Automated Sample-reagent Loader

Abstract

This invention relates to an automatic machine for loading the rotor of a Miniature Fast Analyzer. The machine makes use of a movable table for receiving the rotor. The table has provisions for a sample ring and a reagent ring that contain cups of the samples and reagents for loading into the rotor cavities, and a wash tank for cleaning the transfer pipettes. In an automatic sequence of operation, the table is moved under stationary transfer pipettes in such a manner as to sequentially load precise microliter volumes of the samples and reagents drawn from the cups into their respective associated rotor cavities.

Description

BACKGROUND OF THE INVENTION

This invention was made in the course of, or under, a contract with the United States Atomic Energy Commission.

In a routine clinical laboratory where blood samples, for example, are received in great quantities, there is a need to analyze the samples as rapidly as possible. The Miniature Fast Analyzer has advantages for such an application because it requires only about five minutes for a run. This analyzer is a compact analytical photometer of the rotary cuvette type designed to use small disposable cuvette rotors. Such a photometer is described in the U.S. application of Norman G. Anderson et al., Ser. No. 295,780(70), filed Oct. 6, 1972, U.S. Pat. No. 3,798,459 and having a common assignee with the present application. The extremely small volumes typical of the above analyzer rotors have previously required hand-loading of the rotors in a procedure that ordinarily requires about 15 minutes per rotor and, therefore, the rotor loading has been the rate-limiting operation. Thus, there exists a need for a more rapid means for the loading of such rotors and the present invention was conceived to meet this need in a manner to be described hereinbelow.

SUMMARY OF THE INVENTION

It is the object of the present invention to provide an automatic loader for the fast and efficient loading of photometer analyzer rotors.

The above object has been accomplished in the present invention by providing a rotary table for holding an analyzer rotor, a sample ring, a reagent ring and a wash tank. The rings contain cups of the samples and reagents for sequential loading into the rotor cavities. The table is adapted to be moved horizontally and vertically under stationary transfer pipettes to a loading position in such a manner as to load precise microliter volumes of the samples and reagents into the respective pipettes from the ring cups, and then the table is moved vertically down-horizontally over-vertically up with simultaneous actuation of the pipettes in such a manner as to dispense the respective loaded volumes from the pipettes into their respective rotor cavities. The table is lowered and then rotated to the next position and the above procedure is repeated in a sequential manner until all of the rotor cavities have been filled. The transfer pipettes may be washed by distilled water in the wash tank by inserting them therewithin between each sequential filling operation.

BRIEF DESCRIPTION OF THE DRAWING

The single figure is an isometric view of the automatic loader of the present invention.

DESCRIPTION OF THE PREFERRED EMBODIMENT

There are three possible modes of operation of a photometer analyzer. Single chemistry of a number of samples and multi-chemistry of a single sample are the most common, although a rotor can also be loaded for multi-chemistries of multi-samples. The present invention provides for the flexibility to load a rotor for any of the three modes of operation.

Referring now to the single FIGURE in the drawing, there is illustrated an automatic machine for loading the rotor of a photometer analyzer. A rotor 15 is in place on a rotor table 19 for filling. The rotor 15 is provided with a plurality of cavities for filling in a manner to be described.

The automatic loading machine components are mounted on a generally square base 21. Metallic members 24 and 25 are fixedly attached to the base 21 and these members support a pair of slide rods 34 therebetween. Spaced apart members 20 slidably engage the rods 34 for sliding motion along these rods in a manner to be described. The slidable members 20 constitute a support mechanism for the table 19. Upright posts, or slides, 40 are permanently attached to respective ones of the members 20, two such posts to each member, and a respective sliding member 14 encompasses each of the posts 40, one of said posts 40 and one of said members 14 being hidden from view. A respective spacing member 38 is attached to the tops of respective pairs of posts 40 such as to maintain a given spacing between the slidable members 20. A bracket 35 extends between two of the sliding members 14, as shown, and is permanently affixed thereto. It should be understood that there is another similar bracket 35 extending between and mounted to the other two members 14, one of the members 14 being hidden from view and the other bracket not being shown for the sake of clarity. In addition, there is a cross bracket, not shown, extending between and affixed to the brackets 35.

