EP2569088A1 - Distributeur et procédé pour la distribution de matériaux fluides ou coulants - Google Patents

Distributeur et procédé pour la distribution de matériaux fluides ou coulants

Info

Publication number
EP2569088A1
EP2569088A1 EP11720421A EP11720421A EP2569088A1 EP 2569088 A1 EP2569088 A1 EP 2569088A1 EP 11720421 A EP11720421 A EP 11720421A EP 11720421 A EP11720421 A EP 11720421A EP 2569088 A1 EP2569088 A1 EP 2569088A1
Authority
EP
European Patent Office
Prior art keywords
dispenser
flowable
line
container
outlet end
Prior art date
Legal status (The legal status 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 status listed.)
Withdrawn
Application number
EP11720421A
Other languages
German (de)
English (en)
Inventor
Armin Schriber
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Tecan Trading AG
Original Assignee
Tecan Trading AG
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 Tecan Trading AG filed Critical Tecan Trading AG
Publication of EP2569088A1 publication Critical patent/EP2569088A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B67—OPENING, CLOSING OR CLEANING BOTTLES, JARS OR SIMILAR CONTAINERS; LIQUID HANDLING
    • B67D—DISPENSING, DELIVERING OR TRANSFERRING LIQUIDS, NOT OTHERWISE PROVIDED FOR
    • B67D7/00—Apparatus or devices for transferring liquids from bulk storage containers or reservoirs into vehicles or into portable containers, e.g. for retail sale purposes
    • B67D7/06—Details or accessories
    • B67D7/08—Arrangements of devices for controlling, indicating, metering or registering quantity or price of liquid transferred
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/02—Burettes; Pipettes
    • B01L3/0241—Drop counters; Drop formers
    • B01L3/0265—Drop counters; Drop formers using valves to interrupt or meter fluid flow, e.g. using solenoids or metering valves
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B65—CONVEYING; PACKING; STORING; HANDLING THIN OR FILAMENTARY MATERIAL
    • B65B—MACHINES, APPARATUS OR DEVICES FOR, OR METHODS OF, PACKAGING ARTICLES OR MATERIALS; UNPACKING
    • B65B3/00—Packaging plastic material, semiliquids, liquids or mixed solids and liquids, in individual containers or receptacles, e.g. bags, sacks, boxes, cartons, cans, or jars
    • B65B3/26—Methods or devices for controlling the quantity of the material fed or filled
    • B65B3/34—Methods or devices for controlling the quantity of the material fed or filled by timing of filling operations
    • B65B3/36—Methods or devices for controlling the quantity of the material fed or filled by timing of filling operations and arresting flow by cut-off means
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B67—OPENING, CLOSING OR CLEANING BOTTLES, JARS OR SIMILAR CONTAINERS; LIQUID HANDLING
    • B67D—DISPENSING, DELIVERING OR TRANSFERRING LIQUIDS, NOT OTHERWISE PROVIDED FOR
    • B67D7/00—Apparatus or devices for transferring liquids from bulk storage containers or reservoirs into vehicles or into portable containers, e.g. for retail sale purposes
    • B67D7/06—Details or accessories
    • B67D7/72—Devices for applying air or other gas pressure for forcing liquid to delivery point
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N35/1009—Characterised by arrangements for controlling the aspiration or dispense of liquids
    • G01N35/1016—Control of the volume dispensed or introduced
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/14—Process control and prevention of errors
    • B01L2200/148—Specific details about calibrations
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/02—Identification, exchange or storage of information
    • B01L2300/021—Identification, e.g. bar codes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/02—Identification, exchange or storage of information
    • B01L2300/021—Identification, e.g. bar codes
    • B01L2300/022—Transponder chips
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/06—Valves, specific forms thereof
    • B01L2400/0633—Valves, specific forms thereof with moving parts
    • B01L2400/0655—Valves, specific forms thereof with moving parts pinch valves
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N2035/1027—General features of the devices
    • G01N2035/1034—Transferring microquantities of liquid
    • G01N2035/1039—Micropipettes, e.g. microcapillary tubes
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N2035/1027—General features of the devices
    • G01N2035/1034—Transferring microquantities of liquid
    • G01N2035/1041—Ink-jet like dispensers
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N35/1095—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices for supplying the samples to flow-through analysers
    • G01N35/1097—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices for supplying the samples to flow-through analysers characterised by the valves

Definitions

  • the invention relates according to the preamble of independent claim 1, a dispenser for dispensing flowable or free-flowing materials.
  • This dispenser comprises at least one conduit having an inlet end and an outlet end for transporting a flowable material or a flowable material from a container to the outlet end.
  • the line is positioned with its inlet end in the flowable or free-flowing material of the container or connected to the container, but in each case with the flowable or free-flowing material substantially filled.
