Apparatus and method for causing vortices in a test tube

Abstract: A test tube handling assembly has an elongate member (12) with an end for engaging a test tube (14) and an end opposite thereto driven about an axis of the member for orbital movement with its axis. The member is a slender rod with a spherical bearing about a center part thereon between the ends thereof and along its axis. An arm (23) extends from a support to carry the spherical bearing and permit limited motion of the rod relative to the support. A gripping means (28) on the end for engaging the test tube holds the test tube and its contents during movement of the rod relative to the axis. A drive (34) located on the support near the end opposite causes the test tube to swing about the center part. Contacting means with a seal for closing the open end of the test tube is part of an inflatable bladder (32) which holds the open end of the test tube by fitting in the open end of the test tube. The drive has a motor (35) for providing orbital motion. The motor axis (36) and the member axis (16) are in spaced parallel relation relative to each other with a linkage means therebetween to cause the axis of the member to move about the axis of the motor imparting an orbital motion to the end opposite of the member thereby orbiting the end for engaging the test tube. A three axis positioning means (19) carries the support by connection with a releasable latching means. A method has steps of holding a test tube by the gripping means, moving the test tube repetitively with the drive and generating orbital movement of the test tube and sample therein for producing a vortex in the test tube sample.

Description: Background of the Invention 1. Field of the Invention . This invention relates to an apparatus and method for causing vortices in test tube samples, and more specifically, to an apparatus and method for selectively and automatically causing vortices in a test tube and adding and removing samples therefrom. 2. Background Description . Frequently laboratory samples have to be mixed as part of a test procedure so that the portion of the sample tested or analyzed is representative of the entire specimen. A variety of test equipment available to mix or shake test samples directly stirs the test sample in its container or shakes the container and sample. Stirring devices usually include a member which is placed into the sample within the container to spin the sample about the axis of the member. Typically the member has to be cleaned after use and the container is subject to the stresses imposed by contact with the member during stirring. The most commonly used laboratory sample mixing equipment is designed to shake the container and its contents to eliminate the need to clean a mixing or stirring member. Shaking the container and the contents works well for messy materials including paints and lubricants. Similarly, dangerous substances such as acids and other active chemicals are mixed within the container thus eliminating concern about destruction of, or contact with the stirring member. Biohazardous substances are frequently tested for deadly cancers, virus, infection or the like and thus typically require particular care during handling. Consequently, laboratory mixing and stirring equipment which does not include a member that contacts the hazardous specimens is safer to use than stirring members which have to be handled. Another form of mixer includes a flat shaker table upon which the sample container is placed. Often the laboratory vessel has a flat bottom which can be placed upon the vibrating table that moves in a plane in two directions imparting orbital motion to the container and sample. The orbital motion agitates the sample. Problems with handling and cleaning flat bottomed vessels remain a concern even though vibrating tables are inexpensive to make and use. Vibrating tables are not suited for use with test tubes. Samples are usually in a test tubes with spherically shaped bottoms that are inexpensive and disposable or are easy to clean and reuse. Shakers can be used for the contents of one container with several test tubes. The individual handling of test tubes is slow and automated handling presents the difficulty of being unable to have equal incubation times for all the samples. Specifically, as the samples are prepared one at a time in each test tube prior to mixing as a group, delays occure resulting in some of the samples incubating longer than others. Various test tube shaking, rotating and revolving devices have been developed and used for mixing the contents of a plurality of test tubes. One device holds a number of test tubes in a rack designed to individually support each test tube near the longitudinal middle of each tube so that the rack and tubes can be swung about the midpoint of the axes of the tubes to mix the samples sealed within the tubes. The problem with swinging racks of sealed test tubes is handling since each tube has to be sealed and placed in the rack. A variation of such swinging rack mixers merely swings the tube through a small arc to agitate the contents without spillage even though the tubes are unsealed. Vortex causing mixers are frequently used to mix the contents of individual test tubes by placing the rounded bottom end of a single tube into a rubber pocket which has a switch activated by pressing the test tube into the pocket. Closing the switch makes the vortex causing mixer orbit the rounded test tube bottom about the longitudinal axis of the test tube. The top of the test tube is hand held in substantially one place such that the lower end of the test tube orbits establishing a