US3707354A - Means for mixing and centrifugation - Google Patents

Means for mixing and centrifugation Download PDF

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US3707354A
US3707354A US46630A US3707354DA US3707354A US 3707354 A US3707354 A US 3707354A US 46630 A US46630 A US 46630A US 3707354D A US3707354D A US 3707354DA US 3707354 A US3707354 A US 3707354A
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tray
wells
typing
receptacle
disks
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Harold S Goodman
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HAROLD S GOODMAN
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    • 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
    • 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

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  • An upwardly opening receptacle in the tray has a perimeter providing an inwardly opening pocket to receive the centrifuged matter.
  • a plurality of vertical partitions may divide the receptacle into individual wells or compartments for concurrently performing a number of separate or related tests such as in semi-automatic blood grouping and typing procedures and compatibility or cross-typing tests.
  • the trays are adapted to be made in the form of low cost disposable plastic disks.
  • selected wells in the disks may be provided with predispensed typing reagents such as sera.
  • Well-identifying indicia may be carried on the respective disks.
  • This invention relates to the art of mixing and centrifugation of materials in and from liquid media, and is especially useful in serological and chemical test procedures.
  • An important object of the invention is to provide new and improved means for enhancing the speed and accuracy with which serological and chemical test procedures can be performed.
  • Another object of the invention is to provide new and improved means for the intended purpose which will "ice quantitatively reduce the apparatus required and will qualitatively improve the results gained in carrying out various serological and chemical procedures and more particularly test procedures involving mixing of materials and centrifugation, and including where desirable incubation.
  • a further object of the invention is to provide new and improved apparatus for carrying out efiiciently routine procedures involving incubation, mixing, centrifugation, washing, and repetitions of any one or more of the steps in carrying out a serological or chemical test procedure.
  • Still another object of the invention is to provide new and improved disposable tray means especially suitable for carrying out multiple stage serological and chemical tests.
  • a still further object of the invention is to provide new and improved means especially useful in carrying out blood grouping and typing procedures as well as compatibility and cross-typing tests.
  • FIG. 1 is a top plan view, partially in section, showing a preferred form of multi-well rotary tray embodying features of the invention
  • FIG. 2 is a fragmentary sectional detail view taken substantially along the line II--l1 of FIG. 1;
  • FIG. 3 is a fragmentary sectional detail view taken substantially along the line IIIIII of FIG. 1;
  • FIG. 4 is a view similar to FIG. 3 but showing a modification
  • FIG. 5 is an isometric view of apparatus on and in which trays of the kind disclosed in FIG. 1 are adapted to be used;
  • FIG. 6 is an isometric view, partially in section, showing in greater detail one of the spindles of the apparatus of FIG. 5 on which the trays are to be mounted;
  • FIG. 7 is a schematic illustration of operating circuitry and components of the apparatus of FIG. 5.
  • a preferred form of receptacle unit 10 comprises a circular, rotary tray disk which is desirably constructed from transparent or at least translucent material and lends itself readily to being made as a rigid plastic molding adapted to be supplied as a low cost disposable product equipped to be used in the performance of whatever procedure involving steps of mixing, centrifugation, incubation, washing, and the like that may be demanded.
  • the unit 10 may be employed in any of a great variety of procedures, especially serological and/ or chemical procedures, as a specific example, it will be more particularly described as applied to a semi-automated blood typing procedure.
  • the disk tray unit 10 comprises a central body portion 11 providing a closed top over a downwardly opening recess 12 of substantial diameter defined by an annular depending wall 13 about which is an annular receptacle area defined by a bottom wall 14 and an outer annular perimeter wall 15.
  • the wall -15 at least on its inner side slopes obliquely upwardly and inwardly and thereby defines with the upper or inner surface of the bottom wall 14 a centrifuge pocket 17 which is further accentuated by an inwardly extending limited width overhanging annular rim flange 18 on the upper end of the perimeter wall 15.
  • the inner surface at least of the bottom wall 14 slopes upwardly toward the perimeter wall 15.
  • the receptacle provided by the unit may comprise the entire annulus defined by the annular walls
  • a more generally useful arrangement comprises subdividing the annular receptacle into a plurality of compartments or wells 19 by means of radial vertically extending partitions 20.
  • all of the wells 19 are depicted as of equal size, they may be of any predetermined differential sizes or graduated sizes as may be preferred or most convenient or desirable for the type of materials to be worked upon.
  • the structure provides a thoroughly mutually reinforced arrangement wherein the several walls, the flange 18 and the partitions 20 contribute significantly to provide a rigid, lightweight unitary structure.
  • the receptacle unit 10 may be of about four inches in base diameter with the inside diameter of the central or hub portion topped by the body area 11 of about one and three-quarter inch in diameter, and a height of about five-eighths inch, and other dimensions in proportion.
  • the bottom wall 14 may be of uniform thickness as shown in FIG. 4 with at least a portion 140: sloping obliquely toward the perimeter wall to attain the desirable centrifuge pocket effect.
  • the land or plateau area provided by the body portion 11 may carry appropriate indicia to assist a technician in following the various steps of the procedure. While such indicia may be molded directly on or applied in any desirable manner to the receiving surface, it may be conveniently applied in the form of a label 21 which may be in complementary disk form to be neatly received on the supporting surface. Identification of the several wells 19 may be by way of respective numerals 22 on the margin of the label 21. In addition, or alternatively, the label 21 may have thereon specific orientation indicia 23 relative to the respective wells 19 to identify the particular material or steps involved therein pursuant to the procedure to be carried out with the aid of the particular tray disk 10.
  • a fairly comprehensive range of steps is provided for blood test grouping and typing procedure, wherein one test-tube of a patients blood is prepared with anticoagulant so that the blood cells will be available in suspension, and one test-tube of the same patients blood is treated with a clotting agent so as to provide a supply of serum.
  • respective typing sera are disposed which may be identified by the indicia 23.
  • the typing sera may be placed into the respective wells by the technician at the time of use, in a preferred arrangement such typing sera are supplied with the disk 10 as a predispensed facility, adhered in dry state to the bottom wall 14. This has the distinct advantage of eliminating errors that might be experienced where the addition of the typing sera occurs at the time of use.
  • the grouping and typing procedure may then proceed as follows.
