JP2007071543A - Optical surface plate and biosensor - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an optical surface plate capable of performing temperature control efficiently with a small number of components, and a biosensor equipped with the optical surface plate. <P>SOLUTION: The optical surface plate 80 is equipped with a surface plate body 80A having a ridged shape formed by a first inclined plane 82A and a second inclined plane 82B. The surface plate body 80A is constituted of one metal block. A bottom part of the surface plate body 80A has a constitution wherein a lid member 84 is interfitted into recessed parts 80B. A recessed groove U constituting a passage 86 for temperature control is formed on the recessed parts 80B of the surface plate body 80A. The recessed groove U has a linear shape along the longitudinal direction and a return shape to the reverse direction on the end inside. The open side (lower side) of the recessed groove U is covered with the lid member 84, to thereby constitute the passage 86 for temperature control. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to an optical surface plate for arranging optical members, and a biosensor provided with the optical surface plate.

  In general, the optical surface plate is provided with an optical member for irradiating light to a predetermined place, and it is considered that the optical surface plate is deformed by heat. If the optical surface plate is deformed, adverse effects such as deviation of the light irradiation position occur. Therefore, it is conceivable that temperature control water is supplied and discharged to suppress the temperature increase of the optical surface plate. For example, in Patent Document 1, a hollow frame is attached to the lower side of the optical surface plate to form a flow path, and cooling water is allowed to flow through the flow path to cool the optical surface plate.

However, in Patent Document 1, since the optical surface plate is cooled via the frame, the cooling efficiency is low. Further, since the frame and the optical surface plate are separate members, the number of parts also increases.
JP 2000-53361 A

  The present invention has been made in view of the above facts, and an object of the present invention is to provide an optical surface plate capable of efficiently adjusting the temperature with a small number of parts and a biosensor equipped with the optical surface plate.

  In order to solve the above-mentioned problems, an optical surface plate according to a first aspect of the present invention includes an optical member placement portion that places an optical member that emits light, and a light receiving member that receives light emitted from the optical member. The surface plate main body in which the light receiving member arrangement | positioning part to arrange | position is formed, and the temperature control flow path comprised by the said surface plate main body itself, and was connected with the supply port and discharge port of the liquid.

  In the optical surface plate of the present invention, since the temperature adjustment flow path is configured in the surface plate body itself, compared to the case where it is formed outside the surface plate body or a case where a pipe is embedded. In addition, heat is directly transferred between the surface plate body and the temperature-controlled water, so that the temperature of the optical surface plate can be efficiently controlled. In addition, since the temperature adjusting flow path can be configured by one member, there is no interface between another member and the surface plate body, and temperature resistance can be reduced to suppress temperature unevenness.

  The temperature control flow path of the optical surface plate is configured by forming a concave groove along the temperature control flow path in the surface plate body, and arranging a lid member so as to cover the open surface of the concave groove. Can do.

  In addition, the temperature control flow path of the optical surface plate has a return member configured with a communication flow path that perforates a plurality of through passages in the surface plate body and connects adjacent through passages to the outside of the surface plate body. It can be configured by mounting. The return member causes the liquid that has passed through one through path to be folded back to another through path.

  Further, the surface plate body of the optical surface plate is characterized in that it has a mountain shape with one inclined surface as the optical member arrangement portion and the other inclined surface as the light receiving member arrangement portion. Can do.

  As described above, the configuration of the optical surface plate is a mountain shape, so that the optical member and the light receiving member can be stably arranged.

  In addition, the said temperature control flow path can be characterized by being formed in the bottom part of the surface plate main body made into the mountain shape. If it is a bottom part, the flow path for temperature control can be formed easily.

  Further, the temperature adjusting flow path can be characterized by being formed so as to be arranged in the direction from the top to the bottom of the surface plate body having a mountain shape. By arranging the temperature adjustment flow path in this way, the upper and lower heat distribution can be made uniform.

  A biosensor according to a second aspect of the present invention is a biosensor for measuring a reaction state of a sample using attenuation of total reflection of light, the sensor chip having a ligand immobilized on a flat metal film, A measurement unit that holds the sensor chip; an optical member that emits light toward the metal film of the sensor chip held by the measurement unit; and a light receiving member that receives the light reflected by the metal film; And an optical surface plate according to any one of claims 1 to 6, wherein the optical member is disposed in the optical member disposition portion, and the light receiving member is disposed in the light receiving member disposition portion. It is characterized by.

