MXPA00002019A - Method and apparatus for automatically forming monolayers from particulate matter separated from fluid samples - Google Patents

Method and apparatus for automatically forming monolayers from particulate matter separated from fluid samples

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Publication number
MXPA00002019A
MXPA00002019A MXPA/A/2000/002019A MXPA00002019A MXPA00002019A MX PA00002019 A MXPA00002019 A MX PA00002019A MX PA00002019 A MXPA00002019 A MX PA00002019A MX PA00002019 A MXPA00002019 A MX PA00002019A
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MX
Mexico
Prior art keywords
group
container
sample
slide
containers
Prior art date
Application number
MXPA/A/2000/002019A
Other languages
Spanish (es)
Inventor
Raouf A Guirguis
Frederick J York
Roland T Stafford
John M Christensen
Original Assignee
Lamina Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Lamina Inc filed Critical Lamina Inc
Publication of MXPA00002019A publication Critical patent/MXPA00002019A/en

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Abstract

An automated apparatus and method for batch processing a group of samples in respective containers. A monolayer of particulate matter is filtered from each sample and desposited on a corresponding slide for examination. A controller coordinates each mechanism and sub-assembly of the apparatus, which comprises:a container support arranging a group of containers (20);a conveyer advancing said container support;a group of heads engaging respective containers at said head stage;a pump;a group of filters corresponding to said group of heads, each of said filters communicating with said flow of its respective sample and including:a membrane in a first branch of the sample flow and adapted for collecting a monolayer of particulate matter and a frit being interposed in a second branch circumventing said membrane;a slide support arranging a group of the slides in a second pattern, and a second conveyer advancing said slide support to a deposit stage.

Description

? METHOD AND APPARATUS FOR FORMING MONOCAPAS AUTOMATICALLY FROM PARTICULAR MATTER IN SEPARATE PARTICLES OF FLUID SAMPLES BACKGROUND OF THE INVENTION Field of the Invention The present invention is directed to apparatus and methods for collecting a uniform monolayer of particulate matter. In particular, the present invention is directed to automated and semi-automated devices and methods for collecting a uniform monolayer of cells from body fluids and to preparing the cell monolayer for use in cytological protocols.
Description of the Related Art In a wide variety of technologies, the ability and / or ease of separating matter, typically particulate matter, from a fluid is a critical component in the ability to test the presence of substances in said fluid. fluid. Very often, the interference associated with sample preparation hampers target cells to a degree that the process is not reliable enough, or is too costly. Such a scenario applies to many other fields that involve detection and / or diagnosis, including environmental sampling, radiation research, cancer filtering, cytological examinations, microbiological sampling and contamination with hazardous waste, to name but a few. In the case of cytological examination, a sample of cells is obtained from a patient. Typically, this is done by scraping an area, as in the case of cervical samples, or by collecting body fluids, such as those obtained from the chest cavity, vesicle or spinal canal, or by aspirating with a fine needle In a conventional manual cytological examination, the particulate matter including the cells or tissues in the fluid is transferred to a glass slide by smear and subsequently dried with air. The smear results in uneven densities and uneven distributions of cells and tissues that often obstruct the target cells. Drying with air causes distortion in the cell and prevents subsequent successful examination. In a conventional automated cytological examination, the sample should be rotated in a centrifuge to concentrate the cells, the supernatant should be removed and the cells should then be mixed in a fluid carrier. This process consumes time, often requiring 30 minutes or more per sample, and requires the transfer of the target cells to several containers that must be both cleaned and discarded for each sample, thus increasing the likelihood of contamination. In addition, an experienced person will need to subjectively evaluate the resulting liquid suspension and decide if the process needs to be repeated. A filter is then placed in the liquid suspension to disperse and capture the cells with the filter, again increasing the risk of contamination. The filter is then removed and placed in contact with the microscope slide for observation. In all this effort, the limiting factors in the sample preparation protocol include adequate separation of particulate matter from its carrier liquid (ie, physiological, biological, and environmental fluid) and easy collection and efficiency and concentrate the matter in the form of particles in a readily accessible form for examination by the microscope. The prior art includes various methods, apparatuses and structures for dispersing the cells in the fluid. For example, US Pat. No. 5,143,627 opens the sample container, inserts a dispersion element into the liquid suspension, and the dispersion element is rotated for several minutes. In another example, EP 0 740 142 A exhibits a blood preparation system including ways of sending a blood sample through a tube; Ways to measure the time in which blood flows through a certain length of tube to produce a measure of time; and ways to use this measure of time to control subsequent operations on the blood sample. The time measurements control at least one of the amount of blood in the drop, the angle and velocity of the smear. In another example of the above, the Saccomanno method is used to process sputum, a process that is time consuming and involves a large number of processing steps. It has been found that the rapid processing of urine to obtain fresh cells ensures the accuracy of quantitative results and the analysis of urine. Fresh cells tend to adhere to a glass slide in a much better way than cells in the preserved urine, allowing a more smooth distribution of the cells in the vitreous body. Delays in processing, careless adjustments and lack of refrigeration can lead to a non-optimal preparation of the slide. A known solution for the problem of delay is the use of chemical preservatives in the urine. However, the presence of liquid preservatives in the urine specimen increases the specific gravity of the specimen to immeasurable levels and may limit the potential usefulness of urine for several types of traditional quantitative analyzes, such as that of the microscope slide.
Microbiological diagnosis and / or cytology, particularly in the area of clinical pathology, base their diagnoses on a microscopic examination of cells and other microscopic analyzes. The accuracy of diagnoses and the preparation of optimally interpretable specimens typically depends on proper preparation of the sample. New methodologies such as immunocytochemistry and image analysis require preparations that are reproducible, rapid, that are free of biological risks and that are cheap. Conventional cell preparation techniques do not adequately meet the goal of non-uniform cell densities, uneven cell distribution and air-drying artifacts. A number of urine containers or other specimens of biological fluids have been developed to allow liquid biological specimens to be tested without removing the container cover of urine or biological fluid. None of the above forms solves the problem of the cellular transfer of a uniform layer onto a slide for examination while at the same time preserving the fluid from which the cells were taken. Conventionally, body fluid samples are collected for cytological examination using containers containing a preservative solution to preserve the cytological specimen during shipment from the collection site to the cytology laboratory. In addition, cytological specimens collected from the body cavities using a cotton swab, a paste, a flow or a brush are also preserved in containers with fixatives (ie, alcohol or acetone) before transferring the cells to the slide or membrane for pigmentation. or exam. It is desirable to provide a container of urine or other specimen of biological fluid that allows specimens of biological liquids to be tested without removing the cover of the urine container or biological fluid. However, none of the above forms solves the problems of transferring cells from a monolayer onto a slide for examination without submerging portions of the device in the sample (and increasing the risk of contamination), consistently and repeatedly forming a high quality monolayer. on the microscope slide, and processing the sample in such a way as to preserve the fluid from which the cells were taken. Another limiting factor in the optimal preparation of matter in the form of particles for microscopic examination involves the solution and / or solutions for fixing the material to a microscope slide or the like. The cytological specimens, which constitute the examinable form of the cytological material, can be prepared by means of a well-understood dab or fluid techniques. Because there may be a considerable amount of time before the specimens are subsequently processed by the pigmented, it is important to apply a fixative to the cytological material as a means of preserving and fixing the cells. The proper (ie preserved) fixation of cytological material such as cells, cell aggregates and small fragments of tissue derived from the cytological collection of human or animal tissue is a prerequisite for accurately diagnosing a disease, especially cancer. The cytological material should be fixed as soon as possible after obtaining the material to prevent cell distortion. Cytological specimens pigmented with tetrachrome tincture and air dried, although popular abroad, are not generally used in the United States. Instead, a method of cellular fixation by moisture is used, either by immersing the slides in an alcohol solution, or by saturating the slides with a fixative spray, or directly discharging the cytological material in an alcohol solution. . Cellular fixation is a prerequisite for the interpretation of Papanicolaou, Hermatoxylin and Eosin or other slides of pigmented cytological specimens. Generally, alcohol solutions, with or without other additives such as polyethylene glycol, ranging from 50% to 95% (v / v: methanol, ethanol, isopropanol) are known solutions for use in wet fixation. However, when alcohol solutions greater than 50% (v / v) are used to collect and fix fluids high in protein, a protein sediment is formed that subsequently hardens. The sedimentation of the protein makes the fixed cytological material difficult to transfer to a glass slide for examination, regardless of whether the transfer is carried out by direct application to the glass slide, by cytofiltration through a pore filter. small, or by cytocentrifugation towards glass slides covered with an adhesive such as chromium aluminum gelatin. For almost a century, the fixative compositions for tissues used to preserve and prepare tissues for analytical evaluation have been based on formaldehyde. The normal composition used for the preservation of tissue and the preparation of thin-cut tissues for microscopic examination is Formalin. Formalin is a solution of 3 to 10 percent formaldehyde in water, which generally contains 15 percent methyl alcohol. Alcohol improves the preservative properties of the solution. Despite numerous disadvantages, in which high toxicity and irritant properties are found, formalin remains as the alternative of fixation in typical laboratory applications due to its rapid reaction when exposed to tissue surfaces and the consequent preservation maximized cellular Methanol can adversely affect the texture of a fabric, making it very brittle, or more generally, too soft to be cut during the preparation of the slide. It can also produce spots or impurities that interfere with pigmentation. However, formalin containing methanol provides preserved tissues that can be sectioned satisfactorily and pigmented for microscopic examination. Histologists have long strived to develop effective immunohistochemical fixatives and morphological fixatives. It is also desirable to preserve morphological details of preserved tissue antigens to allow the detection and immunohistochemical localization of the antigens in the tissues. Said fixers produce indissoluble proteins. For example, formaldehyde can be used as a crosslinking agent that forms covalent bonds between the groups of aldehydes and specific amino acids to stabilize the protein structure and transform the cytoplasm of the cell into a gel that prevents the movement of autolytic enzymes. Alternatively, alcohol can be used as a fixative to precipitate the protein by denaturing. A fixative, preferably, should retard autolysis and putrefaction and preserve morphological detail and antigenicity. Unfortunately, a morphologically effective fixative is not necessarily an immunohistochemically effective fixative. In contrast to conventional techniques, the solid matter preparation techniques of the present invention handle the elements of non-uniform matter densities, uneven distribution of matter and sample loss and contamination due to the number of steps involved in sample preparation. . Thus, the preparations according to the present invention result in an even distribution of solids having a superior morphology, in an improved visualization, and are made readily available for analysis by light absorption without the need for further manipulation in the preparation. of the sample.
COMPENDIUM OF THE INVENTION The present invention relates to the apparatuses and methods for collecting matter for its detection, analysis, quantification and / or visualization. The automated devices and methods of the present invention are particularly suited for the separation of matter from biological, physiological and environmental fluids and for the presentation of particulate matter in an improved form for cytological examination.
