Classifications

• • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
  • F24—HEATING; RANGES; VENTILATING
  • F24H—FLUID HEATERS, e.g. WATER OR AIR HEATERS, HAVING HEAT-GENERATING MEANS, e.g. HEAT PUMPS, IN GENERAL
  • F24H9/00—Details
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
  • B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
  • B01J19/0093—Microreactors, e.g. miniaturised or microfabricated reactors
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
  • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
  • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
  • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
  • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
  • B01L7/00—Heating or cooling apparatus; Heat insulating devices
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
  • B01L7/00—Heating or cooling apparatus; Heat insulating devices
  • B01L7/52—Heating or cooling apparatus; Heat insulating devices with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples
  • B01L7/525—Heating or cooling apparatus; Heat insulating devices with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples with physical movement of samples between temperature zones
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
  • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
  • B01J2219/00781—Aspects relating to microreactors
  • B01J2219/00783—Laminate assemblies, i.e. the reactor comprising a stack of plates
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
  • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
  • B01J2219/00781—Aspects relating to microreactors
  • B01J2219/00819—Materials of construction
  • B01J2219/00822—Metal
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
  • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
  • B01J2219/00781—Aspects relating to microreactors
  • B01J2219/00819—Materials of construction
  • B01J2219/00824—Ceramic
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
  • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
  • B01J2219/00781—Aspects relating to microreactors
  • B01J2219/00819—Materials of construction
  • B01J2219/00824—Ceramic
  • B01J2219/00826—Quartz
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
  • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
  • B01J2219/00781—Aspects relating to microreactors
  • B01J2219/00819—Materials of construction
  • B01J2219/00831—Glass
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
  • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
  • B01J2219/00781—Aspects relating to microreactors
  • B01J2219/00851—Additional features
  • B01J2219/00853—Employing electrode arrangements
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
  • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
  • B01J2219/00781—Aspects relating to microreactors
  • B01J2219/00873—Heat exchange
  • B01J2219/0088—Peltier-type elements
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
  • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
  • B01J2219/00781—Aspects relating to microreactors
  • B01J2219/00873—Heat exchange
  • B01J2219/00885—Thin film heaters
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
  • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
  • B01J2219/00781—Aspects relating to microreactors
  • B01J2219/00925—Irradiation
  • B01J2219/0093—Electric or magnetic energy
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
  • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
  • B01J2219/00781—Aspects relating to microreactors
  • B01J2219/0095—Control aspects
  • B01J2219/00952—Sensing operations
  • B01J2219/00954—Measured properties
  • B01J2219/00961—Temperature
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
  • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
  • B01J2219/00781—Aspects relating to microreactors
  • B01J2219/0095—Control aspects
  • B01J2219/00986—Microprocessor
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
  • B01L2300/00—Additional constructional details
  • B01L2300/08—Geometry, shape and general structure
  • B01L2300/0809—Geometry, shape and general structure rectangular shaped
  • B01L2300/0816—Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
  • B01L2300/00—Additional constructional details
  • B01L2300/18—Means for temperature control
  • B01L2300/1805—Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks
  • B01L2300/1827—Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks using resistive heater
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01K—MEASURING TEMPERATURE; MEASURING QUANTITY OF HEAT; THERMALLY-SENSITIVE ELEMENTS NOT OTHERWISE PROVIDED FOR
  • G01K7/00—Measuring temperature based on the use of electric or magnetic elements directly sensitive to heat ; Power supply therefor, e.g. using thermoelectric elements
  • G01K7/16—Measuring temperature based on the use of electric or magnetic elements directly sensitive to heat ; Power supply therefor, e.g. using thermoelectric elements using resistive elements

Definitions

• he present invention relates to a microfluidic
• the present invention relates to a microfluidic apparatus using the microfluidic device .
• Patent Literature 1 a heater is disposed for heating fluid in a micro flow channel on the same substrate as that in which the flow channel is disposed
• Patent Literature 2 a micro reactor in which a temperature sensor, which is independent from a heater, is disposed as a unit for controlling the heater
• Patent Literature 3 an airflow detection sensor having a heater also functioning as a temperature sensor by using a phenomenon that a resistance value of a resistive element as a heater changes in accordance with temperature.
