Pipette calibration station for both single and multi-channel pipettes

Abstract

It is provided a portable, modular, and automated pipette calibration station that calibrates a variety of both single and multi-channel pipettes without additional fixtures. The station can hold multiple pipettes to ran calibration through the night fully automated. The automatic pipette calibration station is consisted of a robotic arm with a pipette gripper as the end effector, a weighing device, an evaporation trap, one or more single or multi-channel pipette holding modules, and a modular base plate. Alternative embodiments include different robot architectures, gripper designs, and sealing methods for evaporation control.

Description

[0001] Pipette Calibration Station for Both Single and Multi-channel Pipettes

[0002] Technical Field of the Disclosure

[0003] The disclosure relates to automated gravimetric calibration of pipettes, including systems and methods for calibrating single- and multichannel pipettes using a robotic station with a pipette gripper, a weighing device, and an evaporation-controlled measurement environment.

[0004] Background of the Disclosure

[0005] Pipettes are widely used in both academic and industrial laboratories whenever precision dispense of fluid samples is required. To ensure the pipettes stay accurate, universities and companies send their pipettes periodically to professional calibration agencies to confirm and certify the pipettes’ accuracy. Existing calibration process involves calibrating each pipette manually. A lab technician measures the dispenses of the pipette using a weighing device multiple times and across the pipette dispense range. The process is labor intensive and time consuming, especially for multichannel pipettes, where each channel needs to be verified individually. Existing automated solutions arc very expensive, bulky, not portable, only work for specific models of the pipettes, and requires custom fixtures for each different pipette model.

[0006] Summary of the Disclosure

[0007] The present invention provides a portable, modular, and automated pipette calibration station that calibrates a variety of both single and multi-channel pipettes without additional fixtures. The station can hold multiple pipettes to run calibration through the night fully automated. The automatic pipette calibration station is consisted of a robotic arm with a pipette gripper as the end effector, a weighing device, an evaporation trap, one or more single or multi-channel pipette holding modules, and a modular base plate. Alternative embodiments include different robot architectures, gripper designs, and sealing methods for evaporation control.

[0008] These and other features of the disclosure will become apparent to those skilled in the art from the following detailed description of the disclosure, taken together with the accompanying drawings.Brief Description of the Drawings

[0009] Figure 1 depicts a perspective view of one embodiment of the pipette calibration station of the present disclosure.

[0010] Figure 2 depicts a perspective view of the pipette gripper 700 of the pipette calibration station in Figure 1.

[0011] Figure 3 depicts a perspective view of the pipette gripper 700 in Figure 2 with the sensor mounting cover 732 removed showing the internal components.

[0012] Figure 4 depicts a perspective view of a single-channel pipette holding module 200 of the pipette calibration station in Figure 1.

[0013] Figure 5 depicts a partially exploded view of the pipette holding module 200 in Figure 4.

[0014] Figure 6 depicts a cutoff section view of the pipette holder 230 of the pipette holding module 200 in Figure 5.

[0015] Figure 7 depicts an exploded view of a multi-channel pipette holding module 200 of the pipette calibration station in Figure 1.

[0016] Figure 8 depicts a perspective view of the weighing device 300 with evaporation trap 400 on top of the pipette calibration station in Figure 1.

[0017] Figure 9 depicts an exploded view of the weighing device 300 with evaporation trap 400 in Figure 8.

[0018] Figure 10 depicts a top view of the trap lid 440 of evaporation trap 400 in Figure 9.

[0019] Figure 11 depicts a perspective view of the top portion (trap lid 440, trap stop 450, and trap cover 460) of evaporation trap 400 in Figure 9.

[0020] Figure 12 depicts a perspective view of the base plate 100 of the pipette calibration station in Figure 1.

[0021] Figure 13 depicts a perspective view of the elevated robot base 500 of the pipette call bration station in Figure 1.Detailed Description

[0022] The present disclosure is an automated pipette calibration station. The station calibrates both single-channel and multi-channel pipettes, can accommodate most pipettes on the market without requiring additional fixtures, can be carried around in luggage-size cases to complete calibration jobs at the client site, and can hold multiple pipettes to run calibration through the night fully automated. The device provides more flexibility, portability, and affordability compared to the existing solutions. Figure 1 depicts one embodiment of the pipette calibration station of the present disclosure.

[0023] Referring now to Figure 1 , there may be seen one embodiment of the pipette calibration station of the present disclosure. The pipette calibration station has a base plate assembly 100. On top of the base plate assembly 100, six pipette holding modules 200, a weighing device set 300, an elevated robot base 500, and a robotic am 600 are installed via screws or other fastening methods such as clamping. A custom evaporation trap assembly 400 is placed on top of the weighing device set 300. Each pipette holding module 200 can hold either two single-channel pipette holders 230 and 240 (not shown), or one multi-channel pipette holder 250. The robotic arm 600 has a pipette gripper 700 as the end-effector. The pipette gripper 700 can grip the pipette 800 up from the pipette holding module 200, move it above the evaporation trap assembly 400, aspirate test liquid, dispense the test liquid into the dispense well 420 (not shown) to be measured by the weighing device set 300, and then return the pipette 800 back to the pipette holding module 200. De-ionized water is a common test liquid used during the calibration process.

