The present invention relates generally to laboratory equipment for homogenization applications, and particularly to attachments and peripherals for holding sample containers for processing by such homogenizing devices.
Homogenization involves disaggregating or emulsifying the components of a sample using a high-shear process with significant micron-level particle-size reduction of the sample components. Homogenization is commonly used for a number of laboratory applications such as creating emulsions, reducing agglomerate particles to increase reaction area, cell destruction for capture of DNA material (proteins, nucleic acids, and related small molecules), DNA and RNA amplification, and similar activities in which the sample is bodily tissue and/or tissue, or another substance. Conventional high-powered mechanical-shear homogenization devices for such applications include bead-mill and shaker-mill style homogenization devices. Some of these-type devices include a plate holding a number of tubes containing the samples and a base unit with a swash-plate that generates and transmits a “swashing” motion to the plate holder to homogenize the samples in the tubes using centrifugal forces to vigorously oscillate the tubes axially.
These bead-mill and shaker-mill devices have proven generally beneficial in accomplishing the desired homogenization of the samples. But in use they have their disadvantages. For example, in some devices the plates include axial end-clamps that secure to the tubes at their ends, thereby limiting the plates to use with only one height of tube. In some other devices, the tubes are secured in place by finger plates, which are labor- and time-intensive to use because they must be manually tightened to secure the tubes in place, and often for best results they then must be untightened, adjusted, and retightened.
Accordingly, it can be seen that needs exist for improvements in homogenization devices relating to mounting the sample tubes in place. It is to the provision of solutions to these and other problems that the present invention is primarily directed.
Generally described, the present invention relates to mounting apparatus for holding tubes of samples for processing by a homogenizer. The mounting apparatus includes a processing plate and at least one cassette, with the plate for mounting to the homogenizer, the cassette for mounting to the plate, and the tube for holding by the cassette. In some embodiments, the cassette includes one or more tube-retention assemblies for removably securing the tube against axial, lateral, and/or rotational movement, for example, using centrifugal forces of the homogenizer for retention assistance. In some embodiments, the cassette is removably mounted to the plate, for example, using centrifugal forces of the homogenizer for retention assistance. And in some embodiments, the tube can be replaced in the cassette with the cassette mounted to the plate adjacent an access opening through which the tube can pass, while centrifugal forces assist in retaining the tubes in the cassette during operation of the homogenizer.
The specific techniques and structures employed by the invention to improve over the drawbacks of the prior devices and accomplish the advantages described herein will become apparent from the following detailed description of example embodiments of the invention and the appended drawings and claims.
The present invention relates to mounting apparatus for holding samples for processing by a homogenization device. In the depicted embodiments, the mounting apparatus are for use with high-powered bead-mill or shaker-mill homogenizer devices that generate centrifugal forces for swash-motion homogenization of the samples, or similar sample-agitation devices that use sinusoidal perturbed axial rotation to transfer force to samples in sample tubes. In other embodiments and/or applications, the mounting apparatus are for use with other types of homogenization devices that generate and impart additional or different forces and motions to the samples.
In addition, the mounting apparatus of the depicted embodiments are typically used to hold tubes containing samples of human or non-human bodily fluid and/or tissue (e.g., blood, bone-marrow cells, a coronary artery segment, or pieces of organs). In other embodiments and/or applications, the tubes hold a different substance such as other organic matter (e.g., plants or food) or other chemicals. As such, use of the term “sample” herein is intended to be broadly construed to cover any type of substance that can be homogenized and for which homogenization could be useful. Furthermore, the mounting apparatus of the depicted embodiments hold a plurality of samples. In other embodiments and/or applications, the mounting apparatus hold only a single sample.
Referring now to the drawings,
The homogenizer that the mounting apparatus 30 is used with can be of a conventional type well-known in the art such as a bead-mill homogenizer commercially available under the BEAD RUPTOR brand from Omni International (Kennesaw, Ga.). Or the homogenizer can be of a conventional type such as those disclosed by U.S. Pat. Nos. 5,567,050 and 7,101,077, which are incorporated herein by reference. The plate 32 can mount to the homogenizer by conventional attachments that are well-known in the art, and the centrifugal forces generated by the homogenizer can be transferred to the plate (to impart the swashing motion to the cassettes 34 and thus the samples) by conventional structures that are well-known in the art. As such, details of the homogenizer are not provided herein.
