WO2022149975A1 - Apparatus and method for automatically preparing thin-layer slides - Google Patents
Apparatus and method for automatically preparing thin-layer slides Download PDFInfo
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- WO2022149975A1 WO2022149975A1 PCT/MY2021/050058 MY2021050058W WO2022149975A1 WO 2022149975 A1 WO2022149975 A1 WO 2022149975A1 MY 2021050058 W MY2021050058 W MY 2021050058W WO 2022149975 A1 WO2022149975 A1 WO 2022149975A1
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- vials
- slides
- lbc
- slide
- pick
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- 238000000034 method Methods 0.000 title claims abstract description 51
- 230000005484 gravity Effects 0.000 claims abstract description 31
- 238000004062 sedimentation Methods 0.000 claims abstract description 28
- 239000007788 liquid Substances 0.000 claims abstract description 25
- 238000012546 transfer Methods 0.000 claims abstract description 10
- 238000002360 preparation method Methods 0.000 claims description 12
- 238000010186 staining Methods 0.000 claims description 8
- 210000003679 cervix uteri Anatomy 0.000 claims description 6
- 230000008021 deposition Effects 0.000 claims description 6
- 238000003780 insertion Methods 0.000 claims description 4
- 230000037431 insertion Effects 0.000 claims description 4
- 210000003813 thumb Anatomy 0.000 claims description 4
- 230000002209 hydrophobic effect Effects 0.000 claims description 3
- 239000008188 pellet Substances 0.000 claims description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 2
- 210000005224 forefinger Anatomy 0.000 claims description 2
- 238000002372 labelling Methods 0.000 claims description 2
- 210000004027 cell Anatomy 0.000 description 36
- 239000010410 layer Substances 0.000 description 23
- 238000012216 screening Methods 0.000 description 8
- 239000012530 fluid Substances 0.000 description 7
- 238000010586 diagram Methods 0.000 description 6
- 238000005070 sampling Methods 0.000 description 6
- 238000009595 pap smear Methods 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 210000003097 mucus Anatomy 0.000 description 4
- 239000002356 single layer Substances 0.000 description 4
- 230000002159 abnormal effect Effects 0.000 description 3
- 210000004969 inflammatory cell Anatomy 0.000 description 3
- 241000701806 Human papillomavirus Species 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000000834 fixative Substances 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 230000003902 lesion Effects 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 206010008342 Cervix carcinoma Diseases 0.000 description 1
- 241000606161 Chlamydia Species 0.000 description 1
- 206010018612 Gonorrhoea Diseases 0.000 description 1
- 208000008636 Neoplastic Processes Diseases 0.000 description 1
- 244000007853 Sarothamnus scoparius Species 0.000 description 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 238000007605 air drying Methods 0.000 description 1
- 238000011166 aliquoting Methods 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 239000013060 biological fluid Substances 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 210000003888 boundary cell Anatomy 0.000 description 1
- 230000021164 cell adhesion Effects 0.000 description 1
- 201000010881 cervical cancer Diseases 0.000 description 1
- 208000019065 cervical carcinoma Diseases 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 210000002726 cyst fluid Anatomy 0.000 description 1
- 230000002380 cytological effect Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
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Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N1/00—Sampling; Preparing specimens for investigation
- G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
- G01N1/30—Staining; Impregnating ; Fixation; Dehydration; Multistep processes for preparing samples of tissue, cell or nucleic acid material and the like for analysis
- G01N1/31—Apparatus therefor
- G01N1/312—Apparatus therefor for samples mounted on planar substrates
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N1/00—Sampling; Preparing specimens for investigation
- G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
- G01N1/2813—Producing thin layers of samples on a substrate, e.g. smearing, spinning-on
Definitions
- LBC liquid-based cytology
- Gynecologic cytology or the Papanicolaou (Pap) test is the most successful screening program albeit the test itself has been estimated to have as low as 50% sensitivity for the detection of abnormalities of the cervix. It is a field of pathology concerned with the investigation of disorders of the female genital tract such as precancerous lesions of the cervix.
- the main reason that the test has been successful in population into which it has been introduced is the fact that annual screening intervals given patient multiple "shots" at the detection of a neoplastic process that has a generally slow progression to invasive carcinoma and which is equally well-treated at each step in this progression. In effect, the principal is that a miss one year will be a hit the next, with no untoward effects.
- Cervical cytology screening by the Papanicolaou (Pap) method involves the microscopic examination of cell samples that have been taken primarily from the ecto- and endocervix, smeared on glass slides and stained using the Papanicolaou Stain procedure. Cervical cytology screening with the Pap smear has decreased the mortality rates of invasive cervical carcinoma by 50 to 60 percent. Because cervical cytology is a screening test, abnormal findings must be confirmed histologically. Nonetheless, the high false-negative rate of the pap test is multifactorial.
- Kelley et al., US 5,480,484 A disclosed an improved cytology centrifuge apparatus includes single or multiple well cell concentrators for being rotated by a centrifugal spinner.
- a rotor is removably supported by the spinner for rotation and is adapted to receive two or four cell concentrators.
- the rotor supports the cell concentrators in an unrestrained manner, thereby enhancing the ease of use and flexibility of the apparatus.
- Each cell concentrator includes a chamber having a top surface in which at least one fluid receiving aperture is disposed and a front surface in which at least one fluid expulsion aperture is disposed.
