The invention relates to clinical and research laboratory products, and in particular, laboratory reservoir kits and liners for liquid samples and reagents.
Automated and semi-automated liquid handling systems often include pipetting heads for either 96 or 384 disposable pipette tips. A 96 pipetting head has an array of 8 by 12 tip mounting shafts with the centerline spacing between the adjacent shafts being 9 mm. A 384 pipetting head has an array of 16 by 24 mounting shafts with the centerline spacing between the adjacent shafts being 4.5 mm. The spacing is set by ANSI/SLAS Microplate standards (formerly known as SBS format). The American National Standards Institute/Society for Laboratory Automation and Screening (ANSI/SLAS) has adopted standardized dimensions for microplates:
ANSI/SLAS 1-2004: Microplates—Footprint Dimensions
ANSI/SLAS 2-2004: Microplates—Height Dimensions
ANSI/SLAS 3-2004: Microplates—Bottom Outside Flange Dimensions
ANSI/SLAS 4-2004: Microplates—Well Positions
ANSI/SLAS 6-2012: Microplates—Well Bottom Elevation
These standards have been developed to facilitate the use of automated liquid handling equipment with plastic consumable products from different manufacturers. Automated or semi-automated liquid handling systems having a matrix of fewer mounting shafts such as a 24 pipetting head or more mounting shafts such as a 1536 pipetting head are also used in the field, although the most common are the 96 and 384 heads. These automated or semi-automated liquid handling systems are typically designed with platforms located underneath the pipetting head, which contain one or more nesting locations for microplates, racks of microtubes or reservoirs for holding samples or reagents. In the art, microplates are sometimes referred to as well plates, and microtubes are sometimes referred to a sample tubes. The nests are sized in accordance with the outside dimensions for microplates for the SBS standard (now ANSI/SLAS) in order to align each of the 96 or 384 pipette tips with the center points of the respective wells in the microplate on the platform.
As mentioned, laboratory reservoirs for holding samples or reagents can also be placed on the platform in the nest. Reservoirs typically have a common basin instead of individual wells and are known to have either a flat bottom or a patterned bottom in order to reduce liquid hang-up. It is also known to use a disposable reservoir liner to avoid the need to clean and/or sterilize reservoirs before starting a new procedure. Many reservoirs and liners are made of polystyrene which is naturally hydrophobic. The hydrophobic surface causes liquid to bead up during final aspiration which is generally thought to facilitate liquid pick up and reduce the residual volume.
One problem that has been found to occur with the use of disposable reservoir liners on automated or semi-automated 96 or 384 head systems is that one or more of the mounted pipette tips may engage the surface of the liner bottom when the pipette head is lowered. A pipette tip engaged with the surface of the liner bottom can unfortunately create a vacuum within the tip when the head aspirates and can draw the liner tight against the orifice at the bottom of the tip. The vacuum within the tip increases as aspiration continues and the orifice is eventually closed off. This situation can lead to inaccurate pipetting, but can also lead to contamination of the pipetting head which is a serious issue. When a pipette tip that has vacuum engaged the liner bottom releases, the reagent or sample, now driven by a significant pressure difference, often sprays upward beyond the pipette tip and the mounting shaft into the respective piston cylinder. If this occurs, it may be necessary to disassemble, clean and sterilize the entire pipette head.
It is often desirable to reduce residual volume or liquid hang-up in the liner when attempting to fully aspirate all the liquid from the liner. To this end, pipette tips are typically lowered as close to the bottom wall of the liner without contacting the bottom wall as reasonably possible in order to reduce the residual volume of liquid that cannot be aspirated. In multi-channel pipetting systems, even automated multi-channel systems where the height of the pipetting head can be controlled precisely, one or more pipette tip orifices can become misaligned with the other tip orifices because, for example, a pipette tip is mismounted or deformed. Tip misalignment can lead to the tip engaging the bottom wall and forming a vacuum. Even if all of the pipette tips are aligned properly, it is possible that the portions of the bottom wall in the liner corresponding to the locations of the pipette tips are not precisely aligned on a plane level with the pipette tip orifices. This sort of unevenness can occur, e.g., when a liner is not fully seated in a reservoir base or is slightly deformed, and can also lead to one or more pipette tips engaging the bottom wall when trying to aspirate the final volume from the container.
