DE102013216891A1 - Three-dimensional, microfluidic, centrifugal force driven device, centrifuge with such device and uses thereof - Google Patents

Abstract

A microfluidic device (10), which is intended to be received in or on a rotor (12) of a centrifuge, comprises at least one first body (20, 22) having at least one first microfluidic chamber (20a, 22a) and in one can be used on the rotor (12) of the centrifuge attachable housing (16). In this case, a stacking direction (18) is defined in the housing (16), in which a second body (22, 24) in the housing (16) can be stacked above or below the first body. Further, upon receiving the device (10) in or on the rotor (12) of the centrifuge, and upon rotation of the rotor (12), the first body is spaced from a rotational axis (14) of the rotor (12). According to the invention, the device comprises at least one first filtration device (32) which is arranged in the chamber (20a, 22a) of the first body (20, 22) and has a filter element (38) which in this chamber (20a, 22b) when receiving the device (10) in or on the rotor (12) of the centrifuge, and during a rotation of the rotor (12), in particular by a fluid flowing in the chamber is flowed.

Description

The invention relates to a three-dimensional microfluidic and centrifugally driven device, a centrifuge with such a device and uses of such a device.

State of the art

There are a variety of systems for automating e.g. biochemical processes, which can be attributed in principle to two categories, namely pipetting robots that can accurately measure liquids such as samples and / or reagents by means of one or a plurality of pipettes and transfer into different functional reaction vessels, and on the other hand, cartridge-based systems in which liquids are typically introduced into a special device arranged in a cartridge and subsequently processed inside the cartridge. Such cartridges can also be used in a rotor of a centrifuge and the rotor can be rotated by means of the centrifuge, wherein the centrifugal force caused by the rotation acts on the liquids contained in the cartridge and the substances dissolved or entrained therein and can influence reactions or process sequences ,

The DE 10 2010 003 223 A1 quite broadly describes the prior art of centrifugal force-based, three-dimensional, microfluidic systems. DE 10 2010 003 223 A1 discloses, in particular, devices for insertion into a rotor of a centrifuge, in which at least two bodies stacked one above the other (so-called revolvers) are inserted in a housing provided for fastening in or on a rotor of a centrifuge, such that the bodies in a stacking direction upon proper incorporation of the device into the rotor of the centrifuge, and upon rotation of the rotor, a distance of a first of the two bodies from the axis of rotation of the rotor is less than a distance of the other, ie the second, of the two bodies the axis of rotation. The first body has at least two cavities and the second body at least one cavity. The bodies are also movably arranged in the housing during rotation in order, for example, to fluidically couple the one and then the other cavity of the first body to the cavity of the second body in response to the rotation of the rotor. The first body or revolver, for example, rotatable about a turret axis relative to the second turret (body) and adjustable, for example by means of a ratchet mechanism in predetermined rotational angle positions, wherein successively predetermined cavities of the first body with certain cavities of the second body are fluidly coupled, and suitable different loading of the cavities of the first body with different reagents in the cavities of the body determinable sequences of eg biochemical reactions can be triggered. The DE 10 2010 003 223 A1 discloses methods and suitable mechanisms for fluidically coupling cavities disposed in different turrets.

Filtration is, for example, in various large-scale and process engineering processes, such as wastewater treatment, treatment of drinking water and process water, or in medical processes, such as in dialysis, or in food production and processing, such as the production of fruit juice concentrates, the compaction of must used in winemaking or the production of non-alcoholic beer.

In order to optimize such filtration processes under process accelerating conditions, such as enhanced gravitational force, it is desirable to have such large scale processes on a smaller scale, such as under laboratory conditions, with variable and, in particular, enhanced gravity, as may be produced in centrifugal force based systems to simulate and to study variations in process control. At present, no three-dimensional, e.g. stacked, centrifugally drivable microfluidic devices in which any method of filtration can be carried out.

Disclosure of the invention

The invention provides a microfluidic device having the features of independent claim 1, a centrifuge having the features of claim 17, a use having the features of independent claim 19, and a use having the features of independent claim 20. Advantageous embodiments of the sensor device and the microfluidic device Device are subject matters of the dependent claims.

The invention is characterized by making it possible to carry out filtration processes in a controllable framework, such as under laboratory conditions, with variable, in particular amplified, gravity.

According to a first aspect of the invention, a microfluidic device is provided which is intended to be received in or on a rotor of a centrifuge. The microfluidic device comprises at least one first body or turret, which has at least one microfluidic chamber and in one at the rotor Centrifuge attachable housing is used. In the housing, a stacking direction is defined in which a second body or turret is stackable in the housing above or below the first body. When properly receiving the device in or on the rotor of the centrifuge, and upon rotation of the rotor, the first body is arranged at a distance from a rotational axis of the rotor.

According to the invention, the microfluidic device comprises at least one first filtration device, which is arranged in the chamber of the first body and comprises a filter element, which in this chamber when properly receiving the device in or on the rotor of the centrifuge, and during a rotation of the rotor, in particular from a flowing fluid in this chamber, can be flowed. Such integration of a filtration device makes it possible to perform a physical, in particular a static filtration in a fluid flowing in the chamber of the first body, which occurs during a rotation of the rotor, i. During operation of the centrifuge, can be influenced or accelerated by a centrifugal force acting variably.

