巴西专利BR112012009300A2 microfluidic cartridge, pneumatic interface plate, fluid drive system within a microfluidic cartridg

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MICROFLUID CARTRIDGE, PNEUMATIC INTERFACE PLATE, SYSTEM FOR DRIVING FLUID INSIDE A MICROFLUID CARTRIDGE, AND PNEUMATIC INSTRUMENTThe invention relates to a design for an interface plate (101) between a microfluidic cartridge (100) and an instrument (102), for actuating a fluid from a disposable cartridge. The pneumatic drive is performed by means of a reversible pneumatic interconnection between the instrument and the cartridge. Pneumatic actuators are integrated into the instrument, in a reliable and low-cost solution. The activation of the fluid in the cartridge is achieved by means of a flexible membrane (105), attached to the larger surface of the disposable cartridge, forming closed compartments only when attached to the instrument. The pressure in these compartments determines the deflection of the membrane, which in turn drives the fluid. This approach takes advantage of the great power and great blow of the pneumatic drive, while, at the same time, keeping the disposable cartridge simple and inexpensive, allowing the easy introduction of other transport, physical through the interface board, such as heat and acoustic vibration . A large number of actuators can be easily integrated into a flat interface plate, since no individual fixing is required, such as a pipe for pneumatic actuation.
公开号:BR112012009300A2
申请号:R112012009300-2
申请日:2010-10-06
公开日:2020-08-18
发明作者:Reinhold Wimberger-Friedl；Roel Penterman；Hendrik Halling Van Amerongen；Theodorus Antonius Johannes Loring；Martijn Jochem Van Uden
申请人:Biocartis Sa；
IPC主号:

专利说明:

