I'm currently fascinated by DNA and RNA polymerases' amazing ability in discriminating between bases with astonishing accuracy. This "proofreading" ability of biological micromachines is well beyond what was allowed by equilibrium thermodynamics of the specific Watson-Crick pairing energies, as first pointed out by physicist John Hopfield in the 1970s. Hopfield, and later Ninio, suggested the concept of "kinetic proofreading". My current interest is to build solid-state devices capable of kinetic proofreading functions.
Nanopore DNA Sequencing: kinetic proofreading
After a sabbatical leave at Delft in the 02-03 academic year, I ventured into the field of nanopore DNA sequencing. I was intrigued by the proposal by John Kasianowiz and coworkers that one may use electrical current variations of a nanopore during DNA translocation (linear motion) to sequence a DNA. After more than a decade spent in studying this problem, I came to the realization that in order for us to develop a DNA sequencing technology without polymerase, we need to develop a nanopore device capable of two key functions of a DNA polymerase: suppression of diffusion and base discrimination beyond equilibrium thermodynamics, i.e. kinetic proofreading. We are currently developing a solid-state nanopore sandwich device for this task in collaboration with SEU in Nanjing:
Daniel Y. Ling and Xinsheng Sean Ling, "On the distribution of DNA translocation times in solid-state nanopores: an analysis using Schrödinger's first-passage-time theory", J. Phys.: Cond. Matt. 25, 375102 (2013).
Xinsheng Sean Ling, "METHODS OF SEQUENCING NUCLEIC ACIDS USING NANOPORES AND ACTIVE KINETIC PROOFREADING", World Intellectual Property Organization, WO2013/119784 A1 (http://patentscope.wipo.int/search/en/WO2013119784)
Xinsheng Sean Ling, "Solid-State Nanopores: Methods of Fabrication and Integration, and Feasibility Issues in DNA Sequencing", p.177 in S.M. Iqbal and R. Bashir (eds.), Nanopores: Sensing and Fundamental Biological Interactions, DOI 10.1007/978-1-4419-8252-0_8, Springer Science+Business Media, LLC 2011
Venkat S.K. Balagurusamy, Paul Weinger, & Xinsheng Sean Ling, "Detection of DNA hybridizations using solid-state nanopores", Nanotechnology 21, 335102 (2010).
Hongbo Peng and X.S. Ling, "Reverse DNA translocation through a solid-state nanopore by magnetic tweezers", Nanotechnology, 20, 185101(2009).
Sang R. Park, H. Peng, and X.S. Ling, "Fabrication of Nanopores in Silicon Chips Using Feedback Chemical Etching", SMALL 3, 116 (2007).
Shanshan Wu, Sang R. Park, and X.S. Ling, "Lithography-Free Formation of Nanopores in Plastic Membranes using Laser Heating", Nano Letters 6, 2571(2006).
A.J. Storm, J.H. Chen, X.S. Ling, H. Zandbergen, and C. Dekker, "Electron-Beam-Induced Deformations of SiO2 Nanostructures", Journal of Applied Physics 98, 014307 (2005).
Arnold J. Storm, Jiang Hua Chen, X.S. Ling, H. Zandbergen, and C. Dekker, "Fabrication of Solid-State Nanopores with Single Nanometer Precision", Nature Materials, 2, 537 (2003).
Colloid Physics: defects
2D colloids provide a convenient model system for studying defects and order in condensed matter physics. We pioneered the method of using optical tweezers to create point defects in a 2D colloidal crystal and taking advantage of the fact that in 2D, point defects can be thermally excited into dislocation pairs, which are topological defects. We were able to observe for the first time the famous "Peierls barrier" proposed by Rudolf Peierls 70 years ago but was never observed in a real experiment. We also carried out a random pinning experiment in which we realized experimentally a "2D solid in random pinning potentials" which was extensively theorized. We showed that the quasi-long-range order (QLRO) of a 2D crystal is destroyed by random pinning, and the system behaves as a "pinned liquid". Upon application of a driving force, instead of depin the system from the random potential, thereby causing the system to re-crystalize, we found that the system exhibits the classic thermally activated creep phenomena, i.e. a slow liquid.
Alexandros Pertsinidis and X.S. Ling, "Statics and Dynamics of 2D Colloidal Crystals in a Random Pinning Potential", Physical Review Letters, 100, 028303 (2008).
A. Pertsinidis and X.S. Ling, "Equilibrium Configurations and Energetics of Point Defects in Two-Dimensional Colloidal Crystals", Physical Review Letters, 87, 098303 (2001).
A. Pertsinidis and X.S. Ling, "Diffusion of Point Defects in Two-Dimensional Colloidal Crystals", Nature, 413, 147 (2001).
Vortex Physics: peak effect and Bragg glass phase
Vortex lines in type-II superconductors form a condensed matter system with long-range order in competition with random potentials. In 1991, while being a graduate student with Prof. J.I. Budnick, I discovered the so-called "peak effect" in high-Tc superconductors. This peak effect was ultimately proven, first by our group at Brown (S.R. Park, et al., using smal angle neutron scattering in collaboration with J. Lynn at NIST), to be a genuine phase transition between a topologically ordered "Bragg glass" and a disordered phase. The topologically ordered 3D Bragg glass phase is reminiscent of the QLRO discovered by J.M. Kosterlitz and D.J. Thouless in 2D X-Y model and Haldane's in 1D quantum spin chain models, it was long thought not possible due to a well-known and powerful Larkin-Imry-Ma theorem which states that any system, below 4D, with broken continuous symmetry cannot have LRO with any amount of random fields. It turns out that, like the Mermin-Wagner theorem for 2D X-Y, the Larkin-Imry-Ma theorem cannot be applied simply to the destruction of the topological order in a 3D vortex-line lattice.
