JP2008233019A - measuring device - Google Patents

Abstract

A measuring apparatus capable of suppressing a decrease in measurement accuracy due to adhesion of bubbles to a specimen substance is provided.
[Solution]
When the solution is supplied to the liquid channel 55 by inserting the outlet of the pipette tip CP into the supply port provided in the measurement tip 50 and moving the stored solution from the discharge port to the supply port, After the solution moves faster than the air layer formed at the tip of the discharge port in the liquid flow channel 55 and moves at a first speed at which the solution flows below the air layer, the first speed The solution is moved from the discharge port to the supply port for a predetermined period with a predetermined speed pattern including a speed pattern that is moved at a slower second speed.
[Selection] Figure 13

Description

  The present invention relates to a measurement apparatus, and more particularly, to a measurement apparatus including a measurement chip in which a liquid channel is formed so that a liquid can flow and a sample substance to be measured is attached to a bottom surface in the liquid channel.

  Conventionally, a liquid flow path is formed so that liquid can flow, and various solutions are individually supplied to the liquid flow path of the measurement chip in which the analyte substance to be measured is attached to the bottom surface in the liquid flow path. There is known a measuring apparatus that measures the characteristics of a sample substance by supplying the sample to the sample and detecting the reaction state of the sample substance.

  For example, in Patent Document 1, various solutions are individually supplied to the liquid flow path, and light beams are incident at various angles on the interface of the adhered portion to which the specimen substance is adhered, and light is totally reflected at the interface. By detecting the light intensity distribution for each beam reflection angle and detecting the reflection angle at which the dark line is generated by the occurrence of total reflection attenuation due to the surface plasmon resonance phenomenon (SPR) from the detected light intensity distribution, A measuring device for measuring properties of a substance is disclosed.

  By the way, in this type of measuring apparatus, as shown in FIG. 15, when a solution is made to flow by replacing the solution in the liquid channel with another type of solution, the velocity distribution of the solution in the liquid channel is A laminar flow state occurs, and the closer to the wall surface in the liquid channel, the slower the solution speed.

For this reason, in this type of measuring apparatus, when the solution in the liquid channel is replaced, as shown in FIG. 16, by flowing the solution at a constant speed for a predetermined period (for example, 5 seconds), The solution is replaced.
JP 2006-98369 A

  By the way, for example, as shown in FIGS. 17A to 17C, using two pipettes, the solution B is supplied from one pipette in which the solution B is stored into the liquid channel at the predetermined speed for the predetermined period. When the solution A is sucked from the liquid channel with the other pipette and the solution in the liquid channel is replaced from the solution A to the solution B, the pipette tip is not filled with air. In many cases, an air layer is not mixed in, but during many times of liquid feeding, an air layer is formed at the tip of one pipette due to the effect of the surface tension of the solution. There is a problem in that the measurement accuracy of the measuring apparatus may be reduced due to the air layer mixed into the liquid flow path and bubbles adhering to the sample substance.

  The present invention has been made to solve the above problems, and an object of the present invention is to provide a measuring apparatus capable of suppressing a decrease in measurement accuracy due to adhesion of bubbles to a specimen substance.

  In order to achieve the above object, the invention described in claim 1 is provided with a supply port for supplying a liquid and a liquid channel through which the liquid supplied from the supply port flows, and is provided on a bottom surface in the liquid channel. A flow path member to which a sample substance to be measured is attached and a solution used for measuring the characteristics of the sample substance are stored, and a discharge port for discharging the solution is formed to be insertable into the supply port. Supplying the solution to the liquid flow path by inserting the storage means and the discharge port into the supply port and moving the solution stored in the storage means from the discharge port to the supply port And when the solution is supplied to the liquid channel, the solution is formed at the tip of the discharge port when the discharge port is inserted into the supply port in the liquid channel. The solution is faster than the air layer The solution is moved at a first speed at which the solution flows below the air layer and then moved at a second speed that is slower than the first speed. Control means for controlling the supply means to move from the discharge port to the supply port for a predetermined period.

