WO2013013253A1

WO2013013253A1 - Container unit for a substantially liquid sample

Info

Publication number: WO2013013253A1
Application number: PCT/AT2012/000193
Authority: WO
Inventors: Khatuna Elizbarowna Gvichiya; Bruno Balluch
Original assignee: Onkotec Gmbh
Priority date: 2011-07-25
Filing date: 2012-07-24
Publication date: 2013-01-31
Also published as: AT511739B1; AT511739A1

Abstract

Container unit (1) for a substantially liquid sample for concentrating particles contained in the sample, comprising a cup (2) for receiving the sample, a filter (6) for separating at least part of the sample from the particles and with a plunger connected to the filter (6) for moving the filter (6) through the sample, wherein the plunger is designed as a movable hollow plunger (4) inserted in a liquid-tight manner into the cup (2), the filter (6) being arranged on the front (5) of said plunger, and the container unit (1) has on the base of the cup (2) an opening (8) for removing at least some of the sample, or at least one observation window (29) for visually evaluating the sample.

Description

Container unit for a substantially liquid sample

The invention relates to a container unit for a substantially liquid sample for concentrating particles contained in the sample, comprising a cup for receiving the sample, a filter for separating at least a portion of the sample from the particles as well as a with the filter associated punch for moving of the filter through the sample.

Devices are known in the art for filtering out particles from liquids by moving filters. For example, filters are arranged on a stamp guided by liquids. When the liquid is in an open-topped container, the corresponding filter can be pushed from above towards the earth's gravity, thereby creating a bottomed up sediment at the bottom of the container. Above the depressed filter remains the filtered liquid. In the household, these types of devices are used as coffee making machines. A disadvantage of these solutions that the filtration is carried out on open or partially open containers and elevated hygiene requirements, such as exist in medical technology, is not enough.

The invention aims to provide a container unit as stated at the beginning, which makes it possible to quickly and easily concentrate particles in a substantially liquid sample and to do so without the risk of contamination of the environment with the sample liquid. Another objective is to construct the container unit as simply as possible.

The container unit according to the invention achieves this by the fact that the stamp is formed as a liquid-tight inserted into the cup and movable hollow die on whose stamp front the filter is arranged, and that the container unit at the base of the cup has an opening for removing at least a portion of the sample or at least one observation window for optically evaluating the sample.

A preferred embodiment of the container unit is characterized in that the hollow stamp has a valve for venting on the side facing away from the stamp front.

In one embodiment of the invention, the opening is temporarily sealed liquid-tight by a seal.

To further embodiment of the invention, the end facing away from the cup of the hollow punch is formed as a stamp.

In one embodiment of the invention, it is preferred that the amount of liquid sample remaining in the cup with the hollow die retracted to the total sample amount is in the ratio of approximately 1 to 20 to approximately 1 to 200.

In another preferred embodiment of the container unit according to the invention, the hollow punch has a ring designed as a lid, which can be snapped or screwed onto the cup.

A preferred embodiment of the container unit is characterized in that the hollow ram is connected to the ring of the lid via a predetermined breaking point.

In one embodiment of the invention, the container unit has, at one of the points in contact with the liquid sample, an amount of a dye by means of which any predetermined particles in the liquid sample can be marked.

For further embodiment of the invention, the valve contains swelling polymers.

In one embodiment of the invention, it is preferred that the cup has a mandrel element, through which the seal can be broken open by the movement of the hollow punch. Alternatively, it is preferred that the cup has a mandrel element, through which releasably by the movement of the hollow punch an elastomeric valve on the cup base is reversibly apparent.

In an embodiment of the container unit according to the invention, it is further preferred that it has, in the flow direction behind the opening, a measuring channel designed as a measuring capillary, which has at least one observation window.

In one embodiment of the invention, the measurement channel contains a chemically or biochemically prepared substrate whose reactions can be optically evaluated with the sample.

For further embodiment of the invention, the filter and / or a chamber in the lid of the hollow punch contains a chemically or bio-chemically prepared substrate with activated surface whose reactions are optically evaluated with the sample.

The invention will be explained in more detail with reference to an embodiment shown in the drawings. 1 shows a schematic cross section through the container unit, FIG. 2 shows a schematic cross section through an alternative embodiment of the container unit, FIG. 3 shows a schematic cross section through a valve for ventilating the hollow punch, and FIG. 4 and FIG. 5 shows a schematic cross section through an alternative embodiment of the container unit.

