JP5147483B2 - Liquid temperature measuring device - Google Patents

Description

  The present invention relates to a liquid temperature measuring device that measures the temperature of a liquid in a microchannel formed in a substrate.

  Conventionally, a method is known in which a temperature sensor that contacts a liquid in a microchannel formed in a substrate is arranged to measure the temperature of the liquid (see Patent Document 1).

  As a method for measuring the refractive index of a liquid, a method is known in which the liquid is accommodated in a triangular prism cell, and the position where transmitted light is detected by a position sensor to detect the refractive index of the liquid (patent) Reference 2).

A method for obtaining the temperature of the fluid to be measured from the relationship between the temperature of the fluid to be measured and the refractive index is also known (see Patent Document 3). In this method, first, laser light that has passed through the optical glass is incident on the fluid to be measured, and the laser light arrival distance due to the change in the refraction angle of the fluid to be measured is measured by a laser light arrival position measuring device that is placed opposite the optical glass. taking measurement. Then, the refractive index is calculated from the refraction angle, and the temperature of the fluid is obtained from the relationship between the temperature of the fluid to be measured and the refractive index obtained in advance.
JP 2006-130599 A Japanese Patent Laid-Open No. 11-295220 JP-A-1-233336

  A micro TAS method for forming a micro flow path in a substrate, flowing a fluid therein, and performing a biochemical reaction has been adopted in many fields, and its usefulness is well known.

  In order to promote this biochemical reaction efficiently, the temperature control of the liquid is important. As shown in Patent Document 1, a liquid temperature sensor is arranged so as to touch the liquid, and the liquid temperature is monitored. ing. However, there are many problems in arranging a sensor in such a small microchannel. For example, it is difficult to manufacture, the liquid temperature can be detected only at a limited point, the flow path layout is restricted, scattered light is generated during other light detection such as fluorescence detection, and the cost of the substrate increases. It is a problem such as. Therefore, a method for measuring the liquid temperature in the flow path in a non-contact manner without arranging the sensor in the substrate is desired.

  As in Patent Document 3, a method is known in which the temperature is obtained by optically detecting the refractive index of a liquid. However, this method also requires a sensor to be disposed in the liquid, and cannot solve the above-described problems.

  The method of Patent Document 2 is a method in which a prism cell is formed from glass and the refractive index of the liquid inside is measured, and the liquid temperature can be obtained from the obtained refractive index. However, when this method is applied to measure the temperature of the liquid in the flow path formed in the substrate, a prism is formed in the flow path, the illumination light is aimed at each thin flow path, and its transmission The arrival position of light must be detected. Therefore, the structure becomes complicated, and high accuracy is required for alignment of the illumination light and the flow path, and there is a problem that it takes time for alignment.

  Therefore, an object of the present invention is to provide a liquid temperature measurement device that does not require a temperature sensor to be arranged in a substrate and does not require high-precision alignment of illumination light with respect to a microchannel in the substrate.

  In order to achieve the above object, a liquid temperature measuring device according to the present invention includes an illumination unit that irradiates substantially parallel light toward a substrate having a microchannel formed therein, and the microchannel of the substantially parallel light. Light separating means for separating first parallel light that is parallel light transmitted through the microchannel after being deflected by the side wall surface, and second parallel light that is parallel light other than the parallel light; The temperature of the liquid in the substrate and the microchannel is determined based on the imaging means disposed at a position for receiving the first parallel light, and the light receiving position of the first parallel light on the imaging means. And a temperature detecting means to be obtained.

  According to the present invention, it is possible to provide a liquid temperature measurement device that does not require a high-precision alignment of illumination light with respect to a microchannel in a substrate without arranging a temperature sensor in the substrate.

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

[First Embodiment]
(Overall configuration of liquid temperature measuring device)
FIG. 1 is a schematic configuration diagram showing a liquid temperature measuring device for measuring the temperature of a liquid in a micro flow channel according to the first embodiment of the present invention.