  • One drop of the patients cells suspension is placed in each of the wells 19 identified as I to 6 inclusive.
  • Two drops of the patients serum is placed in the wells 19 identified as 7 to 12, inclusive.
  • One drop of A cells is placed in the well 8 and one drop of B cells is placed in well 9.
  • One drop of VDRL antigen is placed in well 10 and screening cells I and II are added to wells 11 and 12.
  • the loaded disk 10 is rotated for centrifugation for fifteen seconds, whereafter centrifugal rotation is stopped and for five seconds the disk is actuated to agitate the media in the wells 19.
  • the technician reads the grouping wells 1 through 3 and cell control well 7 and reverse grouping wells 8 and 9, recording the results on the patients record sheet.
  • a combination incubation and mixing action is conducted at either room temperature or at 37 C. as may be deemed necessary from five to sixty minutes.
  • the disk 10 is then subjected to centrifugation and the results observed and hemolysis in any well is recorded. This is followed by a mixing actuation of the disk with observation and recording of agglutination in well 4 as the control well, wells 5 and 6 for Rh typing, well 7 for autoagglutination, well 10 for VDR-L, and wells 11 and 12 for antibody screening.
  • an antiglobulin test is conducted which comprises adding saline solution to negative wells 5, 6, 11 or 12, and washing while subjecting the disk to mixing actuation for a predetermined time between fifteen and thirty seconds and then centrifugation for a predetermined time of one to two minutes.
  • the saline solution is then aspirated and fresh saline solution added and the washing steps of mixing and centrifugation repeated three additional times.
  • two drops of antiglobulin serum are added to the affected wells 19 and a reading step is then conducted comprising centrifugation for a predetermined time of between fifteen and thirty seconds and mixing for a predetermined time of between fifteen and thirty seconds while the Wells are illuminated to facilitate the reading.
  • the results are recorded on the patients record, either manually or if equipment is provided for the purpose the record may be completed by a machine such as a print-out on a data sheet.
  • the indicia label 21 may carry additional indicia markings such as concentrically disposed segmental guide or orien; tation bars comprising a bar 24 having the legend cells and radially aligned with the section of contiguous wells 19 numbered, clockwise, from 12 to 6 and a bar 25 having the legend data serum radially aligned with the section of contiguous wells 19 numbered from 7 to 12.
  • code indicia may be carried by the label 21 for assistance in quick determination as to temperature requirements in respect to the actions carried out in certain of the wells, agglutination tests to be conducted in respect to others of the wells.
  • respective segmental assistance bars 27 aligned with wells contiguous in clockwise relation numbers 12 to 3 and numbers 7 to 9 may be provided and have associated therewith the legend RT referring to room temperature
  • assistance bars 28 may be provided in radial alignment with wells 4 to 6 and 10 to 12, respectively, with the legend AG referring to agglutination.
  • the assistance bars 27 and 28 may be of different, contrasting colors such as the color blue for the bars 27 and the color red for the bars 28.
  • the orientation bars 24 and 25 as one group are relatively offset so that they are more quickly differentiated as well as to enable overlap at the alignment with the well 12.
  • the assistance bars 27 and 28 are relatively offset.
  • tray disk 10 to conduct compatibility or cross-typing tests is advantageous and may comprise one to four tests per disk, using three of the wells 19 for each test.
  • two drops of the recipients serum is added to all three of the selected group of wells 19 and one drop of the donors blood cells is added to each of the three wells.
  • Bromalinase is added to one of the wells.
  • a mixing step is conducted by actuating the disk and the disk is then permitted to stand at room temperature for about fifteen minutes, whereafter centrifugation is effected and observation made for hemolysis.
  • the disk is then subjected to agitation for mixing and examination for agglutination effected. If no agglutination is observed a washing and antiglobulin test is effected in the well to which bromalinase has been added and one of the other wells.
  • instrumentation in various forms may be provided but is desirably of a character to receive the disk 10 replaceably and should have provision for selectively carrying out the various steps in the desired procedure.
  • a compact, portable table or desk-top instrument 30 is provided comprising a cabinet structure 31 housing therein the various mechanisms and preferably electrical connections and devices to perform as desired.
  • a five disk arrangement is provided but as many or few disks may be accommodated as deemed adequate for the particular laboratory requirements where the instrument is to be used.
  • the cabinet 31 includes a horizontal platform or table 32 which is preferably opaque and provided with respective spaced apertures 33 through each of which extends concentrically a vertical spindle shaft 34 carrying a disk-receiving corotative head 35 of a diameter to be reasonably closely but freely received within the downwardly opening hub recess 12 of one of the disks and to support the disk with its bottom wall 14 adjacent to the table 32.
  • Means are provided for releasably latching or interlocking the disk 10 to the head 35 to prevent unintentional escape of the disk from the head.
  • one or more, and in this instance two diametrically opposite peripheral substantially V-notches 37 open from the cylindrical perimeter of the head 35 to receive complementary but narrower respective lugs 38 (FIGS. 1 and 2) integral with the inner side of the hub wall 13 of the disk.
  • each of the corotational interlock lugs 38 has a laterally extending interlock shoulder 39, at the side thereof which trails in centrifugal rotation of the disk in clockwise direction.
  • the width of the shoulder extension 39 is equal to one half the width of the receiving notch 37 and complementary thereto so that the disk hub can be received on the head 35 by an axial assembly movement when the lugs 38 and the shoulder extensions 39 are registered with the respective notches 37.
  • a slight relative turning of the disk 10 relative to the head 35 causes the latching shoulder 39 to interlock within a receiving recess 40 provided at the lower end of the appropriate side of the respective notch 37.
  • Adequate resistance to unintentional unlatching movement of the disk 10 relative to the head 35 is afforded by means such as a compressible, desirably sponge rubber pad 41 mounted fixedly on the crown of the head 35 and of a thickness requiring some compression by the hub wall 11 to enable entry of the interlock shoulders 39 in the interlock recesses 49. This results in sufficient frictional binding of the affected interengaged surfaces of the disk and the head to resist separation of the disk from the head unless the disk is manipulated to overcome the latching bias supplied by the compressible pad.
  • spindle shafts 34 are supported within the housing 31 for unison mixing actuation or centrifugal rotation, as by means of coupling belts 42 between adjacent ones of the shafts (FIG. 7).
