DE202006019795U1 - Micropipette for use in sample dispensing unit comprises upper section which holds sample and nozzle below this section, full pipettes being storable out of dispenser without leaking - Google Patents

Abstract

A micropipette for use in a sample dispensing unit comprises an upper section (2) which holds the sample and a nozzle (7) below this section. Full pipettes can be stored out of the dispenser without leaking. Independent claims are also included for the following: (A) a dispensing unit using the pipettes; (B) using the pipettes in which full pipettes are stored away from the dispensing unit; and (C) use of the pipettes for storing samples separately from the dispensing unit.

Description

The The invention relates to a microdispenser for dispensing a liquid sample in a dispenser.

microdispenser are known for example from WO 99/30168 and are among others for biotechnological or chemical-technological Tasks used to deliver small volumes of liquid in the form of To deliver microdrops controlled. An example of this is the Production of miniaturized DNA arrays for genetic engineering applications, wherein by a small drop size one high density is achieved, for which piezoelectrically actuated microdispenser are particularly well suited. The known microdispenser exist from a glass capillary for receiving the sample liquid to be dispensed, wherein the glass capillary for dispensing the microdrops has a nozzle and for filling with the sample liquid having a hose feed line. The ejection of the microdrops from the Glass capillary is in the known Mikrodispensern by a Piezo actuator causes the glass capillary in the area of a bottleneck jacket-like surrounds and the glass capillary with an electrical control in the radial and / or longitudinal direction, whereby in the glass capillary a shock wave is generated after reflection at the bottleneck of the glass capillary Microdrops over the nozzle ejects from the glass capillary.

adversely on the known microdispenser described above is the Fact that the filling and the operation of the glass capillary via a hose to contamination to lead can, as the plastic hoses typically used biofilms can train. In particular, the sterile handling of the interfaces between the Plastic tube and the glass capillary problematic, since there are corners and edges where contamination (e.g. Biofilms), in turn bacteria, viruses, fungi and yeasts nest can. This problem of contamination when filling the glass capillaries is especially disadvantageous if the microdispenser in the area the diagnostics are used, since the contaminants then too faulty products and misdiagnosis.

Generally When handling the known microdispenser, the problem arises that the microdispensers are subjected to working cycles that are absorbed by (Filling), Dispensing and then do the washing up consist. These work cycles are done with the same microdispenser for the next sample or for repeated a number of samples and can lead to so-called cross-contamination and are associated with a lot of time.

Farther It should be noted in the prior art that the so-called high-throughput screening the substances to be tested usually in DMSO (dimethyl sulfoxide) solved are stored in microtiter plates, the microtiter plates be deep-frozen with a variety of samples. To remove one single sample must then cover the entire microtiter plate with all thawed therein samples, with humidity can condense into the samples, causing an impairment leads the samples.

Furthermore, it is off US 6,191,946 a microdispenser is known, which is filled via the nozzle, cleaned and emptied. In addition, the microdispenser in this case has an externally accessible sample channel and is therefore in the filled state neither storage nor transportable.

Also from WO 97/44 134 A1 discloses a microdispenser is known from the front over the Nozzle is filled and therefore has the same problems as the one described above known microdispenser by the microdispenser in the filled state neither storable or transportable is.

The patent application EP 0 469 444 A1 while disclosing a disposable (disposable) nozzle unit containing the analysis liquid in pre-filled form. The ejection of the analysis liquid takes place here, however, according to the bubble jet technique, which heats the analysis liquid and therefore not suitable for the microdispenser according to the invention, since in the small dimensions of the microdispenser according to the invention required for the generation of vapor bubbles according to the bubble jet method the heating damage, ie denature, biological samples in the sample fluid.

Out US Pat. No. 6,296,811 B1 and US Pat. No. 6,866,825 a microdispenser is known in which the filling of the microdispenser with the sample liquid to be dispensed via lines, which is associated with the problems of contamination described above.

Furthermore, are off DE 26 53 051 A1 and DE 101 06 362 A1 Pipettes for blood sampling are known, which also allow storage. However, these are not microdispensers in the sense according to the invention. The same applies to the WO 02/42175 A1 and US 6,457,612 known pre-filled pipettes.

