Patent Publication Number: US-2005118070-A1

Title: Flow triggering device

Description:
BACKGROUND OF THE INVENTION  
      The present invention is related to the control of the flow behaviour of liquid driven by capillary forces in microfluidic devices.  
     SUMMARY OF THE INVENTION  
      The present invention provides certain unobvious advantages and advancements over the prior art. In particular, the inventors have recognized a need for improvements in flow triggering device design.  
      Although the present invention is not limited to specific advantages or functionality, it is noted that the present invention provides a device that can considerably slow down or even stop volume flow in a microfluidic chamber or channel. Thus, fluid control enables control of chemical or physical processes, for example, dissolution of dried reagents, in the chamber and/or the control of reaction time. Moreover, the present invention enables one to reliably join a liquid from a multitude of channels with a common inlet port in a bubble-free manner.  
      In accordance with one embodiment of the present invention, liquid flow in a passive fluidic device can be controlled without external actuation or a control element. The present invention slows down or accelerates liquid flow in the fluidic device according to the present invention. To that end the microfluidic device having at least one non-closing valve and a channel system, within which a channel branches-off from a first channel, which may define a functional chamber and being connected to a fluidic supply, comprises a trigger channel which branches-off from the first channel prior to the non-closing valve and that re-unites with the first-channel at the location of the non-closing valve. By the design of the trigger channel, i.e., its respective length, its number of windings and its flow resistance, the trigger channel can be adapted to specific needs and requirements of the microfluidic device. The length of the trigger channel has a strong impact on the residence time of the liquid within the functional chamber. The longer the distance through which the liquid to be conveyed has to move until it reaches a valve, such as a geometric or passive valve, known as a non-closing valve, the longer is the residence time achievable. By means of the present invention, the control of the flow behaviour of liquid driven by capillary forces can be controlled.  
      In accordance with the present invention, it is possible either to considerably slow down or even stop liquid flow in a functional chamber to increase the residence time of liquid molecules in the chamber, for example to improve the dissolution of dried reagents within the chamber. Further, a bubble-free reliable joining of liquid from a multitude of channels into one channel is achieved. Besides the dissolution of a dried reagent, being contained within a functional chamber, to give an example, the microfluidic device according to the present invention can be used to control chemical reactions of liquids, to enhance incubation time to mix substances by way of liquid flow control or other specific purposes. The trigger channel does not contain any non-closing valve thus creating an unobstructed liquid flow path connecting the liquid supply compartment with the outlet channel. The triggering function of the trigger channel is established by the respective length thereof. In contrast to U.S. Patent Application Publication No. 2002/0003001 A1, in which two channels are disclosed, each of the channels has a passive valve. Thus, fluid flow in both channels is stopped, if no fluid is present in one of the two channels. According to the present invention, fluid flow within the trigger channel is not stopped, if there is no liquid present in the first channel.  
      The trigger channel, which controls liquid flow through a network of microchannels contained within a substrate of a microfluidic device or microfluidic network may have a width or a diameter, which is smaller as compared to an inlet channel. The length of the respective trigger channel exceeds a length of the flow path of the liquid from the branch-off location to the non-closing valve.  
      The microfluidic device according to the present invention comprises a functional chamber which is provided for dissolution of dried reagent within the liquid. By means of the design of the trigger channel which is passed by a portion of the liquid flow, the mixing of the liquid being processed with substances such as dried reagent in the functional chamber can be significantly improved by extending the residence time of the liquid within the functional chamber. In one embodiment of the present invention, the respective trigger channel branches-off from an outlet channel of the functional chamber. The functional chamber may be arranged as a pillar-array; in a further embodiment of the present invention, the respective trigger channel may branch-off from an inlet channel to the respective functional chamber and is directed downstream of a functional chamber and joins an outlet channel downstream of the functional chamber. Thus, in the latter embodiments, non-dissolved or non-processed liquid is used as medium within the branched-off trigger channel instead of processed liquid, within which the dried reagent contained within the functional chamber already have been dissolved.  
