AUTOMATED PIPETTE MANIPULATION SYSTEM

Abstract

The automated pipette manipulation system of the present invention allows for the automated manipulation of any pipette commercially available to aspire and dispense liquids in a chemical or biochemical laboratory setting. Measuring the amount of liquid aspired or dispensed by a pipette is conducted by a load sensor that records the starting point of the displacement of a pushbutton of said pipette and a motor that drives the displacement of said pushbutton a predetermined distance past the starting point that corresponds to a predetermined volume of liquid aspired or dispensed by said pipette. The automated pipette manipulation system of the present invention further detects whether a pipette tip is attached to said pipette and then automatically ejects said pipette tip at the end of a liquid handling process.

Claims

1. An automated pipette manipulation system comprising: a pipette having a pushbutton; an actuator head assembly that is movable in at least one direction; and having an attachment mechanism to which said pipette is removably attached; an actuator mechanism that is movable to actualize a displacement of said pushbutton of said pipette, and comprising a load cell; wherein said load cell establishes a starting point of said displacement of said pushbutton; and wherein said actuator mechanism displaces said pushbutton downward a predetermined distance past said starting point that corresponds to a predetermined volume of a liquid aspired or dispensed by said pipette.

2. The automated pipette manipulation system of claim 1 wherein said actuator mechanism further comprises a solenoid that actualizes the displacement of an ejector pin to eject a pipette tip from said pipette.

3. The automated pipette manipulation system of claim 1 wherein said actuator head assembly is movable by a first motor interfaced with a first encoder that senses the movement of said actuator head assembly; and wherein said actuator mechanism is movable by a second motor interfaced with a second encoder that senses the movement of said actuator mechanism.

4. The automated pipette manipulation system of claim 1 further comprising a microprocessor that controls the movement of said actuator head assembly and said actuator mechanism.

5. The automated pipette manipulation system of claim 1 that can be calibrated for use with different pipettes of varying shapes and sizes.

6. The automated pipette manipulation system of claim 1 wherein said actuator mechanism displaces said pushbutton further after dispensing said liquid from said pipette so as to purge any residual left in said pipette.

7. The automated pipette manipulation system of claim 1 further comprising a sensor to detect whether a pipette tip is attached to said pipette.

8. An automated pipette manipulation system comprising: a pipette having a pushbutton; a platform assembly that is movable horizontally along a first linear guide; a head assembly that is movable horizontally along a second linear guide that is transverse to said first linear guide; an actuator head assembly that is attached to said head assembly; that s movable vertically along a third linear guide; and having an attachment mechanism to which said pipette is removably attached; an actuator mechanism that is movable vertically along a fourth linear guide to actualize a downward displacement of said pushbutton of said pipette and comprising a load cell and a motor; wherein said load cell establishes a starting point of said downward displacement of said pushbutton; and wherein said motor displaces said pushbutton downward a predetermined distance past said starting point that corresponds to a predetermined volume of a liquid aspired or dispensed by said pipette.

9. The automated pipette manipulation system of claim 8 wherein said actuator mechanism further comprises a solenoid that actualizes the displacement of an ejector pin to eject a pipette tip from said pipette.

10. The automated pipette manipulation system of claim 8 wherein said platform assembly is movable by a first motor interfaced with a first encoder that senses the movement of said platform assembly; wherein said head assembly is movable by a second motor interfaced with a second encoder that senses the movement of said head assembly; wherein said actuator head assembly is movable by a third motor interfaced with a third encoder that senses the movement of said actuator head assembly; and wherein said actuator mechanism is movable by a fourth motor interfaces with a fourth encoder that senses the movement of said actuator mechanism.

11. The automated pipette manipulation system of claim 8 further comprising a microprocessor that controls the movement of said platform assembly, said head assembly; said actuator head assembly; and said actuator mechanism.

12. The automated pipette manipulation system of claim 8 that can be calibrated for use with different pipettes of varying shapes and sizes.

13. The automated pipette manipulation system of claim 8 wherein said actuator mechanism displaces said pushbutton further after dispensing said liquid from said pipette so as to purge any residual left in said pipette.

