Patent Application
20050106756
The present invention relates to a microstructured separation device for separating parts of a liquid which comprises liquid components and at least one type of particle and/or at least one complex of interconnected particles of at least one type.
Most biochemical tests are performed on cell-free blood fluids, blood plasma or blood serum, because the blood cells or their contents can distort the measurement results. In hematology, filtration and centrifugation techniques have hitherto mainly been employed for this separation. Complete separation of blood cells without destroying their membranes, and without releasing their content into the test solution, is achieved for example by means of a 15-minute centrifugation at 1500 revolutions per minute. Such a method is complex and time-consuming, for which reason alternative solutions have been sought. Moreover, the current procedures described here do not permit handling of small volumes in the range of a few microliters, which is of importance especially in the point-of-care area in clinical diagnostics and in pharmaceutical active substance research.
By contrast, extremely small sample quantities can be handled with the aid of microsystem technology. In addition, many analysis system components can be combined within a very small space. Medical diagnosis is in this way often made easier, less expensive, more patient-friendly and, above all, can be carried out closer to the patient.
A microstructured separation device for separating hematocrit from whole blood is known, for example, from document U.S. Pat. No. 6,319,719 B1. This document discloses a separation device having an inlet adjoined by a capillary transport path leading to a reaction region. A large number of obstacles are arranged along the transport path. To separate the hematocrit from a sample of the order of size of a drop of blood, the capillary transport path contains about 105 obstacles. Each obstacle has a concave shape on its downstream side in relation to the direction of flow of the liquid. In the concave area of each obstacle there is a volume of 10−4 to 10−5 microliters in which hematocrit is selectively held back. The volume of all of the concave areas corresponds approximately to the volume of the hematocrit to be separated. The distance between the obstacles is, on the one hand, large enough to ensure that no filter effect is generated, and, on the other hand, the distance is small enough to minimize the volume of liquid contained in the capillary transport path. The smallest distance between two obstacles is preferably about 10−5 meters. The obstacles are preferably arranged as tight hexagons.
It is an object of the invention to propose a separation device with which the separation process can be performed rapidly. A further object of the invention is to propose a separation device with which liquid and particulate components can be separated from a liquid which contains certain particles. For example, it should be possible to separate some of the blood plasma and the white blood cells from the rest of the blood if only white blood cells and blood plasma are required for certain analysis purposes. It should further be possible, for example, for cellular blood components, bacteria or viruses to be separated from the other particles in the blood or to test the liquid which is depleted in blood plasma and in which the particles are present in accumulated form.
A microstructured separation device has an inlet for the liquid, a collection section, and a transport path from the inlet to the collection section. In addition to having a first separation section for holding back the complexes and/or for slowing down the movement of the complexes and/or of at least some of the particles and a second separation section for holding back the complexes and/or at least some of the particles and/or for slowing down the movement of at least some of the particles, the transport path also has a resuspension section and an incubation section which is arranged before the first separation section in the direction of transport. Both the first separation section and also the second separation section have a microstructure with one or several microstructure elements. The microstructure elements are not necessarily configured in a specific manner. They need simply be configured such that the separation sections are able to fulfill the duties assigned to them. The incubation section provided in the separation device of the invention is intended to give substances added to the liquid the possibility of contributing to the formation of the complexes before the liquid reaches the first separation section.
At least one substance for producing the complexes from the particles and/or for promoting the production of the complexes from the particles can be arranged in the resuspension section of the transport path. It is thus not necessary for the substance to be added to the liquid before the separation device is filled. Instead, the liquid is introduced directly into the separation device and, after reaching the resuspension section, the liquid takes up the substance arranged in the resuspension section or, if various substances are arranged there, the substances.
In contrast to the test vessels customarily found in a normal laboratory, the ratio of the surface of the transport path to the enclosed volume of the transport path of the microstructured separation device is much increased. This results, inter alia, in the following deviations from the conditions found in macro technology.