| . 1/16: “MICROFLUID CARTRIDGE, PNEUMATIC INTERFACE PLATE, SYSTEM 'FOR DRIVING FLUID INSIDE A MICROFLUID CARTRIDGE, AND, PNEUMATIC INSTRUMENT”
FIELD OF INVENTION The invention relates to driving fluids in microfluidic cartridges. The invention relates, in particular, to a microfluidic cartridge to be inserted into a pneumatic instrument's parallel pneumatic interface plate, an interface plate to interface with a microfluidic cartridge and between a pneumatic instrument, and, a actuation of the fluid inside the microfluidic cartridge, comprising this cartridge and an interface plate, and, concerns a pneumatic instrument.
BACKGROUND OF THE INVENTION Biosensors are used for the detection of molecules in biological samples, for example, proteins or DNA, for application in diagnostics. They should also be used to detect drugs, in therapies and abuse, in the blood, urine or saliva. These tests are designed to be used in many different environments and establishments, such as, for example, at the point of care in medical applications, or, anywhere you want to abuse drugs, such as on the highways. In all cases, a robust, reliable and sensitive device is required, which must also have a low cost, since it will need to be discarded after measurement.
To carry out this biochemical test requires a certain degree of manipulation of the fluid; the sample fluid must at least be inserted into the sensor device to allow the target molecules to be attached to the sensor surface. Depending on the type of sample, more or less complicated microfluidic systems are designed. Since the sample is contaminating, it must not come into contact with the instrument and must be stored safely in the cartridge during and after measurement.
Microfluidic systems fully integrated in chips or lab in chip systems have recently been developed. One issue in these microfluidic systems is the handling of fluids in and from the different reaction chambers, for which micro actuators, such as pumps and valves, are needed. Pumping and using valves can be done in several ways. Depending on the application, for example, the types of assays, the performance requirements, the activation of the fluid for dissolving the reagents, for incubation, for fixing and washing, for example, is implemented in different ways. There is a trade-off between the degree of control and simplicity, in which simplicity can be identified at low costs. Either the fluid is driven directly by a mechanical meter with pistons, or, the fluid is not driven, but, directed by capillary forces, in, so-called,
It is 2/16 'passive targeting.
The latter is a cost efficient solution, but does not allow the flow to be reversed; the flow rate is limited and is not constant with distance, and, more importantly, it is dependent on the viscosity and surface tension of the fluid. A modification required by the characteristics of the fluid needs to be implemented in the disposable “hardware”, which makes the system less flexible. Mechanical steering, on the other hand, is very flexible, but requires physical contact, which creates problems with the instrument's operational life and contamination and cleaning problems.
Thus, low-cost technology may be required to drive the fluid in microfluidic systems, especially in disposable medical devices, such as biosensors.
SUMMARY OF THE INVENTION It is an object of the invention to provide improved fluid drive in microfluidic cartridges.
The embodiments described in this way belong to the microfluidic cartridge, the pneumatic interface plate, the system comprising the microfluidic cartridge and the pneumatic interface plate, and the pneumatic instrument. Synergistic effects may arise from different combinations of embodiments, although they may not be described in detail.
According to a first embodiment of the present invention, a microfluidic cartridge to be placed on a pneumatic interface plate of a pneumatic instrument, is provided. The cartridge comprises a three-dimensional fluid channel, in which a fluid must be transported, by pneumatic pumping by a pneumatic instrument. Furthermore, the microfluidic cartridge comprises a flexible membrane, the flexible membrane extending in a plane and the flexible membrane building an external surface of the cartridge. In addition, the three-dimensional fluid channel is spatially defined in three dimensions by the inner walls of the cartridge and the flexible membrane, and that the flexible membrane is in a fundamental state when no pressure or vacuum is applied to the flexible membrane. The flexible membrane can be pneumatically deflected from the ground state, perpendicular to the plane of the flexible member in two directions, when the cartridge is placed on the parallel pneumatic interface plate.
In other words, the fluid is not transported on a flat surface, but moved along the three-dimensional liquid channel.
In addition, the flexible membrane can be pneumatically deflected in areas that are part of the outer surface of the cartridge. In other words, in a first region of the flexible membrane, the fluid channel extends, the first region of which forms part of the outer surface of the cartridge. Thus, for this exemplary embodiment,
. 3/16. the flexible membrane can extend further into a second region, under the outer surface of the cartridge, so that the membrane cannot be accessed from outside the cartridge in that second region.
Furthermore, the “fundamental state of the flexible membrane” describes the situation in which no pressure and no vacuum is applied to the flexible membrane. From this situation, the flexible membrane can be deflected towards the inner part of the cartridge, and can also be deflected away from the cartridge. This can be seen, for example, in Fig.1, in which an upward and downward deflection of the membrane, in different positions along the membrane, leads to a desired transport of the liquid. In other words, the flexible membrane can be deflected in two directions, namely, in the direction of the fluid channel and away from the fluid channel. However, this does not exclude the fact that the flexible membrane can be pre-compressed or pre-deflected.
The cartridge, which can in this and other embodiments, for example, be a disposable cartridge, allows a pneumatic drive, which is carried out by means of a pneumatic interconnection between the pneumatic instrument and the cartridge, which interconnection is formed through the flexible membrane. Pneumatic drivers are integrated into the instrument for a low-cost and reliable cartridge solution. The actuation of the fluid, which is contained in the fluid channel inside the cartridge, is achieved by the deflection of the flexible membrane that can be affixed to the most important surface of the cartridge. In this way, when the cartridge is attached or inserted in the pneumatic interface plate, compartments are formed, through the flexible membrane of the cartridge and parts of the pneumatic interface plate. The pressure in these compartments, pressure that can be generated by the separate pneumatic instrument, determines the deflection of the flexible membrane, which in turn drives the fluid through which a movement is caused.
The microfluidic cartridge takes advantage of the high power and great blow of the pneumatic drive, while maintaining a simple and low-cost cartridge, which allows for the easy introduction of other physical transport, through the interface board, such as, for example , heat and acoustic vibration.
In addition, a large number of actuators can be easily integrated into the flat pneumatic interface plate, since individual fixings, such as pipes, are not required for pneumatic actuation.
In other words, as elements of pneumatic pipelines and elements generating pressure and vacuum are not present in the microfluidic cartridge, and, as they are not present in the corresponding interconnect interface board, a large number of actuators can be easily integrated into the interface. In other words, a flat microfluidic cartridge is provided, which can, in connection with the flat pneumatic interface plate, allow convenient and reliable pneumatic targeting
- 4/16. of fluids in the cartridge, without the need for piping inside the cartridge. Furthermore, this can also be easily extended to a large number of pneumatic elements, as the integration of thermal, acoustic and other interface plates in the same plane can be simplified.
: The term pneumatic elements, in this and all other embodiments of the invention, describes positions in which the flexible membrane is pneumatically operated, that is, valves and pumps, or, more generally, areas of interaction. It is also the flexibility of changing positions and the ability to have a position of great proximity that constitutes an advantage of the present invention.
