Abstract:
A problem of a sample analysis device that uses magnetic particles is the difficulty in uniformly capturing magnetic particles, specifically the poor uniformity in the vicinity of channel side walls. This causes poor analysis accuracy and reproducibility. The present invention is intended to provide a means to uniformly capture magnetic particles in the vicinity of channel side walls. Specifically, the present invention provides an analysis device that includes a detection channel with an inlet and an outlet through which a sample liquid containing a specific substance and magnetic particles is flowed in and out of the channel, and magnetic field generating means capable of varying the magnitude of the magnetic field in a predetermined region of the detection channel. The width of the magnet in the detector is greater than the channel width. The detector can improve the analysis accuracy and reproducibility of the analysis device.

Description:
TECHNICAL FIELD 
       [0001]    The present invention relates to devices and methods for analyzing a sample, specifically to a sample analysis device and a sample analysis method that use antigen-antibody reaction. 
       BACKGROUND ART 
       [0002]    The immunoassay is described first as a typical example of a sample analysis. The immunoassay is a test that uses specific antigen-antibody reaction to detect or measure antibodies or antigens in humor (e.g., plasma, serum, and urine) for disease or pathology diagnosis. ELISA (Enzyme-Linked Immunosorbent Assay) is a representative example of the immunoassay. In ELISA, an antibody (first antibody) against an antigen of interest is immobilized to the bottom of a container, and a sample such as plasma, serum, and urine is applied so the antigen in the sample binds to the first antibody. An antibody (second antibody) linked to a labeling reagent is then applied so it binds to the antigen bound to the first antibody. The signal produced by the label is then detected to determine the presence or absence of the antigen, or the amounts of the antigen in the sample. A fluorescent substance is used as the label, for example. In this case, the chromogenic reaction occurs more strongly in direct proportion to the number of the labeled second antibodies, i.e., the amounts of antigen, and the antigen in the sample can be quantified by detecting the luminescence of the fluorescent substance with a device such as a photomultiplier. 
         [0003]    In a specific example of an ELISA immunoassay device, magnetic particles are used as the solid phase, and the first antibody is immobilized on the surfaces of the magnetic particles. The second antibody is linked to a substance (luminescent substance) labeled with a fluorescent dye. The antigen contained in a sample binds to the magnetic particles via the first antibody in response to an antigen-antibody reaction that occurs upon mixing a biological detection substance (antigen) with the magnetic particles immobilizing the first antibody. Upon reaction with the second antibody, the magnetic particles are bound to the luminescent substance via the second antibody, the antigen, and the first antibody. The amounts of the luminescent substance vary with the amounts of the detection substance contained in the sample, i.e., the amounts of the antigen. 
         [0004]    The magnetic particles bound to the detection substance are captured at a specified location, and by using a laser, the luminescent substance bound to the magnetic particles emits luminescence. The luminescence intensity can then be detected to quantitatively determine the amounts of the detection substance, specifically the antigen amounts in the sample. 
         [0005]    A high-sensitive immunoassay uses what is called B/F (bond/free) separation (separation of an antigen-antibody complex and free antibodies or antigens), in which the magnetic particles bound to the detection substance (antigen) are captured at a specified location with a magnet while displacing the solution containing antibodies not bound to the antigens. PTL 1 to PTL 4 describe methods of capturing magnetic particles at the predetermined position with an analysis device. 
       CITATION LIST 
     Patent Literature 
       [0006]    PTL 1: JP-A-8-62224 
         [0007]    PTL 2: JP-A-11-242033 
         [0008]    PTL 3: JP-A-7-248330 
         [0009]    PTL 4: JP-T-2003-502670 
       SUMMARY OF INVENTION 
     Technical Problem 
       [0010]    Capturing of magnetic particles at the predetermined position involves the following problems. As described in the Background Art section, a laser and a detector are usually fixed at specified locations in an analysis device. This necessitates the magnetic particles to be captured at the predetermined position as determined by these locations. It is important that the magnetic particles are uniformly captured at such predetermined position to improve the measurement accuracy of the analysis device. However, this involves many problems, for example, as described below using PTL 1 (JP-A-8-62224), PTL 2 (JP-A-11-242033), PTL 3 (JP-A-7-248330), and PTL 4 (JP-T-2003-502670). 
