JP2008249542A - Clinical analysis system - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To carry out temperature control of a reagent and a sample precisely without upsizing and complicating a device in a clinical analysis system. <P>SOLUTION: The clinical analysis system includes a measurement section 10 that has a dispensing station 42 for performing dispensation of a reagent and a sample to a microchip 100' where a micro passage is formed, and a detection station 46 for detecting an object to be measured in the sample which is dispensed to the microchip. In the system, the microchip 100' is continuously revolved from the upstream to the downstream of the step relatively to the dispensing station 42 and the detection station 46 and thereby the measurement of the object is repeatedly performed. Thus, the microchip 100' in the state the reagent and the sample are injected can be controlled in temperature by a temperature control section 201 before the dispensation of this microchip 100' to the detection station 46. Then, the object in the sample that is dispensed to this microchip is measured. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention relates to a clinical analysis apparatus, in particular, a μTAS-immunoassay system (for example, a microTAS into which a reagent and a sample are introduced into a microchannel). The present invention relates to a clinical analyzer used in a micro total analysis system (enzyme linked immuno-sorbent assay (ELISA)) and the like.

  2. Description of the Related Art Conventionally, a microchip electrophoresis apparatus having a microchip in which microchannels with extremely small width and depth are formed is known as an analysis apparatus (Patent Document 1). In this electrophoresis device, the electrophoresis solution (buffer solution) is injected into the microchip flow path, the sample is injected into the micro flow path, and a high voltage (electrophoresis voltage) is applied to perform measurement in the sample by electrophoresis. The target substance is separated. For example, the separated protein or nucleic acid is detected by the detection unit at the detection point of the microchannel.

  In addition, as a similar microchip electrophoresis device, a series of operations from filling of electrophoresis solution to sample injection including sample, injection of sample into separation channel, electrophoresis, separation and detection are automatically performed. What to process is known (patent document 2). In this microchip electrophoresis apparatus, when repeating the analysis using the same microchip, after the sample remaining in the flow path is washed away with the electrophoresis solution, the sample containing the next sample is injected and the same process is repeated. It is supposed to run. Further, when the microchip is made disposable, the sample remaining in the flow path is discarded without being washed away with an electrophoresis solution.

In addition, the temperature of the liquid consisting of the microchip and the reagent or sample to be injected into the microchannel of the microchip is individually adjusted to substantially the same temperature, and then the liquid is injected into the microchip for measurement. A chip electrophoresis apparatus is also known (Patent Document 3).
JP-A-10-148628 JP-A-10-246721 JP 2006-250622 A

  By the way, in order to individually control the temperature of the microchip and the sample liquid containing the reagent and sample injected into the microchip as described above, a dedicated temperature control device is required, respectively. There may be a temperature difference between the temperature of the sample solution. In order to adjust the temperature of the microchip and the temperature of the sample solution so as to coincide with the target temperature, it is necessary to adjust the temperature of each of the two temperature control devices with high accuracy, and the control of the temperature control is complicated. However, there is a problem that the apparatus size becomes large.

  The present invention has been made in view of the above points, and an object of the present invention is to provide a clinical analyzer capable of accurately controlling the temperature of reagents and samples without increasing the size and complexity of the device. Is.

  The clinical analyzer of the present invention uses a microchip having a microchannel formed therein, introduces a reagent and a sample into the microchannel, and analyzes a measurement target substance contained in the sample. And an arrangement part for arranging the reagent and sample arranged in the housing, a dispensing mechanism part for dispensing the reagent and sample arranged in the arrangement part to the microchip, and the microchip at a predetermined pitch. A measurement mechanism for measuring a substance to be measured in a sample dispensed in a microchannel, and the measurement unit includes a reagent to the microchip by the dispensing mechanism and The dispensing station where the sample is dispensed and the detection station that detects the target substance in the sample dispensed on the microchip are processed in this order. The measurement target substance is arranged so as to correspond to the predetermined pitch from the side to the downstream side, and the microchip is moved relative to each station from the upstream side to the downstream side of the process at a predetermined pitch. The clinical analyzer is configured so that the measurement of the microchip is performed, and the temperature control unit can control the temperature of the microchip in which the reagent and the sample are injected before the microchip is placed in the detection station. It is characterized by having.

  The predetermined pitch means a pitch corresponding to the movement of the microchip between the stations.

  The predetermined pitch can be a predetermined pitch in angle, that is, a predetermined pitch angle.

  The microchip is a chip having a chip substrate made of glass or the like on which fine capillaries (capillaries) are formed, and a sample is introduced into the capillaries. This capillary is referred to as a “microchannel”. The reagent includes a buffer, various labeled antibodies, and the like.

  The temperature control unit adjusts the temperature of the microchip in which the reagent and the sample are injected from before the microchip is placed in the detection station until the detection of the measurement target substance in the detection station is completed. Can be possible.