The stacking direction defined in the microfluidic device is increased during operation of the centrifuge, i. during a rotation of the rotor of the centrifuge, to a substantially radial direction and thus to a direction of action of the centrifugal force generated by the rotation. The stacking direction is defined such that when the housing of the microfluidic device, which usually takes place in a substantially vertical state of the housing, the sides "up" and "down" in the operation of the centrifuge to the sides "radially inward" or "Radially outward" and the directions "up" and "down" in operation in the directions "radially inward" and "radially outward" transition.

According to a second aspect of the invention, a centrifuge is provided with a rotor, wherein according to the invention a microfluidic device according to the first aspect of the invention is incorporated in the rotor as intended. The filtration device included in the microfluidic device makes it possible to carry out in the chamber of the first body a static filtration, which is supported or accelerated in the operation of the centrifuge by the acting centrifugal force.

The microfluidic device with integrated filtration device disclosed herein, when operated or used in a centrifuge, provides the following advantages:
Substances, such as liquid, gaseous, solid substances or mixtures thereof, can not only be purified in the device, but also be physically filtered. The chamber in which the filtration takes place, ie in which the filtration device is arranged, can be made of the same material as the rest of the microfluidic device and thus cost-effectively integrated into the device. The filtration process taking place at the filtration device can be carried out at a constant centrifugation speed and thus can easily be integrated into a centrifuge operating protocol.

Filtration parameters, such as filtration rate and efficiency, can be investigated, variably adjusted and optimized depending on various parameters. The parameters include e.g. Filtration volume, temperature, force, pressure, centrifugation rate, properties of the material to be filtered (such as particle size, solubility, pH, porosity), filter element characteristics (such as pore size, material, thickness, area, density, symmetry or asymmetry, Size, volume) and their spatial arrangement.

The integration of a filtration device in a microfluidic device allows the use of the microfluidic device to concentrate a liquid, e.g. with particles, functionalized beads or glass beads, bacteria, yeasts, cells, cell components, such as antibodies, antigens, proteins or DNA; for concentration of a solid, e.g. with particles with different particle sizes, or for the concentration of a gas. Also, a progressive filtration process, such as the growth of a filter cake upstream of a filter element of the filtration device for the actuation of a microfluidic valve or a microfluidic pump in the microfluidic device.

According to a third aspect of the invention, a microfluidic device according to the first aspect of the invention finds one of the following uses: (i) concentration of a liquid, e.g. with particles, functionalized beads or glass beads, bacteria, yeasts, cells, cell components, such as antibodies, antigens, proteins or DNA, (ii) concentration of a solid, e.g. with particles of different particle sizes, or (iii) concentration of a gas. Such concentrations are possible in the hitherto known, operated under the action of a centrifugal force, microfluidic devices are possible.

According to a fourth aspect of the invention, a microfluidic device according to the first aspect of the invention is used for the actuation of a microfluidic valve or a microfluidic pump of the microfluidic device, wherein the valve or the pump in the same body as the filtration device or in a in the housing is arranged adjacent thereto body. The adjacent body may be arranged in the stacking direction above or below the body in which the filtration device is integrated.

Further advantages of the invention

The filtration device, and in particular the filter element, can limit a sub-chamber downstream in the chamber in an at least locally prevailing flow direction. For this purpose, the filtration device can be arranged at the downstream outlet of the chamber. Alternatively, the filter element may divide the chamber into a first sub-chamber and a second sub-chamber, wherein the first sub-chamber upstream and the second sub-chamber is arranged downstream of the filter element. In these arrangements, the filtration device acts on the entire flow flowing in the chamber or in the entire flow cross-section.

The filtration device may comprise a filter element whose properties, such as pore size, material, thickness, area, density, symmetry, size, volume, can each be varied within wide ranges to different classes of physical filtration, namely Size of the particles to be filtered, for example microfiltration, ultrafiltration, nanofiltration or reverse osmosis.

In the device according to the first aspect of the invention, at least one second body may be provided which has at least one first microfluidic chamber and which is stackable in the housing in the stacking direction above or below the first body and is insertable in the housing together therewith. When properly receiving the device in or on the rotor of the centrifuge, and upon rotation of the rotor, a distance of the second body to the axis of rotation of the rotor may be correspondingly smaller or larger than the distance of the first body to the axis of rotation of the rotor. At least one second filtration device may be arranged in the first chamber of the second body or in a second chamber of the first body and also comprise a filter element which divides the affected chamber into a first partial chamber and a second partial chamber. Such a second filtration device allows, during operation of the centrifuge, the execution of a second static filtration adjacent to and independent of the static filtration performed by the first filtration device.

In the first chamber of the first body, at least one second filtration means may be disposed downstream of the first filtration means with respect to a flow direction prevailing in the chamber. In this case, the first and the second filtration device may have different pore sizes. In this case, the filtration device with the smaller pore size in the flow direction is advantageously arranged downstream of the filtration device with the larger pore size. In this arrangement, the larger pore size filtration device acts as a pre-filter for the smaller pore size filtration device and retains particles of larger sizes or particle diameters. The smaller pore size filtration device can then effectively retain particles of smaller sizes or particle diameters. Upon further exploitation of this advantage, at least a third, and preferably further, filtration means may be arranged in the flow direction one behind the other and downstream of the second filtration means, each downstream filtration means having a smaller pore size than the upstream filtration means.

At least one filtration device may include, in addition to the (first) filter element, a second filter element disposed parallel to or adjacent to the first filter element with respect to a flow direction prevailing in the chamber. In this case, the second filter element may have other filter parameters, such as a different pore size, a different wettability or a different filter element material than the first filter element. Thus, the one filtration device can be optimized so that two more selected substances can be concentrated or filtered out.

