Abstract: Humidified sample preparation station for serial crystallography according to one embodiment is a humidified enclosure that delivers relative humidities above 95% and preferably above 97% in standard operation, and that can allow microscope observation of samples within. Humidified sample preparation station for serial crystallography can be used for preparation of protein crystal samples for examination using X-rays and for protein structure determination by X-ray crystallography, involving addition of liquid to the sample and removal of liquid from the sample using vacuum or suction.

Abstract: A system for cryocooling biological samples includes a first chamber that holds a first amount a cryogenic liquid. A container holder, which is positioned in thermal contact with the first chamber, holds a removable container positioned therein. The container holds a second amount of the cryogenic liquid and forms a second chamber. An elongated tube holder holds a hollow elongated tube into the container. A sample wand holds and transfers a sample holder with a biological sample into the elongated tube while the elongated tube is in the container with the second amount of the cryogenic liquid.

Abstract: A cryogenic cooling manifold and methods incorporating a cryogenic cooling manifold for managing the gas layer(s) above a liquid cryogen to control cooling temperature-time profiles and ice formation for microliter and smaller samples that are plunged through the gas and into the liquid cryogen.

Abstract: A cryogenic cooling manifold and methods incorporating a cryogenic cooling manifold for managing the gas layer(s) above a liquid cryogen to control cooling temperature-time profiles and ice formation for microliter and smaller samples that are plunged through the gas and into the liquid cryogen.

Abstract: Sample support design and sample cooling devices for single-particle cryo-electron microscopy that simplify sample preparation and handling, dramatically reduce errors and improve outcome reproducibility, and dramatically reduce overall costs. The system consisting of grid based sample support system, grid handling tools, grid blotting tools, a plunge cooling system, and jet cooling systems.

Abstract: A fixed target sample holder for serial synchrotron crystallography comprising a goniometer compatible base, a carrier, a sample holding insert which can be placed into the carrier. The sample holding insert comprising fiducials and windows, wherein each of the windows are respectively configured to accept a sample. The windows can also have holes and texture within each window. Additionally, a sample loading workstation for loading crystals into the sample holder and the removal of excess liquid from the sample, comprising a humidity-controlled chamber, a sample support within the chamber, a capture to place the goniometer-compatible base, and a channel in communication with the chamber that allows for the flow of humidified air into the chamber.

Abstract: Humidified sample preparation station for serial crystallography according to one embodiment is a humidified enclosure that delivers relative humidities above 95% and preferably above 97% in standard operation, and that can allow microscope observation of samples within. Humidified sample preparation station for serial crystallography can be used for preparation of protein crystal samples for examination using X-rays and for protein structure determination by X-ray crystallography, involving addition of liquid to the sample and removal of liquid from the sample using vacuum or suction.

Abstract: Apparatus and methods for performing small angle X-ray scattering (SAXS) at low (cryogenic) temperatures for determining the structure of and changes in the structure of proteins, DNA, RNA, and other biological molecules and biomolecular assemblies and structures. A cryogenic, small angle X-ray scattering (SAXS) application sample holder, includes a sample cell including a base portion and at least two parallel walls disposed on the base, wherein the sample cell has a liquid volume capacity defined by the walls and the base portion of 0.001 to 10 microliters.

Abstract: Devices and methods for manual and high-throughput protein crystal growth and growth of other biological and organic crystals. A microplate includes a plurality of cells and a frame that defines the cells in the microplate. In each cell there is at least one well open at top. Each well in a cell may be enclosed at bottom, or it may be open at bottom, in which case the well bottom may be sealed by a separate part, which may be, e.g., a separate film or plate (e.g., of plastic, glass or metal) or a molded part.

Abstract: A cryogenic cooling manifold and methods incorporating a cryogenic cooling manifold for managing the gas layer(s) above a liquid cryogen to control cooling temperature-time profiles and ice formation for microliter and smaller samples that are plunged through the gas and into the liquid cryogen.

Abstract: A method and devices for rapid cooling of small biological samples by plunging them in a cryogenic liquid, such as liquid nitrogen, or contacting them with a cryogenic metal surface, reduce or eliminate the cold gas layer that forms above the liquid cryogens or cryogenic surfaces, producing an abrupt transition from ambient (e.g., room) temperature to the cryogen temperature as the sample enters the liquid or contacts the surface. To reduce or eliminate the effects of the cold gas layer, a flow of warm dry gas can be directed along the plunge path, for example. By removing this cold gas layer, cooling times for a 10 micron sample (the size of single cells and the smallest protein crystals now used protein crystallography) will decrease to ˜0.001 s.

