Cryogenic cooling positioning apparatus, methods and applications

#The present invention relates to the field of biotechnology. More particularly, the invention pertains to the design of systems for cooling biological samples, and to the handling and positioning of sample holders to receive and store cold samples. The invention also pertains to the more general problem of accurately positioning objects that are immersed in cryogenic fluids.

#Cryogenic Sample Cooling and Handling in X-Ray Crystallography:

#X-ray crystallography is the most powerful and widely used tool for determining the molecular structures of proteins, viruses, nucleic acids, and biomolecular complexes. The determination of these molecular structures is critical to modern molecular biology, and to the development of pharmaceutical treatments for various diseases and human conditions.

#One or more aspects of the present invention are particularly pointed out and distinctly claimed as examples in the claims at the conclusion of the specification. The foregoing and other objects, features, and advantages of the invention are apparent from the following description taken in conjunction with the accompanying drawings in which:

#FIG. 1 illustrates a section view of one embodiment of a cryogenic cooling and storage system for use, for instance, with accurate positioning and storage of samples in a cryogenic liquid, in accordance with one or more aspects of the present invention.

#FIG. 2A depicts a cross-sectional view of the cryogenic cooling system, in accordance with one or more aspects of the present invention.

#Aspects of the present invention and certain features, advantages, and details thereof, are explained more fully below with reference to the non-limiting examples illustrated in the accompanying drawings. Descriptions of well-known structures are omitted so as not to unnecessarily obscure the invention in detail. It should be understood, however, that the detailed description and the specific example, while indicating aspects of the invention, are given by way of illustration only, and are not by way of limitation. Various substitutions, modifications, additions, and/or arrangements, within the spirit and/or scope of the underlying inventive concepts will be apparent to those skilled in the art from this disclosure.

#The present invention relates to, inter alia, a method and a cryogenic sample positioning system for precise positioning of samples, and in particular, samples cooled by and immersed in liquid cryogens. By way of example, the cryogenic sample positioning system disclosed herein comprises an epicyclic continuously indexing mechanism with a planet drive gear (commonly referred to as “sun gear”), a carousel gear (commonly referred to as a “planet gear carrier”) and one or more planet gears driven from the edges by extending the planet drive gear out to a large diameter.

#FIG. 1 depicts a cross-sectional view of an exemplary cryogenic cooling and storage system 1000 that includes: a thermally insulated liquid nitrogen filled chamber 10, a cover or lid 20 for the chamber having a passage 30 through which a sample 40 may be positioned in a cryogenic sample positioning system 100. The sample 40 can be translated along a single axis 50 by the vertical translation stage 60 into the liquid nitrogen 70 for cooling and then into one of several openings 80 (also referred disclosed herein as “sample holder receptacles”) in one of several sample holder cassettes 90 of the cryogenic sample positioning system 100. In one embodiment, the cryogenic sample positioning system 1000 disclosed herein positions a desired opening 80 in a desired sample holder cassette 90 directly along the vertical axis 50 of the translation stage 60, allowing the sample 40 to be inserted into or removed from that position in the sample holder cassette. As described further below in greater detail, and in one embodiment, positioning of a sample holder cassette involves rotating the sample holder cassette about its central axis of the sample positioning system (for instance, analogous to orbital motion of a planet about the sun), and rotating the sample holder cassette about its planetary axis. The combination of these two motions allows any sample receptacle position on any sample holder to be positioned along the axis of the sample translation stage.