[0024] More particularly, there may be seen the trap cover 460 rotated to a sideways open position, allowing the tip holder 820 of the pipette 800 to poke through the trap lid 440 while dispensing the pipette. For the robotic arm 600 shown in the current embodiment, the pipette gripper 700 is rotated to face backward when dispensing the pipette 800. The robotic am 600 is preferably the UR3 model from Universal Robots, or any other six degree-of-freedom robot ams of similar size, though four or five degree-of-freedom robot ams can also be used to reduce the system cost. The robot am 600 can be upgraded to seven or more degree-of-freedom robot arms to further improve the maneuverability of the system and the ease of programming.

[0025] Continuing to refer to Figure 1, the pipette calibration station in the current embodiment contains six pipette holding modules 200. However, with the workspaceof a UR3 or similar robot arm 600, the pipette calibration station can accommodate an additional row of pipette holding modules 200 on the outside (not shown). A plurality of outside mounting tabs 113 on the outside plate 110 give the flexibility to expand the base plate assembly 100 by attaching additional base plates and increasing the pipette holding modules 200 up to sixteen units. The current embodiment includes only six pipette holding modules 200 in order to strike a balance among portability, capacity, cost, and table space. A lab technician should be able to fit the current embodiment easily in a luggage size carrying case, and travel with it to do field pipette calibration at the client lab directly. Having the capacity of six pipette holding modules 200 (twelve single-channel pipettes 800, six multi-channel pipettes, or a combination) is sufficient to run the automatic pipette calibration station overnight without human supervision. A larger robot arm such as the UR5 model from Universal Robotics can be installed to increase the workspace to further expand the number of pipette holding modules 200 beyond sixteen.

[0026] Referring now to Figure 2, there may be seen a closeup front perspective view of the pipette gripper 700 in Figure 1. The single-channel pipette 800 includes a plunger 810 for triggering the dispensing and aspiration of the test liquid, an elongated tip holder 820, and a pipette tip 830. The pipette gripper 700 is consisted of a bottom clamping section 710, a middle section 720, and a top section 730. The bottom clamping section 710 is further consisted of two gripper fingers 711, two gripper jaws 712, and two gripper pads 713.

[0027] The gripper pads 713 are made out of soft materials such as silicone rubber, polyurethane, EVA, or other elastomers, and have grippy surfaces to provide a strong hold when clamped around the pipette 800. The shore A hardness of the gripper pads 713 is preferably between fifteen and seventy-five. The grippy surfaces can be part of the soft material as a whole (e.g. sticky silicone rubber and tire surface textures), or they can be made out of different materials applied afterwards such as tape or any other anti-slip materials. The gripper jaws 712 match the shape of the gripper pads 713 so as to provide a solid backing to the soft gripper pads 713 during clamping. The internal shape of the two gripper pads 713 form a diamond shape when clamping the oval or circular-shape pipette 800. The diamond shape clamp provides 4 main points of contact when clamping the oval or circular pipette 800, enabling a strong clamp vertically when the plunger 810 is pressed, while also ensuring the pipette 800 does not tilt or rotate if the press force is off-center.Because the gripper pads 713 is repeatedly compressed during the pipette gripping and releasing cycles, they may lose structural integrity and their grippy surfaces may lose stiction over time. The gripper pads 713 is preferably attached to the gripper jaws 712 through removable means so that the gripper pads 713 can be replaced easily. Figure 2 shows one such example of the removable means. More particularly, each gripper pad 713 has two T-shaped extrusions 713a that goes into matching holes on the gripper jaw 712. The T-shaped extrusions 713a and their matching holes on the gripper jaws 712 do not go all the way from the top to the bottom, so that when the plunger 810 is pressed, the gripper pads do not slide out from the bottom.

[0028] The gripper fingers 711 connects the gripper jaws 712 to the gripper motor 722 (not shown) located inside the motor sleeve 721. The gripper fingers 711 are connected to the gripper jaws 712 via mounting methods such as finger screw holes 711a. There are a plurality of finger screw holes 71 la to not only mount the gripper jaws 712, but also other potential add-on components, such as cameras, distance sensors, etc.

[0029] The top section 730 further includes a robot attachment flange 731, a sensor mounting cover 732, a sensor mounting base 733, a camera 734, a plunging pad 735, an actuator 736 (not shown), and a loadcell 737 (not shown). The robot attachment flange has a plurality of flange screw holes 731a to connect the pipette gripper 700 to the robot ami 600. The camera 734 is preferably a depth sensing machine vision camera that can monitor the location and size of the pipettes during operation.

[0030] Referring now to Figure 3, there may be seen a perspective view of the pipette gripper in Figure 2 with the sensor mounting cover 732 and robot attachment flange 731 removed showing the internal components. An actuator 736 is situated behind the camera 734. The actuator 736 shown in Figure 3 is an electrical linear actuator. In practice, it can also be electromechanical, pneumatic, hydraulic, voice coil, or solenoid actuators, or rotational actuators with a shaft connected. Actuator 736’s shaft 736a is connected to the plunging pad 735. During the aspiration or dispense of the pipette 800, the bottom clamping section 710 clamps onto the pipette 800 securely, while the shaft 736a moves the plunging pad 735 downward to press the pipette plunger 810. The plunging pad 735 preferably has a larger radius than the pipette plunger 810, so that when the pipette plunger 810 is slightly off-center with respect to the shaft 736, the plunger pad 735 can still successfully press down the plunger 810. Different brands of pipette 800 may also have slightly different plunger 810 locations. Having a largerplunging pad 735 allows the pipette calibration station to accommodate more models of the pipette 800.