In at least one filtration device, the filter element in the chamber may delimit a sub-chamber downstream in an at least locally prevailing flow direction, be substantially planar and have an extension plane, and be configured according to one of the following variants: (a) the extension plane is substantially perpendicular to (b) the extension plane is arranged substantially parallel to the stacking direction, or (c) the extension plane is arranged obliquely to the stacking direction. In the variant (a), in the operation of the apparatus in a rotor rotating rapidly in a centrifuge, the centrifugal force is particularly supportive of filtration because the centrifugal force is then substantially perpendicular to the plane of extension of the filter element and into place of rotation without rotation vertical arrangement of the microfluidic arrangement occurs substantially perpendicular to the plane of extension of the filter element acting gravity. In variant (b), during operation of the device in a rapidly rotating rotor, the centrifugal force acts particularly strongly as a shearing force on substances, which can not pass through the filter element and therefore, for example in the form of a so-called filter cake, accumulate on or in one side of the filter element. The accumulating substances or the filter cake is displaced radially outwards by the centrifugal force acting as a shear force, ie due to the arrangement along the surface of the filter element, ie a self-cleaning effect is obtained on the filter element during the rotation of the rotor. In variant (c), during operation of the device in a rapidly rotating rotor, by suitable selection of the angle of inclination, a suitable compromise between the filtration assisting effect of the centrifugal force and the radially outward displacement of the substances accumulating upstream of the filter element, such as a filter cake, be realized.

As an alternative to variants (a) to (c), at least one filter element of at least one filtration device in the chamber can delimit a sub-chamber downstream in an at least locally prevailing flow direction and be configured according to one of the following variants (d) to (f): (i (e) the filter element is essentially spiral-shaped in a cross section perpendicular to the stacking direction, or (f) the filter element is essentially cylindrical in a cross section perpendicular to the stacking direction.

In the variant (d) of the conical design, for the same reasons as for a substantially planar filter element, a compromise between the filtration assisting effect of the centrifugal force and the self-cleaning effect due to the outward displacement of the upstream of the filter element accumulates Substances are realized. The filter element may have the shape of a circular cone or an oblique circular cone. Alternatively or additionally, a cone tip of the filter element can, when the device is received in the rotor of the centrifuge as intended, and in the direction of the axis of rotation of the rotor point away from the rotor when the rotor rotates. In the case where the apex of the cone faces the axis of rotation, substances accumulating upstream of the filter element may move outwardly, thereby causing a self-cleaning effect, and being collected off the filter element. In the event that the apex points away from the axis of rotation, substances accumulating upstream of the filter element may accumulate downstream of the filter element within the apex of the cone.

In variant (f) of the cylindrical formation of the first filtration device, a second cylindrical filtration device may be provided, the axial direction of which is arranged substantially parallel to an axial direction of the first cylindrical filtration device and which is substantially adjacent to the first filtration device. Alternatively, a second cylindrical filtration device may have a diameter different from the diameter of the first cylindrical filtration device and may be disposed substantially coaxially with the first cylindrical filtration device. In this case, the filter element of the second filtration device may have other filter parameters, such as a different pore size, a different wettability or a different filter element material than the first filter element of the first filtration device. Thus, the combination of the first and second cylindrical filtration means can be optimized so that two more selected substances can be concentrated or filtered out.

At least one filtration device can be movable in the chamber associated with it in relation to this chamber. In particular, the filtration device may be movable in the stacking direction. In this embodiment, the filtration device, in particular in the radial direction, move to a position, so that a dependent on the strength of the centrifugal force filter property achieved in the operation of the centrifuge in a dynamic steady state. Alternatively, the at least one filtration device can of course also be arranged fixedly in the chamber assigned to it in relation to this chamber.

The first and / or the second sub-chamber can be enlarged or reduced in a proper recording of the device in or on the rotor of the centrifuge. In this or alternatively, the total volume of the first and second sub-chambers can remain substantially constant or change, for example, increase or decrease.

At least one filtration device may comprise a filter element made from one of the following materials: a fiber-oriented web, in particular a felt, a random fiber web, in particular a spunbond web, a woven fabric, a wound filter bag or a wound filter cartridge with yarns made from at least two different materials , a bed of a plurality of granules and / or granules, a porous solid, such as sintered metal, paper, or a metal. By suitable choice of the material of the filter element, this can be optimized for the filtration or for the effective concentration of a specific, desired substance in a solvent.

At least one openable or activatable capping element can be provided in the microfluidic device. This capping member may be formed as a capping film, associated with a filtration means disposed in a chamber of one of the bodies, and disposed upstream of said filtration means with respect to a flow direction prevailing in that chamber. In this case, the capping element can be arranged in the same chamber as the filtration device, for example at an inlet of this chamber. Alternatively, the capping member may be provided in a second body disposed upstream, ie, in the stacking direction, of the body whose chamber contains the filtration means, such as at an outlet of a chamber of the second body. The capping element or the capping film can be pierceable or have a predetermined breaking point, which can be broken open at a predetermined differential pressure. The activability or Öffenbarkeit the capping element allows the filtration effect of the filtration device not directly from a start of operation of the centrifuge, but only later, from a desired time, namely when the cap element is opened, is effective.

When the device is properly received in or on a rotor of a centrifuge and during a rotation of the rotor, a flow direction can prevail in the chamber in which a filtration device is arranged. Incidentally, either a concentrate of a substance contained in a solvent in the flow direction upstream of the filtration device, or a filtrate downstream of the filtration device, which is depleted of a substance contained in a solvent which accumulates approximately upstream of the filtration device may be depleted or a filter cake forming in the flow direction upstream of the filtration device may be useful as a target product.

