Dielectrophoretic (DEP) Tweezers: New Tool for Molecular Force Spectroscopy

Many recent advances in DNA sequencing technology have taken advantage of single-molecule techniques using fluorescently-labeled oligonucleotides as the principle mode of detection. In spite of the successes of fluorescent-based sequencers, avoidance of labeled nucleotides could substantially reduce the costs of sequencing. This dissertation will describe the development of an alternative sequencing method, in which unlabeled DNA can be manipulated directly on a massively parallel scale using single molecule force spectroscopy. We demonstrated that a combination of a wide-field optical detection technique (evanescent field excitation) with dielectrophoretic (DEP) tweezers could determine the amount of the double-stranded character of DNA. This thesis discusses all aspects of the implementation of DEP tweezers, including the principle of operation, making of polymer force probes, numerical modeling of various designs, fabrication of electrode and disposable chip, force calibration, and the assembly of the device. The feasibility of this technique was demonstrated by conducting force spectroscopy on single DNA molecules using DEP tweezers. The development of such a single molecule force spectroscopy technique shows great potential for genome sequencing and other analytical applications that employ direct manipulation of biomolecules

Plasmonic Optical Tweezers based on Nanostructures: fundamentals, advances and prospects

The ability of metallic nanostructures to confine light at the sub-wavelength scale enables new perspectives and opportunities in the field of nanotechnology. Making use of this unique advantage, nano-optical trapping techniques have been developed to tackle new challenges in a wide range of areas from biology to quantum optics. In this work, starting from basic theories, we present a review of research progress in near-field optical manipulation techniques based on metallic nanostructures, with an emphasis on some of the most promising advances in molecular technology, such as the precise control of single-biomolecules. We also provide an overview of possible future research directions of nano-manipulation techniques.Comment: 19 page

Toward quantum simulations of biological information flow

Recent advances in the spectroscopy of biomolecules have highlighted the possibility of quantum coherence playing an active role in biological energy transport. The revelation that quantum coherence can survive in the hot and wet environment of biology has generated a lively debate across both the physics and biology communities. In particular, it remains unclear to what extent non-trivial quantum effects are utilised in biology and what advantage, if any, they afford. We propose an analogue quantum simulator, based on currently available techniques in ultra-cold atom physics, to study a model of energy and electron transport based on the Holstein Hamiltonian By simulating the salient aspects of a biological system in a tunable laboratory setup, we hope to gain insight into the validity of several theoretical models of biological quantum transport in a variety of relevant parameter regimes.Comment: 8 Pages, 2 Figures, Non-technical contributing article for the Interface Focus Theme Issue `Computability and the Turning centenary'. Interface Focus http://rsfs.royalsocietypublishing.org/content/early/2012/03/22/rsfs.2011.0109.shor

Optical fluid and biomolecule transport with thermal fields

A long standing goal is the direct optical control of biomolecules and water for applications ranging from microfluidics over biomolecule detection to non-equilibrium biophysics. Thermal forces originating from optically applied, dynamic microscale temperature gradients have shown to possess great potential to reach this goal. It was demonstrated that laser heating by a few Kelvin can generate and guide water flow on the micrometre scale in bulk fluid, gel matrices or ice without requiring any lithographic structuring. Biomolecules on the other hand can be transported by thermal gradients, a mechanism termed thermophoresis, thermal diffusion or Soret effect. This molecule transport is the subject of current research, however it can be used to both characterize biomolecules and to record binding curves of important biological binding reactions, even in their native matrix of blood serum. Interestingly, thermophoresis can be easily combined with the optothermal fluid control. As a result, molecule traps can be created in a variety of geometries, enabling the trapping of small biomolecules, like for example very short DNA molecules. The combination with DNA replication from thermal convection allows us to approach molecular evolution with concurrent replication and selection processes inside a single chamber: replication is driven by thermal convection and selection by the concurrent accumulation of the DNA molecules. From the short but intense history of applying thermal fields to control fluid flow and biological molecules, we infer that many unexpected and highly synergistic effects and applications are likely to be explored in the future

Thermal Fluctuations of Elastic Filaments with Spontaneous Curvature and Torsion

We study the effects of thermal flucutations on thin elastic filaments with spontaneous curvature and torsion. We derive analytical expressions for the orientational correlation functions and for the persistence length of helices, and find that this length varies non-monotonically with the strength of thermal fluctuations. In the weak fluctuation regime, the persistence length of a spontaneously twisted helix has three resonance peaks as a function of the twist rate. In the limit of strong fluctuations, all memory of the helical shape is lost.Comment: 1 figur

Torque And Optical Traps

Optical traps are an important tool for research in the field of single molecule biophysics. Recent advances in optical trapping have extended their functionality from simple linear manipulation and measurement of forces, to now the ability to rotate objects and measure torques. This mini review summarizes these recent developments of the optical trap as a tool to apply and measure torque in biophysical applications.Center for Nonlinear Dynamic

Microfluidics for protein biophysics

Microfluidics has the potential to transform experimental approaches across the life sciences. In this review, we discuss recent advances enabled by the development and application of microfluidic approaches to protein biophysics. We focus on areas where key fundamental features of microfluidics open up new possibilities and present advantages beyond low volumes and short time-scale analysis, conventionally provided by microfluidics. We discuss the two most commonly used forms of microfluidic technology, single-phase laminar flow and multiphase microfluidics. We explore how the understanding and control of the characteristic physical features of the microfluidic regime, the integration of microfluidics with orthogonal systems and the generation of well-defined microenvironments can be used to develop novel devices and methods in protein biophysics for sample manipulation, functional and structural studies, detection and material processing