Nanowire based biosensors

Popular abstract (in Danish only)

Den menneskelige arvemasse er nu kortlagt og det næste store spørgsmål er: hvilken funktion har de proteiner som generne koder for? Mange proteiner fungerer ved at binde til andre proteiner, og for disse proteiner er spørgsmålet: hvilke proteiner kan det binde sig til og hvor stærk er bindingen? Generelt er det svært at måle disse ting for proteiner, men vi foreslår her en ny metode, baseret på nano-teknologi, som vil det muligt at udføre disse målinger hurtigt og præcist. Vi vil fremstille sensorer baseret på ekstremt tynde tråde af halvledermaterialer. Udfra disse nanotråde bygges transistorer, som med stor følsomhed registrerer hvad der sker på deres overflade. Ved at behandle trådene med forskellige proteiner, opnåes selektiv detektion af de eftersøgte reaktioner mellem proteiner.

Projektet udføres i tværfagligt samarbejde mellem grupper i nanofysik, bioteknologi og teoretisk protein-kemi. I samspil mellem detaljeret computermodellering af proteinerne og eksperimenter vil protein-sensorer med hidtil uset følsomhed blive udviklet. Eksempelvis vil følsomheden kunne øges ved at dekorere nanotrådene med orienterede proteiner, der er designet til at udvise særligt stor ladningsændring ved reaktion med andre proteiner. Generelt vil metoden kunne udnyttes som platform for en lang række andre interessante biosensorer.

Project

Our overall aim of the project is to develop and optimize ultra-sensitive sensors based on devices incorporating nanowires as the active elements. This will provide a versatile platform for new types of biosensors.

Semiconductor nanowires are solid crystalline rods that are typically 20-100 nm in diameter and several micrometers long. We grow such wires either by Molecular Beam Epitaxy (III-V materials) or Chemical Vapor Deposition (Si/Ge). They can be transferred to standard planar substrates, e.g. Si/SiO2 wafers, and contacted electrically using nanofabrication techniques (e-beam and UV lithography).

Under ambient conditions the nanowire devices can behave as Field-Effect Transistors (FET) where transport is sensitive to a gate voltage - or to changes in the charge distribution at the surface of the nanowire. In the latter case, the devices can effectively operate as sensors in a liquid environment. The nanowire FET sensors can be used as a platform for various types of biosensors as shown in recent reports where changes in the nanowire surface charge due to protein or ligand binding allowed direct detection of local change in transistor conductance.

Our interdisciplinary collaboration is currently developing a novel generation of biosensors using the exquisite properties of membrane proteins with the extreme sensitivity of NW-FETs. The first biosensor under development in our consortium is designed for sensing neurotransmitters and will be of major interest for diagnostic and drug screening.

Particular attention is given to the control of the orientation of the protein to the surface to guarantee its proper functionality and an optimum specificity of the detected signal. The influence on the conductivity of the nanowire of the orientation of the recognition motif and the quantitative modeling of the charge distribution of the protein are currently investigated using advanced computational chemistry methods. Additional parameters for rational design of nanowire based biosensors are under investigation for further applications in proteomics.

The translocation of nanowires to living mammalian cells is also under investigation by our consortium and will be of major interest for intracellular sensing and drug delivery. 

Staff

Trine Berthing (master student, bionano)
Princia Salvatore (master student, nanophysics)
Lars Iversen (PhD student, bionano)
Yi-Chi Liu (PhD student, bionano)
Nathalie Rieben (PhD student, bionano)
David M. Rogers (postdoc, computational chemistry)
Brian Skov Sørensen (postdoc, nanophysics)
Nadia Cherouati (postdoc, bionano)
Claus B. Sørensen (PhD, technical head, nanophysics)
Jesper Nygård (associate professor, nanophysics)
Jan H. Jensen (associate professor, computational chemistry)
Karen Martinez (assistant professor, bionano)

Publications and preprints

"Ambipolar transistor behavior in MBE grown p-doped InAs nanowires", B.S. Sørensen, M. Aagesen, C.B. Sørensen, P. E. Lindelof, K. Martinez, J. Nygård, Applied Physics Letters 92, 012119 (2008).

Other related publications from the groups

"Molecular Beam Epitaxy growth of free standing plane-parallel InAs nanoplates", M. Aagesen, E. Johnson, C.B. Sørensen, S.O. Mariager, R. Feidenhans'l, E. Spiecker, J. Nygård, P. E. Lindelof, Nature Nanotechnology 2, 761 (2007)

"Kondo physics in tunable semiconductor nanowire quantum dots", T. S. Jespersen, M. Aagesen, C. Sørensen, P. E. Lindelof, J. Nygård, Physical Review B 74, 233304 (2006)

"Lipid-coated Nanocrystals as Multi-functionalized Luminescent Scaffolds for Supramolecular Biological Assemblies", I. Geissbuehler, R. Hovius, K. L. Martinez, M. Adrian, K. R.Thampi, H. Vogel, Angewandte Chemie, Int. Ed., , 44: 2-5 (2005)

"Ligand binding to G-protein coupled receptors in tethered cell membranes", K. L. Martinez, B. H. Meyer, R. Hovius, K. Lundstrom, H. Vogel, Langmuir, 19(26):10925-29 (2003

Funding

The primary sources of funding for this work are the project "Rational design of ultra sensitive nanowire based biosensors for proteomics" from the Danish Research Council for Technology and Production Sciences (FTP), "Single Molecules Nanoscience" Programme of Excellence funding from University of Copenhagen, a Skou fellowship from the Danish Natural Science Research Council (FNU), "Arrays of Nanoscopic Biosensors on Surfaces" from the Danish Research Agency - Basic funding NABIIT, and a fellowship from Lundbeckfonden, respectively.

Contacts (group leaders):

-   Nanophysics/nanowires: Jesper Nygård,  (+45) 35 32 04 86
-   Computational chemistry: Jan H. Jensen, (+45) 35 32 02 39
-   Bionanotechnology: Karen Martinez, (+45) 35 32 04 75