US3826622A - Containers for use in an automated centrifuge - Google Patents

Abstract

SYSTEM FOR THE SEQUENTIAL TREATMENT OF LIQUID CHEMICAL SAMPLES COMPRISING THE STEPS OF DEPOSITING THE SAMPLES IN A SERIES OF TOP-LIKE CONTAINERS HAVING A PERIPHERAL SIDE CHAMBER. THE CONTAINERS ARE PLACED ON A BELT AND MOVE PAST A CENTRIFUGAL FIELD WHEREIN THE CONTAINERS ARE ROTATED. THE CONTAINERS ARE THEN REMOVED AT A TERMINAL ZONE AND THE HEAVIER SAMPLE COMPONENT REMAINS IN THE SIDE CHAMBER AS THE LIGHTER COMPONENTS FLOW TO THE BOTTOM OF THE CONTAINER.

Description

s. NATELsoN 3,826,622

CONTAINERS FOR USE IN AN AUTOMATED GENTRIFUG July 30, 1974 8 Sheets-Sheet 1 Filed May l5. 1972 July 30, l974 s. NATELSQN 3,826,622

CONTAINERS FOR USE IN AN AUTOMATED CENTRIFUGE Filed May 15, 1972 8 Sheets-Sheet 2 FIG. 2d FllG. 2c

July 30, 1974 5, NATELSQN 3,826,622

CONTAINERS FOR USE IN AN AUI'OMATED CENTRIFUGE Filed May 15. 1972 l e Smeets-Sheet s LOADING STATION FIG. 5

MW 30, 1974 s. NATELSON $526,622

CONTAINERS FOR USE I AN AUTOMATED CENTRIFUGE 8 Sheets-Sheet 4 Filed May 15. 1972 s. NATELSON 3,826,622

CONTAINERS FOR USE IN AN AUTOMATED GENTRIFUGE July 30, 1974 8 Sheets-Sheet 5 Filed May 15. 1972 s. NATELSON 3,826,622

CONTAINERS FOR USE IN AN AUTOMATED CENTRIFUGE July 30, 1974 8 Sheets-Sheet 6 Filed May l5, 1972 FIG. 6

FIG. 7b

n.Fully 30, 19M s. NATELSON 3,826,622

CONTAINERS FOR USE IN AN AUTOMATED CENTRIFUGE Filed May l5, 1972 8 Sheets-Sheet '7 FIG. 7e

8 Sheets-Sheet 8 5. NATELSON July 30, 1974 CONTAINERS FOR USE IN AN AUTOMATED CENTRIFUGE Filed May l5. 1972 OZ UD gUnited States .Patent 4O CONTAINERS FOR USE IN AN AUTOMATED `Samuel Natelson, Chicago, Ill.,I assiguor to Rohe i l'Scientific'Corporation;"Sauta-Ana, Calif.

Continuation-impart of application Ser. No. 845,992, July Blk-11969, now vPatent'No. 3,722,790. This application May 15, 1972, Ser. No. 253,167 1- U.S. Cl. 23--259 This yapplication is a continuation-in-part of patent application ;Ser. -fNo.-845j,992, 'filed July 30, 1969, now U.S. Pat. 3,722,790.

INVENTION The present invention relates to an automated clinical labgratoryQ-and morelpbarticularlyY toan automated clinical laboratory system wherein samples can be rapidly and efectively. processetknotwithstandingv the fact that the workload of samples processed varies considerably over Werking pertuis-l 'if Numerous attempts have been made to design a laboratory whereblood or,` urine,,or sor ne other biological uid can be processed automatically,v No l.complete system has been; developed: Fonfcxample, -for v`many Chemical determinations. asamplepffserzum needs t to be prepared from the blood. The blood is then centrifuged and the serum sampledrfflhe'.prqcessof placing .l a`rge numbers of tubes in a centrifuge, waiting furthev centrifuge to accelerate, operatingfat.,highfspeedsfand then coming to rest, usually takesapprpximatelyy2030minutesr To this rnust be added the timerequiredl to load ,the` centrifuge and unload it.

`Once the serum is obtained, th automatic instrument isalaaded. Sometcommercialtinstruments do not have the capability of removing proteins. The numberA of tests that can be performed AiS'.thenflinited, ltoythose where protein does not interfere. Other instruments remove protein by` aqdlirlig'a-Y` protein.,pgipitatingreagent and filtering. |In this case a large sample is needed and only a small portion ofthe 'filtrate-is:-obtained. Others-systems remove protein by dialysis; ltlithese.c ases,=only` asmall percentage of the ingredient being tested dialyzes through, 'limiting the sensitivitytand' accuracyi'of. the procedura so that now methodology hasgtov be Afound to; fit the` instrument. In many cases, compromise" has to' bemade with accuracy inventionf solyes K tllese4 problems, making t .automated laboratoryv using con,- A ,A It` .permits the ,processing of the etedff, mithefpatient directly withoutfpref treatmentior 'handlmg. :Itlrreadilypermits any number Ot analysant/beneietmsdeutamatically and the. results ha-rts vdepending upon the togfseparate-redi-cells.fromblood automatically and remove` they serum' 'fro'mfsaid c'.e`lls.1 It? alsoypermits the automatic 'ice precipitation of proteins and their removal by automatic centrifugation.