An essential characteristic of the microfluidic cartridge that is provided can be considered, the fact that the fluids are activated in the cartridge by a pneumatic instrument. The facts that pneumatic steering uses a flexible cartridge membrane and that the pneumatic chambers underlying the membranes are reversible are important. This means that the separation plane between the cartridge and the pneumatic instrument passes through the pneumatic chambers.
In other words, when the cartridge is removed, the pneumatic supply channels, the pneumatic channels and the pneumatic chambers are opened. The pneumatic chambers underlying the driven membrane are formed by the combination of the cartridge and the interface plate on the instrument. When the cartridge is lifted, the pressure can no longer be transferred to the membrane; unlike the tubing, which is not used to drive the membrane, according to the present invention, and which tubing is mechanically attached.
This microfluidic cartridge can be used in combination with a pneumatic instrument that contains supply channels for pneumatic actuation, and that contains a substantially flat interface plate, in the direction of the microfluidic cartridge that contains the fluid channels. The fluid channels are confined by a flexible layer, which can be activated once the cartridge is placed in the instrument. When moving the flexible membrane up and down, the volume is displaced inside the cartridge, and the membrane can close channels, to provide a valve function within the fluid channel.
The deflection stroke of the membrane is based on the height between the position of the membrane, when it touches the pneumatic interface plate of the pneumatic instrument, as can be seen, for example, in Fig.1 below, and / or the position when it touches the substrate chamber, on top of the membrane in the cartridge (control characteristics).
In other words, the microfluidic cartridge comprises a flexible membrane that covers the flow path. In this way, the flexible membrane covers the entire fluid channel system, which can contain multiple fluid paths. It doesn’t have to be the entire outer surface everywhere, but it’s also possible a way of realization in which the
- 5116 'flexible membrane builds the entire outer surface of the cartridge. However, the flexible membrane is always attached to the cartridge. After inserting the cartridge in a pneumatic instrument, the membrane is locally deflected by the tires in the instrument, so that the fluid is displaced along the flow path inside the cartridge. The membrane is locally sucked away, or pushed towards the cartridge, creating a changing volume in the flow path and under the membrane, with such a change in volume the fluid is transported along the cartridge. Furthermore, the cartridge can comprise walls which, together with the flexible membrane, define a changing volume through which the fluid can be transported. In this way, the invention allows the transport of a fluid in the microfluidic cartridge, using a relatively simple interface plate, between the cartridge and the instrument, to process the cartridge. Instead of the pneumatic interface pipes, the interface plate between the cartridge and the instrument is formed by the flexible membrane, which is deflected by the instrument, so that the fluid is transported inside the cartridge.
As the cartridge has no pneumatic and electrical elements, it can be produced in a cheap and reliable way.
The flexible membrane, in combination with the interface board, makes it possible to attach the cartridge to the interface board by means of pneumatic forces only.
In this way, no other means of attachment, such as screws and similar means, are necessary, other than the pneumatic forces generated by the pneumatic instrument. This is the reason why the pneumatic interface board is called a parallel board. In other words, the deflection of the flexible membrane is created, in a closed pneumatic system, which comprises the cartridge and the interface plate; and, deflection, in turn, leads to fixation. The suction of the membrane creates the fixation.
According to another exemplary embodiment of the invention, the cartridge has a substantially cuboidal shape, having six main outer surfaces, whereby the flexible membrane forms one of the main surfaces of the cartridge and through which the flexible membrane extends completely in the fluid channel .
This embodiment can, for example, be seen in Fig.2, as well as in the example in Fig. 8..
According to another exemplary embodiment of the invention, the fluid channel and the flexible membrane are arranged with each other, so that, by deflecting the flexible membrane at various points along the flexible membrane, by the pneumatic pumping of the instrument pneumatic, the fluid can be transported from the beginning of the fluid channel to an end of the fluid channel. 'In this way, the terms "pneumatic pumping" and "pneumatic steering" include the application of an overpressure and / or an underpressure on the surface of the flexible membrane to first attach the microfluidic cartridge to the interface plate
- 6/16. and, in this way in the pneumatic instrument, and, in second place, to deflect the flexible membrane of the cartridge so that the transport of the fluid is achieved, inside the fluid channel in the cartridge, as desired. In other words, the membrane can be locally sucked away or pushed towards the inside of the microfluidic cartridge, which creates a volume change in the fluid channel, as well as under the flexible membrane.
When creating this movement of the flexible membrane, by pneumatic pumping, the fluid in the cartridge is transported.
According to another exemplary embodiment of the invention, the membrane can be deflected by pneumatically pumping the pneumatic instrument, in a way that the membrane closes the fluid channel to provide a valve function.
In other words, the combination of the microfluidic cartridge with the pneumatic interface plate and the pneumatic instrument, in overpressure and / or underpressure, can be applied to the membrane, so that the fluid path is closed by the deflected membrane. In other words, the fluid path can be spatially divided into different sections, with a first section containing fluid, and a second section being free of fluid. These sections can be spatially separable by providing a valve function.
In the event that the valve function is performed, so that the membrane closes the pneumatic channel of the interface plate, that is, the membrane is sucked in the direction of the plate, then this is also used to fix the cartridge on the plate. interface, as described in more detail below.
According to another exemplary embodiment of the invention, the cartridge is free of pneumatic control elements and free of pneumatic pipe elements.
In other words, when compared to a state of the invention, an advantageous physical separation between the microfluidic cartridge and the instrument is provided; This instrument comprises a pneumatic interface board with all the electrical and pneumatic elements necessary for generation and control. The cartridge can be changed quickly and easily, since no screws or other means of fixation are required.
According to this exemplary mode of the invention, the functionality of generating overpressure, underpressure and vacuum, and its application, is completely removed from the cartridge, and can be placed, for example, on an external pneumatic instrument that has a plate pneumatic interface. This can reduce cartridge costs, which is extremely important for a disposable microfluidic cartridge system. Furthermore, the deficiencies of the cartridge can be increased, since a technical complexity is present.
According to another exemplary embodiment of the invention, the microfluidic cartridge comprises control characteristics, whereby the characteristics of
4 o.5o Rê IX. ôAÁLÓCQMôÓAÓ Ô »Ó« PA “2X“ .X »MAR £ OO OOO OO A ÂO“ O º ““ ““ ““ ““ C “º“ OS A AE OÇ — O— O——. 7116: controls are adapted to control the strokes of the flexible diaphragm during pneumatic pumping by the pneumatic instrument.
Furthermore, the control characteristics of this and each of the other embodiments of the invention are also adapted to improve the valve function, which is generated when the flexible membrane is deflected.
