JP2007093444A - Fluid feeder, biosensor, and fluid feeding method - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a fluid feeder, capable of restraining the fluctuations of the feed pressure, when feeding a sample into a flow channel using a pipette, a biosensor equipped with this fluid feeder, and a fluid feeding method. <P>SOLUTION: The difference S between discharge quantity and suction quantity per unit time between a discharge pump 27 and a suction pump 28, and moving speeds α, β (working speeds after compensation α, β)of the discharge pump 27 and the suction pump 28 for canceling the difference S are stored; and when the discharge pump 27 and the suction pump 28 are driven, the compensated working speeds α, β are read from a memory and the discharge pump 27 and the suction pump 28 are driven at the compensated working speeds α, β. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to a liquid feeding device that feeds a sample into a flow path using a pipette, a liquid feeding method thereof, and a biosensor equipped with the liquid feeding device.

  There are known biosensors that measure the reaction of a sample using attenuation of total reflection when measuring interactions between biochemical substances such as proteins and DNA, screening drugs, and the like. For example, in an SPR measuring apparatus known from Patent Document 1 and the like, a surface of a metal film formed on a transparent dielectric is used as a sensor surface, a sample is supplied to the sensor surface, and then reacted, and then a prism is used. Then, the metal film is irradiated from the back side of the sensor surface so as to satisfy the total reflection condition, and the reflected light is measured.

  In the case of such a biosensor, it is necessary to supply a sample on the sensor surface. However, in the technique described in Patent Document 1, the sample is stored through a pipe (tube) connected to a pump or a valve. The sample is sent directly from the container to the flow path. In this method, there is a problem that so-called contamination is likely to occur, in which a sample adhered in the pipe is mixed into a sample to be injected later.

Therefore, it is conceivable to inject the sample from the inlet of the flow path using one pipette and supply the sample to the sensor surface by sucking the sample from the outlet of the flow path using another pipette. According to this method, the above-mentioned contamination problem is solved by exchanging the pipette tip. However, if the discharge amount from the pipette and the suction amount to the pipette are different, the liquid supply pressure fluctuates and the liquid supply is poor. It may cause.
Japanese Patent No. 3294605

  The present invention has been made in consideration of the above-described facts, and includes a liquid feeding device capable of suppressing fluctuations in liquid feeding pressure when a sample is fed into a flow path using a pipette, and the liquid feeding device. It is an object to provide a biosensor and a liquid feeding method.

  In order to solve the above-described problem, a liquid feeding device according to a first aspect of the present invention includes a flow path having a supply port and a discharge port, and a sensor surface that is exposed in the flow path and detects a reaction of a sample. A liquid feeding device for feeding the sample to the sensor surface of a measuring unit comprising: a pipette pair inserted into each of the supply port and the discharge port; and one pipette of the pipette pair A discharge pump for discharging the sample, a suction pump for sucking the sample into the other pipette of the pair of pipettes, a discharge amount per unit time from the pipette by the discharge pump, and from the pipette by the suction pump And an operation speed control means for controlling the operation speed of the discharge pump and the suction pump so that a difference between the suction amount per unit time and the suction amount is canceled.

  In the liquid delivery device, a pipette is inserted into the supply port and the discharge port of the measurement unit, the sample is discharged from one pipette, and the sample is sucked into the other pipette to send the sample to the flow path. . One pipette of the pipette pair discharges the sample in the pipette by the discharge pump, and the other pipette of the pipette pair sucks the sample into the pipette by the suction pump.

  Here, discharge / suction in the present application means that the operation at that time is discharge / suction, and is not necessarily limited to the fact that pipettes and pumps are provided exclusively for discharge and suction, respectively. Not.

  By the way, the discharge pump and the suction pump need to have the same discharge / suction amount per unit time in order to make the liquid feeding pressure constant. However, an error may occur in the amount of liquid delivered by each pump due to an error in the casing size or the like.

  Therefore, the operation speed control means of the liquid feeding device cancels the difference between the discharge amount per unit time from the pipette by the discharge pump and the suction amount per unit time from the pipette by the suction pump. Control the operating speed of the discharge pump and suction pump. For example, when the discharge amount by the discharge pump is larger than the suction amount by the suction pump, each pump is operated so that the operation speed of the discharge pump is slower than the specified operation speed or the operation speed of the suction pump is higher. To control.

