• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
  • 同族专利
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    • 专利摘要:
    SYSTEM FOR AUTOMATIC PREPARATION OR PRE-TREATMENT OF A SAMPLE OR CELLULAR SAMPLES BEFORE FLOW CYTOMETRY ANALYSIS, CAROUSEL / CENTRIFUG ARRANGEMENT, AND SOFTWARE PRODUCT STORED ON A LEGIBLE AND / OR RECORDABLE MEDIA. The present invention provides a system and apparatus / devices capable of automatically carrying out the treatment processes with cells of preparation for flow cytometry and similar cytological studies in a fully automatic and simplified manner. The system and devices / devices are being adapted for the preparation and (pre) processing of cell samples, for example, blood and / or bone marrow samples.
    公开号:BR112014021135B1
    申请号:R112014021135-3
    申请日:2012-02-24
    公开日:2021-03-02
    发明作者:0Ystein Helge Ljungmann；Torstein Ljungmann
    申请人:Instrunor As；
    IPC主号:
    专利说明:

    TECHNICAL FIELD
    [001] The present invention belongs to the sphere of cytology or the study of cells and refers to a system and devices, used in it or alone, for the preparation of a sample or liquid cell samples before the analysis of flow cytometry. The preparation procedure can comprise some of the following steps: staining, lysis and fixation of cells. BACKGROUND OF THE INVENTION
    [002] Flow cytometry represents one of the essential tools used in these fields, such as cytological biology, cellular immunochemistry and cytodiagnosis for cancer detection. Essentially, it aims at the classification of cells, according to their sizes, types, contents of intracellular components and similar characteristics. Flow cytometry involves the pigmentation of cells with fluorescent dyes. The pigment cells are made to flower individually under laser beam irradiation, while flowing through the thin tubing. The fluorescence intensities of individual cells are measured to determine their size, relative amounts of DNA (deoxyribonucleic acid), etc. Flow cytometry analysis can identify and enumerate subsets of lymphocytes in human cells in suspension.
    [003] A use of the system, apparatus and devices, in accordance with the present invention, can be found in immunology and pathology laboratories in hospitals throughout the world.
    [004] Conventionally, this cell pretreatment has, for the most part, been carried out manually at the expense of a lot of time and labor. Manual pretreatment is also undesirable for reasons of unavoidable human errors and the non-uniformity of operations from one individual operator to another. The advent of a device capable of complete automation of cell pretreatment, therefore, has been expected by cytologists for a long time to eliminate human work and to gain stability and constancy in the operations involved. No system or device like this is known to us, due to the complexities of the cell pretreatment processes. However, there are several companies that try to partially automate some of the processes.
    [005] Becton Dickinson (BD) with his BD Facs lysis wash assistant (for automatic lysis, washing and centrifugation) and Beckmann Coulter with his TQ Prep Workstation (for automatic lysis procedure), The PrepPlus 2 Workstation (for pipetting reagents, patient samples, controls and fluorospheres in complementary tubes), and the Antibody Cocktail Preparation Workstation (for cocktail mixing) offer complementary automation to the manual process.
    [006] The BD Facs Lysis Wash Wizard does not pipette reagents or patient samples. The centrifuge solution is based on a single bottle centrifuge (tube), where the bottle rotates around its own axis. The inconvenience with the centrifuge solution is that the cells in the sample will not assemble at the bottom of the flask, but on the walls. A laboratory engineer interviewed mentioned that there is a problem with losing too many cells in the process.
    [007] EP 0 645 631 Bl, assigned to Becton Dickinson, describes an automatic system for preparing samples and for loading samples into an analyzer, in which the system includes a sample carousel that mixes and indexes a plurality of tubes. sample to a sample aspiration station.
    [008] Beckman Coulter offers several instruments in order to automate the complete manual procedure. The unexpected result of using this strategy is that the process will still include several manual activities after purchasing these instruments. After pipetting, patient samples and reagents on the PrepPlus 2 Workstation, the sample (s) must be moved manually to the TQ Prep Workstation for the lysis procedure. The FP1000 Cell Preparation System is also a part of the Beckman Coulter family and is being used for lysis solutions.
    [009] The document EP 1 468 266 A1, attributed to Beckman Coulter, refers to an environmentally controllable containment system adjusted to a flow cytometer to protect both particles being processed by the material contamination flow cytometer biological and non-biological as well as to protect people using the flow cytometer from being exposed to the particles being processed and the chemicals used in the processing of these particles.
    [010] JP 2010133727, attributed to Beckman Coulter, refers to a cleaning mechanism for cleaning an approximately cylindrical dispensing nozzle.
    [011] The document US 2011/017238 Al, attributed to Beckman Coulter, teaches a nozzle cleaning method and a nozzle cleaning device that allows the cleaning of a dispensing nozzle to be safely carried out and that allows a reduction in cleaning time. For this purpose, a nozzle cleaning method for cleaning a dispensing nozzle for suction and disposal of a liquid includes: a first cleaning step in which, after the dispensing is closed, an inner wall surface of the dispensing nozzle is cleaned in an upper part of a storage tank transported with a cleaning liquid when discharging a liquid for preload; and a second cleaning step in which at least one outer wall surface is cleaned by lowering and immersing the dispensing nozzle in the storage tank overflowing with the cleaning liquid.
    [012] EP 2 407 791 A1, assigned to Beckman Coulter, refers to an analyzer comprising: a reading section for storing or obtaining specimen information, including a specimen type of a specimen, and container information for specimen; a liquid level detection section for detecting a liquid level and / or a specimen interface; a dispensing apparatus for dispensing a specimen; a washing apparatus for washing a dispensing probe; a calculation section to calculate a variation in contamination adhesion of an outer wall surface of the dispensing probe, based on the type of sample, specimen suction position and specimen container information stored or obtained by the reading section, as well as liquid level and / or specimen interface information detected by the liquid level detection section; and a wash control section to control a wash variation based on the change in contamination adherence.
    [013] WO 2010/110265 Al, attributed to Beckman Coulter, describes a dispenser comprising a storage section to store a strain correction coefficient for each type of specimen and strain correction coefficients, based on the type of containers containing specimens, an information reader for acquiring specimen information and container information, a calculation section for calculating a limit stress based on the strain correction coefficient of a specimen and the stress correction coefficient of a container, which it was extracted from the storage section, and a determination section for determination to be liquid level detection, when the signal received by a dispensing probe produces the limit voltage for a predetermined or longer period.
    [014] US 5,030,554, assigned to Beckman Coulter, discloses a method for rapidly preparing a complete blood sample for photo-optical analysis.
    [015] EP 0 418 026 A2 refers to an apparatus for pretreating cells for flow cytometry.
    [016] WO 2009/150632 A2 discloses an apparatus for preparing controlled quantities of liquid for cytometry, that apparatus comprises a sampler having: means for granting movement to move a main tray with one or more tubes on it, each containing a controlled amount of liquid; a support and handling unit to support and move a syringe that transfers preparation liquids to the tubes; a mechanism for granting movement to move the piston of the syringe. The apparatus also comprises a centrifuge located behind the sampler and having an access opening to receive the tubes, for the selective removal of residues to be discarded from the controlled quantities of liquid. In addition, the sampler comprises a motorized gripping mechanism arranged in the support and movement unit and coaxial to the syringe, the support and movement unit being movable to allow the tubes to be loaded from the main tray to the centrifuge, and vice versa.
