Christina Hampton

All Publications

• Concentric-flow electrokinetic injector enables serial crystallography of ribosome and photosystem II NATURE METHODS Sierra, R. G., Gati, C., Laksmono, H., Dao, E. H., Gul, S., Fuller, F., Kern, J., Chatterjee, R., Ibrahim, M., Brewster, A. S., Young, I. D., Michels-Clark, T., Aquila, A., Liang, M., Hunter, M. S., Koglin, J. E., Boutet, S., Junco, E. A., Hayes, B., Bogan, M. J., Hampton, C. Y., Puglisi, E. V., Sauter, N. K., Stan, C. A., Zouni, A., Yano, J., Yachandra, V. K., Soltis, S. M., Puglisi, J. D., DeMirci, H. 2016; 13 (1): 59-?

  Abstract

  We describe a concentric-flow electrokinetic injector for efficiently delivering microcrystals for serial femtosecond X-ray crystallography analysis that enables studies of challenging biological systems in their unadulterated mother liquor. We used the injector to analyze microcrystals of Geobacillus stearothermophilus thermolysin (2.2-Å structure), Thermosynechococcus elongatus photosystem II (<3-Å diffraction) and Thermus thermophilus small ribosomal subunit bound to the antibiotic paromomycin at ambient temperature (3.4-Å structure).

  View details for DOI 10.1038/NMETH.3667

  View details for Web of Science ID 000367463600028

  View details for PubMedCentralID PMC4890631

• Single-shot diffraction data from the Mimivirus particle using an X-ray free-electron laser. Scientific data Ekeberg, T., Svenda, M., Seibert, M. M., Abergel, C., Maia, F. R., Seltzer, V., Deponte, D. P., Aquila, A., Andreasson, J., Iwan, B., Jönsson, O., Westphal, D., Odic, D., Andersson, I., Barty, A., Liang, M., Martin, A. V., Gumprecht, L., Fleckenstein, H., Bajt, S., Barthelmess, M., Coppola, N., Claverie, J., Loh, N. D., Bostedt, C., Bozek, J. D., Krzywinski, J., Messerschmidt, M., Bogan, M. J., Hampton, C. Y., Sierra, R. G., Frank, M., Shoeman, R. L., Lomb, L., Foucar, L., Epp, S. W., Rolles, D., Rudenko, A., Hartmann, R., Hartmann, A., Kimmel, N., Holl, P., Weidenspointner, G., Rudek, B., Erk, B., Kassemeyer, S., Schlichting, I., Strüder, L., Ullrich, J., Schmidt, C., Krasniqi, F., Hauser, G., Reich, C., Soltau, H., Schorb, S., Hirsemann, H., Wunderer, C., Graafsma, H., Chapman, H., Hajdu, J. 2016; 3: 160060-?

  Abstract

  Free-electron lasers (FEL) hold the potential to revolutionize structural biology by producing X-ray pules short enough to outrun radiation damage, thus allowing imaging of biological samples without the limitation from radiation damage. Thus, a major part of the scientific case for the first FELs was three-dimensional (3D) reconstruction of non-crystalline biological objects. In a recent publication we demonstrated the first 3D reconstruction of a biological object from an X-ray FEL using this technique. The sample was the giant Mimivirus, which is one of the largest known viruses with a diameter of 450 nm. Here we present the dataset used for this successful reconstruction. Data-analysis methods for single-particle imaging at FELs are undergoing heavy development but data collection relies on very limited time available through a highly competitive proposal process. This dataset provides experimental data to the entire community and could boost algorithm development and provide a benchmark dataset for new algorithms.

  View details for DOI 10.1038/sdata.2016.60

  View details for PubMedID 27479754

  View details for PubMedCentralID PMC4968188

• Anomalous Behavior of the Homogeneous Ice Nucleation Rate in "No-Man's Land" JOURNAL OF PHYSICAL CHEMISTRY LETTERS Laksmono, H., McQueen, T. A., Sellberg, J. A., Loh, N. D., Huang, C., Schlesinger, D., Sierra, R. G., Hampton, C. Y., Nordlund, D., Beye, M., Martin, A. V., Barty, A., Seibert, M. M., Messerschmidt, M., Williams, G. J., Boutet, S., Arnann-Winkel, K., Loerting, T., Pettersson, L. G., Bogan, M. J., Nilsson, A. 2015; 6 (14): 2826-2832

  View details for DOI 10.1021/acs.jpclett.5b01164

  View details for Web of Science ID 000358339600028

• Anomalous Behavior of the Homogeneous Ice Nucleation Rate in "No-Man's Land". journal of physical chemistry letters Laksmono, H., McQueen, T. A., Sellberg, J. A., Loh, N. D., Huang, C., Schlesinger, D., Sierra, R. G., Hampton, C. Y., Nordlund, D., Beye, M., Martin, A. V., Barty, A., Seibert, M. M., Messerschmidt, M., Williams, G. J., Boutet, S., Amann-Winkel, K., Loerting, T., Pettersson, L. G., Bogan, M. J., Nilsson, A. 2015; 6 (14): 2826-2832