- a backing plate is provided with protruding top and bottom edges to vertically align a microscope slide with the chamber so that the fluid expulsion aperture is adjacent to a central portion of the slide.
- Retention clips secure the chamber to the backing plate with the slide sandwiched therebetween in horizontal alignment.
- the cell concentrator is shaped to rest stably on a planar surface in a tilted manner so that a fluid specimen contained therein is prevented from contacting the slide prior to centrifugation.
- the concentrator is also well suited for use as a staining chamber and the backing plate has a viewing aperture aligned with the fluid expulsion aperture to enable viewing of cells on the slide during a staining process.
- US 5,480,484 A is not able to produce homogenous thin-layer liquid-based cytology (LBC) slides, whereas present invention is capable of producing thin-layer LBC slides without the presence of debris, mucus or inflammatory cells.
- a centrifugal cytology swinging bucket for providing multiple dispersions of fixed cells or other particles onto a microscope slide or similar substrate, as disclosed in US 4,250,830 A, by Leif Robert C.
- a fluid tight chamber is formed by pressing and sealing an elastomeric chamber block against a standard 3 by 1-inch microscope slide.
- the slide serves as the base of the pyramidal sample chambers present in the block.
- the incline of the slanted chamber walls follows the radius emanating from the center of the centrifuge. Since materials, such as cells and other particles, follow a radial trajectory, this incline prevents their deposition on the chamber walls.
- the cell containing suspension is first placed in a chamber and then the cells are centrifuged onto the slide. Most of the supernatant is removed and a fixative is added in a manner that does not dislodge the cells.
- a frit is used as a synthetic boundary valve, which limits the delivery of the bulk of the fixative to after the centrifugal field is applied.
- An apparatus for automatically preparing liquid-based cytology (LBC) slides by means of gravity sedimentation comprises of: at least one carrier for holding a plurality of vials containing specimen wherein said vials comprise of an open first end and a closed second end; a slide is coupled with said vials at the open first end of said vial, respectively; and at least one first pick and place module to pick said vials from said carrier and transfer said vials to an inverting means; characterized in that said inverting means is capable of producing at least one thin-layer LBC slide by inverting or shaking of said vials for 1 to 10 times at an angle of 0° to 360°.
- a method for automatically preparing liquid-based cytology (LBC) slides by means of gravity sedimentation comprising of the following steps: (i) placing a plurality of vials containing specimen on a carrier at a first station wherein said vials are coupled with a slide inserted at an open first end of said vials; and
- FIG. 1-A shows an exemplary side view of the present invention.
- FIG. 1-B and FIG. 1-C show exemplary top views of the present invention with a disposable station.
- FIG. 2- A shows an exemplary diagram of the present invention while the inverting means is holding said vials coupled with said slide.
- FIG. 2-B shows another exemplary enlarged diagram of the present invention while the inverting means is holding said vials coupled with said slide.
- FIG. 2-C shows another exemplary diagram of the present invention while said vials are holding by a rotating means.
- FIG. 3 shows an exemplary diagram of the present invention while the carrier holding a plurality of vials with specimen and said vials are coupled with slide.
- FIG. 4 shows an exemplary method flow of the present invention while preparing liquid-based cytology (LBC) slides by means of gravity sedimentation.
- FIG. 5 shows an exemplary method flow of the present invention while performing specimen collection.
- LBC liquid-based cytology
- FIG. 6 shows an exemplary method flow of the present invention while performing vortex of said vials.
- FIG. 7 shows an exemplary method flow of the present invention while performing cell deposition.
- FIG. 8 shows another exemplary method flow of the present invention while performing fixation and Pap staining.
- present invention is claiming an apparatus (1) and method (2) for automatically preparing homogenous thin-layer liquid-based cytology (LBC) slides (101) by means of gravity sedimentation with an inverting means (115).
- Said apparatus (1) comprises of at least one carrier (103) for holding a plurality of vials (105) containing specimen wherein said vials (105) comprise of an open first end (107) and a closed second end (109), wherein the open first end (107) is enclosed with a cap (209), a slide (101) is coupled with said vials (105) at the open first end (107) of said vials (105), respectively, as make reference to FIG. 3.
- said apparatus (1) comprises of at least one first pick and place module (113) to pick said vials (105) from said carrier (103) and transfer said vials (105) to an inverting means (115).
- Said inverting means (115) is capable of producing thin-layer LBC slides (101) by inverting or shaking of said vials (105) for 1 to 10 times at an angle of 0° to 360°.
- Said apparatus (1) further comprises of a second pick and place module (118) to transfer said slides (101) to a slide holder (201) upon completion of the inverting process of said vials (105).
- Present invention utilizes specially designed vials (105) with a cap (209) seal placed directly over said thin-layer LBC slides (101).
- Said thin-layer LBC slides (101) are coated with a layer of hydrophilic positive charges or hydrophobic positive charges.
- Said hydrophilic positive charges carry approximately three times the number of positive charges compared with the commercial positively-charged slides and said thin-layer LBC slides (101) display improved cell-adhesion.
- all commercially available positively-charged microscope slides were found to be hydrophobic.
- Said positively coated charged create electrostatic against cells to bind on said slides (101).
- Said thin-layer LBC slides (101) comprises of a circle with 10mm to 21mm diameter at the center of said slides (101).
- said closed second end (109) of said vials (105) contain cell pellets include gynecological samples as well as non-gynecological samples such as body fluid, urine, cyst fluid, and etc.