  • Identical orientation of each of the disks 10 received upon each of the heads 35 is adapted to be assured by having the interlock notches 37 all in a common orientation.
  • there may be drift or a lag or overrun with respect to stopping of the coupled shafts 34 while to facilitate conducting of the testing procedures it may be desirable at any given time to have certain of the wells 19 in a predetermined position relative to the front of the table 32.
  • Means for this purpose comprise cooperative indexing means on the respective disks 10 and on the table 32, conveniently a fixed index mark 43 (FIG. 5) adjacent to the back of each disk location and an index mark 43a (FIG. 1) on the wall 15 between the wells identified as 12 and 1.
  • Means are also provided, such as a positioning or indexing knob 44, for corotatively operating a shaft 45 operatively connected as by means of a coupling belt 46 with one of the spindle shafts 34 whereby to effect the indexing manually.
  • Means are provided, such as electrically energized and controllable devices for operating the spindle shafts 34 to effect either mixing actuation of the associated tray disks 10 or centrifuging rotation, selectively.
  • a vibrator or oscillator 47 is selectively connectable with one of the spindle shafts 34 as by means of a magnetic clutch '48 to actuate the coupled spindle shafts for mixing agitation of the tray disks 10 and thereby the material and liquid media in the respective wells.
  • Operation of the oscillator 47 and the magnetic clutch 48 is desirably through a timer 49 under the control of a switch 50 in an electrical power supply circuit and manually operable through a knob 51 which may be mounted adjacent to the knob 44 on a control panel 52 at one side of the housing 31.
  • a signal lamp 53 observably located, for example, on a second control panel 54 at the opposite side of the machine.
  • An audible signal may also be provided such as a bell 55 connected with the timer and operated to indicate termination of a predetermined mixing interval.
  • a drive motor '57 is connected as by means of a drive belt coupling 58 with one of the coupled spindle shafts 34 and is adapted to be selectively energized through a timer 59 selectively operable under the control of a switch "60 in the electrical power supply circuit and having a manually operable actuating knob 61 mounted on the control panel 54.
  • the switch 60 is a three-way switch having a neutral or off position and two timer controlling positions, one of which effects operation of the timer 59 for a predetermined time interval of centrifugation and then stop after which the timer must be again signalled by closing of the switch to perform another interval of centrifugation.
  • the timer In the second closing position of the switch 60, the timer operates through a continuous washing cycle of intermittent centrifuging and intervening aspiration dwells. Progress of such a cycle is observable by progressive lighting of a corresponding set of lamps 62 connected with the timer and observable on the control panel 54. At all times that the timer 59 is operating, an indicator lamp 63 is illuminated and observable on the control panel 54.
  • selectively operable heating means may be provided, exemplified by the heater 64 connected in the electrical power supply circuit and under the control of a switch 65 which may be manually operable on the control panel 52.
  • a switch 65 which may be manually operable on the control panel 52.
  • a single resistance heater may comprise individual heaters for each of the tray disks or it may be a single heater for generally maintaining a suitable temperature within the housing 31 or at least in the vicinity of the spindle heads 35, and more particularly for heating the tray disks through the openings 33 which are desirably of the same or nearly the same diameter as the diameter of the disks.
  • means are provided for illuminating the wells 19 of the tray disks 10, comprising lamp means 67 suitably disposed to be operable as for example from beneath the table 32 through the openings 33 so as to be effective through the transparent or translucent bottom wall 14, at least, of the disks 10.
  • Lamp means 67 suitably disposed to be operable as for example from beneath the table 32 through the openings 33 so as to be effective through the transparent or translucent bottom wall 14, at least, of the disks 10.
  • Connection of the lamp means 67 with the electrical power source is through a control switch 68 which may also be manually operable on the control panel 52.
  • the table 32 is desirably provided with suitable test-tube receiving sockets 70 located by pairs adjacent to and desirably rearwardly from the respective holes 33.
  • a hood 71 which is desirably transparent, may be provided as a replaceable cover over the working area provided by the table 32. This hood may be hingedly attached to the housing 31 if desired.
  • Apparatus for mixing and centrifugation comprising:
  • vibrator means operative for vibrating the spindle shaft to vibrate the tray and thereby vibrate the carrier and mix the material until even if no centrifugalizable substance is initially present such a substance may develop;
  • Apparatus according to claim 1 including timing means for controlling said means for rotating the spindle and thereby the tray.
  • Apparatus according to claim 1 including means below the tray for heating the tray.
  • said tray having a hub
  • said spindle having means receptive of the hub, and complementary releasable interlock structure on said hub and said spindle shaft.
  • Apparatus according to claim 1 including a plurality of spindle shafts arranged to support a plurality of the rotatable trays, means coupling said spindle shafts corotatively, means releasably coupling one of said spindle shafts to the vibrator means, means coupling one of said spindle shafts to said means for rotating, indexing means, and means coupled to one of said spindle shafts and operative manually to index all of the spindle shafts in unison with respect to the indexing means.
  • each of said spindles has thereon a head, compressible crown means on said head, said tray having a downwardly opening recess providing a socket in which said head is received and said recess having a top closure, and releasable retaining means cooperating on said tray and said head and maintained in retaining relation by pressure of said compressible crown means pressing against said closure.
  • a rotatable tray having means thereon for attachment to or removal from means for agitating and rotating the tray;
  • said tray providing an upwardly opening receptacle receptive of carrying liquid from which substance is to be centrifuged, and defined by a bottom wall and an outer perimeter structure;
  • Means according to claim 8 including a downwardly hollow central hub on the tray, said hub being closed at the top and providing a downwardly opening recess for reception of a spindle head therein and providing said means for attachment to or removal from means for agitating and rotating the tray, and interlock structure within said recess for interlocking engagement with complementary structure on the spindle head.
  • Means according to claim 8 including a central land on said tray providing for guidance and directional indicia relative to procedures in use of said receptacle.
  • said tray comprises a low cost disposable thin wall self-sustaining plastic molding having radially extending integral reinforcing partition means subdividing said receptacle and perimeter structure into a plurality of upwardly opening wells and inwardly opening pockets.