Further disclosed US 6 232 129 B1 a conventional piezoelectric pipetting device for the transfer of sample drops between two containers. However, this pipetting device does not allow permanent storage in the filled state.

Finally are off US 4 528 579 . U.S. 4,418,354 and US 4 528 578 Microdispensers for inkjet printers are known, which as such are not suitable for dispensing biological samples.

Of the The invention is therefore based on the object, the known microdispenser to improve so that as possible no contamination or impurities occur.

The Task is solved by a microdispenser according to the invention.

The The invention includes the general technical teaching of a microdispenser not only for dispensing use, but also for storage and for transporting the sample to be dispensed, so that a filling of the Microdispenser can be dispensed at the beginning of a dispensing process, whereby the contamination problems occurring in the prior art to be bypassed. Furthermore, no time-consuming flushing operations are performed.

Of the Microdispenser according to the invention is therefore filled with the sample container independently and fluidly separated from the actual dispensing device storage and / or transportable, without that the sample liquid while storage or during transport from the sample container escapes. The known microdispensers described in the introduction are not suitable for this purpose, as will be explained below. In the known Microdispenser with a hose inlet for filling the sample container could the sample liquid namely while storage or during of transport over exit the hose feed line. In the likewise known microdispensers, where the filling from the front over the nozzle done, would be filling over the Nozzles and that subsequent close the nozzles on the other hand very time consuming.

Of the inventive microdispenser draws preferably also characterized in that the filling of the sample container with the sample liquid temporally separate from the dispensing process, whereas the filling in the known Mikrodispensern with a hose feed directly before or during of dispensing. In practice, the sample container of the microdispenser according to the invention namely usually filled in time before dispensing, whereas during the subsequent Dispensing process no refilling is provided.

In A variant of the invention is the microdispenser for disposable use designed, the sample container (e.g., a glass capillary) is not refillable. In this variant Thus, the disposable microdispenser is factory set to the desired one sample liquid filled and subsequently in the filled Condition stored and delivered, i. transported to the customer, where no sample liquid can escape from the microdispenser. This will be contaminants completely prevents the sample liquid in the microdispenser because the sample liquid in which microdispenser is enclosed in a sterile manner. Preferably the sample container Therefore, down to the nozzle Completely ge closed and apart from the nozzle, during storage or transport closed, no other opening on, over the while storage or transport could leak sample liquid.

In another variant of the invention, however, the microdispenser a valve for ventilation of the sample container during dispensing and / or for filling the sample container, which allows reusable use of the microdispenser according to the invention. For example, the Mikrodispenser factory via the Valve with the desired sample liquid filled be, whereupon the valve then during storage and the Transports is closed. To the actual dispensing becomes the valve then for ventilation of the sample container open, so that the sample delivery is not due to the formation of an excessive vacuum in the sample container is hampered. The valve is preferably structurally in the Microdispenser integrates and forms a unit with the microdispenser, creating the dispenser according to the invention differs from the known microdispensers described at the beginning, where a supply line connected to a separate pressure control is.

Under Disposable use is understood in the context of the invention that the Microdispenser once, i. usually factory, with the Sample substance filled becomes. After this filling was dispensed, the dispenser is discarded. A reusable use As used herein, the microdispenser means once or can be used several times in the dispenser. Between the individual dispensing procedures the microdispenser is stored with the contained sample.

The microdispenser according to the invention preferably has a marking which contains information about the microdispenser and / or the sample located in the sample container. This is particularly useful if the microdispenser is filled at the factory and then delivered in the filled state, since the end user then mark the sample in the sample container, thereby avoiding misuse.

The Mark for identifying the microdispenser or the sample may for example consist of an optical code, such as a one-dimensional or two-dimensional bar code, the optical is read out. However, it is alternatively also possible that the microdispenser according to the invention has an integrated transponder, which is read wirelessly which allows a high degree of automation.

