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WO1999010099A1 - Systeme de microdosage - Google Patents

Systeme de microdosage Download PDF

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Publication number
WO1999010099A1
WO1999010099A1 PCT/EP1998/005146 EP9805146W WO9910099A1 WO 1999010099 A1 WO1999010099 A1 WO 1999010099A1 EP 9805146 W EP9805146 W EP 9805146W WO 9910099 A1 WO9910099 A1 WO 9910099A1
Authority
WO
WIPO (PCT)
Prior art keywords
metering
reservoir
liquid
free jet
dosing
Prior art date
Application number
PCT/EP1998/005146
Other languages
German (de)
English (en)
Inventor
Dieter Husar
Rüdiger HUHN
Original Assignee
Eppendorf-Netheler-Hinz Gmbh
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 Eppendorf-Netheler-Hinz Gmbh filed Critical Eppendorf-Netheler-Hinz Gmbh
Priority to EP98946328A priority Critical patent/EP1017497A1/fr
Priority to JP2000507474A priority patent/JP2001513439A/ja
Publication of WO1999010099A1 publication Critical patent/WO1999010099A1/fr

Links

Classifications

    • 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
    • B01L3/0268—Drop counters; Drop formers using pulse dispensing or spraying, eg. inkjet type, piezo actuated ejection of droplets from capillaries
    • 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
    • B01L2300/025—Displaying results or values with integrated means
    • B01L2300/027—Digital display, e.g. LCD, LED
    • 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
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0433—Moving fluids with specific forces or mechanical means specific forces vibrational forces
    • B01L2400/0439—Moving fluids with specific forces or mechanical means specific forces vibrational forces ultrasonic vibrations, vibrating piezo elements
    • 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

