Pipetting instrument

Abstract

A pipetting instrument for loading and dispensing a sample is described. The pipetting apparatus includes an automated liquid pipette having a platen for supporting a pipetting tip cartridge including pipetting tips and a mandrel for engaging the pipetting tips and removing at least some of the pipetting tips from the pipetting tip cartridge. The pipetting instrument further includes a controller configured to control the automated liquid pipettor, the controller further configured to perform a pipette tip removal operation to remove any unwanted pipette tips removed from the pipette tip cartridge using the mandrel.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application was filed as a PCT international patent application on June 6, 2023, and claims the benefit and priority of U.S. Provisional Patent Application No. 63 / 349,913 filed on June 7, 2022 and U.S. Provisional Patent Application No. 63 / 383,281 filed on November 11, 2022, the entire disclosures of which are incorporated herein by reference in their entirety. Background Art

[0003] Liquid handling devices are commonly used in laboratory settings to reliably transfer liquids from one container to another. In commercial laboratory settings, automated liquid pipettes are used to reduce labor costs associated with large liquid handling projects while potentially improving the efficiency, accuracy, and precision of the projects. Automated liquid pipettes frequently use disposable pipette tips to reduce cross-contamination of samples due to inadvertent mixing of residual fluid from one source with residual fluid from another source.

[0004] Disposable pipette tips are usually stored in linear arrays, such as pipette tip boxes, that are accessible to automated liquid pipettes. Automated liquid pipettes must load tips from these arrays in the pipette tip box, or unload tips to these arrays in the pipette tip box. When the pipette tips loaded are less than the entire array of pipette tips, the automated liquid pipette must load a set of pipette tips from the pipette tip box, while the remaining pipette tips remain in the pipette tip box. Summary of the invention

[0005] The present disclosure relates to a pipetting instrument. In some embodiments, and by way of non-limiting example, the pipetting instrument performs loading and unloading operations, wherein a pipette tip is loaded from a pipette tip box onto a mandrel of the pipette instrument, or a pipette tip is unloaded from a mandrel into a pipette tip box. In some embodiments, the mandrels are densely packed together to maximize the number of samples per unit area on the loading or unloading space. In some embodiments, the mandrel has a maximum diameter coupled to a maximum pipette tip diameter. Maximizing the diameter of the pipette tip is desirable because it maximizes the amount of sample that can be extracted into the pipette tip per cycle. Maximizing the surface area of ​​the mandrel and the number of mandrels per unit area can leave very little space between each mandrel. Minimizing the space between the mandrels may cause difficulties in using the mandrel to aim at the required pipette tip. In addition, even if the required pipette tip is loaded or unloaded using the mandrel, the unwanted pipette tip may be unintentionally loaded out of the pipette tip box together with the required pipette tip. These unwanted pipette tips may be loaded due to mechanical or electrostatic coupling with the spindle or the desired pipette tips. Therefore, it is desirable to create a pipetting device and method for loading or unloading desired pipette tips from a pipette tip box while reliably unloading all unwanted pipette tips from the spindle.

[0006] In one example, a pipetting instrument for loading and dispensing samples includes: an automatic liquid pipette, the automatic liquid pipette including a platen and a spindle, the platen being used to support a pipette tip box including pipette tips, and the spindle being used to engage the pipette tips and remove at least some of the pipette tips from the pipette tip box; and a controller configured to control the automatic liquid pipette, the controller also being configured to perform a pipette tip removal operation to remove any unwanted pipette tips removed from the pipette tip box using the spindle.

[0007] In another example, a method for loading a set of pipette tips onto an automated liquid pipette apparatus includes: coupling desired pipette tips to a spindle by positioning the spindle and engaging the pipette tips with the spindle; lifting the spindle to partially remove the desired pipette tips from a pipette tip box and lifting at least one unneeded pipette tip together with the desired pipette tips; moving the spindle to move at least one unneeded pipette tip out of the spindle, thereby returning at least one unneeded pipette tip to the pipette tip box while the desired pipette tips remain coupled to the spindle; and lifting the spindle to completely remove the desired pipette tips from the pipette tip box.

[0008] In yet another example, a method for unloading one or more pipette tips from an automated liquid pipette includes positioning a spindle to engage and insert the pipette tips into a pipette tip box; activating a set of plungers to disconnect the pipette tips from the spindle and unload the pipette tips into the pipette tip box; positioning the spindle to partially insert any pipette tips that remain coupled to the spindle into the pipette tip box; and moving the spindle and pipette tips to disconnect the pipette tips from the spindle and unload the pipette tips into the pipette tip box.

[0009] Various additional aspects will be described in the subsequent description. These aspects may relate to individual features or to combinations of features. It should be understood that the foregoing general description and the following detailed description are only exemplary and explanatory and do not limit the broad inventive concepts on which the examples disclosed herein are based. BRIEF DESCRIPTION OF THE DRAWINGS

[0010] The following drawings illustrate examples of the present disclosure and therefore do not limit the scope of the present disclosure.Examples of the present disclosure will be described below in conjunction with the accompanying drawings, wherein the same reference numerals represent the same elements.

[0011] Figure 1 A block diagram of a pipetting instrument including an automated liquid pipette and optionally a pipette tip magazine according to the principles of the present disclosure is shown.

[0012] Figure 2A Shows Figure 1 A transverse cross-sectional view of a pipetting instrument comprising a spindle, a pipette tip and a pipette tip box, wherein an unneeded pipette tip is connected to the spindle and / or another pipette tip.

[0013] Figure 2B Shows Figure 1 A transverse cross-sectional view of a pipetting instrument comprising a spindle, a pipette tip and a pipette tip box, wherein an unneeded pipette tip is disconnected from the spindle and / or another pipette tip and is placed in the pipette tip box.

[0014] Figure 3A Shows Figure 1 A front view of an example implementation of a pipetting instrument.

[0015] Figure 3B Shows Figure 1 A side view of an example embodiment of a pipetting instrument.

[0016] Figure 4 Shows Figure 1 A perspective view of a pod used in an example embodiment of a pipetting instrument.

[0017] Figure 5 Shows Figure 1A top perspective view of the internal components of another embodiment of a pod used in an example embodiment of a pipetting instrument.

[0018] Figure 6 Shows Figure 1 A side perspective view of the internal components of another embodiment of a pod used in an example embodiment of a pipetting instrument.

[0019] Figure 7 It is a stereogram of the motorized stage moving along the X-axis.

[0020] Fig. 8A A perspective view showing the movement of the motorized stage along the Y-axis is shown.

[0021] Figure 8B A perspective view of a motorized stage moving along the Y-axis is shown, wherein a portion of the motorized stage is cut away to show the Y-axis motor.

[0022] Fig. 9 Shows Figure 1 Block diagram of the basic hardware components of a pipetting instrument, illustrating the movement of the motorized stage along the Z-axis.

[0023] Fig.10 Shows Figure 1 Block diagram of the additional hardware components of an example pipetting instrument.

[0024] Fig.11 A perspective view of an example embodiment of a pipette tip box is shown.

[0025] Fig.12 A perspective view of an example embodiment of a pipette tip box is shown, wherein the spacing of the pipette tips within the pipette tip box may vary slightly.