The tubes 10 that the mounting apparatus 30 is used with can be of a conventional type well-known in the art such as clear, plastic, cylindrical vials with end-caps. For example, typical cylindrical tubes include those that are about 1¾ inches long with a diameter of about ⅜ inch, about 2½ inches by about ½ inch, or about 3¼ inches by about 1 inch. Thus, as used herein the term “tube” is intended to be broadly construed to cover any type of container in any shape that can hold a sample during homogenization, and as such is not limited to traditional cylindrical tubes or vials. For use with a homogenizer of a bead-mill type, the tubes 10 hold—in addition to the sample—a plurality of beads and typically also include a buffer, as is well-known in the art.
Referring particularly to
In other embodiments, the cassette is in the form of a frame or lattice that removably receives and structurally supports the tube. In yet other embodiments, the open side of the cassette is at another portion of the body and/or forms only a portion of a side of the body. In still other embodiments, the cassette body completely encloses the tube thereby providing a sealed container that for purposes of thermal management and/or containment of fluid (gas or liquid) samples. And in still other embodiments, the cassette includes a doorway through which the tube is inserted and removed, and a door or lid that pivots, slides, rotates, or moves otherwise relative to the body between open and closed positions. As such, it will be understood that the body can be in many forms other than those disclosed herein, with many different configurations, sizes, and shapes (e.g., including generally cylindrical).
Referring particularly to
In the depicted embodiment, the axial-retention assembly includes a wedge-shaped element 48 that is positioned in the body 36 adjacent its top wall 40 and that is relatively thinner at its front than at its rear so that it forms the ramped surface 50. The wedge-shaped element 48 can be a separate piece that is attached in place by conventional fasteners such as pins, rivets, an adhesive, a friction fit, or the like (e.g., as depicted), or it can be an integrally formed portion of the cassette body 36 (i.e., the ramped surface 50 is the bottom/inner surface of the top wall).
In addition, the ramped surface 50 can include gripping elements 52 such as steps or ribs that frictionally engage and thereby grip the tube 10 (at its end 12) to help retain it in the chamber 44 from lateral movement. Furthermore, the ramped surface 50 can include tapered (e.g., curved, angled, or otherwise funneling) sidewalls 53 that can frictionally engage and thereby grip the tube 10 (at its side 18) to help retain it in the chamber 44 from lateral movement. As such, the ramped surface 50 can function as a lateral-retention and/or anti-rotation assembly, in addition to an axial-retention assembly.
In use, the axial-retention assembly enables the cassette 34 to hold a range of different-height tubes 10 and still secure them from axial movement during homogenization. For example, the wedge-shaped element 48 will engage and retain a relatively shorter tube 10a and a relatively taller tube 10b (collectively, the tubes 10), with the shorter tube received rearwardly deeper into the chamber 44 and engaging the ramped surface 50 at a location farther rearward relative to the taller tube (see
In other embodiments, the axial-retention assembly is provided in another form. For example, the axial-retention assembly can include a ramped surface defining the inner bottom surface of the chamber for engaging an axial end of the tube and partially defining the varied height of the chamber. Or the axial-retention assembly can include a top or bottom axially-positioned ramped surface that is spring-biased axially inward (downward or upward) for engaging an axial end of the tube and partially defining the varied height of the chamber. Persons of ordinary skill in the art will understand that the height differential and slope of the ramped surface can be selected as needed for providing the described axial-retention functionality.
