Papers by Louis Tiefenauer
Journal of The Electrochemical Society, Dec 1, 1996
This review presents the main principles underlying the theoretical description of the behavior o... more This review presents the main principles underlying the theoretical description of the behavior of regular and random arrays of nanometric active sites. It is further shown how they can be applied for establishing a useful semi-analytical approximation of the arrays responses under diffusion limited conditions when they involve the common situation of active sites with identical sizes. This approximation is general and, as exemplified for different type of arrays, can be employed for describing the behavior of any array involving arbitrary distributions of their active sites onto the substrate surface. Furthermore, this efficient approach allows statistical characterization of active sites distributions of any array based on chronoamperometric data.
Journal of Steroid Biochemistry, 1990
The use of the avidin/biotin complex in immunoassays is well documented. No comprehensive studies... more The use of the avidin/biotin complex in immunoassays is well documented. No comprehensive studies, however, are available on the structural requirements of the linkage between biotin and small molecules to get an optimal antigen-antibody interaction. We have synthesized seven different biotinylated estradiol derivatives. They were evaluated in an antibody- and in an antigen-immobilized enzyme immunoassay system. All three derivatives lacking a spacer group were useless for use in immunoassays, demonstrating the importance of a long distance between the biotin- and estradiol-moiety. In addition, the chemical structure of the linkage at the site of attachment to the steroid skeleton is very important for the antibody recognition: it may either be rigid but identical to that one used in the immunogen (6-carboxymethyloxime), or must be structurally flexible as exemplified by a 6-amido-linkage. A rigid structure (hydrazone) different from that of the immunogen absolutely prevents antibody binding.
Magnetic Resonance Imaging, 1996
Magnetite nanoparticles, coated by three different artificial polypeptides, were conjugated to an... more Magnetite nanoparticles, coated by three different artificial polypeptides, were conjugated to an antibody specific to the carcinoembryonic antigen (CEA). To protect the particles from fast blood elimination, the coats were modified by various sugars, polyethyleneglycol, albumin, and sialoproteins, respectively. The protective effect was determined by using a specific in vitro test and by analyzing the biodistrlbution of the nanoparticles in nude mice grafted with CEA-tumors. In particular, a prolongation of the blood circulation time has been expected, if a natural modifier is attached to the coated nanoparticles. Although the elimination rate could hardly be decreased by any modifiers, the tumor accumulation is slightly improved by using the specific sialoprotein glycophorin B. The usefulness of nanoparticles as image contrast agents is probably limited by their microdistribution within the tumor tissue. The requirements for a contrast agent to be highly tissue specific are discussed.
Biosensors and Bioelectronics, 2011
Functional assays for membrane proteins become increasingly important in biosciences. We demonstr... more Functional assays for membrane proteins become increasingly important in biosciences. We demonstrate the integration of reconstituted bacterial voltage-gated sodium channels (NaChBac) into preformed free-standing lipid bilayers by using the nystatin-ergosterol method to promote proteoliposome fusion. Vesicle delivery and subsequent NaChBac activity were monitored, the orientation of the transferred ion channels was assessed measuring at both, positive and negative holding potentials and the channel specificity was demonstrated by adding the blocker nimodipine. A conductance of 120 pS per channel and an opening time in the range of seconds have been observed. Interestingly, we found that fusion of proteoliposomes into preformed free-standing bilayers is limited, if hydrophobically silanized silicon nitride membranes are used as the supporting material. In this case the diameter of the liposome had to be at least 20 times smaller compared to that of the pore to render fusion possible.