Surface effects and capillary and adsorption phenomena often play a dominant role in relation to volume effects. At dimensions under 100 μm and flow velocities under 100 cm/sec, liquids flow in a laminar fashion, i.e. as a so-called stratified flow. No turbulence occurs. The liquids have low Reynolds numbers, typically below Re=100. In this way, mixing of liquids is not afforded through turbulence. On the other hand, because of the small dimensions, diffusion represents a rapid and efficient mixing mechanism.
The transport path is advantageously so configured that the liquid is moved by capillary force. In addition, liquids can be transported using other drive mechanisms such as electroosmotic force (EOF). The transport path of the device through which the liquid is to be transported is configured accordingly. This applies to its cross-sectional surfaces, cross-sectional configurations and surface properties.
Particles within the meaning of the invention can, for example, be solid particles of materials such as glass, plastics, resins, or particles of biological origin, such as prokaryotic and eukaryotic biological cells, cell agglomerates, cell fragments, organelles, macromolecules such as nucleic acids, proteins, etc., or a combination of solid particles and particles of biological origin, for example glass support coated with cells.
Complexes within the meaning of the invention are any accumulation of several interconnected particles in the liquid. These can be regularly arranged particles or randomly interconnected particles. The connection can be produced by forces acting between the particles. However, the connection can also be produced by an additional substance for connection of individual particles. The particles of a complex can be of identical type or of different types.
The complexes can in principle be generated by naturally occurring processes. According to the invention, however, they are formed, or their formation is accelerated, by the substance or several substances in the resuspension area being added to the liquid.
The separation device according to the invention satisfies the demands placed on it. In particular, it permits a much more rapid separation process. Complexes and/or for example large particles are initially held back or have their movement slowed down by the first separation section in such a way that the liquid components and individual particles not bound in complexes can pass rapidly into the second separation device in which the remaining particles that are not to be collected in the collection section are held back or slowed down. Only the liquid components and, possibly, some of the particles which are to be separated from the rest of the liquid are in the end collected in the collection section. Since, after complete filling of the collection area, no further liquid components with other particles contained in them or even complexes can enter into the collection area thus completely filled, it is possible to obtain rapid and reliable separation. Unlike the separation device known from the art, in a separation device according to the invention a small number of from 5 to 100 microstructure elements is sufficient for a successful separation process.
In the transport path, the separation device has the incubation section which, in the direction of transport, is arranged before the first separation section. A liquid which has taken up a substance in the resuspension section is transported into the incubation section, through which the liquid flows at such a speed that, during the dwell time of the liquid in the incubation section, the substance causes or accelerates the desired formation of the complexes. In this way, it is possible to ensure that, when the liquid reaches the first separation section, the complexes are formed or substantially formed. By means of the design of the incubation section (cross-sectional surface, length, surface properties such as roughness and wettability), the flow speed and thus also the dwell time of the liquid in the incubation section can be set in a reproducible manner.
The microstructure elements of the first separation section have pockets which are open in the direction of the inlet, i.e. counter to the direction of transport, and/or the microstructure elements at least in part enclose, with the boundary surfaces of the transport path adjacent to the microstructure elements, pockets which are open in the direction of the inlet.
A preferred device according to the invention permits separation of blood into plasma and hematocrit without addition of substances, by using the blood's inherent properties of forming cell aggregates, i.e. complexes. An example of complex formation that occurs under natural circumstances (without addition of a chemical) is erythrocyte aggregation, in particular rouleau formation, with slow-flowing or non-circulating blood. Here, the red blood cells (erythrocytes), measuring approximately eight thousandth of a millimeter (μm), arrange themselves in the shape of a roll of coins, partially branched, with the flat surfaces on one another, and form long chains. These can be visualized without too much difficulty using normal microscopy techniques (dark-field illumination or phase-contrast illumination) under a light-optical microscope with attached video camera. The structures of the device are configured to ensure that the flow speeds and, consequently, the shearing forces are so low that this rouleau formation can occur.