vortex in the sample. Motion of the test tube is designed to cause a vortex in the sample due to the eccentrically orbiting resilient pocket into which the bottom of the test tube is manually placed while the top of the test tube is held stationary by a laboratory technician. The technician must control the mixing by varying the angle of contact and pressure on the drive cup during mixing. One such manually operated mixer is the VWR Vortex Mixer manufactured by Scientific Industries, Inc. of Bohemia, New York, as disclosed in US-A-3,061,280. A further mixer is disclosed in US-A-4,042,218. Each test tube and sample must be individually placed in the pocket so samples can be individually caused to vortex. A further apparatus for causing a vortex in a test tube is known from WO 89/04484. This apparatus comprises an elongate member for engaging a test tube with its one end, a support for the member and a drive which moves the member and the test tube. However, this apparatus does not allow for an automatic handling of the test tubes. It is commonly known that certain analytical equipment is designed to handle a plurality of samples carried in special racks from which the samples can be accessed automatically. Such analytical equipment requires that the samples be mixed in order to provide a homogenous or representative portion of the specimen to be tested. Automatic accessing of the samples from each test tube means that each tube with a well mixed sample has to be held in a rack which positions each tube for access. It is the object of the present invention to provide a test tube handling assembly and a method for causing a vortex in a test tube sample which minimizes handling by the technician during mixing and which allows for a cooperation with analytical equipment. The object of the invention is solved with the features of claims 1 and 7, respectively. The preferred embodiment includes an apparatus which is a test tube handling assembly for causing a vortex in a test tube sample. The assembly most preferably may comprise an elongate member with an end for engaging a test tube and an end opposite thereto driven about an axis of the member for movement relative to the axis thereof. The member has a center part thereon between the ends thereof and along the axis. A support for the member may have an arm extending from the support to carry a spherical bearing for the center part of the member and permit limited motion of the member relative to the support. A test tube gripping means on the end for engaging the test tube may hold the test tube and the contents thereof during movement of the member relative to the axis. A drive located on the support near the end opposite is in contact with the gripping means. The preferred drive has a motor for providing rotary motion about a motor axis. The motor axis and the member axis are in spaced parallel relation relative to each other with a linkage means therebetween to cause the axis of the member to orbit by imparting an orbital motion to the end opposite of the member thereby orbiting the end for engaging the test tube. In the preferred handling assembly the test tube gripping means may have test tube contacting means for holding an open end of the test tube during movement of the member. The test tube contacting means includes a seal for substantially closing the open end of the test tube and in the preferred form is an inflatable bladder which upon inflation holds the open end of the test tube. The inflatable bladder fits within the open end of the test tube. The arm preferably extends from the support to carry the member center part in spaced apart relation with respect to the support so that movement of the member about the center part and relative to the axis is permitted without contact between the support and the test tube or the member. The member most preferably includes a slender rod so the spherical bearing permits orbital motion of the axis of the rod and swinging movement about the center part. The center part of the rod has a point on the axis of the rod which is free from movement as the rod orbits about its axis and swings relative to the point about the elongate length of the rod. The end for engaging may carry a passage so samples can be added or removed from the test tube. The support may include a three axis positioning means for the elongate member and wherein one of the axes of movement of the three axis positioning means is substantially parallel with the axis of the member and the other two axes of movement of the three axis positioning means are normal to the axis of the member. The member may be releasably latched to the three axis positioning means to be moved thereby. Another form of the preferred invention is a method for causing a vortex in a test tube sample by the preferred test tube handling assembly with the steps of holding a test tube by the gripping means during movement of the member relative to the axis, moving the test tube repetitively with the drive to cause the test tube to orbit relative to the axis and to swing about the center part of the member and generating orbital movement of the test tube and sample therein for producing a vortex in the test tube sample. The additional step of retaining the test tube by inflating a bladder within an open end of the test tube may also be included in the method. The additional step of sealing the open end of the test tube with the inflated bladder is part of the preferred method. The added step of holding the support on a three axis positioning means with one axis thereof parallel to the axis of the member may be another part of the method. BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 