The invention relates primarily to the placement of anti-vacuum channels on the bottom wall of a disposable reservoir liner used in laboratory reservoir kits.
In one aspect, the invention is directed to features of the disposable liner. In another aspect, the invention is directed to features of the kits including a disposable liner that is held within a reusable reservoir base. The disposable liner and the reusable reservoir base are designed so that the liner fits into the base and provides stable support for the liner with the bottom wall of the liner sitting on the reservoir base. The disposable liner is especially configured to prevent pipette tips from vacuum engaging the bottom wall of the liner basin. To do this, an upper surface of the bottom wall of the liner basin includes multiple anti-vacuum channels that face upwardly towards the volume in which the liquid sample or liquid reagent is held. The bottom wall has a generally rectangular shape configured to enable a matrix of pipette tips to aspirate liquid from the volume in the liner basin. The purpose of the anti-vacuum channels is to provide a fluid accessible void underneath the orifice of the pipette tip even when the tip is pressed against the upper surface of the bottom wall of the liner. It has been found that using the anti-vacuum channels and keeping the bottom wall of the liner straight or flat also generally reduces the residual volume of liquid remaining in the liner when it is attempted to fully aspirate liquid from the liner with a 96 or 384 tip pipetting head, compared to liners without the anti-vacuum channels.
In one embodiment, the liners are made of molded polystyrene which is generally considered to be hydrophobic as discussed above. However, it has been found that corona treating the polystyrene liners with the anti-vacuum channels, in order to render the bottom wall more hydrophilic, further reduces the residual volume remaining in the liner when it is attempted to fully aspirate liquid with a 96 or 384 tip pipetting head. It is preferred that the corona treatment be sufficient to render the measured surface tension of the bottom wall of the liner greater than or equal to about 72 dynes, which is the surface tension for natural water. In another embodiment, the liner is made from molded polypropylene. This embodiment is particularly useful for applications where chemical resistance is more important. Polystyrene is stiffer than polypropylene, however, which is often beneficial in the laboratory.
Desirably, the reusable reservoir base has outside flange dimensions compatible with nests configured to hold SBS-formatted well plates and reservoirs (i.e. ANSI/SLAS 3-2004: Microplates—Bottom Outside Flange Dimensions). If the reservoir is made to be used with a 96 pipetting head, the disposable liner contains a matrix of 96 groupings of anti-vacuum channels with a center point for each grouping spaced 9 mm from the center point of adjacent groupings, consistent with SBS (ANSI/SLAS) formats. If the disposable liner is designed to be used with a 384 pipetting head, the liner desirably contains a matrix of 384 groupings of anti-vacuum channels with the center point for each grouping spaced 4.5 mm from the center point of adjacent groupings, again consistent with SBS (ANSI/SLAS) formats. The disposable liner can also be made with more or less groupings depending on the intended use of the liner; however, in each case the groupings should be centered at the center point at which it is expected that the pipette tips on the pipetting head will be located. In some embodiments, the liner contains a matrix of 96 groupings of anti-vacuum channels with adjacent center points spaced 9 mm apart, as well as a matrix of 384 groupings of anti-vacuum channels having center points spaced apart 4.5 mm. In this manner, the liner is configured to be used both with a 96 pipetting head or a 384 pipetting head.
The groupings of the anti-vacuum channels can take on various configurations in accordance with the invention. The goal is to provide a channel configuration that will provide a fluid accessible void underneath the orifice of the respective pipette tip even if the pipette tip is somewhat off center, which can occur in an automated pipetting system, for example, when a pipette tip is not mounted straight or the tip is slightly deformed. One desired grouping configuration includes a first pair of perpendicular and intersecting channels with the intersection of the channels defining a center point for the grouping, and a second pair of perpendicular channels rotated 45° from the first pair where the second pair of channels are aligned to intersect at the center point but are interrupted in the vicinity of the center point. It is desirable that the channels have a constant width (except for necessary draft angles required for reliable molding) and a constant depth, and that the width of the channels is selected so that the distance across the intersection is less than the outside orifice diameter of the smallest sized pipette tips that will likely be used with that liner. For example, if a 12.5 μl pipette tip has an outside orifice diameter of 0.61 mm, then the width of the channels should be less than or equal to about 0.50 mm to ensure that the distal end of the pipette tip cannot fit into the channels at the intersection. For a 384 application, the desired channel width using the above described grouping configuration is 0.50 mm+/−0.10 mm. For a 96 head application, the desired width is 0.50 mm+/−0.10 mm as well. The grouping may also have other channels located away from the center point towards the perimeter of the grouping in order to provide a larger region covered by anti-vacuum voids in the event that the pipette tip orifice is off center because of how the tip is mounted or constructed, or in the event it is used with a hand-held pipette. Providing a bigger area of coverage by the channels over the bottom wall, also creates a higher likelihood that peripheral liquid will be drawn into the channels of the grouping when liquid is being drawn by a pipette tip, which in turn tends to reduce the dead volume or residual volume, other factors being equal. In one embodiment, a circular channel intersects each of the first and second pair of channels.