    [017] EP 0 628 822 A2 teaches a blood analysis system or instrument in general, including an incubator station, a sample and reagent holding station, a pipette set, a centrifuge, an analysis station and a transport set. In general, the incubation station retains containers, while reagents and fluids are being dispensed into those containers, and, if desired, to incubate the containers. The sample and reagent retention station retains samples and a plurality of reagents, and the pipette assembly transfers fluids from that sample and reagent retention station to the containers in the incubation station. The centrifuge is provided to centrifuge the container, and the analysis station is provided to analyze the containers optically to identify reactions in them. The transport set loads the containers between the incubator station, the centrifuge, and the analysis station. Preferably, the pipette set is automatically operated to collect pre-selected fluids and reagents from the sample and reagent retention station, and to dispense fluids to the containers retained in the incubation station to produce predetermined solutions in them. Also, the transport subset is automatically operated to load containers from the incubator station to the centrifuge after predetermined solutions have been produced in the containers and then to load the containers from the centrifuge to the analysis station.
    [018] One of the problems left unresolved in the flow cytometry technique is how to speed up the complete process of pre-treatment cells to be studied. This pretreatment consists of many steps to be followed strictly in a prescribed order. Among the steps are the introduction of reagents to cell samples inside the sample tubes, centrifugal treatment of the sample and reagent mixtures, removal of unnecessary liquid coverings from the sample tubes, staining of the cells with a fluorescent dye, and filtration of the samples. The actual process is much more complex.
    [019] One aspect of the present invention is to provide an improved system and apparatus / devices for a completely automatic and simplified pre-treatment preparation or procedure, as well as more efficient / effective preparatory cells for their similar flow cytometric or cytological studies.
    [020] It is also an aspect of the present invention to provide the reduction or elimination of any possibility of contamination of cell sample (s) being prepared or pre-treated.
    [021] Another aspect of the present invention is to provide for the reduction of loss of many cells during the preparation or pre-treatment procedure or process.
    [022] Yet, another aspect of the present invention is to provide complete control of the use of antibody and reagent, as well as the minimization of defects in the analysis, due to manual errors, for example, when coloring. SUMMARY OF THE INVENTION
    [023] The present invention aims to provide a system and devices / devices capable of automatically carrying out preparatory cell treatment processes for flow cytometry and similar cytological studies in a completely automatic and simplified manner. The system and devices / devices are being adapted for the preparation and (pre-) processing of blood and / or bone marrow samples.
    [024] The main features of this invention are given in the independent claims. Additional features of the present invention are given in the dependent claims.
    [025] The preparation of a liquid cell sample (in most cases, whole blood) in an immunology or pathology laboratory is similar. The process of washing or not washing whole blood offers two alternative procedures on how to carry out the preparation method or procedure. In immunology laboratories, the non-washing procedure is most commonly used, while in pathology laboratories, the washing procedure is used for the most part. In some cases, a test sample must be centrifuged, in other cases, not. In any case, the InstruNor cell (pre-) treatment system, according to the present invention, can be used with great success, due to the development of software for the system's computer environment, which opens up a flexibility of use.
    [026] The fact that the InstruNor cell treatment system, also called "FlowStainer" or "Flow Stainer", is a 4 in 1 system (1. cocktail mixer medium, 2. carousel / centrifuge medium, 3. lysis / wash aid medium, 4. medium for pipetting reagents and cell samples into complementary tubes) which will save the normal sized laboratory between 1,000-3,000 hours of work per year when using the cell treatment system.
    [027] The work routines of a lab engineer or lab assistant will also change dramatically, using the FlowStainer InstruNor, due to the fact that they can place a regular blood sample in the cell treatment system and collect the test sample for direct placement on the flow cytometer without visiting the system once during its run time. Assistants who work with antibody pipetting and other reagents will also find that work-related health problems (such as suffering or pain in their shoulders and / or arms) will decrease dramatically.
    [028] The characteristics and advantages of the invention and the manner in which they will be made will become more apparent, and the invention itself will be better understood, from the detailed description and the attached claims, with reference to the attached drawings that present some preferred embodiments of the invention. BRIEF DESCRIPTION OF THE DRAWINGS
    [029] These and other aspects of the invention are apparent from and will be further elucidated, by way of example (s), with reference to the drawings, in which:
    [030] Figure 1 is a perspective view of the cell treatment system incorporating the principles of the present invention;
    [031] Figure 2 is another perspective view of the system shown in figure 1, without some elements or parts of the system enclosure;
    [032] Figure 3 shows an embodiment of the main test sample support arrangement or means with a cover removal means;
    [033] Figure 4A shows the main test sample support arrangement or means of figure 3 with the cover removal means retaining the covers in order to penetrate a certain cover through a needle of a needle or syringe arrangement;
    [034] Figure 4B shows the main test sample support arrangement or means of figure 3 with the cover removal means, in which the covers are removed;
    [035] Figures 5A-5B show two realizations of the carousel / centrifuge arrangement or means comprising several sample container retainers;
    [036] Figures 6A-6B show two realizations of a sample container retaining arrangement of the arrangement or carousel / centrifuge means;
    [037] Figures 7A-7D show two realizations of said a sample container retaining arrangement of the carousel / centrifuge arrangement or means (figure 7A-7B), and some elements (figure 7C-7D) of it, in a different position that shown in figure 6A-6B;
    [038] Figures 8A-8C show an embodiment of an antibody / stabilizer and cooling container arrangement or medium;
    [039] Figure 9 shows an embodiment of a needle or syringe arrangement or means, in accordance with the present invention;
    [040] Figure 10 shows an embodiment of a waste station with the indicated pumping medium and the reagent support arrangement or medium; and
    [041] Figures 11A-11P present screen images of an exemplary operating procedure of the system, in accordance with the present invention. DESCRIPTION OF THE PREFERRED ACHIEVEMENTS
    [042] An embodiment of a compact cell treatment system according to the present invention is generally designated by the reference number 1 in figures 1 and 2. System 1 comprises an arrangement or support means of main test sample 2, a carousel / centrifuge arrangement or medium 4, an antibody / stabilizer and cooling container arrangement or medium 6, a robot arrangement or medium 7, and a computer medium 8. The system further comprises a reagent support arrangement or means 12, wherein the reagent support arrangement or means 12 is arranged to accommodate one or more vials of reagent 13, for example, according to one of its bottlenecks and / or open tops facing down. The system may also comprise an enclosure or box 11 having a lid or door or cover 111 movably attached (providing its pivot or sliding) to the enclosure 11 by a suitable hinge or attachment means.
    [043] The reagent support arrangement or medium 12 can be adapted for large or huge volumes of liquid (s), where the liquid (s) or fluid (s) can be at least one of the following: liquid PBS (Phosphate-Buffered Saline), lysis or solution or liquid for lysis, water or physical saline, distilled water, liquid (s) or fluid (s) or rinsing or cleaning agent (s) etc.
    [044] The main test sample support arrangement or means 2, shown in figure 3, can be detachable and is arranged to hold one or more sample containers 3, in which the sample container has an open top and can preferably if a test tube having its open top locked or covered by a cap or stopper or cover 30. The main test sample support arrangement or means 2 still comprises, in its proximity, means 9 for automatic removal of one or more sample container lids 30. The cover removal means 9 may further comprise a cap gripping or retaining means 92 for gripping and / or retaining at least one sample container cover or cover 30. The removal of cover 9 and / or its components (such as, for example, the cap gripping or retaining means 92) is operated and / or driven by at least one motor device 91 comprising suitable gearing and / or reducing means (not presented). The main test sample support arrangement or means 2 may further comprise an additional sample container holding means 25 for retaining one or more sample containers of a different type, such as, for example, small test tubes. The cover removal means 9 can be further adapted to place or remove the lids or stoppers or covers 30 in the sample containers 3, for example, after sampling or sucking a blood sample test.
