US3468474A - Centrifuge accessory - Google Patents

Centrifuge accessory Download PDF

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US3468474A
US3468474A US563585A US3468474DA US3468474A US 3468474 A US3468474 A US 3468474A US 563585 A US563585 A US 563585A US 3468474D A US3468474D A US 3468474DA US 3468474 A US3468474 A US 3468474A
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tube
centrifuge
chamber
tube structure
fluid
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US563585A
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Arvid W Shoblom
Enar E Shoblom
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ARVID W SHOBLOM
ENAR E SHOBLOM
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ARVID W SHOBLOM
ENAR E SHOBLOM
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    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5021Test tubes specially adapted for centrifugation purposes
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B04CENTRIFUGAL APPARATUS OR MACHINES FOR CARRYING-OUT PHYSICAL OR CHEMICAL PROCESSES
    • B04BCENTRIFUGES
    • B04B5/00Other centrifuges
    • B04B5/04Radial chamber apparatus for separating predominantly liquid mixtures, e.g. butyrometers
    • B04B5/0407Radial chamber apparatus for separating predominantly liquid mixtures, e.g. butyrometers for liquids contained in receptacles
    • B04B5/0414Radial chamber apparatus for separating predominantly liquid mixtures, e.g. butyrometers for liquids contained in receptacles comprising test tubes
    • B04B5/0421Radial chamber apparatus for separating predominantly liquid mixtures, e.g. butyrometers for liquids contained in receptacles comprising test tubes pivotably mounted

Definitions

  • a tube structure comprising an upper housing and a lower housing detachably joined together and defining upper and lower chambers.
  • the chambers are separated by a partition having an orifice therein, and a fluid delivery passage having a one-way check valve disposed therein extends through the horrends, and communicates with both chambers for delivering clean wash solution from the upper chamber to the lower chamber.
  • a fluid exhaust passage also communicates with the lower chamber for removing contaminated wash solution therefrom.
  • the delivery and exhaust passage are defined by a single tube, while in an alternative embodiment separate delivery and exhaust tubes are provided.
  • the present invention relates generally to laboratory equipment, and more specifically to an improved tube structure for use in conjunction with a centrifuge for washing, separating, and combining various substances in the laboratory.
  • Coombs antiglobulin test which is performed several million times a year in the United States alone. This test is designed to detect incomplete antibodies in human blood, and is routinely performed on samples of units of blood to be transfused. It is also employed in diagnosing various diseases involving the blood when no transfusion is contemplated.
  • the Coombs antiglomulin test is carried out by incubating a sample of red blood cells with an animal serum for a specified time and at a specified temperature, and watching to see if the blood cells agglutinate or clumpf Agglutination of the cells constitutes a positive reaction indicating the presence of incomplete antibodies in the blood, and failure of the cells to agglutinate constitutes a negative reaction indicating the absence of incomplete antibodies.
  • the incubation serum is prepared from the blood of an animal usually a rabbit, after the animal has been given injections of purified human blood globulins. The injections are a foreign protein to the animal, and his blood reacts by building antibodies which will be present in the incubation serum. These antibodies are opposed or anti to human blood globulins-hence, the term antiglobulin test.
  • red blood cells to be tested In performing the Coombs antiglobulin test the red blood cells to be tested must be thoroughly washed free of globulins which are normally present prior to being incubated with the animal serum. Otherwise these globulins would react with and neutralize the antibodies present in the incubation serum, and this might cause a false negative test result. lt is also necessary to wash red blood cells in the preparation of the incubation serum itself since the serum must be exposed to thoroughly washed human red blood cells to absorb and remove non-specific antibodies present in the animal blood used to prepare the serum.
  • the process currently used to wash red blood cells for 3,468,474 Patented Sept. 23, 1969 the Coombs antiglobulin test comprises suspending the cells in a solution of physiological sodium chloride in a test tube, centrifuging the mixture until the cells are deposited on the bottom of the tube, manually decanting the contaminated saline leaving a button of red blood cells in the tube, adding fresh saline to resuspend the cells, and repeating the process three or four times until the cells have been thoroughly washed.
  • the centrifuging step is accomplished iby placing the tube containing the cells and saline solution in a rotatable centrifuge head adapted to receive the same, and rotating the head to create a centrifugal force field which drives the tube in a radially outward direction causing the cells to be deposited on the bottom of the tube.
  • a rotatable centrifuge head is equipped to receive a plurality of tubes, whereby several samples of cells can be washed simultaneously.
  • washing process described above is an effective process for cleaning red blood cells, it is also a time consuming one since it requires a technician to return to the centrifuge after each -washing cycle, manually decant the contaminated saline from each tube, add fresh saline to each tube and start the centrifuge again. This presents a series of interruptions to other procedures which the technician is carrying out in the laboratory, and is particularly burdensome to a technician working a laboratory night shift alone.
  • a more specific object of this invention is to provide an improved tube structure for use in conjunction with a centrifuge for repetitively washing relatively small quantities of various substances, such as red blood cells, in a more efficient manner than has heretofore been known.
  • Another object of this invention is to provide an improved tube structure adapted for use in conjunction with a centrifuge for substantially automatic repetitive washing of various substances.
  • Yet another object of this invention is the provision of an improved process for washing various substances, such as red blood cells.
  • Another object of this invention is to provide an improved tube structure useful for separating emulsions.
  • Still another object of this invention is to provide an improved tube structure for bringing reactants together, e.g. the bringing together of two liquids to form an insoluble product (a common manipulation in analytical chemistry).
  • FIG. 1 is a partial elevation view showing the rotating head of a centrifuge carrying a pair of tube structures constructed in accordance with the teachings of the present invention
  • FIG. 2 is a sectional elevation view showing in detail the construction of each tube structure shown in FIG. 1;
  • FIG. 3 is a partial sectional elevation view of a modified form of a check valve adapted for use in the tube structure of FIG. 2;
  • FIG. 4 is a sectional elevation view of an alternative embodiment of a tube structure constructed in accordance with the teachings of this invention.
  • FIG. 1 a portion of the upstanding center pedestal 10 of a conventional centrifuge (not shown) having a tube carrying head 12 mounted for rotation on the top thereof.
  • the head 12 includes a pair of radially outwardly extending tube carrying arms 14, 14 each of which is adapted to carry an improved tube structure 16 constructed in accordance with the teachings of the present invention.
  • the tube structures 16, 16 are mounted on the ends of their respective arms 14, 14 for pivotal movement between a substantially horizontal position (solid line position in FIG. l) when the centrifuge head 12 is rotating and a substantially vertical position (phantom line position of FIG. 1) when the head 12 is idle.
  • each arm 14 is provided with a pair of flanges 18, 18 (only one ange 18 is shown on each arm 14 in FIG. l) spaced to receive the tube 16 between them and provided with holes 20, 20 for receiving a pair of radially outwardly extending trunnion pins 22, 22 mounted on a trunnion ring 23 on the tube structure 16.
  • the tube construction 16 comprises an upper housing 24 defining an upper chamber 26 and a lower housing 28 defining a lower chamber 30.
