JP5057968B2 - Microfluidic device having separable operating module and fluid holding module - Google Patents

Description

  The present invention relates generally to devices and valves for controlling fluid flow, and in particular to microfluidic devices and valves.

  The development of miniaturization and large scale integration in fluidics has led to the concept of creating a complete chemical or biological laboratory with respect to the similarity to fluids in electronic microchips. This type of integrated microfluidic devices (known as Micro Total Analysis Systems or μTAS) is an automation and cost-saving tool for many biological analysis applications, including genetic analysis and medical diagnostics. It is considered key technology. However, when performing this type of biological analysis, it is often important to avoid the possibility of cross-contamination between separate samples. For example, if you are using the same instrument and analyzing a series of blood samples from different patients, this is absolutely because any residue from one sample can contaminate later samples if present in the instrument. Unacceptable. This made it possible to remove all components that would come into contact with the sample, leading to the design of an instrument for disposal or cleaning.

  A microfluidic device must be able to fully manipulate multiple fluids. The operation has many functions such as, for example, storage, transportation, heating, cooling and mixing. In order to perform these functions, it is necessary to provide not only the flow channel but also at least a valve, a pump, a heater and a cooler in the microfluidic device. Although all these functions have become apparent to change the degree of success in microfluidic devices, valves and pumps are generally complex devices and difficult to manufacture. Unfortunately, this has been a high manufacturing cost, making it impossible to manufacture disposable devices.

  Accordingly, there is a need for a microfluidic device that can perform various operations on a fluid and that can be manufactured in a manner that is suitable for a disposable device.

DISCLOSURE OF THE INVENTION For convenience of explanation, a “microfluidic” device or valve has one or more channels with at least a one-dimensional dimension of less than 1 mm.

  According to various embodiments of the present invention, the microfluidic device consists of two modules in operative contact, a fluid holding module and an operating module. The fluid retention module incorporates a fluid transport / containment element and other elements that can contact the fluid. The operating module incorporates an operating mechanism for transporting and controlling the fluid. These two modules are used in contact with each other. These modules are detachably secured to each other so that the fluid holding module can be separated from the operating module and disposed of when not needed. On the other hand, the operating module is reusable with other fluid retention modules, eliminating cross contamination between fluids in the two fluid retention modules, which can occur frequently.

  1A and 1B schematically illustrate an embodiment of an operating module 100 that incorporates an operating element embedded in a substrate 102. Examples of operating elements include a Peltier heater / cooler 104, namely a Peltier (thermoelectric) junction for heating and cooling, a resistive heater 106, an electromagnetic coil 108 for generating an electromagnetic field, and a fluid holding module (described below). There is a mechanical plunger 110 that deforms the surface, but is not limited thereto. In this embodiment, the operating module 100 further includes one or more sensing elements such as an optical sensor 112, a thermal sensor 114, and an electrical sensor 116. In this embodiment, the operating module 100 has a substantially flat surface 118 that forms an interface (interface) that is in operative contact with a fluid retention module (described below). In various embodiments, the operating and sensing elements are distributed on or in close proximity to the generally flat surface 118 in a precisely defined pattern. In the illustrated embodiment, the operating elements are distributed in a regular array pattern. However, it should be understood that the operating elements can also be arranged in an irregular pattern.

  2A and 2B diagrammatically illustrate an example of a fluid retention module 200 that incorporates a fluid transport / containment element within the substrate 202. For example, the substrate 202 is formed from an easily molded polymeric material, for example, using polydimethylsiloxane elastomer (PDMS) to mold the flow channel. Examples of transport / containment elements include flow channels 204, sample inlets 206 and outlets 208, reagent reservoirs or storage cells 210, and others such as mixing and reaction cells, thermal cycling cells, embedded magnets, and sensing cells. However, the present invention is not limited thereto. In this embodiment, the fluid retention module 200 has a substantially flat surface 218 that contacts the operational module 100 to provide an operational interface. In various embodiments, the elements in the fluid retention module 200 are distributed on or near the generally flat surface 218 in a precisely defined pattern. In this illustrated embodiment, the fluid transport / containment elements are distributed to interface with their corresponding operating elements on the operating module 100. In this embodiment, not all operating elements on the operating module 100 match the fluid elements on the fluid holding module 200. Some operating elements are redundant for the fluid retention module used in this embodiment, but may be used for fluid retention modules having different layouts. By providing too many operating elements on the operating module, the microfluidic device can be easily reconfigured for different applications by using fluid holding modules with different layouts. In this embodiment, an identification element 224 (for example, a barcode) is provided on the fluid holding module 200 and a reading element 122 is provided on the operation module 100, and the control device for the operation module 100 configures the fluid holding module 200. Be able to decide. In this embodiment, alignment markers 120 and 220 are provided on the operation module 100 and the fluid holding module 200, respectively, so that when the two modules come into contact, the various elements are properly aligned, and the operation elements in the operation module 100 are And ensure that the sensing element can act on the proper fluid transport / containment element in the fluid holding module 200.

  FIGS. 3A and 3B show an example of a multi-function microfluidic device 300 having an operating module 100 and a fluid holding module 200 in combination. In this embodiment, the fluid retention module 200 further includes a cover 222 (eg, a cover sheet) that surrounds the flow channel and prevents fluid trapped within the flow channel from contacting the manipulation module 100. Alternatively or additionally, the operating module 100 can be coated with a protective layer (eg, a disposable protective layer or a protective layer that is easy to clean), so that if the operating module 100 becomes dirty, this It becomes easy to restore the cleanliness of the operation module 100.

  In this embodiment, the operation module 100 and the fluid holding module 200 are detachably fixed to each other by the clamp mechanism 302. For the multifunctional microfluidic device 300 and its components, proper operation of the components requires that the fluid retention module 200 is in good thermal and / or mechanical contact with the operating module 100. is there. In this embodiment, the fluid holding module 200 is held at a predetermined position with respect to the operation module 100 by the clamp mechanism 302. However, if the fluid retention module 200 is formed using a flexible material such as PDMS, for example, small bubbles may accumulate between the two modules, which means that heat conduction through the interface. Will be limited. For other configurations that assemble two modules, the operating module 100 is provided with a plurality of small holes on the surface 118 that align with the fluid holding module 200. These holes are connected to a vacuum source (not shown). When aligning the two modules, a seal is created at the edge of the interface (eg, with an O-ring) and a vacuum source is used to remove air from the space of the two modules. The resulting vacuum ensures good thermal contact while holding the two modules together.

  In some embodiments, a fluid transport / containment module includes a substrate and a fluid holding device having fluid transport / containment elements distributed in the substrate, wherein one or more of the fluid transport / containment elements have microfluidic dimensions. The operating element has a module and an actuation element, and is detachably secured to the fluid holding module so as to interface with the fluid transport / containment element.

  FIG. 3C shows an example of a multi-function microfluidic device 300 ′ having two operating modules 100 ′ and a fluid holding module 200 ′ assembled. In this embodiment, a fluid retaining module 200 'having fluid retaining elements on two surfaces and having at least one flow channel 226 that penetrates the module to connect the two surface fluid retaining elements. Forming an additional function. This configuration not only doubles the number of fluid retaining elements in any arbitrary region, but also allows the flow channels to cross each other without crossing each other, thereby allowing for more complex geometries (configurations). Placement) and increased functionality. In this embodiment, the two operating modules 100 ′ are configured to individually operate the fluid retaining elements on the two sides of the fluid retaining module 200 ′.