As can be seen from the examples in Figs.1 and 2, these control characteristics determine, at some points along the fluid channel, a certain distance between the flexible membrane and the opposite spatial boundary of the fluid channel. In other words, these control characteristics expand the fluid channel. By combining the cartridge with the pneumatic interface plate, as described above, below and in the example in Fig. 1, a relief control feature, above and below the flexible membrane, is provided, with which the specific deflections of the membranes, which are desired, can be caused by the application of an overpressure or an underpressure on the flexible membrane, through the pneumatic chambers of the interface plate.
Furthermore, it is possible, according to an exemplary embodiment of the invention, that rubber structures are only part of the microfluidic cartridge. These can then be placed, for example, inside the microfluidic cartridge. In this way, for example, they can be combined with the flat interface board.
According to another exemplary embodiment of the invention, the rubber structures and the recesses can both be present in the cartridge and the interface plate.
According to another exemplary embodiment of the invention, a pneumatic interface plate, for interfacing with the microfluidic cartridge, according to one of the preceding embodiments, and, among the pneumatic instrument, for applying a pneumatic pumping in the microfluidic cartridge, is provided. The pneumatic interface plate can be inserted between the microfluidic cartridge, according to one of the preceding embodiments, and, between the pneumatic instrument, to apply pneumatic pumping to the microfluidic cartridge. An insertable interface board allows the use of different interface boards with a single pneumatic instrument, resulting in greater flexibility when using the different interface boards of different designs. The pneumatic interface plate comprises an instrument side, which faces the instrument, when the interface plate is inserted into the instrument. Furthermore, the interface board comprises a cartridge side, which faces the cartridge, when the cartridge is inserted into the interface board. This interface board comprises a pneumatic channel, which connects a pneumatic fluid from the pneumatic instrument, from the instrument side to the cartridge side, to allow pneumatic targeting of the flexible membrane of the microfluidic cartridge,
. 8/16. the side of the cartridge having at least one recess, to suck the flexible membrane from the cartridge.
In other words, the cartridge side of the interface board is adapted to receive the cartridge, so that a closed pneumatic system is formed; which allows, first, the fixation of the cartridge by means of pneumatic forces, and, secondly, it allows pneumatic pumping. In this way, no screws or other means of attachment are needed to connect the cartridge with the interface board, and thus connect with the instrument. This is the reason why the pneumatic interface board is called a parallel board. Furthermore, the cartridge can be removed just by turning off the suction of the underpressure on the cartridge.
In this way, the suction must be understood as allowing the deflection of the flexible membrane. Furthermore, the recess can also be part of the cartridge.
The pneumatic interface plate, of this and all other embodiments of the invention, may be part of a microfluidic cartridge, but may also be part of a pneumatic instrument.
It should be explicitly noted that the embodiments below, and those described above, of the pneumatic interface plate may also form a part of a system comprising the microfluidic cartridge, as described above, and below, and such a pneumatic interface plate.
It should be explicitly noted that the pneumatic interface plate can be a substantially unique physical element, which must be integrated into a pneumatic instrument. Furthermore, it is possible that the pneumatic interface plates, described above and below, are a substantial component of such a pneumatic instrument and can be fully integrated with such a pneumatic instrument.
The combination of the pneumatic interface plate allows the assembly of the pneumatic chambers underlying the membranes, as can be seen, for example, in Fig.1. In other words, the plane of separation between the cartridge, which can be a disposable cartridge, and the instrument passes through the pneumatic chambers.
These pneumatic chambers can also be used to keep the cartridge on the interface board, to ensure good thermal and mechanical contact between the interface board and the cartridge, which can be crucial for different functions, such as heating, and the activation of the fluid by ultrasound.
In addition, a large number of zones, or interaction elements, such as the pneumatically operated points, or the heat transfer areas, or others, can be integrated into such a combination of microfluidic cartridge and a pneumatic instrument and a pneumatic interface board, since they do not require an extra footprint, since they are placed underlying the microfluidic cartridge. In this way, the description of the extra footprint, which is avoided according to this embodiment
. 9/16. exemplary of the invention, it is compared with the situation in which a pipe connection should have somewhere, and a separate supply channel, in the direction of the position in which the pneumatic actuation should occur. However, according to the present invention, pneumatic connections are merely through channels on the interface board, so that no additional space is required.
According to another exemplary embodiment of the invention, at least the cartridge side and the instrument side of the pneumatic interface plate are substantially flat.
For example, the cartridge side of the pneumatic interface plate is substantially flat, which makes it possible to combine the pneumatic interface plate with a flexible and substantially flat membrane of such a microfluidic cartridge.
According to another exemplary embodiment of the invention, the pneumatic interface plate comprises at least one element, chosen from a group comprising a heat generating device; a heat transfer device made of aluminum; a heat transfer device made of copper; a heat transfer device made of an aluminum and / or copper alloy; a heat generating device that has heat transfer elements that extend to the microfluidic cartridge; an acoustic energy generating device; a device for the treatment of fluid with ultrasound, focused or unfocused; a piezoelectric driver; a mechanical driver; a magnetic driver; and, any combination thereof.
In other words, the fluid heating functionality that is contained within the cartridge is purely integrated into the pneumatic interface plate, which leads to the fact that the microfluidic cartridge can be produced in an inexpensive, reliable and easy way. Multiple cartridges can be used only with a combination of this pneumatic interface plate and a pneumatic instrument. A quick change of the microfluidic cartridge can be performed, using this cartridge, with reduced functionality.
For example, the heating elements can be separated, by a thermally insulating material, from the pneumatic stainless steel interface plate.
According to another embodiment of the invention, the pneumatic interface plate is made of a material, chosen from a group comprising steel, stainless steel, other chemically resistant and moderately conductive materials, and any combination thereof.
Furthermore, according to another exemplary embodiment, the pneumatic interface plate may further comprise rubber characteristics and / or compressible characteristics, around the pneumatic elements, to provide the seal between the different pneumatic chambers.
According to another exemplary embodiment of the invention, a pneumatic interface plate is provided, which comprises control characteristics, being that
- 10/16: the control characteristics are adapted to control the actuation stroke of the: flexible membrane of the microfluidic cartridge during pumping by the pneumatic instrument.
In addition, the control characteristics can be applied to allow a better closing of the valve, when the membrane bends around these control characteristics, when a pressure is applied.
According to another exemplary embodiment of the invention, a system for driving the fluid inside the cartridge is provided. The system comprises a microfluidic cartridge, according to one of the preceding embodiments, and comprises a pneumatic interface plate, according to one of the preceding embodiments, whereby the flexible membrane of the cartridge can be deflected by pneumatic pumping by through the pneumatic channel, so that a fluid in the fluid channel can be moved along the fluid channel.
The system allows the activation of the fluid inside a cartridge, which can, for example, be disposable. The pneumatic actuation of the fluid is carried out by means of the flexible membrane, which separates the fluid in the cartridge from the pneumatic fluid in the instrument. Pneumatic drivers can be integrated, within the pneumatic instrument, for a low-cost and reliable solution of this system.