         [0011]    What often happens when B/F separation is performed with magnetic particles captured at the predetermined position is that the force exerted by the magnet (the force by which the magnetic particles are attracted to the magnet surface) becomes weaker in the vicinity of the side walls of the channel where the magnet ends are situated (as used herein, magnet ends are portions of the magnet other than the ends with the magnetic poles), with the result that the magnetic particles are captured more at the central portion of the channel, and less sufficiently in the vicinity of the side walls. The result is that the solution displaced in the B/F separation remains in the magnetic particle aggregate because of the interface tension of the solution, and B/F separation becomes insufficient. 
         [0012]    The magnet force becomes weaker in the vicinity of the side walls of the channel where the magnet ends are situated also when, for example, fluorescence detection is performed for the magnetic particles captured at the predetermined position. In this case, the magnetic particles may not be sufficiently captured as above. This may result in poor luminescence sensitivity, and poor measurement performance. 
         [0013]    The detection channels of the analysis devices described in PTL 1 and PTL 2 (JP-A-8-62224, JP-A-11-242033) have a uniform circular shape, or a uniform rectangular shape along the flow direction at the predetermined position where the magnetic particles are captured. On the other hand, the magnet width is smaller than the channel width, and undesirably creates a nonuniform capture distribution of magnetic particles. 
         [0014]    In PTL 3 (JP-A-7-248330), the channel width and the magnet width are both 5 mm. This creates a poor magnetic particle capture distribution in the side walls of the channel, and lowers luminescence intensity. 
         [0015]    In PTL 4 (JP-T-2003-502670), the magnetic particles are captured at the predetermined position under the magnetic field generated by an electromagnet, instead of a permanent magnet as used in PTL 1, PTL 2, and PTL 3. The electromagnet used to capture the magnetic particles is wider than the predetermined position in the flow direction. However, it is not preferable to increase the magnetic field wider than the magnetic particle-capturing predetermined position in the flow direction because it has the possibility of unnecessarily spreading the magnetic particles. This may lower luminescence intensity. 
         [0016]    With the recent movement toward more accurate analysis, there is a greater demand for more uniformly capturing the magnetic particles throughout the predetermined position. This has created the need to increase the capture amounts in the vicinity of the channel side walls, taking into consideration the influence of the magnetic field gradient generated by the magnet, specifically by making the magnetic field gradient smaller in the vicinity of the channel side walls. Accordingly, there is a need for a detector with which the amounts of the magnetic particles captured at the side wall of the channel can be increased for more accurate analysis. 
       Solution to Problem 
       [0017]    In order to solve the foregoing problems, the present invention provides a sample analysis device that includes a detection channel, and magnetic field generating means that captures magnetic particles bound to a specific substance in a sample liquid, wherein the magnet width is greater than the channel width in a predetermined position where the magnetic particles in the detection channel are captured. The device improves capturing of the magnetic particles particularly in the vicinity of the channel side walls, making it possible to improve the capture rate of the magnetic particles, the measurement accuracy, and the reproducibility of the measurement result. 
         [0018]    The present means is described below in detail.  FIG. 2  represents the detection channel of a conventional sample analysis device. The magnet is disposed in such a manner that the surfaces (surfaces A and B) with the magnetic poles are perpendicular to the flow direction of the detection channel, and the surfaces (surfaces D and C) having no magnetic poles are parallel to the flow direction of the detection channel. Note that the surface capturing the magnetic particles is surface E, and the surface held by the slide mechanism is surface F. In the conventional detection channel, the width of the magnet particle-capturing magnet or electromagnet representing magnetic field generating means (the distance between surface D and surface C) is smaller than the channel width of the detection channel in the predetermined position where the magnetic particles are captured, and the magnetic particles cannot be captured in the vicinity of the channel side walls. On the other hand, in the detection channel as shown in  FIG. 1 , the width of the magnet particle-capturing magnet or electromagnet representing magnetic field generating means (the distance between surface D and surface C) is made wider than the channel width to capture the magnetic particles in the vicinity of the side wall of the channel. This increases the proportion of the magnet&#39;s attraction force acting on the magnetic particles that would otherwise remain uncaptured and flow out. The total number of the captured magnetic particles can thus increase, and the capture rate can improve. 
       Advantage Effects of Invention 
       [0019]    The foregoing means allows magnetic particles to be uniformly captured in the measurement region, and can provide improvements in, for example, B/F separation, washing efficiency, measurement accuracy, and reproducibility of the measurement result. 
