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Multidimensional Optical Force NanoSpectroscope

Applicant Jeney Sylvia
Number 121396
Funding scheme R'EQUIP
Research institution Laboratoire de nanostructures et nouveaux matériaux électroniques EPFL - SB - IPMC - LNNME
Institution of higher education EPF Lausanne - EPFL
Main discipline Fluid Dynamics
Start/End 01.06.2009 - 30.09.2010
Approved amount 190'000.00
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All Disciplines (3)

Discipline
Fluid Dynamics
Molecular Biology
Biophysics

Keywords (10)

optical tweezers; microrheology; optical trapping interferometry; single molecule mechanics; Photonic Force Microscopy; DNA sequencing; confined Brownian motion; single cell spectrocopy; molecular recognition; microfluidics

Lay Summary (English)

Lead
Lay summary
We propose the development of a custom-made “Multidimensional Optical Force NanoSpectroscope”, with various applications in biophysics. Diffusion governed by Brownian motion is an efficient transport mechanism on short time and length scales. Even a highly organized system like a living cell relies, among other mechanisms, on the random Brownian motion of its constituents to fulfill complex functions. A Brownian particle will rapidly explore a heterogeneous environment that in turn strongly alters its trajectory. Five years ago, we developed at the LNNME-EPFL, an optical trap with a 3D detection system for thermal noise analysis the so-called Photonic force microscope (PFM) to study in details Brownian Motion in simple model fluids.Our findings showed that the temporal resolution of the PFM can be extended down to time scales where the nature of the fluid influences diffusion, bringing the long discussed idea of using a Brownian particle as a local reporter of the dynamics of complex biological fluids one step further.Currently, all the scientific questions, we are addressing together with a growing number of collaborating laboratories, show that it would be worth to push the actual boundaries in resolution and data acquisition capacity further with a new generation instrument, featuring the most modern components available on the market.In this project, we propose to add new modalities to PFM in order to be able to monitor with a Brownian particle, in 4 dimensions (space and time) and in situ, molecular diffusion processes in bulk, at interfaces and eventually in cellular structures with a resolution non-achievable by any other micro-spectroscopy technique. To monitor biological at highest resolution very long and uninterrupted measurements must be performed, meaning that no dead-time in the data acquisition can be tolerated. This is currently a problem in PFM experiments, where data can only be acquired for short times (few second) at high resolutions. We have only the choice between either a 9 bit effective amplitude resolution with continuous data acquisition or a true 16-bit resolution with unreasonable time gaps of minutes. Therefore, we would like to extend further the time- and frequency-domain of the PFM with a new high-speed and low noise detection, amplification and digitization device of the position signals, and also construct a new generation PFM, the Multidimensional Optical Force NanoSpectroscope. The proposed novel instrument will not only allow us to reach unprecedented sub-nanometer detection but also open the possibility of resolving short biological events occurring during longer lasting biological processes, like single binding-unbinding events between two proteins diffusing within a cell membrane.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Associated projects

Number Title Start Funding scheme
113529 Brownian Motion in confined geometries 01.10.2006 Project funding
126945 Brownian Motion in Viscoelastic Confinement 01.10.2009 Project funding
143703 Diffusion at functional surfaces 01.05.2013 Project funding

Abstract

We propose the development of a custom-made “Multidimensional Optical Force NanoSpectroscope”, with many applications in biophysics. Diffusion governed by Brownian motion is an efficient transport mechanism on short time and length scales. Even a highly organized system like a living cell relies, among other mechanisms, on the random Brownian motion of its constituents to fulfill complex functions. A Brownian particle will rapidly explore a heterogeneous environment that in turn strongly alters its trajectory. Five years ago, we developed at the LNNME-EPFL, an optical trap with a 3D detection system for thermal noise analysis the so-called Photonic force microscope (PFM) to study in details Brownian Motion in simple model fluids.Our findings showed that the temporal resolution of the PFM can be extended down to time scales where the nature of the fluid influences diffusion, bringing the long discussed idea of using a Brownian particle as a local reporter of the dynamics of complex biological fluids one step further.Currently, all the scientific questions, we are addressing together with a growing number of collaborating laboratories, show that it would be worth to push the actual boundaries in resolution and data acquisition capacity further with a new generation instrument, featuring the most modern components available on the market.In this project, we propose to add new modalities to PFM in order to be able to monitor with a Brownian particle, in 4 dimensions (space and time) and in situ, molecular diffusion processes in bulk, at interfaces and eventually in cellular structures with a resolution non-achievable by any other micro-spectroscopy technique. To monitor biological at highest resolution very long and uninterrupted measurements must be performed, meaning that no dead-time in the data acquisition can be tolerated. This is currently a problem in PFM experiments, where data can only be acquired for short times (few second) at high resolutions. We have only the choice between either a 9 bit effective amplitude resolution with continuous data acquisition or a true 16-bit resolution with unreasonable time gaps of minutes.Therefore, we would like to extend further the time- and frequency-domain of the PFM with a new high-speed and low noise detection, amplification and digitization device of the position signals, and also construct a new generation PFM, the Multidimensional Optical Force NanoSpectroscope.The proposed novel instrument will not only allow us to reach unprecedented sub-nanometer detection but also open the possibility of resolving short biological events occurring during longer lasting biological processes, like single binding-unbinding events between two proteins diffusing within a cell membrane.
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