  • the dispenser also includes a check valve to control the delivery of the flowable or free flowing material from the outlet end.
  • the dispenser further includes a control unit which controls opening and closing of the check valve.
  • the invention furthermore relates, according to the preamble of independent claim 20, to a corresponding method for dispensing flowable or free-flowing materials.
  • dispensers It is known to perform the delivery of liquids (the dispensing) more or less automated.
  • the devices used for this purpose are generally referred to as dispensers.
  • dispensers Depending on the requirements on the precision of the delivery with regard to the volume to be dispensed, such dispensers have a different complexity.
  • laboratories for example in diagnostic institutes or in other biological or biochemical laboratories, the efficiency and reproducibility of routine experiments can be considerably increased with the help of automated dispensing processes.
  • laboratory dispensers typically have very high demands on the precision of the volume of liquid dispensed during dispensing. This is because they often work with very expensive reagents (eg enzymes, dyes, etc.), and because the sample volumes to be processed are relatively small (about 0.5 ⁇ to 2 ml).
  • the dispensers include special pumps that control fluid delivery as much as possible.
  • Frequently used pumps are, for example, peristaltic pumps or piston pumps.
  • Peristaltic pumps are preferably used for pure dispensers, which are used for less sensitive laboratory processes.
  • Piston pumps are installed in dispensers and in combined dispensers with aspirating function, which must dispense liquid volumes with very high precision or - in the case of a pipetting device - also aspirate (aspirate).
  • the driving force for dispensing the fluid volume is provided by an additional "drive pressure" provided by a pump to the fluid, but the incorporation of such pumps makes the dispensers used in laboratories relatively complex and therefore expensive.
  • US Pat. No. 6,063,339 discloses a dispenser which can dispense liquids in a preprogrammed array very quickly and with high precision.
  • This dispenser includes a pressure pump that regulates the inflow of liquid to be dispensed to a dispenser head.
  • a control unit then controls a solenoid valve and thus the dispensing (or portioning) of the liquid through the dispenser head.
  • Such a dispenser can deliver accordingly defined volumes of liquid with high precision and speed, but this is very complex in its construction.
  • Easier dispensers with significantly lower precision are known, for example, from hospital infusion systems (see US 3,667,464).
  • the hydrostatic pressure of the infusion fluid is used as the driving force, and a desired dropping speed is set by means of a metering valve (eg a roller clamp). If the fluid volume decreases, the metering valve must be readjusted manually. If, however, the delivery of a constant fluid supply is required, additional infusion pumps (infusion pumps) are used in such infusion systems, so that the fluid can be delivered in a controlled manner by the additional pressure. Again, usually peristaltic pumps are used.
  • EP 0 781 521 B1 discloses a dispenser designed as a soap dispenser, in which a uniform dispenser is provided for maintaining the dispenser
  • Flow rate of the hydrostatic pressure itself is kept constant despite decreasing liquid level. This is achieved by carrying the container with the liquid from an element that responds to weight. If the container is emptied by multiple discharges of a volume of soap, it becomes lighter, whereupon the weight-responsive element raises the container. The height of the container is thus always adjusted to the level of the liquid in this container.
  • weight-responsive elements may be, for example, coil springs adapted to the weight of the container.
  • the volumes dispensed from such soap dispensers do not impose any special requirements on precision with regard to the dispensed volume.
  • the dispenser according to the invention introduced at the outset is characterized in that the line comprises an elastic section which can be inserted into the check valve and completely separates all parts of the check valve from the flowable or free-flowing material, the check valve acting as a pinch valve for stationary compression of this elastic section and is thus designed to close the line.
  • the inventive dispenser is also characterized in that the control unit for dispensing a defined, discrete amount of the flowable or free-flowing material in a sample vessel controls a corresponding opening time t of the check valve, said opening time t is exclusively determined by the properties of the flowable or free-flowing material to be dispensed and the properties of the line substantially filled with these materials.
  • This object according to the second aspect is achieved with the features of independent claim 20.
  • the method according to the invention is based on the use of the dispenser according to the invention introduced at the beginning and is characterized in that an elastic section of the line is inserted into the check valve, this elastic section completely separating all parts of the check valve from the flowable or free-flowing material, and wherein
  • Shut-off valve is designed as a pinch valve and compresses this elastic portion to close the line stationary.
  • the inventive method is also characterized in that the control unit for delivering a defined, discrete amount of the flowable or free-flowing material in a sample vessel controls a corresponding opening time t of the check valve, said opening time t is exclusively determined by the properties of the flowable or free-flowing material to be dispensed and the properties of the line substantially filled with these materials. Additional inventive features will be apparent from the dependent claims, respectively.
