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1.
We develop an approximation for the probability of optically resolving two fluorescent labels on the backbone of a DNA molecule confined in a nanochannel in the Odijk regime as a function of the fluorescence wavelength, channel size, and the properties of the DNA (persistence length and effective width). The theoretical predictions agree well with equivalent data produced by Monte Carlo simulations of a touching wormlike bead model of DNA in a high ionic strength buffer. Although the theory is only strictly valid in the limit where the effective width of the nanochannel is small compared with the persistence length of the DNA, simulations indicate that the theoretical predictions are reasonably accurate for channel widths up to two-thirds of the persistence length. Our results quantify the conjecture that DNA barcoding has kilobase pair resolution-provided the nanochannel lies in the Odijk regime.  相似文献   

2.
Using Monte Carlo simulations of a touching-bead model of double-stranded DNA, we show that DNA extension is enhanced in isosceles triangular nanochannels (relative to a circular nanochannel of the same effective size) due to entropic depletion in the channel corners. The extent of the enhanced extension depends non-monotonically on both the accessible area of the nanochannel and the apex angle of the triangle. We also develop a metric to quantify the extent of entropic depletion, thereby collapsing the extension data for circular, square, and various triangular nanochannels onto a single master curve for channel sizes in the transition between the Odijk and de Gennes regimes.  相似文献   

3.
Investigation of single molecule DNA dynamics in confined environments has led to important applications in DNA analysis, separation, and sequencing. Here, we studied the electrophoretic transport of DNA molecules through nanochannels shorter than the DNA contour length and calculated the associated translocation time curves. We found that the longer T4 DNA molecules required a longer time to traverse a fixed length nanochannel than shorter λ DNA molecules and that the translocation time decreased with increasing electric field which agreed with theoretical predictions. We applied this knowledge to design an asymmetric electric pulse and demonstrate the different responses of λ and T4 DNA to the pulses. We used Brownian dynamics simulations to corroborate our experimental results on DNA translocation behaviour. This work contributes to the fundamental understanding of polymer transport through nanochannels and may help in designing better separation techniques in the future.  相似文献   

4.
We study the behavior of single linear polyelectrolytes condensed by trivalent salt under the action of electric fields through computer simulations. The chain is unfolded when the strength of the electric field is stronger than a critical value. This critical electric field follows a scaling law against chain length, and the exponent of the scaling law is −0.77(1), smaller than the theoretical prediction, −3ν∕2 [R. R. Netz, Phys. Rev. Lett. 90, 128104 (2003)], and the one obtained by simulations in tetravalent salt solutions, −0.453(3) [P.-Y. Hsiao and K.-M. Wu, J. Phys. Chem. B 112, 13177 (2008)]. It demonstrates that the scaling exponent depends sensitively on the salt valence. Hence, it is easier to unfold chains condensed by multivalent salt of a smaller valence. Moreover, the absolute value of chain electrophoretic mobility increases drastically when the chain is unfolded in an electric field. The fact that the mobility depends on electric field and on chain length provides a plausible way to impart chain-length dependence in free-solution electrophoresis via chain unfolding transition induced by electric fields. Finally, we show that, in addition to an elongated structure, a condensed chain can be unfolded into a U-shaped structure. The formation of this structure in our study is purely a result of the electric polarization, not of the elastohydrodynamics dominated in sedimentation of polymers.  相似文献   

5.
Prof. SUN Changpu from the CAS Institute of Theoretical Physics and coworkers from University of Basel in Switzerland have worked out a way --at least in theory --to split a beam of molecules according to their chirality. The technique involves passing the molecules through three different laser beams and is similar to the famous Stern-Gerlach effect, whereby a beam of atoms passing through a magnetic field is split in two according to the atoms' spin states (Phys. Rev. Lett. 99 130403).  相似文献   