  Various components shown in the above-mentioned drawings will be described in detail in the following sections.

Thermal Control Component FIG. 4 includes a fluid holding module 402 and a thermal module 404 shown in combination with the fluid module 402 in an embodiment in the thermal control component 400. The fluid holding module 402 includes a substrate 406 and a thermal control volume element 408 that is recessed and suitable for the substrate 406. For example, the substrate 406 is formed of a material such as polydimethylsiloxane (PDMS) having a lower thermal conductivity than the fluid in the thermal control volume element 408, for example. In this embodiment, the thermal control volume element 408 is occluded by coupling a cover layer 410 to the fluid holding module 402. For example, the cover layer 410 is a thin film of material having a relatively high thermal conductivity (eg, 2 micron thick stainless steel). In some embodiments, the thermal control volume element 408 has a depth of less than 25 microns. Deeper depths are possible, but result in longer thermal equilibration times.

  The thermal module 404 has a heating / cooling element 412 and is removably secured to the fluid holding module 402 so that the heating / cooling element 412 is thermally coupled to the thermal control volume element 408. In this embodiment, the heating / cooling element 412 is a thermoelectric (Peltier) device of geometry designed to ensure that the thermal control volume is heated or cooled substantially uniformly. In this example, the Peltier device is a high conductivity and high thermal conductivity material sandwiched between layers 416 and 418 of n-type and p-type semiconductor thermoelectric materials (eg, bismuth telluride <BiTe>). (Eg, silver) layer 414. In this embodiment, these layers are sandwiched between two layers 420 and 422 of a material with high conductivity and high thermal conductivity (eg, copper) to make electrical contact with the thermoelectric material. In this example, the resulting five-layer sandwich structure is attached to a heat sink 424 formed of a high thermal conductive material 426 (eg, copper or a thermal conductive ceramic). If the heat sink material is conductive, it must also be coated with an electrically insulating material (eg, a thin glass layer 428) to prevent the heat sink from shorting the Peltier junction. If the fluid retention module is covered by a layer of conductive material, the fluid retention module and / or thermal module must be covered with an electrically insulating layer (eg, glass) to prevent short circuiting between Peltier junctions. I must. The heat sink layer may further have a low thermal conductivity region 430 adjacent to the central layer of the five-layer Peltier sandwich structure. It is desirable to maintain the outer surface of the heat sink layer at a constant temperature.

  When the fluid holding module 402 is brought into proper alignment with the thermal module 404, operation of the thermal control component 400 is enabled. As shown in FIG. 4, the thermal control volume element 408 in the fluid retention module 402 is adjacent to the heating / cooling element 412 in the thermal module 404 and is in good thermal contact.

  The five-layer Peltier sandwich structure controls the temperature of the thermal control volume element 408 to be substantially uniform as follows. The current flows through the sandwich structure in the direction from the n-type semiconductor to the p-type semiconductor through the silver layer. This causes heat absorption by the Peltier effect on the side surfaces on both sides of the silver layer. Since the thermal conductivity of silver is on the order of at least two orders of magnitude higher than the thermal conductivity of the materials surrounding the silver layer (including BiTe, fluid, and substrate of fluid retention module 402), the temperature of silver is approximately uniform. Become. The Peltier effect also releases heat at each junction between the BiTe layer and the copper layer. This heat is lost by heat conduction from the copper heat conducting layer to the heat sink layer. In this way, the temperature of the silver layer is maintained at a uniform value lower than the temperature of the heat sink layer. The minimum temperature that can be maintained in the silver layer is limited by heat conduction to all adjacent layers and ohmic heating in the BiTe layer, but if the heat sink is maintained at normal room temperature, water-based fluids Low enough to freeze. When current is passed in the opposite direction from the p-type semiconductor to the n-type semiconductor through the silver layer, the opposite effect is produced. Heat is released at the two sides of the silver layer and absorbed at the copper-BiTe interface. The silver layer can thus be maintained at a uniform temperature above that of the heat sink. The maximum temperature is limited by the heat conduction of all adjacent layers (not in this case by ohmic heating in BiTe, which is a factor of higher temperature) but is water based when the heat sink is maintained at normal room temperature. It is high enough to boil the fluid. The temperature of the silver layer can thus be maintained at any value within the range useful for the process of controlling the magnitude and direction of the current flowing through the sandwich structure. Combining the two modules ensures that there is good thermal contact between the thermal control volume element and the silver layer. Thus, the temperature of the fluid within the thermal control volume element is still maintained at a uniform value within this useful range. In various embodiments, the thermal control volume element 408 has a small dimension in a direction perpendicular to the plane of the interface between the two modules, thereby ensuring that thermal equilibrium is quickly reached. For example, if the thermal control volume element has a depth of 10 microns and the cover layer 410 is formed of stainless steel with a thickness of 2 microns, the water-based fluid in the thermal control volume element 408 is heated / cooled by the heating / cooling element. Equilibrium is reached within 4 milliseconds for 412.

  Temperature control in this system can be realized using the Seebeck effect. In this case, the current of this system is stopped instantaneously. The Seebeck effect creates a potential difference on both sides of the sandwich structure as a function of only the temperature difference between the silver layer and the two copper thermal conduction layers. Alternatively, the temperature difference can be obtained by measuring the voltage-current characteristics of the system without stopping the current.

  In some applications that do not require cooling below ambient temperature, the Peltier sandwich structure can be replaced with an ohmic heater. In various embodiments, a fluid holding module 402 that includes a thermal control volume element 408 can be used interchangeably with a thermal module 404 that includes a Peltier sandwich structure or an ohmic heater.

  In one embodiment, a thermal control device includes a fluid holding module having a substrate and a thermal control volume element (microfluid sized) recessed in the substrate, and a thermal module having a heating / cooling element. The module is removably secured to the fluid holding module, and the heating / cooling element is thermally coupled to the thermal control volume element.

Valve Component FIGS. 5A and 5B show an example of a valve component 500 having a fluid retention module 502 and a thermal module 504 shown assembled to the fluid retention module. The fluid holding module 502 includes a substrate 506 and a flow channel element 508 formed by recessing the substrate 506. For example, the substrate 506 is formed of a material such as, for example, polydimethylsiloxane (PDMS), which has a low thermal conductivity compared to the fluid in the flow channel element 508. In this embodiment, flow channel element 508 is occluded by coupling cover layer 510 to fluid holding module 502. For example, the cover layer 510 is a thin film of a material having a relatively high thermal conductivity (eg, stainless steel having a thickness of 2 microns). In one embodiment, flow channel element 508 is less than 25 microns deep. Although deeper depths are possible, the valve operating time is even longer.

  The thermal module 504 has a heating / cooling element 512 (eg, embedded in the substrate surface), is removably secured to the fluid holding module 502, and thermally couples the heating / cooling element 512 to the flow channel element 508. . In this embodiment, the heating / cooling element 512 is a thermoelectric (Peltier) device of geometry designed to ensure rapid heating or cooling of the flow channel. The Peltier device can have the five-layer configuration described with reference to FIG. 4, or alternatively, the four-layer sandwich structure shown in FIGS. 5A and 5B remains unchanged because it is not necessary to maintain a uniform temperature in the expanded region. The silver layer can be omitted. For example, this four-layer configuration includes layers 516 and 518 of n-type and p-type semiconductor thermoelectric materials (eg, bismuth telluride (BiTe)), which are then electrically connected to the thermoelectric material. In order to make contact, it is sandwiched between two layers 520, 522 of a material with high conductivity and high thermal conductivity (eg copper). In this example, the four-layer sandwich structure is attached to a heat sink 524 formed of a high thermal conductivity material 526 (eg, copper or a thermally conductive ceramic). If the heat sink material is conductive, it must be coated with an electrically insulating material (eg, a thin glass layer 528) to prevent the heat sink from shorting the Peltier junction. When the fluid retention module is coated with a layer of conductive material, the fluid retention module, the operation module, or both must be coated with an electrically insulating layer (eg, glass) to prevent a short circuit across the Peltier junction. . The heat sink layer can also be provided with a low thermal conductivity region 530 adjacent to the central layer of the four layer Peltier sandwich structure. It is desirable to maintain the outer surface of the heat sink layer at a constant temperature.

