Replaceable pipetting system

Abstract

A pipetting system includes a syringe assembly and a probe assembly. The syringe assembly includes a pipetting air chamber that extends about a pipetting axis. The syringe assembly includes a plunger that is configured to travel between an extended state and a retracted state within the pipetting air chamber. The syringe assembly includes a pipette tip receiving region that is configured to receive a pipette tip. The probe assembly includes a probe drive housing that is configured to control movement of the probe assembly about the pipetting axis. The probe assembly includes a plunger attachment structure that is configured to control movement of the plunger about the pipetting axis. The syringe assembly is removably attached to the probe assembly such that the syringe assembly may be removed from the probe assembly without removing the probe assembly from the pipetting system.

Description

REPLACEABLE PIPETTING SYSTEMCROSS-REFERENCE TO RELATED APPLICATION

[0001] This application is being filed as PCT International application and claims the benefit of and priority7to U.S. Application No. 63 / 613,480, filed on December 21, 2023, the disclosure of which is hereby incorporated by reference in its entirety7. To the extent appropriate, a claim of priority is made to the above-disclosed application.BACKGROUND

[0002] Pipetting equipment is often used in laboratory settings to reliably transport fluid from one container to another. In certain laboratory settings, automated liquid pipettors are used to reduce labor costs associated with large pipetting projects while potentially increasing efficiency and accuracy of the project. There is a need for improvements to the maintenance and accuracy of these pipetting systems.SUMMARY

[0003] In general terms, this disclosure is directed to a replaceable pipetting system. In some embodiments, and by non-limiting example, the pipetting system includes a syringe assembly and a probe assembly. The syringe assembly may include a pipetting air chamber that extends about a pipetting axis. The syringe assembly may include a plunger configured to travel between an extended state and a retracted state within the pipetting air chamber. The syringe assembly may include a pipette tip receiving region that is designed to receive a pipette tip. The probe assembly may include a probe drive housing that is designed to control movement of the probe assembly about the pipetting axis. The probe assembly may include a plunger attachment structure that is configured to control movement of the plunger about the pipetting axis. The syringe assembly is removably attached to the probe assembly such that the syringe assembly may be removed from the probe assembly without removing the probe assembly from the pipetting system.

[0004] In some embodiments a syringe assembly includes an attachment structure that is designed to removably connect the syringe assembly to a pipetting assembly. The syringe assembly may include a pipetting air chamber that extends about a pipetting axis. The syringe assembly may include a plunger within the pipetting air chamber where the plunger is configured to travel between an extended state and a retracted state. The syringe assembly may include a pipette tip receiving region that is designed to receive a pipette tip.

[0005] In one example, the syringe assembly includes a positioning feature configured to position the syringe assembly about a probe assembly.

[0006] In another example, the syringe assembly includes at least one fastener and wherein the attachment structure is configured to threadedly engage the at least one fastener.

[0007] In a further example of the syringe assembly, the fastener includes a fastener head configured to enter a corresponding enlarged opening of a keyhole slot of the probe assembly and wherein a shaft of the fastener is configured to seat into a keyhole channel of the keyhole slot of the probe assembly.

[0008] In yet another example, the syringe assembly further includes a pipette tip detection structure, a lower plunger housing, and an optical sensor, wherein the pipette tip detection structure is connected to the lower plunger housing, wherein the lower plunger housing is configured to remove the pipette tip when the plunger moves to an overextended state, wherein the pipette tip detection structure moves away from the optical sensor when the plunger moves to the overextended state.

[0009] In some embodiments a method for removing a syringe assembly from a pipetting system includes removing a plunger head from a plunger on the syringe assembly. The method further includes lowering the plunger and separating the plunger from a plunger attachment structure on a probe assembly. The method further includes detaching at least one probe assembly attachment feature on the syringe assembly from a corresponding at least one syringe assembly attachment structure on the probe assembly.BRIEF DESCRIPTION OF THE DRAWINGS

[0010] FIG. 1 is a perspective view of an example pipetting assembly in accordance with the principles of the present disclosure.

[0011] FIG. 2 is a front view of the pipetting assembly of FIG. 1.

[0012] FIG. 3 is a perspective view of an example of eight pipetting systems grouped together in accordance with the principles of the present disclosure.

[0013] FIG. 4 is a perspective view of an example of a single pipetting system in accordance with the principles of the present disclosure.

[0014] FIG. 5 is a front view of the pipetting system of FIG. 4.

[0015] FIG. 6 is a perspective view of an example probe assembly in accordance with the principles of the present disclosure.

[0016] FIG. 7 is a second side view of the probe assembly of FIG. 6.

[0017] FIG. 8 is a front view of the probe assembly of FIG. 6.

[0018] FIG. 9 is a perspective view of an example syringe assembly in accordance with the principles of the present disclosure.

[0019] FIG. 10 is a first side view of the syringe assembly of FIG. 9.

[0020] FIG. 11 is a second side view of the syringe assembly of FIG. 9.

[0021] FIG. 12 is a perspective view of an example probe assembly housing in accordance with the principles of the present disclosure.

[0022] FIG. 13 is a perspective view of an example probe drive housing in accordance with the principles of the present disclosure.

[0023] FIG. 14 is a perspective view- of an example plunger attachment structure in accordance with the principles of the present disclosure.

[0024] FIG. 15 is a perspective view of an example upper plunger housing in accordance with the principles of the present disclosure.

[0025] FIG. 16 is a perspective view' of an example low er plunger housing in accordance with the principles of the present disclosure.

[0026] FIG. 17 is a perspective view of an example capacitance tube in accordance with the principles of the present disclosure.

[0027] FIG. 18 is a perspective view' of an example insulating tube in accordance with the principles of the present disclosure.

[0028] FIG. 19 is a perspective view of an example plunger in accordance with the principles of the present disclosure.

[0029] FIG. 20 is a perspective view' of an example mandrel in accordance with the principles of the present disclosure.

[0030] FIG. 21 is a perspective view of an example syringe assembly without an upper plunger housing w'hen the plunger is at or between a retracted and extended state in accordance with the principles of the present disclosure.

