公开(公告)号：CA2519830A1

公开(公告)日：2004-11-04

申请号：CA2519830

申请日：2004-03-22

Applicant: CORNELL RES FOUNDATION INC

Inventor： KMETKO JAN ,  O'NEILL KEVIN ,  THORNE ROBERT E ,  STUM ZACHARY

IPC: G01N23/20

Abstract: Sample mounts (10) for mounting microcrystals of biological macromolecules f or 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 tapered 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 samp le 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.

公开(公告)号：AU2004233143A1

公开(公告)日：2004-11-04

申请号：AU2004233143

申请日：2004-03-22

Applicant: CORNELL RES FOUNDATION INC

Inventor： THORNE ROBERT E ,  KMETKO JAN ,  O'NEILL KEVIN ,  STUM ZACHARY

IPC: G01N23/20

公开(公告)号：WO2007123720A2

公开(公告)日：2007-11-01

申请号：PCT/US2007007963

申请日：2007-03-30

Applicant: CORNELL RES FOUNDATION INC ,  WARKENTIN MATTHEW ,  THORNE ROBERT E ,  BEREJNOV VIATCHESLAV

Inventor： WARKENTIN MATTHEW ,  THORNE ROBERT E ,  BEREJNOV VIATCHESLAV

IPC: F25B13/00

CPC classification number: G01N1/42 ,  A01N1/02 ,  A01N1/0242 ,  A01N1/0257 ,  A01N1/0268

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 translation: 一种用于通过将它们浸入低温液体（例如液氮）或将它们与低温金属表面接触来快速冷却小生物样品的方法和装置，减少或消除在液体冷冻剂或低温表面之上形成的冷气层， 当样品进入液体或接触表面时，从环境温度（例如室温）到冷冻剂温度突然转变。 为了减少或消除冷气层的影响，例如，可以沿着插入路径引导暖干燥气体的流动。 通过去除这个冷气层，10微米样品的冷却时间（单个细胞的大小和现在使用蛋白质晶体学的最小的蛋白质晶体）将降低至-0.001秒。

公开(公告)号：WO2004094993A2

公开(公告)日：2004-11-04

申请号：PCT/US2004006088

申请日：2004-03-22

Applicant: CORNELL RES FOUNDATION INC ,  THORNE ROBERT E ,  STUM ZACHARY ,  O'NEILL KEVIN ,  KMETKO JAN

Inventor： THORNE ROBERT E ,  STUM ZACHARY ,  O'NEILL KEVIN ,  KMETKO JAN

IPC: G01N23/20 ,  G01N

CPC classification number: C30B29/58 ,  C30B35/00 ,  G01N23/20 ,  G01N23/20025 ,  Y10S269/90 ,  Y10S269/908 ,  Y10S269/909 ,  Y10T29/53961 ,  Y10T117/1036

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 tapered 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.

Abstract translation: 用于安装用于X射线晶体学的生物大分子的微晶的样品安装件（10）通过使用具有赋予曲率的图案化的聚酰亚胺薄膜（12）来制备，例如通过附接到小金属棒的弯曲外表面 16）。 图案化膜（12）优选地包括用于保持晶体的锥形尖端（24）。 优选地，在膜中设置小的样品孔以接收晶体。 还可以提供第二个较大的孔，其通过排水通道连接到样品孔，允许去除多余的液体并且更容易在粘性溶液中操作。 赋予膜（12）的曲率提高了膜的刚性，并且允许用于取出晶体的方便的勺状作用。 聚酰亚胺对背景和吸收的贡献最小，可以进行处理以获得所需的疏水性或亲水性。

公开(公告)号：WO2007089658A2

公开(公告)日：2007-08-09

申请号：PCT/US2007002292

申请日：2007-01-26

Applicant: CORNELL RES FOUNDATION INC ,  THORNE ROBERT E ,  CHEW GUANHAN

Inventor： THORNE ROBERT E ,  CHEW GUANHAN

IPC: G01N1/00

CPC classification number: G01N1/286 ,  B01L3/505 ,  B01L3/5088 ,  B01L2200/147 ,  B01L2300/028

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. The plastic can also be treated to obtain a desired hydrophobicity or hydrophilicity, mechanically embossed or abraded, or coated with films (for example, of polyethylene glycol via pegylation procedures or of PDMS) that promote or inhibit sample adhesion.

Abstract translation: 用于操作小而精细样品的微型工具由薄塑料膜形成。 膜的厚度（优选为5至50微米，典型为10微米）和较小的横向尺寸（优选2mm或更小，通常为0.1至1毫米），使得它们具有相当的柔性，但优选通过围绕 圆柱形或扁平柱，给它们一些刚性。 塑料的柔软性和薄度降低了与工具偶然接触时样品损坏的风险。 其薄度使其在光学和X-射线透明，使得样品可以在操作过程中清晰可视，从而可以使用这些工具从样品中收集X射线数据。 作为选择，在低浓度下将X射线敏感性荧光体掺入膜中。 这允许X射线束在视觉上位于安装件或工具上。 也可以处理塑料以获得所需的疏水性或亲水性，机械压花或磨损，或涂覆促进或抑制样品粘附的膜（例如聚乙二醇通过聚乙二醇化程序或PDMS）。

公开(公告)号：WO2008040022A3

公开(公告)日：2008-08-14

申请号：PCT/US2007079996

申请日：2007-09-28

Applicant: CORNELL RES FOUNDATION INC ,  THORNE ROBERT E ,  MACFARLANE SCOTT ,  WARKENTIN MATTHEW

Inventor： THORNE ROBERT E ,  MACFARLANE SCOTT ,  WARKENTIN MATTHEW

IPC: F25D17/06

CPC classification number: A01N1/02 ,  A01N1/0257 ,  A01N1/0278

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 translation: 在用于冷冻和随后解冻含有生物成分的液体样品的系统和方法中，将样品分馏成具有1000m-1或更大的表面积与体积比的非常大量的小滴（10）。 液滴投射在液体冷冻剂（40）或高度导热的金属杯或板的固体表面，在那里它们迅速冷冻。 在任何冷表面上形成的冷气层被干燥气流（75）代替。 样品经历的环境温度然后从温暖环境突然变为低温液体或固体表面的温度。 为了解冻具有最高升温速率的液滴，冷冻液滴可以投射到温暖的液体中。 样品用冷气体投射到温暖的液体，这样在环境温度下再次出现突然的转变。

公开(公告)号：EP1623202A4

公开(公告)日：2007-04-18

申请号：EP04722504

申请日：2004-03-22

Applicant: CORNELL RES FOUNDATION INC

Inventor： THORNE ROBERT E ,  STUM ZACHARY ,  O'NEILL KEVIN ,  KMETKO JAN

IPC: G01N23/00 ,  G01N23/20

CPC classification number: C30B29/58 ,  C30B35/00 ,  G01N23/20 ,  G01N23/20025 ,  Y10S269/90 ,  Y10S269/908 ,  Y10S269/909 ,  Y10T29/53961 ,  Y10T117/1036

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 tapered 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.