  To operate the valve component 500, the flow channel element 508 contacts the thermal module 504 so that the flow channel element 508 is in good thermal contact with the thermal manipulation element. The valve is closed using a Peltier device to cool the flow channel below the freezing point of the fluid. As the fluid freezes, the resulting solid plug prevents further flow in the channel. The valve is opened by reversing the direction of the current in the Peltier device to warm the channel or melting the plug, or by turning off the power supply to the Peltier device and heating the flow channel by heat conduction from the surrounding material. The time required to actuate the valve depends on the valve dimensions. For example, a flow channel with a depth of 10 microns and a stainless steel cover layer with a thickness of 2 microns, a valve for a water-based fluid can be opened and closed within 10 milliseconds.

  Thus, in one embodiment, the thermal control device includes a substrate, a fluid holding module having a flow channel (microfluidic dimension) recessed in the substrate, and a thermal module having a Peltier device. A Peltier device is thermally coupled to the flow channel with the module removably secured to the fluid retention module.

  In another embodiment, the valve device includes a substrate, a fluid holding module having a microfluidic flow channel formed on the substrate, and an operation module detachably fixed to the fluid holding module. The operating module has a Peltier device adjacent to the flow channel that changes the phase of the material in the flow channel to form a phase change valve.

Pump Component FIGS. 6A and 6B show an example of a pump component 600 having a fluid retention module 602 and an operating module 604 that is shown in combination with the fluid retention module, and as described above, modules 602 and 604 are Removably fix each other. The fluid holding module 602 has a substrate 606. The main flow channel 608, the control channel 610, and the variable volume cell 612 are formed by recessing the substrate 606 as shown. Cover layer 614 is bonded onto substrate 606. The operating module 604 is a mechanism for changing the volume of the variable volume cell 612 connected to the two valves 620 and 622 (eg, the Peltier actuated valve described above) and the main flow channel 608 between the two valves 620 and 622. (Not shown in this drawing). In this embodiment, the variable volume cell is shown as connected to the main flow channel by a control channel. It should be understood that the variable volume cell can also be aligned with the main flow channel, eliminating the need for a separate control channel. Pumping can also be accomplished by increasing or decreasing the volume of the main flow channel itself.

  In one embodiment, the pump device has a main flow channel and a variable volume cell that merge at the connection, and at least one of the main flow channel and the variable volume cell has a microfluidic dimension, and the fluid And an operation module that is detachably fixed to the holding module. The operation module is provided with two valves arranged adjacent to the main flow channel on both sides of the connection part, and these two valves are connected to the connection part. The control module is selectively controllable to open and close the main flow channel on both sides, and the operation module is provided with a mechanism for selectively controlling the two valves and a mechanism for changing the volume of the variable volume cell. .

  Various mechanisms can be used to perform the volume change while maintaining the ability to separate the module containing the fluid from the operating module.

Electromechanical Operating Mechanism FIGS. 7A and 7B show an example of a pump component 700 having a fluid retention module 702 and an operation module 704 shown in combination with the fluid retention module 702, as described above, the module 702 and 704 are detachably fixed to each other. The fluid holding module 702 has a substrate 706. The main flow channel 708, control channel 710, and variable volume cell 712 are formed by recessing the substrate 706 as shown. Cover layer 714 is bonded onto substrate 706. The operating module 704 includes two valves 720 and 722 (not shown in FIG. 7B for clarity), such as a Peltier actuated valve as described above and a main flow channel 708 between the two valves 720 and 722. And an electromechanical operating mechanism 724 for changing the volume of the connected variable volume cell 712. In this embodiment, the electromechanical operation mechanism 724 includes a plunger member 726 and a drive mechanism 728. The fluid holding module 702 has a flexible membrane 730 disposed adjacent to the electromechanical operating mechanism 724 as shown. For example, the flexible thin film 730 provides a spring load to return to a relaxed state when deformed. In one embodiment, the manipulation module 704 has a movable plunger that deforms the flexible membrane on the variable volume cell when the two modules are assembled and the plunger is projected, thereby , Configured to reduce the volume of the cell. As the plunger retracts, the spring load applied to the flexible membrane applies a force to return the membrane to its relaxed position, thereby restoring the initial volume of the cell. For example, when starting with the plunger retracted, the inflow valve closed, and the outflow valve open, pumping is achieved in the following sequential steps:
1. Pull out the plunger.
2. Close the spill valve.
3. Open the inlet valve.
4. Retract the plunger.
5. Close the inlet valve.
6. Open the spill valve.
After step 6, the pump has returned to its initial state, and this sequential step is repeated as many times as necessary to pump the desired amount of fluid. For ease of explanation, variable volume cell 712 is shown as branching from main flow channel 708 and connected by control channel 710. Variable volume cell 712 may also be incorporated on the line of main flow channel 708. In some applications, it may be advantageous to use the main flow channel 708 itself as a “variable volume cell”. In any case, the plunger member 726 in the manipulation module 704 can be in a position, size, and shape that matches the position, size, and shape of the variable volume cell 712 in the fluid retention module 702. In addition, the pump can be pumped in either direction by making this pump symmetrical and selecting which of the two valves is the inflow valve and which is the outflow valve. I want to be recognized.

Electromagnetic Operating Mechanism FIGS. 8A and 8B show an example of a pump component 800 having a fluid holding module 802 and an operating module 804 shown in combination with the fluid holding module, and as described above, modules 802 and 804 are Removably fix each other. The fluid holding module 802 has a substrate 806. The main flow channel 808, control channel 810, and variable volume cell 812 are formed by recessing the substrate 806 as shown. Cover layer 814 is bonded onto substrate 806. The operating module 804 includes two valves 820 and 822 (not shown in FIG. 8B for clarity), eg, a main flow channel 808 between the Peltier actuated valve as described above and the two valves 820 and 822. And an electromagnetic operating mechanism 824 that changes the volume of the variable volume cell 812 connected to the. In this embodiment, the electromagnetic operating mechanism 824 has an electromagnetic coil 826, thereby avoiding any potential problems that may arise from having a movable component on the operating module 804. In this embodiment, the fluid retention module 802 has a permanent magnet 828 embedded in the substrate 806 adjacent to the variable volume cell 812. In this example, the fluid retention module 802 has a flexible membrane 830 that separates the permanent magnet 828 from the variable volume cell 812, preventing fluid from contacting the magnet, but approaching or moving away from the manipulation module 804. By moving the magnet, the volume of the variable volume cell 812 is decreased or increased, respectively. In this embodiment, when the fluid retention module 802 contacts the action module 804, Peltier heater / coolers 820 and 822 are used to open and close the inflow and outflow valves, as well as electromagnetic elements (electromagnetic coils) in the operating module 804. 826) is used to alternately pull and pull the permanent magnets 828 in the fluid holding module 802 to alternately increase or decrease the volume of the variable volume cell 812. For example, when starting with the electromagnet turned off, the inflow valve closed, and the outflow valve open, pumping is accomplished in the following sequential steps:
1. Attract the permanent magnet.
2. Close the spill valve.
3. Open the inlet valve.
4. Repel the permanent magnet.
5. Close the inlet valve.
6. Open the spill valve.
This sequential step is repeated as many times as necessary to pump the desired amount of fluid. As described above with respect to FIGS. 7A and 7B, the variable volume cell 812 is disposed on the line of the main flow channel 808 or is connected to the main flow channel 808 by a control channel 810. In addition, the pump can be pumped in either direction by making this pump symmetrical and selecting which of the two valves is the inflow valve and which is the outflow valve. I want to be recognized.