14. The automated pipette manipulation system of claim 8 further comprising a sensor to detect whether a pipette tip is attached to said pipette

15. An automated pipette manipulation system comprising: a pipette having a pushbutton; a method of removably attaching said pipette to an actuator head assembly; a method of moving said actuator head assembly in at least one direction; a method of actualizing a displacement of said pushbutton of said pipette; a load cell that establishes the starting point of said displacement of said pushbutton; and a method of displacing said pushbutton a predetermined distance past said starting point that corresponds to a predetermined volume of a liquid aspired or dispensed by said pipette

16. The automated pipette manipulation system of claim 15 further comprising a method of displacing an ejector pin to eject a pipette tip from said pipette.

17. The automated pipette manipulation system of claim 15 further comprising a method of controlling the movement of said actuator head assembly and the displacement of said pushbutton.

18. The automated pipette manipulation system of claim 15 further comprising a method of calibrating said system for use with different pipettes of varying shapes and sizes.

19. The automated pipette manipulation system of claim 15 further comprising a method of purging any residual after said liquid, has been dispensed from said pipette.

20. The automated pipette manipulation system of claim 15 further comprising a method of sensing whether a pipette tip is attached to said pipette.

Description

DESCRIPTION OF THE DRAWINGS

[0017] The accompanying drawings which are incorporated by reference herein and form part of the specification, illustrate various embodiments of the present: invention and, together with the description, further serve to explain the principles of the invention and to enable a person skilled in the pertinent art make and use the invention. In the drawings, like reference numbers indicate identical or functionally similar elements. A more complete appreciation of the invention and many of the attendant advantages thereof will be readily obtained as the same becomes better understood by reference to the following detailed description when considered in connection with the accompanying drawings, wherein:

[0018] FIG. 1 is a front perspective view of the automated pipette manipulation system of the present invention in its assembled state as it would be installed and used in a laboratory setting.

[0019] FIG. 2 is a rear perspective view of the automated pipette manipulation system of the present invention in its assembled state as it would be installed and used in a laboratory setting.

[0020] FIG. 3 is a perspective view of the actuator head assembly as it is attached to the head assembly that moves horizontally on linear guides of the present invention.

[0021] FIG. 4 is a perspective view of the actuator head assembly as it is attached to the head assembly but having the actuator mechanism opened so as to see some internal components of the present invention.

[0022] FIG. 5 depicts an exploded view of the actuator mechanism and the manual pipette of the present invention.

[0023] FIG. 6 depicts a sectional view of the actuator mechanism and the manual pipette of the present invention.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0024] Reference will now be made to the drawings in which various elements of the present invention will be given numerical designations and in which the invention will be discussed so as to enable one skilled in the art to make and use the present invention.

[0025] The present invention is an automated pipette manipulation system 500 that comprises a platform assembly 10, a head assembly 12, an actuator head assembly 14, an actuator mechanism 16, a pipette 250, and a microprocessor 300. The head assembly 12 allows for horizontal movement of the pipette 250 along the x-axis. The actuator head assembly 14 allows for vertical movement of the pipette 250 along the z-axis. The actuator mechanism 16 manipulates the pipette 250 to aspire or dispense liquid, and extract a pipette tip 220 that is attached to the pipette 250. Finally, the platform assembly 10 can be moved horizontally in the direction that is transverse of the horizontal movement of the head assembly 12, thus, along the y-axis. These mechanisms provide the automated pipette manipulation system 500 of the present invention full range of motion that can move the pipette along the x, y, and z axis. The microprocessor 300 ultimately controls the manipulation of the pipette, both its motion and its use.

[0026] As shown in FIG. 1, the platform assembly 10 comprises a platform 30 on which various workstations rest, such as, a pipette tip disposable bin 208, a rack 210 for ready-to-use disposable pipette tips 220, a fluid reservoir 212, and a conventional microwell plate 214. The platform assembly 10 is mounted for horizontal movement on two parallel linear guides 20 by means of slide bearings. The horizontal movement is driven by a first motor 22. Therefore, as the first motor 22 turns, it rotates a first lead screw 24 that is attached to a first screw nut 26 which is fixedly attached to a support block 28, as shown in FIG. 2. The support block 28 is attached to platform 30 by a fastener 32. A sensor 33 is mounted on the platform 30 to detect whether a pipette tip 220 is attached to the pipette 250. A first encoder 25 interfaced with the first lead screw 24 records the rotational motion of the first motor 22 and the first lead screw 24. The recorded data is then used to calculate the linear position and speed of the platform assembly 10. A pair of first limit sensors 35 are interfaced with the respective ends of the path of travel of the platform assembly 10 to indicate the end of the travel.