is a perspective view of an apparatus having a preferred embodiment of a test tube handling assembly for causing a vortex in a test tube sample; a test tube is shown held in a gripper and a probe for adding and removing samples from the test tube and is carried on a three axis position means. Figure 2 is an enlarged front elevational view of the part of the test tube handling assembly for causing a vortex in a test tube sample of Figure 1, showing the gripper lowered toward the test tube. Figure 3 is an enlarged cross sectional view of the preferred form of the inflatable bladder engaged with the open end of a test tube showing the channels which permit air to escape from the test tube when it is substantially closed by the inflated bladder and material is added; also shown is the passage for adding and removing samples. Figure 4 is a view similar to that of Figure 2 but enlarged and partially in cross section to show the solenoid engagement of the probe and the drive for the test tube gripper. Figure 1 illustrates an apparatus 10 containing the preferred embodiment of a test tube handling assembly 11 for causing a vortex in a test tube sample comprising an elongate member 12 with an end for engaging 13 a test tube 14 and an end opposite 15 thereto driven with an axis 16 of the member 12 for orbital movement. The member 12 has a center part 17 thereon between the ends 13 and 15 thereof and the center part 17 is located along the axis 16. A support 18 for the member 12 for carrying the center part 17 of the member 12 and permitting limited motion of the member 12 relative to the support 18. The support 18 includes a three axis positioning means 19 for the elongate member 12 wherein one of the axes 20 of movement of the three axis positioning means 19 is substantially parallel with the axis 16 of the member 12 and the other two axes 21 and 22 of movement of the three axis positioning means 19 are normal to the axis 16 of the member 12. An arm 23 extends from the support to carry the member 12 center part 17 in spaced apart relation with respect to the support 18 so that orbital movement of the member 12 about the center part 17 is permitted without contact between the support 18 and the test tube 14 or the member 12. The center part 17 of the member 12 is supported on the arm 23 to carry the member so a point 24 on the axis 16 of the member 12 is free from movement as the member 12 and its axis 16 orbit and swing relative to the point 24 about the elongate length of the member 12. The member 12 is in the preferred embodiment a slender rod 25 and a spherical bearing is carried in the arm 23 permitting orbital motion of the rod 25 and its axis 16 and swing movement about the point 24 in the center part 17. The end for engaging 13 carries passage 27 to permit material to be transported to and from the test tube 14 to be added or removed from the sample. A test tube gripping means 28 on the end for engaging 13 the test tube 14 is able to hold the test tube 14 and the contents thereof during movement of the member 12 relative to the axis 16. The test tube gripping means 28 has test tube contacting means 29 in Figure 3 for holding an open end 30 of the test tube 14 during movement of the member 12. The contacting means 29 includes a seal 31 for substantially closing the open end 30 of the test tube 14. The contacting means 29 is an inflatable bladder 32 which upon inflation expands and holds against the inside of the open end 30 of the test tube 14. The inflatable bladder 32 fits within the open end 30 of the test tube 14 when the bladder 32 is inflated. The open end 30 of the test tube 14 is substantially closed by the inflatable bladder 32. The bladder 32 having channels 33 thereabout permits air within the test tube 14 to escape when the bladder 32 is inflated and material is added to the test tube 14. A drive 34 located on the support 18 near the end opposite 15 causes the test tube 14 to move relative to its axis 16 thereby swinging the test tube 14 about the center part 17 of the member 12. The drive 34 has a motor 35 for providing orbital motion. A motor axis 36 and the member axis 16 are in spaced parallel relation relative to each other with a linkage means 37 therebetween to cause the axis 16 and the member 12 to orbit imparting an orbital motion to the end opposite 15 of the member 12 thereby orbiting the end for engaging 13 the test tube 14. A method for causing a vortex in a test tube sample with the test tube handling assembly 11 has the member 12 with the end for engaging 13 the test tube 14 and the end opposite 15 thereto driven about the axis 16 of the member 12 for movement relative to the axis 16. The member 12 has the center part 17 thereon between the ends 13 and 15 thereof and along the axis 16 and the support 18 for the member 12 carries the center part 17 of the member 12 and permits limited motion of the member 12 relative to the support 18. The test tube gripping means 28 is on the end for engaging 13 the test tube 14. The drive 34 is located on the support near the end opposite. The method includes the step of holding the test tube 14 by the gripping means 28 during orbital movement of the member 12 and its axis 16. The step of moving the test tube 14 repetitively with the drive 34 to cause the test tube 14 to orbit with the axis 16 and to swing about the center part 17 of the member 12 is also a part of the method. The method has the step of generating orbital movement of the test tube 14 and sample therein for producing a vortex in the test tube sample. The method may also include the additional step of retaining the test tube 14 by inflating the