- the gynecological samples are collected by qualified medical personnel using broom-like devices.
- Said broom-like devices are designed with a unique broom-head detachable function that allowed to drop the entire broom-head into the sample collection vials (105) with the advantage that said samples can be processed without taking out the broom head. This had given an advantage for having
- said apparatus (1) further comprises of a disposable station (207) for the storage of the used vials (105) as illustrated in FIG. 1-B and FIG. 1-C.
- FIG. 2- A there is shown an exemplary diagram of the present invention while the inverting means (115) is holding said vials (105) coupled with said slide (101).
- said inverting means (115) is accomplished to produce thin- layer LBC slides (101) by inverting or shaking of said vials (105) for 1 to 10 times at an angle of 0° to 360°.
- said inverting means (115) By having said inverting means (115), the second and subsequent layers of the specimen will not adhere to said slides (101) and hence, a thin-layer or mono-layer of LBC slides (101) is produced whereby said thin-layer LBC slides (101) contain the diagnostic cell clusters with the absence of mucus, debris or the like.
- FIG. 2-A The enlarged view of FIG. 2-A is illustrated in FIG. 2-B.
- FIG. 2-C shows another exemplary diagram whereby the vials are holding by a rotating means (206) for the untightening of the cap (209) of said vials (105) neither in clockwise direction or anti-clockwise direction.
- an exemplary method (2) for automatically preparing liquid-based cytology (LBC) slides (101) by means of gravity sedimentation Firstly, (i) placing a plurality of vials (105) containing specimen on a carrier (103) at a first station (203) wherein said vials (105) are coupled with a slide (101) inserted at an open first end (107) of said vials (105) (301) and; follow by (ii) picking said vials (105) by a first pick and place module (113) and subsequently placing said vials (105) at a second station (205) (303).
- said second station (205) includes inverting or shaking of said vials (105) by an inverting means (115) for 1 to 10 times at an angle of 0° to 360° to produce thin-layer LBC slides (101) (305).
- Said method (2) further comprises of the following steps after step (ii) picking said vials (105) by a first pick and place module (113) and subsequently placing said vials (105) at a second station (205) (303), first of all, (a) transferring said slides (101) into a slide holder (201) by a second pick and place module (118) after the completion of the inverting process of said vials (101) (307); then (b) transferring said vials (105) into a disposable station (207) by said first pick and place module (113) (309); subsequently (c) repeating step (ii) picking said vials (105) by a first pick and place module (113) and subsequently placing said vials (105) at a second station (205), for continuous preparation of LBC slides (101) (311); and (d) repeating step (i) placing a plurality of vials (105) containing specimen on a carrier (103) at a first station (203) wherein said vials (105) are coupled with a slide (101) inserted at an
- said method (2) further comprises of steps of performing specimen collection (4), performing vortex of said vials (105) (5), and cell deposition (6) prior to step (i) placing a plurality of vials (105) containing specimen on a carrier (103) at a first station (203) wherein said vials (105) are coupled with a slide
- the specimen collection and preparation of said slides (101) are extremely important to accuracy in Pap smears. Randomization or uniform sub-sampling is essential for complete accuracy.
- the conventional Pap smear technique does not provide for mixing of the sample prior to slide preparation. Due to entanglement of cells in mucus on the sampling device, the cells actually transferred to the slide may not be representative of the total population collected. The cells are transferred to the slide in relation to where they happen to be on the sampling device and many cells are left on the device.
- present invention is a method (2) for converting a liquid suspension of a cervical sample into a consistently stained, homogeneous slides (101) while maintaining diagnostic cell clusters.
- said step of performing vortex of said vials (105) (5) are accomplished by a multi-vial vortexer or vortexer for 5 to 30 seconds which aim to utterly mix the specimen at said vials (105) (515), as disclosed in FIG. 6.
- the preserved sample is mixed by vortexing. In approximately 10 minutes, the sample cells in the vials (105) are sedimented by gravity.
- the step of performing cell deposition (6) comprises of the following substeps: (a) loosing the cap (209) of said vials (105) to enable insertion of a slide (101) into the open first end (107) of said vials (105) wherein the insertion will be performed until said vials (105) are positioned at the center circle of said slide (101) (601); (b) holding said slide (101) and cap (209) of said vials (105), rotating a closed second end (109) of said vials (105) to enable tightening of said cap (209) with said slide (101) (603); and (c) inverting said vials (105) for 10 mins to ensure the cells are sedimented by gravity (605), as mentioned in FIG. 7.
- said method (2) further comprises of the steps of performing fixation and Pap staining (7) after step (ii) picking said vials (105) by a first pick and place module (113) and subsequently placing said vials (105) at a second station (205) (303). Firstly (a) removing said slide (101) from the slide holder (201) (701); then (b) transferring said slide (101) to 95% alcohol fixation for 15 minutes (703); and lastly (c) performing Pap staining on said slide (101) (705). Microscopic examination will reveal that the cells have naturally settled onto the slide (101) by gravitation and hence producing a homogenous thin-layer like appearance.
- Present invention is a method (2) for processing LBC slides (101) which serves as a replacement for the conventional Pap smear preparation method for use in cervical cancer screemng.