The present invention relates to automated and semi-automated devices and methods for the collection of uniform layers of particulate matter from fluid specimens in a collection apparatus or test module, and for the transfer of the uniform layer of material in the form of particles towards a slide. Said apparatus, in accordance with the present invention, solves problems associated with conventional equipment for the collection of cells and other particles for cytology, providing a mechanism of relatively simple structure and operation that separates the particles from a liquid solution, collects a approximately known amount of cells in a monolayer and transfer the collected cells to a microscope slide. In some embodiment of the present invention, no elements of the apparatus are placed in the liquid sample, thus preventing unnecessary contamination of the sample. Furthermore, in some embodiment of the present invention, the sample container does not open during the course of collection and transfer of the cells, thus eliminating the possibility of contamination of the sample by the apparatus. In all embodiments of the present invention, a monolayer of the particulate matter is collected from the sample (ie, cells) to a filter by passing two branches through the filter. Said filter is known as US Pat. Nos. 5,139,031, 5,301,685 and 5,471,994. According to one embodiment of the present invention, the collection of a monolayer of cells for cytological examination allows obtaining a uniform cell slide without contamination of the cells by conservators, workers or external material. The transfer of cells from a sample container to the cytological collection apparatus can be carried out without emptying or tubing the collected specimen. The present invention is also directed to a cellular collection container system that can be easily disassembled to allow a face-to-face transfer of cells from the device to the microscope slide for examination. The cell collection container, according to one embodiment of the present invention, provides an apparatus and method for collecting a monolayer of cells that can be transferred to a microscope slide. The apparatuses and methods according to the present invention omit the need for a trained technician to adequately prepare the sample substrate. Hence, the need for time, expense and experience as critical factors in sample preparation protocols is eliminated or reduced.
The apparatuses and methods of the present invention also provide advantages in the preparation of samples because they are suitable for the use of fresh, untreated or unmodified cells and are particularly designed to provide a uniform and thin layer of solid matter (up to approximately 40 microns or more). One embodiment of the present invention is particularly useful for harvesting cells for a pap smear. According to another feature of the present invention, the material collection apparatus may also include additional, removable or integrated modules for the treatment of the sample fluid. For example, the sample fluid can be treated with a material collection module, in combination with a waste removal module, a chromatographic module, a test module, or combinations of these and other devices. These and other treatment modules or protocols provide features that may be desirable to incorporate into a sample preparation apparatus in accordance with the present invention. Examples of suitable devices include those US patents such as 4,953,561; 5,224,489; 5,016,644; 5,139,031; 5,301,685; 5,042,502; and 5,137,031. For example, the apparatuses and methods of the present invention have many advantages to conventional microbiology and hematology. The collected cells are in a predetermined area that is easily accessible to a radiant light source and a wavelength absorption meter. Because the cells are concentrated in a single layer, they are almost always in a focal plane, eliminating or reducing the interference of other particles and virtually eliminating the time and experience of the technician in establishing an adequate reading. The minimal overlap of matter achieved by the present invention ensures that all matter can be easily examined with very little opportunity for critical solids to be obscured by groups of solids or debris. Certain parts of the apparatuses of the present invention can be used in combination with other automated devices to detect and analyze any solid material in a given population. They also allow a detailed analysis of the chemical composition of the material. In tests using the present invention, transferring the cells from the monolayer from the filter to the microscope slide has been shown to be extremely effective without differential cell loss. Examination under the microscope shows that the distribution of cells is substantially the same on the slide as on the filter. An automatic apparatus according to certain embodiments of the present invention concurrently processes a plurality of sample containers mounted on a common transport. In preferred embodiments of the present invention, the cover over the sample container may include a hollow tube with or without a rotating dispersion element. The present invention agitates the sample of the container to ensure the rupture of matter with large particles, i.e. mucosal bodies in the case of sputum samples and even distribution of cells in the fluid. Stirring may occur as the result of a relative movement between the components of the sample container, non-uniform movement of the sample container and / or inertial reaction forces applied to the sample by the container. According to the preferred automatic embodiments of the present invention, the samples, their containers and filters are subject to a number of different movements that include a relative rotation of a dispersion element with respect to the fluid of the sample. Additionally, these preferred embodiments of the present invention can transport the containers to and from a cellular transfer processing stage, such as by a rotation and / or translation movement, and can also perform movements to eliminate the filters and bring them into contact with a slide of the microscope. In a preferred embodiment of the invention, the automated apparatuses include a platform including a plurality of filters, a platform for the placement of a plurality of specimen containers, a platform for the placement of a plurality of microscope slides and filters, a filter charger adjacent to the filter platform, a microscope slide charger adjacent to the microscope slide platform, a microscope slide discharger adjacent to the microscope slide platform, and a control system for operating, monitoring and sequence the different assemblies. The control system monitors the particle collection operation in the form of particles by monitoring the liquid loose parameters to determine when a predetermined amount of particles has been collected in the filter. A top assembly of the instrument places the filter device, with the collected cells on the filter surface, for a splice against the microscope slide. It is important for the method and apparatuses of the invention that the cells maintain the distribution of the monolayer from where they were collected in the filter while the cells are transferred from the filter to the microscope slide. The invention thus provides means for transferring and collecting cells and producing a monolayer of cells on the microscope slide. An instrument according to the present invention preferably employs a fresh sample vial, an unused filter, and an unused microscope slide for each individual cell specimen. In addition, the relatively simple operation, and the multiple functions performed by the instruments, minimize the operator's attention requirements in terms of time, as well as the minimization of maintenance and preparation. One embodiment of the invention includes a mobile platform for the sample container, a container having a cover adapted to interconnected in a coupled manner a filter, a mobile filter platform, one or more microscope slide chargers / arresters adapted to link the filter, and a microscope slide placed on the slide charger / unloader. A preferred embodiment of the invention includes multiple iterations of each of the sub-assemblies described above, such that preferred automated apparatuses according to the invention, can process at least two and typically five or more, specimens at the same time or sequentially. In the description that follows, additional objects and advantages of the invention will be published, which in part will be obvious from the description, or which can be learned through practice. The objects and advantages of the invention can be carried out and obtained by means of the instrumental and combinations particularly indicated in the attached claims BRIEF DESCRIPTION OF THE DRAWINGS The accompanying drawings, which are integrated and constitute a part of the specification, illustrate a present preference of the invention, and, together with the general description given above the detailed description given below, serve to explain the principles of the invention. Figure 1 is an expanded side view of the first filter assembly according to an embodiment of the invention. Figure 2 is a side view of the filter assembly in its closed position according to an embodiment of the invention. Figure 3 is a side view of an exemplary specimen container, including a mechanism for agitation, according to one embodiment of the invention. Figure 4 is a top view of a detail of the filter assembly according to an embodiment of the invention. Figure 5 is a bottom view of a detail of the filter assembly according to an embodiment of the invention. Figure 6 is a top view of the first embodiment of the invention.
Figure 7 is a side view of the first embodiment illustrated in Figure 6. Figure 8 is a top view of the specimen container holder according to the first embodiment of the invention illustrated in Figure 6. Figure 9 is a side view of the assembly illustrated in Figure 8 Figure 10 is a top view of the turntable of the microscope slide according to the first embodiment of the present invention illustrated in Figure 6. Figure 11 is a side view of the assembly illustrated in FIG. Figure 10. Figure 12 is a top view of the filter magazine according to the first embodiment of the present invention illustrated in Figure 6. Figure 13 is a side view of the assembly illustrated in Figure 12. Figure 14_a is a top view of the microscope slide unloader according to the first embodiment of the invention illustrated in Figure 6. Figure 14_b is a side view of the assembly illustrated in Figure 14_a Figure 15 is an extended side view of the detail of the filter assembly and a specimen container according to the first embodiment of the invention illustrated in Figure 6. Figure 16 is a top view of the carrier unloader of the microscope according to the first embodiment of the invention illustrated in Figure 6. Figure 17 is a side view of the assembly illustrated in Figure 16 Figure 18 is a top view of the agitation assembly according to the first embodiment of the invention illustrated in Figure 6. Figure 19 is a perspective view of a second embodiment of the invention. Figure 20 is a front elevation view of the second embodiment illustrated in Figure 19. Figure 21 is a right side view of the second embodiment illustrated in Figure 19. Figure 22 is a left side view of the second embodiment illustrated in FIG. Figure 19 Figure 23 is an elevated rear view of the second embodiment illustrated in Figure 19 Figure 24 is a planar top view of the second embodiment illustrated in Figure 19 Figure 25 is a detailed perspective view of the container support according to the second embodiment illustrated in Figure 19 Figure 26 is a detailed perspective view of the first conveyor belt according to the second embodiment illustrated in Figure 19 Figure 27 is a detailed front view with elevation of the Sampling according to the second embodiment illustrated in Figure 19 Figure 28 is a cross-sectional view of the detail of the sampling station eo illustrated in Figure 27 Figure 29 is a top planar detail view of the slide charger according to the second embodiment shown in Figure 19; Figure 30 is a perspective detail view of the illustrated slide charger; in Figure 29. Figure 31 is a cross-sectional detailed view of the blotter paper according to the second embodiment illustrated in Figure 19 Figure 32 -A is a schematic illustration showing a group of containers transported to the sampling station of According to the second embodiment illustrated in Figure 19 Figure 32-B is a schematic illustration showing a group of sampling heads in fluid communication with the corresponding containers in the sampling station according to the second embodiment illustrated in the Figure 19. Figure 32C is a schematic illustration showing monolayers of particulate matter of respective samples and being transferred to a group of slides corresponding to their respective heads according to the second embodiment illustrated in Figure 19 Figure 33 is a schematic illustration of a fluid management system according to the first modal Figure 6 is a schematic illustration of a fluid handling system according to the second illustrated embodiment of Figure 19. Figure 35 is a detailed schematic illustration of a fluid handling system illustrated in FIG. Figure 34 Figure 36 is a detailed schematic illustration of the fluid handling system according to the second embodiment illustrated in Figure 19. Figure 37 is a schematic illustration of a control system according to the present invention. Figure 38 is a workflow diagram according to an example of the present invention. Figure 39 is a cross-sectional view of the third embodiment of the invention. Figure 40 is a top planar detailed view of the third embodiment illustrated in Figure 39. Figure 41 is a top planar detail view of the third embodiment illustrated in Figure 39. DETAILED DESCRIPTION An apparatus according to the present invention is a collection automated assembly or mechanisms for the batch processing of samples. The apparatus, according to the present invention, is particularly useful for removing matter in the form of particles from a liquid and for transferring said matter to a microscope slide or other element for cytological examination. During the operation of the automated apparatus, the processing of the liquid, particulate material or sample container can be included or involved in one or more of the following steps or steps: opening the container used to ship or transport the container. shows the site where the automated device is located; Attach a sample container cover that extends towards the sample; the removal of at least a portion of the sample from the container by the filter by means of a portion of the particulate matter contained in the sample and