An L-shaped bracket or support member 37 having a vertical portion and a horizontal portion is fixedly attached to the cross bracket 35, as shown, and a vertical motion synchronouS motor 36 is rigidly attached to the vertical portion of support member 37. The horizontal portion of member 37 supports the rotor table 19 that is rotatable by means of a synchronous table motor 41 also mounted on the member 37 by means of a support bracket 12. The table 19 is coupled to the motor 41 by means of the motor shaft 18. The rotational positioning of the table 19 is provided by indexing notches 42 in the underside of the table 19 and an indexing switch 43 also supported by the member 37. In addition to receiving a rotor 15 for loading at its center, the table 19 top has two tracks, not shown, for receiving and aligning the two rings 44 and 45. Ring 44 has holes for reagent cups 33, only one being shown, and ring 45 has similar holes for sample cups, not shown. Proper placement of the rings 44 and 45 on the table 19 is assured by a singular notch 46 in the rings that must mate with a pin, not shown, attached between the two table tracks. The two-ring arrangement can load a different sample and a different reagent in each rotor cavity and will be understood to correspond to the multi-sample, multi-reagent embodiment of the present invention. The L-shaped bracket 37 also is adapted to receive a wash tank 53 positioned in the space outside the outer ring 45.

The wash tank 53 contains two cups, not shown, which are filled with distilled water such that when the transfer pipettes are inserted into the cups at the beginning of each loading sequence, the outside of the pipettes is washed. A diluent from the pipettes is dispensed into the cups which washes the inside of the pipettes. The tank 53 can be removed and emptied by means of the locking screw 52.

The horizontal sliding action for the slidable members 20 is controlled by a horizontal motion synchronous motor 22 which is attached to the base 21. The motor 22 has a crank arm 23 that is connected by a connecting rod to a bearing mount attached to one of the members 20. The connecting rod and bearing mount are hidden from view in the drawing. A pipette support member 26 is rigidly attached to the member 24 and has switches 27 and 28 mounted thereon that detect the end-point travel of the sliding mechanism 20 and an intermediate switch 54 for effecting the loading of the pipettes from the sample and reagent cups in the rings 45 and 44 in a manner to be described.

The pipette support member 26 has an upright post 8 affixed thereto, and the post 8, in turn, supports a stationary sample pipette support 31. The support 31 is provided with horizontal slide members 29 with an end plate and a reagent pipette support 30 slidably encompasses these slide members 29 that allow a slight horizontal movement of the support 30 relative to the stationary support 31. A spring 32 is affixed to one of the members 20 by means of a bracket 10 and to the underside of the support 30 by means of an L-shaped bracket 11, only partially shown. Thus, this movement of the support 30 occurs mechanically with the movement of the spaced apart members 20 to their opposite limit of travel by means of the spring 32. The slides 29 thus accommodate the slight unequalness in spacing that exists between the cavities on the rotor 15 and the fill cups 33 of the rings 44 and 45. The support 31 is provided with a support arm 5 that holds the stainless steel hypodermic needle 16, and the support 30 is provided with a support arm 6 that holds the stainless steel hypodermic needle 17.

Two automatic pipettes 1 and 2 are connected by connecting tubular lines 3 and 4 to the needles 16 and 17, respectively, such that the probe tips from the pipettes extend about 3/8 inch down through the stainless steel needles. The pipettes are electrically connected to the automatic loader through an electrical connector, not shown, mounted on the base 21 which conveys control signals between the loader and the pipettes. The pipettes 1 and 2 may be Model 25004 Automatic Pipette, Micromedic Systems, Inc., Philadelphia, Pa. 19105, for example.

A vertical movement of the rotor table 19 within the table support mechanism is provided by the motor 36 which is connected through a crank arm, not shown, and connecting rod, not shown, to a bearing, not shown, mounted on one of the members 20. When energized, the motor 36 produces a vertical travel of the L-shaped member 37 and the rotor table 19 supported thereby along the slide posts 40. An upper limit switch 39 and a lower limit switch, hidden from view, detect the endpoint limits of travel and these limit switches are supported by the other one of the members 20 and are actuated by means of a suitable bracket affixed to one of the sliding members 14 which is adjacent to these switches.

Digital control devices are mounted within a control box 55 mounted on the base 21, and operational control switches are mounted on a control panel 49 also mounted on the base 21. One of the control switches such as switch 50 (the RUN/RESET switch) is shown on the drawing. Logic elements and solid state switches capable of switching 110 volts from logic level signals are incorporated into a printed circuit control card mounted on the other side of a control panel 13 and hidden from view in the drawing. Electrical leads from the printed circuit card are connected by means of a multi-lead ribbon cable 7, only partially shown, to the control devices in the box 55, and the control panel 49 is also connected to the control device by electrical leads, not shown.

