US 20060073600 A1
This invention relates to a technique for adjusting the temperature of a liquid held on an analyzing instrument (1) to a target value. The invention provides a temperature control method wherein thermal energy is supplied to liquid (10) by passing a magnetic flux across an analyzing instrument (1) for raising the temperature of the liquid. The invention also provides an analyzing instrument (1) and analyzing apparatus (X) which are suited to raising the temperature of a liquid (10) using a magnetic flux.
1. A temperature control method for a liquid in an analyzing instrument which is a method for adjusting the liquid held on an analyzing instrument to a target temperature,
wherein thermal energy is supplied to the liquid by passing a magnetic flux across the analyzing instrument for raising the temperature of the liquid.
2. A temperature control method according to
wherein the temperature of the liquid is raised using the thermal energy from the heating of the heating layer.
3. A temperature control method according to
4. A temperature control method according to
5. A temperature control method according to
6. A temperature control method according to
7. A temperature control method according to
8. A temperature control method according to
9. An analyzing instrument used for analyzing a sample, comprising a heating layer which is heated by passage of a magnetic flux.
10. An analyzing instrument according to
11. An analyzing instrument according to
12. An analyzing instrument according to
13. An analyzing instrument according to
wherein the heating layer is formed where it can supply thermal energy to the liquid present in the reaction zone.
14. An analyzing instrument according to
15. An analyzing instrument according to
16. An analyzing instrument according to
17. An analyzing instrument according to
18. A temperature detecting analyzing apparatus for analyzing a sample with use of a sample-holding analyzing instrument while adjusting a temperature of a liquid held on the analyzing instrument, the analyzing apparatus comprising a magnetic generating coil for generating a magnetic flux across the analyzing instrument.
19. A temperature detecting analyzing apparatus according to
20. A temperature detecting analyzing apparatus according to
The present invention relates to a technique for adjusting the temperature of a liquid held on an analyzing instrument to a target value, in analysis of a sample with use of the analyzing instrument.
Methods of analyzing a sample include methods in which the reaction liquid resulting from the reaction of a sample and a reagent is analyzed by optical means. Such analysis is accomplished for example by mounting an analyzing instrument which provides a reaction field on an analyzing apparatus equipped with an optical system capable of emitting and receiving light (see for example JP-A 8-114539). In this case, it is desirable to adjust the temperature of the analyzing instrument (particularly the reaction liquid), and to react the sample and reaction liquid at roughly the same temperature for each measurement so as to minimize analysis error and increase the reliability of the analysis results. In systems using enzyme reactions in particular, because the reaction speed is highly temperature-dependent the temperature of the system is preferably adjusted to within ±0.1° C. of the target temperature.
Methods of adjusting the temperature of a reaction liquid include for example the method illustrated in
These temperature control methods have the drawback of high energy consumption because it is necessary to heat block 91 or drive heat generator 93 when raising the temperature of reaction liquid 90. Moreover, with heating media such as heat block 91 and heat generator 93, it is difficult to exactly heat only that region where reaction liquid 90 is held when the amount of reaction liquid 90 is small as in a microdevice. Consequently, heating media 91 and 93 need to be relatively large in comparison with the region that needs to be heated (the region directly below reaction liquid 90 in the figure) in order to raise the temperature of reaction liquid 90 with good responsiveness. As a result, when controlling the temperature of a reaction liquid in microdevice energy efficiency is poor because the amount of heat used for raising the temperature of reaction liquid 90 is small in comparison with the amount of heat transmitted by heating media 91 and 93.
Thus, conventional temperature control methods have had the drawback of high energy consumption. Consequently, it has been difficult to apply conventional temperature control methods to analyzing apparatuses driven by internal power sources such as small batteries (for example, batteries widely used for household use), and even if the aforementioned methods were applied to a small analyzing apparatus it would not be practical because the actual working time of the analyzing apparatus would be extremely short. And while the shortness of the actual working time can be improved by increasing the capacity of the internal power source, this impedes miniaturization of the analyzing apparatus and detracts from wide use. Power can also be supplied from an external source, but in that case an adapter is necessary to connect the analyzing apparatus to the external power source, making it less portable and also creating problems for use in other locations.