In some embodiments, additional channels are located between adjacent groupings to fluid dynamically connect adjacent groupings of anti-vacuum channels. In other embodiments, such as those shown in the Figures, no channels extend between adjacent groupings of anti-vacuum channels.
In the disclosed embodiments, the bottom wall of the disposable liner is otherwise flat, and the groupings of anti-vacuum channels are located at the center point for either a 96 pipetting head or a 384 pipetting head configuration or both. The disposable liner desirably is made of a transparent plastic material, such as clear molded polystyrene or polypropylene as mentioned above, and has a shape that closely follows the contour of the basin of the reusable base, in part to facilitate viewing of liquid volume graduation marks on the side walls of the base. Also desirably, the side walls of the reusable reservoir base have distinct liquid volume graduation marks on the surface of the side wall forming a portion of the basin. These liquid volume graduation marks are calibrated to measure a volume of liquid sample contained in the transparent disposable liner and are observable when the disposable liner is set in place within the reusable base. Further, one or more sides of the reusable base may contain one or more viewing windows so that a user can easily view the amount of liquid contained in the disposable liner. The viewing window can be a narrow window or it can be relatively wide as long as the base still has enough support for the disposable liner.
In some embodiments, the laboratory reservoir kit includes a lid to cover liquid contained in a liner placed within the reusable base. It is preferred that the lid be transparent to facilitate viewing of contained liquid or reagent when the lid is latched in place. A gasket is provided optionally on the lid, and a locking mechanism on the reservoir base is used to lock the lid in place and secure the liner between the gasket on the lid and the base to seal the contained liquid. The lid is also preferably configured to facilitate stacking of kits with the lid attached. The locking mechanism can also be used to hold the liner in place during use when the lid is removed.
Advantageously, the use of anti-vacuum channels on the bottom wall of the disposable liner provides a fluid accessible void even if a pipette tip engages the bottom wall of the liner. This means that the pipette tip will not cause a vacuum within the tip while the pipette is aspirating. It also means that, as a practical matter, tips can be placed closer to the bottom wall of the liner and/or engage the bottom wall of the liner when doing so without the anti-vacuum feature would more likely cause vacuum engagement. In turn, with the ability to move the pipette tip orifice very close to or into engagement with the bottom wall of the liner, the pipetting system is able to withdraw liquid from the container with significantly less residual volume. In addition, without being limited to a theory of operation, it is believed that the hydrophilic nature of the corona treated surface causes liquid on the surface to self level, while the channels provide surface tension features that accumulate liquid on the surface. The result is that the liquid draws naturally from the surface between the groupings of channels and forms segregated pools in and above the groupings of channels, as the liquid level is drawn down. This phenomenon effectively lowers the minimum working volume for reliable pipetting. This is particularly important for expensive, scarce or small samples or reagents.
Other features and advantages of the invention may be apparent to those skilled in the art upon reviewing the drawings and the following description thereof.