The L-shaped member 37 also supports swing arms 47 and 48, by means of a post 9, for holding, respectively, a reagent cup and a sample cup. These arms 47 and 48 are each used individually for different modes of loading a rotor in a manner to be described below. The electrical leads to the motors 22, 36 and 41 as well as the leads from the control devices to the pipettes 1 and 2 are not shown for the sake of clarity in the drawing.

Most clinical laboratory use will be either multi-sample, single-chemistry applications, or single-sample, multi-chemistry applications. If multi-sample, single-reagent analyses are to be performed, the reagent (inner) ring 44 is removed from the table 19 and the swing arm 47 is moved to the former reagent cup sampling location. The arm 47 holds a single reagent cup, not shown, stationary at the reagent cup sampling location while the sample ring is sequentially rotated. The end result is that the rotor is loaded with a plurality of samples and a single reagent. For single-sample, multi-reagent analyses, the sample ring 45 (but not the reagent ring 44) is removed from the table 19 and the swing arm 48 containing a sample cup, not shown, is moved to the sample cup sampling location. The end result is that the rotor is loaded with a plurality of reagents and a single sample.

Since all movement of the rotor table 19 is from the motors 22, 36 and 41, and since the motors all operate between limiting switches, end-point programming was chosen as the control method of operation.

A partial operating sequence begins with the RUN/RESET switch 50 in the RESET position. The machine will move to the initial position, which is the pipette tips are over the wash cups with the cups in radial alignment with the first (or No. 1) cups in the rings 44 and 45 and the table 19 down. The switch 50 is moved to its RUN position and a START button, not shown, is pressed. The motor 36 moves the table up bringing the wash cups to the tips of the pipettes. When the table 19 is raised by the motor 36 and the transfer pipettes are inserted into the wash cups of the wash tank 53, the outsides of the pipettes are washed by the distilled water in the cups. Then a diluent from the automatic pipettes is dispensed into the cups which washes the inside of the pipettes. The table 19 is then lowered by the motor 36 and then moved horizontally over by the motor 22 until the No. 1 cups in the rings 45 and 44 are under the tips 16 and 17 as sensed by the switch 54. The motor 36 then moves the table 19 up bringing the sample and reagent cups to the tips of the pipettes. When the limit of vertical travel is reached, the automatic pipettes are enabled and liquids are drawn. The automatic pipettes provide signals when the sampling is completed and the motor 36 then brings the table 19 down. The motor 22 then brings the rotor cavities under the tips 16, 17 as sensed by the switch 28 (the holder 30 moves on the slides 29 to its other limit during this movement) followed by an upward movement of the table 19 by the motor 36 to bring the rotor cavities to the tips. The automatic pipettes then dispense the two liquids into the rotor cavities. The table is then brought down and rotated one increment by the motor 41 such that the No. 2 cups of the rings 44 and 45 are in position for a loading operation. The above procedure is sequentially repeated until all of the rotor cavities have been filled at which time the table signals the completion of the filling operation.

Some additional features of the machine may be pointed out. A push-button switch, not shown, may be pressed to cause the automatic pipettes to operate. This is useful between operations of the machine for flushing out the tips or checking the operation of the Micromedics, particularly the removal of a liquid drop on the tip or an air bubble inside the tip. The motors can be easily replaced by similar motors of different speeds. This feature allows optimizing the amount of time required for each segment of the motion of the rotor.

The automatic pipettes have been evaluated manually and found to provide accuracy and precision in the 2 to 20 microliter volume range to within .+-.1-2 percent and 0.1-0.3 percent, respectively. The automatic pipettes additionally provide for the selection of a range of loading volumes.

The automatic loader described above provides a wide range of operating modes, simple changeover between loadings, much faster speed (less than 5 minutes) than manual loading (about 15 minutes), and 1-2 percent accuracy of loading microliter volumes.

The present invention can be used in a remote testing facility to provide health care in inaccessible and isolated areas. For applications in clinical laboratories where speed is an important consideration, the Miniature Fast Analyzer, while capable of performing an analysis in 5 minutes, has previously been limited to about 15 minutes (the time to load a rotor manually). The ability of the automatic loader of the present invention, as described above, to completely load an analyzer rotor in about five minutes will permit a Miniature Fast Analyzer to analyze up to 192 samples per hour if one rotor can be analyzed every 5 minutes.