In the device, at least one filtration device arranged in a chamber can be associated with a target product collecting chamber. The target product collection chamber may be formed in the same body as the filtration device adjacent or in the stacking direction below this chamber and in fluid communication with one of the first or second sub-chambers of that chamber. The target product collecting chamber can be arranged in fluid communication with this sub-chamber, in particular in a flow prevailing in one sub-chamber downstream of this sub-chamber. A target product collection chamber provided in this way serves as a collection container for a desired target product, which is located in one of the first and the second subchambers, in which the desired target product accumulates in the course of the filtration, whereby the target product is avoided in the vicinity. of the filter element) of the filtration device, which leads to an increasing pressure drop at the filtration device, such as by an increasing blockage of the filter element, and can increasingly affect the filtration effect more.

Alternatively or in addition to the target product collection chamber, there may be provided in the device at least one waste product collection chamber associated with a filtration device disposed in a chamber and formed in the same body as the filtration device adjacent or in the stacking direction below that chamber and in fluid communication with one the first or the second sub-chamber of this chamber can be. In particular, the waste product collecting chamber can be arranged in a flow prevailing in the sub-chamber downstream of this sub-chamber. In this case, if the respective filtration device is also associated with a target product collection chamber, the waste product collection chamber may be the waste product collection chamber in fluid communication with the other of the first or second sub-chambers of that chamber. A waste product collection chamber provided in this way serves as a collection container for a waste product which is undesired, which accumulates in one of the first and the second subchambers, in which the desired target product accumulates during the course of the filtration, whereby the waste product is prevented from accumulating in the product Near the (filter element) of the filtration device accumulates or concentrated, which can lead to an increasing pressure drop across the filtration device, such as by an increasing blockage of the filter element, and increasingly affect the filtration effect more.

In the centrifuge according to the second aspect of the invention, there may be (i) a centrifuging speed of the centrifuge and / or (ii) a rotational angular position and / or an axial position of at least one body inserted in the housing and / or (iii) a temperature in at least one of body inserted in the housing can be controlled in each case as a function of time in accordance with a pre-programmable protocol. In this way, during operation of the microfluidic device, the speed of the filtration process and a final substance concentration can be influenced via the controllable parameter.

Brief description of the figures

The invention will be described in more detail below by way of example with reference to the embodiments of the microfluidic device according to the invention described in de attached schematic figures. Show it:

1 FIG. 2 shows a radial cross section of a first embodiment of a microfluidic device at an early point in time in the course of a filtration process, FIG.

2 a radial cross section through the device of the 1 at a later date in the course of the filtration process than in the 1 .

3 a perspective view of a first embodiment of a usable in a housing of a microfluidic device body with a filtration device contained therein,

4 a perspective view of a second embodiment of an insertable into a housing of a microfluidic device body with a filtration device contained therein,

5a . 5b and 5c radial cross sections of a second, third and fourth embodiment of a microfluidic device,

6a a radial cross-sections of a fifth embodiment of a microfluidic device,

6b an axial cross-sections of the embodiment in a plane VIb in the 6a , and

7 a detail of an axial cross section of a sixth embodiment of a microfluidic device.

Embodiments of the invention

In the in the 1 and 2 The first embodiment shown is a microfluidic device 10 for inclusion in or on a rotor 12 a centrifuge (not shown). The device 10 includes one on the rotor 12 the centrifuge attachable housing 16 and three substantially cylindrical bodies or revolvers 20 . 22 . 24 in the case 16 are used. In the case 16 is a stacking direction 18 defined in which the third body 24 over the second body 22 and the second body 22 over the first body 20 in the case 16 are stacked substantially coaxially. The stacking direction 18 extends substantially parallel to the direction of the common longitudinal axes of the body 20 . 22 . 24 and initially runs essentially vertically. During operation of the centrifuge, ie during rotation of the rotor 12 the centrifuge with an angular velocity ω about an axis of rotation 14 of the rotor 12 changes the stacking direction 18 their direction in space becomes substantially parallel to that with respect to the axis of rotation 14 Radial direction r and thus to a direction of action of the centrifugal force generated by the rotation. The stacking direction 18 is defined so that after loading the housing 16 the device 10 which is usually in a vertical state of the housing 16 takes place during the rotation of the rotor 12 the sides "up" and "down" and the directions "up" and "down" to the sides "radially inward" and "radially outward" and the directions "radially inward", ie in the direction -r, and "radially outward", ie in the + r direction. When properly receiving the device 10 in or on the rotor 12 the centrifuge (not shown), and upon rotation of the rotor 12 is the first body 20 at the greatest distance from the axis of rotation 14 of the rotor 12 , the second body 22 in a lower and the third body 24 at an even closer distance to the axis of rotation 14 arranged. The first body 20 is by means of a first holding element 62 , the second body 22 by means of a second retaining element 64 and the third body 24 by means of a third retaining element 66 in the case 16 supported. The second holding element 64 is of several in the stacking direction 18 penetrated by extending passages, which serve in certain arrangements of the second body 22 in relation to the first body 20 certain desired fluidic couplings (fluid connections) between chambers of the second body 22 and chambers of the first body 20 manufacture. The third holding element 66 is also of several in the stacking direction 18 penetrated by extending passages, which serve in certain arrangements of the third body 24 in relation to the second body 22 certain desired fluidic couplings between chambers of the third body 24 and chambers of the second body 22 manufacture.

