Pipette system

[57] ABSTRACT

An apparatus for transferring a specific quantity of a liquid medium from one receptacle to another with precision. The apparatus comprises a series of movable canals operatively disposed between the same container and the receptacle to which the same is to be transferred. In a preferred aspect, the device is designed to transfer samples taken from human subjects, which samples are to be tested for diagnostically significant features.

1,204,368 11/1916 Lowy....................................73/425.6

Claims, 7 Drawing Figures

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PATENTEDFEB29 1972

3,645,142

SHEET 1 OF 4

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PATENTEOFEB 29 1972

3,645,142

SHEET 2 OF 4

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PATENTEDFEB29 1972

3,645,142

SHEET 3 OF 4

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PATENIEDFEB29I972

SHEET U OF 4

3,645,142

FIG. 3

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FIG. 4 b

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3,645,142 ¹

PIPETTE SYSTEM

DETAILED DESCRIPTION OF THE INVENTION

The present invention relates to an apparatus for transferring a predetermined amount of a liquid sample from a sample container into a receiving receptacle. The liquid transferred to the last-mentioned receptacle is destined to be fed into a machine which analyses such liquids for significant features.

Most preferably, the sample fluids which are to be analyzed are of human origin such as blood, urine and the like. Thus, such samples are to be analyzed for diagnostically significant features.

Since the advent of automated analysis techniques and the widespread practice of screening in order to determine at an early stage, the presence of physiological abnormalities, the need to provide an apparatus which can rapidly and efficiently feed predetermined amounts of a sample into a machine adapted to automatically analyze the sample for a desired characteristic, should be readily apparent. It is the object of this invention to provide a means whereby this end can be effected.

More precisely, the present invention concerns an automated precision pipette system so constructed and arranged as to effect the transfer of a calibrated volume of a liquid from a first receptacle to a second.

Particularly in the field of chemical analysis, industrial chemical analysis, biochemical analysis and the like, the need often exists for transferring a carefully measured volume of a liquid from a first receptacle in which it is stored into a second receptacle containing, for example, a reagent. The present invention has for its object the provision of a pipette system, which permits the transfer of predetermined small quantities of liquids, for example, a few microliters, from one receptacle or container to another.

Another object of the present invention is the provision of an automatic pipette system, which permits a rapid sequence of functions whereby the pipette system performs at a high rate of speed in a precise consistent manner, e.g., withdraws rapidly from a multitude of samples, a constant measured volume thereof at the rate of one withdrawal per second.

Another aim of the invention is the provision of a pipette which permits the transfer of a sample from one container to another without being contaminated by residue from previously transferred liquids. Particularly, with human samples destined for human analysis, the necessity of avoiding cross contamination between samples should be evident.

In order to achieve these objectives, the present invention includes a pipette system adapted to transfer a calibrated or measured volume of a liquid substance from a first container in which it is stored into a second receptacle. The liquid contained in the second receptacle is to be fed into an automatic analyzing machine. The pipette system is characterized by the fact that it comprises an internal distribution means comprising a first member transversed by two separated noncommunication canals and a second member movable with respect to the said first member, said second member being provided with four openings traversing the second member. Each of the two canals in the first member in operative position is in communication with corresponding pairs of the openings in the second member. The internal distribution means, preferably comprises an outer hollow cylindrical stator member (the second member) and an inner rotatable rotor core (the first member). The outer hollow cylindrical member is provided with four transfer openings or passages extending from its inner surface to its outer surface. The inner rotor core is provided as is noted above with two independent noncommunicating canals which traverse the inner core member. The two ends of each canal are opened at the exterior of the rotor core. The open ends of the two canals, when in operative condition, are adapted to communicate with adjacent openings in the outer cylindrical member, thereby permitting a flow of liquid through the passageway, so obtained.

The invention will be better understood by the description of the various modes of carrying out the invention set forth hereinafter. These and other objects, features and advantages will be apparent upon consideration of the following disclo5 sure taken in conjunction with the accompanying drawings in which:

FIGS, la and lb represent schematically a first embodiment of the pipette system respectively showing the positioning of the various members of the pipette system at the start and 1 θ about the finish of the transfer operation.

FIG. 2 represents schematically a pipette system in accordance with that in FIG. 1 and provided with a cleaning and drying means.

FIG. 3 is a schematic view illustrating another embodiment ¹³ of the present invention.