• Patent Literature 3 apart from the technical field of the microfluidic device, there is disclosed an apparatus for heating and annealing a wafer, in which a
• supplemental heater is disposed for heating a
• the temperature of the substrate is lowering as the distance from the center of the heater becomes longer so that the temperature of fluid at a position in the flow channel far from the heater becomes low. That is, depending on a positional relationship between the heater and the flow channel, there exists uneven temperature
• FIG. 5A is a perspective view of a
• FIG. 5B is a plan view of the microfluidic device
• FIG. 5C is a cross-sectional view of the microfluidic device cut along the 5C-5C line of FIG. 5B
• FIG. 5D is an enlarged view of the region B of the microfluidic device of FIG. 5C .
• the reference symbol D denotes the center of the widths of the flow channel and the heater
• the reference symbol E denotes the width of the flow channel.
• FIG. 8 is a graph showing temperature distribution along the C-C line in FIG. 5D when the fluid in the micro flow channel is heated by the heater so as to be 94°C.
• the reference symbol D denotes the center of the widths of the flow channel and the heater
• the reference symbol E denotes the width of the flow channel, respectively.
• the temperature of fluid becomes lower. In genetic testing or the like performed by using a microfluidic device, even a small amount of temperature difference may cause an error of testing which cannot be neglected.
• temperature control system of the device erroneously recognizes that the temperature of fluid in the flow channel has changed so that a control error of fluid temperature is resultantly caused, which needs to be addressed .
• Patent Literature 4 has an effect of improving temperature distribution of an object to be heated, but does not have a function of measuring the temperature in real time to control the temperature. Accordingly, this is not suitable for a device which needs highly accurate temperature
• control such as a microfluidic device which is used for performing genetic testing.
• an object of the present invention is to provide a microfluidic device and a microfluidic apparatus using the same for achieving uniform
• microfluidic device and controlling the temperature with high accuracy.
• a microfluidic device including: a substrate; a flow channel disposed in the substrate for flowing through fluid therein; a first resistive element for primarily heating the fluid in the flow channel; and multiple second resistive elements for supplementarily heating the fluid in the flow channel, the second resistive elements being disposed at positions different from a position where the first resistive element is disposed.
• a microfluidic device including: a substrate; multiple flow channels
• first resistive elements for primarily heating the fluid in the multiple flow channels, the first resistive elements being disposed independent from one another so as to correspond to the number of the multiple flow
• the second resistive element being electrically independent from the first resistive elements and disposed in a region of the substrate exterior to an outermost first resistive element in the substrate among the first resistive elements.
• a microfluidic apparatus including the above-described microfluidic devices for measuring a temperature of the fluid in the flow channel based on a resistance value of the first resistive element and adjusting a heat energy input into the first resistive element to control the temperature of the fluid in the flow channel, in which the microfluidic apparatus stores a relational expression between the temperature of the fluid in the flow channel and the resistance value of the first resistive element, and a fixed value of a ratio between a heat energy input into the first resistive element and a heat energy input into a second
• the microfluidic apparatus controls the temperature of the fluid in the flow channel in accordance with the relational expression and the fixed value.
• a microfluidic apparatus further including an arithmetic unit for calculating the fixed value of the ratio between the heat energy input into the first resistive element and the heat energy input into the second resistive element, in which the arithmetic unit calculates the fixed value by using a size of the microfluidic device and an environmental condition of the
• microfluidic apparatus as input parameters.
• the second resistive element for supplementarily heating the fluid in the flow channel is disposed at the position different from the position where the first resistive element is disposed.
• microfluidic apparatus of the present invention including the above-described microfluidic device stores the relational expression between the
• the microfluidic apparatus can provide such advantageous effects that the temperature of fluid in the flow channel can be controlled with high accuracy and the temperature distribution can be improved.
• the microfluidic apparatus of the present invention further includes the arithmetic unit for calculating the fixed value of the ratio between the heat energy input into the first resistive element and the heat energy input into the second resistive element, and the arithmetic unit can calculate the fixed value by using the size of the microfluidic device and the environmental condition of the microfluidic apparatus as input parameters.