In the third body 24 are, for example for the storage of reagents and solvents, several cavities or chambers 24a . 24b . 24c . 24d , in the second body 22 two cavities or chambers 22a . 22b and in the first body 20 two cavities or chambers 20a . 20b educated. The third body 24 can be relative to the second body 24 be moved axially and in a rotational movement in its circumferential direction, so that desired fluidic couplings between chambers 24a . 24b . 24c . 24d in the third body 24 and chambers 22a . 22b in the second body 22 be prepared and the latter chambers 22a . 22b be charged with reagents and solvents, due to those in the chambers 22a . 22b chemical reactions or biochemical processes take place.

In the microfluidic chamber 20a of the first body 20 is a filtration device according to the invention 32 , the "first" filtration device according to the appended claim 1. The filtration device 32 includes a filter element 38 (see also 5a to 5c and 6a ), in the chamber 20a for one in the chamber 20a flowing fluid can be flowed against. The filtration device 32 or the filter element 38 limited in the chamber 20a a first compartment 26 in an at least locally prevailing flow direction 30 downstream, here in the downstream direction, and divides the chamber 20a in a first compartment 26 and a second sub-chamber 28 , The first compartment 26 is in one in the chamber 20a prevailing flow direction 30 (See the thick arrows in the chamber 20a in 1 ) upstream of the filtration device 32 and a second sub-chamber 28 downstream of the filtration device 32 arranged. The filtration device 38 further comprises a sliding element 42 , which spans the filter element and whose outer peripheral surface is formed as a sliding surface, so that the sliding element 42 with the clamped filter element along the inner wall surface of the chamber 20a in the stacking direction 18 , ie during rotation of the rotor 12 around the axis of rotation 14 essentially in the effective direction of the centrifugal force, can slide.

In the first body 20 is the chamber 20a with the filtration device 32 by one (in the 1 and 2 vertically shown and not labeled) first partition separated from a chamber 20b , in turn, by a (in the 1 and 2 shown horizontally and not labeled) into a target product collection chamber 50 and a waste product collection chamber 52 is divided. A connection channel 76 Penetrates the first partition wall and provides fluid communication between the upstream of the filtration device 32 arranged sub-chamber 26 and the waste product collection chamber 52 ago.

Upstream of the filtration device 32 accumulates in the course of progressing process time one in a liquid entrained (in the 1 schematically represented as a particle) substance 60 having a particle size greater than a pore size of the filter element of the filtration device 32 is, therefore, can not penetrate the filter element and is retained upstream of the same. The substance entraining liquid penetrates the filter element in the flow direction (in 1 indicated by the thick arrows) and collects in the second sub-chamber 28 downstream of the filter element of the filtration device 32 , Because the concentration of the substance 60 in the first compartment 26 is greater than in the second sub-chamber 28 arises on the filter element of the filtration device 32 an osmotic pressure in the direction of the second compartment 28 to the first compartment 26 works, and in the first part chamber 26 existing higher concentration (or density) of the substance 60 to dilute. The osmotic pressure is proportional to the density difference of the substance 60 upstream and downstream of the filter element and causes a force on the filter element or the movable in this direction filtration device 32 , the latter in the direction of the second compartment 28 (in the 1 and 2 down) presses or presses. The osmotic force on the filtration device 32 (in 1 down) acts in the same direction as the centrifugal force (in 1 down), with the centrifugal force acting on both the filtration device 32 as well as those in the sub-chambers 26 . 28 solution and the substance 60 acts. Because the centrifugal force is proportional to the square of the angular velocity ω and the radius r (the distance of the filtration device 32 from the axis of rotation 14 ) is, on the one hand, the equilibrium position of the filtration device 32 , hence the concentration of the substance 60 in the first compartment 26 about the angular velocity ω of the rotation of the rotor 12 be influenced about the axis of rotation, ie the centrifugation speed. On the other hand, the filtration speed can be influenced by the centrifugation speed. Whether in operation, the filtration device 32 due to the centrifugal force is moved up or down, depends on whether the density of the filter element 38 or the density of the material of the filter element 38 less than or greater than the density of the solution and the substance 60 is, the density of the substance 60 often negligible in this context. Is the density of the filter element 38 smaller than the density of the solution, it comes with the action of centrifugal force to a shift of the filtration device 32 through the solution to the top, as the denser solution displaces the thinner filtration device and thus an effective force on the filtration device in the direction of the axis of rotation 14 acts. The ultimately resulting force on the filtration device 32 Thus, in operation, this results in the difference between the above-mentioned effective force, which acts by way of example upward, and the osmotic force, which acts downward. In 2 the resulting force acts as an example in the direction of the axis of rotation 14 and thus causes an increase in the concentration of the substance 60 in the first compartment 26 , An example of the solution is a general water-based fluid whose density is substantially 1 kg / l. Alternatively, glycols (such as PEG, DEG, EG, etc.) and other liquid media are also possible. Preferably, the filter element 38 a lower density (<1kg / l) than the density of the solution. The filter element 38 can be formed in particular from a plastic (associated density <1 kg / m ³ ), carbon, cellulose, paper (associated density about 0.8 kg / l) or wax (associated density 0.9..0.98 kg / l). Preferably, it is the substance 60 around water and the filter element 38 is made of plastic or cellulose. Alternatively, the solution may again be water while the filter element 38 made of carbon, paper or wax.