adhering to a membrane in the filter assembly; provide a slide of mobile microscope in an adjacent position, aligned with and / or resting against a portion of the filter assembly. In addition, the mechanisms and / or the subexetables may include: one or more subassemblies to replace a used microscope slide with an unused one; a transmission of movement to shake the sample; one or more filter chargers; one or more filter unloaders; one or more microscope slide chargers; one or more microscope slide unloaders; one or more bar code readers; one or more bar code printers; one or more transport mechanisms for moving and / or placing one of the structures mentioned above; one or more supports for retaining, positioning and moving one or more of the structures mentioned above; one or more motors for moving or placing one or more of the structures mentioned above; one or more control systems for operating, preferably selectively and / or sequentially, one or more of the various structures mentioned above. The present invention also involves a method for processing a liquid containing matter in the form of a particle, that is, cells, using an automated device configured in accordance with the invention. The present invention also involves removing matter in the form of particles from a liquid and collecting the matter in an appropriate medium for cytological examination. The present invention also includes automated devices and methods for collecting biological physiological or environmental fluids, removing particulate matter from fluids without centrifugation and diagnosing and testing the material. As used herein, "sample" refers to any fluid in combination with a solid material, such as particulate matter and from which it may be desirable to collect the component particles from the sample for the purpose of establishing their identity or presence in the sample. the sample. Typically the fluid component of the sample will be a liquid. However, the fluid can also be air or gas. As an example, it may be desirable to determine the presence of cancer cells or certain proteins in the biological fluid, such as urine. In another example, it may be desirable to evaluate the nature of contaminants, such as molecular contaminants in ultra pure water used in the electronics industry. Other fluids include but are not limited to fluid bodies, such as blood, spinal fluid, or amniotic fluid; bronchial lavage, sputum; fluids extracted from a fine needle, underground layers, fluids for industrial processes; or medical or electronic dialysis fluids to mention just a few. It is intended that the type of fluid being processed should not limit the invention. As used herein, 'particulate matter' refers to any substance in a fluid that can be collected and evaluated, preferably for cytological examination. The example material includes, but is not limited to cells or cell fragments, proteins, molecules, polymers, rubbers, stabilizers, antioxidants, accelerators, silicones, alkaloids, thiocoles, paraffins, thermoplastics, bacteria, pesticides and herbicides. Examples of specific polymers may include, but are not limited to, polyethylene, polypropylene, polyisobutylene, polyacrylonitrile, polyethylene glycol, polyvinyl chloride, polystyrene, polymethyl methacrylate, polyethylene terephthalates, bisphenol A (a common environmental contaminant), ethyl cellulose, nitrocellulose, polyurethane and nylon. Some specific biological materials include cancer cells, including a distinction between metastatic and normal cancer cells; protein, nucleic acids, antibodies or the like. It is intended that the type of material to be processed does not limit the invention. As used herein, 'adapted for communication', 'communication' or similar terms *, refers to any means, structure or methods for establishing fluids of fluids through the system, as they are well known to connoisseurs. Examples of structures are shown in the Figures. For example, a conductor may have a connector / adapter to receive or connect to a paired connector in another conduit. As used herein, "connector" refers to any structure used to form a joint or to join another part. These connectors or connections establish a flow path through various elements of the apparatus, assembly or system. Some typical connections include but are not limited to paired connections, such as Luer type, screw type, friction type or connectors that are linked. As used here, 'adapted for link', 'linked', 'linking' or similar terms, refer to complementary structures that can be aligned, meshed, matched or supported by one another. Some example structures include the connectors described above. As used herein, "batch processing" refers to an operation or operations that are capable of being carried out simultaneously and independently in more than one sample without cross-contamination between the samples. As used herein, 'group' refers to a number of examples of a feature on which it acts identically and concurrently or is used in the course of batch processing. A partial group refers to at least one, but less than a finite maximum number of examples of the characteristic, and a full group refers to a finite maximum number of examples of the characteristic. Sample container and cover In accordance with the invention, a sample is collected using conventional techniques, that is, by collecting urine or other biological fluid in a specimen container, or by placing a cotton or brush in an appropriate fluid in the specimen container ( which is typical in a smear for Papanicolaou). In the most preferred embodiment of the invention, the specimen or sample is collected in a sampling container having the design and function described below. The sampling container is generally covered, and has a portion that may be suitable for bonding a filter as will be described below. In preferred embodiments of the invention, a specimen cup includes a chamber for collecting a liquid specimen and a cover to establish fluid communication between the chamber and the filter to separate the particulate matter from the fluid and collect the material at a site. of collection. In most preferred embodiments of the invention, the separated particulate matter is collected in a monolayer on a membrane according to the invention. Preferred embodiments of the invention also include a cover having a hollow tube which establishes fluid communication between the sample and the filter. More preferably, the hollow tube includes ways of mixing the specimen and / or dispersing the particulate matter in the specimen. In accordance with the preferred embodiments of the invention, a specimen container (20) includes any container suitable for holding a fluid, preferably a biological fluid. The container (20) includes the side walls (21) and the bottom wall (22) which, in combination, provide a chamber (23) having an open end (24) for collecting, maintaining and storing a fluid. Typical fluids include, but are not limited to, biological fluids, such as body fluids, waste water or the like. Some typical body fluids include urine or other biological fluids, such as blood, cerebrospinal fluid (CSF), bronchial lavage, sputum, or fluid obtained with a fine needle. The configuration and materials used to make the cup can be any of a variety of materials, shapes and sizes. For example, the cup can be constructed of any material compatible with the fluid to be processed. It will be appreciated that the container and the assembly of the side walls to the bottom wall can be any conventional assembly. In more preferred embodiments of the invention, the lower wall (22) is a conical member, as shown in Figure 3. Optionally, the lower wall (22) or the side wall (21) may include one or more fins (not shown) that extend into the camera. Said fins may be a desirable part of the invention, described in more detail below, in which the container sample is mixed by rotation thereof. In a preferred embodiment of the invention, the container cover includes a central portion adapted to receive the filter assembly. In some embodiments of the invention, the central portion also communicates with or connects to a hollow tube that extends into the specimen container. Optionally, a portion of the tube may include a dispersing or stirring element. As shown in Figure 3, a specimen container (20) includes a tube (25) or the like to extract the sample from the container (20). Preferably, the tube (25) should be hollow and open at both ends. The tube (25) as illustrated, includes an open end (26) near the bottom of the container (20) and may include one or more openings (27) in the tube (25). The open end (26) and / or the openings (27) allow different layers of fluid to be tested simultaneously, as well as particulate matter and sediments when the sample is removed from the collection chamber (23) In other embodiments Preferred embodiments of the invention, an adaptation between the container and a respective sampling head is interposed and forms at least a portion of the filter chamber. The adaptation can be included with each container, or a group of adapters can be associated respectively with the corresponding group of sampling heads. It is also important to provide structures and means for rotating an agitator in relation to the container and / or displaying it in the container. As described in more detail below, an exemplary device, in accordance with the present invention, may include a cover within a cover, wherein the agitator is attached to a stationary inner cover and the container and outer cover rotate freely. Said relative movement moves the agitator in relation to the sample and disperses the matter in the form of particles in the fluid. A device according to the present invention can also include structures that are configured and / or adapted to mix the collected specimen in a collection chamber. Some examples of structures include, but are not limited to, a collection chamber that has a rotating cover, or a portion of the cover that rotates; a cover or portion of cover that is movable in relation to the collection container; and a tube or something similar that extends to the collection container, in which said tube will include one or more elements that mix the specimen. The cover may also include a portion that is appropriately linked to a portion of the cover in an airtight seal of the liquid. The cover may also include a portion that is appropriately linked to a portion of the cover in a liquid-hermetic and non-fluid-tight seal. In a preferred embodiment of the invention, a specimen cup includes a chamber for collecting a liquid specimen, a fluid communication with the chamber, a particle separation chamber in the form of particles or a module for separating particulate matter. of the fluid and collect the separated matter in a collection area. In most preferred embodiments of the invention, separate material is collected in a monolayer in the collection zone. A preferred embodiment of the invention also includes a hollow tube in fluid communication with the material separation chamber in the form of a particle. More preferably, the hollow tube includes shapes for mixing the specimen and / or dispersing the particulate matter of the specimen. Some example forms include, but are not limited to, an agitator, fins, brush, cotton, brush, spatula or the like. A preferred embodiment of the invention includes a tube having a brush. An example brush is included in U.S. Patent 4,759,376. In accordance with the present invention, the hollow tube (25) includes at least one projection or fin agitator (28) or something similar, as shown in Figure 20. In a preferred embodiment of the invention, the hollow tube (25) is rotatable and the agitator (28) beats the liquid specimen, and in most preferred embodiments , disperses the cells and / or the matter in the form of particles and / or decomposes any large matter such as the mucous bodies. The agitator (28) can also include a body that is independent of the tube (25) and that is induced by a magnetic or electric field to agitate the sample. In an alternate embodiment of the invention, the agitator (28) may include fibers, a brush, cotton or brush or something similar. Preferably, said fiber or brush should be suitable for dispersing the particulate matter in a container when the sample is rotated in relation to the agitator, brush or brush. In a more preferred embodiment of the invention, the brush or brush is also suitable for collection of a patient's material, that is, a cervical brush or brush. It is intended that the brush can be fixed to a portion of the cover, or that the cover can include a slot for rigging a part of the hand at the other end of the brush. In a preferred embodiment of the invention, a slot or opening of the cover can be covered with a removable or penetrable cover that protects the inside of the contamination container until the container is ready for use. For example, a brush or something similar can be used to collect a cervical sample, the cover can be removed and the brush can be placed in the container. As mentioned above, an upper portion of the container and a lower portion of each head can be matched to form a filter chamber. The containers and heads can be configured in various ways. Some example configurations are shown in Figures 2-5. In preferred embodiments of the invention, the chamber (30) includes a base portion (31) formed in part from a link with the cover of the specimen container (20). The base portion (31) defines a wall (32) suitable for placing a filter assembly (33). The wall (32) is provided with a channel (34) communicating with the hollow tube (25). The wall (32) can be an integral base structure (31), or it can be a separate structure. In preferred embodiments of the invention, the wall (32) is a separate structure that is capable of rotating in the base (31). In order to achieve a relative rotational ease while maintaining an assembly with a fluid tightness, the wall (32) can be linked to the base (31) by a tongue and a groove (see Figure 2). As shown in Figures 2 and 3, the filter chamber (30) is preferably a two-piece shell formed by an upper part (41) at the lower end of the head, and a portion of the base (31) at a part of the specimen container. In preferred embodiments of the invention, the upper portion (41) releasably links the base portion (31); any configuration or housing assembly that provides access to the porous array (35) is appropriate. The upper portion (41) and the base portion (31) may be connected or fastened to each of them by any tying connection or by forms that provide a hermetically liquid fit, ie, Luer type (with or without thread). thread), screw type, friction or chamfer connection or a fitting. According to preferred embodiments of the invention, the wall (32) of the base (31) includes a location (60) with one or more spaced projections (61) or something similar.