[0027] As shown in FIGS. 2 and 3, the head assembly 12 can move horizontally in a direction transverse to the movement of the platform assembly 10 on two parallel linear guides 34 by means of slide bearings 36. The horizontal movement is driven by a second motor 38. Therefore, as the second motor 38 turns, it rotates a second lead screw 40 that is attached to a second lead screw nut 42 which is fixedly attached to a plate 44. The plate 44 is then attached to the head assembly 12 with fasteners 46. A second encoder 45 interfaced with the second lead screw 40 records the rotational motion of the second motor 38 and the second lead screw 40. The recorded data is then used to calculate the linear position and speed of the head assembly 12. A pair of second limit sensors 48 are interfaced with the respective ends of the path of travel of the head assembly 12 to indicate the end of travel.

[0028] As shown in FIG. 4, the actuator head assembly 14 is attached to the head assembly 12 in a configuration that supports vertical movement. The actuator head assembly 14 moves vertically along a linear guide 50 by means of two slide bearings 52 which are inline mounted for rigidity. The vertical movement is driven by a third motor 54. Therefore, as the third motor 54 turns, it rotates a third lead screw 56 that is attached to a third lead screw nut 58 which is fixedly attached to an upright support 60. As shown in FIG-. 6, a third encoder 61 interfaced with the third lead screw 56 records the rotational motion of the third motor 54 and the third lead screw 56. The recorded data is then used to calculate the linear position and speed of the actuator head assembly 14. A pair of third limit sensors 62 are interfaced with the respective ends of the path of travel of the actuator head assembly 14 to indicate the end of travel. The actuator head assembly 14 also provides an attachment mechanism to which the pipette 250 is removably attached.

[0029] As shown in FIG. 5, the actuator mechanism. 16 comprises an actuator arm 100, an insert 102, a load cell 104, a pipette tip ejector 106, and a cover 108. The cover 108 is securely fastened to the top of the actuator arm 100 so as to enclose the insert 102, the load cell 104, and the pipette tip ejector 106 therewithin. The actuator head assembly 14 supports the actuator mechanism 16 that is configured to move vertically along a linear guide 78 by means of two slide bearings 80 that are inline mounted for rigidity. The vertical movement is driven by a fourth motor 82 that rotates a fourth lead screw 84 that is attached to a fourth lead screw nut 86 rigidly fixed to the actuator arm 100. A fourth encoder 90 interfaced with the fourth lead screw 84 records the rotational motion of the fourth motor 82 and the fourth lead screw 84. The recorded data is then used to calculate the linear position and speed of the actuator mechanism 16. A pair of fourth limit sensors 92 and 94 are interfaced with the respective ends of the path of travel of the actuator mechanism 16 to indicate the end of travel.

[0030] As shown in FIG-S. 4 and 6, the pipette tip ejector 106 comprises a solenoid 107 having a shaft and mounted securely to the actuator arm 100, and an ejector pin 222 that is attached to the shaft of the solenoid 107. The solenoid 107 in the present invention is normally maintained in the retracted position such that the ejector pin 222 is normally in the upper position. Actuation of the solenoid 107 displaces the ejector pin 222 vertically downward.

[0031] As shown in FIGS. 4 and 5, the pipette 250 is fixedly installed to a bottom plate 64 and a top plate 70 of the actuator head assembly 14. A spring-loaded gripper 72 is attached to the bottom plate 64 and comprising two finger-like elements that rotate around the center axis of fasteners 74. The pipette 250 is pushed in between the finger-like elements of the gripper 72 and on to the top plate 70 such that the pipette 250 is rigidly held therewithin. A spring 76 provides adequate resistance or force for the gripper 72 to hold the pipette 250 firmly upright in the actuator head assembly 14.

[0032] The microprocessor 300 then controls the solenoid 107 and all the motors 22, 38, 54, and 82. In essence, the microprocessor 300 functions to control the sequence of operations of each of these elements, and thus the interrelated movements of the platform assembly 10, the head assembly 12, the actuator head assembly 14, the actuator mechanism 16, and the pipette tip ejector 106. In addition, the microprocessor 300 monitors the movements and operation of the automated pipette manipulation system 500 of the present invention.

[0033] Hereinafter, an explanation of the methods of operation of the automated pipette manipulation system 500 of the present invention will be given.

