WO2022058267A1

WO2022058267A1 - Microfluidic device

Info

Publication number: WO2022058267A1
Application number: PCT/EP2021/075050
Authority: WO
Inventors: Julian Kassel; Martina BUDDE
Original assignee: Robert Bosch Gmbh
Priority date: 2020-09-18
Filing date: 2021-09-13
Publication date: 2022-03-24
Also published as: DE102020211697A1

Abstract

The invention relates to a microfluidic device which has a receiving chamber (111, 112) with an opening to the surrounding area, a closure (130) which is arranged on the exterior of the microfluidic device and is designed to close off the region of the microfluidic device where the opening is arranged from the surrounding area, and a pneumatic channel (140). The pneumatic channel (140) is arranged such that one end (141) of the pneumatic channel (140) lies in the region closed off by the closure (130).

Description

description

title

Microfluidic Device

The present invention relates to a microfluidic device with a shutter. In addition, the invention relates to a method for checking the status of the closure of the microfluidic device.

State of the art

Microfluidic devices, such as microfluidic chips, are used for various areas of application. Such fluidic devices, which are generally made of plastic, can be used, for example, for analytical, preparative or diagnostic applications in medicine. The microfluidic devices can be used, for example, in the form of a so-called lab-on-chip system, with the functionalities of a laboratory being combined to a certain extent in the form of a credit card. In this case, the microfluidic device forms a cartridge in which various analysis components, treatment components, sensors and others are integrated in order to allow complex biochemical processes or the like to take place in the fluidic device, which is tailored to the respective application. In general, such microfluidic devices consist of structured plastic support plates that contain a channel system, various required reaction chambers and other functional elements such as e.g. B. valves and filters integrate. Such systems are particularly suitable for automated applications, so that they can be used, for example, for prompt diagnostics in medical practices or hospitals.

In addition to fluidic channels in which the reagent is transported, at least one pneumatic channel is provided, through which valves are controlled by means of pumped air in the microfluidic device, which close or release the fluidic channels to allow the reagent to pass through the channel system in a targeted manner guide. The microfluidic device is inserted as a cartridge into an analyzer known commercially as Vivalytic®. In the analysis device, a pump is connected to the at least one pneumatic channel via a valve bank and pressure is built up in the at least one pneumatic channel in a targeted manner in order to control the valves and thus carry out an analysis.

Conventionally, the cartridges are filled in advance with the reagents required for the analysis. However, it may also be desirable to fill the cartridge with the reagent on site at short notice. For this purpose, the microfluidic device can have a receiving chamber (also referred to as a pre-storage chamber) with an opening into the environment, which is arranged on an outside of the cartridge and via which the reagent can be filled into the receiving chamber from the outside. The receiving chamber is preferably arranged close to the corresponding analysis component in order to keep the loss of reagent as low as possible. The receiving chamber with the opening is particularly advantageous for lyophilized reagents (also referred to as beads), since in this case transport to the pre-storage chamber, in which the bead is dissolved, and return transport can be dispensed with, which reduces the loss of reagent . A loss of reagent would lead to a change in concentration, which would falsify the analysis.

To use the cartridge, especially in the analysis device, the opening of the receiving chamber must be tightly closed. A closure is provided for this purpose, which is arranged on the outside of the microfluidic device. The closure is set up to close off an area of the microfluidic device, in which the opening is arranged, from the environment.

Disclosure of Invention

A microfluidic device is provided that has a receiving chamber. The receiving chamber has an opening into the environment, which is arranged on an outside of the cartridge. The receiving chamber is accessible from the outside via the opening, so that a reagent can be filled into the receiving chamber. In addition, the microfluidic device has a closure on the outside of the microfluidic device is arranged. The closure is set up to close off an area of the microfluidic device, in which the opening is arranged, from the environment. The closure can be of essentially any shape and can be larger than the opening or can be shaped and sized to fit directly into the opening. The closure thus closes the opening to the environment so that the fluidic sample cannot escape. Different types of closures can be provided, such as preferably a lid or, for example, a closure cap, a stopper, an adhesive film or something else. The closure can be by a folding mechanism such. B. a hinge, or by means of a sliding mechanism between a closed state and an open state.