Before describing the system herein contemplated, it is lirst necessary to see what tests the system is to perform, and, since the system contemplated is particularly useful for processing blood samples, the tests relating to blood will be described.

It goes lwithout saying that for some tests this apparatus is not required. Such blood tests have been described in the Natelson, U.S. Pat. No. 3,260,413. In the tests performed by the system of the present invention the sample cannot be processed in the manner described in the aforesaid Natelson, U.S. Pat. No. 3,260,413 without rst separating some of the components in the sample.

The overall procedure can be. described as follows:

After separating serum or plasma from the cells, one samples the separated serum with an autodilutor. This is an instrument which samples the serum and ejects it with a reagent or diluent. Autodilutors, of varying design, are available commercially.

After separating the serum from the cells, a series of samples can be taken from the serum and processed to (a) Glucose, by heating with alkaline determine the various components. In some cases, the autodilutor adds a protein precipitant. The mixture is then centrifuged, and an aliquot is taken from the supernatent, by an autodilutor. Various reagents are added to produce a color so as to assay the various components.

Thus, one can see that with an automatic centrifuge the technician places the blood sample, contained in a special container hereinafter described, into a holder called a trunnion cup. The sample, eg., blood, is centrifuged automatically. The centrifuged blood moves down a line on a belt Where autodilutors lremove samples t0 do diierent tests. In some cases, no further reagent need be added and the diluted serum is assayed directly. In other cases, a sequence of sampling, centrifuging and further sampling is done. Examples of the various types of components of blood which can be analyzed by a general system of the type described, are listed below.

(I) TESTS WHERE NO` PROTEIN NEEDS TO BE REMOVED FROM THE SE'RUM [n these cases, after passing the automatic centrifuge, the separated serum is sampled andprocessed as indicated.

(a) Proteinserum sampled, biuret reagent added and (e) Oxygen and nitrogen-serum sample taken and4 processed in a gas chromatograph. (f) Ca and Mg-diluted serum aspirated into an automatic absorption instrument.

(I'I) TESTS FOR COMPONENTS WHERE PROT-EIN 1 .IS PRECIPITATED BEFORE ADDING TI-IE COLOR DEVELOPING REAGENTS f Copper, reagent. (b) Urea, by the diacetyl reaction. (c) Creatine,.by alkaline picric acid.

(d) Uric acid, by reduction of phosphotungstic acid.

1 (III) ENZYME TESTS color or a protein precipitant is added. The samples are centrifuged and then reagents are added' for purposes of identification of the products.

The data accumulated at various stations can be accumulated on a tape and fed into a print out device which can supply the data in the form desired with conventional instruments. A panel, with proper keys, can guide the speciment through the system. For example, if only sugar determination is desired on the sample, then activation of this key will make inoperative all sampling positions except that for sugar. On the other hand, if all tests are desired, pressing the proper key will activate all stations for the sample.

From the foregoing description, it will be noted that present technology permits the carrying out of many of the steps described. However, one step cannot be carried out. That step is the automatic centrifuging of the sample y in a continuous manner. The problem is to centrifuge the sample and have it move out of the centrifugal field. In order to perform this task one can conceive of an instrument which would perform the following steps mechanically.

(1) Place a tube in a centrifuge.

(2) Slowly accelerate the specimen to running speed (e.g.,

3000 r.p.m.).

(3) Run the rotor at top speed for ten minutes.

`(4) Decelerate the rotor.

(5) Remove the specimen from the rotor.

While there would be no diiculty in designing such an instrument with present technology, the problem is that such a cycle would take 30 minutes and specimens would be available at two per hour. If a large number of specimens were available, such an instrument would load, for example, 60 specimens, go through the cycle and at the end of say 45 minutes have all 60 unloaded. Unfortunately, laboratories are faced with the complex problem of having at some times only one specimen and at others as much as 300. The problem is to provide an instrument which will process the samples sequentially. Under such a system, the samples would be loaded at one per 30 seconds and unloading at one every 30 seconds. One would wait 20 minutes for the first specimen, but subsequently they would be leaving at 120 per hour so that after a delay of 20 minutes the analytical results would be available at 120 blood samples per hour with as many as 40 results on each blood sample.