  • the dispenser according to the invention comprises the following advantages:
  • Sterile packaged liquids can be processed from simultaneously sterilized containers and lines, ie. be dispensed.
  • a flexible design of the dispenser ensures that different containers, lines and valves can be used depending on the need.
  • liquids which, for example, comprise sensitive material such as cells, do not have to be subjected to any additional pressure except for the locally limited influence of the closing valve.
  • the flexibly selectable cable lengths and the different selectable positions of the valve allow a design with the lowest dead volume, thus a cost-effective operation is possible.
  • FIG. 1 shows a dispenser according to a first embodiment, in which the ascending section of a line is inserted into a standard container for liquids to be dispensed and the descending section is guided through a closing valve, wherein the line is filled when the closing valve is open;
  • FIG. 2 shows a first variant of the dispenser of FIG. 1 in the controlled delivery of liquid into a single sample vessel;
  • FIG. 3 shows a second variant of the dispenser of FIG. 1 in the controlled dispensing of liquid in wells of a microplate
  • FIG. 4 shows a container of a dispenser for liquids to be dispensed according to a second embodiment, which comprises a line connected to this container with an exclusively descending part, which is designed to be used in a closing valve;
  • FIG. 5 shows a container of a dispenser for liquids to be dispensed or free-flowing solids according to a third embodiment, which comprises an insertable into this container line with an exclusively descending part, which is designed to be used in a closing valve;
  • Fig. 6 is a side view of a pinch valve with inserted elastic
  • Section of pipe for transporting the liquids or free-flowing solids to be delivered
  • FIG. 7 3D views of dispenser systems, wherein
  • FIG. 7A shows a dispenser system with a simple pivoting device, on which one or more dispensers can be arranged in a circle and swiveled into a dispensing position;
  • Fig. 7B shows a dispenser system with a complex pivoting device, on which several dispensers can be arranged in a circle and pivoted to a dispensing position, and to which a co-rotating boom is mounted, on which several dispensers in a linear or circular
  • FIG. 8A shows a dispenser system with four parallel channels and individual containers
  • Fig. 8B shows a dispenser system with four parallel channels and a common container.
  • the inventive dispenser is suitable both for dispensing liquids and for dispensing free-flowing solid materials.
  • An important field of application is the dispensing of certain volumes of liquid into the wells of microplates. The content of such wells depends on the geometric shape of these containers and on the number of wells per microplate.
  • SBS standard American National Standards Institute: ANSI / SBS / 1-2004
  • the microplates were standardized as far as possible and are available, for example, from Greiner Bio-One GmbH, D-72636 Frickenhausen, Germany.
  • Table 1 shows an excerpt of standard formats and contents of exemplary polystyrene microplates, which was taken from the "Microplate Dimensions Guide" by Greiner (July 2007 version).
  • AV working volume
  • MV maximum volume
  • FIG. 1 shows a dispenser according to a first embodiment.
  • This dispenser 1 is equipped for dispensing flowable materials 2 and comprises a conduit 3 having an inlet end 4 and an outlet end 5 for transporting a flowable material 2 from a container 6 to the outlet end 5.
  • the container shown here is, for example a vial containing an original component from an enzyme-linked immunosorbent assay (ELISA) kit.
  • ELISA enzyme-linked immunosorbent assay
  • the line 3 is positioned with its inlet end 4 in the flowable material 2 of the container 6 and filled with the flowable material 2 substantially.
  • the filling or "priming" of the conduit 3 is shown here:
  • a primer device 17 of the dispenser in this case a suction balloon, was connected to the discharge end 5 of the conduit 3.
  • the container 6 is sucked into the line 3.
  • the liquid is sucked in just as far (see vertical flow arrow) that its meniscus reaches the outlet end 5 of the line 3.
  • the dispenser 1 also includes a check valve 7 with which the line 3 can be fixed. Further, exemplary attachment possibilities for the line 3 are shown in FIG.
  • This check valve 7 serves to control the delivery of the flowable material 2 from the outlet end 5 of the conduit 3 and is shown here in the open state.
  • the line 3 comprises an elastic and insertable into the check valve 7 section 9 (indicated by dashed lines).
  • This elastic portion 9 is preferably a part of the conduit 3; however, the entire line 3 can also be elastic. In any case, this elastic portion 9 completely separates all parts of the check valve 7 from the flowable material 2.
  • the check valve 7 is designed as a pinch valve for stationary compression of this elastic portion 9 and thus for the reversible closing of the line 3.
  • a combination of a PS-1615-NC pinch valve (Takasago Electric Inc., Nagoya, Japan) and an elastic silicone line has been well proven (see Fig. 6), with repeated crushing (test: 1 '). OOO x) the silicone line could not permanently deform the same, so that a good repeatability of the discharge quantities was ensured.