It can be observed, as an essential characteristic of the system provided, that the fluids inside the cartridge can be driven or directed, that is, transported by an external pneumatic instrument, and that the pneumatic steering makes use of a flexible membrane that is part of the cartridge, and that the pneumatic chambers are formed underlying the flexible membrane, inside the pneumatic interface plate, and reversibly mounted. In other words, the separation plane between the cartridge and the external pneumatic instrument passes through the pneumatic chambers.
According to another exemplary embodiment, the cartridge and the pneumatic interface plate are two separate physical components, which are held together in a reversible way to drive the fluid, only by pneumatic forces.
According to another exemplary embodiment of the invention, the flexible membrane and the cartridge side of the interface plate are adapted in combination, so that, by applying a pressure along the pneumatic channel of the pneumatic interface plate, the cartridge is completely attached to the interface board.
In this way, no other means of fixation, such as, for example, screws and similar means are necessary, besides the pneumatic forces generated by the pneumatic instrument, which can also be part of the system. In other words, the deflection of the flexible membrane is created in a closed pneumatic system, which comprises the cartridge and the interface plate, and the deflection, in turn, leads to fixation. The suction of the membrane creates the fixation.
- 11/16. According to another exemplary embodiment, the system comprises a pneumatic instrument for generating pneumatic pumping for a microfluidic cartridge. In this way, pneumatic pumping comprises the generation and application of over and under pressure.
According to another exemplary embodiment of the invention, the cartridge and the interface board are mechanically connected to each other, by means of a flexible membrane, and via the cartridge side of the interface board.
According to another exemplary embodiment of the invention, the transport of the fluid in the fluid channel is only initiated by pneumatic pumping through the pneumatic channels.
This exemplary embodiment can be seen from the example in Fig. 1, in the figures that follow. On the other hand, to form a closure, several pneumatic chambers are assembled, or are formed, when the cartridge and the interface board are physically connected. These pneumatic chambers, which are below the flexible membrane, are inside the recesses of the pneumatic interface plate.
In addition, these chambers can also be used to maintain a cartridge on the pneumatic interface plate, to ensure good thermal and mechanical contact, between the pneumatic interface plate and the cartridge, which can be crucial for various functionalities.
According to another exemplary embodiment of the invention, the system comprises control characteristics, whereby control characteristics are arranged above and below the flexible membrane, according to which the control characteristics above the flexible membrane are arranged as obstacles for transporting the fluid within the cartridge channel. In addition, the flexible membrane is mechanically supported by the control characteristics, so that the membrane deflects during pneumatic pumping, so that the obstacles can be overcome by the fluid.
'In other words, the spatial distribution, or spatial arrangement, of the control characteristics, along the longitudinal elongation of the flexible membrane, leads to the fact that certain control characteristics block the fluid channel, for fluid movement, when the membrane is in a relaxed state, or pressed against the characteristics by applying an overpressure to the pneumatic chamber. When applying a corresponding pneumatic pumping, which means applying an overpressure and / or an underpressure to the corresponding pneumatic channels within the interface plate, this leads to a deflection of the membrane, so that the fluid can be transported along the fluid channel, without also being blocked by the control feature. In other words, the fluid can be transported around the control characteristics that are in the
- 12/16. fluid channel.
According to another exemplary embodiment of the invention, the system comprises pneumatic chambers, in which, between the flexible membrane and the interface plate, the pneumatic chambers are reversibly mounted.
In other words, the interconnected surface of the cartridge's flexible membrane, which forms the outer surface of the cartridge in combination with the cartridge-side surface of the pneumatic interface plate, leads to certain recesses below the membrane and within the pneumatic device, which can be used to apply an over and / or under pressure, against the membrane, by an external pneumatic device, which can be connected with the pneumatic interface plate.
According to another embodiment of the invention, the system comprises an interface plate, which comprises a plurality of pneumatic channels, for connecting the pneumatic fluid of the pneumatic instrument, from the instrument side to the cartridge side, to allow a pneumatic routing of the flexible membrane of the microfluidic cartridge. In this way, the interconnection between the flexible membrane and the interface plate is adapted, so that alternating pneumatic pumping, which includes the application of pressure and the application of sub-pressure, leads to the transport of the fluid along the fluid channel.
According to another exemplary embodiment of the invention, a pneumatic instrument, for generating pneumatic pumping into a microfluidic cartridge, for transporting fluid within the microfluidic cartridge, is provided. The pneumatic instrument comprises a means of pneumatically actuating a flexible membrane of a microfluidic cartridge, and a pneumatic interface plate, according to one of the embodiments described above. The pneumatic interface plate can be removable from the instrument, leaving an instrument, which comprises a pneumatic actuation means for the flexible membrane of the microfluidic cartridge, and, suitable for receiving a pneumatic interface plate, according to this invention.
It can be seen as the main point of the invention, the supply of a combination of a microfluidic cartridge and a pneumatic interface plate, in which an external surface of the microfluidic cartridge, which is formed by the flexible membrane, is driven by the pneumatic interface plate, which provides the overpressure or underpressure that is created by the pneumatic instrument, for the membrane. This leads to the corresponding deflection of the membrane, which, in turn, initiates the transport of the fluid contained in the cartridge, through the fluid channel in the cartridge.
It should be noted that the embodiments of the invention are described with reference to different materials. In particular, some embodiments are described with reference to cartridge claims, whereas other embodiments are described with reference to pneumatic interface plate claims,
Ss 13/16 'system claims, instrument claims. However, any person skilled in the art will understand, from the descriptions above and below, unless otherwise noted, that in addition to any combinations or characteristics pertaining to a type of matter, and also that any combination of characteristics relating to different matters are considered included in the disclosure of this registration application.
The aspects defined above and additional aspects, characteristics, and advantages of the present invention can also be derived from the examples of the embodiments to be described hereinafter, and are explained with reference to the examples of the embodiments. The invention will be described in greater detail, hereinafter, with reference to examples of embodiments, to which, however, the invention is not limited.
DESCRIPTION OF THE DRAWINGS Fig.1 shows schematically a microfluidic cartridge, a pneumatic interface plate and a pneumatic instrument, according to an exemplary embodiment of the invention.
Figs. 2 - 5 schematically show a microfluidic cartridge and a pneumatic interface plate, according to exemplary embodiments of the invention.
Fig. 6 schematically shows a pneumatic instrument with a microfluidic cartridge and a pneumatic interface plate, according to an exemplary embodiment of the invention.
Fig. 7 schematically shows an instrument in which the microfluidic cartridge and a pneumatic interface plate can be integrated, according to an exemplary embodiment of the invention.
