JP2007003409A - Microchip inspection device - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an energy saving type microchip inspection device. <P>SOLUTION: This microchip inspection device of emitting light to a microchip storing a specimen to carry out measurement has a casing, a light source part for irradiating the microchip with the light of a prescribed wavelength, a chip holder attached with the microchip, and a photoreception part for receiving light emitted from the microchip, the microchip inspection device is provided with a heat transfer means for transferring heat radiated from the light source part to the chip holder, and the microchip is brought thereby into a prescribed temperature, in the microchip inspection device. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to a microchip inspection apparatus for identifying a component to be detected in a liquid sample to be measured by absorptiometry or fluorescence measurement and measuring its concentration. In particular, the present invention relates to a microchip inspection apparatus used for measuring enzyme activities such as GPT (glutamate pyruvate transaminase) and γ-GTP (γ glutamyl transpeptidase) required for diagnosing liver function of the human body.

  In recent years, micromachine technology has been applied to perform microanalysis of chemical analysis, etc., in comparison with conventional devices, and analysis using microchips called microlabs (μ-ToTal Analysis System) and “Lab on a chip”. The method is drawing attention. Patent Document 1 discloses this technique. Such an analysis system using a microchip performs all analysis processes such as mixing, reaction, separation, extraction, and detection of reagents in a fine flow path formed on a small substrate by micromachine fabrication technology. For example, it is used for analysis of blood in the medical field, analysis of biomolecules such as ultra trace amounts of proteins and nucleic acids, and the like.

  In μ-TAS, an optical measurement method such as an absorptiometry or a fluorescence method is often used in order to quantify extracted substances or reactive organisms. In the absorptiometry, a specimen is filled in a very small measuring cell having a cross section of about 10 to 500 μm square formed in a microchip, the measuring light is incident on the measuring cell, and the passing light passing through the measuring cell is measured. This is a method for detecting the component concentration by measuring the amount of light absorption of the liquid based on the received light and the passing light. Similarly, the fluorescence method measures the wavelength and intensity of the fluorescence emitted from a sample when the measurement light is incident on a sample filled in a measurement cell having a cross-section of about 10 to 500 μm square formed in a microchip, and the concentration of the component It is a method of detecting.

  A light source for performing spectrophotometric measurement and fluorescence measurement in an inspection device (hereinafter referred to as a microchip inspection device) using μ-TAS emits a tube bulb that emits continuous light, such as a halogen lamp, or light of a single wavelength. A high brightness LED is used. In the absorptiometry and fluorescence methods of biological substances, it is necessary to warm the body at a normal temperature, for example, blood temperature, around 37 ° C., which is close to the human body temperature, when the reagent is reacted.

Patent Document 2 discloses an apparatus and method for adjusting the temperature of a plate-shaped microchemical device having a microchannel in a member used in a wide range of fields including medical and chemical industries. However, this disclosed technology is a technology having a temperature control block set in a temperature range of a desired setting temperature ± 10 ° C., which is in contact with both front and back outer surfaces of a micro chemical device. In the embodiment, an electric heater is used for heating the temperature control block. Further, Patent Document 2 describes temperature control using a Peltier element, temperature control for flowing a liquid such as hot water, cold water, and oil into a temperature control block, and temperature control using electromagnetic waves such as infrared rays and microwaves. There is no disclosure of how the temperature control block is heated by means other than the electric heater.
JP 2004-109099 A JP 2002-58470 A

In a microchip inspection device that irradiates light to a microchip containing a specimen and performs spectrophotometric measurement or fluorescence measurement, the bulbs such as halogen lamps used for measurement are not only light with a wavelength necessary for measurement and visible light. Also emits thermal energy. In addition, high-brightness LEDs also emit thermal energy in addition to the emitted light.
The thermal energy was discharged outside the microchip inspection apparatus without using any light source, and was inefficient in terms of energy. SUMMARY OF THE INVENTION An object of the present invention is to provide an energy-saving microchip inspection apparatus that raises the temperature of a microchip using thermal energy of a measurement light source.

  In order to solve the above problems, the invention described in claim 1 is a microchip inspection apparatus that performs measurement by irradiating light to a microchip containing a specimen. The microchip inspection apparatus includes a housing, the microchip A light source unit that irradiates light to a chip, a chip holder in which the microchip is incorporated, and a light receiving unit that receives light emitted from the microchip, wherein the chip generates heat generated from the light source unit A microchip inspection apparatus comprising a heat transfer means for transmitting to a holder and setting the microchip to a predetermined temperature.

  According to the present invention, by using the microchip inspection apparatus including the heat transfer means from the light source unit to the microchip, the heat energy generated by the light source unit can be used as a heat source for heating the microchip. Further, it is not necessary to provide a mechanism for heating the microchip with another heat source, or energy supplied to the other heat source can be reduced, so that energy can be saved.

