WO2022137162A1 - Microfluidic device with input actuator system - Google Patents

Abstract

The present invention relates to a microfluidic device, which has at least one fluid input, at least one fluid output, at least one fluid channel, extending between the at least one fluid input and the at least one fluid output, and a microactuator, which has a membrane which can be stretched directly or indirectly by an actuator fluid which is located in the microactuator and electrically connected to electrodes. According to the invention, the at least one fluid input opens into at least one reservoir, which is formed in the microfluidic device and in which there is at least one fluid-absorbing and compressible storage material which is in contact with the membrane of the microactuator.

Description

Microfluidic device with input actuators

The present invention relates to a microfluidic device that has at least one fluid inlet, at least one fluid outlet, at least one fluid channel running between the at least one fluid inlet and the at least one fluid outlet, and a microactuator that has a membrane that is connected to electrodes by a membrane located in the microactuator electrically connected actuator liquid is stretchable directly or indirectly.

Miniaturized systems for the analysis of fluids, preferably liquids, which are generally referred to as "laboratory on a chip" or "lab-on-a-chip", are known from the prior art. Areas of application of such systems include, for example, human diagnostics, veterinary diagnostics and environmental and food analysis. The systems have, for example, a cartridge that can contain liquids and in which these liquids can be transported. Such systems often also have a sensor area that is responsible for the actual analysis.

For the analysis of a sample, it is often necessary to transport liquids in a defined manner. This can be done both via an external actuator that works, for example, pneumatically, mechanically or via external pumps, as well as via an actuator that is part of the cartridge.

An example of such an actuator integrated in a liquid-carrying microstructure is described in publication EP 1 844 936 A1. The micro-actuator described uses hydrogel, which absorbs an actuator liquid, such as water, and is contacted with electrodes, which can trigger electrolysis in the actuator liquid. The oxygen and hydrogen bubbles that form during the electrolysis lead to gas pressure, which acts on a membrane of the microactuator can be closed. The actuator components necessary for the implementation of the actuator principle are thereby can be integrated in the smallest of spaces, which makes it possible, for example, to form a microfluidic device having actuator and sensor components in the size of an EC card.

Another analysis unit described in publication DE 10 2013 219 502 A1 has a cover element with a pressure channel which is closed in a pressureless state by a film provided on the underside of the cover element. A liquid channel for a fluid is formed between the film and a base element of the analysis unit. When pressure is applied to the pressure channel, the foil under the pressure channel bulges downwards, as a result of which the fluid in the liquid channel is displaced. An insulating layer in the form of a thin paraffin layer can be provided between the foil and the cover element, which, after deflection of the foil, melts and covers the foil, which is intended to reduce the vapor permeability of the foil.

A microfluidic device is known from publication DE 10 2015 101 106 A1, which has an actuator which can pump a liquid located in a reservoir from the reservoir into a channel via a flexible membrane. An absorber material is provided in a region of the channel remote from the akor and the membrane, which absorber material can absorb the liquid, as a result of which certain channel regions can be emptied in a targeted manner.

The publication EP 2 041 573 B1 contains a microfluidic card which has a collection reservoir for waste liquid connected to a channel. In the collection reservoir is an absorber pad that swells as it absorbs liquid. A flexible membrane separates a waste liquid channel, in which the absorber pad and the liquid are located, from an air channel. When the membrane bulges in the direction of the air duct due to the swelling of the absorber pad, air is pushed out of the air duct through a liquid-impermeable air outlet.

If a fluid, such as blood, which contains particulate components, is to be analyzed, the fluid channels used for conducting the fluid previously had to be designed with such a large cross section that channel blockages by the particulate components were avoided. This increases the size of the system and dead volumes. If the particulate components of the fluid are to be separated beforehand, for example to avoid clogging of fluid channels, filter membranes are often used. However, these have the disadvantage that they themselves become clogged very quickly or a layer of particulate components forms on them that is largely impenetrable for the remaining liquid. In the case of blood, an even higher pressure is then often required in order to convey further liquid that does not contain particles through the filter membrane, which in turn can lead to haemolysis, which can ultimately falsify the measurement result.

In addition, in some applications it is necessary to introduce the fluid to be analyzed into the system, but not immediately forward it for analysis, which is not possible with the existing systems in a defined manner.

It is therefore the object of the present invention to provide a microfluidic device which can be designed to be very small, largely independently of the fluid to be conducted through.