[0031] Underneath the robot attachment flange 731 (removed and not shown), there may be seen a loadcell 737. The loadcell 737 is further comprised of a top half 737a with screw connections 737c, and a bottom half 737b with screw connections (not shown). The loadcell measures the force and torque differential between the top half 737a and bottom half 737b. The purpose of the loadcell is to detect the plunging force exerted by the plunging pad 735 onto the pipette plunger 810. A pipette plunger 810 usually has two stages: a first stage to dispense or aspire the liquid, and a second stage that offers an additional “push” to blow the remaining droplets off the tip. The second stage requires a stronger force to press the pipette plunger 810 all the way down. Loadcell 737 ensures that the pipette gripper 700 can accurately determine when the first stage is fully pressed and when the second stage is fully pressed. Being able to precisely differentiate the line between first stage and second stage is vital for accurately aspiring the pipettes, while over-pressing the second stage with too much force risks pipette slippage.

[0032] Continuing to refer to Figure 3, the top half 737c of the loadcell 737 is securely connected to the robot attachment flange 731 (not shown) via the screw connections 737c, and the robot attachment flange 731 is in turn securely connected to the sensor mounting base 733, which holds the actuator 736. The bottom half 737b is securely connected to the gripper motor 722 and the motor sleeve 721, which in turn securely connects to the bottom gripping section 710 that holds the pipette 800. The sensor mounting base is not directly connected to the motor sleeve 721. This layout ensures that the plunging pad 735 is connected to the top half 737a, while the pipette plunger 810 is connected to the bottom half 737b, allowing the loadcell 737 to measure the force exerted onto the pipette plunger 810 by the plunging pad 735. The loadcell 737 is preferably a six-axis loadcell able to detect both the force and torque, which would have an added benefit of collision detection in case the pipette gripper 700 bumps into any obstacles.

[0033] Another possible embodiment of the pipette gripper 700 would get rid of the loadcell 737, and replace the plunger pad 735 into a micro loadcell. The micro loadcell will become the new plunging pad 735 and directly measure the plunging force when pushed against the pipette plunger 810. The robot attachment flange 731 (not shown) would securely connect to both the sensor mounting base 733 and the gripper motor722. A potential issue with this new embodiment is that the micro loadcell is constantly moving up and down with the shaft 736a, and the cable (not shown) of the micro loadcell would gradually wear out.

[0034] Referring now to Figure 4, there may be seen a perspective view of the pipette holding module 200. The pipette holding module 200 is holding a pipette 800 vertically using a basic pipette holder 230. There is also another elevated pipette holder 240, used for holding pipettes that are smaller and shorter, such as those with a 2 uL volume. In the current embodiment, the pipette holding module 200 can hold two single-channel pipettes 800, but in other embodiments the pipette holding module 200 can be extended in length or width to include more pipette holders 230 or 240. The pipette holding module 200 also has a shell 220 to protect and hide the internals.

[0035] Referring now to Figure 5, there may be seen a partially exploded view of the pipette holding module with the shell 220 removed showing a better view of the internals. More particularly, there may be seen a module base 210, a basic pipette holder 230, an elevated pipette holder 240, and two locking keys 260. The basic pipette holder 230 is comprised of four holding arms 231 , a basic holder base 233, and base key holes 234 (not shown). Each holding arm 231 can optionally include a plurality of strengthening ridges 232. The tip holder 820 of pipette 800 is held vertically by the four holding arms 231. The basic holder base 233 sits snugly inside the holder slot 211 on the module base 210.

[0036] The elevated pipette holder 240 is comprised of four holding arms 241, an elevated holder base 243, and base key holes 244. Each holding ami 241 can optionally include a plurality of strengthening ridges 242. The elevated holder base 243 is taller than the basic holder base 233, so that the elevated pipette holder 240 can hold smaller and shorter pipettes. The pipette holders 230 and 240 are modular so that a technician can place different pipette holders based on the pipette types being calibrated. To install the elevated pipette holder 240, a technician would slide the elevated base 243 downwards along direction DI into the holder slot 211, and then slide the locking key 260 along direction D2 through the module key holes 212 and base key holes 244 to lock the elevated pipette holder 240 in place. The locking key 260 is consisted of a handle 261 and two key shafts 262. The module base has base mounting holes 213 to connect the pipette holding module 200 to the base plate assembly 100 (not shown).

[0037] Referring now to Figure 6, there may be seen a front cutoff section view of the basic pipette holder 230. More specifically, there may be seen the holding arm 231 witha corresponding concave section 231a and a convex section 231b, the strengthening ridge 232, the basic holder base 233, the base key holes 234, the converging base hole 235, and the steeper converging base hole 236. When holding the pipette 800, the concave section 231a clamps against the tip holder 820 (not shown), while the convex section 231b stays clear. When the robot arm 600 (not shown) is inserting the pipette 800 (not shown) from the top, the pipette tip 830 (not shown) will be centered by the converging base hole 235, and end up resting inside the steeper converging base hole 236. The steeper converging base hole has steeper or vertical walls to hold the pipette tip upright better. For a larger pipette 800 such as the 5 mL and 10 mL models, the convex section 231a may directly hold onto the larger pipette tip 830 instead of the tip holder 820.