Definitions

  • the invention relates to a microdosing system for dosing liquid volumes in the range from about one nanoliter to a few microliters
  • Piston stroke pipettes can be designed as fixed or adjustable pipettes and operate in a volume range of less than 1 ⁇ l up to 10 ml.
  • the sample is drawn into a plastic tip, whereby it is separated from the piston in the pipette by an air cushion as the weight of the liquid column a pipetting error to be corrected "hangs" on the air cushion
  • Pipettes or dispensers that work on the principle of direct displacement do not have these errors. They are used in particular when dispensing liquid with high vapor pressures, high viscosities, high densities and in molecular biology - e.g. in the polymerase chain reaction - You have tips or syringes with an integrated piston , which is coupled to a drive device of the pipette Multi-channel pipettes, dispensers and electronic dosing systems work according to the above principles. Multi-channel pipettes can significantly reduce the number of necessary pipetting processes by using several doses of the same type. This is also the case for dispensers that gradually dispense a quantity of liquid that has been taken in, and which are also available in multi-channel versions. Electronic pipettes and Dosing systems allow pipetting with high reproducibility and have a wide range of applications due to the integrated dispensing function. They work in a volume range from 1 ⁇ l to 50 ml
  • the object of the invention is to create an accurate and simple microdosing system with a dosing volume in the range from a few nanoliters to a few microliters
  • the object is achieved by various microdosing systems, the features of which are specified in claims 1, 13, 21, 25, 36, 43, 60, 67, 72 and 74.
  • Advantageous configurations of these systems are specified in the subclaims
  • the first solution concerns a microdosing system
  • a reservoir a micromembrane pump, the input of which is connected to the reservoir, a free-jet metering device, the input of which is connected to the output of the micromembrane pump, a metering opening connected to the output of the free-jet metering device, and
  • a metering control that is operatively connected to the micro diaphragm pump and free jet metering device
  • the reservoir Before or after integration into the microdosing system, the reservoir can be pre-filled with liquid by means of external devices or filled with liquid by means of the micromembrane pump.
  • the liquid can be a reagent, for example an enzyme.
  • the micromembrane pump can also be liquid from the reservoir or from the outside into the free-jet metering device Pumping
  • the free jet dispenser can dispense the pumped liquid in the free jet.
  • the free jet capability enables dosing quantities in the range from one nanoliter to a few microliters with high dosing accuracies without carry-over. that on a sub- Strate dosing can also be carried out here. Larger dosing quantities can also be dispensed.
  • the micromembrane pump can drive an auxiliary liquid column (e.g. water), which can come from the reservoir or can be sucked in from the outside, the auxiliary liquid column being a pipette piston of an air cushion or seal - Verdrangersystems acts
  • an auxiliary liquid column e.g. water
  • the metered quantity can be controlled via the displacement volume of the free jet device and, moreover, via the stroke volume or several stroke volumes of the micromembrane pump
  • the second solution concerns a microdosing system with a compressible reservoir from which liquid can be compressed by
  • a free jet dosing device can be required, the input of which is connected to the reservoir, a metering opening connected to the output of the free jet metering device and a metering control that is operatively connected to the free jet metering device
  • the reservoir can be filled with liquid (e.g. reagent, enzyme) using external devices before or after integration into the microdosing system.
  • the free-jet dosing device is filled by simply or repeatedly compressing the reservoir.
  • the reservoir can have an externally accessible, movable wall
  • the free-jet dispensing of the liquid from the metering opening can be carried out for this purpose.
  • the metering control controls the free-jet metering device in free-jet mode
  • the dosing quantity can be controlled via the displacement volume of the free jet dosing device
  • the third solution concerns a microdosing system with a single reservoir
  • a free jet dosing device the pressure chamber of which is the aforementioned reservoir, the
  • a metering control that is operatively connected to the free jet metering device
  • the pressure chamber of the free jet dosing device can be filled with liquid before or after integration into the system by means of external devices.
  • the metering control controls the free jet device in free jet mode.
  • the metering quantity can be controlled via the displacement volume of the free jet metering device, i.e. via the Volume displaced when the diaphragm of the free jet dispenser moves
  • the displacement volume of the diaphragm can be controlled in several steps
  • the fourth solution relates to a microdosing system with a reservoir, a micromembrane pump, the input of which is connected to the reservoir,
  • a metering opening connected to the outlet of the micromembrane pump and a metering control that is operatively connected to the micromembrane pump
  • Micro-diaphragm pump and reservoir in microsystem technology or hybrid technology are combined to form a component which can be exchanged and connected to an actuation module
  • the reservoir can be filled with liquid (e.g. reagent, enzyme) from outside or after integration into the system or filled with the micro membrane pump, which can be controlled accordingly by the dosing control.
  • the dosing control controls the dispensing of liquid from the dosing opening the micromembrane pump in pump mode
  • the dosing quantity can be controlled via the stroke volume of the micromembrane pump
  • the actuation module has, in particular, the function of a holder for the component and can in particular be a handle (in the case of a hand-held device) or a stationary device.
  • the actuation module can in principle have all of the system components that are not part of the replaceable component. A connection or coupling of such components to the Component can in particular be done mechanically, via electrical plug connections, optocouplers etc.
  • the actuation module can in particular include actuation devices (switches, buttons, fastening elements etc) and / or display devices (LCD display etc) and / or drive devices and / or the metering control. This also applies for all other solutions that may have an actuation module
  • the fifth solution concerns a microdosing system with a reservoir
  • a micromembrane pump the inlet of which is connected to the reservoir
  • the reservoir can be filled with auxiliary liquid before or after integration into the system.
  • the auxiliary liquid forms a piston which - like a pipette piston - draws or drives liquid through the metering opening.
  • the metered quantity can be controlled via the stroke volume of the micromembrane pump. which is known or can be determined on the basis of a calibration along a measuring section.
  • the metering quantity can also be controlled by moving the auxiliary liquid column along a predetermined section which corresponds to the metering of the desired quantity