[0034] In a nutshell, the operation of the automated pipette manipulation system 500 comprises the method and process of picking up and placing a pipette tip 220 from a rack 210 onto the pipette nozzle 230, moving the pipette 250 to a reservoir 212, extracting fluid therefrom, moving the pipette 250 to a microwell plate 214, dispensing the fluid therein, and finally ejecting the pipette tip 220 into a pipette tip disposable bin 208.

[0035] As shown in FIG. 5, a typical pipette 250 comprises a pushbutton 110 at the top of a stein that is spring-loaded and pushes against a piston, a nozzle 230 to which a pipette tip 220 is attached, and a tip ejector button 228 that is spring-loaded and ejects the pipette tip 220 by releasing it from its frictional engagement with the nozzle 230. Use of a pipette begins with the attachment of a pipette tip 220 to the nozzle 230. Then the pushbutton 110 is pressed downward so as to push against the resistance of the pipette spring until the piston is at its lowermost position. Then dipping the pipette tip 220 into a liquid. Then releasing the pushbutton 110 such that the resistance of the pipette spring forces it to move upwardly causing the liquid to be aspired into the pipette tip 220. Once the desired amount of liquid is aspired, the pushbutton 110 is held in place while the pipette tip 220 is removed from the liquid and the pipette 250 is moved over a tray or some tube into which the liquid is dispensed by pressing the pushbutton 110 downward until the piston is at its lowermost position. Finally, the tip ejector button 228 is pressed to eject or release the pipette tip 220 from the pipette 250.

[0036] Controlled by the microprocessor, the automated pipette manipulation system 500 of the present invention is able to operate a pipette 250 as described above. Furthermore, that which is novel of the automated pipette manipulation system 500 of the present invention, is the method and process of controlling and measuring the amount of liquid that is aspired and dispensed, as explained below.

[0037] First, the automated pipette manipulation system 500 of the present invention manipulates the pipette 250 such that a pipette tip 220 is attached to the nozzle 230. Second, the fourth motor 82 is activated to displace the actuator mechanism 16 downward. As shown in FIG. 6, the bottom surface 216 of the actuator arm 100 has a tapered circular recess 218 that guides the actuator arm 100 onto the pushbutton 110 of the pipette 250 as the actuator mechanism 16 is displaced downwardly. Third, as the actuator mechanism 16 is further displaced downwardly, the pushbutton 110 presses against the insert 102 which is then pushed against the load cell 104. Fourth, as the actuator mechanism 16 is further displaced downwardly, the load cell 104 senses changes in electrical signal and sends stream of data to the microprocessor 300 that uses the data to calculate the force exerted against the pushbutton 110. Fifth, as soon as the force exerted against the pushbutton 110 is greater than zero, the automated pipette manipulation system 500 of the present invention marks or identifies the corresponding vertical location of the actuator mechanism. 16 as the starting point. Sixth, the fourth motor 82 is deactivated so as to stop the displacement of the actuator mechanism 16 at a predetermined distance from the starting point that directly relates to the predetermined volumetric amount of liquid that would be aspired by the pipette 250 when the pushbutton 110 is released. Seventh, the automated pipette manipulation system 500 of the present: invention manipulates the pipette 250 such that the pipette tip 220 is dipped into a desired liquid. Eighth, the actuator mechanism 16 is displaced upwardly so that the pushbutton 110 is released and forced upwardly by the resistance of the pipette spring. The upward force exerted on the pushbutton 110 by the resistance of the spring causes the piston to be displaced upward, which then causes the liquid to be aspired into the pipette tip 220. Ninth, the automated pipette manipulation system 500 of the present invention manipulates the pipette such that the liquid is dispensed into a desired location by the downward movement of the actuator mechanism 16. Finally, the solenoid 107 is activated to displace the ejector pin 222 downward until it exerts pressure against the top surface 226 of the tip ejector button 228 of the pipette 250. This then causes the pipette 250 to release the pipette tip 220 from its frictional engagement with the nozzle 230. It is also noteworthy that a motor and lead screw arrangement can be used instead of a solenoid to drive the pipette tip ejection system.

[0038] In an alternative embodiment of the automated pipette manipulation system 500 of the present invention, the fourth motor 82 is deactivated so as to stop the displacement of the actuator mechanism 16 when the load cell 104 records a predetermined amount of force exerted against the pushbutton 110. Since the pushbutton 110 is spring-loaded, the force exerted against it is proportional to the distance displaced. This linear relationship between the force and distance is dependent on the stiffness of the pipette spring. The predetermined distance of displacement by the piston directly relates to predetermined volumetric amount of liquid that would be aspired by the pipette 250 when the pushbutton 110 is released.