[0038] The materials of the pipette holding arms 231 are preferably soft and flexible but not too soft, so that they can deform and conform snugly to the tip holder 820’s shape (not shown), while still providing sufficient holding force to keep the pipette 800 upright. Example materials include silicone rubber, rubber, TPU, and PU with excellent rebound that are at least Shore A 40 hardness. Alternatively, pipette holding arms 231 can also be spring- actuated to mimic the effect of elastomers while being rigid.

[0039] The surface of the holding arms 231 should be relatively smooth and frictionless, exerting minimal drag force on the pipetie tip 830 (not shown) when the pipette gripper 700 (not shown) is pulling out the pipette 800 (not shown). Otherwise, the pipette tip 830 would be dragged loose by the convex section 231a, and the pipette 800 would no longer be ready for aspiration and dispense. Although in the current embodiment of the pipette holder 230 or 240 is comprised of four holding arms 231, other embodiments may include fewer or more than four holding arms 231.

[0040] Referring now to Figure 7, there may be seen an exploded view of a different version of the pipette holding module 200, where instead of having two singlechannel pipette holders 230 and 240 (not shown), it only includes one multi-channel pipette holder 250. Similar to the basic pipette holder 230, the multi-channel pipette holder 250 has 6 holding arms 251 each with a corresponding concave section 251a and convex section 251b, a multi-channel holder base 253, a plurality of base key holes 254, and a plurality of converging base holes 255. The multi-channel pipette holder 250 shares the same module base 210 with the single-channel pipette holder layout. A technician can choose to install either a multi-channel pipette holder 250 or two basic pipette holders 230 depending on the calibration tasks and pipette types.Notably, the multi-channel pipette holder in this embodiment does not to include the strengthening ridges 232 as it gets the additional strength by including more holding arms 251. Other embodiments of the multi-channel pipette holder 250 may include only four or more than six holding arms 251.

[0041] To install the multi-channel pipette holder 250 into the module base 210, the technician inserts the multi-channel pipette holder 250 along direction DI into the holder slots 211, and inserts the two locking keys 260 through the module base 210 and the base key holes 254. The multi-channel pipette holder 250 shown in Figure 7 has twelve converging base holes 255 designed for a twelve-channel pipette. For pipettes with different number of channels, different customized multi-channel pipette holders can be installed into the same module base 210.

[0042] Referring now to Figure 8, there may be seen a perspective view of the weighing device set 300 with evaporation trap assembly 400 on top. More particularly, the weighing device set 300 includes a weighing device 310 and a balance feet assembly 320. The weighing device 310 is further comprised of a control panel 311 and a static shield 312. The evaporation trap assembly is consisted of a trap body 410 with a dispense well 420 (not shown) inside, an evaporation well 430 situated inside the trap body 410 and around dispense well 20, a trap lid 440, a trap stop 450 affixed to the trap lid 440, a rotating trap cover 460, a servo 470, and an optional aspiration tank 480 at the front. Examples of weighing device 310 commonly used in lab settings are 5-digit or 6-digit analytical balances made by Ragwag and Mettler Toledo.

[0043] Referring now to Figure 9, there may be seen an exploded view of the weighing device set 300 and the evaporation trap assembly 400. More particularly, the balance feet assembly 320 is consisted of a front foot base 321 with two foot slots 321a, a rear foot base 322 with one foot slot 322a, three dampening pucks 323, two front footrests 324 each with a balance foot slot 324a, and a rear footrest 325. The two front dampening pucks 323 rest in and are constrained by the foot slots 321a. The one rear dampening puck 323 rests in and is constrained by the foot slots 322a. The two front feet 314 (only one shown) of the weighing device 310 rest in the foot slots 324a of the front footrests 324, which is in turn nested on top of the dampening pucks 323. The rear foot (not shown) of the weighing device 310 rest on top of the rear footrest 325, which is in turn nested on top of the rear dampening puck 323. The front foot base 321 and the rear foot base 322 are connected securely to the base plate assembly 100 via the screw through-holes 321b and 322b, respectively. Only the two front footrests324 have balance foot slots 324a, while the rear footrest 325 has a flat top surface, because two points of constraints are enough to keep the location of the weighing device 310 secure. Having more than two balance foot slots 324a can risk over constraining the balance. The off-the-shelf weighing device 310 used in the current embodiment only has three feet. For other weighing devices on the market with four feet, the rear foot base 322 can include two rear foot slots 322a, making it similar to the front foot base 321.

[0044] Moving up in Figure 9, there may be seen that the weighing device 310 is comprised of a control panel 311 where the readings are displayed, a sialic shield 312 with two studs 312a, a balance pan 313, and three balance feet 314 (only one shown). The three dampening pucks 323 completely isolates the weighing device 310 from the base plate assembly 100 (not shown), and protect the weighing device 310 from any vibration that may impact the readings. The vibration may come from the movement of the robot 600 or the outside environment such as another nearby pipette calibration station. The static shield 312 is preferably grounded and made out of conductive materials such as metal or carbon infused plastics to avoid interference with the readings.

[0045] Continuing to refer to Figure 9, the dispense well 420 is placed directly on top of the balance pan 313 for measuring the weight of the test liquid inside the dispense well 420. The dispense well 420 has a narrower section 421, a wider section 422, and some locating spokes 423. The wider section 422 is usually used for collecting the dispense of single-channel pipette 800 (not shown), specifically ones with larger volume tips like 0.5 mL and 10 mL that cannot fit inside the narrower section 421. The narrower section is designed to collect the dispense from one of the pipette tips 830 of multi-channel pipettes (not shown), whereas the separation between each pipette tip 830 is usually 9 mm or even smaller.