  Abstract

  We present an analysis of ice nucleation kinetics from near-ambient pressure water as temperature decreases below the homogeneous limit TH by cooling micrometer-sized droplets (microdroplets) evaporatively at 10(3)-10(4) K/s and probing the structure ultrafast using femtosecond pulses from the Linac Coherent Light Source (LCLS) free-electron X-ray laser. Below 232 K, we observed a slower nucleation rate increase with decreasing temperature than anticipated from previous measurements, which we suggest is due to the rapid decrease in water's diffusivity. This is consistent with earlier findings that microdroplets do not crystallize at <227 K, but vitrify at cooling rates of 10(6)-10(7) K/s. We also hypothesize that the slower increase in the nucleation rate is connected with the proposed "fragile-to-strong" transition anomaly in water.

  View details for PubMedID 26207172

• Ultrafast X-ray probing of water structure below the homogeneous ice nucleation temperature NATURE Sellberg, J. A., Huang, C., McQueen, T. A., Loh, N. D., Laksmono, H., Schlesinger, D., Sierra, R. G., Nordlund, D., Hampton, C. Y., Starodub, D., DePonte, D. P., Beye, M., Chen, C., Martin, A. V., Barty, A., Wikfeldt, K. T., Weiss, T. M., Caronna, C., Feldkamp, J., Skinner, L. B., Seibert, M. M., Messerschmidt, M., Williams, G. J., Boutet, S., Pettersson, L. G., Bogan, M. J., Nilsson, A. 2014; 510 (7505): 381-?

  Abstract

  Water has a number of anomalous physical properties, and some of these become drastically enhanced on supercooling below the freezing point. Particular interest has focused on thermodynamic response functions that can be described using a normal component and an anomalous component that seems to diverge at about 228 kelvin (refs 1-3). This has prompted debate about conflicting theories that aim to explain many of the anomalous thermodynamic properties of water. One popular theory attributes the divergence to a phase transition between two forms of liquid water occurring in the 'no man's land' that lies below the homogeneous ice nucleation temperature (TH) at approximately 232 kelvin and above about 160 kelvin, and where rapid ice crystallization has prevented any measurements of the bulk liquid phase. In fact, the reliable determination of the structure of liquid water typically requires temperatures above about 250 kelvin. Water crystallization has been inhibited by using nanoconfinement, nanodroplets and association with biomolecules to give liquid samples at temperatures below TH, but such measurements rely on nanoscopic volumes of water where the interaction with the confining surfaces makes the relevance to bulk water unclear. Here we demonstrate that femtosecond X-ray laser pulses can be used to probe the structure of liquid water in micrometre-sized droplets that have been evaporatively cooled below TH. We find experimental evidence for the existence of metastable bulk liquid water down to temperatures of 227(-1)(+2) kelvin in the previously largely unexplored no man's land. We observe a continuous and accelerating increase in structural ordering on supercooling to approximately 229 kelvin, where the number of droplets containing ice crystals increases rapidly. But a few droplets remain liquid for about a millisecond even at this temperature. The hope now is that these observations and our detailed structural data will help identify those theories that best describe and explain the behaviour of water.

  View details for DOI 10.1038/nature13266

  View details for Web of Science ID 000337350200031

• Sensing the wavefront of x-ray free-electron lasers using aerosol spheres OPTICS EXPRESS Loh, N. D., Starodub, D., Lomb, L., Hampton, C. Y., Martin, A. V., Sierra, R. G., Barty, A., Aquila, A., Schulz, J., Steinbrener, J., Shoeman, R. L., Kassemeyer, S., Bostedt, C., Bozek, J., Epp, S. W., Erk, B., Hartmann, R., Rolles, D., Rudenko, A., Rudek, B., Foucar, L., Kimmel, N., Weidenspointner, G., Hauser, G., Holl, P., Pedersoli, E., Liang, M., Hunter, M. S., Gumprecht, L., Coppola, N., Wunderer, C., Graafsma, H., Maia, F. R., Ekeberg, T., Hantke, M., Fleckenstein, H., Hirsemann, H., Nass, K., White, T. A., Tobias, H. J., Farquar, G. R., Benner, W. H., Hau-Riege, S., Reich, C., Hartmann, A., Soltau, H., Marchesini, S., Bajt, S., Barthelmess, M., Strueder, L., Ullrich, J., Bucksbaum, P., Frank, M., Schlichting, I., Chapman, H. N., Bogan, M. J. 2013; 21 (10): 12385-12394

  Abstract

  Characterizing intense, focused x-ray free electron laser (FEL) pulses is crucial for their use in diffractive imaging. We describe how the distribution of average phase tilts and intensities on hard x-ray pulses with peak intensities of 10(21) W/m(2) can be retrieved from an ensemble of diffraction patterns produced by 70 nm-radius polystyrene spheres, in a manner that mimics wavefront sensors. Besides showing that an adaptive geometric correction may be necessary for diffraction data from randomly injected sample sources, our paper demonstrates the possibility of collecting statistics on structured pulses using only the diffraction patterns they generate and highlights the imperative to study its impact on single-particle diffractive imaging.