FIGS. 4α, 4b and 5 represent schematically still other embodiments of the pipette system in accordance with the present invention.

2Q FIGS, la and lb represent schematically one preferred embodiment of the invention. FIG. la illustrates the said embodiment during the starting phase of the transfer operation. FIG. lb shows the device at about the completion of the transfer operation.

The pipette system is designed to extract a measured quantity of a liquid 10 contained in a container 11 and to inject the measured amount into a receptacle 12.

The pipette system of the present invention includes in combination a hollow needle 1, for example, of the hypodermic 30 type. The hollow needle 1 is fixedly joined to a distribution means 7 (rotary valve or sluice 7). A reservoir 3 is fixedly secured to the valve 7. Valve 7 is also connected to an evacuating container 4; the interior of which is under reduced pressure. That is to say, the container is maintained below at35 mospheric pressure. A stop valve 5 and a liquid detector 8 are disposed between the depressurized container 4 and valve 7. The container 4 may be replaced by any suitable pumping mechanism.

The internal volume of the hollow needle is equal in volume 40 to the volume of that portion of the sample required for precision analysis. The needle 1 is advantageously coated all along its internal surface and at least partially along a portion of its external surface extending from the free end thereof, with a layer of a water-repellent material such as a silicon. By the ⁴³ utilization of a hydrophobic material, it is assured that no substantial portion of the sample liquid will adhere to the needle after the transferring operation is completed. Valve 7 is presented in the Figures as having a rotatable inner core. It should be evident, however, that without departing from the ⁵⁰ scope of the invention, there could be utilized any equivalent distribution valve of a different type provided that it functions in the same manner as the rotary form of valve 7 described herein.

The needle 1 is fixedly secured at its upper end to valve 7 by any appropriate means, i.e., a force-fit or the like. The valve 7, as is indicated above, in the preferred aspect comprises a rotatable inner member, namely, rotor 70. Rotor 70 has formed therein two internal noncommunication independent 6Q canals 71 and 72. Canals 71 and 72 extend through the rotor 70 to the periphery thereof. In the embodiment illustrated in FIGS, la and lh, fire entrances to the canals are spaced 90°, one from the other. The outer member 73 contains four openings 711, 712, 721 and 722. The four openings are 65 disposed about the stator 73 at an angle of 90°, one from the other.

Thus, as seen in FIG. la, the needle 1 is disposed below the opening 721, while the opening 722 is connected to the evacuating means 4 by a conduit 40. Disposed in the path of 70 the internal passage in conduit 40 is a valve 5. Adjacent valve 5 and operatively connected thereto is a liquid passage detector 8. Detector 8 is positioned in the pipette system between stop valve 5 and opening 722 as shown in FIG. la. Detector 8 controls the opening and closing of valve 5. The opening 711 75 in the outer member 73 is connected to a source of com3,645,142 pressed gas 2 (for example, atmospheric air under pressure or a bottle of nitrogen) by a flexible conduit 20. Finally, the opening 712 as seen in FIG. 1 is connected to a small expansion reservoir or tank 3 via conduit 30.

The apparatus performs its designated function in the following manner.

At the beginning of the operation, the valve 7 occupies the position indicated in FIG. la and the valve 5 is opened. The needle 1 is immersed into the liquid 10 to a predetermined, calibrated depth. The valve 7 is in a position whereat the opening in conduit 40 communicates with canal 72 which in turn is in communication with the opening in hollow needle 1. A passageway extending from vessel 4 to container 11 is therefore provided. The liquid 10 passes through needle 1 under the influence of the vessel 4, and then through canal 72 into conduit 40. When the liquid reaches the detector 8, detector 8 gives a command directing that valve 5 be closed. Upon closing of valve 5, the liquid 10 rests in suspension in the needle 1, the canal 72 and the portion of the conduit 40 extending from valve 7 to stop valve 5. It should be noted that the detector 8 need not necessarily be precisely positioned in the system since it is only the liquid contained in the needle which is to be transferred. Also, the valve 5 need not be of a precision type for the same reason. The detector also commands the mechanism which effects movement of the rotor 70 and the pipette system per se.

When the liquid is entering the needle 1, the reservoir 3 which is in communication with the gaseous source 2 adjusts to the pressure of this source via the canal 71 and conduits 20 and 30.

