Project

Discipline

confined soft matter; electrostatics; colloidal information; single molecule trap

Lead
A novel approach to measuring and manipulating single molecules in solution
Lay summary
Any bit of matter in a liquid is pummelled by forces from the surrounding bath of liquid molecules. So a minute particle in a fluid is always wandering off and after a while finds itself at a random location far from where it started. Fascinating things could be done if nanoscopic particles or molecular-scale entities - nearly a million times smaller than the width of a strand of hair - could be made to stay at the same location for long spells of time. One could measure the physical properties and behaviour of single molecules in solution as well as use single nanoparticles to perform useful functions such as data storage. We have recently developed the ability to trap single biological molecules in solution without the application of external fields. Our trap depends sensitively on the electrical charge carried by the molecule. Within the scope of this proposal we will develop new methods to study the behaviour of single trapped molecules in solution and measure their physical properties such as size, electrical charge, and three-dimensional structure. The ability to perform high-sensitivity, high-precision measurements on single molecules will not only have novel and important fundamental impact but also foster the development of ultra-sensitive biomedical detection and analytics at the nanometer scale.

Direct link to Lay Summary

Last update: 24.02.2016

Active participation

Title	Year

Number	Title	Start	Funding scheme

The aspiration to study Nature’s building blocks in isolation can be traced back over 200 years to the diaries of the first german Professor of Experimental Physics, Georg Christoph Lichtenberg, where he envisioned future experiments “suspending the constituents of matter free”. In the last 100 years Lichtenberg’s dream has turned into reality opening up a number of new research fields. In particular the last few decades have witnessed unprecedented advances from quantum optics to biophysics that were a direct consequence of newly acquired abilities to spatially trap and manipulate single entities in free space or solution. Examples include the development of ion traps, and the manipulation of colloidal objects in strongly focused light beams that led to the Bose-Einstein Condensation experiment; both areas were recognized with Nobel Prizes in Physics in 1989 and 1997 respectively.Trapping a single atom or molecule offers us the unique opportunity to study the individual components of matter, above and beyond the average properties of an ensemble, and free of strong interactions with immobilizing surfaces. While the external field-based approach has had revolutionary impact, these methods fail in a vital physical regime namely for small objects at room temperature. Thus while it has been possible for decades now to trap and experiment with cold ions and atoms, a whole class of Nature’s building blocks, i.e., biological macromolecules in aqueous solution had evaded similar control. In 2010 we reported the development of the electrostatic fluidic trap that addressed the long-standing problem of trapping in the regime of warm, small entities in solution. Starting June 2012, in the first three years of the SNF professorship at the University of Zurich, we have achieved the ability to trap single nanometer-scale macromolecules in room temperature solution and measure their properties such as electrical charge with single elementary charge resolution. On a separate front, we have also demonstrated the ability to store, write and readout information in the spatial state of a single, levitating colloidal particle, introducing a new concept in nanomechanical information.In the upcoming phase we wish to: [1] further advance our molecule trapping, detection and measurement abilities, widening the scope to cover single molecule structural biology studies at the fundamental level, and sensitive detection of minute molecular differences from an applied ‘molecular sensing’ perspective, [2] develop the area of “colloidal information” e.g., build single colloid-based logic circuits and possibly demonstrate rudimentary computation, as well as [3] at the fundamental level, pursue the problem of confinement-induced attraction between like-charged entities that has eluded explanation to date.