  As described above, by adjusting the discharge amount / suction amount at the operating speed and correcting the error of the discharge amount / suction amount of each pump, it is possible to suppress fluctuations in the liquid feeding pressure.

  The operation speed control means of the liquid delivery device of the first embodiment stores a corrected operation speed of at least one of the discharge pump and the suction pump for canceling the difference between the discharge amount and the suction amount. The storage unit may include a pump driver that drives the discharge pump and the suction pump at the corrected operation speed.

  The corrected operation speed stored in the storage means may be the operation speed of the discharge pump, the operation speed of the suction pump, or both. By driving the discharge pump and the suction pump at the corrected operation speed, it is possible to adjust an error between the discharge amount from one pipette tip and the suction amount to another pipette tip.

  Further, the liquid feeding device according to the first aspect has a plurality of the pipette pairs, and the operation speed control means cancels the difference between the discharge amount and the suction amount for each of the plurality of pipette pairs. A storage unit that stores the corrected operation speed of each suction pump and a pump driver that drives the suction pump at the corrected operation speed may be included.

  As described above, in the case of a multi-channel liquid feeding device having a plurality of pipette pairs, error adjustment can be easily performed by driving only the suction pump side at the corrected operation speed.

  A biosensor according to a second aspect of the present invention is a biosensor that measures a reaction state of a sample by using a total reflection attenuation of light, and includes a flow path having a supply port and a discharge port, The measurement unit having a sensor surface on which a ligand is fixed on an exposed flat metal film, and the sample is fed to the sensor surface of the measurement unit. The liquid feeding device described above, an optical member that emits light toward the metal film of the sensor chip, and a light receiving member that receives the light reflected by the metal film.

  According to the biosensor, since the fluctuation of the liquid feeding pressure in the liquid feeding device is suppressed, it is difficult to cause liquid feeding failure and a highly reliable biosensor can be obtained.

  According to a third aspect of the present invention, there is provided a liquid feeding method comprising: a flow channel having a supply port and a discharge port; and a sensor surface that is exposed in the flow channel and detects a sample reaction. A liquid feeding method for feeding the sample to a sensor surface, wherein a pipette pair is inserted into each of the supply port and the discharge port, and a unit time by a discharge pump for discharging the sample from one pipette of the pipette pair The operation speed of the discharge pump and the suction pump is adjusted so that the difference between the discharge amount per unit time and the suction amount per unit time by the suction pump that sucks the sample into the other pipette of the pipette pair is canceled. It is something to control.

  According to the liquid feeding method, fluctuations in the liquid feeding pressure can be suppressed by correcting the errors in the discharge amount and the suction amount at the operating speeds of the discharge pump and the suction pump.

  Since this invention was set as the said structure, the fluctuation | variation of a liquid feeding pressure can be suppressed.

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

  The biosensor 10 of the present invention is a so-called surface plasmon sensor that measures the interaction between the ligand D and the analyte A by utilizing surface plasmon resonance generated on the surface of a metal film.

  As shown in FIG. 1, the biosensor 10 includes a tray holding unit 12, a transport unit 14, a container mounting table 16, a liquid suction / discharge unit 20, an optical measurement unit 54, and a control unit 60.

  The tray holding unit 12 includes a mounting table 12A and a belt 12B. The mounting table 12A is attached to a belt 12B spanned in the arrow Y direction, and is movable in the arrow Y direction by the rotation of the belt 12B. A tray T is placed on the mounting table 12A. A sensor stick 40 is stored in the tray T. The sensor stick 40 is a chip to which the ligand D is fixed, and details will be described later. Under the mounting table 12A, a push-up mechanism 12D that pushes up the sensor stick 40 to a position of a stick holding member 14C described later is disposed.

  As shown in FIGS. 2 and 3, the sensor stick 40 includes a dielectric block 42, a flow path member 44, a holding member 46, an adhesive member 48, and an evaporation preventing member 49.

  The dielectric block 42 is made of transparent resin or the like that is transparent to the light beam, and has a prism portion 42A having a trapezoidal cross section, and the prism portion 42A integrally with both ends of the prism portion 42A. The formed held portion 42B is provided. A metal film 50 is formed on the upper surface on the wider side of the two parallel surfaces of the prism portion 42A as shown in FIG. On this metal film 50, the ligand D to be analyzed by the biosensor 10 is fixed. The dielectric block 42 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 42A, and a metal film is formed from the other. The light beam totally reflected at the interface with 50 is emitted.