  • the upper and lower housings 24 and 28 are detachably joined to one another by means of an externally threaded boss 32 on the lower end of the upper housing 24 and a cooperating internally threaded ring 34 on the upper end of the lower housing 28.
  • a sealing ring 36 is provided between the upper and lower housings for preventing leakage of fluid from the lower chamber 3l).
  • the upper housing 24 includes a bottom wall 38 dening a partition which separates the upper and lower chambers 26 and 30, and an orifice 40 is provided in the partition 38 for receiving the lower portion 42 of a cornbination delivery-exhaust tube 44.
  • the delivery-exhaust tube 44 is not physically connected to the lower housing 28, but hangs suspended slightly above the conical bottom portion 45 thereof.
  • the upper or exhaust end 46 of the tube 44 is vented outside the tube structure 16 for exhausting contaminated wash solution to a suitable container (not shown).
  • the trunnion ring 23 is secured around the upper p0rton of the upper housing 24 by any suitable means (not shown) and is prevented from sliding off the upper end of the housing by means of a peripheral flange 48 integrally formed on the upper end thereof.
  • a closure cap S having fluid receiving aperture 52 may be provided for closing the open upper end of the upper housing 24; but such a closure is not absolutely necessary since gravity will keep fluid in the upper housing chamber 26 when the centrifuge head 12 is at rest (phantom line position of the tubes 16, 16 in FIG. 1) and centrifugal force will do the same when the head is rotating (solid line position of the tubes 16, 16 in FIG. 1).
  • the lower housing 28 includes a cup member 54, preferably in the shape of a cone, which is secured to the lower end of the internally threaded ring 34. While the cup 54 may be made of any suitable material, a readily disposable material, such as an inexpensive transparent polycarbonate or polypropylene plastic, is preferred,
  • the ring 34 and upper housing 24 may also be made of disposable plastic material, if desired.
  • Suitable nondisposable materials from which the varions elements of the tube structure may be fabricated include bronze, aluminum and stainless steel.
  • the cup 54 is made of a disposable material and the ring 34 is made of a non-disposable material, the cup should be detachably secured to the ring, such as by glueing, for example.
  • the tube structure should be fabricated of materials which are as light as possible commensurate with strength requirements, heat stable (autoclavable), and relatively chemically inert.
  • the size of the tube structure will depend largely on the size of the centrifuge with which it is used and the type of process in which it is employed.
  • a radially outwardly extending tube section 56 housing a ball and spring type of one-way check valve 58, 60 is integrally attached to the delivery-exhaust tube 44 adjacent the partition 38.
  • the tube section 56 includes an open outer end 62 communicating with the upper chamber 26 and an open inner end 64 communcating with the interior of the delivery exhaust tube 44.
  • the tube section 56 and the middle and lower portions 66 and 42 of the delivery-exhaust tube 44 define a fluid delivery passage communicating with the upper and lower chambers 26 and 30.
  • the ball and spring check valve 58, 60 is adapted to permit uid liow from the upper chamber 26 to the delivery exhaust tube 44 and lower chamber 30 when the pressure in the upper chamber is sufficient to overcome the force of the spring 60 and move the ball 58 radially inwardly away from the open outer end 62 of the tube section 56.
  • the valve 58, 60 will, however, block fluid flow from the delivery-exhaust tube 44 to the upper chamber 26.
  • the tube structure 16 may best be understood by referring to FIG. 2.
  • the substance to be washed such as a few drops of human red blood cells, for example, is deposited in the lower conical portion 45 of the lower housing 28, and the housings are assembled by threading the ring 34 of the lower housing onto the boss 32 of the upper housing.
  • the upper chamber 26 is then filled with a suitable wash solution, such as a sodium chloride solution, for example, and the assembled tube structure is placed in the arm 14 of a rotatable centrifuge head 12 adapted to receive the same (see FIG. l).
  • the centrifuge motor (not shown) is then started, causing the head 12 to rotate and drive the lower end of the tube structure 16 radially outwardly (solid line position of the tubes 16, 16 in FIG. l).
  • Rotation of the centrifuge head 12 creates a centrifugal force field suiiicient to force the wash solution (not shown) in the upper compartment 26 past the ball and spring check valve 58, 60, through the tube section 56 and the delivery-exhaust tube 44, and into the lower chamber 30 where it impinges upon and suspends the substance being washed. If the substance being washed is red blood cells for use in the Coombs anti-globulin test, the globulins or protein contaminating the cells will be taken up by the wash solution as the latter enters the lower chamber 30.
  • the air in the chamber will be compressed; and when the mounting air pressure in the chamber becomes sufficient to offset the fluid head in the upper chamber, no more wash solution will be permitted to enter the lower chamber.
  • the uid head in the upper chamber is determined by the height of the wash solution in the upper chamber and the centrifugal force field created.
  • the amount of wash solution entering the lower chamber 30 may be regulated by varying the speed of rotation of the centrifuge head 12, the shape of the upper chamber 26, the amount of wash solution placed in the upper chamber, and the volume of the lower chamber 30.
  • the substance being washed will be driven to the bottom tip 45 of the lower housing 28. If the substance is red blood cells, it will accumulate and form a button in the bottom of the lower housing.
  • the centrifuge is turned olf (preferably automatically, by a conventional timer) and the rotating head 12 slowly decelerates to a stop. As the head 12 decelerates, the centrifugal force field tending to force wash solution into the lower chamber 30 will disappear, thereby permitting the air in the lower chamber to expand and force the contaminated solution in the lower chamber up the combination delivery-exhaust tube 44. Since the one-way check valve S8, 60 will prevent the contaminated solution being exhausted from entering the upper chamber 26 through the tube section 56, the solution will travel all the way through the tube 44 and will be ejected from the upper end 46 thereof and channeled to a suitable container (not shown). As described more fully hereinafter, the contaminated solution may alternatively be expelled into a separate bag or compartment in the upper chamber 26 where it will maintain the fluid head in that chamber for subsequent wash cycles.
  • the washed substance With substantially all of the contaminated solution exhausted from the lower chamber 30, only the washed substance will remain therein. If the washed substance is red blood cells, it will remain in the form of a button in the bottom tip 45 of the lower housing 28. Since the rotating centrifuge head 12 coasts slowly to a stop, substantially no fluid turbulence will be created in the lower chamber 30, and only an insignificant amount of cells will be carried out of the lower chamber with the contaminated wash solution. The centrifuge motor may then be started again, either manually or by a conventional timing device (such as those currently used on clothes washers and dryers), and a second wash cycle will automatically take place. The quantity of wash solution initially placed in the upper chamber 26 must, of course, be suicient to last throughout the several wash cycles and maintain enough of a uid head in the upper chamber during the last wash cycle to insure injection of the solution into the lower chamber 30.
  • a conventional timing device such as those currently used on clothes washers and dryers
  • the improved tube structure of this invention may be used in conjunction with a centrifuge having a timer for substantially automatic repetitive washing of a substance. lf the centrifuge timer is only capable of stopping the centrifuge after each wash cycle, but not restarting it, the operator will have to return to the centrifuge after each wash cycle, but only to switch it on.
