JP5288635B2 - measuring device - Google Patents

Description

  The present invention relates to an apparatus for measuring a substance to be detected that may be contained in a sample liquid, and more particularly to a measurement apparatus that uses a sensor chip having a microchannel through which a sample liquid flows.

  In bio-measurement, the presence / absence and amount of an antigen (or antibody) as a substance to be detected are measured by detecting a biomolecular reaction such as an antigen-antibody reaction.

  For example, one of two substances that specifically bind to each other (antigen, antibody, various enzymes, receptors, etc.) is immobilized on a substrate and the other substance (this may be the substance to be detected itself, or The presence or amount of the substance to be detected in the sample can be determined by binding this substance to a fixed layer fixed on the substrate and detecting the binding reaction. Can be measured. Specifically, in order to detect an antigen that is a substance to be detected contained in a sample, an antibody that specifically binds to the antigen is immobilized on the substrate, and the sample is supplied onto the substrate to supply the antigen to the antibody. Then, a labeled antibody with a label that specifically binds to the antigen is added and bound to the antigen to form a so-called sandwich of antibody-antigen-labeled antibody. Signal from the label attached to the competitive antigen bound to the immobilized antibody by sandwiching the labeled competitive antigen competitively with the target antigen, and the immobilized antibody. Immunoassays, such as competition methods, that detect.

  In the sandwich method, the antigen that is the substance to be detected corresponds to the “other substance”, and in the competition method, the competitive antigen corresponds to the “other substance”. In the latter competition method, there is a relationship that the more the amount of the competing antigen bound to the immobilized antibody, the smaller the amount of the antigen that is the detection target, and therefore, based on this relationship, the amount of the competing antigen is handled. The amount of antigen can be determined from the signal level from the label.

  Further, a fluorescence detection method is widely used as a highly sensitive and easy measurement method that can be applied to the above-described biomeasurement. In this fluorescence detection method, the presence of a substance to be detected is detected by irradiating a sample considered to contain a substance to be detected that is excited by light of a specific wavelength to emit fluorescence and then detecting the fluorescence at that time. It is a method to confirm. In addition, when the substance to be detected is not a fluorescent substance, this binding, that is, by detecting the fluorescence in the same manner as described above, by contacting a substance labeled with a fluorescent dye and specifically binding to the substance to be detected, and then detecting fluorescence. The existence of a substance to be detected is also widely confirmed.

  Furthermore, in order to improve sensitivity in such a fluorescence detection method, a method using the effect of electric field enhancement by plasmon resonance is proposed in Patent Document 1 and the like. This method uses a sensor chip in which a metal layer is provided in a predetermined area on a transparent support, and totally reflects from the surface opposite to the metal layer formation surface of the support with respect to the interface between the support and the metal film. S / N is improved by making excitation light incident at an incident angle greater than the angle, generating surface plasmons in the metal layer by irradiation of the excitation light, and enhancing fluorescence by the electric field enhancing action.

  In the biomeasurement as described above, it is desired to shorten the measurement time. Therefore, various methods for reducing the measurement time by efficiently generating a reaction in the sensor unit have been proposed. For example, Patent Document 2 proposes to increase the speed of measurement by using a replaceable micro-channel (micro-channel) type sensor chip and causing a sample liquid to flow down at a constant high speed. This type of sensor chip can also be applied to detect the substance to be detected by the above-described fluorescence detection and to perform quantitative analysis. In that case, a sensor part in which a substance that specifically binds to a substance in the sample is fixed is disposed in a part of the microchannel of the sensor chip.

  In a measuring apparatus that performs detection or quantitative analysis of a substance to be detected using this sensor chip, generally, as described in Patent Document 3, for example, a sample liquid is supplied by a pump through a pipe connected to a micro flow path. It is sucked and distributed in the micro flow path.

  As described above, in a measuring device that uses a sensor chip having a sensor part in a microchannel to which a substance that specifically binds to a substance in a sample liquid is fixed, and performs measurement while flowing the sample liquid through the sensor part, Sample liquids having different viscosities may be used for the measurement. In such a case, if the sample liquid suction pump is driven under a constant operating condition, the flow rate of the sample liquid having a higher viscosity becomes lower. Thus, when the flow rate in the sensor section varies greatly from sample solution to sample solution, a difference occurs in the specific binding reaction rate (for example, antigen-antibody reaction rate) described above, resulting in variations in the finally obtained measurement results. . Note that the viscosity of the sample solution may vary depending on the individual even if the sample solution is obtained from the same person or animal.