Referring particularly to
The male element 56 of the cassette 34 is sized and shaped to receive a range of different sized and shaped female elements 14 of tubes 10 when the tubes are positioned in the cassette for use. Thus, when used in conjunction with an axial-retention assembly, the male element 56 is typically not snugly fit into the female element 14, to allow for ease of insertion and removal of the tube 10. In typical embodiments, the male element 56 is generally cylindrical (including oblong and/or two flattened-out plan-view walls), has a height of about 3/16 inch or about 5/16 inch, has a width (side-to-side) of about ⅜ inch or about ¾ inch, and has a depth (front-to-back) of about ½ inch or about ¾ inch.
The bottom inner surface 54 (e.g., including the male element 56) cooperates with the top inner surface 50 to retain the tube 10 in the chamber 44 and prevent axial and lateral-forward movement of the tube. When used with a tube 10 having a relatively axially-shallower female element 14, the tube is supported by the transverse walls of the mating male and female elements (and is thus supported above the rest of the bottom inner surface 54). And when used with a tube 10 having a relatively axially-deeper female element 14, the tube is supported by the peripheral edge of the female element and the portion of the bottom inner surface 54 laterally outward of the male element 56. In use, the lateral-retention assembly thereby enables the cassette 34 to hold a variety of different tubes 10 with a range of different-depth and different-shape female elements 14, or even without a female element (the tube simply rests atop and is supported by the top/inner surface of the male element).
In other embodiments, the lateral-retention assembly is provided in another form. For example, the lateral-retention assembly can include a male element extending axially inward from the top inner surface of the chamber that is received in a female element axially recessed in the tube. Or the lateral-retention assembly can include a male element that is spring-biased axially inward (upward from the bottom-inner surface of the chamber and/or downward from the top inner surface) for receipt in a female element (including an end recess, the annular space peripherally surrounding an end, or the like) of the tube, with such a male element provided by for example a leaf spring, spring-biased clip, or resiliently deformable boss. In such axially spring-biased embodiments, the male element also functions as an axial-retention assembly that helps removably secure the tube from axial movement during homogenization. In still other embodiments, the male element is sized and shaped to fit snugly with and thus frictionally engage the tube, thereby also functioning as an anti-rotation assembly that helps removably secure the tube from rotational movement during homogenization.
Additional embodiments of lateral-retention assemblies are described herein and shown in
The cooperative functionality of the ramped surface 50 and the male element 56 is shown in
Referring particularly to
In the depicted embodiment, the anti-rotation assembly is provided by at least one spring-biased element 58. For example, a set of two aligned and opposing spring-biased elements 58 can be provided adjacent the open front-side 46 of the body 36, and more than one set can be provided (two sets are depicted). The spring-biased elements 58 resiliently deflect laterally relative to the longitudinal axis of the cassette 34 (i.e., generally radially relative to the tubes 10) between a neutral fully extended/inward position and charged fully retracted/outward position. The spring-biased elements 58 are mounted to the body 36 (e.g., on the inner surface of the sidewalls 42) adjacent the open front-side 46 (outward/forward of the plan-view center of the tube), extending laterally inward into the chamber, and resiliently deflecting/retracting outward. In typical embodiments, the spring elements 58 have a deflection range (between extended/inward and retracted/outward positions) of about 1/32 inch, with two generally aligned and opposed spring elements thus having an effective deflection range of about 1/16 inch. The nominal oversizing of the chamber 44 for the tube 10 is less than the deflection range of the spring elements 58 so that when the tube is in the chamber the spring elements are not fully extended inward and contact the tube with an inward force. The spring-biased elements 58 can be provided by commercially available spring-biased push-pins with linear-retraction pins with domed ends, as depicted.
In use, as the tube 10 is inserted into the chamber 44 through the open front-side 46, it contacts the spring-biased elements 58 and laterally deflects them outward (as indicated by the outward directional arrows of
In other embodiments, the anti-rotation assembly is provided in another form. For example, the axial-retention assembly can include other conventional spring-biased elements such as leaf springs, resiliently deformable (e.g., rubber-like) bosses, resiliently deformable (e.g., plastic) snap-fit parts, compression-spring ramps or balls, spring-biased clamps or clips, spring-biased pivot-arms, or spring-biased frictional inner-wall segments of the cassette body. In other embodiments, the cassette body has an open side (an access opening for inserting and removing the tube) positioned elsewhere and the anti-rotation assembly includes spring-biased elements positioned adjacent the other-positioned open side to provide the same functionality. And for applications in which tube rotation during homogenization is desired (or at least not needed to be prevented), the anti-rotation assembly can be eliminated or adapted to include a lock that retains the spring-biased elements in the retracted/outward position.