A container unit 1 according to FIG. 1 consists of a cup 2, in which a sample liquid is located. For example, it is important in medical testing to know whether and at what concentration predetermined particles are in the fluid. Typically, on the one hand, appropriate measuring methods should be carried out under hygienically demanding conditions, on the other hand, there is a very low concentration of the particles. To be fast and reliable too measure, the particles are concentrated in the container unit, measured a portion of the concentrated liquid sample and then downscaled the measured high concentration value on the total liquid sample amount. On a sometimes time-consuming sedimentation of the particles is no longer dependent. Fluids for this purpose include body fluids such as urine or sputum, but also blood and cell suspensions of tissues. The container unit according to the invention can be used for the cytological detection of cancerous diseases, in doping controls or for the counting of particles and bacteria in an advantageous manner.

On the cup 2, a lid 3 is mounted by means of screwing or by means of a snap mechanism. In this case, a hollow punch 4 is arranged at the opening of the cup 2 and closes this air and liquid-tight. This can e.g. take place by suitable rubber ribs 4 '. At a punch front 5 of the hollow punch 4, a filter 6 is arranged. The filter 6 is a conventional filter mesh of a predetermined mesh size or a filter membrane. The hollow die is filled with ambient air before concentration. Via a valve 7, the air can escape when the hollow die 4 is lowered into the cup 2. As a result, the filtered and no longer important for the measurement process sample liquid enters the hollow die 4. Below the hollow punch 4, the remaining liquid is concentrated with any particles.

Typically, the volume of the hollow punch 4 relative to that of the cup 2 is such that the sample liquid is concentrated by a factor of from about 20 to about 200. An example of the volume of the cup 2 is about 50 ml; an example value for the volume of the remaining sample liquid quantity below the hollow punch 4 after its lowering is about 2.5 ml. The hollow punch 4 is depressed so far in the direction of arrow A until it is mechanically seated on the bottom of the cup 2 or brought by other mechanical elements, such as webs or tapers of the cup 2, to a halt. The concentrated liquid can then be removed via an opening 8 arranged in the bottom region of the cup.

Advantageously, the stamp front 5 on the shape of the cup bottom. This is shown in Fig. 1, which is, for example, a cone shape of the bottom and punch front 5.

The venting valve 7 is designed to automatically close upon passage of moisture. This prevents liquid from escaping when handling the container unit.

Fig. 3 shows an embodiment of the valve 7 with sealing elements, which is inserted in the upper side 19 of the hollow punch 4. When inserting the hollow punch 4, the residual air initially escapes through a hollow screw 10 against the resistance of an elastic silicone tube 11, which covers a transverse bore 12 of the hollow screw 10. Likewise, a slightly curved sealing disc 13 allows the residual air to escape through a bore 14 in the free environment. If, however, filtered liquid flows through the hollow screw 10 into the chamber area between the two piston elements 15, 16, then a floating body 17 presses against the sealing disk 13 and closes the valve chamber. The piston elements 15, 16 are used with O-rings 16 'in the top 19 tightly closed and thus form the valve chamber. If necessary, further inflowing liquid only increases the pressure in the chamber on sealing disc 13 and silicone tube 11 until the chamber is sealed thereby. From this point on there is a purely hydraulic system of the container unit 1, and it will also train movements on the hollow ram 4 possible, or in an alternative Embodiment of FIG. 2, oscillating movements of the other punch 9, with which, for example, a clogged filter 6 can be cleared. As an alternative to the floating body 17, the chamber can also be filled with a polymer granulate to improve the position independence, which swells rapidly when liquid contact and thus also presses against the sealing washer 13 and silicone tube 11. This opens up possibilities for miniaturization of the automatic, self-sealing venting unit.

Before use, the lid 3 and the hollow punch

4 are interconnected via a predetermined breaking point to indicate a first-time application or, if necessary, to allow only a single application.

In an alternative embodiment according to FIG. 2, the hollow punch 4 may have a further punch 9. This makes it possible to forcibly press the sample liquid from the opening 8 of the cup 2 after depressing the hollow punch 4. The sample liquid is then fed to a measuring device 20, which may take place more quickly if the user uses the punch 9 to help by lowering in the direction of the arrow A. In Fig. 2, the punch 9 is shown in its basic position, where it simply forms the top of the hollow punch 4.