[0046] Trap body 410 rests on top of the static shield 312 by gravity. The two studs 312a and 312b locates the trap body 410 and prevents it from moving. Evaporation well 430 situates inside the trap body 410, with the evaporation well wall 431 leaning snugly against the inside of the trap body wall 411 to prevent airflow. The dispense well 420 goes through body hole 412 of the trap body 410 and well cavity 434 (not shown) of the evaporation well 430. Dispense well 420’ s locating spokes 423 hover about the matching internal grooves 435 (only one shown) on evaporation well 430. Both the trap body 410 and evaporation well 430 do not touch the dispense well 420nor the balance pan 313, and do not interfere with the readings. The locating spokes 423 ensure that when the dispense well 420 is disturbed and touches the wall of evaporation well 430, the lab technician can simply lift upwards the evaporation trap assembly 400 by a few millimeters to nest the locating spokes 423 into the matching internal grooves 435 to zero the position of the dispense well 420. After zeroing, the technician lowers the evaporation trap 410 back down to isolate the dispense well 420 again. Alternatively, the technician can also zero the position of the dispense well 420 by using an external centering tool or by assessing visually. Another benefit of the locating spokes 423 is that they ensure when the technician removes the evaporation trap assembly 400 by lifting it upwards, the dispense well 420 is removed together, thereby reducing the chance of the dispense well 420 been knocked over accidentally, spilling test liquid onto the expensive weighing device 310.

[0047] The evaporation well 430 is further consisted of two side depressions 432a and 432b (not labeled), and container spaces 433a and 433b (not shown). Trap lid 440 is situated on top of the evaporation well 430, and it is comprised of a narrower hole 441 that matches the narrower section 421 of the dispense well 420, a wider hole 442 that matches the wider section 422 of the dispense well 420, a rear opening 443 that allows the servo 470 to go through and connect to the trap cover 460, mounting feature 444 that connects the trap stop 450 securely to the trap lid 440, and a lid centering grill 445 with slopes that centers the pipette tips 830 of a multi-channel pipette as it moves downward into the narrower hole 441. The aspiration tank 480 is further comprised of a tank space 481 that can hold a lot of test liquid, a narrow aspiration slit 482 to allow a multi-channel pipette to only aspirate one channel at a time, a tank centering grill 483 that mimics the function of the lid centering grill 445 to ensure pipette tip 830 goes into the narrow aspiration slit 482, and a resistance temperature detector (RTD) 484 for measuring the test liquid temperature to aid in the calculation of test liquid density. The aspiration tank can attach to the main evaporation trap assembly 400 via the hanging tabs 413 on the trap body 410. During calibration, after a pipette dispenses into the center well 420, trap cover 460 will move from an open position (shown in Figure 1) to a closed position (shown in Figure 8) to cover up the narrower hole 441 and wider hole 442, and seal up the space within the evaporation trap assembly 400. Test liquid inside container space 433a and 433b has a much larger surface area than the test liquid inside the dispense well 420, and will evaporate much faster to fill in the space of the evaporation trap assembly 400,preventing the test liquid inside the dispense well 420 from evaporating too fast, thereby allowing for an accurate reading of the dispensed amount. Evaporation well 430 with exposed surface area establishes a humidity micro-environment, and optionally a humidity sensor can further provide closed-loop control.

[0048] Referring now to Figure 1 through 9, to certify a multi-channel pipette, the dispense of each channel needs to be calibrated separately. For an evaporation trap assembly 400 without the aspiration tank 480, during the calibration of a twelvechannel pipette, the dispense well 420 and the container space 433a and 433b are prefilled with the test liquid. Camera 734 (preferably 3D imaging camera with depth function) on the pipette gripper 700 would detect the exact location of the multichannel pipette as well as the height of its plunger 810. The pipette gripper 700 would then use its gripper jaws 712 to grip the twelve-channel pipette from its respective pipette holding module 200, placing its plunger 810 directly below the plunging pad 735.

[0049] After that, the actuator 736 moves its shaft 736a in very small increments downward to actuate the plunger 810 while receiving force feedback from the loadcell 737. Pipette plungers 810 have a softer first- stop with precise volume for accurate aspiration, and a stronger second-stop for blow-out at the end of dispenses to remove remaining droplets left inside or under the pipetie tips 830. The force feedback curve should display a steep cliff between the first-stop and second-stop for the algorithm to determine exact how far the actuator shaft should move downwards to activate only the first-stop. The process can be repeated a few times to ensure accuracy.

[0050] Afterwards, the robotic arm 600 maneuvers the multi-channel pipette over the trap lid 440.

[0051] The robotic arm 600 moves the twelve-channel pipette downwards through the narrower hole 441 into the narrower section 421, and dips its first pipette tip 830 under the test liquid, while the other eleven pipette tips 830 go through the lid centering grill 445 into the two side depressions 432a and 432b. The actuator 736 would aspirate the test liquid on the first pipette tip 830, robotic arm 600 then raises the first pipette tip 830 slightly over the test liquid surface, actuator 736 would dispense the pipette, and the whole process is repeated a few times to pre-wet the first pipette tip 830.

