Automatic serum preparation station

Abstract

A centrifuge apparatus for centrifugally separating the lighter components of a sample mixture from its heavier components is disclosed. The apparatus includes a centrifuge drum having vertically aligned separation and aspiration chambers separated by a common wall having valve means therein for connecting the two chambers. The separation chamber has a truncated conical side wall with a larger diameter trap portion located at the base thereof. A motor is included for spinning the centrifuge drum to force the heavier components into the transportion while the lighter components are forced up the conical side wall. A trigger mechanism opens the valve means to pass the lighter components through the common wall into the aspiration chamber while the centrifuge drum is spinning, closing the valve means when the rate at which the centrifuge drum is spinning falls below a desired level. An automatic sample loading mechanism is also provided which utilizes centrifugal forces to load a sample into the separation chamber of the centrifuge drum.

Parent Case Text

This is a division of application Ser. No. 351,631, filed Apr. 16, 1973 now U.S. Pat. No. 3,838,809.

Description

BACKGROUND OF THE INVENTION

The present invention relates generally to centrifugal separation of liquids and more particularly to an apparatus for automatically separating the serum, or plasma, from a whole blood sample for subsequent biochemical analysis.

Reference may be made to the following U.S. Pat. Nos.: 3,586,484; 3,439,871; 3,228,595; 3,211,368; 3,190,547; 3,161,593; 3,129,175; 2,948,462; 2,940,662; 2,906,453; 2,906,452; 2,906,451; 2,906,450; 2,822,315; 2,822,126; 621,706; 436,419; 360,342 and 241,172.

The modern medical research and diagnosic techniques in use today commonly rely on the analysis of blood samples. Whole blood, however, comprises a variety of immiscible components (e.g., the red cells, the white cells and the platelets) suspended in a colloidal serum, or plasma. Often, however, the analysis must be performed solely on the plasma so that the immiscible components are not present to alter or mask the characteristics to be observed.

In spite of the advent in recent years of many automatic and semiautomatic clinical chemistry analyzers, blood processing techniques have remained unchanged and time consuming. The present centrifugal separation technique commonly used for processing whole blood to serum or plasma (heparinized serum) requires the following steps:

1. Collecting a whole blood sample in a test tube;

2. removing the stopper from the test tube;

3. rimming the specimen with a stirring rod;

4. "balancing" the test tube (geometrically and symmetrically) in a centrifuge;

5. centrifuging the test tube for 10 minutes at a relative centrifugal force (RCF) of 850 to 1,000;

6. decanting or aspirating the serum into a serum container; and

7. transporting the serum to an analyzer station.

While this technique is commonly used to process blood samples, it requires approximately 30 minutes to process a single sample. Thus, this technique is ill-suited for use in modern automated laboratories capable of analyzing up to 120 blood samples per hour.

"Batch" centrifuging has been utilized to process a plurality of blood samples simultaneously. However, successive batches may not contain the same number of samples, and accordingly, the centrifuge should be rebalanced after each batch to prevent vibrations which might damage the centrifuge. Moreover, the batch size (i.e., the number of samples in a batch) is limited because the plasma should be decanted or aspirated as soon as possible after the centrifuge is stopped, or the immiscible components will re-diffuse into the plasma.

Accordingly, complex mechanical devices have been devised to automatically separate the serum or plasma from whole blood. However, the systems heretofore devised have generally been so mechanically complex and expensive that their use has been limited.

SUMMARY OF THE INVENTION

According to the present invention, there is provided a centrifuge apparatus for centrifugally separating a sample mixture into its lighter and heavier components. The apparatus comprises a centrifugal drum having a separation chamber and an aspiration chamber positioned directly thereabove, the chambers being separated by a common wall having valve means connecting the separation chamber and the aspiration chamber. The separation chamber has a truncated conical side wall with a larger diameter trap portion located at the base thereof. A motor is provided for spinning the centrifuge drum to force the heavier components into the trap portion while the lighter components are forced up the conical side wall. A trigger mechanism opens the valve means to pass the lighter components through the common wall while the centrifuge drum is spinning, closing the valve means when the rate at which the centrifuge drum is spinning falls below a desired level.

The centrifuge apparatus further includes an automatic sample loading mechanism for loading a sample into the separation chamber of the centrifuge drum through an aperture in its bottom end. The automatic sample loading mechanism comprises a sample cup having an open top end corresponding to the aperture in the centrifuge drum for containing the sample to be loaded into the drum. A transport means selectively moves the centrifuge drum and the sample cup into juxtaposition during loading so that the open top end of the sample cup is coincident with the aperture in the bottom end of the centrifuge drum. When the sample cup is rotated by the spinning centrifuge drum, the sample flows from the sample cup into the centrifuge drum.