Thermal Manipulation Mechanism FIGS. 9A and 9B show an example of a pump component 900 having a fluid retention module 902 and an operation module 904 shown in combination with the fluid retention module, and as described above, the modules 902 and 904 are Removably fix each other. The fluid holding module 902 has a substrate 906. The main flow channel 908, the control channel 910, and the variable volume cell 912 are formed by recessing the substrate 906, as shown. Cover layer 914 is bonded onto substrate 906. The operating module 904 is connected to two valves 920 and 922 (not shown in FIG. 8B for clarity), for example, a Peltier actuated valve as described above and a main flow channel 908 between the two valves 920 and 922. And a thermal operation mechanism 924 for changing the volume of the variable volume cell 912. In this embodiment, the thermal manipulation mechanism 924 includes a thermal control element 926, such as a Peltier heater / cooler. In this embodiment, the first control fluid 932 fills the vicinity of the intersection of the control channel 910 with the main flow channel 908. In this embodiment, the first control fluid 932 does not mix with the fluid being pumped. In this embodiment, the first control fluid 932 has a very low vapor pressure and therefore hardly evaporates over the useful life of any device incorporating this pump. An example of a fluid that meets these requirements is vacuum pump oil. In this example, the second control fluid 934 partially fills the variable volume cell 912 and the control channel 910 and reaches the interface with the first control fluid 932 as shown. In this embodiment, the second control fluid 934 is not mixed with the first control fluid 932. Further, in this embodiment, the second control fluid 934 is a liquid that evaporates at a temperature slightly above the normal temperature around the valve. An example of such a fluid is water. As the second control fluid 934 is heated, some liquid evaporates, pushing the first control fluid 932 to move toward the main flow channel 908. This effectively reduces the volume of the main flow channel 908.

In this example, the operating module 904 incorporates three Peltier heating / cooling elements. These elements are arranged on the pattern and when combining the two modules 902 and 904 of the pump component 900, the two Peltier heated sushi cooling elements are adjacent to the main flow channel 908 and intersect the control channel 910. One on each side. Three Peltier heating / cooling elements are positioned to control the temperature of the variable volume cell 912. For operation, the two modules 902 and 904 of the pump component 900 are combined. For example, starting with the second control fluid 934 at room temperature, closing the inflow valve, and opening the outflow valve, pumping is accomplished in the following sequential steps:
1. Heat and evaporate the second control fluid.
2. Close the spill valve.
3. Open the inlet valve.
4. Cool and condense the second control fluid.
5. Close the inlet valve.
6. Open the spill valve.
This sequential step is repeated as many times as necessary to pump the desired amount of fluid. In addition, the pump can be pumped in either direction by making this pump symmetrical and selecting which of the two valves is the inflow valve and which is the outflow valve. I want to be recognized.

  Because of this pump, when stored for a long period of time, normal changes in ambient temperature cause some of the second control fluid 934 to evaporate, resulting in the first control fluid 932 being pushed into the main flow channel 908. The second control fluid 934 may be lost. To address this concern, the first control fluid 932 is provided as a substance that is solid at the normal ambient temperature of the valve but melts at an appropriate temperature. An example of this type of biphasic material is paraffin wax. This type of configuration is described below.

  FIGS. 10A and 10B show an example of a pump component 1000 that is similar to the pump component 900 (see FIGS. 9A and 9B) except as described below. In this example, a first biphasic material 936 and a second biphasic material 938 are provided in the control channel 910 and variable volume cell 912 as shown. In this example, the operating module 904 includes a heating element 940 that is positioned as shown and that heats and melts the first biphasic material 936 when using the pump. At this time, the pump operates in a cycle as described above. When the pumping action is complete, the first biphasic material 936 cools and solidifies, again confining the second biphasic material 938 within the control channel 910. Alternatively, the first biphasic material 936 is pumped back and forth using a second biphasic material 938 having a relatively low vapor pressure. For example, if the second biphasic material 938 is paraffin wax, it is solid at the normal ambient temperature of the valve and there is no risk of evaporation or loss. The valve is cycled by heating and melting the paraffin, which results in a 2-3% volume increase, followed by cooling and solidification, reversing the volume increase. This volume change is much smaller than that obtained using liquid-vapor phase change, but it is more accurate and may be sufficient for some applications. Paraffin wax can also be used for both the first and second biphasic materials 936 and 938 and can be used without a distinct boundary from each other. Using water as the second biphasic material 938 results in a volume change (about 9%) that is greater than that of paraffin wax, but the phase change generally occurs at a temperature lower than the normal ambient temperature of the valve, so A Peltier device is required. Finally, although not efficient, the pump component can be configured to use the thermal expansion or contraction of the second biphasic material 938 without phase change.

  In another embodiment, a flexible diaphragm is used instead of the first control fluid. In this configuration, the volume of the main flow channel increases or decreases when the control channel is separated from the main flow channel by a flexible diaphragm and the diaphragm is forced to move. The closed control channel is filled with a control fluid, such as water that evaporates when heated and condenses when cooled. The pumping action is performed by a 6-step sequence, as described above. Using a flexible diaphragm instead of the first control fluid provides more flexibility in selecting the second control fluid. That is, it is not necessary to avoid mixed fluids and the potential for fluid loss is reduced.

Bistable valve component In certain applications, it is useful to provide a valve that maintains an open or closed position even without power. In accordance with various embodiments of the present invention, an electrically actuated bistable valve (e.g., a microvalve) uses a phase change control fluid to alternately block or release the flow of working fluid through the valve. . Control fluid is introduced from the side channel and is pumped into and out of the main flow channel when the control fluid is in the liquid phase.

  FIGS. 11A and 11B show an embodiment of a valve device 1100 having a fluid retention module 1102 and an operating module 1104 shown in combination with the fluid retention module, and as described above, the modules 1102 and 1104 are detachable from each other. Secure to. The fluid holding module 1102 has a substrate 1106. In this embodiment, the substrate 1106 is formed from a material having a low thermal conductivity (eg, PDMS). The main flow channel 1108, the control channel 1110, and the reservoir 1112 are formed by recessing the substrate 1106 as shown. In this embodiment, the main flow channel 1108 linearly traverses the valve device 1110 in a horizontal path, and the control channel 1110 is a connection (between the main flow channel 1108 and the control channel 1110). A path from the unit 1114 to the reservoir 1112 is formed. In this example, the valve device 1100 has a biphasic material 1116 that is substantially or completely enclosed within the reservoir 1112 and the control channel 1110 when the valve device 1100 is in an open state. . The biphasic material 1116 is a substance that melts at a temperature higher than the normal outside air temperature of the valve device 1100. Cover layer 1118 is bonded onto substrate 1106.