  • Means according to claim 8 including subdividing structure in said receptacle providing a plurality of wells, and blood typing sera predispensed and in dry state in certain of said wells.
  • said upwardly extending wall sloping inwardly, and said bottom wall having at least a portion of its upper surface sloping generally upwardly toward and joining said upwardly extending wall.
  • Means according to claim 8 including a plurality of partitions subdividing said receptacle and perimeter structure into a plurality of wells each of which has a pocket.
  • a rotatable tray having means thereon for quick attachment to or removal from means for agitating and rotating the tray;
  • said tray providing an upwardly opening receptacle receptive of liquid carrier from which substance is to be centrifuged and defined by an outer perimeter structure;
  • said perimeter structure providing at least one inwardly opening pocket into which substance from the carrier is centrifugally directed by rotation of the tray;
  • said tray comprising a low cost disposable thin wall self-sustaining plastic molding having radially extending integral reinforcing partition means subdividing said receptacle and perimeter structure into a plurality of upwardly opening wells and inwardly opening pockets.
  • a rotatable tray having means thereon for quick attachment to or removal from means for agitating and rotating the tray;
  • said tray providing an upwardly opening receptacle receptive of liquid carrier from which substance is to be centrifuged and defined by an outer perimeter structure;
  • said perimeter structure providing at least one inwardly opening pocket into which substance from the carrier is centrifugally directed by rotation of the tray;
  • means providing identification for said pockets comprising a label attached to said tray and having thereon orientation indicia aligned with the pockets and segmental bars aligned with certain pluralities of the pockets for assisting in blood cell typing procedures.
  • a rotatable tray having means thereon for quick attachment to or removal from means for agitating and rotating the tray;
  • said tray providing an upwardly opening receptacle receptive of liquid carrier from which substance is to be centrifuged and defined by an outer perimeter structure;
  • said perimeter structure providing at least one inwardly opening pocket into which substance from the carrier is centrifugally directed by rotation of the tray;
  • Apparatus for mixing and centrifugation comprising a rotatable tray receptive of material and liquid carrier;
  • said tray having translucent walls; and means for illuminating the tray through the walls.

Abstract

MATERIALS IN LIQUID MEDIUM ARE PLACED IN A ROTARY TRAY WHICH IS ACTURATED TO AGITATE THE MEDIUM AND MIX THE MATERIALS, PRECEDED BY INCUBATION IF DESIRED, AND THE TRAY ROTATED TO CENTRIFUGATE MATTER FROM THE MEDIUM. AN UPWARDLY OPENING RECEPTACLE IN THE TRAY HAS A PERIMETER PROVIDING AN INWARDLY OPENING POCKET TO RECEIVE THE CENTRIFUGED MATTER. A PLURALITY OF VERTICAL PARTITIONS MAY DIVIDE THE RECEPTACLE INTO INDIVIDUAL WELLS OR COMPARTMENTS FOR CONCURRENTLY PERFORMING A NUMBER OF SEPARATE OR RELATED TESTS SUCH AS IN SEMI-AUTOMATIC BLOOD GROUPING AND TYPING PROCEDURES AND COMPATIBILITY OR CROSS-TYPING TESTS. FOR DISPOSABILITY THE TRAYS ARE ADAPTED TO BE MADE IN THE FORM OF LOW COST DISPOSABLE PLASTIC DISKS. AS A BLOOD TYPING DEVICE, SELECTED WELLS IN THE DISKS MAY BE PROVIDED WITH PREDISPENSED TYPING REAGENTS SUCH AS SERA. WELL-IDENTIFYING INDICIA MAY BE CARRIED ON THE RESPECTIVE DISKS.

Description

Dec. 26, 1972 H. s. GOODMAN MEANS FOR MIXING AND GENTRIFUGATION 2 Sheets-Sheet 1 Filed June 16. 1970 INVESTOR.
ffa'zwlddaadmzz in" #4 454 rvrl'olex'ays 1972 H. s. GOODMAN v MEANS FOR MIXING AND CENTRIFUG'ATION 2 Sheets-Sheet 2 Filed June 16. 1970 /L l L h I.\'VE.\'TOR.
weld 54004 272422 W? W a A @g g United States Patent 3,707,354 lVIEANS FOR MIXING AND CENTRIFUGATION Harold S. Goodman, 1300 Lincoln Ave. S., Highland Park, 1]]. 60035 Filed June 16, 1970, Ser. No. 46,630 Int. Cl. B04b /02, 9/00; G01n 33/16 US. Cl. 23253 R 19 Claims ABSTRACT OF THE DISCLOSURE Materials in liquid medium are placed in a rotary tray which is actuated to agitate the medium and mix the materials, preceded by incubation if desired, and the tray rotated to centrifugate matter from the medium. An upwardly opening receptacle in the tray has a perimeter providing an inwardly opening pocket to receive the centrifuged matter. A plurality of vertical partitions may divide the receptacle into individual wells or compartments for concurrently performing a number of separate or related tests such as in semi-automatic blood grouping and typing procedures and compatibility or cross-typing tests. For disposability the trays are adapted to be made in the form of low cost disposable plastic disks. As a blood typing device, selected wells in the disks may be provided with predispensed typing reagents such as sera. Well-identifying indicia may be carried on the respective disks.
This invention relates to the art of mixing and centrifugation of materials in and from liquid media, and is especially useful in serological and chemical test procedures.
Heretofore numerous and varied pieces of separate equipment have been deemed necessary to carry out separate though sequential and sometimes repetitive operations such as may be involved in serological and some chemical procedures.
More particularly, in blood bank serology, blood typing and cross-matching procedures have generally over a long period of time employed the conventional slide and testtube methods. The use of cards impregnated with antisera has not been widely accepted. Neither have certain automated procedures because they have related to only one phase of the problem, for example, applying only to blood typing but not to cross-matching. A difiiculty with the cross-matching appears to have been that a critical part of the test consists in washing of the red cells requiring repeated centrifuging and decanting of the supernatant liquid. Cell washing obviously can not be carried out on cards. In order to satisfy A.A.B.B. standards for crossmatching the serological procedures must include a means for cell washing.
According to the present invention the foregoing and other disadvantages, shortcomings, difiiculties, inefficiencies and problems are overcome by the provision of means for effecting all of the necessary steps and procedures in a single receptacle or tray which is desirably disposable.