    [045] Figure 4A shows the realization of the main test sample support arrangement or means 2 of figure 3, in which the covers or covers 30 are being retained by the cover removal means 9, 91, 92, so that a needle of at least one needle arrangement or medium or syringe is able to penetrate a given cap 30 in order to suck blood from the mother sample tube or container 3, and then the needle will be able to retract without removal or separating the cap 30 from the particular test tube or container 3 and making it attached to said needle. In other words, the so-called cover retention or removal means 9, 91, 92 is therefore able to retain the cap 30 throughout the above mentioned process, in order not to make it separate from the particular test tube or container 3.
    [046] Figure 4B shows the realization of the main test sample support arrangement or means 2 of figure 3, in which the lids or covers 30 are removed from the sample containers 3 by the cover removal means 9, 91, 92 A sample container of a different type 3 '' ', which is being retained in said additional sample container retention means 25, is also shown in figure 4B.
    [047] As shown in figures 1, 2 and 9, the robot arrangement or means 7 is adapted or arranged to serve, mechanically or physically, the system or instrument 1 and comprises at least one arm arrangement 72 and at least one arrangement or needle or syringe means 71 which can be mounted on said at least one arm arrangement 72 and can comprise at least one of: syringe, needle, plunger. In one embodiment, the needle or syringe arrangement or means 71 may comprise: i) two syringes 73S, 73L placed substantially vertically and parallel to each other and operated at least by a motor-driven mechanism 76, wherein a syringe 73S is adapted for small volumes of liquid (s) (within, for example, the microliter (μl) range) and the other 73L syringe is adapted for large or large volumes of liquid (s) (within, for example, the milliliter range (ml)): and ii) a common needle 74 arranged and adapted for service and operation with both syringes 73S, 73L. Alternatively, a separate needle may be arranged for each syringe in the arrangement. In another embodiment, each syringe 73S, 73L can be operated independently by its own motor-driven mechanism 76. The robot arrangement or means 7 can comprise three axes (x, y, z) and, together with their elements / components , allows and provides movement of said at least one needle or syringe arrangement or medium 71 in all directions within x, y, z or 3D (three-dimensional) area or space of system 1. The syringe plunger 75 in the arrangement or medium syringe 71 can be operated, for example, pushed up or down, by said at least one motor-driven mechanism 76.
    [048] System 1 may further comprise a rinsing or rinsing arrangement or station 10, shown in figure 2, wherein said at least one needle of said at least one needle or syringe arrangement or means 71 can be washed or rinsed with the help of at least one fluid or liquid or solution and / or chemical component for cleaning or rinsing, such as, for example, distilled water, but it is not limited to that. The cleaning or rinsing arrangement 10 may comprise at least one or a predetermined number of chambers and / or bottles having automatic supply of said at least one fluid or liquid or solution and / or chemical cleaning or rinse component for internal and external cleaning of the syringes and / or needle (s) / cannula (s). The cleaning or rinsing arrangement 10 may further comprise at least one chamber or bottle or waste container, in which the test sample syringes can pump out the fluid (s) and / or chemical (s) ( s) used for cleaning or rinsing. The cleaning or rinsing arrangement 10 may further comprise pumping means 90 for pumping residual fluid (s) into at least one bottle or chamber or waste container 95 (from a waste station 95), shown in figure 10. At least one flask 13 with liquid or chemical rinse from the reagent arrangement or support medium 12 may be connected to the cleaning or flushing station or rinse 10. In addition, the waste station, which comprises said at least one flask or chamber or waste container 95, it may further comprise sensor means for detecting the liquid level in said at least one bottle or waste chamber 95 and for sending the liquid level data to the computer medium 8, so that, when said at least one bottle or waste chamber 95 is filled with the liquid, the computer medium 8 produces and sends a message to the laboratory assistant or operator requesting and / or requiring the emptying of the entire bottle or waste chamber 9 5 or replacing this with another void.
    [049] The computer medium 8 comprises at least one CPU (not shown) and is provided for control and / or operation and / or administration of all components, apparatus or devices in system 1. The computer medium 8 can further comprise a screen or monitor 80 (output interface) and / or a keyboard or a set of control button (s) (input interface). In one embodiment, said screen or monitor 80 is a touch screen, on which a keyboard or at least one button can be viewed on the touch screen.
    [050] A suitable software product that can comprise a number of software modules and be stored on readable and recordable media (not shown) and can also comprise at least one instruction set (s) to enable the medium to computer 8 provides control and / or administration and / or operation of system 1 and / or each of its components or devices or devices themselves or these, for example, when executing at least one instruction.
    [051] The computer medium 8 can comprise memory media (not shown) for storing different types of software modules, various information and / or data etc., such as, for example, current positions, volume quantities and maturity data for antibodies / stabilizers / reagents, for example, in the antibody and cooler arrangement 6 and / or in the reagent support arrangement 12.
    [052] The system or instrument 1 may have means (not shown) for wired and / or wireless and / or Bluetooth communication with external devices, such as, among others, a printer, for example, to print a protocol list or an antibody / reagent list, etc., or an external PC or tablet or notebook or cell phone. It may also be possible to send a message to the external PC or tablet / notebook or cell phone or similar, in order to inform the assistant or laboratory engineer that a certain test sample preparation has been completed, giving him some warning or result messages etc. .
    [053] The two embodiments of the carousel / centrifuge arrangement or means 4, shown in figure 5A-5B, comprise a number of holding means 5 for secondary or complementary sample or test containers 3 '. Said two embodiments reveal two different alternatives of the test tube retention means 5. Within the retainer casing 50, shown in figure 6A-7D, each of the retention means 5 having titration or agitation functions, may have arranged a optical fiber detection means (not shown) to detect whether a secondary or complementary test container or sample 3 'has been placed in the retention means 5, when it is in the resting or lowered or lower position. In addition, the carousel / centrifuge arrangement or means 4 may further comprise a housing 45 and a mechanically or motor driven or operated cover or latch 44.
    [054] Figures 6A-6B and 7A-7D show the two embodiments of the carousel / centrifuge arrangement or means 4, according to the present invention, which illustrate and give several different details than is shown in figure 5A-5B.