      The trigger channel as disclosed may be used as a trigger channel within a flow splitter device having an array of splitted channels to one of which a trigger channel is assigned. In this flow-splitter device, the openings of each of the microchannels of the array of splitted channels may contain a geometric or passive valve. The splitted channels may be arranged on both sides of a planar substrate overlapping each other, thus forming the geometric passive valves. The first channel is split into the second channel and an array of at least two splitted channels, each of the splitted channels having at least one non-closing valve, located downstream of the branch-off of the second channel and wherein the second channel re-unites with each of the splitted channels of the array downstream of the non-closing valve to form an outlet channel.  
      Microfluidic devices or microfluidic networks may be etched or replicated, for example by replication by means of plastic injection, hot embossing ceramic replication. One means of replication may be a CD-replication. According to the present invention, the portions of the disk may each comprise a functional chamber, to which a respective trigger channel is assigned, to control liquid flow from a reservoir to a containing element. In the alternative, a cascade arrangement of the microfluidic structures may be comprised on the portions, controlling liquid flow from a liquid storage by the length of a respective trigger channel. Depending on the design of the cascade arrangement a number of microfluidic devices may be arranged on the portions of the CD.  
      These and other features and advantages of the present invention will be more fully understood from the following detailed description of the invention taken together with the accompanying claims. It is noted that the scope of the claims is defined by the recitations therein and not by the specific discussion of features and advantages set forth in the present description. 
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
      The following detailed description of the embodiments of the present invention can be best understood when read in conjunction with the following drawings, where like structure is indicated with like reference numerals and in which:  
       FIGS. 1-2  show two embodiments of passive geometric valves;  
       FIG. 3  shows an inlet and the trigger channel arranged in communication with each other;  
       FIG. 4  shows a meniscus preventing the flow through the inlet channel according to  FIG. 3 ;  
       FIG. 5  shows an amount of liquid being stored in the trigger channel;  
       FIG. 6  shows the liquid volumes in the trigger and inlet channel joining each other forming a common meniscus towards the outlet channel;  
       FIG. 7  shows an outlet flow of liquid through an outlet channel;  
       FIG. 8  shows a further alternative embodiment of an inlet and a trigger channel arrangement;  
       FIGS. 9-12  show schematic embodiments for combining a trigger element with a further functional chamber;  
       FIG. 13  shows a planar design of flow-splitter device;  
       FIG. 14  shows a flow-splitter device within which geometric stop valves are generated;  
       FIGS. 15-17  show fluidic trigger structures to be replicated in plastic for fluidic evaluation; and  
       FIG. 18  shows schematically a non-closing valve. 
    
    
      Skilled artisans appreciate that elements in the figures are illustrated for simplicity and clarity and have not necessarily been drawn to scale. For example, the dimensions of some of the elements in the figures may be exaggerated relative to other elements to help improve understanding of the embodiment(s) of the present invention.  
     DETAILED DESCRIPTION OF THE INVENTION  
       FIGS. 1 and 2  show two embodiments of passive geometric valves which constitute functional elements in the context of the present invention and are known per se. In the microfluidic devices, further described hereinafter, a transport of a liquid  19  is established by capillary forces without application of external energy, created by a pumping element or the like. The transfer of liquid  19  within the microfluidic devices further described below is established by capillary forces. The system liquid  19  surface of channels within which the liquid  19  is conveyed, has a contact angle of less than 90°. It is understood that the respective contact angle as described before can vary according to the type of liquid  19  which is conveyed. Within the system of liquid  19 /surface of channels the contact angle can be changed by changing the surface properties of the respective channels, being formed on the front side, the backside, or on both sides of a substrate  3 . Materials for the respective substrates are—to give examples—polymeric materials (for example polycarbonate, polystyrol, Poly(methyl methacrylate)) that may be replicated, etchable materials (for example silicon, steel, glass) or materials that may be milled conventionally (for example polycarbonate, polystyrol, Poly(methyl methacrylate), steel).  
      The examples according to  FIGS. 1 and 2 , respectively, show known non-closing valves  1 . In a substrate  3 , a channel  2  is provided forming a non-closing valve  1 . The width  4  of channel  2  in the substrate  3  is constant. In the example given in  FIG. 1  the channel  2  has a substantially rectangular shape being a U-profile. The open side of the channel  2  on top of the substrate  3  may be covered by a further substrate which is not shown here. Instead of U-profiled channels  2  according to the embodiment given in  FIG. 1  the channels  2  may be shaped as tubes with a continuously closed circumference.  
