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NANOTECHNOLOGY AND HEALTHCARE MODULE HOME PAGE

MSc in Nanotechnology Module NTH [NANOGE01]
MEng in Electronic Engineering and Nanotechnology 4th Year Course [NANOME01]
Master of Research Doctoral Training Centre (DTC) in Photonic Systems Development Elective Module

Academic year     2011 − 2012
Term: First Term
Pre-Requisites: None
Lecturer/s: Mick Flanagan (2011-2012 Academic Year)        [Academic year 2012-2013: to be announced]
Timetables:This module has now been delivered for the 2011-2012 academic year. See NTH 2012-2013 for details of this module for the academic year 2012-2013.
Examination: Examination Description       Past Papers        Revision.

AIMS

  • This course covers the application of nanotechnology to both devices and instrumentation for the doctor-patient interface, the hospital environment and the medical research laboratory.
  • The course includes descriptions and discussions of the underpinning techniques and aims to leave those attending the course with a good appreciation of the present state of the art, the future potential, the business context and the regulatory constraints.



SYLLABUS

The 2011−2012 syllabus will cover those topics covered in the 2010−2011 syllabus (listed below). Small changes of emphasis recognising the rapidly advancing research in many of these topics may be announced later.
  • Biosensors - present state of art and future potential:
    Devices for testing in the Doctor’s Office, e.g. of blood and urine samples, for Home Monitoring; for Ambulance Monitoring; for Bedside Monitoring.
    Blocks to a full present implementation of such sensors:
             Technical Problems, Business constraints, Regulatory constraints.
    The potential of nanotechnology to remove these blocks.
  • Underpinning Electronic and Optical Techniques:
    Amperometric sensors;
    Potentiometric sensors, including chemically sensitive field effect transistors;
    Optical sensors, including evanescent field sensors; Optical waveguide sensors;
    Fluorescent labels: organic dyes and quantum dots
    Surface Plasmon Resonance sensors;
    Capillary Fill devices;
    Electrochemical Impedance Spectroscopy;
    Electro-mechanical devices, e.g. cantilever sensors;
  • Underpinning Biological Techniques:
    Enzyme-based assays;
    Antibody-based assays;
    Nucleic-acid based techniques, e.g. Polymerase Chain Reaction (PCR)
    Synthesis of the above onto a ‘lab-on-a-chip’
    Tethered membranes
  • Hospital Environment:
    • Imaging and targetted drug delivery
      This section will address the novel nanoscale imaging and drug delivery agents now arising at the research level.
    • Stem cell research
      This section will examine some of the techniques arising from nanotecholgy processing that may contribute to such aspects of tissue engineering as better stem cell scaffolds.                


READING LIST

  • Links to papers may only display the full paper if you are logged onto a UCL terminal.
  • Most of the journals cited are available in on-line electronic journal format accessible through the UCL Library Services' Electronic journals web-page.
  • Most of the books and journals required by this course will be found in the UCL Science Library [DMS Watson Building] but some may be found in the Cruciform Library [Clinical and Medical Sciences Library, Cruciform Building].

GENERAL BACKGROUND READING

INTRODUCTION TO MOLECULAR AND CELL BIOLOGY

  • The following link provides a very simple introduction to cell biology:
    National Center for Biotechnology Information’s What is a Cell

  • An ideal reference book for the cell and molecular biology aspects of the NTH module is
    Molecular Biology of the Cell; B Alberts, A Johnson, J Lewis, M Raff and P Walter; Garland; New York.
    UCL Library codes: MEDICAL SCIENCES D 5 ALB & CRUCIFORM QH 581 ALB
    Its introduction to biochemical structures also contains an excellent introduction to the relevant organic chemistry for those who have not taken this subject.

  • BookBooN.com publish a range of free on-line downloadable textbooks including an introduction to protein structure:
          Molecular Conformations, Christopher Wood, 2010

BIOSENSORS AND BIOELECTRONICS

  • Biosensors and bioelectronics represent a major aspect of research and development, relevant to health care, preceding, underpinning and now incorporating much of nanotechnology research on medical diagnostic applications.

  • There is a good selection of books on biosensors in the DMS Watson Science Library, especially in the ENGINEERING QQ 90 section.

    Jacqueline Edge, a MSc in Nanotechnology Postgraduate [2007-2009], has carried out an excellent review of the NTH relevant textbooks in the ENGINEERING QQ 90 section of the UCL library. This is far more valuable than any review I might post which would be coloured by my years of working in the area and hence risking not recognizing when my tacit knowledge is leading me to recommend texts that are not clear to someone new to the area. I enthusiastically commend this review - Mick Flanagan.