The object is achieved by a microfluidic device that has at least one fluid inlet, at least one fluid outlet, at least one fluid channel running between the at least one fluid inlet and the at least one fluid outlet, and a microactuator, which has a membrane that is connected by a membrane located in the microactuator and with The actuator liquid electrically connected to the electrodes can be stretched directly or indirectly, with the at least one fluid inlet opening into at least one reservoir formed in the microfluidic device, in which at least one fluid-absorbing and compressible storage material is located, which is in contact with the membrane of the microactuator, the membrane on the storage material located in the reservoir is adjacent.

A fluid is first introduced into the microfluidic device according to the invention via the at least one fluid inlet. The fluid can, for example, be a liquid to be analyzed with regard to its ingredients or other properties. According to the invention, the term “fluid” includes all media that are fluid at room temperature and 1 bar ambient pressure, except for gases or gas mixtures or vapors. For example, the term "fluid" includes water, liquid alcohols, urine, blood, aqueous solutions and suspensions, solutions containing alcoholic solvents, gels, and oils further flowing media, which, for example, can be of natural origin, such as blood or petroleum, but can also be produced synthetically.

The fluid first reaches the at least one reservoir, in which the at least one fluid-absorbing and compressible storage material is located, via at least one fluid channel of the microfluidic device or directly from the fluid inlet. The fluid is at least partially absorbed by this storage material, including any particulate components contained in the fluid.

The storage material preferably fills the reservoir in such a way that no fluid can flow via the reservoir into a fluid channel of the microfluidic device adjoining the reservoir in the direction of the fluid outlet without first having flowed through the storage material.

The reservoir is preferably rectangular in cross-section, but may have a domed bottom or other shape.

The storage material is in contact with the membrane of the micro-actuator, i. H. in direct contact. For example, the membrane forms a floor and/or a ceiling and/or a side wall of the reservoir.

The membrane is a flexible membrane. The storage material is a fluid absorbent material that is preferably at least 30% by volume compressible.

The microactuator used in the microfluidic device according to the invention has an actuator liquid that is preferably received in an actuator liquid reservoir of the microactuator and electrodes that are electrically connected to the actuator liquid. The actuator liquid is thus located on a first side of the membrane, and the storage material directly adjoining the membrane is located on a second side of the membrane. The fluid-absorbing and compressible storage material is therefore located on the opposite side of the membrane to the micro-actuator. The storage material is thus directly above the actuator. The position of the membrane that can be directly influenced by the actuator liquid therefore has a direct and immediate effect on the storage material and thus on the amount of fluid that can be accommodated in the storage material. The micro-actuator can be controlled by the electrodes. Like the micro-actuator described in publication EP 1 844 936 A1, the micro-actuator can be designed as an electrolysis actuator. The micro-actuator functioning as an electrolysis actuator can contain hydrogel, which absorbs the actuator liquid, such as water, and is in contact with electrodes, by means of which electrolysis can be triggered in the actuator liquid. However, the actuator liquid does not necessarily have to be stored in a hydrogel, but can be thickened, for example.

The oxygen and hydrogen bubbles that form during the electrolysis of the actuator liquid lead to gas pressure, which acts on the membrane of the microactuator. As a result, the membrane arches and presses against the storage material located in the reservoir and adjoining the membrane. Due to the bulging of the membrane, the fluid is at least partially pushed out or pressed out of the storage material and can then flow in the direction of the fluid outlet.

The storage material thus offers the possibility of temporarily storing the fluid.

When the fluid is at least partially pressed out of the storage material by means of the microactuator, particulate components from the fluid originally introduced into the microfluidic device are retained by the storage material. The storage material therefore acts as a filter material that at least partially filters the particulate components out of the fluid. The fluid flowing further in the direction of the fluid outlet is thus at least partially filtered. The risk of blockages in the fluid channels leading to the fluid outlet is therefore reduced, even if they have very small diameters.

The storage material preferably has at least one sponge, at least one textile, cotton wool, cellulose, porous inorganic material, porous organic material and/or at least one gel. These materials are distinguished by the fact that they have capillaries and/or pores and/or material gaps in which liquid can be absorbed, can be simply pressed together in order to release the liquid again, and also have a structure that contains particulates in the fluid retains components. In a preferred embodiment of the present invention, the storage material has areas with different and/or gradually changing absorptivity and/or filter effect. This makes it possible, for example, to take up particulate components of the fluid only in a first region of the storage material in the fluid conveying direction and to use a second region of the storage material in the fluid conveying direction as a barrier to preventing the particulate components from being passed on.

