The present invention relates generally to an apparatus for processing samples, such as chemical and biological samples, and, more particularly, concerns such an apparatus which can perform disruption as well as centrifugation.
Today, chemical and biological samples are typically prepared in titer plates or individual vials. An extracting solvent or buffer may be added, if needed, and the samples are then shaken, either manually or by means of a mechanical disrupter, homogenizer, shaker, agitator, or vortexer (hereafter referred to generically as a “disrupter”). Thereafter, the samples are removed from the mechanical device and transferred to a centrifuge, where they are spun high speed to effect separation. This includes, but is not limited to separation of solids from liquids, separation of liquids of different density, and collection of DNA or RNA.
Since disruption and centrifugation involve two different pieces of equipment, the operator must manually transfer the sample containers from one piece of equipment to the other. This requires him to be present for both steps and requires time and effort to transfer samples and start the operation of the second piece of equipment. The skill and time of the operator could be utilized in much more meaningful and profitable ways.
It is therefore an object of the present invention to provide a sample processing apparatus which can perform both disruption and centrifugation of samples. It is specifically an object of the invention that the apparatus be capable of transitioning between disruption and centrifugation modes of operation automatically and with minimal operator intervention, other than to select the mode of operation, and without the operator handling samples, other than to insert or remove them from the apparatus. It is specifically contemplated that the operator should not be required to achieve a change in the mode of operation of the apparatus.
It is yet another object of the invention to provide a sample processing apparatus which is reliable in construction, yet relatively easy and convenient to use.
In accordance with one aspect of the present invention, a machine which has a platform for specimen container and which is constructed to spin the platform to produce centrifugation of the specimen is provided with a linkage that can selectively convert the spinning to a more complex form of motion effective to produce disruption of the specimen on the platform. Preferably, the linkage causes tilting of the platform relative to the axis of spinning, thereby providing a conical motion of the platform central axis and a complex, oscillatory motion of the samples. In a preferred embodiment, the linkage is constructed to provide the complex motion when the drive mechanism is rotated in one direction and to provide spinning of the platform when the drive mechanism is later rotated in the opposite direction.
The foregoing brief description and further objects, features and advantages of the present invention will be understood more completely from the following detailed description of the presently preferred, but nonetheless illustrative embodiment in accordance with the present invention, with reference being had to the accompanying drawings in which:
The mode of operation will depend upon the direction of movement of sample plate 14. A motor drive, for example via a pulley (not shown), is applied to bottom offset 18. In order to enter the disrupter mode, bottom offset 18 is rotated counterclockwise. As will be explained in more detail below, counterclockwise movement of bottom offset 18 relative to top offset 16 produces an interaction between the two offsets which causes the offset 16, sample plate 14 a sprag clutch 22 (discussed further below), and an upper portion of shaft 12 to tilt, as a unit, relative to offset 18 and a lower portion of shaft 12 (compare
When disruption is complete, the motor drive of bottom offset 18 is slowed and then reversed, so that it rotates clockwise. Clockwise rotation of offset 18 relative to offset 16, through their interaction, then brings the two offsets and sample plate 14 into axial alignment with shaft 12 (see
Those skilled in the art will appreciate that the transition between disrupter and centrifuge modes of operation could simply be accomplished through operator manipulation of controls. However, it is well within the skill of the art to incorporate automatic control, including timers, which can be preset to desired durations for disruption and centrifugation. Of course, automatic control also allows presetting of operating speeds, acceleration, and other operating parameters.
A sprag clutch 22 is provided between sample plate 14 and top offset 16, which holds sample plate 14 to shaft 12, while permitting free rotation about top offset 16, during disruption (counterclockwise rotation of offset 18). At the same time, a sprag cover 23 mounted on shaft 12 above platform 14 holds the platform to sprag clutch 22. This results in transfer of the complex motion to sample plate 14 with it not rotating about shaft 12. When apparatus 10 switches modes (clockwise rotation of offset 18 transferred to offset 16) clutch 22 permits free clockwise rotation of top offset 16 and holds it to sample plate 14, transferring rotational motion to sample plate 14.
Top offset 16 and bottom offset 18 have opposed surfaces 24, 26, which are formed at an acute angle to the axis of shaft 12. That is, they are not in a plane perpendicular to the axis of shaft 12. A bearing 28 permits relative rotation of offsets 16, 18 about an axis perpendicular to surfaces 24, 26.
In operation, when bottom offset 18 is driven counterclockwise, it will rotate relative to top offset 16 about the shaft 12 until its most counterclockwise edge 30 comes into contact with the most clockwise edge 32 of top offset 16. As bottom offset 18 rotates counterclockwise relative to top offset 16, top offset 16 also rotates about bearing 28 and begins to tilt, carrying sample plate 14 with it. When edges 30 and 32, come into contact, bottom offset 18 pushes tilted top offset 16, driving sample plate 14 in a conical pattern. As can be seen in
Later, when bottom of offset 18 is driven clockwise, edge 34 moves towards edge 36 (see
When centrifugation is complete, the sample can be removed by the operator and replaced with a new sample, which can be subjected to both disruption and centrifugation.
While the example shown herein uses a linkage to impart a first type of motion in one direction and a second type of motion in the other direction, the direction of rotation need not change. Instead, the change in type of motion can occur even if rotation is in the same direction for both types of motion. In this case, the additional linkage causing the more complex type of motion might take a different form or be eliminated.
Generally, the disruption motion desired in the preferred embodiment is an oscillatory tilting of the axis of rotation of the sample plate, coupled with rotation of the tilted axis. In the centrifuge mode, the sample plate is to be rotated about the axis of rotation. By switching between these modes after a predetermined time, or after a parameter indicative of sample disruption has occurred, both required processes can be performed in the same apparatus without having to change samples and/or vessels.
Rather than switch the type of motion after a predetermined time, other parameters indicative of the completion of the disruption or other first mode of motion can be used. For example, the system could measure the number of cycles of motion executed during the first mode, or could include a detector to determine when the proper amount of separation or disruption has been achieved. Any parameter sufficient to indicate when the first mode is complete may be used instead of a timer. Moreover, the switch between the two types of motion could be manual, as an operator may wish to activate such switch based upon a visual inspection of the sample as it undergoes the processing via the first type of motion.
Although a preferred embodiment of the invention has been disclosed for illustrative purposes, those skilled in the art will appreciate that many additions, modifications, and substitutions are possible without departing from the scope and spirit of the invention as defined by the accompanying claims. For example, a variety of gearing and bearing arrangement may be used to alter the type of motion imparted on the sample.