As described above, the spring-biased elements 58 also function as a lateral-retention assembly that helps removably secure the tube 10 in the chamber 44 from forward lateral movement through the open front-side 46 of the body 36 during homogenization. As such, some embodiments include the spring-biased elements 58 but not the male element 56 (or another lateral-retention assembly). In addition, the male element 56 can also function as an axial-retention and/or anti-rotation assembly. As such, some embodiments include the male element 56 (or another lateral-retention assembly) but not both the ramped surface 50 (or another axial-retention assembly) and the spring-biased elements 58 (or another anti-rotation assembly). Furthermore, the ramped surface 50 can also function as a lateral-retention and/or anti-rotation assembly. As such, some embodiments include the ramped surface 50 (or another axial-retention assembly) but not both the male element 56 (or another lateral-retention assembly) and the spring-biased elements 58 (or another anti-rotation assembly). Accordingly, it will be understood that all three of the disclosed tube-retention assemblies, the axial-retention assembly (e.g., with a ramped surface 30), the lateral-retention assembly (e.g., with a male element 56), and the anti-rotation assembly (with a spring-biased element 58), can each be provided individually in a cassette, in any combination with each other, or in combination with other tube-retention assemblies, as may be desirable for a given application.
In addition, the cassette body 36 and the tube-retention assemblies (particularly the anti-rotation and axial-retention assemblies) are configured so that the centrifugal forces generated by the homogenizer urge the tube 10 into, not out of, the chamber 44. In particular, the cassette body 36 is configured so that it mounts to the plate 32 with its open front-side 46 facing radially inward toward the center of the plate. So the tube-retention assemblies (e.g., the spring-biased elements 56) do not need to secure the tube 10 in the cassette chamber 44 so as to withstand the radially outward centrifugal forces, and instead these forces assist in the tube retention. In this way, the tubes 10 are easier to insert and remove from the cassette chambers 44 (less manual force and dexterity is required by the user's hands/fingers) while still secured in place during homogenization at least in part by the centrifugal forces generated.
Having described details of the cassettes 34, details of the processing plate 32 and its interrelationship with the cassettes will now be described with particular reference to
In the depicted embodiment, the plate 32 includes access openings 60a adjacent and in communication with the corresponding open sides 46 of the cassettes 34. The access openings 60a are configured with a shape and size providing sufficient clearance to permit the tubes 10 to be inserted into and removed from the cassette chamber 44 through the cooperating open sides 46 (via the respective access openings) while the cassettes are mounted to the plate 32. For example, a tube 10 can be tilted forward/inward through the open side 46 of its cassette 34 and into its access opening 60 of the plate 32 (see
In addition, the access openings 60a are typically positioned radially inward of the cassettes 34, and the cassettes are oriented with the open sides 46 facing radially inward. In this way, the centrifugal forces generated by the homogenizer urge the tubes 10 against lateral/radial inward movement through the cooperating open sides 46 and access openings 60a, thereby providing a centrifugal-assist in locking the tubes in place during homogenizing.
Furthermore, the plate 32 and cassettes 34 typically include removable mounting features permitting the cassettes to be removed from the plate for cleaning or replacement (e.g., to install a plate configured for different cassettes or to change out a damaged one). In the depicted embodiment, an innovative removable mounting assembly includes collective openings 60 in the plate 32 and support shoulders 62 on the cassette bodies 36. The collective openings 60 each include an access opening 60a and a corresponding mounting opening 60b in communication with each other. And the support shoulder 62 can be provided by a flange (as shown), peripherally spaced tabs or pins, or at least one other form of protrusion extending radially outward from the cassette body 36.
