JP2005055317A - Thermal type flowmeter - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a thermal type flowmeter capable of highly accurate measurement of a micro-flow. <P>SOLUTION: This thermal type flowmeter is equipped with a passage tube 1 wherein a fluid or the like comprising a nucleic acid such as DNA or RNA, or a protein, a micro-heater 11 for supplying heat to the fluid, the first temperature sensor 3a provided on the upstream side of the micro-heater, and the second temperature sensor 3b provided on the downstream side, and is used for measuring the flow rate of the fluid based on the temperature difference between the two temperature sensors. The micro-heater 11 is provided inside the wall of the passage tube so that the fluid is brought into contact therewith, and is constituted so that a heat radiation member 12 is provided on the fluid side surface and a heat absorption member 13 is provided on the fluid side surface of the temperature sensor. The material of the passage tube is a stainless steel or a polymer resin, and the heat radiation member may be a metal wire, and the heat absorption member may be a metal film. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

  The present invention relates to a thermal flow meter capable of measuring a low flow rate.

A conventional thermal flow meter performs measurement with high accuracy in a state where it is difficult to be influenced by a temperature change of a fluid or in a state where pressure loss is reduced (see, for example, Patent Document 1).
FIG. 4 is a block diagram showing a conventional thermal flow meter. In FIG. 4, 1 is a flow channel pipe through which fluid flows, 2 is a heater, 3 is a temperature sensor, 4, 5 and 8 are resistors, 6 is a capacitor, 7 is a transistor, 9 is an amplifier, and 10 is a constant temperature difference control device. It is.
The heater 2 is formed by winding a resistance wire having a small temperature coefficient around the outer periphery of the flow channel tube 1 and applies heat to the fluid. The temperature sensor 3 includes a temperature sensor 3 a provided outside the upstream channel pipe 1 with respect to the heater 2 and a temperature sensor 3 b provided outside the downstream channel pipe 1. The temperature of the fluid in 1 is measured. The constant temperature difference control device 10 is a constant temperature difference control device for converting a signal obtained from the temperature sensors 3a and 3b into a fluid flow rate.
Next, the operation of this thermal flow meter will be described.
(1) First, a current is passed through the heater 2 provided in the flow channel tube 1 to heat the flow channel tube 1. The temperature of the fluid before being heated by the temperature sensor 3 a on the upstream side of the heater 2 is detected through the wall of the flow path pipe 1. The temperature sensor 3 b installed on the downstream side of the heater 2 detects the temperature of the fluid immediately after being heated by the heater 2 through the wall of the flow path tube 1.
(2) The minute change of the temperature difference ΔT detected by the temperature sensors 3a and 3b is amplified as an electric signal by the amplifier 9 and input to the base side of the transistor 7. In the transistor 7, a current flowing from the positive power source + Vs connected to the collector side is output to the emitter side and supplied to the heater 2 in accordance with a signal input to the base side. That is, since the heater heat generation amount is excessive when the temperature difference ΔT is small, the current I supplied to the heater 2 is reduced. If the temperature difference ΔT is large, the current I is increased so as to increase the heater heat generation amount. . Thereby, the temperature difference between the temperature sensors 3a and 3b can be kept constant.
(3) The temperature difference ΔT is set by changing the values of the resistors 4 and 5 and the negative power source −Vs, and the current I flowing through the heater 2 is measured by measuring the voltage applied across the resistor 8. I want.
(4) Thus, the conventional thermal flow meter requires the heating power consumed from the value of the current I and the resistance value of the heater 2 so that the flow rate of the fluid can be measured by the correlation between the heating power and the flow rate. It has become.
Japanese Utility Model Publication No. 5-57624 (page 4-6, Fig. 1)

However, in the above-described conventional thermal flow meter, when measuring a minute flow rate of several hundreds nL / min to several μL / min, the heater 2 and the temperature sensors 3a and 3b are installed outside the flow channel tube 1. Therefore, since the heat generated from the heater 2 is transferred to the temperature sensors 3a and 3b via the flow path pipe 1, the temperature difference ΔT is reduced. In this case, since the current I supplied to the heater 2 needs to be reduced, there is a problem that an error occurs in the value of the heating power consumed by the heater, and accurate measurement cannot be performed. In addition, since there is no mechanism for adjusting the fluid upstream of the temperature sensor 3a, pulsation generated from the liquid feed pump (not shown) is directly transmitted to the temperature sensors 3a and 3b through the fluid. In addition to this, the way in which the heat generated from the heater 2 is transferred to the fluid also changes, so that a minute flow rate cannot be measured.
Therefore, the present invention has been made in view of such problems, and is not affected by pulsation generated from the inside of the liquid feed pump, and has a minute fluid flow rate of several hundreds nL / min to several μL / min. It is an object of the present invention to provide a thermal flow meter capable of measuring the above, and capable of measuring with high sensitivity and high accuracy.