The projections (61) will preferably be of a size and shape sufficient to prevent porous arrays (35) of well-supplied contact locations (47). In the illustrated embodiment, the projections (61) are concentric rings (see Figure 4). As will be described in more detail below, the projections (61) break the surface tension between the porous arrangements (35) and the locations (60) in such a way that, during use, when removing the porous array (35) from its location (60), the first porous means (36) does not remain in contact with the locality (60). In a preferred embodiment of the invention, the projections (60) function in one or more of the following ways: The projections (60) can break the surface tension between the porous arrays (35) and the locality (39) in such a way that , during its use, when the porous arrangement (35) is removed from the locality (39), the first porous medium (36) does not remain in contact with the locality (39); The projections (60) can distribute pressure uniformly of the porous arrangements of the casing; the projections (60) can prevent or suppress compression of the porous array; and the projections (60) can be configured to distribute any particulate matter collected in a predetermined configuration or spatial distribution. According to the present invention, the surface of the location (39) may include one or more structures, configurations or surface textures that promote the ability of the porous array to be released from the location, which promotes a predetermined spatial distribution of the material in the form of particles at the site of collection, and / or prevent or suppress compression of the porous array. One embodiment of the invention includes concentric projections, such as the projections (60) described above. In a more preferred embodiment of the invention, the surface of the locality is configured in a structure in the form of a clock or a solar dial. Both embodiments, as well as other surface configurations disclosed herein, promote the collection of particulate matter at the collection site in a predetermined spatial arrangement. Other configurations include, but are not limited to, a grid, a transverse hatching or the like, to concentric rectangles or squares, or to a series of continuous or separate structures, protuberances, granulations or the like. It is intended that any element, structure or chemistry that provides a texture to the surface of the locality be appropriate for use in the present invention. According to another embodiment of the invention, the location (39) and / or the lower portion (32) may optionally include a channel or something similar. In a preferred embodiment of the invention, the location (39) slopes slightly out of the channel. The slight slope of the locality and the channel, promote an improvement in the flow of fluid through the housing and decrease the surface tension of the locality, promoting both the ability of the porous arrangement to uncouple from the lower portion (32) of the Porous arrangement shell. This aspect of the invention is another structure (s) that promotes the release of the porous array. In a preferred embodiment of the invention illustrated in Figure 5, the filter chamber includes an upper portion (41) that connects the base (31), and in combination, forms the filter chamber (30). The portion (41) includes a locality (42) or the like configured to link the porous array (35) in preferred embodiments of the invention, the locality (42) places the porous array (35) in the wall (32) in such a way that the porous array (35) does not move while the sample is being removed from its respective container. In most preferred embodiments of the invention, the location (42) includes a plurality of projections or posts (43) of a size and number shape such that they place the filter assembly in the filter chamber (30) , to substantially promote even distribution of pressure against the porous array, and to reduce or prevent compression of the porous array which would interfere with the flow of fluid through the porous array. Alternatively or additionally, the porous array (35) may include a notched portion (63), as shown in Figures 2 and 3 that reduces or prevents compression of the porous array. Filter assembly In accordance with the invention, the chamber of the filter assembly (30) is configured to receive a porous array (35) which has a particle collection site in the form of particles (36) adapted to collect matter in the form of particles while the sample containing the material passes through the chamber (30). The porous array (35) having a collection site (36) adapted to collect matter can be placed in the path of the fluid flow in such a way that the collection site (36) communicates with the hollow tube (25). The porous array (35) within the filter chamber is preferably adapted to define the first and second branching of the fluid flow path. The first branch (39_a) extends through the collection site (36) and the second branch (39_b) diverts the collection site (36) (See Figure 1).
In the preferred embodiments of the invention, the porous array (35) includes a first porous medium (37) suitable for preventing the passage of matter, and a second porous medium (38) is suitable for allowing the sample to pass. The second porous medium may or may not be able to remove the matter in the form of particles from the sample, according to the needs of the particular device. In more preferred embodiments of the invention, the first porous medium is suitable for capturing or collecting particulate matter, and even more preferably, capturing or collecting solid matter in a single uniform layer, that is, a monolayer. Preferred embodiments also include a second porous medium which is suitable as a support for the first porous medium. The preferred porous media are shown in US Patent Nos. 5,301,685 and 5,471,994. The nature of the material used to make the porous medium, the compatibility of the materials selected for the porous medium with another and with the liquid to be processed are all factors to consider when selecting a particular material for a porous medium for an application Dadaist. The first porous medium and the second porous medium can be placed in any way that works with described herein. As any person skilled in the art recognizes, the porous array can be configured in various ways and placed as required to achieve a particular result. For example, the first and second porous media can be separated; the two media can be laminated together; the first means may be integral or removably linked with the second porous medium; or the collection element may comprise a zone of greater density that resembles the function of the first porous medium as described above, and a zone of lower density that resembles the function of the second porous medium as described above. The selection of these different configurations is fine for the skill of experts in the field. Below, variations in the strue and composition of porous arrays will be described in more detail. The porous arrangements (35) may include a unitary strue having a first portion of density and / or pore size suitable for preventing the passage of cells and a second portion of density and / or pore size suitable for passing the fluid. In preferred embodiments, the porous array includes a first porous medium comprising a porous polycarbonate membrane, suitable for preventing the passage of cells. The porous array may subsequently include a second porous medium comprising a depth filter or porous glass. This porous glass can be made of polypropylene or porous plastics P0REX7 of high density polyethylene. It should be noted that various types of porous arrangements can be used interchangeably with those of the present modality. While a polycarbonate membrane is especially suitable for use in cytological collection apparatus of the present invention, other porous membranes are also suitable. The porous membrane preferably has a pore size of about 0.22 microns to 8 microns, more preferably from 1 miera to about 6 microns, more preferably to about 2 microns, which makes it possible to trap cells that are larger than 3 microns. The membrane is appropriate to allow the flow of the fluid to pass while preventing the passage of matter in the form of a particle. The second porous medium is suitable for passing fluid and may also be able to remove matter in the form of particles from the sample. The pore size of the second porous medium can be between 5 and 60 microns, preferably between 15 and 45 microns and more preferably in the 35 microns. As any expert in the art would recognize, adjust the pore size of the porous membrane and the depth of the porous filter according to the type and / or size of the material to be collected, allows the collection of material at the collection site (14) In preferred embodiments of the invention, the pore size is selected such that a uniform layer of material, preferably a monolayer, is formed at the collection site. For example, it has been shown that there is effectiveness between 3 um and 40 um or more, but it is intended that the invention is not limited to a certain range of pore size. In preferred embodiments of the invention, the first porous medium (37) can be attached to a second porous medium (38) using an adhesive that is soluble in the sample.
Said soluble adhesives include, but are not limited to, sugar compositions, gels and the like. While the cytological collection apparatus (10) can be used for any biological fluid, it is particularly useful for preparing test samples of urine and its associated cells and for pap smears. Sample container holder A group of specimen containers are manually or mechanically placed on a container holder for further processing in an automated apparatus in accordance with the present invention. The container support is preferably a substantially flat platform, disc, sheet, shelf, tray or the like. In preferred embodiments of the invention, a sample container includes suitable guides for positioning and / or retaining one or more specimen containers. In more preferred embodiments of the invention, the container support includes one or more cavities adapted to accommodate at least one sample container size. In a preferred embodiment of the invention, the container support includes at least two cavities to accommodate at least two different sizes of sample containers. The support of the container is preferably mobile, that is, adapted to rotate on an axis or be moved along a route. According to the invention, the support of the container is movable for certain positions or stations, including one or more stations that align a portion or portions of the support of the container adjacent or next to another element of the automated apparatus, that is, a sampling head , a charger or a discharger. According to a preferred embodiment of the present invention, the sample containers can be rotated within the container support, and a portion of the container cover, fixedly associated with an agitator, can be held relatively stationary with respect to the rotation of the containers. . Agitation Assembly A mixer, according to the preferred embodiments of the invention, may include a stirrer to beat each sample in its respective specimen container. As noted above, each head can include a portion that links to a stirring element that extends to the sample. This portion of each head is adapted to be connected to a transmission movement, that is, a motor rotating a band or something similar that rotates the portion of each head. The transmission movement can link to a single head, or preferably, link all the heads. The transmission movement band can alternatively be activated by rotating the specimen container supports about an axis. According to a preferred embodiment of the present invention, the structures link a portion of the cover of a collection container, and one or more structures rotate the collection containers. The devices can be configured to process a single sample or more than one, or it can be operated automatically or semiautomatically. In some embodiments of the invention, the cover may be a stationary outer cover and a rotating inner cover. In preferred embodiments of the invention, the inner and outer covers are not rotatable with respect to each in a first position, and are freely rotatable with respect to each in a second position. According to preferred embodiments of the present invention, one structure or element rotates the sample container and another structure or element links a portion of the sample container, that is, a portion of the cover, to keep that portion relatively stationary. The most preferred embodiments of the invention include a cover having an inner portion or cover and an outer portion or cover, and from here closing the cover and releasing one of the covers or portions in such a way as to rotate freely in a multi-step process . When the inner and outer covers are used to seal the container, it is preferable that the inner and outer covers do not freely rotate one in relation to the other. Both covers seal the container to the first position. In a second position, a seal or snap is broken, that is, by an additional turn of the outer cover, thus releasing the outer cover of its connection with the inner cover. In the second position, the outer cover rotates freely in relation to the inner cover. In a preferred embodiment of the invention, the cover comprises a first portion that is fixedly attached to the container and a second portion that can be rotatable relative to the container. As used herein, being rotatable in relation to the container refers to the relative movement of the first portion and the second portion; the first portion may be fixed and the second portion may be mobile, or the first portion may be mobile and the second portion may be fixed. In a more preferred embodiment, the second or internal portion