.
Fredrik Öisjöen
High-T SQUIDs for
c
Biomedical Applications:
Immunoassays,
Magnetoencephalography,
and Ultra-Low Field
Magnetic Resonance
Imaging
Doctoral Thesis accepted by
the Chalmers University of Technology
123
Author Supervisor
Dr. FredrikÖisjöen Prof.Dr. AlexeyKalabukhov
Department of Microtechnologyand Department of Microtechnologyand
Nanoscience–MC2 Nanoscience–MC2
Chalmers UniversityofTechnology Chalmers UniversityofTechnology
Gothenburg Gothenburg
Sweden Sweden
ISSN 2190-5053 ISSN 2190-5061 (electronic)
ISBN 978-3-642-31355-4 ISBN 978-3-642-31356-1 (eBook)
DOI 10.1007/978-3-642-31356-1
SpringerHeidelbergNewYorkDordrechtLondon
LibraryofCongressControlNumber:2012941624
(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
theCopyrightLawofthePublisher’slocation,initscurrentversion,andpermissionforusemustalways
beobtainedfromSpringer.PermissionsforusemaybeobtainedthroughRightsLinkattheCopyright
ClearanceCenter.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)
Parts of this thesis have been published in the following journal articles:
I. F. Öisjöen, P. Magnelind, A. Kalaboukhov, D. Winkler. ‘‘High-T SQUID
c
gradiometer system for immunoassays’’. Supercond. Sci. Technol. 2. 034004
(4pp), 2008.
II. F. Öisjöen, J. F. Schneiderman, M. Zaborowska, S. Karthikeyan, P. Magne-
lind, A. Kalabukhov, K. Petersson, A. P. Astalan, C. Johansson, D. Winkler.
‘‘Fast and sensitive measurement of specific antigen-antibody binding reac-
tions with magnetic nanoparticles and HTS SQUID’’. IEEE Trans. Appl.
Supercond. 19(3). 848–852, 2009.
III. V.Schaller,A.Sanz-Velasco,A.Kalabukhov,J.F.Schneiderman,F.Öisjöen,
A. Jesorka, A. P. Astalan, A. Krozer, C. Rusu, P. Enoksson, D.Winkler.
‘‘Towards an electrowetting-based digital microfluidic platform for magnetic
immunoassays’’. Lab on a Chip. 9. 3433–3436, 2009.
IV. F. Öisjöen, J. F. Schneiderman, A. P. Astalan, A. Kalabukhov, C. Johansson,
D. Winkler. ‘‘A new approach for bioassays based on frequency- and time-
domain measurements of magnetic nanoparticles’’. Biosensors and Bioelec-
tronics. 25. 1008–1013, 2010.
V. F. Öisjöen, J. F. Schneiderman, A. P. Astalan, A. Kalabukhov, C. Johansson,
D. Winkler. ‘‘The need for stable, mono-dispersed, and biofunctional mag-
netic nanoparticles for one-step immunoassays’’. J. Phys: Conf. Ser. 200.
122006, 2010. doi:10.1088/1742-6596/200/12/122006.
VI. F. Öisjöen, J. F. Schneiderman, G. A. Figueras, M. L. Chukharkin,
A. Kalabukhov, A. Hedström, M. Elam, D. Winkler. ‘‘High-T supercon-
c
ductingquantuminterferencedevicerecordingsofspontaneousbrainactivity:
Towards high-T magnetoencephalography. Appl. Phys. Lett. 100. 132601,
c
2012. doi:10.1063/1.3698152.
Supervisor’s Foreword
It is our great pleasure to introduce Dr. Fredrik Öisjöen’s thesis work for the
SpringerThesisPrize.Thischallengingresearchhasfocusedondevelopingproof-
of-principle measurements with systems that incorporate superconducting tech-
nology in the biomedical arena. The activities include two topic areas, both of
whicharespecifictobiomedicalapplicationsofhighcriticaltemperature(high-T )
c
superconducting quantum interference devices (SQUIDs). The most significant
contributions to the field were:
I. Both theoretically and experimentally demonstrating the efficacy and com-
patibility of biomolecular detection via rapid time-domain and high-resolu-
tion frequency domain SQUID-based recordings of bio-functionalized
magnetic nanoparticles.