In a particular embodiment of the microdispenser according to the invention this is equipped with a transponder that has both a "read only" area as well has a "read and write" area. In this embodiment For example, sample tracking is particularly advantageous solved, because every storage process and dispensing process, for example, with Date stamp, number of dispensed drops or batch number the array produced directly stored on the microdispenser itself becomes.

at the microdispenser according to the invention can for example be prevented by a sponge located in the sample container be that the sample liquid on the Nozzle off the sample container exits by the sponge on the sample liquid a capillary force exerts in the sample container creates a holding vacuum. The holding vacuum can at the microdispenser according to the invention between 1 mbar and 100 mbar, however, the invention is in terms of of holding vacuum is not limited to this range of values.

It however, it is also possible as an alternative that the nozzle for transport and / or storage by a stopper, a foil, is closed by wax or by a cap.

Preferably points the sample container (For example, a glass capillary) in the microdispenser according to the invention a cross-sectional jump on, at the shockwaves to be reflected by an actuator (e.g., a conventional one Piezo actuator) are generated. In a variant of the invention the cross-sectional jump of a cross-sectional constriction, as they is known from the prior art. In another variant the invention, however, the cross-sectional jump consists of a cross-sectional widening, which also leads to a reflection of shock waves in the region of the cross-sectional jump. Regarding the structural design of the cross-sectional jump to achieve the desired Reflection effect on Wolfgang Wehl: "Acoustics and fluid mechanics in channels and nozzles of Ink writing works " Dissertation TU Munich, 2nd edition 2002, the content of which is the subject of this description attributed in full, so at this point to a detailed description of the structural design of the cross-sectional jump can be waived.

Of the sample container and / or the nozzle can in the microdispenser according to the invention, for example made of plastic, glass or ceramic, but the invention in terms of materials for the sample container or the nozzle not limited to the above materials, but in principle also possible with other materials.

Preferably consist of the sample container and / or the nozzle in the inventive microdispenser however, from an inert material such as glass.

Furthermore has the microdispenser according to the invention Preferably, an actuator for ejecting the located in the sample container Sample, wherein the actuator is preferably structurally in the microdispenser is integrated.

It however, it is also possible as an alternative that the actuator is structurally separated from the microdispenser and only is brought together for dispensing with the actuator. Warehousing and the transport of the microdispenser according to the invention can then without take the actuator.

For example the actuator can cohesively, frictionally and / or form-fitting with the sample container be connected.

Preferably The actuator surrounds the sample container sleeve-shaped, like it is known per se from the prior art. Here, the sleeve-shaped actuator on the sample container be attached, the actuator in the plugged state by a mounting sleeve can be fixed. The mounting sleeve can, for example, by fixed a screw or a circlip on the sample container become. About that In addition, it is advantageous if the mounting sleeve has an axially extending Spring slot has, so that the mounting sleeve in the radial direction easily can expand.

Furthermore, it is advantageous if the nozzle and / or the sample container is provided with a coating which immobilizes protein or acts as a DNA-immobilizing agent. Such coatings are for example in EP 0 880 535 B1 . DE 44 470 15 A1 . US 6,852,851 . US 5 650 506 . US 5,705,628 . US 5,898,071 . US 5,447,864 , WO 97/21090, so that the content of these publications of the present description with respect to the Structure and composition of the immobilizing coating is fully attributable.

Farther it is advantageous if the nozzle and / or the sample container provided with a coating that has a specific adsorption of biomolecules allows, a coagulation of a filled in the microdispenser sample prevented, and / or for a purification and / or concentration of the sample is suitable. Suitable substances for Such coatings are from standard biotechnology processes and biochemistry known per se.

Farther is to mention that the sample container preferably has a volume in the range of 1 nl to 1 ml, while the nozzle preferably a nozzle diameter in the range of 10 microns up to 100 μm Has. However, the invention is in terms of the volume of the sample container and the nozzle diameter not limited to the aforementioned ranges, but basically too achievable with other values.

Further points the sample container preferably both a sample reservoir and a working space on. The working space serves to eject a single sample the microdispenser. For this purpose, the work space, for example by means of a piezoelectric actuator are compressed radially and / or longitudinally, which is known in itself. The sample reservoir, however, serves to accommodate a sufficient sample volume to without a reusable contamination of the Microdispenser succession to be able to submit multiple samples. The Sample reservoir therefore preferably has a larger volume on as the working space of the sample container.