The problem is further complicated by the fact that blood is often talken with heparin, in which case the blood does not clot. On centrifuging, the packed cells are relatively loose. Further, if the serum is allowed to remain in contact with the cells for any length of time, diusion of, for example, potassium ion from the cell (concentration 90 meq./l.) into the plasma (concentration 5 meq./l.) destroys the value of the determination. Glycolysis going on in the cell also metabolizes the glucose in the plasma, Alowering the result. This requires that the centrifuge operation -be done not once but twice. The blood is centrifuged, the serum is poured off, recentrifuged and poured off again to remove all cells.

If the blood is clotted, the cells will pack more efficiently and sometimes it is possible to -pour off clear serum, if one is willing to sacrifice some serum over the clot.

From the foregoing description, it is quite apparent that the bottleneck in any completely automated system is in the centrifuging step. This invention solves this problem. This invention'describes a practical procedure and instrumentation for continuously centrifuging samples in sequence at a rapid rate.

The invention as well ,as the objects and advantages thereof will become more apparent from the following detailed description when taken together with the accompanying drawings, in which:

FIG. l is a schematic and block diagram .of the system contemplated herein;

FIG. 2a is a perspective view ofone type of sample container contemplated herein;

FIG. 2b is a side view of the sample in FIG. 2a;

FIG. 2c shows a side view of another tainer contemplated herein; l

FIG. 2d illustrates a side view of still anothervtype ,of container contemplated herein; v

FIG. 2e shows a perspective view of yet another typev of container contemplated herein; l l

FIG. 2f is a side view of the container shown in FIG. 2e;

FIG. 2g is an illustration of the action that takes place container depicted type of conwithin the container shown in FIG. 2a while that con-v tainer is in operation;

FIG. 2h is an illustration of the action that takes place in the container shown in FIG. 2a`after the operation illustrated in FIG. 2g; t

FIG. 2i is an illustration of-anotherY container contemplated herein;

FIG. 3 is a longitudinal perspective vievvof an appartus contemplated herein to perform the systemv shown in FIG. l;

FIG. 3a shows an enlarged perspective view of a portion of FIG. 3; FIG. 3b is a perspective view similar to FIG. 3a showing a slightly modified arrangement;

FIG. 3c is a cross-sectional view of a portionof the apparatus shown in FIG. 3;

FIG. 4 is a perspective explanation of a terminal station of an apparatus contemplatedl herein; Y

FIG. 5 is a schematic and block electrical circuit diagram used in connection with the terminal station shown in FIG. 4;

FIG. 6 is a side view of another embodiment of the apparatus contemplated herein;

FIG. 7 shows a variation of the` drive arrangement; FIG. 7a is a side view of still another embodiment of the apparatus contemplated herein using the drive arrangement of FIG. 7;

FIG. 7b is a cross-sectional view of the apparatus shown in FIG. 7a;

FIG. 7c is a perspective illustration of a variation of the concept shown in FIG. 7a;

FIG. 7d presents yet another shown in FIG. 7a; =FIG. 7e is a partly perspective and partially sectional view of an apparatus embodying the concepts depicted in FIGS. 7a to 7d; and l FIG. 8 is a similar view of `an actualapparatus.

variation of the conceptl for an automatic and continuous centrifuging operation which will provide each separate samplewith the required work period without stopping between operations and"v furthermore provide a sequential system so that one or many samples may be rapidly andseqti'entially loaded atY one end of the apparatus and unloaded at the'lother. A schematic and block diagram of the Vsystem is illustrated in FIG. l'which shows an apparatus 100having a revolving line 102 driven by turning means V104 and supported by a driven element 106. The revolving? line 102 i is designed to hold a sample container 108. The sample"- container is rotatable and has axed thereto a rotator 110. This sample container will be mounted on the rotating line 102 and carried along a path of travel having one or more work stations. One of these work stations willbe the centrifuging -field and will have rotator turning means 112 which lwill cause the rotator 110 to turn so as to centrifuge any liquid in the container. After the centrifuge station there will be a sample container unloading station 114 where the sample containers are unloaded andcarried to other work stations.

The Containers FIG. 2a is the design of a collecting sample container useful for the purposes of the present invention. FIG. 2a shows a top-shaped round container with a central disc-shaped section 17 which may be called the side chamber. It will be seen that a neck 19 is provided which can be stoppered so that the container can be evacuated. By using a double needle, one inserted in the vein of a patient and the other through a rubber stopper, blood will be aspirated into the container. These containers substitute for and are used in lieu of test tubes with the ability to act as vacuum containers. As an alternative, the blood from the patient can be placed directly in the container from a syringe and the container can be stoppered. The containers 15 can be described as top-shaped with a a'nged neck 19, a barrel-shaped center 21, a side chamber defined by a central disc 17, a narrowing bottom 23, a cylindrical section Z5 to hold the container, with inner bottom depressions 27 to serve as holding or spinning means.