The opening 8 of the cup 2 may further be sealed with a seal 21, which remains closed as long as the container unit is filled, concentrated and optionally still connected to a measuring device 20. The concentrated residual amount of the sample liquid can be reduced again, for example to a few microliters (μΐ). The hollow punch 4 can be pressed down to the bottom of the cup, and a subsequent removal of the liquid is made possible by the impressing of the punch 9 in the hollow die 4. By further lowering the punch 9 after the measurement, moreover, a measuring channel 22 of be cleaned a particle-carrying liquid, since the subsequent liquid comes from the hollow die 4 and is already freed of particles.

The container unit 1 may finally have a suitable stored dye 23 and other agents and biomarkers at a suitable location, such as on the inner wall of the cup 2 or on the inner wall of the hollow punch 4, which distribute, for example, in contact with moisture in the sample liquid of The particles to be measured are recorded and then enable or facilitate the counting or other measurement of the particles after concentration. A seal of filter 6 and vent hole 14 of the valve 7 by means of peelable protective films can prevent the ingress of atmospheric moisture and contamination of the stored in the hollow die 4 dyes 23 during the storage period of the container unit 1 until its use.

In one embodiment, the hollow punch 4 is lowered so far into the filled cup 2, that all the air has departed from the hollow die 4 and the valve 7 closes due to moisture contact. Furthermore, the hollow punch 4 can not move into the liquid-tight cup 2 in this state. This leaves a concentrated residual amount of the sample liquid in the cup 2 outside the hollow punch 4, eg 2.5 ml. Subsequently, the seal 21 is opened at the opening 8 of the cup, so that now by further pressure on the hollow die 4, the concentrated residual amount of any Measuring method outside the cup 2 can be supplied. It is advantageous that the residual amount of the sample liquid are chosen to be very small and thereby again prevents contamination or contamination of the environment or can be greatly reduced. Another advantage of this embodiment lies in the possibility of being able to select an optimum setting for a sedimentation method from a larger range of flow rates through the measuring channel 22, whereby the duration of the entire analysis process is greatly reduced even at very slow settings Sample volume can be significantly shortened. Nevertheless, liquid samples with biological cells undergo a gentle manipulation of the cell material compared to cytocentrifuges.

Other embodiments with a simpler or with a complex structure are possible as follows.

System without venting: In this simplest design variant, after lowering the hollow punch 4, the compressed air can be used to inject the liquid sample into a connected measuring system 20 by opening the seal 21, the concentrated liquid sample. However, inflow velocities here are highly time-dependent, depending on the initial fill level of the cup 2 and can only be influenced by additional control measures.

Automatic unidirectional blocking vent, e.g.

Needle valve with floating body, float ball or vapor-permeable, but liquid-tight synthetic material membrane, Hi-Tec fabric: In a preferred variant, the outward-acting venting can allow air to flow back into the die cavity with the seal 21 closed and the hollow punch 4 briefly pulled up. In this case, filtered sample liquid flows back through the filter 6 in the direction of the vessel base. This allows flushing of the filter front in reverse operation and causes a slight dilution and mixing or swirling of the concentrated sample by movement of the flexible filter membrane. Supporting can be a vibration excitation of the membrane by means of ultrasound and / or by mixing beads (eg glass beads, not shown), which rest in the hollow ram on the back of the filter and flow-related by pulse-like piston joints are set in motion and thus solve by their own weight the filter cake on the opposite side of the membrane mechanically.

Bidirectional, self-sealing vent: In this further preferred variant, the system can also be vented by a special arrangement of two valves. As soon as the liquid wets or fills the chamber of the valve 7, the float 17 or a polymer granulate swirling rapidly through liquid contact (not shown) inside the valve chamber closes the valve 7. A reentry of air by lifting movements of the hollow punch 4 is thus irreversibly prevented. As a result, lifting movements after opening the seal 21 can be used to at least partially suck the discharged concentrated sample liquid back into the cup 2. Likewise, a cleaning liquid can be sucked in through the outlet of a measuring device 20 connected to the vessel base from the outside in the direction of the container unit 1, whereby this outlet can be cleaned by flushing before removing this functional unit from a device mechanism. Another advantage is that flushed by train-push cycles of the hollow punch 4 blocked channels in a liquid-tight connected measuring device 20.