[0031] FIG. 22 is a perspective view' of the syringe assembly of FIG. 21 when the plunger is in an overextended state in accordance with the principles of the present disclosure.

[0032] FIG. 23 is a focused cross-sectional view of an example syringe assembly about a circuit board attachment region in accordance w'ith the principles of the present disclosure.

[0033] FIG. 24 is a focused perspective view of an example pipetting system when the plunger is at or between a retracted and extended state in accordance with the principles of the present disclosure.

[0034] FIG. 25 is a focused perspective view of the pipetting system of FIG. 24 when the plunger is in an overextended state in accordance with the principles of the present disclosure.

[0035] FIG. 26 is a focused cross-sectional view of an example pipette tip attachment region of an example syringe assembly when the plunger is at or between a retracted and extended state in accordance with the principles of the present disclosure.

[0036] FIG. 27 is a focused cross-sectional view of the syringe assembly of FIG. 26 when the plunger is in an overextended state in accordance with the principles of the present disclosure.

[0037] FIG. 28 is a focused cross-sectional view of an example pipette tip attachment region of an example syringe assembly when the plunger is at or between a retracted and extended state in accordance with the principles of the present disclosure.

[0038] FIG. 29 is a focused cross-sectional view of the syringe assembly of FIG. 28 when the plunger is in an overextended state in accordance with the principles of the present disclosure.

[0039] FIG. 30 is a focused second side view of an example syringe assembly attachment structure of the probe assembly of FIG. 6.

[0040] FIG. 31 is a focused perspective view of an example attachment structure between a probe assembly and a syringe assembly when the probe assembly housing is transparent in accordance with the principles of the present disclosure.

[0041] FIG. 32 is an example of pressure sensor data collected during a pipetting operation when the pipette tip is functioning normally in accordance with the principles of the present disclosure.

[0042] FIG. 33 is an example of pressure sensor data collected during a pipetting operation when there is no pipette tip present in accordance with the principles of the present disclosure.

[0043] FIG. 34 is an example of pressure sensor data collected during a pipetting operation when the pipette tip is clogged in accordance with the principles of the present disclosure.

[0044] FIG. 35 is a schematic representation of an example pipetting operation in accordance with the principles of the present disclosure.

[0045] FIG. 36 is a schematic representation of an example syringe assembly removal operation in accordance with the principles of the present disclosure.DETAILED DESCRIPTION

[0046] Various embodiments will be described in detail with reference to the drawings, wherein like reference numerals represent like parts and assemblies throughout the several views. Reference to various embodiments does not limit the scope of the claims attached hereto. Additionally, any examples set forth in this specification are not intended to be limiting and merely set forth some of the many possible embodiments for the appended claims.

[0047] FIGS. 1 and 2 show an example pipetting assembly 100 that includes a number of pipetting systems 150 in accordance with the principles of the present disclosure. As shown in FIG. 2, the pipetting assembly 100 includes a first gantry system 110 that controls movement of the pipetting systems 150 about an X-axis. The pipetting assembly 100 also includes a second gantry system, not shown, that controls the movement of the pipetting systems 150 about the Z-axis. In certain examples, the pipetting systems 150 are controlled individually about the X and / or Z axes. In certain examples, there are between one and eight pipetting systems 150 in the pipetting assembly 100.

[0048] FIG. 3 shows an example of eight pipetting systems 150 grouped together. Each pipetting system 150 includes a pipette tip 120. The pipetting system 150 may move as a group or, in certain examples, individually. The pipetting systems 150 may be held together by a framework 160 about one or more axes, such that the pipetting systems 150 may move together about that those axes. For example, the framework 160. may hold the pipetting systems 150 together during movement about the X and Z axes. The pipetting systems 150 may then be free to move independently about the Y axis.

[0049] FIGS. 4 and 5 show an example of a single pipetting system 150. The pipetting system 150 includes a probe assembly 200 and a syringe assembly 300. Each will be discussed in turn.

[0050] FIGS. 6, 7, and 8 show' the probe assembly 200 independent of the syringe assembly 300. As shown, the probe assembly 200 includes a gantry' attachment structure 170, that is configured to attach the probe assembly 200 to the pipetting assembly 100, such that the pipetting assembly’s gantry systems are able to move the pipetting system 150 about the pipetting assembly 100 at least about the X and / or Zaxes. In the example shown, the probe assembly 200 includes two motors, a first motor 112 and a second motor 114. The probe assembly 200 further includes a probe assembly housing 210 that houses a first rail and a second rail 115, 117 which are associated with first and second drive screws 116, 118.

[0051] FIGS. 9, 10, and 11 show an example of the syringe assembly 300 separate from the probe assembly 200. In the example shown, the syringe assembly 300 includes an upper plunger housing 310 and lower plunger housing 330. A capacitance tube 340 and an insulating tube 350 extend at least partially through the upper plunger housing 310 and the lower plunger housing 330. As will be discussed later, the insulating tube 350 is the innermost tube surrounding a plunger 360. The capacitance tube 340 is positioned radially between the insulating tube 350 and the upper and lower plunger housings 310, 330.The plunger 360 extends through the upper plunger housing 310 and at least partially into each of the lower plunger housing 330, the capacitance tube 340, and the insulating tube 350 about a pipetting axis 172. In the example shown, the pipetting axis 172 is along the Y-axis. The syringe assembly 300 also includes a circuit board 370 that enables data collection and analysis to take place regarding various aspects of pipetting. For example, data may be collected on the amount of fluid present in the pipette tip 120, the position of the syringe assembly 300, the presence of a pipette tip 120, etc. The circuit board 370 may include, for example, a capacitance sensor 376, a pressure sensor 374, and a pipette tip detection sensor 372, as will be discussed in greater detail later.

[0052] The example syringe assembly 300 show n in the figures is an example of an air displacement pipetting system where a body of air is sealed within a chamber and variations in pressure are caused by a movable plunger and used to move fluid in and out of the pipette tips 120. Many of the teachings of the present disclosure apply to other pipetting systems. For example, a pump pipetting system may be used that relies on an external pump to vary pressure and move fluid.