  The temperature control unit can control the temperature of the microchip in which the reagent and sample are injected from when the microchip is placed in the dispensing station until the detection of the measurement target substance at the detection station is completed. Can be.

  The temperature control unit can control the temperature of the microchip only before the microchip is placed in the dispensing station.

  The temperature control unit may determine a target temperature for temperature control of the microchip in a state where the reagent and the sample are injected according to the measurement content measured in the measurement unit.

  The temperature adjustment unit may individually adjust the temperature of the microchip in which the reagent and the sample are injected for each station.

  The temperature control unit may perform temperature control of the microchip in a state where a reagent and a sample are injected, for a plurality of stations.

  Further, an introduction station that introduces the reagent and the sample by pressurization and / or inhalation into the microchannel of the microchip may be arranged between the dispensing station and the detection station.

  The microchip can be a disposable microchip.

  The clinical analyzer is configured to measure the measurement target substance by moving the microchip in one direction at a predetermined pitch from the upstream side to the downstream side of the process relative to each station. It is also good.

  The clinical analyzer is configured to repeatedly measure the measurement target substance by continuously rotating the microchip relative to each station from the upstream side to the downstream side of the process at a predetermined pitch. It may be configured.

  A clinical analyzer configured so that the measurement target substance is repeatedly measured by rotating the microchip around each station can be configured as follows.

  A detaching station for detaching the microchip may be arranged at an arbitrary position.

  In addition, a cleaning station for cleaning the microchip after the measurement target substance is detected can be arranged.

  Here, in the measurement unit, the dispensing station, the detection station, and the cleaning station can be arranged in order from the upstream side of the process so as to correspond to a predetermined pitch.

  Further, the cleaning station sucks the residual liquid remaining in the water cleaning step, a chemical cleaning step for cleaning the chemicals attached to the microchip, a water cleaning step for cleaning the microchip with water after the chemical cleaning by the chemical cleaning step. Each of the remaining liquid suction steps can be configured. Each process of the cleaning station is preferably independent as a station.

  It is preferable that the transport mechanism unit has a rotary table on which microchips are arranged.

  In the clinical analyzer, the number of stations and the number of microchips mounted on the rotary table are preferably the same.

  The turntable can be configured such that a series of operations for one microchip is completed when the turntable rotates once.

  The rotary table preferably includes a recording unit that records on the microchip that a series of operations on the microchip has been completed by one rotation.

  In addition, a clinical analyzer configured to move the microchip in one direction with respect to each station and perform measurement of the measurement target substance, or repeatedly measure the measurement target substance by rotating the microchip around each station. In a clinical analyzer configured to perform the above, it is preferable that the microchip has a recording unit for recording information on processing. This recording unit can be a wireless tag.

  The clinical analyzer of the present invention is configured so that the measurement of the measurement target substance is repeatedly performed by continuously circling the microchip from the upstream side to the downstream side of the process relative to each station. Before the microchip is placed at the detection station, the microchip in a state where the reagent and the sample are injected is provided with a temperature control unit capable of controlling the temperature, so that the apparatus is not enlarged or complicated. The temperature of the reagent and the sample when detecting the measurement target substance at the detection station can be more accurately controlled.

  That is, since temperature control can be performed in a state in which a reagent and a sample (hereinafter collectively referred to as a sample solution) are injected into the microchip, when the temperature of the microchip and the sample solution are individually controlled as in the past, In comparison, it is easier to match the temperature of the microchip and the sample solution. In addition, since the temperature of the upper sample solution is controlled while the sample solution is contained in the microchip, complication of the apparatus can be suppressed as compared with the case where the temperature of the microchip and the sample solution are individually controlled. Furthermore, since the temperature control can be started from a process prior to the detection at the detection station, the temperature control time in a state where the sample liquid is injected into the microchip can be further extended. As described above, the measurement can be performed by more accurately determining the temperature of the sample liquid when detecting the measurement target substance at the detection station without increasing the size of the apparatus or complicating the apparatus.

  In addition, with respect to the microchip in a state where the reagent and the sample are injected, the temperature control unit is from before the microchip is arranged in the detection station until the detection of the measurement target substance in the detection station is completed. If the temperature can be adjusted, the effect of more accurately determining the temperature of the sample liquid when the measurement target substance is detected at the detection station can be more reliably exhibited.

  In addition, the temperature control unit is used for the microchip in which the reagent and the sample are injected, from the time when the microchip is placed in the dispensing station until the detection of the measurement target substance at the detection station is completed. If it can be adjusted, the effect of more accurately determining the temperature of the sample solution when detecting the measurement target substance at the detection station can be more reliably exhibited.

  In addition, if the temperature control unit determines the target temperature for temperature control of the microchip in which the reagent and the sample are injected according to the measurement content to be measured in the measurement unit, the measurement target substance is detected at the detection station. Since the temperature of the sample liquid at that time can be set to the target temperature earlier, the measurement target substance can be detected more efficiently.