of the cover is stationary and the first or outer portion is rotatable. In a preferred embodiment of the invention, the agitator is attached or fixed to the second portion of the cover. According to the invention, the first and second portions can be individual covers that are rigged. For example, referring to Figure 39, the inner cover (72) can be used to seal the container and the outer cover (71) can fit over the inner cover. In this embodiment of the invention, a tongue on the inside of the outer cover can prevent relative movement of the inner and outer covers when the respective covers are in the first position. Moving the outer cover to a second position, that is, breaking the tongue or removing the spacer allowing a relative axial displacement of the inner and outer covers, allows the rotation of the outer cover relative to the inner cover. An apparatus of the present invention can be configured to hold, link and rotate a portion of a collection container, such that the sample is mixed according to the present invention. An example collecting container would include a container or cup suitable for collecting and maintaining a specimen sample, a cover having a first position that is not rotatable relative to the container and a second position that is rotatable relative to the container, and a agitator linked or fixed to a portion of the cover that extends into the container. As used herein, configured to hold, link and rotate, it refers to various configurations that can be adapted to carry out the specific function. For example, an apparatus according to the invention can include a container support for positioning at least one sample container and rotating the chamber portion of the container, and a sleeve or staple for attaching and fixing a portion of the cover that is communicate with the dispersing element. Alternatively, the support can hold the container in a fixed position and a pulley, sleeve or staple can link and rotate the portion of the cover that links to the agitator. In a preferred embodiment of the invention, the sleeve links an inner or second portion of the cover, and holds the second portion of the cover in a stationary position relative to the first portion of the cover. As shown in Figure 39, the cover (31) includes a structure and ways to allow an outer portion of the cover to move relative to an internal portion. As illustrated, the cover (31) includes an outer cover (71) and an inner cover (72). The inner cover (72) will preferably be fixed to or in fluid communication with the tube (50). In a preferred embodiment of the invention, the cover (71) when attached to the container (23) rotates with respect to the inner cover (72) and the tube (50). Said relative movement between the outer cover (71) and the inner cover (72) moves the sample in the container (23) in relation to the agitator (51). In a preferred embodiment of the invention, a slot or opening in the cover can be covered with a penetrable or removable layer that protects the interior of the container from contamination until the container is ready for use. For example, you can use a brush or something similar to collect a cervical sample, the layer can be removed from the cover and the brush can be placed in the container. An example of the brush is found in U.S. Patent 4,759,376. Sampling Station An apparatus according to the invention also includes a group of sample heads adapted to link a portion of the corresponding containers of the specimen. In accordance with preferred embodiments of the invention, the number of arrangements or patterns of head groups and specimen containers, correspond to each other. In preferred embodiments of the invention, each head assembly includes a portion having a cavity that receives or bonds a filter as described below. In more preferred embodiments, a portion of the sampling head is loosely and removably linked to a portion of the cover, and in a rigged link, forms a chamber adapted to position and accommodate a filter assembly. According to the invention, the filter assembly and the chamber provide at least two branches of fluid flow through the chamber. A portion of the sampling head assembly will preferably be movable in one direction to link the specimen containers in the container holder. In accordance with preferred embodiments of the invention, the container supports will move sequentially with respect to a stationary reference frame within the position to be linked by the sampling heads. In other preferred embodiments of the invention, an adjustment adapter is interposed between the container and the respective head and forms at least a portion of the filter chamber. The adjustment adapter can be included with each container, or can be associated respectively to a group of adapters with the corresponding group of heads. Each head assembly is connected to a pump or something similar. In this embodiment of the invention, the various structures provide a fluid flow path from the specimen container, through the filter in the filter chamber, and from the specimen container to the pump. Slide Way A device according to the invention also includes one or more slide holders. A group of slides is placed by hand or mechanically on a support - slides for further processing in an automated device according to the invention. In preferred embodiments of the invention, a slide container includes suitable guides for positioning and / or retaining one or more slides. The carrier of the slide will preferably be mobile, that is, adapted to rotate about an axis or to be moved along a route. According to the invention, the slide holder is movable for certain positions or steps, including one or more stages that align a portion or portions of the support adjacent to or in proximity to another element of the automated apparatus, that is, a magazine or unloader. Fixture A composition according to the invention includes one or more solvents, preferably an alkanol, between 35 and 45% by volume; ketone, between 2 and 3% by volume, a diluent, preferably a diol or triol of between 1 and 3% by volume; a crosslinker, preferably an aldehyde, of between 0.4 and 3% by volume; glycerol, between 0.5 and 2% by volume; one or more detergent and / or dispersing agents, preferably non-ionic, of between 0.01 and 0.05% by volume; a regulator between 45 and 65% by volume. In a preferred embodiment of the invention, the pH of the composition is between 4 and 7. The present invention also includes a method of preparing the material in the form of particles, such as cells and the like for histological or cytological examination comprising the collection of matter in the form of particles in a uniform layer, preferably a monolayer, and fixing the cells in a composition according to the present invention. Table 1 summarizes the preferred range and concentrations of the components of a fixative formulation according to the present invention.
Component preferred range and example (by volume,%) (by volume,%) Solvent 35-45 37 -42 alkanol ketone 2-3 2. 1-2. 4 acetone diluent 1-3 1. 6-1. 9 diol, triol glycerol 0.5-2 0. 8-1. 2 glycerol crosslinker 0.4-3 0. 6-0. 8 aldehyde detergent 0.01-0.05 0. 02 Nonidet p40 regulator 45-65 50-55 Tris A composition according to the invention includes one or more solvents for penetrating the tissue of the cells, dehydrating the cells and / or inhibiting vital and bacterial activity. In a preferred embodiment of the invention, the solvent is a mixture of alkanols, which slowly penetrates and when combined with other reagents, fixes the sample rapidly. This denatures the protein by precipitation, precipitates glycogen and dissolves fats and lipids. The alkanol may be any of the three well-known alcohols having from one to four carbons, ie, methanol, ethanol, normal propanol, isopropanol, normal butanol and several branched butanols. The most preferred solvent is a mixture of methanol and isopropanol, typically at 30% and 10% by volume respectively. The ketone is a fixative with action similar to that of alcohol, except that glycogen is not well preserved. The ketone acts as a fixative and additionally allows the entire composition to penetrate the cells. Acetone is the preferred ketone. The thinner forms a layer on the specimen and helps protect it from the effects of drying. The preferred diluent is a diol or a triol, more preferably a polyethylene glycol (PEG) that is, PEG-1500 (average molecular weight of about 1450) also called Carbowax. Glycerol prevents drying of the cells during the sampling process. Cells that have been kept in a fixative solution for a long time usually get stiff due to the fixation process and are less likely to be distributed on the slide. Glycerol helps the cells level off on the slide. The crosslinker reacts with the protein end groups to crosslink the molecules and produces an indissoluble product. The groups of proteins involved include amino, imino and amido, peptide, hydroxyl, carboxyl and sulfhydryl. Methylene bridges are also commonly formed between similar groups such as NH2 and NH but are supposed to be reversible by washing them in water. Some crosslinkers such as formaldehyde are an antiseptic. Preferred crosslinkers are aldehydes, more preferably formaldehyde. The detergent is a non-ionic detergent and a dispersing agent used for the solubilization of proteins and membrane components to decrease cellular aggregation. The preferred detergents are Nonidet P40 or Triton X-100, both well-known detergents. The regulator maintains the solution at a pH between 4 and 7, and provides a means of transport. The preferred regulator is Tris, a well-known regulator. In accordance with the present invention, the regulator may also include a fixative that precipitates the core-proteins and one or more of the osmolarity maintainers. The preferred core-protein precipitator is glacial acetic acid, typically in a range between 0.2% and 0.3% by weight, and which helps maintain the regulator between 7.4 and 7.8 pH. The maintainers of the osmolarity are dextrose, typically in a range between 0.1 and 0.2% by weight, and sodium chloride, typically in a range between 0.7 and 0.8% by weight.
In the preferred embodiment, the described active fixing ingredients can be dissolved in an appropriate solvent such as distilled water, and this solution can then be used as a fixing agent in a number of ways that would be obvious to one skilled in the art. For example, the fixative solution can be used to preserve samples of tissues that are being sent to the examination site. In this process, small jars or jars having liquid-tight seals are filled with the reagent of the invention, and the sample tissues are placed in the vial containing the reagent to preserve the samples until they reach an area where they can occur later the processing. Water or another diluent is also used in an amount of between 80 to 90 percent by volume. Any suitable diluent that does not modify the important physical or chemical characteristics of the formulation can be used. The tissues prepared for their study using a fixative of the invention can be prepared for histological study in any conventional manner, such as with the use of paraffin, sectioning equipment, pigmented, slide assembly or other common steps used prior to the microscope or another test. The present invention thus provides a convenient and effective fixation solution, which can be used in many of the known histological methods employing such solutions. Structures for the movement of fluids According to embodiments of the invention, the automated apparatuses include one or more elements for altering the differential pressure in the apparatus in such a way that the sample can be moved through a portion of the automated apparatus. According to embodiments of the invention, the fluid component of the sample can be either gaseous or liquid, depending on the use. For example, inducing a vacuum in a conduit that communicates with the sample container, will suck the sample into the container through the filter assembly. It may also be desirable to induce a positive pressure to return any uncollected portion of sample to the specimen container, or to move the filtered liquid to the waste container or to the chamber. A reversible pump is an example of a preferred vacuum / pressure element. Additionally, it may be desirable to clean or rinse a portion of the subassembly, that is, a portion of the head assembly. In preferred embodiments of the invention, the pump can move a rinsing solution from the source container through a conduit to the head assembly. Included with the present invention are a variety of source containers, differential pressure generators and conduits for establishing fluid communications between or to preselected elements of the automated apparatus. The movement of a fluid through the system can be carried out by maintaining a differential pressure between a fluid source and a fluid destination. Some means of establishing this differential pressure can be by applying pressure to any part of the system on the inner side of the filter chamber; applying a vacuum to any part of the system on the outside of the filter chamber; or any form of pump, such as an angel hair filter (manufactured by Genex Corporation); gravity heads; or a collapsible and flexible container, such as a specimen container, which can be compressed to force the sample through the filter. Controllers According to preferred embodiments of the invention, the automated apparatus may include one or more controllers for selectively moving and positioning an element of the automated apparatus, for starting or stopping an operation of the automated apparatus, or for monitoring the progress of the operation of an automated device. automated device. An example of a preferred controller is a computer and a computer program. Other uses of a controller will be apparent to one skilled in the art, and are included with the invention.