For the needle 1 to be transferred from the position thereof shown in FIG. la to the position thereof shown in FIG. lb, the pipette system is transported as a whole to a position whereat needle 1 is above the receptacle 12 by any suitable means. If the receptacle 12 is closed, (e.g., if a closed pouch is used) the needle can be conveniently adapted either by designing it to be able to partake of a supplementary translational movement in order to pierce the receptacle wall. The rotor 70 is then turned a quarter of a turn clockwise, i.e., through an angle of 90°. The movements of the rotor 70 can be effected by a motor of the step-by-step type. Alternatively, rotor 70 can move through a smaller angle, namely one-eighth one-sixteenth or smaller increments of a complete 360° turn. By having the rotor 70 move through such smaller increments under the influence of the step-by-step type motor, the motor 70 can have an intermediate position between that shown in FIGS, la and lb at which the canals or channels 71 and 72 are not in communication with the openings 711, 712, 721 and 722. In this case, the passage from the first position (FIG. la) into the second position (FIG. lb) will be accomplished by several successive movements of the step-by-step motor.

In the position shown in FIG. lb, the volume of the liquid contained in the needle which is forced by the compressed air of the reservoir 3 which expands in accordance with adiabatic law. Simultaneously, the liquid contained in canal 72 and communicating conduit 40 is drawn into the evacuating vessel 4 from which it is discarded. Thus, vessel 4 serves as a draining receptacle for the sample liquid which is not utilized in the subsequent analysis procedure.

The volume ofthe liquid transferred from the container 11 into the receptacle 12 is precisely determined by the volume of the needle (including, of course, the amount contained in the opening 721 in the outer cylindrical member 73). In any event, the volume transferred from opening 721 and the needle 1 is easily calculated and can be kept constant and ascertainable with accuracy. Taking into account the slight volume found in opening 721, the precise amount of liquid is obtained by the fact that canal 72 is cut off from communication with opening 721 as the device moves from the position shown in FIG. la to that shown in FIG. lb.

The pressure in the reservoir 3 decreases exponentially. Thus, the force exerted on the liquid is maximal at the beginning ofthe decantation and weak at the end of the opera tion. As a consequence of this, the needle is quickly emptied of liquid and excessive bubble formation is avoided. The draining off and cleansing of the canal 72 and conduit 40 are assured by the jet of air derived from the compressed gas 2 being forced into the passageway provided when canal 72 and conduits 20 and 40 are in communication.

Valve 5 can be regulated whereby it will close when specified volumes of gas enter the evacuating container 4. The force which is exerted on the liquid and the needle can be adjusted by regulating the amount of compressed air 2 entering the system with the volume of container 3 in view. In certain cases, it will be desirable to utilize a pressure reducer such as a relief valve associated with conduit 20 placed in series in the system.

In an alternate embodiment and to obtain a force of ejection of liquid adapted specifically to a need, several reservoirs of the type illustrated by reservoir 3 can be disposed in the system in series separated by valves with controllable delivery provided by diaphragms or lost-load devices. There is illustrated in FIG. 3 such an embodiment. In the embodiment shown in FIG. 3, several reservoirs 3, 31 and 32 are disposed in series and are separated by the valves 35 and 36 so arranged as to provide a controllable delivery.

The number of reservoirs, the volume and the number of valves are chosen by taking into account the volume of the sample to be transferred, the viscosity thereof, its specific gravity, its propensity for turbity and the like during the operation and at the finish thereof. It should be evident that these characteristics are well within the skill of the artisan to recognize and then to adapt the device to compensate for the influence thereof.

FIG. 2 represents schematically a pipette system identical to that illustrated in FIGS, la and lb but which includes additionally a supplementary means for permitting a sequential cleaning and drying of the canals between each transferring operation.

To accomplish this end, the reservoir 3 is placed in communication with a cleaning conduit 37 closed by a valve 38. Conduit 20 also communicates with an additional conduit 21. A cleaning liquid is adapted to enter the system via conduit 21. The entry of the cleaning liquid into the system is controlled by valve 22. There is also provided a valve 23 which permits the cutting off of the entry of compressed gas 2 into the valve 7. Thus, the compressed gas is prevented from entering the valve during the cleaning operation. In the same manner, in order to permit conduit 40 to be cleaned, one could dispose between the opening 722 and the valve 5, an inlet 25 for a cleaning liquid, which inlet is closed by a valve 26. The drying of conduit 30 and reservoir 3 is effected by the compressed gas 2. Conduit 40 is dried by connecting to it an inlet which permits entry of a compressed gas 27. The last-mentioned inlet is closed by valve 28.