[0053] Referring now to certain components of the probe assembly 200, in certain examples, the first motor 112 drives a first drive screw 116 that is configured to control the movement of the pipetting system 150 about the Y-axis, or pipetting axis 172, within the pipetting assembly 100. In the example shown in FIGS. 4-7, the first drive screw- 116 attaches to a probe drive housing 220 that connects through a rail mount 227 to a first rail 115 that is housed, at least partially, in the probe assembly housing 210. The syringe assembly 300 attaches to the probe assembly 200 at a syringe assemblyattachment region 240 of the probe assembly housing 210. When the first motor 112 drives the first drive screw 116, the first rail 115, the probe assembly housing 210, and the syringe assembly 300 all move relative to the probe drive housing 220 and parallel to the pipetting axis 172.

[0054] The second motor 114 drives a second drive screw 118 that is configured to control the aspirating and purging of fluid within the pipette tip 120 through movement of the plunger 360 when attached to the syringe assembly 300. In the example shown, the second drive screw 118 connects to a plunger attachment structure 230 that removably holds a plunger head 365 of the plunger 360 such that when the second motor 114 drives the second drive screw 118, the plunger attachment structure 230 moves the plunger 360 about the pipetting axis 172.

[0055] In other examples, the first and second motors 112 and 114 may actuate the pipetting system 150 without drive screws, for example, through brushless DC motors, linear induction motors, or other drive means. In certain examples, one or more power sources actuate the pipetting system 150. In the example shown, the syringe assembly 300 shows a plunger 360 that is driven by the second drive screw 1 18 to control the aspirating and purging of fluid within the pipette tip 120. The pipetting system 150 may be used with a variety of different pipette tips 120. In the example show n in FIGS. 4 and 5, the pipetting system 150 is configured to work with at least two differently sized pipette tips 120. Pipette tips 120a and 120b are used as examples, but other sizes and types of pipette tips 120 may be used. Pipette tip 120a is larger than pipette tip 120b.

[0056] An example of the probe assembly housing 210 is show n in FIG. 12. The probe assembly housing 210 extends a length along the pipetting axis 172 from a first end 211 adjacent the first and second motors 112. 114 down to a second end 212. The syringe assembly attachment region 240 is nearer the second end 212 than the first end 211. The probe assembly housing 210 attaches to the first and second motors 112, 114 at the first end 211. The probe assembly housing 210 includes a first side 213 adjacent the first motor 112 and a second side 214 adjacent the second motor 114. The probe assembly housing 210 includes an attachment structure 215 for the first and second rails 115, 117 which each extend at least partially along the length of the probe assembly housing 210. The first rail 115 extends along the first side 213 and the second rail 117 extends along the second side 214.

[0057] An example of the syringe assembly attachment region 240, where the syringe assembly 300 joins the probe assembly 200, is shown in FIGS. 7, 12, and 29.The syringe assembly atachment region 240 is configured to facilitate atachment and removal of the syringe assembly 300 without the need to disconnect the probe assembly 200 from the pipeting assembly 100. For example, if the pipetting system 150 crashes in the pipeting assembly 100, the syringe assembly 300 can become damaged and require replacement. Separating the probe assembly 200 and the syringe assembly 300 from each other enables replacement of only the damaged part. In certain examples, the syringe assembly atachment region 240 includes at least one atachment structure 242. The attachment structure 242 may be any suitable structure for removable atachment. In certain examples, the atachment structure 242 is a keyhole slot 244. In certain examples, the syringe assembly atachment region 240 includes a positioning feature 246 to facilitate positioning between the probe assembly 200 and syringe assembly 300 when the syringe assembly 300 is being atached to the probe assembly 200. In certain examples, the positioning feature 246 may be spring loaded.

[0058] An example of the probe drive housing 220 is shown in FIG. 13. The probe drive housing 220 connects to a drive screw nut 228 at a first end 222. The probe drive housing 220 includes a drive screw channel 226 which extends parallel to the pipetting axis 172 and is designed to provide clearance for the first drive screw 116 as the first drive screw' 116 moves up and down the probe drive housing 220 as facilitated by the drive screw nut 228. The probe drive housing 220 also includes two reliefs 229 for rail mounts 227. The rail mounts 227 are atached to the probe drive housing 220 and provide a slidable connection to the first rail 1 15 as the first drive screw 11 moves the probe assembly housing 210 parallel to the pipeting axis 172 in order to maintain stability' and proper positioning. Each rail mount 227 is connected to the probe drive housing 220 with two screws or fasteners, with one on each side of the drive screw channel 226.

[0059] An example of the plunger atachment structure 230 is shown on FIG. 14. The plunger atachment structure 230 includes an upper portion 232 that includes an opening 233 for the plunger 360 to extend through. The opening 233 is open in the direction of the pipeting axis 172 when in the assembled state. The upper portion 232 further includes a slot 231 above and adjacent the opening 233. The slot 231 is designed to hold a plunger head 365 such that the plunger 360 moves wfien the plunger atachment structure 230 moves parallel to the pipeting axis 172. The slot 231 also includes openings to fix a drive screw nut 235 to the plunger atachment structure 230. The upper portion 232 also connects to the drive screw nut 235. The plungerattachment structure 230 includes a lower portion 234 that includes an open channel 237 that is transverse to the pipetting axis 172 and provides an opening for the plunger 360 to run through. The open channel 237 provides additional stability to the plunger 360 as the plunger 360 is compressed. A through hole 239 extends through both the upper portion 232 and the lower portion 234 and is designed to provide clearance for the second drive screw 118 as the plunger attachment structure 230 moves up and down the second drive screw 118. The movement of the plunger attachment structure 230 is facilitated by the drive screw nut 235 which translates rotational movement in the second drive screw 118 to axial movement of the plunger attachment structure 230 about the pipetting axis 172. A rail mount 227 attaches to a first side 236 of the plunger attachment structure 230 that is opposite the location of the open channel 237 and slot 231 about a direction extending between the first and second rails 115, 117. The rail mount 227 is attached to the plunger attachment structure 230 to provide a slidable connection to the second rail 117 as the second drive screw 118 moves the plunger attachment structure 230 parallel to the pipetting axis 172. The rail mount 227 helps to maintain stability and proper positioning when the second drive screw 118 moves the plunger attachment structure 230.

