JP2007071542A - Measuring cell holding mechanism and biosensor - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a measuring cell holding mechanism capable of preventing movement of the flat surface on which a ligand is immobilized, of a measuring cell at a measuring time, and preventing deformation of a passage member, and a biosensor equipped with the measuring cell holding mechanism. <P>SOLUTION: Sandwiching parts K of a dielectric block 42 by a pressing stick 27A and a spring part 27C are arranged on the upper side of the dielectric block 42. The tip part 26P of a block presser 26K has a sharpened shape, bites into the dielectric block 42, and holds the dielectric block 26. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to a measurement cell holding mechanism that holds a measurement cell having a flow path for supplying an analyte solution containing an analyte to a ligand at a measurement position, and a biosensor provided with the measurement cell holding mechanism.

Conventionally, a ligand is fixed on a measurement cell, a flow path is formed in a portion where the ligand is fixed, an analyte solution containing an analyte is supplied to the flow path, and light is emitted from the opposite side of the flow path. Measurement of the interaction between a ligand and an analyte by making a beam incident (see Patent Document 1). Such a measurement needs to hold the measurement cell firmly so that the measurement cell does not move during the measurement.
Japanese Patent No. 3294605

  By the way, when a liquid such as an analyte solution is supplied to the flow path by directly accessing the flow path, the measurement cell is easily moved during the access. In particular, since the movement of the measurement surface on which the ligand is fixed affects the measurement, it is necessary to suppress the movement of the measurement surface.

  The present invention has been made in consideration of the above facts, and provides a measurement cell holding mechanism capable of efficiently suppressing movement of a measurement cell during measurement, and a biosensor equipped with the measurement cell holding mechanism The purpose is to do.

  In order to solve the above problems, the measurement cell holding mechanism according to the first aspect of the present invention is in close contact with a dielectric block having a flat surface on which a ligand is fixed and the flat surface of the dielectric block. A flow path member formed between the flat surface and a flow path member having an opening communicating with the flow path and opening upward; and A base member to be placed, a liquid supply member that enters the opening from above and supplies liquid to the flow path, and a distance S between the base member and the opening, from the base member Dielectric block holding means for holding the dielectric block at the measurement position on the opening side with respect to a height position of 30% of the distance S.

  In the measurement cell holding mechanism of the present invention, the dielectric block is held by the dielectric block holding means. The holding of the dielectric block can restrict the movement of the measurement surface (flat surface on which the ligand is fixed) with a smaller force in the holding on the opening side than in the holding on the side close to the base member.

  In addition, in this application, a ligand means the high molecular substance with physiological activity, and protein, DNA, RNA, saccharides etc. are illustrated, but it is not restricted to them.

  Therefore, in the present invention, the holding position is set to the opening side relative to the height position of 30% of the distance S between the base member and the opening. By holding the dielectric block at this holding position, the dielectric block can be efficiently held with a smaller holding force.

  The dielectric block holding means may include a clamping member that sandwiches two opposing side surfaces of the dielectric block in the horizontal direction.

  In this manner, by sandwiching and holding the two side surfaces of the dielectric block with the sandwiching member, it is possible to suppress the sandwiched horizontal movement.

  Further, the dielectric block holding means may include a biting member that bites into the flat surface of the dielectric block by a pressing force.

  Here, the biting of the dielectric block into the flat surface means that the flat surface is deformed and a part of the biting member enters inside. In this way, by causing the biting member to bite into the flat surface of the dielectric block, it is possible to suppress the displacement of the dielectric block due to slippage between the dielectric block and the dielectric block holding means, and to efficiently generate the dielectric. The movement of the body block can be suppressed.

  Further, the dielectric block holding means may include a flow path pressing member that presses the flow path member from the opposite side of the side where the dielectric block is disposed.

  By pressing the flow path member with the flow path pressing member, the dielectric block is held between the flow path member and the base member, and the vertical movement of the dielectric block can be suppressed.

  The flow path pressing member may be characterized by biting into the flow path member with a pressing force.

  In this way, by causing the flow path pressing member to bite into the flow path member, it is possible to suppress the displacement of the dielectric block due to the slip between the flow path member and the flow path holding member.