In According to a variant of the invention, the nozzle consists only of one shaped nozzle opening of the Sample container. However, there is also the alternative possibility that the nozzle by a separate nozzle foil, a nozzle cap or a nozzle plug is formed, which has an opening in the sample container close.

Further There is also the possibility within the scope of the invention that the sample reservoir due to the material used or by design a volume change allows. For example, the sample reservoir may be a compliant and preferably have elastic wall, so that the volume of the sample reservoir lessen, by placing the sample container in the area of the sample reservoir.

The Sample reservoir, for example, by an elastic membrane or a flexible hose. The volume change This can for example be done by a from the outside applied fluidic pressure on the membrane or the hose becomes. Alternatively, it is possible to that the volume of the sample reservoir is thereby changed, that a stamp presses against the membrane or on the hose. at A tube is another way to reduce of the volume to roll up or fold the tube.

Further it is possible, that the sample reservoir consists of a tube in which a stamp is displaceable, so that the position of the punch in the pipe determines the volume of the sample reservoir. The stamp can here be integral part of the sample container or by applying an external force (e.g., pressure, lever).

Farther is to mention the sample reservoir preferably has a resilient wall, so that the volume of the sample reservoir at a sample delivery can adjust according to the dispensed sample volume.

Farther the invention is not on the microdispenser according to the invention described above limited as a single part, but also includes a complete dispenser with at least a microdispenser according to the invention. in this connection can the dispenser characterized in that no sample supply line for the microdispenser is provided, so that the microdispenser fluidly separated from the dispenser is. The dispenser causes in this case only the control of the associated actuator for drop delivery and possibly also the spatial positioning and orientation of the microdispenser.

The microdispenser according to the invention is particularly advantageous in the production of so-called working copies for the screening process, for example in the pharmaceutical industry. These are, for example, the production of so-called microarrays or the production of multiple assays. In the prior art working procedures, aliquots of the substances, which are generally in microtiter plates or other containers, are collected and distributed in microtiter plates. Of these so-called grandmother's plates, first mother and then daughter plates (copies) are produced by a two-time aliquoting and duplicating step. For this purpose, the filled with the sample substances and frozen stored microtiter plates must first be thawed to allow removal of the liquid sample substances. In this thawing humidity can condense in the sample substances, what leads to an impairment of the sample substances, which has already been mentioned in the beginning. After thawing, the sample substances are then removed from the respective mother plate and transferred to a so-called daughter plate. In the same way, another copy is then made by the daughter plate, which is called a screening plate or a microarray. This workflow, which corresponds to the prior art, is complicated, complicated and consists of many individual steps, which can lead to contamination, cross contamination, carry-over, dilution errors or dilution by condensing water. Also, a single sample can only be taken by working the entire microtiter plate. In contrast, the microdispenser according to the invention is particularly well suited for the production of working copies in the screening process in the form of microarrays, multiple assays or for the production of so-called diagnostic chips. In this case, the sample substance is filled directly from the grandmother plate into the microdispenser and used for the production of, for example, the arrays. The otherwise necessary production of mother and daughter plates is eliminated. Individual samples can be dispensed without having to thaw a whole microtiter plate.

The Handling of the microdispenser according to the invention can in conventional Manually done by an operator.

It however, it is also possible as an alternative that the handling of the microdispenser according to the invention by a Robot takes place. The microdispenser according to the invention is therefore point of view of its dimensions and shape preferably compatible with conventional Robots for the handling of Mikrodispensers, so that the microdispenser according to the invention also from conventional Robots can be handled without making structural adjustments are required on the robots.

Other advantageous developments of the invention are characterized in the subclaims or will be discussed below together with the description of the preferred Exemplary embodiments closer to the figures explained. Show it:

1 a cross-sectional view of a disposable microdispenser according to the invention,

2 a cross-sectional drawing of an alternative embodiment of a multi-use Mikrodispensers invention with a valve for ventilation and filling of the microdispenser,

3 a cross-sectional view of another embodiment of a microdispenser according to the invention with a cross-sectional widening for reflection of shock waves in the sample container,

4a . 4b Various embodiments of the valve for the microdispenser according to 2 .

