Liquid handling tool having porous plunger

A robotically manipulable sample handling tool, such as a colony picking head or robotic pipetting tool, includes needles arranged on the tool. Actuators are associated with each needle to control flow for the needle. A plurality of plungers are each associated with a needle, and movement of the plungers can actuate a corresponding needle. Each of the plungers has a passageway that may be opened or closed, e.g., to move the corresponding needle and/or draw fluid into/expel fluid from the needle when the plunger is moved in the tool body. The actuators are arranged so that plunger passageways may be individually controlled by a controller.

BACKGROUND OF THE INVENTION

1. Field of Invention

This invention relates to sample handling tools, such as robotically manipulated pipetting devices.

2. Related Art

Robotically manipulated tools having a plurality of sample handling needles are widely used, for example, in proteomic and genomic research. These devices are used to move material samples both to and from a variety of different work areas, such as microtiter trays, gels having separated DNA fragments, and other material holding devices. Some such tools may have a plurality of needles arranged in an array that corresponds to wells in a microtiter tray, such as the commonly-known 96-well or 384-well plate. The array of needles arranged to correspond with all of the wells in a microtiter tray may allow material to be simultaneously deposited in, and removed from, wells in the microtiter tray, thus increasing the speed at which a plurality of samples in a microtiter tray may be processed.

SUMMARY OF THE INVENTION

In one illustrative embodiment in accordance with the invention, a robotically manipulable material handling tool includes a tool body and a plurality of needles mounted to the tool body. Each of the plurality of needles is constructed and arranged to remove material from a work area and deposit material on a work area. The tool also includes a plurality of plungers with each of the plurality of plungers associated with a corresponding one of the plurality of needles. The plungers may be movable in a channel to create suction/pressure that causes the corresponding needle to be actuated. The plungers may be porous, e.g., have a hole, channel or other passageway that allows fluid (i.e., gas or liquid) to pass through the plunger. In some embodiments, the passageway in the plunger may be controllably opened or closed so that the plunger and associated needle may be controlled to aspirate or dispense liquid or not. For example, if the passageway is closed, movement of the plunger in an associated channel (e.g., cylindrical bore) may create a suction at the needle and cause the needle to aspirate a liquid. In contrast, if the passageway is opened, movement of the plunger may not create a suction at the needle since air or other fluid may pass through the passageway.

In another illustrative embodiment, passageways in plungers may be individually addressed, e.g., opened or closed, so that each of the needles may be individually controlled to pick up and/or dispense samples. For example, a plurality of plungers may be all mounted to a common drive mechanism that moves all of the plungers relative to a channel block. For plungers that have their passageway closed, the plunger may create suction/pressure to actuate its corresponding needle as the plungers move. However, for plungers that have their passageway open, the plunger may not create suction/pressure to actuate its corresponding needle. As a result, if passageways in individual plungers can be individually addressed, individual needles can be actuated while other needles may be inactive.

In another aspect of the invention, individual passageways in plungers may be addressed using a matrix of membrane valves. The valves and associated control devices may be arranged to minimize the number of control signals needed to individually address plungers/needles.

These and other aspects of the invention will be apparent and/or obvious from the following description of illustrative embodiments and the appended claims.

DETAILED DESCRIPTION

Various aspects of the invention are described below with reference to illustrative embodiments. However, it should be understood that the invention is not limited to those embodiments described below, but instead may be used in any suitable system or arrangement.

In one aspect of the invention, plungers in a sample handling tool may have a passageway that can be selectively opened or closed. Selective opening or closing of the passageway may allow a needle associated with each plunger to be selectively actuated. Such actuation may include moving a needle relative to the tool, such as extending the needle away from the tool apart from other needles on the body, controlling flow in the needle, such as drawing fluid into or expelling fluid out from the needle, or otherwise causing the needle to perform one or more material handling functions. In addition, the tool controller may simultaneously actuate all needles in the array, or simultaneously actuate selected groups of needles, such as all or selected needles in a particular row or column of needles. This arrangement may allow individual control of needles without requiring a controller to output an individual control signal for each needle.