    Jacqueline Edge’s Text Book Review

  • Relevant text-books may also be found in the CHEMISTRY section, e.g.
    • Biosensors and modern biospecific analytical techniques, Volume 44 of Wilson & Wilson’s Comprehensive Analytical Chemistry; Ed. L Gorton; Elsevier, Amsterdam, London; 2005 [CHEMISTRY C 5 WIL]
    Generally the books in these sections of the library are not specifically oriented to applications in nanotechnology, it is too new an area, but browsing in these sections, in light of the lectures, will enable you to gain sufficient knowledge of the background to biosensor development in nanotechnology.

  • The journal Biosensors and Bioelectronics [DMS Watson Science Library, ENGINEERING Pers & on-line electronic resource] is an excellent source for recent advances in the area.

ELECTROCHEMISTRY

  • An elementary understanding of electrochemistry is essential to an understanding of the many surface phenomena that are critical to diagnostic devices. The following text covers the basic electrochemistry needed in this module:
    • Electrochemical Methods : Fundamentals and Applications; Allen J Bard and Larry R Faulkner; Wiley, New York, Chichester : 2nd ed.; 2001 [CHEMISTRY D 180 BAR]

CHEMICALLY SENSITIVE FIELD EFFECT TRANSISTORS

  • All good biosensor books (see Biosensors and Bioelectronics above) cover Chemically Sensitive Field Effect Transistors (ChemFETs).
    All good electonics device books cover the underpinning Field Effect Transistor (FET), e.g.
    • Fundamentals of Semiconductor Devices; Edward S Yang; McGraw-Hill, New York, London; 1978 [ENGINEERING TE 51 YAN]

    Recent work on FETs with ionic conduction:
    • A polysaccharide bioprotonic field-effect transistor; Chao Zhong, Yingxin Deng, Anita Fadavi Roudsari, Adnan Kapetanovic, M.P. Anantram & Marco Rolandi,Nature Communications 2, 20 September 2011.

    The originator of the ChemFET, Jiri Janata, has written a review of ChemFETs

    The derivation of the Gouy-Chapman-Equation can be found in Bard and Faulkner (see above) and through the link:

    The derivation of the Donnan Potential can be found through the link:

THE ARTIFICIAL SYNAPSE

  • This paper on the Artificial Synapse indicates both the immense advances that nanotechniques have facilitated in this area but also the extent of the problems yet to be solved:

IMMUNOASSAY TECHNIQUES

  • An understanding of antibody-based diagnostic techniques (immunoassay) is required if you are to comprehend both the importance and the mechanism of micro- and nano-immunosensors. The following reference books cover this required background area:

    • Principles and Practice of Immunoassay; Eds. Christopher P Price, David J Newman; Macmillan Press, New York : Stockton; 1996 [MEDICAL SCIENCES FR 50 PRI] (The library’s earlier editions are fine)

    • The Immunoassay Handbook; Ed. David Wild; 3rd ed.; Amsterdam : Elsevier; 2005 [MEDICAL SCIENCES FR 50 WIL] (The library’s earlier editions are fine)

    • Alternative Immunoassays; Ed. W P Collins; Chichester : Wiley; 1985 [MEDICAL SCIENCES LK 9 COL]

OPTICAL WAVEGUIDE SENSORS (Evanascent Field Sensors)

FLUORESCENCE ENERGY TRANSFER (FRET) IMMUNOSENSORS

  • A miniaturized heterogeneous fluorescence immunoassay on gold-coated nano-titer plates, Michael Seidel, Daniela M. Dankbar and Günter Gauglitz, Anal Bioanal Chem (2004) 379: 904−912

PHOTO-ACTIVATED ANTIBODY IMMOBILISATION

  • Photonic activation of disulfide bridges achieving oriented protein immobilization on biosensor surfaces, Maria Teresa Neves-Petersen, Torben Snabe, Søren Klitgaard, Meg Duroux and Steffen B. Petersen, Protein Sci. 2006 15: 343-351
    [http://onlinelibrary.wiley.com/doi/10.1110/ps.051885306/pdf]

SURFACE PLASMON RESONANCE (SPR)

  • All good biosensor books cover surface plasmon resonance based sensors (see Biosensors and Bioelectronics above)

  • Surface Plasmon Resonance Based Sensors in Springer Series on Chemical Sensors and Biosensors; Volume Four; Ed.Jiri Homola; Springer, Berlin; 2006 [ENGINEERING QQ 90 SPR]

  • The link: http://www.sprpages.nl/index.html covers the basics and several applications.

  • The Biacore instrument is probably the most important commercialisation of SPR.

LANGMUIR-BLODGETT FILMS

ELECTROCHEMICAL IMPEDANCE SPECTROSCOPY (EIS)

  • Impedance analysis of phosphatidylcholine membranes modified with valinomycin, Monika Naumowicz, Joanna Kotynska, Aneta Petelska and Zbigniew Figaszewski, Eur Biophys J (2006) 35: 239−246.

