WO2001036100A1

WO2001036100A1 - Non-contact droplet dispensing system and methods

Info

Publication number: WO2001036100A1
Application number: PCT/US2000/028621
Authority: WO
Inventors: Andrew J. G. Kelly; Haim Kedar
Original assignee: Glaxo Group Limited
Priority date: 1999-10-12
Filing date: 2000-10-12
Publication date: 2001-05-25
Also published as: AU8026000A; WO2001036100A9

Abstract

A liquid dispensing device (10) has a hollow tube with a lumen (20). A plunger (14) is moveable within the lumen (20) and has a conical end (38) that mates with the conical end (28) of the lumen (20) when the plunger (14) is moved to expel fluid from the lumen (20).

Description

NON-CONTACT DROPLET DISPENSING SYSTEM AND METHODS

BACKGROUND OF THE INVENTION This invention relates generally to the field of dispensing, and in particular to the dispensing of small liquid droplets. In one aspect, the invention relates to devices and techniques for accurately dispensing small volumes in a non-contact manner.

In many fields, such as chemistry, biology, drug discovery, medicine, and the like, there is a need to accurately dispense small volumes of liquid. For example, many procedures now utilize multi-well plates to organize and hold various liquids. For instance, in the field of drug discovery, multi-well plates are often employed to hold various chemicals, reagents, or other solutions. To introduce and withdraw the various liquids into and from the wells of such plates, a variety of dispensing devices and systems have been developed. However, as the wells of such plates become smaller in size, the design of existing dispensing devices needs to be reconsidered. For example, some multi-well plates now include wells that hold volumes of about 200 nanoliters or less. Existing dispensing devices are generally ill- suited for dispensing such small volumes in an accurate and efficient manner.

When attempting to dispense such small volumes, a number of challenges are presented. For example, with many existing dispensing devices, such as syringes or syringe pumps, the introduction of liquids into such devices can often also introduce gas bubbles.

Since gases are generally compressible, when the liquid is forced out of such devices, the gas tends to compress. In this manner, the accuracy of such dispensing devices is compromised.

Another challenge relates to the expulsion of the liquid from the distal tip. Because of surface tension forces, the liquid expelled from such dispensing devices tends to adhere to the distal end. This problem is increased as the volume being dispensed decreases. Hence, some have proposed contacting the droplet with a body of liquid or other surface to cause the droplet to adhere to the contacted liquid or surface. However, such a solution may be undesirable in certain circumstances because it may lead to contamination issues. Hence, this invention is related to dispensing devices and methods for accurately dispensing small liquid droplets. The dispensing devices and methods of the invention may be employed to dispense the liquid droplets without contacting a body of liquid or other contact surface. SUMMARY OF THE INVENTION

In one embodiment, a liquid dispensing device is provided and comprises a tubular body having a proximal end, a distal end, and a lumen extending between the proximal and the distal end to form an opening in the distal end. The lumen has a proximal section, a center section, and a distal section. Further, the lumen tapers along the distal section from the center section to the distal end. A plunger is also provided that is reciprocative within the lumen between a retracted position and a fully extended position. The plunger comprises a plunger body having a proximal end, a distal end, a plunger member and a tapered distal section that tapers from the plunger member to the distal end. The plunger member has a cross-sectional dimension that matches a cross-sectional dimension of the center section of the lumen to create a vacuum in the lumen when the plunger is retracted. Further, the tapered distal section of the plunger mates with or closely approximates the shape of the tapered distal section of the lumen when the plunger is in the fully extended position.