  According to the first aspect of the present invention, a supply port for supplying a liquid to the flow channel member and a liquid flow channel through which the liquid supplied from the supply port flows are provided. A specimen substance to be measured is attached to the bottom surface of the substrate. The storage means stores a solution used for measuring the characteristics of the specimen substance, and a discharge port for discharging the solution to the storage means is formed so as to be insertable into the supply port. Thus, the solution is supplied to the liquid channel by inserting the discharge port into the supply port and moving the solution stored in the storage means from the discharge port to the supply port.

  And when this invention supplies a solution with respect to a liquid flow path with a control means, when a discharge port is inserted in a supply port in a liquid flow path, a solution is formed in the front-end | tip part of a discharge port. A predetermined pattern including a speed pattern in which the solution moves faster than the air layer and moves at a first speed at which the solution flows below the air layer and then moves at a second speed slower than the first speed. The supply means is controlled so as to move the solution from the discharge port to the supply port for a predetermined period according to the speed pattern.

  Thus, according to the first aspect of the present invention, when the solution is supplied to the liquid channel by inserting the discharge port into the supply port and moving the stored solution from the discharge port to the supply port, After the solution moves faster than the air layer formed at the tip of the discharge port in the liquid flow path and moves at a first speed at which the solution flows below the air layer, the first speed Since the solution is controlled to move from the discharge port to the supply port for a predetermined period in a predetermined speed pattern including a speed pattern that is moved at a slower second speed, the measurement accuracy due to the adhesion of bubbles to the specimen substance Can be suppressed.

  According to the present invention, as in the second aspect of the present invention, at least during the period of moving the solution from the discharge port at the first speed, at least the air layer has an attachment region of the analyte substance in the liquid channel. It is preferable that it is a period to pass.

  According to the present invention, as in the invention described in claim 3, the predetermined period is a period required for the solution in the vicinity of the bottom surface in the liquid channel to diffuse to the center of the cross section of the liquid channel. Is preferred.

  Thus, according to the present invention, when the solution is supplied to the liquid channel by moving the stored solution by inserting the discharge port into the supply port from the discharge port to the supply port, After the solution moves faster than the air layer formed at the tip of the discharge port in the liquid flow path and moves at a first speed at which the solution flows below the air layer, it is slower than the first speed. Since the solution is controlled to move from the discharge port to the supply port for a predetermined period in a predetermined speed pattern including the speed pattern to be moved at the second speed, the measurement accuracy is reduced due to the adhesion of bubbles to the sample substance. The effect that it can suppress is acquired.

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

  The biosensor 10 as a measuring apparatus according to the present embodiment is a so-called surface plasmon sensor that measures the interaction between the protein Ta and the sample A using the surface plasmon resonance phenomenon generated on the surface of the metal film. .

  As shown in FIGS. 1 to 4, the biosensor 10 includes a lower housing 11 and an upper housing 12. The upper housing 12 is made of a heat insulating member and covers the entire upper half of the biosensor 10. The interior of the upper housing 12 is insulated from the outside and the interior of the lower housing 11. The front side of the upper housing 12 can be opened upward, and a handle 13 is attached. A display 14 and an input unit 16 are installed outside the upper housing 12.

  2 is a view showing the inside of the biosensor 10 as seen from the back side of FIG. 1 with the upper case 12 removed, FIG. 3 is a view of the inside of the case from the top, and FIG. 4 is a front view of FIG. It is an internal side view seen from the side.

  Disposed inside the upper housing 12 are a dispensing head 20, a measurement unit 30, a sample stock unit 40, a pipette tip stock unit 42, a buffer stock unit 44, a cold insulation unit 46, a measurement tip stock unit 48, a radiator 60, and a radiator blower fan. 62, a horizontal blower fan 64 is provided.

  The sample stock unit 40 includes a sample stacking unit 40A and a sample setting unit 40B. In the sample stacking section 40A, sample plates 40P for stocking different analyte solutions as samples used for measuring the characteristics of the specimen substance are stacked in the Z direction (vertical direction) and stored in individual cells. One sample plate 40P is transported and set from the sample stacking section 40A by a transport mechanism (not shown) to the sample setting section 40B.