  View details for DOI 10.1364/OE.21.012385

  View details for Web of Science ID 000319339600072

  View details for PubMedID 23736456

• Single-particle structure determination by correlations of snapshot X-ray diffraction patterns NATURE COMMUNICATIONS Starodub, D., Aquila, A., Bajt, S., Barthelmess, M., Barty, A., Bostedt, C., Bozek, J. D., Coppola, N., Doak, R. B., Epp, S. W., Erk, B., Foucar, L., GUMPRECHT, L., Hampton, C. Y., Hartmann, A., Hartmann, R., Holl, P., Kassemeyer, S., Kimmel, N., Laksmono, H., Liang, M., Loh, N. D., Lomb, L., Martin, A. V., Nass, K., Reich, C., Rolles, D., Rudek, B., Rudenko, A., Schulz, J., Shoeman, R. L., Sierra, R. G., Soltau, H., Steinbrener, J., Stellato, F., Stern, S., Weidenspointner, G., Frank, M., Ullrich, J., Strueder, L., Schlichting, I., Chapman, H. N., Spence, J. C., Bogan, M. J. 2012; 3

  Abstract

  Diffractive imaging with free-electron lasers allows structure determination from ensembles of weakly scattering identical nanoparticles. The ultra-short, ultra-bright X-ray pulses provide snapshots of the randomly oriented particles frozen in time, and terminate before the onset of structural damage. As signal strength diminishes for small particles, the synthesis of a three-dimensional diffraction volume requires simultaneous involvement of all data. Here we report the first application of a three-dimensional spatial frequency correlation analysis to carry out this synthesis from noisy single-particle femtosecond X-ray diffraction patterns of nearly identical samples in random and unknown orientations, collected at the Linac Coherent Light Source. Our demonstration uses unsupported test particles created via aerosol self-assembly, and composed of two polystyrene spheres of equal diameter. The correlation analysis avoids the need for orientation determination entirely. This method may be applied to the structural determination of biological macromolecules in solution.

  View details for DOI 10.1038/ncomms2288

  View details for Web of Science ID 000316356700043

  View details for PubMedID 23232406

• Nanoflow electrospinning serial femtosecond crystallography ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY Sierra, R. G., Laksmono, H., Kern, J., Rosalie Tran, R., Hattne, J., Alonso-Mori, R., Lassalle-Kaiser, B., Gloeckner, C., Hellmich, J., Schafer, D. W., Echols, N., Gildea, R. J., Grosse-Kunstleve, R. W., Sellberg, J., McQueen, T. A., Fry, A. R., Messerschmidt, M. M., Miahnahri, A., Seibert, M. M., Hampton, C. Y., Starodub, D., Loh, N. D., Sokaras, D., Weng, T., Zwart, P. H., Glatzel, P., Milathianaki, D., White, W. E., Adams, P. D., Williams, G. J., Boutet, S., Zouni, A., Messinger, J., Sauter, N. K., Bergmann, U., Yano, J., Yachandra, V. K., Bogan, M. J. 2012; 68: 1584-1587

  Abstract

  An electrospun liquid microjet has been developed that delivers protein microcrystal suspensions at flow rates of 0.14-3.1 µl min(-1) to perform serial femtosecond crystallography (SFX) studies with X-ray lasers. Thermolysin microcrystals flowed at 0.17 µl min(-1) and diffracted to beyond 4 Å resolution, producing 14,000 indexable diffraction patterns, or four per second, from 140 µg of protein. Nanoflow electrospinning extends SFX to biological samples that necessitate minimal sample consumption.

  View details for DOI 10.1107/S0907444912038152

  View details for Web of Science ID 000310069500017

  View details for PubMedID 23090408

  View details for PubMedCentralID PMC3478121

• High-Resolution Protein Structure Determination by Serial Femtosecond Crystallography SCIENCE Boutet, S., Lomb, L., Williams, G. J., Barends, T. R., Aquila, A., Doak, R. B., Weierstall, U., Deponte, D. P., Steinbrener, J., Shoeman, R. L., Messerschmidt, M., Barty, A., White, T. A., Kassemeyer, S., Kirian, R. A., Seibert, M. M., Montanez, P. A., Kenney, C., Herbst, R., Hart, P., Pines, J., Haller, G., Gruner, S. M., Philipp, H. T., Tate, M. W., Hromalik, M., Koerner, L. J., van Bakel, N., Morse, J., Ghonsalves, W., Arnlund, D., Bogan, M. J., Caleman, C., Fromme, R., Hampton, C. Y., Hunter, M. S., Johansson, L. C., Katona, G., Kupitz, C., Liang, M., Martin, A. V., Nass, K., Redecke, L., Stellato, F., Timneanu, N., Wang, D., Zatsepin, N. A., Schafer, D., Defever, J., Neutze, R., Fromme, P., Spence, J. C., Chapman, H. N., Schlichting, I. 2012; 337 (6092): 362-364