It is an object of the present invention to allow a liquid held in an analyzing instrument to be adjusted to a target temperature with low energy consumption and without making the analyzing apparatus large.
According to a first aspect of the present invention, a method is provided for controlling the temperature of a liquid held on an analyzing instrument to a target value, wherein thermal energy is supplied to the liquid by the passing a magnetic flux across the analyzing instrument for raising the temperature of the liquid.
According to a second aspect of the present invention, an analyzing instrument is provided which is an analyzing instrument to be used in analyzing a sample. The analyzing instrument comprises a heating layer which heats up when magnetic flux is passed through it.
When using the analyzing instrument, the temperature of the liquid is raised using the thermal energy from the heating layer which has been heated.
The heating layer is formed for example as a thin metal film. Materials which can be used for forming the thin metal film include typically aluminum, nickel, copper, iron and stainless steel for example. When forming the thin metal film using a material (such as aluminum, nickel or copper) with low resistance, the thin metal film is preferably formed to a thickness of 1-200 μm for example. This is because if the thin metal film is unsuitably thick the resistance of the thin metal film will be reduced and it will be impossible to generate sufficient thermal energy in the thin metal film, while if the thin metal film is unsuitably thin the resistance of the thin metal film will be greater and it will melt, making it difficult to supply the target thermal energy to the liquid.
The heating layer can also be formed from a conductive resin material. Conductive resin materials which can be used include for example either insulating resins in which conductive fillers have been dispersed to make them conductive and conductive polymers which are intrinsically conductive. Examples of conductive polymers include polyacetylene, polypyrrole, polythiophene, polyaniline, polyisothianaphthene, polyazulene, poly-P-phenylene, poly-P-phenylenevinylene, poly-2,5-thienylenevinylene and polyperinaphthalene. As in the case of a thin metal film, when the heating layer is formed from a conductive polymer material the thickness of the heating layer is set within a range at which it can appropriately provide thermal energy to the liquid.
The heating layer is formed either by direct film formation on a constituent element of the analyzing instrument, or by working the material into a sheet which is affixed to or fit into an indentation in the aforementioned constituent element. Methods of forming the heating layer as a film include vapor deposition, sputtering and CVD for example. These methods are useful when aluminum, nickel or copper is used as the metal material.
The analyzing instrument of the present invention can be made to comprise a reaction zone for reacting a sample and a reagent for example. In this case at least the liquid present in the reaction zone should be heated. In the analyzing instrument the heating layer is preferably formed in a location where it can supply thermal energy to the liquid in the reaction zone. More specifically, the heating layer is formed in a location covering the periphery of the reaction zone, a location covering the reaction zone or a location inside the reaction zone.
In the present invention the temperature of the liquid can be controlled by monitoring the temperature of the liquid and using the monitoring results as feedback for repeatedly controlling the state of magnetic flux passed through the analyzing instrument. The temperature of the liquid can also be controlled by first ascertaining the relationship between the environmental. temperature around the liquid and the passage state of magnetic flux in the analyzing instrument necessary for raising the liquid to the target temperature, determining the amount of control necessary to achieve the target state of the magnetic flux based on the aforementioned relationship and the measured environmental temperature, and then controlling the state of the magnetic flux in the analyzing instrument according to this amount of control.
According to a third aspect of the present invention, a temperature detecting analyzing apparatus is provided for analyzing a sample with use of a sample-holding analyzing instrument while adjusting a temperature of a liquid held on the analyzing instrument. The analyzing apparatus comprises a magnetic generating coil for generating a magnetic flux across the analyzing instrument.
Desirably, the analyzing apparatus of the present invention may also comprise a temperature detector for measuring the temperature of the liquid or the environmental temperature around the liquid, and a controller for controlling the generation of magnetic flux in the magnetic generating coil based on the measurement results of the temperature detector.