According to the invention, at least some of the microstructure elements of the first separation section can be columns or steles, which can have a circular, hexagonal, quadratic, rectangular or oval cross section. Moreover, at least some of the microstructure elements can have one or more webs. The web or webs can be arranged transversely or obliquely with respect to the direction of transport. The webs can also be bent or angled in a U-shape or V-shape so that they have open pockets counter to the direction of transport.
The microstructure elements of the first separation section advantageously delimit one or more first through-openings which have geometric dimensions allowing at least some of the particles and smaller complexes and also the liquid components of the liquid to pass through. Although the first through-openings thus configured allow some of the particles and/or at least some of the smaller complexes to pass through, they nevertheless slow down the transport of the particles and/or complexes, because these are temporarily held back on the microstructures or are able to pass through the first through-openings only after a deformation, for example in the case of red blood cells. Liquid components can pass unimpeded through the first through-openings. As a result of a collision of several such complexes, it is possible for larger complexes to form within one of the first through-openings.
The microstructure elements of the first separation section can also delimit first and/or second through-openings which have geometric dimensions allowing only the particles or certain types of particles and the liquid components to pass through. Complexes are held back by means of these first and/or second through-openings, whereas the particles or the certain types of particles are able to pass through, slowed down, or only after a deformation, which also slows down the transport of these particles. Liquid components can pass unimpeded through these first and/or second through-openings. Some of the second through-openings can be provided starting in or on the pockets of the microstructure elements of the first separation section. It is thus possible to ensure that, although some of the complexes are collected in the pockets and their further transport is impeded, some particles or some of the complexes and the liquid components can nevertheless flow onward through the second through-openings in the direction of transport. According to the invention, the first through-openings can have a width and/or height of 1 μm to 500 μm. The area of passage of the first through-openings can decrease in the direction of transport.
According to the invention, the width of the second through-openings can be from 1 μm to 500 μm, while the height can be from 0.1 μm to 100 μm. The area of passage of the second through-openings can, like the area of passage of the first through-openings, decrease in the direction of transport.
One possible way of arranging the substances in the resuspension section of a device according to the invention is for the substance or substances to adhere, dried on, to at least one boundary surface of the resuspension section. Another possibility is for at least one of the substances to be arranged in the form of a pellet, a tablet or a powder in the resuspension section. It is likewise possible for at least one of the substances to be mounted on a support, said support being arranged in the resuspension section. The substance or the support can in this case be arranged in a recess in one of the boundary surfaces of the resuspension section.
At least some of the particles can be of biological origin, for example cells or their organelles, viruses or similar. The creation of complexes from particles is generated, promoted or accelerated by means of one or more substances, by aggregation, agglutination and/or coagulation, etc.
In hematology, aggregation is understood as the reversible clumping-together of red blood cells by relative increase (fluid loss) or absolute increase of, above all, large proteins of the blood (agglomerins, e.g. fibrinogen, haptoglobin). Agglutination is understood as the in most cases irreversible bonding of antigen-carrying particles (erythrocytes, bacteria, or in passive indirect agglutination of latex particles, polystyrene particles) by suitable agglutinins such as antibodies or lectins. The antigen-antibody reaction causes clumping of particulate antigens. In direct agglutination, the agglutinating antibodies are directed against bacterial or cell-bound antigens; in indirect agglutination, soluble antigens are coupled to a solid carrier. The particles concerned are in most cases large enough to be visible by microscope.
To realize the invention, agglutinating substances used can also be agglutinating antibodies which agglutinate antigen-carrying particles located in the sample so that these form complexes. Such a reaction can be used, on the one hand, as an isolation method for removing certain particles from a particle-containing solution or, on the other hand, as an analysis method for detection of a certain particle in the sample solution. To this end, the separation section can be used simultaneously as a detection area. Particles that are difficult to identify visually are rendered visible by combining them into complexes and they are enriched (concentrated) in the separation area. They can thus be identified easily and conveniently by optical methods, for example by scatter or turbidity measurements, or by light-optical microscopy.