  In Patent Document 4, a control valve that opens and closes the flow path through which the sample liquid is sucked is provided, and the control valve is opened and closed instantaneously according to the differential pressure between the inside and the outside of the flow path, thereby providing a highly viscous liquid. There has been disclosed a sample liquid suction device that can suck a low-viscosity sample liquid under appropriate conditions even when a relatively high output sample liquid suction pump suitable for sample liquid suction is used.

JP-A-10-307141 JP 2007-101221 A JP 2008-128906 A JP 2004-257804 A

  However, the apparatus described in Patent Document 4 has problems such that the apparatus is complicated to provide a control valve that opens and closes at high speed, and the reliability is low because the control valve is opened and closed at high speed. .

  The present invention has been made in view of the above circumstances, and in a measuring apparatus using a sensor chip as described above, the flow rate of each sample liquid during measurement is constant even when sample liquids having different viscosities are supplied. Or it aims at making it possible to maintain the value close to it.

The measuring device according to the present invention comprises:
As described above, a sensor having a microchannel through which a sample liquid flows is provided, and a sensor unit in which a substance that specifically binds to a substance in the sample liquid is fixed is disposed in a part of the microchannel. Use the tip
In a measuring apparatus for measuring a target substance that can be contained in the sample liquid by sucking and circulating the sample liquid through a pipe connected to the microchannel,
Before the measurement is made, a characteristic detecting means for detecting a characteristic related to the viscosity of the sample liquid that is sucked by the pump and flows through the microchannel toward the sensor unit;
When the measurement is performed, pump operation control means is provided for controlling the pump operating condition to increase the suction speed as the viscosity indicated by the characteristic is higher.

  More specifically, the operation condition includes changing the piston moving speed of the pump. In this case, controlling the operating condition to increase the suction speed means increasing the rotational speed (drive oscillation frequency) of the pump piston drive motor.

  On the other hand, as the above characteristic detection means, a means for detecting the time required for the sample liquid tip to pass through a predetermined section in the microchannel is suitably used. When detecting such a time, it is necessary to detect that the tip of the sample solution passes through two points that define the predetermined section.

  Specifically, the characteristic detecting means for realizing this is that the tip of the sample liquid passes through the flow path cross-sectional area change point defining the predetermined section, based on the change by measuring the pressure in the micro flow path. Can be applied.

  Alternatively, the predetermined position in the microchannel defining the predetermined section is irradiated with light, the light transmitted through the microchannel is detected at that time, and the predetermined position is determined based on the change in the detected light quantity. It is also possible to apply a characteristic detecting means for detecting that the tip of the sample liquid passes through.

  Furthermore, the microchannel is irradiated with light at a predetermined position in the microchannel defining the predetermined section, and the fluorescence emitted from the fluorescent substance contained in the sample liquid flowing through the microchannel is detected. And the characteristic detection means which detects that the sample liquid front-end | tip passes through this predetermined position is also applicable.

  In the measurement apparatus of the present invention, before the measurement is made, a characteristic detection means for detecting a characteristic related to the viscosity of the sample liquid that is sucked by the pump and flows through the microchannel toward the sensor unit is provided. When the above measurement is performed, the pump operation control means for controlling the pump operating condition to the suction speed increasing side as the viscosity indicated by the characteristic is higher is provided. The decrease in the flow rate can be compensated by controlling the operation of the pump. Therefore, according to the measuring apparatus of the present invention, even when sample solutions having different viscosities are supplied during measurement, the flow rate of each sample solution can be maintained at a constant value or a value close thereto.

1 is a schematic configuration diagram showing a measuring apparatus according to an embodiment of the present invention. The perspective view which shows the microchannel type | mold sensor chip used for the said measuring apparatus. The figure explaining the state at the time of the biological substance detection in the sensor chip of FIG. 1 is a graph showing an example of change characteristics of the pressure in the microchannel detected by the apparatus of FIG. FIG. 1 is a schematic diagram showing a sample liquid tip detection position in a microchannel in the apparatus of FIG.

  Hereinafter, embodiments of the present invention will be described in detail with reference to the drawings. FIG. 1 shows a schematic configuration of a measuring apparatus according to an embodiment of the present invention. The measurement apparatus of the present embodiment is configured as an apparatus for detecting a biological substance using a micro-channel sensor chip (hereinafter simply referred to as a sensor chip) 10 as described above. First, the sensor chip 10 will be described with reference to FIGS.

