Patent Application
20220065888
The present disclosure relates to an apparatus and method for limiting pipette movement and/or rotation with respect to a support surface for placing sample containers, and, more particularly, to an apparatus and method for restricting the orientation or the movement of the pipette as predetermined by a stand for (a) limiting the insertion depth of the pipette tips into sample containers or (b) restricting unwanted movements and/or rotations of the pipette or (c) maintaining the desired alignments of the pipette tips with the sample containers.
The approaches described in this section are approaches that could be pursued, but not necessarily approaches that have been previously conceived or pursued. Therefore, unless otherwise indicated, the approaches described in this section may not be prior art to the claims in this application and are not admitted to be prior art by inclusion in this section.
In laboratory settings, a single-channel pipette and/or a multichannel pipette may be used to transfer fluids into and out of containers, often in tubes of sample rack or wells of a microplate. When aspirating from containers in certain sample processing step, one may desire to leave a defined residual volume in the containers—for example, to avoid disturbing or aspirating particles at the bottoms of the containers. Certain processing steps require consistent remaining volumes or undisturbed pellets at the bottoms of the containers. However, handheld pipette devices make this defined-level aspiration a manual, subjective process; and the process becomes particularly challenging when a multichannel pipette is used where the user has to keep the two terminal pipette tips aligned with the target wells simultaneously (the rest of the pipette tips are aligned correspondingly) as the tips are inserted into the containers, a process requiring steady and sustained control of the orientations and movements of the pipette and thus being attention-demanding. This is exacerbated in applications involving small fluid volume where there is more limited wiggle room allowed for the pipette tips. Additionally, variation in the inserting depth of a pipette tip is one of common factors for pipetting inaccuracy.
Fully-automated liquid handling robots, which can accomplish consistent defined-level aspiration, are commercially available, but they are expensive and require a different skill set for operation from the skills available to the typical laboratory operator. Consistent results for defined-level aspiration are difficult to achieve with the current manually operated single or multichannel pipettes.
U.S. Pat. No. 10,232,376 (issued on Mar. 19, 2019) describes an apparatus for limiting insertion of a pipette into a tube. While the concept of the device described, a spacer block for restricting the pipette travel beyond a predetermined limit, makes good sense, many difficulties would be encountered in actual use of the described device. First, the device has to be customized for almost every model of pipette to ensure the proper fit of the pipette heads with the holes on the top surface of the device. Second, the height of the spacer block, which correlates to the pipette tips insertion depth, cannot be adjusted once the device is made. In reality, a lab, or even a single user, may use a variety of pipettes, which may differ in size, manufacture, and model, in a variety of experimental procedures which may use a variety of pipette tip insertion depth; and also a pipette may be used with pipette tips of different length. All those may change frequently. This makes the device described in the patent less attractive or even impractical, except for an experiment with a fixed protocol and a fixed set of pipettes and pipette tips. Third, the device needs to be essentially disposable in the described ways of use. In one described way the device would be ejected along with the pipette tips for each pipette tip ejection by the ejection mechanism on the pipette, and in another described way the narrow holes on the top surface could be easily contaminated due to unintentional but difficult-to-avoid touching by the pipette tips when the tips are withdrawn out of the holes. The need for being disposable may make the device cost prohibitive. And fourth, the use of the device makes pipetting less efficient. Before mounting the pipette tips onto the multichannel pipette heads, the device has to be mounted either onto the pipette heads or over the sample tubes, which is an extra step one does not need to take in normal pipetting. Moreover, with the device mounted on the pipette heads, it is not straightforward to mount the pipette tips, because the device, a spacer block, may prevent the pipette heads travel close enough to the table surface to pick up the pipette tips, and thus another “spacer block” may be needed to raise the pipette tip rack.
The apparatus described in this disclosure aims for not only truly consistent results for defined-level aspiration in manual pipetting without the above limitations but also a less attention-demanding pipetting and more ergonomic process in general.