[0060] Referring now to certain components of the syringe assembly 300, an example of the upper plunger housing 310 is shown on FIG. 15. The upper plunger housing 310 includes a first end 311, nearest the plunger attachment structure 230 of the probe assembly 200, and a second end 312 adjacent the lower plunger housing 330. The upper plunger housing 310 includes a first side 313 and a second side 314. The first side 313 is partly cylindrical, semi-circular about a length betw een the first and second ends 311, 312. The first side 313 forms an outer surface of an upper plunger tube 315. The second side 314 is generally flat and forms a probe assembly attachment region 316, and a circuit board attachment region 317. The first and second sides 313, 314 meet at curved transitions. The upper plunger tube 315 extends through the first end 311 and through the second end 312. The upper plunger tube 315 includes an upper plunger housing tube step 323, shown in FIG. 23. that prevents the capacitance tube 340 and insulating tube 350 from being removed when the plunger 360 moves to a retracted state. The upper plunger housing 310 also includes a mandrel tube 318 that extends from the first end 311 to a mandrel channel 319. The mandrel channel 319 continuing in the direction of the opening of the mandrel tube 318 and extending to the second end 312. The mandrel channel 319 includes a channel opening 320 runningalong and open to the second side 314. The mandrel tube 318 and mandrel channel 319 are shaped to allow a mandrel 380 to extend from the first end 311 to the second end 312 of the upper plunger housing 310. The upper plunger housing 310 also includes a pipette tip detection channel 321 on the second side 314 that extends partially along the length of the upper plunger housing 310 from the second end 312 and parallel to the mandrel channel 319. The pipette tip detection channel 321 extends from the second end 312 to a first sensor cavity 322. The pipette tip detection channel 321 is sized to allow a pipette tip detection structure 386 to travel into and out of the first sensor cavity 322 about the pipetting axis 172. A second sensor cavity 325 and a third sensor cavity 326 are located at the second side 314 of the upper plunger housing 310. The second sensor cavity 325 may be used for a different sensor than the first sensor cavity 322 and the third sensor cavity 326 may be used for a different sensor than both the first and second sensor cavities 322, 325. In the example shown, the first sensor cavity 322 forms a rectangular prism-shaped cavity and the second and third sensor cavities 325, 326 form cylindrical-shaped cavities. The second and third sensor cavities 325, 326 extend into the upper plunger tube 315. The first, second, and third sensor cavities 322, 325, 326 are all located in the circuit board attachment region 317 of the upper plunger housing 310. In certain examples, the upper plunger housing 310 is made of a nonconductive material. For example, the upper plunger housing 310 may be formed of plastic.

[0061] The probe assembly attachment region 316 may be any suitable structure for removable attachment to the probe assembly 200. In certain examples, there is at least one attachment feature 324 that corresponds to the attachment structure 242 of the syringe assembly attachment region 240. FIG. 15 shows three attachment features 324. In the example shown, each attachment feature 324 is a threaded hole designed to threadedly receive a screw- or bolt 328. The attachment features 324 are spaced from each other about the length of the upper plunger housing 310 betw een the first end 311 and the second end 312. The probe assembly attachment region 316 may also include a positioning hole 327 that is designed to receive the positioning feature 246.

[0062] An example of the lower plunger housing 330 is shown on FIG. 16, the low er plunger housing 330 extends between a first end 331 to a second end 332 about the pipetting axis 172. The first end 331 of the lower plunger housing 330 is adjacent the second end 312 of the upper plunger housing 310 when the plunger 360 is at or between an extended state and a retracted state. The second end 332 terminates at apipete tip receiving region 158. The pipete tip 120a may terminate against the second end 332. The lower plunger housing 330 includes a tubular structure 333 extending through the first end 331 and through the second end 332. The tubular structure 333 is designed to house at least a portion of the plunger 360, the capacitance tube 340, the insulating tube 350, and an end of pipette tip 120b. The lower plunger housing 330 also includes a mandrel interface 334 which extends transverse to a length of the tubular structure 333 and adjacent the first end 331. The mandrel interface 334 may include a cavity to receive an end of the mandrel 380. The mandrel interface 334 may also include a cavity to receive an end of the pipete tip detection structure 386. In the present example, the mandrel interface 334 forms an outcropping from the tubular structure 333 that is partly shaped around the tubular structure 333. As will be discussed later in greater detail, when the mandrel 380 is pressed downward by the plunger attachment structure 230, the lower plunger housing 330 moves downward so as to remove pipete tip 120a from the capacitance tube 340.

[0063] The capacitance tube 340 is an electrically conductive tube which extends about the pipeting axis 172 between a first end 341 and a second end 342 and is radially outward of the plunger 360 and the insulating tube 350 about the pipeting axis 172. The capacitance tube 340 is radially inward of the upper and lower plunger housings 310, 330 about the pipetting axis 172. The capacitance tube 340 includes a first portion 343 positioned adjacent the capacitance sensor 376 extending from the circuit board 370 and through the second sensor cavity 325 of the upper plunger housing 310 when in an assembled state. The capacitance tube 340 includes a second portion 344 at the pipette tip receiving region 158. The second portion 344 includes a first step 345 with an inner and outer diameter that is smaller than an inner and outer diameter of the first portion 343. The first step 345 is sized such that the pipete tip 120a can slide onto the outer diameter of the first step 345. The second portion 344 also includes a second step 346 with a smaller inner and outer diameter than the first step 345. The second step 346 is adjacent the first step 345 and extends to the second end 342 of the capacitance tube 340. The second step 346 is sized such that the pipete tip 120b can slide onto the outer diameter of the second step 346. An end of the pipete tip 120b would be stopped by the transition between the first and second steps 345, 346. The capacitance tube 340 extends into the upper plunger tube 315 of the upper plunger housing 310 about the pipeting axis 172. The capacitance tube 340 also extends into the tubular structure 333 of the lower plunger housing 330. In certain examples, thefirst and second steps 345, 346 extend out of the second end 332 of the lower plunger housing 330 at least when the plunger 360 is at or between the extended and retracted states. In certain examples, the capacitance tube 340 is made of metal. In an assembled state, the capacitance tube 340 is insulated by the insulating tube 350, such that the capacitance tube 340 does not contact any conductive surfaces within the syringe assembly 300, with the possible exception of the capacitance sensor 376 and any fluid present within the pipette tip 120.