[0052] After the pre-wet procedure, the actuator 736 would press down on the plunger 810 to the first-stop, and the robotic arm 600 dips the first pipette tip 830 under thetest liquid again, while the other eleven pipette tips 830 go through the lid centering grill 445 into the two side depressions 432a and 432b. Actuator 736 slowly releases to aspirate the test liquid on the first pipette tip 830 before robotic arm 600 lifts the pipette 800 above the trap lid 440. The servo 470 would close the trap cover 460, wait for the reading on the weighing device 310 to stabilize and record, and then open the trap cover 460 back up for the pipette tip 830 to go back down into the narrower section 421.

[0053] The robot arm 600 would tilt the pipette gripper 700 and twelve-channel pipette by between ten and forty-five degrees into a slanted position before dispensing the test liquid back into the dispense well 420. After that, the robotic arm 600 would again lift the pipette 800 above the trap lid 440 for the trap cover 460 to seal the internal evaporation trap space. After the weighing device 310 records the new weight including the dispense of the first pipette tip 830, the whole process is repeated for a few times for the same pipette tip 830 for validation. The volume dispensed is calculated by dividing the differential weight measured before and after the dispense by the density of the test liquid. The density of the test liquid is by comparing the test liquid temperature measured with RTD 484 against a known density chart.

[0054] Finally, the whole twelve-channel pipette is moved one tip over by 9 mm for the station to test the second pipette tip 830. The process is repeated for the second pipette tip 830, with the first pipette tip 830 and the remaining ten pipette tips 830 dipping underneath the lid centering grill 445, and the second pipette tip 830 dipping into the dispense well 420. The whole process is repeated twelve times for the twelve-channel pipette to complete one round of measurements.

[0055] For an evaporation trap assembly 400 with the aspiration tank 480, the pipette would aspirate from the aspiration tank 480 while the trap cover 460 is closed for the weighing device 310 to stabilize for readings, accelerating the measurement process. The aspiration tank 480 preferably has a test liquid level measurement device installed or a loadcell installed underneath, so that the test liquid level is always known. For single-channel pipettes, the process is only repeated once and the calibration can be done through the wider hole 442.

[0056] The material of the evaporation trap assembly 400 is preferably conductive and anti-static, such as metal, so that there are no static forces on the inside that can affect the balance readings. The trap lid 440 rests on top of the evaporation trap 410 via gravity, or can be connected via removable snap fits, fasteners, or magnets. Theevaporation trap assembly 400 in the current embodiment utilizes a servo 470 and a rotational trap cover 460. Alternatively in a second different embodiment, the narrower hole 441 and wider hole 442 may be made out of flexible materials, with a slit cutout. When the pipette tip 830 moves through them, it pushes open the slit creating a larger opening, and then the pipette tip 830 retracts, the slit closes back in. In a third different embodiment, the trap cover 460 does not need to be rotational. Instead, it can be sliding, hinged, or iris-type, and may employ low-friction coatings (e.g., PTFE) on a polished surface to minimize debris during movement.

[0057] Referring now to Figure 10, there may be seen a clearer top view of the evaporation well 430. The evaporation well is consisted of an evaporation well wall 431, two side depressions 432a and 432b, two container spaces 433a and 433b, well cavity 434, and multiple internal grooves 435. The two container spaces 433a and 433b hold test liquid for evaporation, and the well cavity 434 lets the center well 420 pass through without touching the evaporation well 430.

[0058] Referring now to Figure 11, there may be seen a closeup view of the top portion of the evaporation well assembly 400, including the trap lid 440, the trap stop 450, and the trap cover 460 rotated to the open position. The trap lid 440 is consisted of the narrower hole 441, the wider hole 442, the rear opening 443 (not shown), the mounting feature 444 (not shown), the lid centering grill 445 and the top surface 446. The top surface 446 is preferably low friction so that the trap cover 460 can rotate freely without generating debris over time, which may impact the highly precise weighing device 310’s readings. The top surface 446 can be polished smooth, or coated with low friction materials such as Teflon PTFE. The trap stop 450 is mounted to the trap lid 440 securely via the mounting feature 444 (not shown). In order to keep the internal space of the evaporation assembly 400 as sealed as possible, the trap cover has a sloped cover surface 461 that can jam into the opposite sloped stop surface 451 on the trap stop 450, pushing the trap cover 460 against the top surface 446, sealing the narrower hole 441 and the wider hole 442.

[0059] Referring now to Figure 12, there may be seen an exploded view of the base plate assembly 100. The base plate assembly 100 is modular and currently consisted of the outside plate 110 and the balance plate 120. More plates can be added around the outside plate to expand the pipette calibration station to include more pipette holding modules 200. The outside plate 110 can be replaced to accommodate different robot arm 600, and the balance plate 120 can be replaced to accommodate differentmodels of the weighing device 310. The outside plate 110 has fastening holes 111 on the surface for mounting components (e.g. the pipette holding module 200 and the elevated robot base 500), inside mounting tabs 112 for connecting to the balance plate 120, outside mounting tabs 113 for expansion, and a plurality of hollow spaces 114 to reduce the weight for ease of transportation. The balance plate 120 has fastening holes 121 on the surface for mounting the balance feel assembly 320, mounting tabs 122 for connecting to the outside plate 110, and a plurality of hollow spaces 124 to reduce the weight for ease of transportation. When joining the balance plate 120 to the outside plate 110, the technician moves the balance plate 120 along direction DI, align the mounting tabs 122 to the inside mounting tabs 112, and then joining them together by screws or other fastening methods such as snapping.