  • the sixth solution relates to a microdosing system with a reservoir having a capillary compensation system, a free jet metering device, the input of which is connected to the capillary compensation system, a metering opening connected to the output of the free jet metering device, and a metering control which is operatively connected to the free jet metering device
  • the capillary compensation system is used to store and capillary transport the liquid from the reservoir into the free jet dispenser.It can also compensate for fluctuations in ambient conditions such as air pressure and temperature and the liquid volume consumed by the free jet dispenser.
  • the capillary compensation system comprises one or more connected capillaries that hold the storage volume of the reservoir. It can have at least one capillary with a meandering or preferably spiral shape
  • the capillary compensation system can only transport liquid from the reservoir into the free-jet metering device, due to the fact that capillary forces take effect, to the inlet of which it is connected. In principle, this does not require any additional suction or pressure forces, which had to be applied, for example, by means of an additional pump or a compressible reservoir
  • the metering control controls the free jet meter into the free jet mode.
  • the capillary forces can effect a uniform liquid transport into the free jet meter.
  • Laral compensation system prevent liquid from being pressed back into the reservoir
  • the capillary compensation system prevents bubbles from appearing in the stored liquid volume during acceleration, for example when the reservoir falls, which can disrupt the metering process. This is particularly the case with a meandering and spiral course of the capillary, since when accelerating essentially forces are perpendicular to the Occurrence of the capillary wall A corner and edge-free or low-profile course of the capillary, as is possible in particular with a meandering or spiral-shaped course of the capillary, furthermore favors filling of the reservoir without the inclusion of bubbles
  • the capillary compensation system can be ventilated at at least one point away from the connection to the free jet dispenser, so that the outflow of liquid is compensated for by the inflow of air.
  • the capillary forces then simultaneously prevent the reservoir from leaking out.
  • the capillary compensation system can also be caused by a migrating with the liquid Be plugged closed, the environmental contact of the liquid prevents and additionally counteracts leakage
  • the reservoir with the capillary compensation system can also be designed to be compressible
  • a reservoir with a capillary compensation system can also advantageously be used in the other solutions for a microdosing system.
  • the patent application includes these variants
  • the seventh solution concerns a microdosing system a plastic reservoir
  • a metering control that is operatively connected to the delivery device
  • this microdosing system is based on a hybrid component, which comprises the plastic reservoir and the microsystem-technical delivery device.
  • This favors relatively large-volume reservoirs, unlike a microdosing system in which the reservoir and delivery device are designed as a microsystem-technical component.
  • this configuration enables the construction of the microdosing system favored, especially if the hybrid component is replaceably connected to an actuation module
  • a corresponding hybrid component can advantageously also be present in the other solutions for a microdosing system.
  • the patent application includes these variants
  • the eighth solution relates to a microdosing system with a reservoir, a delivery device with a micromembrane pump and / or a free-jet metering device, the input of which is connected to the reservoir, a metering opening connected to the output of the delivery device, a metering control in operative connection with the delivery device, an actuation module with which the component comprising the reservoir is exchangeably connected, and a temperature-controlled carrier in which the component removed from the actuation module can be inserted
  • the component which comprises the reservoir can comprise at least one further component of the microdosing system, for example at least part of the delivery device and / or the dosing control.It can be designed as a hybrid component or as a whole microsystem technology by inserting the component into one Temperature-adjustable carrier before and / or after dosing enables a targeted and thus energetically favorable temperature control of the dosing liquid.
  • the carrier can be used to store one or more components in a laboratory refrigerator. However, it can also be used to transport at least one component between a refrigerator and the workplace Furthermore, the wearer can temper the components at the workplace. In particular, passive temperature control systems come into consideration for the wearer, for example with a cow battery filled with brine. However, it can also be an active temp erier system, especially with a Peltier element.
  • the system is particularly suitable for the dosing of enzymes
  • the ninth solution concerns a microdosing system with a reservoir
  • a delivery device with a micromembrane pump and / or a free-jet metering device, the inlet of which is connected to the reservoir, a metering opening connected to the outlet of the delivery device,
  • a component comprising the reservoir and / or the conveying device is interchangeably connected to an actuation module, has a coding and the actuation module has a scanning device for coding the component
  • the coding can relate to information about a full substance and / or one or more dosing properties of the interchangeable component.It can contain information about which enzyme is in a reservoir, when the reservoir was filled, an expiration date, what amount or residual amount of liquid
  • the reservoir contains the dosing quantity which the delivery device delivers when a certain actuation or control is carried out, etc.
  • the actuation module can scan the coding by means of the scanning device, so that the information, if necessary after processing by an evaluation device, can be used as a basis for the dosing, displayed or otherwise used
  • the other solutions for a microdosing system can also be equipped with a coding and a scanning device, provided that they have a component that is interchangeably connected to an actuation module.
  • the patent application includes these variants
  • the tenth solution concerns a microdosing system with a reservoir
  • a light source for a light beam the emission axis of which is aligned with the metering opening in such a way that the light beam characterizes the axis of movement and / or the point of impact of the liquid dispensed from the metering opening
  • the microdosing system can eject drops or fluid jets, the total liquid volume of which is typically in the range from 10 to 200 nl. These cannot be seen with the naked eye, which impairs precise dosing.
  • the light source characterizes the path of movement and / or the impact of the Liquid and thereby enables a safe supply of the metered quantity to the desired location.
  • This "light pointer" is preferably used as a hand-held device when the microdosing system is implemented. It can be integrated into the microdosing system by means of a laser diode The light beam can take place directly, via light guides or via an integrated light guide structure of a microsystem component of the microdosing system
  • Such a light pointer can advantageously also be present in the other solutions for a microdosing system which have a free-jet dosing device.
  • the patent application includes these variants