The analyzing apparatus may further comprise for example with An AC voltage applier for causing the magnetic generating coil to generate a magnetic flux. In this case, the controller controls the generation of the magnetic flux in the magnetic generating coil by controlling the an AC voltage applier. More specifically, the controller controls the strength of the magnetic flux (effective value of AC voltage), the frequency (frequency of applied voltage) of repetitively altering the direction of the magnetic flux, and the time for passing the magnetic flux (time for applying the AC voltage). In this way, the generation of magnetic flux in the magnetic generating coil and hence the amount of heat generated when the magnetic flux is passed through the analyzing instrument is controlled, and ultimately it is possible to control the amount of thermal energy which should be transmitted to the liquid.
The present invention can be applied to controlling the temperature of a liquid in a microdevice for analyzing a tiny sample quantity. “Tiny sample quantity” here signifies a sample of 100 μL or less.
It should be pointed out that the term “liquid” as used in the present invention refers to a portion of liquids held in the analyzing instrument which is subject to temperature control, which in the absence of special limitations may be all of the liquids on the analyzing instrument or part of those liquids. For example, in a system for reacting a liquid sample with a liquid reagent, it may signify either the liquid sample, the liquid reagent or the reaction liquid of these, or it may signify more than one of these, or in the case of a reaction liquid it may signify a portion of the reaction liquid present in a specific region.
Embodiments 1 through 5 of the present invention are explained below with reference to
First, the first embodiment of the present invention is explained with reference to
The analyzing apparatus X shown in
Mount 20 is for holding analyzing instrument 1. Temperature detector 21 is embedded in mount 20. This temperature detector 21 is arranged so as to be in a region directly underneath liquid 10 (measurement site 11Cb) held on analyzing instrument 1 when analyzing instrument 1 is mounted on mount 20. This means that the temperature measured by temperature detector 21 is closer to the actual temperature of liquid 10. A thermistor or thermocouple can be used as temperature detector 21. Of course, a non-contact type thermometer such as a radiation thermometer may also be used.
Control calculator 22 computes the amount of energy to be applied to liquid 10 based on the temperature measurement results of temperature detector 21, and calculates the amount of control for AC voltage applier 24.
Magnetic generating coil 23 is for generating a magnetic flux to pass through analyzing instrument 1. AC voltage applier 24 is for applying voltage to magnetic generating coil 23. An AC voltage applier 24 capable of applying AC voltage of a frequency selected from the range of 40-200 khz for example can be used. In magnetic generating coil 23, a magnetic flux is generated In response to voltage applied by AC voltage applier 24. The state of the magnetic flux generated by magnetic generating coil 23 can be controlled by means of the voltage applied to magnetic generating coil 23. More specifically, the generation of the magnetic flux by magnetic generating coil 23 can be controlled by controlling the effective value of AC voltage applied to magnetic generating coil 23, the frequency of the applied voltage and the application times of AC voltage.
Light source 25 is for illuminating liquid 10 (measurement site 11Cb) with light, while light detector 26 is for receiving reflected light from liquid 10. Light source 25 is comprised for example by a mercury lamp or white LED. When these light sources are used, the light from light source 25 passes through a filter before illuminating liquid 10. This is done in order to select with the filter light of a wavelength matched to the light-absorption characteristics of the components to be analyzed in liquid 10. Light detector 26 is comprised for example by a photo diode.
Concentration calculator 27 is for computing the concentration of the sample liquid based on the results for light received at light detector 26. Concentration is computed for example by calculating reflectance based on results for liquid received by light detector 26 for example, and comparing it against reflectance previously computed on z calibration curve showing the relationship between reflectance and concentration.
Controller 28 is for controlling AC voltage applier 24 based on the amount of control computed by control calculator 22, and for controlling the generation of magnetic flux by magnetic generating coil 23. Controller 28 also selects whether light source 25 is lit or unlit, and controls the operations of control calculator 22 and concentration calculator 27.
Control calculator 22, concentration calculator 27 and controller 28 can be comprised for example by a CPU, ROM and RAM, and in this case the program recorded in ROM is executed by the CPU using RAM in order to control AC voltage applier 24 and control the generation of magnetic flux by magnetic generating coil 23.
