• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
  • 同族专利
  • 引用文献
  • 法律状态
  • 优先权
    • 专利摘要:
    Connector device for microfluidic circuits. The object of the present invention relates to a connector device (1) for its application to a microfluidic circuit (2), wherein said device (1) comprises at least one coupling (5) between an external microfluidic component and an inlet (3) or outlet (4) of said microfluidic circuit (2). Advantageously, said coupling (5) is adapted to house a connection means between the external component and the connector device (1) and which additionally comprises an exhaust opening (6) configured as a means for evacuating gas during the connection of said external component to the inlet (3) or outlet (4) of the microfluidic circuit (2). The main advantage of the device (1) is that it allows the elimination of air and bubbles during the connection of the system, so that it does not require the use of encapsulations or complex coupling methods.
    公开号:ES2667430A1
    申请号:ES201631295
    申请日:2016-10-05
    公开日:2018-05-10
    发明作者:Luis J FERNÁNDEZ LEDESMA；Rosa MONGE；Guillermo LLAMAZARES；Jose María AYUSO；María VIRUMBRALES；Clara ALCAINE；Rebeca GUERRERO；José Luis CALAVIA；Alan VIGUERAS；Jorge SANTOLARIA；Ignacio OCHOA GARRIDO
    申请人:Universidad de Zaragoza；Centro de Investigacion Biomedica en Red CIBER；
    IPC主号:
    专利说明:

    CONNECTOR DEVICE FOR MICROFLUIDIC CIRCUITS
    5 FIELD OF THE INVENTION
    The present invention is framed in the field of microfluidic devices and, in general, in the technical field related to microfluidics for cell culture and in vitro analysis. More specifically, the object of the invention relates to a connector for microfluidic devices 10, which allows to avoid the insertion of the bubbles present in the working fluids during the connection of the components of a fluidic circuit to said devices
    microfluidics
    BACKGROUND OF THE INVENTION
    In vitro cell culture is a widely used technique, which allows the observation of the behavior, morphology and physical state of the cells, or the performance of biochemical analyzes and assays under certain biological conditions. On the other hand, microfluidics is the science in charge of studying the behavior of microfluids,
    20 discipline of great importance in the study of microscale and mesoscale biological processes in which devices are used for this purpose, called microfluidic devices or microfluidic devices.
    In microfluidic devices for cell culture and biological analysis, the
    25 fluid in which the cells are immersed, in order to simulate biomimetic environments in the cultures, thus obtaining in vitro results that are extrapolated to situations in vivo to a greater or lesser extent, depending on the reproducibility in the test of the conditions that the cell would experience in a living organism. It is, therefore, of vital importance to have devices that allow an optimal circulation of the fluids of
    30 work, avoiding problems derived from the characteristics of said devices, with the aim of improving the reproducibility of the processes in a living organism.
    It is known in the state of the art that one of the main problems related to the use of microfluidic devices, both for cell cultures and in other types of applications, is the accidental appearance of air bubbles in the fluid. These

    bubbles appear especially in certain areas of the devices, such as connections with fluid circulation channels or the inputs and outputs of the microfluidic chips in which the crop is housed. This problem implies serious limitations in practice, so that, in recent years, various fluid bubble removal systems have been developed in its passage through the microfluidic device, either by confining them in a localized area of said device or by avoiding its presence therein, through the use of bubble traps, such as the system used in European patent EP 1792655 81. In this context, there are microfluidic devices on the market with different bubble removal systems, which can be integrated into the device itself, or placed at the entrance of the device, so that the incoming fluid no longer contains air bubbles.
    Another of the existing solutions on the market, of less complexity and proposed as an improvement to those mentioned above, is the use of encapsulated parts or systems as the device of the international patent application WO 2014/053678 A1. However, these systems have limitations derived from the connections between the encapsulation and the device such as, for example, the possibility of contamination with unwanted or contaminating flows from other fluid circulation channels. Likewise, the use of encapsulated parts or systems implies a risk of the appearance of connection errors due to manufacturing tolerances, and entails the need to use elastic parts in the joints, to ensure that said connections are tight.