[0060] Referring now to Figure 13, there may be seen a front perspective view of the elevated robot base 500. The elevated robot base 500 is consisted of a foundation 510, a tower 520, and two wall panels 530 (only one is shown). The foundation 510 has fastening holes 511 to connect itself to the outside plate 110 (not shown). The tower 520 has fastening holes 531 at the top to securely connect itself to the foundation 510, screw holes 532 for connecting the robot arm 600 (not shown), and a hollow center 533 for all of the cables from the robot arm 600 and the sensors in the pipette gripper 700 to pass down into the foundation 510. The two wall panels 530 are removably attached to the foundation 510 via fastening holes 531, and they have openings 532 for the cables to pass through. The front wall panel 53O’s opening 532 allows for the cables from the weighing device 310 and RTD 484 to pass through, while the rear wall panel 530' s opening 532 (not shown) allows for all of the cables from the pipette calibration station to go out to connect to power and processing units such as a computer and robot control box. The internal of the foundation 510 is hollow in order to accommodate all of the cables and adaptors. The tower 520 is optional and the robot arm 600 can directly connect to the foundation 510, though having the tower 520 is advantageous when the robot arm 600 is UR3 or similar models in order to maximize the arm workspace. The tower 520 and the foundation 510 can be combined into one element, though having them separated is advantageous for transportation purposes, so that a technician can fold down and disassemble the pipette calibration station to a flatter state to better fit inside a luggage.

[0061] In the current embodiment, the pipette calibration station includes embedded electronics comprising processors, memory chipsets, and I / O interfaces (collectively,“station electronics”). The gripper electronics (i) acquire mass-versus-time data from the weighing device, (ii) compute delivered volume using a temperature-dependent liquid density, with optional buoyancy correction, (iii) evaluate a stability criterion (e.g., mass change

[0062]

[0063] A over a dwell time T or variance threshold) before accepting a reading, (iv) sequence multi-channel measurements while positioning non-measured tips into side depressions of the evaporation trap, and (v) generate a tamper-evident audit record containing time-stamped data, environmental readings, tolerances, and pass / fail outcomes. Optional routines include vision-based tip alignment and droplet detection via the gripper camera, and force-controlled plunger actuation using load-cell feedback to achieve a target force or flow profile. The gripper electronics communicate with the balance via RS-232 / USB / Ethemet and with the robot arm over its native interface.

[0064] While the present disclosure has been described with respect to the embodiment set forth above, the present disclosure is not necessarily limited to the current embodiment. Accordingly, other embodiments, variations, and improvements not described herein are not excluded from the scope of the present disclosure. Such variations include but arc not limited to different layouts of the pipette calibration station, different shapes of the pipette holders, different robot arm, different weighing device, different pipette holder materials, and modifications to the evaporation trap based on different designs of commercially available weighing devices or pipettes.

[0065] Although the present disclosure and its advantages have been described in detail, it should be understood that various changes, substitutions and alterations can be made herein without departing from the spirit and scope of the disclosure as defined by the appended claims.

Claims

What is claimed is:1 . A pipette calibration station, comprising:a base assembly,a robotic arm having at least four degrees of freedom mounted to said base assembly,at least one pipette holding module located on said base assembly,a weighing device having a balance pan,said weighing device located on said base assembly,an evaporation trap positioned on top of said weighing device,a pipette gripper installed securely to the end of said robotic arm, andsaid pipette gripper having a frame, a gripper motor, two gripper fingers securely connected to the said gripper motor, and at least one actuator arranged to depress a pipette plunger along a pipette axis.

2. The pipette calibration station of claim 1, wherein said base assembly is modular, comprising at least two plate members that removably connect to each other.

3. The pipette calibration station of claim 1, further comprising vibration isolation members mechanically decoupling said weighing device from said robotic arm and said base assembly.

4. The pipette calibration station of claim 1, wherein said pipette holding module further comprises:at least one holder body defining a receiving aperture about a central axis, said holder body having one or more holding members circumferentially disposed about the aperture,each said holding member having an upper gripping segment whose inner face converges toward said axis to clamp the lower half of a pipette, and a lower clearance segment that flares away from said axis to avoid contact with one or more pipette tips,a tip-centering feature aligned with said axis and having a tapered entrance to guide and axially locate a pipette tip during robotic pickup and return, andwherein said holder body is able to accommodate pipettes with different shapes and tip holder diameters within a predetermined range without tooling change to a different holder body.

5. The holder body of claim 4, wherein the number of said holding members is at least three when staging a single-channel pipette, at least four when staging a multi-channel pipette, and one when said holding members are interconnected forming one single slotted-ring holding member.

6. The holder body of claim 4, wherein each holding member is made out of an elastomer having a Shore A hardness of at least forty durometer or includes a spring- actuated mechanism that allows said holding members to open up when a pipette is staged and rebound when removed.

7. The pipette calibration station of claim 1 , wherein said evaporation trap further comprises:a housing defining an internal volume,a center well containing test liquid located inside said internal volume and positioned on top of said balance pan, andtwo side depressions configured to exclude unmeasured tips of a multichannel pipette from said internal volume.

8. The evaporation trap of claim 7, wherein said center well has a narrow section sized to accommodate the narrow channel spacing of multi-channel pipettes, and a wide section sized to accommodate the pipette tips of large volume single-channel pipettes.