  An embodiment of the present invention will be described with reference to FIGS. FIG. 1 is an apparatus for measuring absorptiometry, which is an embodiment of the present invention, and is shown as a schematic sectional view of the apparatus. The microchip inspection apparatus of the present invention includes a housing 1, a light source unit 2, a chip holder 3, and a light receiving unit 4 in the housing 1.

  The light source of the light source unit 2 is a lamp 201 housed in a lamp holder 202. In this embodiment, a short arc xenon lamp is used as the lamp 201. Radiation light from the short arc xenon lamp is emitted from the opening 203 of the lamp holder 202, and the radiation light is made almost parallel light when passing through the optical lens 5, and passes through the light in the wavelength range necessary for measurement. And reaches a metal chip holder 3 in which a resin microchip 10 described later is incorporated, passes through an aperture 31, and passes through the measurement cell 11 of the microchip 10 in which a liquid specimen made of blood or the like is accommodated. The light is received by the photodiode of the light receiving unit 4.

  The lamp holder 202 and the chip holder 3 are connected by a metal heat conduction member 30. The heat conducting member 30 is constructed by placing a flat lid member 30b on a member 30a provided with a bowl-shaped groove standing from a base plate 35 as a base plate member. FIG.1 (b) shows AA 'sectional drawing. An optical path is formed between the member 30a having a bowl-shaped groove and the flat lid member 30b.

  Of the light components emitted from the short arc xenon lamp, light in the infrared region warms the lamp holder 202, travels through the heat conducting member 30 connected to the lamp holder 202, and conducts heat to the chip holder 3. The chip holder 3 rises in temperature and reaches a target temperature, for example, 37 ° C. The temperature of the microchip 10 incorporated in the chip holder 3 also reaches 37 ° C.

  In the present embodiment, the temperature of the tip holder is adjusted to 37 ° C. by increasing / decreasing the input to the short arc xenon lamp before starting the absorbance measurement. In this embodiment, the short arc xenon lamp is used as the light source. However, an incandescent lamp such as a halogen lamp may be used.

  FIG. 2 shows another embodiment of the present invention and is shown as a schematic cross-sectional view. The housing 55 has a light source unit 40, a chip holder 43, and a light receiving unit 45 in the housing 55. The housing 55 includes slits 55a and 55b for supplying and exhausting air. A combination of a directional light emitting diode 401 and a heat sink 44 is used as the light source unit 40. Since it is a directional light emitting diode, an optical lens is not required separately from the embodiment of FIG. Note that the light-emitting diode 401 and the heat sink 44 are external views for convenience and are not cross-sectional views.

  The light emitted from the light emitting diode 401 is light in the wavelength range necessary for measurement, reaches the chip holder 43, passes through the aperture 49, passes through the measurement cell 51 of the microchip 50, and is received by the photodiode of the light receiving unit 45. . The light emitting diode 401 has a temperature of 50 to 60 ° C. during light emission. The heat sink 44 is attached to the surface opposite to the light emitting surface of the light emitting diode 401, and the heat from the heat sink 44 that stores the heat generated from the light emitting diode 401 by the blower of the blower fan 47 is transported toward the chip holder 43.

  A temperature sensor 46 is disposed in the chip holder 43 so as to be positioned in the vicinity of the microchip 10, and although not shown, the rotational speed of the blower fan 47 is controlled by feedback control using temperature rise / fall data. The chip holder 43 is allowed to reach a predetermined temperature, for example, 37 ° C.

FIG. 3 shows another embodiment of the present invention and is shown as a schematic diagram. The case is omitted. Unlike FIG. 1 and FIG. 2, FIG. 3 shows the arrangement of the light source unit and the chip holder as viewed from above, and FIG. 3B shows a BB ′ cross section.
Although FIG. 3B shows the base plate 80, the base plate 80 is omitted in FIG. In the present embodiment, an electric heater 75 is incorporated in the chip holder 63, and the heat from the light source unit 300 additionally contributes to the temperature increase of the microchip 60. The light source unit 300 is a lamp 301 housed in a lamp holder 302. A halogen lamp is used as the lamp 301. The light emitted from the lamp 301 is emitted through the opening 303 of the lamp holder 302, is made to be substantially parallel light by the optical lens 65, and the light selected by the filter 66 that transmits light in the wavelength region necessary for measurement is the chip. The light reaches the holder 63, passes through the aperture 69, passes through the microchip measurement cell 61, and is received by the photodiode of the light receiving unit 64. The lamp holder 302 and the chip holder 63 are connected by a heat pipe 70 filled with a heat medium such as pure water.