The container shown in FIGS. 2a and 2b is designed to hold 5 ml. of blood. These can be made in any size. They may or may not contain an anticoagulant.

l If the container shown in FIG. 2a is spun around ifs vertical axis, the blood is driven laterally by centrifugal forces taking the position shown in lFIG. 2g. When spinning stops the serum or plasma will slide down taking the position shown in FIG. 2h. The heavier cells, with or without the clot, will be driven into the side chamber, i.e., disc like section. The disc portion has a narrow orifice of theorder of 2-3 mm. By means of its design, it can be made to hold a volume somewhat larger than the volume of the erythrocytes.

l The volume of a cylinder is given by vrrzh. If one subtracts the volume of the inner cylindrical ring from the outer cylindrical disc, one obtains the volume held by the disc. If h is the height of the disc, R the total disc radius and r the radius of the inner ring, this volume would be -rrR2h- 1rr2h, or vrh(R2-'r2). In FIGS. 2b and 2a, the volume held in the side container would be 3 ml. for a 0.3 mm. height and a 1.5 cm. distance shown. This means that 3 ml. of the blood Would be in this chamber and the remainder outside. When the`rotation stops, the serum or `plasma will slide to the bottom of the container leaving the cells with a small amount of serum or plasma in the side chamber and cell free serum or plasma at the bottom of the container. This is so because of the well known phenomenon that if water is placed in a tube sealed at oneY end, and with a narrow orifice, then inverting the tube will cause no liquid to ow out because it is held in by air pressure. This principle is used in perfume bottles and hairtonic bottles. One must shake vigorously to obtain some iiow out of the bottle.

The design of the container can take the form of FIG. 2c showing a container 15a with the side chamber having knob-like wings 17a in which case a large volume can collect in the` side chamber without making the container orifice unduly wide.

Other shapes are also possible and one is shown in FIG. 2d showing a container 15b with large wings 17b. It is also advantageous to use the configuration shown in FIGS. 2c and 2f with inclined wings 17o. The container with the conguration shown in FIGS. 2e and 2f have the advantage that a narrow orifice to the side chamber is unnecessary. When the container stops spinning, the erythrocytes will remain in the side chamber held by gravity. This is particularly useful where larger volumes are used.

When spinning, the device shown in FIG. 2a will drive the cells 29 into the outer disc (FIG. 2g). AThe cell free serum or plasma 31 will then fall free when the spinning stops leaving the cell behind in the disc (FIG. 2h).

In subsequent operations, where a protein precipitant is added to the serum, the precipitate has strong coherence; In this case, a design such as FIG. 2d can be used. If spun at 12,000 r.p.m. this precipitate will collect in the corners of wings 17b and pack. On stopping the rotation the centrifugate will drop to the bottom, the precipitate adhering to the corners.

The type of container shown in FIGS. 2a to 2h has an additional advantage. If these containers are used in subsequent sampling there is no danger of picking up the cells in the pipette since they are locked in the side chamber. This is a serious problem in sampling fromtest tubes. Further, when returning serum to the test tubes, the cells are stirred up and the tube needs to be recentrifuged. This is avoided in the container of FIGS. 2a, 2c and 2e. The advantages of such containers may then be summarized as follows:

(l) The tube may be spun to separate the cells from clotted or unclotted blood.

(2) The cells are separated into a separate compartment.

(3) The serum or plasma is isolated from the cells and components are therefore more stable.

(4) Sampling from the container is done without fear of cell contamination.

(5) Serum or plasma may be returned to the container without stirring up the cells.

In eifect, the container becomes a serum or plasma separator. Since blood contains, usually from 35-47% of erythrocytes, by removing 60%, one is assured of removal of all the cells. From 5 m1., 2 ml. of clear serum or plasma is thus obtained. This is approximately what is obtained with conventional techniques.

The containers of FIGS. 2a-2h then permit the design of a continuous centrifuge system. One form of this invention can Ibe seen in FIG. 3. The objective is to rotate the cups in a sequential fashion. Each cup needs to be rotated for at least 5-10 minutes. If it is desired to have them delivered at the rate of one every 30 seconds and spin each for tive minutes, then ten cups must be spinning at the same time.

In some cases, it is not necessary to remove the serum from the clot, after centrifugation. In this case, a simpler design can be used for the cup. This takes the form of a small Erlenmeyer flask in whichthe bottom has been pushed up so as to create a side chamber, disposed laterally at the bottom of the container. In this case, after centrifugation, the clot moves into the side chambers leaving the serum above it.