      A further example of a channel  2  having a non-constant width is given in  FIG. 2 . The channel  2  according to  FIG. 2  has a first width  5  and a second width  6  within the area of a gap  7 . A first surface  8  and a second surface  9  of adjacently arranged substrate  3  limit the gap  7 . The gap  7  having a second width  6  constitutes a non-closing valve element  1  such as a geometric valve.  
       FIG. 3  shows an inlet and a trigger channel of a microfluidic device arranged in liquid communication with each other. An inlet channel  10  which either can have the shape of a tube or of a rectangular formed channel such as given in  FIG. 1 , conveys a liquid  19 . The width or in the alternative the diameter of the inlet channel  10  is depicted by reference numeral  11 . At a branch-off location  16 , a trigger channel  12  branches off from the inlet channel  10 . The liquid  19  contained within the inlet channel  10  is propelled by means of capillary forces. Seen in flow direction of the liquid  19 , a non-closing valve  1  such as a geometric valve is provided. In this context a non-closing valve  1  refers to valves in which a liquid  19  is stopped at a specific location of a channel even if the channel at the valve position is opened and is not obstructed by physical means. Geometric valves are non-closing valves, in which the valve function is obtained by a specific curvature or geometry of the channel, whereby the surface characteristics are constant with respect to a channel. Reference numeral  17  depicts the area where the trigger channel  12  and the non-closing valve  1  meet, i.e., constituting a joining location.  
      At the branch-off location  16  the trigger channel  12  branches off. The trigger channel  12  has a diameter or a width, respectively, labelled with reference numeral  13 . The diameter or the width  13  of the trigger channel  12  is smaller as compared to the diameter or the width  11  of the inlet channel  10 . The length of the trigger channel  12  between the branch-off location  16  and the joining location  17  is substantially higher than the distance within the inlet channel  10  from the branch-off location  16  to the end of the geometric valve  1 , i.e., an edge  26  of support element  3  and exceeds the length of the flow path of the liquid from the branch-off location  16  to the non-closing valve.  
       FIG. 4  shows a meniscus formed, preventing further flow through the inlet channel according to  FIG. 3 .  
      Due to the action of the non-closing valve  1 , such as a geometric valve, the liquid  19  flowing in the inlet channel  10  is stopped. Due to capillary forces, which depend on the width or the diameter  13 , respectively, of the trigger channel  12 , some amount of liquid  19  is drawn into the trigger channel  12 . The liquid flow between branch off location  16  and joining location  17  is stopped within channel  10  at the first meniscus  20 . However, liquid enters slowly into a trigger channel  12 . A first meniscus  20  is formed in the region of the non-closing valve  1 , such as a geometric valve. In this stage, no liquid  19  is present in the joining location  17  of the outlet channel  14 .  
       FIG. 5  shows an amount of liquid flowing in the length of the trigger channel.  
      Due to the restricted width or diameter  13  of the trigger channel  12  the liquid  19  needs some time to flow towards the joining location  17  of the trigger channel  12  opening into the funnel-shaped area  18 . The first meniscus  20  at the bottom of inlet channel  10  is still prevailing, the fluid flow between branch-off location  16  and joining location  17  is stopped, however liquid slowly enters into trigger channel  12 . The liquid  19  stored within the trigger channel  12  has not reached the joining location  17  yet. As long as liquid  19  is present within the trigger channel  12 , the main flow of liquid  19  within the inlet channel  10  before the branch-off location  16  is slowed down, when compared to the situation given according to  FIG. 3 . The flow of liquid  19  within the inlet channel  10  is dependent on the cross section  13  of the trigger channel  12 . The narrower channel  12  is as compared to the channel  10 , the slower the fluid flows.  
       FIG. 6  shows the liquid volumes in the trigger channel and the inlet channel joining each other forming a common meniscus towards the outlet channel.  
      In the stage given in  FIG. 6 , the liquid  19  stored within the trigger channel  12  has reached the joining location  17 . Once the liquid  19  flows out of the trigger channel  12 , a second, common meniscus  21  is formed. The liquid  19  consequently is pulled towards the outlet channel  14 , having a width or diameter  15 , respectively, which may correspond to the cross sections  11 ,  13  of the inlet channel  10  and the trigger channel  12 , respectively. The two flows through the inlet channel  10  and the trigger channel  12  join each other and are drawn due to capillary forces into the outlet channel  14 .  