Typically but not necessarily, an axial-retaining shoulder 64 can also be provided on the cassette body 36 and positioned (e.g., below) the support shoulder 62, as in the depicted embodiment. The axial-retaining shoulder 64 and the support shoulder 62 cooperatively form a mounting channel 66 therebetween that receives a lip portion 68 of the plate 32 that forms the mounting opening 60b. The axial-retaining shoulder 64 can be provided by a flange (as shown), peripherally spaced tabs or pins, a resilient element (e.g., a clip or leaf spring), or at least one other form of protrusion extending radially outward from the cassette body 36.
The support shoulders 62 have a radius (or other transverse dimension) RS that is greater than the radius RA of the access openings 60a, the mounting channels 66 have a radius (or other transverse dimension) RC that is less than the access-opening radius RA and (thus also less than the support-shoulder radius RS), and the retaining shoulders 64 have a radius (or other transverse dimension) RR that is less (typically only slightly less) than the access-opening radius RA (thus also less than the support-shoulder radius RS) but greater than the mounting-channel radius RC (see
In use, the cassette 34 is inserted axially downward (as indicated by the directional arrow of
In addition, the access openings 60a are typically positioned radially inward of the mounting openings 60b. In this way, the centrifugal forces generated by the homogenizer urge the cassettes 34 against lateral/radial inward movement back into the access openings 60a, thereby providing a centrifugal-assist in locking the cassettes in place during homogenizing.
Furthermore, to orient the cassettes 34 in the mounting openings 60b with their open sides 46 facing radially inward, the plate 32 and the cassettes can include keyed elements. In the depicted embodiment, for example, the plate 32 includes at least one protrusion (e.g., a pin or rib) 72 adjacent each mounting opening 60b and the cassette bodies 36 each include at least one recess (e.g., a notch or channel) 74 in the support shoulder 62 that receives the protrusion only when the cassette 34 is properly oriented (see
In other embodiments, the plate does not include the access openings (so the tubes cannot be removed while the cassettes are mounted to the plate), or they are included but not positioned radially inward of the cassette open sides (in applications where centrifugal forces are no or less of an issue), as may be desired in given applications. In yet other embodiments, the plate does not include the mounting openings (the cassettes are not removable or they are removable by another mounting mechanism), or they are included but not positioned radially inward of the cassette open sides (in applications where centrifugal forces are no or less of an issue), as may be desired in given applications. In other embodiments, the plate and cassette are adapted for bottom insertion and removal of the cassettes. In still other embodiments, the plate and the cassette include conventional removable or permanent mounting structures known in the art. And in yet still other embodiments, the mounting apparatus 30 includes one or more of the tube-retention assemblies but not the removable-mounting assembly, and vice versa.
In another aspect, the mounting apparatus 130 includes cassettes 134 with a different tube-retention assembly, in particular a different lateral-retention assembly. A transverse member (e.g., a rod, bar, or panel) 176 extends across the open side 146 of the cassette body 136, typically adjacent the top or bottom of the open side, to removably secure the tube 10 in the chamber 144 from lateral movement during homogenization. The transverse member 176 typically extends all the way across the open side 146 and is attached to opposing sidewalls of the cassette body 136, though in some embodiments they extend only partially across sufficiently to provide the lateral-retention functionality. Also, in this embodiment the tubes 10 can be installed cap-up (as depicted) or cap-down.
And in another aspect, the mounting apparatus 130 includes a different removable-mounting assembly that removably mounts the cassettes 134 to the plate 132. For example, the mounting openings 160b are typically sized larger for receiving the larger dual-tube cassettes 134. And two access openings 160a are typically provided in communication with each mounting opening 160b, each access opening positioned radially inward and in communication with the portion of the mounting opening where the respective cassette chamber 144 is positioned.
In this embodiment, the mounting openings 160b are provided by notches formed in the peripheral edge 182 of the plate 134 and recessed radially inward therefrom. As such, the cassettes 134 are installed and removed by sliding them radially inward and outward, respectively, through the open outer ends 183 of the mounting openings 160b. Accordingly, the access openings 160a are configured only for installing and removing the tubes 10, and need not be sized larger or otherwise configured for also installing and removing the larger cassettes 134 that hold the tubes. As such, this embodiment is well-suited for use with homogenizers regardless of centrifugal or other forces being generated during homogenizing.