5 a cross-sectional view of a plug for closing the microdispenser according to the invention during transport and storage,

6 3 a cross-sectional view of a further embodiment of a microdispenser according to the invention without a valve, but with a cross-sectional widening,

7a . 7b 3 is a cross-sectional view and a side view of another embodiment of a microdispenser according to the invention with an enlarged sample reservoir,

8a - 8c various views of a further embodiment of a microdispenser according to the invention with a nozzle cap which forms the nozzle,

9a - 9c various views of a further embodiment of a microdispenser according to the invention with a glued-on nozzle foil, which forms the nozzle,

10a - 10e various views of another embodiment of a microdispenser according to the invention with a glued-on closure foil, which closes the nozzle during storage and transport, as well as

11a - 11c different views of another embodiment of a Mikrodispensers invention with a plugged piezoelectric actuator, which is secured by a mounting sleeve and a retaining ring.

The cross-sectional view in 1 shows a microdispenser according to the invention 1 which can be used in a dispenser (not shown) to deliver microdrops.

For receiving a sample liquid has the microdispenser 1 a sample container 2 in the form of a glass capillary with a volume of 20 μl, the sample container 2 a bottleneck 3 comprising the sample container 2 in a sample reservoir 4 and a workroom 5 separates.

In the sample reservoir 4 is a sponge 6 arranged, which exerts on the sample liquid capillary forces in the sample reservoir 4 one Create holding negative pressure, which prevents the sample liquid from the sample container 2 expires.

In addition, the sample container has 2 a nozzle 7 with a nozzle diameter of 70 microns, over the microdrops 8th can be delivered.

The delivery of the microdrops 8th is through a piezoelectric actuator 9 causes the sample container 2 in the area of the bottleneck 3 jacket-shaped surrounds and the sample container 2 expands or compresses in an electrical drive in the radial and / or longitudinal direction. This will in the in the sample container 2 located sample liquid generated a shock wave at the bottleneck 3 is reflected and to eject the microdrops 8th from the nozzle 7 leads.

Of particular importance in this embodiment is the fact of the sample container 2 down to the nozzle 7 completely closed and not refillable, so the microdispenser 1 designed for one-way use. The microdispenser 1 is therefore filled at the factory with a given sample liquid and then delivered in the filled state, so that contamination by refilling are completely excluded. During storage and transport, the nozzle can 7 additionally sealed by a stopper, a foil or by wax to the sample container 2 hermetically seal. An exemplary embodiment of a plug for closing the nozzle 7 is in 5 and will be described in detail later.

In addition, the microdispenser points 1 a barcode 10 on, the information about the microdispenser 1 (Eg nozzle diameter, container volume) and in the sample container 2 containing sample liquid in coded form.

This in 2 illustrated alternative embodiment is largely consistent with that described above and in 1 illustrated embodiment, so that to avoid repetition, reference is made largely to the above description, wherein the same reference numerals are used for corresponding components or elements.

A special feature of this embodiment is that the sample container 2 not hermetically sealed, but a valve 11 having. The valve 11 allows for a ventilation of the sample container 2 during dispensing, hence the delivery of the microdrops 8th not by building up a vacuum in the sample container 2 is hampered. In addition, the valve allows 11 a refill of the sample container 2 what a reusable use of the microdispenser 1 allowed. The valve 11 However, it is structurally integrated into the microdispenser and closable, so that during transport and storage of the microdispenser 1 no sample liquid from the filled sample container 2 can escape. In the 4a and 4b are different embodiments of the valve 11 shown in detail later.

3 shows a further embodiment of a Mikrodispensers invention 1 , which in turn is largely consistent with the embodiments described above, so that to avoid repetition, reference is made largely to the above description, wherein the same reference numerals are used for corresponding components.