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Abstract
The present invention relates to an apparatus (1) and method for automatically preparing liquid-based cytology (LBC) slides (101) by means of gravity sedimentation comprising of at least one carrier (103) for holding a plurality of vials (105) containing specimen wherein said vials (105) comprise of an open first end (107) and a closed second end (109), a slide (101) is coupled with said vials (105) at the open first end (107) of said vials (105), respectively; and at least one first pick and place module (113) to pick said vials (105) from said carrier (103) and transfer said vials (105) to an inverting means (115), wherein said inverting means (115) is capable of producing thin-layer LBC slides (101) by inverting or shaking of said vials (105) for 1 to 10 times at an angle of 0° to 360°.
Description
APPARATUS AND METHOD FOR AUTOMATICALLY PREPARING THIN-
LAYER SLIDES
1. TECHNICAL FIELD OF THE INVENTION
The present invention relates to an apparatus and method for automatically preparing liquid-based cytology (LBC) slides by means of gravity sedimentation comprises of at least one carrier for holding a plurality of vials containing specimen wherein said vials comprise of an open first end and a closed second end, a slide is coupled with said vials at the open first end of said vial, respectively, and at least one first pick and place module to pick said vials from said carrier and transfer said vials to an inverting means, wherein said inverting means is capable of producing homogenous thin-layer or mono-layer LBC slides by inverting or shaking of said vials for 1 to 10 times at an angle of 0° to 360°.
2. BACKGROUND OF THE INVENTION
Gynecologic cytology or the Papanicolaou (Pap) test is the most successful screening program albeit the test itself has been estimated to have as low as 50% sensitivity for the detection of abnormalities of the cervix. It is a field of pathology concerned with the investigation of disorders of the female genital tract such as precancerous lesions of the cervix. The main reason that the test has been successful in population into which it has been introduced is the fact that annual screening intervals given patient multiple "shots" at the detection of a neoplastic process that has a generally slow progression to invasive carcinoma and which is equally well-treated at each step in this progression. In effect, the principal is that a miss one year will be a hit the next, with no untoward effects. Cervical cytology screening by the Papanicolaou (Pap) method involves the microscopic examination of cell samples that have been taken primarily from the ecto- and endocervix, smeared on glass slides and stained using the Papanicolaou Stain procedure. Cervical cytology screening with the Pap smear has decreased the mortality rates of invasive cervical carcinoma by 50 to 60 percent. Because cervical cytology is a screening test, abnormal findings must be confirmed histologically.
Nonetheless, the high false-negative rate of the pap test is multifactorial. The reason ranges from inadequate sampling of lesions present, which may be small, incomplete transfer of abnormal cells from those collected on the sampling device to a glass slide (typically in conventional smears), poor preparation, screening errors, and misinterpretation of abnormal cells identified on screening. The introduction of modern sampling devices, liquid-based specimen preparation, offers several clears advantages over conventional smears. For instances, the opportunity to prepare duplicate slides and even cell block preparations from the residual samples; the option of out-of- vial" aliquo ting for human papillomavirus (HPV), chlamydia, and gonorrhea testing; an improved substrate for automated screening devices; and a thinner cell preparation that most pathologists and cytotechnologists find less tiring to review than smears.
Kelley et al., US 5,480,484 A, disclosed an improved cytology centrifuge apparatus includes single or multiple well cell concentrators for being rotated by a centrifugal spinner. A rotor is removably supported by the spinner for rotation and is adapted to receive two or four cell concentrators. The rotor supports the cell concentrators in an unrestrained manner, thereby enhancing the ease of use and
flexibility of the apparatus. Each cell concentrator includes a chamber having a top surface in which at least one fluid receiving aperture is disposed and a front surface in which at least one fluid expulsion aperture is disposed. A backing plate is provided with protruding top and bottom edges to vertically align a microscope slide with the chamber so that the fluid expulsion aperture is adjacent to a central portion of the slide. Retention clips secure the chamber to the backing plate with the slide sandwiched therebetween in horizontal alignment. The cell concentrator is shaped to rest stably on a planar surface in a tilted manner so that a fluid specimen contained therein is prevented from contacting the slide prior to centrifugation. The concentrator is also well suited for use as a staining chamber and the backing plate has a viewing aperture aligned with the fluid expulsion aperture to enable viewing of cells on the slide during a staining process. Nonetheless, US 5,480,484 A is not able to produce homogenous thin-layer liquid-based cytology (LBC) slides, whereas present invention is capable of producing thin-layer LBC slides without the presence of debris, mucus or inflammatory cells.
Furthermore, there is provided a centrifugal cytology swinging bucket for providing multiple dispersions of fixed cells or other particles onto a microscope slide or similar substrate, as disclosed in US 4,250,830 A, by Leif Robert C. Either an aluminum carrier serves as a replacement for the standard swing-out cup of a swinging bucket rotor, or a special plastic carrier is supported by a swing-cup of a swinging bucket rotor. In either case, a fluid tight chamber is formed by pressing and sealing an elastomeric chamber block against a standard 3 by 1-inch microscope slide. The slide serves as the base of the pyramidal sample chambers present in the block. The incline of the slanted chamber walls follows the radius emanating from the center of the centrifuge. Since materials, such as cells and other particles, follow a radial trajectory, this incline prevents their deposition on the chamber walls. The cell containing suspension is first placed in a chamber and then the cells are centrifuged onto the slide. Most of the supernatant is removed and a fixative is added in a manner that does not dislodge the cells. A frit is used as a synthetic boundary valve, which limits the delivery of the bulk of the fixative to after the centrifugal field is applied.