When it is desired to dilute a transferred specimen by a calibrated quantity of a dilution liquid, the device is modified as shown in FIGS. 4α and 4b and two valves of the type represented by the character 7 in FIGS, la and lb, namely, valves 7 and 107 are used. The valves 7 and 107 are connected thusly. Valve 7 is connected to the needle 1. The receptacle 4 has disposed between it and valve 7, the stop valve 5 and the detector 8. Valve 7 is connected to the valve 107 by a conduit 200 having a calibrated internal volume. Valve 7 is also connected to a depressurized draining vat 9. Between the two is a liquid detector 90. Valve 107 is connected to a reservoir containing a dilution liquid 110. In the path of movement of the dilution liquid, there is disposed a valve 50 controlled by liquid detector 90. This embodiment functions as follows:

At the start of the operation, the rotor of the valve 7 and 107 take the position represented in FIG. 4α. In this position, the valves 5 and 50 are open. Because of the vacuum created in the receptacle 4, the liquid to be transferred or decanted rises into needle 1. Concurrently, the reservoir 3 fills with compressed gas. The conduit 200 fills with the dilution liquid under the influence of evacuating vat 9. When the liquid to be

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3,645,142 sampled reaches the detector 8, the valve 5 closes as a result of command given by the detector. In the same manner, when the dilution liquid reaches the detector 90, the valve 50 is commanded to close and the aspiration of liquid 110 ceases. Then, the rotors of valves 7 and 107 are displaced a quarter of a turn from the position shown in FIG. 4a to the position shown in FIG. 4b. Then, communication is established between the needle 1 and the reservoir 3 via the conduit 200. The pressure exerted by the gas contained in reservoir 3 causes a predetermined measured amount of the liquid sample contained in needle 1 and the diluting liquid contained in conduit 200 to enter the receptacle 12. The tube 200 being calibrated and the volume of the internal canals in valves 7 and 107 being previously measured, one can obtain an extremely precise dilution of the sample in a relatively rapid and feasible manner. While the aforesaid combination of dilution and sample liquids is taking place, conduit 40 and one of the internal canals of valve 7 are in communication with the evacuating container 9 and the residual liquids contained therein are emptied into container 9. The apparatus is now ready to recommence the novel sequence of operation in order to provide another sample of the product after a rotation of a quarter of a turn of the rotors of the valves 7 and 107 back to the position thereof shown in FIG. 4&lt;z.

FIG. 5 represents another embodiment of the pipette system of the present invention. It comprises a distribution valve having four canals in the rotor and eight corresponding openings in the stator. More generally, it should be recognized that one could utilize a distribution sluice having n canals in the rotor and 2n openings in the stator. The four canals are spaced equidistant from each other about the axis of the rotor. Openings 801,802,803 and 804 are respectively connected to a source of gas 2, to an expansion reservoir 3, a hollow needle 1 and a depressurized trough 4 separated from the valve 7 by a stop valve 5 and a liquid detector 8. The four other outlets are connected in the following manner:

Outlet 805 is connected to an inlet for a cleaning liquid, outlet 807 to an inlet for clean and dry air and outlets 806 and 808 are for evacuation and thus are connected to an exhaust. By moving the rotor of valve 7α through an angle of oneeighth of a complete turn by a motor of the step-by-step type counterclockwise as shown in FIG. 5 in the manner described above, one can perform the transfer operation. In this new position the access of cleaning liquid and drying air has to be prevented by respective block valves (not shown). After the decantation of the sample liquid another one-eighth counterclockwise turn is effected whereby canal 811 is in a position for being cleaned, canal 813 is in a position for being dried, canal 812 serves for pressurizing the reservoir 3, and canal 810 connects hollow needle 1 to trough 4 for the next sample aspiration. Thus a new operation cycle is initiated.

Although the device which has been described above in the most preferred form for carrying out the invention, the diverse modifications to it can be made without departing from the scope of the present invention. Furthermore, certain elements can be replaced by other elements capable of functioning similarly. Thus, while there have been shown preferred embodiments of the invention, it should be understood that the invention may be embodied otherwise than that herein specifically illustrated and described and that certain changes in the form and arrangement of parts and in the specific manner of practicing the invention may be made without departing from the underlying ideas and principles of the invention within the scope of the appended claims.