[0026] Fig.13 Shows Figure 1 A perspective view of a spindle assembly used in an example embodiment of a pipetting instrument.

[0027] Fig.14A Shows Figure 1 A perspective view of an alternative spindle assembly for use in an example embodiment of a pipetting instrument.

[0028] Fig. 14B Shows Figure 1 A perspective view of an alternative spindle assembly for use in an example embodiment of a pipetting instrument, wherein the spindle is partially inserted into a pipette tip box or housing plate.

[0029] Fig.15 Shows Figure 1 A segmented spindle is used in an example embodiment of a pipetting instrument.

[0030] Fig.16A A transverse cross-sectional view of a spindle inserted into a pipette tip is shown, wherein the spindle includes a plunger for unloading the pipette tip when the plunger engages a filter.

[0031] Fig. 16B Shows the insertion Fig.16A A transverse cross-sectional view of a spindle within a pipette tip with the plunger engaging the filter.

[0032] Fig.17 An example computing device is shown.

[0033] Fig.18 Shows the depiction according to Figure 1 A flow chart of loading a partial set or a desired set of pipette tips of an example embodiment of a pipetting instrument.

[0034] Fig.19 A shows a transverse cross-sectional view of the spindle, pipette tip box and pipette tips, which depicts Fig.18 In the first step, the spindle approaches and enters the pipette tip in the pipette tip box.

[0035] Fig.19 B shows a transverse cross-sectional view of the spindle, pipette tip box and pipette tips, which depicts Fig.18 In a first step, a spindle is coupled to a pipette tip in a pipette tip box.

[0036] Fig. 20A A transverse cross-sectional view of a spindle, a pipette tip box, and a pipette tip is shown, depicting Fig.18 The second step comprises coupling the spindle to a pipette tip in a pipette tip box.

[0037] Fig. 20B A transverse cross-sectional view of a spindle, a pipette tip box, and a pipette tip is shown, depicting Fig.18 A second step is provided in which the spindle partially removes the pipette tip from the pipette tip box.

[0038] Fig.21 A schematic diagram is shown depicting the coordinated movement of the spindles to move any unwanted pipette tips off the spindles or to move wanted pipette tips out.

[0039] Fig. 22 A transverse cross-sectional view of a spindle, a pipette tip box, and a pipette tip is shown, depicting Fig.18 In the fourth step, the required pipette tip has been completely removed from the pipette tip box and connected to the spindle.

[0040] Fig.23 Shows the depiction according to Figure 1A flow chart of unloading pipette tips from a spindle into a pipette tip box according to an example embodiment of a pipetting instrument.

[0041] Fig.24 A transverse cross-sectional view of a spindle, a pipette tip box, and a pipette tip is shown, depicting Fig.23 The first step is to position the spindle to engage and insert the pipette tip into the pipette tip box.

[0042] Fig.25 A transverse cross-sectional view of a spindle, a pipette tip box, and a pipette tip is shown, depicting Fig.23 The second step comprises a plunger on the spindle being activated to disconnect the pipette tip from the spindle and unload the pipette tip into a pipette tip box.

[0043] Fig.26 A transverse cross-sectional view of a spindle, a pipette tip box, and a pipette tip is shown, depicting Fig.23 The third step comprises positioning the spindle such that any pipette tips remaining coupled to the spindle are partially inserted into the pipette tip box.

[0044] Fig. 27 A schematic diagram depicting the coordinated motion of the spindles is shown for depicting Fig.23 In the fourth step the spindle removes any unwanted pipette tips.

[0045] Fig.28 A transverse cross-sectional view of a spindle, a pipette tip box, and a pipette tip is shown, depicting Fig.23 A fifth step in which the spindle is removed from the pipette tip box and each of the pipette tips has been unloaded into the pipette tip box.

[0046] Fig.29 Shown is a front view of the top portion of a pipette tip having pipette tip features that may have an impact on the process of loading or unloading a desired pipette tip.

[0047] In the drawings, similar components and / or features may have the same reference numeral. In addition, various components of the same type may be distinguished by following the reference numeral with a dash and a second reference numeral that distinguishes the similar components. If only the first reference numeral is used in the specification, the description is applicable to any of the similar components having the same first reference numeral, regardless of the second reference numeral. DETAILED DESCRIPTION

[0048] Various examples will be described in detail with reference to the drawings, wherein like reference numerals represent like parts and assemblies throughout the several views.

[0049] Figure 1is a block diagram of an example pipetting instrument 100. The example pipetting instrument 100 includes an automated liquid pipette 102, a pipette tip box 104, and a controller 106. In some embodiments, the controller 106 is configured to execute a tip removal procedure 108.

[0050] The pipetting instrument 100 is an instrument that performs a pipetting operation, such as a laboratory instrument. An example of the pipetting instrument 100 is a sample preparation instrument. Figure 3A , Figure 3B , Figure 4 , Figure 5 , Figure 6 , Fig. 9 as well as Fig. 22 Examples of sample preparation instruments are illustrated and described in more detail.

[0051] The automatic liquid pipette 102 is a system that performs automatic pipetting functions. Figure 3A and Figure 3B Examples of automated liquid pipettes are illustrated and described in greater detail.

[0052] The pipette tip box 104 is a container configured to store pipette tips 110. In some embodiments, the pipette tip box 104 stores the pipette tips 110 in a linear manner. The pipette tips 110 can be stored in the pipette tip box 104 at a uniform distance from each other. In some embodiments, the pipette tip box 104 can accommodate 384 pipette tips 110, wherein each pipette tip 110 has a uniform spacing of 4.5 mm. In some embodiments, the pipette tip box 104 can accommodate 96 pipette tips 110, wherein each pipette tip 110 has a uniform spacing of 9 mm. In some embodiments, the positioning of the pipette tips 110 in the pipette tip box 104 can comply with industry standards for microplates, such as industry standards established by the Society for Laboratory Automation and Screening (SLAS), the American National Standards Institute (ANSI), or other industry standards. Reference Fig.11 Examples of pipette tip boxes 104 are illustrated and described in greater detail.

[0053] The controller 106 is configured to control the automated liquid pipette 102. In some embodiments, the automated liquid pipette 102 receives instructions from the controller 106 and retrieves and / or returns the pipette tips 110 from the pipette tip box 104 to the pipette tip box 104 to load or unload the pipette tips 110 onto the automated liquid pipette 102. The controller 106 is configured to execute a tip removal program 108 that removes any unwanted pipette tips 132 from the automated liquid pipette 102 as the automated liquid pipette 102 loads or unloads the pipette tips 110 from the pipette tip box 104.

[0054] Figure 2A Shows Figure 1 FIG. 1 is a transverse cross-sectional view of a pipetting instrument 100 including a spindle 130 , a pipette tip 110 and a pipette tip box 104 , wherein an unneeded pipette tip 132 is coupled to the spindle 130 and / or another pipette tip 110 .

