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Sequencing the genomes of individual cells enables the direct determination of genetic heterogeneity amongst cells within a population. We have developed an injection-moulded valveless microfluidic device in which single cells from colorectal cancer derived cell lines (LS174T, LS180 and RKO) and fresh colorectal tumors have been individually trapped, their genomes extracted and prepared for sequencing using multiple displacement amplification (MDA). Ninety nine percent of the DNA sequences obtained mapped to a reference human genome, indicating that there was effectively no contamination of these samples from non-human sources. In addition, most of the reads are correctly paired, with a low percentage of singletons (0.17 +/- 0.06%) and we obtain genome coverages approaching 90%. To achieve this high quality, our device design and process shows that amplification can be conducted in microliter volumes as long as the lysis is in sub-nanoliter volumes. Our data thus demonstrates that high quality whole genome sequencing of single cells can be achieved using a relatively simple, inexpensive and scalable device. Detection of genetic heterogeneity at the single cell level, as we have demonstrated for freshly obtained single cancer cells, could soon become available as a clinical tool to precisely match treatment with the properties of a patient's own tumor.

Understanding the dynamics of the glass transition of polymers and molecular liquids has been a goal of physicists for more than a half-century. The nature of this transition is directly linked to the heterogeneity of the dynamics, reflected in spatial and temporal correlations of molecular motions, as well as a distribution of relaxation times. The former can be quantified by a dynamic correlation length that grows on approaching the glassy state and the latter from the breadth of the relaxation function or dynamic susceptibility. The majority of experimental studies of this topic rely on dielectric spectroscopy, which provides relaxation spectra over many decades of frequency. However, the higher order susceptibilities involving both spatial and temporal correlations cannot be obtained from linear relaxation measurements without assumptions. Characterizing the spatial distribution of the dynamics requires other methods., Published in Macromolecules, 2013. The original document contains color images. Prepared in collaboration with the Center for Neutron Research, National Institute of Standards and Technology, Gaithersburg, MD. Prepared in cooperation with the Center for Research and Technology, Bridgestone Americas, Akron, OH and the Department of Materials Science and Engineering, University of Maryland, College Park.

The dynamics of a large number of liquids and polymers exhibit scaling properties characteristic of a simple repulsive inverse power-law potential, most notably the superpositioning of relaxation data as a function of the variable TV gamma , where T is temperature, V the specific volume, and gamma a material constant. A related scaling law Tm Vm Gamma , with the same exponent Gamma = gamma, links the melting temperature Tm and volume Vm of the model IPL liquid; liquid dynamics is then invariant at the melting point. Motivated by a similar invariance of dynamics experimentally observed at transitions of liquid crystals, we determine dynamic and melting-point scaling exponents and Gamma for a large number of nonassociating liquids. Rigid, spherical molecules containing no polar bonds have Gamma = gramma; consequently, the reduced relaxation time, viscosity, and diffusion coefficient are each constant along the melting line. For other liquids gamma Gamma always; that is, the dynamics is more sensitive to volume than is the melting point, and for these liquids the dynamics at the melting point slows down with increasing Tm (that is, increasing pressure)., Published in Physical Review E v83, article 031504, 8p, 2011.

From measurements of the specific volume as a function of temperature and pressure, the phase diagram for the liquid crystal forming isopentylcyanobiphenyl (5*CB) was determined. There are a number of phases (isotropic liquid, glass, cholesteric, and crystalline), and we show that the phase boundaries differ from previous reports, reflecting the slow crystallization kinetics of the system. Using dielectric spectroscopy at ambient and elevated pressure, we identify the relaxation processes in the isotropic and cholesteric phases. From application of density scaling to the dynamics, we obtain scaling exponents, which were found to vary with the type of motion. Moreover, unlike previous results for many other liquid crystals, the scaling exponent for the isotropic state differs from the thermodynamic potential parameter, and hence the relaxation time along the clearing line varies significantly with pressure. The distinctive properties of 5*CB reflect the very different volume dependences of the thermodynamics and the dynamics., Published in Journal of Physical Chemistry B, v118 p6437-6444, 2011. The original document contains color images.