6.
We investigate the fluctuation-relaxation dynamics of entropically restricted DNA molecules in square nanochannels ranging from 0.09 to 19.9 times the persistence length. In nanochannels smaller than the persistence length, the chain relaxation time is found to have cubic dependence on the channel size. It is found that the effective polymer width significantly alter the chain conformation and relaxation time in strong confinement. For thinner chains, looped chain configurations are found in channels with height comparable to the persistence length, with very slow relaxation compared to un-looped chains. Larger effective chain widths inhibit the formation of hairpin loops.  相似文献   

7.
There is currently a growing interest in control of stretching of DNA inside nanoconfined regions due to the possibility to analyze and manipulate single biomolecules for applications such as DNA mapping and barcoding, which are based on stretching the DNA in a linear fashion. In the present work, we couple Finite Element Methods and Monte Carlo simulations in order to study the conformation of DNA molecules confined in nanofluidic channels with neutral and charged walls. We find that the electrostatic forces become more and more important when lowering the ionic strength of the solution. The influence of the nanochannel cross section geometry is also studied by evaluating the DNA elongation in square, rectangular, and triangular channels. We demonstrate that coupling electrostatically interacting walls with a triangular geometry is an efficient way to stretch DNA molecules at the scale of hundreds of nanometers. The paper reports experimental observations of λ-DNA molecules in poly(dimethylsiloxane) nanochannels filled with solutions of different ionic strength. The results are in good agreement with the theoretical predictions, confirming the crucial role of the electrostatic repulsion of the constraining walls on the molecule stretching.  相似文献   

8.
Oscillating electrowetting on dielectrics (EWOD) with coplanar electrodes is investigated in this paper as a way to provide efficient stirring within a drop with biological content. A supporting model inspired from Ko et al. [Appl. Phys. Lett. 94, 194102 (2009)] is proposed allowing to interpret oscillating EWOD-induced drop internal flow as the result of a current streaming along the drop surface deformed by capillary waves. Current streaming behaves essentially as a surface flow generator and the momentum it sustains within the (viscous) drop is even more significant as the surface to volume ratio is small. With the circular electrode pair considered in this paper, oscillating EWOD sustains toroidal vortical flows when the experiments are conducted with aqueous drops in air as ambient phase. But when oil is used as ambient phase, it is demonstrated that the presence of an electrode gap is responsible for a change in drop shape: a pinch-off at the electrode gap yields a peanut-shaped drop and a symmetry break-up of the EWOD-induced flow pattern. Viscosity of oil is also responsible for promoting an efficient damping of the capillary waves which populate the surface of the actuated drop. As a result, the capillary network switches from one standing wave to two superimposed traveling waves of different mechanical energy, provided that actuation frequency is large enough, for instance, as large as the one commonly used in electrowetting applications (f ∼ 500 Hz and beyond). Special emphasis is put on stirring of biological samples. As a typical application, it is demonstrated how beads or cell clusters can be focused under flow either at mid-height of the drop or near the wetting plane, depending on how the nature of the capillary waves is (standing or traveling), and therefore, depending on the actuation frequency (150 Hz–1 KHz).  相似文献   

9.
The translocation process of star polymers through a nanochannel is investigated by dissipative particle dynamics simulations. The translocation process is strongly influenced by the star arm arrangement as the polymer enters the channel, and a scaling relation between the translocation time τ and the total number of beads Ntot is obtained. Qualitative agreements are found with predictions of the nucleation and growth model for linear block co-polymer translocation. In the intermediate stage where the center of the star polymer is at the channel entrance, the translocation time is found to have power law-dependence on the number of arms outside the channel and very weakly dependent on the number of arms in the channel. Increasing the total number of star arms also increases the star translocation time.  相似文献   