In addition, the microfluidic device has a pneumatic channel that runs within the microfluidic device. Air is guided in the pneumatic channel and an overpressure or a negative pressure can be built up in it. The pneumatic channel has an end and is arranged such that the end lies in the area closed off by the closure. Consequently, in the closed state, the closure closes off the end of the pneumatic channel and the opening of the receiving chamber at the same time. Based on the overpressure or underpressure built up in the pneumatic channel, it can be determined whether the closure closes gas-tight. When the closure closes off the area with the opening, the end of the pneumatic channel is also sealed as a result, so that no air can escape and/or enter and the predetermined positive pressure or negative pressure is maintained. Please also refer to the procedure below. This means that if the predetermined positive pressure or negative pressure is maintained in the pneumatic channel, the closure tightly seals the entire area—that is, both the pneumatic channel and the opening of the receiving chamber. This has the advantage that it can be ensured that the closure seals the opening tightly, thereby preventing the reagent from escaping. Reagent spillage could result in contamination of the microfluidic device, analyzer, and/or the environment that is potentially hazardous to a person.

Advantageously, the pneumatic channel is already part of the microfluidic device and is used to control valves. Optionally, from the already existing pneumatic channel, a secondary channel with the branch off at the above end. This offers the advantage that an already existing duct can be used and, if at all, this only has to be expanded by the auxiliary duct, which enables simple production.

The pneumatic channel preferably has another end via which a pump can be connected. The pump can be part of an analysis device, for example. The overpressure or the underpressure is built up in the pneumatic channel by means of the pump.

The microfluidic device can also have multiple pneumatic channels. These are arranged in such a way that one end of the pneumatic channel is in different positions relative to one another in the area closed off by the closure. The plurality of pneumatic channels are preferably designed as described above. A wedged closure can be determined by the several ends of the pneumatic channels at different positions in the area closed by the closure. In the case of a wedged closure, in particular when it is a cover, some pneumatic channels are closed so that they maintain the predetermined positive pressure or negative pressure, whereas the positive pressure or negative pressure is reduced in other pneumatic channels. If the closure is a foil that is glued on, the several pneumatic channels can be used to determine whether the foil is correctly sticking at all the intended points and whether the opening is closed. In addition, by using several pneumatic channels in all types of closures, the difference between the predetermined overpressure or underpressure and the actual overpressure or

be increased.

In addition, a method for checking the status of a closure of a microfluidic device, as described above, is proposed. A pump is connected to another end of the pneumatic duct, i.e. to an end that is not in the area closed off by the closure. The other end of the pneumatic channel is preferably already set up to be connected to the pump or a pressure supply and advantageously has corresponding connections. An overpressure or a negative pressure is generated in the pneumatic channel by means of the pump. Based on the overpressure or underpressure built up in the pneumatic channel, it can be determined whether the closure closes gas-tight. When the closure closes the area with the opening, the end of the pneumatic channel is also sealed off, so that no air can escape and/or enter and the predetermined positive pressure or negative pressure is maintained. This means that if the predetermined positive pressure or negative pressure is maintained in the pneumatic channel, the closure tightly seals the entire area—that is, both the pneumatic channel and the opening of the receiving chamber. This has the advantage that it can be ensured that the closure closes the opening, thereby preventing the reagent from escaping. The emergence of reagent could lead to contamination of the microfluidic device, the analyzer and/or the environment that is potentially hazardous to a person.

The microfluidic device can be introduced into an analysis device for measurement. The pump described above is preferably a pump of the analysis device, which is connected to the other end of the pneumatic channel in order to generate the positive pressure or the negative pressure in the pneumatic channel.

In order to monitor the overpressure or the underpressure, at least one performance parameter of the pump can be determined, which is dependent on the pressure generated in the pneumatic channel. When the shutter is partially open, the pump requires more power to maintain positive or negative pressure. The status of the closure is then determined from the status of the performance parameter - i.e. a tightly closed closure or a (partially) open closure or leaky closure.