  The pipette tip stock portion 42 includes a pipette tip stacking portion 42A and a pipette tip setting portion 42B. In the pipette chip stacking part 42A, pipette chip stockers 42P for holding a plurality of pipette chips are stacked and accommodated in the Z direction. One pipette chip stocker 42P is transported and set from the pipette chip stacking section 42A by a transport mechanism (not shown) to the pipette chip setting section 42B.

  The buffer stock unit 44 includes a bottle storage unit 44A and a buffer supply unit 44B. A plurality of bottles 44C storing a buffer solution as a reference sample serving as a reference for measurement are stored in the bottle storage portion 44A. A buffer plate 44P is set in the buffer supply unit 44B. The buffer plate 44P is partitioned into a plurality of muscles, and buffer solutions having different concentrations are stored in each partition. Further, a hole H into which the pipette tip CP is inserted when the dispensing head 20 is accessed is formed in the upper part of the buffer plate 44P. The buffer liquid is supplied from the bottle 44C to the buffer plate 44P through the hose 44H.

  A correction plate 45 is disposed next to the buffer supply unit 44B, and a cold insulation unit 46 is disposed next to the correction plate 45. The correction plate 45 is a plate for adjusting the concentration of the buffer solution, and a plurality of cells are formed in a matrix. A sample that needs to be refrigerated is placed in the cold insulation unit 46. The cold insulation part is set to a low temperature, and the sample is kept at a low temperature.

  In the measurement chip stock portion 48, a measurement chip accommodation plate 48P is set. A plurality of measurement chips 50 are accommodated in the measurement chip accommodation plate 48P.

  A measurement chip transport mechanism 49 is provided between the measurement chip stock unit 48 and the measurement unit 30. The measuring chip transport mechanism 49 includes a holding arm 49A that sandwiches and holds the measuring chip 50 from both sides, a ball screw 49B that moves the holding arm 49A in the Y direction by rotation, and a transport rail on which the measuring chip 50 is placed. 49C. At the time of measurement, one measurement chip 50 is placed on the transport rail 49C from the measurement chip storage plate 48P by the measurement chip transport mechanism 49, and is moved and set to the measurement unit 30 while being held by the holding arm 49A. .

  As shown in FIGS. 5 and 6, the measurement chip 50 includes a dielectric block 52, a flow path member 54, and a holding member 56.

  The dielectric block 52 is made of a transparent resin or the like that is transparent to the light beam, and has a prism portion 52A having a trapezoidal cross section, and the prism portion 52A integrally with both ends of the prism portion 52A. A formed held portion 52B is provided. A metallic thin film 57 is formed on the upper surface on the wider side of the two parallel surfaces of the prism portion 52A. The dielectric block 52 functions as a so-called prism. When the measurement is performed by the biosensor 10, a light beam is incident from one of two opposing non-parallel sides of the prism portion 52A and the thin film 57 is incident from the other. A light beam totally reflected at the interface is emitted.

  On the surface of the thin film 57, there is formed a linker layer 57A for attaching protein Ta on the thin film 57 as a sample substance to be measured. Protein Ta is attached on this linker layer 57A.

  Engaging convex portions 52C that are engaged with the holding member 56 are formed along the upper side edge on both side surfaces of the prism portion 52A. Further, a flange portion 52D that is engaged with the transport rail 49C is formed along the side end side below the prism portion 52A.

  As shown in FIG. 6, the flow path member 54 includes six base portions 54A, and four cylindrical members 54B are erected on each of the base portions 54A. In the base portion 54A, for each of the three base portions 54A, one upper portion of the standing cylindrical members 54B is connected by a connecting member 54D. The channel member 54 is made of a soft and elastically deformable material, for example, an amorphous polyolefin elastomer. In this manner, by configuring the flow path member 54 with a material that can be elastically deformed, the adhesion with the dielectric block 52 is enhanced, and the sealing performance of the liquid flow path 55 configured between the dielectric block 52 is improved. Secured.