[0055] The spindle 130 is connected to the pipetting instrument 100 and is configured to engage the pipette tip 110 by pressing the spindle into the pipette tip 110. The bottom of the spindle can be configured to attach to the top of the pipette tip 110 via a friction fit. Thus, pushing the spindle 130 into the pipette tip 110 within the pipette tip box 104 can force the pipette tip 110 onto the spindle 130 and provide an airtight connection between the pipette tip 110 and the spindle 130. Fig.13 Examples of mandrels 130 are illustrated and described in greater detail.

[0056] An unwanted pipette tip 132 is a pipette tip 110 that unintentionally remains coupled to the spindle 130 or another pipette tip 110 after the spindle is lifted from the pipette tip magazine 104. The unwanted pipette tip 132 may be unintentionally lifted by the spindle 130 due to mechanical or electrostatic coupling between the unwanted pipette tip 132 and the spindle 130, between the unwanted pipette tip 132 and the desired pipette tip 134, or between the unwanted pipette tip 132 and both the spindle 130 and the desired pipette tip 134. In some embodiments, the controller 106 can control the automated liquid pipette 102 and provide instructions to load every other pipette tip 110 from the pipette tip magazine 104. In these examples, the required pipette tips 134 are defined by the controller as every other pipette tip 110 in the pipette tip box 104, and the unrequired pipette tips 132 are defined as every pipette tip 110 that is not defined as a required pipette tip 134. Figure 2A In the embodiment shown in FIG. 1 , an unwanted pipette tip 132 is located between two needed pipette tips 134 , wherein the unwanted pipette tip 132 is unintentionally lifted from the pipette tip box 104 .

[0057] Figure 2B Shows Figure 11 is a transverse cross-sectional view of a pipette instrument 100 including a spindle 130, a pipette tip 110, a tray 111, and a pipette tip box 104, wherein an unwanted pipette tip 132 is disconnected from the spindle 130 and / or another pipette tip 110 and rests within the pipette tip box 104. The unwanted pipette tip 132 can be disconnected from the spindle 130 by partially inserting the unwanted pipette tip 132 into the pipette tip box 104 and completing a coordinated movement 136 of the spindle 130. The coordinated movement 136 of the spindle 130 is a movement in which each spindle 130 moves together synchronously to provide a similar movement between each spindle 130. The tray 111 is positioned above the pipette tip box 104 to guide the pipette tip 110 into the pipette tip box 104 as the spindle 130 passes through the tray 111. Referring to Fig.21 and Fig. 27 Examples of coordinated movement 136 are illustrated and described in greater detail.

[0058] In some embodiments, the pipetting instrument 100 can include at least one sensor for identifying when an unwanted pipette tip 132 is coupled to a spindle 130 or a desired pipette tip 134. If any unwanted pipette tips 132 are sensed, the sensor can identify a group of spindles 130 to perform a coordinated motion 136. If the sensor fails to sense any unwanted pipette tips 132, it can provide feedback to the controller 106 to abort the step of performing the coordinated motion 136.

[0059] Figure 3A Shows Figure 1 1 is a front view of an example embodiment of a pipetting instrument 100 that may include any combination of the various systems or components shown. For example, the pipetting instrument 100 may include one or more (or none) of a pod 150, a spindle 130, a pipette tip box 104, a platen 152, and a motorized stage 154. An overview of these various components of the pipetting instrument 100 is provided below.

[0060] In some embodiments, the pipetting instrument 100 can include a motorized stage 154. In some of such embodiments, the motorized stage 154 can be movable along one or more axes. For example, the motorized stage 154 can slide laterally along the length of the pipetting instrument 100. In some embodiments, the pipetting instrument 100 can include a pod 150 mechanically coupled to the motorized stage 154. As shown in the figure, the pod 150 can have an elongated housing along a vertical axis that is held upright by the motorized stage 154. Figure 4The bottom of the pod 150, shown in more detail in FIG. 1 , may include a spindle 130 configured to engage and / or connect with one or more pipette tips 110 in the pipette tip box 104. In some embodiments, the pod 150 is capable of moving along the motorized stage 154 in one or more axes. For example, as shown in the figure, the pod 150 can slide laterally along the length of the motorized stage 154. In addition, in some embodiments, the pod 150 can slide vertically relative to the motorized stage 154 so that the bottom of the pod 150 can be positioned higher or lower. Thus, the bottom of the pod 150 can be repositioned with precise 3-axis motion by adjusting the following combination: the height of the pod 150 relative to the motorized stage 154 (e.g., Z axis), the lateral position of the pod 150 along the motorized stage 154 (e.g., Y axis 182), and the lateral position of the motorized stage 154 along the length of the pipetting instrument 100 (e.g., X axis 180). In this figure, the lateral movement of the motorized stage 154 illustrates movement along the Y-axis 182 .

[0061] In some embodiments, the pod 150 can be a multi-channel pod configured to engage and connect with multiple pipette tips 110 that can be used to perform pipetting operations simultaneously. In some embodiments, the pod 150 can include various components that allow various pipetting and fluid handling operations to be performed using the attached pipette tips 110.

[0062] The deck 152 may be located within the pipetting instrument 100, wherein the deck is used to support various laboratory materials associated with the pipetting instrument 100. In this figure, the deck 152 supports a pipette tip box 104, which is positioned to engage the spindle 130 to perform pipetting operations.

[0063] Figure 3B Shows Figure 1 1. A front view of an example embodiment of a pipetting instrument 100 that may include any combination of the various systems or components shown. In this figure, the lateral movement of the motorized stage 154 illustrates movement along the X-axis 180.

[0064] Figure 4 Shows Figure 11. A front view of a pod 150 used in an example embodiment of a pipetting instrument of the present invention. In some embodiments, the pod 150 may include a spindle 130 located at the bottom of the pod 150. Each spindle 130 may be configured to be coupled to a pipette tip 110, and each spindle 130 may have an elongated channel (not shown) running through the vertical length of the spindle 130. The elongated channel may allow each spindle 130 to facilitate performing a pipetting operation on an attached pipette tip. For example, the elongated channel may be used to generate different degrees of pressure within the attached pipette tip, thereby allowing liquid to be drawn into or discharged from the bottom of the pipette tip 110.

[0065] The pod 150 includes a pod motor 156. In an example embodiment of the pod 150, the pod 150 may include three pod motors 156 located at the top of the pod 150. The pod motor 156 may control the plunger 190, which removes the pipette tip 110 from the spindle 130 along the plunger path 312. Referring to FIGS. Fig.25 Examples of the plunger 190 and plunger path 312 are shown and described in more detail. In addition, the pod motor 156 can control the position of the spindle 130 along the Z-axis 184, which is referred to as Figures 4 to 6 Illustrated and described in more detail.

[0066] Additionally, the pod 150 may include an arm 158 for grasping an object beneath the pod 150. In some embodiments, the arm 158 may extend downward to grasp a lab appliance beneath the pod 150, thereby stabilizing the lab appliance and allowing the spindle 130 connected to the pod 150 to engage the lab appliance. In some embodiments, the arm 158 may be controlled by at least one of the pod motors 156, wherein the pod motor is configured to engage and disengage the arm 158 to grasp or release the lab appliance.