[0064] An example of the insulating tube 350 is shown on FIG. 18. The insulating tube 350 has a first end 352 and a second end 354 extending about the pipetting axis 172. The insulating tube 350 has a hollow portion 356 which extends through the first end 352 and through the second end 354. The insulating tube 350 provides a nonconductive barrier between the plunger 360 and the capacitance tube 340. The insulating tube 350 extends into the upper plunger tube 315 of the upper plunger housing 310 about the pipetting axis 172. The insulating tube 350 also extends into the tubular structure 333 of the lower plunger housing 330. The insulating tube 350 helps to ensure that the capacitance tube 340 can obtain accurate capacitance measurements and may also help obtain accurate pressure sensor 376 data by positioning the capacitance tube 340. The insulating tube 350 is a tubular structure. In the example shown in FIG. 18, the insulating tube 350 has a constant wall thickness. The first end 352 is adjacent the first end 341 of the capacitance tube 340 when assembled in the syringe assembly 300. Both the first end 341 of the capacitance tube 340 and the first end 352 of the insulating tube 350 terminate within the upper plunger housing 310 at or near the upper plunger housing tube step 323. The second end 354 of the insulating tube 350 terminates at or near the transition between the first portion 343 and the first step 345 of the capacitance tube 340.

[0065] An example of the plunger 360 is shown on FIG. 19. As shown, the plunger 360 extends from a first end 362 to a second end 364 about the pipetting axis 172. The plunger 360 includes a plunger head 365 adjacent the first end 362. The plunger head 365 includes a head ring 366 that is designed to fit within the plunger attachment structure 230, such that the plunger attachment structure 230 moves together with the plunger 360 about the Y-axis. In certain examples, the head ring 366 is made of a flexible material. The plunger 360 includes a main shaft 367 that extends a majority of the length between the first and second ends 362, 364 and extends from the plunger head 365. The main shaft 367 is designed to form a close fit within the hollow portion356 of the insulating tube 350. The plunger 360 also includes a pipette tip removal shaft 368 that extends from the second end 364 to a transition between the main shaft 367 and the pipette tip removal shaft 368. The pipette tip removal shaft 368 is designed to extend through the second step 346 of the capacitance tube 340 and push the pipette tip 120b off of the capacitance tube 340 when the plunger 360 reaches an overextended state.

[0066] The syringe assembly 300 also includes a mandrel 380. An example of the mandrel 380 is shown on FIG. 20. The mandrel 380 extends from a first end 381 to a second end 382. The mandrel 380 includes a mandrel head 383 adjacent the first end 381. A mandrel shaft 384 extends from a lower end of the mandrel head to the second end 382. The mandrel 380 can be used to detach pipette tips 120a (the larger pipette tips 120, such as 120a, terminate at the second end 332 of the lower plunger housing 330) by pressing the lower plunger housing 330 downward when the plunger 360 reaches the overextended state.

[0067] In an assembled state, the mandrel 380 extends through the mandrel tube 318 and mandrel channel 319 of the upper plunger housing 310 and connects to the lower plunger housing 330 at the mandrel interface 334. When the plunger 360 drives downward about the pipetting axis 172, such as would be done when aspirating the pipette tip 120 (moving to an extended state), the lower portion 234 of the plunger attachment structure 230 eventually contacts the mandrel head 383. When the lower portion 234 of the plunger attachment structure 230 contacts the mandrel head 383, the mandrel 380 is driven downward which, in turn, drives the lower plunger housing 330 downward (moving to the overextended state). Comparing FIG. 21 with FIG. 22 shows an example of how the plunger attachment structure 230 moves and subsequently contacts, and causes movement of, the mandrel 380 as the plunger 360 moves to an overextended state. When the lower plunger housing 330 is driven downward, the pipette tip 120a becomes disconnected from the first step 345 of the capacitance tube 340.

[0068] Attached to the lower plunger housing 330 is a pipette tip detection structure 386. As can be seen comparing FIG. 21 with FIG. 22, an example of the pipette tip detection structure 386 moves with the lower plunger housing 330 such that when the low er plunger housing 330 is displaced, or driven downward, during pipette tip 120 removal (when the plunger 360 moves into the overextended state), the pipette tip detection structure 386 leaves the first sensor cavity 322 as the pipette tip detectionstructure 386 moves parallel to the pipetting axis 172 within the pipette tip detection channel 321 (not shown in FIGS. 21 and 22).

[0069] An example of the circuit board 370 can be seen on FIGS. 21 and 22. In certain examples, the circuit board 370 is configured to transfer data collected by the vary ing sensors to data processing and data storage structures within the pipetting assembly 100. In certain examples, the data collected by the varying sensors is used to control pipetting and provide feedback to a user.

[0070] In certain examples, a pipette tip detection sensor 372 forms part of the circuit board 370. The pipette tip detection sensor 372 fits within the first sensor cavity' 322 when in an assembled state. In certain examples, the pipette tip detection sensor 372 is an optical sensor. In the example shown on FIG. 22, the pipette tip detection sensor 372 includes a light emitter and light emission sensor with a space 373 between the two, such that when the lower plunger housing 330 is in a pipette tip removal position, or overextended state, the pipette tip detection structure 386 is removed from a light path extending across the space 373 between the light emitted and the light emission sensor, such that the light emission sensor detects light. When the lower plunger housing 330 is in a pipette holding position, at or between the extended and retracted states, the pipette tip detection structure 386 sits within the space 373 and blocks the emitted light from reaching the light emission sensor. FIGS. 21 and 22 show the movement of the pipette tip detection structure 386 between the pipette holding position and the pipette removal position.