  In this embodiment, the operating module 1104 has a thermal control element 1120 that, when combined with the two modules, causes the thermal control element 1120 to include the entire reservoir 1112, as well as the control channel 1110 and the main flow channel 1108. Is positioned such that it can be heated to a temperature above the melting point of the biphasic material 1116. For example, the thermal control element 1120 can be a simple resistance heater, in which case after switching off the thermal control element 1120, heat is released to the environment by conduction and the biphasic material 1116 re-solidifies. . Alternatively, the thermal control element 1120 can be a Peltier junction, in which case the biphasic material 1116 operates the Peltier junction as a cooler to reverse the direction of the current to cool and solidify. In this embodiment, the valve device 1100 has a pump mechanism (not shown in this figure) that allows the biphasic material 1116 to enter and exit the connection portion 1114 by pumping. As described herein, various pump mechanisms such as, but not limited to, a plunger operating mechanism, an electromagnetic operating mechanism, or a thermal phase change operating mechanism can be used.

  When the valve device 1100 is in the open state, the biphasic material 1116 is in a solid phase and does not block the main flow channel 1108. To close valve device 1100, the entire region occupied by biphasic material 1116, as well as connection 1114, is heated to a temperature above the melting point of biphasic material 1116. After the phase change to “control fluid”, the biphasic material 1116 fills the biphasic material 1116 until it fully fills the connection 1114 between the two channels 1108 and 1110 and some additional portions of the main flow channel 1108. Pump to main flow channel 1108. Thereafter, when the thermal control element 1120 is stopped, the biphasic material 1116 can be solidified. Referring to FIGS. 12A and 12B, the flow of working fluid (not shown) through the valve device 1100 is blocked by the solid plug 1122 of the biphasic material 1116, thus causing the valve device 1100 to be closed. In both the open and closed states, the biphasic material 1116 is normally in a solid phase and heats to its melting point only to switch the state of the valve device 1100. In order to reopen valve device 1100, thermal control element 1120 is used to melt biphasic material 1116. Once again a “control fluid”, the biphasic material 1116 is then pumped back into the reservoir 1112 to cool and solidify again. The valve device 1100 thus returns to the open state (see FIGS. 11A and 11B). The valve device 1100 can be cycled repeatedly by power supply, but no power is required to maintain the valve device 1100 in the open and closed states. If the biphasic material 1116 is not lost during cycling, there is basically no limit to the number of times that the valve device 1100 can be cycled.

  In one embodiment, the valve device includes a substrate, a channel formed in the substrate, wherein at least one channel has a microfluidic dimension and joins at a connection main flow channel and control channel; and A fluid holding module having a biphasic material in the control channel and an operating module removably secured to the fluid holding module are provided, the operating module having a heating element adjacent to the control channel and the connection, The element shall generate sufficient energy to change the biphasic material from solid phase to liquid phase, and selectively force the biphasic material to the connection when the biphasic material is in liquid phase A pump mechanism for taking in and out is provided to form a bistable phase change valve.

  In some applications, it may be preferable to store fluid in a storage cell in a microfluidic device for an extended period of time until the device is needed. When using the device, the fluid is released, for example acting as a reagent for analyzing the sample. Once the fluid is released and used, there is no need to reseal the storage cell. For this type of application, it is useful to have a disposable bistable valve.

  In various embodiments, the valve device is configured to remain closed until activated, then switch to the open position and maintain this open state. For example, this type of “single use” valve device can be used to seal fluid in a closed volume over an extended period of time (eg, fluid storage in a microfluidic device). 13A and 13B show an embodiment of a valve device 1300 that is similar to the valve device 1100 (see FIGS. 11A, 11B, 12A, and 12B) except as described below. In this embodiment, the fluid retention module 1102 is provided with an end volume 1302 filled with a porous material 1304 (eg, a wick as a suction means) that is easily wetted by the liquid phase biphasic material 1116. In this valve, the biphasic material 1116 is initially in a solid state, blocking the connection 1114 between the main flow channel 1108 and the control channel 1110. The biphasic material 1116, which is initially in the solid phase, also fills the control channel 1110 except for the end volume 1302. The fluid retention module 1102 aligns with the operating module 1104 (provides an operational interface), and the operating module 1104 has a thermal control element 1120 that heats the biphasic material 1116. The valve device 1300 operates by heating the biphasic material 1116. As the biphasic material 1116 is liquefied, it is drawn by capillary action into the end volume 1302 at the end of the control channel 1110, thereby sucking it out of the main flow channel 1108. Next, the thermal control element 1120 switches to cool the control fluid and the control fluid solidifies. In this configuration, the valve device 1300 is open and the working fluid can freely pass through the main flow channel 1108.

  In one embodiment, the valve device includes a substrate, a channel formed in the substrate, wherein at least one channel has a microfluidic dimension, and a main flow channel and a control channel that join each other at a connection, A biphasic material in the control channel, a fluid holding module having a mechanism for sucking out the biphasic material from the connection portion by capillary action when the biphasic material is in a liquid phase, and an operation module for detachably fixing to the fluid holding module The operating module is equipped with a heating element adjacent to the control channel and connection, which can be controlled to generate enough energy to change the biphasic material from solid to liquid phase And make a single use phase change valve.

  As a modification of this valve, a plurality of microchannels considerably smaller than the control channel are used instead of the porous material. 14A and 14B show an embodiment of a valve device 1400 that is similar to the valve device 1100 (see FIGS. 11A, 11B, 12A, and 12B), except as described below. In this embodiment, the fluid retention module 1102 has a plurality of microchannels 1402 disposed within the control channel 1110. Microchannel 1402 is initially free of biphasic material 1116. When the valve device 1400 is heated to melt the biphasic material 1116, the resulting control fluid flows into the microchannel 1402 by capillary action and draws the control fluid from the main flow channel 1108. Thereafter, when the thermal control element 1120 is turned off, the control fluid can be solidified while the valve device 1400 remains open.

  In various embodiments, the disposable bistable valve device is initially open. In such an embodiment, the power supply causes the valve device to close and after power is turned off, it remains closed. 15A, 15B, 16A, and 16B show an embodiment of a valve device 1500 that is similar to the valve device 1100 (see FIGS. 11A, 11B, 12A, and 12B) except as described below. In this embodiment, the fluid retention module 1102 has a control volume 1502 that is closed on at least one side of the control volume by a flexible diaphragm 1504 (eg, a spring loaded metal diaphragm) and a cover layer 1506. Control channel 1110 reaches control volume 1502 and both are filled with biphasic material 1116. However, the connecting portion 1114 is not filled, and the working fluid can freely flow in the valve device 1500. In particular, the control volume 1502 fills up to the point (see FIGS. 15A and 15B) where the flexible diaphragm 1504 is pushed outward by the stress so that the control volume 1502 is larger than the relaxed state. Because the biphasic material 1116 is a solid, the flexible diaphragm 1504 cannot move to its relaxed state and remains pushed outward. The valve device 1500 operates by heating the control volume 1502, the control channel 1110 and the connection 1114 to a temperature above the melting point of the biphasic material 1116. At this time, the diaphragm 1504 relaxes, the size of the control volume 1502 is reduced, and the fluid flows into the connecting portion 1114. Next, the thermal control element 1120 is switched to cooling, and the control fluid is solidified. The valve device 1500 does not require additional power supply and is stable in the closed position as shown in FIGS. 16A and 16B.