  If there is an introduction station between the dispensing station and the detection station that introduces the reagent and sample by pressurization and / or inhalation into the microchannel of the microchip, the reagent and sample can be introduced quickly and sufficiently. Can be introduced into the microchannel.

  If the desorption station is located at an arbitrary position, the microchip can be easily replaced as necessary. In other words, the microchip can be used repeatedly until it reaches the end of its life, and when it reaches the end of its life, it can be easily replaced with a new microchip at this detachment station.

  When the cleaning station is configured to have a chemical cleaning process, a water cleaning process, and a residual liquid suction process that sucks the residual liquid after water cleaning, the chemical cleaning process performs chemical cleaning and the water cleaning process. The chemical used in the chemical cleaning is discharged and further cleaned, and the residual liquid is sucked in the residual liquid suction step, so that the microchannel can be cleaned to a very high degree and hardly affects the next measurement. Therefore, it is possible to obtain an extremely reliable analysis result.

  When the transport mechanism unit has a turntable on which microchips are arranged, the transport mechanism unit can be easily configured.

  When the number of each station and the number of microchips mounted on the rotary table are the same, work is performed at each station for every pitch, so that the measurement can be performed efficiently.

When the rotation table is rotated once, when a series of operations of one microchip is completed, the measurement of one microchip is completed every time the rotation table is rotated by one pitch. The measurement can be performed efficiently with this.

When the microchip has a recording unit that records information on processing, the microchip can be managed individually, and highly reliable data that is less likely to cause errors can be obtained.

  Hereinafter, an example of the clinical analyzer of the present invention will be described in detail with reference to the accompanying drawings. First, a microchip used for detecting a liver cancer marker, for example, used in this clinical analyzer (hereinafter simply referred to as “device 1”; see FIG. 3) will be described with reference to FIGS. .

  FIG. 1 shows an example of a microchip used in the apparatus 1. FIG. 1 (a) is a perspective view seen from the front side of the microchip 100, and FIG. 1 (b) is a perspective view seen from the back side. Show.

  The microchip 100 has a substantially rectangular or arrow shape formed from a synthetic resin, and a glass plate (transparent plate-like) is formed as a substantially rectangular chip substrate at the center of the recess 100b on the back surface of the microchip 100, for example. Member) 102 is attached. This glass plate 102 is composed of two glass plates, and a micro-channel (capillary) (hereinafter simply referred to as a channel) 110 (FIG. 2), which will be described later, formed on one glass plate is placed inside. Then, they are bonded together to form a single glass plate 102. Both of the two glass plates may be transparent, or only one of the two glass plates that will be described later may be transparent.

  On the other hand, on the surface of the microchip 100, that is, the main surface 100a, as shown in FIG. 1A, a plurality of cylindrical protrusions having a hole 106a having an inner diameter of 1.2 mm, for example, aligned with the flow path 110, A well 106 is formed. The hole 106a of the well 106 reaches the flow path 110 through one of the two glass plates described above.

  Therefore, when a sample liquid containing a reagent and a sample is dropped into the well 106, the sample liquid is guided to the flow path 110. The chip substrate may be made of glass or synthetic resin.

  Next, the flow path 110 will be described with reference to FIG. FIG. 2 is a plan view showing an example of the flow path 110 formed in the microchip 100. The channel 110 has a width of 100 μm and a depth of 15 μm, for example, and is formed by a fine processing technique such as etching or photolithography. In the microchip 100, for example, two sets of the flow paths 110 are independently formed. In FIG. 2, the flow path 110 includes a main flow path 110 a that extends horizontally in a straight line and branch flow paths 110 b to 110 e that extend at a short distance perpendicular to the main flow path 110 a. The wells 106 described above are located at both ends of the main channel 110a and the ends of the branch channels 110b to 110e. These wells 106 are indicated by AG for identification. That is, wells A to G are collectively referred to as well 106.

  The branch channels 110b, 110c, and 110d are sequentially formed on one side (the upper side in FIG. 2) of the main channel 110a from the well A side at intervals. The ends of the branch channels 110b, 110c, and 110d communicate with the wells B, E, and F, respectively.

  A branch channel 110e is formed on the other side (lower side in FIG. 2) of the main channel 110a. This branch channel 110e is formed between the branch channels 110b and 110c. At the tip of the branch channel 110e, a channel extending to both sides is formed in parallel with the T-shaped main channel 110a, and both ends of the channel communicate with the wells C and D, respectively.