,An important object of the invention is to provide new and improved means for enhancing the speed and accuracy with which serological and chemical test procedures can be performed.
Another object of the invention is to provide new and improved means for the intended purpose which will "ice quantitatively reduce the apparatus required and will qualitatively improve the results gained in carrying out various serological and chemical procedures and more particularly test procedures involving mixing of materials and centrifugation, and including where desirable incubation.
A further object of the invention is to provide new and improved apparatus for carrying out efiiciently routine procedures involving incubation, mixing, centrifugation, washing, and repetitions of any one or more of the steps in carrying out a serological or chemical test procedure.
Still another object of the invention is to provide new and improved disposable tray means especially suitable for carrying out multiple stage serological and chemical tests.
A still further object of the invention is to provide new and improved means especially useful in carrying out blood grouping and typing procedures as well as compatibility and cross-typing tests.
Other objects, features and advantages of the invention will be readily apparent from the following description of certain preferred embodiments thereof, taken in conjunction with the accompanying drawings, although variations and modifications may be effected without departing from the spirit and scope of the novel concepts embodied in the disclosure, and in which:
FIG. 1 is a top plan view, partially in section, showing a preferred form of multi-well rotary tray embodying features of the invention;
FIG. 2 is a fragmentary sectional detail view taken substantially along the line II--l1 of FIG. 1;
FIG. 3 is a fragmentary sectional detail view taken substantially along the line IIIIII of FIG. 1;
FIG. 4 is a view similar to FIG. 3 but showing a modification;
FIG. 5 is an isometric view of apparatus on and in which trays of the kind disclosed in FIG. 1 are adapted to be used;
FIG. 6 is an isometric view, partially in section, showing in greater detail one of the spindles of the apparatus of FIG. 5 on which the trays are to be mounted; and
FIG. 7 is a schematic illustration of operating circuitry and components of the apparatus of FIG. 5.
As principal means for practicing the present invention, a preferred form of receptacle unit 10 (FIGS. 1-3) comprises a circular, rotary tray disk which is desirably constructed from transparent or at least translucent material and lends itself readily to being made as a rigid plastic molding adapted to be supplied as a low cost disposable product equipped to be used in the performance of whatever procedure involving steps of mixing, centrifugation, incubation, washing, and the like that may be demanded. Although the unit 10 may be employed in any of a great variety of procedures, especially serological and/ or chemical procedures, as a specific example, it will be more particularly described as applied to a semi-automated blood typing procedure.
As a rigid plastic molding, the disk tray unit 10 comprises a central body portion 11 providing a closed top over a downwardly opening recess 12 of substantial diameter defined by an annular depending wall 13 about which is an annular receptacle area defined by a bottom wall 14 and an outer annular perimeter wall 15. As best seen in FIG. 3, the wall -15 at least on its inner side slopes obliquely upwardly and inwardly and thereby defines with the upper or inner surface of the bottom wall 14 a centrifuge pocket 17 which is further accentuated by an inwardly extending limited width overhanging annular rim flange 18 on the upper end of the perimeter wall 15. To improve centrifugal action and collection of centrifuged matter, the inner surface at least of the bottom wall 14 slopes upwardly toward the perimeter wall 15. While, for large quantity treatment, the receptacle provided by the unit may comprise the entire annulus defined by the annular walls, a more generally useful arrangement comprises subdividing the annular receptacle into a plurality of compartments or wells 19 by means of radial vertically extending partitions 20. Although all of the wells 19 are depicted as of equal size, they may be of any predetermined differential sizes or graduated sizes as may be preferred or most convenient or desirable for the type of materials to be worked upon. In addition to providing a multi-well receptacle unit in which each of the wells has an ample upward opening for ready access thereinto and a depth, width and breadth to receive a satisfactory volume of material to be worked upon, the structure provides a thoroughly mutually reinforced arrangement wherein the several walls, the flange 18 and the partitions 20 contribute significantly to provide a rigid, lightweight unitary structure. By way of example, for semi-automated blood typing purposes, the receptacle unit 10 may be of about four inches in base diameter with the inside diameter of the central or hub portion topped by the body area 11 of about one and three-quarter inch in diameter, and a height of about five-eighths inch, and other dimensions in proportion.
If preferred, instead of having the bottom wall 14 progressively thicker toward the perimeter of the unit as shown in FIG. 3, thebottom wall may be of uniform thickness as shown in FIG. 4 with at least a portion 140: sloping obliquely toward the perimeter wall to attain the desirable centrifuge pocket effect.
For the specific purpose of equipping the receptacle unit 10 for blood bank typing procedures, the land or plateau area provided by the body portion 11 may carry appropriate indicia to assist a technician in following the various steps of the procedure. While such indicia may be molded directly on or applied in any desirable manner to the receiving surface, it may be conveniently applied in the form of a label 21 which may be in complementary disk form to be neatly received on the supporting surface. Identification of the several wells 19 may be by way of respective numerals 22 on the margin of the label 21. In addition, or alternatively, the label 21 may have thereon specific orientation indicia 23 relative to the respective wells 19 to identify the particular material or steps involved therein pursuant to the procedure to be carried out with the aid of the particular tray disk 10. In the representative example shown in FIG. 1, a fairly comprehensive range of steps is provided for blood test grouping and typing procedure, wherein one test-tube of a patients blood is prepared with anticoagulant so that the blood cells will be available in suspension, and one test-tube of the same patients blood is treated with a clotting agent so as to provide a supply of serum. Into the wells 19 which are identified by the indicia 22 as numbers 1 to 6, inclusive, respective typing sera are disposed which may be identified by the indicia 23. Although the typing sera may be placed into the respective wells by the technician at the time of use, in a preferred arrangement such typing sera are supplied with the disk 10 as a predispensed facility, adhered in dry state to the bottom wall 14. This has the distinct advantage of eliminating errors that might be experienced where the addition of the typing sera occurs at the time of use.