  • a “microdosing system” is a dosing system that comprises at least one microsystem component
  • a “microsystem technology” component is a preferably micromechanical component that is at least partially manufactured in semiconductor technology, preferably silicon technology
  • Micromembrane pump, free-jet metering device and / or other components of the microdosing systems according to the invention can be produced in microsystem technology from a semiconductor chip compactly or from several semiconductor chips in hybrid construction.
  • Microsystem technology components can also be combined with conventional components, for example a plastic reservoir, to form a hybrid component
  • a “micromembrane pump” is a microsystem-technical diaphragm pump with a pump chamber having inlet and outlet, a pump membrane assigned to it and an electrostatic, piezoelectric, thermo-mechanical or similar drive or actuator assigned to it It is characteristic of a micromembrane pump that it pumps the liquid against a counterpressure which is limited with regard to overcoming capillary forces, viscosity forces and surface tensions.
  • the pump pressure is not sufficient to expel the liquid from a metering opening, ie to dispense it in the free jet, rather it runs or drips Liquid from the metering opening driven by the acceleration of gravity
  • a micromembrane pump can typically - compared to a free jet meter - pump large volume flows.It is particularly suitable for continuous operation and, depending on the design, can pump in different directions.Typical - but not absolutely necessary - is furthermore the presence of active or passive valves at the inlet and / or outlet of the pumping chamber
  • a “free jet metering device” is a metering element with a pressure chamber, to which a pressure pulse can be exerted on the liquid contained therein by means of a membrane and an actuator acting thereon, which leads to the ejection of liquid from a metering opening.
  • the metering opening of the free jet metering device is typically - but not absolutely necessary Executed on a nozzle
  • a free jet dosing device is therefore able to accelerate a liquid volume in such a way that the interfacial tension is liquid / solid at the metering opening and the liquid volume is thrown off.
  • drops or jets are formed is preferably a microsystem element, but does not necessarily have to be microsystem technology
  • Dispenser / diluter with inert flask and calibration section in a schematic block diagram
  • FIG. 9 another reservoir in snap connection with a dosing chip in front view (FIG. 8) and in longitudinal section (FIG. 9),
  • FIG. 10 another reservoir in snap connection with a dosing chip in side view with cutout, 1 and 12 foot area of an actuation module with inserted fluid module according to FIG. 10 in a side view (FIG. 11) and in a front view (FIG. 12),
  • the microdosing system according to FIG. 1 has a reservoir 1, which has a filter 2 at the top for pressure equalization with the surroundings and is connected at the bottom via a line 3 to the input of a micromembrane pump 4, the output of which is connected via a line 5 to the input of a free jet meter 6 , which has a nozzle 7 with a metering opening 8 on the outlet side
  • the second shows an example of the microsystem design of the micromembrane pump 4 and free jet meter 6 in a single component. These components are made up of several semiconductor layers.
  • the lines 3 and 5 are formed in the bottom layer 9.
  • the pressure chamber is located in the layer 9a above 10 of the free jet meter 6 and the outlet valve 14 of the micromembrane pump 4 Furthermore, it has a membrane 13 assigned to the pressure chamber 10.
  • the layer 11 arranged above it has the end sections of the lines 3 and 5.
  • a fourth layer 18 forms the inlet valve 14a of the micromembrane pump 4 and the counter bearing for the piezoelectric actuating element 17 for the membrane 13
  • the layer 15a arranged above forms the pump chamber 12 of the micromembrane pump 4 with the associated membrane 15.
  • An actuating element 16 acts on the membrane 15 and is supported on the layer 15a via a bridge-shaped counter bearing 18a
  • a metering controller 19 which has a microcontroller 20, a control panel (including volume input) 21, a display 22 and an energy supply in the form of a battery 23.
  • the microcontroller 20 is connected to the micro diaphragm pump 4 via a level adjustment 24 and the free jet dosing device 6.
  • the system can be operated as follows using the dosing control 9
  • the free jet meter 6 can be filled with liquid by means of the micromembrane pump 4. The filled liquid is then thrown out of the nozzle 7 in a free jet by the free jet meter 6
  • the system can also be filled by the micro-diaphragm pump 4 working in the opposite direction and sucking liquid through the nozzle 7 of the free jet meter 6 and pumping it into the reservoir 1
  • liquid 25 can be pumped out of the reservoir 1 by the micromembrane pump 4 through the stationary free-jet metering device 6, so that it runs out of the nozzle 7.
  • This metering method enables metering onto a substrate with a larger volume flow.
  • the metering quantity can be controlled via the known stroke volume of the micromembrane pump 4 become
  • a column of an auxiliary liquid 25 is driven by the micromembrane pump 4.
  • the column acts as an inert pipette piston which draws in or ejects external liquid through the nozzle 7.
  • An exchangeable pipette tip 26 with a metering opening 8 ′ can be plugged onto the nozzle 7
  • the liquid column can be pressed into the pipette tip 26. After dosing, part of the auxiliary liquid 25 can be discarded by pumping it out of the nozzle 7
  • a reservoir 1 'with a filter 2' and a capillary compensation system 1 '' can also be used, which replenishes liquid evenly and prevents it from leaking
  • the microdosing system according to FIG. 3 has a dosing and reagent unit 27 which is implemented in microsystem technology. This has a reservoir 1 with a filter 2 for pressure equalization with the environment and a micromembrane pump 4 connected to it via a line 3. Instead or in addition, it can also have a free jet dosing device Furthermore, it has an externally protruding delivery tube 28 with a metering opening 8. Finally, there is an electrical contact 29 for coupling the micromembrane pump 4 to a metering control 19
  • the dosing and reagent unit 27 has a receptacle 30 on the side in the foot region 31 of a housing 32, so that the dispensing tube 28 protrudes axially beyond the foot region.
  • the dosing control 19 is arranged on a printed circuit board 34, which controller 20, control panel 21, display 22 and level adjustment 24 has the dosing control 19 is connected to a counter contact 35 in the receptacle 30, which interacts with the contact 29 of the dosing and reagent unit 27.
  • the dosing control 19 is arranged with a fixed base 31 in the housing Optical sensor 36 connected to the dispensing tube 27 of the dosing and reagent unit 27 that can be used. Then the dosing control 19 is also connected to a dispenser button 37, which is located on the side of the housing foot 31. Finally, it has a connection to a battery 23 in the head area 38 of the Housing 1
  • This dosing system is prepared for operation by inserting a dosing and reagent unit 27 pre-filled with a reagent (e.g. an enzyme) into the receptacle 30.
  • a reagent e.g. an enzyme
  • Operating mode or dosing quantity can be specified via the keyboard 21.
  • the micromembrane pump 4 pumps liquid 25 out of the Reservoir 1 until the sensor 36 detects the meniscus and thus reaches a defined zero position.