  As shown in FIG. 2, a detection device 6 having an optical system for detecting a measurement target substance in the sample contained in the sample liquid is installed in the vicinity of the flow path 110. The sample solution stored in the flow path is measured at a predetermined position of the main flow path 110a. The substance to be measured in the sample solution is processed so as to be excited and emit fluorescence when receiving light from the outside. In order to excite the fluorescence of the measurement target substance, the laser beam 140 emitted from the laser diode 138 of the detection device 6 is used. The laser beam 140 passes through the BPF, that is, the band pass filter 142, is reflected by the dichroic mirror 144, passes through the condenser lens 146, and reaches the sample liquid. As a result, the substance to be measured in the sample solution is excited and emits fluorescence. This fluorescence is detected by a photodetector 152 through a condenser lens 146, a dichroic mirror 144, a band pass filter 148, and a condenser lens 150.

  Samples to be measured include body fluids such as serum and lymph, excreta such as urine, biological substances such as pus, and various liquids such as beverages and river water. Also, the reagent is not limited to the above-mentioned types, and it goes without saying that various types of reagents are used depending on the type of the substance to be measured in the sample.

  Next, the device 1 of the present invention will be described in detail with reference to FIGS. FIG. 3 is a perspective view showing the external appearance of the device 1. The apparatus 1 reciprocates between the housing 2, the placement unit 8 disposed in the housing 2, the measurement unit 10 provided in parallel in the vicinity of the placement unit 8, and the placement unit 8 and the measurement unit 10. And a dispensing mechanism section 12 that performs the same. Moreover, the covers 4 and 5 provided in the housing | casing 2 so that opening and closing is possible are for covering the measurement part 10 and the arrangement | positioning part 8, respectively. In FIG. 3, these covers 4 and 5 show an open state. These covers 4 and 5 cannot be opened during sample detection and cleaning operations.

  The placement unit 8 includes a circular reagent storage 8a and a sample holding unit 8b. The sample holding part 8b has an annular member 14 arranged so as to surround the reagent storage 8a. In addition, although the annular member 14 of the reagent storage 8a and the sample holding part 8b rotates, illustration is abbreviate | omitted about power sources, such as a motor for rotating. The annular member 14 is formed with a plurality of notches 14a in which sample containers 3b are arranged at predetermined intervals. In addition, the inside of the arrangement | positioning part 8 is cooled with the refrigerator which is not shown in figure.

  Further, a display panel 16 such as a liquid crystal is provided on the upper surface 2 a of the housing 2. The display panel 16 displays the name of the test, and the measurement content (measurement item) can be selected for each sample accommodated in the sample container 3b. Further, a printer 18 is arranged in the vicinity of the display panel 16 so that the detection result at the detection station 46 is printed out. Two rectangular washing water containers 20 and a waste liquid container 22 are attached to the outside of the housing 2 and in the vicinity of the arrangement portion 8. The cleaning water container 20 is for storing cleaning water for cleaning the microchip 100 and the like, and the waste liquid container 22 is for storing all the waste liquid.

  The dispensing mechanism unit 12 includes a moving body 12a and a probe 12b attached to the moving body 12a. In the present invention, one probe 12b is used. However, since a sample or a plurality of types of reagents are sucked and transported, the probe 12b is washed each time a different liquid is transported. This cleaning is performed by the probe cleaning unit 66 located between the measurement unit 10 and the placement unit 8. That is, the probe 12b is inserted into the opening 66a of the probe cleaning unit 66 and cleaned with a cleaning liquid (not shown) in the probe cleaning unit 66.

  Next, referring to FIG. 3 again, the measurement unit 10 will be described in detail with reference to FIGS. FIG. 4 is an enlarged perspective view showing a state where the microchip 100 ′ is arranged in the measurement unit 10. The microchip 100 ′ used here is different in shape from the above-described microchip 100, but is the same in principle. Each part of the microchip 100 ′ will be described by adding “′” to each corresponding part of the microchip 100. FIG. 5 is a schematic plan view of the main part of the apparatus 1 schematically showing the placement unit 8 and the measurement unit 10.

  FIG. 6 is a perspective view showing a state in which a reagent and a sample are injected before the microchip 100 ′ is placed in the detection station and is arranged on a temperature control unit 201 described later. The microchip 100 ′ has the glass plate 102 ′ (see FIGS. 2 and 6) corresponding to the glass plate 102 (see FIG. 1B) of the microchip 100 described above. It arrange | positions on the said temperature control part 201 so that 'may contact on the temperature control part 201. FIG. FIG. 7 is a perspective view showing a state in which the temperature control unit 201 is made visible at the top by removing the microchip 100 ′ from FIG. 6.

  The measurement unit 10 includes a power source (not shown) as a transport mechanism unit for moving the microchip 100 ′, and a rotary table 40 that is driven to rotate counterclockwise by the power source. The rotation direction is only one direction counterclockwise, and is not reversely rotated.