  A biosensor according to a second aspect of the present invention includes a measurement cell holding mechanism according to any one of claims 1 to 5, and light passing through the dielectric block on the flat surface of the measurement cell. A light source that makes the beam incident; and a light receiving member that receives the reflected light of the light beam reflected by the flat surface.

  According to the above configuration, the dielectric block can be efficiently held with a smaller force, and accurate measurement can be performed.

  Since the present invention is configured as described above, the movement of the measurement cell during measurement can be efficiently suppressed, and accurate measurement can be performed.

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

  The biosensor 10 of the present embodiment is a so-called surface plasmon sensor that measures the interaction between the ligand D and the analyte A using 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, a pressing unit 26, 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. Two trays T are positioned and placed on the mounting table 12A. In the tray T, eight sensor sticks 40 are stored. 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, a ligand D is fixed and a measurement region E1 in which a reaction between the analyte A and the ligand D occurs, and a ligand D is not fixed, and a reference signal for signal measurement in the measurement region E1 is obtained. A reference region E2 is formed. 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 method of constructing the reference region E2, for example, if alkylthiol is arranged in the reference region E2 instead of carboxylmethyldextran, 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, vertical convex portions 42D perpendicular to the upper surface of the prism portion 42A are formed at seven locations along the upper edge. 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 disposed on the metal film 50 of the dielectric block 42 so as to be separated from each other as shown in FIG. . 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.

  Since it is assumed that a liquid containing protein is supplied to the liquid channel 45, the material of the channel member 44 is non-specific to the protein in order to prevent the protein from adhering to the channel wall. It preferably has no adsorptivity.

  The holding member 46 is long and includes an upper plate 46A and two side plates 46B. The holding member 46 is placed on the dielectric block 42 with the six flow path members 44 interposed therebetween. Note that an engagement hole (for example, an engagement hole is formed in the side plate 46B of the holding member 46 so that the dielectric block 42 and the holding member 46 are engaged with each other as necessary, and the engagement is performed in this engagement hole. The engaging projections to be formed on the dielectric block). In the present embodiment, the holding member 46 is placed on the dielectric block 42, whereby the flow path member 44 is attached to the dielectric block 42 while being adhered. 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. Further, a positioning boss 46E is formed between two pipette insertion holes 46D arranged at positions facing the supply port 45A and the discharge port 45B of one flow path member 44. Further, a pressing hole 46F into which a prism pressing member 26K (to be described later) can be inserted is formed at a position opposite to the separated portion where the flow path member 44 is spaced apart.

  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, a positioning hole 48E is formed at a position facing the boss 46E, and a position facing the pressing hole 46F. A hole 48F is formed. In addition, a slit 49D that is a cross-shaped cut is formed at a position facing the pipette insertion hole 46D of the evaporation preventing member 49, a positioning hole 49E is formed at a position facing the boss 46E, and a pressing hole 46F. A hole 49F is formed at the facing position. 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 46, 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.

  On the side opposite to the stick holding member 14C across the lower guide rail 14B of the measurement unit 56, a pressing unit 26 for pressing the sensor stick 40 during measurement is provided. As shown in FIGS. 6 and 7, the pressing portion 26 includes a support portion 26A, and a stage 26B is attached to the support portion 26A. A drive guide 26C is attached to the side surface of the stage 26B. The drive guide 26C is movable in the Z direction (vertical direction) along the side surface of the stage 26B by the driving force of the drive motor 26D disposed on the upper portion of the stage 26B. A pressing spring 26F is attached to the drive guide 26C via a connecting member 26E. A stick 26G is disposed below the pressing spring 26F, a plate member 26H is attached to the lower side of the stick 26G, and a pressing plate 26I is attached to the lower side surface of the plate member 26H. As shown in FIG. 7, a hole H is formed in the horizontal direction above the stick 26 </ b> G, and a pin P protruding from the connecting member 26 </ b> E is inserted into the hole H. The hole H is a long hole so that the pin P can move downward in the hole H. The stick 26G, the plate member 26H, and the presser plate 26I are pressed by the presser spring 26F and moved downward when the drive guide 26C is lowered. The pressing spring 26F is set such that a prism pressing 26K, which will be described later, presses the dielectric block 42 with a predetermined pressing force when contracted by a predetermined amount. Here, the predetermined pressing force refers to a pressing force such that the distal end portion 26P of the prism holder 26K can bite into the dielectric block 42 and the prism block 26 can hold the dielectric block 42. Further, the stick 26G, the plate member 26H, and the pressing plate 26I are lifted by the pin P by the raising of the drive guide 26C.