10.
This study describes a novel microfluidic reactor capable of flow-through polymerase chain reactions (PCR). For one-heater PCR devices in previous studies, comprehensive simulations and experiments for the chip geometry and the heater arrangement were usually needed before the fabrication of the device. In order to improve the flexibility of the one-heater PCR device, two heat pipes with one fan are used to create the requisite temperature regions in our device. With the integration of one heater onto the chip, the high temperature required for the denaturation stage can be generated at the chip center. By arranging the heat pipes on the opposite sides of the chip, the low temperature needed for the annealing stage is easy to regulate. Numerical calculations and thermal measurements have shown that the temperature distribution in the five-temperature-region PCR chip would be suitable for DNA amplification. In order to ensure temperature uniformity at specific reaction regions, the Re of the sample flow is less than 1. When the microchannel width increases and then decreases gradually between the denaturation and annealing regions, the extension region located in the enlarged part of the channel can be observed numerically and experimentally. From the simulations, the residence time at the extension region with the enlarged channel is 4.25 times longer than that without an enlarged channel at a flow rate of 2 μl/min. The treated surfaces of the flow-through microchannel are characterized using the water contact angle, while the effects of the hydrophilicity of the treated polydimethylsiloxane (PDMS) microchannels on PCR efficiency are determined using gel electrophoresis. By increasing the hydrophilicity of the channel surface after immersing the PDMS substrates into Tween 20 (20%) or BSA (1 mg/ml) solutions, efficient amplifications of DNA segments were proved to occur in our chip device. To our knowledge, our group is the first to introduce heat pipes into the cooling module that has been designed for a PCR device. The unique architecture utilized in this flow-through PCR device is well applied to a low-cost PCR system.  相似文献   

11.
This paper looks at the sensitivity of thickness to variation of friction. The models of friction used are: the classic Amontons-Coulomb; a nonlinear pressure-dependent model proposed by Wriggers, vu Van and Stein; and a velocity-dependent model proposed by Molinari, Estrin and Mercier. They are coded in FORTRAN for use with finite element program ABAQUS. The contact problem is then formulated in the total Lagrangian formulation for contact between an elastic-plastic body and rigid tools. The variational (weak) form of the formulation is given and this is discretized by finite element method. To test and compare the models, one common metal forming processes is simulated: deep drawing of a square-cup. The sensitivity graphs showing each of the three friction models together is given at the end. One other conclusion although not major part of this work is that Amonton-Coulomb is not the best model suited for contact conditions in metal forming processes, because Wriggers et al. model and Molinari et al. model provide better results for modelling bends and corners.  相似文献   

12.
Myoglobin is one of the premature identifying cardiac markers, whose concentration increases from 90 pg∕ml or less to over 250 ng∕ml in the blood serum of human beings after minor heart attack. Separation, detection, and quantification of myoglobin play a vital role in revealing the cardiac arrest in advance, which is the challenging part of ongoing research. In the present work, one of the electrokinetic approaches, i.e., dielectrophoresis (DEP), is chosen to separate the myoglobin. A mathematical model is developed for simulating dielectrophoretic behavior of a myoglobin molecule in a microchannel to provide a theoretical basis for the above application. This model is based on the introduction of a dielectrophoretic force and a dielectric myoglobin model. A dielectric myoglobin model is developed by approximating the shape of the myoglobin molecule as sphere, oblate, and prolate spheroids. A generalized theoretical expression for the dielectrophoretic force acting on respective shapes of the molecule is derived. The microchannel considered for analysis has an array of parallel rectangular electrodes at the bottom surface. The potential and electric field distributions are calculated using Green’s theorem method and finite element method. These results also compared to the Fourier series method, closed form solutions by Morgan et al. [J. Phys. D: Appl. Phys. 34, 1553 (2001)] and Chang et al. [J. Phys. D: Appl. Phys. 36, 3073 (2003)]. It is observed that both Green’s theorem based analytical solution and finite element based numerical solution for proposed model are closely matched for electric field and square electric field gradients. The crossover frequency is obtained as 40 MHz for given properties of myoglobin and for all approximated shapes of myoglobin molecule. The effect of conductivity of medium and myoglobin on the crossover frequency is also demonstrated. Further, the effect of hydration layer on the crossover frequency of myoglobin molecules is also presented. Both positive and negative DEP effects on myoglobin molecules are obtained by switching the frequency of applied electric field. The effect of different shapes of myoglobin on DEP force is studied and no significant effect on DEP force is observed. Finally, repulsion of myoglobin molecules from the electrode plane at 1 KHz frequency and 10 V applied voltage is observed. These results provide the ability of applying DEP force for manipulating nanosized biomolecules such as myoglobin.  相似文献   