Anticancer research
A biotinyl-derivative of 17 beta-estradiol has been used to demonstrate a site of recognition and... more A biotinyl-derivative of 17 beta-estradiol has been used to demonstrate a site of recognition and binding of estradiol located on the plasma membrane of human breast cancer MCF-7 cells by using the biotin/avidin-FITC system. The specificity of this binding has been shown by a displacement of the fluorescent label by 17 beta-estradiol. No displacement was observed when testosterone was added. Quantification of this phenomenon has been shown by laser scanning cytometry while preserving the cells adhesiveness to their growth support as well as their membrane integrity. An analysis by confocal laser scanning microscopy suggested that the fluorescence distribution on MCF-7 cells treated with estradiol-biotin was on the cell periphery. The results obtained are in favour of the recognition and binding site of 17 beta-estradiol located on the plasma membrane of MCF-7 cells and they would indicate that the biological activity of estradiol, among others, could be initiated by an interaction w...
Research Integrity and Peer Review, 2016
Conferences were established as global forums for discussion of ideas, policies and empirical fin... more Conferences were established as global forums for discussion of ideas, policies and empirical findings related to the responsible conduct of research. The Conferences aim to galvanise the global effort to strengthen the trustworthiness and reliability of research and encourage researchers worldwide to be accountable for their findings. Earlier conferences were held in Lisbon (2007), Singapore (2010) and Montréal (2010). The Rio conference attracted over 470 delegates from 42 countries, including leaders of research institutions and funding agencies, policy makers, editors and publishers, legal experts, researchers and graduate students. The theme of the conference was Research Rewards and Integrity: Improving Systems to Promote Responsible Research. These Proceedings contain the abstracts of the presentations given at the 4th World Conference in concurrent sessions, partner symposia, and poster sessions. Also included are summaries of the discussions in three focus tracks, which allowed delegates to consider and work on questions about the roles of funders, institutions, and countries in improving research systems and strengthening research integrity. Videos of the plenary presentations are available at the conference website (www.wcri2015.org).
Biosensors '92 Proceedings, 1992
The sensitivity and stability of a biosensor is dependent upon the method used to fix biomolecule... more The sensitivity and stability of a biosensor is dependent upon the method used to fix biomolecules on the sensing element. A new concept for an immunosensor is presented. The egg white protein avidin is covalently bound to a glassy carbon electrode surface in a virtual monolayer. Biotinylated ferrocene derivatives bind to avidin and were electrochemically detected. Regarding the results, immunosensors for a sub-nanomolar range seems to be feasible.
Advanced Materials, 2007
We thank Oliver Dubochet and Dr. Patrick Surbled (Axetris) for nanopore chips fabrication. The su... more We thank Oliver Dubochet and Dr. Patrick Surbled (Axetris) for nanopore chips fabrication. The support of Konrad Vogelsang and Jean-Jacques Hefti (PSI) for the silanization is kindly acknowledged. We also thank Dr. Michel Steinmetz and Prof. Dr. Ehud M. Landau for helpful discussions. The research was partially supported by the Swiss Commission for Technology and Innovation (CTI) grant #7644.2
Journal of Steroid Biochemistry, 1986
Journal of Clinical Biochemistry and Nutrition, 1987
TATuP - Zeitschrift für Technikfolgenabschätzung in Theorie und Praxis
TA-SWISS hat die Auswirkungen bezüglich Chancen und Risiken, welche durch Anwendung von Nanotechn... more TA-SWISS hat die Auswirkungen bezüglich Chancen und Risiken, welche durch Anwendung von Nanotechnik in der Medizin zu erwarten sind, durch die Beraterfirma Basics AG untersuchen lassen. Die Studie basiert auf zwei Expertenbefragungen. In der ersten Runde wurden Naturwissenschaftler und Mediziner zu ihren Vorstellungen bezüglich der Auswirkungen der Nanotechnologie für den Bereich Medizin in einem Zeithorizont von 20 Jahren befragt. In der zweiten Runde wurden Sozial-und Geisteswissenschaftler zu gesellschaftlichen und ethischen Auswirkungen befragt. Das Ergebnis dieser Befragungen ist von einer Begleitgruppe zur Studie intensiv diskutiert und analysiert worden. Die Studie der TA-SWISS wird im Folgenden kurz vorgestellt und aus der Sicht eines Mitgliedes der Begleitgruppe kritisch beleuchtet.