  • the lower housing 28 of the tube structure 16 is detached from the upper housing 24 and the substance is removed therefrom. lf only the cup 54 of the tube structure is disposable, it is detached from the ring member 34 of the lower housing 28 and discarded after the substance has 'been recovered. Of course if the entire tube structure is disposable, it is discarded after the washed substance is recovered.
  • FIG. 3 shows a modified one-way check valve structure 70 which may be used in place of the ball and spring Valve 58, 60 employed in the tube structure 16 of FIG. 3.
  • the valve structure 70 includes a pair of mating flaps 68, 68 made of relatively hard but fiexible material, such as hard rubber, and formed to be normally closed at their radially inward end 72 adjacent the inner end 64 of the tube section 56, and open at their radially outer end 74 adjacent the outer end 62 of the tube section 56.
  • the inward end 72 of the flaps 68, 68 are adapted to be opened, however, by the flow of fluid under pressure approaching from their open outer end 74.
  • a peripheral flange 76 on the outer end 74 of the flaps 68, 68 and a cooperating orificed cap member 78 are provided for securing the flap valve 70 in tube section 56.
  • the flap valve 70 will permit the How of fluid under pressure from the upper chamber 26 to the interior of the delivery-exhaust tube 44 and the lower chamber 30, but will prevent iluid flow in the opposite direction.
  • FIG. 4 shows an alternative embodiment of a tube structure 80 constructed in accordance with the teachings of the present invention.
  • This tube structure includes an upper housing 82 defining an upper chamber 84 and a lower housing 86 defining a lower chamber 88.
  • the upper and lower housings are detachably connected to one another by means of an externally threaded boss 90 on the lower end of the upper housing 82 and a cooperating internally threaded section 92 on the upper portion of the lower housing, and an O-ring seal 94 is disposed between the upper and lower housings for preventing fluid leakage from the lower chamber 88.
  • a trunnion pin supporting ring 96 is formed on the outer surface of the upper housing 82 for carrying trunnion pins (not shown) adapted t0 fit in the pin receiving holes 20 at the outer end of an arm 14 of a rotatable centrifuge head 12 (see FIG. l).
  • a removable insert 98 is disposed in the lower chamber 88 and is provided with a central, longitudinally extending passage 100 for receiving and supporting a conventional laboratory test tube 102.
  • the upper housing 82 includes a bottom wall 104 which serves as a partition separating the upper and lower chambers 84 and 88, and an orifice 106 extends through the partition 104 and communicates with both chambers.
  • a uid delivery tube 108 communicates with the orifice 106 and terminates in an open lower end 110 adjacent the bottom of the test tube 102.
  • the upper end 112 of the delivery tube 108 is also open and is enlarged to receive a ball and spring type of one-way check valve 114, 116.
  • check valve 114, 116 in tube structure 80 is designed to permit the flow of fiuid under pressure from the upper chamber 84 to the lower chamber 88, but prevent uid ow in the opposite direction.
  • the tube structure 80 is further provided with an exhaust tube 118 which extends through the partition 104 and terminates in an open lower end 120 adjacent the bottom of the test tube 102.
  • the upper end 122 of the exhaust tube 118 is connected to receptacle means in the form of a flexible container 124 disposed in the upper chamber 84 for receiving contaminated wash solution exhausted from the lower chamber 88.
  • the receptacle means may be in the form of a separate compartment (not shown) provided in the upper chamber 84 for receiving contaminated solution from the exhaust tube 118.
  • tube structures 16 or 80 shown in the drawings may be provided with an exhaust tube which empties either outside the tube structure (FIG. 2 embodiment), into a (flexible container disposed in the upper chamber of the tube structure (FIG. 4 embodiment), or into a separate compartment provided in the upper chamber (not shown).
  • Operation of the tube structure 80 is quite similar to that of the tube structure 16 shown in FIG. 2.
  • the upper and lower housings 82 and 86 disassembled, the substance to be washed is deposited in the lower chamber 88.
  • the housings are then assembled by screwing the boss 90 of the upper housing into the internally threaded upper portion 92 of the lower housing, and the upper chamber 84 is filled with a suflicient quantity of cleansing solution 128 to last throughout the number of wash cycles contemplated.
  • the spring biased check valve 114, 116 will prevent any of the solution from initially entering the lower chamber 88.
  • the assembled tube structure 80 is then placed in a rotatable centrifuge head (such as head 12 in PIG. l) and the centrifuge motor is switched on to start the head rotating.
  • a centrifugal force field will be created in the tube structure 80 to drive cleansing solution past the check valve ball 114, through the delivery tube 108 and into the lower portion of the test tube 102 where it will impinge upon the substance to be washed (not shown).
  • the substance to be washed will initially be suspended in the cleansing solution, but as the centrifuge head continues to spin the substance will be driven to the bottom of the test tube 102.
  • the air in the chamber will be compressed until the mounting air pressure is sufficient to offset the fluid head in the upper chamber 84. When this occurs, no more cleansing solution will be driven into the lower chamber.
  • the centrifuge motor is switched off, preferably by a suitable timing device, and the centrifuge head will coast to a stop.
  • the centrifugal force field tending to force cleansing solution 128 into the lower chamber 88 will disappear, thereby permitting the air in the lower chamber to expand and drive the contaminated cleansing solution up the exhaust tube 118 and into the receptacle 124.
  • the one-way check valve 114, 116 in the delivery tube 108 will, of course, prevent the contaminated wash solution from being driven up through the delivery tube 108.
  • the centrifuge motor may then be restarted, preferably by a suitable timing device, to start another wash cycle.
  • the present invention provides an improved laboratory tube structure and process for washing relatively small quantities of various substances.
  • the improved tube structure may be employed in conjunction with a centrifuge equipped with a suitable timing device vfor repetitively washing such substance substantially automatically.
  • the tube structure of this invention is particularly adapted for use in laboratory procedures which require repetitive washing of red blood cells such as the Coombs antiglobulin test. It is contemplated, however, that the tube structure of this invention may be effectively employed in numerous other laboratory procedures, both in and outside the field of medicine, wherein various other substances (such as bacterial suspensions, chemical precipitates and yeast suspensions, for example) must be washed.
  • various other substances such as bacterial suspensions, chemical precipitates and yeast suspensions, for example
  • the tube structure may be employed to separate emulsions.
  • an emulsion of carbon tetrachloride and water is poured into the upper chamber of the tube structure (16 or 80) and the tube structure is placed in a centrifuge, the centrifugal force field created when the centrifuge motor is switched on will initially force the emulsion past the one-way check valve, down the delivery tube, and into the lower chamber.
  • the centrifuge head continues to rotate, the carbon tetrachloride and water will separate or layer out in the lower chamber, with the water (being less dense) accumulating on top.
  • the centrifuge is thereafter switched off and the rotating head comes to a stop the expanding air in the lower chamber will drive the water up and out of the exhaust tube.
  • the lower end of the exhaust tube must be positioned at such a height above the bottom of the lower chamber as to exhaust substantially all of the water, but none of the carbon tetrachloride. It is contemplated that numerous other emulsions may also be separated utilizing the tube structure of this invention in the manner described below.
  • Still another contemplated use of the tube structure of this invention is for bringing reactants together under conditions of high liquid pressure with a resulting separation of a solid product, e.g. a solution of barium chloride and sodium sulfate to form insoluble barium sulfate.