       FIG. 7  shows an outlet flow of liquid through the outlet channel.  
      Once the flow through the trigger channel  12  has reached the joining location  17 , opening into outlet channel  14 , a main flow  23  of liquid  19  is generated having a flow direction as indicated by reference numeral  24 . In the stage according to  FIG. 7  the flow through inlet channel  10  has restarted again, whereas a partial volume of liquid  19  still flows within the trigger channel  12 . In this stage the non-closing valve  1  at the bottom edge  26  of the inlet channel  10  is no longer active. If the flow resistance in the trigger channel  12  is chosen to be high, the portion of liquid flowing in the trigger channel is very low.  
      By controlling a flow rate of a liquid  19  in a microfluidic device with no external actuation or control elements the liquid flow can be slowed down considerably or even be stopped, thus increasing the residence time of liquid molecules, for instance in a processing or functional chamber, to improve the dissolution of dried reagents comprised in the functional chamber. Another significant advantage of the trigger channel  12  is a reliable joining of liquids from a multitude of channels, having a common inlet port, such as split inlet channels into one common outlet channel, as will be described in more detail below.  
       FIG. 8  shows a further alternative embodiment of an inlet channel and a trigger channel arrangement. In the alternative embodiment given in  FIG. 8 , the inlet channel  10  and the outlet channel  14  are connected to one another by means of a non-closing valve  1  which engages the outlet channel  14  in an arc-shaped recess portion  30  thereof. In the embodiment according to  FIG. 8 , the angle α between the non-closing valve  1  and the end of the trigger channel  12  is about 45°, whereas the angle α according to the embodiments given in  FIGS. 1 and 2 , respectively, is about 90°. The angle α between in the joining area of the trigger channel  12  and the non-closing valve  1  can be chosen depending on the properties of the system surface/liquid and other specific requirements, for example the size and the material of the substrate  3  or the like. The material of the substantially plane substrate  3  may be chosen from one of the below listed materials: polymeric materials (for example polycarbonate, polystyrol, Poly(methyl methacrylate)) that may be replicated, etchable materials (for example silicon, steel, glass) or materials that may be milled conventionally (for example polycarbonate, polystyrol, Poly(methyl methacrylate), steel). The respective inlet channels  10 , outlet channels  14  and the trigger channel  12  may be manufactured in silicon substrates by etching or plastic replication.  
       FIGS. 9-12  show schematic embodiments of a microfluidic device provided with a functional chamber.  
      A functional chamber  40  may allow functions such as for dissolving dried reagents. To dissolve the dried reagents within the functional chamber  40  an increase of the residence time of the liquid molecules of the liquid  19  is advantageous. The functional chamber  40  further may serve the purpose to allow for chemical reactions, dissolving dry reagents, or for mixing up substances. A further function to be performed in the functional chamber  40  is the incubation, i.e., to lengthen the residence time of liquid. Depending on the system liquid  19 /dried reagents the time interval within which the dried reagents are dissolved, may vary considerably. Thus, the respective residence time of the mixture liquid  19  and dried reagents can be adapted depending on the dissolving time of each system liquid  19 /dried reagents. This is possible by varying the length of the trigger channel  12 , which does itself not contain any non-closing valve, thus creating an unobstructed liquid flow path connecting the liquid supply compartment with the outlet channel  14 .  
      The trigger channel  12 , as described in connection with the embodiments according to  FIGS. 3-8  in greater detail above, allows a functional chamber  40  to be filled with a liquid  19 . Once the liquid  19  reaches the non-closing valve  1 , the flow rate into the functional chamber  40  is considerably lowered to allow for more time for specific functions to take place in the functional chamber  40  as mentioned above. The functional chamber  40  may be constituted as a simple liquid container or may contain an array of pillars or even may contain a number of liquid channels. It is further conceivable to form the first channel which is connected to a fluid supply as a functional chamber.  