  As shown in FIG. 4, a linker layer 50 </ b> A is formed on the surface of the metal film 50. The linker layer 50 </ b> A is a layer for immobilizing the ligand D on the metal film 50. On the linker layer 50A, the measurement region (E1) in which the ligand D is fixed and the reaction between the analyte A and the ligand D occurs, and the reference signal for signal measurement in the measurement region E1 is obtained without the ligand D being fixed. And a reference region (E2) for forming the same. The reference region E2 is formed when the linker layer 50A described above is formed. As a formation method, for example, the linker layer 50A is subjected to a surface treatment to deactivate a binding group that binds to the ligand D. Thereby, half of the linker layer 50A becomes the measurement region E1, and the other half becomes the reference region E2. Thus, in order to deactivate a bonding group, the ethanolamine-hydrochloride used for the above-mentioned blocking can be used. As another configuration method of the reference region E2, for example, if alkyl thiol is arranged in the reference region E2 instead of carboxymethyl dextran, an alkyl group can be arranged on the surface. Since the ligand cannot be bound by the coupling method, it can be used as the reference region E2.

  As shown in FIG. 5, the ligand D is fixed to a portion of the linker layer 50 </ b> A exposed to the liquid channel 45 other than the reference region E <b> 2. The ligand D is not fixed in the reference region E2. Light beams L2 and L1 are incident on the reference region E2 and the measurement region E1 located on the upstream side of the reference region E2, respectively. The reference area E2 is an area provided for correcting data obtained from the measurement area E1 where the ligand D is fixed.

  On both side surfaces of the prism portion 42A, engaging convex portions 42C that are engaged with the holding member 52 along the upper edge are virtual surfaces perpendicular to the upper surface of the prism portion 42A along the lower edge. Vertical protrusions 42D configured on the extension are formed at seven locations, respectively. Further, an engagement groove 42E is formed in the center portion along the longitudinal direction of the lower surface of the dielectric block 42.

  The flow path member 44 has a rectangular parallelepiped shape slightly narrower than the dielectric block 42, and is arranged side by side on the metal film 50 of the dielectric block 42 as shown in FIG. 3. A channel groove 44 </ b> A is formed on the lower surface of each channel member 44, communicated with the supply port 45 </ b> A and the discharge port 45 </ b> B formed on the upper surface, and the liquid channel 45 between the metal film 50. Composed. Accordingly, six independent liquid channels 45 are formed in one sensor stick 40. On the side wall of the flow path member 44, a convex portion 44 </ b> B is formed that is press-fitted into a concave portion (not shown) inside the holding member 46 to ensure adhesion with the holding member 46.

  In addition, since it is assumed that the liquid flow path 45 is supplied with a liquid containing protein, in order to prevent the protein from adhering to the flow path member 44, the material of the flow path member 44 is a non-protein. It is preferable not to have specific adsorptivity.

  The holding member 46 is long and includes an upper plate 46A and two side plates 46B. The side plate 46B is formed with an engagement hole 46C that is engaged with the engagement convex portion 42C of the dielectric block 42. The holding member 46 is attached to the dielectric block 42 with the engagement holes 46 </ b> C and the engagement protrusions 42 </ b> C engaged with the six flow path members 44 interposed therebetween. Thereby, the flow path member 44 is attached to the dielectric block 42. In the upper surface plate 46A, a tapered pipette insertion hole 46D that narrows toward the flow path member 44 is formed at a position facing the supply port 45A and the discharge port 45B of the flow path member 44. A positioning boss 46E is formed between the adjacent pipette insertion hole 46D and the pipette insertion hole 46D.

  An evaporation preventing member 49 is bonded to the upper surface of the holding member 46 via an adhesive member 48. A pipette insertion hole 48D is formed at a position facing the pipette insertion hole 46D of the adhesive member 48, and a positioning hole 48E is formed at a position facing the boss 46E. Further, a slit 49D, which is a cross-shaped cut, is formed at a position facing the pipette insertion hole 46D of the evaporation preventing member 49, and a positioning hole 49E is formed at a position facing the boss 46E. By inserting the boss 46E into the holes 48E and 49E and bonding the evaporation preventing member 49 to the upper surface of the holding member 52, the slit 49D of the evaporation preventing member 49 and the supply port 45A and the discharge port 45B of the flow path member 44 are formed. Configured to face each other. When the pipette tip CP is not inserted, the slit 49D covers the supply port 45A, and evaporation of the liquid supplied to the liquid channel 45 is prevented.