     
    
     
       BRIEF DESCRIPTION OF DRAWINGS 
         [0020]      FIG. 1  shows a top view and a cross sectional view of the shapes of a detection channel and a magnet of the present invention. 
           [0021]      FIG. 2  shows a top view and a cross sectional view of the shapes of a conventional detection channel and a conventional magnet. 
           [0022]      FIG. 3  is a schematic diagram of an immunoassay device. 
           [0023]      FIG. 4  is a magnified view of the detection channel. 
           [0024]      FIG. 5  represents distributions of the force acting on magnetic particles in a measurement region in the present invention and the related art. 
           [0025]      FIG. 6  is a flowchart representing a magnetic particle movement analysis. 
           [0026]      FIG. 7  shows diagrams comparing the capture distributions in the measurement regions of the present invention and the related art. 
           [0027]      FIG. 8  is a diagram representing the relationship between the magnet width-to-channel width ratio and the uniformity of a capture distribution. 
           [0028]      FIG. 9  is a diagram comparing the measured luminescence between the proposed shape and the conventional shape. 
           [0029]      FIG. 10  is a diagram representing the overall configuration of an analysis device. 
       
    
    
     DESCRIPTION OF EMBODIMENTS 
       [0030]    An embodiment of the present invention is described below with reference to the accompanying drawings. 
         [0031]    An immunoassay device as an example of a sample analysis device of the present embodiment is described first. The present invention is not limited to immunoassays, and is applicable to any sample analysis device, provided that it uses magnetic particles, and captures magnetic particles by switching magnetic field strengths. The technique of the present invention is also applicable to analytical devices used in the field of DNA, chemistry, and other applications. 
         [0032]      FIG. 3  represents a schematic structure of the immunoassay device. Referring to  FIG. 3 , a detection channel  10  is connected to a nozzle  27  and a pump  28  via a tube  24  and a tube  25 . The nozzle  27  is movably installed on an arm  29 , and a suspension container  30 , a buffer container  31 , and a washing liquid container  32  are installed within the movable range of the nozzle  27 . 
         [0033]    A valve  33  is provided on the tube  25  between the detection channel  10  and the pump  28 . The pump  28  enables accurate volumes of liquid to be suctioned and ejected under the control of a controller  38  via a signal line  39   a . The pump  28  is in communication with a waste liquid container  35  via a tube  26 . 
         [0034]    A detector has a detection channel window  18  and a detection channel base  20 , both of which are made of transparent material. Inside the detector is the detection channel for flowing a solution. Because the whole channel is transparent, the detector passes light to allow an observer to see the state of the flow inside the channel. The side walls of the channel are not necessarily required to be formed of transparent material, and only the window for passing light may be made of transparent material. 
         [0035]    The side walls of the transparent channel of the detector is preferably made of a material that is substantially transparent for the wavelength of the light emitted by the labeled substance of the magnetic particle complex captured in a measurement region inside the flow cell. Materials, for example, such as glass, quartz, and plastic are preferably used. 
         [0036]    A laser light source  16 , and a condensing lens  17  are installed in areas beneath the detection channel base  20 . The laser emitted by the laser light source  16  is condensed through the condensing lens  17 , and can irradiate a measurement region  15  in the detection channel  10 . 
         [0037]    The detector uses a magnet  21  (magnetic field applying means) used as a means to capture magnetic particles. The magnetic pole surfaces (surface A and surface B) of the magnet are perpendicular to the flow direction. Referring to  FIG. 3 , the magnet surfaces out of and into the plane of the paper are surfaces C and D, respectively. For capturing magnetic particles  14 , the magnet  21  is moved to directly below the detection channel base  20 . For example, the magnet  21  is installed on a slide mechanism  22  that is freely movable along the horizontal direction, and is moved to directly below the channel to capture magnetic particles. For washing the inside of the detection channel  10 , the magnet  21  can be moved away from the detection channel  10  to sufficiently reduce its effect so that the detection channel  10  can be sufficiently washed. Here, the magnet  21  is described as being horizontally moved with the slide mechanism  22 . However, the magnet  21  may be vertically moved, as long as the effect of the magnetic field of the magnet  21  can be sufficiently reduced for washing. 
         [0038]    The controller  38  is connected to the arm  29 , a photodetector  40 , the slide mechanism  22 , the laser light source  16 , the pump  28 , the valve  33 , and a valve  34  to control these members. 