      In the embodiment according to  FIG. 9  by means of the inlet channel  10  the functional chamber  40  may be filled with a liquid  19 . To the outlet of the functional chamber  40  according to the embodiment given in  FIG. 9 a  trigger channel  12  is assigned. The outlet of the functional chamber  40  constitutes the inlet with respect to the non-closing valve element  1  which is arranged below the functional chamber  40 . At a branch-off location  16  the trigger channel  12  branches-off from the outlet downstream of the functional chamber  40 . The trigger channel  12  joins the outlet channel  14  at a joining location below the geometric valve  1  given in greater detail in  FIGS. 3-7 .  FIG. 10  shows an embodiment of a functional chamber  40 , the outlet of which is arranged as a plurality  42  of parallel channels  41  each having a non-closing valve. A pillar-array may be integrated within the functional chamber  40 .  
      The trigger channel  12  joins the outlet channel  14  at the joining location  17  (see embodiments according to  FIGS. 3-7 ). Depending on the cross section  13  and the length of the trigger channel  12 , the residence time of liquid  19  within the functional chamber  40  can be increased, e.g., to allow for performance of chemical reactions within the functional chamber  40 , or in the alternative to allow for dissolving of dried reagents within the functional chamber  40  of the microfluidic device according to the present invention.  
       FIG. 11  shows a different embodiment of a microfluidic device, comprising a functional chamber  40 . According to this embodiment, an elongated trigger channel  43  circumvents the functional chamber  40 . The first circumventing trigger channel  43  branches-off at a second branch-off location  45  prior to the entry of the inlet channel  10  into a functional chamber  40 . In this embodiment, the circumventing trigger channel  43  branches-off from the first channel  10  upstream of the functional chamber  40 . The first circumventing trigger channel  43  joins the outlet channel  14  below an arrangement of parallel channels  42  having a non-closing valve element below the functional chamber  40 . The first circumventing trigger channel  43  branching-off at the respective second branch-off location  45  allows for a branching-off of liquid, prior to the entry thereof into the functional chamber  40 . The liquid  19  contained within the first circumventing trigger channel  43  does not contain any functionalized liquid of functional chamber  40 , but rather is pure liquid  19 . Consequently, the amount of liquid contained within the functional chamber  40  can be fully used without having any portion thereof to be branched-off into the respective trigger channel  12  as in the embodiments given in  FIGS. 9 and 10 , respectively.  
       FIG. 12  shows a further embodiment of a functional chamber integrated into a microfluidic device according to the present invention.  
      In the embodiment according to  FIG. 12 a  second circumventing trigger channel  44  branches-off at second branch-off location  45  arranged above the entry of inlet channel  10  into the functional chamber  40 , i.e., upstream of the functional chamber  40 . The second circumventing trigger channel  44  joins the outlet channel  14  within an area  18 . Within the outlet channel  14  of the functional chamber  40  according to the embodiment of  FIG. 12 a  non-closing valve  1  such as a geometric valve is integrated. Reference numeral  24  depicts the flow direction of the main flow from the functional chamber  40 , once the second circumventing trigger channel  44  is entirely filled with the liquid  19 .  
       FIG. 13  shows a planar design of a flow-splitter device according to the present invention. Reagents are often deposited in microfluidic channels as described above and are dissolved with a liquid  19 . The speed of the dissolving procedure is limited by the diffusion of the involved molecules. Generally, in microfluidic systems there is no turbulent flow, i.e., the intermixing of molecules is process-limited mainly by diffusion. A further aspect is the solubility of the product of reagent and the solvent. With the flow-splitter devices according to the present invention the surface to volume ratio of a flow-splitter device, embodied as a microfluidic device can be significantly increased. With the embodiments of a flow-splitter device described in more detail below, an inlet channel generally is split into several channels which increases the surface to volume ratio. The solution according to the present invention offers the advantage to join the liquid  19  flowing in these splitted channels in one single outlet channel again in a controlled manner without introducing or producing bubbles within the outlet flow. Additionally, it slows down the liquid flow in the splitted channels.  