  As shown in FIG. 1, the transport unit 14 of the biosensor 10 includes an upper guide rail 14A, a lower guide rail 14B, and a stick holding member 14C. The upper guide rail 14 </ b> A and the lower guide rail 14 </ b> B are horizontally disposed in the arrow X direction perpendicular to the arrow Y direction, above the tray holding unit 12 and the optical measurement unit 54. A stick holding member 14C is attached to the upper guide rail 14A. The stick holding member 14C can hold the held parts 42B at both ends of the sensor stick 40 and can move along the upper guide rail 14A. The engagement groove 42E of the sensor stick 40 held by the stick holding member 14C and the lower guide rail 14B are engaged, and the stick holding member 14C moves in the arrow X direction, so that the sensor stick 40 is placed on the optical measurement unit 54. To the measurement unit 56. The measuring unit 56 is provided with a pressing member 58 that presses the sensor stick 40 during measurement. The pressing member 58 is movable in the Z direction by a driving mechanism (not shown), and presses the sensor stick 40 disposed in the measurement unit 56 from above.

  On the container mounting table 16, an analyte solution plate 17, a buffer liquid stock container 18, and a waste liquid container 19 are mounted. The analyte solution plate 17 is partitioned in a matrix shape, and various types of analyte solutions are stocked. The buffer liquid stock container 18 includes containers 18A to 18E, and various buffer liquids are stocked. In the containers 18A to 18E, an opening K into which a pipette tip CP described later can be inserted is formed. The waste liquid container 19 includes a plurality of containers 19A to 19E, and an opening K into which the pipette tip CP can be inserted is formed in the same manner as the buffer liquid stock container.

  The liquid suction / discharge unit 20 includes a head 24 and a suction / discharge drive unit 26. The head 24 is movable in the arrow Y direction along a conveyance rail (not shown). The head 24 is also movable in the vertical direction (arrow Z direction) by a drive mechanism (not shown) inside the head 24. As shown in FIG. 6, the head 24 includes a pair of pipette portions 24A and 24B. Pipette tips CP are attached to the tip portions of the pipette portions 24A and 24B, and the length in the Z direction can be individually adjusted. Many pipette tips CP are stocked in a pipette tip stocker (not shown) and can be replaced as necessary.

  The intake / exhaust drive unit 26 includes a discharge pump 27 and a suction pump 28. The discharge pump 27 includes a syringe pump, and includes a discharge cylinder 27A, a discharge piston 27B, and a discharge motor 27C that drives the discharge piston 27B. The suction pump 28 is also a syringe pump, and includes a suction cylinder 28A, a suction piston 28B, and a suction motor 28C that drives the suction piston 28B. The discharge motor 27C and the suction motor 28C are connected to a discharge driver 60D and a suction driver 60E in the control unit 60 described later.

  As shown in FIG. 7, the optical measurement unit 54 includes a light source 54A, a first optical system 54B, a second optical system 54C, a light receiving unit 54D, and a signal processing unit 54E. A divergent light beam L is emitted from the light source 54A. The light beam L becomes two light beams L1 and L2 via the first optical system 54B, and is incident on the measurement region E1 and the reference region E2 of the dielectric block 42 arranged in the measurement unit 56. In the measurement region E1 and the reference region E2, the light beams L1 and L2 include various incident angle components with respect to the interface between the metal film 50 and the dielectric block 42 and are incident at an angle greater than the total reflection angle. The light beams L 1 and L 2 are totally reflected at the interface between the dielectric block 42 and the metal film 50. The totally reflected light beams L1 and L2 are also reflected with various reflection angle components. The totally reflected light beams L1 and L2 are received by the light receiving unit 54D through the second optical system 54C, are photoelectrically converted, and a light detection signal is output to the signal processing unit 54E. In the signal processing unit 54E, predetermined processing is performed based on the input photodetection signal, and total reflection attenuation angle data (hereinafter referred to as “total reflection attenuation angle data”) of the measurement region E1 and the reference region E2 is obtained. . The total reflection attenuation angle data is output to the control unit 60.

  The control unit 60 has a function of controlling the entire biosensor 10, and is connected to a light source 54A, a signal processing unit 54E, and a drive system (not shown) of the biosensor 10 as shown in FIG.