Thus, the containers contemplated herein for use in an automated centrifugal arrangement are so constructed as to be rotatable about a substantially vertical axis and have a flanged neck, a center portion, a sidechamber at least partially surrounding the center and a narrowing bottom. The ilanged neck forms a cylinder suitable for insertion of a stopper with an upper wall continuous with the neck at the lower end of the cylinder, the upper wall making an angle greater than with the neck. `The `upper wall meets and is continuous with a lower wall so that the side chamber of the container is formed between portions of the upper and lower walls at least partially surrounding the central axis. The container will have holding means for firmly holding it in a rotating trunnion cup. The container may take several shapes, e.g., the side chamber may be disc-shaped, have a pushed-up bottom,

and may also include "'a crest-like junction 4"downwards into said'si'de chamber. 1 1r 'The "cups" shown in -FIGS.' 2a-2hV show? the Aside cham'- bers-to'be"'at1diiferent angles. The rate'v of 'settling will-bc affected by the angle the walls make with the horizontal. As 'thecups4 rotate ontheir'rcentral axis the solid particles movel outward and 'if the vwall is vertical, 'would reach th'ei-'wall land 'stay there. There would be no downward component' ofthe forcef When the wall is at an angle, the reaction" of the walltonthe'particle tends to drive it back ina-motion perpendicular vto the wall. This motion may be' divided-into ahorizontal or remixing component and a downward component. If the wall is at 45 to the base, then both components are equal. If the angle is substantially greater than-.60 the downward component is small and a long time will be needed for settling. In order to achieve a compromise between excessive width to the container and minimal mixing on decelerating, an angle of approximately 57 is suitable for practical purposes.

The Processing Apparatus Friction Drive In FIG. 3 is shown an apparatus 33 for rotating the containers 15. The drive apparatus 33 has a large sprocket 35, driven by a small sprocket 37, by means of a chain 39. Mounted on the chain 39 are a plurality of C-shaped brackets 41 as shown in FIG. 3a or box-like brackets as shown in FIG. 3b, having upperand lower ball bearing apertures 43, 45 holding therein a flexible rod 47 disposed normal to the chain, i.e., the chain moves horizontally and the rods are disposed vertically at the bottom of each rodwis an outwardly tapered rotor 49 while at the top is an open trunnion cup 51. The chain 39 is engaged by the sprockets 35,l 37 and rotates slowly in the horizontal plane driven by motor 65. At the sample loading station 53 the containers e.g., those shown in FIGS. 2a-2h are loaded on the trunnion cups.

The chain is driven by a motor 57a which rotates slowly. This turns the sprocket 37 which turns the larger sprocket 35. The large sprocket 35 is pinned on an axle 36. This motion serves to Ibring the assembly of the container 15H, the trunnion cup 51, its shaft 47 and a small rotor 49 around the large sprocket 35. As this assembly approaches the sprocket, the small rotor 49 engages the friction disc 61-which is moving at high speed driven by motor 57. Since, as it approaches, it gradually makes contact 'with this disc, the rotors 49 engage slowly, and are accelerated until they reach top speed as they move around the friction disc 63. This rotation will continue during the travel of the container 15 around the large sprocket 35. After the cups leave the spinning area, they idle, slowing down gradually. They are then removed to a belt line for further processing such as in a system of the type described.

Thus, the containers 15 are placed in trunnion cup 51, i.e., in holders. Each container has two little recesses 27 on the bottom (FIG. 2b) which t into two corresponding nipples in the trunnion cup holders. The edges of the trunnion cup are exible on the end so that when the cup is inserted, it clips over the edge serving to hold it in place. These trunnion cups 51 are mounted on the chain through the bracket 41 and ball bearings 43, 45. The rod 47` supporting the' cup in somewhat 4ilexible so as to take advantage of the self-balancing principle well known to 'operators of high speed centrifuges or even laundry centrifuges. `At the bottom of the rod is thefrotor 49 which is rubber edged. This edge is bevelled in such-a way so that lifting of t-he centrifuge motor 57 and friction disc attached, will make contact. This permits adjustment so that all small rotors make contact and are still not too tight.

As-the friction disc 61 spins, it causes the small rotor 49 to spin under each cup. In one model, the friction disc was seven inches across and t-he small rotor was one inch across, the ratio of circumferences is approximately 21:3, o r sevenrto one. This is an advantage since 8 the centrifugal 'motor 57 need not spin-as rapidly-.f-Tlhe higher" the speed of centrifugin'g,the faster rwill'th'e Vred cells settle. In one application the friction fdisc'vwas moved atv 2000 r.p.m. causing the small rotor to spin at 14,000: r.p.m.'lf the' frictiondisc "i's'spunf'at '51000 r.p.m.', then the small rotor moves at 7000l r.p.m. Even at the lower speed the cells are separated inten minutes. The chain is rotated slowly by a second motor :65.1This motor is a slow gear motor moving counter 'to the-ro tation of the centrifugal motor. This moves the'specimens into and out of the centrifugal eld. This gear motors speed is adjustable since the time required for separation of various precipitates is variable andin certain applications more or less time is required. i

