HK1182048B - Microfluidic test carrier for dividing a liquid quantity into subquantities - Google Patents
Microfluidic test carrier for dividing a liquid quantity into subquantities Download PDFInfo
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- HK1182048B HK1182048B HK13109544.7A HK13109544A HK1182048B HK 1182048 B HK1182048 B HK 1182048B HK 13109544 A HK13109544 A HK 13109544A HK 1182048 B HK1182048 B HK 1182048B
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Description
The invention relates to a microfluidic test carrier for dispensing an amount of liquid into a component amount. The test carrier comprises a substrate and a cover layer and a capillary structure surrounded by the substrate and the cover layer, wherein the capillary structure comprises a containing cavity, a sample cavity and a connecting channel between the containing cavity and the sample cavity. The receiving chamber has two opposite limiting surfaces and a side wall, wherein one limiting surface is the bottom surface of the receiving chamber, and the other limiting surface is the cover of the receiving chamber.
Microfluidic elements for analyzing liquid samples are used In diagnostic tests for In Vitro diagnostics (In-Vitro-diagnostic). In the case of this test, one or more analytes contained in a bodily fluid sample are assayed for pharmaceutical purposes. An important component in this analysis is the test carrier on which a microfluidic channel structure for receiving and transporting the liquid sample is present in order to enable complex and multistage test instructions (test reports).
The test carriers, which are often referred to as "Lab-on-CD (Lab on a CD)" or "Lab-on-a-chip (Lab on a chip), are made of a carrier material, which is usually a substrate made of plastic. Suitable materials are, for example, COC (Cyclo-olefin-Copolymer) or plastics, such as PMMA (polymethyl methacrylate), polycarbonate or polystyrene. The test carrier has a channel structure which is formed in the base plate and is surrounded by a cover or cover layer. The channel structure is often composed of a plurality of channels and channel segments in succession and chambers located between them which are expanded compared to the channels and channel segments. The structure and dimensioning of the channel structures are defined by the structuring of the plastic particles of the substrate and can be produced, for example, by die-casting techniques or other suitable methods. Also included as methods are methods of material stripping, such as milling and the like.
Microfluidic test carriers are additionally used in the case of immunochemical analyses with multistage test procedures, such as enzyme-linked immunosorbent assays (ELISA), in which case, for example, separation of bound or free reaction components takes place. A controlled liquid delivery is required for this purpose. The process flow can be controlled by internal (within the flow element) or external (outside the flow element) measures. The control may be based on the application of a pressure difference or on a change in force. In this case, the test carrier is often rotated to apply a centrifugal force with which a control is effected by changing the rotational speed, the rotational direction or the acceleration. A combination of capillary and centrifugal forces is also often employed to control the applied fluidics.
Analytical systems with rotating test carriers are known, for example, from the following publications:
EP 0 626 071 B1;
WO 2007/042219 A1;
WO 01/46465 A2;
WO 95/33986;
US 5,160,702;
WO 93/19827。
the overview of test elements for microfluidics and methods of controlling them, and of test elements for microfluidics as a rotating plate, for example in the form of a Compact Disc (CD), is from marccoaou and others; lab on CD (laboratory on CD); annual Review of Biomedical Engineering, 2006, 8 th, pages 601 to 628 (online @ http:// bioenc.
In the case of microfluidic test carriers, a plurality of juxtaposed partial structures are often situated on a test carrier in order to be able to carry out different analyses in a process flow. In order not to require the user to have to apply a sample liquid in small quantities several times, dispensing structures are proposed in test carriers which dispense the liquid in a plurality of partial volumes of the same or different size. Furthermore, the distribution structure ensures that: the effect of sample application or sampling does not distort the results convincing (Aussagekraft). For all analyses, the same sample material is used, which increases the persuasion, for example in the case of multiple determinations.
In the prior art, dispensing structures are known, for example from US 6,919,058, in which case the liquid is accommodated in an elongate channel which is constructed in the form of a plurality of V-shaped structures arranged one behind the other. The distribution structure is annularly arranged on a centrifugal platform. At the radially inner ends of the flanges of the V-shaped structure, gas exchange capillaries are respectively provided. At the radially outer part of the V-shaped structure, discharge capillaries are arranged, which are equipped with a trap. Thus, a capillary force based liquid predistribution in the respective V-shaped structures is achieved. But this distribution is particularly slow. After the liquid is accommodated in the V-shaped distribution structure, the test carrier is rotated at an increased speed, so that the liquid penetrates the hydrophobic stop at a certain frequency and is discharged through the radially outwardly extending discharge capillary on the base body of the V-shaped structure. The liquid is separated at the point of time when the valve is pierced. The splitting of the pre-distributed split fluid is realized. The derived volume is preset in particular by the building architecture of the radially inner part of the structure. If the structures are the same size, the derived volumes are maximally equal.
US 4,154,793 discloses a rotating test carrier with a central receiving opening in the lid. A receiving chamber is arranged below the opening of the cover, in which receiving chamber the liquid is supported. A plurality of sample chambers are arranged around the receiving space and are connected to the receiving space via a connecting channel. The entry of liquid into the sample chamber is effected at a radially outer position. In order to vent the sample chamber, a vent opening is provided, which is connected to the receiving chamber at a position radially further inside the inlet opening and the sample chamber. By rotating the test carrier, the liquid contained in the receiving chambers is emptied into the respective sample chamber, wherein air flows radially inward from the sample chamber into the receiving chamber and finally escapes through the central opening in the cover.
US 7,125,711 discloses a test carrier with an elongated distribution channel to which a plurality of measurement chambers are connected, which measurement chambers are filled capillary-like. Each measurement chamber includes a component and has an outlet with a valve having a geometry. By rotating the test carrier, the component is emptied from the measurement chamber into the sample analysis chamber.