  Abstract

  Structure determination of proteins and other macromolecules has historically required the growth of high-quality crystals sufficiently large to diffract x-rays efficiently while withstanding radiation damage. We applied serial femtosecond crystallography (SFX) using an x-ray free-electron laser (XFEL) to obtain high-resolution structural information from microcrystals (less than 1 micrometer by 1 micrometer by 3 micrometers) of the well-characterized model protein lysozyme. The agreement with synchrotron data demonstrates the immediate relevance of SFX for analyzing the structure of the large group of difficult-to-crystallize molecules.

  View details for DOI 10.1126/science.1217737

  View details for Web of Science ID 000306542600057

  View details for PubMedID 22653729

• In vivo protein crystallization opens new routes in structural biology NATURE METHODS Koopmann, R., Cupelli, K., Redecke, L., Nass, K., Deponte, D. P., White, T. A., Stellato, F., Rehders, D., Liang, M., Andreasson, J., Aquila, A., Bajt, S., Barthelmess, M., Barty, A., Bogan, M. J., Bostedt, C., Boutet, S., Bozek, J. D., Caleman, C., Coppola, N., Davidsson, J., Doak, R. B., Ekeberg, T., Epp, S. W., Erk, B., Fleckenstein, H., Foucar, L., Graafsma, H., Gumprecht, L., Hajdu, J., Hampton, C. Y., Hartmann, A., Hartmann, R., Hauser, G., Hirsemann, H., Holl, P., Hunter, M. S., Kassemeyer, S., Kirian, R. A., Lomb, L., Maia, F. R., Kimmel, N., Martin, A. V., Messerschmidt, M., Reich, C., Rolles, D., Rudek, B., Rudenko, A., Schlichting, I., Schulz, J., Seibert, M. M., Shoeman, R. L., Sierra, R. G., Soltau, H., Stern, S., Strueder, L., Timneanu, N., Ullrich, J., Wang, X., Weidenspointner, G., Weierstall, U., Williams, G. J., Wunderer, C. B., Fromme, P., Spence, J. C., Stehle, T., Chapman, H. N., Betzel, C., Duszenko, M. 2012; 9 (3): 259-U54

  Abstract

  Protein crystallization in cells has been observed several times in nature. However, owing to their small size these crystals have not yet been used for X-ray crystallographic analysis. We prepared nano-sized in vivo-grown crystals of Trypanosoma brucei enzymes and applied the emerging method of free-electron laser-based serial femtosecond crystallography to record interpretable diffraction data. This combined approach will open new opportunities in structural systems biology.

  View details for DOI 10.1038/NMETH.1859

  View details for Web of Science ID 000300890400020

  View details for PubMedID 22286384

  View details for PubMedCentralID PMC3429599

• Lipidic phase membrane protein serial femtosecond crystallography NATURE METHODS Johansson, L. C., Arnlund, D., White, T. A., Katona, G., Deponte, D. P., Weierstall, U., Doak, R. B., Shoeman, R. L., Lomb, L., Malmerberg, E., Davidsson, J., Nass, K., Liang, M., Andreasson, J., Aquila, A., Bajt, S., Barthelmess, M., Barty, A., Bogan, M. J., Bostedt, C., Bozek, J. D., Caleman, C., Coffee, R., Coppola, N., Ekeberg, T., Epp, S. W., Erk, B., Fleckenstein, H., Foucar, L., Graafsma, H., Gumprecht, L., Hajdu, J., Hampton, C. Y., Hartmann, R., Hartmann, A., Hauser, G., Hirsemann, H., Holl, P., Hunter, M. S., Kassemeyer, S., Kimmel, N., Kirian, R. A., Maia, F. R., Marchesini, S., Martin, A. V., Reich, C., Rolles, D., Rudek, B., Rudenko, A., Schlichting, I., Schulz, J., Seibert, M. M., Sierra, R. G., Soltau, H., Starodub, D., Stellato, F., Stern, S., Strueder, L., Timneanu, N., Ullrich, J., Wahlgren, W. Y., Wang, X., Weidenspointner, G., Wunderer, C., Fromme, P., Chapman, H. N., Spence, J. C., Neutze, R. 2012; 9 (3): 263-U59

  Abstract

  X-ray free electron laser (X-FEL)-based serial femtosecond crystallography is an emerging method with potential to rapidly advance the challenging field of membrane protein structural biology. Here we recorded interpretable diffraction data from micrometer-sized lipidic sponge phase crystals of the Blastochloris viridis photosynthetic reaction center delivered into an X-FEL beam using a sponge phase micro-jet.