In this way, zero or near zero dead volume exists in the distal section of the plunger when the plunger is moved to the fully extended position. Hence, when aspirating a liquid, essentially no gases will initially be present in the lumen. In this manner, the lumen may be filled with liquid without any substantial gas bubbles. As such, the plunger may be rapidly translated or accelerated through the lumen to dispense the liquid without compressing any gas within the lumen. Further, because of the reduction in cross-sectional area of the lumen, as the plunger is moved through the lumen, the fluid is accelerated. In this way, when movement of the plunger is stopped, essentially no droplets or built-up liquid remains attached to the distal end. In this manner, the liquid may be dispensed in a non-contact manner. Hence, the dispensing device is configured to accurately dispense a known volume of liquid during each dispensing. In one aspect, the distal section of the plunger has an angle of taper. For example, the angle of taper may be about 2 degrees or greater, more preferably in the range of about 5 degrees to about 25 degrees. The taper may be formed from a linear surface, a curved surface, or the like. The length of the tapered section of the lumen and the size of the opening at the distal end may be varied depending on the angle of taper. The diameter of the center section may be varied depending on the volume to be dispensed. Further, the size of the exit opening may be varied depending on the desired droplet size. For example, when dispensing a liquid, such as water, the size of the exit opening may be about half the size of the desired diameter of the liquid droplet.

In one aspect, the exterior surface of the distal end of the tubular body may have a hydrophobic material, such as a silicon based coating or a polytetrafluoroethylene (Teflon) coating. Such a material helps to prevent the buildup of liquid at the distal end so that the liquid will cleanly eject from the exit opening. Further, the distal end may have a sharpened or pointed tip to reduce the surface area available at the distal end for liquid buildup so that the liquid may cleanly eject.

Conveniently, multiple dispensing devices may be included as part of a dispensing system that includes a rack to hold the dispensing devices in a vertical orientation. A header may be coupled to the proximal ends of the plungers to reciprocate the plungers in unison. In one aspect, the rack may be coupled to a base member. Also, a dispensing motor may be provided to move the header in a reciprocating pattern. The base member may be employed to hold a multi-well plate or other device having multiple wells. The multi-well plate may be moved relative to the dispensing devices simply by raising and lowering the multi-well plate relative to the base member or vice versa. Conveniently, a positioning motor may be provided to move the multi-well plate vertically with respect to the base member. Alternatively, a robot may be employed to move the multi-well plate. Further, a controller may be coupled to the dispensing motor and the positioning motor to control both dispensing and placement of the dispensing devices relative to the wells. In one aspect, the rack may be configured to hold the dispensing devices in a linear array. In this manner, a column or row of wells in a multi-well plate may be filled simultaneously.

The invention further provides an exemplary method for dispensing a liquid. According to the method, a dispensing device is provided that comprises a tubular body having a proximal end, a distal end, and a lumen that tapers at the distal end. A plunger is reciprocative within the tubular body between a retracted position and a fully extended position. The plunger comprises a plunger body having a proximal end, a distal end, and a plunger member. The plunger body is tapered from the plunger member to the distal end. With such a configuration, the distal end of the tubular body is placed into a liquid, and the plunger is retracted within the tubular body to draw the liquid into the lumen. When filled with liquid, essentially no gas bubbles will exist in the lumen. The plunger is rapidly accelerated within the lumen to dispense the liquid within the lumen. Due to the reduction in cross-section of the lumen, the liquid is accelerated as the plunger is moved within the lumen. In this way, the dispensing device may be spaced apart from a body of liquid or other location that is to receive the liquid, with the liquid being expelled from the distal end before contacting the liquid or other contact surface. In this manner, the chances for contamination are significantly reduced or eliminated. Moreover, because essentially no gases are present in the lumen, the plunger may be rapidly translated to dispense the liquid without compressing any gases. Hence, the method provides a way to accurately dispense known volumes of liquid when rapidly accelerating the plunger. In turn, rapid acceleration of the plunger, in combination with the reduction in cross-sectional area of the lumen, ensures that essentially no droplets or built-up liquid will remain attached to the distal end when translation of the plunger is stopped.

In one aspect, the droplet has a volume down to about 50 nl, and for many applications may be in the range of about 100 nl to about 5 μl, although larger volumes are possible. In another aspect, the plunger and the lumen are provided with an angle of taper. For example, the taper may be greater than about 2 degrees, and in some cases in the range from about 5° to about 25° to accelerate the liquid as the plunger is moved to the fully extended position.