  The liquid temperature measuring apparatus shown in FIG. 1 has a laser light source 1, a laser shutter 2, a beam expander 3, and a beam homogenizer 4, and these constitute light irradiation means for irradiating substantially parallel illumination light. Yes. Further, the liquid temperature measuring device includes a substrate mounting table 5 on which a microchannel substrate 6 having a microchannel is disposed. Further, a light separating prism 7 is arranged on the side of the substrate mounting table 5 where the illumination light emitted from the light irradiating means is transmitted through the microchannel substrate 6 and emitted. The light separation prism 7 is a first parallel light transmitted through the microchannel after the illumination light (parallel light) is refracted and deflected by the side wall surface of the microchannel formed in the microchannel substrate 6. , And the other second parallel light. An image sensor 8 is disposed on the light exit side of the light separation prism 7. The image sensor 8 is connected to a control circuit 9 having a CPU 10, a memory 11, an A / D conversion circuit 12, and the like. The output from the image sensor 8 is input to the control circuit 9, converted into a digital signal by the A / D conversion circuit 12, and stored in the memory 11. The parallel light flux of the illumination light may not be strictly parallel, and the object of the present invention is achieved as long as it does not affect the temperature measurement described below.

(Microchannel substrate)
FIG. 2 is a plan view of the microchannel substrate shown in FIG.

  Microchannels 101 to 104 are formed in the microchannel substrate 6, and each microchannel is connected to the inlets 105 to 108 and the waste liquid ports 109 to 112, respectively. Further, the microchannels 101 and 102 are connected to a reagent reservoir 113, and the microchannels 103 and 104 are connected to a reagent reservoir 114.

  Heaters 115 to 118 are formed on the upper surface of the microchannel substrate 6 by platinum etching or the like, and electrodes 119 to 126 are connected to the respective heaters via a circuit pattern.

  A region indicated by a broken line in FIG. 2 is a PCR amplification unit 6P that performs a PCR (Polymerase Chain Reaction) reaction. The PCR amplification unit 6P controls the temperature of the liquid in the microchannels 101 to 104 using the heaters 115 to 118 and the temperature block described later, and monitors whether the temperature control is appropriately performed.

(Measurement method)
Next, a method for measuring the temperature of the liquid in the microchannel in the microchannel substrate using the liquid temperature measuring device having such a configuration will be described.

  Referring to FIG. 1, when laser beam light is emitted from the laser light source 1 and the laser shutter 2 is opened, the laser beam light is introduced into the beam expander 3. The beam diameter of the laser beam light is expanded by the beam expander 3 and then introduced into the beam homogenizer 4. The beam homogenizer 4 is composed of a filter having a reduced transmittance near the optical axis, and the laser beam light is converted into a laser beam light having a substantially uniform intensity by correcting the Gaussian distribution by the beam homogenizer 4. . Then, the laser beam light emitted from the beam homogenizer 4 illuminates the PCR amplification unit 6P of the microchannel substrate 6 placed on the substrate mounting table 5. Note that parallel light is output from the laser light source 1, and the entire PCR amplification unit 6P is irradiated with parallel light with substantially the same incident angle.

  FIG. 3 is a diagram illustrating a cross section of the microchannel substrate, the substrate mounting table, the light separation prism, and the imaging device illustrated in FIG. 1. With reference to FIG. 3, how the light beam that has entered the microchannel substrate travels will be described.

  The microchannels 101 to 104 are formed by a bottom surface and an upper surface that are substantially parallel to the plane (the lower surface 6A and the upper surface 6B) of the substrate 6, and left and right side surfaces that are substantially perpendicular to the plane of the substrate 6. It has a rectangular cross-sectional shape. The substrate mounting table 5 has a role of a temperature adjusting block, and a light transmissive heat insulating glass 5A is disposed in a region facing the PCR amplification unit 6P (FIG. 2). Peltier elements 5B and 5C are attached to the lower part of the substrate mounting table 5 so that the temperature of the microchannel substrate 6 can be adjusted.

  As shown in FIG. 3, the laser beam emitted from the light irradiating means is microscopic in a direction perpendicular to the microchannels 101 to 104 and obliquely with respect to the lower surface 6A of the microchannel substrate 6. Illuminate the temperature measurement region of the channels 101-104. As described above, since this light beam is parallel light, the incident angle to the microchannel substrate 6 is the same in the illumination region.

  However, since the way in which light is refracted by the microchannels 101 to 104 differs depending on the incident position of the light, the light emission angle varies depending on the path through which the light passes. Hereinafter, the light beams 130 to 135 passing through different paths will be described.