  View details for DOI 10.1038/NMETH.1867

  View details for Web of Science ID 000300890400021

  View details for PubMedID 22286383

  View details for PubMedCentralID PMC3438231

• Femtosecond free-electron laser x-ray diffraction data sets for algorithm development OPTICS EXPRESS Kassemeyer, S., Steinbrener, J., Lomb, L., Hartmann, E., Aquila, A., Barty, A., Martin, A. V., Hampton, C. Y., Bajt, S., Barthelmess, M., Barends, T. R., Bostedt, C., Bott, M., Bozek, J. D., Coppola, N., Cryle, M., Deponte, D. P., Doak, R. B., Epp, S. W., Erk, B., Fleckenstein, H., Foucar, L., Graafsma, H., Gumprecht, L., Hartmann, A., Hartmann, R., Hauser, G., Hirsemann, H., Hoemke, A., Holl, P., Jonsson, O., Kimmel, N., Krasniqi, F., Liang, M., Maia, F. R., Marchesini, S., Nass, K., Reich, C., Rolles, D., Rudek, B., Rudenko, A., Schmidt, C., Schulz, J., Shoeman, R. L., Sierra, R. G., Soltau, H., Spence, J. C., Starodub, D., Stellato, F., Stern, S., Stier, G., Svenda, M., Weidenspointner, G., Weierstall, U., White, T. A., Wunderer, C., Frank, M., Chapman, H. N., Ullrich, J., Strueder, L., Bogan, M. J., Schlichting, I. 2012; 20 (4): 4149-4158

  Abstract

  We describe femtosecond X-ray diffraction data sets of viruses and nanoparticles collected at the Linac Coherent Light Source. The data establish the first large benchmark data sets for coherent diffraction methods freely available to the public, to bolster the development of algorithms that are essential for developing this novel approach as a useful imaging technique. Applications are 2D reconstructions, orientation classification and finally 3D imaging by assembling 2D patterns into a 3D diffraction volume.

  View details for Web of Science ID 000301041900078

  View details for PubMedID 22418172

• Self-terminating diffraction gates femtosecond X-ray nanocrystallography measurements NATURE PHOTONICS Barty, A., Caleman, C., Aquila, A., Timneanu, N., Lomb, L., White, T. A., Andreasson, J., Arnlund, D., Bajt, S., Barends, T. R., Barthelmess, M., Bogan, M. J., Bostedt, C., Bozek, J. D., Coffee, R., Coppola, N., Davidsson, J., Deponte, D. P., Doak, R. B., Ekeberg, T., Elser, V., Epp, S. W., Erk, B., Fleckenstein, H., Foucar, L., Fromme, P., Graafsma, H., Gumprecht, L., Hajdu, J., Hampton, C. Y., Hartmann, R., Hartmann, A., Hauser, G., Hirsemann, H., Holl, P., Hunter, M. S., Johansson, L., Kassemeyer, S., Kimmel, N., Kirian, R. A., Liang, M., Maia, F. R., Malmerberg, E., Marchesini, S., Martin, A. V., Nass, K., Neutze, R., Reich, C., Rolles, D., Rudek, B., Rudenko, A., Scott, H., Schlichting, I., Schulz, J., Seibert, M. M., Shoeman, R. L., Sierra, R. G., Soltau, H., Spence, J. C., Stellato, F., Stern, S., Strueder, L., Ullrich, J., Wang, X., Weidenspointner, G., Weierstall, U., Wunderer, C. B., Chapman, H. N. 2012; 6 (1): 35-40

  Abstract

  X-ray free-electron lasers have enabled new approaches to the structural determination of protein crystals that are too small or radiation-sensitive for conventional analysis1. For sufficiently short pulses, diffraction is collected before significant changes occur to the sample, and it has been predicted that pulses as short as 10 fs may be required to acquire atomic-resolution structural information1-4. Here, we describe a mechanism unique to ultrafast, ultra-intense X-ray experiments that allows structural information to be collected from crystalline samples using high radiation doses without the requirement for the pulse to terminate before the onset of sample damage. Instead, the diffracted X-rays are gated by a rapid loss of crystalline periodicity, producing apparent pulse lengths significantly shorter than the duration of the incident pulse. The shortest apparent pulse lengths occur at the highest resolution, and our measurements indicate that current X-ray free-electron laser technology5 should enable structural determination from submicrometre protein crystals with atomic resolution.