Examples of controllers are described in more detail below. Chargers In accordance with preferred embodiments of the invention, at least one charger may be adjacent to, or be part of the automated apparatus. It is intended that a variety of chargers can be used in conjunction with the operation of the automated apparatus. For example, an automated device may include one or more of the following: A filter charger; a microscope slide charger; a specimen container loader; an encapsulator, designed to place a cover over an open specimen container; a magazine for placing and linking together a portion of the head assembly on a group of specimen containers; a loader to place and link together a portion of each filter assembly to their respective slides. Examples of loaders are described in more detail below. Dischargers In accordance with the preferred embodiments of the invention, at least one unloader may be adjacent to or be part of the automated apparatus. It is intended that a variety of arresters can be used in conjunction with the operation of the automated apparatus. For example, a discharger can be used for any item for which there is a charger, as described above. Examples of unloaders are described in more detail below. Tracking mechanism According to preferred embodiments of the invention, the automated apparatus may include one or more tracking mechanisms to track the progress of a sample through the automated apparatus, and / or track a sample after Aesta has been processed by the automated device. An example of a tracking mechanism involves the use of a bar code. In this embodiment of the invention, the automated apparatus may include one or more bar code readers and a printer. Examples of tracking mechanisms are described below in more detail. Miscellaneous Structures An automated apparatus, according to the invention may also include a variety of motion transmitters including belts, motors, pulleys, anti-friction elements, elevators, conveyors and supports, as well as conduits, a cleaning or rinsing head and its source of supply (ie, a container) of cleaning or rinsing solution, a fixator applicator and the source of supply (ie, a container) of the fixing solution, and something to carry out the operation of the elements of the apparatus automated Other substitute or additional structures will be apparent to one skilled in the art, and are included with the invention. Examples of structures are described in more detail below. Method of operation: * It will be clear from the description of the various elements of the automated apparatus that a wide variety of operating methods can be used. An example mode of operation is described below, and the nature, sequence and number of steps are intended to be examples. A group of specimen containers containing respective samples are accommodated on a container holder, either manually by means of a magazine. In some embodiments of the invention, technicians capture in the controller one or more of the following parameters for each specimen container: type of specimen (ie, sputum, blood, urine, spinal fluid, etc.), mixing rate, time of specimen mixed, suction level, suction time, fixative (this is whether it bears or not), and drying time. After having loaded the appropriate parameters into the automated device, it starts the sampling process. In preferred embodiments of the present invention, a bar code reader detects a bar code on each container, and the controller selects appropriate parameters based on the bar codes of each container. A filter assembly loader can be used to place an appropriate filter assembly (corresponding to the information received from the bar code and preselected parameters) in the respective filter chamber for each sample. The container support is then advanced to the sampling stage, that is, a predetermined position with respect to the assembly of heads, and the group of heads is then linked to the corresponding group of containers. Concurrently, a group of slides is accommodated on the slide holder in a pattern corresponding to the group of heads. The slide group then proceeds to the deposition stage where the respective monolayers of particulate matter from each sample are transferred to a slide of their respective filter assembly. The mixer is activated by the controller thus managing the agitators to beat their respective samples. The controller then activates the pump to apply an appropriate vacuum in each head, removing at least a portion of each sample from its respective container. After each sample has passed the container through its respective filter assembly, the controller deactivates the pump, and the group of heads is disconnected from the corresponding group of containers. The filter group of their respective samples is then transported to link to their corresponding group of slides, thus transferring each monolayer of particulate matter to their respective slide, and then the filters are discharged from their respective slides. In some embodiments of the invention, a portion of the filter assembly, typically the portion of the membrane, remains bonded to the microscope slide; In other embodiments, the complete filter assembly is unlinked from the microscope slide. In preferred embodiments of the invention, a fixator applicator provides a supply of fixer to adhere the monolayer of particulate matter to its respective slide. The controller activates the fixator applicator, providing an appropriate amount (ie, four drops) of fixative on the microscope slide. A blotting paper can be used to absorb excess fixative and to remove any portion of the filter that remains on the slide. In preferred embodiments of the invention, each slide of the microscope having a monolayer of particulate matter deposited is marked, that is, with a bar code and indicated by a printer listing, the corresponding bar code on the containers and the slides. Thus, each monolayer of matter in the form of particles can be associated with its respective sample using the coding of the container and the slide. In preferred embodiments of the invention, the slide holder is advanced and the groups of slides are removed from the apparatus, either manually or by a discharger. Preferred embodiments of the invention may also include a blower or dryer to dry the surface of each microscope slide and / or remove any residual portion of the filter such as the membrane (if present). Again, the controller can coordinate the operation of the blower / dryer with the operations of the other mechanisms and sub-assemblies of the apparatus. Preferred embodiments may also include a rinse rate which may then be aligned with each filter head. The controller activates the cleaning process in such a way that any portion of each head that requires rinsing or cleaning comes in contact with the cleaning solution. Preferred modes may also include a sub-amble to recover each container with its original cover or with an unused cover. The used covers can be taken to a waste area. The covered specimen containers can then be removed, either manually or by a discharger, from the automated apparatus for storage. Again, the controller would coordinate all the automated operations associated with the coating and storage of the containers.
FIRST MODALITY AS AN EXAMPLE OF THE INVENTION According to the first example embodiment of the present invention shown in Figures 6-18, an automated apparatus (10) includes a group of specimen containers (20) arranged on a container platform. specimen (100), an assembly of filter heads (40) placed in a filter head holder (200), and a holder for a microscope slide (300). In the first exemplary embodiment of the invention, the holder of the specimen container (100), the filter head holder (200) and the microscope slide holder (300) rotate about the central axis or arrow (11). As shown in the Figures (6) and (7), the automated apparatus (10) can also include at least one filter assembly magazine (50), one microscope slide magazine (70), one microscope slide discharger (80), one bar code printer (90), a bar code reader (91), a fixer container (92), an air container (93), a rinsing liquid container (94), a liquid container cleaning (95), a waste container (96) and a controller (400). Each of these elements will now be described in more detail. The holder of the specimen container (100) as illustrated, includes a group of five landings (101) adapted to receive and position a specimen container (20). As shown in Figure 8, the rest can be configured to receive more than one specimen container size, a larger size (101) and a smaller size (102). In the embodiment shown in Figures 8 and 9, the holder of the specimen container (100) is circular and is movable up, down and axially about a central axis or arrow (11). To accommodate this movement, the automated apparatus may include one or more bearings (103) or the like, and a walker (104) or similar element to move the support (100) up and down the arrow (11). The holder of the specimen cup (100) can be moved radially about the shaft using a belt (105) or gear or something similar. The head assembly (200) as illustrated in Figure 15, may include a lower portion (41) adapted to removably link, position and retain a filter assembly (33). In the first example embodiment of the invention, the lower portion (41) is adapted to link the filter assembly with a fluid-tight or liquid-tight seal, but such a link will preferably be releasable in such a way that the filter assembly can be removed from the lower portion (41) during another step in the operation of the automated apparatus. A portion of the head assembly (200) may include a gear or teeth (201) adapted to link a band such that the lower portion (41) can rotate. As noted above, this rotational movement generated by the band is transferred to a portion of the covers of the specimen cup in such a way that the agitators extending in the container beat the mixture. The head assembly (200) also preferably includes an adjuster (202) adapted to link one or more conduits to establish fluid communication with at least one of the air containers (93), a container of rinsing liquid (94), a container of cleaning liquid (95), and a waste container (96). Communication with the air vessel (93) can be used to unbind the filter assembly (33) from the portion (41) during another step in the operation of the automated device (10), or it can be used to push a plunger that pull the filter assembly out of the portion (41). As shown in Figure 15, the filter head assembly may also include one or more springs (203) to link a portion of the specimen container or cover (97), one or more springs (204) to allow a portion (41) of the assembly of the filter heads move elastically, and one or more bearings (205) that allow a rotational movement of a portion of the head assembly. In most preferred embodiments of the invention, the assembly of the heads (200) comprises a cylinder within a cylindrical construction. In preferred embodiments of the invention, the slide holder includes a plurality of radial projections adapted to receive a microscope slide with or without a filter. The slide holder must be rotatable with respect to the same axis of the container support. In accordance with preferred embodiments of the invention, the carrier support is placeable at an intermediate level between the container support and the head assembly. In accordance with the preferred embodiments of the invention, the microscope slide holder is movable for certain positions, including one or more positions that align a portion or portions of the support adjacent to or in proximity to the respective filters. The microscope slide holder (300), as shown in Figures 10-12, is adapted to receive a group of microscope slides and a group of filter assemblies (33). In a preferred embodiment of the invention, the support (300) includes radial extensions (301). In a more preferred embodiment, each projection (301) includes a recess (302) adapted to receive and position the microscope slide., And each projection includes a recess (303) adapted to receive and place a filter assembly. (33).
According to the invention, the support of the microscope slide (300) is rotatable about the axis (11) and vertically along the axis (11). The bearings can be provided that they facilitate the movement of the support (300), and can also withstand loads or pressures on the projections (301) of the support (300). The support (300) can also be rotatable by belt transmission, meshing, etc., and be vertically movable using a walker or the like. The filter charger assembly (50), as shown in Figures 7 and 13, preferably receives and places groups of the filter assemblies (33), and is adapted to deposit a filter assembly (33) in a resting on the support of the microscope slide. In the first embodiment of examples, the filter assemblies (33) are stacked in a tube or channel, and a motor or solenoid moves a plate having a hole from the first position where the filter stack is closed to a second one. position where the filter stack is open. In the open position, a spring or something similar can push a single filter assembly through the hole and into the microscope slide holder. Alternatively, the spring can be used to retain all but one of the filter assemblies, so that when the hole is aligned with the stack of filter assemblies, the non-retained filter assembly is allowed to fall on the slide holder. of the microscope. The microscope slide loader (70) preferably retains and places groups of microscope slides and is adapted to move a single microscope slide at a break in the microscope slide holder. In preferred embodiments, the slides are accommodated in a tube having a closed lower end, and, adjacent to this lower end, one or more slots (81) through which a single microscope slide can pass. An arm on the slide charger pushes the slide from the stack and into the microscope slide holder. When the arm retracts, the next microscope slide falls into position. The present invention also includes a method for removing matter in the form of particles from a sample, and for transferring a monolayer of matter in the form of a particle, such as a cell, to a microscope slide. According to preferred embodiments of the present invention, a filtration membrane provides a method of depositing the cells in evenly distributed form on the microscope slide with a minimum of overlap. This allows clear observation and optimal diagnostic accuracy. An example of the method of using the invention includes collecting a sample containing matter in the form of particles in a collection container (20). The container (20) is then covered with a cover assembly (500) which includes one or more of the following: base (31), wall (501), and at least a portion of the filter chamber (30). When the sample is taken out of the container (20), the fluid will flow through a porous array (35) as shown in Figures 1 and 2, so that a monolayer of the particulate matter is formed in the collection site (36). Once the cell monolayer is formed, the fluid flow is reduced in the center of the porous array (35) and increases toward the edges of the porous array. At least in part, this is due to a blockage of the flow of the collected cells while forming the monolayer on the surface of the porous array. When the monolayer has mostly covered the surface (45) of the porous array, the flow bridges the first porous medium and passes through the extended lateral area of the second porous medium. Thus, the area of the second porous medium that extends beyond the extreme wall or skirt of the upper portion acts as a vent (with low resistance to flow) which prevents the cells from clumping or collecting in more than one. monolayer The fluid can be passed back and forth through the porous array as many times as desired. The first porous medium can then be pressed against a microscope slide to transfer the monolayer of the particulate matter from the collection site to the slide. This allows the cytological examination to be carried out on the cells by a practitioner without the interference of the pores in the membrane or without delays due to the processing requirements. Figure 33 shows an exemplary fluid flow diagram according to the first preferred embodiment. Figure 37 shows an example of arrangements for controlling the process according to the first preferred embodiment.