  Eight base parts 200 are arranged at a predetermined pitch on the rotary table 40, and a temperature control part 201 is arranged on the base part 200. When the rotary table 40 is viewed from above, as shown in FIG. 4, eight recesses 42a are formed at a predetermined pitch (pitch angle), and the temperature control unit 201 and the base are formed in the recesses 42a. The base part 200 is accommodated. Therefore, when the microchip 100 ′ is disposed in the recess 42a, the microchip 100 ′ is placed on the upper surface 201U of the temperature control unit 201 disposed in correspondence with the recess 42a. Is done.

  Further, eight stations 42 to 56 are arranged on the housing 2 side at a predetermined pitch (pitch angle) similar to the above. Therefore, one microchip 100 'is arranged so as to correspond to each station 42-56.

  The first station where the measurement process is started is a dispensing station 42 where the moving body 12a of the dispensing mechanism unit 12 moves to dispense a sample or the like. This is the part that performs the first stage process.

  Next, the introduction station 44, the detection station 46, the cleaning station 47, and the detachment station 56 for detaching the microchip 100 'are arranged counterclockwise. In the present embodiment, the cleaning station 47 includes four parts, that is, a chemical cleaning station 48, water cleaning stations 50 and 52, and a residual liquid suction station 54. In these four cleaning stations 48, 50, 52 and 54, a chemical cleaning process, a water cleaning process, a water cleaning process and a residual liquid suction process are performed, respectively. A UI unit (user interface unit) indicated by 13 in FIG. 5 is a so-called operation panel.

  Next, with reference to FIG. 4, each station 42, 44, 46, 47 (48, 50, 52, 54), 56 is demonstrated further.

  The cover members 44b, 46b, 52b are attached to the casing 2 side so as to be openable and closable so as to approach or separate from the rotary table 40. Therefore, only the rotary table 40 rotates and the cover members 44 b to 52 b do not rotate in a plane parallel to the rotary table 40.

  Since the rotary table 40 is equally allocated to the eight stations 42 to 56 along the circumference thereof as described above, the work at each station 42 to 56 takes the same time, for example, 200 seconds. . Accordingly, when 200 seconds elapse, the rotary table 40 is rotated and moved to the next process, so that one cycle is completed in one rotation, that is, 200 × 8 = 1600 seconds, and the measurement of the first microchip 100 ′ is completed. Thereafter, the measurement of the subsequent microchip 100 'is sequentially completed every 200 seconds.

  When the microchip 100 ′ is disposed at a position corresponding to the dispensing station 42, the moving body 12a of the dispensing mechanism unit 12 moves onto the microchip 100 ′, and the microchip 100 is moved from the probe 12b. A predetermined well 106 reagent or sample is dropped. This operation is repeated for all wells 106 that require reagents and samples (first stage process).

  In the introduction station 44, a cover member 44b is disposed so as to be openable and closable. A tube 44 c is attached to the cover member 44 b so as to communicate with a predetermined well 106 ′ of the microchip 100 ′ when the microchip 100 ′ is disposed with respect to the introduction station 44. The pressurized gas is supplied to the predetermined wells C and D shown in FIG. 2 through the tube 44c (second stage process).

  A cover member 46 b is also attached to the detection station 46. An electrode (not shown) for generating a voltage for electrophoresis projects from the lower surface of the cover member 46b. These electrodes are arranged corresponding to the wells A, F, and G for applying the voltage described above.

  The photometry unit 58 of the detection station 46 incorporates the above-described detection device 6 (see FIG. 2), is located on the cover member 46b at the time of detection, and interferes with the cover member 46b when the cover member 46b is opened. In order to avoid such a situation, the outer side of the rotary table 40 is retracted. In the detection station 46, an electrophoresis voltage is applied to the electrodes, and the sample is electrophoresed (step 3). In the electrophoresis, electrophoresis is performed in a state where the temperature of the sample liquid is maintained at 10 ° C., for example, depending on the type of the sample.

  In the step of switching the well 106 to which the voltage is applied (step 4), the electrophoresis of the sample liquid is maintained at 10 ° C., and then the measurement object is measured. A process to be performed (step 5) is performed.

  When the above measurement is performed, since there are two sets of the flow paths 110 ′, it is possible to drop the reagent and the like on each flow path 110 ′ at different times, and each of the flow paths 110 ′ is electrophoresed. Measurements can be sequentially performed by shifting the time for the measurement target substance to reach the measurement position.

  Since the two flow paths 110 ′ are slightly shifted in the plane of the glass plate 102 ′, the optical axis of the optical system is measured in accordance with the first flow path 110 ′ at the time of measurement. The optical axis is slightly moved, and the optical axis is aligned with the second flow path 110 ′ for measurement.

  Here, the temperature control by the temperature control unit 201 will be described in detail.

  For example, a Peltier element can be used as the temperature control unit 201 disposed on the base unit 200, and the upper surface 201U of the temperature control unit 201 comes into contact with the glass plate 102 'on which the flow path is formed. The microchip 100 'is supported from below.