  As shown in FIG. 1 and FIG. 2, the sensor chip 10 includes a flow path member 12 having a micro flow path 11 through which a sample solution flows and a part of the micro flow path 11 that specifically binds to each other. A sensor unit 14 that fixes one of the substances 13 to the wall surface and an upper plate member 17 fixed on the flow path member 12 are provided. In the present embodiment, an example of performing an assay by a sandwich method in an antigen-antibody reaction will be described as an example, and the substance 13 will be described as an antibody that specifically binds to the antigen A as a substance to be detected.

  The antibody 13 may be directly fixed to the wall surface of the microchannel 11. However, as will be described later, when fluorescence is enhanced by electric field enhancement by surface plasmon, a metal film (not shown) is formed on the wall surface. The antibody 13 is immobilized thereon.

  As shown in FIG. 2, the upper plate member 17 communicates the sample liquid inlet 16 a and the sample liquid outlet 16 b opened on the upper surface, and the sample liquid inlet 16 a and the upstream end of the microchannel 11. It has an opening 15a and an opening 15a that allows the sample solution outlet 16b and the downstream end of the microchannel 11 to communicate with each other. The upper plate member 17 and the flow path member 12 are joined by, for example, ultrasonic welding.

  The flow path member 12 and the upper plate member 17 are made of a transparent dielectric material such as polystyrene, and are respectively molded by injection molding. As an example, the microchannel 11 has a width of about 2 mm and a depth of about 2 mm. As clearly shown in FIG. 1, in the present embodiment, the sensor unit 14 is shallower than the microchannel 11 before and after that, that is, the depth is formed to be about 50 μm.

  In the sensor chip 10 of this example, as shown in FIG. 3, the labeled antibody 20 is attached to the inner surface of the microchannel 11 on the upstream side of the region where the antibody 13 is fixed. The labeled antibody 20 is composed of an antibody 23 that specifically binds to an epitope different from the antibody 13 described above and a fluorescent label 22 with respect to the substance to be detected. Here, as the fluorescent label 22, fluorescent fine particles comprising a large number of fluorescent dye molecules F and a light-transmitting material 21 enclosing the fluorescent dye molecules F are used.

The size of the fluorescent fine particles is not particularly limited, but is preferably about several tens of nm to several hundreds of nm. Here, for example, one having a diameter of 100 nm is used. Specific examples of the light-transmitting material 21 include polystyrene and SiO ₂ , but those that can encapsulate the fluorescent dye molecule F and transmit the fluorescence from the fluorescent dye molecule F to be emitted to the outside. There is no particular limitation. The labeled antibody 20 in this example is configured by surface-modifying a fluorescent label 22 with a smaller antibody 23.

Next, returning to FIG. 1, the measuring apparatus will be described. This measuring apparatus includes a prism 30 on which the sensor chip 10 is placed via, for example, a refractive index matching oil, and excitation light at an incident angle that is a total reflection condition with respect to the interface between the prism 30 and the sensor chip 10. A light source 31 composed of a semiconductor laser or the like for entering L ₀ , a pipe 33 having one end communicating with the sample liquid outlet 16 b of the sensor chip 10 via a nozzle 32, and a suction port connected to the other end of the pipe 33. A sample suction pump 34, an open valve 35 provided in the pipe 33, and a photodetector 36 for detecting fluorescence Lf emitted from the vicinity of the sensor portion 14 of the sensor chip 10 as described later. Yes. The excitation light L ₀ is incident on the interface as p-polarized light so as to induce surface plasmons.

  Further, this measuring apparatus receives a pressure sensor 40 for detecting the internal pressure of the pipe 33, a control unit 41 for controlling the operation of the sample suction pump 34 and the release valve 35, and a light detection signal of the light detector 36. A signal processing unit 42, a storage unit 43 including a memory that temporarily stores data output from the signal processing unit 42, a calculation unit 44 that reads data from the storage unit 43 and performs a predetermined calculation, and the calculation The display unit 45 includes a liquid crystal panel connected to the unit 44, and the input unit 46 includes a keyboard, a mouse, and the like, which is connected to the control unit 41 and forms a user interface together with the display unit 45.

  In the above description, the element described as “XX” may be composed of individual circuits or the like, or may be composed of software that functions as a part of a computer system. Good.