  • Impedance Analysis and Single-Channel Recordings on Nano-Black Lipid Membranes Based on Porous Alumina, Winfried Römer and Claudia Steinem, Biophys J. 2004 February; 86(2): 955−965.

  • Impedance Spectroscopy Technique for DNA Hybridization, S. Hleli, A. Abdelghani and A. Tlili, Sensors 2003, 3, 472−479.

  • An impedance array biosensor for detection of multiple antibody−antigen interactions, Xiaobo Yu, Renji Lv, Zhenqiu Ma, Zhihong Liu, Yanhong Hao, Qingzhang Li and Danke Xu, Analyst, 2006, 131, 745−750

  • Ultrathin Electrochemical Chemo- and Biosensors: Technology and Performance in Springer Series on Chemical Sensors and Biosensors; Volume Two, Ed. Vladimir M. Mirsky; Springer, Berlin; 2004 [ENGINEERING QQ 90 SPR]

  • The Gamry Instrument Company web site contains links to excellent descriptions of many aspects of conventional EIS:

  • Mick Flanagan's Java library contains classes for both fitting EIS data and simulating EIS responses:

  • Matrix Algebra
    A knowledge of matrix algebra will not be required in answering the NTH examination questions but is needed if you wish to delve further into Impedance Spectroscopy, especially in following the non-linear regression techniques essential to the analysis of impedance spectra. The Holistic Numerical Methods Institute host an excellent web site on numerical methods including:
    Introduction to Matrix Algebra

  • Computational Techniques
    A knowledge of computer programming will not be required in answering the NTH examination questions but may well be needed if you wish to delve further into regression analysis and many other aspects of numerical analysis applied to nanotechnology. The following series of books provide an excellent introduction to many topics in scientific computing relevant to numerical analysis:
    William H. Press, Saul A. Teukolsky, William T. Vetterling and Brian P. Flannery
    Numerical Recipes: The Art of Scientific Computing,             Numerical recipes in C: The Art of Scientific Computing
    Numerical recipes in C++: The Art of Scientific Computing,            Numerical recipes in FORTRAN: The Art of Scientific Computing
    DMS Watson Library: COMPUTER SCIENCE G 10 PRE

TETHERED LIPID MEMBRANES

  • F Separovic and B A Cornell, Gated-Ion Channel-Based Biosensor Device, in Biological Membrane Ion Channels: Dynamics, Structure and Applications, (Eds: S H Chung, O S Andersen & V. Krishnamurthy), Springer, August 22, 2006, 595-622.

  • Ultrathin Electrochemical Chemo- and Biosensors: Technology and Performance in Springer Series on Chemical Sensors and Biosensors; Volume Two; Ed. Vladimir M. Mirsky; Springer, Berlin; 2004 [ENGINEERING QQ 90 SPR]

STEM CELL, TISSUE ENGINEERING AND SCAFFOLDS

  • Scaffolds for stem cells, N D Evans, E Gentleman & J M Polak, MaterialsToday, 9, Issue 12 , December 2006, 26-33.

  • Laser Fabrication of Three-Dimensional CAD Scaffolds from Photosensitive Gelatin for Applications in Tissue Engineering
    Aleksandr Ovsianikov, Andrea Deiwick, Sandra Van Vlierberghe, Peter Dubruel, Lena Möller, Gerald Dräger, and Boris Chichkov
    Biomacromolecules, 12, 851-858 (2011)

  • Fully Biodegradable Self-Rolled Polymer Tubes: A Candidate for Tissue Engineering Scaffolds
    Svetlana Zakharchenko, Evgeni Sperling, and Leonid Ionov
    Biomacromolecules, ASAP, April 27, 2011.

  • Applications of Nanotechnology in Tissue Engineering,
    Xuejun Wen, Donglu Shi & Ning Zhang,
    Handbook of Nanostructured Biomaterials and Their Applications, American Scientific Publishers, Vol 2, 393-414, 2005.

  • Self-Assembling Nanofibers Inhibit Glial Scar Formation and Promote Axon Elongation after Spinal Cord Injury
    Vicki M. Tysseling-Mattiace, Vibhu Sahni, Krista L. Niece, Derin Birch, Catherine Czeisler, Michael G. Fehlings, Samuel I. Stupp, and John A. Kessler
    The Journal of Neuroscience, April 2, 2008, 28(14):3814-3823

STEM CELLS AND QUANTUM DOT LABELLING

  • Human stem cell delivery for treatment of large segmental bone defects, Kenneth M. Dupont, Kapil Sharma, Hazel Y. Stevens, Joel D. Boerckel, Andrs J. Garca and Robert E. Guldberg, PNAS, 107 (8), 3305-3310, (February 23, 2010)

  • Labeling of Mesenchymal Stem Cells by Bioconjugated Quantum Dots, Bhranti S. Shah, Paul A. Clark, Eduardo K. Moioli, Michael A. Stroscio and Jeremy J. Mao, Nano Letters, 7 (10), 3071-3079, (2007)

  • Quantum Dots − Characterization, Preparation and Usage in Biological Systems, Jana Drbohlavova, Vojtech Adam, Rene Kizek and Jaromir Hubalek, International Journal of Molecular Sciences, (2009), 10, 656-673.