  In one embodiment, the valve device is a substrate, a channel formed in the substrate, wherein at least one channel has a microfluidic dimension, and a main flow channel and a control channel that join together at a connection, a control A biphasic material in the channel, a flexible diaphragm adjacent to the biphasic material, biased to bias the biphasic material toward the connection when the biphasic material is in liquid phase A fluid holding module and an operation module that is detachably fixed to the fluid holding module are provided. The operation module is provided with a heating element adjacent to the control channel and the connection, and the heating element generates sufficient energy. To control the biphasic material to change from solid phase to liquid phase, To form an phase change valve times used.

  Similar pumping methodologies can be applied to make disposable bistable valve devices that are initially closed. 17A, 17B, 18A, and 18B show an embodiment of a valve device 1700 that is similar to the valve device 1500 (see FIGS. 15A, 15B, 16A, and 16B), except as described below. In this example, the two-phase material 1116 initially fills the control volume 1502, the control channel 1110, and the connection 1114 and blocks the flow of working fluid through the main flow channel 1108. In this embodiment, the diaphragm is displaced inwardly against the spring load while the control volume 1502 is filled. When power is applied to heat and melt the biphasic material 1116, the diaphragm 1504 relaxes, increasing the control volume 1502 and withdrawing the control fluid from the main flow channel 1108. Next, when the power supply is stopped to cool and solidify the control fluid, the valve device 1700 remains in the form shown in FIGS. 18A and 18B, and at this time, the working fluid can freely flow.

  In one embodiment, the valve device is a substrate, a channel formed in the substrate, wherein at least one channel has a microfluidic dimension, and a main flow channel and a control channel that join each other at a connection, A biphasic material in the control channel, and a flexible diaphragm adjacent to the biphasic material, biased to draw the biphasic material from the connection when the biphasic material is in liquid phase. A fluid holding module having an operating module that is detachably secured to the fluid holding module, the operating module having a heating element adjacent to the control channel and the connection, the heating element having sufficient energy Can be controlled to change the biphasic material from a solid phase to a liquid phase. Accordingly, to as to form a phase change valve single use.

  In each of the embodiments described above, switching the valve includes changing the biphasic material 1116 to a liquid phase, which can potentially be swept downstream of the main flow channel 1108. It can be a problem if there are parts downstream of the system where the solid biphasic material 1116 particles can block small flow channels or interfere with chemical or biological processes or analysis. Any flow through the cycling valve can be a loss of control fluid. In the embodiment described above, this potential problem is addressed by providing a second valve of another type in the valve device in series with the bistable valve. In this way, when the bistable valve is cycled, it can be guaranteed that there is no pressure drop and no flow in the bistable valve. For example, referring to FIG. 19, a valve device 1900 (similar to valve device 1100) is provided with a Peltier actuated valve 1902 in series with a bistable valve. In this figure, the bistable valve is in an open state. To close the bistable valve, power is first supplied to the Peltier actuated valve 1902. This stops all flow in the system. Next, the bistable valve is cycled as described above. After the control fluid solidifies, the Peltier actuation valve 1902 can be turned off. Thereby, it rearranges to the valve apparatus 1900 in the closed state shown in FIG. The valve device 1900 is stable in a closed state without supplying power. In order to open the valve device 1900 again, power is first supplied to close the Peltier actuating valve 1902. This ensures that there is no pressure drop across the bistable valve. Next, there is no concern that the bistable valve is cycled as described above, causing a sudden torrent of working fluid that may push some amount of control fluid downstream. After the bistable valve has completed cycling and the control fluid has solidified, the Peltier actuated valve 1902 can be turned off, allowing fluid flow. The Peltier actuated valve 1902 can be combined with any bistable valve and is not limited to the embodiments described above.

  Although the present invention has been described with reference to the above embodiments, it will be apparent to those skilled in the art that many changes and / or additions can be made to the embodiments described above. The scope of the present invention is intended to cover all such modifications and / or additions.

It is a diagrammatic front view of an embodiment of the operation module. FIG. 3 is a diagrammatic side view of an embodiment of an operation module. FIG. 3 is a diagrammatic front view of an embodiment of a fluid holding module. FIG. 6 is a diagrammatic side view of an embodiment of a fluid retention module. It is a front view of the Example of a multifunction microfluidic device. It is a side view of the Example of a multifunction microfluidic device. FIG. 2 is a side view of an embodiment of a multi-function microfluidic device having two operating modules and a fluid holding module. 1 is a longitudinal cross-sectional view of an example of a thermal control component. FIG. 4 is a cross section at the top of an example of a valve component. FIG. 3 is a longitudinal sectional view of an example of a valve component. FIG. 3 is a front view of an example of a pump component. FIG. 6 is a side view of an example of a pump component. 1 is a front view of an embodiment of a pump component having an electromechanical operating mechanism. FIG. FIG. 4 is a side view of an example of a pump component having an electromechanical operating mechanism. 1 is a front view of an embodiment of a pump component having an electromagnetic operating mechanism. FIG. FIG. 3 is a side view of an embodiment of a pump component having an electromagnetic operating mechanism. 1 is a front view of an embodiment of a pump component having a thermal operating mechanism. FIG. FIG. 3 is a side view of an example of a pump component having a thermal operating mechanism. FIG. 6 is a front view showing an example of another pump component having a thermal operation mechanism. FIG. 5 is a side view of an example of another pump component having a thermal operating mechanism. It is a front view in the Example of the valve apparatus which takes the open position. It is a side view in the Example of the valve apparatus which takes an open position. It is a front view which shows the state which the valve apparatus shown to FIG. 11A and 11B takes a closed position. It is a side view which shows the state which the valve apparatus shown to FIG. 11A and 11B takes a closed position. It is a front view in the Example of the valve apparatus which has a wick mechanism (sucking means). It is a side view in the Example of the valve apparatus which has a wick mechanism. It is a front view in the Example of the valve apparatus which has a capillary action mechanism. It is a side view in the Example of the valve apparatus which has a capillary action mechanism. It is a front view in the Example of the valve apparatus which provides the pump mechanism which has a flexible diaphragm, and is in an open state. It is a side view in the Example of the valve apparatus which provides the pump mechanism which has a flexible diaphragm, and is in an open state. It is a front view which shows the closed state in the valve apparatus of FIG. 15A and 15B. It is a side view which shows the closed state in the valve apparatus of 15A and 15B. It is a front view in the Example of the valve apparatus which provides the pump mechanism which has a flexible diaphragm, and exists in a closed state. It is a side view in the Example of the valve apparatus which provides the pump mechanism which has a flexible diaphragm, and exists in a closed state. It is a front view which shows the open state of the valve apparatus shown to FIG. 17A and 17B. It is a side view which shows the open state of the valve apparatus shown to FIG. 17A and 17B. It is a front view which shows the Example of the valve apparatus which provides the Peltier operation valve arranged in series with the bistable valve, and exists in an open state. It is a front view which shows the Example of the valve apparatus which provides the Peltier operation valve arranged in series with the bistable valve, and is in a closed state.