  Next, detection of a substance to be detected by this measuring apparatus will be described. Here, as an example, a case where an antigen A that may be contained in a sample solution S that is plasma will be described. First, the sample liquid S is injected into the sample liquid inlet 16a shown in FIG. 1, and the sample suction pump 34 is driven at the same time, so that the sample liquid S is introduced into the microchannel 11 of the sensor chip 10. The inhalation of the sample solution S will be described in detail later. Prior to driving the sample suction pump 34, the release valve 35 is set from the open state to the closed state.

  The sample solution S introduced into the microchannel 11 is mixed with the labeled antibody 20 adsorbed and fixed to the channel 11 as schematically shown in FIG. As a result, the antigen A binds to the antibody 23 of the labeled antibody 20, the antigen A bound to the antibody 23 binds to the antibody 13 of the sensor unit 14, and the antigen A is sandwiched between the antibody 13 and the antibody 23. Is formed.

The antigen A adsorbed on the sensor unit 14 in this way is detected as follows. The excitation light L ₀ emitted from the light source 31 is incident on the interface between the prism 30 and the sensor chip 10 at an incident angle that is a total reflection condition. Then, in this case, an evanescent wave oozes out in the sample solution S on the metal film (not shown) interposed between the antibody 13 and the wall surface of the microchannel 11, and the evanescent wave enters the metal film. Surface plasmons are excited. This surface plasmon causes an electric field distribution on the surface of the metal film, thereby forming an electric field enhancement region.

  At this time, if the fluorescent label 22 exists in the area where the evanescent wave oozes, the fluorescent label 22 is excited to generate fluorescence Lf. Here, the fluorescence Lf is enhanced by the electric field enhancement effect due to the surface plasmons existing in a region substantially equivalent to the region where the evanescent wave oozes out. The photodetector 36 detects this enhanced fluorescence Lf. The detection of the presence of the fluorescent label 22 as described above means that the presence of the antigen A bound to the antibody 13 is detected.

  The fluorescence detection signal output from the photodetector 36 is sent to the signal processing unit 42, where it is sampled at a predetermined time interval, and the sampled signal is subjected to processing such as amplification and A / D conversion to meet a predetermined standard. Fluorescence measurement data. This fluorescence measurement data is temporarily stored in the storage unit 43. The calculation unit 44 reads the fluorescence measurement data from the storage unit 43, adds calculation processing to the fluorescence measurement data, and outputs the result as a final measurement result. This measurement result is, for example, a relationship between a measurement time and a calculated value corresponding to the measurement time (for example, a fixed amount of antigen A per unit area in the sensor unit 14).

  Note that the antigen A and the labeled antibody 20 that are not bound to the immobilized antibody 13 are suspended in the microchannel 11, and the labeled antibody 20 is non-specifically adsorbed to the sensor unit 14. In order to remove these, a cleaning solution may be appropriately introduced into the flow path before the detection of the fluorescence Lf.

For example, when laser light having a central wavelength of 780 nm is used as the excitation light L ₀ and a gold (Au) film is used as the metal film, the thickness of the metal film is preferably 50 nm ± 20 nm. More preferably, it is 47 nm ± 10 nm. The metal thin film is preferably composed mainly of at least one metal selected from the group consisting of Au, Ag, Cu, Al, Pt, Ni, Ti, and alloys thereof.

Next, the flow rate control of the sample liquid S performed in this measuring apparatus will be described. The pressure in the pipe 33 detected by the pressure sensor 40 after the sample suction pump 34 starts sucking the sample liquid S, that is, the pressure (negative pressure) in the microchannel 11 basically changes as shown in FIG. To do. Time range in the figure indicated by A measurement front i.e., the sample solution S prior to the detection of fluorescence Lf shows the step of sending to the sensor unit 14, the time T ₂ after the detection time range indicated by the fluorescence Lf in B It is a measurement stage to perform. In addition, after the said measurement front stage, the temporary release valve 35 is opened and the inside of the piping 33 is open | released to air | atmosphere.

As shown in the figure, from the start of the sample sucked into the time T ₀ in the measurement front, at a subsequent time T _1, the pressure of the microfluidic channel 11 (negative pressure) increases rapidly. This point will be described with reference to FIG. In FIG. 5, the same elements as those in FIGS. 1 to 3 are denoted by the same reference numerals, and description thereof will be omitted unless particularly required. As described above, the sensor unit 14 is formed to be remarkably shallower than the microchannel 11 before and after that. That is, in the portion indicated by (4) in FIG. 5, the cross-sectional area of the microchannel 11 is rapidly decreased from the upstream side toward the downstream side. When the tip portion of the sample liquid S passes through such a portion, the flow path resistance increases rapidly, so that the pressure (negative pressure) detected by the pressure sensor 40 increases rapidly.