A special feature of this embodiment is that the sample container 2 instead of the bottleneck 3 a cross-sectional extension 12 at which a reflection of shock waves also takes place, as is explained in the aforementioned dissertation by Wolfgang Wehl: "Acoustics and Fluid Mechanics in Channels and Nozzles of Ink Writing Engines".

4a shows a cross-sectional view of an embodiment of the valve 11 with a plastic valve housing 13 placed on the sample container 2 is shrunk and then firmly and gas-tight with the sample container 2 connected is. For this purpose, the slightly undersized valve housing 13 heated and then in the heated and thus expanded state on the sample container 2 postponed. During the subsequent cooling to the ambient temperature, the valve housing pulls 13 then back together, resulting in a tight fit of the valve body 13 on the sample container 2 leads.

However, it is alternatively also possible that the valve housing 13 by an adhesive bond with the sample container 2 connected is.

In the valve housing 13 becomes a valve ball 14 from a spiral spring 15 against a valve seat 16 pressed. The valve 11 So opens only in one direction when the pressure acting from the outside differential pressure is sufficiently large to the valve ball 14 against the force of the coil spring 15 from the valve seat 16 to lift. The preload and spring stiffness of the coil spring 15 are chosen so that the valve 11 with a control of the piezoelectric actuator 9 and increasing emptying of the sample container 2 slowly opens to the sample container 2 to ventilate.

In addition, the valve points 11 in this embodiment, a sieve 17 (or a membrane), which when filling the sample container 2 the penetration of foreign bodies into the sample container 2 prevented.

4b shows an alternative embodiment of the valve 11 , which largely corresponds to the embodiment described above, so that to avoid repetition largely to the above description 4a is referenced, wherein the same reference numerals are used for corresponding components.

A special feature of this embodiment is that the sample container 2 when mounting on the valve body 13 is shrunk. This is done with the slightly undersized sample container 2 heated and then in the heated and thereby expanded state on the valve body 13 postponed. During the subsequent cooling to the ambient temperature, the sample container pulls 2 then back together, resulting in a tight fit of the sample container 2 on the valve body 13 leads.

Finally shows 5 a cross-sectional view of a plug 18 in the nozzle 7 of the sample container 2 can be pressed to prevent sample liquid from the sample container during storage or transport 2 exit. The stopper 18 It is made of plastic and is slightly tapered, which means inserting the plug 18 in the nozzle 7 facilitated. At its conical lateral surface, the plug 18 a plurality of annular sealing ribs 19 on, reducing the surface pressure between the plug 18 and the inside of the nozzle 7 increases and thus the sealing effect is improved.

In addition, the stopper 18 cup-shaped and open to the outside, so that the plug 18 by means of a stamp 20 in the nozzle 7 can be pressed into it.

This in 6 illustrated alternative embodiment is largely consistent with the embodiments described above 1 and 3 to avoid repetition, reference is made largely to the above description, wherein the same reference numerals are used for corresponding components or elements.

This embodiment combines the closed structure according to the embodiment 1 with the cross-sectional widening in the embodiment according to 3 ,

The 7a and 7b show a further embodiment of a Mikrodispensers invention 1 , which in turn is largely consistent with the embodiments described above, so that to avoid repetition, reference is made largely to the above description, wherein the same reference numerals are used for corresponding components.

A special feature of this embodiment is that the sample reservoir 4 has a significantly larger diameter than the working space 5 of the sample container 2 , Accordingly, the sample reservoir also has a larger volume than the working space 5 , This offers the advantage that the microdispenser 1 successively a multitude of more than a million microdrops 8th can deliver without a temporary refilling of the microdispenser is required.

Another special feature of this embodiment is that the nozzle 7 is formed by a nozzle plug, which in a corresponding opening in the working space 5 is pressed. The geometry of the nozzle is thus not affected by the shape of the opening in the working space 5 determines what, in the design of the nozzle geometry opens up a greater structural design freedom.

Furthermore, the microdispenser has 1 in this embodiment, a special construction of the valve 11 with the valve ball 14 , the valve seat 16 and a stopper 21 on, with the coil spring 15 inside the plug 21 supports and the coil spring 15 in the valve seat 16 suppressed.