The designs of synthetic boundary cells, which are a means to transfer fluid in a centrifuge into a centrifugation chamber, have been described by Schachman and
another design to deliver a reagent into a cuvette mounted in a centrifuge has been described by Goldstein et al. U.S. Pat. No. 4,119,407. During fixation, the cells are pressed onto the slide by centrifugal force. After fixation, the slide is separated from the chamber block and can then be processed by conventional staining techniques. The centrifugal cytology bucket was designed to facilitate the cytological examination of cells from dilute biological fluids. The centrifugal cytology bucket can be used clinically to prepare cells for human screening and shows great potential for automated clinical cytology. However, this method come across limitation alike US 5,480,484 A, as the system are unable to produce homogenous thin-layer liquid-based cytology (LBC) slides.
Hence, it would be advantageous to alleviate the shortcomings by having an apparatus and method for automatically preparing homogenous thin-layer or mono layer liquid-based cytology (LBC) slides by means of gravity sedimentation with an inverting means while maintaining diagnostic cell clusters.
3. SUMMARY OF THE INVENTION
Accordingly, it is the primary aim of the present invention to provide an apparatus and method for automatically preparing liquid-based cytology (LBC) slides by means of gravity sedimentation whereby said apparatus and method are capable of producing homogenous thin-layer or mono-layer LBC slides while maintaining the diagnostic cell clusters.
It is yet another object of the present invention to provide an apparatus and method for automatically preparing LBC slides by means of gravity sedimentation whereby said apparatus and method are aimed to minimize the presence of debris, inflammatory cells, mucus or the like.
It is yet another object of the present invention to provide an apparatus and method for automatically preparing LBC slides by means of gravity sedimentation whereby said apparatus and method are aimed to produce LBC slides with improved cellular morphology.
It is yet another object of the present invention to provide an apparatus and method for automatically preparing LBC slides by means of gravity sedimentation which is user friendly. It is yet another object of the present invention to provide an apparatus and method for automatically preparing LBC slides by means of gravity sedimentation which is environmentally friendly.
It is yet another object of the present invention to provide an apparatus and method for automatically preparing LBC slides by means of gravity sedimentation which aim to increase system throughput.
Other further objects of the invention will become apparent with an understanding of the following detailed description of the invention or upon employment of the invention in practise.
According to the preferred embodiment of the present invention the following is provided:
An apparatus for automatically preparing liquid-based cytology (LBC) slides by means of gravity sedimentation comprises of: at least one carrier for holding a plurality of vials containing specimen wherein said vials comprise of an open first end and a closed second end; a slide is coupled with said vials at the open first end of said vial, respectively; and at least one first pick and place module to pick said vials from said carrier and transfer said vials to an inverting means; characterized in that said inverting means is capable of producing at least one thin-layer LBC slide by inverting or shaking of said vials for 1 to 10 times at an angle of 0° to 360°.
In another embodiment of the invention there is provided:
A method for automatically preparing liquid-based cytology (LBC) slides by means of gravity sedimentation, comprising of the following steps:
(i) placing a plurality of vials containing specimen on a carrier at a first station wherein said vials are coupled with a slide inserted at an open first end of said vials; and
(ii) picking said vials by a first pick and place module and subsequently placing said vials at a second station; characterized in that said second station includes inverting or shaking of said vials by an inverting means for 1 to 10 times at an angle of 0° to 360° to produce at least one thin-layer LBC slide.
4. BRIEF DESCRIPTION OF THE DRAWINGS Other aspect of the present invention and their advantages will be discerned after studying the Detailed Description in conjunction with the accompanying drawings in which:
FIG. 1-A shows an exemplary side view of the present invention.
FIG. 1-B and FIG. 1-C show exemplary top views of the present invention with a disposable station.
FIG. 2- A shows an exemplary diagram of the present invention while the inverting means is holding said vials coupled with said slide.
FIG. 2-B shows another exemplary enlarged diagram of the present invention while the inverting means is holding said vials coupled with said slide. FIG. 2-C shows another exemplary diagram of the present invention while said vials are holding by a rotating means.
FIG. 3 shows an exemplary diagram of the present invention while the carrier holding a plurality of vials with specimen and said vials are coupled with slide.
FIG. 4 shows an exemplary method flow of the present invention while preparing liquid-based cytology (LBC) slides by means of gravity sedimentation.
FIG. 5 shows an exemplary method flow of the present invention while performing specimen collection.
FIG. 6 shows an exemplary method flow of the present invention while performing vortex of said vials.
FIG. 7 shows an exemplary method flow of the present invention while performing cell deposition. FIG. 8 shows another exemplary method flow of the present invention while performing fixation and Pap staining.
5. DETAILED DESCRIPTION OF THE DRAWINGS
In the following detailed description, numerous specific details are set forth in order to provide a thorough understanding of the invention. However, it will be understood by those with ordinary skill in the art that the invention may be practiced without these
specific details. In other instances, well known methods, procedures and/ or components have not been described in detail so as not to obscure the invention.
The invention will be more clearly understood from the following description of the embodiments thereof, given by way of example only with reference to the accompanying drawings, which are not drawn to scale.