• the temperature can be calculated by using the size of the microfluidic device and the environmental condition of the microfluidic apparatus as input parameters.
• microfluidic device can be started to operate in a short period.
• the present invention includes a method of heating fluid, a method of treating fluid, and a method of controlling a temperature of fluid with use of the above-described microfluidic device.
• FIG. 1A is a perspective view illustrating an
• FIG. IB is a plan view illustrating the example of the embodiment of the microfluidic device according to the present invention.
• FIG. 1C is a cross-sectional view cut along the 1C- 1C line of FIG. IB, illustrating the example of the embodiment of the microfluidic device according to the present invention.
• FIG. ID is an enlarged view of the region B of FIG. 1C, illustrating the example of the embodiment of the microfluidic device according to the present invention .
• FIG. 2A is a perspective view illustrating another example of an embodiment of a microfluidic device according to the present invention.
• FIG. 2B is a plan view illustrating another example of the embodiment of the microfluidic device
• FIG. 2C is a cross-sectional view cut along the 2C- 2C line of FIG. 2B, illustrating another example of the embodiment of the microfluidic device according to the present invention.
• FIG. 3A is a perspective view illustrating still another example of an embodiment of a microfluidic device according to the present invention.
• FIG. 3B is a plan view illustrating the still another example of the embodiment of the
• FIG. 3C is a cross-sectional view cut along the 3C- 3C line of FIG. 3B, illustrating the still another example of the embodiment of the microfluidic device according to the present invention.
• FIG. 4A is an exploded view of FIG. 1A illustrating the example of the embodiment of the microfluidic device according to the present invention, and is a perspective view of a substrate in which a flow channel is formed.
• FIG. 4B is an exploded view of FIG. 1A illustrating the example of the embodiment of the microfluidic device according to the present invention, and is a perspective view of an insulating layer.
• FIG. 4C is an exploded view of FIG. 1A illustrating the example of the embodiment of the microfluidic device according to the present invention, and is a perspective view of a layer in which first and second resistive elements and electrode wiring of the first and second resistive elements are formed.
• FIG. 4D is an exploded view of FIG. 1A illustrating the example of the embodiment of the microfluidic device according to the present invention, and is a perspective view of a supporting substrate.
• FIG. 5A is a perspective view illustrating a
• microfluidic device to be compared with the
• FIG. 5B is a plan view illustrating the microfluidic device to be compared with the microfluidic device according to the present invention.
• FIG. 5C is a cross-sectional view cut along the 5C- 5C line of FIG. 5B, illustrating the microfluidic device to be compared with the microfluidic device according to the present invention.
• FIG. 5D is an enlarged view of the region B of FIG. 5C, illustrating the microfluidic device to be compared with the microfluidic device according to the present invention.
• FIG. 6 is a block, diagram of a microfluidic
• FIG. 7A is an exploded view of FIG. 5A illustrating the microfluidic device to be compared with the microfluidic device according to the present
• FIG. 7B is an exploded view of FIG. 5A illustrating the microfluidic device to be compared with the microfluidic device according to the present
• FIG. 7C is an exploded view of FIG. 5A illustrating the microfluidic device to be compared with the microfluidic device according to the present
• FIG. 7D is an exploded view of FIG. 5A illustrating the microfluidic device to be compared with the microfluidic device according to the present
• FIG. 8 is a graph showing temperature distribution of fluid in the flow channel in the comparative example of the microfluidic device and a
• FIG. 9 is a graph showing temperature distribution of fluid in the flow channel in Example 1 of the microfluidic device and the microfluidic apparatus according to the present invention.
• FIG. 10 is a graph showing temperature distribution of fluid in the flow channel in Example 2 of the microfluidic device and the microfluidic apparatus according to the present invention.
• a microfluidic device of the present invention is described hereinafter.
• FIG. 1A is a perspective view illustrating an
• FIG. IB is a plan view of the microfluidic device.
• FIG. 1C is a cross-sectional view of the microfluidic device, cut along the 1C-1C line of FIG. IB.
• FIG. ID is an enlarged view of the region B of the microfluidic device of FIG. 1C.
