Chemical apparatus and process disinfecting – deodorizing – preser – Control element responsive to a sensed operating condition
Reexamination Certificate
1999-08-17
2001-06-05
Warden, Jill (Department: 1743)
Chemical apparatus and process disinfecting, deodorizing, preser
Control element responsive to a sensed operating condition
C422S091000, C422S105000, C422S105000, C422S105000, C422S105000, C435S287300, C435S293200, C435S300100
Reexamination Certificate
active
06241949
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to microtitre trays and their spill-resistant open lids that prevent cross contamination of samples and also accommodate fragile and flexible probes of automated biological sample analysis systems.
BACKGROUND OF THE INVENTION
Referring to
FIG. 1
, a conventional microtitre tray includes a two-dimensional array of wells arranged in one common plane when viewed from its top. Liquid biological samples are placed in some or all of the wells and analyzed. For instance, biological samples, e.g., for DNA sequencing, are often placed and transported in microtitre trays. In addition, reagents can be added to the samples in the wells and/or other treatments such as heating, cooling, centrifuging, filtering, diluting can be performed on the samples in the wells. Subsequently, in many cases the samples are taken directly from a microtitre tray and inserted into an analysis system, e.g., a DNA sequencer, for further detailed clinical analysis.
During the above described processes, the samples in the wells can spill or leak out from the wells. In some instances, the leaked out samples can flow into other wells. This causes loss of valuable samples, cross contamination thereof and renders the samples useless for any clinical analysis. Further, even if there is only a negligible probability of the cross contamination, when the results of the clinical analysis are to be presented to a peer review or a lay person review, i.e., a jury or a tribunal, the process of reducing the chance of cross contamination may become relevant evidence in interpreting the results of the clinical analysis.
In order to avoid the cross contamination problem, conventional microtitre trays are provided with closed lids that tightly fit over each of the wells. The lids may reduce the chance of the cross contamination and the loss of samples to nil. However, this solution, hinders the use of automated analysis systems by requiring the use of cumbersome robotic arms to remove the lids.
An automated system utilizes the uniform characteristics of microtitre trays, e.g., the location and sizes of well openings. In other words, introduction of samples into microtitre wells can be achieved by a two-dimensional array of syringes arranged to match with the locations of the well openings. Further, a two-dimensional array of probes can be inserted into the wells of a microtitre tray for clinical analysis of the sample simultaneously. Other examples of automated analysis systems include micropipeting work station, which is a robotic station, that would perform all of the sample transfer and other processes automatically.
In the above described exemplary automated systems, the closed lids require an additional step of removing the lids. If this lid removal step is to be automatically performed, then an additional mechanism to remove the lids and to test whether or not all the lids have been removed would be required. This makes automated analysis systems more cumbersome and expensive.
In one alternative embodiment, loose-fitting lids are provided to lessen the force required to remove the lids by the automated analysis systems. The loose lids, however, introduce additional risks, such as unwanted removal during sample transport, and the need to ensure the lid was properly replaced after the sample was accessed.
As another alternative, an aluminum foil or an adhesive backed aluminum foil can be used to cover the opening of the wells. In this alternative, the foil is peeled away or pierced through by syringes or probes that need to access the wells. Another alternative is to use septum-based sample lids. Similar to the foil, the septum-based lid is pierced by the syringes or probes to access the wells. All of those embodiments require additional hardware to automate. For instance they require feedback systems to ensure that the piercing or removing the foil is in fact achieved.
In some automated analysis systems, only fragile or flexible probes can be utilized. These probes would not be sufficiently rigid to penetrate or pierce through the foils or the septum-based lids discussed above. An example of these types of probes is used in an automated capillary electrophoresis system described in U.S. Pat. No. 5,885,430 which is incorporated herein by reference. Another example of fragile and flexible probes are small fiberoptic tips utilized for analysis of samples using absorption or emission techniques.
Therefore, it would be desirable to provide a lid mechanism to microtitre trays that can prevent cross contamination of samples and, simultaneously, can accommodate the fragile and flexible probes described above.
SUMMARY OF THE INVENTION
Accordingly, the present invention provides microtitre trays with a one or two-dimensional array of wells and with open-lids that are spill-resistant to prevent cross contamination of samples and also to accommodate fragile and flexible probes of the automated biological sample analysis systems.
More specifically, the present invention includes an array of connected wells. Each well includes a circumferential wall forming a hollow, elongated mid-section having a first and second ends. The circumferential wall defines an opening at the first end. Each well further includes a bottom section liquid tightly closing the second end and a circumferential sleeve located near the first end of the wall and extending toward the second end. When the well is tilted, a liquid sample is trapped between the sleeve and the wall. The bottom section of each well includes a side portion connected to the second end of the circumferential wall, and a center portion sagging below the side portion, wherein the liquid sample collects on the center portion when the liquid sample is introduced into the well.
The circumferential sleeve forms substantially similar shape as that of its well and includes an opening in its bottom section. The sleeve around the opening is made from moderately flexible and elastic plastic material. This allows the opening to be opened or closed depending upon whether a probe is inserted therethough or not, respectively.
The present invention further provides a method of manufacturing open-lids for a microtitre tray. The method includes the steps of fabricating a modified microtitre tray which includes wells without respective bottom sections, fabricating an unmodified microtitre tray which includes wells having a same spacing as those in the modified microtitre tray, and stacking the modified microtitre tray onto the unmodified microtitre tray.
The step of fabricating the modified microtitre tray may further include the step of either molding a microtitre tray without bottom sections of its wells or severing bottom sections of a microtitre tray. If desired, the severing step may cut the bottom sections of each well simultaneously.
The present invention also includes a cutting tool for severing bottom sections of wells of a microtitre tray. The cutting tool includes a blade and a tray holder configured to grip the microtitre tray. The tray holder renders the microtitre tray substantially immovable when the bottom sections are being cut by the blade. The cutting tool also includes a blade guide configured to direct the blade to sever the bottom sections of the wells.
The cutting tool also may include a clamp pivotally mounted on the tray holder and configured to securely grip the microtitre tray when the clamp is pivoted toward the tray holder.
If desired the blade may also include an array of openings defined therein to receive the bottom portions of the wells and an array of crescent-shaped blades located on one side of each opening. This embodiment severs the bottom sections when the blade is moved in a predetermined direction. Further, the blade can be mounted on the microtitre holder to be moved laterally with respect thereto.
Also the cutting tool may include a lever pivotally mounted on the tray holder and a link operationally coupled to the lever and the blade and configured to convert rotating force exerted by the lever into lateral movement
Handy Dwayne K.
Pennie & Edmonds LLP
Spectrumedix Corporation
Warden Jill
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