II. Openingthefieldofhigh-T SQUID-basedmagnetoencephalography(MEG)
c
forrecordingbrainfunction.Thiswasmadepossiblebyproving(contraryto
the common belief) that a simple and reliable fabrication process could
generatehigh-T SQUIDdetectorssensitiveenoughtomatch,orpotentially
c
exceed, the signal-to-noise ratios of their conventional low-T counterparts
c
when recording magnetic signals generated by brain activity. Remarkably,
the manuscript reporting the MEG results demonstrating spontaneous brain
signals using high-T SQUIDs, was accepted within just 5 working days of
c
submission to Applied Physics Letters.
The work by Fredrik Öisjöen does not simply improve on existing technology
but opens possibilities for novel advanced medical devices and techniques. Fast
magnetic immunoassays can be used to improve the sensitivity of existing bio-
molecular detection techniques or create new, unique point-of-care diagnostic
systems.High-T SQUIDtechnologycanpossiblyimprovetheclinicalavailability
c
of MEG systems as well as provide new insights into how our brain works.
Combined together with ultra-low field magnetic resonance imaging, this tech-
nology can be used to acquire both functional and structural brain images at the
sametime.Suchacapabilityiscriticalforimprovingpatientoutcomesinavariety
of clinical applications. Successful development of three different techniques
vii
viii Supervisor’sForeword
based on the same sensor technology makes Dr. Öisjöen’s thesis work of high
scientificqualitythatisworthy ofrecognition.Wehopethereaderwillenjoythis
very well-written and exciting thesis.
Gothenburg, Sweden, 26 April 2012 Dag Winkler
Alexey Kalabukhov
Justin F. Schneiderman
Acknowledgments
First of all I would like to thank my examiner and main supervisor Dag Winkler
forgivingmetheopportunitytoworkinthisexcitingfieldaftermydiplomawork
and for guidance and advice leading to this thesis.
I wish to express my gratitude to my co-supervisor, Alexey Kalabukhov, for
valuablediscussions,forexcellentteachingofcleanroomprocessingandforallthe
time and effort he has put in to support me.
Iamgratefultomyco-supervisorJustinSchneidermanforteachingmegeneral
experimental techniques, all the support in the laboratory, and for help with
articles.
I would like to thank John Clarke at UC Berkeley for allowing me to work in
his lab for 3 months. This is where I learned the basics of ULF-MRI in ‘‘team
Scandinavia’’ together with Koos Zerenhoven. Thanks also to Sarah Busch and
Michael Hatridge.
Many thanks to Andrea Prieto Astalan, Jakob Blomgren, Karolina Petersson,
Magdalena Zaborowska, and Christer Johansson at Imego AB for all the collab-
orativeworkandvaluablediscussionsregardingmagneticnanoparticlesandassay
experiments. Special thanks also to Christer for comments on this thesis.
I thank Vincent Schaller and Anke Sanz-Velasco for the efforts on the EWOD
platform and I am hopeful about the ongoing and future collaborative efforts.
I would like to thank Mikael Elam and Anders Hedström at the Sahlgrenska
hospital for useful input and discussions regarding the MEG experiments and for
thehighlyvaluableEEGsessions.Iamlookingforwardtocontinuingtheongoing
efforts. Thanks also to Göran Pegenius for help in setting up the EEG recordings.
Thanks to Maxim Chukharkin for helping out in the laboratory and in the
cleanroom.
I am also thankful for the great work by Magnus Jönsson on the ULF-MRI
system. Magnus is one of the main contributors in this project.
Thanks to the cleanroom staff of MC2 for helping out with fabrication issues
and training, special thanks to Henrik Fredriksen for all his help.
StaffanPehrsonandLarsJönssonareacknowledgedformachiningpartsforthe
experimental setups and Ann-Mari Frykestig and Marie Fredriksson for all the
administrative support and Jan Jacobsson for technical support.
ix
x Acknowledgments
Ithankmyoffice-mateSamuelLaraforinspiringdiscussions.Iwouldalsolike
to thank all the past and present members of the Quantum Device Physics labo-
ratory at MC2 for creating the nice atmosphere and environment to work in.
Iwouldliketothankmylovelyfamily(Maria,Hans,Johanna,Dan,Sally,and
everyone else) and all of my friends for their support and finally, thank you
Magdalena for always supporting and encouraging me!
FinancialsupportisacknowledgedfromtheEuropeanCommissionFramework
Program 7 (FP7/2007–2013) project MEGMRI (grant ageement no. 200859), the
European Commission Framework Program 6 (FP6/2005–2008) project Bio-
diagnostics (grant ageement no. NMP4-CT-2005-017002) the Kristina Stenborgs
foundation, Knut och Alice Wallenberg fund, the Swedish research council, the
Swedish foundation for strategic research, Chalmers friends, and Chalmerska
forskningsfonden.