  The light beams 130 to 133 are transmitted through the heat insulating glass 5A, refracted on the lower surface 6A of the substrate 6, and then refracted and deflected on the vertical side wall surfaces of the microchannels 101 to 104, respectively. Get inside. Then, the light is refracted again on the upper surfaces of the microchannels 101 to 104 and is emitted from the upper surface 6 </ b> B of the substrate 6. At this time, the emission angles of the light beams 130 to 133 emitted from the upper surface 6B of the substrate 6 are incident on the lower surface 6A of the substrate 2 by the refraction action twice on the wall surfaces of the microchannels 101 to 104. It is smaller than the corner. The light beams 130 to 133 emitted from the substrate 6 enter the light separation prism 7, and are totally reflected by the reflection surface 7 </ b> R of the light separation prism 7 and reach the image sensor 8.

  The light beam 134 passes through the heat insulating glass 5A, is refracted by the lower surface 6A of the substrate 6, and then enters the microchannel 103 from the bottom surface of the microchannel 103. Thereafter, the light beam 134 is refracted again on the vertical side wall surface of the microchannel 103 and enters the substrate 6 again, and reaches the upper surface 6B of the substrate 6. At this time, if the incident angle of the light beam 134 on the upper surface 6B of the substrate 6 exceeds the critical angle, it is totally reflected, and the light beam 134 enters the substrate 6 again. When the incident angle is smaller than the critical angle, the light beam 134 is emitted from the upper surface 6B of the substrate 6, but the emission angle is larger than the incident angle of the light beam 134 on the lower surface 6A of the substrate 6. When the light beam 134 is emitted from the upper surface 6B of the substrate 6, the light beam 134 is incident on the light beam separation prism 7, but is refracted on this surface because the incident angle to the total reflection surface 7R is smaller than the critical angle. The light is emitted out of the separation prism 7.

  The light beam 135 passes through the heat insulating glass 5A, is refracted on the lower surface 6A of the substrate 6, passes through the microchannels 102 and 103, and exits from the upper surface 6B of the substrate 6. That is, the light beam 135 does not pass through any microchannel. The emission angle of the light beam 135 emitted from the upper surface 6B of the substrate 6 is equal to the incident angle of the light beam 135 on the lower surface 6A of the substrate 2. This light beam 135 also enters the light beam separation prism 7, but is refracted on this surface because the angle of incidence on the total reflection surface 7 R is smaller than the critical angle, and is emitted outside the light beam separation prism 7.

  Similarly to the above-described light rays, some of the light rays that have entered the substrate 6 are reflected by the heaters 115 and 116, and such light rays are not emitted from the upper surface 6 </ b> B of the substrate 6.

  Thus, among the parallel light incident from the lower surface 6 </ b> A of the substrate 6, the first parallel light that has been refracted and deflected by the side wall surfaces of the microchannels 101 to 104 and then transmitted through the microchannel is the substrate 6. It is emitted from the upper surface 6B. The first parallel light is totally reflected by the total reflection surface 7 </ b> R of the light beam separating prism 7 and reaches the image sensor 8.

  On the other hand, among the parallel light incident from the lower surface 6A of the substrate 6, the second parallel light other than the first parallel light is totally reflected by the upper surface 6B of the substrate 6 and is not emitted from the upper surface 6B; And the light emitted from the upper surface 6B. Among these lights, the light emitted from the upper surface 6B of the substrate 6 without being refracted by the side wall surface of the microchannel also enters the light beam separating prism 7. However, the light emitted from the upper surface 6B of the substrate 6 without being refracted at the side wall surfaces of the microchannels 101 to 104 is refracted at the side wall surface of the microchannels 101 to 104 and emitted from the upper surface 6B of the substrate 6. Is different from the exit angle from the upper surface 6B. Therefore, the light emitted from the upper surface 6B of the substrate 6 without being refracted by the side walls of the microchannels 101 to 104 is refracted by the total reflection surface 7R of the light separating prism 7 and is emitted from the light separating prism 7. The image sensor 8 is not reached.

  Therefore, according to the light beam splitting prism 7 in the present embodiment, only the first parallel light that is refracted and deflected on the side wall surface of the microchannel and then transmitted through the microchannel and emitted from the upper surface 6B of the substrate 6 is obtained. Can be selectively extracted. Therefore, the image sensor 8 receives only the first parallel light.

  FIG. 4 is a diagram showing the light receiving positions of the light beams 130 to 133 on the image sensor 8.