FIG. 1is a schematic diagram of a robot1manipulating a material handling tool10in accordance with the invention. The robot1may move the material handling tool10and allow needles4on the tool10to pick up and/or deposit material on one or more work areas, such as microtiter trays, gels containing separated DNA fragments or other biologic materials, etc. For example, the robot1may move the tool10so that one or more needles4are appropriately positioned with respect to a microtiter tray and then actuate one or more needles4to remove material from, or deposit material in, wells in the microtiter tray. Those of skill in the art will understand that the needles may be actuated to perform other material handling operations, such as colony or plaque picking at the direction of a machine vision system. The purposes and methods for such material handling are well known to those in the art and not described in detail herein.

Although the robot1is shown inFIG. 1as having a base and an articulated arm, the robot1may be of any suitable type or construction and may be capable of moving the tool10in any suitable number of degrees of freedom. For example, the robot may be a gantry-type robot capable of moving the tool10in three degrees of freedom. Of course, other suitable robotic configurations capable of moving the tool10in one or more degrees of freedom may be used. The tool10and robot1may include a coupling to allow the robot1to exchange the tool10for other tools, thereby allowing the robot1to perform automated operations with different tools. The robot1or system controller may include a vision system or other suitable device to control positioning of needles4with respect to target areas, as is well known. In addition, a connection, e.g., quick disconnect coupling, between the tool10and the robot1may provide physical support to the tool10as well as provide electrical power, control signals, a fluid supply or other fluid signal, etc. As used herein, “fluid” refers to gases and/or liquids.

In the illustrative embodiment ofFIG. 1, the tool10includes a controller2that outputs signals to actuators in the controller that cause corresponding needles4to be actuated. As discussed above, actuation of a needle4may cause the needle4to move relative to the tool10, such as extend away from the tool to pick or place material on a work area, control flow in the needle, such as drawing fluid into or expelling fluid out from the needle, or otherwise cause the needle to perform one or more material handling functions. In this illustrative embodiment, the controller2and needles4are all mounted to a body5of the tool10, but portions of the controller2may be located off the tool10. Although in this illustrative embodiment the body5has a box-like shape, the body5may be arranged in any suitable way. Further, the needles4in this illustrative embodiment are arranged in a 5×4 array and extend from a bottom of the body5, but any suitable number of needles4may be arranged in any suitable way on the body5, e.g., to accommodate particular well patterns in a microtiter tray. The needles4may be arranged to receive removable pipette tips or other devices to handle materials, or may be arranged to handle materials directly.

The controller2, which may in some embodiments be provided off of the tool10, may provide any suitable signal or combination of signals to the actuators to actuate the needles4. For example, the controller2may provide electrical signals, magnetic signals, optical signals, fluid signals (e.g., changes in fluid pressure and/or flow), or combinations of such signals, such as providing both an electrical signal and a fluid signal to the actuators. Typically, signals provided by the controller2will depend upon the type of actuators. For example, the actuators may be pneumatically-controlled fluid valves that open, close or otherwise change state based on a fluid signal. Of course, the actuators may include electrically-controlled fluid valves, relays, or other suitable devices to actuate a corresponding needle. For example, the tool10may include one actuator for each needle, where each actuator includes a valve and associated pneumatic ram such that when the valve is open and air pressure is supplied through the open valve, the pneumatic ram may extend, and thereby extend a corresponding needle4from the body5. Thus, the actuators may be responsive to two signals received from the controller2to actuate the needles4. Having the actuators respond to two signals from the controller2may allow for matrix-type addressing of the actuators, as discussed in more detail below.