  As described above, one microchip 100 'is arranged on the turntable 40 corresponding to each station 42 to 56. That is, the base table 200 and the temperature control unit 201 are arranged on the rotary table 40 so as to correspond to each of the eight stations 42 to 56, and each temperature control unit rotates while supporting the microchip 100 ′. Be transported.

  The temperature control unit 201 can control the temperature of the microchip 100 ′ in a state in which a sample liquid including a reagent and a sample is injected before the microchip 100 ′ is arranged in the detection station 46.

  The temperature control unit 201 ends the detection of the measurement target substance in the detection station 46 before the microchip 100 ′ into which the sample liquid has been injected is placed in the detection station 46. Until then, the temperature may be adjusted.

  Further, when the sample liquid is injected into the microchip 100 ′ at the dispensing station 42 by the temperature control unit 201, that is, the microchip in which the sample liquid has been injected into the dispensing station 42. The temperature may be adjusted from when it is placed until the detection of the substance to be measured at the detection station 46 is completed.

  In addition, the temperature control unit 201 may determine a target temperature for temperature control of each microchip 100 ′ in accordance with measurement contents (measurement items) measured by the measurement unit 10.

  Furthermore, the temperature control unit 201 may individually control the temperature of the microchip 100 ′ in which the sample solution is injected for each station. More specifically, in each of the eight stations 42, 44, 46, 48, 50, 52, 54, and 56, the microchip 100 ′ that is transported by setting a different target temperature for each station is individually heated. It may be adjusted.

  The temperature control unit 201 is not necessarily limited to the case where the temperature is controlled by bringing the Peltier element into contact with the glass plate on which the flow path is formed, but the state in which the sample liquid is injected by any temperature control method. The temperature of the microchip may be adjusted.

Next, the cleaning station 47 will be described in detail. As described above, the cleaning station 47 includes four stations 48, 50, 52, and 54 that perform four processes. The chemical cleaning station 48 is a process of cleaning the flow path 110 ′ of the detected microchip 100 ′ using a chemical (detergent) such as NaOH (sodium hydroxide). The chemical cleaning station 48 cleans the well 106 'contaminated with the sample by discharging and sucking the chemical. At this time, at the same chemical cleaning station 48, a chemical or the like is also sucked from the flow path 110 from the well 106 ′ at a negative pressure of, for example, 300 g / cm ² .

  This operation is performed, for example, as shown in FIG. FIG. 8 is an enlarged perspective view showing a main part of the chemical cleaning station 48. Two flow paths 110 ′ are formed in the microchip 100 ′. The probes 48p and 48q are adapted to discharge and suck chemicals corresponding to each flow path 110 'and can move linearly in the direction indicated by the arrow 60. This movement is performed in the chemical cleaning station 48 using a motor 48c and a screw shaft 48d driven by the motor 48c as shown in FIG. That is, the member 48e that supports the microchip 100 'is engaged with the screw shaft 48d, and the microchip 100' can reciprocate in the radial direction of the rotary table 40 by the rotation of the screw shaft 48d.

  In FIG. 8, probes 48p and 48q are shown only at the tip, but in actuality, they are extended as indicated by phantom lines or tubes are attached. Reference numerals 15 and 17 denote a chemical (detergent) container and a probe cleaning tank, respectively. The chemical container 15 contains a detergent, and the detergent is supplied to the well 106 'via the probes 48p and 48q.

  Since the tips of the probes 48p and 48q are inserted into the well 106 'of the microchip 100' at the time of washing, the tips of the probes 48p and 48q are washed in the probe washing tank 17 each time. Further, the seal plate denoted by reference numeral 65 has an opening 65a communicating with a syringe pump (not shown) at a position corresponding to the well 106 ', and the chemical is introduced into the well 106', by the air pressure supplied from the syringe pump. Used to push out from microchannel 110 '.

The medicine is discharged from the probe 48p to the plurality of wells 106 ′ aligned in one row, and the well 106 ′ in the other row is sucked at the negative pressure of the above-mentioned magnitude, that is, 300 g / cm ² . The manner of cleaning at this time will be described with reference to FIG. FIG. 9 is an enlarged cross-sectional view showing the concept when the well 106 ′ is cleaned and a negative pressure is applied to the well 106 ′. The probe 48p is inserted into the well 106 ′, and the medicine 62 is discharged and sucked so that the medicine 62 does not overflow from the well 106 ′. In the other well 106 ′, the well 106 ′ is sealed and sealed by a seal member 64 and a seal plate 65 that presses the seal member 64 against the well 106 ′, which are not shown in FIG. The state of being sucked by pressure is shown. As the probes 48p and 48q move in this way, the sample and chemicals 62 in the well 106 'and the flow path 110' are also sucked, so that the flow path 110 'is sufficiently washed. Therefore, the degree of cleaning is very high. In addition, the part shown by code | symbol 102 'in FIG. 9 respond | corresponds to the above-mentioned glass plate 102'.

