Nanobiotechnology

The aim of the proposed project is to initiate a research program that can integrate and sustain cell culture in micro- and nanostructures, with state-of-the-art biological read-out systems, extracting the signals from such diverse sources as neuronal electrical activity and cellular gene and protein expression. Within this scope three post-doc positions are established.

The various post doc projects will have primary affiliations at The Microelectronics Centre in Lyngby, at the Department of Cell and Organism Biology and the Arthand project in Lund, and at the Division of Solid State Physics and the Nanometer Consortium in Lund, but will, for shorter periods, perform work at the collaborating institutions in Lund, Sweden and Lyngby, Denmark, respectively.

On-line bio-array monitoring of on-chip cell culture
The aim of this research project is to investigate and integrate on-chip thermal regulation for micro- and nanoscale analysis, specifically focusing on cell culture chambers and hybridisation chambers for bio-molecular assays.
Combining in-vitro cell culturing facilities on chip, with on-chip functions, like DNA micro arrays, will enable the development of integrated systems for cell culturing and monitoring e.g. for genotyping and gene expression analysis. The combination of a hybrisation-based detection methods and culturing of cells on-chip however, can only be realised by use of a precisely regulated thermal control mechanism, ensuring both proper cell culture conditions and the ability to perform molecular biology reactions (as e.g. gene amplification or hybridisation). In relation to micro- and nano-scale analysis, the thermal mass of the sample is orders of magnitude lower than the analysing structure itself, and often discrete temperatures are needed on dicrete locations and at specific time-points in the analysis. The use of external Peltier elements can make sub-ambient temparature cycling possible, but temperature cycling of the entire thermal mass is a slow process, and cannot be restricted to smaller localised areas of the chip. Integration of functional micro-Peltier elements on chip, have not until recently been possible for temperature cycling at ambient room temperature conditions. In this project the use of thin-film Peltier elements will be investigated as local heat and cooling source for use in micro-and nano-systems, especially focusing on temperature stability in cell culture chambers and furthermore temperature cycling in bio-molecular reaction chambers.
Contact for further information:
Associate Professor Claus BV Christensen. Post Doc Sarunas Petronis
The Microelectronics Centre, Technical University of Denmark.

On-chip in-vitro neural interfacing
Study and develop a nanoelectronic chip allowing monitoring and stimulation of electrical activity in the nervous system with cellular resolution. The work will encompass biological approaches ranging from in vitro culturing of neurons to in vivo implantation.
The last decade has witnessed an increased capability to image and fabricate nanostructures with a very high precision that has revolutionized several fields of sciences. However, in the life science area the usage of nanotechnology is still in its very early phase. In this proposal we will employ nanostructured surfaces to increase the possibility to direct nerve cell growth and to enhance the possibility to detect the nerve cell signal traffic. Generally speaking we can play with morphology, geometry and chemistry in combination with buried and insulated electrodes and the set of detecting electrodes. We have to use a combination of methods including cultures of dissociated neurons, whole ganglia (collection of nerve cell bodies) which represents neurons from the peripheral nervous system (PNS) and spinal cord slices (central nervous system, CNS,) to be able to measure interactions between the chip surface and the nervous system. The dissociated cultures are used to study the surface properties of the chip with respect to the adhesion of neurons. This is achieved by seeding a pre-determined number of neurons on the chip and then, after various periods of time counting the number of neurons which remains attached to the chip surface. In this manner the adhesive properties of different surfaces can be determined as can the effects of covering the chip surface with e.g. laminin and growth factors.
Contact for further information:
Professor Martin Kanje. Post Doc Cecilia Eriksson
Department of Cell and Organism Biology, Lund University, Sweden.

Single molecule detection using nanotechnology
Development of nanotechnology methods and tools that allow characterization and detection of single cells, single molecules and single molecular events, e.g. DNA hybridization and protein-protein interactions etc.
We will utilize nanotechnology to fabricate a sensing area that allows detection of binding events for only a few or single molecules. The procedure will be to selectively immobilize a binding agent on the sensor area, and to monitor the change of the electrical, mechanical or optical properties of the “smart sensor” as a function of the binding reaction with the target. Improved sensitivity will be a key parameter in micro-and nanoscale assays, where minimum of sample and reagents are used. By studying molecules and cells one by one, information is made accessible that would otherwise be averaged out in standard population based assays. Examples of research activities within this project are: i) By employing an integrated near-field source and a microfluidic channel defined to pass a stretched DNA molecule over the source, DNA and any labels attached to it may be imaged at a high resolution. The aim is to exceed the resolution of standard optical microscopy in order to analyze DNA with respect to size, genetic contents, bound ligands. ii) Nanomechanical systems, e.g. nanosized cantilevers of silicon/metals or semiconductor whiskers have resonance frequencies that upon adsorption of molecules change with a targeted attogram sensitivity, i.e. allow single molecule detection. iii) Using 1-D nanostructures one may detect single or few antibody-antigen interactions by monitoring how local environment around and at the surface of the 1-dimensional nanostructure affect e.g. the current through such systems.
Contact for further information:
Professor Lars Montelius. Post Doc Christelle Printz
Division of Solid State Physics, The Nanometer Consortium, Lund University, Sweden.