    [055] The carousel / centrifuge arrangement or means 4 still comprises a motor drive arrangement or means 41 that allows movement or centrifugation in the clockwise and / or counterclockwise direction. The carousel / centrifuge arrangement or means 4 can function as a centrifuge and also apply the "mobile bucket" principle. All movements and / or rotations of the arrangement or carousel / centrifuge medium 4 can be programmed and / or stored in the computer medium 8. For example, the mixing and / or shaking of the test samples can be done by short rotating movements and clockwise and counterclockwise. According to the first embodiment (figure 5A, 6A, 7A), the carousel / centrifuge arrangement or means 4 can further comprise a titration or stirring arm or means 51 which can be driven by a motor arrangement or device 52 in order to stirring and / or swirling the contents of the 3 'sample test tube or container. In figure 6A two opposite movements (up and down) of the titration or agitation arm or medium 51 are shown with the arrows. According to the second embodiment (figure 5B, 6B, 7B-7D), the titration or agitation function of the carousel / centrifuge arrangement or means 4 can alternatively be performed or performed by a launch support or pinion means 53 operated by a motor-driven gear-wheel means 54. In figure 6B, two opposite movements (up and down) of the launching support or titration or stirring pinion means 53 are shown with the arrows. In addition, the titration or stirring arm or means 51 of the first embodiment can be adapted to raise, as shown in figure 7A, the test tube retaining means 5, in order to empty or pour excess liquid from the tube or container of secondary or complementary sample test 3 'in a medium for disposing of excess liquid 42 (figure 7C-7D), which can be connected to residue station 95. Alternatively, the launching support or titration or stirring pinion medium 53 of the second embodiment can be adapted to lift, as shown in figure 7B-7C, the test tube holding means 5 in order to empty or pour excess liquid from the secondary or complementary sample test tube or container 3 'into a medium for disposal of excess liquid 42 (figure 7C-7D), which can be connected to the waste station 95. The titration or agitation arm 51 and the launching support or titration or agitation pinion medium 53, respectively, the arra njo or engine device 52 and means of gear-wheels driven by engine 54, of said two embodiments, can be summarized and named for a titration or agitation arrangement 51; 53, and a motor-driven arrangement 52; 54, respectively. The means for disposing of excess liquid 42 may be a type of chamber or compartment or room / cavity within the retainer housing 50 and above the motor driven arrangement 52; 54 and having an outlet 43 (figure 7D) to facilitate coupling or connection with the help of means suitable for said waste station 95.
    [056] In addition, the arrangement or means of the carousel / centrifuge 4 can be made detachable. The carousel / centrifuge arrangement or means 4 can additionally comprise a handle 4H, shown in figure 5A-5B, in order to be easily removed from the system 1. In order to fix the centrifugation process of the carousel / centrifuge arrangement or means 4 , a sensor means, for example, among others, reflection laser sensor means, are used to confirm the locked position of the carousel / centrifuge device and / or its handle 4H. The same sensor or additional means can be used to determine whether the cover or lock actuated or operated mechanically or by motor 44 of the arrangement or carousel / centrifuge means 4 is in its closed or locked position. The operator should attempt to open the carousel / centrifuge cover or lock 44 during the centrifugation process, an alarm means will alert the operator at the same time that the carousel / centrifuge device is being rapidly stopped and controlled and the operator will not be able to reach any moving parts.
    [057] Figures 8A-8C show an embodiment of an antibody / stabilizer and cooling container arrangement or medium 6, in accordance with the present invention. It is arranged to hold a desired temperature or temperature range therein and comprises a box-shaped casing 61 and a cover 62 having several holes 63 placed along a plurality of tubes or containers designed especially 3 "for antibodies / stabilizers / reagents , or already mixed cocktails etc. and / or several bottles or containers, of at least one type, of at least one antibody fluid supplier, where each orifice 63 is adapted for and is substantially small, but large enough for the needle through it and also to the 3 "test tube or container and / or supplier's bottle or container below it, in order to suck liquid from the specially designated 3" tube or container or from the supplier's bottle or container without removing the cover 62, thus avoiding temperature changes, such as, for example, temperature increase, within the antibody and cooling container arrangement 6. The temperature variation desires within the antibody / stabilizer and cooling container arrangement or medium 6 is about 0.1 ° C to about 15 ° C, and more particularly, about 1 ° C to about 12 ° C, and even more particularly, between about 2 ° C and about 8 ° C. The antibody and cooling container arrangement 6 may further comprise at least two cartridges or cassettes 64, 65 for a plurality of tubes or containers specially designed 3 "for antibodies / stabilizers / reagents, or already mixed cocktails etc. and / or for several bottles or containers, of at least one type, of at least one antibody fluid supplier. The plurality of tubes or containers specially designed 3 "for antibodies / stabilizers / reagents, or already mixed cocktails etc. and / or the number of vials or containers in each cartridge or cassette 64 or 65 can be practically or properly arranged and chosen by the producer or system supplier. In addition, at least one of said cartridges or cassettes 64, 65 can be made detachable, in order to be exchanged for another one having different arrangements and placement of the 3 "tubes or containers and / or the supplier's bottles or containers; tube and / or bottle supplier arrangements or placements for each 64 or 65 cartridge or cassette may be pre-programmed in advance (by the producer or supplier of system 1, prior to the initial use of the system or instrument 1) or, alternatively, before initial use of the cartridge or cassette, they can be programmed or changed thereafter by the system user or responsible for maintenance, as needed or desired.In an alternative embodiment, each cartridge or cassette 64 or 65 can be comprised in a sleeve or liner. aluminum for each specially designed 3 "tube or container and / or supplier’s bottle or container in order to maintain a substantially uniform temperature in it (avoiding, with i (large temperature differences between the fluid temperature at the top and bottom). In yet another alternative embodiment, each vial or container of supplier in each cartridge or cassette 64 or 65 can be retained in it slightly tilted, thus allowing the needle of the arrangement or needle or syringe means 71 to be able to cross the neck. of the bottle and is capable of drawing fluid from the corner or bottom edge of said supplier bottle or container.
    [058] For each cartridge or cassette 64 or 65, a contact indication means 6 6 comprising at least two and, preferably, at least three contact indication devices for producing a "contact" or a "no" signal contact ", for example, among others, by means of tab contacts, can be arranged in the antibody and cooling container arrangement 6. The three contact indication devices allow nine different combinations for cartridges or cassettes 64 or 65. Each cartridge or cassette 64 or 65 can have a certain combination of pins or contacts or tabs, so that, when placed in the antibody and cooling container arrangement 6, the given combination of pins or contacts or tabs on the given cartridge or cassette 64 or 65 come into contact with the contact indication means 66 comprising contact indication devices and then a special signal (depending on the contact / pin / tongue combination) will be produced through the contact indication means 66 and will send the special signal to the computer medium 8, so that said cartridge or cassette 64 or 65 is easily recognized by the computer medium 8 in system 1. This means that the computer medium 8 in system 1 you will know the exact location or placement (which has been pre-programmed) of each ready mixed antibody / stabilizer / reagent or cocktail or similar in the given cartridge or cassette 64 or 65 that was placed in the antibody / stabilizer container arrangement or medium and cooling 6. Alternatively, each contact indication device can send its "contact" or "non-contact" signal to computer medium 8, and computer medium 8 will be based on these signals and will be able to recognize the particular cartridge or cassette 64 or 65.
    [059] In an alternative embodiment, each cartridge or cassette 64 or 65 can comprise at least one orientation means 67, for example, among others, an orientation pin, which allows only a possible placement of the cartridge or cassette 64 or 65 in the antibody / stabilizer and cooling container arrangement or means 6, and which does not allow the 64 or 65 cartridge or cassette to be overturned, for example, 90 or 180 degrees and thereafter placed in the antibody container arrangement or medium / stabilizer and cooling 6 (incorrect positioning).
    [060] The antibody and cooling container arrangement 6 comprises a cooling medium 68 comprising at least one inlet circulation fan 681 and at least one outflow circulation fan 682. The cooling medium 68 may further comprise a heat sink. heat 69 with several Peltier elements or heat dissipating elements (for example, from one and above). In the embodiment shown in figure 8B, there are four of these elements.
    [061] Additionally, each cartridge or cassette 64 or 65 can comprise, respectively, a 64H or 65H handle, so that it can be easily removed from the antibody and cooling container arrangement 6.
    [062] All tubes, bottles and containers can be made of glass, plastic or other material suitable for this purpose. .