  • the metered quantity is then controlled via the known stroke volume of the micromembrane pump 4.
  • the metering control 19 can assume that the liquid column is present at the end of the dispensing tube 28 To avoid carryover, small amounts of reagent are discarded.
  • the dosing and reagent unit 27 is emptied, it is replaced by a new, prefilled unit. Instead, it can be filled up through the delivery tube 28 by the micromembrane pump 4 in reverse Ric is operated
  • the microdosing system according to FIG. 4 has a reservoir 1 with a pressure equalization to the environment via a filter 2, which via a line 3 with a Micromembrane pump 4 is connected to reservoir 1 and micromembrane pump 4 are combined to form an interchangeable pump unit 39, the reservoir being pre-filled with an auxiliary liquid 25
  • a dosing control 19 with a microcontroller 20, control panel 21, display 22, power supply 23, which is connected to the micro-diaphragm pump 4 via a level adjustment 24 (and separable contacts) .
  • Microcontroller 20 also has a connection to an optical sensor 40, which is one dispensing line 41 connected to the outlet of the micro-diaphragm pump 4 is assigned to the end of the dispensing line 41, an exchangeable pipette tip 42 is attached which has an aerosol filter 43 at its plug-in opening and a metering opening 8 'at its end
  • This system works as an air cushion pipette.
  • the auxiliary liquid 25 is shifted by the micromembrane pump 4 so that the liquid column is detected by the sensor 40. Then the system has reached its zero position.
  • the micromembrane pump 4 shifts the liquid column so that it closes like a pipette piston Dosing liquid is sucked into or ejected from the pipette tip 42.
  • the desired dosing volume is achieved via the control of the known stroke volume of the micromembrane pump 4. After a dosing process, the pipette tip 40 and part of the liquid column can be discarded.
  • a new pump unit is used 39 used
  • the control of the metering quantity is also based on the reproducible and therefore calibratable stroke volume of the micromembrane pump 4.
  • the auxiliary fluid column for a calibration of the stroke volume is shifted between the two optical sensors 40 ', 40 "if a diluter 44 ', several liquid quantities Vi, V 2 to V n can be sucked in separately from each other by air bubbles and mixed in the desired quantity ratio when dispensed
  • FIG. 6 differs from the embodiment according to FIG. 4 in that a second sensor 40 "is present, which is also connected to the metering control 19 and is displaceable along the discharge line 41.
  • the sensor 40" is fastened to a nut 46 which is fastened by means of a spindle 47 is displaceable, which is held in rotary bearings 48, 49.
  • the spindle 47 has a rotary wheel 50 for manual adjustment. It also carries an encoder 51, which is read by the metering control 19
  • the distance between the sensors 40 ', 40 is set so that it corresponds to the desired metering volume. speaks The dosing control 19 then shifts the auxiliary liquid column between the positions of the sensors 40 ', 40 "in order to draw liquid into the pipette tip 42 or to eject it from the latter
  • a reservoir 52 has an essentially plate-shaped plastic body 53, in which an essentially spiral, capillary liquid channel 54 is formed, which has straight and interconnected channel sections.
  • the liquid channel 54 is in the plastic body of an upwardly open, U-shaped groove It is delimited at the top by a cover plate 55, which can also be made of plastic.
  • the cover plate can advantageously be welded without a gap using a laser method, ultrasonically jointed or heat-sealed as a film
  • the design of the reservoir 52 made of plastic favors a large storage volume
  • the outer end of the liquid channel 54 opens into a front side of the plastic body 53 in a filling opening 56. This can be closed by means of a filter 57, which is slightly pressed into the liquid channel 54.
  • the filter 57 enables air compensation when emptying the reservoir 52, but prevents contamination of the liquid in the liquid channel and the environment through the liquid. Wetting properties of the filter 57 can also prevent liquid from escaping to the outside
  • a capillary passage opening 58 extends through the plastic body 53.
  • the passage opening 58 opens out above the entrance of a microsystem technology nically designed delivery device 59
  • This is a plate-shaped semiconductor chip (dosing chip) which is inserted in a step 60 on the underside of the plastic body 53.
  • the delivery device 59 can be a free-jet metering device in particular
  • Capillary forces acting on the filled liquid in the liquid channel 54 force the liquid through the passage opening 58 into the delivery device 59, from which it is released.
  • the capillary forces also counteract an unintentional leakage of the liquid from the filling opening 56.
  • the spiral arrangement of the liquid channel prevents that the liquid thread in the liquid channel 54 tears due to accelerations that can occur during handling, for example due to a fall. Such accelerations essentially result in forces perpendicular to the wall of the liquid channel 54, which in turn causes bubbles to occur which can interfere with the metering process, is prevented
  • a reservoir can also have two wound foils, which are at a short distance from one another and form a spiral liquid channel.
  • An embodiment with a wound capillary e.g. with a wound hose
  • a reservoir 61 has a base plate 62 and an associated receiving body 63, in which a rectangular storage space 64 is formed. From the storage space 64, liquid is supplied through a supply capillary 65 to a conical nozzle 66 on the other side of the base plate 62
  • Hook-shaped snap elements 67 protrude from the sides of the base plate 62.
  • a delivery device in the form of a semiconductor chip 68 (dosing chip) is held with respect to the base plate 62 in such a way that the connecting piece 66 presses against a sealing surface around an inlet 69 of the delivery device 68, reservoir 61 and dosing chip 68 together form a fluid module
  • the reservoir 61 can be made entirely of plastic.
  • the configuration of the feed capillary 65 is favored by its formation from two parts 62, 63
  • FIG. 10 shows a fluid module 70 of a similar design, but with the reservoir 61 'projecting laterally beyond the dosing chip 68.
  • the storage space 64 'for liquid is formed, which extends into the base plate 62' as well extends into the receiving body 63 '
  • the semiconductor chip 68 has its metering opening at 71, from which liquid is dispensed in the dispensing direction (arrow A).
  • the fluid module 70 is directed downward so that the storage space 64 'is always arranged above the supply capillary 65' care of the dosing chip 68 by gravity and the action of the feed capillary 65 '
  • an actuation module 72 has a receiving shaft 73 at the lower end, into which a fluid module 70 according to FIG. 10 is inserted. It is held on the projecting section of its reservoir 61 '. In the case shown, between elastic pressure elements 74, 75, one of which against the base plate 62 'and the other against the receiving body 63'. Furthermore, the actuation module 72 has assigned an actuator 76 to the receiving shaft 73, which rests without a gap on a membrane of the dosing chip 68.
  • holding tongs 77, 78 print the dosing chip 68 with the membrane against the Actuator 76
  • the holding tongs 77, 78 are closed at the end of the axial insertion movement of the fluid module 70 in direction E into the receiving shaft 73.