  The pressing plate 26I has a rectangular plate shape, and is disposed so that the plate surface faces the sensor stick 40 and the longitudinal direction is parallel to the lower guide rail 14B. The presser plate 26I is formed with two holes 26J into which a pipette tip CP described later can be inserted.

  Further, as shown in FIG. 8, a prism retainer 26K and a flow path retainer 26L are provided below the retainer plate 26I. Two prism holders 26K are provided at positions corresponding to the holding holes 46F formed in the holding member 46 of the sensor stick 40, and have such a length that they can be inserted into the holding holes 46F and come into contact with the prism portion 42A. The distal end portion 26P of the prism holder 26K has a sharp shape so as to be able to bite into the surface of the dielectric block 42. As shown in FIG. 9, the flow path retainer 26 </ b> L is configured by a leaf spring whose base end is attached to the plate member 26 </ b> H and can be elastically deformed in the Z direction. The plate spring of the flow path holder 26L is set in contact with the boss 46E so as to press the boss 46E with a pressing force smaller than that of the presser spring 26F.

  The pressing force by the prism holder 26K and the flow path holder 26L is received by the lower guide rail 14B.

  A clamping member 27 is provided below the measurement unit 56. The clamping member 27 is disposed on the side opposite to the pressing stick 27A with the pressing stick 27A disposed on the pressing portion 26 side of the lower guide rail 14B, the holding member 27B that holds the pressing stick 27A, and the lower guide rail 14B interposed therebetween. The spring portion 27C is included. The spring portion 27C includes a ball 27D and a spring 27E (see FIG. 14), and receives the pressing force of the pressing stick 27A. The sensor stick 40 is sandwiched between the pressing stick 27A and the spring portion 27C, and movement in the Y direction is restricted.

  Here, as shown in FIG. 14, the clamping position K of the dielectric block 42 between the pressing stick 27A and the spring portion 27C is the upper side of the dielectric block 42, that is, the measurement area E1 and the reference area E2. The position is close to the other side. Specifically, when the distance between the lower guide rail 14B and the pipette insertion hole 46D is a distance S, the distance is set above the height position H that is 30% of the distance S.

  As shown in FIG. 15 (B), it is more preferable to hold at the holding position K on the upper side as shown in FIG. 15 (A) than to hold it at the holding position K0 on the lower side of the dielectric block 42. This is because the rotation YR in the Y direction of the dielectric block 42 can be regulated with a small force. When held at the clamping position K, the disturbance force F2 due to pipette access rotates the dielectric block 42 as it is, whereas when held at the clamping position K0, rotation behavior due to the disturbance force F2 occurs. The bottom surface in contact with the lower guide rail 14B horizontally moves in the direction opposite to the disturbance force F2, and this horizontal movement includes friction force F3 = F1 (pressing force by the pressing plate 26I) between the bottom surface and the lower guide rail 14B. This is because a force larger than x μ (friction coefficient) is required.

  Further, assuming that the distance from the lower guide rail 14B to the clamping position K is S2, and the distance from the clamping position K to the pipette insertion hole 46D is S1, the dielectric block 42 has a disturbance force when S2 · F3 ≧ S1 · F2. It is considered to be stationary without being affected by F2. Here, when F1 is 1000 gf (9.8 N) and the friction coefficient μ is about 0.15, it is considered that the frictional force F3 = 150 gf (1.47 N) and the disturbance force F2 is about 30 gf (0.294 N). Therefore, if F2 = 30 gf × 2 = 60 gf (0.588N) in consideration of the safety factor, S2 ≧ (S1 · 60) /150=0.4S1. Therefore, if the distance S2 is greater than about 30% of the distance S (S1 ≧ 0.3S), the dielectric block 42 is kept stationary.

  Note that the larger the distance S2, the more efficiently the dielectric block can be held with a smaller holding force, and it is preferable that the distance S is greater than 50% of the distance S (above the center of the distance S).

Further, the force F4 when the disturbance force F2 acts in the Y direction is
Since 60 gf (0.588 N) / (S2 / S) = 210 gf (2.058 N), the pressing force with the pressing stick 27 </ b> A needs to be 210 gf (2.058 N) or more.

