Humidity Dependence of Charge Transport through DNA Revealed by Silicon-Based Nanotweezers Manipulation

AbstractThe study of the electrical properties of DNA has aroused increasing interest since the last decade. So far, controversial arguments have been put forward to explain the electrical charge transport through DNA. Our experiments on DNA bundles manipulated with silicon-based actuated tweezers demonstrate undoubtedly that humidity is the main factor affecting the electrical conduction in DNA. We explain the quasi-Ohmic behavior of DNA and the exponential dependence of its conductivity with relative humidity from the adsorption of water on the DNA backbone. We propose a quantitative model that is consistent with previous studies on DNA and other materials, like porous silicon, subjected to different humidity conditions

Closed-loop Control of Silicon Nanotweezers for Improvement of Sensitivity to Mechanical Stiffness Measurement and Bio-Sensing on DNA Molecules

International audienceIn this work we show that implementation of closed loop control to silicon nanotweezers improves the sensitivity of the tool for mechanical characterizations of biological molecules. Micromachined tweezers have already been used for the characterizations of mechanical properties of DNA molecules as well as for the sensing of enzymatic reactions on DNA bundle. However the resolution of the experiments does not allow the sensing on single molecules. Hereafter we show theoretically and experimentally that, reducing the resonance frequency of the system by the implementation of a state feedback, the sensitivity to stiffness variation is enhanced. Such improvement leads to better resolution for detection of enzymatic reactions on DNA

Silicon Nanotweezers for Molecules and Cells Manipulation and Characterization

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Effect of Substrate Wettability in Liquid Dielectrophoresis (LDEP) Based Droplets Generation: Theoretical Analysis and Experimental Confirmation

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Fabricating Silicon Resonators for Analysing Biological Samples

The adaptability of microscale devices allows microtechnologies to be used for a wide range of applications. Biology and medicine are among those fields that, in recent decades, have applied microtechnologies to achieve new and improved functionality. However, despite their ability to achieve assay sensitivities that rival or exceed conventional standards, silicon-based microelectromechanical systems remain underutilised for biological and biomedical applications. Although microelectromechanical resonators and actuators do not always exhibit optimal performance in liquid due to electrical double layer formation and high damping, these issues have been solved with some innovative fabrication processes or alternative experimental approaches. This paper focuses on several examples of silicon-based resonating devices with a brief look at their fundamental sensing elements and key fabrication steps, as well as current and potential biological/biomedical applications

Improvement of Silicon Nanotweezers Sensitivity for Mechanical Characterization of Biomolecules Using Closed-Loop Control

International audienceIn this paper, we show that closed-loop control can be advantageously used for the characterization of mechanical properties of biomolecules using silicon nanotweezers (SNT). SNT have already been used in open-loop mode for the characterization of mechanical properties of DNA molecules. Up to now, such an approach allows the detection of stiffness variations equivalent to about 15 DNA molecules. Here, it is shown that this resolution is inversely proportional to the resonance frequency of the whole system and that real-time feedback control with state observer can drastically improve the performances of the tweezers used as biosensors. Such improvement is experimentally validated in the case of the manipulation of fibronectin molecules. The results are promising for the accurate characterization of biopolymers such as DNA molecules

Direct measurement of the mechanical properties of a chromatin analog and the epigenetic effects of para-sulphonato-calix[4]arene

International audienceBy means of Silicon Nano Tweezers (SNTs) the effects on the mechanical properties of λ-phage DNA during interaction with calf thymus nucleosome to form an artificial chromatin analog were measured. At a concentration of 100 nM, a nucleosome solution induced a strong stiffening effect on DNA (1.1 N m −1). This can be compared to the effects of the histone proteins, H1, H2A, H3 where no changes in the mechanical properties of DNA were observed and the complex of the H3/H4 proteins where a smaller increase in the stiffness is observed (0.2 N m −1). Para-sulphonato-calix[4]arene, SC4, known for epigenetic activity by interacting specifically with the lysine groups of histone proteins, was studied for its effect on an artificial chromatin. Using a microfluidic SNT device, SC4 was titrated against the artificial chromatin, at a concentration of 1 mM in SC4 a considerable increase in stiffness, 15 N m −1 , was observed. Simultaneously optical microscopy showed a physical change in the DNA structure between the tips of the SNT device. Electronic and Atomic Force microscopy confirmed this structural rearrangement. Negative control experiments confirmed that these mechanical and physical effects were induced neither by the acidity of SC4 nor through nonspecific interactions of SC4 on DNA. With the recent and better knowledge on how gene regulation occurs and after intense debate in the academic community 1 , epigenetics has been commonly defined as "the study of changes in gene function that are mitoti-cally and/or meiotically heritable and that do not entail a change in DNA sequence" 2. Over the past years, epigenetics has been shown to play a central role in many different key functions at the cellular level, including differentiation, replication, and gene transcription 3. In a larger context, its contribution in physiological disorders has been revealed in cardio vascular illnesses, mental disorders and various cancers 4. Despite its inheritable character, epigenetics paradoxically possesses a reversible nature 5 that can be illustrated through its two main covalent modifications either directly on DNA with the methylation of cytosine nucleic bases or indirectly with various post translational modifications on proteins interacting with DNA such as histone proteins or other proteins called writers, erasers or readers 6. New therapeutic treatments are expected to target and reverse these modifications by inactivating the enzymes responsible for the deregulation of specific genes 7. Some inhibitors have been already approved by FDA, such as Azacitidine and Decitabine as DNA methyltrans-ferase inhibitors for the treatment of myelodysplastic syndrome 8 and Vorinostat and Romidepsin as inhibitors of histone deacetylase for the treatment of peripheral T-cell lymphoma 9. A new class of DNA artificial binders that directly block the methyllysine reading functions of reader enzymes in charge of conveying the methylation signal downstream has recently arisen as promising epigenetic drugs 10

DNA Manipulation Based on Nanotweezers

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DNA Manipulation Based on Nanotweezers

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