As used in this disclosure and the appended claims herein, the singular forms "a", "an", and "the" include plural referents unless the context clearly dictates or denotes otherwise. Throughout the disclosure and claims of this specification, the word "comprise" and variations of the word, such as "comprising" and "comprises," means "including but not limited to," and is not intended to exclude, for example, other components, integers or steps. "Exemplary" means "an example of" and is not intended to convey an indication of a preferred or ideal embodiment, "such as" is not used in a restrictive sense, but for explanatory purposes.
Typically, present invention is claiming an apparatus (1) and method (2) for automatically preparing homogenous thin-layer liquid-based cytology (LBC) slides (101) by means of gravity sedimentation with an inverting means (115). Referring to FIG. 1-A, there is shown an exemplary side view of the present invention. Said apparatus (1) comprises of at least one carrier (103) for holding a plurality of vials (105) containing specimen wherein said vials (105) comprise of an open first end (107) and a closed second end (109), wherein the open first end (107) is enclosed with a cap (209), a slide (101) is coupled with said vials (105) at the open first end (107) of said vials (105), respectively, as make reference to FIG. 3. In addition, said apparatus (1) comprises of at least one first pick and place module (113) to pick said vials (105) from said carrier (103) and transfer said vials (105) to an inverting means (115). Said inverting means (115) is capable of producing thin-layer LBC slides (101) by inverting or shaking of said vials (105) for 1 to 10 times at an angle of 0° to 360°. Said apparatus (1) further comprises of a second pick and place module (118) to transfer said slides (101) to a slide holder (201) upon completion of the inverting process of said vials (105). Present invention utilizes specially designed vials (105) with a cap (209) seal placed directly over said thin-layer LBC slides (101).
Said thin-layer LBC slides (101) are coated with a layer of hydrophilic positive charges or hydrophobic positive charges. Said hydrophilic positive charges carry approximately three times the number of positive charges compared with the commercial positively-charged slides and said thin-layer LBC slides (101) display improved cell-adhesion. Typically, all commercially available positively-charged microscope slides were found to be hydrophobic. Said positively coated charged create electrostatic against cells to bind on said slides (101). Said thin-layer LBC slides (101) comprises of a circle with 10mm to 21mm diameter at the center of said slides (101). Moreover, said closed second end (109) of said vials (105) contain cell pellets include gynecological samples as well as non-gynecological samples such as body fluid, urine, cyst fluid, and etc. The gynecological samples are collected by qualified medical personnel using broom-like devices. Said broom-like devices are designed with a unique broom-head detachable function that allowed to drop the entire broom-head into the sample collection vials (105) with the advantage that said samples can be processed without taking out the broom head. This had given an advantage for having
100% of sample which is collected to be process and transfer during smearing.
Additionally, said apparatus (1) further comprises of a disposable station (207) for the storage of the used vials (105) as illustrated in FIG. 1-B and FIG. 1-C.
Referring now to FIG. 2- A, there is shown an exemplary diagram of the present invention while the inverting means (115) is holding said vials (105) coupled with said slide (101). As mentioned, said inverting means (115) is accomplished to produce thin- layer LBC slides (101) by inverting or shaking of said vials (105) for 1 to 10 times at an angle of 0° to 360°. By having said inverting means (115), the second and subsequent layers of the specimen will not adhere to said slides (101) and hence, a thin-layer or mono-layer of LBC slides (101) is produced whereby said thin-layer LBC slides (101) contain the diagnostic cell clusters with the absence of mucus, debris or the like. The existing devices to prepare the LBC slides (101) do not comprise of said inverting means (115) and thus there is no remarkable way to produce homogenous thin-layer LBC slides (101) by means of gravity sedimentation. Therefore, the present invention is novel and it is not taught by existing prior art and hence the existing devices do not provide any teaching, suggestion, or motivation for a person skilled in the art to arrive at the present invention.
The enlarged view of FIG. 2-A is illustrated in FIG. 2-B. In addition, FIG. 2-C shows another exemplary diagram whereby the vials are holding by a rotating means (206) for the untightening of the cap (209) of said vials (105) neither in clockwise direction or anti-clockwise direction. As illustrates in FIG. 4, there is shown an exemplary method (2) for automatically preparing liquid-based cytology (LBC) slides (101) by means of gravity sedimentation. Firstly, (i) placing a plurality of vials (105) containing specimen on a carrier (103) at a first station (203) wherein said vials (105) are coupled with a slide (101) inserted at an open first end (107) of said vials (105) (301) and; follow by (ii) picking said vials (105) by a first pick and place module (113) and subsequently placing said vials (105) at a second station (205) (303). In this case, said second station (205) includes inverting or shaking of said vials (105) by an inverting means (115) for 1 to 10 times at an angle of 0° to 360° to produce thin-layer LBC slides (101) (305).
Said method (2) further comprises of the following steps after step (ii) picking said vials (105) by a first pick and place module (113) and subsequently placing said vials (105) at a second station (205) (303), first of all, (a) transferring said slides (101)
into a slide holder (201) by a second pick and place module (118) after the completion of the inverting process of said vials (101) (307); then (b) transferring said vials (105) into a disposable station (207) by said first pick and place module (113) (309); subsequently (c) repeating step (ii) picking said vials (105) by a first pick and place module (113) and subsequently placing said vials (105) at a second station (205), for continuous preparation of LBC slides (101) (311); and (d) repeating step (i) placing a plurality of vials (105) containing specimen on a carrier (103) at a first station (203) wherein said vials (105) are coupled with a slide (101) inserted at an open first end (107) of said vials (105) (301), upon completion of the step (c) repeating step (ii) picking said vials (105) by a first pick and place module (113) and subsequently placing said vials (105) at a second station (205), for continuous preparation of LBC slides (101)
(313).