FIG. 4 shows the flow of heat by the heat pipe in the embodiment of the present invention. One of the heat pipes 70 disposed between the light source unit 300 and the chip holder 63 is shown. Exhaust heat from the halogen lamp is transferred to the heat medium in the heat pipe 70 ((A) in the figure), and from the boiling of the heat medium ((B) in the figure) to the low temperature part of the heat medium vapor inside the heat pipe. Of the heat medium ((c) in the figure), there is agglomeration of the heat medium ((d) in the figure), and heat is released ((e) in the figure). Then, a cycle of recirculation of the heat medium ((F) in the figure) due to capillary action occurs, and heat is transported to the chip holder 63 through the exchange of latent heat during this period.
In the present embodiment, an example in which a halogen lamp is used as a light source has been described, but a short arc xenon lamp may be used.

  Although the microchip shown in FIGS. 1 to 3 shows an example of a single-chip single measurement cell having only one measurement cell for storing a sample in one chip, the present invention sets the temperature of the microchip to a predetermined value. The applied microchip is not limited to a single-chip single measurement cell, and includes a plurality of measurement cells containing different specimens in a single chip. Of course, the present invention can also be applied to a microchip of a single-chip multiple measurement cell capable of performing component analysis on a single chip.

  FIG. 5 shows a configuration example of the microchip 10 and the chip holder 6 used in the microchip inspection apparatus of the present invention. The microchip 10 is made of a plastic material such as a thermoplastic resin such as PMMA (polymethyl methacrylate), PET (polyethylene terephthalate), PC (polycarbonate), or a thermosetting resin such as an epoxy resin. The microchip 10 shown in this example is formed by bonding two plate members. A groove is formed in advance on one side of the bonding surface, and the groove forms a cavity by bonding. Then, an analysis solution introduction unit 14 that communicates with the outside of the chip and introduces the analysis solution into the chip, a reagent reservoir unit 15 filled with a reagent for reacting with the analysis solution, and a reagent mixing unit 13 that mixes the analysis solution and the reagent are mixed. A measurement cell 11 is provided for allowing light to pass from the outside to the completed test solution. The measurement cell 11 is linearly arranged along one end surface of the plate member.

  A specific example of maintaining a predetermined temperature in the apparatus configuration of FIG. 1 will be described. The lamp of the light source unit 2 was a short arc xenon lamp, loaded in the lamp holder 202, and lit at 65W. The microchip 10 is made of PET (polyethylene terephthalate) resin having a length of 32 mm, a width of 30 mm, and a thickness of 2 mm, and is set in a 30 mm square t2 mm chip holder 3. In the optical system, the lens 5 is a plano-convex lens of Φ15, the filter 6 is a band-pass filter of 340 nm, the diameter of the aperture 31 is 0.3 mm, and the light receiver 4 is a silicon photodiode.

  The object to be measured is GOT (Glutamic-oxaloacetic tramsminase) of an enzyme in blood analysis, and the measurement time is 10 minutes per chip when the set temperature of the microchip is 37 ° C.

As the heat conducting member 30, a metal block having good heat conductivity such as copper or aluminum is processed to form a hollow prismatic member, and the hollow portion is connected as an optical path between the lamp holder and the chip holder. did. As shown in FIG. 1B, an optical path is formed between the member 30a having a bowl-shaped groove and the flat lid member 30b. In designing the microchip inspection apparatus, the dimensions of the chip holder 3 and the heat conducting member 30 were calculated by calculating their heat capacities, and the temperature of the microchip 10 was determined to be around 37 ° C. In particular, when the size of the chip holder 3 is increased, the heat capacity is increased, and the lamp power is constant during optical measurement, the temperature change of the macro chip is reduced.
Before starting the absorbance measurement, the input to the short arc xenon lamp was increased or decreased to adjust the temperature of the tip holder to 37 ° C. At that time, thermal equilibrium was reached 10 minutes after the lamp was turned on. At the time of optical measurement, it was 36.8 ° C. at the start of measurement, and 37.2 at the end of measurement after 10 minutes. As described above, the temperature change during 10 minutes during the measurement is within 0.4 eg, and the accuracy of the temperature control is sufficient for the GOT measurement.

  A specific example of maintaining the predetermined temperature in the apparatus configuration of FIG. 2 will be described. The light-emitting diode 401 having an emission wavelength of 405 nm is turned on for 6 W, the microchip is made of PET (polyethylene terephthalate) resin having a length of 32 mm, a width of 30 mm, and a thickness of 2 mm, and is set in a chip holder 43 having a 30 mm square and a thickness of 2 mm. The diameter of the aperture 49 is 0.3 mm, and the light receiver 45 is a silicon photodiode.