9. The evaporation trap of claim 7, further comprising:a trap lid having at least one lid opening,a movable cover configured to selectively open and close said lid opening to isolate said internal volume from outside disturbances and reduce evaporation during weighing stabilization, andsaid movable cover can be any of: a rotary cover, a sliding cover, a hinged cover, a flexible cover, or an iris type shutter.

10. The evaporation trap of claim 7, further comprising one or more of the following: a reservoir within said housing having an exposed surface to establish a humidity micro-environment, andan external reservoir accessible to a pipette for aspiration.11 . The pipette calibration station of claim 1, wherein said pipette gripper further comprises one or more of the following:gripper pads on inner-facing surfaces of said gripper fingers forming a four-point and diamond-shaped contact to self-center a pipette,said gripper pads having high friction surface texture or material, and a camera module.

12. The pipette gripper of claim 11, further comprising one or more of the following:a load cell operatively coupled to said pipette gripper to measure actuation force, said load cell being located between said gripper motor and said frame, said actuator and said frame, within said actuator, or on an exterior of said actuator, wherein said actuator is selected from electromechanical, pneumatic, hydraulic, voice coil, solenoid, linear, or rotational actuators,a second actuator arranged to actuate the tip ejector of a pipette, anda third actuator arranged to rotate a volume adjustment dial of the pipette.

13. A method for automated gravimetric calibration of a pipette using a station comprising a robotic arm, a pipette gripper having at least one actuator and load cell, an evaporation trap on a weighing device, and controlling electronics; the method comprising:(a) gripping a pipette with said pipette gripper,(b) determining, using load-cell feedback, a transition threshold between a first stop and a second stop of the pipette plunger,(c) actuating said pipette plunger to said first stop using said actuator to aspirate a test liquid,(d) causing said robotic arm to align one pipette tip with a well inside said evaporation trap,(e) actuating said pipette plunger all the way to said second stop to dispense said test liquid into the well,(f) waiting for the mass data from said weighing device to stabilize,(g) receiving stabilized mass data and determining delivered volume using a temperature-dependent density, and(h) repeating the steps (c) - (g) for each channel in the case of a multi-channel pipette and multiple times to produce a pass / fail result and a calibration record.

14. The method of claim 13, further comprising staging said pipette on a universal pipette holding module able to accommodate pipettes with different shapes and tip holder diameters without requiring custom fixtures before step (a).

15. The method of claim 13, further comprising pre-wetting said pipette tips by aspirating and dispensing multiple times before collecting data before step (c).

16. The method of claim 13, further comprising computer-vision-based determination of pipette overall length so that said robotic arm can vertically align said pipette tip with said well for pipettes of different sizes.

17. The method of claim 13, further comprising excluding non-measured tips of a multi-channel pipette from the internal volume of said evaporation trap with side depressions during step (d).

18. The method of claim 13, further comprising one or more of the following steps:immersing the pipette tip of said pipette under said well’s existing liquid surface during or after dispense in step (e) to rid said pipette tip of remaining liquid droplets,tilting said pipette during step (e) to prevent liquid droplets from forming on said pipette tip,aspirating said test liquid directly from said well during the first or repeated step (c) so that said well will never overfill due to repeats in step (h),causing a multi-channel pipette to align with a narrow section of said well in step (d),causing a single channel pipette to align with a wider section of said well in step (d),using a pipette to drain said well of liquid when said well is filled after repeated tests, andrunning a repeating step (c) while simultaneously waiting for step (f) and (g) to complete from the previous cycle to save time.

19. A pipette holding module to be used in an automatic pipette calibration station, comprising:at least one holder body defining a receiving aperture about a central axis, said holder body having a plurality of holding members circumferentially disposed about the aperture,each said holding member having an upper gripping segment whose inner face converges toward said axis to clamp the lower half of a pipette, and a lower clearance segment that flares away from said axis to avoid contact with one or more pipette tips,a tip-centering feature aligned with said axis and having a tapered entrance to guide and axially locate a pipette tip during robotic pickup and return, and wherein said holder body is able to accommodate pipettes with different shapes and tip holder diameters within a predetermined range without tooling change to a different holder body.

20. The holder body of claim 19, wherein the number of said holding members is at least three when staging a single -channel pipette, at least four when staging a multi-channel pipette, and one when said holding members are interconnected forming one single slotted-ring holding member.21 . The holder body of claim 19, wherein each holding member is made out of an elastomer having a Shore A hardness of at least forty durometer or includes a spring-actuated mechanism that allows said holding members to open up when a pipette is staged and rebound when removed.

22. An evaporation trap to be used in an automatic pipette calibration station,comprising:a housing defining an internal volume configured to rest on a weighing device around a balance pan,two side depressions to exclude the non-measured tips of a multi-channel pipette from said internal volume,a center well holding testing liquid located on top of said balance pan having narrow and wide sections,a reservoir situated inside said housing with an exposed surface to promote evaporation,a trap lid on top of said housing with at least one opening,a movable cover movable between an open position exposing said opening and a closed position reducing humidity changes inside the internal volume.

23. The evaporation trap of claim 22, further comprising one or more of following:Aligning members on the exterior for guiding pipette tips into said center well, an external liquid reservoir accessible to pipettes for aspiration, andA temperature probe for measuring temperature used for density calculation of said testing liquid.

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