    [063] In one embodiment of the invention, 3 "reagent or antibody containers can be designed to have a pointed bottom, so that small remaining volumes can be easily sucked or pumped from them by the needle or syringe arrangement or medium 71. In addition in addition, a small volume of an expired reagent or antibody mixture / cocktail or the like in a particular 3 "reagent or antibody container can, for example, be sucked or pumped out of it by the needle or syringe arrangement or medium 71, and thereafter , the needle or syringe arrangement or medium 71 can optionally wash or rinse said reagent or antibody container 3 "with the help of the needle or syringe arrangement or medium 71. Finally, fresh reagent or antibody can be filled into said determinate 3 "container. Alternatively, the given 3 "container reagent or antibody and / or supplier vial or container, which contains an expired reagent or antibody or the like, can be replaced with a new one containing fresh or similar reagent or antibody. Alternatively, since the medium computer 8 keeps track of all fluids / liquids in system 1, a particular reagent or antibody container 3 "and / or supplier flask or container containing a small remaining volume of reagent or antibody or mixture / cocktail or similar, which it will expire soon, it can be filled in relation to the reagent or antibody or fresh mix / cocktail or similar, and the new expiration date would be remembered by the storage medium or memory in the computer medium 8.
    [064] System or instrument 1 may further comprise a cell density detection means for detecting and / or measuring the cell density of cells in a given main sample or mother test tube or container 3, for example, in order to calculate and / or estimate, with the help of computer medium 8, the volume / amount of reagent fluid or antibody needed to be added, and / or whether it is necessary to adjust or correct the volume / amount of reagent fluid or antibody, and / or whether it is necessary to dispense more blood from the source or mother sample test tube or container 3 placed in the main test sample support arrangement 2. The cell density detection means may comprise: a) an optical fiber means comprising a light source or emitter and willing to send or emit light through a suitable plate or slide (having cells in it), for example, a plate or slide made of thin transparent plastic or glass, or a suitable container (containing itself) the cells), for example, the 3 'complementary test tube or one of the syringes of the needle or syringe arrangement or means 71 (for example, the 73S for small volumes, shown in figure 9), being able to retain itself or contain within itself the cells to be examined by means of cell density detection; and b) a means of receiving or detecting light arranged on the opposite side or end and adapted to receive the light emitted for further processing and / or estimation (by means of analogous signal measurement, for example, with the help of a signal amplifier analog) with the help of computer means 8. The cell density detection means can also be mounted in the array or robot means 7 in order to be able to be moved in all directions within x, y, z or 3D area or space of the system or instrument 1. If a thin glass or plastic plate or slide is to be used for the above process, system 1 may comprise a storage or stack / pile of several disposable plates or slides.
    [065] The system or instrument 1 may also comprise a fluid level measurement means to measure and / or control / check, with the help of computer means 8, the current fluid level in a container or chamber, etc. . arranged in at least one of the following: the antibody and cooler arrangement 6; possible / optionally the reagent support arrangement 12 with said at least one vial 13; possible / optionally the cleaning or rinsing arrangement 10; the main test sample holder arrangement is possible / optionally 2. The fluid level measurement medium can be arranged in an electronic circuit with at least one of the needle (s) of the arrangement or needle or syringe medium 71, in which the electronic circuit can register when the tip of the needle touches the surface of the fluid in the container or chamber that must be checked. Based on the height of the liquid or fluid from the bottom of the container or chamber to the surface of the internal fluid and the vertical or z-axis direction, this fluid height can be defined by the tip of the needle, the volume or amount of fluid remaining can be determined. calculated with the help of the computer medium 8 and the shape / shape of the container or chamber and / or information or data of capacity or volume assigned to it or connected with the predetermined position of that container or chamber, where the information or data can be stored or recorded on the computer medium 8 and, particularly, on its storage medium or memory.
    [066] The current level in said at least one vial 13 of the reagent support arrangement 12 and / or in said at least one vial or chamber or waste container 95 from waste station 95 can be controlled or visually checked by the assistant laboratory or operator. Alternatively, for the reagent support arrangement 12 and / or the waste station 95, at least one level monitoring means may be arranged, in which the level monitoring means may comprise at least one sensor placed in or within the respective flask or container adapted to detect a certain level, for example, a minimum and / or a maximum level. Several different known techniques can be chosen for use in this process.
    [067] Computer medium 8 can be programmed to control and / or measure fluid volumes, for example, antibody volumes, for example, at the beginning of the system / instrument 1 and / or at or with any period or interval predetermined time.
    [068] If it is necessary to refill a certain container of antibody or reagent or similar, laboratory assistant or operator can be notified, for example, by visual and / or audio alert message produced by the computer medium 8 of the system / instrument 1, and / or by a wired and / or wireless message sent for communication with the external system device, for example, a PC or tablet or notebook or external cell phone etc.
    [069] In addition, the robot arrangement or means 7, and particularly its arm arrangement 7, 72, can be directed by computer means 8 to be placed correctly, so that it is capable of presenting or pointing the container or exact chamber that must be refilled or replaced (for example, due to the date of birth) by means of at least one of: one of the needle (s); an indicator means (for example, a type of an arrow, physical or applied / painted, for example, on a wall or side of the robot arrangement 7); and a light-pointing beam, produced by an LED or light source, which can be mounted on the robot arrangement or medium 7 and, particularly, on its arm arrangement 7, 72. Thus, any possibility of making an error when the laboratory assistant or operator performs the necessary operation, is minimized or omitted.
    [070] It is also possible to use T-coupling (s) in the middle of the hose or tube arrangement of the system that connects or couples different container (s) and / or chamber (s) itself, in order to connect the rinsing or rinsing arrangement or station 10 and the surplus liquid medium 42 of the arrangement or • carousel / centrifuge 4 in addition to the waste station 95, for example, possibly by means of pumping medium 90 (shown in figure 10) .
    [071] Figure 9 shows, in detail, an embodiment of a needle or syringe arrangement or means, according to the present invention. As mentioned before, said at least one needle or syringe arrangement or means 71 can be disposed in an arm 72 of the robot arrangement or means 7 and can comprise at least one syringe 73S, 73L having a plunger 75 and a needle or cannula 74. Plunger 75 can be operated, for example, pushed up or down, by at least one motor-driven mechanism 76. In one embodiment, the needle or syringe arrangement or means 71 can comprise two syringes 73S, 73L placed substantially vertically and parallel to each other and operated by said at least one motor-driven mechanism 76. In another embodiment, each syringe 73S, 73L can be operated independently by its own motor-driven mechanism 76. According to one embodiment , the cell density detection means 77 may be disposed together or within the needle or syringe arrangement or means 71 and may comprise a fiber optic means 78 arranged to send or emit light through the syringe 73S p for small volumes, and a means of receiving or detecting light 79 arranged on its opposite side or end and adapted to receive the light emitted for further processing and / or estimation of cell density. THEORY OF OPERATION OF THE INSTRUMENT OR SYSTEM
    [072] Execution of a protocol
    [073] A standard example: The preparation procedure in the FlowStainer InstruNor can have the following steps, for example, in a CD4 Enumeration (differentiation cluster 4) levels, for example in HIV-infected cultures, in an immunology laboratory:
    [074] i) The laboratory assistant selects, for example, on the touch screen 80, the test program must be run or executed (see graphical user interface in figure 11A-11P).
    [075] The FlowStainer InstruNor can also provide, for this step, a barcode reader arrangement (not shown) to program tests on the instrument or system 1.