    The main drawback of the bubble removal systems currently available is that bubbles removed from the fluid are trapped inside the traps or channels of the device, which implies the need to empty said channels from time to time, adding risks and problems derived from said operation. Another disadvantage is the complexity that they add to the microfluidic systems in which they are integrated, either internally or externally to the microfluidic devices.
    Therefore, it is necessary to have on the market simpler alternatives for the elimination of bubbles in microfluidic devices, which do not require the use of encapsulates or other more complex methods, such as those that involve the use of membranes or generation of vacuum in the device and, in addition, channel the bubbles removed from the fluid to the outside of the device, so that they are not left

    trapped inside it, making it necessary to empty or cyclically clean the microfluidic channels.
    In view of the aforementioned technical problems, the connector object of the present invention is intended to solve said need, by means of a connector that effectively prevents the presence of bubbles in microfluidic devices, without the need for an accessory encapsulation and with a simple design. Thus, the invention allows bubbles to be removed during the connection of a fluidic circuit to one or more microfluidic devices, as well as to purge said fluidic circuit prior to its connection to the devices in situ.
    BRIEF DESCRIPTION OF THE INVENTION
    An object of the present invention is, therefore, to provide a solution to avoid the presence of bubbles in microfluidic devices, as an alternative to the solutions existing in the state of the art. For this, a connector for microfluidic devices is proposed, comprising a coupling for one or more fluid circulation channels, adapted for the entry or exit of said fluid to / from the microfluidic device through the connector.
    More specifically, the object of the invention is a connector device suitable for application to a microfluidic circuit, wherein said device comprises at least one coupling between an external microfluidic component and an input or output of said microfluidic circuit. Advantageously, said coupling is adapted to accommodate a connection means between the external component and the connecting device; and further comprises an exhaust opening configured as a means of evacuating gas (for example, air) during the connection of said external component to the inlet or outlet of the microfluidic circuit.
    It is thus possible to avoid the presence of bubbles in the device, eliminating them during the connection and the passage of fluid from the microfluidic circuit to the microfluidic device, through the coupling object of the invention and its associated exhaust opening. Thus, the fluid entering the microfluidic device is free of bubbles without the need to use other more complex systems, such as encapsulation systems. In a preferred embodiment of the invention, the connecting device comprises at least

    a fluid discharge well from the exhaust opening, whose origin is either the microfluidic circuit itself, or the external components to be connected to the device. The above described eliminates the periodic need to empty and clean the connector during the purge phase prior to connection. In this way, the elimination of the air entering the circuit is facilitated due to changes in the pressure of the circuit, accidental suction or drag of the air into the circuit, allowing a safe and bubble-free connection. Likewise, the isolation of the fluid with discarded bubbles from the fluid circuit is achieved.
    In an embodiment of the invention based on the use of a pouring well, the connecting device comprises at least two couplings arranged on the same pouring well. Alternatively or in addition, the device comprises a pouring well arranged so that it picks up the fluid from a single coupling through its corresponding exhaust opening. The pouring well allows the excess fluid to be collected and the fluid circuit to be purged, so that there is no uncontrolled transfer of liquid into the microfluidic device, and a gain in hygiene during liquid collection. This translates into ease of handling for the end user and a lower probability of contamination.
    In another preferred embodiment of the invention, the microfluidic circuit comprises one or more of the following elements, in isolation or in combination: channels or microchannels for circulation, cameras or microchambers housing biological samples, microfluidic chips. This achieves great versatility, which makes the device suitable for a wide variety of biological and microfluidic applications.
    In another preferred embodiment of the invention, the device comprises couplings to at least one inlet and one outlet of the microfluidic circuit. This ensures that the fluid that arrives and leaves the microfluidic circuit makes it free of air bubbles.