  • a solid product e.g. a solution of barium chloride and sodium sulfate to form insoluble barium sulfate.
  • the upper and lower chambers can be formed by a single continuous housing and a partition in the form ot plug that is friction tted into an intermediate position in said housing.
  • An improved tube structure for use in a centrifuge having a rotatable head, said tube structure comprising: housing means defining an upper chamber for containing a quantity of fluid; housing means connected to said upper chamber and defining a lower chamber; partition means disposed between and separating said upper and lower chambers; means defining a fluid delivery passage extending through'said partition means and communicating with said upper and lower chambers; one way check valve means disposed in said fluid delivery passage for blocking the flow of fluid from said lower chamber to said upper chamber, but permitting the flow of fluid under pressure from said upper chamber to said lower chamber; and means defining a fluid exhaust passage having an inner end communicating with the interior of said lower chamber and an outer end extending outside of said lower chamber for exhausting fluid from said lower chamber.
  • said means defining a fluid exhaust passage comprises a fluid exhaust tube having an open first end communicating with the interior of said lower chamber and a second end disposed within said upper chamber; and further including receptacle means connected to the said second end of said fluid exhaust tube and disposed in said upper chamber for receiving fluid exhausted from said lower chamber.
  • a tube structure according to claim 2, wherein said receptacle means comprises a flexible container connected to and communicating with said second end of said fluid exhaust tube.
  • a tube structure according to claim 2 wherein said receptacle means comprises means defining a compartment in said upper chamber communicating with said outer end of said fluid exhaust tube and adapted to receive fluid exhausted from said lower chamber.
  • said means defining a fluid delivery passage and said means delining a fluid exhaust passage comprise: a single combination delivery-exhaust tube having an open lower end communicating with said lower chamber, a lower section extending through a portion of said lower chamber, an intermediate section extending through said partition means, and an upper section extending through at least a portion of said upper chamber and terminating in an upper end; and means defining a fluid delivery orifice in the upper section of said combination delivery-exhaust tube for admitting fluid under pressure from said upper chamber, through said combination delivery-exhaust tube, and to said lower chamber; and wherein said one way check valve means is disposed adjacent to said fluid delivery orifice.
  • a tube structure according to claim S wherein said fluid delivery passage further comprises a tubular section having an open rst end communicating with said uid delivery orifice in said tube, and an open second end spaced from said combination delivery-exhaust tube and communicating with said upper chamber; and wherein said one way check valve means is disposed in said tubular section.
  • said means defining a uid delivery passage comprises means defining a fluid delivery orifice extending through said partition means, and a uid delivery tube having an open upper end communicating with said uid delivery himself and an open lower end communicating with said lower chamber; and wherein said one way check valve means is disposed adjacent to said uid delivery orifice.
  • said means defining a fluid exhaust passage comprises a separate fluid exhaust tube spaced from said uid delivery References Cited UNITED STATES PATENTS 3,133,881 5/1964 Childs 233-20 3,190,546 6/ 1965 Raccuglia et al. 233-20 3,347,454 10/ 1967 Bellamy et al. 233-26 X WILLIAM I. PRICE, Primary Examiner U.S. Cl. X.R. 233-26

Description

Sept. 23, 1969 A. w. sHoBLoM ET AL 3,468,474
CENTRIFUGE ACCESSORY Filed July 7. 1966 United States Patent O 3,468,474 CENTRIFUGE ACCESSORY Arvid W. Shoblom, 5408 Melody Ave., and Enar E. Shoblom, Rte. 6, Box 279, both of Olympia, Wash.
Filed July 7, 1966, Ser. No. 563,585 Int. Cl. B04b 5/02, 11/02 U.S. Cl. 233-27 8 Claims ABSTRACT OF THE DISCLOSURE A tube structure comprising an upper housing and a lower housing detachably joined together and defining upper and lower chambers. The chambers are separated by a partition having an orifice therein, and a fluid delivery passage having a one-way check valve disposed therein extends through the orice and communicates with both chambers for delivering clean wash solution from the upper chamber to the lower chamber. A fluid exhaust passage also communicates with the lower chamber for removing contaminated wash solution therefrom. In one embodiment the delivery and exhaust passage are defined by a single tube, while in an alternative embodiment separate delivery and exhaust tubes are provided.
The present invention relates generally to laboratory equipment, and more specifically to an improved tube structure for use in conjunction with a centrifuge for washing, separating, and combining various substances in the laboratory.
Numerous laboratory procedures require the repetitive washing of relatively small quantities of various substances. One such procedure, for example, is the so-called Coombs antiglobulin test which is performed several million times a year in the United States alone. This test is designed to detect incomplete antibodies in human blood, and is routinely performed on samples of units of blood to be transfused. It is also employed in diagnosing various diseases involving the blood when no transfusion is contemplated.
Briefly, the Coombs antiglomulin test is carried out by incubating a sample of red blood cells with an animal serum for a specified time and at a specified temperature, and watching to see if the blood cells agglutinate or clumpf Agglutination of the cells constitutes a positive reaction indicating the presence of incomplete antibodies in the blood, and failure of the cells to agglutinate constitutes a negative reaction indicating the absence of incomplete antibodies. The incubation serum is prepared from the blood of an animal usually a rabbit, after the animal has been given injections of purified human blood globulins. The injections are a foreign protein to the animal, and his blood reacts by building antibodies which will be present in the incubation serum. These antibodies are opposed or anti to human blood globulins-hence, the term antiglobulin test.
In performing the Coombs antiglobulin test the red blood cells to be tested must be thoroughly washed free of globulins which are normally present prior to being incubated with the animal serum. Otherwise these globulins would react with and neutralize the antibodies present in the incubation serum, and this might cause a false negative test result. lt is also necessary to wash red blood cells in the preparation of the incubation serum itself since the serum must be exposed to thoroughly washed human red blood cells to absorb and remove non-specific antibodies present in the animal blood used to prepare the serum.
The process currently used to wash red blood cells for 3,468,474 Patented Sept. 23, 1969 the Coombs antiglobulin test comprises suspending the cells in a solution of physiological sodium chloride in a test tube, centrifuging the mixture until the cells are deposited on the bottom of the tube, manually decanting the contaminated saline leaving a button of red blood cells in the tube, adding fresh saline to resuspend the cells, and repeating the process three or four times until the cells have been thoroughly washed.
The centrifuging step is accomplished iby placing the tube containing the cells and saline solution in a rotatable centrifuge head adapted to receive the same, and rotating the head to create a centrifugal force field which drives the tube in a radially outward direction causing the cells to be deposited on the bottom of the tube. Ordinarily the rotatable centrifuge head is equipped to receive a plurality of tubes, whereby several samples of cells can be washed simultaneously.
While the washing process described above is an effective process for cleaning red blood cells, it is also a time consuming one since it requires a technician to return to the centrifuge after each -washing cycle, manually decant the contaminated saline from each tube, add fresh saline to each tube and start the centrifuge again. This presents a series of interruptions to other procedures which the technician is carrying out in the laboratory, and is particularly burdensome to a technician working a laboratory night shift alone.