  • FIG. 13 shows a section of a fluid module 70 'consisting of a dosing chip 68' and a reservoir 61 ', the storage space 64 "of which is connected at one end to a supply capillary 65" to the dosing chip 68' and on the other side is open to the atmosphere.
  • a piston 79 is inserted in a sealing manner. This seals off the storage space 64 "from the atmosphere and brings about a pressure equalization by adding pressure through the supply capillary 65" when the liquid is withdrawn.
  • the piston 79 can also be used to actuate liquid from the outside into the supply capillary 65 "and to print into the dosing chip 68 '.
  • the piston 79 can be pulled out in order to refill the reservoir 61'
  • FIG. 14 shows a section of another fluid module 70 ", the reservoir 61" of which also has a storage space 64 '", the opening to the atmosphere of which is closed by a bag or balloon 80 made of flexible material (for example silicone).
  • the reservoir 61" is transverse to Storage space 64 '"divided and the balloon 80 is clamped on the edge in the division plane between the two molded part halves of the reservoir 61"
  • the balloon 80 also shields the liquid in the storage space 64 '"from the atmosphere. However, if liquid is discharged from the storage space 64'" through the supply capillary 65 '"to the dosing chip 68', the flexible balloon 80 adapts to the respective liquid volume by deformation. as indicated in the drawing for two situations in thin lines 80 ', 80 ". If the restoring force of the balloon 80 is negligible, refilling is facilitated.
  • a balloon 80 made of elastic material can support the liquid requirement to the dosing chip 68'
  • the balloon 80 can also consist of a material which can be pierced by the hollow needle of a filling device and which heals itself after the hollow needle has been pulled out at the puncture site
  • the fluid modules 70 ′ ′′ shown in FIGS. 15 to 19 can fundamentally have a structure as is shown in particular in FIGS. 7 to 10. They all have a reservoir, but they essentially have one box-shaped housing 81, which has a dispensing head 82 at the bottom, which has the metering opening at the lower end
  • a temperature-adjustable carrier 83 which is box-shaped and has a plurality of receptacles 84 for fluid modules 70'" which are open towards the top and have a cross section corresponding to the box-shaped part of the housing 81.
  • the receptacles 84 have a wall which tightly surrounds the fluid modules 70 '"used.
  • the walls of the receptacles 84 are surrounded by at least one cavity of the carrier 83, into which a temperature fluid can be filled in order to form a cow battery.
  • the temperature fluid can be act as a brine
  • the salt concentration in the cow's accumulators can be adjusted, which influences the melting temperature.
  • the concentration is adjusted so that the melting temperature is minus 10 ° C in order to cool the fluid modules 70 '"accordingly. to be reached
  • the set temperature is on a label t 85 noted, which is glued to the outside of the carrier 83
  • the fluid modules 70 ''' can be color-coded and / or labeled, for example on an outer surface 86.
  • Corresponding color tabs or plug-in elements 87 can be arranged in corresponding receptacles 88 or places next to the receptacles 84 in which the correspondingly encoded fluid modules 70'"are located or to which they are to be assigned. This prevents confusion between different fluid modules 70 ′ ′′
  • Such a temperature control system can be used to store filled fluid modules 70 ′′ in the laboratory refrigerator, at the workplace and for transport
  • a fluid module 70 is inserted into an actuation module 72 ', from which, however, in contrast to FIG. 11, it protrudes.
  • the fluid module 70' "is aligned with an actively tempered carrier 83 '.
  • This has a single receptacle 84' with a complementary cross section to that of the housing 81 of the fluid module 70 '"and a downwardly projecting housing section 72" of the actuation module 72', which will be discussed in connection with FIG. 19.
  • the carrier 83 ' Have Peltier elements These are supplied with power via a connecting cable 89.
  • the carrier 83 ′ can have a heat sink 90 on the outside
  • This cooling system is particularly suitable for stationary arrangement at the workplace.
  • the heat sink 90 also favors use for transport purposes and charging in a laboratory refrigerator
  • a fluid module 70' By attaching an actuation module 72 ', a fluid module 70' "can be removed from the respective carrier 83 or 83 '
  • FIG. 17 and 18 show a fluid module 70 '"which has a coding 91 on the housing 81, more precisely on an upper edge thereof.
  • the coding 91 is formed by the fact that at certain locations 92, 92', 92", 92 '"there is a depression 93 or no depression
  • an actuation module has a scanning device 94 which, at the places 92, 92 ', 92 ", 92'", corresponds to probe pins 95 or other sensors which can detect the absence and / or the presence of a recess 93 the actuation module can recognize the fluid module 70 '' used in each case
  • FIG. 19 again shows the lower part of the actuation module 72 'with the fluid module 70' "inserted, in order to explain a further peculiarity of this system.
  • the actuation module 72' has a housing section 72 projecting laterally and downwards ", in which a laser diode 96 is arranged. It is aligned in such a way that it characterizes the movement axis and the impact point of the liquid emitted by the fluid module 70 '". As can be seen better from FIG.
  • the radiation axis 98 of the laser diode 96 intersects the movement axis 99 for this purpose of the liquid emerging from the dispensing head 82 at an acute angle ⁇ and is focused on the point of intersection with the movement axis 99. If a substrate 100 with its surface is exactly in the point of intersection, the light beam 98 marks the point of impact exactly in the event of deviations in the position of the substrate 100 in a focus area 101 around the intersection The marking is only in a target area 102 on the surface of the substrate, which is very small due to the acute cutting angle ⁇
  • the housing section 72 ′′ can also house an optical fiber that aligns the light of a laser diode with the radiation axis 98
  • the dosing chip 68 is rectangular, but has a beveled one Corner 103 on In a lower layer 104, a delivery device, which is a free jet meter and possibly a micro-diaphragm pump, is formed in semiconductor technology.This has its metering opening in the lower section 103 'of the beveled corner. The movement axis 99' of the liquid jet is perpendicular to the bevel of the Corner 103 aligned
  • the layer 104 there is a glass layer 105 which has a light-guiding structure.
  • the light-guiding structure guides light from an external light source 106, which is assigned to one side of the glass layer 105, to an upper section 103 "of the chamfered corner 103.
  • an external light source 106 which is assigned to one side of the glass layer 105
  • an upper section 103 "of the chamfered corner 103 there is the glass layer 105 a micromechanically manufactured lens 107 is integrated.
  • the bundled light emerges perpendicular to the bevel of the corner 103 along the radiation axis 98 ', which is parallel to the movement axis 99' of the liquid
  • the outside of the glass layer can have a light-tight cover 108 in order to avoid light losses
  • a reservoir for liquid can be integrated in the layer 104 or 105.
  • the reservoir can also be formed by an additional layer in microsystem technology, or it can be superimposed in a conventional design or arranged externally
  • liquid delivery can be indicated by a perceptible signal, for example an acoustic signal, a “flickering” of the light pointer or simply by a marked pressure point on an actuation button