[0067] In addition, the pod 150 includes three pod motors 156A, 156B, and 156C. The pod motors 156A and 156C are mechanically coupled to two lead screws 160A and 160B, respectively. The lead screws 160A and 160B are coupled to two nuts 162A and 162B, respectively, fixed to the bracket, and as the pod motors 156A and 156C rotate the two lead screws 160A and 160B, the lead screws 160A and 160B allow the pod 150 to move along the Z axis 184. In this figure, the pod motor 156B can be used to operate the plunger 190 stored in the spindle 130 attached to the pod 150.

[0068] Figure 5 Shows Figure 11 is a top perspective view of the internal components of another embodiment of the pod 150 used in an example embodiment of the pipetting instrument 100. The pod 150 includes a first lead screw 170, a second lead screw 172, a first Z-axis motor 174, a second Z-axis motor 176, and a mounting plate 178. More specifically, Figure 5 The diagram illustrates how the lead screws, such as the first lead screw 170 and the second lead screw 172, can be rotated in various embodiments of the pod 150. It is contemplated that any method and configuration may be used to rotate the lead screws, not just by using a motor mechanically coupled to the lead screws. In addition, any number of motors mechanically coupled to any number of lead screws may be provided. Figures 7 to 9 Examples of motors are illustrated and described in greater detail.

[0069] As shown in the figure, each individual lead screw is mechanically coupled to an independent motor. For example, the top of the first lead screw 170 can be mechanically coupled to the first Z-axis motor 174. In some embodiments, the first Z-axis motor 174 can be located within the enclosure and mechanically coupled to the first lead screw 170 via a pulley and belt, both of which can also be contained within the pod 150. The operation of the first Z-axis motor 174 can be used to rotate the first lead screw 170 clockwise and counterclockwise. The top of the second lead screw 172 can be mechanically coupled to the second Z-axis motor 176. In some embodiments, the second Z-axis motor 176 can also be mechanically coupled to the second lead screw 172 via a pulley and belt, both of which can also be contained within the pod 150. The operation of the second Z-axis motor 176 can be used to rotate the second lead screw 172 clockwise and counterclockwise. Both lead screws may extend through the vertical dimension of the nacelle 150 and may be anchored at the top of the nacelle 150 and at the bottom of the nacelle 150 .

[0070] Thus, in various embodiments, each lead screw can be mechanically coupled to an independent motor that drives it. This configuration can also provide many advantages to allow loading of a partial rack of pipette tips 110 as opposed to loading all of the pipette tips 110 in the pipette tip box 104. In the typical case of loading a full load of pipette tip boxes 104, a symmetrical downward force can be used. For example, the workstation can reposition the bottom of the pod so that it is centered in a full tip tray.

[0071] The mounting plate 178 is coupled to the first lead screw 170 and the second lead screw and is driven by the first Z-axis motor 174 and the second Z-axis motor 176 to move along the lead screws along the Z-axis 184. In some embodiments, the mounting plate 178 moves the lead screws up and down along the Z-axis 184 to position the spindle 130 and engage the spindle 130 with the pipette tips 110 stored in the pipette tip box.

[0072] Figure 6 Shows Figure 1 18. A side perspective view of the interior components of another embodiment of a pod 150 used in an example embodiment of a pipetting instrument of the present invention. The figure illustrates a view of the interior components of the pod 150 according to an example embodiment utilizing a first lead screw 170 and a second lead screw 172, wherein, as described above, the first lead screw 170 is mechanically coupled to a first Z-axis motor 174 and the second lead screw 172 is mechanically coupled to a second motor to provide vertical movement of the mounting plate 178 along the Z-axis 184. This movement allows the pod 150 to be positioned so that the pod 150 engages with a pipette tip box 104 to remove a pipette tip 110 from the pipette tip box 104.

[0073] Figure 7 1 is a perspective view of the motorized stage 154 moving along the X-axis 180. The liquid handling instrument 100 includes the motorized stage 154, which is configured to move the pod 150 along the X-axis 180 and the Y-axis 182. Fig. 8A and Figure 8B The movement of the motorized stage 154 along the Y-axis 182 is illustrated and described in greater detail.

[0074] The movement of the motorized stage 154 along the X-axis 180 is driven by an X-axis motor 186. The X-axis motor 186 is configured to drive a timing pulley and a timing belt respectively to move the motorized stage 154 along the X-axis 180. In some embodiments, the X-axis motor 186 can drive the motorized stage 154 along a lead screw.

[0075] Fig. 8A A perspective view of the motorized stage moving along the Y-axis 182 is shown. The pipetting instrument 100 includes a motorized stage 154 configured to move the pod 150 along the X-axis 180 and the Y-axis 182. The motorized stage 154 moves along the Y-axis 182 by sliding along a bridge 191. The bridge 191 serves as a linear guide to guide the motorized stage along the Y-axis 182.

[0076] Figure 8B A perspective view of the motorized stage moving along the Y-axis is shown, wherein a portion of the motorized stage is cut away to show the Y-axis motor. In this figure, a portion of the pipetting instrument 100 is cut away to reveal the Y-axis motor 188. The Y-axis motor 188 drives the motorized stage 154 along the Y-axis 182 by driving a timing pulley and a timing belt. In some embodiments, the Y-axis motor 188 can drive the motorized stage 154 along a lead screw.

[0077] Fig. 9 Shows Figure 11 is a block diagram of the basic hardware components in the pipetting instrument of FIG. 1 , which illustrates the movement of the motorized stage along the Z-axis 184. The block diagram includes the controller 106, the first lead screw 170, the second lead screw 172, the first Z-axis motor 174, the second Z-axis motor 176, and the mounting plate 178. Specifically, the block diagram also illustrates the movement of the mounting plate 178 along the Z-axis 184.

[0078] The mounting plate 178 is configured to move along the first lead screw and the second lead screw as follows: The controller 106 controls the first Z-axis motor 174 and the second Z-axis motor 176 to rotationally drive the lead screws, thereby moving the mounting plate along the Z-axis 184 .

[0079] Fig.10 Shows Figure 1 1 is a block diagram of additional hardware components of an example pipetting instrument. The block diagram illustrates a pipetting instrument 100 configured to input a sample and output a prepared sample. The pipetting instrument 100 includes a computing device 230, which also includes a system memory 238 and a processing device 232, a display device 268, a sample manipulation station 200, an automatic liquid pipette 102 including a controller 106, and the pipetting instrument 100 also includes a tip removal program, a motorized rack 154, a pod 150, and a deck 152, wherein a pipette tip box can be stored on the deck within the pipetting instrument 100, as indicated by the dashed outline.

[0080] Reference Fig.17 Examples of computing device 230, system memory 238, processing device 232, and display device 268 are illustrated and described in more detail. Computing device 230 can be used to execute operating systems, applications, and software modules (including software engines) described herein. Display device 268 can communicate with an operator and provide feedback from computing device 230. The computing device can provide input to the automatic liquid pipette 102, or receive input from the automatic liquid pipette 102.

[0081] Samples loaded into the automated liquid pipette 102 may be manipulated at a sample manipulation station 200, which is configured to manipulate input samples to output prepared samples. The sample manipulation station 200 may perform many different tasks to prepare samples, including pipetting, mixing, heating, or otherwise manipulating samples to prepare output samples.