bladder 32 within the open end 30 of the test tube 14. The method of retaining can further have the additional step of sealing the open end 30 of the test tube with the inflated bladder 32. The method of generating could be provided with the added step of holding the support 18 on the three axis positioning means 19 wherein one axis 20 thereof is parallel to the axis 16 of the member 12. The method of generating may include the step of moving the test tube 14 with the drive 34 by driving the end opposite 15 with an eccentric on the end opposite 15 of the member 12. In use, the apparatus and method herein are part of a handling system for rack of twelve by seventy-five test tubes. That is to say that each test tube has a diameter of twelve millimeters and a length of seventy-five millimeters and there are twenty of these test tubes in a rack 39 as in Figure 1. Eight racks 39 are placed in a Tecan RSP 5301 three axis positioning means 19 arranged such that a sample of, for example, human blood can be picked up by a probe 40 and portions of that sample dispensed into each of the eight test tubes 14 held in each rack 39. The probe 40 also has access to as many as twelve containers 41 holding monoclonal antibodies which can be added to the test tubes 14 as required by the protocol and as controlled by the program in a microprocessor 42 which operates the three axis positioning means 19. The probe 40 also is capable of accessing reagent bottles 43 by means of syringe pumps 44. The reagent bottles 43 have bulk quantities of reagent such that as required by the protocol the reagent may be added to the test tubes 14. Between each excursion of the probe into the test tubes and back to the supply, be it reagent, monoclonal or blood there is a washing operation which includes a well 45 into which the probe 40 is dipped and operated to clean the tip 46 of the probe 40 and the inside thereby removing any remaining material supplied during the previous operation. Once the particular test tube 14 has been filled with the appropriate supplies and samples the test tube handling assembly 11 can be used to grip and move the test tube in order to cause a vortex of the material in the test tube 14. There is also the passage 27 carried on the member 12 for permitting the addition of material or removal of material from the test tube 14 during the vortex generating movement. As shown in Figure 3 passage 27 passes through a mandrel 47 carried on the end for engaging 13 of the member 12. The mandrel 47 also has a supply port 48 for providing air to inflate the bladder 32. An O-ring 49 is carried over the top of the bladder to hold the bladder on the mandrel 47. As shown in Figure 2 the mandrel 47 has a detector 50 which includes a quide 51 for allowing a finger 52 to move when in contact with open end 30. A switch 53 is located on the support 18 such that movement of the finger 52 in the quide 51 due to contact with open end 30 causes the switch 53 to signal the micro processor 42 indicating that a test tube 14 in fully in place on the mandrel 47. The relationship between the mandrel 47 and the bladder 32 is clear from the cross sectional view of Figure 3 wherein the upper rim 54 of the bladder 32 seats in an annular recess 55 on the mandrel 47. Annular recess 55 is near where the O-ring 49 is carried. Ribs 56 longitudinally positioned on the side of the mandrel 47 which engages the inside open end 30 have channels 57 therebetween. The channels 57 permit air within the test tube 14 to escape when the bladder 32 is inflated and material is added to the test tube 14. A fitting 58 is used to sealing attach the mandrel 47 and the bladder 32 while providing an exit 59 for the passage 27. An extension tube 60 can be placed over fitting 58 to reach into the sample in the test tube 14. In Figure 2 the probe 40 is carried on a linear rack 61 which is a part of the three axis positioning means 19. Movement of the linear rack 61 is controlled by the micro processor 42 and in the well known manner is also moved to and from and across the apparatus in the three directions of linear motion of axes 20, 21 and 22. A holder 62 for the probe 40 connects the linear rack 61 and the probe 40. Holder 62 has a drive notch 63 positioned to receive a plunger 64 from a solenoid 65 as part of a releasable latching means 66 between the assembly 11 and the probe 40. In particular the assembly 11 is slidably carried on the support 18 by a guide shaft 68 as in Figure 4 wherein a bushing 69 is between the support 18 and the shaft 68. A cord and spring loaded pulley arrangement 70 is used to support the weight of the assembly 11 such that when the solenoid plunger 64 is not engaged in the notch 63, the assembly 11 will not fall. When the plunger 64 is in the notch 63, the probe 40 and the assembly move together in the direction of axis 20. Motor 35 turns a pinion 71 to drive a gear 72 attached to drive shaft 73. The drive shaft 73 is drivingly connected to an inverted cup 74 which is eccentrically mounted on the drive shaft 73 in Figure 4. The centers of the drive shaft 73 and the cup 74 are in the preferred embodiment 0.4 mm. apart and parallel to each other. In the cup 74 is a spacer 75 which engages the end opposite 15 of the member 12. An O-ring 76 is carried between the spacer 75 and the end opposite 15 in a groove 77 as a resilient coupling therebetween to permit wobble of the member 12 relative to the cup 74. A bracket 78 is connected to the arm 23 to surround the member 12 above the center part 17 and prevent rotation of the member 12. Springs 79 are used to attach the bracket 78 to the arm 23 and allow accommodation of the orbital motion.