  • silicone tubing used to empty a container once and then disposed of is considered acceptable for a maximum of a few thousand closures.
  • shut-off valve mentioned here is preferably of the "normally closed” type and the dimensional stability is specified as approximately 10 7 cycles Depending on requirements, the shut-off valve 7 can be opened by a certain amount so that the opening of the line is either partial or complete If the check valve 7 is only partially opened, this is done with highest reproducibility, preferably by a mechanically defined, adjustable open end position.
  • a "discrete amount” is considered to be a clearly defined, defined volume.
  • the term "priming” refers to the first, virtually complete filling of the conduit 3.
  • "practically completely filled” means that smaller gas or air bubbles are tolerable, as long as they have the cohesion of priming Do not endanger the liquid column formed in line 3.
  • conditioning designates the opening and closing of the conduit 3 (see Fig. 2 and Fig. 3) .
  • This conditioning is preferably carried out after priming and immediately before the first dispensing, and it is also preferred after longer periods of use a line 3 (in the range of up to several hours) immediately before the next dispensing to perform such a conditioning step.
  • the dispenser 1 further comprises a control unit 8, which controls an opening and closing of the check valve 7.
  • a control unit 8 preferably comprises an actuator for determining the opening time of the check valve 7.
  • the control unit 8 operatively connected actuators are, for example, rotary capacitors, actuators or a processor which calculates the actual opening time t of the check valve 7.
  • the control unit 8 controls a corresponding opening time t of the shut-off valve 7 and thus the delivery of a defined, discrete amount of the flowable material 2, which is conducted into a sample vessel 11.
  • this opening time t is determined exclusively by the properties of the flowable material 2 to be delivered and the properties of the essentially filled line 3.
  • software activated in the control unit 8 preferably uses identifications existing on the containers 6 for recognizing these containers, their geometry, content and volume.
  • identifications can be, for example, barcodes (eg as a barcode or as a 2D barcode) and / or radiofrequency labels (RFID tags).
  • This software is also preferably suitable for tracking the liquid level in the containers, i. for evaluating the residual volume remaining in the containers (see component C in Fig. 2).
  • the control unit 8 is also preferably designed to track the drop in the liquid level in the individual (previously identified) containers 6 and to correct the opening times of the valves for the slightly changed hydrostatic pressure in the container / line combination. This tracking of the liquid level can be done mathematically on the basis of the delivered liquid volumes. Alternatively, there can Liquid level can be determined in the containers with, for example, optical or capacitive methods.
  • the properties of the flowable material include, for example, the viscosity of a liquid, its vapor pressure, its friction on the inner surface of the conduit 3 and their specific gravity.
  • the properties of the line include, for example, its geometry (inner diameter, length and height difference) and their material and elasticity (in particular in section 9, which is inserted into the check valve 7).
  • the properties of a substantially filled conduit 3 include the properties of the flowable material 2 (the hydrostatic pressure prevailing in the conduit) and of the flowable material 2 '(the potential energy of the material particles).
  • the hydrostatic pressure can be superimposed by a pressure additionally generated in the container 6 and / or in the line 3.
  • the rising section 14 of the line 3 is inserted through an opening 16 into a standard container 6 for liquids to be dispensed.
  • the descending portion 15 of this line comprises the outlet end 5 and is guided by the closing valve 7.
  • the dispenser 1 preferably comprises a holding device 12 with the aid of which the container 6 can be arranged with the inlet end 4 of the line 3 at a first height level H 1 (cf. also FIG. 2).
  • the holding device 12 is preferably designed for placing the container 6 so that the inlet end 4 of the line 3 is located at the lowest point of the container 6 as possible.
  • FIG. 2 shows a first variant of the dispenser 1 of FIG.
  • the resulting hydrostatic pressure here determines the transport of the flowable material 2 from the container 6 to the outlet end 5 of the conduit 3.
  • the check valve 7 is here arranged close to the outlet end 5 of the conduit 3. However, it could also be fastened, for example, to the holding device 12 (not shown).
  • the line 3 preferably comprises a removable, the line reversibly closing plug 20 at its outlet end 5; this serves to protect the outlet end against contamination when the dispenser 1 is not currently in operation, for example.
  • the plug 20 was removed here and deposited on a housing in which the control unit 8 and at least one processor 10 are housed. In the illustrated moment, the check valve 7 is opened, so that soon a certain volume (shown here in drop form) will leave the outlet end 5 of the line 3.
  • the blunt end of the line is used as outlet end 5, preferably larger volumes in the microliter or milliliter range are reproducible as single drops (> 10 ⁇ ) or in constant flow (> 100 ⁇ ) (C v ⁇ 1.6%). ).