In addition, the piezoelectric actuator 9 in this embodiment completely in the area of the working space 5 arranged, ie on the nozzle side of the bottleneck 3 ,

The 8a to 8d show a further embodiment of a Mikrodispensers invention 1 , in turn, largely with the one described above and in the 7a and 7b illustrated embodiment, so to avoid repetition, reference is made largely to the above description, wherein the same reference numerals are used for corresponding components.

A special feature of this embodiment is that the nozzle 7 through a nozzle cap 22 is formed on the front end of the work space 5 is attached and has a nozzle opening in its end face. The geometry of the nozzle is thus not affected by the shape of the opening in the working space 5 determines what in the design of the nozzle geometry a larger con opens up creative scope.

The 9a to 9c show a further embodiment of a Mikrodispensers invention 1 , in turn, largely with the one described above and in the 7a and 7b illustrated embodiment, so to avoid repetition, reference is made largely to the above description, wherein the same reference numerals are used for corresponding components.

A special feature of this embodiment is that the nozzle 7 through a nozzle foil 23 is formed on the front end of the work space 5 glued or welded and has a nozzle opening in the middle. The nozzle geometry is therefore also not affected by the shape of the opening in the working space 5 determines what, in the design of the nozzle geometry opens up a greater structural design freedom.

The 10a to 10e show a further embodiment of a Mikrodispensers invention 1 , in turn, largely with the one described above and in the 7a and 7b illustrated embodiment, so to avoid repetition, reference is made largely to the above description, wherein the same reference numerals are used for corresponding components.

A special feature of this embodiment is that the nozzle 7 through a sealing film 24 is closed, which prevents during storage and transport of the microdispenser over the nozzle 7 Sample liquid from the sample container 2 can escape. Before dispensing, the sealing foil 24 then just from the nozzle 7 peeled off, taking off the sealing film 24 from the nozzle 7 is facilitated by laterally protruding grip tabs.

The 11a and 11c show a further embodiment of a Mikrodispensers invention 1 , which in turn is largely consistent with the embodiments described above, so that to avoid repetition, reference is made largely to the above description, wherein the same reference numerals are used for corresponding components.

A special feature of this embodiment is that the piezoelectric actuator 9 axially on the sample container 2 is plugged, wherein the piezoelectric actuator 9 abuts an annular circumferential stop. For mechanical fixation of the piezo actuator 9 on the microdispenser 1 is a mounting sleeve 25 provided axially on the piezoelectric actuator 9 is attached and on both sides each having an axially extending slot, which is a slight radial expansion of the mounting sleeve 25 allowed, thereby attaching the mounting sleeve 25 is relieved. After attaching the mounting sleeve 25 this is done by a circlip 26 mechanically fixed.

The Invention is not limited to those described above embodiments limited. Rather, a variety of variants and modifications is possible, the also make use of the idea of the invention and therefore in fall within the scope of protection.

Claims (30)