The grouping and typing procedure may then proceed as follows. One drop of the patients cells suspension is placed in each of the wells 19 identified as I to 6 inclusive. Two drops of the patients serum is placed in the wells 19 identified as 7 to 12, inclusive. One drop of A cells is placed in the well 8 and one drop of B cells is placed in well 9. One drop of VDRL antigen is placed in well 10 and screening cells I and II are added to wells 11 and 12. Then the loaded disk 10 is rotated for centrifugation for fifteen seconds, whereafter centrifugal rotation is stopped and for five seconds the disk is actuated to agitate the media in the wells 19. Thereupon, the technician reads the grouping wells 1 through 3 and cell control well 7 and reverse grouping wells 8 and 9, recording the results on the patients record sheet. Next, in order, a combination incubation and mixing action is conducted at either room temperature or at 37 C. as may be deemed necessary from five to sixty minutes. The disk 10 is then subjected to centrifugation and the results observed and hemolysis in any well is recorded. This is followed by a mixing actuation of the disk with observation and recording of agglutination in well 4 as the control well, wells 5 and 6 for Rh typing, well 7 for autoagglutination, well 10 for VDR-L, and wells 11 and 12 for antibody screening. If wells 5, 6, 11 or 12 show negative results, an antiglobulin test is conducted which comprises adding saline solution to negative wells 5, 6, 11 or 12, and washing while subjecting the disk to mixing actuation for a predetermined time between fifteen and thirty seconds and then centrifugation for a predetermined time of one to two minutes. The saline solution is then aspirated and fresh saline solution added and the washing steps of mixing and centrifugation repeated three additional times. Then two drops of antiglobulin serum are added to the affected wells 19 and a reading step is then conducted comprising centrifugation for a predetermined time of between fifteen and thirty seconds and mixing for a predetermined time of between fifteen and thirty seconds while the Wells are illuminated to facilitate the reading. The results are recorded on the patients record, either manually or if equipment is provided for the purpose the record may be completed by a machine such as a print-out on a data sheet.
For convenience, and to assist the technician in ready identification of the purpose and function of the several wells 19 in carrying out the blood typing procedure, the indicia label 21 may carry additional indicia markings such as concentrically disposed segmental guide or orien; tation bars comprising a bar 24 having the legend cells and radially aligned with the section of contiguous wells 19 numbered, clockwise, from 12 to 6 and a bar 25 having the legend data serum radially aligned with the section of contiguous wells 19 numbered from 7 to 12. In addition, code indicia may be carried by the label 21 for assistance in quick determination as to temperature requirements in respect to the actions carried out in certain of the wells, agglutination tests to be conducted in respect to others of the wells. Thus, respective segmental assistance bars 27 aligned with wells contiguous in clockwise relation numbers 12 to 3 and numbers 7 to 9 may be provided and have associated therewith the legend RT referring to room temperature, while assistance bars 28 may be provided in radial alignment with wells 4 to 6 and 10 to 12, respectively, with the legend AG referring to agglutination. For quick visual differentiation, the assistance bars 27 and 28 may be of different, contrasting colors such as the color blue for the bars 27 and the color red for the bars 28. In addition, it will be noted that the orientation bars 24 and 25 as one group are relatively offset so that they are more quickly differentiated as well as to enable overlap at the alignment with the well 12. Similarly the assistance bars 27 and 28 are relatively offset.
Use of the tray disk 10 to conduct compatibility or cross-typing tests is advantageous and may comprise one to four tests per disk, using three of the wells 19 for each test. In each test, two drops of the recipients serum is added to all three of the selected group of wells 19 and one drop of the donors blood cells is added to each of the three wells. Bromalinase is added to one of the wells.
A mixing step is conducted by actuating the disk and the disk is then permitted to stand at room temperature for about fifteen minutes, whereafter centrifugation is effected and observation made for hemolysis. The disk is then subjected to agitation for mixing and examination for agglutination effected. If no agglutination is observed a washing and antiglobulin test is effected in the well to which bromalinase has been added and one of the other wells.
While certain blood bank procedures have been described in some detail, other procedures such as complete Rh and Hr typing, identification of irregular antibodies and other less frequently conducted procedures may be carried out with the same apparatus.
For effecting mixing actuation and centrifugation rotation of the tray disk 10, instrumentation in various forms may be provided but is desirably of a character to receive the disk 10 replaceably and should have provision for selectively carrying out the various steps in the desired procedure. In one desirable arrangement, as depicted in FIGS. -7 a compact, portable table or desk-top instrument 30 is provided comprising a cabinet structure 31 housing therein the various mechanisms and preferably electrical connections and devices to perform as desired. In this instance, a five disk arrangement is provided but as many or few disks may be accommodated as deemed adequate for the particular laboratory requirements where the instrument is to be used. As shown, the cabinet 31 includes a horizontal platform or table 32 which is preferably opaque and provided with respective spaced apertures 33 through each of which extends concentrically a vertical spindle shaft 34 carrying a disk-receiving corotative head 35 of a diameter to be reasonably closely but freely received within the downwardly opening hub recess 12 of one of the disks and to support the disk with its bottom wall 14 adjacent to the table 32.
Means are provided for releasably latching or interlocking the disk 10 to the head 35 to prevent unintentional escape of the disk from the head. To this end, one or more, and in this instance two diametrically opposite peripheral substantially V-notches 37 (FIG. 6) open from the cylindrical perimeter of the head 35 to receive complementary but narrower respective lugs 38 (FIGS. 1 and 2) integral with the inner side of the hub wall 13 of the disk. At its lower end portion each of the corotational interlock lugs 38 has a laterally extending interlock shoulder 39, at the side thereof which trails in centrifugal rotation of the disk in clockwise direction. The width of the shoulder extension 39 is equal to one half the width of the receiving notch 37 and complementary thereto so that the disk hub can be received on the head 35 by an axial assembly movement when the lugs 38 and the shoulder extensions 39 are registered with the respective notches 37. When axial assembly has been completed, a slight relative turning of the disk 10 relative to the head 35 causes the latching shoulder 39 to interlock within a receiving recess 40 provided at the lower end of the appropriate side of the respective notch 37. Adequate resistance to unintentional unlatching movement of the disk 10 relative to the head 35 is afforded by means such as a compressible, desirably sponge rubber pad 41 mounted fixedly on the crown of the head 35 and of a thickness requiring some compression by the hub wall 11 to enable entry of the interlock shoulders 39 in the interlock recesses 49. This results in sufficient frictional binding of the affected interengaged surfaces of the disk and the head to resist separation of the disk from the head unless the disk is manipulated to overcome the latching bias supplied by the compressible pad.