Microfluidic dispensing structures known from the prior art for dispensing liquid quantities into component volumes are particularly suitable for small volumes up to approximately 10 μ l, since these structures fill purely "passively" by capillary forces. This in turn makes the system strongly dependent on the fluid properties of the sample, which has an adverse effect on the robustness. In the case of larger volumes, the dispensing leads to a significant delay through the elongated dispensing structure. This is due to the fact that, in the case of larger volumes, the surface area to volume relationship of the capillary becomes increasingly unfavorable, which in turn leads to a reduction in the capillary force. In some cases, the filling of the capillary and the component chamber provided for the component may even stop. Furthermore, there is the risk that, in the case of larger volumes, air flows into the capillary, which distorts the dispensing and leads to incorrect volumes. In general, in the case of dispensing systems which operate mostly in the capillary manner, the formation of air inclusions (luftensischlusse) and foam has a considerable influence on the accuracy of the partial volumes which are discharged, as a function of the design. This sensitivity of capillary-operated dispensing systems reduces the robustness of processes, such as analytical processes. The reduced robustness must be balanced by external factors, such as by using an automated dispensing robot. The known test carriers are therefore only suitable for automated pipetting (Pipettierungen) of liquid quantities. The manual pipetting by different users, which often occurs in a time-critical manner, leads to an increased formation of bubbles and foam during pipetting. The known test carriers are not suitable for manual use. Since the surface properties dominate the process, in the case of the capillary effect used here, in addition, the manufacturing effect and the effects of the surface treatment (such as activation, hydrophilicity) play a major role. This increases the production and testing costs of the test carrier during mass production, due to the narrow tolerances, and furthermore leads to an excessively high rejection rate.
There is therefore also a great need in the prior art to provide a test carrier with which a reliable dispensing of a liquid quantity in a predetermined portion can be achieved. Such a test carrier should be suitable not only for automated pipetting and liquid volume transfer, but also for manual transfer by different users, and should therefore be characterized by increased robustness.
This problem is solved by a microfluidic test carrier for dispensing an amount of liquid into a component amount having the features of claim 1.
The microfluidic test carrier according to the invention has a substrate in which a capillary structure is formed. The capillary structure is surrounded by a substrate and a cover layer. The capillary structure comprises a receiving chamber for receiving an amount of sample liquid, at least one sample chamber, and a connecting channel extending between the receiving chamber and the sample chamber, wherein the sample chamber has a volume which is smaller than the receiving chamber. The combination formed by the receiving chamber, the connecting channel and the sample chamber serves to distribute the sample liquid volume into one or more partial volumes, which are smaller than the initial liquid volume.
The receiving chamber has two opposite limiting surfaces and a side wall, wherein one of the limiting surfaces is a bottom surface of the receiving chamber, and the other limiting surface is a cover of the receiving chamber. The chamber has a circumferential discharge duct and a likewise circumferential dam which is arranged between the interior of the receiving chamber and the discharge duct. The dams located between the receiving chambers of the exhaust gas ducts are arranged and constructed in such a way that they form a geometric valve together with the exhaust gas ducts. The geometric valve is a capillary stop for the liquid, but through which air can be discharged from the receiving chamber into the venting channel. The geometric valve prevents the sample liquid from being dispensed into the connecting channel in a capillary manner without external forces acting on the liquid for controlling the movement of the liquid or the flow of the liquid. Preferably the dam is located above so that air can be evacuated from the cavity.
According to the invention, the venting channel has at least one outlet opening which is in fluid connection with the connecting channel between the receiving chamber and the sample chamber and provides a connection between the outlet opening of the venting channel and the inlet opening of the sample chamber. In this way, it is achieved that the liquid is transported from the receiving chamber into the sample chamber as soon as it passes over the geometric valve formed by the dam and the vent channel. When a sufficient force is applied to the liquid, the valve opens. This may be, for example, an external force, which is generated by acceleration or rotation. The geometric valve can be overridden, for example, when a certain rotational frequency of the rotating test carrier is reached. The capillary stop formed by the geometric valve is designed in such a way that automatic liquid transport from the receiving space, for example by capillary forces, is reliably prevented. With the valve open, liquid also comes out of the inner space of the receiving chamber, flows into the connecting channel through the vent channel, and then flows into the sample chamber.
The receiving chamber, the exhaust passage, and the dam are configured in such a manner that an inner space of the receiving chamber is positioned innermost in a radial direction. If the test element is viewed in cross section, the three components are arranged radially from the inside to the outside in such a way that the inner space of the receiving chamber is arranged inside, followed by the surrounding dam and outermost (radially outside) the surrounding venting channel. In this case, at least some regions of the dam and at least some regions of the vent channel lie in a plane which extends parallel to the cover layer of the test element. Thus, the dam forms a side wall of the exhaust gas passage.
Thus, the receiving chamber can be filled first as a dispensing chamber or dispensing structure. This preferably takes place in the case of stationary microfluidic test carriers. The robustness of the system is increased by the round design of the receiving space and preferably by the smallest possible surface-to-volume ratio of the receiving space. Capillary forces and surface structures or surface treatments have only a negligible effect on the robustness of the dispensing system. By suitably selecting the surface area-volume ratio of the chambers, in which case the chambers are preferably as high as possible, it is possible to achieve as equal a distribution of the liquid as possible even in the case of first unequal distribution in the sample addition. A capillary force based pre-dispensing as is common in the prior art is not necessary. The quality of the dispensed volumes and the uniformity of the individual partial volumes are independent of the sample charge. Thus enabling higher sample feed rates. When the receiving chamber is filled, the liquid sample can flow into the chamber particularly quickly. Such a receiving chamber is particularly suitable for manual pipetting.
Furthermore, the geometric valve extending at least partially or locally (abschnittweise) along the periphery of the receiving chamber ensures that the sample distribution in the receiving chamber does not affect the quality of the distribution volume compared to the above-described prior art systems. The geometric valve can only be overcome by an additional force for controlling the liquid supply and the liquid can be discharged from the receiving space. By means of this embodiment, a filling of the receiving space is achieved which is independent of the distribution of the total liquid quantity to the partial quantities. The filling and dispensing into the partial volume are completely decoupled.
According to the invention, the dispensing of the liquid is not performed by capillary forces, but by controlled forces, such as centrifugal forces. Problems arising in the case of capillary force based liquid dispensing are avoided. The bubbles will be conducted radially inwards by their density which is reduced in the case of centrifugation. The liquid sample is actively degassed during the factorization or portioning (dispensing) so that air inclusions (luftensischlusse) and foam do not influence the process and thus bypass the problems prevailing in the prior art. The test carrier according to the invention thus achieves a distribution of the sample liquid which is not prone to malfunction and stable and which has no correlation with possible contamination in the distribution structure or with surface properties of the distribution structure.
In a preferred embodiment, the microfluidic test carrier is a rotating disk, for example a disk like Compact Disk (CD), and rotates about a rotation axis, which preferably extends through the test carrier. In a preferred embodiment, the test carrier is designed in such a way that the axis of rotation extends through a center point or center of gravity of the test carrier.
It has proven advantageous for the emptying of the receiving space, which in a preferred embodiment is arranged on the test carrier in such a way that the axis of rotation extends through the receiving space. A centrifugal force is generated by the rotation of the test carrier, which presses the liquid located in the receiving chamber radially outward, so that the circumferential dam and the geometric valve formed by the dam are crossed and the liquid can flow into the air outlet channel. Thereafter, liquid flows from the venting channel through the connecting channel into the sample or portion chamber and fills it.