These antibodies counted among the substances within the meaning of the invention can also be applied to spherical supports. These spherical supports are often polymer or glass particles with a diameter of 0.05 μm to 100 μm.
The microstructure elements of the second separation section can comprise a stairway, spaced apart columns and/or one or more webs which, with a top part or cover of the device, form a gap or one of more through-openings. In principle, the second separation section can be designed in the manner described for example for the separation area of a separation device disclosed in the German patent application 10313201.5/44.
A further embodiment of the separation device according to the invention can have a branch section before the first separation section or between the first separation section and the second separation section, starting from which branch section a second transport path branches off from the first transport path. The branch section and the second transport path starting from the branch section ensure that, in the event of blockage of the first or second separation section through formation of a so-called “filter cake”, the liquid following on automatically flushes the first or second separation section. The particles or complexes deposited before the entrance or in the entrance area of the first or second separation section are carried off by the continuous flow of liquid into the second transport path. This ensures that the first or second separation section is always kept free for the separation process.
According to the invention, the length of the first transport path up to the second transport section is dimensioned in such a way that, because of the limited mobility of the complexes, the liquid components or liquid components and particles are first to reach the second separation section. In terms of its length, cross section, surface properties, and the design of the microstructure elements, the transport path can advantageously be configured such that only liquid components, possibly with certain particles, reach the collection area.
Because of the preferably hydrophilic properties of at least parts of the transport path, the more mobile liquid components of the sample fill the collection area more rapidly than do the particles or complexes which, on account of their mass, volume and size, are partially or completely held back in the separation area.
The method for separating parts of a liquid, the liquid components and at least one type of particle and/or at least one complex of interconnected particles of at least one type, has the following steps: After an incubation period during which at least individual complexes have formed, the liquid is applied to a first separation section of a separation device, for example of a separation device according to the invention. In the first separation section, the complexes are held back and/or the movement of the complexes and/or of certain types of particles or of all the particles is slowed down.
The separated parts of the liquid collected in the collection area can be analyzed in the collection section or they can be removed from the collection area for further analysis outside the separation device. The enriched particles and/or complexes can also be analyzed in the separation section itself or in the remaining part of the transport paths.
The complexes and/or the particles can be held back and/or the movement of certain types of particles or of all the particles can be slowed down in a second separation section of the separation device.
Prior to the start of the incubation period, at least one substance producing and/or promoting the production of complexes of interconnected particles can be added to the liquid. The liquid can be incubated in an incubation section of the separation device. It is also possible for the substance to be added to the liquid and resuspended from the liquid in a resuspension section of the separation device.
The complexes can be formed at least in part by agglomeration, agglutination and/or coagulation of the particles. The substance that can be added to the liquid can contain supports (parts) which are coated with antibodies or lectins and which, for example by an antigen-antibody reaction with surface antigens of the particles, can effect formation of agglutinates (complexes).
The mobility of the complexes and/or of the particles can be restricted at least in part by the microstructure elements in the first separation section, and the complexes can at least in part be held back by the microstructure elements of the first separation section.
According to the invention, the complexes can be held back by the microstructure elements of the second separation device and/or some of the particles can be held back by these microstructure elements and/or the movement of at least some of the particles can be slowed down by these microstructure elements.
According to the invention, the liquid or the separated parts of the liquid can be transported by capillary force and/or by another force of comparable magnitude.
According to the invention, the device can comprise a sample support in which the inlet, the transport path and the collection section are formed, and the device can comprise a top part or cover which advantageously covers the transport path and the collection section, i.e. the microstructured side of the sample support except for the inlet. The structured side of the sample support can be at least partially hydrophilized if the device is intended for samples with hydrophilic properties, e.g. aqueous samples or blood.