  According to the biosensor having the above configuration, since the optical member and the light receiving member are arranged on the optical surface plate that is efficiently temperature-controlled, more accurate measurement can be performed.

  Since the present invention has the above configuration, the temperature of the optical surface plate can be efficiently controlled with a small number of parts.

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

  The biosensor 10 according to 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. A ligand D is fixed on the metal film 50. 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.

  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 45B, and the liquid supplied to the liquid channel 45 is prevented from evaporating.

  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 14A and the lower guide rail 14B are horizontally disposed in the arrow X direction orthogonal to the arrow Y direction. 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. Are conveyed onto an optical surface plate 80 described later.

  On the container mounting table 16, an analyte solution plate 17, a recovery liquid stock container 18, and a dissociation liquid stock container 19 are mounted. 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 recovery containers 18A to 18E, and an opening K into which a pipette tip CP (to be described later) can be inserted is formed in the recovery containers 18A to 18E. The dissociation liquid stock container 19 includes a plurality of stock containers 19A to 19E, and an opening K into which a pipette tip CP can be inserted is formed in the same manner as the recovery 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). As shown in FIG. 6, the head 24 includes two 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.

  In this embodiment, the liquid is supplied to the sensor stick 40 by the pipette tip CP. Instead of the pipette tip, one end is connected to the solution plate and the other end is connectable to the sensor stick 40. An injection tube may be provided, and the liquid may be supplied by a liquid feed pump.

  As shown in FIG. 7, the optical measuring unit 54 includes an optical surface plate 80, 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.

  As shown in FIG. 8, the optical surface plate 80 includes a surface plate body 80A in which a mountain shape is formed by the first inclined surface 82A and the second inclined surface 82B. The surface plate main body 80A is composed of one metal block. A flat surface 82C is formed at the top of the mountain shape of the surface plate main body 80A. The flat surface 82C is disposed along the lower guide rail 14B, and the sensor stick 40 is conveyed on the flat surface 82C.

  As shown in FIG. 9, the bottom portion of the surface plate main body 80 </ b> A is configured by fitting a lid member 84 into a notch recess 80 </ b> B. A concave groove U that constitutes a temperature adjusting flow path 86 is formed in the notched concave portion 80B of the surface plate main body 80A. The concave groove U is linear along the longitudinal direction of the flat surface 82C, and is shaped to be folded back in the opposite direction inside the end portion. The open side (lower side) of the concave groove U is covered with a lid member 84 to form a temperature adjustment flow path 86. The temperature adjustment channel 86 is in communication with the supply port 86A and the discharge port 86B of the temperature adjustment water.

  From the supply port 86A and the discharge port 86B, as shown in FIG. 1, the piping P connected with the temperature control part 88 is arrange | positioned. The temperature adjustment unit 88 is provided with a pump for circulating the temperature adjustment water and a temperature adjustment element (both not shown) for adjusting the temperature of the temperature adjustment water to an appropriate temperature. The temperature-controlled water is supplied from the supply port 86A, passes through the temperature adjustment channel 86 in the optical surface plate 80, and is discharged from the discharge port 86B.

  A light source 54A and a first optical system 54B (hereinafter collectively referred to as “optical member 55A”) are disposed on the first inclined surface 82A. The second inclined surface 82B is provided with a second optical system 54C and a light receiving portion 54D (hereinafter collectively referred to as “light receiving member 55B”).

  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 enters the measurement region E1 and the reference region E2 of the dielectric block 42 arranged on the optical surface plate 80. 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, and the reaction between the ligand D and the analyte A is measured.

  In the present embodiment, since the temperature adjusting flow path 86 is formed in the surface plate body 80A of the optical surface plate 80 on which the optical member 55A and the light receiving member 55B are placed, the temperature adjustment channel 86 is formed outside the surface plate body 80A. In this case, the temperature of the optical surface plate 80 can be efficiently controlled as compared with the case where the optical surface plate 80 is formed by embedding a pipe. In addition, since the surface plate main body 80A is composed of a single member, the temperature resistance at the joint surface between the members can be reduced and temperature unevenness can be suppressed compared to the case where the surface plate body 80A is composed of a plurality of members. Can do.