An analyzing instrument 1 such as that shown in
Channel 11 has sample inlet 11A, reagent inlet 11B and reaction channel 11C. Sample inlet 11A and reagent inlet 11B are connected to end 11Ca of reaction channel 11C. Reaction channel 11C is arranged in accordion folds so as to increase the length of the channel. Reaction channel 11C is provided with measurement site 11Cb (see
Correspondingly, cover 13 has sample inlet 13 a, reagent inlet 13 b and air vent 13 c. Sample inlet 13 a, reagent inlet 13 b and air vent 13 c are formed at sites corresponding to end 11Aa of sample inlet 11A, end 11Ba of reagent inlet 11B and end 11Cc of reaction channel 11C, respectively. Heating layer 14 is formed in cover 13.
Heating layer 14 is heated by induction current resulting from the passage of magnetic flux generated by magnetic generating coil 23 (see
So as to function effectively, heating layer 14 is formed as a film with a thickness of 1-200 μm by a method such as vapor deposition, sputtering or plating of aluminum, nickel or copper for example. Heating layer 14 can also be formed by affixing a sheet formed from metal material to the surface of cover 13. The metal material used in this case can by iron or stainless steel in addition to aluminum, nickel and copper for example. Heating layer 14 can also be formed from a conductive resin material.
The analyzing instrument 1 shown in
When analyzing a sample, the sample is introduced into analyzing instrument 1 through sample inlet 13 a and reagent through reagent inlet 13 b. This sample and reagent move through sample inlet 11A and reagent inlet 11B by capillary action, converging at reaction channel 11C. In this way, the sample and reagent begin to react. The sample and reagent continue to react as they move through reaction channel 11C towards air vent 13 c by capillary action, finally arriving at measurement site 11Cb.
During this time, the temperature of the reaction liquid (liquid 10) arriving at measurement site 11Cb is measured continuously by the temperature detector 21 shown in
This control calculator 22 compares the target temperature of liquid 10 with the actual measured temperature, and when the measured temperature is lower than the target temperature it computes the control for AC voltage applier 24. Computation of control is performed by entering the measured temperature (or difference between target temperature and measured temperature) into a previous determined formula. The computation results are sent to controller 28.
In response, controller 28 controls AC voltage applier 24 according to the computation results from control calculator 22, thus controlling generation of magnetic flux by magnetic generating coil 23. In this way, a magnetic flux is passed across heating layer 14, causing heating layer 14 to heat up and raise the temperature of liquid 10 by thermal energy just by the difference between the measured temperature and the target temperature. On the other hand, if the measured temperature is higher than the target temperature, controller 28 controls AC voltage applier 24 so that voltage is not applied to magnetic generating coil 23. This control of AC voltage applier 24 and hence control of the generation of magnetic flux by magnetic generating coil 23 is performed repeatedly based on feedback of measurement results from temperature detector 21, so that the temperature of liquid 10 is kept roughly constant.
Temperature control of liquid 10 can also be accomplished based on the environmental temperature which is measured around liquid 10. More specifically the relationship between the environmental temperature and the amount of control of magnetic generating coil 23 (AC voltage applier 24) needed to raise liquid 10 to a target temperature is ascertained in advance. This relationship is made into a table and recorded on control calculator 22 and the like. The amount of control (control of AC voltage applier 24) needed to achieve the target passage state of the magnetic flux is determined based on the measured environmental temperature and the aforementioned relationship, and the passage of the magnetic flux through heating layer 14 is controlled according to this amount of control. In this method, control can be exercised once rather than AC voltage applier 24 being controlled repeatedly using the measured environmental temperature results for example as feedback.
As explained above, in this embodiment the temperature of liquid 10 is raised using thermal energy which occurs when induced current is generated in heating layer 14. Consequently, in the present invention the usage efficiency of supplied energy is improved because concentrated heating of liquid 10 is possible. Moreover, thermal energy can be transmitted efficiently from heating layer 14 to liquid 10 because heating layer 14 can be placed close to liquid 10. This also means an improvement in the usage efficiency of supplied energy. Consequently, in the present invention it is possible to reduce the power consumption required for temperature control. As a result, even if AC voltage applier 24 is constructed with a small battery as its internal power source, it will be possible to adequately raise the temperature of liquid 10 without dramatically reducing battery life. Consequently, temperature control of liquid 10 can be accomplished using a small battery in a small analyzing apparatus X without enlarging the apparatus. Moreover, if this can be accomplished with an internal power source there is no need to attach an external power source, and no adapter is required. Portability is therefore good because there is no need to carry an adapter when carrying analyzing instrument X.