         [0039]    The magnetic particles  14  spread in a planar fashion as they travel along the gradually widening path inside the detection channel  10 , and are captured in the measurement region  15  under the magnetic force of the magnet  21 . The measurement region also can be called capture region. For luminescence measurement, the magnet  21  cancels the magnetic force. Here, there is no liquid flow inside the detection channel  10 , and the magnetic particles  14  remain captured in the measurement region  15 , and stay inside the detection channel  10 . Under no applied magnetic field to the detection channel  10 , the laser light source  16  installed beneath the detection channel  10  emits a laser beam to the magnetic particles  14  remaining in the measurement region  15 . The resulting luminescence from the labeled substance on the magnetic particles  14  can then be measured to determine the luminescence from the solid phase at high sensitivity. 
         [0040]    The detection channel  10  is formed of a light transmissive material, specifically a material selected from high optical transmittance materials such as acryl. The photodetector  40  may be realized by, for example, a photomultiplier. 
         [0041]    The detection channel  10  has a width that is 2 to 20 times its depth (thickness), so that the flow of the particles introduced with the fluid flow can easily spread laterally. Ideally, the magnetic particles preferably spread in the form of a single layer with respect to the detection channel  10 . In actual practice, however, the particles may have some overlap, and form multiple layers under the influence of the magnetic field. 
         [0042]    The capture distribution of the particles in the detection channel  10  is determined by the balance between the magnetic force of the magnetic field from the magnet  21  disposed on the lower side of the detection channel  10 , and the drag created upon introduction of the suspension containing the reaction mixture. The magnetic field inside the detection channel  10  is preferably about 0.1 to 0.5 T. The accompanying liquid flow rate is preferably about 0.05 to 0.10 m/s. The flow rate needs to be appropriately selected, because particle separation occurs when the force created by the flow rate exceeds the force that captures the particles under the magnetic force. 
         [0043]    The magnetic particles  14  are preferably any of the following particles. 
         [0044]    (1) Paramagnetic, superparamagnetic, ferromagnetic, or ferrimagnetic particles 
         [0045]    (2) Paramagnetic, superparamagnetic, ferromagnetic, or ferrimagnetic particles encapsulated in materials such as synthetic high molecular compounds (e.g., polystyrene, nylon), natural polymers (e.g., cellulose, agarose), and inorganic compounds (e.g., silica, glass). 
         [0046]    The particle diameter of the magnetic particles  14  is preferably 0.01 μm to 200 μm, more preferably 1 μm to 10 μm. The specific gravity is preferably 1.3 to 1.5. Such magnetic particles  14  do not easily settle, and are easily suspended in the liquid. The magnetic particle surface is bound to a substance that has a specific binding property for the analyte, for example, an antibody having a specific binding property for antigen. 
         [0047]    The labeled substance is preferably any of the following. The labeled substance is specifically bound to the analyte by using an appropriate means, and luminescence is produced by using an appropriate means. 
         [0048]    (1) Labeled substance used for fluorescent immunoassays. For example, an antibody labeled with fluorescein isothiocyanate. 
         [0049]    (2) Labeled substance used for chemiluminescent immunoassays. For example, an antibody labeled with acridinium ester. 
         [0050]    (3) Labeled substance used for chemiluminescent enzyme immunoassays. For example, an antibody labeled with a chemiluminescent enzyme that uses luminol or adamantyl derivatives as a substrate. 
         [0051]    The sample analyzed is a sample of biological fluid origin, for example, such as serum and urine. When the sample is a serum, examples of the analyzed components include various tumor markers, antibodies, antigen-antibody complex, and single protein. Here, the specific component is TSH (thyroid hormone). 
         [0052]    The suspension container  30  stores a sample mixture prepared in advance by mixing the analyte sample with a beads solution, a first reagent, a second reagent, and a buffer, and reacting the mixture for a certain time period at a certain temperature (37° C.) 
         [0053]    The beads solution is a solution obtained by dispersing the magnetic particles  14  in a buffer after embedding a particulate magnetic substance in a matrix such as polystyrene. The matrix surface is bound to streptavidin that can bind to biotin. 
         [0054]    The washing liquid container  32  stores a washing liquid used to wash inside of the detection channel  10  and the tube  24 . 
         [0055]    The operation of the present embodiment is described below. One cycle of analysis consists of a suspension suction period, a particle capture period, a detection period, a washing period, a reset period, and a preliminary suction period. A cycle begins upon setting the suspension container  30  in the predetermined position after the suspension processed in a reaction unit  37  is stored in the suspension container  30 . 