  The holding member 56 is long and has a shape in which the upper surface member 56A and the two side plates 56B are formed in a lid shape. The side plate 56B is formed with an engagement hole 56C to be engaged with the engagement protrusion 52C of the dielectric block 52, and a window 56D at a portion corresponding to the optical path of the light beam. The holding member 56 is attached to the dielectric block 52 with the engagement hole 56 </ b> C and the engagement protrusion 52 </ b> C engaged. The flow path member 54 is integrally formed with the holding member 56 and is disposed between the holding member 56 and the dielectric block 52. A receiving portion 59 is formed on the upper surface member 56A at a position corresponding to the cylindrical member 54B of the flow path member 54. The receiving part 59 is substantially cylindrical.

  As shown in FIG. 7, the base portion 54A has two substantially S-shaped channel grooves 54C formed on the bottom surface side. Each of the end portions of the flow channel 54C communicates with the hollow portion of one cylindrical member 54B. The bottom surface of the base portion 54A is in close contact with the upper surface of the dielectric block 52, and the liquid channel 55 is configured by the space formed between the channel groove 54C and the upper surface of the dielectric block 52 and the hollow portion. The In addition, the height of the flow path of the hollow part of the cylindrical member 54B according to the present embodiment is 200 to 500 μm, and the capacity of the liquid flow path 55 is 7 μl.

  Two liquid channels 55 are formed in one base portion 54A. In each liquid channel 55, an entrance / exit 53 of the liquid channel 55 is formed on the upper end surface of the cylindrical member 54B.

  Here, one of the two liquid channels 55 is used as the measurement channel 55A, and the other one is used as the reference channel 55R. The measurement is performed in a state where the protein Ta is attached on the thin film 57 (on the linker layer 57A) of the measurement channel 55A and the protein Ta is not attached on the thin film 57 (on the linker layer 57A) of the reference channel 55R.

  As shown in FIG. 7, light beams L1 and L2 are incident on the measurement channel 55A and the reference channel 55R, respectively. As shown in FIG. 8, the light beams L1 and L2 are applied to an S-shaped bent portion disposed on the center line M of the base portion 54A. Hereinafter, the irradiation region of the light beam L1 in the measurement channel 55A is referred to as a measurement region E1, and the irradiation region of the light beam L2 in the reference channel 55R is referred to as a reference region E2. The reference area E2 is an area for performing measurement for correcting data obtained from the measurement area E1 to which the protein Ta is attached.

  FIG. 9 shows a detailed configuration of the dispensing head 20.

  The dispensing head 20 includes 12 dispensing tubes 20A. Each dispensing tube 20A is held by a holding member 20B so as to be arranged in a line along an arrow Y direction orthogonal to the X direction. Two adjacent pipes 20A are used as a pair, one for supplying liquid and the other for discharging liquid. A pipette tip CP is attached to the tip of the dispensing tube 20A. The pipette tip CP is stocked in the pipette tip stocker 42P and can be exchanged as necessary.

  As shown in FIG. 2, the dispensing head 20 is provided in the upper part of the upper housing 12 and can be moved in the arrow X direction by the horizontal drive mechanism 22. The horizontal drive mechanism 22 includes a ball screw 22A, a motor 22B, and a guide rail 22C. The ball screw 22A and the guide rail 22C are arranged in the X direction. Two guide rails 22C are arranged in parallel, and one of them is arranged below the ball screw 22A at a predetermined interval. The dispensing head 20 is moved in the X direction along the guide rail 22C when the ball screw 22A is rotated by the rotational drive of the motor 22B. By this movement in the X direction, the dispensing head 20 is cooled, the correction plate 45, the buffer supply unit 44B (buffer plate 44P), the measurement unit 30 (measurement chip 50), the sample setting unit 40B (sample plate 40P), The pipette tip set unit 42B (pipette tip stocker 42P) can be moved to a position facing it.

  As shown in FIG. 9, the dispensing head 20 is provided with a vertical drive mechanism 24 that moves the dispensing head 20 in the arrow Z direction. The vertical drive mechanism 24 includes a motor 24A and a drive shaft 24B disposed in the Z direction, and the drive shaft 24B is rotated by the rotational drive of the motor 24A, thereby moving the dispensing head 20 in the Z direction. By this movement in the Z direction, the dispensing head 20 has a pipette tip stocker 42P set in the pipette tip setting portion 42B, a sample plate 40P set in the sample setting portion 40B, a buffer plate 44P set in the buffer supply portion 44B, The correction plate 45, the plate set in the cold insulation unit 46, the measurement chip 50 set in the measurement unit 30, and the like can be accessed.

