Biomedical subjects

Koen Visscher

Publications and source records attributed to Koen Visscher.

5 recordsLinked to original sources

PubMed2004

Suppression of noise in a noisy optical trap.

We have experimentally explored and clarified the concept of noise suppression in intrinsically noisy systems by adding noise at the input using a microscopic bead held in a moving and intensity-modulated optical trap. By coupling the stiffness of the optical trap to its position, we have explicitly constructed an experimental model system in which added fluctuations in the trap position result in reduced variance of the observed bead position as compared to a stationary trap. This reduction in variance and the spectral properties of the observed output noise agree with theoretical predictions. Our experiment demonstrates that the essential aspect of noise reduction in such a system is that the added fluctuations drive the system into states with a reduced intensity of intrinsic noise sufficiently often.

Journal Article↗

PubMed2004

Elastic properties of a single-stranded charged homopolymeric ribonucleotide.

We have investigated the elastic properties of poly(U), homopolymeric single-stranded RNA molecules that lack any base pairing and stacking interactions and conform to a random-coil structure. Using single-molecule stretching experiments we show that the elastic properties are described by a wormlike chain model for polymer elasticity rather than by a freely jointed chain model as is commonly used for single-stranded DNA. At low [Na+], introduction of a scale-dependent persistence length is required to account for electrostatic contributions.

Computer Simulation↗

PubMed2004

Noise suppression and spectral decomposition for state-dependent noise in the presence of a stationary fluctuating input.

It recently has been shown that the observed noise amplitude of an intrinsically noisy system may be reduced by causing the underlying state to fluctuate [Phys. Rev. Lett. 86, 950 (2001)]]. This paper extends the previous theory by considering the full power spectrum of the output signal, interpreting noise reduction in terms of the low-frequency end of the spectrum as well as the integrated spectrum. Our treatment accounts for arbitrarily sized fluctuations and deals with both continuous and discretely sampled observations. We show that noise suppression is possible if and only if the stationary average of the intensity of state-dependent noise decreases. We apply our analysis to an example involving saturable electrical conduction discussed in the original paper by Vilar and Rubí.

Biophysics↗

PubMed2004

Single-molecule techniques for drug discovery.

Single-molecule techniques offer a number of key benefits over conventional in vitro assay methods for drug screening, as they use less material and unlock the ability to observe transient states. By observing such states, it should be possible to screen for chemical compounds that isolate these steps. The benefit of this is twofold: (a) inhibitors can be found that target key phases in biochemical processes, e.g., transcription initiation; and (b) the total number of drug targets increases as many biochemical processes consist of many transient steps, e.g., transcription promoter binding, initiation, elongation, and termination. Although single-molecule methods offer exciting opportunities for new ways of discovering drugs, there are a number of obstacles to their adoption for drug screening. The main hurdle is to develop robust apparatus that will allow many thousands of individual single molecule experiments to be performed in parallel. By using recently developed integrated microfluidics technology, this hurdle may be overcome. Here, a number of potential single-molecule approaches to drug screening are presented along with a discussion of the benefits and technical obstacles that must be overcome.

Drug Evaluation, Preclinical↗

PubMed2003

Colloidal epitaxy: playing with the boundary conditions of colloidal crystallization.

We have studied, with quantitative confocal microscopy, epitaxial colloidal crystal growth of particles interacting with an almost hard-sphere (HS) potential in a gravitational field and density matched colloids interacting with a long-range (LR) repulsive potential with a body-centred cubic (BCC) equilibrium crystal phase. We show that in both cases it is possible to grow thick, stacking fault-free metastable crystals: close-packed crystals with any stacking sequence, including hexagonal close packed (HCP), for the HS particles and face-centred cubic (FCC) in the case of the LR colloids. In accordance with recent computer simulations done for HS particles it was found that the optimal lattice constant to grow HS HCP crystals was larger than that of equilibrium FCC crystals. In addition, because of the absence of gravity, pre-freezing could be observed for the particles with the LR potential on a template of charged lines. We also argue that the ability to manipulate colloids with highly focused light, optical traps or tweezers, will become an important tool in both the study of colloidal crystallization and in making new structures. We show how cheap 2D and 3D templates can be made with optical tweezers and demonstrate, in proof of principle experiments with core-shell colloids, how light fields can generate crystal nuclei and other structures in the bulk of concentrated dispersions and how the effect of these structures on the rest of a dispersion can be studied quantitatively in 3D.

Journal Article↗