The design of the receiving chamber according to the invention allows particularly rapid receiving of the sample. Since in practice, particularly in the case of manual filling by the user, significantly different pipetting speeds are to be expected, it is ensured that in any case no overflow of the sample opening occurs. The overflow can cause contamination of the test carrier surface and, in particular in the case of rotating test carriers, contamination of the equipment. Furthermore, with small volumes and slow pipetting processes, there is a risk of the specimen drying up at the interface. The possibility of rapid pipetting thus also improves the robustness, accuracy and reliability of the test carrier.
In a preferred embodiment, the receiving space is designed in such a way that a surface-volume ratio which is as small as possible is produced. Ideally, the receiving space is spherically formed, since there is a minimum surface-to-volume ratio. In the case of a typical chamber volume of between 100. mu.l and 200. mu.l, for example 160. mu.l, the surface-to-volume ratio lies at 0.9mm2/mm3The numerical value of (c). Within the framework of the invention, it has been found that the surface-to-volume ratio of the receiving space should have a maximum of 2.5mm2/mm3Preferably at most 2mm2/mm3The numerical value of (c).
One of the defining faces of the receiving chamber has an inlet port for externally adding a liquid sample. Preferably, the access opening is arranged in a cover of the receiving chamber. Thus, the liquid sample can be added by the user from above. If the cover of the test carrier, at least in the region of the receiving space, is made of a transparent material, the user can observe the filling of the receiving space. During filling, visual feedback occurs at the user.
In connection with improved filling of the receiving space, it has proven advantageous if one of the limiting surfaces of the receiving space is curved. In this case, two different preferred embodiments are possible. In a first embodiment, the curved delimiting surface of the receiving space is a cover. In another embodiment, the curved defining surface forms the bottom surface. Preferably, the bottom surface is curved in such a manner that it rises toward the edge of the receiving cavity.
In the case of the microfluidic test carrier according to the invention with a capillary structure having a receiving chamber, at least one sample chamber and a connecting channel arranged between the chambers, two ways of dispensing the liquid amount into the components can be achieved. On the one hand, a parallel distribution to a plurality of sample chambers is achieved; on the other hand, a serial distribution of the entire liquid sample volume to a plurality of chambers is achieved.
In order to achieve a parallel distribution of the liquid quantity into a plurality of portions, the outlet channel preferably has a plurality of outlets, which are each in fluid connection with a connecting channel, which extends from the receiving chamber to a respective sample chamber. In a preferred embodiment, the outflow openings (discharge openings) are distributed equidistantly at the exhaust channel, so that an even distribution along the circumference of the exhaust channel is achieved. The individual sample chambers may have the same or different volumes, so that the total liquid volume can be dispensed in the same or different partial volumes. With the same volume of the sample chambers, an (absolutely) uniform distribution of the liquid is achieved until all sample chambers are filled or the receiving chamber is emptied. Further channels, chambers or capillary channel structures or tubing can be connected to the individual sample chambers.
In the case where the total liquid amount is serially distributed to the partial volumes, the gas discharge channel has only one outlet port (discharge port), so that the liquid contained in the accommodating channel flows into the first sample chamber through the outlet port and through a connecting channel connected to the outlet port. The first sample chamber is connected to at least one other chamber via a discharge channel, so that liquid can flow from the sample chamber into the discharge channel via a discharge opening of the sample chamber. The chamber may likewise be a sample chamber, for example. The other fluid chamber may also be a Waste chamber (Waste-Kammer) in which excess fluid is collected. In this way, the total sample volume can be distributed over a plurality of sample chambers arranged one behind the other. Of course, further (additional) channels, chambers or capillary-like tubing may be arranged in succession or side by side at one or more of the sample chambers.
The invention will be explained in detail below with reference to specific embodiments shown in the drawings. The features shown therein can be used individually or in combination to provide preferred embodiments of the invention. The described embodiments show exemplary rotating test carriers in the form of circular disks and serve to illustrate the invention and special features. These embodiments do not represent any limitations to the invention as defined by the claims in their generality. Wherein:
FIG. 1 shows a schematic sketch of a microfluidic test carrier and three sample chambers, which are fluidically connected in series;
FIG. 2 shows a detailed view of a receiving cavity in the test carrier of FIG. 1;
FIGS. 3a, b show two cross-sections through the test carrier of FIG. 1;
FIGS. 4a-c show a partial view of the test carrier of FIG. 1, respectively, for illustrating the filling and the dispensing;
FIG. 5 illustrates an alternative embodiment of a test carrier for dispensing liquid samples side-by-side onto a plurality of sample chambers;
FIG. 6 shows a detailed view of the receiving cavity of the test carrier of FIG. 5;
FIG. 7 shows a cross-sectional view through the receiving cavity of FIG. 6;
FIG. 8 shows a perspective view of the receiving cavity of FIG. 6;
FIG. 9 shows a perspective cross-sectional view of the receiving cavity of FIG. 6;
FIG. 10 shows a schematic sketch for filling and dispensing a liquid in the test carrier of FIG. 5.
Fig. 1 to 10 show an embodiment of a microfluidic test carrier 1 according to the invention, which comprises a channel system 2 having a capillary-type channel structure 3. The channel structure 3 is formed in a base plate 4 made of plastic. Preferably, the capillary structure 3 is made by die casting techniques or by a material stripping process from the substrate. The test carrier 1 further comprises a cover layer, not shown in fig. 1, which lies flat on the substrate 4 in such a way that the channel structure 3 is enclosed by the substrate 4 and the cover layer.
In a preferred embodiment, the test carrier 1 is a rotating test carrier 1 which rotates about an axis of rotation 5. The test carrier 1 is configured in the form of a sheet, for example in the form of a CD. It is held in a rotating device having a rotation axis aligned with the rotation axis 5. In a preferred embodiment, the axis of rotation 5 extends through the test carrier 1, preferably through its center point or its center of gravity.
The capillary structure 3 comprises a receiving chamber 6 having an inlet opening 7 through which a liquid sample or an amount of liquid can be fed into the receiving chamber 6. The addition of the liquid sample is carried out, for example, by manual or automated pipetting. The receiving chamber 6 shown here by way of example has a volume of 160 μ l. In the preferred embodiment, the surface area-to-volume ratio is about 1.8mm2/mm3And thus lies at the preferred value of 2.5mm2/mm3Or 2.0mm2/mm3The following. The receiving chamber 6 designed in this way reliably allows rapid pipetting, so that the pipetting can also be carried out manually.