    In another preferred embodiment of the invention, the coupling is based on a threaded connection means. However, said coupling can be based on other means, such as a pressure connection means, or by clip.
    In another preferred embodiment of the invention, the inlet or outlet of the microfluidic circuit is equipped with a sealed connection means. More preferably, said connection comprises one or more O-rings, eliminating the need for other internal connection means and avoiding the problems derived from their own tolerances.
    In another preferred embodiment of the invention, one or more of the elements that make up the
    5 connector device are manufactured with a biocompatible material. More preferably,said material comprises methacrylate (PMMA), polycarbonate (eg), polymers or copolymersof cyclic olefin, polymeric photoresists or related materials.
    In another preferred embodiment of the invention, one or more of the elements that make up the connector device are made of an optically transparent or radiolucent material.
    Definitions of some of the main terms used in the present description are given below, and of their scope of interpretation in the light of the invention claimed herein:
    A connector device is to be interpreted as a means of connecting a microfluidic circuit housed in said device with one or more microfluidic components external to said device.
    20 A microfluidic circuit must be interpreted as any microfluidic elements housed in the connecting device, such as channels or microchannels, accommodation or culture microcamera or cameras, microfluidic chips, or similar elements used in the field of microfluidics or system technologies Chip laboratory.
    An entrance to the microfluidic circuit must be interpreted as any means of passage through which fluid is introduced into said circuit, and where said input is configured for connection with a microfluidic component external to the connector device.
    An output of the microfluidic circuit must be interpreted as any means of passage through which fluid is extracted from said circuit, and where said output is configured for connection with a microfluidic component external to the connector device.
    A coupling of external microfluidic components to the connector device must be interpreted as any means configured to connect an input or an output of the
    microfluidic circuit with a circulation channel connected to a microfluidic component external to the connector device.
    An external microfluidic component has to be interpreted as any element
    5 configured with means of circulation or fluid housing in a microfluidic system,such as additional external circuits, circulation pumps, power suppliesfluid, etc.
    An escape opening must be interpreted as an opening made in itself
    10 coupling of the connector device, arranged so as to allow the exit or expulsion of gases during the process of purging or pre-connecting an external microfluidic component to an entrance or exit of the connector device. As an example, in a threaded coupling, the opening can be arranged parallel to the axis of the thread and its outer longitudinal perimeter, so that a portion of said opening is always free for the
    15 air escape until the closing path of said thread is completed.
    A pouring well must be interpreted as any means for receiving and / or housing the fluid from the exhaust opening during the procedure of connecting an external microfluidic component to an inlet or outlet of the device
    20 connector, for storage or disposal of said fluid, isolating it from the fluidic connection zone and channels of the device.
    The expression "comprises" must be interpreted, when applied to the relationship between amain element compared to other secondary elements, such as said element
    The principal includes or contains such secondary elements, but without exclusion of other additional elements.
    DESCRIPTION OF THE FIGURES
    To complete the description of the invention and in order to help a better understanding of its technical characteristics, the present document is accompanied by a set of figures where, for illustrative and non-limiting purposes, the following is represented:
    Figure 1 shows a top perspective view of the connector object of the invention, according to a preferred embodiment thereof.
    Figure 2 shows two plan and elevation views of the connector object of the invention, according to another preferred embodiment thereof.
    Figure 3 shows an isometric perspective external view of the connector object of the invention, according to the preferred embodiment thereof according to Figure 2.
    NUMERICAL REFERENCES USED IN THE FIGURES
    (one ) Connector device
    (2) Microfluidic circuit
    (3) Microfluidic circuit inputs
    (4 ) Microfluidic circuit outputs
    (5) Component coupling device connectormicrofluidics external to
    (6) Escape opening
    (7) Pouring well
    Detailed description of the invention
    A detailed description of the invention, referring to a preferred embodiment thereof based on Figures 1-3 of this document, is set forth below.