[0071] In certain examples, the circuit board 370 also includes a pressure sensor 374. An example of the pressure sensor 374 can be seen in FIGS. 21 and 22. The pressure sensor 374 fits within the third sensor cavity 326 when in an assembled state with the upper plunger housing 310. As can be seen in FIG. 23, the pressure sensor 374 is in fluidic communication with a pipetting air chamber 390 that extends between a plunger seal 392 to a fluid present in the pipette tip 120 about the pipetting axis 172. The pipetting air chamber 390 forms a sealed chamber when liquid is present in the pipette tip 120. The plunger seal 392 slidably seals against the main shaft 367 of the plunger 360 at the first end 31 1 of the upper plunger housing 310. The pipetting air chamber 390 extends from the plunger seal 392 through the upper plunger tube 315, through the capacitance tube 340, and to a fluid level within the pipette tip 120. As the plunger 360 moves within the pipetting air chamber 390, the fluid level in the pipette tip 120 varies as a result of the change in pressure of air present in the pipetting airchamber 390. The pressure varies as the plunger 360 occupies more or less space within the pipeting air chamber 390 and thus compressing or decompressing the air trapped between the plunger seal 392 and the fluid in the pipette tip 120. When the plunger 360 occupies less space in the pipeting air chamber 390, the pressure in the pipeting air chamber 390 is decreased and the fluid level in the pipete tip 120 rises. When the plunger 360 occupies more space in the pipeting air chamber 390. the pressure in the pipeting air chamber 390 is increased and the fluid level in the pipete tip 120 decreases. The pressure sensor 374 detects changes in the pressure within the pipeting air chamber 390 and can be calibrated to measure fluid levels within the pipete tip 120. The pressure sensor 374 may include a seal 375 that seals between the circuit board 370 and the third sensor cavity 326 of the upper plunger housing 310.

[0072] In certain examples, the pressure sensor 374 is sensitive enough to detect various conditions within the pipeting air chamber 390. For example, certain error conditions may be detected when purging, aspirating, or mixing fluid in the pipete tip 120. These error conditions may be measured, recorded, and used to provide user feedback and pipeting control. FIG. 32 shows an example pressure sensor 374 reading during a mixing operation performed by the plunger 360 when the pipete tip 120 is functioning normally. In the example shown, fluid, such as water, is first aspirated to create an air pocket in the pipetting air chamber 390, then dispensed, then mixing occurs where the fluid is aspirated and purged a series of times, then a final blowout of the fluid is performed. FIG. 33 shows an error condition where the same mixing operation is performed by the plunger 360 when a pipete tip 120 is not present on the syringe assembly 300. In this example, the pressure remains in a very small band near ambient pressure. In certain examples, the pressure sensor 374 is able to measure the momentary pressure changes created within the pipeting air chamber 390 when the plunger 360 is moved and the pipete tip 120 is in air and not submersed in a different fluid. There is a delay between the movement and the pressure normalization that occurs. FIG. 33 shows a combination of the error in the sensor and the brief changes in pressure that occur, even without a pipete tip 120 atached. FIG. 34 shows another error condition where the pipete tip 120 is clogged. In this example, flat lines in the pressure curve are observed between the aspirating and purging operations of the mixing, whereas pressure decay is observed during the same process in the normal operation shown in FIG. 32. Other error conditions may also be measured. For example, when a pipete tip 120 contains fluid when it is expected to be empty, a rise inpressure occurs that exceeds expectation. Conversely, when a pipette tip 120 is expected to have fluid but is actually empty, a nearly flat line at ambient pressure occurs, similar to what is shown in FIG. 33. Other conditions may also be observed using the pressure sensor 374. For example, when a pipette tip 120 has been previously used and has a small amount of residual fluid present at a tip of the pipette tip 120, the starting pressure is higher than the ending pressure, after the mixing operation is performed. In another example, if fluid is still present after the final blowout of the mixing operation, the ending pressure will be higher than the starting pressure. In certain examples, the pressure sensor 374 is sensitive enough to detect a pressure change when the pipette tip 120 is dipped into another fluid, without purging or aspirating.

[0073] The examples shown in FIGS. 32 through 34 provide examples of pressure changes that may occur in water. The pressure changes that the pressure sensor 374 detects will vary based on the specific gravity and viscosity being pipetted. In certain examples, the pipetting assembly 100 can calibrate expected behavior with different types of fluid. In certain examples, the pipetting assembly 100 can detect error conditions, such as the ones previously described by comparing real-time data to known error conditions. And in certain examples, the pipetting assembly 100 can provide feedback to a user by means of an alert, alarm, notification, or change in operation when an error condition is detected. As an example, if during an aspirating, purging, or mixing routine, the pressure remains relatively constant (as seen in FIG. 33), the pipetting assembly 100 may determine that there is no pipette tip 120 present and may subsequently cease operation and / or notify via an alarm or display that the pipette tip 120 is missing.

[0074] FIG. 35 shows an example of a pipetting operation 400 that collects and analyzes pressure sensor data to control pipetting within a pipetting assembly 100. In the present example, the pipetting operation 400 includes a first operation 410 that involves beginning a chosen pipetting routine, such as purging, aspirating, or mixing. This operation may be performed as part of an automated process or may be selected by a user. Once the first operation begins, a second operation 420 starts. The second operation 420 involves the operation of at least one of the sensors 372, 374, 376 to measure real-time data within the pipetting air chamber 390. As an example, operation 420 utilizes pressure sensor 374. Once the pressure sensor 374 begins collecting realtime sensor data, a third operation, operation 430, is performed. Operation 430 involvestransferring the sensor data from the pressure sensor 374 to a data storage and data processing device. The processing device may be within, or external to, the pipetting assembly 100. Once the sensor data is available to the processing device, a fourth operation, operation 440, is performed. Operation 440 involves analyzing the sensor data to look for specific characteristics of know n error conditions, examples of these characteristics have been previously discussed. The processing device then performs a fifth operation, operation 450. Operation 450 is a decision to determine whether an error condition is present based on the comparison made in operation 440. If an error condition is determined to be present, operation 460 is performed. Operation 460 may incorporate a number of different actions. In certain examples, the different actions may be determined by the user. In certain examples, the different actions may be built into the pipetting assembly 100. In certain examples, operation 460 includes providing feedback to a user such as a notification, alert, alarm, or other display of the error condition. In certain examples, operation 460 includes stopping the pipetting routine. In certain examples, operation 460 includes remedying the error condition. If operation 450 determines that no error condition is present, then operation 470 is performed and the pipetting routine is continued. Operations, 420, 430, 440, and 450, may be continuously performed as new real time sensor data becomes available.