Abstract: Apparatus and methods for performing small angle X-ray scattering (SAXS) at low (cryogenic) temperatures for determining the structure of and changes in the structure of proteins, DNA, RNA, and other biological molecules and biomolecular assemblies and structures. A cryogenic, small angle X-ray scattering (SAXS) application sample holder, includes a sample cell including a base portion and at least two parallel walls disposed on the base, wherein the sample cell has a liquid volume capacity defined by the walls and the base portion of 0.001 to 10 microliters.

Abstract: Devices and methods for manual and high-throughput protein crystal growth and growth of other biological and organic crystals. A microplate includes a plurality of cells and a frame that defines the cells in the microplate. In each cell there is at least one well open at top. Each well in a cell may be enclosed at bottom, or it may be open at bottom, in which case the well bottom may be sealed by a separate part, which may be, e.g., a separate film or plate (e.g., of plastic, glass or metal) or a molded part.

Abstract: A goniometer base for X-ray crystallography comprises a magnetic steel part with a cylindrical hole, a compliant cylindrical part that is inserted into this hole, and a cylindrical tube that is press-fit into the hole and holds the compliant part in place, such that when a crystal mounting tool is inserted through the concentric holes in each part, it is positively gripped and held in place at both T=300 K and T=100 K.

Abstract: Microfabricated tools useful for manipulating small, delicate samples are formed from thin plastic films. The films have a small thickness (preferably 5 to 50 micrometers and typically 10 micrometers) and small lateral dimensions (preferably 2 mm or less and typically 0.1 to 1 mm) so that they are reasonably flexible, but are preferably curved by being wrapped around a cylindrical or flat post to give them some rigidity. The softness and thinness of the plastic reduce risk of sample damage during incidental contact with the tool. Its thinness makes it optically and X-ray transparent, so that the samples can be clearly visualized during manipulations and so that the tools can be used to collect X-ray data from samples. As an option, an X-ray sensitive phosphor is incorporated in the film at low concentration. This allows the X-ray beam to be visually located on the mount or tool.

Abstract: A goniometer base for X-ray crystallography comprises a magnetic steel part with a cylindrical hole, a compliant cylindrical part that is inserted into this hole, and a cylindrical tube that is press-fit into the hole and holds the compliant part in place, such that when a crystal mounting tool is inserted through the concentric holes in each part, it is positively gripped and held in place at both T=300 K and T=100 K.

Abstract: In systems and methods for freezing and subsequently thawing liquid samples containing biological components, a sample is fractioned into a very large number of small drops (10) having surface area to volume ratios of 1000 m-1 or greater. The drops are projected at a liquid cryogen (40) or at the solid surface of a highly thermally conducting metal cup or plate, where they rapidly freeze. The cold gas layer that develops above any cold surface is replaced with a dry gas stream (75). The environmental temperature experienced by the sample then abruptly changes from the warm ambient to the temperature of the cryogenic liquid or solid surface. To thaw drops with the highest warming rates, the frozen drops may be projected into warm liquids. The sample is projected with cold gas to the warm liquid, so that again there is an abrupt transition in the environmental temperature.

Abstract: Microfabricated tools useful for manipulating small, delicate samples are formed from thin plastic films. The films have a small thickness (preferably 5 to 50 micrometers and typically 10 micrometers) and small lateral dimensions (preferably 2 mm or less and typically 0.1 to 1 mm) so that they are reasonably flexible, but are preferably curved by being wrapped around a cylindrical or flat post to give them some rigidity. The softness and thinness of the plastic reduce risk of sample damage during incidental contact with the tool. Its thinness makes it optically and X-ray transparent, so that the samples can be clearly visualized during manipulations and so that the tools can be used to collect X-ray data from samples. As an option, an X-ray sensitive phosphor is incorporated in the film at low concentration. This allows the X-ray beam to be visually located on the mount or tool.

Abstract: In one embodiment, a crystallization and screening plate comprises a plurality of cells open at a top and a bottom, a frame that defines the cells in the plate, and at least two films. The first film seals a top of the plate and the second film seals a bottom of the plate. At least one of the films is patterned to strongly pin the contact lines of drops dispensed onto it, fixing their position and shape. The present invention also includes methods and other devices for manual and high-throughput protein crystal growth.

Abstract: Sample mounts (10) for mounting microcrystals of biological macromolecules for X-ray crystallography are prepared by using patterned thin polyimide films (12) that have curvature imparted thereto, for example, by being attached to a curved outer surface of a small metal rod (16). The patterned film (12) preferably includes a tip end (24) for holding a crystal. Preferably, a small sample aperture is disposed in the film for reception of the crystal. A second, larger aperture can also be provided that is connected to the sample aperture by a drainage channel, allowing removal of excess liquid and easier manipulation in viscous solutions. The curvature imparted to the film (12) increases the film's rigidity and allows a convenient scoop-like action for retrieving crystals. The polyimide contributes minimally to background and absorption, and can be treated to obtain desired hydrophobicity or hydrophilicity.