Fig. 8 schematically shows a microfluidic cartridge, according to an exemplary embodiment of the invention.
DETAILED DESCRIPTION OF THE MODES OF CARRYING OUT The similar or related components in the various figures are provided with the same reference numbers. The view in the figure is schematic and is not fully scaled.
Fig. 1 shows the top part of a system 121 for driving fluid, inside a microfluidic cartridge 100, in a first state, where, the bottom part of Fig. 1 shows this system 121, in a second state, in which the fluid contained within the cartridge was transported. Both the top and bottom systems consist of the same elements.
Fig. 1 shows a microfluidic cartridge 100, to be inserted into the parallel pneumatic interface plate 101 of a pneumatic instrument, in which the cartridge comprises a three-dimensional fluid channel 103, in which fluid 104 should be 14/16. transported. Furthermore, the cartridge comprises a flexible membrane 105, according to which the flexible membrane extends a plane. The plane extends along direction 107. Furthermore, the flexible membrane builds an external surface of the cartridge, in which the fluid channel is spatially defined by the walls of the cartridge and the flexible membrane. Furthermore, the flexible membrane is in a relaxed state, in which no overpressure, or underpressure, or vacuum is applied to the flexible membrane. The flexible membrane can be pneumatically deflected, from a relaxed state, perpendicular to the plane of the flexible membrane, in two directions. In other words, the membrane 105 can be directed in the direction 106 first upwards, and secondly, in the direction downwards.
Furthermore, it can be seen that the flexible membrane is deflected at various points 109, 110, 111 and 114 by pneumatic pumping 108. In this way, pneumatic pumping means that an overpressure, and / or an underpressure, is applied to the membrane in pneumatic chambers such as 137. The external pneumatic instrument 102 can create this pneumatic pumping 108. By applying a corresponding under pressure in the two pneumatic channels 122 and 123, inside the pneumatic interface plate 101, the flexible membrane 105 is sucked into recesses, above these pneumatic channels. By changing the pressure situation within the pneumatic channels of the pneumatic interface plate, which is shown in the figure below in Figure 1, the flexible membrane is pressed, towards the inside of the cartridge, into the pneumatic channel in the middle of the cartridge. Additionally, a sub-pressure is applied to the pneumatic channel 130, on the right side, so that the fluid is transported from the left side of Fig. 1, to the right side of Fig.1, inside the fluid channel.
As can be seen from Fig.1, the interface board has an instrument side 119, which faces the instrument, when the interface board is inserted in instrument 102. Furthermore, the interface board has one side cartridge number 120, which faces the cartridge, when the cartridge is inserted into the interface board. Pneumatic channels 122, 123 and 138 are provided to connect a pneumatic fluid, such as air, from the instrument side to the cartridge side, to allow pneumatic routing of the flexible membrane of the microfluidic cartridge. The recesses 124 to 126 allow the suction of the flexible membrane into the recesses. As can be seen at the bottom of Fig. 1, in the middle of the pneumatic channel 122, the membrane closes the fluid channel, to provide a valve 114 within the fluid channel.
With the application of this method, with successive application of overpressure and / or underpressure, in a corresponding way, the fluid can be transported from the beginning 112 of the fluid channel, to the end 113 of the fluid channel, inside the microfluidic cartridge .
s 15/16 'It can be seen that the cartridge side of the pneumatic interface plate has a ladder-shaped surface, with recesses and pneumatic channels, which are formed in a T-like manner when viewed from within the channels tires and recesses in a cross section.
In other words, this embodiment provides a cartridge, comprising an external flexible membrane, which covers the fluid path. After inserting the cartridge into the instrument, the membrane is locally deflected by the instrument's tires, so that the fluid is displaced along the fluid path. The membrane is either sucked away locally, or pushed towards the cartridge, creating a changing volume in the fluid path, which is the fluid channel and under the membrane, with which the fluid is transported along the cartridge. The cartridge may comprise walls which, together with the flexible membrane, define a changing volume, through which the fluid can be transported.
Fig. 2 shows a system 121 comprising a microfluidic cartridge 100 and a pneumatic interface plate 101. A pneumatic instrument (not shown) can also be understood.
The interface plate may be substantially flat, and may contain features to improve the sealing of the pneumatic chambers, and / or may contain features that control the drive stroke of the cartridge's flexible membrane. In an alternative embodiment, shown in Fig.3, these stroke control characteristics 127, 128, 129 and 130, as well as 115 and 116 are integrated into the cartridge.
Fig. 3 shows a stroke control feature 127 through 130 on the cartridge side of the pneumatic interface plate 101.
Fig. 4 shows a system 121 with a cartridge 100 and an interface plate 101, in which the rubber structures 139 are part of the interface plate, and the recesses 140, 141 are present partially in the cartridge and partially in the interface plate. .
Furthermore, it is possible, according to another exemplary embodiment of the invention, that the rubber structures are only part of the microfluidic cartridge. They can then be placed, for example, into the microfluidic cartridge. They can, for example, be combined with the flat interface board.
According to another exemplary embodiment of the invention, the rubber structures and the recesses can both be present in the cartridge and the interface plate.
As can be seen from Fig. 5, the interface plate, as described above and below, can be used to hold the cartridge by applying a vacuum 131 in areas between the actuators, through the instrument interface plate. . Furthermore, on the side of the cartridge 101, the rubber structures 139 are applied, which can also be seen in Fig. 8, with reference to the mark 139. These structures are “AS“ OS O a ——.— -. 16/16 rubber allow tight sealing of pneumatic chambers.
The actuators' are attached to the pneumatic channels, on the underside (of the instrument) of 100. In this way, the actuation is all positions in which the membrane is reversibly deflected by the pneumatic system.
In areas where you want to hold the cartridge under vacuum, the membrane will not be deflected.
In addition, it is possible to apply another layer on the outer side (on top of the membrane) to prevent delamination of the membrane by vacuum forces.
In Fig. 6 a pneumatic instrument 102 is shown, which comprises a pneumatic interface plate 101. The instrument may have switches and heaters that are integrated within the box shown.
Furthermore, pneumatic tubing 1 is comprised within instrument 102; in addition, pneumatic switches and heaters are integrated into this instrument.
Fig. 7 shows a system 12, according to another exemplary embodiment of the invention.
The system consists of a pneumatic instrument 102 and a pneumatic interface plate 101, which is adapted to receive a microfluidic cartridge (not shown here, but, shown in Fig. 8). Various heaters 135, 136 are shown inside the interface plate and, in addition, pneumatic channels 122, 123 and 138 are shown.
Furthermore, recesses 124, 125 and 126 can be seen from Fig. 7. The pneumatic interface plate shown 101 corresponds to the interface plate shown in Fig.2. The rubber structures 101 correspond to the interface plate shown in Fig.2. The rubber structures 139 are also shown and described in Fig. 5, can be clearly seen.
Fig. 8 shows a microfluidic cartridge 100 which can, for example, be integrated into the interface plate 1001 of Fig. 7, and can thus be inserted into instrument 102. This corresponding cartridge of instrument 102 of Fig 7 has individual addressable valves, which can be directed by the instrument shown in Fig. 7. In this way, the term directed refers to pneumatic pumping.
For example, the valves can be closed by applying up to 1.5 bar of overpressure to the valves, which allows a reliable sealing of the individual compartments.
Pumping speeds of more than 1 ml in 10 seconds can be achieved.
These are just examples of values.
Other higher or lower pressures, and higher and lower pumping speeds can also be achieved.