The 3 shows a perspective view of an embodiment of a usable in a housing (not shown) of a microfluidic device body 20 with several in the stacking direction 18 through the body 20 extending through chambers 20a . 20b . 20c and 20d , In the chamber 20a are according to the invention a first filtration device 32 and further a second filtration device 46 , one for each in the chamber 20a flowing fluid arranged to flow and extend over the entire, the fluid flow cross section available. The filter element of the first filtration device 32 has a pore size (in 3 represented as a screen with a larger mesh size) larger than a pore size of the second filtration device 46 is (in 3 shown as a sieve with a smaller mesh size). The second filtration device 46 is in one in the chamber 20a prevailing flow direction 30 , the stacking direction 18 directed substantially opposite, downstream of the first filtration device 32 arranged. Both filtration devices 32 and 46 are in the chamber 20a not displaceable, ie in the chamber 20a stationary, arranged. In this arrangement, the first filtration device acts 32 as a pre-filter retaining larger particle size substances for the second filtration device 46 which acts as a post-filter and retains substances with smaller particle sizes. At the upstream end of the chamber 20a is designed as a cover foil, openable cap element 48 arranged. The capping element 48 or the capping film has a predetermined breaking point (not shown) which is adapted to break at a predetermined pressure acting on the capping film. This pressure acting on the capping film is proportional to the centrifugal force acting on a fluid backed up upstream of the capping member, more specifically on the fluid particles contained therein. The centrifugal force and thus the pressure on the capping element 48 is proportional to the density of the fluid and to the centrifugation speed ω, so that over the latter the breaking of the predetermined breaking point of the capping element 48 is controllable.

The 4 shows a perspective view of another embodiment of a usable in a housing (not shown) of a microfluidic device body 20 with several (in 4 eight) in the stacking direction 18 through the body 20 extending through chambers. In one of the chambers according to the invention is a filtration device 32 fixed in this chamber. This in the 4 shown filtration device 32 includes a filter element 38 and a tenter 40 that is the filter element 38 spans and over the the filtration device 32 orstfest on the inner wall surface of the chamber 20a is attached. On the substantially cylindrical outer surface of the body 20 extends in the circumferential direction extending in a zig-zag pattern shoulder 70 , On the outer surface of the body 20 are also a variety of (in 4 eight) surveys 72 formed spaced in the circumferential direction at regular intervals. The shoulder 70 and the surveys 72 Together they form elements of a ballpoint pen mechanism 68 that is designed and provided to the body 20 a displacement in an axial direction in its circumferential direction by one by the distance of the elevations 72 or the period length of the zigzag-shaped shoulder 70 predetermined angle (360 ° / 8) is rotated in its circumferential direction and engages in a shift in an opposite axial direction in the new predetermined rotational angular position. The ballpoint pen mechanism 68 serves to be a next of the chambers of the body shown 20 with a chamber one in the stacking direction 18 neighboring (in the 4 not shown) to fluidly couple another body.

In the in the 5a to 5c and 6a shown embodiments comprises a microfluidic device 10 each on the rotor 12 the centrifuge attachable housing 16 and three in the stacking direction 18 stacked in the housing 16 used, substantially cylindrical body, of which in these figures in the stacking direction 18 middle body 22 is shown. In the body 22 are a first chamber 22a and a second chamber 22b educated. In the first chamber 22a each is a filtration device 32 with a serving as a clamping frame fastener 44 for fixedly attaching the filtration device 32 on an inner wall of the chamber 22a and one of which also serves as a clamping frame fastener 44 clamped or held filter element 38 , During the rotation of the device 10 around the axis of rotation 14 of the rotor 12 the centrifuge rules in the chamber 22a one flow direction each 30 , the stacking direction 18 is directed opposite.

In the in the 5a to 5c the embodiments shown is the filter element 38 each formed in a substantially planar shape and has an extension plane 34 on. In 5a is the extension plane 34 of the filter element 38 essentially perpendicular to the flow direction 30 arranged. In 5b is the extension plane 34 of the filter element 38 essentially parallel to the flow direction 30 arranged. And in 5a is the extension plane 34 of the filter element 38 diagonally to the flow direction 30 arranged.

In the in 5a embodiment shown acts on a rotation of the device 10 around the axis of rotation 14 the rotor's centrifugal force is particularly supportive of the filtration because the centrifugal force is then substantially perpendicular to the plane of extent 34 of the filter element 38 is arranged and in place of the rotation without vertical arrangement of the microfluidic device 10 substantially perpendicular to the plane of extent 34 of the filter element 38 acting gravity occurs. In the in 5b embodiment shown acts on a rotation of the device 10 the centrifugal force is particularly strong as a shearing force on substances not passing through the filter element 38 can pass through and therefore, for example in the form of a so-called filter cake, at one with respect to the filter element 38 in the chamber 22a defined inflow side (in 5b right on the filter element 38 accumulate). The accumulating substances or the filter cake is due to the centrifugal force acting as a shear force along the surface of the filter element 38 radially outward ( 5b down), so that during the rotation of the rotor to the filter element 38 gets a self-cleaning effect. In the in 5c shown embodiment can in a fast rotating rotor 12 by a suitable choice of the angle of inclination of the plane of extent 34 a suitable compromise between the filtration assisting effect of the centrifugal force and along the surface of the filter element 38 directed displacement of the upstream of the filter element 38 accumulating substance, such as a filter cake, and thus the self-cleaning effect on the filter element 38 will be realized.