The channel structure 3 further comprises at least one sample chamber 8 and a connection channel 9, which extends between the receiving chamber 6 and the sample chamber 8 and establishes a fluid connection between the two chambers 6, 8. The connecting channel 9 is constructed as a relatively short channel. Preferably, the connecting channel 9 hasA length of between 1mm and 5mm, particularly preferably between 2mm and 3 mm. In the example shown here, the length of the connecting channel 9 is equal to 2.7 mm. The cross-sectional area of the channel is preferably 0.01mm2To 0.25mm2In the range of (a). Typical values are for example 0.09mm2. The channel shown here has, for example, a width of 0.2mm and a height of 0.15 mm. So that its cross-sectional area is 0.03mm2. The dimensioning of the connecting channel 9 has an effect on the complete emptying of the receiving chamber, which preferably should take place substantially more slowly than the uniform distribution of the liquid in the receiving chamber 6. In the example shown here, the duration of the complete emptying of the receiving chamber 6 is approximately six times longer than the duration for an even distribution (equalization) of the liquid in the receiving chamber 6. The complete evacuation lasts in this example about 10 seconds.
Fig. 1 to 4 show an exemplary embodiment of a test carrier 1 with a capillary structure 3 having three sample chambers 8, 10, 11. The three sample chambers 8, 10, 11 are connected one after the other (in series) and are each connected to one another via a channel 12. The three sample chambers 8, 10, 11 form a fluidic series connection (Reihenschaltung) or series connection (serienschalltung), so that liquid can flow from the receiving chamber 6 first into the sample chamber 8, and from there into the sample chamber 10 and then into the sample chamber 11. A further chamber 13 is connected to the last sample chamber 11, which is embodied as a waste chamber 14 and forms a waste reservoir for the fluid of the excess liquid. The volume common to all sample chambers 8, 9, 10 and waste chamber 14 is preferably approximately the same size as the volume of the receiving chamber 6, preferably slightly larger.
A total of three sample chambers 8, 9, 10 makes it possible to distribute the volume of liquid fed into the receiving chamber 6 into a total of three components, which are determined by the geometry of the sample chambers 8, 9, 10. Of course, multiple sample chambers may be used. Embodiments with two sample chambers are likewise conceivable.
The sample chambers 8, 9, 10 arranged in fluid series allow the distribution of a (small) liquid volume, which is smaller than the total volume of the three sample chambers. In the case of smaller volumes, liquid is dispensed into only one or two chambers, since the sample chambers 8, 9, 10 are filled one after the other and, only when the preceding sample chamber 8 is completely filled, the subsequent sample chamber 10 is filled. Thus, an analysis for multiple or only one parameter using the same test carrier is achieved. This greatly simplifies production, since only one production line and one tool are required for manufacturing the test carrier, whether the test carrier should be marketed as a single-parameter test carrier or as a multi-parameter test carrier. This sample distribution approach also provides great advantages to the user, since only 1/3 sample volumes are required for analysis of one parameter, or only 2/3 sample volumes are required for analysis of two parameters. But the same test carriers can be used separately.
The receiving space 6 is preferably arranged on the test carrier 1 in such a way that the axis of rotation 5 extends through the receiving space 6. Preferably, the axis of rotation extends through the inlet opening 7 of the receiving chamber 6, preferably through a center point of the inlet opening 7. The receiving chamber 6 can be arranged in the test carrier 1 in such a way that the axis of rotation 5 extends through a center point or center of gravity of the receiving chamber 6. In a preferred embodiment, as shown here, the receiving chamber 6 is arranged eccentrically with respect to the center point of the test carrier 1 or with respect to its center of gravity. The center point of the circular (round) receiving chamber 6 is located outside the center point of the test carrier 1. The axis of rotation 5 therefore also does not extend through the center point of the receiving space 6. An inlet opening 7 arranged eccentrically with respect to the receiving space 6 is arranged concentrically with respect to the axis of rotation 5.
Fig. 2 shows a detailed view of the receiving chamber 6 from the underside. The inlet opening 7 is arranged centrally in the test carrier 1 and is arranged eccentrically with respect to a center point of the receiving chamber 6. The receiving chamber 6 has a circumferential channel 15, which is an exhaust channel 16. Between the interior 17 of the receiving chamber 6 and the surrounding exhaust gas duct 16, a dam 18 is formed, which extends concentrically with the exhaust gas duct 16. The dam 18 and the exhaust gas duct 16 are arranged at least partially in a plane, the surface normal of which extends parallel to the axis of rotation. The vent channel 16 has a radially inner side wall (which is formed by the dam 18), a radially outer side wall 27 (which is the outer wall of the receiving chamber 6) and a bottom surface (which is arranged substantially parallel to the cover layer 21 of the test element). The exhaust channel 16 may have a constant width and a constant height over its entire circumference. But it may also have dimensions that vary over the circumference, but preferably at least its height is constant. Of course, the exhaust duct 16 and/or the dam 18 can be partially or sectionally or partially (abschnitssweise) interrupted. In particular, the dam 18 can be interrupted in sections in such a way that a side wall of the cover extending to the receiving space is formed. Preferably, the dam and/or the gas discharge duct extends over at least 50% of the circumference of the receiving chamber 6, preferably over at least 80% of the circumference and particularly preferably over at least 90% of the chamber circumference. In the case of an interrupted exhaust gas duct 16 or dam 18, however, it must be ensured that the geometric valve function formed by it is maintained.
The dam 18 is formed by a wall 19 having a thickness (dimension in the radial direction) which preferably corresponds to the width of the connected exhaust gas duct 16. The height of the wall 19 is less than the height of the (radially outer) side wall 27 of the vent channel 16, so that a gap 29 is produced between the cover layer 21 of the test carrier 1 and the upper side 20 of the wall 19. The gap height is smaller than the height of the exhaust channel 16.
Fig. 3a and 3b each show a section through the test carrier 1. The receiving chamber 6 has two defining faces 22, 23. The limiting surface 22 is the bottom surface 24 of the receiving chamber 6 and the opposite limiting surface 23 is the cover 25. In fig. 3a, the bottom surface 24 is formed by the substrate 4. The limiting surface 23 is formed by a cover layer 21, which lies flat on the substrate 4 of the test carrier 1. In the embodiment according to fig. 3b, the lid 25 is formed by the substrate 4, while the bottom surface 24 is the cover layer 21 contacting the substrate 4.