SECOND MODALITY AS AN EXAMPLE OF THE INVENTION A second example part of the present invention is shown in Figures 19-31C. A container support (100 ') has a group of three containers (20) in a linear pattern. The container support (100 ') cooperatively holds the containers (20) to prevent rotation between the containers (20) and the container support (100'). Alternatively, if the containers (20) are to be overturned, the container holder can facilitate rotation by providing access to the containers (20) (for example, an opening in the base through which a pin is inserted can be provided). of lifting to provide a pivot shaft for the containers (20)). A conveyor system for the containers (600) for advancing groups of containers (20) in their respective container supports (100). A first transmission, including an Ml motor that drives at least one band (two are shown in Figures 19-24, three are shown in Figure 26), which advances the container supports (100) to a front (602) of the Conveyor belt system (600). To the front (602) of the conveyor belt system (600), the samples in the containers (20) are agitated. According to the preferred embodiment, a transmission driven by an M2 motor lifts the containers (20) to a link with respect to the agitator motors M2A corresponding to each of the containers (20). Respective stirring heads (610) link the container covers (20). The containers (20) may be relatively stationary, or they may be allowed to rotate due to the rotation of their covers agitated by the M2A motors. The degree of agitation can be selected according to the samples being treated. The M2A motors can be driven according to various routines and hence combinations, including but not limited to: acceleration at a desired constant speed that is maintained for a predetermined time before deceleration; variable acceleration and deceleration; and reverse the direction of rotation. After the agitation is carried out, the containers are lowered back to the container support (100) by the transmission driven by the M2 engine. Another transmission, including an M3 motor that drives at least one band, that sequentially forward other individual vessel supports (100) off the side (604) of the conveyor system (600) to the sampling station (620). As best seen in Figure 27, the sampling station (620) includes a set of sampling heads (622) (three as shown) corresponding to a number of containers (20) that can be processed in each batch. The arrangement of the sampling heads (622) also corresponds to the containers (20) in the container support (100), such that each of the containers (20) is aligned under a respective sampling head (622) . The sampling heads (622) move vertically, as a group, by means of a transmission (that is, a stringing roller) driven by an M4 motor. A system of springs ensures an adequate linkage of the heads (622) with respect to the containers. As shown in Figure 28, an adapter (700) is coupled to the container (20). The adapter (700) firmly retains the filter assembly (33), and by friction is retained with respect to the container (20). Each sampling head (622) includes three ports; a first port for communicating with the sample via the adapter (700), a second port for communication with the pump, and a third port for releasably linking the adapter (700) to the sampling head (622). Connecting a vacuum source to the third port will cause the adapter (700) to adhere to the sampling head (622), allowing the sampling head (622) to separate the adapter (700) from the container (20) against opposition by friction retaining the adapter (700) with respect to the container (20). Disconnecting the vacuum source will allow gravity to separate the adapter (700) from the sampling head (622), thus allowing the filter (33) to be placed in its respective slide. A slide loader system (630) includes a magazine (310) providing new slides on at least one slide support band (300 ') (two are shown) in a certain pattern. The projections (301 ') on the band of the slide holder (300') sequentially removes the slides from the slide store (310). The linear arrangement and spacing of the slides on the bands of the slide holder (300 ') correspond to the linear arrangement and spacing of a group of containers (20) in each container holder (100'). A slide unloader system (640) includes another set of slide holding strips (304) to collect the slides once the monolayer has been transferred to the slides. The carrier support strips (304) have another set of projections (305) that are more closely spaced than the projections (301 ') on the support strips (300'). The sets of bands (300 ', 304) are moved back and forth at different relative speeds in such a way that the relatively widely spaced slides are transferred over the support bands (300') at a relatively narrow spacing in the webs of the webs. support (304). The small space between the slides in the support strips (304) provides a longer adjustment time for any fastener that has been applied to facilitate the transfer of the monolayer to the slide. The support bands (304) move the slides to a collection system (307). The collection system (307) may include one or more handling assemblies for placing the slides in a cartridge or other arrangement for a subsequent treatment, i.e., pigmentation. A container unloader system (650) includes another transmission driven by an M5 motor, for the organization of a plurality of container supports (100 '). From the container unloader system (650), the containers (20) are removed either manually or mechanically from the container supports (100 '). The container supports (100 ') are then reused and the containers (20) are advanced for storage or disposal.
A method for using the second explanatory part is illustrated in Figures 32A-32C. In Figure 32A, a group of containers (20) in a container support (100 ') has been advanced by the second transmission to the sampling station. The group of sampling heads (622) corresponding to the group of containers (20) is aligned and separated from their respective adapters (700). The slide support strips (300 ') extend parallel to the groups of vessels and slides and are located laterally on opposite sides of the group of adapters (700). In Figure 32B, the group of sampling heads (622) has been displaced in such a way that it links with their respective adapters (700). A vacuum source is connected to the third port to securely connect each sampling head (622) to its respective adapter (700). The sample can be mixed by rotating each of the sampling heads (622) relative to its respective container (20), thus causing a subsequent agitation in each sample with which the matter is dispersed in the form of a particle. A vacuum source is connected to the second ports of each sampling head (622) to extract at least a portion of the sample in each container (20) through its respective filter (33) thereby collecting a monolayer of matter in the form of a particle. In Figure 32C, the sampling heads (622) move away from their respective containers (20). Each adapter (700) is secured relative to its respective sampling heads (622) by virtue of the vacuum source connected to its third ports of each sampling head (622). The slide support strips (300 ') are activated to align a respective slide under each of the sampling heads (622). Then the sampling heads (622) are lowered to make contact and the monolayer is transferred to its respective slide. Figures 34-36 show an example fluid flow according to the second preferred embodiment. Figures 37 and 38 show an example arrangement for controlling a process according to the second preferred embodiment.
ALTERNATIVE CONFIGURATIONS FOR AUTOMATIC PROCESSES Additionally, fixative can be applied to the slide before and / or after transferring the monolayer to the slide. According to the preferred embodiment of the present invention, a fixator dispenser applies at least one drop of fixative to each of the slides on the support band (300 ') before the monolayer is transferred to its respective slide. Optionally, a second drop of fixative can be applied to each of the slides on the support band (304) after the monolayer has been transferred to its respective slide.
As best seen in Figure 31, a blotting paper system (635) can be installed in front of the collection system (307). The blotting paper system (635) includes at least one supply of tape (636) to absorb excess fixative. Additionally, a second supply of tape (637) can, by means of the adhesive, collect any membrane that remains adhered to the monolayer. Of course, both tapes (636, 637) are advanced before making contact with another slide thus avoiding cross-contamination of the monolayers. The material or module collection apparatus described above can be used in combination with other suitable filtration or treatment devices. Some example devices include other devices or modules of waste and / or tests that can be connected to the housing (10) Typically, these additional modules will include a housing having an inlet and an outlet, and including filtering, testing or sensing elements, placed through the path of fluid flow in the housing. For example, the apparatus may comprise a housing that includes input and output ports that define a flow path between the input and the output; a filter placed through the flow path; and a freely moving chromatographic or test element, such as substrate foam, placed on the outside of the filter. The chromatographic or test element can be freely mixed with the matter in the fluid, capture the matter, and can then be tested for presence of matter. Some suitable devices are included in the American patents 4,953,561; 5,224,489; 5,016,644; 5,139,031; 5,301,685; 5,042,502 and 5,137,031. The cytological collection apparatus (10) of the present invention also allows isolation and collection of fresh cells and / or microorganisms from biological fluids to carry out DNA testing and chromosomal analysis once the cells are found. hemolysed by the appropriate regulator. The most widely used pigmentation for the visualization of cell changes in cytology is the Papanicolaou pigmentation procedure. This pigmentation, which is used for both gynecological and non-gynecological applications, is basically composed of nuclear blue and orange, red and green cytoplasmic counterpigments. Nuclear pigmentation demonstrates the chromatic patterns associated with normal and abnormal cells, while cytoplasmic pigmentation helps to indicate the origin of the cell. The success of this procedure can be attributed to the ability to observe several factors, including the definition of the nuclear detail and the differentiation of the cell. This pigmentation procedure also results in a multicolored preparation that is aesthetic, possibly reducing the effort of the eye. Since the cellular detail is dependent on the fixation, it is preferable that the cells are fixed immediately after being deposited on the slide. A too great delay between the preparation and the fixation can expose the cells to dryness, which can be detrimental to the cellular structure. Moreover, air drying apparatuses can adversely affect the subsequent results of pigmentation. An exception is when the cells are pigmented with Wright-Giemsa Staiu, in which air drying is used as a step in the fixation. In another embodiment of the present invention, the cell monolayer can be fixed directly at the site of collection. This can be carried out by first depositing a monolayer of cells at the collection site of the cytological collection apparatus, as described above and subsequently passing a solution containing a fixative, such as alcohol or acetone, through the cytological collection apparatus. . Included within the scope of the present invention is the production of multiple specimens from a single sample of the patient. Additional slides can easily be prepared for other pigmentation applications. The human papillomavirus test can be carried out, for example, by new methods such as immunocytochemistry or in-situ hybridization on additional slides. When developing oncogenic products or other immunocytochemical tests, more slides may be necessary. The different fixations that these tests may require can easily be incorporated into the process since the invention does not require that the slides are fixed in one way only. This same slide preparation procedure can be used for virtually all forms of cytology. In addition, the use of completely contained disposable components refers to biological risk issues. Finally, enhanced cell presentation, which provides improved cytological interpretation, can expand the role of cytology by providing more consistent and reliable diagnoses to patients. Also, the captured microorganisms can be incubated in a culture medium. After a monolayer of cells has been collected in the cytological collection apparatus, the fluid can be used for the reflux of the collection site, thus transferring any microorganism collected from the collection site. In bacteria tests, the first porous medium can be used for culture with a Qualture device (not shown) to determine the presence of specific bacterial colonies. The Qualture device is a plastic capsule that contains a membrane filter and four nutrient patches of a dehydrated selective medium. The Qualture technique is more sensitive than the agar plate method and faster in determining a pres diagnosis. The screens of the device isolate and presumably diagnose bacterial isolates in one step, more or less in 4-6 hours. Tests have shown that the recovery of fifty millimeters of fluid is excellent and sensitive.
SEMI-AUTOMATIC APPARATUS Another apparatus for the processing of simple current samples is illustrated with respect to Figures 39-41. A configuration or structure that links a portion of the cover or container typically includes any member that positions, fixes or moves the portion of the cover or container. Some example members include but are not limited to a hose, one or more belts, one or more pulleys, one or more elastic bands, etc. A preferred embodiment of the present invention includes a support sleeve A for positioning and rotating the container and the outer cover. In a more preferred embodiment of the invention, the outer portion of the cover also includes one or more elastic bands B that in a first or loose position (Figure 40) does not link with the outer cover (71), and in a second position or tight (Figure 41) does link and place the outer cover (71) while the outer cover and the container are rotating. In an alternative embodiment, the band B can rotate the outer cover and the container around the inner cover (82) and the tube / agitator (52). Although the present invention has been described in terms of particular preferred embodiments, it is not limited to those embodiments. The alternative embodiments, examples and modifications that are still encompassed by the invention, may be made by those skilled in the art, particularly in light of the foregoing techniques. The advantages and additional modifications will easily occur to those skilled in the art. Therefore, the invention, in its broadest aspect, is not limited to the specific details and representative devices shown and described herein. Accordingly, various modifications can be made without departing from the spirit and scope of the concept of general inventiveness, defined by the included claims and their equivalents.