Landscapes

  • Health & Medical Sciences (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Feeding, Discharge, Calcimining, Fusing, And Gas-Generation Devices (AREA)
  • Reciprocating Pumps (AREA)
  • Sampling And Sample Adjustment (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)
  • Devices For Use In Laboratory Experiments (AREA)

Abstract

L'invention concerne un système de microdosage avec un réservoir (1), une pompe micromembranaire, dont l'entrée est reliée au réservoir (1), un doseur à jet libre (6) dont l'entrée est reliée à la sortie de la pompe micromembranaire (4), une ouverture de dosage (8) reliée à la sortie du doseur à jet libre (6) et une commande de dosage (19) coopérant avec la pompe micromembranaire (4) et le doseur à jet libre.
PCT/EP1998/005146 1997-08-26 1998-08-13 Systeme de microdosage WO1999010099A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
EP98946328A EP1017497A1 (fr) 1997-08-26 1998-08-13 Systeme de microdosage
JP2000507474A JP2001513439A (ja) 1997-08-26 1998-08-13 マイクロ投与システム

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE1997137173 DE19737173B4 (de) 1997-08-26 1997-08-26 Mikrodosiersystem
DE19737173.6 1997-08-26

Related Child Applications (2)

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US09486531 A-371-Of-International 2000-05-22
US10/790,165 Continuation US7485263B2 (en) 1997-08-26 2004-03-01 Microproportioning system

Publications (1)

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WO1999010099A1 true WO1999010099A1 (fr) 1999-03-04

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JP2002018800A (ja) * 2000-04-28 2002-01-22 Eppendorf Ag ガスクッション式分配マイクロシステム
DE10116674A1 (de) * 2001-04-04 2002-10-17 Eppendorf Ag Systen zur Detektion von Fluiden in einem Mikrofluidischen Bauteil
DE10123259A1 (de) * 2001-05-12 2002-11-21 Eppendorf Ag Mikrofluidisches Speicher- und/oder Dosierbauteil
DE10133062A1 (de) * 2001-06-29 2003-01-16 Eppendorf Ag System zum Verschließen und Handlen von Dosiermodulen und Komponenten zur Anwendung in dem System
US6620383B1 (en) 2000-02-29 2003-09-16 Boston Innovation Inc. Microvolume liquid dispensing device
DE10238564A1 (de) * 2002-08-22 2004-03-11 Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. Pipetiereinrichtung und Verfahren zum Betreiben einer Pipetiereinrichtung
US6706538B1 (en) 2000-02-29 2004-03-16 Boston Innovation Inc. Microvolume liquid dispensing array
EP1561484A1 (fr) * 2004-02-05 2005-08-10 Ing. Erich Pfeiffer GmbH Dispositif microdoseur
EP1946831A1 (fr) * 2006-12-12 2008-07-23 Konica Minolta Medical & Graphic, Inc. Appareil d'inspection de micro-puce modulaire
US7413710B2 (en) 2000-10-24 2008-08-19 Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. Pipette system and pipette array
US7479388B2 (en) 2004-04-28 2009-01-20 Fujitsu Limited Apparatus for injecting solution into cell
EP3450020A1 (fr) 2017-09-01 2019-03-06 Eppendorf AG Dispositif de microdosage permettant le dosage de plus petits échantillons de fluide
EP3485974A1 (fr) 2017-11-17 2019-05-22 Eppendorf AG Dispositif de microdosage permettant le dosage de plus petits échantillons de fluide