• FIGS. 2A to 2C and FIGS. 3A to 3C are views illustrating other examples of an
• micro flow channel substrate 1 provided a micro flow channel substrate 1
• a flow channel 2 for primarily heating fluid in the flow channel
• second resistive elements 6 which are disposed at positions different from the position of the first resistive element 5, for supplementally heating the fluid in the flow channel.
• electrode wiring 7 of the first resistive element electrode wiring 8 of the second resistive elements, and an insulating layer 9.
• the first resistive element 5 is disposed on the flow channel 2, and the second resistive elements 6 are disposed apart from the flow channel .
• FIGS. 1A to ID In each of FIGS. 1A to ID, FIGS . 2A to 2C, and FIGS.
• the first resistive element for primarily- heating the fluid in the flow channel and the flow channel provided in the substrate are disposed parallel with each other in their longitudinal directions .
• FIGS. 1A to ID there are disposed a single flow channel, a single first resistive element, and two second resistive elements which are symmetrically positioned across the first resistive element.
• FIGS. 2A to 2C there are disposed a single flow channel, a single first resistive element, and four second resistive elements. Two of the second
• resistive elements are positioned on the same
• flow channels are disposed in parallel to one another, and the first resistive elements are disposed independent from one another so as to correspond to the number of the multiple flow
• the second resistive elements are disposed in regions of the substrate exterior to an outermost first resistive element in the substrate so as to be parallel with the longitudinal direction of the first resistive element.
• FIGS. 4A to 4D are exploded views of FIG. 1A.
• FIG. 4A illustrates the substrate in which the flow channel is formed.
• FIG. 4B illustrates the
• FIG. 4C illustrates the layer in which the first and second resistive elements and the electrode wiring of the first and second resistive elements are formed.
• FIG. 4D illustrates the
• the insulating layer is disposed so as to insulate the resistive elements, the electrode wiring, and the flow channel from one another. This insulating layer is not essential.
• a glass material such as quartz
• a material other than glass such as silicon and ceramics
• a resistive elements a metal, such as platinum, or an oxide, such as ruthenium oxide
• the electrode wiring a metal, such as gold and aluminum
• the insulating layer an insulating material, such as silicon oxide and silicon nitride, is used.
• the first resistive element and the second resistive elements are individually supplied with energy from different voltage supply systems. That is, the first resistive element and the second resistive elements are
• the amount of heat generation is preferred to be controlled by a system which regulates an amount of current input into the second resistive element.
• a system which regulates an amount of current input into the second resistive element even when an optimum value regarding temperature control of fluid in the flow channel varies due to manufacturing variations of the device (such as in thickness of an adhesive material), there is produced an effect that the optimization can be achieved easily.
• the amount of heat generation of the resistive elements can be controlled by the value of voltage or the amount of current.
• second resistive elements may be connected with each other by common wiring.
• the first resistive element and the second resistive elements are independently positioned so that the respective surrounding environments are different from each other.
• the first resistive element and the second resistive element have the same shape and the same area.
• the first and second resistive elements have voltages applied thereto, the voltages exhibiting values different from each other so that temperature distribution of the fluid in the flow channel becomes uniform.
• the first resistive element and the second resistive element have shapes or areas different from each other.
• ID includes the flow inlet 3 and the flow outlet 4 of the fluid, to which tubes for interfaces are
• resistive elements such as platinum, change in accordance with temperature thereof, and hence the resistive elements can also function as temperature sensors.
• temperature of fluid is measured based on the changes in resistance value of the resistive element, and the heat energy to be input into the resistive element is adjusted by a control method, such as PID control, so as to adjust the temperature of fluid to a targeted temperature .
• a control method such as PID control
• the heat energy input into the second resistive elements produces an effect of improving the temperature distribution of the fluid.
• the heat energy needs to be input at an optimum ratio in accordance with the configuration of the microfluidic device.
• the microfluidic device can be operated so as to optimize the temperature distribution of the fluid in the flow channel by calibrating, in advance before the actual operation of the device, the relationship between the temperature distribution of fluid in the flow channel and the ratio of the heat energy input into the first resistive element and the second resistive elements.
• the temperature distribution of fluid in the flow channel can be indirectly measured by using a measuring instrument such as a radiation thermometer.