The chain encompasses Vs of the large sprocket. Thus 3A; 21=approx. 15 inches is available for the centrifugal operation. Since the center of each specimen is a 3 inch distance from its neighbor, the model could simultaneously spin 5 specimens. If it is desired` to have each specimen to be in the centrifugal eld forten minutes, this means that the large sprocket mustmove 3/s of its circumference in ten minutes, or one rotation inV` 14 minutes. The model with this setting delivers a centrifuged specimen every two minutes.l The. rate of specimen deli-very can be increased by increasing the size of the large rotor or decreasing the centrifuging time. The latter is achieved by increasing the speed of the centrifugal motor. Rotors as large as l0 inches across havebeen found quite practicable. Speeds up to 3600 r.p.m. of the centrifugal rotor are also practicable. The rotors are made preferably of aluminum. A silicone rubber'belt emcompasses the rotor to provide the necessary friction drive. If the rotors are rubber edged, the friction'disc need not be and still maintains adequate friction for spinrnng.

After the sample has spun, the sample can be remove by hand. As a table top centrifuge, for a few specimens, the operator adds a few samples and sets the machine to automatic stop. When the last sample exits, the instrument stops and the operator can pick up his specimens.

The engagement between the friction disc 61 and the small rotor used to turn the trunnion cup 51 may perhaps best be understood from FIGS. 3b and 3c. In this lfigure, the motor 57 drives the friction disc 61 having a hard silicone rubber wall 63a. Disposed for rotation above rotor drive disc 61 is a chain 39 held by` a large sprocket 35 which engages chain 39. Mounted on the outside of the chain 39 is a bearing unit 41a similar to the one shown in FIG. 3a. This bearing unit 41a holds a flexible shaft or rod 47 having a trunnion cup 51 on top which holds the container 15, and, a small rotor 49a made of metal with a rubber wall `65. The side of the rubber wall 65 is inclined and will dovetail alongside of the adjacent silicone wall 63a. .l

At the end of the run, a transfer device for removing the sample from the automatic centrifuge and transferring it to a belt line is necessary. A device with some similar elements has already been described in the Samuel Natelson U.S. Pat. No. 3,331,665, and the device required is shown in FIG. 4.

A clamp A67 which resembles in appearance that of a spring clothes pin rotates in a circle. A cam 69 operated by a cam motor 70 rotates to lift and lower a rod 71 having a gear 72 thereon. The rod moves in a thrust bearing 72a which is fixed `in place. This gear 72 is engaged by a 1A thick driver gear 74. Gear 72 is 111/2" in thickness so that the rod can be lifted without disengaging from gear 72. Gear 74 is operated by a turn motor 76. The clamp is 3 inches in length from jaw to axis so that it moves in a six inch circle. When operated in conjunction with the automatic centrifuge, motor 65 operating the sprocket of the centrifuge stops when clamp is positioned over the sample container, and turn motor 76 also stops. A solenoid 79 with an armature 81l is activated and the clamp 67 is lowered bythe cam over 9 thel neck 19 of the'container 15. `rThe solenoid is deactivatedandzthe conatiner is clamped. .T he cam now raises the rod. sol thatY the container clears the trunnion cup 51. Motor. 65 andgturn motor v'76.;are reactivated and the lclamp continues its-rotation carrying the container in 4the clamp, to a position overa belt line 83 driven by a belt-motor 85; `Whenthe. clamp. is positioned over the belt line,:;.the. belt-.line motor .85 stops as well as turn Imotor 76.l The cam: lowers the container into a container holder87; The solenoid isreactivated releasing the containeriThe cam raises the clamp. Turn motor 76 and belt'motor :85 are reactivated and the cycle is repeated.