    As shown in Figure 1, the present invention relates to a connecting device (1) for application to a microfluidic circuit (2), wherein said circuit (2) can comprise one or more means of circulation or housing of fluids, such as circulation channels, cameras or microcamera housing, microfluidic chips, or the like. From
    In this way, the connecting device (1) of the invention is preferably designed as a means of connection between one or more inputs (3) and / or outputs (4) of the microfluidic circuit (2) and one or more microfluidic components external, where the design and the elements that make up the connecting device (1) guarantee that the fluid in circulation through said microfluidic circuit (2) arrives or leaves it avoiding the presence of
    25 bubbles in the purge and connection phase.

    In different embodiments of the invention, the connecting device (1) can house elements intended for in vitro analysis (including, for example, housing chambers or culture chips as part of the microfluidic circuit (2 ') or can be considered as a means of elimination of bubbles between several external components (including, for example, connection or distribution microchannels as circuit elements (2), as shown in Figure 1), where they are connected to the inputs (3) and / or to the outputs (4) of the device (1).
    Also, in an embodiment of the invention illustrated by Figure 2, the connecting device
    (1) can comprise both inputs (3) and outputs (4) arranged at different points of connection with the microfluidic circuit (2). By means of said embodiment, the absence of bubbles is guaranteed both upon arrival and upon leaving the circuit (2).
    For the connection of the inputs (3) and / or the outputs (4) of the device (1) with the external components (for example, additional external fluid circuits, circulation pumps, fluid power supplies, etc.), It raises the use of corresponding couplings (5) (Figures 1-3), where each of said couplings (5) is adapted to accommodate a connection channel between the external component and the connecting device (1) of the invention. Preferably, the couplings (5) are based on threaded connection means, although other mechanisms such as pressure or clip connection means are also possible within the scope of the invention.
    To prevent the formation of bubbles when connecting the external fluidic components with the coupling (5) and their respective inlet (3) or outlet (4), said coupling (5) is equipped with an exhaust opening (6) configured as a means of evacuation of air during the purge phase prior to the connection of said external component. In this way, any bubble coming from the component to be connected will be evacuated through the exhaust opening (6). This also avoids having to use other more complex systems.
    or that imply the need to empty said channels from time to time, which adds risks of contamination and problems derived from said operation. In the exemplary embodiment of Figures 1-3 based on couplings (5) by threading, all air bubbles produced during the connection process (that is, during threading of the external connection channel to the coupling (5 ') are eliminated through the exhaust opening (6) existing in said threaded couplings (5).

    As an additional advantage of the connecting device (1) object of the invention, the existence of
    An exhaust opening (6) allows the excess fluid to escape during the closing process of the microfluidic device (2), thus avoiding overpressures inside the microfluidic circuit (2).
    Also, in a preferred embodiment of the invention, the connecting device (1) object of the invention comprises at least one well for pouring (7) of fluid from the exhaust opening (6), whose origin is either the microfluidic circuit itself (2), or the external components to be connected to the device (1). The pouring well (7) provides additional advantages to the invention, since it allows collecting waste fluid lost during connection, storing it for analysis or subsequent disposal, at the desired time. Preferably, the pouring well (7) is an open well, to facilitate access to its contents for analysis or disposal purposes.
    In different embodiments of the invention, each exhaust opening (6) can be connected to a single pouring well (7), or the same well (7) can be arranged to collect the fluid from several openings (6). The first case is advantageous in analysis applications, since it allows to keep each fluid isolated by each external component connected to the device (1). On the other hand, the use of a common pouring well (7) may be suitable in fluid removal applications.
    In different embodiments of the invention, it is possible to configure the couplings (5), the inputs (3) or the outputs (4) of the microfluidic circuit (2) with sealed connection means, such as O-rings, which is an additional measure to ensure proper coupling of the connecting device (1) of the invention with the external microfluidic components.
    Likewise, the elements that make up the connecting device (1) of the invention are preferably made of biocompatible materials (that is, of one or more pharmacologically inert compounds that do not negatively interfere with the cultures or biological materials housed in the microfluidic circuit) , such as methacrylate (PMMA), polycarbonate (PC), polymeric photoresins such as SU-B, cyclic olefin polymers or copolymers, etc.