[0082] Fig.11A perspective view of an example embodiment of a pipette tip box 104 is shown. As shown in the figure, the pipette tips 110 are held upright in the pipette tip box 104 in a 16×24 configuration for a total of 384 pipette tips. These pipette tips will be used with a corresponding set of spindles 130 having the same 16×24 configuration to allow pipetting operations using up to 384 pipette tips. The pipette tip box 104 can be supported by a platen 152 within the pipetting instrument 100. In some embodiments, the pipette tip box 104 can hold the pipette tips 110 upright in an 8×12 configuration for a total of 96 pipette tips 110. These pipette tips 110 will be used with a corresponding set of spindles 130 having the same 8×12 configuration to allow pipetting operations using up to 96 pipette tips 110.

[0083] Fig.12 A perspective view of an example embodiment of a pipette tip box 104 is shown in which the spacing of the pipette tips 110 within the pipette tip box 104 may vary slightly. In this figure, the pipette tips 110 may touch in certain locations or be spaced further apart than the average spacing between the pipette tips 110. The spacing between the pipette tips 110 that is less than the average spacing between the pipette tips 110 may further result in undesirable pipette tips 132 being unnecessarily loaded onto the spindle 130 or desired pipette tips 134.

[0084] Fig.13 Shown include Figure 1 A perspective view of a spindle assembly of a spindle 130 used in an example embodiment of a pipetting instrument. As shown in the figure, the spindle 130 is an 8×12 configuration for a total of 96 spindles. Therefore, the spindle 130 can be attached to 96 pipette tips 110 at the same time. In some embodiments, the spindle 130 can be a 16×24 configuration for a total of 384 spindles 130. In some embodiments, each spindle 130 can be generally cylindrical, with an elongated channel running through the vertical length of the spindle. The elongated channel can allow each spindle 130 to facilitate performing pipetting operations on the attached pipette head. For example, the elongated channel can be used to generate different degrees of pressure in the attached pipette tip 110, thereby allowing liquid to be sucked into the bottom of the pipette tip 110 or discharged from the bottom of the pipette tip 110. In some embodiments, each spindle 130 may taper toward the bottom end or have features at the bottom end that facilitate an airtight friction fit with the top of the corresponding pipette tip 110 .

[0085] Fig.14A Shown include Figure 1 1 is a perspective view of an alternative spindle assembly of a spindle 130 used in an example embodiment of a pipetting instrument. As shown in the figure, the spindle 130 is a 1×8 configuration with a total of 8 spindles 130. The spindle 130 can be coupled to a pod 150.

[0086] Fig. 14B Shows Figure 1 104, wherein the mandrels are partially inserted into a pipette tip box 104 or a housing plate. As shown in the figure, the mandrels 130 are in a 1×8 configuration for a total of 8 mandrels 130. The pod 150 can be positioned so that the mandrels 130 are at least partially inserted into the pipette tip box 104 to engage the pipette tips 110. The pipette tip box can be stored on a deck 152.

[0087] Fig.15 Shows Figure 1 A segmented spindle 130 is used in an example embodiment of a pipetting instrument. The spindle 130 can be segmented so that it includes sections of different diameters. In some embodiments, the different diameters can correspond to the diameters of the pipette tips 110 stored in the pipette tip box 104. In some embodiments, the different diameters can correspond to the diameters of the pipette tips 110 standardized by an organization that regulates pipette microplates. In some embodiments, these standards may be regulated by the Society for Laboratory Automation and Screening (SLAS). In some embodiments, a section of the spindle 130 can correspond to a pipette tip stored in a microplate such as Fig.11 104 having 384 pipette tips 110. In some embodiments, a section of the mandrel 130 may correspond to a diameter of a pipette tip 110 stored in a pipette tip box 104 having 384 pipette tips 110. Fig.13 The diameter of the pipette tips 110 in the pipette tip box 104 of 96 pipette tips 110 shown in the spindle assembly with 96 spindles 130. In some embodiments, the spindle 130 can include stainless steel. In some embodiments, the spindle 130 can be installed on the automatic liquid pipette 102 using an interference fit.

[0088] Fig.16A 1 is a transverse cross-sectional view of a spindle 130 inserted into a pipette tip 110, wherein the spindle 130 includes a plunger 190 for unloading the pipette tip 110 when the plunger 190 filter 192 is engaged. In some embodiments, the plunger 190 is driven by a pod motor 156. The plunger 190 unloads the pipette tip 110 by applying a downward force along the plunger path 312 toward the bottom of the spindle 130. Fig.25 The plunger path 312 is described and illustrated in greater detail. As the plunger 190 moves along the plunger path 312, the plunger 190 may contact the filter 192, wherein the filter 192 exerts an equal and opposite force on the spindle 130 with an upward force toward the top of the spindle 130. These forces cause the pipette tip 110 to move out of the spindle 130.

[0089] The filter 192 is configured to provide a barrier between the spindle 130 and fluid drawn from the sample using the pipette tip 110. The filter 192 is configured to allow air to flow through the filter while blocking liquid, such as a sample drawn into the pipette tip 110.

[0090] Fig. 16B Yes Insert Fig.16A FIG. 1 is a transverse cross-sectional view of the spindle 130 within the pipette tip 110 of FIG. 1 , wherein the plunger 190 is engaging the filter 192. In this figure, the plunger 190 is engaging the filter 192 to remove the pipette tip 110 from the spindle 130.

[0091] Fig.17 An exemplary architecture of a computing device that may be used to implement aspects of the present disclosure is shown, including any of a plurality of computing devices 230 , a controller 106 , and the like. Fig.17 The computing device illustrated in can be used to execute the operating systems, applications, software modules (including software engines, and including the tip removal program 108) described herein.

[0092] In some embodiments, the computing device 230 includes at least one processing device 232, such as a central processing unit (CPU). A variety of processing devices are available from a variety of manufacturers, such as Intel or Advanced Micro devices. In this example, the computing device 230 also includes a system memory 234 and a system bus 236, which connects various system components including the system memory 234 to the processing device 232. The system bus 236 is: a type of bus structure in any number of types of bus structures including a memory bus or a memory controller; a peripheral bus; and a local bus using any of a variety of bus architectures.

[0093] Examples of computing devices suitable for computing device 230 include server computers, desktop computers, laptop computers, tablet computers, mobile computing devices (such as smartphones, or mobile digital device or other mobile device) or other device configured to process digital instructions.

[0094] The system memory 234 includes read-only memory 238 and random access memory 240. A basic input / output system 242, containing the basic routines used to transfer information within the computing device 230, such as during startup, is typically stored in the read-only memory 238.

[0095] In some embodiments, the computing device 230 also includes a secondary storage device 244, such as a hard disk drive, for storing digital data. The secondary storage device 244 is connected to the system bus 236 via a secondary storage interface 246. The secondary storage device 244 and its associated computer-readable media provide non-volatile storage of computer-readable instructions (including applications and program modules), data structures, and other data for the computing device 230.

[0096] Although the exemplary environment described herein uses a hard disk drive as a secondary storage device, other types of computer-readable storage media are used in other embodiments. Examples of these other types of computer-readable storage media include magnetic tape cassettes, flash memory cards, digital video disks, Bernoulli cartridges, compact disk read-only memories, digital versatile disk read-only memories, random access memories, or read-only memories. Some embodiments include non-transient media. Additionally, such computer-readable storage media may include local storage or cloud-based storage.