  As shown in FIG. 1, an analyte solution plate 17, a recovery liquid stock container 18, and a supply liquid stock container 19 are placed on the container mounting table 16. The analyte solution plate 17 is partitioned in a matrix form so that various types of analyte solutions can be stocked. The recovery liquid stock container 18 is composed of a plurality of recovery containers, and each recovery container is formed with an opening K into which a pipette tip CP described later can be inserted. The supply liquid stock container 19 is composed of a plurality of stock containers, and an opening K into which a pipette tip CP can be inserted is formed in the same manner as the collection container.

  The liquid suction / discharge section 20 is configured to include a cross rail 22 and a head 24 that are bridged in the arrow Y direction above the upper guide rail 14A and the guide rail 16B. The cross rail 22 can be moved in the arrow X direction by a drive mechanism (not shown). The head 24 is attached to the cross rail 22 and is movable in the arrow Y direction. The head 24 is also movable in the vertical direction (arrow Z direction) by a drive mechanism (not shown). Two pipette tips CP are attached to the head 24.

  As shown in FIG. 10, 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 disposed in the measurement unit 56 (FIG. 5). reference). 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 light detection signal, and data of the total reflection attenuation angle (hereinafter referred to as “total reflection attenuation data”) of the measurement region E1 and the reference region E2 is obtained. The total reflection attenuation 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. 11, the control unit 60 includes a CPU 60A, a ROM 60B, a RAM 60C, a memory 60D, and an interface I / F 60E that are connected to each other via a bus B, and a display unit 62 that displays various types of information. These are connected to an input unit 64 for inputting various instructions and information.

  Various programs for controlling the biosensor 10 and various data are recorded in the memory 60D.

  Next, a procedure for fixing the sensor stick 40 to the measurement unit 56 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 and a supply solution (buffer solution, dissociation solution, washing solution, etc.) are set in the analyte solution plate 17 and the supply solution stock container 19.

  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 stick holding member 14C stops at the measurement position of the measurement unit 56, and the sensor stick 40 is held between the pressing stick 27A of the holding member 27 and the spring portion 27C by the vertical convex portion 42D on the side surface of the prism portion 42A.

  Further, the drive guide 26C of the pressing portion 26 is moved downward and is pressed by the pressing spring 26F, so that the stick 26G, the plate member 26H, and the pressing plate 26I are lowered. As a result, the prism holder 26K is inserted into the holder hole 46F, and the distal end portion 26P bites into the prism portion 42A as shown in FIG. 12B and FIG. At this time, as shown in FIG. 12A, the hole 26 </ b> J is disposed at a position overlapping the liquid flow path 45. In FIGS. 12A and 12B, members other than the dielectric block 42 and the flow path member 44 that constitute the sensor stick 40 are omitted.

  The drive guide 26C moves downward in the Z direction and stops so that the pressing spring 26F contracts by a predetermined amount set in advance. Thus, the dielectric block 42 is pressed and fixed to the prism holder 26K with a predetermined pressing force. Further, the flow path member 44 is pressed against the flow path holder 26L via the holding member 46 with a predetermined pressing force. The pressing force to the flow path member 44 is set to be smaller than the pressing force to the dielectric block 42.

  When a liquid such as an analyte solution is supplied to the sensor stick 40 fixed as described above, or when the supplied liquid is recovered (discarded), the pipette tip CP is placed at the upper part as shown in FIG. Is inserted into or pulled out from the liquid channel 45 of the channel member 44 through the insertion hole 46D. At this time, disturbance force is applied by the pipette tip CP coming into contact with the holding member 46 and the flow path member 44, but the upper portion of the dielectric block 42 is held by the holding member 27, and the distal end portion 26 </ b> P of the prism holder 26 </ b> K is dielectrically connected. The body block 42 bites into the body block 42 and is pressed downward, and further pressed down and fixed by the flow path holder 26L. Therefore, the movement of the dielectric block 42 during measurement can be prevented.

  Further, since the flow path member 44 is pressed with a pressing force smaller than that of the dielectric block 42, a signal fluctuation in a drift state occurs during measurement due to the flow path member 44 being pressed with a strong force. Such inconveniences can be prevented.

  In the present embodiment, the prism retainer 26K is disposed in the separation portion formed between the adjacent flow path members 44, but the prism retainer may be disposed at another position.