    For those applications of the invention intended for biological analysis by means of optical instruments, one or more of the elements that make up the connecting device (1) can be optically transparent or radiolucent, to facilitate access to the biological material of said instrument.
    权利要求:
    Claims (12)
    [1]
    1.-Connector device (1) for application to a microfluidic circuit (2), wherein said device (1) comprises at least one coupling (5) between an external microfluidic component and an input (3) or output (4) of said microfluidic circuit (2),
    characterized in that said coupling (5) is adapted to accommodate a connection means between the external component and the connecting device (1); and further comprises an exhaust opening (6) configured as a means of gas evacuation during the connection of said external component to the inlet (3) or outlet (4) of the microfluidic circuit (2).
    [2]
    2.-Connector device (1) according to the preceding claim, wherein the microfluidic circuit (2) comprises one or more of the following elements, in isolation or in combination: channels or microchannels for circulation, cameras or microchambers housing biological samples, chips microfluidics
    [3]
    3.-Connector device (1) according to any of the preceding claims, comprising couplings (5) to at least one inlet (3) and one outlet (4) of the microfluidic circuit (2).
    [4]
    4.-Connector device (1) according to any of the preceding claims, wherein the coupling (5) comprises a threaded connection means.
    [5]
    5.-Connector device (1) according to any of the preceding claims, wherein the coupling (5) comprises a means of connection by pressure or by clip.
    [6]
    6.-Connector device (1) according to any one of the preceding claims, comprising at least one well for pouring (7) of fluid from the exhaust opening (6), whose origin is either the microfluidic circuit itself (2), or the external components to be connected to the device (1).
    [7]
    7.-Connector device (1) according to the preceding claim, comprising at least two couplings (5) arranged on the same pouring well (7).
    [8]
    8.-Connector device (1) according to any of claims 6-7, comprising a pouring well (7) arranged so as to collect the fluid from a single coupling (5) through its exhaust opening (7 ) correspondent.
    5. Connector device (1) according to any of claims 6-7, wherein thepouring well (7) is an open well.
    [10]
    10.-Connector device (1) according to any of the preceding claims, wherein the coupling (5), the inlet (3) or the outlet (4) of the microfluidic circuit (2) is equipped with airtight connection means.
    [11 ]
    11.-Connector device (1) according to the preceding claim, wherein the sealed connection means comprise one or more O-rings.
    12. Connector device (1) according to any of the preceding claims, wherein one or more of the elements that make up said device (1) are made of a biocompatible material.
    [13]
    13.-Connector device (1) according to the preceding claim, wherein the biocompatible material comprises methacrylate (PMMA), polycarbonate (eg), polymers or copolymers of cyclic olefin, or polymeric photoresists.
    [14]
    14.-Connector device (1) according to any of the preceding claims, wherein one or more of the elements that make up said device (1) are made of an optically transparent or radiolucent material.
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    引用文献:
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    ES2459269B1|2012-10-04|2015-03-24|Universidad De Zaragoza|DEVICE AND METHOD OF ENCAPSULATED MICROFLUIDIC SYSTEMS|
    GB2536114B|2013-06-26|2019-06-05|Harvard College|Interconnect adaptor|
    法律状态:
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    优先权:
    申请号 | 申请日 | 专利标题
    ES201631295A|ES2667430B1|2016-10-05|2016-10-05|CONNECTOR DEVICE FOR MICROFLUIDIC CIRCUITS|ES201631295A| ES2667430B1|2016-10-05|2016-10-05|CONNECTOR DEVICE FOR MICROFLUIDIC CIRCUITS|
    EP17857881.1A| EP3524349A4|2016-10-05|2017-10-02|Connector device for microfluidic circuits|
    PCT/ES2017/070643| WO2018065648A1|2016-10-05|2017-10-02|Connector device for microfluidic circuits|
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