[0097] A number of program modules may be stored in the secondary storage device 244 or memory 234, including an operating system 248, one or more application programs 250, other program modules 252 (such as the software engines described herein), and program data 254. The computing device 230 may use any suitable operating system, such as Microsoft Windows TM , Google Chrome TM , Apple OS, and any other operating system suitable for a computing device.

[0098] In some embodiments, a user provides input to the computing device 230 through one or more input devices 256. Examples of input devices 256 include a keyboard 258, a mouse 260, a microphone 262, and a touch sensor 264 (such as a touch pad or touch-sensitive display). Other embodiments include other input devices 256. The input devices are typically connected to the processing device 232 through an input / output interface 266 coupled to the system bus 236. These input devices 256 can be connected through any number of input / output interfaces such as a parallel port, a serial port, a game port, or a universal serial bus. Wireless communication between the input device and the interface 266 is also possible, and in some possible embodiments includes infrared, Wireless technology, 802.11a / b / g / n, cellular or other radio frequency communications systems.

[0099] In this example embodiment, a display device 268, such as a monitor, liquid crystal display device, projector, or touch-sensitive display device, is also connected to the system bus 236 via an interface, such as a video adapter 270. In addition to the display device 268, the computing device 230 may also include various other peripheral devices (not shown), such as speakers or a printer.

[0100] When used in a local area network environment or a wide area network environment (such as the Internet), the computing device 230 is typically connected to the network through a network interface 272, such as an Ethernet interface. Other possible implementations use other communication devices. For example, some implementations of the computing device 230 include a modem for communicating across the network.

[0101] Computing device 230 typically includes at least some form of computer-readable media. Computer-readable media include any available media that can be accessed by computing device 230. Computer-readable media include, by way of example, computer-readable storage media and computer-readable communication media.

[0102] Computer-readable storage media include volatile and nonvolatile, removable and non-removable media implemented in any device configured to store information such as computer-readable instructions, data structures, program modules or other data. Computer-readable storage media include, but are not limited to, random access memory, read-only memory, electrically erasable programmable read-only memory, flash memory or other storage technology, compact disk read-only memory, digital versatile disk or other optical storage, cassettes, magnetic tape, magnetic disk storage or other magnetic storage devices, or any other medium that can be used to store the desired information and can be accessed by the computing device 230. Computer-readable storage media do not include computer-readable communication media.

[0103] Computer-readable communication media typically include computer-readable instructions, data structures, program modules, or other data in a modulated data signal such as a carrier wave or other transmission mechanism, and computer-readable communication media include any information delivery media. The term "modulated data signal" refers to a signal that has one or more of its characteristics set or changed in a manner that is convenient for encoding information in the signal. For example, computer-readable communication media include wired media such as a wired network or a direct wired connection and wireless media such as acoustic, radio frequency, infrared and other wireless media. Any combination of the above is also included in the scope of computer-readable media.

[0104] Fig.17The computing device illustrated in the figure is also an example of a programmable electronic device. A programmable electronic device may include one or more such computing devices, and when multiple computing devices are included, such computing devices may be connected together via a suitable data communication network to jointly perform the various functions, methods, or operations disclosed herein.

[0105] Fig.18 Shows the depiction according to Figure 1 Flow chart of loading required pipette tips 134 of an exemplary embodiment of a pipette instrument. The figure includes a first step 280 of engaging the pipette tip 110 with the spindle 130; a second step 282 of partially removing the pipette tip 110 from the pipette tip box 104 by lifting the pipette tip 110 with the spindle 130; a third step 284 of moving the pipette tip 110 and the spindle 130 by coordinating the motion 136 to remove the unnecessary pipette tip 132; and a fourth step 286 of completely removing the necessary pipette tip 134 from the pipette tip box 104 using the spindle 130. Refer to Fig.19 Figure 20 Fig.21 and Fig. 22 Examples of each of the first step, the second step, the third step, and the fourth step are illustrated and described in more detail.

[0106] Fig.19 A shows a transverse cross-sectional view of a pipetting instrument 100 including a spindle 130, a pipette tip box 104, and a pipette tip 110, which depicts Fig.18 The first step 280 is shown in which the spindle 130 approaches and enters the pipette tips 110 in the pipette tip box 104. In some embodiments, the spindle 130 can only approach and enter a partial subset of the pipette tips 110, wherein the targeted partial subset is the desired pipette tips 134 and any non-target subset is the undesired pipette tips 132. In some embodiments, the desired pipette tips 134 can include pipette tips 110 in an organized pattern, such as every other pipette tip 110. This would mean that every other pipette tip 110 is a desired pipette tip 134, while the remaining pipette tips 110 are undesired pipette tips 132. As shown in the figure, the outer pipette tips are the desired pipette tips 134 that the spindle 130 is targeting, while the inner pipette tips are the undesired pipette tips 132 that the spindle 130 is not targeting. In some embodiments, by moving the pod 150 along the Z-axis 184, the spindle can approach and enter a desired pipette tip 134. Figure 5 , Figure 6 and Fig. 9 Examples illustrating movement of the pod 150 along the Z-axis 184 are shown and described in greater detail.

[0107] Fig.19B shows a transverse cross-sectional view of the pipetting instrument 100 including the spindle 130, the pipette tip box 104 and the pipette tip 110, which depicts Fig.18 The first step 280 is shown in which the spindle 130 is coupled to the pipette tips 110 in the pipette tip box 104. In this figure and in some embodiments, the spindle 130 is aimed at the outside pipette tips 110. Therefore, the outside pipette tips 110 are the required pipette tips 134, and the inside pipette tips 110 are the unrequired pipette tips 132. The spindle 130 is coupled to the required pipette tips 134 by pressing the spindle 130 into the required pipette tips 134 to form an airtight interference fit. With reference to Figure 2, an example of an airtight interference fit between the spindle 130 and the required pipette tips 134 is illustrated and described in more detail.

[0108] Fig. 20A A transverse cross-sectional view of the spindle 130, the pipette tip box 104, and the pipette tip 110 is shown, depicting Fig.18 The second step 282, wherein the spindle 130 is coupled to the pipette tip 110 in the pipette tip box 104. Fig.10 and Fig.13 B illustrates and describes the following step in more detail: In this step, the spindle 130 is coupled to the pipette tips 110 in the pipette tip box 104 with an airtight friction fit between the spindle 130 and the desired pipette tip 134. In this figure and in some embodiments, the desired pipette tip 134 is the outer pipette tip 110, while the undesired pipette tip 132 is illustrated by the inner pipette tip 110.

[0109] Fig. 20B A transverse cross-sectional view of the spindle 130, the pipette tip box 104, and the pipette tip 110 is shown, depicting Fig.18 The second step 282 is performed in which the spindle 130 partially removes the pipette tip 110 from the pipette tip box 104.