BRIEF DESCRIPTION OF THE DRAWINGS

Fig. 1 is a side view of one embodiment of a dispensing device according to the invention.

Fig. 2 is a more detailed view of a center section and a distal section of the dispensing device of Fig. 1. Fig. 2A is a cross-sectional end view of the dispensing device of Fig. 2 taken along lines A-A.

Fig. 3 illustrates the dispensing device of Fig. 2 with a plunger being moved to a fully extended position according to the invention.

Fig. 3A is a cross-sectional end view of the dispensing device of Fig. 3 taken along lines A-A. Fig. 3B is a cross-sectional end view of the dispensing device of Fig. 3 taken along lines B-B.

Fig. 4 illustrates the distal end of the dispensing device of Fig. 3 when dispensing a droplet of liquid into a well according to the invention. Fig. 5A is a perspective view of a rack that may be employed to hold multiple dispensing devices according to the invention.

Fig. 5B is a front view of the rack of Fig. 5A.

Fig. 6A is a perspective view of a dispensing system employing the rack of Fig. 5 according to the invention. Fig. 6B is a front view of the dispensing system of Fig. 6A.

Fig. 7 illustrates an alternative configuration of a distal end of a dispensing device according to the invention.

DESCRIPTION OF THE SPECIFIC EMBODIMENTS The invention provides exemplary noncontact droplet dispensing devices and methods for their use. The dispensing devices of the invention are configured such that little or no gases are present prior to aspiration of any liquids. In this way, the devices may be filled essentially only with liquid. More specifically, the dispensing devices of the invention are constructed to have zero or near zero dead volume when ready to be filled. Hence, with the devices of the invention, a precise amount of liquid may be metered regardless of how fast the devices are operated.

The dispensing devices of the invention are also configured to accelerate the liquid during dispensing so that the liquid will not adhere to the distal end when dispensing is stopped. Hence, a precise amount of liquid may be dispensed in a noncontact manner. Such a technique is particularly advantageous in that liquids may be dispensed without an increased risk of contamination.

The dispensing devices of the invention may be configured to dispense liquid droplets having volumes down to about 50 nl, and for many applications within in the range from about 100 nl to about 5 μl. Of course, larger volumes may also be dispensed. Dispensing devices of the invention may be utilized to dispense a wide variety of noncompressible fluids, including buffer solutions, reagents, and various chemicals, as well as cells in solution, small particles and the like.

When dispensing liquids, the exiting liquid changes into the form of discrete droplets, rather than remaining as a stream of liquid. In this way, a certain number of droplets of known volume may be ejected to dispense a known volume of liquid. The size of the liquid droplets may be controlled based on the size of the exit opening. For liquids, the size of the exit opening may be about half the size of the diameter of the ejected droplet. Using conventional machining techniques, the exit opening may be produced having a diameter down to about 200 microns so that liquid droplets down to about 50 nl may be produced. In some cases, other techniques may be used to form smaller openings such that even smaller liquid droplets may be produced. For example, the exit opening may be formed from a ceramic capillary, a sapphire orifice, or the like.

To further assist in ensuring that discrete droplets of a known volume are dispensed, the outer surface of the distal end may include a hydrophobic material. The hydrophobic material may be a coating, or the distal end may be constructed of a hydrophobic material. Such materials include, for example, silicone, Teflon, and the like. The coating extends to the inner lumen and prevent liquids, such a small liquid droplets, from creeping along the outer surface and accumulating at the distal end during use. By preventing such liquid build-up, the liquid is more cleanly ejected from the distal end. Optionally, the distal tip may include a pointed or sharpened edge to minimize the surface area at the distal tip. In this way, liquid buildup may be prevented to ensure that the liquid is cleanly ejected.