权利要求:
Claims (15)
[1]
- '13: CLAIMS i 1. Microfluidic cartridge (100) to be placed on a parallel pneumatic interface plate (101) of a pneumatic instrument (102), the cartridge characterized by the fact that it comprises: a three-dimensional fluid channel (103) , in which a fluid (104) is to be transported, a flexible membrane (105), in which the flexible membrane extends in a plane, in which the flexible membrane is part of an external surface of the cartridge, in which the fluid channel three-dimensional is spatially defined in three dimensions by the inner walls of the cartridge and by the flexible membrane, in which the flexible membrane is in a fundamental state, in which no pressure or vacuum is applied to the flexible membrane, and in which the flexible membrane can be pneumatically deflected , from the perpendicular ground state (106) to the plane of the flexible membrane in two directions when the cartridge is placed on the parallel pneumatic interface plate.
[2]
2. Microfluidic cartridge, according to claim 1, characterized by the fact that the fluid channel and the flexible membrane are arranged with each other in a way that, by deflection of the flexible membrane at different points (109, 110, 111, 114) along the pneumatically pumped flexible membrane (108) of the pneumatic instrument, the fluid is transportable from a beginning (112) of the fluid channel to an end (113) of the fluid channel.
[3]
Microfluidic cartridge according to claim 1 or 2, characterized in that the membrane can be deflected by pneumatically pumping the pneumatic instrument, so that the membrane closes the fluid channel to provide a valve function (114) .
[4]
Microfluidic cartridge according to any one of claims 1 to 3, characterized in that the cartridge is free of pneumatic control elements and free of pneumatic piping elements (113).
[5]
5. Pneumatic interface plate (101) for interfacing with a microfluidic cartridge (100) of the type defined in any of claims 1 to 4, and between a pneumatic instrument (102) for pneumatically securing the microfluidic cartridge, and apply pneumatic pumping to the microfluidic cartridge, the pneumatic interface plate characterized by the fact that it comprises: an instrument side (119) that faces the instrument when the interface plate is inserted into the instrument,
: 2/3 a cartridge side that faces the cartridge when the cartridge is placed 'on the interface board, a pneumatic channel (122, 123, 138) to connect a pneumatic fluid from the pneumatic instrument, from the instrument side to the side of the cartridge, to allow pneumatic activation of the flexible membrane of the microfluidic cartridge.
[6]
6. Pneumatic interface plate according to claim 5, characterized by the fact that the side of the cartridge has at least one recess (124, 125, 126) to suck in the flexible membrane of the cartridge when an under pressure is applied to the membrane.
[7]
Pneumatic interface plate according to claim 5 or 6, characterized in that the interface plate comprises at least one element, chosen from a group comprising a heat generating device (135, 136); a heat transfer element made of aluminum; a heat transfer element made of copper; a heat transfer element made of an aluminum and / or copper alloy, the heat generating device having heat transfer elements extending to the microfluidic cartridge, an acoustic energy generating device; a fluid treatment device with focused and non-focused ultrasound; a piezoelectric actuator, a mechanical actuator; a magnetic actuator; and any combination thereof.
[8]
Pneumatic interface plate according to any one of claims 5 to 7, characterized in that the interface plate is made of a material, chosen from a group comprising steel; stainless steel; glass; elastomer; polymer; other chemically resistant and moderately conductive materials, and any combination thereof.
[9]
9. System (121) for actuation of fluid inside a microfluidic cartridge, the system characterized by the fact that it comprises: a microfluidic cartridge, of the type defined in any one of claims 1 to 4, a pneumatic interface plate, of the type defined in any one of claims 5 to 8, wherein the flexible membrane of the cartridge can be deflected by pneumatically pumping, through the pneumatic channel of the interface plate, in a way that a fluid in the fluid channel can be moved along the channel of fluid.
[10]
10. System according to claim 9, characterized by the fact that the cartridge and the pneumatic interface plate are two physically separate components, which are held together in a reversible manner, for the actuation of fluid only
[11]
- 3/3 by pneumatic forces. : 11. System according to claim 9 or 10, characterized by the fact that the flexible membrane and the cartridge side of the interface board are adapted in combination, in a way that, by applying a sub-pressure through the channel pneumatic interface board, the cartridge is fully attached to the interface board.
[12]
12. System according to any one of claims 9 to 11, further characterized by the fact that it comprises: a pneumatic instrument for generating pneumatic pumping for the microfluidic cartridge.
[13]
13. The system according to any one of claims 9 to 12, further characterized by the fact that it comprises: control characteristics (115, 116), in which the control characteristics are arranged above or below the flexible membrane, in which the characteristics of control systems above the flexible diaphragm are arranged as obstacles for transporting the fluid within the fluid channel, and in which the flexible diaphragm is mechanically supported by the control characteristics, in a way that the diaphragm deflects during pneumatic pumping, in a way where obstacles can be overcome by the fluid.
[14]
14. System according to any one of claims 9 to 13, characterized in that: between the flexible membrane and the pneumatic interface plate chambers are reversibly mounted.
[15]
15. Pneumatic instrument (102) for generating pneumatic pumping to a microfluidic cartridge (100) for the transport of fluid within the microfluidic cartridge, the pneumatic instrument characterized by the fact that it comprises: means for pneumatically actuating a flexible membrane of the microfluidic cartridge, and a pneumatic interface plate of the type defined in any one of claims 5 to 8.
o 17 1NM2; 8; 5. (asia PP 16 13.103: mo | | 196 ips LT ds this 107 o A MID Il 1 AdaG o 1 NA 19 120 o wo TMB NM 18 “os OX 127124 128 2 429 126 5; 1o [NZ NVN NH] - Pi PA EEE - “CI Mo 1, Ex WET US 108 102 13711418 137 138 Fig. 1
—————— N 2/6 121 113 Í, 103 103 (j 7 “| Ce | DM AO nd E ds AO 115 116" Fig. 2 121 12 113 (115 108 108 (100 the Ar 128 2 gel on BO, 2 + Fig. 3 o: Ss ONLY> DS = a | 2
R | and
H o | LT] = Hj LA 3 | mm i '= Í + | S H => = | a 1: Fi - f = - o H oe Ex H = - lh A H o | O | =
E LI 3 s = =
DOC | 4/6. SP TIO EPE OH A. (E E 101. 183 122 Fig. 5 102 - / P).
Fig. 6
NICOLE 5/6: 102 17º 126 125 123 /
UU EAR i ã & 2711 Ria DD ELOA 1393 x 136 134 134 Fig. 7
N Us l Fig. 8 o