An electrical current applied to the pump, which can be measured, is regarded as a preferred performance parameter. When the shutter is (partially) open, the pump needs more power to maintain the positive or negative pressure, and therefore a higher electrical current. If the electrical current applied to the pump is below a current threshold value defined for the pump, a closed closure is determined. If the electrical current is above the defined current threshold value, an open closure is determined.

Alternatively, the pressure at the pump-side end of the channel can be measured directly. This is possible from the outside. In particular, the pressure in a Valve bank is measured, which is connected to the pump and which is connected to the pneumatic channel. The valve bank is preferably part of the analysis device and is placed directly on the pneumatic channel when the microfluidic device is moved into the analysis device. If the measured pressure changes by more than a pressure threshold - i.e. if the positive pressure decreases by more than the pressure threshold or if the negative pressure increases by more than the pressure threshold - a (partially) open occlusion is determined. Optionally, different pressure threshold values can be provided for the positive pressure and for the negative pressure.

The method described can also be applied to several pneumatic channels described above. In this case, the positive pressure or negative pressure is preferably determined separately for each pneumatic channel. By comparing the results obtained, it is possible to conclude that the closure is wedged, particularly if the closure is a lid. If the closure is a foil that is glued on, the several pneumatic channels can be used to determine whether the foil is correctly sticking at all the intended points and whether the opening is closed. In addition, the difference between the predetermined positive pressure or negative pressure and the actual positive pressure or negative pressure can be increased by using a plurality of pneumatic channels in all types of closures.

The computer program is set up to carry out each step of the method. It enables the method to be implemented in a conventional control unit without having to make structural changes to it. For this purpose, it is stored on the machine-readable storage medium.

By loading the computer program onto a conventional electronic control unit, the electronic control unit is obtained, which is set up to carry out the status check of the closure. The electronic control unit is preferably part of the analysis device.

Brief description of the drawings

Embodiments of the invention are shown in the drawings and explained in more detail in the following description. FIG. 1 shows a plan view of an exemplary embodiment of the microfluidic device according to the invention.

FIG. 2 shows a side view of the exemplary embodiment of the microfluidic device according to the invention.

FIG. 3 shows a diagram of the electrical current applied to a pump of an analysis device over time, with which an exemplary embodiment of the method according to the invention for checking the condition of a closure is carried out.

Embodiments of the invention

FIGS. 1 and 2 show an exemplary embodiment of the microfluidic device according to the invention in a plan view (FIG. 1) and in a side view (FIG. 2). The microfluidic device is designed as a lab-on-chip in the form of a cartridge 100 . The microfluidic device has a plurality of reaction chambers 110 and a channel system 120 which connects the reaction chambers 110 (see FIG. 1). In this exemplary embodiment, two of the reaction chambers are designed as receiving chambers 111, 112 into which a lyophilized reagent (Beat) can be placed (not shown). For this purpose, the receiving chambers 111, 112 have an opening to the outside, in this exemplary embodiment to the top, of the cartridge 100. A cover 130 is provided, which in this exemplary embodiment is designed as a flat disc which is inserted into a recess 101 of the cartridge 100 without protruding. The depression 101 is arranged above the receiving chambers 111, 112 on an outside of the cartridge 100 and extends over both receiving chambers 111, 112 away. The cover 130 is inserted into the depression 101 and thus closes the openings of the receiving chambers 111, 112 in the closed state.

In addition, a pneumatic channel 140 is provided inside the cartridge 100 . The pneumatic channel 140 ends with a first end 141 in the recess 101 on the outside of the cartridge 100. If the cover 130 is inserted into the recess 101, it closes not only the receiving chambers 111, 112 but also the first end 141 of the pneumatic channel 140. A second End 142 of pneumatic passage 140 is designed to connect to a pressure supply to be connected, for which the second end 142 has corresponding connections. Apart from the ends 141, 142 described, the pneumatic channel 140 has no further ends or openings to the environment. For reasons of clarity, only one pneumatic channel 140 is shown here. In further exemplary embodiments, a plurality of pneumatic channels can also be provided in a cartridge 100, the first ends of which are arranged at different positions and are each covered by the cover 130.