    [076] ii) The laboratory assistant places the liquid human cell sample tube (s) 3 in the mother sample holder or main test sample holder arrangement or medium 2 (holder 1), still places several complementary test tubes 3 'in the carousel / centrifuge arrangement 4 (support 2), according to the machine instructions, depending on the programmed number of main test tubes 3 and the test (s) programmed to be performed, lock the cover or main door 111, and press the << EXECUTE 0 TEST >> button.
    [077] iii) Now, instrument / system 1 will automatically perform the rest of the steps. The cap or stopper 30 on the sample test tube or container 3 is lifted automatically (see figures 3 and 4) and the robotic arm arrangement 7, 72 uses, for example, the number one / 73L syringe of the needle arrangement or syringe 71, and dispenses, for example, about 100 μl of the whole blood from the tube or mother sample container 3 in the tube or complementary sample test container 3 ', placed in the carousel / centrifuge arrangement 4 (support 2) ( see, for example, figures 4 and 6).
    [078] In a washing procedure, an optical light can be used to detect the volume of buffer needed to add to the test sample. The optical light can detect low cell count, which opens the possibility for the Flow Stainer InstruNor to dispense more blood in the complementary test tube 3 ', if necessary. This also optimizes the use of expensive antibody or antibodies in a test, and thus minimizes overuse or excessive and unnecessary use of the expensive antibody or antibodies.
    [079] Alternatively, blood cell density measurement can be performed using blood from the main sample test tube or container 3, before the blood sample is added or placed in at least one sample test tube or container complementary 3 ', thus giving the operator sufficient information and good control over necessary amounts of antibodies, buffer reagents etc. to be used for that particular blood sample.
    [080] iv) The needle is then cleaned at the rinsing station 10, for example, with distilled water or other liquid (s) and / or suitable chemical (s).
    [081] v) The robot arrangement 7 with the arm arrangement 72, then uses, for example, syringe number two / 73S of the needle arrangement or syringe 71, and dispenses in the whole blood, for example, about 20 μl of CD4 reagent found in the antibody and cooling arrangement or medium 6 (support 3) (see figure 8A-8C). The needle is then rinsed, for example, with PBS liquid or a liquid similar to the Coulter Clenz product in the rinsing station 10.
    [082] vi) While the CD4 reagent is added to the whole blood, the titration or agitation arrangement 51; 53 can swirl the test sample in a subtle way (see figure 6). An incubation time of, for example, approximately 15-45 minutes can then be allowed. This is done, for example, at room temperature (from about 20 ° C to about 25 ° C) and possibly in the dark.
    [083] vii) Then, the number one / 73L syringe is used to add, for example, about 2 ml of lysis solution (placed in the reagent support arrangement or medium 12 (support 4)) to the complementary tube 3 ' , for example, at room temperature, followed by centrifugation of the test sample, for example, at about 1,500 RPM or more. An incubation period of about 10-12 minutes can elapse, possibly being done in the dark and, for example, at room temperature. The needle is then taken to the rinsing station 10 for cleaning, using at least one cleaning liquid, for example, Coulter Clenz.
    [084] viii) The titration arrangement 51; 53 can then spill the excess liquid to / at the waste station 42.
    [085] ix) The test is then washed with 1 x PBS, for example, with about 0.1% azide, adding, for example, about 0.5 ml, for example, about 1% of paraformaldehyde, using, for example, syringe number two / 73S. This is also used as a carrier liquid that can fix the cells before going to the flow cytometer. The needle is then rinsed, for example, with distilled water at the rinsing station 10.
    [086] x) The Flow Stainer InstruNor now ends the automatic preparation procedure and sends an alert signal, as well as providing visible information (see also figure 11H) on the touchscreen 80 to download the instrument or system 1. The complementary test tube 3 'can now be directly transported to the flow cytometer for complete analysis.
    [087] Performing the test on the instrument's touchscreen
    [088] The exemplary test mentioned above is easy to run on a programmed FlowStainer InstruNor instrument or system, ready to run 1, in accordance with the present invention. The following steps are necessary to perform this exemplary test:
    [089] Figure 11A shows a screen image of the Operation Menu.
    [090] When a FlowStainer InstruNor 1 system is in "Operation mode", the Operation Menu (figure 11A) is the screen image that will be standard at any time. The software product has several protocols and panels already programmed (multiple protocols) that are easy to access at any time. The. When the engineer / lab assistant is ready to run a test, he / she verifies that the preferred protocol is "green", which means that he / she has confirmed that he / she is ready for the instrument or system 1. "Red" sign means "not ready" or "non-rotatable" or "non-executable", or the like. B. Press the << Load Main Test Sample >> button.
    [091] Figure 11B presents a screen image of the procedure for choosing a test tube protocol in position.
    [092] On the screen shown in figure 11B, the laboratory engineer or laboratory assistant selects which protocol or panel (multiple protocols) to be run or executed. All protocols or panels are programmed in the Main Menu in advance. If protocols or panels are programmed in advance, there will be nothing to choose from on this screen.
    [093] iii) The protocol or panel is chosen by pressing on the text line and then pressing the << CONFIRM >> button. If the protocol or panel is chosen and an additional protocol is required, press << PROTOCOL NAME >> and << ADD >>, then choose or select an additional protocol and finally press << CONFIRM >>. In the upper right box, some information is displayed on how many complementary secondary 3 'test tubes were placed in the carousel / centrifuge arrangement 4.
    [094] iv) When this is done, press the << CONFIRM >> button.
    [095] Figure 11C presents a screen image of the procedure for loading the main test tube (s).
    [096] v) An immediate pop-up requests a liquid human cell sample in the main test sample holder 2 medium or support (support 1). At the same time, the main door seal 111 is opened. When a sample tube 3 is placed in position, press the << CONFIRM >> button.
    [097] Figure 11D shows a screen image of the procedure for loading the complementary test tube (s).
    [098] vi) The number of 3 'complementary or secondary test tubes, which are requested to be placed in the carousel / centrifuge support arrangement 4, is indicated on the screen shown in figure 11D. The requested complementary or secondary test tubes 3 'are applied or placed or inserted, one by one, in the carousel / centrifuge support arrangement or means 4, and the inserted tube is detected by means of a suitable detection device or sensor, for example, in order for the next tube to be inserted, alternatively or additionally, followed by pressing the << CONFIRM >> button. The Cover / Main Door 111 must then be closed.
    [099] Figure 11E shows a screen image of the instrument calibration procedure.
    [0100] vii) A calibration procedure is now started in order to find out if the instrument is ready to perform the test without errors.
    [0101] Figure 11F presents a screen image of the procedure or step to Continue.
    [0102] viii) When the calibration has been done and found to be approved, the instrument or system 1 will automatically proceed to the next step. A choice to add more test samples 3 is now given, as is the option / button << RUN TEST >>.
    [0103] Figure 11G shows a screen image of the Executing screen process.
    [0104] ix) When << EXECUTE TEST »is pressed on the screen image shown in figure 11F, the execution screen gives, in real time, updated information on the progress of the operation.
    [0105] Figure 11H shows a screen image of the Unloading step.
    [0106] x) When the screen image, shown in figure 11H, is visible on the touch screen 80, the main cover 111 is unlocked and it is now possible to remove the test sample (s) and the main sample (s) of the supports. The complementary tube (s) 3 'is (are) now ready to go directly to the flow cytometer for further analysis.
    [0107] Programming the protocol on the instrument's touchscreen
    [0108] In order to be able to perform tests on the Flow Stainer InstruNor 1 instrument, there are several pre-programming activities to perform, in addition to the filling of reagents / antibodies in the vial holder (holder 4) and the antibody holder (holder 3).
