US 3645142 A
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.
Description (OCR text may contain errors)
States atent Turpin 1 Feb. 29, 1972  PKPETTE SYSTEM 3,119,524 1/1964 King et a1 141/26  inventor: Pierre Turpin, Burs S/Yvette France 3,137,172 6/1964 Harrison ..73/425.4 P
 Assignee: Hoffmann-La Roche, Inc., Nutley, NJ, FOREIGN PATENTS OR APPUCATIONS 22 Filed: Oct 29 1970 I 109,753 1917 Great Britain ..73/425.4 P
 Appl. No.: 85,056 Primary Examiner-S. Clement Swisher Attorney-Samuel L. Welt, Jon S. Saxe, Bernard 8 Leon. Wil-  Foreign Application Priority Data liam G. lsgro, Margaret C. Bogosian and Jacob Frank Nov. 3, 1969 France ..6937726  ABSTRACT  U S CI 73/425 6 23/259 An apparatus for transferring a specific quantity of a liquid  In} .0 ln l/M medium from one receptacle to another with precision The  Fie'ld I259 apparatus comprises a series of movable canals operatively 41718 26 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 sub-  References Cited jects, which samples are to be tested for diagnostically signifi- UNITED STATES PATENTS Cam featuresl,204,368 11/1916 Lowy ..73/425.6 13 Claims, 7 Drawing Figures mcmgumza I912 SHEET 2 [IF 4 FIG. 117
l. rrrE'r'rE 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 disclosure 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 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 of the present invention.
FIGS. 4a, 4b and 5 represent schematically still other embodiments of the pipette system in accordance with the present invention.
FIGS. la and 1b represent schematically one preferred embodiment of the invention. FIG. la illustrates the said embodiment during the starting phase of the transfer operation. FIG. 1b 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 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 atmospheric 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 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 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 scope of the invention, there could be utilized any equivalent distribution valve of a difierent 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 canals 71 and 72. Canals 71 and 72 extend through the rotor 70 to the periphery thereof. In the embodiment illustrated in FIGS. 1a and lb, the entrances to the canals are spaced one from the other. The outer member 73 contains four openings 7111, 712, 721 and 722. The four openings are 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 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 7 11 in the outer member 73 is connected to a source of coml0l025 Ol 39 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. 1a and the valve is opened. The needle 1 is immersed into the liquid 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 and 30.
For the needle I to be transferred from the position thereof shown in FIG. la to the position thereof shown in FIG. 1b, 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. 10 and 1b 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. 1a) 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 4t) 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 of the 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. 1a to that shown in FIG. 1b.
The pressure in the reservoir 3 decreases exponentially. Thus, the force exerted on the liquid is maximal at the beginning of the decantation and weak at the end of the opera- 10 justed 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 opera tion 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. 10 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. 4a and 4b and two valves of the type represented by the character 7 in FIGS. 1a 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. 4a. 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 sampled reaches the detector 0, the valve 5 closes as a result of command given by the detector. In the same manner, when the dilution liquid reaches the detector the valve 50 is commanded to close and the aspiration of liquid 110 ceases. Then, the rotors of valves 7 and 1107 are displaced a quarter of a turn from the position shown in FIG. 4a to the position shown in H6. 4b. Then, communication is established between the needle 11 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 H6. 4a.
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 Zn openings in the stator. The four canals are spaced equidistant from each other about the axis of the rotor. Openings 801i, 802, 003 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 005 is connected to an inlet for a cleaning liquid, outlet 807 to an inlet for clean and dry air and outlets 806 and 000 are for evacuation and thus are connected to an exhaust. By moving the rotor of valve 7a 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 8111 is in a position for being cleaned, canal 8113 is in a position for being dried, canal 012 serves for pressurizing the reservoir 3, and canal 8110 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.
l. A pipette system for transferring a desired volume of a liquid sample from a sample container in which it is stored into a receiving receptacle which comprises a distribution means including a first member having formed therein at least two independent, noncommunicating canals, the ends of which open at the periphery of the first member and a second member movable with respect to the first member, said second member being traversed by at least four noncommunicating openings, each canal when in operative condition being in communication with two of said openings, a sampling means adapted to be immersed into the container and joined to said distribution means, said sampling means having an opening therein in communication with a first of said openings, a depressurized evacuating container connected to a second of said openings, a reservoir connected to a third of said openings, a source of compressed gaseous material connected to a fourth of said openings, one of the canals in the first member in a first operative position being in communication with a first and a second of said openings thereby forming a passageway leading to the evacuating container, into which passageway the sample is withdrawn from the sample container, another of said canals being in communication with a third and fourth of said openings, thereby forming a passageway therewith, means for moving said first member relative to said second member from said first operative position to another operative position, said one of said canals in said another operative position being in communication with said first and third openings thereby forming a passageway therewith whereby gaseous material contained in the reservoir causes sample liquid contained in the sampling means to be decanted into the receiving receptacle.