In one aspect, the liquids are dispensed by moving a plunger through a lumen. The lumen has a reduction in cross-sectional area to accelerate the liquids as they are forced from the lumen. Further, the plunger is preferably rapidly translated or accelerated through the lumen so that when translation is stopped, no droplets will remain on the distal end. As previously described, the devices are also configured so that little or no gases will be present in the lumen. Hence, when the plunger is rapidly translated, no gases will be compressed, thereby ensuring accurate dispensing.

To fill the lumen, the distal end may simply be placed into a liquid and the plunger slowly retracted to draw a metered amount of liquid into the lumen. A variety of techniques may be employed to control translation of the plungers so that a metered amount of liquid may be dispensed. For example, a computer controlled motion control system may be employed to monitor the amount of movement. As another example, mechanical stops may be employed. As still another example, the device may be visually marked to indicate when a certain amount of liquid has been metered. Referring now to Fig. 1, one embodiment of a dispensing device 10 will be described. Device 10 comprises a tubular body 12 and a plunger 14 that is reciprocative within tubular body 12. Tubular body 12 has a proximal end 16, a distal end 18, and a lumen 20 (shown in phantom line) that extends between proximal and 16 and distal end 18. As lumen 20 terminates at distal end 18, a distal opening 22 is formed. Lumen 20 has a proximal section 24, a center section 26, and a distal section 28. As shown, distal section 28 tapers from center section 26 to distal opening 22.

Plunger 14 comprises a plunger body 30 that has a proximal end 32, a distal end 34, a plunger member 36, and a tapered distal section 38 that tapers from plunger member 36 to distal end 34. Plunger 14 is reciprocative within lumen 20 to essentially any location within lumen 20. When fully inserted into lumen 20, plunger 14 is in a fully extended position (see Fig. 3). Plunger 14 may be retracted any length from the fully extended position. The amount of retraction will determine the volume of liquid that is drawn into lumen 20 between tapered distal section 38 and distal opening 22. Conveniently, a motion control sensor and an associated controller may be employed to meter a certain volume of liquid. Alternatively, markings may be provided on tubular body 12 and/or plunger 14 to indicate the volume of liquid that has been metered into lumen 20 upon retraction of plunger 14. As another alternative, one or more mechanical stops may be provided to stop retraction of plunger 14 relative to tubular body 12. In this way, when retraction of plunger 14 is prevented, a known volume of liquid will have been metered. Referring also now to Figs. 2 and 2A, construction of dispensing device 10 will be described in greater detail. Plunger member 36 is constructed so that it engages the walls of lumen 20. In this way, when plunger 14 is retracted within tubular body 12, a vacuum is created within lumen 20 to draw liquids into lumen 20. Further, when plunger 14 is extended, the seal between plunger member 36 and the walls of lumen 20 causes the liquid within lumen 20 to be forced out opening 22. Tapered distal section 38 of plunger 14 and distal section 28 of lumen 20 both have the same constant angle of taper. Further, tapered distal section 38 and distal section 28 have approximately the same length. The angle of taper of tapered distal section 38 and distal section 28 may be in the range from about 5° to about 25°. However, other angles may be used. For example, the angle may be down to about 2 degrees, and up to about 45 degrees or greater. The angle of taper of distal section 28 reduces the cross-sectional area and causes the liquid to accelerate as it is being forced out of opening 22. In this way, the liquid will be ejected from tubular body 12 as it leaves opening 22. In this manner, liquids may be dispensed from device 10 without requiring the liquid to be contacted with a surface in order to transfer the liquid from distal end 18. Although shown as a constant angle of taper, it will be appreciated that the cross sectional area may be reduced using other surface geometry's, including, for example, non-linear surfaces, curved surfaces, and the like.