After the chemical cleaning, at the water cleaning station 50, water discharge and suction are repeated for all the wells 106 ′ in the same manner as shown in FIG. Furthermore, in the water washing station 52 of the next step, for example, the chemicals in the flow path 110 ′ are pushed out with water at an atmospheric pressure of 10 kg / cm ² . At this time, the well 106 ′ on the side to be pushed out is opened to the atmosphere, and the pushed waste liquid is stored in the waste liquid container 22. Next, the residual liquid in the well 106 ′ is sucked in the residual liquid suction station 54. This operation is performed by inserting the probe 54p (FIG. 4) connected to the negative pressure source into the well 106 ′.

  Next, the cleaned microchip 100 'is sent to a desorption station 56 for demounting the chip. At the detaching station 56, the microchip 100 'that has been used repeatedly and has reached a predetermined number of times, for example, 10 to 200 times, is taken out, and a new microchip 100' is loaded on the rotary table 40. The detaching station 56 functions only when the microchip 100 'is replaced, and does not function during normal measurement.

  FIG. 10 is a partially enlarged perspective view showing a state where the microchip 100 ′ is exchanged at the detaching station 56. In the detaching station 56, for example, an opening 56 c is formed in the housing 2 corresponding to the recess 56 a of the turntable 40. The opening 56c may be in an open state or may be closed with an appropriate lid (not shown) so as to be opened and closed.

  From the opening 56c, the microchip 100 'can be accessed to remove the microchip 100' which has reached the end of its life and can be loaded with a new microchip 100 '. In order to determine the lifetime of the microchip 100 ′, for example, the number of times of use is automatically recorded by the wireless tag (recording unit) 101 ′ attached to the microchip 100 ′, and the predetermined number of times is reached. In addition, it is possible to display on the display panel 16 to instruct replacement. At that time, the operator may be notified by an appropriate acoustic signal. The count of the number of uses for detecting the lifetime and the number of uses for the wireless tag 101 ′ can be managed by, for example, the control unit 11 (FIG. 5) provided on the back side of the apparatus 1. The wireless tag 101 'can be attached to an arbitrary position by various modes such as sticking and embedding on the microchip 100'.

  As described above, the apparatus 1 of the present invention can perform accurate measurement efficiently and is suitable for clinical use. In addition, since the microchips 100 and 100 ′ are formed with a plurality of flow paths 110 and 110 ′, the same measurement item is measured for a plurality of patients with one microchip, or, alternatively, one patient. It can be used to measure a plurality of measurement items. Furthermore, the number of the flow paths 110 and 110 ′ can be increased, and a plurality of measurement items can be measured for a plurality of patients with a single microchip as necessary.

  In the above embodiment, the microchips 100 and 100 'are circulated, but each station can be circulated. Further, although the cleaning station 47 is divided into a plurality of cleaning stations that perform different processes, it is also possible to have a single cleaning station and perform a plurality of cleaning processes there. In the above embodiment, the case where the reagent and the sample are pressurized and introduced into the well has been described. However, instead of being pressurized, the reagent and the sample may be sucked and introduced from the opposite well. In this way, pressurization or suction may be performed independently, or both pressurization and suction may be performed simultaneously.

  In the above embodiment, the reagent and the sample are electrophoresed in the microchannels 110 and 110 ′. However, the present invention is not limited to this, and the microchannels 110 and 110 are applied by pressurization and / or suction. It is also possible to move and separate inside.

  The temperature control unit may be configured to adjust the temperature of a microchip in which a reagent and a sample are injected before only the microchip is placed in a dispensing station.

  The temperature control unit may perform temperature control of the microchip in a state where a reagent and a sample are injected, for a plurality of stations.

  FIG. 11 is a diagram showing an embodiment of another clinical analysis device 2 different from the device 1 described above.

  The apparatus 1 already described is configured such that the measurement of the measurement target substance is repeatedly performed by rotating the microchip continuously at a predetermined pitch relative to each station from the upstream side to the downstream side of the process. It has been done.

  In contrast, the clinical analyzer 2 (hereinafter simply referred to as “device 2”) moves the microchip in one direction at a predetermined pitch from the upstream side to the downstream side of the process relative to each station. The measurement target substance is configured to be measured.

  More specifically, the apparatus 2 removes the cleaning station 47 and the desorption station 56 from the apparatus 1 and adds a chip supply station 72 upstream of the dispensing station 42 and a chip disposal station 74 downstream of the detection station 46. It is what.

  In this device 2, the microchip is discarded after being used for clinical analysis. That is, the device 2 performs clinical analysis using a disposable microchip 100 ″.