  As shown in FIG. 8, the control unit 60 includes a CPU 60A, ROM 60B, RAM 60C, ejection driver 60D, suction driver 60E, memory 60F, interfaces 60H, 60I, and 60J, which are connected to each other via a bus 60G. Has been. The discharge driver 60D is connected to the discharge motor 27C, and the suction driver 60E is connected to the suction motor 28C. The control unit 60 is connected to a display unit 62 for displaying various types of information and an input unit 64 for inputting various types of instructions and information via an interface 60H. The signal processing unit 54E, The light source 54A is connected, and the head 24 is connected via the interface 60J. The ROM 60B stores a control program for the head 24, the discharge pump 27, and the suction pump 28, and the like.

  In the memory 60F, as shown in FIG. 9, the difference S between the discharge amount per unit time and the suction amount between the discharge pump 27 and the suction pump 28, the discharge pump 27 for canceling this difference S, and A correction table T in which the operation speeds α and β (after-correction operation speeds α and β) of the suction pump 28 are associated is stored. The difference S here is due to an error in the inner diameter of the cylinder of the syringe pump. Further, the post-correction operating speeds α and β do not necessarily have to be the speed itself, and may be the number of pulses of the pulse motor or the speed increase / decrease rate. Further, only the corrected operation speed of only the discharge pump 27 or the suction pump 28 may be used. The difference S in the biosensor 10 of the present embodiment is obtained in advance by measurement, and the operation speeds α and β to be adopted are selected. The respective values are S1, α1, and β1.

  Next, measurement with the biosensor 10 will be described.

  On the mounting table 12A of the biosensor 10, a tray containing the sensor stick 40 in which the ligand D is fixed and the liquid channel 45 is filled with the storage solution C is set. A predetermined analyte solution is set on the analyte solution plate 17.

  First, one sensor stick 40 is pushed up to the position of the stick holding member 14C by the push-up mechanism 12D, and is held by the stick holding member 14C. The stick holding member 14 </ b> C moves along the lower guide rail 14 </ b> B while holding the sensor stick 40, and conveys the sensor stick 40 to the measuring unit 56. The sensor stick 40 conveyed to the measurement unit 56 is positioned at a predetermined measurement position and is pressed and fixed from above by a pressing member 58.

  When an instruction to start measurement is input from the input unit 64, the control unit 60 executes a measurement process shown in FIG.

  First, in step S12, an output instruction signal for the light beam L is output to the light source 54A. Thereby, the light beam L is emitted from the light source 54A. The emitted light beam L is converted into two light beams L1 and L2 by the first optical system 54B, and is incident on the measurement region E1 and the reference region E2 of the liquid channel 45, respectively. In step S14, an operation instruction signal is output to the light receiving unit 54D and the signal processing unit 54E. Thus, the light beams L1 and L2 that are totally reflected by the measurement region E1 and the reference region E2 and pass through the second optical system 54C are received by the light receiving unit 54D, and the received light is received for each of the measurement region E1 and the reference region E2. The photoelectric conversion is performed and a light detection signal is output to the signal processing unit 54E. In the signal processing unit 54E, predetermined processing is applied to the light detection signal, total reflection attenuation angle data is generated, and output to the control unit 60.

  In step S16, the controller 60 determines whether or not a predetermined time has elapsed. After the predetermined time has elapsed, the controller 60 stores the input total reflection attenuation angle data in the memory 60F in step S18. In step S20, the total reflection attenuation angle data obtained from the photodetection signal from the measurement region E1 is corrected with the total reflection attenuation angle data obtained from the photodetection signal from the reference region E2, and the ligand D and the analyte are corrected. Binding state data indicating the binding state with the analyte A in the solution YA is generated. In step S22, the combined state data is output to the display unit 62. As a result, the coupling state data for each predetermined time is stored in the memory 60F and displayed on the display unit 62. To the display unit 62, the combined state data for each time is graphed and output. This measurement process is continued until a measurement process end signal is received.

  On the other hand, when an instruction to start supplying analyte is input from the input unit 64, the control unit 60 executes the analyte supply process shown in FIG.

  First, in step S30, the analyte solution YA is obtained by sucking the analyte solution YA into the pipette tip CPA. That is, the head 24 is moved to the upper part of the analyte solution plate 17 in which the analyte solution YA is set, the pipette portion 24A is lowered, and only the tip of the pipette tip CPA attached to the pipette portion 24A is moved. Insert into the cell where the analyte solution YA is stored. Then, the discharge piston 27B is driven by the discharge motor 27C so that the discharge cylinder 27A has a negative pressure, and the analyte solution YA is sucked into the pipette tip CPA.