  As described above, the images 401 to 404 corresponding to the microchannels 101 to 104 are formed on the image sensor 8 by the light beams 130 to 133 that have passed through the microchannels 101 to 104 and reached the image sensor 8. The The site | part in each image 401-404 respond | corresponds to the equivalent site | part in the corresponding micro flow path 101-104. Therefore, by analyzing the images 401 to 404, the liquid temperature of each part in the flow direction of the microchannels 101 to 104 can be measured.

(Relationship between angle of incidence on substrate and light deflection on side wall of microchannel)
In the above description, it has been described that the light incident from the lower surface 6A of the substrate 6 is refracted and deflected on the vertical side wall surface of the microchannel and enters the microchannel. However, when the incident angle of the light beam on the lower surface 6A of the substrate 6 is small, the light beam is totally reflected by the vertical side wall surface of the microchannel and does not enter the microchannel. Cannot be measured.

  As an example, a case where synthetic quartz (refractive index 1.461) is used as the material of the substrate 6 and water (refractive index 1.333) is allowed to flow through the microchannel will be described.

  The broken lines in FIG. 5 indicate the critical angle of light rays that enter the microchannel from the substrate 6 at the interface between quartz and water on the vertical side surface of the microchannel. Its critical angle is 65.84 ° (= ASIN (1.333 / 1.461)). Since the refraction angle of the light beam incident at the critical angle on the lower surface 6A of the substrate 6 is 24.16 ° (= 90 ° −65.84 °), the light beam incident at the critical angle is incident on the lower surface 6A of the substrate 6. The angle is 36.72 °. When the incident angle of the light beam on the lower surface 6A of the substrate 6 is smaller than this angle, the light beam is totally reflected by the vertical side wall surface of the micro flow channel, so that the liquid temperature in the micro flow channel cannot be detected. Therefore, the incident angle of the irradiation light on the lower surface 6A of the substrate 6 must be larger than 36.72 °.

  For example, when the incident angle of the irradiation light on the lower surface 6A of the substrate 6 is set to 45 ° as shown by the solid line in FIG. 5, the refraction angle of the irradiation light on the lower surface 6A of the substrate 6 is 28.95 °. The incident angle to the vertical side wall surface of the microchannel is 61.05 ° (= 90 ° −28.95 °). Since this angle is smaller than the above critical angle, the irradiated light is refracted on the side wall surface and enters the microchannel. The refraction angle of the irradiation light on the side wall surface is 73.55 °, and therefore the incident angle to the upper surface of the microchannel is 16.45 (= 90 ° −73.55 °). Irradiation light is refracted at a refraction angle of 14.97 on the top surface of the microchannel, and exits from the top surface 6B of the substrate 6 at a refraction angle of 22.17 °.

  Although the case where the side wall surface of the microchannel is perpendicular to the plane (upper surface and lower surface) of the substrate has been described above, the minimum incident angle of the irradiation light to the lower surface 6A of the substrate 6 is the microchannel. The angle differs between the side wall surface of the substrate and the plane (upper surface and lower surface) of the substrate. Therefore, the incident angle of the irradiation light on the lower surface 6A of the substrate 6 is determined by calculation based on the total reflection angle as described above.

(Relationship between temperature and refractive index)
FIG. 6 is a graph showing the temperature characteristics of the refractive index of synthetic quartz glass and water.

  As shown in FIG. 6, the refractive index of synthetic quartz glass slightly increases with increasing temperature, but the refractive index of water decreases with increasing temperature. Since the refraction angle at the side wall surface of the microchannel is determined by this refractive index difference, the refraction angle of the light beam is obtained from the position of the light beam on the image sensor 8, and the temperature of the liquid in the microchannel is measured based on the refraction angle. can do.

(Temperature and ray angle)
In FIG. 7, illumination light incident from the lower surface 6 </ b> A of the microchannel substrate 6 enters the microchannel from the side wall surface of the microchannel, and exits from the upper surface of the microchannel and the upper surface 6 </ b> B of the microchannel substrate 6. It is a figure which shows the optical path to do. In the figure, the incident angle (A0) is 45 °, and the symbols A1 to A6 indicate the incident angle or the emission angle of each part.

  Further, FIG. 8 shows a light beam angle at each part indicated by reference numerals A1 to A6 in FIG. 7 when the temperature of the microchannel substrate is changed from 25 ° C. to 95 ° C. and a sensor arranged 100 mm away from the upper surface of the substrate. It is a table | surface which shows the change (= (DELTA) D) of the light ray arrival position of.