This invention has been described by way of illustration rather than by limitation and it should be apparent that it is equally applicable in fields other than those described.

Claims

What is claimed is:

1. An automatic loader for loading a photometer analyzer rotor provided with a plurality of cavities, comprising a rotor table for holding said rotor at the center thereof during a loading operation; an inner ring provided with a plurality of holes for receiving and holding a plurality of respective reagent cups, said ring adapted to be positioned on said table and encompassing said rotor; an outer ring provided with a plurality of holes for receiving and holding a plurality of respective sample cups, said outer ring adapted to be positioned on said table encompassing said inner ring such that respective pairs of said reagent cups and sample cups are in radial alignment with corresponding cavities in said rotor; a base plate; a pair of horizontal slide rods mounted on said plate; a rotor table support mechanism slidably mounted on said slide rods; a first pipette support member affixed to said base plate; a second pipette support member slidably supported by said first support member to provide slight relative motion therebetween; an off-center spring mounted between said second pipette support and said support mechanism to effect said slight motion when said support mechanism is moved from one limit position to another limit position; four vertical slide rods mounted on said support mechanism, each of said vertical slide rods being spaced apart each from the other at a given distance; respective slide members encompassing respective ones of said vertical rods; a respective horizontal bracket member extending between and affixed to respective pairs of said slide members; an L-shaped bracket having a vertical portion and a horizontal portion and being affixed to one of said bracket members; a vertical motion synchronous motor affixed to the vertical portion of said L-shaped bracket, the horizontal portion of said L-shaped bracket supporting said rotor table on the top thereof, a first crank arm coupled between said vertical motion motor and said support mechanism; a first pair of limit switches mounted on said support mechanism for sensing the limits of vertical travel of said L-shaped bracket and rotor table; a synchronous table motor mounted beneath the horizontal portion of said L-shaped bracket and supported thereby and being coupled to said rotor table; a horizontal motion synchronous motor mounted on said base plate; a second crank arm coupled between said horizontal motion motor and said slidable support mechanism; a second pair of limit switches mounted on said first pipette support member for sensing the limits of horizontal travel of said table support mechanism; a plurality of indexing notches provided in the underside of said rotor table; an indexing switch for sequentially engaging each of said notches during said loading operation; a pair of automatic pipettes provided with respective tips and coupled to respective ones of said pipette supports; electrical control means mounted on said base plate connected to and controlling said vertical motion motor, said synchronous table motor, said horizontal motion motor, and said automatic pipettes; said control means being provided with a RUN/RESET switch and a START switch, whereby said control means under control of said switches is adapted to effect the bringing of the table and one of said sample cups and one of said reagent cups underneath the pipette tips, effect the bringing of said cups to said tips by upward table movement, effect the drawing of liquids from said cups by said automatic pipettes, effect the bringing of said cups and table down, effect the movement of the table horizontally over to bring the rotor cavities under said tips followed by an upward movement of said table to bring said cavities to said tips, and effect the dispensing of said drawn liquids into said cavities by said automatic pipettes after which said table is brought down, effect the rotating of said table to its next indexed position and sequentially effecting a repetition of the above procedure until all of the rotor cavities are filled.

2. The automatic loader set forth in claim 1, and further including a vertical post mounted on said L-shaped bracket, and a pair of separately movable swing arms mounted on top of said vertical post, said vertical post and swing arms mounted outside the periphery of said outer sample ring, said swing arms being positioned higher than said rings, each of said swing arms provided with a hole in the end thereof for respectively holding a sample cup and a reagent cup, whereby either said reagent ring or said sample ring may be removed from said rotor table and the corresponding swing arm moved over the table in the position of the removed ring to provide for different modes of loading of said rotor cavities.

3. The automatic loader set forth in claim 1, wherein said electrical control means includes a printed circuit control card for effecting a given program of operation of said loader.

4. The automatic loader set forth in claim 1, and further including a wash tank provided with two wash cups containing distilled water, said wash tank positioned on said L-shaped bracket outside said outer sample ring, and another limit switch positioned on said first pipette support member, said another switch effecting the insertion of said pipette tips into said wash cups for a cleaning operation thereof in accordance with a given program of operation effected by said electrical control means.