  Next, in step S31, the head 24 is moved onto the sensor stick 40, and in step S32, the pipette tip CPA is inserted into the supply port 45A, and the pipette tip CPB is inserted into the discharge port 45B.

  In step S33, the corrected operation speeds α1 and β1 are read from the memory 60F, and in step S34, the discharge driver 60D and the suction driver are driven so that the discharge motor 27C and the suction motor 28C are driven at the corrected operation speeds α1 and β1. An instruction is output to 60E. As a result, the discharge pump 27 and the suction pump 28 are driven, the analyte solution YA is discharged from the pipette tip CPA and injected into the liquid flow path 45, and the buffer that has been filled in the liquid flow path 45 to the pipette chip CPB. Liquid is aspirated.

  In step S35, the process waits until a predetermined time for supplying a predetermined amount of the analyte solution YA elapses. After the predetermined time elapses, the discharge pump 27 and the suction pump 28 are stopped in step S36.

  In step S37, the pipette tip CPA and the pipette tip CPB are extracted from the supply port 45A and the discharge port 45B, and in step S38, the buffer solution sucked into the pipette tip CPB is discharged to the waste liquid container 19, and this analyte supply process Ends.

  On the other hand, the measurement process is also terminated in response to the measurement end instruction signal.

  In the present embodiment, the supply of the analyte solution YA to the liquid channel 45 is performed by driving the discharge pump 27 and the suction pump 28 at the corrected operation speeds α1 and β1, so that the liquid channel 45 per unit time is supplied. The error between the amount discharged to the liquid and the amount of suction from the liquid channel 45 is canceled, and fluctuations in the liquid supply pressure can be suppressed. And since the fluctuation | variation of liquid feeding pressure is suppressed, it becomes difficult to produce liquid feeding defect and the reliability of the biosensor 10 can be made high.

  In the present embodiment, the correction of the operation speed of the discharge pump 27 and the suction pump 28 during the feeding of the analyte solution YA has been described. However, even in the case of feeding other liquids, for example, a buffer solution or a cleaning solution. By performing the same control, it is possible to suppress fluctuations in the liquid feeding pressure.

  In the present embodiment, the example in which the pair of pipettes 24A and 24B is provided in the head 24 has been described. However, a multi-channel configuration in which a plurality of pairs of pipettes are provided and liquid is supplied to a plurality of liquid flow paths 45 at a time. It is good. In this case, for example, as shown in FIG. 12, the head 74 is provided with six pairs and twelve pipette portions 74A to 74L. And each discharge pump 27 of the pipette part 74A, 74C, 74E, 74G, 74I, 74K on the side to be inserted into the supply port 45A is driven by one discharge driver 60D. On the other hand, the suction pumps 28 of the pipette portions 74B, 74D, 74F, 74H, 74J, and 74L on the side to be inserted into the discharge port 45B are driven by the corresponding suction driver 60E.

  As for the corrected operation speed for canceling the difference S between the discharge amount and the suction amount, as shown in FIG. 13, only the corrected operation speed β of the suction pump 28 is stored for each pair of pipettes. Each suction pump 28 is driven at each corrected operation speed β using each suction driver 60E.

  In the case of the multi-channel configuration, as described above, by adjusting only the operation speed on the suction pump 28 side, an error between the discharge amount and the suction amount can be canceled with a simple configuration.

  In the present embodiment, the supply of various liquids to the liquid flow path 45 is performed by discharging the liquid from the pipette tip CPA side and sucking it from the pipette tip CPB side. However, if desired, the liquid is supplied from the pipette tip CPB side. It is good also as a structure which can flow back to the pipette tip CPA side. In this case, the discharge pump 27 performs the suction operation and the suction pump 28 performs the discharge operation, and adopts the negative values of the correction table T described above as the corrected operation speeds α and β, respectively. Even during reverse flow, the error can be corrected and fluctuations in the liquid supply pressure can be suppressed.

  In the present embodiment, the surface plasmon sensor is described as an example of the biosensor, but the biosensor is not limited to the surface plasmon sensor. In addition, for example, quartz crystal microbalance (QCM) measurement technology, optical measurement technology using a functionalized surface from colloidal gold particles to ultrafine particles, and the like. Can be applied.