    [0109] The protocols and panels are programmed as follows on the touchscreen (starts in the Operation Menu, as shown in figure 11A): a. In order to be able to program the system, press the << SETTINGS >> button at the bottom of screen 80.
    [0110] Figure 111 presents a screen image of the Main Menu.
    [0111] ii) The << PROTOCOL / PANEL >> button takes you to a creation page for programming a protocol.
    [0112] Figure 11J presents a screen image of the Protocol / Panel window.
    [0113] iii) If no protocol or panel is pre-programmed, then the boxes in it will be empty. Press the << CREATE PROTOCOL >> button.
    [0114] Figure 11K presents a screen image of the protocol creation procedure (Create Protocol).
    [0115] iv) Initially, the Create Protocol page may be empty. In order to program a protocol, a name is written in the upper left box. By using << ADD STEP >>, any and all steps in the protocol can be programmed.
    [0116] Figure 11L presents a screen image of the procedure for choosing the step of the protocol creation procedure (Create Protocol - Choose step)
    [0117] v) All "activities" or "steps" that the instrument or system 1 can manipulate are activated by pressing the text line and then the << CONFIRM >> button.
    [0118] Figure 11M shows a screen image of the Volume / Time / Speed entry procedure within the procedure for choosing the stage of the protocol creation procedure.
    [0119] vi) For the following activities, the Volume / Time / Speed pop-up is automatically received when programming a protocol: Blood recovery, Centrifuge, Incubation, Vibration, Titration and Shaking.
    [0120] Figure UN presents a screen image of the Coloring / Washing / Lysis insertion procedure within the procedure for choosing the stage of the protocol creation procedure, in which antibodies or other reagents can be chosen and regulated, etc.
    [0121] vii) For the following activities, the Coloring / washing / Lise popup is automatically received when programming a protocol: Coloring process, Sample washing, and Lise solution.
    [0122] Figure 110 shows a screen image of the procedure for selecting the color solution (s) (Create protocol - Select color solution).
    [0123] xiii) By pressing << Antibody >> or << Other reagents >> (as shown in figure 11N), the Select Staining Solution window opens. The difference between the two views is how the antibody / reagent list is classified. Based on the antibody / reagent ID in the left box, shown in figure 110, the staining solution is selected. When pressing the button called << SAVE AND CONTINUE >>, the system will return to the "Create Protocol" screen image, shown in figure 11K, in order to add more steps to the protocol program.
    [0124] ix) When the protocol is completed, pressing the << SAVE PROTOCOL >> button will end the programming.
    [0125] Figure IIP presents a screen image of the Protocol / Panel window that is similar to the one shown in figure 11J, but with the new programmed protocol (called, for example, cell T 1) visible on the screen.
    [0126] x) The new programmed protocol is now visible on the Protocol / Panel screen or window. The << SETTINGS >> button is selected in order to return to the Main Menu. The new programmed protocol, cell T 1, is now possible to choose on the screen image, shown in figure 11B, in relation to the procedure for choosing a test tube protocol in position (Choose Protocol for test tube in position) .
    [0127] As can also be seen in figure IIP, there are other operations that can be performed, such as: printing a protocol list (Print Protocol list), creation of a new protocol (Create Protocol) etc.
    [0128] Additional steps or operations, for example, as described outside the "Instrument or System Theory of Operation" section here, connected to the system's operational, maintenance and programming functions can also be programmed into the software product and executed or performed on the system or instrument.
    [0129] Modifications, alterations, additional adaptations of the present invention will appear on their own, to those skilled in the art, without departing from the scope of the invention, as expressed and declared in the following patent claims.
    权利要求:
    Claims (32)
    [0001]
    1. FULLY AUTOMATED CELL PRE-TREATMENT PROCESS INSTRUMENT FOR THE PREPARATION OF AT LEAST ONE CELL SAMPLE, the instrument being encapsulated in an instrument housing, the instrument housing being characterized by comprising: - a sample support arrangement main test (2) for a certain number of sample containers (3); - a carousel and centrifuge arrangement (4) comprising several retaining means (5) for one or more secondary sample containers (3 '); - a cooling vessel arrangement (6) for a predetermined number of stabilizers being at least one of the following: antibodies, reagents, cocktail mixtures, and providing, for support, a desired temperature variation in itself; - a robot arrangement or means (7) arranged to serve, mechanically or physically, the instrument (1); and - a computer means (8) comprising at least one CPU and provided to control and / or operate all components, apparatus or devices of the instrument (1), in order to achieve complete automation of the entire pre-treatment process cell, in which said carousel and centrifuge arrangement (4) is detachable from the instrument and being arranged to function as a centrifuge, the various retaining means (5) for one or more secondary sample containers (3 ') are articulated articulated to provide a “movable bucket” principle and the carousel and centrifuge arrangement (4) further comprises arms or titration or agitation means (51; 53) for individual titration or agitation of sample containers (3 ') secondary driven by a motor driven arrangement (52; 54), in order to agitate the contents of the sample container (3 ') in the holding medium (5), the arm or the titration or agitation means (51; 53) it is further adapted to lift the retaining means (5) in order to empty or pour excess liquid into said sample container (3 ') for excess liquid waste means (42).
    [0002]
    2. INSTRUMENT according to claim 1, in which the instrument (1) is characterized by still comprising a reagent support arrangement (12) arranged to accommodate one or more reagent bottles (13).
    [0003]
    INSTRUMENT, according to either of claims 1 or 2, characterized in that the main test sample support arrangement (2) comprises, in its proximity, means (9) for automatic removal and / or placement of one or more covers sample container (30).
    [0004]
    4. INSTRUMENT according to any one of claims 1 to 3, characterized in that the main test sample holder arrangement (2) further comprises an additional sample container holding means (25) for retaining one or more sample containers of a different type.
    [0005]
    5. INSTRUMENT, according to any one of claims 1 to 4, characterized by the robot arrangement (7) next to its elements / components, allowing and providing movement (s) in all directions within x, y, z or area or 3D space of the instrument (1).
    [0006]
    6. INSTRUMENT according to any one of claims 1 to 5, characterized in that the robot arrangement (7) comprises at least one arm arrangement (72) and at least one needle or syringe arrangement (71) comprising at least one needle or cannula (74) and at least one syringe (73S, 73L) having a plunger (75), wherein the plunger (75) can be operated by at least one motor-driven mechanism (76).
    [0007]
    7. INSTRUMENT according to claim 6, characterized in that said at least one needle or syringe arrangement (71) comprises two syringes (73S, 73L) placed substantially vertically and parallel to each other, a first of the two syringes (73S ) is one with a microliter range (μl) and a second of the two syringes (73L) is one with a milliliter range (ml).
    [0008]
    8. INSTRUMENT, according to any one of claims 1 to 7, in which the instrument (1) is characterized by still comprising a cleaning or rinsing station (10), wherein said at least one syringe (73S, 73L) of the needle or syringe arrangement (71) is being cleaned or rinsed with the help of at least one fluid or liquid or solution and / or chemical component for cleaning or rinsing.
    [0009]
    9. INSTRUMENT, according to any one of claims 1 to 8, in which the instrument (1) is characterized by still comprising a waste station (95) having pumping means (90) and adapted to collect fluid (s), liquid (s), stabilizer (s), reagent (s), antibodies and / or residual sample (s).
    [0010]
    10. INSTRUMENT according to any one of claims 1 to 9, characterized in that the computer means (8) comprises an output interface and an input interface, such as at least one of the following: a screen or monitor (80), a keyboard and a set of command button (s).