The methods according to the invention can also be applied to complex-forming liquids different than blood. Thus, certain particles can be complexed in a liquid, enriched (concentrated), and detected. For this purpose, the complexes enriched in the separation areas may also be of interest for analysis purposes, for example.
According to the invention, the agglutinating substances used can also be agglutinating antibodies which agglutinate antigen-carrying particles located in the liquid so that these form complexes. Such a reaction can be used, on the one hand, as an isolation method for removing certain particles from a particle-containing solution or, on the other hand, as an analysis method for detection of a certain particle in the sample solution. To this end, the separation section is used simultaneously as a detection area. Particles that are difficult to identify visually are rendered visible by combining them into complexes and they are enriched (concentrated) in the separation area, by which means they can be identified easily and conveniently by optical methods.
These substances can also be applied to spherical supports. These spherical supports are often polymer or glass particles with a diameter of 0.005 μm to 100 μm.
Illustrative embodiments for separation devices according to the invention are described in more detail with reference to the drawing, in which:
FIGS. 9 to 11 show a lower part of fourth, fifth and sixth illustrative embodiments, respectively, of a separation device according to the invention in plan view;
The illustrative embodiments shown in the figures for separation devices according to the invention show in some cases identical features and in some cases corresponding features, which are labeled with the same reference numbers.
The first illustrative embodiment shown in FIGS. 1 to 3 has a lower part 1a in which an inlet 2 of circular cross section is formed. From this inlet 2, a first transport path 15 branches off laterally and extends as far as a collection section 11. The collection section 11 is connected to the environment via a vent channel 9. A capillary plug in the transport channel 9 can prevent escape of the liquid components collected in the collection section 11.
Such a capillary plug can be realized by means of abruptly changing geometric dimensions of the transport channel 9. Likewise, surface properties of the transport channel 9 can abruptly change, for example from hydrophilic to hydrophobic surfaces.
The transport path 15 between the inlet 2 and the collection section 11 is divided into different sections. Situated one after the other in the direction of transport of the liquid, that is to say in the direction from the inlet 2 to the collection section 11, there is a resuspension section 3, an incubation section 4, a first separation section 5 and a second separation section 8. Both the first separation section 5 and the second separation section 8 have a microstructure with microstructure elements 53, 54 in the first separation section 5 and microstructure elements 83 in the second separation section 8.
Besides the lower part 1a, which can be a support for a sample, the first separation device shown in cross section in FIGS. 1 to 3 has a cover 1b which covers the transport path 15, the collection section 11 and the vent channel 9 and leaves only the inlet 2 free.
The first separation device shown in FIGS. 1 to 3 is suitable for obtaining blood plasma from blood, where the hematocrit, during transport along the transport path 15, remains in the first separation section 5 and in the second separation section 8 of the transport path 15, so that only blood plasma collects in the collection section 11.
The hematocrit is separated from the blood plasma on account of the surface effects which arise during transport of the blood along the transport path 15.
The particle-containing liquid is separated in the first separation section 5 according to the following principle: The mobility of particles and complexes is so limited, compared to that of the rest of the liquid, that they are transported more slowly through a capillary than are the remaining components of the liquid. Through the formation of the complexes (bringing about an increase in mass, volume and size), the particles bound in complexes are less mobile than the unbound particles.
The movement and speed of the complexes in the continuous through-flow is further impaired by the microstructure elements 53, 54 arranged in the separation section 5 and preferably lying transversely with respect to the direction of flow. The particles thus bound in complexes are separated from the particle-containing sample liquid on account of the aforementioned change in mass, volume, charge and size.