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DE10046034B4 (de) 2000-09-18 2006-07-27 Eppendorf Ag Verwendung von Lebensmittelfarbstoffen zur Anfärbung von Enzymlösungen
DE10117064A1 (de) * 2001-04-05 2003-02-06 Morphochem Ag Vorrichtung zum automatischen Dispensieren mikroskopischer Volumina von Fluiden
DE10220371A1 (de) * 2002-05-07 2003-11-27 Fraunhofer Ges Forschung Freistrahldosiermodul und Verfahren zu seiner Herstellung
JP4077256B2 (ja) * 2002-07-09 2008-04-16 株式会社マイクロジェット 吐出装置および注入装置
DE10327380A1 (de) * 2003-06-18 2005-01-13 Eppendorf Ag System zum Dosieren von Probenflüssigkeit
US7097070B2 (en) 2003-08-15 2006-08-29 Protedyne Corporation Method and apparatus for handling small volume fluid samples
WO2007145040A1 (fr) * 2006-06-12 2007-12-21 Konica Minolta Medical & Graphic, Inc. Micro-système d'analyse générale avec mécanisme pour empêcher les fuites de liquide
DE102007045637A1 (de) * 2007-09-25 2009-04-02 Robert Bosch Gmbh Mikrodosiervorrichtung zum Dosieren von Kleinstmengen eines Mediums
DE102007045638A1 (de) 2007-09-25 2009-04-02 Robert Bosch Gmbh Mikrodosiervorrichtung zum Dosieren von Kleinstmengen eines Mediums
DE102010051743B4 (de) 2010-11-19 2022-09-01 C. Miethke Gmbh & Co. Kg Programmierbares Hydrocephalusventil
EP2777499B1 (fr) * 2013-03-15 2015-09-16 Ortho-Clinical Diagnostics Inc Dispositif de collecte d'échantillon de fluide rotatif
KR102034540B1 (ko) * 2017-09-25 2019-10-21 주식회사 큐리오시스 점도계
DE102017218198A1 (de) * 2017-10-12 2019-04-18 Robert Bosch Gmbh Passives Ventil, Mikropumpe und Verfahren zur Herstellung eines passiven Ventils

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Cited By (19)

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Publication number Priority date Publication date Assignee Title
US6620383B1 (en) 2000-02-29 2003-09-16 Boston Innovation Inc. Microvolume liquid dispensing device
US6706538B1 (en) 2000-02-29 2004-03-16 Boston Innovation Inc. Microvolume liquid dispensing array
EP1150105A3 (fr) * 2000-04-28 2002-08-07 Eppendorf Ag Système microdoseur à coussin de gaz
JP2002018800A (ja) * 2000-04-28 2002-01-22 Eppendorf Ag ガスクッション式分配マイクロシステム
US7413710B2 (en) 2000-10-24 2008-08-19 Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. Pipette system and pipette array
DE10116674A1 (de) * 2001-04-04 2002-10-17 Eppendorf Ag Systen zur Detektion von Fluiden in einem Mikrofluidischen Bauteil
DE10116674C2 (de) * 2001-04-04 2003-08-14 Eppendorf Ag Vorrichtung zur Detektion von Fluiden in einem mikrofluidischen Bauteil
DE10123259A1 (de) * 2001-05-12 2002-11-21 Eppendorf Ag Mikrofluidisches Speicher- und/oder Dosierbauteil
DE10133062A1 (de) * 2001-06-29 2003-01-16 Eppendorf Ag System zum Verschließen und Handlen von Dosiermodulen und Komponenten zur Anwendung in dem System
DE10133062B4 (de) * 2001-06-29 2004-02-05 Eppendorf Ag System zum Handhaben von Dosiermodulen und Komponenten zur Anwendung in dem System
DE10238564A1 (de) * 2002-08-22 2004-03-11 Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. Pipetiereinrichtung und Verfahren zum Betreiben einer Pipetiereinrichtung
DE10238564B4 (de) * 2002-08-22 2005-05-04 Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. Pipettiereinrichtung
EP1561484A1 (fr) * 2004-02-05 2005-08-10 Ing. Erich Pfeiffer GmbH Dispositif microdoseur
US7479388B2 (en) 2004-04-28 2009-01-20 Fujitsu Limited Apparatus for injecting solution into cell
EP1946831A1 (fr) * 2006-12-12 2008-07-23 Konica Minolta Medical & Graphic, Inc. Appareil d'inspection de micro-puce modulaire
EP3450020A1 (fr) 2017-09-01 2019-03-06 Eppendorf AG Dispositif de microdosage permettant le dosage de plus petits échantillons de fluide
WO2019043159A1 (fr) 2017-09-01 2019-03-07 Eppendorf Ag Dispositif de microdosage pour le dosage de micro-échantillons de fluide
EP3485974A1 (fr) 2017-11-17 2019-05-22 Eppendorf AG Dispositif de microdosage permettant le dosage de plus petits échantillons de fluide
WO2019096993A1 (fr) 2017-11-17 2019-05-23 Eppendorf Ag Dispositif de microdosage pour le dosage de micro-échantillons de fluide

Also Published As

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DE19737173B4 (de) 2007-04-05
EP1017497A1 (fr) 2000-07-12
DE19737173A1 (de) 1999-03-18
JP2001513439A (ja) 2001-09-04

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