As shown in Figs. 3 and 3B, when plunger 14 is moved to the fully extended position, tapered distal section 38 completely fills distal section 28. In this way, no dead volume exists within dispensing device 10. In this manner, when plunger 14 is moved to the fully extended position, substantially all of the liquid within lumen 20 is dispensed. Further, because of the seal provided between plunger member 36 and lumen 20, when distal end 18 is placed into a body of liquid and plunger 14 is retracted, the liquid is drawn into lumen 12. Another advantage of constructing device 10 to have zero dead volume is that no gases exist in lumen 20 when plunger 14 is in the fully extended position. Hence, no gases will be present in lumen 20 when aspirating liquids into lumen 20. In this manner, no gases exist that may otherwise be compressed when dispensing liquids so that accurate dispensing may be ensured. Although plunger body 30 is shown to substantially fill the length of lumen 20, it will be appreciated that proximal to plunger member 36, plunger body 30 may be of essentially any size or configuration.

The size of lumen 22 may be varied depending on the desired volume that is to be dispensed. Opening 22 may be sized according to the desired droplet size. For example, the diameter for opening 22 may be one half the size as the desired droplet size. Hence, for a 50 nl droplet having a diameter of 457 microns, the exit opening may be about 228 microns. Conveniently, device 10 may be used to dispense volumes of liquid that are down to about 50 nl, and for some applications may be in the range from about 100 nl to about 5 μl, although larger volumes are possible. Conventional machining techniques may be used to form the central lumen and the exit opening. For sizes less than about 200 microns, alternative techniques may be used as is known in the art. In this way, volumes of less than about 50 nl may be produced. Tubular body 12 may be constructed from essentially any rigid material, such as metals, plastics, composites, and the like. In some cases, dispensing device may be employed to dispense corrosive materials. In such cases, materials such as glass may be employed. Plunger member 36 may be constructed of a variety of materials, including PTFE. Conveniently, plunger member 36 may be coupled to plunger body 30 by a barb, glue, a screw, a rivet, or the like. Tapered distal section 38 may then be coupled on top of plunger member 36. Further, the exterior surface of distal end 18 may include a hydrophobic material to prevent liquid buildup at the distal tip.

To operate dispensing device 10, plunger 14 is moved to the fully extended position as shown in Fig. 3. Distal end 18 is then placed into a reservoir of liquid and plunger 14 is slowly retracted to aspirate liquid into device 10. Dispensing device 10 is then moved over a location that is to receive the liquid. Plunger 14 is then accelerated a certain distance to dispense a certain volume of liquid from opening 22. For example, as shown in Fig. 4, dispensing device 10 may be placed over a well 40 of a multi-well plate 42. As the plunger is moved within lumen 22 a volume of liquid 44 is dispensed from distal end 18 as shown. One particular advantage of utilizing dispensing device 10 is that distal end 18 may be positioned above any liquid within plate 42 when dispensing a liquid. In this way, liquid 44 may be ejected in a noncontact manner into liquid 46 within well 40, thereby reducing the chances of contaminating device 10.

Multiple dispensing devices that are constructed in a manner similar to dispensing device 10 may be organized together such that multiple wells may receive a volume of liquid in unison. For example, shown in Figs. 6A and 6B is a dispensing system 50 which utilizes multiple dispensing devices 10 (only one being shown for convenience of illustration) to dispense multiple volumes of liquid in unison.

Dispensing system 50 comprises a base member 52 to which a rack 54 is coupled. Although not shown, base member 52 may include one or more attachment mechanisms for receiving a multi-well plate that is positioned below rack 54. For example, such mechanisms for holding multi-well plates are described in copending U.S. Application Serial No. 09/260,368, filed March 1, 1999 the complete disclosure of which is herein incorporated by reference. Alternatively, a mechanical arm, robot, or the like may be employed to position the plate relative to the dispersing devices. For example, one such system that may be employed is described in U.S. Patent Application Serial No. 08/937,139, filed September 24, 1997, the complete disclosure of which is herein incorporated by reference.