Contamination protection: By various measures, such as a meandering extension of the leading or trailing path of the venting area and the Oberflächenbe ^¬ treatment of the channel walls (increase the wetting angle or the surface tension, especially in the flow, hydrophobic channel walls), and the installation of a Filterschwämmchens in After-run, contamination can be prevented by leaking even the smallest amount of liquid when bleeding. The liquid sample thus remains entirely within the closed system of container unit 1 and meter 20. The measuring channel 22 may have a particle filter (not shown) on the input side, so that subsequently filtered sample liquid flows through it. The measuring channel 22 from the particle filter may be formed as, for example meandering, measuring capillary 28 and has at least one observation window 27 for optical or fluorescence spectroscopic evaluation of the filtered sample at the molecular level (eg by absorption, reflection, transmission, scattering). In the measuring capillary 28, preferably in the region of the observation window 27, for this purpose, a (bio) -chemically prepared substrate (eg Bio-chip matrix / ELISA, color change to pH measuring strips, measurable by interferometer reaction-dependent changes in the refractive indices of activated surfaces of Optical waveguides, which are flowed around by the sample) may be present. These explanations apply mutatis mutandis to the variants of the container unit 1, as shown in FIGS. 4 and 5.

Mechanical connection, drives: Depending on the version, the functional unit for sample concentration can be controlled by one or more drives. In any case, all variants are based on the characteristic of concentrating the particulate fraction of a liquid sample to be examined in order to substantially reduce the liquid volume of interest and then opening a seal 21 or a valve (not shown) at the base of the cup 2 and in the course of the filter rinsing a sample with the highest particulate yield of further processing (eg a spectroscopic measuring cell) to supply.

Variant with simple piston drive, without punch vent: In this minimal variant, the hollow punch 4 is lowered by a drive up to a stop in the cup 2. The stop determined by its height, the concentrated sample volume. He can as a spacer ring 24 in the empty cup. 2 be inserted. During the concentration, the retracting hollow punch 4 moves down until it sits on this spacer ring.

The spacer ring 24 can also serve as a suspension for a by means of elastic web elements 24 'centrally positioned downwardly facing mandrel element 25 as shown in FIG. This mandrel element 25 is held suspended by the suspension at a safe distance above the seal 21. Only pressing the stamp face 5 against the mandrel element 25 leads it down from its locally stable raised position, whereby the seal 21 is broken through. The opening 8 at the cup base may be closed instead of a seal 21 with a conventional elastomeric valve. This elastomeric valve is reversibly apparent by the mandrel element 25.

In a preferred embodiment, a sleeve 26 of the mandrel member 25 forms a connecting tube between the filter 6 and opening 8 on the cup base, which suppresses as an undesirable slipping the collected particles in edge zones of the stamp face during the sampling. The compressed air injects the concentrated sample liquid into an optionally connected measuring system 20. The sealing film of the seal 21 preferably has a lower specific gravity than the sample liquid, so that fragments of the film preferably float and release the fluidic path after seal breakage. Parameters such as the volume of the punch body, the level of the cup 2, the dimensions of the spacer ring 24, sleeve 26 and mandrel element 25, determine the transient flow rate after seal breakage. The single-piston variant requires precise system tuning and compliance with the fill level.

Variant with a piston drive, including automatic, unidirectional punch venting: In this modified minimal variant, when lowering the hollow punch 4 the punch chamber vented. After seating of the hollow punch 4 on the ring member 24 and the associated seal fracture is now in turn formed as a stamp 9 lid 19 of the hollow punch 4 after overcoming a predetermined breaking point (or eg snap spring element) additionally lowered until the automatic valve 7 fills with the filtered sample liquid and seals. As a result, then determines the Absenkge ^¬ speed of the punch 9, the flow rate of the aufkonzentrier ^¬ th sample upon introduction into a connected cell. DIE se variant requires a special vote (Leichtgängig- ness) of the automatic venting, since the seal 21 is already broken at the base of the cup 2 without additional con ^¬ design measures, while the vent is given if not already completed. A pressure sensor and control the fluctuation width of the desired flow rate minimie ^¬ ren.

Variant with two piston drives: In this case, hollow punches 4 (determines the degree of concentration) and movable punches 9 of the punch chamber designed as lids can be controlled independently of one another, which increases the flexibility of the process control. In the case of bidirectional effect ^¬ automated venting with self-sealing, by pulling movements blocked fluidic paths are flushed in a FLÜS ^¬ sigkeitsdicht connected system.

Version with three piston drives: In this further be ^¬ vorzugten variant can now be a third piston drive loading ^¬ cher 2 itself pressing targeted against a connected measuring device 20, whereby the holding power of those locking elements is overcome, which contained one between the base of the cup 2 and measuring system 20 Keeps thorn at a distance. The cup 2 thus lowers to the connected measuring device 20 and the mandrel breaks through the seal 21. So this third drive is used for Realization of an independent. Control of the valve at the base of cup 2 and container unit 1.