The reservoir base 12 contains a basin 18 into which the disposable liner 14 is placed. The contour of the disposable liner 14 closely follows the shape and contour of the basin 18 of the reusable base 12. Outer side walls 22 and end walls 20 on the reusable base 12 provide support for the reservoir base 12 and its basin 18 on flat surfaces such as a laboratory bench top. While the reservoir base 12 can be made of a variety of materials, it is preferred that the base 12 be made of relatively rigid injection molded plastic having an opaque color such as white ABS. It is preferred that the surface of the basin 18 have a satin finish. On the other hand, as mentioned above, it is preferred that the disposable liner 14 be made of clear transparent plastic and have a polished surface (at least the sidewalls and peripheral flange), such as clear injection molded polystyrene or polypropylene having a thickness of approximately 0.51 mm. The polished or shiny surface of the clear liner, in contrast to the satin finish on the opaque color basin 18 in the base 12, renders the transparent liner 14 more conspicuous to laboratory workers trying to determine whether or not it is present within the reservoir base 12. Injection molding is the preferred method to manufacture the disposable liner 14 because it is desirable for the liner thickness to be constant throughout. It should be recognized, however, that other manufacturing methods and thickness specifications may be possible for both the disposable liner 14 and the reusable base 12.
When the disposable liner 14 is made of molded polystyrene or polypropylene, e.g., it is desirable to corona treat or otherwise treat the liner after molding in order to render s the plastic surface more hydrophilic, which means that small amounts of liquid remaining in the liner tend to flatten out on the surface of the bottom wall rather than bead up. However, the capillary action of the channels tends to draw the liquid into pools above the channel groupings as the liquid is drawn down. It is generally believed in the art that providing a hydrophobic surface, so that small amounts of liquid tend to bead up, would normally be the best way to reduce the amount of residual volume after pipetting from a reservoir or a reservoir liner. With the use of anti-vacuum channels as described herein, the inventors have found it advantageous to corona treat the surface rendering it more wettable and hydrophilic, thereby providing a surface on which the liquid tends to spread evenly, with the capillary action of the channels being responsible for creating pools or beads of liquid suitable for effective pipetting at the final draw down. With the anti-vacuum channels and the fluid accessible voids underneath the pipette tip orifices, even if tips are engaging the bottom surface of the liner, the hydrophilic surface facilitates more even fluid distribution available for aspiration from multiple pipette tips and less residual volume after complete aspiration of liquid from the container. As mentioned, it is desirable to treat the surface so that its surface tension is greater than or equal to 72 dynes, which is the surface tension for natural water.
The disposable liner 14 can be made of polypropylene for applications in which chemical resistance is desired. The polypropylene liner should likewise be corona treated or otherwise treated so that its surface tension is greater than or equal to the surface tension of water, 72 dynes.
The basin 18 in the reusable base 12 is rectangular and extends between the bottom of the end walls 20 and the side walls 22. The rectangular basin is compatible with the SBS format and is sized for a 384 pipetting head or a 96 pipetting head. The disposable liner 14 shown in
Referring to
Liquid volume graduation marks (62), see
Referring again to
The peripheral flange 332 of the liner 214 also includes cut outs having a shape and location corresponding to the cut outs 338 on the lid 315. The cut outs in the peripheral flange 332 of the liner 214 allow the flange of the liner to be placed flat on the top of the wall of the reusable base 312. The locking mechanisms 317 can be slid into the locking position, when the lid 315 is not in place, in order to hold the liner 214 flat in the reusable base 312. Keeping the bottom of the liner 214 flat reduces the retained volume of liquid after attempting to fully aspirate all the liquid from the liner 214 with a 96 or 384 pipetting head.
Referring now to
In this embodiment, some of the anti-vacuum channels are shared between groupings 329 for the 96 pipetting head and the groupings 429 for the 384 pipetting head.
Although not illustrated in the embodiments shown in Figures, additional channels can be optionally located between adjacent groupings to fluid dynamically connect adjacent groupings of anti-vacuum channels. Some or all of the groupings can be fluid dynamically connected directly or indirectly in this manner. The capillary action tends to even fluid distribution among the connected channels, which can in turn reduce the minimum working volume for reliable pipetting with multiple pipette tips.
As described above, the liner 314 is desirably made of a molded transparent plastic, in part so that graduation marks (not shown) on the inside surface of the sidewall of the base 314 can be read by the user, as described with respect to the embodiment disclosed in
The present invention is not limited to the exemplary embodiments described above so long as it is covered by the subject matter of the claims that follow.
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Number | Date | Country | |
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20180353955 A1 | Dec 2018 | US |
Number | Date | Country | |
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62516842 | Jun 2017 | US |