• the radiation thermometer cannot directly measure the temperature of fluid in the flow channel, but can measure the temperature of the surface of the substrate of the microfluidic device.
• a physical numerical simulation such as a finite element method, the relationship between the temperature distribution of the substrate surface and the temperature distribution of fluid in the flow channel is obtained in advance.
• temperature distribution of fluid in the flow channel can be indirectly measured based on the actually measured temperature distribution of the substrate surface .
• the microfluidic device which has been calibrated as described above, stores the relational expression between the temperature of fluid in the flow channel and the resistance value of the first resistive element, and the fixed value of the ratio of heat energy input into the first resistive element and the second resistive elements.
• the temperature of fluid in the flow channel is controlled in accordance with the above-mentioned relational expression and fixed value.
• the microfluidic apparatus of the present invention includes an arithmetic unit for calculating the above-mentioned fixed value of the ratio between the heat energy input into the first resistive element and the heat energy input into the second resistive elements, and hence the above- mentioned value can be simply obtained. Accordingly, the microfluidic device can be started to operate in a short period of time.
• microfluidic device and an environmental condition of the apparatus are input.
• the size of microfluidic device means elements including the size of the substrate, the size and positions of the resistive elements, the size and positions of the wiring electrodes, and the size and position of the flow channel.
• the environmental condition of the microfluidic device means elements including the size of the substrate, the size and positions of the resistive elements, the size and positions of the wiring electrodes, and the size and position of the flow channel.
• apparatus means elements including the temperature at the place where the apparatus is installed, and the heat transfer coefficient when the heat from the device transfers into air.
• the arithmetic unit includes a numerical calculation program for performing a physical simulation, and a calculator for actually performing the calculation.
• the arithmetic unit performs two cases of
• a physical simulation is actually performed using an input parameter, and in the other case, a simplified calculation is performed using simulation results which have been pre-stored as a database.
• microfluidic device stores the relational expression between the temperature of fluid in the flow channel and the resistance value of the first resistive element, and the fixed value obtained by calculating the heat energy ratio input into the first resistive element and the second resistive elements.
• the fluid temperature in the flow channel is controlled based on the above-mentioned fixed value of the ratio of heat energy and the above-mentioned relationship between the temperature of fluid in the flow channel and the resistance value of the first resistive element.
• FIG. 6 is a block diagram of the microfluidic
• microfluidic device 30 there are provided a microfluidic device 30, and an apparatus environment measuring apparatus 40 for measuring an apparatus environment. Size data 28 of the microfluidic device and parameters 29 of the environmental condition of the apparatus are
• a result calculated by the calculator 38 may be
• calculated by the calculator 36 may be transmitted from the storage area 37 of the database. There is provided a temperature distribution measuring
• apparatus 34 such as a radiation thermometer, for measuring the temperature distribution.
• the value of the heat energy ratio input into the first resistive element and the second resistive elements may be calculated.
• a storage area 32 stores the relational expression between the fluid temperature in the flow channel and the resistance value of the first resistive element.
• a resistance value 22 of the first resistive element is output from the microfluidic device 30 to an output control apparatus 31. The heat energy to be input into the resistive element is calculated based on the
• an output value 21 of the heat energy for heating the resistive elements is output to the microfluidic device 30.
• Example 1 is not limited to the following examples.
• Example 1 is not limited to the following examples.
• FIGS . 1A to ID illustrate the microfluidic device
• Example 1 of the present invention comparing to a comparative example described later, there are
• the distance between the edge of the first resistive element for primarily heating the fluid in the flow channel and the edge of the second resistive element was set to be 100 ⁇ .
• the microfluidic device was manufactured by the same method as that for the comparative example, and PCR reaction was performed similarly to the comparative example. Heat energy identical with the heat energy input into the first resistive element was input into the respective second resistive elements.
• FIG. 9 shows the temperature distribution along the
• microfluidic device of FIGS. 1A to ID Comparing to the comparative example, the amount of lowering in temperature at the edges of fluid in the flow channel was decreased so that the temperature distribution was improved.