As best shown in Figs. 5A and 5B, rack 54 includes a bottom member 56 and a top member 58. Bottom member 56 includes a plurality of holes 60, and top member 58 includes a plurality of holes 62. Holes 60 each include a ledge 61 upon which one of the dispensing devices rests when inserted into one of the holes. In this way, ledge 61 serves to fix the vertical position of dispensing device 10 while hole 60 is used to locate the lateral position of the dispensing device. As shown, distal end 18 of device 10 extends below bottom member 56. One of the holes 62 in top member 58 is aligned with a corresponding hole 60 in bottom member 56 and is sized such that plunger body 30 may slide therethrough. In this way, plunger 14 may be reciprocated back and forth within plunger body 12 in a manner similar to that previously described. The number of holes in bottom member 56 and top member 58 may be varied depending on the particular application. As shown, twelve holes are provided for holding twelve dispensing devices. In this way, rack 54 may be particularly useful with multi-well plates having a 96 well format, or any multiple thereof, e.g., 364, 864, and 1536 well plates. However, it will be appreciated that other arrangements may be provided for other configurations of multi-well plates as is known in the art.

Positioned above top member 58 is a header 64 (see Figs. 6A and 6B). Header 64 includes a plurality of grooves 66 which are each adapted to receive proximal end 32 of plunger 14. One or more blocks 68 may then be employed to secure proximal end 32 of plunger body 30 to header 64. As shown in Figs. 6A and 6B, header 64 is spaced apart from top member 58 to permit header 64 to be moved up and down relative to rack 54. In this way, plungers 14 may be reciprocated back and forth within their respective tubular body 12 to draw liquids into dispensing devices 10 and dispense liquids from dispensing devices 10 in a manner similar to that previously described. Since header 64 is coupled to each dispensing device, liquids will be withdrawn and expelled in unison. Rack 54 is coupled to base member 52 by multiple screws 70. In this way, rack 54 is non-movably mounted relative to base member 52. Header 64 is screwed to a platform 72 by screws 74. Further, base member 52 includes a linear slide 76 to which platform 72 is coupled. In this way, platform 72 may be moved up and down on linear slide 76. Conveniently, a dispensing motor 78 is provided to move platform 72 along linear slide 76. In this way, motor 78 may be operated to cause header 64 to be moved downward, thereby dispensing a volume of liquid from each dispensing device 10. Similarly, dispensing motor 78 may be operated to raise header 64 when drawing liquids into each dispensing device 10. Although not shown, a controller may be conveniently coupled to motor 78. In this way, operation of the dispensing devices and movement of a multi-well plate relative to the dispensing devices may be controlled. In one aspect, a motion control system with an optical encoder may be employed with motor 78 to control the amount of translation of header 64. The motion control system measures the amount of rotation of the shaft of motor 78. The controller may be programmed to use this information to determine the amount of translation of header 64. The controller may further be programmed so that it will cause dispensing devices 10 to dispense known volumes of liquid.

To help ensure that discrete liquid droplets are formed, the distal tip may have a pointed or sharpened edge. Such a configuration is illustrated in Fig. 7. In Fig. 7, distal end 18' has a pointed edge 19 at opening 22' to reduce the surface area at the distal tip, thereby preventing liquid buildup at this location. Optionally, the exterior surface of distal end 18' may have a hydrophobic material that extends to lumen 20' to further prevent liquid buildup.

The invention has now been described in detail for purposes of clarity of understanding. However, it will be appreciated that certain changes and modifications may be practiced within the scope of the appended claims.

Claims

WHAT IS CLAIMED IS:

1. A liquid dispensing device, comprising: a tubular body having a proximal end, a distal end, and a lumen extending between the proximal end and the distal end to form an opening at the distal end, wherein the lumen has a proximal section, a center section, and a distal section, and wherein the lumen tapers along the distal section from the center section to the distal end; and a plunger movable within the lumen between a retracted position and a fully extended position, the plunger comprising a plunger body having a proximal end, a distal end, a plunger member and a tapered distal section that tapers from the plunger member to the distal end; wherein the plunger member has a cross sectional dimension that substantially matches a cross sectional dimension of the center section of the lumen to create a vacuum in the lumen when the plunger is retracted, and wherein the tapered distal section of the plunger substantially mates with the tapered distal section of the lumen when the plunger is in the fully extended position such that essentially zero dead volume exists in the distal section of the plunger when the plunger is moved to the fully extended position.