In order to solve the above problems, the present invention is configured as follows.
According to the first aspect of the present invention, there is provided a flow path tube through which a fluid comprising DNA or RNA nucleic acid or protein flows, a microheater for supplying heat to the fluid, and a first heater provided upstream of the microheater. A thermal flow meter that measures the flow rate of the fluid based on a temperature difference between the two temperature sensors, and the micro heater is in contact with the fluid It is provided in the wall of the flow channel tube and a heat radiating member is provided on the fluid side surface, and the temperature sensor is provided in the wall of the flow channel tube so that the fluid is in contact, In addition, a heat absorbing member is provided on the fluid side surface.
According to the first aspect of the present invention, the heat from the microheater is directly transferred to the fluid, so that the microheater does not generate excessive heat and no bubbles are generated even when a fluid having a low boiling point is used. . Further, since the heat absorbing member is disposed in the flow path pipe so as to be in contact with the fluid in the flow path pipe, the temperature of the fluid can be measured with high sensitivity even at a minute flow rate.
In the invention according to claim 2, the material of the channel tube is stainless steel or polymer resin, the heat radiating member is a metal wire, and the heat absorbing member is a metal film.
According to the invention described in claim 2, since the heat conduction is improved by the metal wire and the metal film, the temperature of the fluid can be measured with high sensitivity even at a minute flow rate.
According to a third aspect of the present invention, the surfaces of the heat radiating member and the heat absorbing member are made of at least one inert material of PTFE (polytetrafluoroethylene), PE (polypropylene), PS (polystyrene), and carbon nanotubes. It is covered with a protective member.
According to the invention described in claim 3, even if the fluid is corrosive, the surfaces of the microheater, the wire member, and the metal film are not corroded.
According to a fourth aspect of the present invention, a rectifying unit is provided upstream of the first temperature sensor to make the fluid flow laminar.
According to the fourth aspect of the present invention, the pulsation generated from the inside of the liquid feed pump is canceled while passing through the rectifying unit, so that the possibility of noise entering the temperature sensor that measures the temperature of the fluid is reduced. Therefore, the temperature of the fluid that changes slightly can be measured with high sensitivity.
According to a fifth aspect of the present invention, the rectifying unit is made of a material of PTFE (polytetrafluoroethylene) or PEEK (polyetheretherketone).
According to the fifth aspect of the invention, not only strong acid and strong alkali but also various organic solvents can be flowed as the fluid, so that the degree of freedom of fluid selection is widened.

According to the thermal type flow meter of the present invention, the heat generated from the micro heater is directly transmitted to the fluid through the metal wire, so that the heater generates excessive heat and no bubbles are generated. Therefore, it can be applied to a fluid having a low boiling point.
According to the invention of claim 2, the material of the flow path tube is stainless steel or polymer resin, the heat radiating member is a metal wire, the heat absorbing member is a metal film, and a material having good thermal conductivity is used. Therefore, even at a minute flow rate, the temperature difference of the fluid can be measured with high sensitivity. In addition, since a metal wire is used, the flow of fluid can be stably maintained. According to the invention of claim 3, an inert material such as PTFE, PE, PS, and carbon nanotube is used as a microheater. Since the metal wire provided on the surface of the microheater and the metal film on the surface of the temperature sensor are coated, the microheater, the wire and the metal film are not corroded even if the fluid is corrosive.
According to the fourth aspect of the present invention, since the rectifying unit that makes the flow of the fluid laminar flow is provided on the upstream side of the first temperature sensor, the pulsation due to the liquid feeding pump is canceled while passing through the rectifying unit. This prevents noise from entering the temperature sensor. Therefore, the temperature of the fluid that changes slightly can be measured with high sensitivity.
According to the fifth aspect of the present invention, since the rectifying unit is made of PTFE or PEEK material, strong acid, strong alkali, and various organic solvents can be flowed as the fluid, so that the degree of freedom of fluid selection is widened. There is an effect that it becomes possible to measure the flow rate stably for a long time.