  FIG. 8 shows that the light beam arrival position moves approximately 0.14 mm with respect to a temperature change of 5 ° C. Therefore, it can be seen that when the image sensor 8 having a size of one pixel of about 7 μm is used, a temperature change of 0.25 ° C. occurs when the light beam arrival position changes by one pixel. The correlation between the light beam arrival position and the temperature shown in FIG. 8 is stored in the memory 11 of the control circuit 9 shown in FIG.

(Separation of rays)
FIG. 9 shows the first parallel light that is refracted and deflected by the light separation prism on the side wall surface of the microchannel formed in the microchannel substrate and transmitted through the microchannel, and the other parts. It is a figure which shows a mode that it isolate | separates into the 2nd parallel light.

  When a right angle prism made of glass having a refractive index of 1.51633 is used as the light separating prism 7, the critical angle at the total reflection surface 7R is 41.26 ° as shown in FIG. The refraction angle at the bottom of the prism is 3.74 °. The incident angle of this light beam is 5.68 °, and when the angle formed between the prism bottom surface and the top surface 6B of the substrate 6 is 22.5 °, the exit angle from the substrate 6 is 28.18 °. Like the light beam indicated by the broken line 9A in the drawing, the light beam having an emission angle from the substrate 6 larger than 28.18 ° is refracted by the total reflection surface 7R, but the emission angle is 28. Light rays smaller than 18 ° are reflected by the total reflection surface 7R. That is, as shown in the table of FIG. 8, the exit angle (A6) of the light beam refracted on the side surface of the microchannel formed in the microchannel substrate is in the range of 21 ° to 23 °. Since it is smaller than 28.18 °, it is totally reflected by the total reflection surface 7R. Since the exit angle of the light beam that is not refracted on the side surface of the microchannel is 45 °, which is the same as the incident angle, such a light beam is not totally reflected by the total reflection surface 7R but is transmitted through the total reflection surface 7R. Means 8 are not reached. In this way, the light separation prism 7 refracts and deflects the parallel light on the side wall surface of the microchannel formed in the microchannel substrate, and transmits the parallel light through the microchannel. It can be separated into other second parallel light.

(Temperature measurement)
Next, an operation for measuring the temperature of the liquid in the microchannel using the liquid temperature measuring apparatus of the present embodiment will be described.

  The inspector sets the sample liquid in the liquid inlets 105 to 108 on the substrate 6 shown in FIG. 2 and attaches a syringe (not shown) to the liquid outlets 109 to 112, Aspirate the sample liquid. The sample sucked into the microchannels 101 to 104 in this way is mixed with the reagents in the reservoirs 113 and 114 and reaches the PCR amplification unit 6P. In the PCR amplifying unit 6P, a thermal cycle is performed in the range of 55 ° C. to 90 ° C. by heating with the heaters 115 to 118 and heating and cooling with the Peltier elements 5B and 5C (see FIG. 3), thereby performing a PCR reaction.

  At this time, whether or not this thermal cycle is properly performed is detected by the liquid temperature measuring device of the present embodiment.

  First, as the liquid is introduced, the substrate 6 is irradiated with laser light (illumination light) as described above, and the image sensor 8 receives the light refracted on the side surface of the microchannel in the substrate 6. When the liquid introduced into the microchannel in the substrate 6 and the substrate 6 are at 25 ° C. corresponding to room temperature, an image of light rays indicated by reference numerals 601 to 604 in FIG. This image is read out, A / D converted, and recorded in the memory 11 as image data.

  Next, in order to raise the liquid temperature to 55 ° C., the heater and the Peltier element are operated. When the liquid introduced into the microchannel in the substrate 6 and the substrate 6 are at 55 ° C., the image of the light beam indicated by reference numerals 605 to 608 in FIG. As described above, the correlation between the light beam arrival position and the temperature shown in FIG. 8 is stored in the memory 11 of the control circuit 9 shown in FIG. Therefore, the control circuit 9 obtains the temperature of the liquid in the substrate 6 and the microchannel based on the difference in the light receiving positions of the images 605 to 608 with respect to the light beam images 601 to 604 on the image sensor 8. The temperature of the liquid inside can be detected. As described above, the control circuit 9 also has a function as temperature detection means for obtaining the temperature of the liquid in the substrate 6 and the microchannel based on the light receiving position of the first parallel light in the image sensor 8.