The pressure sensor 40 inputs a pressure detection signal Sp indicating the measured pressure to the control unit 41. Based on the pressure detection signal Sp, the control unit 41 detects that the tip of the sample liquid S has reached the position (4) shown in FIG. The control unit 41 calculates the time T ₁ where the detection is made. The time T ₁ is i.e., the section from the portion (1) to position the tip of the sample liquid S before the suction, as shown in FIG. 5 to the position of (4), the time required for the sample liquid S passes is there. The portion (1) where the tip of the sample liquid S injected into the sample liquid inlet 16a is located is generally almost constant.

Here, as long as setting the operating condition of the sample suction pump 34 constant, since when the viscosity is higher suction speed of the sample liquid S is decreased, the required time T ₁ is longer. If the operating conditions of the sample suction pump 34 are left as they are, the flow rate of the sample liquid S passing through the sensor unit 14 at a later measurement stage is reduced. As described above, if the flow rate of the sample liquid S varies depending on the viscosity, accurate measurement cannot be performed. Hereinafter, the point which prevents the occurrence of such a situation will be described.

Prior to normal measurement, the piston drive motor rotation speed (drive oscillation frequency), which is one operating condition of the sample suction pump 34, is set to a reference value REF, and a reference sample solution S is used. Measurements as usual are made. At this time, the required time T ₁ is obtained, it is defined as the reference required time Tr. In the internal memory of the control unit 41, the correspondence relationship between the correction factor K and the ratio T ₁ / Tr of the required time T ₁ that can be measured in the pre-measurement stage to the reference required time Tr in actual measurement is shown in the table below. It is stored in the form of a correction table shown. These correction coefficients K are values that correct the piston drive motor rotation speed (drive oscillation frequency) toward the suction speed increase side from K1 to K7.

At each actual measurement, the control unit 41 obtains the ratio T ₁ / Tr of the required time T ₁ actually obtained in the previous stage of measurement to the reference required time Tr, and obtains the value of the correction coefficient K corresponding thereto from the above table. . The control unit 41, in the measurement step to be made from time T ₂ of the 4, the piston drive motor rotation speed of the sample suction pump 34 (drive oscillation frequency), the canonical value REF to a value obtained by multiplying the coefficient K Set. By doing so, as the required time T ₁ determined at the measurement front is large, i.e. as when the viscosity of the sample liquid S is higher, the piston drive motor rotation speed of the sample suction pump 34 in the measuring step (driving oscillation frequency ) Is corrected to the suction speed increase side. Therefore, since the sample liquid S always flows at a constant flow rate or a flow rate close to it at the sensor unit 14 regardless of its viscosity, it is possible to prevent the measurement result from being varied due to the difference in flow rate. .

  As is apparent from the above description, in the present embodiment, the pressure sensor 40 and the control unit 41 constitute the characteristic detection means in the present invention, and the control unit 41 constitutes the pump operation control means in the present invention.

As a correction table for correcting the rotation speed (drive oscillation frequency) of the piston drive motor of the sample suction pump 34, instead of the required time ratio T ₁ / Tr shown in Table 1, (1) of the microchannel 11 is used. (4) to the section divided by the required time T ₁ the measured volume V (see FIG. 5), i.e. the like is also applicable that using the average flow rate of the sample liquid S in this section.

  In addition, in order to detect that the tip of the sample liquid S has passed through a predetermined position in the microchannel 11, the pressure in the microchannel 11 is detected and detected based on the change as in the above embodiment. Alternatively, it may be detected optically. More specifically, light is irradiated to a predetermined position of the microchannel 11, and the light transmitted through the microchannel 11 is detected at that time, and the passage of the tip of the sample liquid is detected based on the change in the detected light quantity. A thing etc. are applicable. Such an optical detection means is provided, for example, at the position (2) in FIG. 5, and a section between the position (2) and the position (1) is defined as a predetermined section, and the section is the tip of the sample liquid S. What is necessary is just to detect the time required for passing. Alternatively, for example, the optical detection means may be arranged at the positions (2) and (3) in FIG. 5, and the interval between the position (2) and the position (3) may be set as a predetermined section. Here, the change in the detected light amount will be described in detail. When the sample liquid S is not present in the microchannel 11, the amount of light detected is relatively small because a large amount of light irradiated there is reflected at the interface between the channel 11 and the channel member 12. On the other hand, when the sample liquid S is present in the microchannel 11, the light applied thereto is difficult to be reflected at the interface, so that more light is transmitted through the microchannel 11, so that the detected light quantity is Relatively many. Therefore, it is possible to detect that the tip of the sample liquid S has passed through the light irradiation position of the microchannel 11 by detecting that the detected light amount has suddenly changed from a low level state to a high level.