In accordance with one embodiment of the invention, a plurality of samples are simultaneously centrifugally separated into their components by an automatic centrifuging apparatus comprising a plurality of centrifuge units, each unit comprising a centrifuge drum and a motor for spinning the drum. Loading means are provided for sequentially loading each of the drums with one of the samples and brake means for braking the drum to a stop after the sample therein has been centrifugally separated. One of the components is removed from the drum by an aspiration means, and the drum is then washed by wash means to remove any remaining sample from the drum. The centrifuge drum is then rinsed by rinse means and dried by a drying means. Means are provided for sequentially advancing each of the centrifuge units past the loading means, the brake means, the aspiration means, the wash means, the rinse means and the drying means to simultaneously process a plurality of samples.

BRIEF DESCRIPTION OF THE DRAWINGS

The features of this invention which are believed to be novel are set forth with particularity in the appended claims. The invention together with its further objects and advantages thereof, may be best understood, however, by reference to the following description taken in conjunction with the accompanying drawings, in which like reference numerals identify like elements in the several figures and in which:

FIG. 1 is a perspective view of a centrifuge unit in accordance with a preferred embodiment of the invention;

FIG. 2 is a sectional view of the centrifuge unit taken along lines 2--2 of FIG. 1 illustrating a method of loading a sample into the centrifuge drum of the centrifuge unit;

FIG. 3 is a detailed sectional view of the centrifuge drum taken along lines 2--2 of FIG. 1; and

FIG. 4 is a schematic representation of an automatic serum preparation apparatus utilizing a plurality of the centrifuge units shown in FIG. 1.

PREFERRED EMBODIMENT OF THE INVENTION

In accordance with one embodiment of the present invention, the centrifuge unit shown in FIG. 1 includes a centrifuge drum 10 for centrifuging whole blood to obtain plasma samples for biochemical analysis.

More particuarly, the drum 10 is mounted on a shaft 11, coincident with its longitudinal axis, and rotated at high speeds by a hydraulic motor 12 to centrifuge the blood sample, separating the packed red cells from the plasma.

A sample loading mechanism is positioned directly below the drum 10 for automatically loading the whole blood into the drum 10 for subsequent centrifugal separation. The loading mechanism comprises a substantially cylindrical cup 13 removably mounted on a horizontal plate 14 by means of a shaft 15 on the bottom of cup 13 which is insertable into an aperture in plate 14. Further, an arrangement comprising several ball bearings (not shown) mounted in an annular sleeve 16 is interposed between plate 14 and the bottom of cup 13. Accordingly, cup 13 is free to spin about its longitudinal axis (i.e., shaft 15). Moreover, the longitudinal axis of cup 13 is aligned with the rotational axis (i.e., shaft 11) of centrifuge drum 10.

A pair of air cylinders 17, positioned at opposite ends of plate 14, are effective to vertically reposition plate 14 relative to the bottom of centrifuge drum 10 whenever compressed air is introduced, or released as the case may be, into the cylinders through tubing 18. Consequently, cup 13 can be moved along its longitudinal axis until its open top end is coincident, or in juxtaposition, with a corresponding aperture 19 (not shown) in the bottom end of centrifuge drum 10.

Operationally, the blood sample is initially placed in cup 13 for subsequent loading into the centrifuge drum 10. The automatic loading feature of the present invention may be more readily understood by reference now to FIG. 2. Once the sample is placed therein, cup 13 is repositioned so that its open end is in juxtaposition with the aperture 19 in the bottom of drum 10. The top edge of cup 13 is beveled to fit the correspondingly beveled edge of aperture 19. Consequently, when the centrifuge drum is rotated while in juxtaposition with cup 13, the cup 13 is also rotated. A pair of alignment bars 20 (FIG. 1) extend from base 21 and pass through corresponding apertures in plate 14 to prevent twisting.

When the drum 10 and the cup 13 are rotated at high speed about their common axis, the blood sample is subjected to powerful centrifugal forces which displace the blood, pressing it against the cylindrical wall of cup 13. Consequently, the blood is also subjected to lateral forces resulting from the pressure developed between the blood sample and the wall. Accordingly, the sample, in effect, flows up the cylindrical wall and into the centrifuge drum 10. Thus, when drum 10 reaches a certain rotational speed, the entire sample, for all practical purposes, is loaded therein. While still spinning, the cup 13 is then "dropped away" from aperture 14 by the loading mechansim. Because drum 10 is still spinning, however, the blood sample is pressed against the drum's interior wall so that it can not escape through aperture 19.