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同族专利:

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KR20130058654A|2013-06-04|

ES2578778T3|2016-08-01|

CA2777445C|2014-08-05|

RU2542235C2|2015-02-20|

EP2490812A1|2012-08-29|

AU2010309456B2|2013-09-05|

JP5456904B2|2014-04-02|

WO2011048521A1|2011-04-28|

JP2013508715A|2013-03-07|

CN102665915A|2012-09-12|

EP2490812B1|2016-05-11|

US9044752B2|2015-06-02|

US20120266986A1|2012-10-25|

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法律状态:
2020-09-08| B06U| Preliminary requirement: requests with searches performed by other patent offices: procedure suspended [chapter 6.21 patent gazette]|

2020-10-13| B25A| Requested transfer of rights approved|Owner name: BIOCARTIS NV (BE) |

2020-10-27| B08F| Application dismissed because of non-payment of annual fees [chapter 8.6 patent gazette]|Free format text: REFERENTE A 10A ANUIDADE. |

2020-12-22| B11B| Dismissal acc. art. 36, par 1 of ipl - no reply within 90 days to fullfil the necessary requirements|

2021-11-03| B350| Update of information on the portal [chapter 15.35 patent gazette]|

优先权:

申请号 | 申请日 | 专利标题

EP09173589.4|2009-10-21|

EP09173589|2009-10-21|

PCT/IB2010/054520|WO2011048521A1|2009-10-21|2010-10-06|Microfluidic cartridge with parallel pneumatic interface plate|

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