  As shown in FIG. 10, a suction / discharge drive unit 26 is connected to the dispensing head 20. The intake / exhaust drive unit 26 includes a first pump 27 and a second pump 28. The first pump 27 and the second pump 28 are provided corresponding to the pair of dispensing pipes 20A described above. The first pump 27 includes a syringe pump, and includes a first cylinder 27A, a first piston 27B, and a first motor 27C that drives the first piston 27B. The first cylinder 27A is connected to the dispensing head 20 via a pipe 27H. The second pump 28 is also a syringe pump, and includes a second cylinder 28A, a second piston 28B, and a second motor 28C that drives the second piston 28B. The second cylinder 28A is connected to the dispensing head 20 via a pipe 28H.

  The dispensing head 20 controls the rotational drive of the first motor 27C and the second motor 28C, and controls the drive of the first piston 27B and the second piston 28B. In addition, the speed of the solution when sucking and discharging is adjustable.

  On the other hand, as shown in FIG. 4, the measuring unit 30 includes an optical surface plate 32, a light emitting unit 34, and a light receiving unit 36. The optical surface plate 32 has an upper base 32A composed of a horizontal plane in the upper center as viewed from the side, an outgoing inclined portion 32B that decreases in a direction away from the upper base 32A, and an outgoing slope across the upper base 32A. A light receiving inclined portion 32C disposed on the side opposite to the portion 32B is formed. The measurement chip 50 is set on the upper base 32A along the Y direction. A light emitting portion 34 that emits the light beams L 1 and L 2 toward the measurement chip 50 is installed on the emission inclined portion 32 B of the optical surface plate 32. In addition, a light receiving portion 36 is installed in the light receiving inclined portion 32C. Next to the optical surface plate 32, a water cooling jacket 32J for cooling the optical surface plate 32 is provided.

  As shown in FIG. 11, the light emitting unit 34 includes a light source 34A and a lens unit 34B. Further, the light receiving unit 36 includes a lens unit 36A and a CCD 36B. The CCD 36B is connected to an image processing unit 38 to which a control unit 70 that controls the entire biosensor 10 is connected.

  A divergent light beam L is emitted from the light source 34A. The lens unit 34B has a built-in polarization beam splitter, which separates the P-polarized component and the S-polarized component of the light beam L incident from the light source 34A. The P-polarized component of the light beam L has a certain width with respect to the Z direction. Are divided into two relatively thick parallel light beams L1 and L2. The lens unit 34B then applies the two parallel light beams L1 and L2 at various incident angles that are greater than the total reflection angle with respect to the measurement region E1 and the reference region E2 at the interface between the thin film 57 and the dielectric block 52. Incident light is incident on the measurement region E1 and the reference region E2 so as to be in a convergent light state. Therefore, the light beams L1 and L2 incident on the measurement region E1 and the reference region E2 are totally reflected at various reflection angles at the interface between the dielectric block 52 and the thin film 57. The totally reflected light beams L1 and L2 are focused on the CCD 36B through the lens unit 36A. The CCD 36B is an area sensor having a light receiving surface having an area capable of receiving both of the totally reflected light beams L1 and L2, and generates and outputs image information indicating an image formed on the light receiving surface. . The output image information is input to the image processing unit 38. The image processing unit 38 performs predetermined processing based on the input image information to derive refractive index change data in the measurement region E1 and the reference region E2. The derived refractive index change data is output to the control unit 70.