The interior features of the centrifuge drum 10 are shown in FIG. 3. There, it may be seen that the centrifuge drum 10 is divided into a pair of adjacent chambers, a separation chamber identified generally at 22 and an aspiration chamber identified generally at 23, separated by a common wall 24. In addition to aperture 19 in the bottom of separation chamber 22, a similar aperture 25 is provided in the top end of the aspiration, or pick-up, chamber 23. Thus, the shaft 11 is passed through aperture 25 and is attached to the center of common wall 24 by a suitable fastening arrangement 26.

The interior wall 27 of separation chamber 22 comprises three essentially distinct sections: 27a defining a truncated conical portion while 27b and 27c define a larger diameter trap portion, identified generally at 28, located at its base. During loading, the blood is initially forced into the trap portion 28 where the heavier immiscible cellular components 29 are trapped. Even when the volume of blood loaded into the separation chamber 22 exceeds the volume of trap portion 28, the packed red cells are captured in the trap 28 while the lighter plasma forms a distinct layer 30 interior to the packed red cells. By loading a precise amount of blood into the separation chamber 22, it is insured the volume of trap 28 is sufficient to contain the entire volume of packed red cells in the sample. Consequently, the same lateral forces resulting from centrifugation that were utilized to load the sample into the separation chamber 22 will prevail to force the plasma up the conical wall portion 27a toward the aspiration chamber 23.

As previously mentioned, the separation chamber 22 and the aspiration chamber 23 are separated by a common wall 24. However, a valve orifice 31 is provided in wall 24 to connect the two chambers at a point near the juncture of the conical wall portion 27a and the common wall 24. During centrifuging, therefore, the plasma is forced into the aspiration chamber 23 while the heavy blood cells are retained in the trap portion 28. At all other times, the orifice 31 is closed by a valve plug 32 insertable therein. Thus, if the centrifuge drum 10 is stopped, the plasma cannot flow back into the separation chamber 22 through orifice 31.

More particularly, at a predetermined time during centrifuging, a trigger mechanism, comprising air cylinder 33, bar 34, plate 11a, and L-shaped rod 35 (FIG. 1) combine to remove the plug 32 from the orifice 31. In operation, the air cylinder 33, controlled by an influx of compressed air, forces bar 34 downward. The L-shaped rod 35, which is secured to the plate 11a rotating with shaft 11, passes through a guide slot 36 in the common wall 24 and, in turn, is effective to disengage the plug 32 when the bar 34 pushes plate 11a downward on shaft 11. Subsequently, when the trigger mechanism (i.e., air cylinder 33) is released just prior to the end of centrifuging, a spring 37 on shaft 11 forces the bar 34 upward so that plug 32 seals the orifice 31, permanently separating the plasma from the packed red cells. Accordingly, when the centrifuge drum 10 stops spinning, the plasma may be manually or automatically aspirated from the pick-up chamber 23 through the aperture 25. A barrier 38 is also provided to contain the plasma within a limited area of the base of aspiration chamber 23 after the drum 10 stops spinning so that the plasma may be more easily aspirated.

The centrifuge unit of the present invention is especially well suited for adaptation to provide an automatic serum preparation apparatus, such as that shown schematically in FIG. 4. That is, because each centrifuge unit is virtually independent of the other units, several units may be combined to provide an automatic serum preparation unit for simultaneously processing several blood samples.

As shown in FIG. 4, a number of centrifuge units (e.g., 18) are mounted on a conveyor such as circular plate 39 approximately 16 inches in diameter. The plate 39, in turn, is sequentially rotated at a predetermined rate to various positions, or stations, by a stepping motor 40. At input station 41, a centrifuge unit 42 is centered over an automatic loading mechanism so that the cup containing the whole blood can be raised into juxtaposition with the centrifuge drum. Subsequently, the centrifuge motor spins the drum and the cup in the manner previously described, causing the sample to be loaded into the drum. Once the whole blood is loaded, the cup is dropped away, and the stepping motor 40 advances the plate 39, moving centrifuge unit 42 to the next station. Accordingly, blood samples can be introduced into successive centrifuge units at a single input station 41 by loading the sample into a unit and advancing the plate 39 so that the loaded unit is replaced by an empty unit.

As the centrifuge 42 is advanced, the plasma and packed red cells are separated, and the plasma is isolated in the aspiration chamber of the drum. Subsequently, the centrifuge unit 42 reaches "brake stop" station 43 where the spinning drum is stopped. The stepping motor 40 next advances the unit 42 to the "aspirate" station 44 where aspiration of the plasma may be manually or automatically accomplished. The centrifuge unit 42 is then moved to the "wash" station 45 where a soap solution is sprayed into both chambers of the drums, cleaning both of all traces of the blood sample. In turn, the unit 42 is advanced to the "rinse" station 46 where both chambers are thoroughly rinsed, and finally, it is stepped through two successive "dry" stations 47 and 48 where the centrifuge drum is dried. After completion of this sequence, the centrifuge unit 42, as well as successive centrifuge units, is ready to centrifuge a new sample; and thus, when it once again reaches input station 41, it is loaded with a new blood sample.