Microdispenser ( 1 ) for dispensing a liquid sample in a dispensing apparatus, comprising a) a sample container ( 2 ) for receiving the liquid sample and b) a nozzle ( 7 ) for dispensing in the sample container ( 2 ), characterized in that c) that the microdispenser ( 1 ) independently and fluidically separated from the dispenser with the filled sample container ( 2 ) is storable without the sample being removed from the sample container during storage ( 2 ), and d) that the sample container ( 2 ) an integrated sample reservoir ( 4 ) in order to be able to deliver a plurality of samples one after the other without refilling. Microdispenser according to claim 1, characterized by a design for a disposable use, wherein the sample container ( 2 ) is not refillable. Microdispenser according to one of the preceding claims, characterized in that the sample container ( 2 ) except for the nozzle ( 7 ) is completely closed and apart from the nozzle ( 7 ) has no opening. Microdispenser according to one of claims 1 or 2, characterized by a valve ( 11 ) for aeration of the sample container ( 2 ) during dispensing and / or for filling the sample container ( 2 ). Microdispenser according to claim 4, characterized in that the valve ( 11 ) by a shrink connection or by a bond to the sample container ( 2 ) connected is. Microdispenser according to one of the preceding claims, characterized by a marking ( 10 ), the information about the microdispenser ( 1 ) and / or in the sample container ( 2 ) contained sample. Microdispenser according to claim 6, characterized in that the marking ( 10 ) is an optical code, in particular a one-dimensional or two-dimensional bar code, or a transponder. Microdispenser according to claim 7, characterized the transponder has a first memory area and a second memory area Memory area, wherein the first memory area only readable is while the second memory area is also rewritable. Microdispenser according to one of the preceding claims, characterized in that in the sample container ( 2 ) A sponge ( 6 ) is arranged, which by the capillary forces acting on the liquid sample, a holding negative pressure in the sample container ( 2 ) generated. Microdispenser according to one of the preceding claims, characterized in that the sample container ( 2 ) inside a cross-sectional jump ( 3 . 12 ) having. Microdispenser according to claim 10, characterized in that the cross-sectional jump ( 3 . 12 ) either a bottleneck ( 3 ) or a cross-sectional extension ( 12 ). Microdispenser according to one of the preceding claims, characterized in that the sample container ( 2 ) and / or the nozzle ( 7 ) made of plastic or glass or ceramic. Microdispenser according to one of the preceding claims, characterized by an actuator ( 9 ) for ejecting the in the sample container ( 2 ) through the nozzle ( 7 ). Microdispenser according to claim 13, characterized in that the actuator ( 9 ) structurally into the microdispenser ( 1 ) is integrated. Microdispenser according to claim 13, characterized in that the actuator ( 9 ) from the microdispenser ( 1 ) is structurally separated. Microdispenser according to one of the preceding claims, characterized in that the actuator ( 9 ) cohesively, frictionally and / or positively with the sample container ( 2 ) connected is. Microdispenser according to one of claims 13 to 16, characterized in that the actuator ( 9 ) is a piezoelectric actuator. Microdispenser according to one of the preceding claims, characterized in that the actuator ( 9 ) the sample container ( 2 ) sleeve-shaped outside and the sample container ( 2 ) at an electrical control of the actuator ( 9 ) compresses and / or expands. Microdispenser according to one of the preceding claims, characterized in that the actuator ( 9 ) on the sample container ( 2 ) through a mounting sleeve ( 25 ) is fixed. Microdispenser according to claim 19, characterized in that the mounting sleeve ( 25 ) has an axially extending spring slot. Microdispenser according to claim 19 or 20, characterized in that the mounting sleeve ( 25 ) on the sample container ( 2 ) by a screw connection or by a retaining ring ( 26 ) is fixed. Microdispenser according to one of the preceding claims, characterized in that the nozzle ( 7 ) and / or the sample container ( 2 ) is provided with a coating, wherein the coating is preferably protein-immobilizing or DNA-immobilizing, allows a specific adsorption of biomolecules, prevents coagulation of a filled sample, and / or is suitable for a purification and / or concentration of the sample. Microdispenser according to one of the preceding claims, characterized in that the nozzle ( 7 ) is closed for storage. Microdispenser according to claim 23, characterized in that the nozzle ( 7 ) for storage by a stopper ( 18 ), a sealing film ( 24 ), is closed by wax or by a closure cap. Microdispenser according to one of the preceding claims, characterized in that the sample container ( 2 ) has a volume in the range of 1 nl to 1 ml. Microdispenser according to one of the preceding claims, characterized in that the nozzle ( 7 ) has a nozzle diameter in the range of 10 .mu.m to 100 .mu.m. Microdispenser according to one of the preceding claims, characterized in that the sample container ( 2 ) in addition to the sample reservoir ( 4 ) a work space ( 5 ), the sample reservoir ( 4 ) has a larger volume than the working space ( 5 ). Microdispenser according to one of the preceding claims, characterized in that the nozzle ( 7 ) through a nozzle foil ( 23 ) or a Dü cut ( 22 ) or a nozzle plug is formed. Dispenser with at least one microdispenser ( 1 ) according to any one of the preceding claims. Dispensiergerät according to claim 29, characterized in that no sample supply line for the microdispenser ( 1 ) is provided.