In the in 6a the embodiment shown is the filter element 38 the filtration device 32 tapered, with a tip of the cone in one of the flow direction 30 opposite direction. In this way, the surface of the filter element 38 - similar to in 5c - obliquely to the flow direction 30 employed, so that analogous as before with respect to 5c described a compromise between the filtration assisting effect of the centrifugal force and the self-cleaning effect on the filter element 38 by shifting the upstream accumulating substance 60 can be realized.

In the in 6a The embodiment shown is the chamber 22a with the filtration device disposed therein 32 through a partition 74 from a chamber 22b separated. The partition 74 is near the fastener 44 from a first connection channel 76 and in the vicinity of the holding element 64 from a second connection channel 78 penetrated. The first connection channel 76 provides fluid communication between the upstream of the filter element 38 arranged first sub-chamber 26 the chamber 22a and the chamber 22b ago. The first connection channel 76 starts in the partition 74 at the side of the chamber 22a in the area where the from the cone-shaped filter element 38 retained substance 60 accumulates (concentrated), so that a part of the accumulating substance through the first connection channel 76 is dissipated. It flows downstream into the chamber 22b in one area 52 into the filter element 38 retained and through the first connection channel 76 dissipated substance accumulates. If this substance is considered a waste product (as in the 6a accepted), then the area functions 52 the chamber 22b as a waste product collection chamber 52 ,

The second connection channel 78 provides fluid communication between the downstream of the filter element 38 arranged second sub-chamber 28 the chamber 22a and the chamber 22b ago. The second connection channel 78 starts in the partition 74 at the side of the chamber 22a in the most downstream region, away from the filtration device 32 where is that from the filter element 38 transmitted and from the substance 60 depleted fluid accumulates, so that a portion of the accumulating fluid through the second connection channel 78 is dissipated. It flows downstream into the chamber 22b in one area 50 , in the of the filter element 38 passed through and through the second connection channel 78 discharged fluid accumulates. If this fluid is considered as the target product (as in the 6a accepted), then the area functions 50 the chamber 22b as target product collection chamber 50 ,

In the in 7 embodiment shown is in the chamber 22a of the body 22 a filter element 38 a filtration device in the cross section shown perpendicular to the stacking direction 38 seen spirally formed and extends (with the spiral-shaped cross section) in the stacking direction, ie in 7 perpendicular to the drawing plane. The filter element 38 surrounds an interior, in the case of a rotation of the body 22 a fluid carrying substance along the axis of rotation of a rotor (not shown) flows in, and the fluid upstream of the filter element 38 arranged first sub-chamber 26 formed. The filter element 38 is surrounded by an outside space, in the case of a rotation of the body 22 around the axis of rotation of a rotor (not shown), the fluid after passing through the filter element 38 flows in, and the downstream of the filter element 38 arranged second sub-chamber 26 formed. In the second compartment 28 opens a connection channel 76 , the one the chamber 22a bounding partition 74 penetrates and the fluid passing through the filter element 38 passed through and of the filter element 34 in the first compartment 26 depleted substance as a target product to a target product collection chamber (in 7 not shown).

LIST OF REFERENCE NUMBERS

10

 microfluidic device

12

 rotor

14

 axis of rotation

16

 casing

18

 stacking direction

20

 first body

20a

 first chamber

20b

 second chamber

20c

 third chamber

22

 second body

22a

 first chamber

22b

 second chamber

24

 third body

24a

 first chamber

24b

 second chamber

24c

 third chamber

26

 first compartment

28

 second sub-chamber

30

 flow direction

32

 first filtration device

34

 extension plane

36

 movement direction

38

 filter element

40

 tenter

42

 Slide

44

 fastener

46

 second filtration device

48

 capping element

50

 Target product-collecting chamber

52

 Waste product collection chamber

54

 concentrate

56

 filtrate

58

 filter cake

60

 substance

62

 first holding element

64

 second holding element

66

 third retaining element

68

 Pens mechanics

70

 shoulder

72

 survey

74

 partition wall

76

 first connection channel

78

 second connection channel

r

 radius

ω

 angular velocity

QUOTES INCLUDE IN THE DESCRIPTION

This list of the documents listed by the applicant has been generated automatically and is included solely for the better information of the reader. The list is not part of the German patent or utility model application. The DPMA assumes no liability for any errors or omissions.

Cited patent literature

• DE 102010003223 A1 [0003, 0003]

Claims (17)