In an effort to facilitate the above described centrifuge technique for washing red blood cells, a so-called manifold washing process has been devised. This process is described in detail in an article entitled A Simple Manifold Washing Process for the Preparation of Erythrocytes for the Antiglobulin Test authored by Mary B. Gibbs and Frank R. Camp, Jr. and appearing in the May-J une, 1965, issue of Transfusion, vol. 5, No. 3. Briefly, this process contemplates the use of a manifold coupled to a suction device for removing the contaminated saline from the several tubes in the centrifuge and adding fresh saline following each washing cycle. This process will reduce the time the technician must spend at the centrifuge after each washing cycle since it is not necessary for him to manually decant and rell each tube individually, but it still requires him to interrupt his other duties and return to the centrifuge to operate the manifold after each washing cycle.
In view of the foregoing, it is a general object of the present invention to provide an improved tube structure for washing relatively small quantities of various substances.
A more specific object of this invention is to provide an improved tube structure for use in conjunction with a centrifuge for repetitively washing relatively small quantities of various substances, such as red blood cells, in a more efficient manner than has heretofore been known.
Another object of this invention is to provide an improved tube structure adapted for use in conjunction with a centrifuge for substantially automatic repetitive washing of various substances.
Yet another object of this invention is the provision of an improved process for washing various substances, such as red blood cells.
Another object of this invention is to provide an improved tube structure useful for separating emulsions.
Still another object of this invention is to provide an improved tube structure for bringing reactants together, e.g. the bringing together of two liquids to form an insoluble product (a common manipulation in analytical chemistry).
The foregoing and other objects, features and advantages of the invention will be apparent from the following more particular description of preferred embodiments of the invention, as illustrated in the accompanying drawings.
In the drawings:
FIG. 1 is a partial elevation view showing the rotating head of a centrifuge carrying a pair of tube structures constructed in accordance with the teachings of the present invention;
FIG. 2 is a sectional elevation view showing in detail the construction of each tube structure shown in FIG. 1;
FIG. 3 is a partial sectional elevation view of a modified form of a check valve adapted for use in the tube structure of FIG. 2; and
FIG. 4 is a sectional elevation view of an alternative embodiment of a tube structure constructed in accordance with the teachings of this invention.
Referring now to the drawings, there is shown in FIG. 1 a portion of the upstanding center pedestal 10 of a conventional centrifuge (not shown) having a tube carrying head 12 mounted for rotation on the top thereof. The head 12 includes a pair of radially outwardly extending tube carrying arms 14, 14 each of which is adapted to carry an improved tube structure 16 constructed in accordance with the teachings of the present invention. The tube structures 16, 16 are mounted on the ends of their respective arms 14, 14 for pivotal movement between a substantially horizontal position (solid line position in FIG. l) when the centrifuge head 12 is rotating and a substantially vertical position (phantom line position of FIG. 1) when the head 12 is idle. To this end, the outer end of each arm 14 is provided with a pair of flanges 18, 18 (only one ange 18 is shown on each arm 14 in FIG. l) spaced to receive the tube 16 between them and provided with holes 20, 20 for receiving a pair of radially outwardly extending trunnion pins 22, 22 mounted on a trunnion ring 23 on the tube structure 16.
As best shown in FIG. 2, the tube construction 16 comprises an upper housing 24 defining an upper chamber 26 and a lower housing 28 defining a lower chamber 30. The upper and lower housings 24 and 28 are detachably joined to one another by means of an externally threaded boss 32 on the lower end of the upper housing 24 and a cooperating internally threaded ring 34 on the upper end of the lower housing 28. A sealing ring 36 is provided between the upper and lower housings for preventing leakage of fluid from the lower chamber 3l).
The upper housing 24 includes a bottom wall 38 dening a partition which separates the upper and lower chambers 26 and 30, and an orifice 40 is provided in the partition 38 for receiving the lower portion 42 of a cornbination delivery-exhaust tube 44. The delivery-exhaust tube 44 is not physically connected to the lower housing 28, but hangs suspended slightly above the conical bottom portion 45 thereof. The upper or exhaust end 46 of the tube 44 is vented outside the tube structure 16 for exhausting contaminated wash solution to a suitable container (not shown).
The trunnion ring 23 is secured around the upper p0rton of the upper housing 24 by any suitable means (not shown) and is prevented from sliding off the upper end of the housing by means of a peripheral flange 48 integrally formed on the upper end thereof. A closure cap S having fluid receiving aperture 52 may be provided for closing the open upper end of the upper housing 24; but such a closure is not absolutely necessary since gravity will keep fluid in the upper housing chamber 26 when the centrifuge head 12 is at rest (phantom line position of the tubes 16, 16 in FIG. 1) and centrifugal force will do the same when the head is rotating (solid line position of the tubes 16, 16 in FIG. 1).
The lower housing 28 includes a cup member 54, preferably in the shape of a cone, which is secured to the lower end of the internally threaded ring 34. While the cup 54 may be made of any suitable material, a readily disposable material, such as an inexpensive transparent polycarbonate or polypropylene plastic, is preferred,
whereby it may be discarded after a single use. The ring 34 and upper housing 24 may also be made of disposable plastic material, if desired.
Suitable nondisposable materials from which the varions elements of the tube structure may be fabricated include bronze, aluminum and stainless steel. Of course, if the cup 54 is made of a disposable material and the ring 34 is made of a non-disposable material, the cup should be detachably secured to the ring, such as by glueing, for example.
For widest application, the tube structure should be fabricated of materials which are as light as possible commensurate with strength requirements, heat stable (autoclavable), and relatively chemically inert. The size of the tube structure will depend largely on the size of the centrifuge with which it is used and the type of process in which it is employed.
A radially outwardly extending tube section 56 housing a ball and spring type of one-way check valve 58, 60 is integrally attached to the delivery-exhaust tube 44 adjacent the partition 38. The tube section 56 includes an open outer end 62 communicating with the upper chamber 26 and an open inner end 64 communcating with the interior of the delivery exhaust tube 44. Thus, the tube section 56 and the middle and lower portions 66 and 42 of the delivery-exhaust tube 44 define a fluid delivery passage communicating with the upper and lower chambers 26 and 30. As described more fully hereinafter, the ball and spring check valve 58, 60 is adapted to permit uid liow from the upper chamber 26 to the delivery exhaust tube 44 and lower chamber 30 when the pressure in the upper chamber is sufficient to overcome the force of the spring 60 and move the ball 58 radially inwardly away from the open outer end 62 of the tube section 56. The valve 58, 60 will, however, block fluid flow from the delivery-exhaust tube 44 to the upper chamber 26.
Operation of the tube structure 16 may best be understood by referring to FIG. 2. With the upper and lower housings 24 and 28 disassembled, the substance to be washed, such as a few drops of human red blood cells, for example, is deposited in the lower conical portion 45 of the lower housing 28, and the housings are assembled by threading the ring 34 of the lower housing onto the boss 32 of the upper housing. The upper chamber 26 is then filled with a suitable wash solution, such as a sodium chloride solution, for example, and the assembled tube structure is placed in the arm 14 of a rotatable centrifuge head 12 adapted to receive the same (see FIG. l). The centrifuge motor (not shown) is then started, causing the head 12 to rotate and drive the lower end of the tube structure 16 radially outwardly (solid line position of the tubes 16, 16 in FIG. l).