Superpositioning of relaxation data as a function of the product variable TV gamma , where T is temperature, V the specific volume, and gamma a material constant, is an experimental fact demonstrated for approximately 100 liquids and polymers. Such scaling behavior would result from the intermolecular potential having the form of an inverse power law (IPL), suggesting that an IPL is a good approximation for certain relaxation properties over the relevant range of intermolecular distances. However, the derivation of the scaling property of an IPL liquid is based on reduced quantities, for example, the reduced relaxation time equal to T(exp 1/2V-1/3) times the actual relaxation time. The difference between scaling using reduced rather than unreduced units is negligible in the supercooled regime; however, at higher temperature the difference can be substantial, accounting for the purported breakdown of the scaling and giving rise to different values of the scaling exponent. Only the gamma obtained using reduced quantities can be sensibly related to the intermolecular potential., Published in Journal of Chemical Physics, v134 p044504-1/044504-3, 2011. Sponsored in part by the National Academy of Sciences-National Research Council, Washington, DC.

Dielectric relaxation times were measured for 1,4-polyisoprenes (PI) of different molecular weight. From the data, the number of dynamically correlated segments, Nc, was calculated using an approximation to the dynamic susceptibility. Nc increases with approach to the glass transition in the usual fashion and also increases with increasing molecular weight of the PI. The latter effect is ascribed to the loss of the configurational mobility conferred by the chain ends. The correlation volume was also estimated from calorimetry and, because PI has a dielectrically active normal mode, from the intersection of the extrapolated segmental and normal mode relaxation times. The three methods yield consistent results, although the last has large uncertainty due to the ambiguous connection between dynamic correlation lengths and volumes. Using the equation of state for the polymers, the dependence of the relaxation times on the scaling variable TVγ,where V is specific volume and γ is a material constant, was calculated. For the lowest molecular weight PI,there is a small difference in γ for the segmental and chain modes. The scaling exponent is also marginally smaller for the lower molecular weight sample, suggesting, in contrast with the behavior of other polymers,that in PI the volume dependence becomes weaker with decreasing molecular weight., Published in Macromolecules v44 p1149-1155, 2011. The original document contains color images.

Various properties of vitrifying liquids are correlated with the dispersity of the dynamics, the latter reflected in the magnitude of the nonexponentiality parameter, Beta K, describing the distribution of relaxation times. These properties include the mean relaxation time, , the fragility, and the dynamic crossover. The correlations with Beta K are observed in both experimental data and the results from molecular dynamics simulations on Lennard-Jones LJ type systems. Another, rather obvious property to correlate with Beta K is the dynamic heterogeneity, which can be quantified from the number of molecules, Nc, dynamically correlated over a time span. For a given LJ system, Nc can be rigorously calculated and we find that it does indeed correlate with Beta K over a range of thermodynamic conditions. However, the analysis of experimental data for a broad range of real materials, wherein an approximation is required to obtain Nc, reveals the absence of any relationship between Nc and K among different materials., Published in the Journal of Chemical Physics, v133 p124507-1/124507-4, 2010. Sponsored in part by the National Academy of Sciences-National Research Council, Washington, DC.

We present numerical calculations of a four-point dynamic susceptibility, chi4(t), for the Kob-Andersen Lennard-Jones mixture as a function of temperature Tau and density rho. Over a relevant range of Tau and rho, the full tau-dependence of chi4(t) and thus the maximum in chi4(tau), which is proportional to the dynamic correlation volume, are invariant for state points for which the scaling variable rho(gamma)/Tau is constant. The value of the material constant gamma is the same as that which superposes the relaxation time, tau, of the system versus rho(gamma)/Tau. Thus, the dynamic correlation volume is a unique function of tau for any thermodynamic condition in the regime where density scaling holds. Finally, we examine the conditions under which the density scaling properties are related to the existence of strong correlations between pressure and energy fluctuations., Published in the Journal of Chemical Physics, v131 p151103-1 through 151103-5, 2009. Prepared in collaboration with Technische Universitaet Wien, Austria. The original document contains color images.