Referring now to FIG. 5, said method (2) further comprises of steps of performing specimen collection (4), performing vortex of said vials (105) (5), and cell deposition (6) prior to step (i) placing a plurality of vials (105) containing specimen on a carrier (103) at a first station (203) wherein said vials (105) are coupled with a slide
(101) inserted at an open first end (107) of said vials (105) (301). The detailed
explanation of the substeps of performing specimen collection (4) are as following, (a) inserting a broom-like device such as cervical brush into an endocervical canal of a cervix to collect cells, and applying gentle pressure until bristles of said broom-like device form against said cervix (401); then (b) maintaining the gentle pressure and holding a stem between the thumb and forefinger (403); next (c) rotating a brush of said broom-like device 3 to 5 times in a clockwise direction (405); (d) placing said thumb against the back of said brush pad and subsequently disconnecting said brush from said stem into vials (105) (407); (e) placing a cap (209) on said vials (105) and tighten it (409); (f) labelling said vials (105) and executing a lab requisition form with patient's name and/ or phone number, physician name and date, if desired (511); lastly (g) placing said vials (105) and said lab requisition form into a specimen bag and send to a laboratory (513). In general, the specimen collection and preparation of said slides (101) are extremely important to accuracy in Pap smears. Randomization or uniform sub-sampling is essential for complete accuracy. The conventional Pap smear technique does not provide for mixing of the sample prior to slide preparation. Due to entanglement of cells in mucus on the sampling device, the cells actually transferred to the slide may not be representative of the total population collected. The cells are
transferred to the slide in relation to where they happen to be on the sampling device and many cells are left on the device.
The non-homogeneity of a typical cervical sample can make conventional smears difficult to prepare, screen and interpret. Large areas of the conventional slide are often covered with debris, inflammatory cells and sheets of epithelial cells that can be obscure valuable diagnostic material. Furthermore, if the smear is not fixed immediately after preparation, cellular morphology can be distorted as the smear dries (air drying artifact). Present invention is a method (2) for converting a liquid suspension of a cervical sample into a consistently stained, homogeneous slides (101) while maintaining diagnostic cell clusters.
In addition, said step of performing vortex of said vials (105) (5) are accomplished by a multi-vial vortexer or vortexer for 5 to 30 seconds which aim to utterly mix the specimen at said vials (105) (515), as disclosed in FIG. 6. In the laboratory, the preserved sample is mixed by vortexing. In approximately 10 minutes, the sample cells in the vials (105) are sedimented by gravity.
On top of that, the step of performing cell deposition (6) comprises of the following substeps: (a) loosing the cap (209) of said vials (105) to enable insertion of a slide (101) into the open first end (107) of said vials (105) wherein the insertion will be performed until said vials (105) are positioned at the center circle of said slide (101) (601); (b) holding said slide (101) and cap (209) of said vials (105), rotating a closed second end (109) of said vials (105) to enable tightening of said cap (209) with said slide (101) (603); and (c) inverting said vials (105) for 10 mins to ensure the cells are sedimented by gravity (605), as mentioned in FIG. 7.
Referring now to FIG. 8, said method (2) further comprises of the steps of performing fixation and Pap staining (7) after step (ii) picking said vials (105) by a first pick and place module (113) and subsequently placing said vials (105) at a second station (205) (303). Firstly (a) removing said slide (101) from the slide holder (201) (701); then (b) transferring said slide (101) to 95% alcohol fixation for 15 minutes (703); and lastly (c) performing Pap staining on said slide (101) (705). Microscopic examination will reveal that the cells have naturally settled onto the slide (101) by gravitation and hence producing a homogenous thin-layer like appearance. Present invention is a method (2) for processing LBC slides (101) which serves as a
replacement for the conventional Pap smear preparation method for use in cervical cancer screemng.
Claims
WHAT IS CLAIMED IS:
1. An apparatus (1) for automatically preparing liquid-based cytology (LBC) slides (101) by means of gravity sedimentation comprises of: at least one carrier (103) for holding a plurality of vials (105) containing specimen wherein said vials (105) comprise of an open first end (107) and a closed second end (109); a slide (101) is coupled with said vials (105) at the open first end (107) of said vials (105), respectively; and at least one first pick and place module (113) to pick said vials (105) from said carrier (103) and transfer said vials (105) to an inverting means (115); characterized in that said inverting means (115) is capable of producing thin-layer LBC slides (101) by inverting or shaking of said vials (105) for 1 to 10 times at an angle of 0° to 360°.
2. The apparatus (1) for automatically preparing liquid-based cytology (LBC) slides (101) by means of gravity sedimentation as claimed in Claim 1, wherein said thin-layer LBC slides (101) comprises of a circle with 10mm to 21mm diameter at the center of said slides (101). 3. The apparatus (1) for automatically preparing liquid-based cytology (LBC) slides (101) by means of gravity sedimentation as claimed in Claim 1, wherein said thin-layer LBC slides (101) are coated with a layer of hydrophilic positive charges or hydrophobic positive charges.