  • the Cv value indicates the coefficient of variation; this is calculated according to the formula
  • VK ⁇ x 100
  • the silicone tube selected as line 3 was designated "SF 1303 medical grade 0.062 ID x 0.125 AD" (article No. FT 06 5205 3162, Angst + Pfizer AG, Zurich, Switzerland), was 410 mm long and had an inner diameter of 1.6 mm and an outside diameter of 3.2 mm., This line 3 was fixed in the container 6 so that its inlet end 4 was placed close to the bottom of the vessel 6.
  • the container 6 contained 100 ml of deionized water used as the test liquid 2. Before dispensing the test volumes were given a "conditioning dispensing" for 80 ms. At the control unit 8, the valve opening time of 110 ms per dispensing was set; The accuracy of the total valve opening time, which was controlled in steps of 10 ms, was about 1 ms or +/- 1%.
  • Dispensing was carried out in a collecting vessel, which was located in a room protected against drafts on a calibrated analytical balance (SAG 285, Mettler-Toledo, Gsammlungsee, Switzerland). The experiments were carried out at a room temperature of 21.3 ° Celsius and a relative humidity of 41%. The following amounts of fluid (in mg) were measured:
  • FIG. 3 shows a second variant of the dispenser 1 of FIG. 1 in the controlled delivery of liquid 2 in wells of a microplate 11 '.
  • a filter 30 inserted into the opening 16 of the container 6, so that no contaminating bacteria from the ambient air can get into the liquid by the resulting suction in the container in the delivery of the liquid 2.
  • the closing elements of the valve 7 are arranged here so that the elastic portion 9 of the line 3 is stationary, ie locally scattered and always pressed together at the same point.
  • the line 3 here comprises a dispenser tip 19 at its outlet end 5.
  • the dispenser tip 19 preferably comprises a removable stopper 20, which reversibly closes the dispenser tip 19; this serves to protect the outlet end 5 from contamination if, for example, the dispenser 1 is not currently in operation.
  • the plug 20 was also removed here (not shown). While in FIG. 2 a single sample vessel 11 is depicted on a sample holder 21 specially provided for this purpose, a microplate 11 'with a number of 96 flat-bottomed wells was placed on this sample holder 21 or placed in this sample holder 21. sets.
  • a motorized drive 22 moves the sample holder 21 with the microplate 11 'so that certain wells of the microplate 11' and the outlet end 5 of the conduit or dispenser tip 19 can be correctly positioned relative to each other.
  • the positioning of the sample holder 21 and / or the outlet end 5 of the line 3 relative to one another preferably takes place by means of at least one motorized drive 22, the corresponding movements being controlled by the control unit 8 and the processor 10.
  • the sample vessels 11, 11 'that can be positioned by the sample holder 21 are selected from the group consisting of wells of microplates, sample tubes and gel cassettes and MALDI-TOF mass spectrometry targets (Matrix Assisted Laser Desorption / Ionization-Time Of Flight) and slide (for example, for light microscopy).
  • the sample vessels can define a certain volume, have only small depressions or even be formed completely flat.
  • the flowable material 2 is preferably selected from the
  • the check valve 7 is closed, so that just a certain volume (in drop form) leaves the outlet end 5 of the line 3 (not visible).
  • a dispenser tip 19 is used as the outlet end 5, preferably smaller volumes in the nanoliter or microliter range are reproducibly delivered as single drops ( ⁇ 10 ⁇ ).
  • a smaller diameter tube may also be used to dispense smaller volumes with its end simply cut clean and serving as a "dispenser outlet.”
  • dispensing smaller volumes in nanoliters or microliter region the demolition of a drop or liquid jet to be delivered is reproducibly effected by the closing momentum of the check valve 7.
  • FIG. 4 shows a container 6 of a dispenser 1 for liquids to be dispensed according to a second embodiment.
  • the container 6 comprises a line 3 connected to this container with an exclusively descending section 15 which is designed to be usable in a closing valve 7.
  • This container 6 is here a plastic bag, as used for example in hospitals for infusions.
  • the holding device 12 is slightly beveled to store the container 6 so that the inlet end 4 of the conduit 3 is arranged at the lowest point of the bag-shaped container 6.
  • a simple printing device 13 (in the form of a weight placed on the bag) is shown here. With this printing device 13 in the flowable material 2 containing container 6 and in the line 3, an overpressure is generated.
  • an ideal target pressure is generated for each individual container / line combination (with or without dispenser tip).
  • the ideal target pressure is z.
  • the properties of the liquid to be dispensed vapor pressure, viscosity, specific gravity, etc.
  • the pressure in a container / conduit combination can be increased to the same Dispense liquid volumes in a shorter time.