Preferred embodiments of the present invention, their structure, function and advantages are explained in more detail below with the aid of figures, with FIGS. FIGS. 2a to 2d schematically show a detail of an embodiment of the microfluidic device according to the invention with an input stage filter in different method stages in a sectional side view; FIGS. 3a to 3d schematically show a detail of an embodiment of the microfluidic device according to the invention with pump volume definition in different method stages in a sectional side view; and FIGS. 4a to 4d schematically show a detail of a further embodiment of the microfluidic device according to the invention with pump volume definition in different method stages in a sectional side view.

FIGS. 1 to 4 schematically show different embodiments of the microfluidic device 1, 1' according to the invention. All embodiments have in common that in a fluid conveying direction A at or near a fluid inlet 2 of the respective microfluidic device 1, 1′ there is a reservoir 4 fluidly connected to the fluid inlet 2 with a microactuator 10 connected thereto. Included at least one fluid-absorbing and compressible storage material 5, 5' is located in the reservoir 4 in each case.

In the embodiments shown, the storage material 5, 5' is at least one sponge, but in other embodiments of the invention it can also be at least one textile, cotton wool, cellulose, porous inorganic material, porous organic material and/or at least one gel.

The respective microactuator 10 has a flexible membrane 9 that borders on the reservoir 4 and thus on the storage material 5, 5' located in the reservoir 4. The flexible membrane 9 thus simultaneously forms a cover membrane of the microactuator 10 and a cover membrane of the reservoir 4.

Furthermore, the micro-actuator 10 has an actuator liquid 11 . In the exemplary embodiments shown, the actuator liquid 11 is held by a hydrogel 6 in each case. In addition, the micro-actuator 10 has electrodes 7 , 8 which are electrically connected to the actuator liquid 11 . Electrical connecting lines, which are not shown in the illustrations, run outwards from the electrodes 7, 8.

As can be seen in the figures, the respective microfluidic device 1 , T has at least one fluid channel 3 which is in fluid connection with the reservoir 4 . The at least one fluid channel 3 leads directly or indirectly to a fluid outlet 12 of the microfluidic device 1, T.

A fluid introduced into the microfluidic device 1, T via the fluid inlet 2 flows along the fluid conveying direction A first through the reservoir 4 and only then in the direction of the fluid outlet 12, whereby on its way to the fluid outlet 12 it flows through the at least one fluid channel 3 and optionally at least a micropump and/or at least one analysis unit can pass.

The reservoir 4 and the storage material 5, 5′ together with the microactuator 10 in each of the embodiments shown form an input actuator system for the respective microfluidic device 1, T and, as can be seen in the figures, can fulfill different functions. In the microfluidic device 1 shown in FIGS. 1a to 1d as well as in the microfluidic device 1′ shown in FIGS. 2a to 2d, the input actuator system serves primarily as an input filter.

FIG. 1a shows the microfluidic device 1 without introduced fluid.

In the case of the microfluidic device 1, a homogeneous storage material 5, preferably a sponge, is introduced into the reservoir 4. In FIG. 1 b, a fluid 20 enters the reservoir 4 via the fluid inlet 2 and is at least partially sucked up there by the storage material 5 . For example, the fluid 20 is pipetted into the fluid inlet 2 . The fluid 20 contains particulate components 21.

Then, as shown in FIG. 1c, the fluid inlet 2 is closed with a cover 13.

By applying a voltage between the electrodes 7, 8, electrolysis in the actuator liquid 11 is initiated, as shown in FIG. 1d. The oxygen and hydrogen bubbles 14 that form during the electrolysis generate a gas pressure, as a result of which the membrane 9 arches. As a result, the storage material 5 located above is compressed and the fluid 20 contained therein is pressed out of the storage material 5 into the channel 3 adjoining the reservoir 4 .

In the process, the particulate components 21 remain in the storage material 5 . The fluid 20 is filtered.

FIG. 2a shows the microfluidic device 1′ without introduced fluid. In contrast to the microfluidic device 1, two different storage materials, namely a first storage material 5 and a second storage material 5', are introduced into the reservoir 4 of the microfluidic device 1'. The first storage material 5 has larger pores than the second storage material 5'. In other specific embodiments of the present invention that are not shown, the absorbency and/or the filterability of the storage material 5 can change gradually within the reservoir 4 in the fluid conveying direction A. In FIG. 2b, a fluid 20 enters the reservoir 4 via the fluid inlet 2 and is first sucked up there by the first storage material 5 . The fluid 20 contains particulate components 21. The fluid 20 is then sucked up by the second storage material 5', which is arranged after the first storage material 5 in the fluid conveying direction A. Due to the smaller pores of the second storage material 5', the particulate components 21 or a large part of them remain in the first storage material 5.