Dielectric relaxation measurements on a chlorinated biphenyl (PCB62) were carried out over a broad frequency range, with variation of both temperature and pressure. In combination with calorimetric determinations of the configurational entropy, these data could be described using the Adam-Gibbs model. Specifically, the experimental results were interpreted using a recently introduced equation for both the temperature and pressure dependencies of the structural relaxation time. The tau(T,P) data for PCB62 yielded values of the fitting parameters consistent with known physical properties of the material. A change of the dynamics was evident in isobaric measurements at atmospheric pressure, corresponding to a value of the relaxation time tauB~5x10(-5). A related change of dynamics was observed in isothermal experiments at varying pressures. It is noteworthy that the latter transpired at a very similar tau~tauB. Moreover, the shape of the relaxation function depended only on the value of tau. We believe this is the first reported evidence of such a change of dynamics in experiments using pressure as a variable. These results suggest that this change is governed by the time scale of the relaxation, independently of any particular combination of T and P., Published in the Journal of Chemical Physics, v117 n10 p4901-4906, 8 September 2002.

A process for modifying elastomeric structures to improve mechanical properties involves subjecting a pre-cured shape of elastomeric material to an orientation technique to result in an oriented elastomeric material; and curing the oriented elastomeric material while maintaining the orientation of the elastomeric material under conditions effective to result in an elastomeric structure having a predetermined cross-link density and enhanced modulus, the magnitude of orientation being sufficient to result in the enhanced modulus. Typically, the orientation techniques used may include uniaxial extension, biaxial extension, simple shear, planar shear, and inflation. The elastomeric material be capable of strain induced crystallization or incapable of strain induced crystallization. The enhanced modulus is obtained while at least maintaining failure performance of the elastomeric structure, and the conditions during the curing are sufficient to maintain a constant cross-link density in the double network elastomer while the modulus is enhanced.

Surface epoxidized elastomeric articles containing unsaturation are obtained by immersing the articles in an epoxidizing solution for a time sufficient to epoxidize at least some surface unsaturation in the articles.

Material failure corresponds to the propagation of damage to a catastrophic level. The damage may be intrinsic or have arisen during deformation. In cross-linked rubbers it is known that even the most carefully prepared laboratory specimens have inherent flaws which are capable of initiating crack growth. Fracture is made possible when the strain energy release rate (i.e., the tearing energy) exceeds a critical value., Presented at the 134th Meeting Ribber Division, American Chemical Society, Cincinnati, OH on 18-21 Oct 1988.

Recent studies of miscible blends of 1, 2-polybutadiene with cis-1,4- polyisoprene revealed that for certain compositions the glass to rubber transition occurs over a very broad temperature range. Measurements of the dynamic properties of carbon black filled rubber can be carried out on most- instrumentation at strains within the limits of linear behavior, thus, assessments of acoustic performance can readily be made. The equivalence of small strain dynamic mechanical testing and acoustic measurements has been demonstrated herein. Blends of Natural Rubber with a high concentration of 1,2- Butyl Rubber are attractive candidates for damping applications because of the extended frequency range of the glass to rubber transition. One approach to improving the magnitude of the damping is to incorporate high levels of carbon black into the material. Significant interaggregate interaction, promoted for example by a low degree of carbon black dispersion, will amplify the energy dissipation. The strain dependence of the dynamic properties implicit in such an approach can result in a damping performance sensitive to deformation. This sensitivity to deformation will impact more on constrained layer damping applications than on simple extensional damping. For the materials tested in the present study, complete recovery of the damage to the carbon black network (which engenders the changes in dynamic mechanical properties) requires more than a day at room temperature.

The thermal crystallization behavior of cross-linked rubbers formed by endlinking monodisperse and bidisperse linear polytetrahydrofurans was investigated. The introduction of crosslinkages in PTHF inhibits the ability of chain units in proximity to the crosslinks to crystallize. From melting point depression measurements, it is estimated that the suppression in crystallizability extends as much as 15 chain units away from the crosslinkage. This estimate is consistent with the degree of equilibrium crystallinity measured in the various PTHF networks. The equilibrium melting point for uncrosslinked PTHF was deduced from melting point depression in the crosslinked rubbers to be 368 K. This is in satisfactory agreement with the T determined linear PTHF, 361 K, but significantly higher than previously reported values. The distribution in the lengths of network chains exerted a trivial influence on thermal crystallization behavior, at least under the present experimental conditions. Polytetrahydrofuran, Crystallization, Cross-linking, Network architecture. (jes)