Biochimica et Biophysica Acta (BBA) - Biomembranes, 2017
The octa-peptide angiotensin II (Ang II, (H2NAspArgValTyrIleHisProPheCOOH)) is one of the key pla... more The octa-peptide angiotensin II (Ang II, (H2NAspArgValTyrIleHisProPheCOOH)) is one of the key player on blood pressure regulation in mammals. Predominantly binding to the Angiotensin type 1 and 2 receptors, the hormone is one of several peptide ligands binding to G protein coupled receptors (GPCR). The active hormone derives from a high molecular weight precursor sequentially cleaved by the proteases renin and the angiotensin converting enzyme (ACE). The chemical nature of the amino acid sequence has an impact on the behavior in the proximity of membranes, demonstrated using different membrane model systems and biophysical methods. Applying electrochemical impedance spectroscopy and small angle X-ray scattering a detailed view on the adhesion of the peptide with model membrane surfaces was performed. The role of specific amino acids involved in the interaction with the phospholipid head group were investigated and, studying a truncated version of Ang II, Ang (1-7), the key role of the C-terminal phenylalanine was proven. Truncation of the C-terminal amino acid abolishes the binding of the peptide to the membrane surface. A shift in pH, altering the protonation state of the central histidine residue impairs the adhesion of Ang II.
Journal of the Electrochemical Society, Nov 30, 1996
Chimia International Journal For Chemistry, Feb 28, 1999
Biosensor research is strongly interdisciplinary as it requires experience in chemistry, biochemi... more Biosensor research is strongly interdisciplinary as it requires experience in chemistry, biochemistry, biology, material science, electronics and engineering. The recent progress in micro-and nanotechnology allows to miniaturize complex systems as well as to address problems at a molecular level. The architecture and even the function of single molecules on a sensor surface have been investigated and can to some extent even be predetermined. At present, microtechnology is well established in the production of micro-fluid transport systems and has a high potential for cell-culturing and monitoring devices in the future. Three different running projects are presented which illustrate the usefulness of micro-and nanotechnology for biosensor research: 1)Investigations on amperometric immunosensor devices, 2) the measurement of binding forces of individual antigen-antibody pairs, and 3) the fabrication of microchannels suitable for neuron-cell growth and recording. Big efforts, however, will be required to integrate the recognition element of a sensor into a device for an intended application
Journal of materials science. Materials in medicine, 1999
Designed networks of neurons are potentially very useful to investigate neural activities. Using ... more Designed networks of neurons are potentially very useful to investigate neural activities. Using photolithography microgrooves suited in size for single neurons have been produced on glass chips. Two conducting gold lanes ending in each microgroove allow extracelluar stimulation of the neurons and recording of their activity. A cell adhesive surface was created by functionalization of glass with the adhesion peptide RGDC. In addition, in order to optimize the contact of the neuronal cell membrane to the electrode surface axonin-1, a specific neural adhesion protein was used. A recombinant form of axonin-1 was produced and immobilized in a correct orientation on protected gold surfaces through a C-terminal cysteine residue. Neurite outgrowth of neurons cultured on chips derivatized with RGDC or axonin-1 were compared. The developed materials and methods represent a first step towards establishing designed functionalized glass surfaces for neurophysiological investigations.
Blood, 1983
A patient with an X-linked genetic disease resembling chronic granulomatous disease (CGD) but dif... more A patient with an X-linked genetic disease resembling chronic granulomatous disease (CGD) but differing in several aspects from previously studied cases is described. The oxidase enzyme of the patient's granulocytes was normally activated, but had reduced activity as shown by an increased Michaelis constant and decreased maximum velocity of NADPH-dependent superoxide production. Cytochrome-b was undetectable in dithionite difference spectra. This CGD-like disease further implicates cytochrome-b as an important component of the microbicidal NADPH oxidase system and provides insight into its role in the enzyme complex.
Uploads
Papers by Louis Tiefenauer