Of course, the present invention is not limited by the embodiments above and various design changes are possible. For example, in this embodiment an example was given of an analyzing instrument designed to perform analysis based on reflected light when a liquid is exposed to light, but the present invention is also applicable to an analyzing tool and analyzing apparatus designed to analyze a liquid based on transmitted light. Moreover, temperature control may be applied not only to with respect to the liquid at measurement site 11Cb but also or alternatively to a liquid present in at least one of sample inlet 11A, reagent inlet 11B and reaction channel 11C (other than measurement site 11Cb).
In the analyzing instrument 1 shown in
The magnetic generating coil is not limited need not be positioned underneath analyzing apparatus 1 as shown in
Next, the second embodiment of the present invention is explained with reference to
In the analyzing instrument 3 shown in
In analyzing instrument 3 measurement site 32 is provided partway along channel 31, reagent part 30 is held in this measurement site 32, and heating layer 33 is provided directly above measurement site 32. This analyzing instrument 3 is designed so that sample introduced from sample inlet 34 moves by capillary action towards air vent 35, and is supplied to measurement site 32.
In measurement site 32 reagent 30 is dissolved by the supply of sample to construct a liquid reaction system. Thermal energy generated in heating layer 33 by the passage of magnetic lines of force through heating layer 33 can be supplied to the liquid (liquid phase reaction system) held in this measurement site 32.
Next, the third and fourth embodiments of the present invention are explained with reference to
The analyzing instrument 4 shown in
Channels 40 and 41 are both filled with migration buffer, and during analysis potential difference is applied to both ends of channels 40 and 41 so that sample introduced through inlet 42 moves through channel 41 towards measurement site 43 while reacting in channel 41.
Heating layer 44 is provided directly above measurement site 43. In this analyzing instrument 4, the temperature of the liquid held in measurement site 43 can be raised by heating layer 44 using magnetic flux.
The analyzing instrument 5 shown in
In this analyzing instrument 5, suction part 53 is connected to an external pump, and sample is moved by the power of the pump. Of course, it could also be an analyzing instrument constructed so as to move sample and the like by means of an internal micropump using a piezoelectric element.
In the analyzing instruments 4 and 5 shown in
Next, an analyzing instrument according to the fourth embodiment of the present invention is explained with reference to
The analyzing instrument 6 shown in
Working electrode 64 which is the measurement electrode is provided on substrate 60 along with counter electrode 65 and a pair of detection electrodes 66. Correspondingly, the analyzing apparatus has measurement terminals 7 a and 7 b and detection terminals 7 c and 7 d for contacting electrodes 64 through 66. Terminals 7 b and 7 d are connected to a ground while terminals 7 a and 7 c can be connected to power source 70. By switching switch S, it is possible to select either a state in which power source 70 applies a potential difference between working electrode 64 and counter electrode 65, or one in which a potential difference is applied between the pair of detection electrodes 66.
In this analyzing instrument 6, voltage is applied to the reaction liquid of a sample and reagent 67 for example to achieve electron transfer between the reaction product and the electrodes, and the analyzing apparatus is constructed so as to measure response current corresponding to the amount of electron transfer.
The reaction system is also constructed in capillary 60 a in this analyzing instrument 6, and the temperature of the reaction system can be raised and hence the temperature of the reaction system can be controlled by supplying the reaction system with thermal energy generated by the passage of magnetic flux through heating layer 68.
In analyzing instrument 6, because electrodes 64 through 66 are formed from conductors induction current can be produced for electrodes 64 through 66. Consequently, heating layer 68 can be omitted and the temperature of the liquid raised by passing magnetic flux through electrodes 64 through 66 to heat them.
Of course, the analyzing instrument 6 shown in