[0075] In certain examples, the circuit board 370 also includes a capacitance sensor 376. An example of the capacitance sensor 376 can be seen in FIGS. 21 and 22. The capacitance sensor 376 fits within the second sensor cavity 325 of the upper plunger housing 310 when in an assembled state. As can be seen in FIG. 23, the capacitance sensor 376 contacts, or nearly contacts, the capacitance tube 340. The capacitance sensor 376 can measure changes in an electrical field created by the capacitance sensor 376. The capacitance sensor 376 can measure the presence of fluid and fluid amounts within a pipette tip 120. The capacitance sensor 376 can also measure direct contact with metal by detecting an electrical short by the inability to create an electric field. The capacitance sensor 376 may also measure position of the plunger 360 within the pipetting assembly 100 by detecting slight changes in the electrical field.

[0076] FIGS. 24 and 25 show the movement of the plunger attachment structure 230, the plunger 360, and the mandrel 380 when the plunger attachment structure 230 is driven by the second motor 114 and second drive screw- 118. FIG. 25 show s the plunger 360 in the overextended state where the mandrel 380 is pressed downward parallel to the pipetting axis 172 such that the lower plunger housing 330 is moveddownward about the pipetting axis 172, which subsequently removes the pipette tip 120a that was attached to the capacitance tube 340.

[0077] FIGS. 26 and 27 show the movement of certain syringe assembly 300 components at the pipette tip receiving region 158 when the plunger 360 travels. FIG. 26 shows the plunger 360 in a position at or between the extended and retracted states such that the pipette tip 120a is attached to the first step 345 of the capacitance tube 340. FIG. 27 shows the plunger 360 in the overextended state. In FIGS. 26 and 27. the capacitance tube 340 remains in the same position, as does the insulating tube 350. Comparing FIG. 26 with FIG. 27 shows that when the plunger 360 moves to the overextended state, the lower plunger housing 330 also moves such that the pipette tip 120a is slid off of the first step 345 of the capacitance tube 340.

[0078] Similarly, FIGS. 28 and 29 show the movement of certain syringe assembly 300 components at the pipette tip receiving region 158 when the plunger 360 travels with the smaller pipette tip, pipette tip 120b. FIG. 28 shows the plunger 360 in a position at or between the extended and retracted states such that the pipette tip 120b is attached to the second step 346 of the capacitance tube 340. FIG. 29 shows the plunger 360 in the overextended state. In the FIGS. 28 and 29, the capacitance tube 340 remains in the same position, as does the insulating tube 350. Comparing FIG. 28 with FIG. 29 shows that when the plunger 360 moves to the overextended state, the pipette tip removal shaft 368 pushes the pipette tip 120b off of the second step 346 of the capacitance tube 340. When pipette tip 120b is attached, the lower plunger housing 330 does not contact the pipette tip 120b even though the lower plunger housing 330 moves downward about the pipetting axis 172 as shown in FIGS. 27 and 29.

[0079] FIG. 30 shows a detailed view of an example of the syringe assembly attachment region 240 that includes three attachment structures 242. Each attachment structure 242 is a keyhole slot 244 that includes an enlarged opening 241 positioned above a keyhole channel 243. In the example shown, the enlarged opening 241 is designed to allow the head 329 of a bolt or screw 328 to pass through, while the keyhole channel 243 is designed to retain the head 329 of a bolt or screw 328about the pass through direction by having a keyhole channel 243 width W that is less than the diameter of the head 329of a bolt or screw 328. The keyhole channel 243 width W is larger than a shaft diameter of the bolt or screw 328. As an example, the bolt 328 may connect to the syringe assembly 300. The head 329 of the bolt 328 may then be inserted through the enlarged opening 241 of the keyhole slot 244 and then the shaft of the bolt328 may move into the keyhole channel 243 such that the bolt 328 cannot exit about the direction that it entered. The keyhole slot 244 is shaped to allow the shaft of the bolt to seat into the slot. In certain examples, the bolt 328 may be easily removed by first lifting the syringe assembly 300 about the pipetting axis 172 and then pulling the bolt328 out through the enlarged opening 241 about a direction transverse to the pipetting axis 172.

[0080] An example of the connection between the syringe assembly attachment region 240 and the probe assembly attachment region 316 is shown on FIG. 31. The heads 329 of two of the bolts 328 are seated in the keyhole channels 243. The bolts 328 extend from the attachment feature 324. The enlarged opening 241 extends between the first and second sides 213. 214 of the probe assembly housing 210. In certain examples, the one or more enlarged openings 241 align with corresponding fastener openings 122 of the first rail 115. In certain examples, and as shown in FIG. 31, the positioning feature 246 extends between the upper plunger housing 310 and the probe assembly housing 210.

[0081] In certain examples, the bolts 328 are attached to the probe assembly attachment features 324 of the syringe assembly 300. In certain examples, the bolts 328 are part of the attachment features 324. In certain examples the syringe assembly 300 may be attached to the probe assembly 200 by moving the syringe assembly 300 toward the probe assembly 200 in a direction transverse to the pipetting axis 172 such that the heads 329 of the bolts 328 are moved into the enlarged openings 241 of the keyhole slot 244, then lowering the syringe assembly 300 about the pipetting axis 172 such that the shaft of the bolts 328 are lowered into the keyhole channels 243. In this example, the syringe assembly 300 is prevented from moving away from the probe assembly 200 without first lifting the probe assembly 200. In certain examples, the syringe assembly 300 is detached in a reverse order, where the syringe assembly 300 is first raised about the pipetting axis 172, then the syringe assembly 300 is pulled away from the probe assembly 200, transverse to the pipetting axis 172, such that the heads329 of the bolts 328 move through the enlarged openings 241 of the attachment structures 242.

[0082] In certain examples, the bolt 328 is attached and / or tightened to the probe assembly attachment feature 324 from the first side 213 of the probe assembly housing 210 through a fastener opening 122 of the first rail 115 using a tool. FIG. 32 shows a number of fastener openings 122 along the first rail 1 15. In certain examples, thefastener openings are aligned with the enlarged openings 241 of the syringe assembly attachment structure 215. In certain examples, the bolt 328 is loosened using a tool by accessing the head 329 of the bolt 328 from the fastener opening 122 of the first rail 115. In certain examples, the syringe assembly 300 does not need to be lifted in order to remove the syringe assembly 300 from the probe assembly 200.