  • a motor-driven punch could be pressed onto the bag (not shown). It can also be provided to place a bag between two surfaces, wherein at least one of these two surfaces is pressed against the other surface (clamp or press, not shown). It can also be provided that the line 3 from the flexible container 6 (bag) is at least partially formed as an ascending line (not shown).
  • FIG. 5 shows a container 6 of a dispenser 1 for liquids 2 to be dispensed or free-flowing solids 2 'according to a third embodiment.
  • the container 6 is designed as a plastic bag, in which a line 3 is inserted. This line comprises an exclusively descending section 15, which in a Closing valve 7 is designed to be used.
  • the holding device 12 is formed here as a suspension hook, which engages in a suspension eyelet 26 of the container 6.
  • the inlet end 4 of the conduit 3 pierces a membrane 18, which otherwise closes the container 6.
  • this is preferably selected from the group comprising powders, grains, spheres and comminuted solids.
  • Container 6 and lines 3 as shown in Figures 1 to 3, or bags and lines, as shown in Figures 5 and 6, regardless of whether they are each separable from each other or not, are preferably designed as plastic disposable articles , Also, glass containers are preferably treated as disposable articles in order to exclude cross-contamination as possible.
  • FIG. 6 shows a side view of a pinch valve of the type PS-1615-NC with an inserted elastic section of the silicone line 3 for transporting the liquids 2 or free-flowing solids 2 'to be delivered.
  • the diameter of the silicone pipe 3 is for example 3.2 mm outside and 1.6 mm inside and the permissible working pressure 0 to 1.5 bar.
  • this pinch valve 7 only one driven by an electric coil slide 27 is moved back and forth.
  • the elastic portion 9 of the conduit 3 is inserted into one of the two seats 29, so that the slide 27 presses this line 3 against an immovable counterpart 28 in an end position. In the other end position of the spool 27 (not shown), the conduit 3 is open.
  • the part of the valve 7 with the two counterparts 28 and the slide 27 is dismantled and replaced by new, uncontaminated or no Abrasion pointing spare parts with the two counterparts 28 and the slider 27.
  • FIG. 7 shows 3D views of dispenser systems 23 with at least one, but preferably at least two, of the previously described dispenser 1.
  • a dispenser system 23 preferably comprises at least two lines 3 each having an inlet end 4, outlet End 5 and elastic section 9; two as Pinch valves formed check valves 7 for inserting the elastic portions 9 of the lines 3; and a control unit 8 with a processor 10 for calculating the opening time t of the shut-off valves 7 and for controlling these shut-off valves 7.
  • each outlet end 5 of the lines 3 preferably comprises a dispenser tip 19, these dispensing tips 19 in one row or in one Circle can be arranged.
  • such a dispenser system 23 comprises a pivoting device 24, with which each dispenser tip 19 with the outlet end 5 of a line 3 in this dispenser system 23 is pivotable into a specific dispensing position 25.
  • the dispensing tips 19 at the outlet ends 5 of the lines 3 in this dispenser system 23 can be arranged linearly at a distance from each other, this distance corresponding to the center distance of wells of a microplate 11 '.
  • FIG. 7A shows a dispenser system with a simple swiveling device 24, on which several dispensers 1 can be arranged in a circle and can be swiveled into a dispensing position 25. Shown is a mounted dispenser 1, as shown in FIG. This dispenser 1 can with the
  • Pivoting device 24 are rotated about a central axis 31, wherein the pivoting device 24 can be moved by means of a motorized drive 22.
  • the sample holder 21 with the microplate 11 ' can also be moved linearly by means of a motorized drive 22 here.
  • certain wells can be positioned under the dispensing tip 19, which is currently in the dispensing position 25. These movements are preferably controlled and controlled by the control unit 8 or by the processor 10 or another computer.
  • a dispenser system 23 comprises a corresponding reading device (not shown), which forwards the read information to the control unit 8. So the control unit 8 knows every- time, which liquid is present in the container 6, so that it can be used on stored physical characteristic data and the dispensing process can be modified accordingly (preferably automatically). At the same time, the control unit 8 knows the initial volume present in the container 6 and (because the control unit 8 controls the dispensing) also the current volume of the liquid 2 in the container 6.
  • FIG. 7B shows a dispenser system 23 with a complex swivel device 24, on which several dispensers 1 can be arranged in a circle and swiveled into a dispensing position 25.
  • a pivoting boom 32 is mounted on this pivoting device 24 to which a plurality of dispensers 1 are mounted in a linear (not shown) or circular arrangement (shown). If the dispensers 1 of the cantilever 32 are arranged linearly, several wells of a microplate 11 'can be filled simultaneously. All other elements correspond to the representation in FIG. 7A.
  • containers 6 are arranged substantially circular.