Rotation of the centrifuge head 12 creates a centrifugal force field suiiicient to force the wash solution (not shown) in the upper compartment 26 past the ball and spring check valve 58, 60, through the tube section 56 and the delivery-exhaust tube 44, and into the lower chamber 30 where it impinges upon and suspends the substance being washed. If the substance being washed is red blood cells for use in the Coombs anti-globulin test, the globulins or protein contaminating the cells will be taken up by the wash solution as the latter enters the lower chamber 30.
As the level of the wash solution in the lower chamber 30 rises, the air in the chamber will be compressed; and when the mounting air pressure in the chamber becomes sufficient to offset the fluid head in the upper chamber, no more wash solution will be permitted to enter the lower chamber. The uid head in the upper chamber is determined by the height of the wash solution in the upper chamber and the centrifugal force field created. Thus, the amount of wash solution entering the lower chamber 30 may be regulated by varying the speed of rotation of the centrifuge head 12, the shape of the upper chamber 26, the amount of wash solution placed in the upper chamber, and the volume of the lower chamber 30.
As the centrifuge head 12 continues to rotate, the substance being washed will be driven to the bottom tip 45 of the lower housing 28. If the substance is red blood cells, it will accumulate and form a button in the bottom of the lower housing.
After a predetermined period of time, the centrifuge is turned olf (preferably automatically, by a conventional timer) and the rotating head 12 slowly decelerates to a stop. As the head 12 decelerates, the centrifugal force field tending to force wash solution into the lower chamber 30 will disappear, thereby permitting the air in the lower chamber to expand and force the contaminated solution in the lower chamber up the combination delivery-exhaust tube 44. Since the one-way check valve S8, 60 will prevent the contaminated solution being exhausted from entering the upper chamber 26 through the tube section 56, the solution will travel all the way through the tube 44 and will be ejected from the upper end 46 thereof and channeled to a suitable container (not shown). As described more fully hereinafter, the contaminated solution may alternatively be expelled into a separate bag or compartment in the upper chamber 26 where it will maintain the fluid head in that chamber for subsequent wash cycles.
With substantially all of the contaminated solution exhausted from the lower chamber 30, only the washed substance will remain therein. If the washed substance is red blood cells, it will remain in the form of a button in the bottom tip 45 of the lower housing 28. Since the rotating centrifuge head 12 coasts slowly to a stop, substantially no fluid turbulence will be created in the lower chamber 30, and only an insignificant amount of cells will be carried out of the lower chamber with the contaminated wash solution. The centrifuge motor may then be started again, either manually or by a conventional timing device (such as those currently used on clothes washers and dryers), and a second wash cycle will automatically take place. The quantity of wash solution initially placed in the upper chamber 26 must, of course, be suicient to last throughout the several wash cycles and maintain enough of a uid head in the upper chamber during the last wash cycle to insure injection of the solution into the lower chamber 30.
lf a timing device capable of stopping and restarting the centrifuge motor automatically is employed, the several required wash cycles will take place automatically, and the laboratory technician operating the apparatus need only return to the centrifuge to recover the washed substance and load the centrifuge with additional tubes containing substances to be washed. Thus, the improved tube structure of this invention may be used in conjunction with a centrifuge having a timer for substantially automatic repetitive washing of a substance. lf the centrifuge timer is only capable of stopping the centrifuge after each wash cycle, but not restarting it, the operator will have to return to the centrifuge after each wash cycle, but only to switch it on.
After the substance has been washed, the lower housing 28 of the tube structure 16 is detached from the upper housing 24 and the substance is removed therefrom. lf only the cup 54 of the tube structure is disposable, it is detached from the ring member 34 of the lower housing 28 and discarded after the substance has 'been recovered. Of course if the entire tube structure is disposable, it is discarded after the washed substance is recovered.
FIG. 3 shows a modified one-way check valve structure 70 which may be used in place of the ball and spring Valve 58, 60 employed in the tube structure 16 of FIG. 3. The valve structure 70 includes a pair of mating flaps 68, 68 made of relatively hard but fiexible material, such as hard rubber, and formed to be normally closed at their radially inward end 72 adjacent the inner end 64 of the tube section 56, and open at their radially outer end 74 adjacent the outer end 62 of the tube section 56. The inward end 72 of the flaps 68, 68 are adapted to be opened, however, by the flow of fluid under pressure approaching from their open outer end 74. A peripheral flange 76 on the outer end 74 of the flaps 68, 68 and a cooperating orificed cap member 78 are provided for securing the flap valve 70 in tube section 56. Like the ball and spring valve 58,- 60 of the FIG. 2 structure, the flap valve 70 will permit the How of fluid under pressure from the upper chamber 26 to the interior of the delivery-exhaust tube 44 and the lower chamber 30, but will prevent iluid flow in the opposite direction.
FIG. 4 shows an alternative embodiment of a tube structure 80 constructed in accordance with the teachings of the present invention. This tube structure includes an upper housing 82 defining an upper chamber 84 and a lower housing 86 defining a lower chamber 88. The upper and lower housings are detachably connected to one another by means of an externally threaded boss 90 on the lower end of the upper housing 82 and a cooperating internally threaded section 92 on the upper portion of the lower housing, and an O-ring seal 94 is disposed between the upper and lower housings for preventing fluid leakage from the lower chamber 88. A trunnion pin supporting ring 96 is formed on the outer surface of the upper housing 82 for carrying trunnion pins (not shown) adapted t0 fit in the pin receiving holes 20 at the outer end of an arm 14 of a rotatable centrifuge head 12 (see FIG. l).
A removable insert 98 is disposed in the lower chamber 88 and is provided with a central, longitudinally extending passage 100 for receiving and supporting a conventional laboratory test tube 102. The upper housing 82 includes a bottom wall 104 which serves as a partition separating the upper and lower chambers 84 and 88, and an orifice 106 extends through the partition 104 and communicates with both chambers. A uid delivery tube 108 communicates with the orifice 106 and terminates in an open lower end 110 adjacent the bottom of the test tube 102. The upper end 112 of the delivery tube 108 is also open and is enlarged to receive a ball and spring type of one- way check valve 114, 116. Like the ball and spring check valve 58, 60 of the FIG. 2 tube structure 16, check valve 114, 116 in tube structure 80 is designed to permit the flow of fiuid under pressure from the upper chamber 84 to the lower chamber 88, but prevent uid ow in the opposite direction.
rThe tube structure 80 is further provided with an exhaust tube 118 which extends through the partition 104 and terminates in an open lower end 120 adjacent the bottom of the test tube 102. The upper end 122 of the exhaust tube 118 is connected to receptacle means in the form of a flexible container 124 disposed in the upper chamber 84 for receiving contaminated wash solution exhausted from the lower chamber 88. With this exhaust tube and receptacle arrangement the contaminated wash solution will return to the upper chamber 84 after each wash cycle, thereby maintaining the fiuid head in the upper chamber substantially constant for each succeeding wash cycle, but the contaminated wash solution will be kept separate from the fresh wash solution 128. Where space considerations for the tube structure 80 are not critical, the receptacle means may be in the form of a separate compartment (not shown) provided in the upper chamber 84 for receiving contaminated solution from the exhaust tube 118.