  Based on the temperature detection value, the heaters 115 to 118 and the Peltier elements 5B and 5C are controlled in order to make the temperature uniform throughout the PCR amplification section 6P of the flow paths 101 to 104. Further, when the temperature of the liquid introduced into the micro flow path in the substrate 6 and the temperature of the substrate 6 is increased to 95 ° C., the image sensor 8 similarly receives light rays as indicated by reference numerals 609 to 612 in FIG. A line image appears in a position further away from the images 601 to 604. The image sensor 8 outputs image data to the control circuit 9 at a constant cycle, and the control circuit 9 collates this data with the correlation shown in FIG. 8 stored in the memory 11 to determine the temperature of the liquid in the microchannel. Ask. The control circuit 9 also serves to drive and control the heaters 115 to 118 and the Peltier elements 5B and 5C, and the control circuit 9 feedback-controls the heaters 115 to 118 and the Peltier elements 5B and 5C based on the obtained liquid temperature.

[Second Embodiment]
In the first embodiment described above, the configuration in which light is incident from the back surface 6A of the substrate 6 has been described. Instead of this configuration, as shown in FIG. 11, the mirror surface of the surface 5R of the substrate mounting table 5 that comes into contact with the substrate back surface 6A is finished to be highly specular, and this surface 5R is used as a reflective surface. It is good also as a structure which injects.

  In the configuration shown in FIG. 11, light beams denoted by reference numerals 201 to 204 are incident on the substrate 6 from the upper surface 6 </ b> B, reflected by the reflecting surface 5 </ b> R of the substrate mounting table 5, and refracted and deflected by the sidewall surfaces of the microchannels 101 to 104. And enters the microchannel. Then, the light is refracted on the upper surface of the microchannel and enters the substrate 6 again. Then, the light is refracted on the upper surface 6B of the substrate 6 and emitted from the substrate 6, enters the light beam separation prism 7, is totally reflected by the total reflection surface 7R, and reaches the imaging device 8.

  The light beam denoted by reference numeral 207 enters the substrate 6 from the upper surface 6B and is refracted and deflected by the side wall surfaces of the microchannels 101 to 104 before being reflected by the reflecting surface 5R of the substrate mounting table 5. The light enters the inside, is refracted at the lower surface of the microchannel, and enters the substrate 6 again. Then, the light is reflected by the reflecting surface 5R of the substrate mounting table 5, is refracted by the upper surface 6B of the substrate 6, is emitted from the substrate 6, is incident on the light separation prism 7, is totally reflected by the total reflecting surface 7R, and is reflected on the imaging device 8. Reach.

  On the other hand, the light beam denoted by reference numeral 205 is incident on the substrate 6 from the upper surface 6B, and then is reflected by the reflecting surface 5R of the substrate mounting table 5 and refracted by the upper surface 6B of the substrate 6 without entering the microchannel. The light is emitted from the substrate 6. The light ray 207 is emitted from the substrate 6 at the same angle as the incident angle on the substrate upper surface 6B, and is transmitted through the total reflection surface 7R even when incident on the light beam separation prism 7, similarly to the light ray 135 shown in FIG. Therefore, the image sensor 8 is not reached. A light beam denoted by reference numeral 206 is incident on the substrate 6 from the upper surface 6B, then is reflected by the reflecting surface 5R of the substrate mounting table 5, is refracted on the lower surface of the microchannel, enters the microchannel, and flows into the microstream. The light is refracted on the side wall surface of the road and enters the substrate 6 again. Since the light ray 206 is totally reflected by the upper surface 6B of the substrate 6 after that, similarly to the light beam 134 shown in FIG. 3, it is not emitted from the upper surface 6B of the substrate.

  According to the configuration shown in FIG. 11, first, similarly to the apparatus described in the first embodiment, the light is reflected by the reflecting surface 5 </ b> R of the substrate mounting table 5 and then refracted by the side wall surfaces of the microchannels 101 to 104. Light beams 201 to 204 that are deflected and transmitted through the microchannel can be imaged by the image sensor 8. In addition to this, in the configuration shown in FIG. 11, the light beam 207 is refracted and deflected on the side wall surfaces of the microchannels 101 to 104, is transmitted through the microchannel, and then is reflected by the reflecting surface 5 </ b> R of the substrate platform 5. Can also be imaged by the image sensor 8. As described above, in the configuration shown in FIG. 11, more light rays that have passed through the microchannels 101 to 104 can be imaged, and as much information is obtained as much, thereby improving the accuracy of temperature measurement. Can do.