The controller2may operate autonomously to actuate the needles4or operate at the direction of a higher level controller that is part of a material handling system. For example, the controller2may receive a signal to activate a particular needle or group of needles at a particular time and/or position of the tool10, and generate and output appropriate signals to cause the desired actuation. The controller2may receive the signals in any suitable way, such as by wired and/or wireless link, and in any suitable format and/or communications protocol. The controller2and/or higher level controller may include any suitable general purpose data processing system, which can be, or include, a suitably programmed general purpose computer, or network of general purpose computers, and other associated devices, including communication devices, and/or other circuitry or components necessary to perform the desired input/output or other functions. The controllers can also be implemented at least in part as single special purpose integrated circuits (e.g., ASICs), or an array of ASICs, each having a main or central processor section for overall, system-level control and separate sections dedicated to performing various different specific computations, functions and other processes under the control of the central processor section. The controllers can also be implemented using a plurality of separate dedicated programmable integrated or other electronic circuits or devices, e.g., hardwired electronic or logic circuits, such as discrete element circuits or programmable logic devices. The controllers may also include other devices, such as an information display device, user input devices, such as a keyboard, user pointing device, touch screen or other user interface, data storage devices, communication devices or other electronic circuitry or components.

FIG. 2shows a perspective view of a tool10in accordance with the invention. In this illustrative embodiment, the controller2includes a 5×4 array of actuators3that are each associated with a corresponding needle4. Thus, when an actuator3receives appropriate signals, the corresponding needle4may be actuated, e.g., fluid flow in the needle may be controlled and/or the needle4may be moved relative to the body5. In this illustrative embodiment, the controller2includes four control switches21that are associated with actuators3in rows across the tool10, and drive switches22that are associated with actuators3in columns on the tool10. Control signals may be provided to the control switches21and drive switches22by a portion of the controller2(e.g., a data processor and associated memory) on the tool10, or by another source off of the tool10. Based on these control signals, the control switches21and drive switches22may provide suitable signals to the actuators3to actuate a particular needle or needles. The switches21and22may be any suitable device capable of responding to a control signal and providing a signal to corresponding actuators3. For example, the switches21and22may include electrically-controlled valves capable of switching an associated line between one or more fluid lines, e.g., sources of relatively high or low pressure, or sources of fluid flow. Pressure or other fluid flow sources may be provided to the switches21and22by lines (not shown) that lead to a pump, metering piston, reservoir or other devices off of the tool body10.

It should be understood that although the actuators3in this illustrative embodiment are arranged in columns and rows, the actuators3may be logically grouped in any suitable way and in any suitable pattern. Further, the tool10is not limited to a 5×4 array, but instead may have any suitable number of actuators and/or needles arranged in any suitable pattern, such as a pattern that allows the needles4to interact with standard 96-well, 384-well or other size/configuration microtiter trays or other material sample holders. Thus, the 5×4 array in this illustrative embodiment is used for simplicity and ease of reference, but should in no way be interpreted as limiting aspects of the invention in any way.

In this illustrative embodiment, the tool10also includes a drive mechanism9that is capable of moving an upper portion5aof the body5relative to the lower portion5b,e.g., in a direction shown by the arrow91. Such movement may cause plungers6secured to the upper portion5ato move relative to the lower portion5band create suction/pressure for each of the needles4to aspirate/dispense a sample. The drive mechanism9may take any suitable form as is well known in the art. For example, the drive mechanism9may include guideways for guiding the movement of the upper portion5arelative to the bottom portion5b,a linear motor that provides the motive force to move the upper portion5a,and a linear encoder that provides position feedback so the upper portion5amay be positioned accurately relative to the bottom portion5b.It should be understood that the although in this embodiment the upper portion is moved relative to the bottom portion5b,the bottom portion5bmay be moved relative to the upper portion5a.Additionally, the tool body5may have more than two portions, e.g., the tool10may include an intermediate portion between the upper and lower portions, and the various portions may be moved relative to each other in any suitable way. Moreover, the tool5need not have movable portions like that shown, and instead the needles4may be actuated using other mechanisms.