Claims (86)

In fluid transport / containment devices,
A fluid holding module having a substrate and fluid transport / containment elements distributed on the substrate, wherein one or more of the fluid transport / containment elements have microfluidic dimensions;
An operating module having an operating element, wherein the operating element is detachably secured to the fluid holding module so that the operating element contacts the fluid transport / containment element to provide an active interface;
A cover layer provided on the fluid transport / containment element in the fluid holding module ;
The operation module is provided with a plurality of small holes on the surface that is aligned with the fluid holding module, and these holes are connected to a vacuum source, and when these two modules are aligned, air is passed from the space between the two modules. The fluid transport / containment device is configured to generate a clamping force for holding the two modules together .   2. The fluid transport / containment device of claim 1, wherein the substrate is formed from a polymer material. In fluid transport / containment apparatus of claim 1, wherein, the fluid transport / containment device formed poly-di-methyl polysiloxane (PDMS) the substrate.   2. The fluid transport / containment device according to claim 1, wherein the cover layer is thermally conductive.   2. The fluid transport / containment device according to claim 1, wherein the cover layer is stainless steel.   2. The fluid transport / containment device according to claim 1, wherein the fluid holding module and the operation module are fixed to each other by a clamp mechanism.   2. A fluid transport / containment device according to claim 1, wherein the transport / containment element comprises one or more flow channels.   2. The fluid transport / containment device according to claim 1, wherein the transport / containment element has one or more intake / exhaust inlets and outlets.   The fluid transport / containment device of claim 1, wherein the transport / containment element comprises one or more reservoirs.   2. A fluid transport / containment device according to claim 1, wherein the operating element comprises one or more electromechanical operating mechanisms.   11. The fluid transport / containment device according to claim 10, wherein the electromechanical operation mechanism includes a plunger member and a drive mechanism.   2. The fluid transport / containment device according to claim 1, wherein the operating element has one or more electromagnetic operation mechanisms.   13. The fluid transport / containment device according to claim 12, wherein the electromagnetic operating mechanism includes an electromagnetic coil.   2. The fluid transport / containment device according to claim 1, wherein the operating element has one or more thermal operation mechanisms.   15. A fluid transport / containment device according to claim 14, wherein the thermal operating mechanism comprises a Peltier heater / cooler.   15. A fluid transport / containment device according to claim 14, wherein the thermal operating mechanism comprises an ohmic heater.   2. The fluid transport / containment device according to claim 1, wherein the operating module includes one or more sensing elements.   18. The fluid transportation / containment device according to claim 17, wherein the sensing element is an optical sensor.   18. The fluid transport / containment device according to claim 17, wherein the sensing element is a thermal sensor.   18. A fluid transport / containment device according to claim 17, wherein the sensing element is an electrical sensor. In the thermal control device,
A fluid holding module having a substrate, and a thermally controlled volume element formed by recessing the substrate and having a microfluidic dimension;
A thermal module having a heating / cooling element, wherein the thermal module is detachably fixed to the fluid holding module so that the heating / cooling element is thermally coupled to the thermal control volume element; ,
A cover layer provided on the thermal control volume element in the fluid holding module ,
The operation module is provided with a plurality of small holes on the surface that is aligned with the fluid holding module, and these holes are connected to a vacuum source, and when these two modules are aligned, air is passed from the space between the two modules. The heat control device is characterized in that it is configured to generate a clamping force for holding the two modules together .   The thermal control device according to claim 21, wherein the substrate is formed of a polymer material. In the heat control device according to claim 21, wherein the thermal control device formed of poly-di-methyl-cyclo Sun (PDMS) the substrate.   The thermal control device of claim 21, wherein the thermal control volume element has a depth of less than 25 microns.   The thermal control device according to claim 21, wherein the cover layer is a thermally conductive layer.   The thermal control device according to claim 21, wherein the cover layer is made of stainless steel.   The thermal control device according to claim 21, wherein the fluid holding module and the thermal module are fixed to each other by a clamp mechanism.   The thermal control device according to claim 21, wherein the heating / cooling element is a thermoelectric device.   The thermal control device according to claim 21, wherein the heating / cooling element is a Peltier device.   The thermal control device according to claim 21, wherein the thermal module includes a heat sink element thermally coupled to the heating / cooling element. In the thermal control device,
A fluid holding module having a substrate and a flow channel formed by recessing the substrate and having a microfluidic dimension;
A thermal module having a Peltier device, wherein the thermal module is detachably fixed to the fluid holding module so that the Peltier device is thermally coupled to the flow channel;
A cover provided on the substrate in the fluid holding module ,
The operation module is provided with a plurality of small holes on the surface that is aligned with the fluid holding module, and these holes are connected to a vacuum source, and when these two modules are aligned, air is passed from the space between the two modules. The heat control device is characterized in that it is configured to generate a clamping force for holding the two modules together .   32. The thermal control device according to claim 31, wherein the Peltier device includes two semiconductor thermoelectric material layers that form a Peltier junction adjacent to the flow channel, and two semiconductor thermoelectric material layers sandwiching the two semiconductor thermoelectric material layers. A thermal control device having a four-layer structure having a conductive layer.   32. The thermal control device according to claim 31, wherein the Peltier device comprises a conductive layer adjacent to the flow channel, two semiconductor thermoelectric material layers sandwiching the conductive layer, and the two semiconductor thermoelectric material layers. A thermal control device having a five-layer structure having two other conductive layers sandwiching the substrate. In the pump device,
A fluid holding module having a main flow channel and a variable volume cell that merge at a connection, wherein at least one of the main flow channel and the variable volume cell has a microfluidic dimension; and
An operation module that is detachably fixed to the fluid holding module, and is provided with two valves disposed adjacent to the main flow channel on both sides of the connection portion, and these two valves are connected to the connection portion. In connection with selectively controlling the two valves by means for selectively controlling to open and close the main flow channel on both sides and further providing means for changing the volume of the variable volume cell The operation module adapted to form a pump;
A cover layer provided on the main flow channel and the variable volume cell in the fluid holding module ,
The operation module is provided with a plurality of small holes on the surface that is aligned with the fluid holding module, and these holes are connected to a vacuum source, and when these two modules are aligned, air is passed from the space between the two modules. And a pumping device characterized by generating a clamping force for holding the two modules together .   The pump device according to claim 34, wherein at least one of the two valves is a Peltier operating valve.   35. The pump device according to claim 34, wherein the cover layer is a thermally conductive layer.   The pump device according to claim 34, wherein the cover layer is stainless steel.   The pump device according to claim 34, wherein the fluid holding module and the operation module are fixed to each other by a clamp mechanism.   35. The pump device according to claim 34, wherein the means for changing the volume has an electromechanical operation mechanism adjacent to the variable volume cell.   40. The pump device according to claim 39, wherein the fluid holding module has a flexible thin film facing an electromechanical operation mechanism.   41. The pump device according to claim 40, wherein the flexible thin film is spring loaded.   40. The pump device according to claim 39, wherein the electromechanical operation mechanism includes a plunger member and a drive mechanism.   35. The pump apparatus according to claim 34, wherein the means for changing the volume has an electromagnetic operation mechanism adjacent to the variable volume cell.   44. The pump device according to claim 43, wherein the electromagnetic operation mechanism has an electromagnetic coil, and the fluid holding module has a magnet mechanically connected to the variable volume cell.   35. The pump device according to claim 34, wherein the means for changing the volume has a thermal operation mechanism adjacent to the variable volume cell.   46. The pump device according to claim 45, wherein the thermal operation mechanism is a Peltier heating / cooling element.   46. The pump device according to claim 45, wherein the fluid holding module has one or more control fluids in the variable volume cell.   46. The pump device according to claim 45, wherein the fluid holding module has one or more biphasic materials in the variable volume cell. In the valve device,