  For example, as shown in FIG. 17, a prism pressing member 26 </ b> M may be provided in which the flow path member 44 is disposed so as to straddle the Y direction which is the short direction of the dielectric block 42. In this case, a hole for inserting the prism holder 26M is formed at a position corresponding to the prism holder 26M on the upper surface of the holding member 46.

  In the present embodiment, the example in which the tip portion 26P of the prism holder 26K bites into the dielectric block 42 has been described, but it is not always necessary to bite into the dielectric block 42. In particular, by biting in, the movement of the dielectric block 42 can be more efficiently suppressed as compared with the case where it is simply held in contact.

  In the present embodiment, the flow path holder 26L contacts the boss 46E and presses the dielectric block 42 via the holding member 46. However, as shown in FIG. 18, the flow path holder 26L bites into the boss 46E and presses it. Also good. In this case, it is possible to easily bite into the boss 46E by sharpening the tip of the flow path holder 26L. Thus, by biting into the boss 46E, the displacement of the dielectric block 42 due to the slip between the dielectric block 42 and the flow path holder 26L can be suppressed, and the movement of the dielectric block 42 can be efficiently performed. Can be suppressed.

  In the present embodiment, the surface plasmon sensor is described as an example of the biosensor. However, the biosensor can also be applied to a leaky mode sensor that uses total reflection attenuation. The leakage mode sensor is composed of a dielectric, 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 perspective view of the pressing part of this embodiment. It is the front of the holding | suppressing part of this embodiment. It is a front view near the pressing position in the pressing part of the present embodiment. It is a side view near the pressing position in the pressing 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. 4A is a top view and FIG. 4B is a side view showing a state in which the prism presser according to the present embodiment is pressed into a dielectric block. It is a figure which shows the state by which the pipette tip is inserted in the liquid flow path by this embodiment. It is the figure seen from the longitudinal direction of the dielectric block which shows the state which is pressing down the dielectric block with the clamping member of this embodiment. It is a figure explaining the relationship between the clamping position of the dielectric material block of this embodiment, and rotation. It is the figure seen from the longitudinal direction of the dielectric material block which shows the state which has made the prism pressing member of this embodiment bite into a dielectric material block. (A) which shows the state which is pressing down a dielectric block with the prism pressing of the modification of this embodiment is a top view, (B) is a side view. It is the figure seen from the longitudinal direction which shows the state which bites and presses down the channel presser of the modification of this embodiment to the boss.

Explanation of symbols

10 Biosensor 26P Tip portion 26K Prism pressing member 27C Spring portion 27A Press stick 27 Holding member 40 Sensor stick 42A Prism portion 42 Dielectric block 44 Channel member 46E Boss 46 Holding member 54 Optical measurement unit 54A Light source 54D Light receiving unit 56 Measurement unit

Claims (6)

A dielectric block having a flat surface on which a ligand is fixed and a flat surface of the dielectric block that is in close contact with the flat surface constitute a flow path and communicate with the flow path and open upward. A flow path member in which the opening is formed, and a measurement cell configured to include:
A base member on which the measurement cell is placed;
A liquid supply member that enters the opening from above and supplies liquid to the flow path;
The distance between the base member and the opening is a distance S, and the dielectric block holds the dielectric block at the measurement position on the opening side of the base member at a position 30% higher than the distance S. Holding means;
Measuring cell holding mechanism.   The measurement cell holding mechanism according to claim 1, wherein the dielectric block holding means includes a holding member that horizontally holds two opposing side surfaces of the dielectric block.   The measurement cell holding mechanism according to claim 1, wherein the dielectric block holding means includes a biting member that bites into the flat surface of the dielectric block by a pressing force. .   The said dielectric block holding means is comprised including the flow-path press member which presses the said flow-path member from the reverse side of the side by which the said dielectric block is arrange | positioned. The measurement cell holding mechanism according to claim 3.   The measurement cell holding mechanism according to claim 4, wherein the flow path pressing member bites into the flow path member with a pressing force. A measurement cell holding mechanism according to any one of claims 1 to 5,
A light source that makes a light beam incident on the flat surface of the measurement cell via the dielectric block;
A light receiving member that receives reflected light of the light beam reflected by the flat surface;
Biosensor equipped with.

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