  View details for DOI 10.1038/NPHOTON.2011.297

  View details for Web of Science ID 000298416200013

  View details for PubMedCentralID PMC3783007

• Radiation damage in protein serial femtosecond crystallography using an x-ray free-electron laser PHYSICAL REVIEW B Lomb, L., Barends, T. R., Kassemeyer, S., Aquila, A., Epp, S. W., Erk, B., Foucar, L., Hartmann, R., Rudek, B., Rolles, D., Rudenko, A., Shoeman, R. L., Andreasson, J., Bajt, S., Barthelmess, M., Barty, A., Bogan, M. J., Bostedt, C., Bozek, J. D., Caleman, C., Coffee, R., Coppola, N., Deponte, D. P., Doak, R. B., Ekeberg, T., Fleckenstein, H., Fromme, P., Gebhardt, M., Graafsma, H., Gumprecht, L., Hampton, C. Y., Hartmann, A., Hauser, G., Hirsemann, H., Holl, P., Holton, J. M., Hunter, M. S., Kabsch, W., Kimmel, N., Kirian, R. A., Liang, M., Maia, F. R., Meinhart, A., Marchesini, S., Martin, A. V., Nass, K., Reich, C., Schulz, J., Seibert, M. M., Sierra, R., Soltau, H., Spence, J. C., Steinbrener, J., Stellato, F., Stern, S., Timneanu, N., Wang, X., Weidenspointner, G., Weierstall, U., White, T. A., Wunderer, C., Chapman, H. N., Ullrich, J., Strueder, L., Schlichting, I. 2011; 84 (21)

  Abstract

  X-ray free-electron lasers deliver intense femtosecond pulses that promise to yield high resolution diffraction data of nanocrystals before the destruction of the sample by radiation damage. Diffraction intensities of lysozyme nanocrystals collected at the Linac Coherent Light Source using 2 keV photons were used for structure determination by molecular replacement and analyzed for radiation damage as a function of pulse length and fluence. Signatures of radiation damage are observed for pulses as short as 70 fs. Parametric scaling used in conventional crystallography does not account for the observed effects.

  View details for DOI 10.1103/PhysRevB.84.214111

  View details for Web of Science ID 000298487500004

  View details for PubMedCentralID PMC3786679

• Single particle imaging with soft X-rays at the Linac Coherent Light Source Conference on Advances in X-ray Free-Electron Lasers - Radiation Schemes, X-ray Optics, and Instrumentation Martin, A. V., Andreasson, J., Aquila, A., Bajt, S., Barends, T. R., Barthelmess, M., Barty, A., Benner, W. H., Bostedt, C., Bozek, J. D., Bucksbaum, P., Caleman, C., Coppola, N., Deponte, D. P., Ekeberg, T., Epp, S. W., Erk, B., Farquar, G. R., Fleckenstein, H., Foucar, L., Frank, M., Gumprecht, L., Hampton, C. Y., Hantke, M., Hartmann, A., Hartmann, E., Hartmann, R., Hau-Riege, S. P., Hauser, G., Holl, P., Hoemke, A., Jonssonn, O., Kassemeyer, S., Kimmel, N., Kiskinova, M., Krasniqi, F., Krzywinski, J., Liang, M., Loh, N. D., Lomb, L., Maia, F. R., Marchesini, S., Messerschmidt, M., Nass, K., Odic, D., Pedersoli, E., Reich, C., Rolles, D., Rudek, B., Rudenko, A., Schmidt, C., Schulz, J., Seibert, M. M., Shoeman, R. L., Sierra, R. G., Soltau, H., Starodub, D., Steinbrener, J., Stellato, F., Strueder, L., Svenda, M., Tobias, H., Ullrich, J., Weidenspointner, G., Westphal, D., White, T. A., Williams, G., Hajdu, J., Schlichting, I., Bogan, M. J., Chapman, H. N. SPIE-INT SOC OPTICAL ENGINEERING. 2011

  View details for DOI 10.1117/12.886754

  View details for Web of Science ID 000293180500004

• Single-particle coherent diffractive imaging with a soft x-ray free electron laser: towards soot aerosol morphology JOURNAL OF PHYSICS B-ATOMIC MOLECULAR AND OPTICAL PHYSICS Bogan, M. J., Starodub, D., Hampton, C. Y., Sierra, R. G. 2010; 43 (19)

  View details for DOI 10.1088/0953-4075/43/19/194013

  View details for Web of Science ID 000281958100014

• Peptidyl alpha-ketoamides with nucleobases, methylpiperazine, and dimethylaminoalkyl substituents as calpain inhibitors. Journal of medicinal chemistry Ovat, A., Li, Z. Z., Hampton, C. Y., Asress, S. A., Fernández, F. M., Glass, J. D., Powers, J. C. 2010; 53 (17): 6326-36

  Abstract

  A series of peptidyl alpha-ketoamides with the general structure Cbz-L-Leu-D,L-AA-CONH-R were synthesized and evaluated as inhibitors for the cysteine proteases calpain I, calpain II, and cathepsin B. Nucleobases, methylpiperazine, and dimethylaminoalkyl groups were incorporated into the primed region of the inhibitors to generate compounds that potentially cross the blood-brain barrier. Two of these compounds (Cbz-Leu-D,L-Abu-CONH-(CH(2))(3)-adenin-9-yl and Cbz-Leu-D,L-Abu-CONH-(CH(2))(3)-(4-methylpiperazin-1-yl) have been shown to have useful concentrations in the brain in animals. The best inhibitor for calpain I was Cbz-Leu-D,L-Abu-CONH-(CH(2))(3)-2-methoxyadenin-9-yl (K(i) = 23 nM), and the best inhibitor for calpain II was Cbz-Leu-D,L-Phe-CONH-(CH(2))(3)-adenin-9-yl (K(i) = 68 nM). On the basis of the crystal structure obtained with heterocyclic peptidyl alpha-ketoamides, we have improved inhibitor potency by introducing a small hydrophobic group on the adenine ring. These inhibitors have good potential to be used in the treatment of neurodegenerative diseases.