In an embodiment, an apparatus for limiting pipette travel with respect to a support surface, for placing sample containers is described. A stand controls the spatial positions relative to the support surface. A mechanism couples the pipette being used with the stand. The orientation and movement of the pipette is restricted to certain extent by the stand as predetermined.
For a better understanding, reference may be made to the accompanying drawings, in which:
A component or a feature that is common to more than one drawing is indicated with the same reference number in each of the drawings.
This technology comprises, the following features, in any combination.
The apparatus 100 includes bottom surface 104 on base frame 106, with which the apparatus stands on support surface 102. Optionally, the bottom surface 104 may be defined by the lowermost edges of 106, rather than being a separately provided “bottom surface” element. Also optionally, the bottom surface 104 may be contoured or otherwise configured to engage a feature of the support surface 102 as desired, such as to orient or position the apparatus 100 into a predetermined position with respect to the support surface 102.
The apparatus 100 also includes two linear slides. Linear slide rail 108 is mounted horizontally on base frame 106. Vertical pillar 110 is mounted on slide carriage 112 and is allowed to slide along slide rail 108 in horizontal direction (y direction). Linear slide rail 114 is mounted on vertical pillar 110. Horizontal bar 116 is mounted on slide carriage 118 and is allowed to slide along slide rail 114 in vertical direction (z direction). Vertical slide stop 120 is mounted on vertical pillar 110 for limiting the downward movement of slide carriage 118 or bar 116. In this configuration, the movement of arm 116 is allowed in the y and z directions within predetermined ranges but not in the x direction, and any rotations are limited. Microplate 122 is disposed on support surface 102 and is secured in position by plate holder 124 which is attached to base frame 104. After the pipette 128 is coupled with apparatus 100 through coupler 126, the movement of the pipette is restricted to the extent the linear slides allow, and the pipette tips are aligned with the target wells 130 of the microplate 122 (the row of tips and the row of target wells are parallel and any corresponding matching tip-well pair has essentially the same x direction coordinate shown in
An example sequence for pipetting with the assistance of the apparatus may include, (a) raise the horizontal bar 116 somewhat, (b) attach the pipette to the horizontal bar 116, (c) move the pipette along with horizontal bar 116 until the pipette tips are directly over the target wells for aspiration, (d) lower the pipette along with the horizontal bars 116 until vertical stop 120 is met (the horizontal bar 116 is now at the predetermined height), (e) aspirate fluid from the wells, (f) raise the pipette along with bar 116 and, slide the bar 116 along with the pipette horizontally towards the target wells for dispensing (the target wells can be on the same microplate or on another microplate), and lower the pipette along with bar 116, and (g) dispense the fluid from the pipette tips. In regular pipetting with a multichannel pipette, a user has to monitor and control the movement of the two terminal pipette tips in x, y, and z directions simultaneously. With the assistance of the device depicted schematically in
Examples of the mechanism for coupling the pipette with the stand are shown in
The frame of the stand 100 is generally thin, rather than unnecessarily thick, to permit minimally obstructed view of the microplate wells and pipette tips during pipetting.
One of ordinary skill in the art could configure the sub-assembly for the adjustment of the position/height of vertical stop 120, e.g. using a screw jack operated either manually or electrically.
As is the case for a garage door, arm 116 can be spring-loaded so that it takes less force to lift arm 116 in the upward direction.
Plate holder 124 can be integrated into base frame 106, or a separate frame that can be attached to and detached from base frame 106 as needed. Plate holder 124 can be configured to hold one or more microplates in various orientation combinations.
In certain circumstances, one may desire to “semi-permanently” fix bar 400 or matching strike plate 302 onto the pipette, using means including a less “permanent” double-sided glue strip or more “permanent” epoxy glue.