  Object to be measured: γ-GTP (γ-Glutamyltranspeptidase), the set temperature of the microchip 50 is 37 ° C., and the measurement time is 10 minutes per chip. On the base plate 48, the light emitting diode 401 with a heat sink, the blower fan 47, and the chip holder 43 were attached. The dimensions of the chip holder 43 were determined so that the wind from the blower fan 47 could be received sufficiently. Slits 55a and 55b communicating with the outside of the housing are provided on the back surface of the blower fan 47 of the housing 55 and the back surface of the chip holder 43 so that the wind flows smoothly. The temperature adjustment was realized by controlling the number of rotations of the blower fan 47 with temperature data from a temperature sensor installed in the chip holder 43 to increase or decrease the air volume. Thermal equilibrium was reached 25 minutes after the light emitting diode was turned on, and the temperature during temperature adjustment was 37 ± 0.2 ° C. The optical measurement was 36.8 ° C. at the end of the measurement after 37.1 ° C. for 10 minutes at the start of the measurement. Thus, the temperature change for 10 minutes during the measurement is within 0.3 deg, and the accuracy of the temperature control is sufficient for the measurement of γ-GTP.

  A specific example of maintaining the predetermined temperature in the apparatus configuration of FIG. 3 will be described. FIG. 3 (a) does not show the housing, but shows the device viewed from above. FIG. 3B is a cross-sectional view taken along the line BB ′, and shows the base plate 80 omitted in FIG. The lamp 301 of the light source unit 300 is a halogen lamp, loaded in the lamp holder 302, and lit at 55W. The microchip 60 is made of PET resin having a length of 32 mm, a width of 30 mm, and a thickness of 2 mm, and is set in a chip holder 63 having a 30 mm square and a thickness of 2 mm. A 5 W electric heater 75 is housed inside the chip holder 63. In the optical system, the optical lens 65 is a plano-convex lens of Φ15, the filter 66 is a 405 nm band-pass filter, the diameter of the aperture 69 is 0.3 mm, and the light receiver 64 is a silicon photodiode.

  The object to be measured is γ-GTP, the set temperature of the microchip 60 is 37 ° C., and the measurement time is 10 minutes per chip. On the base plate 80, the lamp holder 302, the chip holder 63, the optical lens 65, and the filter 66 were attached. A heat pipe 70 was attached between the lamp holder 302 and the chip holder 63 so as to surround the lamp 301 and the aperture 69. The performance of the heat pipe 70 to be attached was determined by experiment so that the temperature of the microchip 60 was slightly lower than the set value. Thermal equilibrium was reached 10 minutes after the halogen lamp was turned on, and the temperature when the electric heater 75 was OFF was 35 ° C. When the electric heater 75 was turned on and the temperature was adjusted by controlling the voltage applied to the electric heater 75 based on the temperature data from the temperature sensor 67 installed in the chip holder, the temperature was 37 ± 0.1 ° C.

  Although not shown, a resin pipe filled with a cooling liquid is connected between the lamp holder and the chip holder instead of the heat pipe, and the cooling liquid is circulated by a pump to be thermally transported from the lamp holder to the chip holder. A method can also be adopted. In that case, the temperature is adjusted by changing the circulation rate of the coolant.

An embodiment of the present invention will be described. Another embodiment of the present invention will be described. Another embodiment of the present invention will be described. The heat flow by the heat pipe in embodiment of this invention is shown. An example of a microchip and a chip holder used in the microchip inspection apparatus of the present invention is shown.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 Case 2 Light source part 201 Lamp 202 Lamp holder 203 Opening part 3 Chip holder 4 Light receiving part 5 Optical lens 6 Filter 10 Microchip 11 Measurement cell 12 Aperture part 13 Reagent mixing part 14 Analyte introduction part 15 Reagent reservoir part 30 Thermal conduction Member 30a Member 30b with bowl-shaped groove Lid member 31 Aperture 35 Base plate 40 Light source unit 401 Light emitting diode 43 Chip holder 44 Heat sink 45 Light receiving unit 46 Temperature sensor 47 Blower fan 48 Base plate 49 Aperture 50 Microchip 51 Measurement cell 55 Housing 55a, 55b Slit 300 Light source 301 Lamp 302 Lamp holder 303 Opening 60 Microchip 61 Measurement cell 63 Chip holder 64 Light receiver 65 Lens 66 Filter 67 Temperature sensor 69 Aperture 70 Heat Toppipe 75 Electric heater 80 Base plate

Claims (1)

In a microchip inspection apparatus that performs measurement by irradiating light to a microchip containing a specimen,
The microchip inspection apparatus includes a housing,
A light source unit for irradiating the microchip with light;
A chip holder to which the microchip is attached;
A light receiving portion for receiving light emitted from the microchip,
Heat transfer means for transferring heat generated from the light source unit to the chip holder;
A microchip inspection apparatus characterized by bringing the microchip to a predetermined temperature.

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