In a preferred embodiment, one of the limiting surfaces 22, 23 of the receiving space 6 is curved. In the present example according to fig. 3b, the cover 25 formed by the substrate 4 is curved. The limiting surface 22 forming the bottom surface 4 is flat. The cover 25 has a funnel-shaped access opening 7 through which the liquid quantity to be dispensed is fed into the receiving chamber 6.
Fig. 3a shows an embodiment, in which the base surface 24 is designed as a curved delimiting surface 22. The flat cover layer 21 forms a lid 25 and has an access opening 7. If the cover layer 21 is a transparent film as the cover 25, a better visual feedback of the volume which has been metered into the receiving chamber 6 can be obtained in the case of a manual pipetting of liquid. If the access opening 7 is formed in the substrate 4, visual feedback is likewise achieved when the substrate is transparent at least in the region of the receiving chamber.
The curved embodiment of the limiting surfaces 22, 23 has the advantage that the incoming air is conducted towards the inlet opening 7 in the case of a curved cover 25 or towards the side walls of the interior space 17 in the case of a curved bottom surface 24. In this way it is ensured that: air that has entered or has pipetted with the liquid can escape from the receiving chamber 6 and is not contained in the liquid, which would otherwise lead to volume errors.
The venting channel 16 has exactly one outflow opening 26 in the case of a fluidic series connection of the series-connected sample chambers 8, 10, 11. The outflow opening is preferably arranged in the exhaust channel side wall 27 at a position which, in the case of an eccentrically arranged receiving space 6, is furthest away from the axis of rotation 5. In the embodiment shown, in which the axis of rotation 5 is arranged concentrically to the circular inlet opening 7, the spacing between the outlet opening 26 and the inlet opening 7 is the maximum spacing present in the cavity 6. With rotation of the test carrier 1, the liquid is pressed radially outward and collects anyway in the region around the outflow opening 26. Thus, it is ensured that: the entire liquid flows out of the receiving space 6, since the last remaining amount is also pressed against the outlet opening 26.
The dam 18 and the exhaust passage 16 together form a geometric valve 28. The liquid which is to flow from the receiving chamber 6 into the sample chamber 8 must flow through this valve 28, i.e. via the dam 18 and through the vent channel 16, in order to pass through the connecting channel 9 into the sample chamber 8. The capillary gap 29 formed between the upper side 20 of the dam 18 and the opposing limiting surface 22 is smaller than the height of the subsequent exhaust channel 16. In this example, the capillary gap 29 is formed between the upper side surface 20 and the bottom surface 24, as can be seen in fig. 3 a.
With the geometric valve 28, the interior 17 and the gap 29 are first filled with liquid only when the receiving space 6 is filled. But liquid does not enter the exhaust channel 16 itself. The receiving chamber 6 can thus be completely or partially filled with the sample liquid or the liquid amount to be dispensed.
Fig. 4a shows a partial filling of the receiving chamber 6, while fig. 4b shows a complete filling. The air 60 contained in the receiving chamber 6 can pass through the geometric valve 28 and escape via the vent channel 16 into the subsequent connecting channel 9 until it exits from one of the vent channels 32 of the following sample chambers 8, 10, 11 into the environment (see fig. 1).
As soon as the test carrier 1 is set in rotation and the rotational frequency exceeds the feedthrough frequency predetermined by the geometry of the geometric valve 28, the geometric valve 28 opens. The liquid flows radially outward from the receiving chamber 6 into the exhaust channel 16. The liquid exits from the discharge channel through the outlet opening 26 into the connecting channel 9, which in the example shown has a further valve 30 of alternative geometry. The geometric valve 30 is also opened by centrifugal force, so that liquid flows into the first sample chamber 8, fig. 4 c.
In the case of rotation in the direction of the arrow R (fig. 1), the liquid is introduced not only into the upper part of the sample chamber 8 but also into its stirrup-like chamber structure 31, wherein the liquid moves along the side wall 31a of the chamber structure 31, which movement is opposite to the direction of rotation. At the opposite side wall 31b of the chamber structure 31, air can flow from the structure 31 into the sample chamber 8 and be discharged via a discharge channel 32. As soon as the sample chamber 8 is completely filled, the liquid passes through the outlet opening 33 into the outlet channel 34 connected thereto. The outlet channel 34 is itself connected to the inlet 35 of the subsequent sample chamber 10, so that liquid can flow into the sample chamber 10.
Since the air contained in the chambers can be discharged from the respective sample chamber 8, 10, 11 to the environment via their respective air outlet 32, only the flow resistance of the discharge channel 34 prevents the further flow of liquid from one sample chamber to the next. The pressure of the liquid, which builds up by centrifugal force when leaving the receiving space 6, is significantly greater than the flow resistance. The receiving chamber 6 is thus completely emptied, wherein excess liquid flows from the last sample chamber 11 into the subsequent waste chamber 14.
The series arrangement of the three sample chambers 8, 10, 11 not only allows a distribution of the total volume formed by the three chambers; likewise, the receiving chamber 6 can be filled with only one quantity of liquid, which corresponds to the volume of the two sample chambers 8 and 10 and the connecting channel 9 and the discharge channel 34. In this case, the dispensing or dividing or portioning of the liquid quantity onto only two sample chambers 8, 10 takes place. If the amount of liquid in the receiving chamber 6 corresponds only to the volume of the sample chamber 8, only the first sample chamber 8 is filled. In this case, the cavities are always completely filled. The volume of a sample chamber and the (substantially negligible) volume of the connecting channel 9 thus form a minimum volume for filling the receiving chamber 6.
Furthermore, the receiving chamber 6 can be designed to be significantly larger than the total volume of the three sample chambers 8, 10, 11. This achieves that the work is carried out as far as possible without metering for the end user. In other words: the reliability of the defect-free (fluidic) function of the subsequent structure is always ensured, irrespective of whether the minimum quantity required by the three sample chambers 8, 10, 11 is metered or the maximum quantity to fill the receiving chamber 6 completely. In this example, the volume of each of the three equal sample chambers 8, 10, 11 comprises 30 μ l each. The total volume of the accommodating chamber 6 was 160. mu.l. If the receiving chamber 6 is filled with more liquid than the three sample chambers 8, 10, 11, the excess liquid is received in the waste chamber 14.
The advantage of the test carrier 1 according to the invention is that the filling of the distribution structure formed by the receiving chambers 6 by the geometric valves 28 is completely decoupled from the division or distribution (portioning) of the liquid. There is no time limit in the sample filling, i.e. in the filling of the receiving chamber 6, for example by the customer.