N. D. Daniilidis, S. R. Park, I. K. Dimitrov, J. W. Lynn, X. S. Ling, "Emergence of Quasi-Long-Range Order below the Bragg Glass Transition", Physical Review Letters, 99, 147007 (2007).
I. K. Dimitrov, N. D. Daniilidis, C. Elbaum, J. W. Lynn, X. S. Ling, “Peak Effect in Polycrystalline Vortex Matter” Physical Review Letters, 99, 047001 (2007).
N. D. Daniilidis, I. K. Dimitrov, V. F. Mitrovic, C. Elbaum, X. S. Ling, “Magnetocaloric Studies of the Peak Effect in Nb”, Physical Review B 75, 174519 (2007).
S.R. Park, S.M. Choi, D.C. Dender, J.W. Lynn, and X.S. Ling, “Fate of the Peak Effect in a Type-II Superconductor: Multicriticality of the Bragg-Glass Transition", Physical Review Letters, 91, 167003 (2003).
X.S. Ling, S.R. Park, B.A. McClain, S.M. Choi, D.C. Dender, and J.W. Lynn, "Superheating and Supercooling of Vortex Matter in a Nb Single Crystal: Direct Evidence for a Phase Transition at the Peak Effect from Neutron Diffraction", Physical Review Letters, 86, 712 (2001).
J. Shi, X. S. Ling, R. Liang, D.A. Bonn, W.N. Hardy, "Giant Peak Effect Observed in an Ultra-pure YBa2Cu3O7 Crystal", Physical Review, B Rapid Communications, 60, R12593 (1999).
X.S. Ling, J.E. Berger, and D. E. Prober, "Nature of Vortex Lattice Disordering at the Onset of the Peak Effect", Physical Review, B Rapid Communications, 57, R3249 (1998).
X.S. Ling, J.I. Budnick, and B.W. Veal, "Peak Effect and Its Disappearance in Superconducting YBCO Crystals", Physica C, 282, 2191 (1997).
C. Tang, X.S. Ling, S. Bhattacharya, and P.M. Chaikin, "Peak Effect in Superconductors: Melting of Larkin Domains", Europhysics Letters, 35, 597 (1996).
X. S. Ling, "Flux dynamics in high-temperature superconductors", (Ph.D. thesis, University of Connecticut, May 1992), reprints available from UMI Microfilm.
X.S. Ling and J.I. Budnick, "AC Magnetic Susceptibility Studies of Type-II Superconductors: Vortex Dynamics", in Magnetic Susceptibility of Superconductors and Other Spin Systems, Edited by R.A. Hein, T.L. Francavilla, & D.H. Liebenberg, (Plenum, New York, 1991), p.377.
Vortex Physics: 2D superconducting periodic wire networks
A 2D periodic Nb wire network in a perpendicular magnetic field is a realization of frustrated X-Y models:(1) At f=1/2, the system has both broken U(1) and Z2 symmetries, as such we expect both Kosterlitz-Thouless and Ising transitions. The question was whether the two transitions occur at the same temperature. My experiment at NEC (with S. Bhattacharya and P.M. Chaikin) showed that the two occur at the same temperature. (2) At f=2/5, the theory predicted a first-order transition; At f=0.618, the theory predicted no transition. My experiment showed that in both cases the system exhibits the features of a continuous transition.
X.S. Ling, H.J. Lezec, M.J. Higgins, J.S. Tsai, J. Fujita, Y. Nakamura, Chao Tang, P.M. Chaikin, and S. Bhattacharya, Physical Review Letters, 76, 2989 (1996), “Nature of Phase Transitions of Superconducting Wire Networks in a Magnetic Field".
Vortex Physics: finite-size effect of a vortex glass phase
NbTi wires are dirty type-II superconductors. In a strong magnetic field, the vortex phase is that of a vortex glass, a structurally disordered vortex lines phase with divergent activation barrier for vortex creep. The Fisher-Fisher-Huse theory of vortex glass implied that for a finite-size system, there should be ohmic resistance determined by the sample size, which indeed was observed in our experiment. (I was a postdoc under Professor D.E. Prober at Yale University where this work was finished.)
X.S. Ling, J.D. McCambridge, N.D. Rizzo, J.W. Sleight, D.E. Prober, L.R. Motowidlo, and B.A. Zeitlin, Physical Review Letters, 74, 805 (1995), “Fluctuation Effects on a Strongly Pinned Vortex Lattice in a Thin Type-II Superconducting Wire”.
X.S. Ling, J.D. McCambridge, N.D. Rizzo, J.W. Sleight, D.E. Prober, L.R. Motowidlo, and B.A. Zeitlin, Physica B, 194-196, 1867 (1994), “Flux Dynamics in Submicron Superconducting NbTi Wires”.
Vortex Physics: vortex avalanches in the Bean critical state
NbTi tube provides an excellent system for studying vortex avalanches in the Bean critical state. The question was whether such a system exhibits the "self-organized criticality" proposed in the famous Bak-Tang-Wiesenfeld sandpile model since we can make the system thermally stable and vortices are known to have no inertia effects (the real sand particles do). Stuart Field (at Michigan at the time, now at Colorado State) and I (at Yale at the time) joined the forces in making the experiment successful (I made the NbTi tube sample at Yale and his student Jeff Witt built the amplifier, the measurements were done at Michigan).
S. Field, J. Witt, F. Nori, and X.S. Ling, Physical Review Letters, 74, 1206 (1995), “Superconducting Vortex Avalanches”.