  View details for DOI 10.1021/jm901221v

  View details for PubMedID 20690647

  View details for PubMedCentralID PMC2954059

• Comparison of the internal energy deposition of direct analysis in real time and electrospray ionization time-of-flight mass spectrometry. Journal of the American Society for Mass Spectrometry Harris, G. A., Hostetler, D. M., Hampton, C. Y., Fernández, F. M. 2010; 21 (5): 855-63

  Abstract

  The internal energy (E(int)) distributions of a series of p-substituted benzylpyridinium ions generated by both direct analysis in real time (DART) and electrospray ionization (ESI) were compared using the "survival yield" method. DART mean E(int) values at gas flow rates of 2, 4, and 6 L min(-1), and at set temperatures of 175, 250, and 325 degrees C were in the 1.92-2.21 eV range. ESI mean E(int) at identical temperatures in aqueous and 50% methanol solutions ranged between 1.71 and 1.96 eV, and 1.53 and 1.63 eV, respectively. Although the results indicated that ESI is a "softer" ionization technique than DART, there was overlap between the two techniques for the particular time-of-flight mass spectrometer used. As a whole, there was an increase in E(int) with increasing reactive and drying gas temperatures for DART and ESI, respectively, indicating thermal ion activation. Three dimensional computational fluid dynamic simulations in combination with direct temperature measurements within the DART ionization region revealed complex inversely coupled fluid-thermal phenomena affecting ion E(int) values during atmospheric transport. Primarily, that DART gas temperature in the ionization region was appreciably less than the set gas temperature of DART due to the set gas flow rates. There was no evidence of E(int) deposition pathways from metastable-stimulated desorption, but fragmentation induced by high-energy helium metastables was observed at the highest gas flow rates and temperatures.

  View details for DOI 10.1016/j.jasms.2010.01.019

  View details for PubMedID 20181493

• Transmission-mode direct analysis in real time and desorption electrospray ionization mass spectrometry of insecticide-treated bednets for malaria control. The Analyst Pérez, J. J., Harris, G. A., Chipuk, J. E., Brodbelt, J. S., Green, M. D., Hampton, C. Y., Fernández, F. M. 2010; 135 (4): 712-9

  Abstract

  Transmission-mode direct analysis in real time (TM-DART) is presented as an alternative sampling strategy to traditional methods of sample introduction for DART MS analysis. A custom-designed sample holder was fabricated to rapidly and reproducibly position insecticide-treated nets normal to the ionizing metastable gas stream, enabling transmission of desorbed analyte ions through the holder cavity and into the MS. Introduction of the sample at this fixed geometry eliminates the need for optimizing sample position and allows spectra based on factors such as metastable gas temperature and flow to be systematically evaluated. The results presented here, supported by computational fluid dynamic simulations, demonstrate the effects of these factors on the resulting mass spectra and the potential of this sampling strategy to be used for qualitative and quantitative analyses. Transmission-mode desorption electrospray ionization (TM-DESI) experiments on similar insecticide-treated nets were performed for comparison purposes.

  View details for DOI 10.1039/b924533b

  View details for PubMedID 20309445

• Ovarian cancer detection from metabolomic liquid chromatography/mass spectrometry data by support vector machines. BMC bioinformatics Guan, W., Zhou, M., Hampton, C. Y., Benigno, B. B., Walker, L. D., Gray, A., McDonald, J. F., Fernández, F. M. 2009; 10: 259

  Abstract

  The majority of ovarian cancer biomarker discovery efforts focus on the identification of proteins that can improve the predictive power of presently available diagnostic tests. We here show that metabolomics, the study of metabolic changes in biological systems, can also provide characteristic small molecule fingerprints related to this disease.In this work, new approaches to automatic classification of metabolomic data produced from sera of ovarian cancer patients and benign controls are investigated. The performance of support vector machines (SVM) for the classification of liquid chromatography/time-of-flight mass spectrometry (LC/TOF MS) metabolomic data focusing on recognizing combinations or "panels" of potential metabolic diagnostic biomarkers was evaluated. Utilizing LC/TOF MS, sera from 37 ovarian cancer patients and 35 benign controls were studied. Optimum panels of spectral features observed in positive or/and negative ion mode electrospray (ESI) MS with the ability to distinguish between control and ovarian cancer samples were selected using state-of-the-art feature selection methods such as recursive feature elimination and L1-norm SVM.Three evaluation processes (leave-one-out-cross-validation, 12-fold-cross-validation, 52-20-split-validation) were used to examine the SVM models based on the selected panels in terms of their ability for differentiating control vs. disease serum samples. The statistical significance for these feature selection results were comprehensively investigated. Classification of the serum sample test set was over 90% accurate indicating promise that the above approach may lead to the development of an accurate and reliable metabolomic-based approach for detecting ovarian cancer.