  Further, since the optical surface plate 80 is composed of the same member, the optical axes of the optical member 55A and the light receiving member 55B can be easily aligned.

  Moreover, the optical member 55A and the light receiving member 55B can be stably arranged by making the configuration of the optical surface plate 80 into a mountain shape.

  In addition, although the temperature control flow path 86 in the present embodiment is formed along the bottom of the optical surface plate 80, as shown in FIG. 10, it is arranged so as to be aligned in the bottom direction from the top of the surface plate body 80A. You can also. In this case, as shown in FIG. 11, the temperature adjusting flow path 90 is formed by perforating through passages 90A along the longitudinal direction of the flat surface 82C (six in FIG. 11), and the adjacent through passages 90A are returned to the return member. Connect at 90B. As shown in FIG. 11, the return member 90B is a cap in which a space R is formed, and is attached to the outside of the surface plate main body 80A so that the space R covers the openings of two adjacent through passages 90A. As shown in FIG. 12, the temperature-controlled water from one through passage 90A enters the space R and is turned back to the other through passage 90A.

  As described above, by arranging the temperature adjusting flow path 90, the heat distribution of the upper and lower portions of the optical surface plate 80 can be made uniform.

  In this embodiment, after forming the surface plate main body 80A, the concave groove U is formed or the through passage 90A is perforated to configure the temperature control flow path. However, the surface plate main body 80A is formed of a mold. At the time of forming, a substance that can be removed in a subsequent process is arranged in a portion constituting the flow path for hot water, and after the surface plate main body 80A is formed, the substance arranged in the flow path portion for hot water is removed by melting or the like. May be manufactured.

  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 side view of the pipette part which comprises the liquid supply part of this embodiment. It is the schematic of the optical measurement part vicinity of the biosensor of this embodiment. It is a perspective view of the optical surface plate of this embodiment. It is a disassembled perspective view of the optical surface plate of this embodiment. It is a perspective view of the modification of the optical surface plate of this embodiment. It is a disassembled perspective view of the modification of the optical surface plate of this embodiment. It is sectional drawing of the flow-path part for temperature control of the optical surface plate of this embodiment.

Explanation of symbols

DESCRIPTION OF SYMBOLS 10 Biosensor 40 Sensor stick 54 Optical measurement part 55A Optical member 55B Light receiving member 56 Measurement part 60 Control part 80 Optical surface plate 80A Surface plate main body 82A 1st inclined surface 82B 2nd inclined surface 84 Lid member 86 Temperature control flow path 90B Return Member 90 Temperature control channel 90A Through-channel

Claims (7)

A surface plate main body formed with an optical member placement portion for placing an optical member that emits light, and a light receiving member placement portion for placing a light receiving member that receives light emitted from the optical member,
The temperature control flow path composed of the platen body itself and communicated with the liquid supply port and the discharge port;
Optical surface plate equipped with.   2. The optical surface plate according to claim 1, wherein the temperature adjustment flow path includes a concave groove formed in the surface plate main body and a lid member that covers an open surface of the concave groove. .   The temperature control flow path is a return constituted by a plurality of through passages perforated in the surface plate body and a communication flow path that is attached to the outside of the surface plate body and connects adjacent openings of the through passages. The optical surface plate according to claim 1, comprising: a member.   The said surface plate main body is a mountain shape which makes the one inclined surface the said optical member arrangement | positioning part, and makes another inclined surface the said light receiving member arrangement | positioning part, The Claim 1 thru | or 3 characterized by the above-mentioned. The optical surface plate according to any one of the above.   5. The optical surface plate according to claim 4, wherein the temperature adjustment channel is formed at a bottom portion of the surface plate main body having the mountain shape.   5. The optical surface plate according to claim 4, wherein the temperature adjusting flow path is formed so as to be arranged in a direction from a top portion to a bottom portion of the surface plate main body having the mountain shape. A biosensor that measures the reaction state of a sample using attenuation of total reflection of light,
A sensor chip in which a ligand is fixed on a flat metal film;
A measurement unit for holding the sensor chip;
An optical member that emits light toward the metal film of the sensor chip held by the measurement unit;
A light receiving member that receives the light reflected by the metal film;
An optical surface plate according to any one of claims 1 to 6,
With
The biosensor, wherein the optical member is arranged in the optical member arrangement part, and the light receiving member is arranged in the light receiving member arrangement part.

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