         [0056]    In the suspension suction period, the slide mechanism  22  comes into operation in response to the received signal from the controller  38 , and moves the magnet  21  to below the detection channel  10 . Here, the valve  33  is open, and the valve  34  is closed. The arm  29  comes into operation in response to the received signal from the controller  38 , and inserts the nozzle  27  into the suspension container  30 . The pump  28  then starts a certain suction operation upon receiving a signal from the controller  38 . In response, the suspension in the suspension container  30  enters the tube  24  via the nozzle  27 . The pump  28  is arrested in this state, and the arm  29  is operated to insert the nozzle  27  into a washing mechanism  36 . The nozzle tip is washed as it passes through the washing mechanism  36 . 
         [0057]    In the particle capture period, the pump  28  creates suction at a certain rate in response to the received signal from the controller  38 , drawing the suspension inside the tube  24  into and through the detection channel  10 . Because of the magnetic field created by the magnet  21  in the detection channel  10 , the magnetic particles  14  contained in the suspension are drawn toward the magnet  21 , and captured to the surface in the measurement region  15 . 
         [0058]    In the detection period, the slide mechanism  22  comes into operation, and the magnet  21  is moved away from the detection channel  10 . The laser light source  16  then emits a laser beam in response to the received signal from the controller  38 , and irradiates the measurement region  15  through the condensing lens  17 . The fluorescent dye bound to the magnetic particles  14  in the measurement region  15  exhibits luminescence. A fluorescence filter cuts off certain wavelengths, and the selected wavelength is detected by the photodetector  40  realized by, for example, a CCD camera, or a photomultiplier. The photodetector  40  detects the luminescence intensity, and sends the detected signal to the controller  38 . The laser is turned off after a certain time period. While in the detection period, the arm  29  operates to insert the nozzle  27  into the washing mechanism  36 . 
         [0059]    In the washing period, the pump  28  creates suction to draw the washing liquid out of the washing liquid container  32  into and through the detection channel  10 . Here, because the magnetic field is away from the detection channel  10 , the magnetic particles  14  do not stay on the measurement region  15 , and flow out with the buffer. 
         [0060]    In the reset period, the valve  33  is closed, and the valve  34  is opened for the ejection operation of the pump  28 . The liquid in the pump  28  discharges to the waste liquid container  35 . 
         [0061]    In the preliminary suction period, the buffer is suctioned to fill the tube  24  and the detection channel  10  with the buffer. The next cycle is ready to begin after the preliminary suction period. 
         [0062]      FIG. 1  represents what is considered to be the best relative positions of the detection channel  10  and the magnet  21  in the present embodiment. For comparison with  FIG. 1 ,  FIG. 2  represents the conventional relative positions of the detection channel  10  and the magnet  21 . Referring to  FIGS. 1 and 2 , the magnet is disposed in such a manner that the end surfaces (surfaces A and B) with the magnetic poles are perpendicular to the direction of the flow in the detection channel, and that the end surfaces (surfaces D and C) having no magnetic poles are parallel to the direction of the flow in the detection channel. Note that the surface capturing the magnetic particles is surface E, and the surface held by the slide mechanism is surface F. Referring to  FIG. 2 , the relative positions of the detection channel  10  and the magnet  21  are such that the width a (the distance between surface D and surface C) of the magnet is equal to or smaller than the channel width b of the measurement region (also referred to as the capture region of the magnetic particles). On the other hand, referring to  FIG. 1 , the width a of the magnet  21  is greater than the channel width b. 
         [0063]    The following describes how the magnet width of the capture region affects the capturing of the magnetic particles.  FIG. 5  represents the force exerted by the magnet on the magnetic particles in the capture region as calculated from the magnetic moment on the magnetic field and the magnetic particles using general-purpose magnetic field analysis software. In  FIG. 5(   a ), the ratio (a/b) of magnet width a and channel width b is 0.93 (the magnet width is smaller than the channel width). In  FIG. 5(   b ), the ratio a/b is 1.11 (the magnet width is greater than the channel width). In these diagrams, the vertical component of the force exerted by the magnet is represented by a contour diagram (representing the force acting to capture the magnetic particles in a direction perpendicular to surface E), and the horizontal component is represented by a vector diagram (representing the force acting on the magnetic particles in a direction parallel to surface E). The channel and the magnet are also shown to clarify the relative positions of these members with regard to the channel width and the magnet width. Since these diagrams are symmetrical about the horizontal axis, only the top half is shown. 