Optionally, two or more further chambers are connected to the receiving chamber 6, wherein further chambers can be connected to the further chambers, for example, in order to achieve parallel reaction guidance (Reaktionsfurung). These chambers may be separation chambers for separating liquid and cellular sample components, reagent chambers for dissolving reagents, mixing chambers, waste chambers or other chambers.
In this embodiment, in the case of an assay of blood, the separation of liquid and cellular sample components takes place in the stirrup-like chamber structure 31 of the sample chambers 8, 10, 11. A separation thus takes place in the cavity structure 31. In this way it is achieved that: analysis of the plasma remaining in the measurement chamber 37.
Fig. 5 to 10 show an alternative embodiment of a test carrier 1 according to the invention with, for example, a parallel arrangement of the fluids of three test chambers 8, 10, 11 instead of the series arrangement of the test chambers 8, 10, 11 according to the exemplary embodiment of fig. 1 to 4. In this embodiment, two or more sample chambers may also be configured. The following illustrates substantial differences:
in this parallel arrangement, a central receiving chamber 6 is likewise arranged, the center point or center of gravity of which is preferably identical to that of the test carrier 1. The axis of rotation 5 about which the test carrier 1 rotates preferably extends through a center point of the receiving chamber 6. In a particularly preferred embodiment, the inlet opening 7 of the receiving space 6 is likewise concentric with the axis of rotation 5.
In this embodiment, three sample chambers 8, 10, 11 with a stirrup-like channel structure 31 are shown, which are fluidically connected in parallel. Each of the sample chambers 8, 10, 11 has a connecting channel 9 for the receiving chamber 6, which extends from the outlet opening 26 of the venting channel 16 to the inlet opening 35 of the sample chamber 8, 10, 11. The connecting channel 9 is S-shaped in this embodiment and is significantly longer than the connecting channels 9 in the series arrangement, as shown in fig. 1 to 4. Of course, even in this parallel arrangement, a short, radially outwardly extending connecting channel 9 can be used. S-shaped channels 9 can also be used in a series design.
In this example, the length of the long connecting channel is typically at least 7 mm. Preferably, the length is at least 9mm, particularly preferably at least 10 mm. The S-shaped design of the elongated channel has the advantage that space is saved in the radial direction. Furthermore, it achieves a radius as small as possible during the transition into the sample chamber and thus a centrifugal force as small as possible at this point. This has a positive effect on the evacuation rate, which should be as low as possible in order to ensure uniform evacuation of the receiving chamber 6. The above statements regarding the cross-sectional area are valid also for the long channels. The cross-sectional area should preferably lie between 0.01 and 0.25mm2In the meantime. In this example, the connecting channel 9 has a width of 0.3mm and a height of 0.3mm at the outflow opening 26 of 0.09mm2Cross-sectional area of (a). At its end at the discharge opening 35The connecting channel 9 is tapered and has a width of 0.2mm and a height of 0.15 mm. So that its cross-sectional area is 0.03mm2. With this type of connection channel it is achieved that: the evacuation duration required for completely evacuating the receiving chamber 6 is designed to be approximately three to four times longer than the duration for an even distribution of the liquid in the receiving chamber 6 (this is also referred to as equalization). In the case of the parallel design of the capillary structure 3, the duration for equalisation (Egalisieren) is 1.5 seconds, as in the case of the series design. In the case of the parallel embodiment, the complete evacuation is completed in about 5 seconds.
The outlet channel 16 forms, together with the circumferential, radially inner dam 18, a geometric valve 28 which prevents an automatic outflow of liquid, for example blood. Only when the valve 30 is open, liquid can flow into the sample chambers 8, 10, 11. The gap 29 between the upper side 20 and the cover layer 21 is smaller than the height of the subsequent venting channel 16.
The sample chambers 8, 10, 11 preferably each have a discharge opening 33, through which liquid can flow from the sample chambers 8, 10, 11 into the discharge channel 34. At the end of the discharge channel 34, a further fluid chamber 13 is arranged, which has an inlet 39, which is in fluid connection with the sample chambers 8, 10, 11. The fluid chamber 13 is preferably a Waste chamber (Waste-Kammer) and contains excess fluid. The sample chambers 8, 10, 11 each have a volume of 30. mu.l, and the receiving chamber 6 has a volume of 160. mu.l. The volume of liquid emerging from the receiving chamber 6 is distributed uniformly over the sample chambers 8, 10, 11, the remaining liquid flowing into the respective waste chamber 14.
The receiving chamber 6 can be filled both with a minimum filling quantity (corresponding to the sum of all the connecting channels 9 and the sample chambers 8, 10, 11) and completely with a maximum filling quantity. In this case, it is ensured that the total volume of the receiving chamber is less than the total volume of all sample chambers and waste chambers. Of course, the receiving space 6 can also be filled with any amount of liquid between the minimum filling amount and the maximum filling amount. A wide liquid range for liquid analysis, such as analysis of blood or another body fluid, is thereby obtained. This makes it possible for the user to improve the pipetting and feeding of liquid and to facilitate the operation, particularly in the case of manual pipetting.
In the case of a parallel arrangement of the sample chambers 8, 10, 11, with which a simultaneous distribution of the liquid quantity to the partial quantities is achieved, the vent channel 16 has a plurality of outlet openings 26 which are in fluid connection with one connection channel 9 each. It is particularly preferred that the outflow openings 26 are equidistant, i.e. evenly distributed, over the circumference of the exhaust channel 16. Preferably, the vent channel 16 extends over the entire circumference of the receiving chamber 6.
This is valid for the channels 16 in all embodiments according to fig. 1 to 10. Of course, as already explained in the case of the series arrangement, the dam 18 and/or the exhaust gas duct 16 can also be interrupted in sections or in sections even in the case of a parallel arrangement. However, it is preferred that the interruption of the vent channel 16 is not located in the region of the outlet opening 26.
Within the framework of the invention, it has been recognized that the flow resistance of the distribution capillary formed by the connecting channel 9 can be used as a control unit in the case of parallel distribution of liquid volumes. In the case of short connecting capillaries with large cross-sectional areas and therefore fast flow speeds, the liquid sample breaks, i.e. it has no time to distribute evenly in the receiving chamber, which results in different volumes. The integration of a longer channel with a very small cross-sectional area according to the invention, which acts as a flow stopper over its length and slows down the dispensing process, improves the uniform dispensing into a large number of segments without the need for a uniform capillary pre-dispensing. The integration of the connection channels allows for splitting (distribution) at high frequencies (good controllability) and at the same time independently of the position of the sample.