  • Four of these containers 6 are bags which are suspended in their suspension eye 26 (see Fig. 8) on a bracket of the holding device 12 (see front side of the
  • All containers 6 shown preferably comprise an identification 36 in the form of a barcode (preferably as a barcode or as a 2D barcode) and / or in the form of a barcode.
  • RFID tag Radio Frequency Identification Tag
  • FIG. 7B This was symbolized in FIG. 7B by showing at least one container of the different types of containers with an identification 36 attached or arranged on the container 6.
  • the alignment of the identifications which are to be optically read out must advantageously be positioned so that all of these identifications 36 are arranged at substantially the same height and thus are easy to read, for example when the pivoting device is rotated. According to the scanning direction of the optical reading device while the identification is arranged standing or lying. Because RFID labels are not optically read, these identifications 36 can be arbitrarily arranged on the containers 6.
  • FIGS. 7A and 7B impressively show how the most varied containers 6 (in the form of bags, bottles or troughs) can be held with identical or only slightly modified holding devices 12 of the dispenser system 23 according to the invention.
  • Figure 8 shows piping schemes for the parallel dispensing of liquid samples.
  • the outlet ends 5 of the conduits 3 are arranged so that they have an average distance from each other, which corresponds just to the center distance of the wells of a standard microplate.
  • Shown here are embodiments with a microplate 11 'with 384 flat-bottomed wells. These microplates 11 'are arranged on a sample holder 21, which can be moved in a motorized manner preferably in an X direction and in a Y direction substantially horizontally (see arrows in FIGS. 8A and 8B). These movements are preferably controlled via the control unit 8 of the dispenser system 23, which also controls the dispensing of liquid samples from the containers 6.
  • such a control unit comprises a processor with corresponding software.
  • the opening and closing of these lines 3 happens here synchronously via a common Shut-off valve 7.
  • Figure 8A shows a dispenser system 23 with four parallel channels (lines 3) and four individual containers 6. These containers 6 are each preferably designed as a bag and hooked into a respective hook of the holding device 12.
  • Such commercially available bags include z. B. a bag wall of a laminate whose innermost layer of polypropylene and / or polyethylene. The laminate preferably comprises an aluminum layer as light protection for sensitive liquids.
  • the lines 3 are guided through the valve 7, that a single slide 27 whose elastic portions 9 (not marked here, see Fig. 3) can see closing quet-.
  • the check valve 7 is preferably operatively connected to the control unit 8, so that its opening time can be controlled by the control unit 8.
  • the outlet ends 5 of the conduits 3 are held in a straight line by means of a guide 35 in the vicinity of the outlet ends 5 so that their average distance from one another corresponds to the spacing of the wells of the 384 microplate of 4.5 mm.
  • FIG. 8B shows a similar dispenser system 23 with four parallel channels (lines 3), but with a single, common container 6 resting on a holding device 12.
  • the inlet ends 4 of the lines 3 are embedded in the bottom of the container 6 and the descending portions 15 of the lines 3 are also guided by a common check valve 7 and held near its outlet end 5 by a guide 35.
  • the closing member of this stopper valve 7 is an elastic pipe 33 which can be pressurized by a pressing unit 34 so that the elastic pipe 33 expands and squeezes the elastic portions 9 of the pipes 3.
  • a pressure unit 34 includes, for example, a pump, a pressure vessel and a valve (all not shown).
  • This pressure unit 34 is also operatively connected to the control unit 8, so that the opening time of this pinch valve 7 is regulated and controlled as already described. can be.
  • the control unit 8 is always equipped with a processor 10.
  • Magnetic stirrers are known per se to a person skilled in the art and serve, for example, to keep suspended particles (eg living cells) in liquids. Alternative means for maintaining suspensions, such.
  • B. Rockers can be provided as an alternative or in addition to the magnetic stirrers. Magnetic stirrers are preferably used in bottle-shaped containers 6, whereas rockers are more suitable when using containers 6 in the form of lying bags.
  • the control unit 8 (with or without processor 10) is preferably used again.
  • the corresponding measuring device is arranged next to, at or below the sample vessels 11 / microplates 11 'or under their carriers can be :
  • the discharged liquid droplet or jet is collected in the sample vessel 11 or in the well of a microplate 11 ', whereby it disturbs or alters the electric field of a capacitive circuit.
  • the severity of this disorder or change is proportional to the volume of liquid dispensed.
  • the delivered liquid droplet or jet is monitored optically (eg by CCD) in flight between outlet end 5 and upper edge of the sample vessel. Thereby, the stop time of the opening time of the shut-off valve 7 at runtime for the set the desired volume. This is done by means of a processor that converts the shadow of the liquid that has already passed the CCD sensor into a corresponding volume.
  • the variable environmental influences are continuously recorded, so that device parameters can preferably be corrected immediately. This provides a delivery monitor or self-correcting delivery control.