Claims: A test tube handling assembly for causing a vortex in a test tube sample comprising: an elongate member (12) with a first end (13) for engaging a test tube (14) and a second end (15) opposite thereto, the member (12) having a center part (17) thereon between its ends (13,15) and along the axis (16) of the elongate member (12), a support (18) for the member (12) with an arm (23) extending therefrom and a drive (34) located on the support (18) near the second end (15) and in contact with the elongate member (12), characterized in that the centre part (17) of the member (12) is held pivotable about its axis (16) by said arm (23), the second end (15) is driven for orbital movement, thus causing an orbital movement of the first end (13), the first end (13) of the member carries a test tube gripping means (28) including test tube contacting means (29) for engaging the test tube open end (30) to cause the test tube (14) to orbit. The test tube handling assembly of claim 1 wherein the contacting means (29) includes a seal (31) for substantially closing the open end (30) of the test tube (14) wherein the contacting means (29) is an inflatable bladder (32) which upon inflation expands and holds the open end (30) od the test tube (14). The test tube handling assembly of claim 2 wherein the inflatable bladder (32) fits within the open end (30) of the test tube (14) and when the bladder (32) is inflated, the open end (30) of the test tube (14) is substantially closed by the inflatable bladder (32), the bladder (32) having channels (57) thereabout to permit air within the test tube (14) to escape when the bladder (32) is inflated and the material is added to the test tube (14). The test tube handling assembly of one of claims 1 to 3 wherein the arm (23) extends from the support (18) near the member center part (17) in spaced apart relation with respect to the support (18) so that orbital movement of the member (12) is permitted. The test tube handling assembly of claim 4 wherein the member (12) is a slender rod (25) with a spherical bearing carried on the support (18) near the second end (15) for engaging for permitting orbital motion of the rod (25) and swing movement relative to the center part (17), the first rod end (13) for engaging carries a passage (27) thereon to permit material to be added to or removed from the test tube (14), the drive (34) has a motor (35) carried on the support (18) for providing rotary motion about a motor axis (36), the motor axis (36) and the member axis (16) are in spaced apart relation relative to each other with a linkage means (37) therebetween to cause the axis (16) of the member (12) to orbit for imparting an orbital motion to the second end (15) of the member (12) thereby orbiting the first end (13) for engaging the test tube (14). The test tube handling assembly of one of claims 1 to 5 wherein the support (18) includes a three axis positioning means (19) for carrying the elongate member (12) and wherein one (20) of the axes (20,21,22) of movement of the three axis positioning means (19) is substantially parallel with the axis (16) of the member (12) and the other two axes (21,22) of movement of the three axis positioning means (19) are normal to the axis (16) of the member (12). A method for causing a vortex in a test tube sample using a test tube handling assembly (11) according to one of claims 1 to 6, comprising the following steps: holding a test tube (14) by the gripping means during orbital movement of the test tube (14), moving the test tube (14,) repetitively with the drive (34) to cause the test tube (14) to orbit and to swing relative to the center part (17) of the member (12), and generating orbital movement of the test tube (14) and the sample therein for producing a vortex in the test tube sample. The method of claim 7 wherein the step of holding includes the additional step of temporarily retaining the test tube (14) by inflating a bladder (32) within an open end (30) of the test tube (14) and the additional step of substantially sealing the open end (30) of the test tube (14) with the inflatable bladder (32). The method of claim 7 or 8 including the additional step of carrying the support (18) on a three axis positioning means (19) wherein one axis (20) thereof is parallel to the axis (16) of the member (12).

Inventors: NOTO SAL, SCHULTE HARVEY, NOTO, SAL, SCHULTE, HARVEY
Applicants: BECTON DICKINSON CO, BECTON DICKINSON AND COMPANY
Application year: 1990
Main classification: B01F11
IPC codes: B01L11, B01F11, B01L3