  Hereinafter, specific embodiments of the present invention will be described with reference to the drawings.

FIG. 1 is a configuration diagram showing the configuration of the thermal flow meter of the present invention. In the figure, 11 is a microheater, 3 is a temperature sensor, 12 is a metal wire as a heat radiating member, 13, 13a and 13b are metal films as a heat absorbing member, and 14, 14a, 14b and 14c are protections made of an inert material. It is a member.
The channel tube 1 is made of stainless steel or polymer resin. A microheater 11 is fixed to the wall surface in the flow path tube 1, and a metal wire 12 having a very small length is attached to the top of the microheater 11. On the other hand, a temperature sensor 3 a is fixed at a sufficient distance upstream from the microheater 11 1, and a thin metal film 13 a is fixed on the surface of the temperature sensor 3 a so as to be in contact with the fluid in the flow channel tube 1. Further, immediately after the downstream side of the micro heater 11, the temperature sensor 3 b is fixed, and a thin metal film 13 b is also fixed to the upper part of the temperature sensor 3 b so as to be in contact with the fluid in the flow channel tube 1. . The arrows in the figure indicate the direction of fluid flow.
First, the temperature T ₁ of the fluid passing through the flow channel pipe 1 is measured with the metal film 13a. The heat generated from the microheater 11 is transmitted to the metal wire 12 and supplied to the fluid, and the temperature T _{2 of} the fluid that has absorbed the heat generated from the metal wire 12 is measured at the point of the metal film 13b. The temperature difference ΔT is calculated as in 1).
ΔT = T ₂ -T ₁ (1)
The amount of heat Q that the fluid obtains from the microheater 11 using this temperature difference ΔT is expressed by the following equation (2).
Q = α × S × ΔT (2)
S: Area within the flow path pipe 1 (area of fluid)
α: When the heat transfer coefficient α is expressed as a function of the number of Ray nozzles Re, the following equation (3) is obtained.
α = 0.023 × (Re) ^0.8 × (Pr) ^0.4 × λ / D (3)
Re: Ray nozzle number Pr: Prandtl number λ: Thermal conductivity From the above, if ΔT and λ are constant, the heat quantity Q is proportional to α. Since α is a function of Re, the amount of heat Q is proportional to the flow velocity. Therefore, the flow rate of the fluid is measured by measuring the amount of heat Q transferred to the fluid.
Therefore, the heat generated from the microheater 11 is directly transmitted to the fluid through the metal wire 12 as compared with the case where heat is supplied from the outside of the flow channel tube 1, so that the microheater 11 generates excessive heat. There is no. Therefore, the possibility that bubbles are generated is reduced even when a fluid having a low boiling point is used. Further, since the metal films 13a and 13b are arranged so as to be in contact with the fluid in the flow channel tube 1 and have good thermal conductivity such as copper and aluminum which are good as electrode materials, a minute flow rate is used. Even in the case of flowing in, the temperature difference (ΔT) of the fluid can be measured with high sensitivity. Furthermore, since the metal wire 12 having a very small length protrudes into the flow channel tube 1, the fluid flow can be stably maintained.
Note that a plate electrode may be used instead of a wire for the heat transfer means from the microheater 11 to the fluid, but a wire shape is preferred, and a carbon nanotube may be used as the electrode material for the electrode material.