[0110] In this figure and in some embodiments, the desired pipette tip 134 is an outer pipette tip 110, while the undesired pipette tip 132 is illustrated by the inner pipette tip 110. In some embodiments, the spindle 130 may inadvertently remove the pipette tip 132 from the pipette tip box 104 as the undesired pipette tip 132 is coupled to the spindle 130, the desired pipette tip 134, or both the spindle 130 and the desired pipette tip 134. In some embodiments, the undesired pipette tip may be coupled to the spindle 130, the desired pipette tip 134, or both the spindle 130 and the desired pipette tip 134 by mechanical coupling or electrostatic coupling. To remove an unwanted pipette tip 132 from the spindle 130, the spindle 130 lifts the pipette tip 110 from the pipette tip box 104 while keeping the pipette tip 110 partially inserted into the pipette tip box 104 before performing a coordinated motion 136 to remove any unwanted pipette tips 132 from the spindle 130 and / or the wanted pipette tips 134. Fig.21 and Fig. 27 An example illustrating the coordinated movement 136 of the spindles 130 is shown and described in further detail.

[0111] Fig.21 A schematic diagram is shown depicting the coordinated movement 136 of the spindle 130 to remove any unwanted pipette tips 132 from the spindle 130 or a desired pipette tip 134 .

[0112] The coordinated motion 136 includes moving each of the spindles in a similar motion to move any unwanted pipette tips 132 away from the desired pipette tips 134 or spindles 130. In some embodiments, the coordinated motion 136 can include moving the spindles 130 in a motion that includes a horizontal component and / or a vertical component within the pipette tip box 104 to press the pipette tips 110 against the pipette tip box 104. Interference between the unwanted pipette tips 132 and the pipette tip box 104 can provide sufficient force to decouple the unwanted pipette tips 132 from the desired pipette tips 134 and / or spindles 130. It should be understood that the coordinated motion 136 can include any number of motions that include a horizontal component and a vertical component within the pipette tip box 104 to press the pipette tips 110 against the pipette tip box 104. In some embodiments, the coordinated motion 136 can start from the center of each recess in the pipette tip box 104 for storing the pipette tips 110, wherein the pipette tips 110 are partially inserted into the pipette tip box 104. The spindle can then move the pipette tips diagonally to the corners of the recesses in the pipette tip box 104, and then move the pipette tips 110 to each of the other corners of the recesses in the pipette tip box 104. The spindle 130 can then return the pipette tips 110 to the center of the recesses in the pipette tip box 104 and allow the unwanted pipette tips to be moved out of the pipette tip box 104. In some embodiments, the recesses in the pipette tip box 104 for receiving the pipette tips 110 can be defined by a cylindrical space. In some embodiments, the coordinated motion 136 can be adjusted to match any type of recess in the pipette tip box 104 by pressing the pipette tips 110 against the pipette tip box 104. In some embodiments, coordinated motion 136 may include radial motion having a horizontal component and a vertical component. In some embodiments, coordinated motion may include motion in the horizontal direction only. In some embodiments, coordinated motion may include motion in the vertical direction only.

[0113] Fig. 22 A transverse cross-sectional view of the spindle 130, the pipette tip box 104, and the pipette tip 110 is shown, depicting Fig.18 104 and 106. The fourth step 286 is now performed, at which point the desired pipette tips 134 have been completely removed from the pipette tip magazine 104 and coupled to the spindle 130, while any unneeded pipette tips 132 have been disconnected from the spindle 130. As can be seen in this figure, the desired pipette tips 134 remain coupled to the spindle 130, while the unneeded pipette tips 132 have been removed from the spindle 130 and returned to the pipette tip magazine 104.

[0114] Fig.23 Shows the depiction according to Figure 1An example embodiment of a pipetting instrument of the present invention is a flow chart of unloading pipette tips from a spindle into a pipette tip box.

[0115] The figure includes: a first step 302 for positioning the spindle 130 to engage and insert the pipette tip 110 into the pipette tip box 104; a second step 304 for activating a set of plungers to disconnect the pipette tip 110 from the spindle 130 and unload the pipette tip 110 into the pipette tip box 104; a third step 306 for positioning the spindle 130 so that any pipette tip 110 remaining coupled to the spindle 130 is partially inserted into the pipette tip box 104; a fourth step 308 for moving the spindle 130 and the pipette tip 110 to disconnect the pipette tip 110 from the spindle 130 and unload the pipette tip 110 into the pipette tip box 104; and a fifth step 310 for removing the spindle 130 from the pipette tip box 104. Reference Fig.24 , Fig.25 , Fig.26 , Fig. 27 and Fig.28 Examples of each of the first step, the second step, the third step, the fourth step, and the fifth step are respectively illustrated and described in more detail.

[0116] Fig.24 A transverse cross-sectional view of the spindle 130, the pipette tip box 104, and the pipette tip 110 is shown, depicting Fig.23 In a first step 302, the spindle 130 is positioned to engage and insert the pipette tip 110 into the pipette tip box 104. In this figure, the spindle 130 is at least partially inserted into the pipette tip 110. Fig.19 Examples for engaging and inserting the spindle 130 into the pipette tip 110 are illustrated and described in greater detail.

[0117] Fig.25 A transverse cross-sectional view of the spindle 130, the pipette tip box 104, and the pipette tip 110 is shown, depicting Fig.23 A second step 304 is performed in which the plunger is activated along a plunger path 312 on the spindle 130 to disconnect the pipette tip 110 from the spindle 130 and unload the pipette tip 110 into the pipette tip box 104.

[0118] The plunger path 312 defines a channel for the plunger within each of the spindles 130 to unload the desired pipette tips 134 into the pipette tip box 104. The plunger is configured to apply a downward force toward the bottom of the spindle 130 along the plunger path 312 to move the desired pipette tips 134 out. The desired pipette tips 134 remain partially inserted into the pipette tip box 104 to guide the desired pipette tips 134 into the pipette tip box 104. In some embodiments, the unwanted pipette tips 132 can be mechanically or electrically coupled to the spindle 130, the desired pipette tips 134, or both the spindle 130 and the desired pipette tips 134. In some embodiments, the desired pipette tips 134 can be defined by a pattern of every other pipette tip 110, where in this figure, both pipette tips 110 are desired pipette tips 134. In some embodiments, the undesired pipette tips 132 can be mechanically or electrostatically coupled to the spindle 130, the desired pipette tips 134, or coupled to both the spindle 130 and the desired pipette tips 134 intermediate the desired pipette tips 134. In some embodiments, if the plunger fails to decouple the desired pipette tips 134 from the spindle 130, the plunger can be reactivated as needed to decouple the desired pipette tips 134 from the spindle 130 along the plunger path 312.

[0119] Fig.26 A transverse cross-sectional view of the spindle 130, the pipette tip box 104, and the pipette tip 110 is shown, depicting Fig.23 306, wherein the spindle 130 is positioned so that any pipette tips 110 that remain coupled to the spindle 130 are partially inserted into the pipette tip box 104. In this figure, the desired pipette tips 134 have been removed from the spindle 130 in the second step 304, and only a single, undesired pipette tip 132 remains coupled to the spindle.