2. A pipette system in accordance with claim 1 characterized by the fact that the said means for moving the first member of the distribution system relative to the second member includes a motor means of the step-by-step type thereby permitting incremental movements, said motor means being energized in response to commands given by a liquid detector, said liquid detector being positioned in the system between the depressurized container and the said second of the openings and being responsive to passage of the liquid sample through the said passageway into which it is withdrawn.
3. A pipette system in accordance with claim 2, characterized by the fact that it includes a valve placed between the depressurized container and the liquid detector, the opening and the closing of said valve being controlled by the detector.
4. A pipette system in accordance with claim l characterized by the fact that the two members of the distribution means are movable rotatively relative to each other, and the said at least four openings are spaced equidistant one from another.
5. A pipette system in accordance with claim 1 characterized by the fact that it comprises a cleaning liquid conduit for entry of a cleaning liquid operatively connected to the said fourth of said openings between the latter and said source of gaseous material, said cleaning liquid conduit having a valve disposed in the path of the passageway provided by the interior of the cleaning liquid conduit, and an inlet conduit and outlet conduit operatively connected to the said second of said openings between the said second opening and the depressurized evacuating container, a source of drying gas connected to the inlet conduit, said outlet conduit being adapted to permit the escape of the drying gas and first and second valve means on said inlet and outlet conduits and disposed in the entering and escape path, respectively, of the drying gas and adapted to control die entry and escape of the drying gas.
6. A pipette system in accordance with claim 1, characterized by the fact that the reservoir comprises at least two reservoir chambers connected in series via a valve means adapted to control delivery to the reservoir chambers.
7. A pipette system in accordance with claim 1 in which the first member is a rotor and the second member is a stator which rotatably receives the rotor.
8. A pipette system in accordance with claim 1 characterized by the fact that the second member of the distribution means includes a fifth and sixth opening, said fifth and sixth openings adapted to communicate with a third canal in the first member in the said first operative positions, one of said last-mentioned fifth and sixth openings being connected to a source of cleaning liquid and the other being connected to an evacuating depressurized vessel.
9. A pipette system as in claim 8 wherein the distribution means additionally includes an additional pair of openings in the second member, which pair of openings communicate with a fourth canal in said first member in the first operative position, one of said last-mentioned pair of openings being connected to a source of drying air and the other being connected to an exhaust.
10. A pipette in accordance with claim 1 wherein the sampling means includes a hollow needle coated all along its internal surface and at least partially along its external surface with a water-repellent coating.
11. A pipette system as in claim 1 wherein the water-repellent coating is silicon based.
12. A pipette system in accordance with claim 1 wherein the said openings and said canals can be moved to a position between the first operative position and the second operative position wherein the open ends of the canals do not communicate with the said openings in the second member.
13. A pipette system for the sampling of a calibrated volume of a liquid substance contained in a first container and for the transfer of this volume and an additional calibrated volume of a dilution liquid into a receiving receptacle, characterized by the fact that it comprises a first and a second distribution means, each including a first member and a second member, each of said first members having formed therein at least two independent noncommunicating channels, the ends of which open at the periphery of the first member, said second members being movable with respect to the first members, each of said second members being provided with at least four transverse openings extending through the second member, each channel being adapted to be placed in communication with two of said openings, a sampling means integral with the first distribution means and connected to a first of said openings in the second member of the first distribution means, a first depressurized container connected to a second opening in the second member of the first distribution means adjacent to the said first opening, a second depressurized container connected to a third opening in the second member of the first distribution means adjacent to the last-mentioned second opening, a fourth opening in the second member of the first distribution means, and being connected via a conduit having a calibrated internal volume to a first opening in the second member of the second distribution means, a second opening in the said second member of the said second distribution means adjacent to the first opening, said last-mentioned second opening being connected to a reservoir, a third opening in the second member of the said second distribution means adjacent to the last-mentioned second opening and being connected to a source of compressed gas and a fourth opening in the second member of the second distribution means connected to a source of a dilution liquid.