         [0064]    When the ratio a/b of magnet width and channel width is 0.93 as in  FIG. 5(   a ), the horizontal component of the force is directed toward the center of the channel in the vicinity of the side walls of the channel where the surface D or C of the magnet are situated, and the vertical component of the force acting to capture the magnetic particles to surface E is small, as shown in the contour diagram representing the vertical force. It was also found that the horizontal component of the force acting on the magnetic particles is directed toward the center of the channel in the vicinity of the channel side walls. As demonstrated above, the force acts on the magnetic particles more strongly in the horizontal direction toward the center of the channel than in the vertical direction in the vicinity of the channel side walls, and the magnetic particles are not captured as easily in the vicinity of the channel side walls, and tend to accumulate in layers near the center of the channel. 
         [0065]    On the other hand, when the magnet width is larger than the channel width as in  FIG. 5(   b ), the force hardly acts in the horizontal direction as compared to  FIG. 5(   a ). This is because the surfaces D and C of the magnet are more distant away from the vicinity of the side wall of the channel, creating a more gradual magnetic field gradient (smaller magnetic field changes), and reducing the horizontal component of the force that acts on the magnetic particles in the vicinity of the channel side walls. The magnetic particles can thus be more uniformly captured in the vicinity of the side walls and the center of the channel than in  FIG. 5(   a ). 
         [0066]    On the basis of these findings, a movement analysis of magnetic particles was conducted to examine the effect of making the magnet width wider than the channel width.  FIG. 6  represents a flowchart of the movement analysis. The analysis is performed for the flow field inside the channel flowing the magnetic particles, using general-purpose fluid analysis software. Simultaneously, the magnetic field generated by the magnet is analyzed with general-purpose magnetic field analysis software. The states of these fields are used to analyze the forces acting on the magnetic particles, specifically, the force exerted by the flow, the force due to the pressure gradient of the flow, the buoyancy force acting on the particles, and the force exerted by the magnet. The movement of the magnetic particles can then be analyzed by solving an equation of motion for each particle in small increments of time, taking into equation these various external forces acting on each magnetic particle. 
         [0067]      FIGS. 7(   a ) and ( b ) represent the results of the analysis of the capture distribution of the magnetic particles when the ratio a/b of magnet width a and channel width b is 1.11 ( FIG. 7(   a )) and 0.93 ( FIG. 7(   b )). It can be seen that more magnetic particles are captured in the vicinity of the channel side walls when the magnet width is greater than the channel width. This is because the wider magnet width than the channel width decreases the horizontal component of the force that acts on the magnetic particles in the vicinity of the channel side walls, as described in  FIG. 5 . The magnetic particles are also captured more uniformly throughout the channel width as compared to  FIG. 7(   b ). 
         [0068]    The best mode of the magnet width is that the magnet width is wider than the channel width over the whole region. It is not difficult to imagine that more magnetic particles will be captured, and the luminescence intensity will increase even when the magnet width is increased wider than the channel width only in a part of the region. For example, the surface E of the magnet may be trapezoidal in shape, and may partially extend beyond the side walls of the channel in the capture region. 
         [0069]    The effect of magnet width on capture distribution was systematically examined.  FIG. 8  represents the uniformity of capture distribution examined with gradually increasing magnet widths relative to a constant channel width using a magnetic particle movement program. The horizontal axis in the graph represents the ratio of magnet width to channel width. The ratio increases as the magnet width increases relative to the channel width. The vertical axis is the inverse of capture distribution uniformity. Smaller values mean that the magnetic particles are more uniformly captured. 
         [0070]    It can be seen that the uniformity of capture distribution in the measurement region improves as the ratio a/b of magnet width a and channel width b increases. The effect can be obtained as long as the magnet width is wider than at least the channel width, and the optimum effect can be obtained when the ratio a/b of magnet width and channel width is about 1.67. As can be seen in the graph, increasing the magnet width further beyond this ratio causes poor uniformity in the capture distribution. The result suggests that there are optimal values for the magnet width. 
         [0071]    The analysis suggested that more magnetic particles can be captured in the vicinity of the channel side walls when the magnet width a and the channel width b are 6.0 mm and 5.4 mm, respectively. Typically, the slope of the magnetic field distribution in the vicinity of the ends of the magnet does not have large effects with regard to size. Accordingly, effects can be obtained when the magnet width a is wider than the channel width b by at least 0.6 mm. 