Fig. 4 shows a further variant of the container unit 1, which manages on the one hand without opening 8, and on the other hand allows a further optical evaluation. The cup 2 has at its base a window 29 through which the concentrated sample liquid after lowering the hollow punch 4 in the direction A is observable. Accordingly, the liquid does not escape to the outside during the measurement, which minimizes the risk of contamination or contamination of the environment. Furthermore, the filtered liquid is transported within the hollow punch 4 through a channel 30 to a point at which the liquid can also be evaluated visually. This is done via a further window 31 at the end of the channel 30, which is located in the region of the lid of the hollow punch 4 as shown in FIG. 4. An evaluation device, such as a camera 32, moves along the direction B and observes a chemically or biochemically prepared substrate 34 with optionally activated surface, which has interacted with the filtered sample liquid. This can e.g. done by color change. The substrate 34 may also be arranged in the hollow die 4 or in the cup.

In a further embodiment according to FIG. 5, the hollow punch 4 has a means for observing the rear side of the filter 6. For this purpose, an evaluation device, such as a camera 32, held within the hollow punch 4 near the back of the filter 6 through a tubular access 33, wherein the camera 32 performs the optical evaluation through the window 31 looking. The filter 6 has a chemically or biochemically prepared filter substrate with optionally activated surface. The embodiments of FIGS. 4 and 5 can also be combined. It is understood that the described Ausführungsbei games within the scope of the inventive concept variously be changed from, for example, in terms of quantities, the intrinsic shafts of the filter material, as well as the surface or shape de filter.

Claims

Claims:

A container unit (1) for a substantially liquid sample for concentrating particles contained in the sample, comprising a cup (2) for receiving the sample, a filter (6) for separating at least a portion of the sample from the particles and with a with the filter (6) connected punch for moving the filter (6) through the sample, characterized in that the punch as liquid-tight in the cup (2) inserted and movable hollow punch (4) is formed, at the front of the punch ( 5) of the filter (6) is arranged, and that the container unit (1) at the base of the cup (2) has an opening (8) for removing at least a portion of the sample or at least one observation window (29) for the optical evaluation of the sample ,

2. Container unit according to claim 1, characterized in that the hollow punch (4) on the stamp front (5) facing away from a valve (7) for venting.

3. Container unit according to claim 1 or 2, characterized in that the opening (8) by a seal (21) is temporarily closed liquid-tight.

4. container unit according to one of the preceding Ansprü ^¬ che, characterized in that the cup (2) facing away from the end of the hollow punch (4) is designed as a punch (9).

5. Container unit according to one of the preceding Ansprü ^¬ che, characterized in that the amount of in the cup (2) remaining liquid sample with a sunk hollow punch (4) to the total sample amount in the ratio of about 1 to 20 to about 1 to 200 ,

6. Container unit according to one of the preceding claims, characterized in that the hollow punch (4) has a lid (3) formed ring which can be snapped or screwed onto the cup (2).

7. Container unit according to claim 6, characterized in that the hollow punch (4) is connected to the ring of the lid (3) via a predetermined breaking point.

8. Container unit according to one of the preceding claims, characterized in that the container unit at one of the points in contact with the liquid sample having a quantity of a dye (23) through which any predetermined particles in the liquid sample can be marked.

9. Container unit according to one of the preceding claims, characterized in that the valve (7) contains swelling polymers.

10. Container unit according to one of claims 3 to 9, characterized in that the cup (2) has a mandrel member (25) through which releasably by the movement of the hollow punch (4), the seal (21) is rupturable.

11. Container unit according to one of claims 3 to 9, characterized in that the cup (2) has a mandrel element (25) through which releasably by the movement of the hollow ^¬ stamp (4) an elastomeric valve on the cup base is reversibly apparent.

12. Container unit according to one of the preceding claims, characterized in that it has in the flow direction behind the opening (8) designed as a measuring capillary measuring channel (22) which has at least one observation window.

13. Container unit according to claim 12, characterized in that the measuring channel (22) contains a chemically or bio-chemically prepared substrate whose reactions are optically evaluable with the sample.

14. Container unit according to one of the preceding claims, characterized in that the filter (6) and / or a chamber in the lid of the hollow punch (4) contains a chemically or biochemically prepared substrate with activated surface.