Centrifugation begins and, by virtue of the flow resistance in the connecting channel between the receiving chamber and the sample chamber, an even distribution of liquid can be formed in the receiving chamber (liquid does not pass through into the sample chamber in an uncontrolled manner). The liquid is distributed in such a way that it flows towards the chamber edges and is arranged at said chamber edges, while the air of the chamber is positioned in the middle of the chamber (see fig. 10 c). The air built in the middle of the chamber is also known in the industry as the "meniscus" (Meniskus). The meniscus arranged concentrically around the axis of rotation leads to a particularly accurate division into whole parts and thus to the greatest possible identical volume in the sample chamber.
In the prior art, the individual components in each partial structure are dependent on the position of the liquid in the receiving structure or in the distribution structure, unlike the distribution structures known from the prior art, in the case of the test carrier according to the invention the distribution of the liquid is independent of the position of the liquid sample in the receiving chamber. The design of the channel structure according to the invention thus enables a particularly precise dispensing of the liquid quantity and avoids the inaccuracies that occur in the prior art.
The capillary structures 3 in a juxtaposed configuration achieve a simultaneous distribution of the liquid amounts to the respective sample chambers 8, 10, 11. In particular in the case of in vitro analysis and assay of blood as a liquid, the simultaneous dispensing ensures: the same hematocrit value (H ä mathrit-Werte) and the same lipemic fraction-Plasma-ratio of the erythrocytes (lip ä mische Teile dererythorytren zu Plasma-Verh ä ltnisse) were achieved in all the parallel chambers. Therefore, it is preferable that the bottom surface 24 formed by the substrate 4 is curved. In fig. 7 it is shown that the lid 25 is formed by a flat cover layer 21 and has a round access opening 7. The circumferential dam 18 and the circumferential venting channel 16 are in this case arranged adjacent to the cover layer 21. The dam and the vent channel are arranged concentrically and in a plane extending substantially parallel to the cap layer 21. Preferably, the curved bottom 24 of the receiving space 6 rises toward the dam 18. The liquid flowing into the receiving chamber 6 is already guided in a targeted manner radially outward by the capillary action produced in the resting state of the test carrier 1.
Preferably, the transport of the liquid in the receiving chamber 6 is assisted by a (central) projection 40 on the bottom surface 24. Preferably, the projections are conically configured, as can be seen in fig. 6 to 9. The conical projection 40 is preferably a cone 41 and is preferably arranged opposite the access opening 7 of the lid 25. Preferably, the tip of said cone 41 is aligned with said rotation axis 5. Particularly preferably, the conical projection 40 can also be embodied as a truncated cone. Alternatively, the projection can also be embodied in a completely different shape, for example in the form of a hemisphere or the like.
In the case of pipetting liquids, for example blood, the blood is forced onto the cone 41. The cone influences the flow speed during pipetting by friction between the blood and the base plate 4 of the test carrier 1 and adjusts it. At the same time, the cone 41 is responsible for holding the blood in the middle by adhesion. The remaining sample flows into the environment of the cone 41 in the direction of the surrounding dam 18, which is reinforced by cohesion. The cone 41 also represents a flow stop in the intake opening 7 during pipetting, which to a certain extent leads to a standardization of the pipetting speed. The cone 41 causes homogenization of the different assays and contributes to the robustness of the assay system.
In a preferred embodiment, the bottom 24 of the receiving space 6 is curved in such a way that a recess 43 is formed in the collecting region 42 in the vicinity of the outlet opening 26, into which recess the liquid flows and collects. Preferably, a recess 43 is formed in front of each outlet opening 26. In the case of three sample chambers 8, 10, 11, the receiving chamber 6 has three collecting areas 42 and three recesses 43.
In the case of this embodiment in which the cover 25 of the receiving chamber 6 is curved, the curvature is preferably performed in such a way that the height at the access opening 7 is maximal. Thereby, the liquid flows outwards and is purposefully conducted outwards from the middle of the cavity (the liquid itself is intended to stay in the middle, but the capillary action increases outwards).
The curvature of the cover 25 prevents air bubbles from remaining in the cavity, which air bubbles reach the cavity with the liquid entering through the inlet opening 7 and are for example pipetted together. The gas bubbles are conducted towards the edge and can there be discharged through the geometric valve 28 into the subsequent capillary structure and through its gas outlet.
Preferably, the receiving space 6 of the test carrier 1 has a lateral bulge or recess (Ausbuchtung) 44. Preferably, a radially outwardly directed ridge 44 is disposed in each collection area 42. The receiving space 6 bulges in its side wall formed by the vent channel side wall 27, extending away from the center of the receiving space 6. The receiving chamber 6 has in this example three radially outwardly extending elevations 44 in which the outlet openings 26 are arranged in each case, at which the connection channels 9 to the sample chambers 8, 10, 11 are connected. Once the test carrier 1 is set in rotation, the liquid is pressed into the bulge 44 and is thus guided directly towards the outflow opening 26.
In order to assist the inflow of the liquid into the receiving space 6 and to already give a preferred direction to the liquid, the receiving space has a recess 45 in the base 24, which extends radially outward. The groove 45 extends from the foot of the pyramid 41 towards the protuberance 44. The function of the recess 45 is to receive a hydrophilizing solution during the production process in order to hydrophilize the receiving chamber 6, which is formed by the substrate 4 made of hydrophilic plastic. Other measures for hydrophilization or geometric arrangements can also be used.
The recesses 43 arranged in front of the outlet opening 26 extend in the direction of the elevations 44, and the receiving space 6 has radially extending projections 46 between the respective recesses 43. This configuration of the bottom surface 24 facilitates an even distribution of the liquid to the individual sample chambers 8, 10, 11.
The filling of the receiving chamber 6 and the distribution of the liquid from the receiving chamber 6 into the respective sample chamber 8, 10, 11 are shown in three steps in fig. 10a to c. Fig. 10a shows that, during partial filling of the receiving space 6, a gas bubble 60 is first formed, which is arranged in front of the outflow opening 26. Air can escape through the exhaust channel 16 and the outflow opening 26 arranged therein. The possibility of continued filling of the cavity thus remains until complete filling (fig. 10 b).
Fig. 10c shows the situation in which the receiving chamber 6 is partially emptied after the test carrier 1 has been set in rotation and the rotational frequency (rotational speed) lies above the passage frequency of the valve 28 formed by the dam 18 and the vent channel 16. Starting from the rotational speed, the valve 28 opens and liquid flows uniformly through the outlet opening 26 into the connecting channel 9. The liquid is pressed into the elevations 44 and into the recesses 43 arranged in the collecting area 42. If the receiving chamber 6 continues to be emptied, a separation of the individual collecting areas 42 or of the liquid collected in the individual collecting areas 42 takes place. The separation is assisted by the protrusion 46 (ridge) and the protuberance 44. In this way, a further homogenization of the distribution of the liquid into the individual receiving chambers 8, 10, 11 is achieved.