Because of their viscoelastic properties, erythrocytes can also flow through gaps or capillaries which are smaller than their diameter or their thickness. The passage of an erythrocyte through capillary gaps with a gap opening of less than 5 μm is complex and is effected, after a delay, by a rolling movement which cannot be described according to the Hagen-Poiseuille law. If plasma is to be isolated from blood, the gap height between the web 83 of the second separation section 8 and the upper part of the device is preferably smaller than 5 μm, in order to hold back individual unbound blood cells from the sample liquid in the separation section 8. While the separation section 8 does not represent an obstacle, or represents only a minor obstacle, for plasma, the red blood cells are held up and slowed down in the separation section and can pass through the latter only slowly. Here, the depth of penetration of the red blood cells depends on the height of the gap and on the time till the collection chamber 11 is filled completely with liquid. The length of the separation sections 8 in the direction of flow is chosen such that the collection chamber 11 is already filled completely with the more mobile plasma before the first individual red blood cells have completely negotiated the separation section 8.
In the first separation section 5 in particular, the microstructure elements 53, 54 form pockets 6a, 6b which are open counter to the direction of transport, that is to say in the direction of the inlet 2. Seen in plan view, the microstructure elements 54 are designed as U-shaped webs whose two arms point in the direction of the inlet 2. The pocket 6a is formed between the U-shaped arms. The microstructure elements 53 of the first separation section 5 are designed as webs 53 which point obliquely in the direction of the inlet and which are connected to the lateral boundary surface of the transport path 15. The acute-angled area formed between the webs 53 and the lateral boundary surface of the transport path 15 forms the pocket 6b of these second microstructure elements 53. Complexes and particles of the blood (hematocrit) collect in the pockets 6a, 6b of the microstructure elements 54, 53 and their movement along the transport path is thus suppressed or at least slowed down, whereas smaller particles of the blood, although being slowed down, can still pass through the first separation section 5. These smaller particles, however, are held back in the second separation section 8 in which a web 83 checks or at least slows down the movement of the smaller particles of the hematocrit. Larger particles which, although being slowed down, still pass through the first separation section 5 of the transport path 15 are in any case held back by the microstructure element of the second separation section 8.
The separation device according to FIGS. 1 to 3 has a further feature, which concerns in particular the second embodiment of the invention as claimed in claim 3. Before the first separation section, the transport path 15 comprises the incubation section 4. In this section, or in incubation sections 4 in one of the other illustrative embodiments of separation devices according to the invention, substances added beforehand to the blood or to another liquid to be treated are able to act on the liquid. These substances are chosen such that they cause or at least accelerate the formation of complexes from particles contained in the liquid, for example the formation of complexes of red blood cells. Particularly in the case of blood, these complexes can be generated by aggregation, agglutination or coagulation of red and/or white blood cells or other cells or viruses contained in the blood.
The substances or substance causing or promoting the formation of complexes is received in a resuspension area 3 of the first separation device. While the liquid is flowing through the incubation section 4 in the direction of transport, the substance acts on the liquid so that the complexes are formed, or are substantially formed, when the liquid reaches the first separation section 5. Some of the complexes of the particles and blood cells are stopped by the microstructure elements 53, 54, while some are slowed down. The complexes which are stopped are collected in the pockets 6a, 6b of the microstructure elements, for example. The total volume of all the pockets preferably corresponds to the volume of the particles contained in the liquid, that is to say of the hematrocrit. At the end of the first separation section 5, a liquid is obtained which by and large only contains individual particles or blood cells that are not bound in complexes. These last particles or blood cells are stopped or slowed down in the second separation section 8 by the web 83 arranged there, so that only blood plasma without cellular components or the like arrives at the collection section, until said collection section is completely filled.
The substance 3a arranged in the resuspension section 3 can be applied, in tablet form, on the lower boundary surface of the transport path 15 or resuspension section 3.
The cross section, shown in
The variants of microstructure elements shown in
The microstructure element e is a web extending across the full width of the transport path 15 from a first lateral boundary surface to a second lateral boundary surface. Second through-openings 17 are included in this web. A variant of the microstructure element e is formed by the microstructure element f, which is a single horseshoe-shaped web and, like the web e, contains second through-openings 17 and extends from a first lateral boundary surface to the second lateral boundary surface of the transport path. The microstructure elements g are webs which are arranged at an acute angle to the direction of transport in order to stop and/or slow down the complexes and to slow down individual particles, but allow liquid components to pass through largely unimpeded.