13.
Confirmatory composite analysis (CCA) is a structural equation modeling (SEM) technique that specifies and assesses composite models. In a composite model, the construct emerges as a linear combination of observed variables. CCA was invented by Jörg Henseler and Theo K. Dijkstra in 2014, was subsequently fully elaborated by Schuberth et al. (2018), and was then introduced into business research by Henseler and Schuberth (2020b). Inspired by Hair et al. (2020), a recent article in the International Journal of Information Management (Motamarri et al., 2020) used the same term ‘confirmatory composite analysis’ as a technique for confirming measurement quality in partial least squares structural equation modeling (PLS-SEM) specifically. However, the original CCA (Henseler et al., 2014; Schuberth et al., 2018) and the Hair et al. (2020) technique are very different methods, used for entirely different purposes and objectives. So as to not confuse researchers, we advocate that the later-published Hair et al. (2020) method of confirming measurement quality in PLS-SEM be termed ‘method of confirming measurement quality’ (MCMQ) or ‘partial least squares confirmatory composite analysis’ (PLS-CCA). We write this research note to clarify the differences between CCA and PLS-CCA.  相似文献   

14.
An easy method is introduced allowing fast polydimethylsiloxane (PDMS) replication of nanofluidic lab-on-chip devices using accurately fabricated molds featuring cross-sections down to 60 nm. A high quality master is obtained through proton beam writing and UV lithography. This master can be used more than 200 times to replicate nanofluidic devices capable of handling single DNA molecules. This method allows to fabricate nanofluidic devices through simple PDMS casting. The extensions of YOYO-1 stained bacteriophage T4 and λ−DNA inside these nanochannels have been investigated using fluorescence microscopy and follow the scaling prediction of a large, locally coiled polymer chain confined in nanochannels.  相似文献   

15.
This paper presents a continuous flow microfluidic device for the separation of DNA from blood using magnetophoresis for biological applications and analysis. This microfluidic bio-separation device has several benefits, including decreased sample handling, smaller sample and reagent volumes, faster isolation time, and decreased cost to perform DNA isolation. One of the key features of this device is the use of short-range magnetic field gradients, generated by a micro-patterned nickel array on the bottom surface of the separation channel. In addition, the device utilizes an array of oppositely oriented, external permanent magnets to produce strong long-range field gradients at the interfaces between magnets, further increasing the effectiveness of the device. A comprehensive simulation is performed using COMSOL Multiphysics to study the effect of various parameters on the magnetic flux within the separation channel. Additionally, a microfluidic device is designed, fabricated, and tested to isolate DNA from blood. The results show that the device has the capability of separating DNA from a blood sample with a purity of 1.8 or higher, a yield of up to 33 μg of polymerase chain reaction ready DNA per milliliter of blood, and a volumetric throughput of up to 50 ml/h.  相似文献   

16.
Nitrogen-vacancy (NV) centers in diamond are promising quantum sensors because of their long spin coherence time under ambient conditions. However, their spin resonances are relatively insensitive to non-magnetic parameters such as temperature. A magnetic-nanoparticle-nanodiamond hybrid thermometer, where the temperature change is converted to the magnetic field variation near the Curie temperature, were demonstrated to have enhanced temperature sensitivity () (Wang N, Liu G-Q and Leong W-H et al. Phys Rev X 2018; 8: 011042), but the sensitivity was limited by the large spectral broadening of ensemble spins in nanodiamonds. To overcome this limitation, here we show an improved design of a hybrid nanothermometer using a single NV center in a diamond nanopillar coupled with a single magnetic nanoparticle of copper-nickel alloy, and demonstrate a temperature sensitivity of . This hybrid design enables detection of 2 mK temperature changes with temporal resolution of 5 ms. The ultra-sensitive nanothermometer offers a new tool to investigate thermal processes in nanoscale systems.  相似文献   