Of course, it is contemplated that either of the tube structures 16 or 80 shown in the drawings may be provided With an exhaust tube which empties either outside the tube structure (FIG. 2 embodiment), into a (flexible container disposed in the upper chamber of the tube structure (FIG. 4 embodiment), or into a separate compartment provided in the upper chamber (not shown).
Operation of the tube structure 80 is quite similar to that of the tube structure 16 shown in FIG. 2. With the upper and lower housings 82 and 86 disassembled, the substance to be washed is deposited in the lower chamber 88. The housings are then assembled by screwing the boss 90 of the upper housing into the internally threaded upper portion 92 of the lower housing, and the upper chamber 84 is filled with a suflicient quantity of cleansing solution 128 to last throughout the number of wash cycles contemplated. The spring biased check valve 114, 116 will prevent any of the solution from initially entering the lower chamber 88.
The assembled tube structure 80 is then placed in a rotatable centrifuge head (such as head 12 in PIG. l) and the centrifuge motor is switched on to start the head rotating. As the centrifuge head rotates a centrifugal force field will be created in the tube structure 80 to drive cleansing solution past the check valve ball 114, through the delivery tube 108 and into the lower portion of the test tube 102 where it will impinge upon the substance to be washed (not shown). The substance to be washed will initially be suspended in the cleansing solution, but as the centrifuge head continues to spin the substance will be driven to the bottom of the test tube 102. As the level of the wash solution in the lower chamber 88 rises, the air in the chamber will be compressed until the mounting air pressure is sufficient to offset the fluid head in the upper chamber 84. When this occurs, no more cleansing solution will be driven into the lower chamber.
Thereafter, the centrifuge motor is switched off, preferably by a suitable timing device, and the centrifuge head will coast to a stop. As the head decelerates, the centrifugal force field tending to force cleansing solution 128 into the lower chamber 88 will disappear, thereby permitting the air in the lower chamber to expand and drive the contaminated cleansing solution up the exhaust tube 118 and into the receptacle 124. The one- way check valve 114, 116 in the delivery tube 108 will, of course, prevent the contaminated wash solution from being driven up through the delivery tube 108. After substantially all of the contaminated cleansing solution has been exhausted from the test tube 102, only the washed substance will remain therein, and the centrifuge motor may then be restarted, preferably by a suitable timing device, to start another wash cycle.
As can be seen from the foregoing, the present invention provides an improved laboratory tube structure and process for washing relatively small quantities of various substances. The improved tube structure may be employed in conjunction with a centrifuge equipped with a suitable timing device vfor repetitively washing such substance substantially automatically.
As indicated above, the tube structure of this invention is particularly adapted for use in laboratory procedures which require repetitive washing of red blood cells such as the Coombs antiglobulin test. It is contemplated, however, that the tube structure of this invention may be effectively employed in numerous other laboratory procedures, both in and outside the field of medicine, wherein various other substances (such as bacterial suspensions, chemical precipitates and yeast suspensions, for example) must be washed.
In addition, the tube structure may be employed to separate emulsions. For example, if an emulsion of carbon tetrachloride and water is poured into the upper chamber of the tube structure (16 or 80) and the tube structure is placed in a centrifuge, the centrifugal force field created when the centrifuge motor is switched on will initially force the emulsion past the one-way check valve, down the delivery tube, and into the lower chamber. As the centrifuge head continues to rotate, the carbon tetrachloride and water will separate or layer out in the lower chamber, with the water (being less dense) accumulating on top. When the centrifuge is thereafter switched off and the rotating head comes to a stop the expanding air in the lower chamber will drive the water up and out of the exhaust tube. Of course the lower end of the exhaust tube must be positioned at such a height above the bottom of the lower chamber as to exhaust substantially all of the water, but none of the carbon tetrachloride. It is contemplated that numerous other emulsions may also be separated utilizing the tube structure of this invention in the manner described below.
Still another contemplated use of the tube structure of this invention is for bringing reactants together under conditions of high liquid pressure with a resulting separation of a solid product, e.g. a solution of barium chloride and sodium sulfate to form insoluble barium sulfate.
While the invention has been shown and described with reference to preferred embodiments thereof, it will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the spirit and scope of the invention. For example, the upper and lower chambers can be formed by a single continuous housing and a partition in the form ot plug that is friction tted into an intermediate position in said housing.
What is claimed is:
1. An improved tube structure for use in a centrifuge having a rotatable head, said tube structure comprising: housing means defining an upper chamber for containing a quantity of fluid; housing means connected to said upper chamber and defining a lower chamber; partition means disposed between and separating said upper and lower chambers; means defining a fluid delivery passage extending through'said partition means and communicating with said upper and lower chambers; one way check valve means disposed in said fluid delivery passage for blocking the flow of fluid from said lower chamber to said upper chamber, but permitting the flow of fluid under pressure from said upper chamber to said lower chamber; and means defining a fluid exhaust passage having an inner end communicating with the interior of said lower chamber and an outer end extending outside of said lower chamber for exhausting fluid from said lower chamber.
2. A tube structure according to claim 1, wherein said means defining a fluid exhaust passage comprises a fluid exhaust tube having an open first end communicating with the interior of said lower chamber and a second end disposed within said upper chamber; and further including receptacle means connected to the said second end of said fluid exhaust tube and disposed in said upper chamber for receiving fluid exhausted from said lower chamber.
3. A tube structure according to claim 2, wherein said receptacle means comprises a flexible container connected to and communicating with said second end of said fluid exhaust tube.
4. A tube structure according to claim 2 wherein said receptacle means comprises means defining a compartment in said upper chamber communicating with said outer end of said fluid exhaust tube and adapted to receive fluid exhausted from said lower chamber.
5. A tube structure according to claim 1, wherein said means defining a fluid delivery passage and said means delining a fluid exhaust passage comprise: a single combination delivery-exhaust tube having an open lower end communicating with said lower chamber, a lower section extending through a portion of said lower chamber, an intermediate section extending through said partition means, and an upper section extending through at least a portion of said upper chamber and terminating in an upper end; and means defining a fluid delivery orifice in the upper section of said combination delivery-exhaust tube for admitting fluid under pressure from said upper chamber, through said combination delivery-exhaust tube, and to said lower chamber; and wherein said one way check valve means is disposed adjacent to said fluid delivery orifice.
6. A tube structure according to claim S, wherein said fluid delivery passage further comprises a tubular section having an open rst end communicating with said uid delivery orifice in said tube, and an open second end spaced from said combination delivery-exhaust tube and communicating with said upper chamber; and wherein said one way check valve means is disposed in said tubular section.
7. A tube structure according to claim 1, wherein said means defining a uid delivery passage comprises means defining a fluid delivery orifice extending through said partition means, and a uid delivery tube having an open upper end communicating with said uid delivery orice and an open lower end communicating with said lower chamber; and wherein said one way check valve means is disposed adjacent to said uid delivery orifice.