  In the first embodiment described above, the micro flow path of the substrate 6 is formed by both side wall surfaces perpendicular to the plane (upper surface and lower surface) of the substrate 6 and upper and lower surfaces parallel to the plane of the substrate 6. An example was described. Instead of this configuration, as shown in FIG. 12, microchannels 301 to 304 whose bottom surface is parallel to the plane (upper surface and lower surface) of substrate 6 and whose cross section is a right triangle may be formed in substrate 6. Good. Thereby, the incident angle of the illumination light to the substrate 6 can be made perpendicular to the lower surface 6 </ b> A of the substrate 6. Even in this configuration, by using the light beam separation prism 7, it is possible to separate light beams that have passed through the microchannels 301 to 304, and the same effects as described above can be obtained.

  The apparatus of the present invention can be used for temperature management when a biochemical reaction in a clinical test is performed using a microchannel.

It is a schematic block diagram which shows the liquid temperature measuring device which measures the temperature of the liquid in the microchannel based on the 1st Embodiment of this invention. It is a top view of the microchannel substrate shown in FIG. It is a figure which shows the cross section of the microchannel substrate shown in FIG. 1, a substrate mounting base, a light separation prism, and an image pick-up element. It is a figure which shows the light-receiving position on the image pick-up element of the light ray which approached into the micro flow path from the side wall surface of the micro flow path, and permeate | transmitted the inside of the micro flow path. It is a figure which shows the relationship between the incident angle to a board | substrate, and the deflection | deviation of the light in the side wall surface of a microchannel. It is a graph which shows the temperature characteristic of the refractive index of synthetic quartz glass and water. It is a figure which shows the optical path from which the illumination light which injected from the lower surface of the microchannel substrate enters into a microchannel from the side wall surface of a microchannel, and radiate | emits from the upper surface of a microchannel, and the upper surface of a microchannel substrate. When the temperature of the microchannel substrate changes from 25 ° C. to 95 ° C., the change in the light beam angle at each part indicated by reference numerals A1 to A6 in FIG. 7 and the light beam arrival position at a distance of 100 mm from the upper surface of the substrate It is a table | surface which shows. The parallel light is refracted and deflected on the side wall surface of the microchannel formed in the microchannel substrate by the light separation prism, and the other second parallel light is transmitted through the microchannel. It is a figure which shows a mode that it isolate | separates into parallel light. It is a figure which shows the light-receiving position of the light ray on an image sensor. It is a figure which shows the cross section of the micro flow-path board | substrate, the substrate mounting base, the light separation prism, and the image pick-up element in the 2nd Embodiment of this invention. It is a figure which shows the cross section of the micro flow-path board | substrate, the substrate mounting base, the light separation prism, and the image pick-up element in the other example of the 2nd Embodiment of this invention.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 Laser light source 3 Beam expander 6 Micro flow path board 7 Light separation prism 8 Image pick-up element 9 Control circuit

Claims (3)

Illumination means for irradiating substantially parallel light toward a substrate having a microchannel formed therein;
Light that separates the substantially parallel light into first parallel light that has been deflected by the side wall surface of the microchannel and then transmitted through the microchannel, and second parallel light that is other parallel light. Separating means;
An imaging means disposed at a position for receiving the first parallel light;
Temperature detecting means for determining the temperature of the liquid in the substrate and the microchannel based on the light receiving position of the first parallel light on the imaging means;
A liquid temperature measuring device. The light separating means is composed of a prism having a total reflection surface,
In the prism, the first parallel light is incident on the total reflection surface of the prism at an angle larger than the critical angle, and the second parallel light is greater than the critical angle with respect to the total reflection surface of the prism. The liquid temperature measuring device according to claim 1, wherein the liquid temperature measuring device is arranged so as to be incident at a small angle.   3. The liquid temperature measurement according to claim 1, wherein the illumination unit includes a laser light source that emits a laser beam that is substantially parallel light, and a beam expander that expands a beam diameter of the laser beam. apparatus.

Images