The separation of the liquid volume in the receiving space 6 is particularly advantageous when the connecting channels 9 have cross-sectional areas of different sizes. With a reduced amount of liquid in the receiving chamber 6, a liquid passage 9 with a larger cross-sectional area will generally receive more liquid and allow the liquid to flow out quickly. This is prevented by the dispensing of liquid into the first partial volume. The separated liquid portions can only flow out of the associated outflow openings 26. Liquid cannot flow from one recess 43 into an adjacent recess 43.
Even in the case of an initially uneven distribution of the liquid in the receiving space 6, for example in the case of a partial filling of the receiving space 6, the liquid levels out when the test carrier 1 begins to rotate and flows radially outward toward the edge of the receiving space 6. The rate of liquid flow out of the receiving space 6 can be set by the design of the circumferential dam 18 in the receiving space 6, in particular by the design of the gap 29.
By means of a suitable design, the liquid flows out of the receiving chamber 6 slowly in such a way that the gas bubbles in the receiving chamber 6 can be pushed out of the liquid even at high rotational speeds and do not cause volume errors. This is of course also effective in the case where bubbles are aspirated together in the liquid sample. The foam produced likewise does not lead to volume errors when dispensing liquid quantities, since the gas bubbles are pressed uniformly by their very low density into the interior of the chamber toward the outlet opening.
In the case of parallel portioning of the liquid amounts, the liquid outputs are carried out in particular synchronously. The distribution of liquid into each of the sub-structures with sample chambers is approximately equal. In particular suspensions and emulsions which can play a critical role due to their unique density differences in the centrifugal field can be distributed exactly identically by parallel equal differentiation (aliquotieng), so that each sample chamber has the same particle-liquid ratio or the same content of cellular constituents. The suspension and emulsion are thus distributed with a homogeneous liquid-solid ratio or ratio of one liquid to the other. In the case of blood, a similar proportional relationship of the lipemic or erythrocytic fraction of the plasma fraction results.
Claims (20)
1. A microfluidic test carrier for dispensing a quantity of liquid into component quantities,
the test carrier has a base plate and a cover layer and a capillary structure formed in the base plate, which is surrounded by the base plate and the cover layer,
-the capillary structure comprises a receiving chamber, a sample chamber and a connecting channel between the receiving chamber and the sample chamber,
the receiving chamber has two opposite limiting surfaces and a side wall, wherein one of the limiting surfaces has an access opening and this limiting surface is the bottom surface of the receiving chamber and the other limiting surface is the cover of the receiving chamber,
the receiving chamber has a circumferential venting channel and a circumferential dam which is arranged between the receiving chamber and the venting channel, wherein the dam is arranged closer to the inlet opening than the venting channel,
the dam is designed in such a way that a capillary stop is formed by the dam and the exhaust channel, which capillary stop is designed as a geometric valve, through which air can be discharged from the exhaust channel,
the connecting channel extends between the outlet opening of the venting channel and the inlet opening of the sample chamber in such a way that a fluid transfer from the receiving chamber into the sample chamber is achieved, and
the valve is designed in such a way that an automatic fluid discharge from the receiving chamber is prevented.
2. The microfluidic test carrier of claim 1, wherein one of the cavity-defining faces is curved.
3. The microfluidic test carrier of claim 2, wherein the other of the defined faces of the containment cavity is formed by the cap layer.
4. The microfluidic test carrier of claim 2, wherein the curved defining surface is a lid of the receiving cavity.
5. The microfluidic test carrier of claim 2, wherein the curved defining surface is a bottom surface of the receiving cavity.
6. The microfluidic test carrier according to claim 5, wherein the bottom surface is curved in such a way that it rises towards the bank of the receiving cavity.
7. The microfluidic test carrier of claim 1, wherein the test carrier rotates about an axis of rotation extending through the test carrier.
8. The microfluidic test carrier of claim 7, wherein the axis of rotation extends through a center point or center of gravity of the test carrier.
9. The microfluidic test carrier of claim 7, wherein the receiving cavity is disposed in the test carrier such that the axis of rotation extends through the inlet port.
10. The microfluidic test carrier according to claim 7 or 9, wherein the receiving chamber is arranged in the test carrier in such a way that the axis of rotation extends through a center point or center of gravity of the receiving chamber.
11. The microfluidic test carrier according to claim 1, wherein the receiving cavity is arranged eccentrically with respect to a center point of the test carrier or with respect to a center of gravity of the test carrier.
12. The microfluidic test carrier according to claim 1, wherein the bottom surface of the receiving chamber is curved in such a way that a recess is formed in the collecting region in the vicinity of the outflow opening, into which recess the liquid flows.
13. Microfluidic test carrier according to claim 7, wherein a projection is formed in the receiving chamber at the bottom, which projection is arranged in the cover (25) opposite the access opening.
14. The microfluidic test carrier of claim 13, wherein the preferred protrusion is tapered.
15. The microfluidic test carrier of claim 13, wherein the protrusion is aligned with the axis of rotation.
16. The microfluidic test carrier according to claim 1, wherein a plurality of outflow openings are arranged in the vent channel, each outflow opening being in fluid connection with a connecting channel extending from the receiving chamber.
17. The microfluidic test carrier of claim 16, wherein the outflow ports are equally spaced around the periphery of the exhaust channel.
18. The microfluidic test carrier according to claim 1, wherein the sample chamber has an outlet opening which is in fluid connection with an outlet channel in such a way that liquid can flow out of the sample chamber.
19. The microfluidic test carrier of claim 18, wherein an additional fluid chamber is connected at the exhaust channel, the fluid chamber having an inlet port in fluid connection with the sample chamber through the exhaust channel.
20. The microfluidic test carrier of claim 1, wherein the sidewall has a protuberance extending distally from a center point of the containment cavity, and the exit port is disposed in the protuberance.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP10189261.0 | 2010-10-28 | ||
| EP10189261A EP2486978A1 (en) | 2010-10-28 | 2010-10-28 | Microfluid test carrier for separating a fluid volume in partial volumes |
| PCT/EP2011/067929 WO2012055707A1 (en) | 2010-10-28 | 2011-10-13 | Microfluidic test carrier for dividing a liquid quantity into subquantities |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| HK1182048A1 HK1182048A1 (en) | 2013-11-22 |
| HK1182048B true HK1182048B (en) | 2016-07-29 |
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