The positioning of the clamp above the centrifuge holder and belt holder iscontrolled by two light and photocell assemblies-which control two timer switches. .Theftimer `arrangement 90 is shown in FIG. 5. Referring to FIG. 5, movement of the chain of FIG. 4 between light f9.2. and photocell 94 closes a photoswitch 96. When photoswitch` 96 is closed, relayv 98 closes. This activates timer motor 122a which moves from stop to a pin 122 whichj has a iiag.1'I'his delivers current to motor 76, which startslto` run. Whenrelay was depressed with switch closed; the motor stopped because `a rst circuit a was interruptedaThe turn lmotor 76 could not run forthe time 'period that :the flag was travelling. When theV pin Ais finally-closed (after 8seconds) bypass is provided vthrough. a circuit b which originates behind the photo'switch'f.v The turnmotor176.operating rotation rod 72 Ystarts andirnoves'the clamparound and out of the field .of the photoswitch. The photoswitch opens and relayV 98-isv1inactivated reactivating circuit a. Current to theftimer motorv122a isl interrupted and the tiag flips backto flag stop. The cycle is then: repeated. r@When turnmo`tor76::is `:activated a second motor M can be attached in parallel. Thus when turn motor 76 is running so does motor M` `when yturn motor 76 stops so does motor M'. Thusthe automatic-centrifuge stops when the clamp is positioned overthe specimen. A third mofor can 'also be attachedto' `the 'arrangement so that when the clamp AinterruptsV the "second photoswitch positioned above' abeltmovingthe specimens, the movement of the belt 'stopsLThi's permits Vthe container to be deposited in the cup. In actual .practice it is preferable to have two independent systems. lOne stops and starts the automatic centrifuge. The otherl starts and stops the belt. In both cases the clamp holding the container stops at each station at the time that station isnot moving. TheY instrument hereinbefore described operates in the Acircular mode. The operation can be in the linear mode. This is shown in FIG. 6 showing a belt 123 driven by gears 125 in FIG. 7a showing a chain 120 driven by gears. These gears are activated by motor and pulley attachment 12:1. This chain 120 rotates in the vertical plane, and has a series of bearings 124 holding shafts 126 therein. The outer ends of shafts 126 have trunnion cups 128 to hold a container 15. The lower end of the shaft has a rotor member 130 similar to the small rotor 49 of FIG. 3a. Alongside chain 120 is a plastic friction belt 132 rotating in the horizontal plane driven by a motor 134. Chain 120 runs at high speeds spinning the containers 15 supported on trunnion cups. The container is first placed in the cup. It then moves across until the rotor engages the plastic belt 132 which is driven by the centrifugal motor 134. This causes the rotor to spin. As it moves falong, it moves out of the centrifugal field. The container slows down and stops spinning. The container is then removed by the device shown in FIGS. 4 and 5. The holder now moves below the belt. The gears 122 are four inches in diameter so that as the trunnion cups move below the belt, clearance is allowed for the rotors. In the inverted position, they clear the plastic belt so they are not spun.

In both the circular and horizontal mode contact between the rotor of the trunnion cup and centrifugal rotor or belt is made slowly and gradually so that the cup starts to spin at a lesser speed due to slippage. As it l0 moves on, firmer contact is made.. This has the effect of gradually accelerating the containers and avoids splashing.

The Processing Apparatus Gas Drive The containers shown in FIG. 6 may also be spun by compressed air as shown in FIGS. 7a, 7b,'7c. The arrangement shown in FIG. 7a is similar to FIG. 6 but the belt 132 and motor 134 are removed. The belt is replaced with a source of compressed air. The rotors are replaced by turbines to spin as the air flows across them. These air driven turbines consists of a housing cage 152 holding a plurality of curved radial vanes 154. The curvature of the vanes will determine the direction of rotation of the shaft 126. At the side of turbine 150 is an air supply 156 consisting of a rectangular box-like outlet 158 fed by air, with a plurality of parallel partitions to guide the air ow. As the turbine approaches the air supply 156 it starts to rotate and continues to rotate well past the air supply 156. The container 15 is removed at the end of the run by the device of FIG. 4 while the trunnion cup 128 and shaft 126 pass under the air supply. The turbine is at the center of the belt and clears the axle connecting the gears driving the belt.

The instrument of FIG. 3 can also be modified to spin the cups by compressed air. In this case, the friction drive 61 and motor 57 (shown in FIG.. 3c) are removed and replaced by the arrangement shown in FIG. 7c. The small rotors 49 are replaced with fan blades or turbines 147. A source of compressed air 156a blows over the turbines while they are in the centrifugal field. In this mode, the trunnion cups are not turned over.. The compressed air is released from radial chambers 157:1 defined in a horizontally disposed drum 157.' The centrifugal field may be defined by blocking oif some of the chambers by a blank 15711.

As a variation of this design, the drum delivering the compressed air can rotate. This is shown in FIG. 7d. The drum 159 delivering the compressed air is fed by a compressed air supply 156b. The `drum 159 is mounted on a sleeve 156e which rotates while feeding air out of the drum through nozzles 159a. The centrifugal field is again defined this time by a shoe 159b.