  View details for DOI 10.1186/1471-2105-10-259

  View details for PubMedID 19698113

  View details for PubMedCentralID PMC2741455

• Comparison of the internal energy deposition of Venturi-assisted electrospray ionization and a Venturi-assisted array of micromachined ultrasonic electrosprays (AMUSE). Journal of the American Society for Mass Spectrometry Hampton, C. Y., Silvestri, C. J., Forbes, T. P., Varady, M. J., Meacham, J. M., Fedorov, A. G., Degertekin, F. L., Fernández, F. M. 2008; 19 (9): 1320-9

  Abstract

  The internal energy deposition of a Venturi-assisted array of micromachined ultrasonic electrosprays (AMUSE), with and without the application of a DC charging potential, is compared with equivalent experiments for Venturi-assisted electrospray ionization (ESI) using the "survival yield" method on a series of para-substituted benzylpyridinium salts. Under conditions previously shown to provide maximum ion yields for standard compounds, the observed mean internal energies were nearly identical (1.93-2.01 eV). Operation of AMUSE without nitrogen flow to sustain the air amplifier focusing effect generated energetically colder ions with mean internal energies that were up to 39% lower than those for ESI. A balance between improved ion transfer, adequate desolvation, and favorable ion energetics was achieved by selection of optimum operational ranges for the parameters that most strongly influence the ion population: the air amplifier gas flow rate and API capillary temperature. Examination of the energy landscapes obtained for combinations of these parameters showed that a low internal energy region (

  View details for DOI 10.1016/j.jasms.2008.06.012

  View details for PubMedID 18650100

  View details for PubMedCentralID PMC2563429

• Analytical performance of a venturi-assisted array of micromachined ultrasonic electrosprays coupled to ion trap mass spectrometry for the analysis of peptides and proteins. Analytical chemistry Hampton, C. Y., Forbes, T. P., Varady, M. J., Meacham, J. M., Fedorov, A. G., Degertekin, F. L., Fernández, F. M. 2007; 79 (21): 8154-61

  Abstract

  The analytical characterization of a novel ion source for mass spectrometry named array of micromachined ultrasonic electrosprays (AMUSE) is presented here. This is a fundamentally different type of ion generation device, consisting of three major components: (1) a piezoelectric transducer that creates ultrasonic waves at one of the resonant frequencies of the sample-filled device, (2) an array of pyramidally shaped nozzles micromachined on a silicon wafer, and (3) a spacer which prevents contact between the array and transducer ensuring the transfer of acoustic energy to the sample. A high-pressure gradient generated at the apexes of the nozzle pyramids forces the periodic ejection of multiple droplet streams from the device. With this device, the processes of droplet formation and droplet charging are separated; hence, the limitations of conventional electrospray-type ion sources, including the need for high charging potentials and the addition of organic solvent to decrease surface tension, can be avoided. In this work, a Venturi device is coupled with AMUSE in order to increase desolvation, droplet focusing, and signal stability. Results show that ionization of model peptides and small tuning molecules is possible with dc charging potentials of 100 Vdc or less. Ionization in rf-only mode (without dc biasing) was also possible. It was observed that, when combined with AMUSE, the Venturi device provides a 10-fold gain in signal-to-noise ratio for 90% aqueous sample solutions. Further reduction in the diameter of the orifices of the micromachined arrays led to an additional signal gain of at least 3 orders of magnitude, a 2-10-fold gain in the signal-to-noise ratio and an improvement in signal stability from 47% to 8.5% RSD. The effectiveness of this device for the soft ionization of model proteins in aqueous media, such as cytochrome c, was also examined, yielding spectra with an average charge state of 8.8 when analyzed with a 100 Vdc charging potential. Ionization of model proteins was also possible in rf-only mode.

  View details for DOI 10.1021/ac071297n

  View details for PubMedID 17914864

  View details for PubMedCentralID PMC2543123

• Characterization of solid counterfeit drug samples by desorption electrospray ionization and direct-analysis-in-real-time coupled to time-of-flight mass spectrometry. ChemMedChem Fernández, F. M., Cody, R. B., Green, M. D., Hampton, C. Y., McGready, R., Sengaloundeth, S., White, N. J., Newton, P. N. 2006; 1 (7): 702-5

  View details for DOI 10.1002/cmdc.200600041

  View details for PubMedID 16902921