Here, the refractive index change data is obtained by supplying the sample and the buffer solution individually to the measurement chip 50 and emitting the light beam L from the light emitting unit 34, respectively, to the measurement region E1 and the reference region E2. When the reflection angles at which dark lines are generated in the light beams L1 and L2 that are irradiated with L2 and are totally reflected in the measurement region E1 and the reference region E2 are obtained, the reflections in which dark lines are generated in the sample and the buffer solution in the measurement region E1. This is obtained based on the difference between the angle difference and the angle difference between the reflection angles at which dark lines are generated in the reference region E2 in the sample and the buffer solution. The light beams L1 and L2 incident on the interface between the thin film 57 and the dielectric block 52 at a specific incident angle excite surface plasmons on the interface, thereby reflecting the light beams L1 and L2 incident on the specific incident angle. The intensity of light sharply decreases and is observed as a dark line. A light beam L1, L2 incident angle ATR angle theta _SP of the dark lines, the difference in refractive index of the change in the attenuated total reflection angle theta _SP detected in the measurement region E1 and the reference region E2 (angular difference) Change data.

  FIG. 12 is a block diagram showing a functional configuration of a control system that controls the operation of the biosensor 10.

  As shown in the figure, the display unit 14 and the input unit 16 are connected to the control unit 70.

  The controller 70 is connected to the motor 22B, the motor 24A, the first motor 27C, and the second motor 28C.

  The control unit 70 controls the movement of the dispensing head 20 in the X direction and the Z direction by controlling the rotational drive of the motor 22B and the motor 24A. Further, the control unit 70 controls the rotational drive of the first motor 27C and the second motor 28C, so that the sample and the buffer liquid are applied to the pipette tip CP attached to each dispensing tube 20A of the dispensing head 20. Control suction and discharge.

  In the control unit 70, injection of a solution such as a sample or a buffer solution into each liquid channel 55 of the measurement chip 50 in accordance with an operation instruction to the biosensor 10 input by the operator via the input unit 16, and refractive index data Measurement processing including acquisition, analysis, etc. is executed. The control unit 70 measures the reaction state between the protein Ta and the sample A based on the refractive index change data input from the image processing unit 38 and displays the measurement result on the display 14.

  Next, the action of the biosensor 10 according to the present embodiment when measuring the characteristics of the protein Ta will be described.

  When the biosensor 10 supplies a solution such as a sample or a buffer solution to each liquid channel 55 of the measurement chip 50, the biosensor 10 uses the dispensing head 20 as a cold storage unit 46 in which the solution to be supplied is stored, or a sample setting unit. 40B, moved onto the buffer supply unit 44B, and the solution is sucked with a pipette tip CP attached to one of the pair of pipetting tubes 20A (total of six). Since the suction amount at this time is supplied to the pair of liquid flow paths 55A and 55R, the suction amount is two. Then, the pipette tips CP on the side of the six dispensing tubes 20A that have sucked the solution are inserted into one of the inlet / outlet ports 53 (hereinafter referred to as “supply ports 53A”) on the side of the measurement flow channel 55A of the measurement tip 50, and for discharge. The pipette tips CP attached to the six dispensing tubes 20A in this row are inserted into the other inlet / outlet 53 (hereinafter referred to as “exhaust port 53B”). Then, half of the solution is supplied from the dispensing tube 20A on the supply port 53A side and the liquid is sucked through the dispensing tube 20A on the discharge port 53B side. Subsequently, the remaining half of the solution of the pipette tip CP is also supplied to the reference channel 55R side in the same manner.

  When the solution is supplied to the measurement flow path 55A and the reference flow path 55R of the measurement chip 50, the control unit 70 controls the rotational drive of the first motor 27C and the second motor 28C, so that FIG. As shown, the solution is supplied at a first rate (eg, 9 [μl / sec]) for 1 second, and then the solution is supplied at a second rate (eg, 4 [μl / sec]) for 4 seconds. Is controlling.

  As described above, the volume of the liquid channel 55 is 7 μl, and each sample and buffer solution according to the present embodiment has a liquid viscosity equivalent to that of water. The air layer formed at the tip of this is 2 to 5 μl.

  Thereby, for example, as shown in FIG. 17A, when the solution B is supplied from the dispensing head 20 and the solution A in the liquid channel 55 is to be replaced with the solution B, the tip of the pipette tip CP Even if an air layer is formed, the solution B is supplied from the pipette tip CP at the first speed for 1 second, so that the solution B is higher than the air layer in the liquid channel 55 as shown in FIG. The solution B moves quickly and flows below the air layer, the air layer floats in the liquid channel 55, and the air layer forms a thin layer on the ceiling surface in the liquid channel 55 and passes through the channel. Therefore, the air layer is prevented from coming into contact with the measurement region E1 and the reference region E2 on the bottom surface in the liquid channel 55.