4. The apparatus (1) for automatically preparing liquid-based cytology (LBC) slides (101) by means of gravity sedimentation as claimed in Claim 1, wherein said closed second end (109) of said vials (105) contain cell pellets include gynecological samples or non-gynecological samples.
5. The apparatus (1) for automatically preparing liquid-based cytology (LBC) slides (101) by means of gravity sedimentation as claimed in Claim 1, wherein said apparatus (1) further comprises of a second pick and place module (118) to transfer
said slides (101) to a slide holder (201) upon completion of the inverting process of said vials (105).
6. A method (2) for automatically preparing liquid-based cytology (LBC) slides (101) by means of gravity sedimentation, comprising of the following steps: (i) placing a plurality of vials (105) containing specimen on a carrier (103) at a first station (203) wherein said vials (105) are coupled with a slide (101) inserted at an open first end (107) of said vials (105) (301); and
(ii) picking said vials (105) by a first pick and place module (113) and subsequently placing said vials (105) at a second station (205) (303); characterized in that said second station (205) includes inverting or shaking of said vials (105) by an inverting means (115) for 1 to 10 times at an angle of 0° to 360° to produce thin-layer
LBC slides (101) (305).
7. The method (2) for automatically preparing liquid-based cytology (LBC) slides (101) by means of gravity sedimentation as claimed in Claim 6, wherein said method (2) further comprises of the following steps after step (ii) picking said vials (105) by a first pick and place module (113) and subsequently placing said vials (105) at a second station (205) (303):
(a) transferring said slides (101) into a slide holder (201) by a second pick and place module (118) after the completion of the inverting process of said vials (101)
(307);
(b) transferring said vials (105) into a disposable station (207) by said first pick and place module (113) (309);
(c) repeating step (ii) picking said vials (105) by a first pick and place module (113) and subsequently placing said vials (105) at a second station (205), for continuous preparation of LBC slides (101) (311); and
(d) repeating step (i) placing a plurality of vials (105) containing specimen on a carrier (103) at a first station (203) wherein said vials (105) are coupled with a slide
(101) inserted at an open first end (107) of said vials (105) (301), upon completion of the
step (c) repeating step (ii) picking said vials (105) by a first pick and place module (113) and subsequently placing said vials (105) at a second station (205), for continuous preparation of LBC slides (101) (313).
8. The method (2) for automatically preparing liquid-based cytology (LBC) slides (101) by means of gravity sedimentation as claimed in Claim 6, wherein said method
(2) further comprises of steps of performing specimen collection (4), performing vortex of said vials (105) (5), and cell deposition (6) prior to step (i) placing a plurality of vials (105) containing specimen on a carrier (103) at a first station (203) wherein said vials (105) are coupled with a slide (101) inserted at an open first end (107) of said vials (105) (301).
9. The method (2) for automatically preparing liquid-based cytology (LBC) slides (101) by means of gravity sedimentation as claimed in Claim 6, wherein said step of performing specimen collection (4) comprises of the following substeps:
(a) inserting a broom-like device into an endocervical canal of a cervix and applying gentle pressure until bristles of said broom-like device form against said cervix (401);
(b) maintaining the gentle pressure and holding a stem between the thumb and forefinger (403);
(c) rotating a brush of said broom-like device 3 to 5 times in a clockwise direction (405); (d) placing said thumb against the back of said brush pad and subsequently disconnecting said brush from said stem into vials (105) (407);
(e) placing a cap (209) on said vials (105) and tighten it (409);
(f) labelling said vials (105) and executing a lab requisition form with patient's name and/ or phone number, physician name and date, if desired (511); and (g) placing said vials (105) and said lab requisition form into a specimen bag and send to a laboratory (513).
10. The method (2) for automatically preparing liquid-based cytology (LBC) slides
(101) by means of gravity sedimentation as claimed in Claim 6, wherein said step of performing vortex of said vials (105) (5) are accomplished by a multi-vial vortexer or
vortexer for 5 to 30 seconds which aim to utterly mix the specimen at said vials (105) (515).
11. The method (2) for automatically preparing liquid-based cytology (LBC) slides (101) by means of gravity sedimentation as claimed in Claim 6, wherein said step of performing cell deposition (6) comprises of the following substeps:
(a) loosing the cap (209) of said vials (105) to enable insertion of a slide (101) into the open first end (107) of said vials (105) wherein the insertion will be performed until said vials (105) are positioned at the center circle of said slide (101) (601);
(b) holding said slide (101) and cap (209) of said vials (105), rotating a closed second end (109) of said vials (105) to enable tightening of said cap (209) with said slide (101) (603); and
(c) inverting said vials (105) for 10 mins to ensure the cells are sedimented by gravity (605).
12. The method (2) for automatically preparing liquid-based cytology (LBC) slides (101) by means of gravity sedimentation as claimed in Claim 6, wherein said method
(2) further comprises of the steps of performing fixation and Pap staining (7) after step
(ii) picking said vials (105) by a first pick and place module (113) and subsequently placing said vials (105) at a second station (205) (303):
(a) removing said slide (101) from the slide holder (201) (701); (b) transferring said slide (101) to 95% alcohol fixation for 15 minutes (703); and
(c) performing Pap staining on said slide (101) (705).
13. The method (2) for automatically preparing liquid-based cytology (LBC) slides
(101) by means of gravity sedimentation as claimed in Claim 6, wherein said vials (105) further comprises of a closed second end (109) which contains cell pellets include gynecological samples or non-gynecological samples.
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