Microfluidic device ( 10 ) for inclusion in or on a rotor ( 12 ) of a centrifuge, comprising: at least one first body ( 20 . 22 ), the at least one first microfluidic chamber ( 20a . 22a ) and in one of the rotor ( 12 ) of the centrifuge mountable housing ( 16 ), wherein in the housing ( 16 ) a stacking direction ( 18 ) in which a second body ( 22 . 24 ) in the housing ( 16 ) is stackable above or below the first body, wherein upon receiving the device ( 10 ) in or on the rotor ( 12 ) of the centrifuge, and upon rotation of the rotor ( 12 ), the first body at a distance to a rotation axis ( 14 ) of the rotor ( 12 ), wherein at least one first filtration device ( 32 ), in the Chamber ( 20a . 22a ) of the first body ( 20 . 22 ), which is a filter element ( 38 ) contained in the chamber ( 20a . 22b ) when receiving the device ( 10 ) in or on the rotor ( 12 ) of the centrifuge, and upon rotation of the rotor ( 12 ), is vorströmbar. Device according to claim 1, characterized in that in the first chamber ( 20a ) of the first body ( 20 ) at least one second filtration device ( 46 ) with respect to a prevailing in the chamber flow direction ( 30 ) downstream of the first filtration device ( 32 ) is arranged to flow against. Apparatus according to claim 2, characterized in that the first and the second filtration device ( 32 . 46 ) have different pore sizes and that the filtration device ( 46 ) with the smaller pore size in the flow direction downstream of the filtration device ( 32 ) is arranged with the larger pore size. Device according to one of claims 1 to 3, characterized in that in at least one of the first and second filtration means ( 32 . 46 ) the filter element ( 38 ) a sub-chamber ( 26 ) in an at least locally prevailing flow direction ( 30 ) is limited downstream, is substantially planar and an extension plane ( 34 ) arranged according to one of the following variants: (a) the plane of extent ( 34 ) is substantially perpendicular to the stacking direction (FIG. 18 ), (b) the plane of extent ( 34 ) is parallel to the stacking direction ( 18 ), or (c) the plane of extent ( 34 ) is oblique to the stacking direction ( 18 ) arranged. Device according to one of claims 1 to 3, characterized in that the filter element ( 38 ) of at least one filtration device ( 32 . 46 ) a sub-chamber ( 26 ) in an at least locally prevailing flow direction ( 30 ) downstream and is formed according to one of the following variants: (d) the filter element ( 38 ) is substantially conical, (e) the filter element ( 38 ) is in a cross section perpendicular to the stacking direction ( 18 ) substantially spiral-shaped, or (f) the filter element ( 38 ) is formed substantially cylindrically in a cross section perpendicular to the stacking direction. Device according to one of claims 1 to 5, characterized in that the filtration device ( 32 ) in the chamber assigned to it ( 20a ) in relation to this chamber ( 20a ), in particular in the stacking direction ( 18 ) is movable, is arranged. Device according to one of claims 1 to 6, characterized in that the first and / or the second partial chamber ( 26 . 28 ) at a recording of the device ( 10 ) in or on the rotor ( 12 ) of the centrifuge is increased or reduced. Apparatus according to claim 7, characterized in that the total volume of the first and second sub-chamber ( 26 . 28 ) can change. Device according to one of claims 1 to 8, characterized in that the one filter element ( 38 ) is made of one of the following materials: a fiber - oriented nonwoven, in particular a felt, a random fiber, in particular a spunbonded fabric, a woven fabric, a wound filter tube or a wound filter candle with yarns made of at least two different materials, a bed of a plurality of grains and / or a granulate, a porous solid, such as sintered metal, paper, or a metal. Device according to one of claims 1 to 9, characterized by at least one openable capping element ( 48 ), one in a chamber of one of the bodies ( 20 . 22 . 24 ) arranged filtration device ( 32 . 46 ) and with respect to a flow direction prevailing in this chamber ( 30 ) upstream of the filtration device ( 32 . 46 ) is arranged. Device according to one of claims 1 to 10, characterized in that when receiving the device ( 10 ) in or on a rotor ( 12 ) of a centrifuge and during a rotation of the rotor ( 12 ) in the first chamber ( 20a ) a flow direction ( 30 ) prevails, and that either one in the flow direction ( 30 ) upstream of the filtration device ( 32 ) forming concentrate ( 54 ) of a substance contained in a solvent ( 60 ), or in the flow direction ( 30 ) downstream of the filtration device ( 32 ) forming filtrate ( 56 ), relating to a substance contained in a solvent ( 60 ) is depleted, or in the flow direction ( 30 ) upstream of the filtration device ( 32 ) forming filter cake is obtainable as a target product. Device according to one of claims 1 to 9, characterized by at least one of a filtration device arranged in a chamber ( 32 . 46 ) associated target product collection chamber ( 50 ) contained in the same body as the filtration device ( 32 . 46 ) next to or in the stacking direction ( 18 ) formed below this chamber and in fluid communication ( 78 ) with one of the first or the second sub-chamber ( 26 . 28 ) of this chamber is. Device according to one of claims 1 to 12, characterized by at least one of a filtration device arranged in a chamber ( 32 . 46 ) associated waste product collection chamber ( 52 ) contained in the same body as the filtration device ( 32 . 46 ) next to or in the stacking direction ( 18 ) formed below this chamber and in fluid communication ( 76 ) with one of the first or the second sub-chamber ( 26 . 28 ) of this chamber is. Centrifuge with a rotor ( 12 ), characterized in that in the rotor ( 12 ) a microfluidic device ( 10 ) is received according to one of claims 1 to 13. Centrifuge according to claim 14, characterized in that: (i) a centrifuging speed of the centrifuge and / or (ii) a rotational angular position and / or an axial position of at least one in the housing ( 12 ) body ( 20 . 22 . 24 ) and / or (iii) a temperature in at least one in the housing ( 12 ) body ( 20 . 22 . 24 ) is controllable as a function of time in accordance with a pre-programmable sequence. Use of a microfluidic device ( 10 ) according to one of claims 1 to 13 for the following: concentration of a liquid, eg with particles, functionalized beads or glass beads, bacteria, yeasts, cells, cell components, such as antibodies, antigens, proteins or DNA, concentration of a solid, eg with particles with different particle sizes, or concentration of a gas. Using a in a microfluidic device ( 10 ) according to any one of claims 1 to 13 contained filtration device ( 32 . 46 ) for the actuation of a microfluidic valve or a microfluidic pump of the microfluidic device ( 10 ), wherein the valve or the pump in the same body ( 20 . 22 . 24 ) like the filtration device ( 32 . 46 ) or in one in the housing ( 16 ) adjacent thereto, in particular in the stacking direction ( 18 ) arranged above or below, body is arranged.

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