FIG. 3shows a schematic cross-sectional view of the tool10shown inFIG. 2. In this illustrative embodiment, the plungers6are secured at a top end to the upper portion5aof the tool body5and move up and down in the direction shown by arrow91when the upper portion5ais driven by the drive mechanism9. This causes the plungers6to move relative to the lower portion5bin a corresponding channel7, e.g., a cylindrical bore in the lower portion5b.One or more seals8, such as an elastomeric member, resist fluid flow from within the channel7past the plunger6. The seal(s)8may be stationary relative to the channel7, or move with the plunger in the channel wall. The seal created may be enhanced by the use of a suitable lubricant or other material on the plunger6. Movement of the plungers6in their respective channels7can create a suction/pressure at a corresponding needle4, e.g., so a liquid can be aspirated or dispensed, as is well known in the art. The needles4may carry a replaceable pipette tip41as is known in the art.

In this embodiment, the plungers6are porous, e.g., the plungers6have a hole or passageway that extends through the length of the plungers6. The passageway allows fluid (gas or liquid) to pass through the plunger6. The passageways for each plunger6communicate with an actuator3, e.g., a membrane valve as shown inFIG. 3, via a line32. The actuators3may open or close the passageways by operation of the membrane valve. For example, as shown inFIG. 4, when a suitable control signal, e.g., fluid pressure, is supplied on a line23to the actuators3, the flexible member31may deform and prevent communication between the line32and a line24. Alternately, as shown inFIG. 5, when the fluid pressure is released and/or a vacuum is applied, the flexible member31may retract, allowing communication between the line32and the line24. As a result, the passageways may be opened or closed by the valves. A closed passageway allows a plunger6to create a suction/pressure in the channel7when the plunger6moves. However, an open passageway may prevent a suction/pressure from being created by movement of the plunger6since fluid may be supplied from the line24to the plunger passageway. That is, the line24may be open to ambient air pressure or supplied with a fluid at a suitable pressure to prevent movement of the plunger from causing the needle to aspirate/dispense a sample.

Control of the action at the needles4may be further controlled by controlling the fluid in the line24. For example, the line24may be open to ambient air pressure so that opening and closing of the actuators3effectively closes or opens the passageway. Alternately, fluid may be supplied under pressure to the line24, e.g., so that a liquid or gas may be selectively supplied through an open valve, through the plunger6and expelled from the corresponding needle. A vacuum may also be applied to the lines24so that when a passageway is opened by an actuator3, fluid may be aspirated by a selected needle without requiring movement of plungers6. Thus, aspirating/dispensing samples from needles4may be controlled by controlling fluid flow through the passageways independent of, or in conjunction with, movement of the plungers6Switching of fluid flow to the lines23and24may be controlled by the switches21and22, respectively. The switches21and22may be electrically operated valves that switch the lines23and24between one or more fluid supply lines, e.g., lines that provide a vacuum, fluid under pressure or ambient air pressure.

As should be appreciated by those of skill in the art, the membrane valves shown are only one way that an actuator3for controlling the passageways may be implemented. The actuators3may include two or more membrane valves in a cascaded arrangement to allow truly individual control of the passageways, and of course other types of valves or other devices may be used to open or close the passageways. Of course, individually controlled valves could be used to open or close each passageway rather than using the matrix type valve arrangement shown.

FIG. 6shows a schematic plan view of the upper portion5aof the tool10. In this schematic view, the lines23provide control signals to rows A-D of actuators3via a corresponding switch21. Drive signals are provided to columns1-5of actuators3via a corresponding switch22. Thus, in this illustrative embodiment, each control switch21provides a control signal approximately simultaneously to all actuators3in the corresponding row via a control line23. The control signal provided to a row of actuators3may cause the actuators3to change state between an open and closed state. Similarly, each of the drive switches22may approximately simultaneously provide a drive signal to all actuators3in a corresponding column along a drive line24. Accordingly, individual passageways may be addressed, e.g., opened or closed, by providing a control signal along the actuator's corresponding control line23, and a drive signal along the actuator's corresponding drive line24may control the actuation of the needle. For example, the passageway corresponding to the actuator3in the top right corner of the tool10as shown inFIG. 3(position A-5) may be opened by providing a control signal from the control switch21for row A suitable to open the valve and allow flow through the passageway. Flow through the passageway may be controlled by controlling flow through the lines24. That is, even if the valve for the passageway at position A-5is opened, if flow is not allowed in the line24for that valve, e.g., the switch22for column5prevents flow in the line24, fluid will not flow in the passageway. Thus, flow for the passageway may be controlled by controlling flow in the lines24as well. As a result, individual needles4may be actuated by providing appropriate signals to the lines23and24, e.g., rows and/or columns, of actuators in the tool10.