[0039] However, in the preferred embodiment of the automated pipette manipulation system 500 of the present invention, the volumetric measurement of the liquid aspired into the pipette tip 220 is done by using the load cell 104 to determine the starting point and using the fourth encoder 90 interfaced with the fourth lead screw 84 and the fourth motor 82 to measure the distance that the actuator mechanism 16 is displaced until the fourth motor 82 is deactivated when the actuator mechanism 16 is displaced a predetermined distance corresponding to a predetermined volumetric measurement.

[0040] With the configuration described above, the automated pipette manipulation system 500 of the present invention allows for a pipette 250 to be manipulated so as to aspire and dispense an accurate volume of liquid in a laboratory setting. Furthermore, the configuration described above allows for the automated pipette manipulation system 500 of the present invention to operate with a wide range of manual pipettes that are commercially available and manufactured by third-parties. Despite varying sizes and heights, different pipettes can be used with the automated pipette manipulation system 500 of the present invention because the actuator mechanism 16 can be moved high enough to accommodate any commercially available pipette 250 and then calibrated for a particular pipette 250 by the process of using the load cell 104 to establish the starting point, as described above.

[0041] Furthermore, the use of a load cell 104 to establish the starting point and subsequently tracking the displacement of the pushbutton 110 via the fourth encoder 90 interfaced with the fourth lead screw 84 and the fourth motor 82, allows the automated pipette manipulation system 500 of the present invention to aspire and dispense varying volume of liquid without re-sizing or changing the settings in the pipette 250.

[0042] Most commercially available pipettes 250 have pistons that can be moved upward or downward so as to set a predetermined volume. Once the volume is set, displacing the pushbutton 110 to the lowest position ensures that the pipette 250 will aspire the set volume of liquid. Other pipette manipulation systems commercially available always displace the pushbutton 110 to its lowest point so that a preset volume of liquid is aspired and dispensed. The disadvantage of said systems is that the operator is required to always manually set the volume of the pipette 250 before each use. Such task, especially when done repeatedly, can be cumbersome, inefficient, and susceptible to human error. The automated pipette manipulation system 500 of the present invention, however, eliminates this disadvantage by its use of the load cell 104 in conjunction with the fourth encoder 90 interfaced with the fourth lead screw 84 and the fourth motor 82 to aspire and dispense a predetermined volume of liquid without changing the volume settings of the pipette 250.

[0043] Alternatively, the automated pipette manipulation system 500 of the present invention can be used to aspire the maximum amount of volume of liquid and dispense partially in multiple areas. With this methodology, the actuator mechanism 16 is first displaced down to its lowest point. Second, the pipette tip 220 is dipped into a desired liquid. Third, the actuator mechanism 16 is displaced upwardly so that the pushbutton 110 is released and forced upwardly by the resistance of the pipette spring. The upward force exerted on the pushbutton 110 by the resistance of the pipette spring causes the piston to be displaced upward, which then causes the liquid to be aspired into the pipette tip 220. Fourth, the starting point is marked or identified as described above by use of the load cell 104. Fifth, the automated pipette manipulation system 500 of the present :invention manipulates the pipette such that the liquid is dispensed into various desired locations by the downward movement of the actuator mechanism 16. In essence, at the first location, the actuator mechanism 16 is displaced downward a predetermined distance from the starting point that directly relates to the predetermined volumetric amount of liquid that would be dispensed by the pipette 250 at the first location. Then, the process is repeated at the second and subsequent locations until all the liquid in the pipette tip 220 is dispensed.

[0044] Calibration of the automated pipette manipulation system 500 of the present ion is accomplished by reference to a library of pipette specifications stored in the microprocessor 300. The library includes specifications related to the correlation of volume of liquid aspired and the distance that the pushbutton 110 or piston is displaced. Reference to the library enables the automated pipette manipulation system 500 of the present invention to use any commercially available pipette 250 and aspire or dispense an accurate volume of liquid required by the user. Alternatively, the automated pipette manipulation system 500 of the present invention allows for its calibration with any pipette 250 not found in the library.

[0045] It is understood that the described embodiments of the present invention are illustrative only, and that modifications thereof may occur to those skilled in the art. Accordingly, this invention is not to be regarded as limited to the embodiments disclosed, but to be limited only as defined by the appended claims herein.