Patent Application
20080009072
Embodiments of the present invention are described below. It is, however, expressly noted that the present invention is not limited to these embodiments, but rather the intention is that modifications that are apparent to the person skilled in the art and equivalents thereof are also included.
Aspects of the current invention provide for the use of ultrasound energy to mix the contents of a vial within an instrument. The use of ultrasound energy, or sonication, is more superior mixing technique than mechanical mixing because ultrasound can be used on a closed vial, which virtually eliminates splashes and spilling of the contents of the vial within the instrument. Furthermore, when the vial cap is removed, sonication creates much smaller ripples within the vial and therefore minimizes unwanted spills. When used with ThinPrep® TP2000 and TP3000 instruments, an added ultrasound device can continue mixing the contents of the vial while cells are being removed from the sample, thereby assure a homogenous sample from which cells are obtained. This leads to a more accurate representation of the contents of the sample on the slide.
Thus, in a first aspect, disclosed herein is a method of preparing a slide for viewing biological material, comprising obtaining a vial containing the biological material in a solution; sonicating the solution to obtain a mixed solution; selectively removing cells from the mixed solution by aspirating a portion of the solution through a membrane such that the cells adhere to the membrane; and transferring the cells adhered to the membrane to a microscope slide.
In some embodiments, the biological material is obtained from the cervix. In certain embodiments, the biological material comprises cervical cells, blood, and mucous. In other embodiments, the biological sample is blood sample. In yet other embodiments, the biological sample is urine.
In some embodiments, the biological sample is in PreservCyt® (Cytyc Corp.). In other embodiments, the biological sample is in water. In yet other embodiments, the biological sample is in a buffer solution, such as HEPES (N-(2-hydroxyethyl)piperazine-N′-(2-ethanesulfonic acid)), MES (2-(N-morpholino)ethane-sulfonic acid), MOPS (3-(N-morpholino)propanesulfonic acid), TRIS, TBS (Tris buffered saline), BIS-TRIS Propane (1,3-Bis[tris(hydroxymethyl)methylamino]propane), PBS (phosphate buffered saline), and the like.
In some embodiments, the sonication is performed by using ultrasound energy.
In some embodiments, the sonicating step produces a homogenized solution. In certain embodiments, the sonicating step breaks up mucous, blood, or cell clusters.
With some automated slide preparation devices, such as ThinPrep® TP2000 and TP3000 instruments, the instruments obtains a membrane and aspirates some of the solution containing the biological sample through the membrane. Some of the cells in the sample solution adhere to the membrane. The instrument, then presses the membrane against a glass slide, thereby transferring the cells to the glass slide.
In some embodiments, the above method further comprises sonicating the solution prior to aspirating the portion of the solution through the membrane. In these embodiments, the solution is sonicated for long enough time to ensure that all of the cell clusters have been broken up and that the solution is sufficiently homogenized.
In other embodiments, the above method further comprises sonicating the solution while aspirating the portion of the solution through the membrane. In these embodiments, continued sonication while aspirating ensures that very few, if any, new cell clusters are re-formed prior to obtaining the cells on the membrane.
In another aspect, disclosed herein is an apparatus for preparing a slide for viewing biological material, comprising a specimen preparing apparatus; a first loading station for receiving a plurality of samples; a sample transfer assembly for removing a first sample from the first loading station and transferring the first sample to the specimen preparing apparatus for preparing a first specimen from the first sample and thereafter returning the the sample to the first loading station; a sonicator for sonicating the first sample in the specimen preparing apparatus; a specimen transfer assembly for transferring the first specimen to an unloading area; and a processor for automatically controlling the the specimen preparing apparatus, the sample transfer assembly, the sonicator, and the specimen transfer assembly, such that remaining ones of the plurality of samples are processed to prepare subsequent specimens until all of the plurality of samples have been processed.
In some embodiments, each sample comprises particles in a liquid suspension. In further embodiments, the particles comprise cells
In some embodiments, the above apparatus further comprises a coating station for coating each prepared specimen with a fixative solution.
Some embodiments of the above apparatus further comprise a second loading station for receiving a plurality of membranes; and a membrane transfer assembly under control of the processor for removing a first membrane from the first loading station and transferring the first membrane to the specimen preparing apparatus for preparing a first specimen from the first sample and thereafter discarding the first membrane, where the processor automatically controls the membrane transfer assembly, such that a next one of the plurality of membranes is transferred to the specimen preparing apparatus to prepare a next specimen from a next sample until all of the plurality of samples have been processed.
In some embodiments, the sonicator sonicates the first sample in the first loading station. In other embodiments, the sonicator sonicates the first sample in the specimen preparing apparatus. In yet other embodiments, the sonicator sonicates the first sample prior to the first membrane being transferred to the specimen preparing apparatus. In yet other embodiments, the sonicator sonicates the first sample while the first membrane is being transferred to the specimen preparing apparatus. In certain embodiments, the sonicator sonicates the first sample in the first loading station and continues to sonicate the sample until the membrane has obtained a sufficient number of cells.
The invention may be embodied in other specific forms besides and beyond those described herein. The foregoing embodiments are therefore to be considered in all respects illustrative rather than limiting, and the scope of the invention is defined and limited only by the appended claims and their equivalents, rather than by the foregoing description.