Accordingly, there has been shown an automatic loading centrifuge unit which is adaptable for use in a "batch" processing automatic serum preparation arrangement. Because the plasma, or serum, is automatically separated from the whole blood and isolated in a pick-up chamber where the packed red cells cannot recombine with the plasma, there is less urgency for removing the plasma from the centrifuge. Further, less care need be taken in aspirating the plasma since only the plasma is separated into the pick-up chamber. If that were not the case, as in prior art systems, care would have to be exercised to insure that the end of the aspirating needle is not inserted too deeply into the plasma layer, aspirating the immiscible components as well as the plasma. Finally, the unit's relatively simple design maintains the cost of each unit at a minimal level, making it extremely attractive for use in hospitals and research laboratories.

While a particular embodiment of the present invention has been shown and described, it will be obvious to those skilled in the art that various changes and modifications may be made without departing from the invention in its broader aspects. Accordingly, the aim in the appended claims is to cover all such changes and modifications as may fall within the true spirit and scope of the invention.

Claims

I claim:

1. A centrifuge apparatus for centrifugally separating a sample mixture into its lighter and heavier components, the apparatus comprising:

a centrifuge drum having a separation chamber and an aspiration chamber positioned directly above the separation chamber, the centrifuge drum further having a common wall separating the separation chamber and the aspiration chamber,

the separation chamber having a bottom end wall and a truncated conical interior side wall having a top edge adjacent the common wall and a larger diameter bottom edge and further having a trap portion located at the bottom edge of the interior side wall and adjacent the bottom end wall, the trap portion having a larger diameter than the bottom edge of the interior side wall;

valve means in the common wall for selectively interconnecting the separation chamber and the aspiration chamber;

a motor for spinning the centrifuge drum to force the heavier components into the trap portion while the lighter components are forced up the conical interior side wall; and

a trigger mechanism for opening the valve means to pass the lighter components through the common wall while the centrifuge drum is spinning and closing the valve means when the rate at which the centrifuge drum is spinning falls below a desired level.

2. A centrifuge apparatus in accordance with claim 1 wherein the aspiration chamber has a top end having an aperture therein for aspirating the lighter components from the aspiration chamber.

3. A centrifuge apparatus in accordance with claim 1 wherein the bottom end wall of the separation chamber includes an aperture and including means for initially loading the sample mixture into the separation chamber through the bottom end wall aperture.

4. A centrifuge apparatus in accordance with claim 1 wherein the valve means comprises an orifice in the common wall and a corresponding plug, the plug being removable from the orifice by the trigger mechanism.

5. A centrifuge apparatus in accordance with claim 4 wherein the trigger mechanism comprises an L-shaped rod extending through the common wall and attached to the plug and includes means for selectively moving the L-shaped rod in an up-down direction to selectively remove the plug from the orifice.

6. A centrifuge apparatus in accordance with claim 1 wherein the sample mixture to be centrifugally separated is whole blood and the lighter components thereof comprises plasma while the heavier components comprise red blood cells.

7. In a centrifuge apparatus including a centrifuge drum having an aperture in its bottom end and a motor for spinning the centrifuge drum, an automatic sample loading mechanism comprising:

a sample cup having end open top and corresponding to the aperture in the centrifuge drum, the sample cup containing the sample to be loaded into the centrifuge drum, and

transport means for selectively moving the centrifuge drum and the sample cup into juxtaposition during loading so that the open end of the sample cup is coincident with the aperture in the bottom end of the centrifuge drum, the sample cup being rotated by the spinning centrifuge drum causing the sample to flow from the sample cup into the centrifuge drum.

8. An automatic sample loading mechanism in accordance with claim 7 wherein the sample cup is rotatably mounted on the transport means, the transport means comprising a plate having means attached thereto for vertically repositioning the plate relative to the centrifuge drum, the sample cup being aligned with the aperture in the bottom end of the centrifuge drum.

9. An automatic sample loading mechanism in accordance with claim 7 wherein the top edge of the sample cup is beveled to fit the correspondingly beveled edge of the aperture in the centrifuge drum.

10. A method of loading a sample into a centrifuge drum having an aperture in its bottom end comprising:

pouring the sample into a sample cup having an open top end corresponding to the aperture in the bottom end of the centrifuge drum;

moving the sample cup and the centrifuge drum into juxtaposition so that the open top end of the sample cup is coincident with the aperture in the bottom end of the centrifuge drum; and,

spinning the centrifuge drum and the sample cup about a common longitudinal axis to cause the sample to flow from the sample cup into the centrifuge drum.