2. A device as in claim 1, wherein the distal end of the tubular body has a pointed tip.

3. A device as in claim 1, wherein an exterior surface of the distal end of the tubular body includes a hydrophobic material.

4. A device as in claim 1, wherein the distal section of the plunger has a constant angle of taper.

5. A device as in claim 4, wherein the angle of taper is at least about 2 degrees.

6. A device as in claim 5, wherein the angle of taper is in the range from about 5 degrees to about 25 degrees.

7. A device as in claim 1, wherein the opening has a diameter of about 200 microns or greater.

8. A method for dispensing a liquid, the method comprising: providing a dispensing device that comprises a tubular body having a proximal end, a distal end, and a lumen that tapers at the distal end, and a plunger that is movable within the tubular body between a retracted position and a fully extended position, wherein the plunger comprises a plunger body having a proximal end, a distal end, and a plunger member, wherein the plunger is tapered from the plunger member to the distal end so that essentially zero dead volume exists within the lumen at the distal end when the plunger is in the fully extended position; placing the distal end of the tubular body into a liquid when the plunger is in the fully extended position; retracting the plunger within the tubular body to draw the liquid into the lumen in the absence of essentially any gas bubbles; and moving the plunger within the lumen to dispense a certain known volume of the liquid from the lumen.

9. A method as in claim 8, wherein the liquid is in the form of at least one droplet, and wherein the droplet has a volume of about 50 nl or greater.

10. A method as in claim 9, wherein the droplet has a volume in the range from about 100 nl to about 5 μl.

11. A method as in claim 8, further comprising dispensing the volume of liquid above a body of liquid such that substantially all of the volume of liquid leaves the distal end of the tubular body before contacting the body of liquid.

12. A method as in claim 8, further comprising providing the plunger and the lumen with a constant angle of taper.

13. A method as in claim 12, wherein the angle of taper is in the range from about 5 degrees to about 25 degrees to accelerate the liquid as the plunger is moved within the lumen.

14. A method as in claim 8, further comprising providing multiple dispensing devices and operating the dispensing devices to dispense a volume of liquid into each well of an array of wells.

15. A method as in claim 8, further comprising repelling liquid from the distal end of the tubular body with a hydrophobic material.

16. A liquid dispensing system, comprising: a plurality of dispensing devices, wherein each device comprises a tubular body having a proximal end, a distal end, and a lumen extending between the proximal end and the distal end to form an opening at the distal end, wherein the lumen has a proximal section, a center section, and a distal section, and wherein the lumen tapers along the distal section from the center section to the distal end, and a plunger movable within the lumen between a retracted position and a fully extended position, the plunger comprising a plunger body having a proximal end, a distal end, a plunger member and a tapered distal section that tapers from the plunger member to the distal end, wherein the plunger member has a cross sectional dimension that substantially matches a cross sectional dimension of the center section of the lumen to create a vacuum in the lumen when the plunger is retracted, and wherein the tapered distal section of the plunger substantially mates with the tapered distal section of the lumen when the plunger is in the fully extended position such that essentially zero dead volume exists in the distal section of the plunger when the plunger is moved to the fully extended position; a rack to hold the dispensing devices in a vertical orientation; and a header coupled to the proximal ends of the plungers to reciprocate the plungers in unison.

17. A system as in claim 16, further comprising a base member to which the rack is coupled.

18. A system as in claim 17, further comprising a dispensing motor to move the header in a reciprocating pattern.

19. A system as in claim 18, further comprising a controller coupled to the dispensing motor to control dispensing of the dispensing devices.

20. A system as in claim 17, wherein the rack is configured to hold the dispensing devices in a linear array.

21. A system as in claim 16, wherein the distal end of each tubular body has a pointed tip.

22. A system as in claim 16, wherein an exterior surface of the distal end of each tubular body includes a hydrophobic material.