      The embodiment according to  FIG. 13  shows a planar design which may by replicated in plastics as shown in greater detail. A first flow-splitter device is identified by reference numeral  60  and comprises an inlet channel  10 ,  62 , respectively. The planar design according to  FIG. 13  includes an array  64  of splitted channels  63 . The splitted channels  63  extend substantially in parallel to one another. The first flow-splitter device  60  comprises the trigger channel  12 . Each of the splitted channels  63  has at least one non-closing valve  65  located downstream of the branch-off of the second channel  12 , i.e., the trigger channel. The trigger channel  12  re-unites with each of the splitted channels  63  of the array  64  downstream of the non-closing valves  65  to form an outlet channel  14 . Each of the splitted channels  63  opens into a common outlet channel  14 . The openings of each of the splitted channels  63  constitute a non-closing valve  65 . The trigger point of the array  64  of splitted channels  63  is identified with reference numeral  61 . Once the liquid  19  enters the first flow-splitter device  60  and has entered into the trigger channel  12  and the respective splitted channels  63 , the liquid in the respective splitted channels  63  stops at a non-closing valve  65  one of which is arranged at each end of the respective splitted channels  63 . When liquid flow to trigger channel  12  reaches the trigger point  61 , liquid flow begins in a sequential manner beginning in the splitted channel  63  which is arranged closest to the respective trigger point  61 . The liquid  19  flowing—according to the embodiment given in  FIG. 13 —in vertical direction downwards, fills the common outlet channel  14 , the cross-section of which gradually increases in liquid flow direction out of the first flow splitter devices  60 .  
       FIG. 14  shows a further embodiment of a flow-splitter device within which geometric stop valves are generated by means of overlapping.  
      The embodiment of a flow-splitter device according to  FIG. 14  shows a common inlet channel  10 ,  62  respectively, which is split up into a plurality of splitted channels  63 , forming a splitted channel array  64 . The splitted channels  63  substantially extend in parallel to one another. The flow-splitter device according to  FIG. 14  is in general a planar design which may be etched into a substrate  3  such as a very thin steel foil. In the embodiment according to  FIG. 14 , the substrate  3  such as a steel foil is etched on both sides thereof. Thus, the splitted channels  63  on one side of the foil  71  overlap etched channels on the rear-side on the foil  71  according to  FIG. 14 , thus forming overlapping regions  72  at the end of each splitted channel  63 . In the overlapping region  72  which is arranged at the respective joining locations into a common outlet channel  14 , geometric valves  73  are established. The array  64  of splitted channels  63  is connected to the common outlet channel  14  on the backside of the foil  71  by means of an opening connecting the trigger channel  12  arranged on the front side of the foil  71  with the common outlet channel  14  arranged on the respective other side of the foil  71 . With this embodiment of a flow splitter device a change of planes, i.e., from the front side to the rearside and vice versa, can be achieved. The single splitted channels  63  each comprise an end portion which is formed as a geometric (non-closing) valve  73 .  
       FIG. 15-17  show fluidic trigger structures to be replicated in plastics for fluidic evaluation.  
       FIG. 15  shows a support-structure  3  such as an injection moulded or hot embossed substrate or the like. On the top-side of the support-structure  3  according to  FIG. 15  three different microfluidic systems are arranged.  
      On the support-structure section  3  shown in  FIG. 15  the different microfluidic systems for evaluation of liquid are arranged. Each of the three systems comprises a liquid supply  81  and a liquid reservoir  82 , respectively. Liquid is fed from the liquid supply  81  in flow direction  83  via the inlet channel  10  to a flow splitter device, which according to  FIG. 15  is shaped in a cascade arrangement  84 . To each of the stages of the cascade arrangement  84  an individual trigger-channel  12  is assigned to allow for bubble free flow via outlet channel  14  into the liquid reservoir  82 . The branches, comprised in the cascade arrangement  84  according to  FIG. 15  may vary between 2 and 4 each being triggered by a trigger channel  12  arranged to the respective cascade  84 .  
       FIG. 16  shows a second liquid trigger structure according to the present invention arranged on a support-structure element  3 .  
      The support-structure element  3  may be as previously mentioned a plastic material into which the microfluidic devices according to  FIG. 16  may be replicated.  