  Then, after the air layer has passed through the liquid channel 55, the solution A near the bottom surface in the liquid channel 55 gradually becomes a cross section of the liquid channel 55 by continuing to supply the solution at the second speed for 4 seconds. The solution A in the liquid channel 55 is replaced with the solution B.

  As described above, according to the present embodiment, when the air layer passes through the liquid channel 55, the air layer is prevented from contacting the measurement region E1 and the reference region E2 on the bottom surface in the liquid channel 55. Therefore, it is possible to suppress the measurement accuracy from being lowered due to bubbles adhering to the specimen substance.

  In the present embodiment, the case where the solution is supplied at the first speed for 1 second when the solution is supplied from the dispensing head 20 has been described. However, the present invention is not limited to this, for example, It is sufficient to supply the solution at the first speed only at least while the air layer passes through the analyte substance adhesion region on the bottom surface in the flow channel of the measurement chip 50.

  In addition, in this Embodiment, the surface plasmon sensor was demonstrated as an example as a measuring apparatus, However, As a measuring apparatus, it is not limited to a surface plasmon sensor.

It is a perspective view of the whole biosensor which concerns on embodiment. It is a perspective view inside the biosensor which concerns on embodiment. It is a top view inside the biosensor which concerns on embodiment. It is an internal side view of the biosensor which concerns on embodiment. It is a perspective view of the measurement chip concerning an embodiment. It is a disassembled perspective view of the measuring chip concerning an embodiment. It is a figure which shows the state in which the light beam is injecting into the measurement area | region and reference area of the measurement chip which concerns on embodiment. It is the figure which looked at the channel member of the measuring chip concerning an embodiment from the lower side. It is a perspective view which shows the vertical drive mechanism of the dispensing head of the biosensor which concerns on embodiment. It is a schematic block diagram of the liquid suction / discharge part of the biosensor according to the embodiment. It is the schematic of the optical measurement part vicinity of the biosensor which concerns on embodiment. It is a schematic block diagram of the control part of the biosensor which concerns on embodiment, and its periphery. It is a graph which shows the speed | rate which supplies a solution with respect to the liquid flow path which concerns on embodiment. It is a schematic diagram which shows the state of the air layer in the liquid flow path which concerns on embodiment. It is a figure which shows the velocity distribution of the solution in the flow path at the time of supplying the conventional solution. It is a graph which shows the speed | rate which supplies a solution with respect to the conventional liquid channel. It is a schematic diagram which shows the replacement state of the solution in the conventional liquid channel.

Explanation of symbols

10 Biosensor 20 Dispensing head (supplying means)
50 Measuring chip (channel member)
70 Control unit (control means)
CP pipette tip (storage means)

Claims (3)

A flow channel member in which a liquid supply channel for supplying a liquid and a liquid flow channel through which the liquid supplied from the supply port flows are provided, and a specimen substance to be measured is attached to a bottom surface in the liquid flow channel;
Reserving means in which a solution used for measuring the characteristics of the specimen substance is stored, and a discharge port for discharging the solution is formed to be insertable into the supply port;
Supply means for supplying the solution to the liquid channel by inserting the discharge port into the supply port and moving the solution stored in the storage means from the discharge port to the supply port;
When supplying the solution to the liquid channel, the air layer formed at the tip of the discharge port when the solution is inserted into the supply port in the liquid channel. A predetermined speed including a speed pattern in which the solution moves faster and moves at a first speed at which the solution flows below the air layer and then moves at a second speed slower than the first speed. Control means for controlling the supply means to move the solution in a pattern from the discharge port to the supply port for a predetermined period;
Measuring device. The measuring apparatus according to claim 1, wherein a period during which the solution is moved from the discharge port at the first speed is a period in which at least the air layer passes through the adhesion region of the specimen substance in the liquid channel. The measuring apparatus according to claim 1, wherein the predetermined period is a period required for the solution in the vicinity of the bottom surface in the liquid channel to diffuse to the center of the cross section of the liquid channel.

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