In a preferred arrangement all of the spindle shafts 34 are supported within the housing 31 for unison mixing actuation or centrifugal rotation, as by means of coupling belts 42 between adjacent ones of the shafts (FIG. 7). Identical orientation of each of the disks 10 received upon each of the heads 35 is adapted to be assured by having the interlock notches 37 all in a common orientation. However, there may be drift or a lag or overrun with respect to stopping of the coupled shafts 34, while to facilitate conducting of the testing procedures it may be desirable at any given time to have certain of the wells 19 in a predetermined position relative to the front of the table 32. Means for this purpose comprise cooperative indexing means on the respective disks 10 and on the table 32, conveniently a fixed index mark 43 (FIG. 5) adjacent to the back of each disk location and an index mark 43a (FIG. 1) on the wall 15 between the wells identified as 12 and 1. Means are also provided, such as a positioning or indexing knob 44, for corotatively operating a shaft 45 operatively connected as by means of a coupling belt 46 with one of the spindle shafts 34 whereby to effect the indexing manually.
Means are provided, such as electrically energized and controllable devices for operating the spindle shafts 34 to effect either mixing actuation of the associated tray disks 10 or centrifuging rotation, selectively. To this end, a vibrator or oscillator 47 is selectively connectable with one of the spindle shafts 34 as by means of a magnetic clutch '48 to actuate the coupled spindle shafts for mixing agitation of the tray disks 10 and thereby the material and liquid media in the respective wells. Operation of the oscillator 47 and the magnetic clutch 48 is desirably through a timer 49 under the control of a switch 50 in an electrical power supply circuit and manually operable through a knob 51 which may be mounted adjacent to the knob 44 on a control panel 52 at one side of the housing 31. Also operated by the timer 49 is a signal lamp 53 observably located, for example, on a second control panel 54 at the opposite side of the machine. An audible signal may also be provided such as a bell 55 connected with the timer and operated to indicate termination of a predetermined mixing interval.
For centrifugation, a drive motor '57 is connected as by means of a drive belt coupling 58 with one of the coupled spindle shafts 34 and is adapted to be selectively energized through a timer 59 selectively operable under the control of a switch "60 in the electrical power supply circuit and having a manually operable actuating knob 61 mounted on the control panel 54. Desirably the switch 60 is a three-way switch having a neutral or off position and two timer controlling positions, one of which effects operation of the timer 59 for a predetermined time interval of centrifugation and then stop after which the timer must be again signalled by closing of the switch to perform another interval of centrifugation. In the second closing position of the switch 60, the timer operates through a continuous washing cycle of intermittent centrifuging and intervening aspiration dwells. Progress of such a cycle is observable by progressive lighting of a corresponding set of lamps 62 connected with the timer and observable on the control panel 54. At all times that the timer 59 is operating, an indicator lamp 63 is illuminated and observable on the control panel 54.
In order to assure a proper incubation temperature, whether that be at room temperature or higher, under prevailing conditions at the work site, selectively operable heating means may be provided, exemplified by the heater 64 connected in the electrical power supply circuit and under the control of a switch 65 which may be manually operable on the control panel 52. Although schematically a single resistance heater is shown, it will be understood that this may comprise individual heaters for each of the tray disks or it may be a single heater for generally maintaining a suitable temperature within the housing 31 or at least in the vicinity of the spindle heads 35, and more particularly for heating the tray disks through the openings 33 which are desirably of the same or nearly the same diameter as the diameter of the disks.
In addition, means are provided for illuminating the wells 19 of the tray disks 10, comprising lamp means 67 suitably disposed to be operable as for example from beneath the table 32 through the openings 33 so as to be effective through the transparent or translucent bottom wall 14, at least, of the disks 10. Connection of the lamp means 67 with the electrical power source is through a control switch 68 which may also be manually operable on the control panel 52.
For convenience in locating and supporting test-tubes 69 containing respectively the blood cell sample and the serum sample for any given patient for whom a grouping and typing procedure is to be conducted with a respective tray disk at any selected one of the operating stations of the instrument 30, the table 32 is desirably provided with suitable test-tube receiving sockets 70 located by pairs adjacent to and desirably rearwardly from the respective holes 33.
A hood 71, which is desirably transparent, may be provided as a replaceable cover over the working area provided by the table 32. This hood may be hingedly attached to the housing 31 if desired.
It will be understood that variations and modifications may be effected without departing from the spirit and scope of the novel concepts of this invention.
I claim as my invention:
. 1. Apparatus for mixing and centrifugation, comprising:
a rotatable tray receptive of material and liquid carrier;
a spindle shaft supporting the tray;
vibrator means operative for vibrating the spindle shaft to vibrate the tray and thereby vibrate the carrier and mix the material until even if no centrifugalizable substance is initially present such a substance may develop;
means for rotating the spindle shaft and thereby the tray at a speed suflicient to centrifuge said substance from the carrier;
and means for alternately connecting the vibrating means or the rotating means with said spindle shaft.
2. Apparatus according to claim 1, including timing means for controlling said vibrator.
3. Apparatus according to claim 1, including timing means for controlling said means for rotating the spindle and thereby the tray.
4. Apparatus according to claim 1, including means below the tray for heating the tray.
5. Apparatus according to claim 1, said tray having a hub, said spindle having means receptive of the hub, and complementary releasable interlock structure on said hub and said spindle shaft.
6. Apparatus according to claim 1, including a plurality of spindle shafts arranged to support a plurality of the rotatable trays, means coupling said spindle shafts corotatively, means releasably coupling one of said spindle shafts to the vibrator means, means coupling one of said spindle shafts to said means for rotating, indexing means, and means coupled to one of said spindle shafts and operative manually to index all of the spindle shafts in unison with respect to the indexing means.
7. Apparatus according to claim 1, wherein each of said spindles has thereon a head, compressible crown means on said head, said tray having a downwardly opening recess providing a socket in which said head is received and said recess having a top closure, and releasable retaining means cooperating on said tray and said head and maintained in retaining relation by pressure of said compressible crown means pressing against said closure.