    [0011]
    11. INSTRUMENT according to any one of claims 1 to 10, characterized in that the computer medium (8) still comprises storage medium or memory.
    [0012]
    12. INSTRUMENT, according to any one of claims 1 to 11, in which the instrument (1) is characterized by still comprising means for wired and / or wireless communication and / or by Bluetooth with external devices.
    [0013]
    13. INSTRUMENT according to any one of claims 1 to 12, characterized in that the carousel and centrifugal arrangement or means (4) further comprise a motor drive arrangement or means (41) that allows movement or centrifugation in a direction clockwise and / or counterclockwise.
    [0014]
    14. INSTRUMENT according to any one of claims 1 to 13, wherein the instrument (1) is further characterized by comprising a cell density detection means for detecting the cell density of cells in a given test tube or container. main sample (3).
    [0015]
    15. INSTRUMENT, according to claim 14, characterized in that the cell density detection means comprises an optical fiber means arranged to send or emit light through the cells that are on or on a suitable transparent plate, and a receiving means or detection of light arranged on its side or opposite end and adapted to receive the light emitted for processing and / or additional estimate of cell density.
    [0016]
    16. INSTRUMENT according to any one of claims 1 to 15, in which the instrument (1) is further characterized by comprising a hose or tube arrangement means that connects or couples different container (s) and / or chamber (s) ) and / or bottle (s) together inside the instrument case.
    [0017]
    17. INSTRUMENT according to any one of claims 2 to 16, wherein the instrument (1) is further characterized by comprising a fluid level measurement means for measuring and / or controlling the fluid level in a container or chamber arranged in at least one of the following: the container and cooling arrangement (6); the reagent support arrangement (12) with said at least one vial (13); cleaning or rinsing arrangement (10); and the main test sample support arrangement (2), where the fluid level measurement medium is arranged in an electronic circuit with at least one of the needle (s) of the needle or syringe arrangement (71) , so that the electronic circuit records when the tip of the needle touches the surface of the fluid in the container or chamber to be checked, and, based on the height of the liquid or fluid from the bottom of the container or chamber to the surface of the fluid in it and in the vertical or z-axis direction, the volume or amount of fluid remaining is being calculated.
    [0018]
    18. INSTRUMENT according to any one of claims 1 to 17, characterized in that the container and cooling arrangement (6) comprises a housing (61) and a cover (62) having several holes (63) where each hole (63) it is adapted for a needle to pass through it, and also for the tube or container (3 ”) and / or vial or container of supplier below it, in order to suck liquid from these, without removing the cover (62), avoiding, thus, temperature changes within said container and cooling arrangement (6).
    [0019]
    19. INSTRUMENT according to any one of claims 1 to 18, characterized in that the container and cooling arrangement (6) further comprises a cooling means (68) comprising at least one inlet circulation fan (681), at least an outlet circulation fan (682), and a heat sink (69) having several Peltier elements, to fix the support of the desired temperature variation itself.
    [0020]
    20. INSTRUMENT according to any one of claims 1 to 19, characterized in that the container and cooling arrangement (6) further comprises at least two cartridges or cassettes (64, 65) for a plurality of specially designed tubes or containers (3 ”) And / or for several vials or containers, of at least one type, of at least one antibody fluid supplier, wherein the at least one of said cartridges or cassettes (64, 65) is made detachably.
    [0021]
    21. INSTRUMENT according to any one of claims 1 to 20, characterized in that the motor-driven titration or agitation arrangement includes a launching pinion or pinion operated by a motor-driven wheel gear.
    [0022]
    22. INSTRUMENT according to claim 21, characterized in that the motor-driven titration or agitation launch support arrangement rotates one of the sample container holdings to empty or spill excess liquid from the secondary or complementary sample test tube or container 3 'in an excess liquid disposal medium (42).
    [0023]
    23. INSTRUMENT according to any one of claims 1 to 22, characterized in that the container and cooling arrangement further comprises a cooling means comprising at least one inlet circulation fan and one outlet circulation fan.
    [0024]
    24. CAROUSEL AND CENTRIFUGAL ARRANGEMENT (4), characterized by comprising different retaining means (5) for one or several sample containers (3 '), in which said carousel / centrifuge arrangement (4) is arranged to function as a centrifuge, the various holding means (5) for one or more secondary sample containers (3 ') are articulated in an articulated manner to provide a “movable bucket” principle, and further comprise: arm or means of titration or agitation ( 51; 53) driven by a motor driven arrangement (52; 54), in order to agitate the contents of said sample container (3 ') in the holding means (5), the titration or agitation arm or means (51 53) is further adapted to lift the retaining means (5) in order to empty or pour excess liquid into said sample container (3 ').
    [0025]
    25. ARRANGEMENT, according to claim 24, characterized in that it also comprises a motor drive arrangement (41) that allows movement or centrifugation in the clockwise and / or counterclockwise direction.
    [0026]
    26. ARRANGEMENT, according to claim 26, characterized in that it further comprises a means of detecting cell density to detect the cell density of cells in a given main sample test tube or container (3).
    [0027]
    27. ARRANGEMENT, according to claim 26, characterized in that the cell density detection means comprises an optical fiber means arranged to send or emit light through the cells that are on or in a suitable plate / slide or transparent container, and a means of receiving or detecting light disposed on its side or opposite end and adapted to receive the light emitted for further processing and / or estimation of cell density.
    [0028]
    28. ARRANGEMENT, according to any one of claims 24 to 27, characterized in that it is still arranged to be detachable.
    [0029]
    29. ARRANGEMENT according to any one of claims 24 to 28, characterized in that it further comprises a housing (45) and a cover (44).
    [0030]
    30. ARRANGEMENT, according to any one of claims 24 to 29, characterized in that the cover is driven by a motor.
    [0031]
    31. ARRANGEMENT according to any one of claims 24 to 30, characterized in that it further comprises a sensor means configured for confirming the locked position to indicate whether the lid is locked or opened.
    [0032]
    32. ARRANGEMENT according to any one of claims 24 to 31, characterized in that the motor-driven titration or agitation arrangement includes a launching or pinion support operated by a motor-driven wheel gear.
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    AU2012370530B2|2016-11-17|
    JP2015508177A|2015-03-16|
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    AU2012370530A1|2014-09-18|
    CN104272083B|2018-01-02|
    WO2013125959A1|2013-08-29|
    HK1201917A1|2015-09-11|
    US20130224851A1|2013-08-29|
    CN104272083A|2015-01-07|
    EP2817606A1|2014-12-31|
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    法律状态:
    2019-09-17| B06F| Objections, documents and/or translations needed after an examination request according [chapter 6.6 patent gazette]|
    2019-12-17| B06U| Preliminary requirement: requests with searches performed by other patent offices: procedure suspended [chapter 6.21 patent gazette]|
    2020-07-07| B06A| Notification to applicant to reply to the report for non-patentability or inadequacy of the application [chapter 6.1 patent gazette]|
    2021-01-19| B09A| Decision: intention to grant [chapter 9.1 patent gazette]|
    2021-03-02| B16A| Patent or certificate of addition of invention granted|Free format text: PRAZO DE VALIDADE: 20 (VINTE) ANOS CONTADOS A PARTIR DE 24/02/2012, OBSERVADAS AS CONDICOES LEGAIS. |
    优先权:
    申请号 | 申请日 | 专利标题
    PCT/NO2012/050031|WO2013125959A1|2012-02-24|2012-02-24|System, apparatuses and devices for pretreating cells|
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