For analysis, the microfluidic device is introduced into a Vivalytic® analysis device (not shown). There, a valve bank, which is connected to a pump, is pressed onto the cartridge 100 with a sealing mat and a valve opening of the valve bank is connected to the second end 142 of the pneumatic channel 140 . If there are several pneumatic channels, one valve opening of the valve bank is assigned to one of the second ends. The pump builds up an overpressure in the valve bank, which is then conducted into the pneumatic channel 140 via the valve openings. Instead of the positive pressure, a negative pressure can also be used. The excess pressure can only dissipate via the first end 141 . When the cover 130 is inserted into the depression 101 and thereby tightly closes the receiving chambers 111, 112, it also seals the first end 141 of the pneumatic channel 140 at the same time and the excess pressure cannot be reduced. In the event that the cover 130 does not close tightly, the excess pressure can be released via the first end 141 . As a result, the pump has to use more power to maintain the overpressure in the pneumatic channel 140 . An electrical current I applied to the pump is directly related to its applied power and is measured.

FIG. 3 shows a diagram for two curves 201, 202 of the electrical current I, which is present at the pump, over time t. In both cases, after an initial rise and spike, the electric current I essentially levels off to a plateau. For the first course 201, the electric current I falls below a current threshold value Si. The pump thus applies less power and, as described above, a tightly closed cover 130 is detected. For the second course 202, the electric current I is above the current threshold value Si. The pump has to work harder, from which it can be concluded that the cover 130 does not close tightly. In this case, a warning can be issued. In further exemplary embodiments, the pressure in the valve bank can also be measured directly instead of a performance parameter of the pump, such as the electric current I. If the overpressure drops by more than a pressure threshold value during the measurement, an open cover 130 is determined. Otherwise, a closed lid 130 is detected.

In the exemplary embodiments with several pneumatic channels, the first ends of which are each covered by the cover 130, an overpressure can be built up separately for each pneumatic channel and a performance parameter of the pump can be determined or the pressure can be measured directly (see above). From the measured data it can be determined whether the lid is tilted.

Claims

Expectations

1. Having a microfluidic device,

- a receiving chamber (111, 112) with an opening to the environment;

- a closure (130), which is arranged on an outer side of the microfluidic device and is set up to close off an area of the microfluidic device, in which the opening is arranged, from the environment;

- A pneumatic duct (140), characterized in that the pneumatic duct (140) is arranged such that one end (141) of the pneumatic duct (140) is in the area closed off by the closure (130).

2. The microfluidic device as claimed in claim 1, characterized in that the microfluidic device has a plurality of pneumatic channels which are arranged in such a way that one end of the pneumatic channel lies in the area closed off by the closure.

3. Method for monitoring the condition of a closure (130) of a microfluidic device according to claim 1 or 2, characterized in that a pump is connected to another end (142) of the pneumatic channel (140) and an overpressure or a negative pressure in the pneumatic channel (140) generated.

4. The method according to claim 3, characterized in that at least one performance parameter of the pump is determined, which is dependent on the pressure generated in the pneumatic channel (140), and the state of the closure (130) is determined from the performance parameter.

5. The method according to claim 4, characterized in that the performance parameter is an electrical current (I) present at the pump and that a closed shutter (130) is determined when the electrical current (I) is below a current threshold value (Si) lies and that an open shutter (130) is determined when the electric current (I) is above the current threshold value (Si).

6. The method according to claim 3, characterized in that a pressure at the pump-side end (142) of the pneumatic channel (140) is measured, with an open closure (130) being determined if the pressure changes by more than a pressure threshold value and otherwise a closed shutter (130) is determined.

7. The method according to any one of the preceding claims, characterized in that the microfluidic device is inserted into an analysis device and a pump of the analysis device is connected to the other end (142) of the pneumatic channel (140) in order to generate the positive pressure or the negative pressure.

8. A computer program which is set up to carry out each step of the method according to any one of claims 3 to 7.

9. Machine-readable storage medium on which a computer program according to claim 8 is stored.

10. Electronic control unit which is set up to carry out a status check of a closure by means of a method according to one of claims 3 to 7.