         [0072]    The analysis result that the uniformity improves with the wider magnet width than the channel width was tested with a test magnet used in the actual device. 
         [0073]      FIG. 9  represents the result of luminescence intensity measurement at a/b of 0.93 and 1.11. As can be seen in the graph, the luminescence improves 23% by increasing the magnet width wider than the channel width. As demonstrated above, the magnetic particles can be uniformly captured by the magnet, and the luminescence can be improved by increasing the magnet width wider than the channel width. Further, because of the uniform capture distribution, improvements can be expected in, for example, B/F separation performance, washing efficiency, measurement accuracy, and measurement result reproducibility. 
         [0074]    The embodiment represented in  FIG. 1  was described through the case where the channel width is substantially constant. However, the idea behind the magnet width is the same for the channel width that varies along the flow direction. Specifically, the magnetic particles can be captured also in the vicinity of the channel side walls, and a uniform capture distribution can be obtained when the magnet width (the distance between surface D and surface C) is wider than the channel width over the whole channel width of the measurement region. Improved uniformity also can be expected when the magnet width is wider only in apart of the region instead of the whole region, though the effect will be limited. 
         [0075]    The idea concerning the magnet length and the capture region length in the flow direction is described below. 
         [0076]    The capture distribution of magnetic particles spreads when the magnet length (the distance between surface A and surface B) is greater than the measurement region. Specifically, the magnetic particles are captured also outside of the region intended for capturing the magnetic particles. It is not difficult to imagine that this will lower the luminescence intensity. The magnet length thus needs to be smaller than the measurement region. 
         [0077]      FIG. 10  represents an example of the actual implementation of the present embodiment as an automated immunoassay device. 
         [0078]    A controller  119  of an assay device  100  creates an analysis plan upon receipt of a measurement request from an operator, and controls the operation of each mechanism by following the plan. 
         [0079]    A sample container  102  for holding samples is installed in a rack  101  of the assay device  100 , and a rack transport line  117  moves the sample container  102  to a sample dispensing position in the vicinity of a sample dispensing nozzle  103 . A plurality of reaction vessels  105  is installable in an incubator disc  104 . The incubator disc  104  is capable of rotational motion that moves the reaction vessels  105  installed along the circumferential direction to predetermined positions, including, for example, reaction vessel installation position, reagent ejection position, sample ejection position, detection position, and reaction vessel discarding position. A sample dispensing tip and reaction vessel transport mechanism  106  is movable in three directions along the X, Y, and Z axes, and transports a sample dispensing tip and a reaction vessel by moving over the range covering a sample dispensing tip and reaction vessel holding member  107 , a reaction vessel mixing mechanism  108 , a sample dispensing tip and reaction vessel discarding hole  109 , a sample dispensing tip attaching position  110 , and a predetermined position of the incubator disc  104 . 
         [0080]    A plurality of unused reaction vessels, and a plurality of unused sample dispensing tips are installed in the sample dispensing tip and reaction vessel holding member  107 . The sample dispensing tip and reaction vessel transport mechanism  106  moves to above the sample dispensing tip and reaction vessel holding member  107 , and lifts down to pick up one of the unused reaction vessels. After lifting up, the sample dispensing tip and reaction vessel transport mechanism  106  moves to above the reaction vessel installation position of the incubator disc  104 , and lifts down to install the reaction vessel. 
         [0081]    A plurality of reagent vessels  118  with reagents and diluting solutions is installed in a reagent disc  111 . A reagent disc cover  112  is provided above the reagent disc  111  to maintain a predetermined temperature inside the reagent disc  111 . A reagent disc cover opening  113  is provided in a portion of the reagent disc cover  112 . A reagent dispensing nozzle  114  is capable of rotation and vertical motion. By undergoing rotation, the reagent dispensing nozzle  114  moves to above the opening  113  of the reagent disc cover  112 , and lifts down to contact the tip of the reagent dispensing nozzle  114  to the reagent or diluting solution contained in the predetermined reagent vessel. The reagent or diluting solution is then suctioned into the reagent dispensing nozzle  114  in a predetermined amount. After lifting up, the reagent dispensing nozzle  114  moves to above the reagent ejection position of the incubator disc  104 , and ejects the reagent or diluting solution into one of the reaction vessels  105 . 