8. In means for mixing and centrifugation:
a rotatable tray having means thereon for attachment to or removal from means for agitating and rotating the tray;
said tray providing an upwardly opening receptacle receptive of carrying liquid from which substance is to be centrifuged, and defined by a bottom wall and an outer perimeter structure; and
9. Means according to claim 8, including a downwardly hollow central hub on the tray, said hub being closed at the top and providing a downwardly opening recess for reception of a spindle head therein and providing said means for attachment to or removal from means for agitating and rotating the tray, and interlock structure within said recess for interlocking engagement with complementary structure on the spindle head.
10. Means according to claim 8, including a central land on said tray providing for guidance and directional indicia relative to procedures in use of said receptacle.
11. Means according to claim 8, wherein said tray comprises a low cost disposable thin wall self-sustaining plastic molding having radially extending integral reinforcing partition means subdividing said receptacle and perimeter structure into a plurality of upwardly opening wells and inwardly opening pockets.
12. Means according to claim 8, including subdividing structure in said receptacle providing a plurality of wells, and blood typing sera predispensed and in dry state in certain of said wells.
13. Means according to claim 8, said upwardly extending wall sloping inwardly, and said bottom wall having at least a portion of its upper surface sloping generally upwardly toward and joining said upwardly extending wall.
14. Means according to claim 8, including a plurality of partitions subdividing said receptacle and perimeter structure into a plurality of wells each of which has a pocket.
15. Means according to claim 14, including means providing identification for said pockets, said identification means comprising a label attached to said tray and having thereon orientation indicia aligned with the pockets and segmental bars aligned with certain pluralities of the pockets, for assisting in blood cell typing procedures.
16. In means for mixing and centrifugation:
a rotatable tray having means thereon for quick attachment to or removal from means for agitating and rotating the tray;
said tray providing an upwardly opening receptacle receptive of liquid carrier from which substance is to be centrifuged and defined by an outer perimeter structure; and
said perimeter structure providing at least one inwardly opening pocket into which substance from the carrier is centrifugally directed by rotation of the tray;
said tray comprising a low cost disposable thin wall self-sustaining plastic molding having radially extending integral reinforcing partition means subdividing said receptacle and perimeter structure into a plurality of upwardly opening wells and inwardly opening pockets.
17. In means for mixing and centrifugation:
a rotatable tray having means thereon for quick attachment to or removal from means for agitating and rotating the tray;
said tray providing an upwardly opening receptacle receptive of liquid carrier from which substance is to be centrifuged and defined by an outer perimeter structure;
said perimeter structure providing at least one inwardly opening pocket into which substance from the carrier is centrifugally directed by rotation of the tray;
a plurality of partitions subdividing said receptacle and perimeter structure into a plurality of wells each of which has a pocket; and
means providing identification for said pockets comprising a label attached to said tray and having thereon orientation indicia aligned with the pockets and segmental bars aligned with certain pluralities of the pockets for assisting in blood cell typing procedures.
18. In means for mixing and centrifugation:
a rotatable tray having means thereon for quick attachment to or removal from means for agitating and rotating the tray;
said tray providing an upwardly opening receptacle receptive of liquid carrier from which substance is to be centrifuged and defined by an outer perimeter structure;
said perimeter structure providing at least one inwardly opening pocket into which substance from the carrier is centrifugally directed by rotation of the tray;
subdividing structure in said receptacle providing a plurality of wells; and
blood typing sera predispensed and in dry state in certain of said wells.
19. Apparatus for mixing and centrifugation, comprisa rotatable tray receptive of material and liquid carrier;
means operative to agitate the tray and thereby agitate the carrier and mix the material until even if no centrifugalizable substance is initially present such a substance may develop;
means for rotating the tray at a speed sufiicient to centrifuge said substance from the carrier;
10 said tray having translucent walls; and means for illuminating the tray through the walls.
References Cited UNITED STATES PATENTS OTHER REFERENCES Ito et al., Anal. Chem. 41, No. 12, October 1969, 1579- 1584.
MORRIS O. WOLK, Primary Examiner R. M. REESE, Assistant Examiner US. Cl. X.R.
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Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3856470A (en) * 1973-01-10 1974-12-24 Baxter Laboratories Inc Rotor apparatus
US3905772A (en) * 1965-05-17 1975-09-16 Medical Laboratory Automation Apparatus for performing blood typing tests
USRE30391E (en) * 1976-02-23 1980-09-02 Abbott Laboratories Chemical analysis cuvette
US4290997A (en) * 1978-02-28 1981-09-22 Kommandiittiyhtio Finnpipette Osmo A. Suovaniemi Apparatus for automatic measurement of the results of agglutination tests
EP0052770A1 (en) * 1980-11-25 1982-06-02 Roche Diagnostics GmbH Rotor unit with removable segments for a centrifugal analyzer
WO1986003008A1 (en) * 1984-11-13 1986-05-22 Cedars-Sinai Medical Center Portable blood typing apparatus and method
US5061381A (en) * 1990-06-04 1991-10-29 Abaxis, Inc. Apparatus and method for separating cells from biological fluids
US6872360B1 (en) * 1998-10-14 2005-03-29 Fondation Jean Dausset-Ceph Centrifuging device for laboratory analyzer

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3905772A (en) * 1965-05-17 1975-09-16 Medical Laboratory Automation Apparatus for performing blood typing tests
US3856470A (en) * 1973-01-10 1974-12-24 Baxter Laboratories Inc Rotor apparatus
USRE30391E (en) * 1976-02-23 1980-09-02 Abbott Laboratories Chemical analysis cuvette
US4290997A (en) * 1978-02-28 1981-09-22 Kommandiittiyhtio Finnpipette Osmo A. Suovaniemi Apparatus for automatic measurement of the results of agglutination tests
EP0052770A1 (en) * 1980-11-25 1982-06-02 Roche Diagnostics GmbH Rotor unit with removable segments for a centrifugal analyzer
WO1986003008A1 (en) * 1984-11-13 1986-05-22 Cedars-Sinai Medical Center Portable blood typing apparatus and method
US5061381A (en) * 1990-06-04 1991-10-29 Abaxis, Inc. Apparatus and method for separating cells from biological fluids
US6872360B1 (en) * 1998-10-14 2005-03-29 Fondation Jean Dausset-Ceph Centrifuging device for laboratory analyzer

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