In carrying the foregoing concepts into practice, the embodiment depicted in FIG. 7e is equite useful. The compressed air supply is fed through a rotating central system into passages 160 which carry the compressed air to a position under the turbine where it is blown at the turbine byy a vertical passage 162. The travel path of the apparatus is in the horizontalplane as shown in FIG. 3. The drive is by means of a chain 239a driven by a sprocket arrangement, part'of the arrangement of sprockets 235 being shown in FIG. 7e driving the chain. Held by the chain is a bracket type bearing arrangement 241 holding a tubine 250 at the bottom and a trunnion cup 251 over the bearing arrangement so that the compressed air coming out of vertical passage 162 will hit the turbine 250 and turn the trunnion cup 251. Mounted in the trunnion cup 251 is a centrifugal cup lock 253. The container 15 is placed in the trunnion cup 251 and as long as it is not spinning, the cup lock 253 will not latch onto the container 15. However, the cup lock 253 is formed of an engaging portion and a heavy tail and is pivoted towards the engaging portion. As the trunnion cup starts to spin, the heavy tail will tend to fly outwardly pushing the engaging portion against the container 15 held in the trunnion cup. The engaging portion will engage a flange or indentation and hold the container tight. When the spinning stops, the engaging portion will release and allow the container to be removed.

The automated centrifuge may also be used as an automated micro hematocrit centrifuge. In this case, capillaries containing blood are disposed in recesses on a plate supported on spinners. Rotation drives the red cells to the bottom of the capillaries and the hematocrit may then be measured when the carriers emerge from the centri- 1 1 fuge. Another application is a micro centrifuge. In this case, a plate with holes angularly bored on the plate spins on the rotors. Small plastic test tubes are driven to the bottom as the spinners pass through the automated centrifuge.

A variation of the instrument shown in FIG. 8 which eliminates the use of a chain uses a metal disc 802. The supports for the trunnion cup 804, 806, and fan assembly 808, are mounted at the periphery of this metal disc 802. The metal disc 802 is rotated slowly by means of a gearmotor or belt drive assembly from below or above the dise. Compressed air from an air inlet 810 and air passages 811 blows across the fans during their travel over a/s of the circumference of the disc. The trunnion cups 804 and containers 815 contained therein rotate at high speed as they pass the compressed air area. They then slow down, their rotation being damped by the spinning blades in air, and come to rest when they move out of the air jet llow area. In this mode the trunnion cup assembly moves in a circle.

The turbine and jet assembly is also practical in this arrangement. The jets come from a series of pipes radially disposed from the central disc which rotates and moves along with the fans maintaining their relative position. When these turbine assemblies have moved through 1% of the circle, the air jet ow in the pipe activating them is interrupted so that the rotation ceases and the cups can be removed. The containers are held by a centrifugal lock 817 having an inwardly biased spring 819 and a locking piece 820. The extent of the centrifugal work field may be defined by an air cut off shoe 822.

What is claimed is:

1. A small milliliters quantity container for use in an automated centrifuge apparatus comprising: means for being grasped for transport comprising a anged neck portion, a barrel-shaped center portion, a side chamber at least partially surrounding said barrel-shaped center portion, a narrowing bottom portion, and, means for being releasably held for rotation about a vertical axis through said neck portion and said bottom portion.

2. A container as claimed in claim 1 wherein said side chamber is disc-shaped.

3. A container as claimed in claim 1 wherein said side chamber is knob-shaped.

4. A container as claimed in claim 1, said side chamber including a crest-like junction with said barrel-shaped center whereby uid moving out by centrifuging action from said center flows over said crest-like junction downwards into said side chamber.

5. A small millilite'r's quantity 'container for use in an automated centrifuge whereby said container may berotated on its substantially vertical axis so as to separate materials of different density which comprises, means for being grasped for transport comprising a anged neck forming generally a cylinder around said vertical axis, an upper wall continuous with said neck at the lower end of the cylinder, said upper wall making an angle greater than degrees with said cylinder, said upper wall havinga section meeting and continuous with a lower wall so that said container is formed with a side chamber between portions of said upper and lowerwall at least partially surrounding said central axis.

6. A container as claimed in claim 5, including bottom holding means for holding firmly said container in a trunnion cup on a centrifuge apparatus during .its rotation on its axis.

7. A container as claimed in claim 5, wherein theupper and lower walls are substantially parallel to each other in the section forming the side chamber. t

8. A container as claimed in claim 5, wherein a depression is formed in the center of the lower wall to forma center compartment and a crestlike junction between said center compartment and said. side chamber, so that iluid moving out of said center compartment, byrcentrifugal force, flows over said crestlike junction into said side chamber so that ondeceleration, separation is maintained between the components separated by the centrifugal process.

9. A container as claimed in claim 1 wherein said con` tainer comprises a generally continuous thin wall container;

10. A container as claimed in claim 4 wherein said container comprises a generally continuous thin wall container.

11. A container as claimed in clairn'S, wherein said container comprises a generally continuous thin wall container.

References Cited UNITED STATES PATENTS Shapiro 23-25 3 MORRIS O. WOLK, Primary Examiner T. W. HAGAN, Assistant Examiner us. c1. xn. 23492

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