From the above description and discussion, it should be clear that the apparatus disclosed in this application overcomes or address limitations of the device described in U.S. Pat. No. 10,232,376. The pipetting may be proceeded without extra step for mounting a device to the pipette heads or over the microplate wells before each aspiration; the apparatus 100 can be reused and has no tendency to cause contamination; the vertical stop height correlating to the pipette tip insertion depth is adjustable; and it is possible to mount a single bar to a wide variety of pipettes, for example, by using magnetic coupling of the bar to the pipette body. Hence, truly consistent results for defined-level aspiration in manual pipetting, without the many limitations of the prior art becomes achievable. Additionally, since the unwanted motion or rotation can be restricted, the pipetting process, with the assistance of the device, becomes less attention-demanding and more consistent. Once the pipette is coupled with the stand, the force needed to hold the pipette up at a given position is reduced and this may help avoid repetitive pipetting stress injuries.
Regardless of the exact nature of the relative configurations and locations of the pipette 128, microplate 122, and the mechanism to couple the pipette with the stand, it should be understood that the apparatus 100 can be used to limit an insertion depth of the pipette tips into the microplate well 130 by blocking downward travel of the multichannel pipette 128 beyond a predetermined distance with respect to support surface 102, in order to provide reproducible and consistent pipetting (e.g., aspiration) operations, such as in a laboratory bench environment. This property may be particularly desirable when the multichannel pipette 128 and associated parts of apparatus 100 are being operated manually by a user.
While aspects of this disclosure have been particularly shown and described with reference to the example embodiments above, it will be understood by those of ordinary skill in the art that various additional embodiments may be contemplated. For example, the specific methods described above for using the apparatus are merely illustrative; one of ordinary skill in the art could readily determine any number of tools, sequences of steps, or other means/options for placing the above-described apparatus, or components thereof, into positions substantively similar to those shown and described herein. Bar 400 can be an integrated part of pipette 128. Arm 402 may have marks to indicate the corresponding well location of the microplate, or grooves or channels on the top surface which acts as receptacles for guiding bar 400 into the proper location. These grooves or receptacles can be fixed at the predetermined location, or can be moved around as desired manually, staying “freely” or temporally and gently locked after each movement, or can be moved automatically by a motor or manually with a digital display such as with a caliper. Any of the described structures and components could be integrally formed as a single unitary or monolithic piece or made up of separate sub-components, with either of these formations involving any suitable stock or bespoke components and/or any suitable material or combinations of materials. Though certain components described herein are shown as having specific geometric shapes, all structures of this disclosure may have any suitable shapes, sizes, configurations, relative relationships, cross-sectional areas, or any other physical characteristics as desirable for a particular application. Any structures or features described with reference to one embodiment or configuration could be provided, singly or in combination with other structures or features, to any other embodiment or configuration, as it would be impractical to describe each of the embodiments and configurations discussed herein as having all of the options discussed with respect to all of the other embodiments and configurations. One may also combine with other pipette accessories to further ease the burden and demand placed on the user, such as computer software or hardware guides that direct the user to particular well, rows of wells, or well groups, e.g., those discussed in U.S. Pat. No. 7,167,774. A device or method incorporating any of these features should be understood to fall under the scope of this disclosure as determined based upon the claims below and any equivalents thereof.
Other aspects, objects, and advantages can be obtained from a study of the drawings, the disclosure, and the appended claims.
The techniques described herein are exemplary, and should not be construed as implying any particular limitation on the present disclosure. It should be understood that various alternatives, combinations and modifications could be devised by those skilled in the art. For example, steps associated with the processes described herein can be performed in any order, unless otherwise specified or dictated by the steps themselves. The present disclosure is intended to embrace all such alternatives, modifications and variances that fall within the scope of the appended claims.
The terms “comprises” or “comprising” are to be interpreted as specifying the presence of the stated features, integers, steps or components, but not precluding the presence of one or more other features, integers, steps or components or groups thereof
This application claims priority from provisional patent application Ser. No. 63/072,188, filed on Aug. 30, 2020, which is incorporated herein by reference, in its entirety, for all purposes.
| Number | Date | Country | |
|---|---|---|---|
| 63072188 | Aug 2020 | US |