         [0082]    The sample dispensing tip and reaction vessel transport mechanism  106  then moves to above the sample dispensing tip and reaction vessel holding member  107 , and lifts down to pick up one of the unused sample dispensing tips. After lifting up, the sample dispensing tip and reaction vessel transport mechanism  106  moves to above the sample dispensing tip attaching position  110 , and lifts down to install the sample dispensing tip. The sample dispensing nozzle  103  is capable of rotation and vertical motion. The sample dispensing nozzle  103  moves to above the sample dispensing tip attaching position  110 , and lifts down to install the sample dispensing tip to the tip of the sample dispensing nozzle  103 . The sample dispensing nozzle  103  with the installed sample dispensing tip moves to above the sample container  102  mounted on the transport rack  101 , and lifts down to draw a predetermined amount of the sample held in the sample container  102 . The sample dispensing nozzle  103  with the sample moves to the sample ejection position of the incubator disc  104 , and lifts down to eject the sample into the reaction vessel  105  on the incubator disc  104  into which the reagent was dispensed. After ejecting the sample, the sample dispensing nozzle  103  moves to above the sample dispensing tip and reaction vessel discarding hole  109 , and discards the used sample dispensing tip into the discarding hole. 
         [0083]    The reaction vessel  105  with the ejected sample and reagent is moved to the reaction vessel transport position by the rotation of the incubator disc  104 , and transported to the reaction vessel mixing mechanism  108  by the sample dispensing tip and reaction vessel transport mechanism  106 . The reaction vessel mixing mechanism  108  rotates the reaction vessel to mix the sample and the reagent in the reaction vessel. The agitated reaction vessel is transported back to the reaction vessel transport position of the incubator disc  104  by the sample dispensing tip and reaction vessel transport mechanism  106 . A reaction liquid suction nozzle  115  is capable of rotation and vertical motion. The reaction liquid suction nozzle  115  moves to above the reaction vessel  105  resting on the incubator disc  104  for a predetermined time period after the sample and the reagent were mixed. The reaction liquid suction nozzle  115  then lifts down, and draws the reaction mixture out of the reaction vessel  105 . The reaction mixture drawn into the reaction liquid suction nozzle  115  is sent to a detector unit  116 , and the subject of measurement is detected. The controller  119  then outputs and displays the measurement result based on the detection value of the subject. The reaction vessel  105  with the reaction mixture is moved to the reaction vessel discarding position by the rotation of the incubator disc  104 . The sample dispensing tip and reaction vessel transport mechanism  106  then moves the reaction vessel  105  from the incubator disc  105  to above the sample dispensing tip and reaction vessel discarding hole  109 , and the reaction vessel  105  is discarded through the discarding hole. 
         [0084]    The present embodiment enables the magnetic particles to be uniformly captured, and can improve the accuracy and reproducibility of an analysis in an automated immunoassay device. 
       REFERENCE SIGN LIST 
       [0000]    
       
           10  Detection channel 
           12  Inlet of detection channel 
           13  Outlet of detection channel 
           14  Magnetic particle 
           15  Measurement region 
           16  Laser light source 
           17  Condensing lens 
           18  Detection channel window 
           19  Side wall of detection channel 
           20  Base of detection channel 
           21  Magnet 
           22  Slide mechanism 
           24 ,  25 ,  26  Tube 
           27  Nozzle 
           28  Pump 
           29  Arm 
           30  Suspension container 
           31  Buffer container 
           32  Washing liquid container 
           33 ,  34  Valve 
           35  Waste liquid container 
           36  Washing mechanism 
           37  Reaction unit 
           38  Controller 
           39  Signal line 
           40  Photodetector 
           100  Assay device 
           101  Rack 
           102  Sample container 
           103  Sample dispensing nozzle 
           104  Incubator disc 
           105  Reaction vessel 
           106  Sample dispensing tip and reaction vessel mixing transport mechanism 
           107  Sample dispensing tip and reaction vessel holding member 
           108  Reaction vessel mixing mechanism 
           109  Sample dispensing tip and reaction vessel discarding hole 
           110  Sample dispensing tip attaching position 
           111  Reagent disc 
           112  Reagent disc cover opening 
           114  Reagent dispensing nozzle 
           115  Reaction liquid suction nozzle 
           116  Detection unit 
           117  Rack transport line 
           118  Reagent vessel 
           119  Controller