It should also be appreciated that selected groups of actuators3may be addressed by providing appropriate signals along the rows A-D and columns1-5. For example, all needles on the tool10, or selected needles, in a particular row or column may be approximately simultaneously actuated in a similar way, e.g., all of the actuators3in row A may aspirate a liquid by providing an appropriate control signal from the control switch21for row A to close the valves in the row A, providing appropriate control signals from the switches21for rows B-D to open the valves in rows B-D, and providing appropriate drive signals from the drive switches22for columns1-5to allow flow through the lines24while the plungers6are moved upwardly by the drive mechanism9. Such a set of control signals may allow only the needles in row A to aspirate/dispense a sample. It will be appreciated that other selected groups of needles may be approximately simultaneously actuated by providing signals on appropriate control and drive lines23and24and/or moving the plungers6appropriately by the drive mechanism9.

The plungers6and upper and lower portions5aand5bmay be made of any suitable material(s), such as plastic, glass or suitable metal, and the channels, lines, chambers and other features may be formed in any suitable way using any suitable process. For example, the upper and lower portions5aand5bmay be made of multiple layers of plastic material that have grooves, channels or are otherwise formed to create the desired lines, channels, etc. in the tool body10. These layers may be joined together, e.g., by heating the layers and pressing them together, to form a unitary block. The membrane valves31may be formed by positioning a flexible member6, such as a sheet of silicone rubber, between the layers of the upper portion5aand securing the layers. The construction of membrane valves is well known, and alternate methods of construction will be appreciated by those of skill in the art.

The control and drive signals may also cause the membrane valves to perform other actuation operations with respect to the needles, such as pumping fluid through a corresponding needle and/or drawing or expelling a metered amount of fluid into or out of a corresponding needle4. Pumping and metering operations may be performed by, for example, moving the flexible member in a valve to a closed state, closing a drive line24for the valve at a drive switch22, and moving the flexible member in the valve to an open state, thereby causing fluid to be drawn into the needle4. Movement of the flexible member may be closely controlled to perform accurate fluid metering through the valve's needle, e.g., by controlling the amount of fluid drawn from the valve by the control line23. Such control can be performed by a metering piston coupled to the control line23or drive line24, by accurately timing the opening and closing of a valve in the control switch21while supplying a constant fluid flow through the valve, or other means as will be appreciated by those of skill in the art.

It should be appreciated that although the control and drive switches in this illustrative embodiment control fluid flow to corresponding rows and columns of valves, the switches may provide other signal types to the actuators, such as electrical, optical, magnetic and other signal types. Similarly, the actuators and/or valves in this embodiment may include or be replaced with any other suitable element(s), such as electrical or optical relays, transistors, optical valves, etc., and the actuators3may include other drive elements, such as hydraulic rams, solenoid actuators, motors, and so on. Therefore, any suitable arrangement of elements may be used as actuators to receive control and drive signals and actuate a corresponding needle.

While the invention has been described with reference to various illustrative embodiments, the invention is not limited to the embodiments described. Thus, it is evident that many alternatives, modifications, and variations of the embodiments described will be apparent to those skilled in the art. For example, the porosity of the passageways in the plungers may be arranged to operate as a filter for fluid supplied to or drawn from a needle. Accordingly, embodiments of the invention as set forth herein are intended to be illustrative, not limiting. Various changes may be made without departing from the invention.