Then, as shown in FIG. 2c, the fluid inlet 2 is closed with a cover 13.

By applying a voltage between the electrodes 7, 8, electrolysis in the actuator liquid 11 is started, as can be seen in FIG. 2d. The oxygen and hydrogen bubbles 14 that form during the electrolysis generate a gas pressure, as a result of which the membrane 9 arches. As a result, the storage materials 5, 5' located above are pressed together and the fluid 20 contained therein is pressed out of the storage materials 5, 5' into the channel 3 adjoining the reservoir 4.

The particulate components 21 remain in the first storage material 5 . The fluid 20 is filtered.

In the microfluidic device 1 shown in FIGS. 3a to 3d, the input actuator primarily serves as a temporary fluid store and for defining the pump volume.

FIG. 3a shows the microfluidic device 1 without introduced fluid.

In FIG. 3b, a fluid 20 enters the reservoir 4 via the fluid inlet 2 and is at least partially sucked up there by the storage material 5 .

Then, as shown in FIG. 3c, the fluid inlet 2 is closed with a cover 13.

By applying a voltage between the electrodes 7, 8, electrolysis in the actuator liquid 11 is initiated, as shown in FIG. 3d. The oxygen and hydrogen bubbles 14 that form during the electrolysis generate a gas pressure as a result of which the membrane 9 bulges. As a result, the storage material 5 located above is compressed and the fluid 20 contained therein is pressed out of the storage material 5 into the channel 3 adjoining the reservoir 4 . Since no more fluid 20 can be pumped into channel 3 than was previously taken up by storage material 5 , storage material 5 can set a defined volume of fluid 20 that is to be pumped into channel 3 . Insofar as less of the fluid 20 reaches the reservoir 4 than the storage material 5 contained therein can absorb, correspondingly less of the fluid 20 is passed on into the channel 3 . The storage material 5 therefore determines the maximum volume of fluid that can be passed on.

In the microfluidic device 1″ shown in FIGS. 4a to 4d, the input actuator system is used, similar to that in FIGS. 3a to 3d, to define the pump volume and to distribute the fluid.

FIG. 4a shows the microfluidic device 1″ without introduced fluid.

In FIG. 4b, a fluid 20 enters the reservoir 4 via the fluid inlet 2 and a fluid channel 3' and is at least partially sucked up there by the storage material 5.

Then, as shown in FIG. 4c, the fluid inlet 2 is closed with a cover 13.

By applying a voltage between the electrodes 7, 8, electrolysis in the actuator liquid 11 is initiated, as shown in FIG. 4d. The oxygen and hydrogen bubbles 14 that form during the electrolysis generate a gas pressure, as a result of which the membrane 9 arches. As a result, the storage material 5 located above is compressed and the fluid 20 contained therein from the storage material 5 is partially back into the fluid channel 3' located in front of the reservoir 4 in the fluid conveying direction A and also partially into the fluid channel 3' that adjoins the reservoir 4 in the fluid conveying direction A Channel 3 pressed. Thus, only part of the fluid 20 is released for further transport in the microfluidic device 1″. Correspondingly, the fluid volume that can be introduced into the fluid channel 3 can be well defined via the input actuator system.

Claims

Microfluidic device (1) having at least one fluid inlet (2), at least one fluid outlet (12), at least one fluid channel (3) running between the at least one fluid inlet (2) and the at least one fluid outlet (12), and a microactuator (10) which has a membrane (9) which can be stretched directly or indirectly by an actuator liquid (11) located in the micro-actuator (10) and electrically connected to electrodes (7, 8), characterized in that the at least one fluid inlet (2nd ) opens into at least one reservoir (4) formed in the microfluidic device (1), in which at least one fluid-absorbing and compressible storage material (5, 5') is located, which is in contact with the membrane (9) of the microactuator (10), the membrane (9) adjoining the storage material (5, 5') located in the reservoir (4). Microfluidic device according to Claim 1, characterized in that the storage material (5, 5') has at least one sponge, at least one textile, cotton wool, cellulose, porous inorganic material, porous organic material and/or at least one gel. Microfluidic device according to one of the preceding claims, characterized in that the storage material (5, 5') has areas with different and/or gradually changing absorptivity and/or filter effect. Microfluidic device according to one of the preceding claims, characterized in that the microactuator (10) is an electrolysis actuator.