FIG. 2 is a diagram showing the configuration of the second embodiment. An inert material 18 is coated on the surface of the microheater 11 and the metal wire 12 affixed to the upper surface of the microheater 11, and the inert material 19 is also applied to the surfaces of the metal film 13 a and the metal film 13 b. 20 is coated.
Thus, a polymer resin such as PTEF or PEEK (peak) having chemical resistance or a carbon nanotube having a characteristic of poor chemical reactivity, which is made of metal attached to the top of the microheater 11 and the microheater 11. Since the surface of the wire 12, the metal film 13a, and the metal film 13b is thinly and uniformly coated, hydrochloric acid (HCl), sulfuric acid (H ₂ SO ₄ ), nitric acid (HNO ₃ ), hydrofluoric acid Even if a solvent such as (HF), sodium hydroxide (NaOH), acetone (CH ₃ COCH ₃ ), chloroform (CHCl ₃ ) is flowed as a fluid, the components of the electrode, such as copper and aluminum, undergo chemical changes and are in the fluid. In addition, biomolecules such as nucleic acids and proteins and organic compounds contained in the fluid are not adsorbed and remain on the electrode surface. With it. Therefore, it is possible to measure the flow rate stably for a long period of time without lowering the sensitivity of the electrode or causing a contamination from the inside of the flow meter.
In addition, when using a carbon nanotube as a coating material, it is preferable to use a material that has been subjected to an inert treatment on the end surface, such as bonding fluorine (F) to both end surfaces of the tube.

FIG. 3 is a diagram showing a third embodiment. In the flow path pipe 1, 15 is provided with a rectification unit 15 upstream of the rectification unit temperature sensor 3b. Thus, since the fluid sent from the liquid feed pump (not shown) has a structure that passes through a large number of holes formed in a lattice shape in the rectifying unit 15, the liquid feed pump The generated pulsation is gradually canceled while passing through the rectifying unit 15. Therefore, the possibility of noise entering the metal film 13a and the metal film 13b for measuring the temperature of the fluid can be reduced. Further, since a polymer resin such as PTFE or PEEK is used as the material of the rectifying unit 15, not only strong acid / strong alkali such as hydrochloric acid, nitric acid, sulfuric acid, hydrofluoric acid, sodium hydroxide, but also alcohol, acetone, hexane In addition, an organic solvent such as chloroform can be allowed to flow.

  In the present invention, since there is no need to limit the kind of fluid, chemical synthesis in a microreactor, high performance liquid chromatography (HPLC), FIA (Flow Injection Analysis) apparatus, SPR apparatus, etc. are used. The present invention can be applied to the measurement of organic compounds in a solution and the flow rate control of a liquid feed pump used for highly sensitive measurement such as DNA-DNA interaction and protein-protein interaction.

1 is a side sectional view of a thermal flow meter showing a first embodiment of the present invention. The sectional side view of the thermal type flow meter which shows 2nd Example of this invention. The partial expanded side sectional view of the thermal type flow meter which shows 3rd Example of this invention. The block diagram which shows the structure of the conventional thermal type flow meter.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 Channel pipe 2 Heater 3 Temperature sensor 3a 1st temperature sensor 3b 2nd temperature sensor 4, 5, 8 Resistor 6 Capacitor 7 Transistor 9 Amplifier 10 Constant temperature difference control apparatus 11 Micro heater 12 Heat radiating member (metal wire )
13, 13a, 13b Endothermic member (metal film)
14, 14a, 14b, 14c protection member 15 rectification unit

Claims (5)

A flow path tube through which a fluid such as DNA or RNA nucleic acid or protein flows, a microheater for supplying heat to the fluid, a first temperature sensor provided on the upstream side of the microheater, provided on the downstream side A thermal flow meter that includes a second temperature sensor and measures the flow rate of the fluid based on a temperature difference between the two temperature sensors;
The microheater is provided in the wall of the flow path tube so that the fluid comes into contact, and a heat radiating member is provided on the fluid side surface, and the temperature sensor is arranged so that the fluid comes into contact with the flow path. A thermal flow meter provided in a wall of a pipe and provided with a heat absorbing member on the fluid side surface. 2. The thermal flow meter according to claim 1, wherein the material of the flow path tube is stainless steel or polymer resin, the heat radiating member is a metal wire, and the heat absorbing member is a metal film. The surfaces of the heat radiating member and the heat absorbing member are covered with a protective member made of at least one inert material of PTFE (polytetrafluoroethylene), PE (polypropylene), PS (polystyrene) and carbon nanotubes. The thermal flow meter according to claim 1 or 2. 4. The thermal flow meter according to claim 1, further comprising a rectification unit configured to make the flow of the fluid laminar on the upstream side of the first temperature sensor. 5. The thermal flow meter according to claim 4, wherein the rectifying unit is made of a material made of PTFE (polytetrafluoroethylene) or PEEK (polyetheretherketone).

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