17.
Global dissipativity of stochastic neural networks with time delay   总被引:1,自引:0,他引:1  
Liao and Wang [Global dissipativity of continuous-time recurrent neural networks with time delay, Phys. Rev. E 68 (2003) 016118] firstly studied the dissipativity of neural networks. In this paper, the neural network model is generalized to a stochastic case, and the global dissipativity in mean of such stochastic system is investigated. By constructing several proper Lyapunov functionals combining with Jensen's inequality, Itô's formula and some analytic techniques, several sufficient conditions for the global dissipativity in mean of such stochastic neural networks are derived in LMIs forms, which can be easily verified in practice. Three numerical examples are provided to demonstrate the effectiveness of our criteria.  相似文献   

18.
李越冬  严青 《科研管理》2019,40(8):101-112
文章基于风险投资的"认证监督假说"和"道德风险假说",利用我国创业板上市公司2010—2014年的数据,实证检验风险投资对上市公司内部控制缺陷的作用是"抑制"还是"放纵",结果发现:(1)风险投资能"抑制"被投资企业内部控制缺陷,且随着风险投资持股比例的增加,其"抑制"作用更加显著;(2)采用分组检验的办法,发现在风险投资持股比例高的样本中,其对内部控制缺陷有显著的"抑制"作用,在风险投资持股比例低的样本中,风险投资对于内部控制具有不显著的"放纵"作用;(3)文章还发现股权集中度越高,会削弱风险投资对于内部控制缺陷的"抑制"作用;(4)不同背景风险投资对内部控制缺陷的作用不同,政府背景和企业背景风险投资对企业内部控制缺陷具有"抑制"作用,其中企业背景风险投资的"抑制"作用显著,而独资背景的风险投资对内部控制缺陷具有不显著的"放纵"作用。  相似文献   

19.
Planar nanochannels are fabricated using sacrificial etching technology with sacrificial cores consisting of aluminum, chromium, and germanium, with heights ranging from 18 to 98 nm. Transient filling via capillary action is compared against the Washburn equation [E. W. Washburn, Phys. Rev. 17, 273 (1921)], showing experimental filling speeds significantly lower than classical continuum theory predicts. Departure from theory is expressed in terms of a varying dynamic contact angle, reaching values as high as 83° in channels with heights of 18 nm. The dynamic contact angle varies significantly from the macroscopic contact angle and increases with decreasing channel dimensions.  相似文献   

20.
Demand for analysis of rare cells such as circulating tumor cells in blood at the single molecule level has recently grown. For this purpose, several cell separation methods based on antibody-coated micropillars have been developed (e.g., Nagrath et al., Nature 450, 1235–1239 (2007)). However, it is difficult to ensure capture of targeted cells by these methods because capture depends on the probability of cell-micropillar collisions. We developed a new structure that actively exploits cellular flexibility for more efficient capture of a small number of cells in a target area. The depth of the sandwiching channel was slightly smaller than the diameter of the cells to ensure contact with the channel wall. For cell selection, we used anti-epithelial cell adhesion molecule antibodies, which specifically bind epithelial cells. First, we demonstrated cell capture with human promyelocytic leukemia (HL-60) cells, which are relatively homogeneous in size; in situ single molecule analysis was verified by our rolling circle amplification (RCA) method. Then, we used breast cancer cells (SK-BR-3) in blood, and demonstrated selective capture and cancer marker (HER2) detection by RCA. Cell capture by antibody-coated microchannels was greater than with negative control cells (RPMI-1788 lymphocytes) and non-coated microchannels. This system can be used to analyze small numbers of target cells in large quantities of mixed samples.  相似文献   

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