      In contrast to the first fluidic trigger structure  80  according to  FIG. 15 , the second fluidic trigger structure  90  according to  FIG. 16  comprises two microfluidic systems. One of the microfluidic systems given on the support-structure element  3  according to  FIG. 16  comprises a functional chamber  40 , which is fed by an inlet channel  10  from a liquid supply  91 . The flow direction of the liquid is indicated by arrow  93 . A portion of the liquid contained in the functional chamber  40  enters into the trigger channel  12  assigned to a series of four outlet channels (array  42 ) of the functional chamber  40  each of the outlet channels having a non-closing valve. The outlet of the functional chamber  40  constitutes the inlet with respect to the trigger channel  12 . The length and the cross section of the trigger channel  12  assigned to the functional chamber  40  determines the residence time of the liquid  19  contained in the functional chamber  40 . Further, in the embodiment of a second fluidic trigger structure  90  according to  FIG. 16 a  flow-split device  60  is integrated. From the liquid supply  91  liquid is fed in flow direction  93  via inlet channel  10  to a first flow-splitter device  60  having a cascade arrangement  94 . Each of the cascades comprises four microchannels in parallel to one of which a trigger channel  12  is assigned to allow for bubble-free conveying of liquid to the reservoir  92 . It should be understood, that each outlet of a previous cascade  84 ,  94 ,  104 , constitutes the inlet for the following cascade of the cascade arrangement  94  of the first flow-splitter device  60  according to the embodiments given in  FIGS. 16 and 17 , respectively.  
      In the embodiment according to  FIG. 17 a  third liquid trigger structure according to the present invention is arranged on a support structure element  3 .  
      According to this embodiment, liquid contained within a liquid supply  101  flows via inlet channel  10  in flow direction  103  to a reservoir  102 . The inlet channel  10  is connected to a cascade arrangement  104  having three (3) trigger channels  12  assigned thereto. According to the third liquid trigger structure  100 , as given in  FIG. 17 , the substrate  3  comprises further trigger structures by means of which liquid from liquid supply  101  is transmitted to a reservoir  102 . In one embodiment given on the substrate  3  according to  FIG. 17  the cascade arrangement  104  comprises flow splitter devices to each of which a respective trigger channel  12  is assigned. On the right hand side on top of  FIG. 17 a  cascade arrangement  104  is shown which comprises two channels extending parallel to one another. According to this embodiment to each of the pair of channels extending substantially parallel to one another a separate trigger channel  12  is assigned.  
       FIG. 18  schematically shows a non-closing valve as previously mentioned herein. According to the embodiment of a non-closing valve  1 , a first channel  110  is etched into a front side  113  of a thin substrate  3  having a thickness  116 . The first channel  110  is connected to a second channel  111  on the backside  114  of the thin substrate  3 , made for instance of a very thin, etchable steel foil, a polyimide-foil, or the like. The first channel  110  and the second channel  111  are connected to one another by an opening  115 . The depth of the first channel  110  is identified by reference numeral  117 . The second channel  111 , etched on the respective backside  114  of the very thin substrate  3  has a similar depth. Both the depth  117  of the first channel  110  and the depth of the second channel  111  are chosen that both channels  110 ,  111  establish a fluid communication, thus allowing for a transfer of liquid via opening  115  from the front side  113  of the very thin substrate  3  to the respective backside  114  thereof. The channels&#39; surfaces are labelled  112 .  
      The microfluidic devices according to the present invention may be used for processing human blood, liquor or other body fluid samples, aqueous solutions of reagents, liquids containing organic solutions or oil. The microfluidic devices according to the present invention can be used for the extension of incubation time or reaction time, to allow for enhancing the residence time of liquid  19  to dissolve dried reagents, which are for example contained within the functional chamber  40 .  
      It is noted that terms like “preferably”, “commonly”, and “typically” are not utilized herein to limit the scope of the claimed invention or to imply that certain features are critical, essential, or even important to the structure or function of the claimed invention. Rather, these terms are merely intended to highlight alternative or additional features that may or may not be utilized in a particular embodiment of the present invention.  
      For the purposes of describing and defining the present invention it is noted that the term “substantially” is utilized herein to represent the inherent degree of uncertainty that may be attributed to any quantitative comparison, value, measurement, or other representation. The term “substantially” is also utilized herein to represent the degree by which a quantitative representation may vary from a stated reference without resulting in a change in the basic function of the subject matter at issue.  
      Having described the invention in detail and by reference to specific embodiments thereof, it will be apparent that modifications and variations are possible without departing from the scope of the invention defined in the appended claims. More specifically, although some aspects of the present invention are identified herein as preferred or particularly advantageous, it is contemplated that the present invention is not necessarily limited to these preferred aspects of the invention.