  • Biological applications of quantum dots, Timothy Jamieson, Raheleh Bakhshi, Daniela Petrova, Rachael Pocock, Mo Imani and Alexander M. Seifalian, Biomaterials 28 (31), 4717-4732, (November 2007)

  • How Quantum Dots Work, Evident Technologies Web Site: http://www.evidenttech.com/quantum-dots-explained/how-quantum-dots-work.html [last accessed 26 February 2010]

THE POLYMERASE CHAIN REACTION (PCR)

  • Animation
    The following link provides an animation of the PCR procedure with an accompanying narration: http://www.sumanasinc.com/webcontent/anisamples/molecularbiology/pcr.html

  • DNA Profiling
    The following link provides an excellent introduction DNA profiling:
    European Initiative for Biotechnology Education DNA Profiling

  • PCR Lab-on-a-chip
    Lab-on-a-chip PCR in continuous-flow: an ultrafast analytical tool for B-agents, Claudia Gärtner, Holger Becker, Thomas Clemens, Richard Klemm, Matthias Klotz, Nadine Hlawatsch, Proc. of SPIE Vol. 7304 73040G-1 (2009)

    Methods and instruments for continuous-flow PCR on a chip, Claudia Gärtner, Richard Klemm, Holger Becker, http://www.microfluidic-chipshop.com/files.php?dl_mg_id=33&file=dl_mg_1199801133.pdf

  • Real time PCR
    A Real-Time PCR Analyzer Compatible with High-Throughput Automated Processing of 2-µn;L Reactions in Glass Capillaries, Patrick N. Ngatchou, Mark R. Holl, Member, Charles H. Fisher, Mohan S. Saini, Jianchun Dong, Timothy and Deirdre R. Meldrum, IEEE Transactions on Automation and Science Engineering, 3, 141-151 (2006)

  • MEMS and Micro-heaters
    A Micromachine-based On-Chip Temperature Control System for Biomedical Applications, Chia-Yen Lee, Gwo-Bin Lee, Heng-Hui Liu, Fu-Chun Huang
    http://mbl.pme.nthu.edu.tw/english/eresearch/core/fd/Micro-PCR-ICMN-1.pdf

CANTILEVER SENSORS

  • Cantilever Array Sensors, H P Lang, M Hegner & C Gerber, MaterialsToday, April 2005, 30-36

  • Multiple label-free biodetection and quantitative DNA binding assays on a nanomechanical cantilever array, R A McKendry, J Zhang, Y Arntz, T Strunz, M Hegner, H-P Lang, M K Baller, U Certa, H-J Guntherodt, & Ch Gerber, Proc. Natl. Acad Sci. U.S.A. 99, 9783-9788 (2002).

ENVIRONMENTAL MONITORING

  • Lawrence Livermore Laboratories - APDS: the autonomous pathogen detection system, Benjamin J. Hindson, Anthony J. Makarewicz, Ujwal S. Setlur, Bruce D. Henderer, Mary T. McBride, John M. Dzenitis, (2005) Biosensors and Bioelectronics 20, 1925-1931.
    On-line summary at http://www.pathobiologics.org/btac/ref/APDS_Dzenitis92106.pdf.

PROCESS CONTROL

TARGETTED DRUG DELIVERY AND CELL IDENTIFICATION

  • Magnetic Nanoparticles, Q A Pankhurst, J Connolly, S K Jones & J Dobson Applications of magnetic nanoparticles in biomedicine, J. Phys. D: Appl. Phys. 36 (2003) R167-R181

  • Cancer cell targetting
    The Michigan Nanotechnology Institute Cancer cell targetted drug delivery programme
    Dendrimer-Based Nanomedicine, Edited by Istvan Majoros and James Baker, Pan Stanford Publishing, (2008) [ISBN-10: 9814241040, ISBN-13: 978-9814241045]

  • Cancer cell analysis
    Cell Surface as a Fractal: Normal and Cancerous Cervical Cells Demonstrate Different Fractal Behavior of Surface Adhesion Maps at the Nanoscale, M. E. Dokukin, N.V. Guz, R. M. Gaikwad, C. D. Woodworth, and I. Sokolov, Physical Review Letters, (2011), 107 (2), 028101-1 - 028101-4.

  • Fluorescence Activated Cell Sorting (FACS)
    http://www.bio.davidson.edu/courses/genomics/method/FACS.html

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NANOTECHNOLOGY AND HEALTHCARE (NTH) EXAMINATION


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