  In addition, a leaky mode detector can be used as another biosensor using total reflection attenuation. The leakage mode sensor is composed of a dielectric, and a thin film composed of a clad layer and an optical waveguide layer that are sequentially layered thereon. One surface of the thin film serves as a sensor surface, and the other surface receives light. It becomes a surface. When light is incident on the light incident surface so as to satisfy the total reflection condition, a part of the light is transmitted through the cladding layer and taken into the optical waveguide layer. In this optical waveguide layer, when the waveguide mode is excited, the reflected light at the light incident surface is greatly attenuated. The incident angle at which the waveguide mode is excited varies according to the refractive index of the medium on the sensor surface, similarly to the surface plasmon resonance angle. By detecting the attenuation of the reflected light, the reaction on the sensor surface can be measured.

It is a whole perspective view of the biosensor of this embodiment. It is a perspective view of the sensor stick of this embodiment. It is a disassembled perspective view of the sensor stick of this embodiment. It is sectional drawing of the 1 liquid flow path part of the sensor stick of this embodiment. It is a figure which shows the state in which the light beam is injecting into the measurement area | region and reference area | region of the sensor stick of this embodiment. It is a schematic block diagram of the liquid suction / discharge part of this embodiment. It is the schematic of the optical measurement part vicinity of the biosensor of this embodiment. It is a schematic block diagram of the control part of this embodiment, and its periphery. It is a correction table of this embodiment. It is a flowchart of the measurement process of this embodiment. It is a flowchart of the analyte supply process of this embodiment. It is a schematic block diagram which shows the modification of the liquid suction / discharge part of this embodiment. It is a figure which shows the modification of the correction table of this embodiment.

Explanation of symbols

DESCRIPTION OF SYMBOLS 10 Biosensor 20 Liquid suction / discharge part 24A Pipette part 24B Pipette part 24 Head 26 Suction / discharge drive part 27 Discharge pump 28 Suction pump 40 Sensor stick 44 Channel member 45 Liquid channel 45A Supply port 45B Discharge port 60F Memory 60E Suction driver 60 Control Portion 60D Discharge driver 74A Pipette portion 74B Pipette portion 74 Head CPA Pipette tip CPB Pipette tip S Difference T Correction table α Corrected operating speed β Corrected operating speed

Claims (5)

A liquid feeding device for feeding the sample to the sensor surface of a measurement unit having a flow path having a supply port and a discharge port, and a sensor surface that is exposed in the flow path and detects a reaction of the sample. There,
A pair of pipettes inserted into each of the supply port and the discharge port;
A discharge pump for discharging a sample from one pipette of the pair of pipettes;
A suction pump for aspirating the sample into the other pipette of the pair of pipettes;
The operating speed of the discharge pump and the suction pump so that the difference between the discharge amount per unit time from the pipette by the discharge pump and the suction amount per unit time from the pipette by the suction pump is canceled Operating speed control means for controlling
A liquid feeding device comprising:   The operation speed control means includes storage means for storing a corrected operation speed of at least one of the discharge pump and the suction pump for canceling a difference between the discharge amount and the suction amount, and the corrected operation speed. The liquid delivery device according to claim 1, comprising: a pump driver that drives the discharge pump and the suction pump. A plurality of pipette pairs;
The operation speed control means includes a storage means for storing the corrected operation speed of each of the suction pumps for canceling the difference between the discharge amount and the suction amount for each of the plurality of pipette pairs; The liquid feeding device according to claim 1, further comprising: a pump driver that drives the suction pump at an operating speed. A biosensor that measures the reaction state of a sample using attenuation of total reflection of light,
A measurement unit having a flow path having a supply port and a discharge port, and a sensor surface having a ligand fixed on a flat metal film exposed in the flow path,
The liquid feeding device according to any one of claims 1 to 3, wherein the sample is fed to the sensor surface of the measurement unit.
An optical member that emits light toward the metal film of the sensor chip;
A light receiving member that receives the light reflected by the metal film;
A biosensor with A liquid feeding method for feeding the sample to the sensor surface of a measurement unit having a flow path having a supply port and a discharge port, and a sensor surface exposed in the flow path for detecting a reaction of the sample. There,
Insert a pipette pair into each of the supply and discharge ports,
A discharge amount per unit time by a discharge pump that discharges a sample from one pipette of the pipette pair, and a suction amount per unit time by a suction pump that sucks a sample to the other pipette of the pipette pair, Controlling the operation speed of the discharge pump and the suction pump so that the difference of
Delivery method.

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