In addition, the support and retaining shoulders 162 and 164 include aligned axial lock openings 178 and 179 that align with an axial lock opening 180 in the plate 134 when the cassette 134 is properly mounted in place. The three aligned lock openings 178-180 removably receive a lock pin 181 to form a releasable lock mechanism that secures the cassette 134 to the plate 132 during homogenization. In other embodiments, the cassettes can be held in place by snap-fit or other conventional releasable lock mechanisms.
In the depicted embodiment, the plate 332 includes the access openings 360a and the mounting openings 360b. But instead of being sized and shaped relative to shoulders of cassettes, they are sized and shaped relative to the tubes 10 themselves. Thus, each access opening 360a is sized to axially receive the tube body 18 and the radially-larger tube endcap 16 (and a tube flange 15 adjacent the endcap), while each corresponding mounting opening 360b is sized to axially receive the tube body but not the radially-larger endcap and flange (see
In addition, the tube-retention cassette ring 334 includes a support plate 385 defining a plurality of chambers 344 each sized and shaped to receive one of the tubes 10 by its endcap 16, each having an open side 346 through which the respective tube 10 can slidingly pass, and each positioned under and axially aligned with a corresponding one of the mounting openings 360b. And the cassette ring 334 includes at least one tube-retention assembly that removably secures the tubes 10 in their respective chambers 344. In typical embodiments such as that depicted, each tube-retention assembly is a lateral-retention assembly including at least one spring-biased element 356 that resiliently deflects between a neutral radially inward extended position and a charged radially outward retracted position. In other embodiments, the spring-biased elements can be provided by other conventional retention structures known in the art and/or by other tube-retention assembly components described with respect to the other embodiments disclosed herein.
In use, each tube 10 is oriented with its endcap 16 down, axially aligned with one of the access openings 360a, and moved axially downward (as indicated by the directional arrow of
Accordingly, the various embodiments of the invention provide various advantages over known tube-mounting apparatus for homogenizers. Advantages include using centrifugal forces generated by a homogenizer to process samples in tubes, and using the same centrifugal forces to secure the tubes in cassettes (even tubes of varied dimensions) and also secure the cassettes to a processing plate. In addition, the tubes can still be easily removed from the cassettes and the cassettes easily removed from the plate when the homogenizer is not in operation, as needed. Further, the tubes can be easily removed from the cassettes, without first removing the cassettes from the plate.
It is to be understood that this invention is not limited to the specific devices, methods, conditions, or parameters described and/or shown herein, and that the terminology used herein is for the purpose of describing particular embodiments by way of example only. Thus, the terminology is intended to be broadly construed and is not intended to be limiting of the claimed invention. For example, as used in the specification including the appended claims, the singular forms “a,” “an,” and “one” include the plural, the term “or” means “and/or,” and reference to a particular numerical value includes at least that particular value, unless the context clearly dictates otherwise. In addition, any methods described herein are not intended to be limited to the sequence of steps described but can be carried out in other sequences, unless expressly stated otherwise herein.
While the invention has been shown and described in exemplary forms, it will be apparent to those skilled in the art that many modifications, additions, and deletions can be made therein without departing from the spirit and scope of the invention as defined by the following claims.
This application claims the priority benefit of U.S. provisional Patent Application Ser. No. 61/853,136 filed Mar. 29, 2013, which is hereby incorporated herein by reference.
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Entry |
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International Search Report for EP 14161867.8; dated Jul. 10 2014; 6 pages. |
Omni International. “Omni Bead Ruptor Bead Mill Homogenizers.” <www.omni-inc.com>. <www.beadruptor.com>. 2 pages. |
Number | Date | Country | |
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20140293735 A1 | Oct 2014 | US |
Number | Date | Country | |
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61853136 | Mar 2013 | US |