[0120] Fig. 27 A schematic diagram depicting the coordinated movement 136 of the spindle 130 is shown. Fig.23 In the fourth step 308, the spindle 130 removes any unwanted pipette tips 132. Fig.21 An example illustrating the coordinated movement 136 of the spindles 130 is shown and described in further detail.

[0121] Fig.28 A transverse cross-sectional view of the spindle 130, the pipette tip box 104, and the pipette tip 110 is shown, depicting Fig.23 A fifth step 310 is performed in which the spindle 130 is removed from the pipette tip box 104 and each of the pipette tips 110 has been unloaded into the pipette tip box 104 .

[0122] Fig.29 A front view of the top of a pipette tip 110 with a pipette tip feature 320 is shown, which may affect the process of loading or unloading a desired pipette tip. In some embodiments, the pipette tip feature 320 may cause an unwanted pipette tip 132 to be loaded onto the mandrel 130 or the desired pipette tip 134. In this figure, the pipette tip 110 on the left includes a filament that can be connected to an adjacent pipette tip 110 stored in a pipette tip box 104. In this figure, the pipette tip 110 on the right includes a protrusion that is not flush with the cylindrical head of the pipette tip 110. The protrusion from the pipette tip 110 can be connected to an adjacent pipette tip 110 stored in a pipette tip box 104. It is contemplated that a variety of pipette tip features on a pipette tip 110 may engage with an adjacent pipette tip 110 and affect the process of loading or unloading a desired pipette tip, and the above examples are not limited to these pipette tip features 320 .

[0123] The above description is illustrative only and not restrictive. After reading this disclosure, many variations of the present invention will become apparent to those skilled in the art. Therefore, the scope of the present invention should not be determined with reference to the above description, but should be determined with reference to pending claims and their full scope or equivalents.

[0124] One or more features from any embodiment may be combined with one or more features from any other embodiment without departing from the scope of the present invention.

Claims

1. A liquid transfer instrument for loading and dispensing a sample, the liquid transfer instrument comprising: an automated liquid pipette comprising a platen for supporting a pipette tip box comprising pipette tips and a spindle for engaging the pipette tips and removing at least some of the pipette tips from the pipette tip box; as well as A controller is configured to control the automated liquid pipette and is further configured to perform a pipette tip removal operation to remove any unwanted pipette tips removed from the pipette tip magazine using the spindle.

2. The liquid transfer instrument according to claim 1, wherein: The spindle is configured to engage pipette tips having different sizes.

3. The liquid transfer instrument according to any one of claims 1 to 2, wherein: The pipette tips have a spacing of less than 0.30 mm between adjacent pipette tips in the pipette tip box.

4. The automatic liquid pipette of any one of claims 1 to 3, further comprising a motorized positioning system configured to position the spindle.

5. The liquid transfer instrument according to claim 4, wherein: The motorized positioning system includes at least one motor and is configured to move the spindle in three dimensions.

6. The motorized positioning system according to claim 5, wherein: The at least one motor is mechanically coupled to drive the spindle horizontally about an axis.

7. The motorized positioning system according to any one of claims 5 to 6, wherein: The spindle is movable along the X-axis and the Y-axis by a motorized gantry to which the spindle is coupled, wherein the spindle is configured to move along the Z-axis by adjusting the height of a pod, wherein the pod is positioned between the motorized gantry and the spindle.

8. The automatic liquid pipette of any one of claims 1 to 7, further comprising a sensor configured to sense the unwanted pipette tip coupled to the spindle or the wanted pipette tip.

9. A method for loading a set of pipette tips onto an automatic liquid pipette, the method comprising: coupling a desired pipette tip to the spindle by positioning the spindle and engaging the pipette tip with the spindle; lifting the spindle to partially remove the desired pipette tip from the pipette tip box and lifting at least one undesired pipette tip together with the desired pipette tip; moving the spindle to remove the at least one unneeded pipette tip from the spindle, thereby returning the at least one unneeded pipette tip to the pipette tip magazine while a group of the desired pipette tips remain coupled to the spindle; as well as The spindle is lifted to completely remove the desired pipette tip from the pipette tip magazine.

10. The method according to claim 9, wherein: The spindle is coupled to the desired pipette tip using a friction fit.

11. The method according to any one of claims 9 to 10, wherein: The unneeded pipette tip is coupled to the desired pipette tip and is not coupled to the spindle.

12. The method according to any one of claims 9 to 11, wherein: The spindle moves with a motion that includes a horizontal component to press the pipette tips against the pipette tip box.

13. The method according to any one of claims 9 to 12, wherein: The spindle moves with a motion that includes a vertical component.

14. The method according to any one of claims 9 to 13, wherein: The spindle moves with a motion that includes a horizontal component and a vertical component.

15. The method according to any one of claims 9 to 14, wherein: The spindle moves in a radial motion having a horizontal component and a vertical component.

16. The method according to any one of claims 9 to 15, wherein: While any unwanted pipette tips remain coupled to a desired pipette tip or the spindle, the process of moving the spindle to remove the at least one unwanted pipette tip from the spindle can be repeated.

17. The method according to any one of claims 9 to 16 further includes using a sensor to sense whether any unwanted pipette tip is connected to the spindle or any required pipette tip, and identifying a group consisting of the spindle and pipette tips to be moved that are connected to the unwanted pipette tips.

18. A method for unloading one or more pipette tips from an automated liquid pipette, the method comprising: positioning the spindle to engage and insert the pipette tip into a pipette tip box; activating a set of plungers to disconnect the one or more pipette tips from the spindle and unload the pipette tips into the pipette tip magazine; positioning the spindle to partially insert any pipette tips remaining coupled to the spindle into the pipette tip magazine; moving the spindle and the pipette tips to disconnect the pipette tips from the spindle and unload the pipette tips into the pipette tip box; as well as The spindle is removed from the pipette tip box.

19. The method according to claim 18, wherein: Positioning the spindle to engage and insert the pipette tip into a pipette tip magazine also includes fully inserting the pipette tip into the pipette tip magazine.

20. The method according to any one of claims 18 to 19, wherein: Moving the spindle and the pipette tip to decouple the pipette tip from the spindle further comprises moving the spindle within the pipette tip box in a motion that includes a horizontal component to press the pipette tip against the pipette tip box.

21. The method according to any one of claims 18 to 20, wherein: Moving the spindle and the pipette tip to decouple the pipette tip from the spindle further comprises moving the spindle within the pipette tip magazine with a motion that includes a vertical component to press the pipette tip against the pipette tip magazine.

22. The method according to any one of claims 18 to 21, wherein: Moving the spindle and the pipette tip to disconnect the pipette tip from the spindle also includes moving the spindle within the pipette tip box with a motion including a horizontal component and a vertical component to press the pipette tip against the pipette tip box.

23. The method according to any one of claims 18 to 22, wherein: Moving the spindle and the pipette tip to disconnect the pipette tip from the spindle also includes moving the spindle within the pipette tip box with a radial motion including a horizontal component and a vertical component to press the pipette tip against the pipette tip box.

24. The method according to any one of claims 18 to 23 further includes using a sensor to sense whether an unwanted pipette tip is connected to the spindle or the required pipette tip, and identifying a group consisting of the spindle to be moved and the pipette tip connected to the unwanted pipette tip.

Images