  • the dispensed liquid droplet or jet is collected in the sample vessel 11 or in the well of a microplate 11 ', where it changes the acoustic signal of an ultrasound source circuit.
  • the strength of this change is proportional to the dispensed volume of liquid.

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  • Physics & Mathematics (AREA)
  • Engineering & Computer Science (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Mechanical Engineering (AREA)
  • General Physics & Mathematics (AREA)
  • Pathology (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Immunology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Clinical Laboratory Science (AREA)
  • Fluid Mechanics (AREA)
  • Mathematical Physics (AREA)
  • Theoretical Computer Science (AREA)
  • Feeding, Discharge, Calcimining, Fusing, And Gas-Generation Devices (AREA)
  • Sampling And Sample Adjustment (AREA)
  • Containers And Packaging Bodies Having A Special Means To Remove Contents (AREA)

Abstract

L'invention concerne un distributeur (1) pour la distribution de matériaux fluides ou coulants (2, 2') et un procédé correspondant. Le distributeur (1) comprend au moins une conduite (3) possédant une extrémité orifice d'entrée (4) et une extrémité orifice de sortie (5) pour le transport d'un matériau fluide (2) ou d'un matériau coulant (2) depuis un récipient (6) vers l'extrémité orifice de sortie (5). La conduite (3) pouvant être sensiblement remplie de ces matériaux (2, 2') est positionnable avec son extrémité orifice d'entrée (4) dans le matériau fluide ou coulant (2, 2') du récipient (6) ou est reliée au récipient. Une soupape d'arrêt (7) est réalisée pour le contrôle de la distribution du matériau fluide ou coulant (2, 2') à partir de l'extrémité orifice de sortie (5) et une unité de commande (8) commande une ouverture et une fermeture de la soupape d'arrêt (7). Le distributeur (1) selon la présente invention est caractérisé en ce que la conduite (3) comprend une section (9) élastique et pouvant être disposée dans la soupape d'arrêt (7), la soupape d'arrêt (7) étant réalisée sous la forme d'une soupape à manchon déformable pour la compression stationnaire de cette section élastique (9) et de ce fait pour la fermeture de la conduite (3) ; en outre, l'unité de commande (8) commande à la soupape d'arrêt (7) pour la distribution d'une quantité discrète définie du matériau fluide ou coulant (2, 2') dans un récipient à échantillon (11) un temps d'ouverture correspondant (t), ce temps d'ouverture (t) étant déterminé exclusivement par les propriétés du matériau fluide ou coulant (2, 2') à distribuer, ainsi que les propriétés de la conduite (3) sensiblement remplie de ces matériaux (2, 2').
EP11720421A 2010-05-12 2011-05-06 Distributeur et procédé pour la distribution de matériaux fluides ou coulants Withdrawn EP2569088A1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
CH00738/10A CH703127A1 (de) 2010-05-12 2010-05-12 Dispenser und Verfahren zum Abgeben von fliess- oder rieselfähigen Materialien.
US33433210P 2010-05-13 2010-05-13
PCT/EP2011/057260 WO2011141357A1 (fr) 2010-05-12 2011-05-06 Distributeur et procédé pour la distribution de matériaux fluides ou coulants

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EP2569088A1 true EP2569088A1 (fr) 2013-03-20

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US (1) US20130092288A1 (fr)
EP (1) EP2569088A1 (fr)
CN (1) CN102985180A (fr)
CH (1) CH703127A1 (fr)
WO (1) WO2011141357A1 (fr)

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GB2524004A (en) 2014-03-10 2015-09-16 Stratec Biomedical Ag Dispenser
EP3218029A4 (fr) 2014-11-12 2018-08-08 The General Hospital Corporation Mesure de débit et commande de dispositif de perfusion
CN107462734B (zh) * 2017-08-08 2020-05-22 领航基因科技（杭州）有限公司 一种应用于液态生物反应系统的加样装置及控制方法
CN107828640B (zh) * 2017-12-05 2024-02-02 绿城农科检测技术有限公司 水中微生物采集器
CN109174222A (zh) * 2018-08-24 2019-01-11 深圳市科晶智达科技有限公司 一种高通量配液系统
CN114323856B (zh) * 2021-12-29 2022-09-16 安徽三义堂生物科技有限公司 一种针对中药饮片中残留重金属的智能检测设备
CN114799163B (zh) * 2022-04-02 2022-12-02 山东格美钨钼材料股份有限公司 一种低氧钼铌合金靶材生产线及其工艺流程

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CN102985180A (zh) 2013-03-20
CH703127A1 (de) 2011-11-15
WO2011141357A1 (fr) 2011-11-17
US20130092288A1 (en) 2013-04-18

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