• Example 1 the PCR yield was about 80% of the
• the reason why the PCR yield was improved is that a region subjected to a PCR cycle was increased due to the improvement of the
• Example 2 similarly to Example 1, the
• microfluidic device illustrated in FIGS. 1A to ID was used. Similarly to Example 1, PCR reaction was performed. In Example 2, before the actual operation, calibration was performed for obtaining the ratio of heat energy input into the first resistive element and the second resistive elements, which optimizes the temperature distribution of fluid in the flow channel. The calibration was performed by using a radiation thermometer. The temperature distribution of the substrate surface of the microfluidic device was measured by the radiation thermometer, and the fluid temperature in the flow channel was estimated based on the relationship between the surface
• the value for the optimum temperature distribution was obtained by changing the ratio of heat energy input into the above-mentioned resistive elements.
• the optimum temperature distribution. was achieved when the heat energy input into the second resistive elements was about 1.5 to 2.5 times higher than that of the first resistive element.
• IG. 10 shows the temperature distribution along the C-C line of FIG. ID when the fluid temperature in the flow channel was raised to 94 °C by using the
• the heat energy input into the second resistive elements was set to be twice as high as that of the first restive element, and this value and the amount of heat energy input into the resistive elements in accordance with the relational expression between the fluid temperature in the flow channel and the
• Example 2 Comparing to Example 1, the amount of lowering in temperature at the edges of fluid in the flow channel was further decreased so as to improve the temperature distribution.
• Example 2 the PCR yield was about 95% of the
• Example 3 similarly to Examples 1 and 2, the
• microfluidic device illustrated in FIGS. 1A to ID was used. Similarly to Examples 1 and 2, PCR reaction was performed. The ratio of heat energy input into the first resistive element and the second resistive elements was obtained by the arithmetic unit.
• the size of the substrate of the microfluidic device As the input parameters, the size of the substrate of the microfluidic device, the size and positions of the resistive elements, the size and positions of the wiring electrodes, the size and position of the flow channel, the temperature of the place where the apparatus was installed, and the heat transfer
• Example 2 the ratio of heat energy to be input into the first resistive element and the second resistive elements so as to optimize the temperature distribution of fluid in the flow channel was calculated. Similarly to Example 2, the optimum temperature distribution was achieved when the above-mentioned value of ratio of heat energy was about 1.5 to 2.5 times. Comparing to Example 2, a calibration operation was omitted so that the time until the start of actual operation of the device was shortened.
• FIGS. 5A to 5D illustrate the configuration of the microfluidic device used in the comparative example.
• FIGS. 7A to 7D are exploded views of the microfluidic device of FIGS. 5A to 5D.
• FIG. 7A illustrates the substrate in which the flow channel is formed
• FIG. 7D illustrates the supporting substrate.
• the material was a synthetic silica substrate having a heat conductivity of about 1.4 W/m/K at 20°C.
• the flow channel of FIG. 7A disposed in the substrate through which fluid flows was formed by sandblast so as to have the width of about 200 ⁇ and the depth of about 50 ⁇ .
• the first resistive element was formed by depositing a platinum film having a thickness of about 100 nm by a sputtering method and adjusting the width to about 300 ym by a photolithography method.
• the electrode wiring was formed by continuously depositing a titanium-gold- titanium film having a thickness of about 300 nm by a sputtering method and a photolithography method.
• the insulating layer was formed by
• PCR polymerase chain reaction
• microfluidic apparatus is performed by introducing a PCR solution into the flow channel of the
• a reaction solution contains ingredients such as DNA to be amplified, a primer, a DNA polymerase, and a buffer solution.
• a reaction solution is heated to about 94 °C so as to divide double-stranded DNA into single strands.
• the solution is rapidly cooled to about 50 °C so as to combine a primer with the single-stranded DNA for annealing.
• the solution is heated to 70°C so as to allow a DNA polymerase to react with DNA and elongate DNA.
• DNA is amplified through the repetition of this cycle. It is generally estimated that DNA is amplified by 2 n times after n cycles.
• FIG. 8 shows the temperature distribution along the
• microfluidic device of FIGS. 5A to 5D The
• the present invention can be applied to a
• microfluidic device for performing chemosynthesis , environment analysis, and clinical specimen analysis, which involves a heating or cooling process.
• Patent Application No. 2011-108345 filed May 13, 2011, which is hereby incorporated by reference herein in its entirety.

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