8. A tube structure according to claim 7, wherein said means defining a fluid exhaust passage comprises a separate fluid exhaust tube spaced from said uid delivery References Cited UNITED STATES PATENTS 3,133,881 5/1964 Childs 233-20 3,190,546 6/ 1965 Raccuglia et al. 233-20 3,347,454 10/ 1967 Bellamy et al. 233-26 X WILLIAM I. PRICE, Primary Examiner U.S. Cl. X.R. 233-26
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Cited By (16)

* Cited by examiner, † Cited by third party
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US3578240A (en) * 1968-04-13 1971-05-11 Gunter Eberle Receptacle holder for centrifuges
US3666171A (en) * 1969-10-20 1972-05-30 Sorvall Inc Ivan Swinging bucket centrifuge rotor
US3849072A (en) * 1972-04-25 1974-11-19 Becton Dickinson Co Plasma separator
US3858795A (en) * 1973-02-08 1975-01-07 Int Equipment Co Method for washing blood cells
US3905528A (en) * 1974-04-10 1975-09-16 Hugh V Maiocco Two-piece concentric centrifuge sample container
US4142668A (en) * 1976-10-01 1979-03-06 Lee Jae Y Serum-plasma separator and transfer apparatus
EP0072201A2 (en) * 1981-08-05 1983-02-16 Ortho Diagnostic Systems Inc. Particle washing system and method of use
EP0104947A2 (en) * 1982-09-29 1984-04-04 Ortho Diagnostic Systems Inc. Multiple particle washing system and method of use
US4828716A (en) * 1987-04-03 1989-05-09 Andronic Devices, Ltd. Apparatus and method for separating phases of blood
US5271852A (en) * 1992-05-01 1993-12-21 E. I. Du Pont De Nemours And Company Centrifugal methods using a phase-separation tube
US5282981A (en) * 1992-05-01 1994-02-01 E. I. Du Pont De Nemours And Company Flow restrictor-separation device
US5372945A (en) * 1985-06-06 1994-12-13 Alchas; Paul G. Device and method for collecting and processing fat tissue and procuring microvessel endothelial cells to produce endothelial cell product
EP0734767A2 (en) * 1995-04-01 1996-10-02 Roche Diagnostics GmbH Container for treating fluids with reduced contamination risk
WO1998035758A1 (en) * 1997-02-14 1998-08-20 Dendreon Corporation Cell washing device and method
US6254834B1 (en) * 1998-03-10 2001-07-03 Large Scale Proteomics Corp. Detection and characterization of microorganisms
WO2010072271A1 (en) * 2008-12-23 2010-07-01 Symbion Medical Systems Sarl Device and analyzing system for conducting agglutination assays

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US3133881A (en) * 1959-07-27 1964-05-19 Giovanni Raccuglia Apparatus for separating liquid mixtures
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Cited By (33)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3578240A (en) * 1968-04-13 1971-05-11 Gunter Eberle Receptacle holder for centrifuges
US3666171A (en) * 1969-10-20 1972-05-30 Sorvall Inc Ivan Swinging bucket centrifuge rotor
US3849072A (en) * 1972-04-25 1974-11-19 Becton Dickinson Co Plasma separator
US3858795A (en) * 1973-02-08 1975-01-07 Int Equipment Co Method for washing blood cells
US3905528A (en) * 1974-04-10 1975-09-16 Hugh V Maiocco Two-piece concentric centrifuge sample container
US4142668A (en) * 1976-10-01 1979-03-06 Lee Jae Y Serum-plasma separator and transfer apparatus
EP0072201A3 (en) * 1981-08-05 1985-05-22 Ortho Diagnostic Systems Inc. Particle washing system and method of use
EP0072201A2 (en) * 1981-08-05 1983-02-16 Ortho Diagnostic Systems Inc. Particle washing system and method of use
EP0104947A2 (en) * 1982-09-29 1984-04-04 Ortho Diagnostic Systems Inc. Multiple particle washing system and method of use
EP0104947A3 (en) * 1982-09-29 1985-12-18 Ortho Diagnostic Systems Inc. Multiple particle washing system and method of use
US5372945A (en) * 1985-06-06 1994-12-13 Alchas; Paul G. Device and method for collecting and processing fat tissue and procuring microvessel endothelial cells to produce endothelial cell product
US4828716A (en) * 1987-04-03 1989-05-09 Andronic Devices, Ltd. Apparatus and method for separating phases of blood
US5308506A (en) * 1987-04-03 1994-05-03 Mcewen James A Apparatus and method for separating a sample of blood
US5271852A (en) * 1992-05-01 1993-12-21 E. I. Du Pont De Nemours And Company Centrifugal methods using a phase-separation tube
US5282981A (en) * 1992-05-01 1994-02-01 E. I. Du Pont De Nemours And Company Flow restrictor-separation device
US5419835A (en) * 1992-05-01 1995-05-30 E. I. Du Pont De Nemours And Company Flow restrictor-separation device
EP0734767A2 (en) * 1995-04-01 1996-10-02 Roche Diagnostics GmbH Container for treating fluids with reduced contamination risk
EP0734767A3 (en) * 1995-04-01 1998-06-03 Roche Diagnostics GmbH Container for treating fluids with reduced contamination risk
WO1998035758A1 (en) * 1997-02-14 1998-08-20 Dendreon Corporation Cell washing device and method
US6197579B1 (en) 1997-02-14 2001-03-06 Dendreon Corporation Cell washing device and method
US6254834B1 (en) * 1998-03-10 2001-07-03 Large Scale Proteomics Corp. Detection and characterization of microorganisms
US6340570B1 (en) 1998-03-10 2002-01-22 Large Scale Proteomics Corp. Detection and characterization of microorganisms
US6346421B1 (en) 1998-03-10 2002-02-12 Large Scale Proteomics Corp. Methods for concentrating and detecting microorganisms using centrifuge tubes
US20020127546A1 (en) * 1998-03-10 2002-09-12 Anderson Norman G. Detection and characterization of microorganisms
US20020137026A1 (en) * 1998-03-10 2002-09-26 Anderson Norman G. Detection and characterization of microorganisms
US6479239B1 (en) 1998-03-10 2002-11-12 Large Scale Biology Corporation Detection and characterization of microorganisms
US6911312B2 (en) 1998-03-10 2005-06-28 Large Scale Proteomics Corporation Detection and characterization of microorganisms
US7070739B1 (en) 1998-03-10 2006-07-04 Large Scale Proteomics Corporation Detection and characterization of microorganisms
WO2010072271A1 (en) * 2008-12-23 2010-07-01 Symbion Medical Systems Sarl Device and analyzing system for conducting agglutination assays
CN102281949A (en) * 2008-12-23 2011-12-14 新彼奥医疗系统公司 Device and analyzing system for conducting agglutination assays
JP2012513596A (en) * 2008-12-23 2012-06-14 シンビオン・メディカル・システムズ・ソシエテ・ア・レスポンサビリテ・リミテ Apparatus and analysis system for agglutination inspection
CN102281949B (en) * 2008-12-23 2014-10-22 新彼奥医疗系统公司 Device and analyzing system for conducting agglutination assays
US8999729B2 (en) 2008-12-23 2015-04-07 Symbion Medical Systems Sarl Device and analyzing system for conducting agglutination assays

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