A fluid holding module having a substrate and a flow channel formed in the substrate and having microfluidic dimensions;
An operation module detachably fixed to the fluid holding module;
A cover provided on the substrate in the fluid holding module, and the operation module is provided with a Peltier device adjacent to the flow channel, the Peltier device changing the material in the flow channel. Make it controllable, thus making a phase change valve ,
The operation module is provided with a plurality of small holes on the surface that is aligned with the fluid holding module, and these holes are connected to a vacuum source, and when these two modules are aligned, air is passed from the space between the two modules. The valve device is configured to generate a clamping force for holding the two modules together .   50. A valve device according to claim 49, wherein the Peltier device comprises two semiconductor thermoelectric material layers forming a Peltier junction adjacent to the flow channel, and two conductive layers sandwiching the two semiconductor thermoelectric material layers. A valve device having a four-layer structure including layers.   50. The valve device according to claim 49, wherein the Peltier device comprises a conductive layer adjacent to the flow channel, two semiconductor thermoelectric material layers sandwiching the conductive layer, and the two semiconductor thermoelectric material layers. A valve device having a five-layer structure sandwiched between two other conductive layers.   50. The valve device according to claim 49, wherein the cover is a thermally conductive cover. In the valve device,
A substrate, and a channel formed in the substrate, wherein at least one channel has a microfluidic dimension, a main flow channel and a control channel that merge at a connection, and a biphasic feature provided in the control channel A fluid holding module having a material;
An operation module that is detachably fixed to the fluid holding module.
A heating element adjacent to the control channel and connection, the heating element being controllable to generate sufficient energy to change the biphasic material from a solid phase to a liquid phase;
When the biphasic material is in a liquid phase, pump means for selectively forcing the biphasic material to enter and exit the connection portion;
A cover provided on the substrate in the fluid holding module, thereby forming a bistable phase change valve ;
The operation module is provided with a plurality of small holes on the surface that is aligned with the fluid holding module, and these holes are connected to a vacuum source, and when these two modules are aligned, air is passed from the space between the two modules. The valve device is configured to generate a clamping force for holding the two modules together . In the valve device of claim 53, the valve device forming the substrate with a poly-di-methyl-cyclo Sun (PDMS).   54. A valve device according to claim 53, wherein the biphasic material is paraffin wax.   54. The valve device according to claim 53, wherein the cover is a heat conductive cover.   54. A valve device according to claim 53, wherein the heating element is a thermoelectric device.   54. A valve device according to claim 53, wherein the heating element is a Peltier device. 54. The valve device of claim 53, wherein the pump means is
An expansion control material adjacent to the biphasic material;
A valve device comprising a heating / cooling element adjacent to the expansion control material, the heating / cooling element being controllable to transmit energy to increase or decrease the volume of the expansion control material.   54. A valve device according to claim 53, wherein the pump means comprises an electromechanical actuator.   54. A valve device according to claim 53, wherein the pump means comprises an electromagnetic actuator.   54. A valve device according to claim 53, wherein the pump means comprises a thermal phase change actuator.   54. The valve device according to claim 53, further comprising another valve of a different type arranged in series with respect to the bistable phase change valve.   64. A valve device according to claim 63, wherein said additional valve is a Peltier actuated valve. In the valve device,
A substrate, and a channel formed in the substrate, wherein at least one channel has a microfluidic dimension, a main flow channel and a control channel that merge at a connection portion, and a two-phase property provided in the control channel A fluid holding module having a material and a suction means for sucking out the biphasic material from the connection when the biphasic material is in a liquid phase;
An operation module detachably fixed to the fluid holding module;
A cover provided on the substrate in the fluid holding module, the operation module,
A heating element adjacent to the control channel and connection, the heating element being controllable to generate sufficient energy to change the biphasic material from a solid phase to a liquid phase;
Therefore, so as to form a phase change valve single use, also
The operation module is provided with a plurality of small holes on the surface that is aligned with the fluid holding module, and these holes are connected to a vacuum source, and when these two modules are aligned, air is passed from the space between the two modules. The valve device is configured to generate a clamping force for holding the two modules together . In the valve apparatus according to claim 65, wherein, the valve device forming the substrate with a poly-di-methyl-cyclo Sun (PDMS).   66. A valve device according to claim 65, wherein the biphasic material is paraffin wax.   66. The valve device according to claim 65, wherein the cover is a heat conductive cover.   66. The valve device according to claim 65, wherein the heating element is a thermoelectric device.   66. The valve device according to claim 65, wherein the heating element is a Peltier device.   66. The valve device according to claim 65, wherein the suction means includes a reservoir adjacent to the control channel and a porous material provided in the reservoir.   66. The valve device according to claim 65, wherein the suction means includes a reservoir adjacent to the control channel and a microchannel provided in the reservoir. In the valve device,
A substrate, and a channel formed in the substrate, wherein at least one channel has a microfluidic dimension, a main flow channel and a control channel that merge at a connection portion, and a two-phase property provided in the control channel A flexible diaphragm adjacent to the material and the biphasic material, the fluid holding module having the diaphragm for pushing the biphasic material into the connection when the biphasic material is in a liquid phase;
An operation module detachably fixed to the fluid holding module;
A cover provided on the substrate in the fluid holding module, the operation module,
A heating element adjacent to the control channel and connection, the heating element being controllable to generate sufficient energy to change the biphasic material from a solid phase to a liquid phase;
Therefore, so as to form a phase change valve single use, also
The operation module is provided with a plurality of small holes on the surface that is aligned with the fluid holding module, and these holes are connected to a vacuum source, and when these two modules are aligned, air is passed from the space between the two modules. The valve device is configured to generate a clamping force for holding the two modules together . In the valve device of claim 73, the valve device forming the substrate with a poly-di-methyl-cyclo Sun (PDMS).   75. The valve device according to claim 73, wherein the biphasic material is paraffin wax.   75. The valve device according to claim 73, wherein the cover is a heat conductive cover.   75. The valve device according to claim 73, wherein the heating element is a thermoelectric device.   The valve device according to claim 73, wherein the heating element is a Peltier device.   75. The valve device according to claim 73, wherein the flexible diaphragm is made of metal. In the valve device,
A substrate, and a channel formed in the substrate, wherein at least one channel has a microfluidic dimension, a main flow channel and a control channel that merge at a connection portion, and a two-phase property provided in the control channel A flexible diaphragm adjacent to the material and the biphasic material, the fluid holding module having the diaphragm for extruding the biphasic material from the connection when the biphasic material is in a liquid phase;
An operation module detachably fixed to the fluid holding module;
A cover provided on the substrate in the fluid holding module, the operation module,
A heating element adjacent to the control channel and connection, the heating element being controllable to generate sufficient energy to change the biphasic material from a solid phase to a liquid phase;
Therefore, make a single use phase change valve ,
The operation module is provided with a plurality of small holes on the surface that is aligned with the fluid holding module, and these holes are connected to a vacuum source, and when these two modules are aligned, air is passed from the space between the two modules. The valve device is configured to generate a clamping force for holding the two modules together . In the valve apparatus according to claim 80, wherein, the valve device forming the substrate with a poly-di-methyl-cyclo Sun (PDMS).   The valve device according to claim 80, wherein the biphasic material is paraffin wax.   The valve device according to claim 80, wherein the cover is a heat conductive cover.   81. The valve device according to claim 80, wherein the heating element is a thermoelectric device.   The valve device according to claim 80, wherein the heating element is a Peltier device.   The valve device according to claim 80, wherein the flexible diaphragm is made of metal.

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