Claims (36)

1. An automated apparatus for the batch processing of a set of samples in respective containers, a monolayer of matter in the form of particles of each sample being deposited on its corresponding slide in order to examine it. The apparatus comprises: a container holder accommodating a group of containers in a first pattern; a first conveyor belt carrying * said container holder with respect to a mixing step and a head stage; a group of mixers corresponding to said group of containers, each of said group of mixers includes an agitator that disperses the particles of matter in a respective sample in said mixing step; a group of heads that correspond to the group of containers and that are connected to their respective containers in the head stage, in such a way that each of the group of heads communicates with their respective sample; a pump that produces a flow of each sample from its respective container by means of its respective head; a group of filters corresponding to the group of heads, in which, each filter communicates with each flow of its respective sample and that includes: a membrane that is interposed in a first branch of its respective sample flow and that collects its respective monolayer of matter in the form of particles; and a porous glass that is interposed in a second branch of its respective flow and that circumvents said membrane; a second conveyor belt accommodating a group of slides in a second pattern, said group of slides corresponding to the respective group of heads, in which this second container transports the group of slides to a storage stage in order to receive a monolayer respective of matter in the form of particles transferred from said membrane; a controller that coordinates each of: the first conveyor belt that in turn transports the container support, the group of mixers that agitate the respective samples, the group of heads that connect to the group of containers, the pump that produces the flow of each sample and the second conveyor belt that transports to the group of slides; wherein, the controller coordinates the automatic output of the sample and correlates each sample container with its corresponding slide.
2. The automated apparatus according to claim 1, wherein the first pattern corresponds to the second pattern.
3. The automated apparatus according to claim 1, wherein the group of mixers further includes an impeller that rotates each of the heads, and each of the group of containers is fixed with respect to the container holder.
4. The automated apparatus according to claim 1, wherein the group of mixers further includes an impeller that rotates each of the group of containers in relation to the container holder, and wherein there is a respective cover for each one. of the group of containers in order to prevent the turn.
5. The automated apparatus according to any of the preceding claims wherein each of the agitators beats their respective sample in such a manner that their respective particles are dispersed.
6. The automated apparatus, according to any of the preceding claims further comprising: a container loader that places the group of containers in the container holder in the first pattern; wherein the controller will further coordinate the S6 container loader that accommodates the group of containers in the container holder such that the first conveyor belt transports to said container holder.
The automated apparatus according to any of the preceding claims which further includes: a container unloader that removes the container group from the container holder in the unloading stage; wherein the first conveyor belt transports the container support from the head stage to the container discharge stage; and wherein the controller further coordinates the container unloader by removing the container group from the container holder with the first conveyor belt transporting the container holder.
The automated apparatus according to any of the preceding claims further comprising: a slide charger accommodating the group of slides in the second conveyor belt in the second pattern; wherein the controller further coordinates the slide charger accommodating the group of slides on the second conveyor belt.
9. The automated apparatus according to any of the preceding claims further comprising: a slide unloader that removes the slides from the second conveyor belt in a slide unloading step; wherein the second conveyor belt transports the group of slides from the deposition stage to the slide discharge stage; and wherein the controller additionally coordinates the slide unloader by removing the slide group from the second conveyor belt.
10. The automated apparatus according to any of the preceding claims further comprising: a first reader that detects the first identifiers in the respective containers, - a second reader that detects the second identifiers in their respective holders; and a printer that provides a list of the first and second corresponding identifiers; wherein said first and second identifiers associate the sample in its respective container with the monolayer of matter in the form of particles in its respective slide; and wherein the controller further coordinates the first and second readers that detect the first and second identifiers and directs the printer by marking the corresponding list. ll.
The automated apparatus according to any of the preceding claims, wherein the group of heads alternates with respect to the group of vessels along a path and wherein the deposition stage rests along the path.
The automated apparatus according to any of the preceding claims further comprising: a plurality of filtering sources each supplying a different filter; and a filter charger that transports each filter from one of the filter sources to a filtering chamber formed by each of the group of heads that are linked to its respective container; wherein the controller additionally coordinates the filtering loader that transports the filters from the filtering sources with the head group linking to the group of containers.
The automated apparatus according to any one of the preceding claims further comprising: an applicator providing a fastener securing for the monolayer of the particulate matter on the slide; wherein the controller further coordinates the applicator by supplying a fastener with the second conveyor belt carrying the group of slides.
14. The automated apparatus according to claim 13, further comprising: a blotting paper that absorbs excess fixative; wherein the controller additionally coordinates the blotting paper that absorbs the excess fixative with the applicator that provides a fixative.
15. The automated apparatus, according to claim 13, further comprising: a blower that dries to the fixative; wherein the controller additionally coordinates the blower that dries the fixer with the applicator that provides a fixator.
16. The automated apparatus, according to any of the preceding claims, comprising: a tape separating the membrane from the monolayer of particulate matter that is on the slide; wherein the controller additionally coordinates the advance of the tape.
17. The automated apparatus according to any of the preceding claims further comprises: a blower that separates the membrane from the monolayer of particulate matter that is on the slide, - wherein said controller additionally coordinates the separating blower. the membrane of the monolayer of matter in the form of particles that is on the slide with the second conveyor belt that transports the group of slides.
18. The automated apparatus, according to any of the preceding claims, further comprising: a solution bath for cleaning the head group; wherein the controller additionally coordinates the solution bath to clean the group of heads with the group of heads linking to the group of containers.
19. The automated apparatus, according to any of the preceding claims, wherein the first and second branches of each flow passes through the porous glass for its respective sample.
20. An automated method for batch processing a set of samples in their respective containers, a monolayer of particulate matter being deposited on a corresponding slide for examination. The method comprises: mixing each sample with respect to its corresponding container; attaching a group of heads to a corresponding group of sample containers, wherein each of said group of heads communicates with their respective sample; pump a flow of each sample from its respective container by means of its corresponding head; filter each flow with its respective filter group in such a way that they correspond to a group of heads. The filtrate includes: collecting the monolayer of matter in the form of particles with a membrane in a first branch of each flow and: avoiding said membrane through a porous glass in a second branch of each flow; transferring each membrane with its respective monolayer of matter in the form of particles to its respective group of slides, corresponding the group of slides to the group of heads, and; control the coordination of each of the operations of mixing, annexing, pumping, filtering and transfer to automatically deposit the monolayer of matter in the form of particles from its respective sample to its corresponding slide.
21. The automated method, according to claim 20 will further comprise: the concurrent processing of new groups of vessels for different operations of annexing, pumping, filtering and transferring; and repeating said annexing, pumping, filtering and transfer operations for each new group of containers; wherein said control further coordinates said concurrent process for each group of vessels with the operations of appended, pumped, filtered and transferred mixing.
22. The automated method, according to any of claims 20 and 21, further comprising: accommodating said group of containers on a container support in a first pattern; and transporting said container support with a first conveyor belt to the linking operation; wherein the control additionally coordinates the accommodation of the group of containers and the transport of the container support for the mixing, appended, pumped, filtered and transfer operations.
23. The automated method, according to any of claims 20-22 further comprising: removing the container group from the container holder; wherein the control additionally coordinates the removal of the group of containers for the operations of mixing, appended, pumped, filtered and transfer.
24. The automated method, according to any of claims 20-23, further comprising: accommodating the group of slides on a slide holder in a second pattern; and transporting the group of slides by a second conveyor belt to the transfer operation; wherein the control additionally coordinates the accommodation of the group of slides and transports by means of a second conveyor the operations of mixing, appended, pumped, filtered and transferred.
25. The automated method, according to any of claims 20-24, further comprises: removal of the group of slides from its support; wherein the control additionally coordinates the removal of the group of slides for the operations of mixing, appended, pumped, filtered and transfer.
26. In the automated method, according to claim 20, wherein the mixing includes the rotation of each of the heads in relation to their respective container.
27. The automated method, according to any of claims 20-26, further comprising: reading the first identifiers in the respective containers; and printing the second identifiers on the respective slides; wherein the first and second identifiers associate the sample in the corresponding container with the monolayer of the particulate matter of the respective slide; and where the control additionally coordinates the reading and printing with the mixing, appended, pumped, filtered and transfer operations.
28. The automated method, according to any of claims 20-27, further comprising: selecting the filter from a plurality of filtering sources; and transporting the filter from one of the filtering sources to a filtering chamber formed by each of the group of heads linked to its respective container; where the control additionally coordinates the selection and transport with the mixing, appended, pumped, filtered and transfer operations.
29. The automated method according to any of claims 20-28, further comprising: applying a fixative to the monolayer of the particulate matter on its respective slide; where the control additionally coordinates the application with the operations of mixing, appended, pumped, filtered and transfer.
30. The automated method, according to claim 29, further comprises: the absorption with blotting paper of excess fixative; wherein the control additionally coordinates the absorption with blotting paper with the operations of mixing, appended, pumped, filtered, transfer and application.
31. The automated method, according to claim 29 or 30, further comprising: drying the fixative by a blower; the control additionally coordinates the drying for the mixed, appended, pumped, filtered, transfer and application operations.
32. The automated method according to any of claims 29-31, further comprising: separating with a blower the membrane of its respective monolayer of particulate matter on the slide; where the control additionally coordinates the separation with the mixing, appended, pumped, filtered, transfer and application operations.
33. The automated method according to any of claims 29-31, further comprising: separating the membrane of its respective monolayer of particulate matter on the slide by means of a belt; wherein the control additionally coordinates the separation with the mixing, appended, pumping, filtering, transfer and application operations.
34. The automated method, according to any of claims 29-33, further comprising: cleaning the group of heads in a solution bath; where the control additionally coordinates the cleaning with the operations of mixing, appended, pumped, filtered and transfer.
35. The automated method, according to any of claims 29-34, further comprising: storing the containers that have not collected their respective portions of each sample; where the control additionally coordinates the storage with the operations of mixing, appended, pumped, filtered, transfer and return.
36. The automated method according to any of claims 29-35, further comprising: collectively accommodating the deposited slides with their respective monolayers of matter in the form of particles; where the control additionally coordinates the collective accommodation with the operations of mixing, annexing, pumping, filtering and transfer.
MXPA/A/2000/002019A 1997-08-25 2000-02-25 Method and apparatus for automatically forming monolayers from particulate matter separated from fluid samples MXPA00002019A (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US60/056,445 1997-08-25
US09/053,010 1998-04-01

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