Further, when the sample liquid S contains a fluorescent substance, it is irradiated with excitation light L ₀ which is originally unnecessary in the pre-measurement stage, and when the tip of the sample liquid reaches the position (5) in FIG. If the substance is excited, it can be detected that the tip of the sample solution has reached the position (5) based on the output of the photodetector 36 shown in FIG. In this case, the predetermined section for detecting the tip of the sample solution may be between the position (1) and the position (5), or the position (2) where the optical detection means is disposed. It may be between the positions of (5).

  In the embodiment described above, the fluorescence intensity is increased by utilizing the electric field enhancement by the surface plasmon, but light irradiation by a normal epi-illumination method may be applied. In that case, it is not necessary to form the metal film described above on the sensor portion 14.

  Furthermore, the substance to be detected (analyte) targeted by the measurement apparatus of the present invention is not particularly limited as long as it is a biologically derived substance that can be observed by solidifying genes, cells, etc. in addition to antigens and antibodies. When detecting genes and cells, a substance that specifically adsorbs them may be fixed to the inner wall of the microchannel. On the other hand, it is also possible to detect a substance that specifically adsorbs to a gene or a cell by the measuring apparatus of the present invention. In that case, the gene and the cell may be fixed to the inner wall of the microchannel.

In addition, the substance to be detected or the substance that specifically binds to the competing substance that competes with the substance to be detected in the sample does not need to be directly fixed to the sensor surface, but is self-assembled monolayer (SAM), SiO _It may be fixed via a dielectric film such as ₂ or a polymer film such as carboxymethyl dextran.

  In addition, the combination of a substance to be detected or a competing substance that competes with the substance to be detected in the sample solution and a substance that specifically binds to it is not limited to the antigen and the antibody described above. The present invention is also applicable to the case where a combination of substances that bind by a reaction used in a bioassay such as a biotin reaction and an enzyme / substrate reaction is used.

  Furthermore, when applying an immunoassay, not only the sandwich assay described above but also a competition method can be applied.

  In addition, the labeling substance is not limited to fluorescent molecules, and those made of other substances having photoresponsiveness such as fluorescent beads and metal fine particles are also applicable.

DESCRIPTION OF SYMBOLS 10 Microchannel type sensor chip 11 Microchannel 12 Channel member 13 Antibody 14 Sensor part 20 Labeled antibody 22 Label 23 Antibody 30 Prism 31 Light source 32 Nozzle 33 Piping 34 Sample suction pump 36 Photo detector 40 Pressure sensor 41 Control part 44 Calculation unit 45 Display means 46 Input means A Antigen L ₀ Excitation light Lf Fluorescence

Claims (4)

Using a sensor chip in which a microchannel for circulating a sample liquid is provided, and a sensor unit in which a substance that specifically binds to a substance in the sample liquid is fixed is disposed in a part of the microchannel,
In a measuring apparatus for measuring a target substance that can be contained in the sample liquid by sucking and circulating the sample liquid through a pipe connected to the microchannel,
Before the measurement, the sample liquid sucked by the pump and flowing through the microchannel toward the sensor section has characteristics relating to its viscosity, and the tip of the sample liquid passes through a predetermined section in the microchannel. Characteristic detecting means for detecting the time required to perform,
And a pump operation control means for controlling the pump operating condition to the suction speed increasing side as the viscosity indicated by the characteristic is higher when the measurement is performed. The characteristic detection means measures the pressure in the microchannel and detects that the tip of the sample liquid passes through the channel cross-sectional area change point defining the predetermined section based on the change. The measuring apparatus according to claim 1 . The characteristic detecting means irradiates light at a predetermined position of the microchannel defining the predetermined section, detects light transmitted through the microchannel, and determines the predetermined position based on a change in the detected light quantity. The measuring apparatus according to claim 1 , wherein the measuring apparatus detects that the tip of the sample liquid passes. The characteristic detection means irradiates light to the microchannel at a predetermined position in the microchannel defining the predetermined section, and the fluorescent substance contained in the sample liquid flowing through the microchannel is excited by the light and emitted. by detecting the fluorescence measuring apparatus according to claim 1, wherein the the said predetermined position is intended to detect that the sample liquid tip passes.

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