In addition to having the inlet 2 and the collection section 11, the fourth illustrative embodiment of a separation device according to the invention shown in
In contrast to the previous examples, a volume flow is present, during the entire separation process, from the branch point in the direction toward the second transport path 18 and toward the second separation section 8. The liquid to be filtered flows parallel to the second separation section 8. Some of the liquid is accordingly drawn off transversely in the direction to the collection section 11. Because of the continuous flow of the liquid to be separated at the branch section 19, particles are carried with the volume flow into the second transport path 18, and the coverage of surface of the second separation section 8 is reduced. The degree of coverage can be varied as a function of the volume flow. However, the volume flow is always laminar, with Reynolds numbers of less than 100. In illustrative embodiments in which the liquid is driven exclusively by capillary force, the volume flow can be set via the dimensions of the channel and the surface properties.
The sixth illustrative embodiment of a separation device according to the invention shown in
The seventh illustrative embodiment of a separation device according to the invention, shown in
The separation device according to the invention shown in FIGS. 13 to 15 functions in the following way. The liquid is introduced into the inlet 2, from where it is transported by capillary force from the start to the end of the first area A of the first separation section 5. In this process, individual complexes and/or particles are stopped or slowed down by the microstructure elements 53, 54, 55 in the first area A. The liquid components and individual particles pass into the slits 23 in the U-shaped web. Since the cross-over from the slits 23 to the second area B of the separation section 5 represents a capillary stop for the liquid components, the liquid is initially not transported through the slits 23 into the second area B. The through-opening 21 provided in the arch is not configured as a capillary stop, and the liquid entering this through-opening 21 is able to pass into the second area B unimpeded. This can be achieved, for example, by notching or similar. As soon as the liquid components have completely filled the first area A and the through-opening 21 in the arch of the U-shaped web is wetted, liquid passes through the through-opening 21 into the second area B and fills the latter. The liquid wets the outside of the U-shaped web and the slits 23, by which means the capillary stop on the outside of the U-shaped web is annulled. The liquid lying in the slits 23 can then emerge from said slits 23, and the liquid and the individual particles contained in it then begin to be transported from the first area A into the second area B of the first separation section 5. Liquid components of the liquid collect with individual particles in the second area B. Because of the capillary force acting in the second area B and in the transport channel 22, this mixture of liquid components and individual particles is transported to a second separation section in which the individual particles are removed from the liquid in the manner already described several times above.
In an alternative design of the separation device according to FIGS. 13 to 15, the U-shaped web with its microstructure elements (slits) can be configured such that said U-shaped web already forms the second separation section of the separation device according to the invention, and such that the second area outside the U-shaped web serves as the collection section of the separation device according to the invention.
The device in
After the particle-containing liquid has been introduced into the inlet area, the separation section is completely filled by means of capillary force. Particles and complexes are partially held back by the microstructure elements 53- and 54. As soon as the liquid has filled the through-opening 21, the liquid flows into the collection channel 102 and fills this in the direction of the inlet opening (see arrow 104). The cross section of the collection channel 102 is smaller than the cross section of the collection channel 100, by which means the liquid passing through the through-opening 21 preferably first fills the collection area 102 and only then flows onward through the collection channel 100. During the process of filling of the collection area 102, the individual slits 23 are wetted, by which means their capillary stop function is annulled, with the result that the practically stationary liquid present inside the web 103 can flow through the individual slits 23 in the direction of the collection channel 100. In this process, some particles or complexes are held back in the microstructures 54, now lying in the direction of flow, and by the slits 23, so that a solution largely depleted in particles flows through the collection area 102 in the direction of the collection channel 100, which leads to the second separation section (not shown).
The sample support shown in
| Number | Date | Country | Kind |
|---|---|---|---|
| 103 52 535.1 | Nov 2003 | DE | national |