[0083] As an example, FIG. 36 shows an operation 500 for detaching a syringe assembly 300 from the probe assembly 200 that may include a number of operations. In the example shown on FIG. 36, operation 500 includes a first operation 510 that involves lowering the pipetting system 150 to a pipetting position such that the first side 213 of the probe assembly housing 210 is accessible (for example, if one of the pipetting systems 150 from the group of pipetting systems 150 as shown in FIG.3 is separated from the group by lowering the pipetting system 150 about the pipetting axis 172). Lowering the pipetting system 150 about the pipetting axis 172 also ensures that the probe drive housing 220 does not block access to the fastener openings 122 of the first rail 115. Then, a second operation 520 is performed. The second operation 520 involves removing the plunger head 365 from the plunger 360. In certain examples, operation 520 may include first removing a plunger head support bar 238 that holds the plunger head 365 in place. Then, a third operation 530 is performed. The third operation 530 involves removing the plunger 360 from the plunger attachment structure 230. The plunger 360 may be lowered about the pipetting axis 172 such that the plunger 360 is removed from the plunger attachment structure 230. In certain examples, operation 530 may include removing the plunger head ring 366 from the plunger attachment structure 230. Then, a fourth operation 540 is performed. The fourth operation 540 involves detaching the syringe assembly 300 from the probe assembly 200. The fourth operation 540 also involves detaching the at least one probe assembly attachment feature on the syringe assembly 300 from the corresponding at least one syringe assembly attachment structure on the probe assembly 200. In certain examples, the operation 540 includes lifting the syringe assembly 300 about the pipetting axis 172 to a removal position and pulling the syringe assembly 300 away from the probe assembly 200 in a transverse direction to the pipetting axis 172 while the syringe assembly 300 is in the removal position. In certain examples, the operation 540 includes unscrewing at least one fastener extending between the at least one probe assembly attachment feature 324 and the corresponding at least one syringe assemblyattachment structure 215 and pulling the syringe assembly 300 away from the probe assembly 200 in a transverse direction to the pipetting axis 172.

[0084] The various embodiments described above are provided by way of illustration only and should not be construed to limit the claims attached hereto. Those skilled in the art will readily recognize various modifications and changes that may be made without following the example embodiments and applications illustrated and described herein, and without departing from the full scope of the following claims.

Claims

WHAT IS CLAIMED IS:

1. A pipetting system comprising: a syringe assembly comprising: a pipetting air chamber extending about a pipetting axis; a plunger configured to travel between an extended state and a retracted state within the pipetting air chamber; and a pipette tip receiving region configured to receive a pipette tip; and a probe assembly comprising: a probe drive housing configured to control movement of the probe assembly about the pipetting axis; and a plunger attachment structure configured to control movement of the plunger about the pipetting axis; wherein the syringe assembly is removably attached to the probe assembly such that the syringe assembly may be removed from the probe assembly without removing the probe assembly from the pipetting system.

2. The pipetting system of claim 1, wherein a first motor drives a first lead screw that connects to the probe drive housing and wherein a second motor controls a second lead screw that connects to the plunger attachment structure.

3. The pipetting system of any one of claims 1-2, wherein the syringe assembly further includes a circuit board configured to detect the presence of the pipette tip.

4. The pipetting system of claim 3, wherein the circuit board includes an optical sensor configured to detect the presence of the pipette tip.

5. The pipetting system of claim 4, wherein the optical sensor detects the presence of a pipette tip detection structure to determine the presence of the pipette tip.

6. The pipetting system of claim 5, wherein the pipette tip detection structure is connected to a lower plunger housing that is configured to remove the pipette tip whenthe plunger moves to an overextended state, wherein the pipette tip detection structure moves away from the optical sensor when the plunger moves into the overextended state.

7. The pipetting system of any one of claims 1-6, wherein the syringe assembly is removably attached to the probe assembly by at least one attachment structure on the probe assembly connecting to a corresponding at least one attachment feature on the syringe assembly.

8. The pipetting system of claim 7, wherein the at least one attachment feature is configured to threadedly engage a fastener.

9. The pipetting system of claim 8, wherein the at least one attachment structure is a keyhole slot including an enlarged opening and a keyhole channel, wherein the enlarged opening is configured to allow a head of the fastener through while the keyhole channel is configured to retain the head of the fastener.

10. The pipetting system of any one of claims 1-9, wherein the syringe assembly further includes a mandrel extending parallel to the pipetting axis, the mandrel configured to move a lower plunger housing and remove the pipette tip from the syringe assembly when the plunger is in an overextended state.

11. The pipetting system of any one of claims 1-10, wherein the plunger further includes a pipette tip removal shaft configured to remove the pipette tip when the plunger is in an overextended state.

12. A method for removing a syringe assembly from a pipetting system comprising: removing a plunger head from a plunger on the syringe assembly; lowering the plunger and separating the plunger from a plunger attachment structure on a probe assembly; anddetaching at least one probe assembly attachment feature on the syringe assembly from a corresponding at least one syringe assembly attachment structure on the probe assembly.

13. The method of claim 12, wherein prior to removing the plunger head, the pipetting system is lowered to a pipetting position.

14. The method of any one of claims 12-13, wherein detaching the at least one probe assembly attachment feature on the syringe assembly from the corresponding at least one syringe assembly attachment structure on the probe assembly further includes lifting the syringe assembly about a pipetting axis to a removal position and pulling the syringe assembly away from the probe assembly in a transverse direction to the pipetting axis while the syringe assembly is in the removal position.

15. The method of any one of claims 12-14, wherein detaching the at least one probe assembly attachment feature on the syringe assembly from the corresponding at least one syringe assembly attachment structure on the probe assembly further includes unscrewing at least one fastener extending between the at least one probe assembly attachment feature and the corresponding at least one syringe assembly attachment structure and pulling the syringe assembly away from the probe assembly in a transverse direction to the pipetting axis.

Images