  In the apparatus 2, a one-way moving table 40 ′ for moving the disposable microchip 100 ″ in one direction is arranged as a transport mechanism for moving the disposable microchip 100 ″. The movement of the disposable microchip 100 ″ in one direction is one direction from the upstream side to the downstream side.

  The one-way moving table 40 ′ moves the disposable microchip 100 ″ from the dispensing station 42 to the detection station 46 in one direction at a predetermined pitch.

  Since the device 2 is similar to the configuration of the device 1 as described above, the same components as those of the device 1 are denoted by the same reference numerals, and detailed description thereof is omitted.

  Hereinafter, the apparatus 2 which is a clinical analyzer will be described.

  The chip supply station 72 arranged on the downstream side of the dispensing station 42 stores a large number of disposable microchips 100 ″, and the stored disposable microchips 100 ″ are stored in accordance with instructions from the control unit 11. This is supplied to the dispensing station 42.

  A chip disposal station 74 disposed after the detection station 46 discards the disposable microchip 100 ″ that has been detected at the detection station 46. This chip disposal station 74 is operated by a command from the control unit 11. The disposable microchip 100 ″ after detection is removed from the detection station 46 and discarded.

  In addition, the temperature control unit 76a, which is a part of the temperature control unit included in the apparatus 2, is configured so that the disposable microchip 100 ″ is disposed before the disposable microchip 100 ″ is disposed in the dispensing station 42. Only the chip 100 ″ can be temperature-controlled. In other words, the temperature adjustment unit 76a can adjust the temperature of the disposable microchip 100 ″ disposed in the chip supply station 72.

  In addition, the other temperature adjustment unit 76b included in the apparatus 2 adjusts the temperature of the disposable microchip 100 ″ in a state where the reagent and the sample are injected into a plurality of stations, here, the dispensing station 42, the introduction station 44, and This is performed collectively for the detection station 46. The temperature adjustment unit 76b adjusts the temperature of the disposable microchip 100 ″ with the reagent and the sample injected therein, the dispensing station 42, the introduction station, and the detection station. Each of 46 may be performed individually.

  Other configurations of the device 2 are the same as those of the device 1.

  In the apparatus 2, the temperature control unit 76a and the temperature control unit 76b are operated in advance, the disposable microchip 100 ″ is supplied from the chip supply station 72 to the dispensing station 42, and then the disposable microchip 100 ″ is introduced. The station 44 and the detection station 46 are sequentially moved to perform detection at the detection station 46, and then the chip disposal station 74 takes out and discards the microchip 100 ″ that has been detected at the detection station 46.

  The operation of the dispensing station 42, the introduction station 44, the detection station 46, the dispensing mechanism 12, the UI unit 13, the control unit 11, the arrangement unit 8 and the like in this apparatus 2 is the same as that of the dispensing station 42 and introduction in the apparatus 1. The operations of the station 44, the detection station 46, the dispensing mechanism 12, the UI unit 13, the control unit 11, the arrangement unit 8, and the like are the same.

An example of the microchip used for the clinical analyzer of this invention is shown, (a) is the perspective view seen from the surface side of the microchip, (b) shows the perspective view seen from the back surface side, respectively. The top view which shows an example of the microchannel formed in the microchip of FIG. The perspective view which shows the external appearance of the clinical analyzer of this invention FIG. 3 is an enlarged perspective view showing a state in which a microchip is arranged in the measurement unit of the clinical analyzer of FIG. Schematic plan view of the main part of a clinical analyzer schematically showing the placement unit and measurement unit The perspective view which shows a mode that the microchip of the state in which the reagent and the sample were inject | poured was arrange | positioned on a temperature control part It is a perspective view which shows the state which removes the microchip in FIG. 6, and the temperature control part can be seen on the uppermost part. FIG. 3 is an enlarged perspective view showing the main part of the chemical cleaning station of the clinical analyzer of FIG. Enlarged cross-sectional view showing the concept of washing wells and applying negative pressure to the wells The partial expansion perspective view which shows the state which replaces | exchanges a microchip in the removal | desorption station of the clinical analyzer of FIG. The figure which shows embodiment of another clinical analyzer

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 Clinical analyzer 2 Case 8 Arrangement part 10 Measurement part 12 Dispensing mechanism part 40 Transport mechanism part (rotary table)
42 Dispensing station 44 Introduction station 46 Detection station 47 Cleaning station 48 Chemical cleaning station 50, 52 Water cleaning station 54 Residual liquid suction station 56 Desorption station 100, 100 'Microchip 102, 102' Glass plate 110, 110 'Micro flow path 101 'recording unit <wireless tag>
200 Base part 201 Temperature control part

Claims (15)

In a clinical analyzer that uses a microchip with a microchannel formed therein, introduces a reagent and a sample into the microchannel, and analyzes a measurement target substance contained in the sample.
A housing,
An arrangement part for arranging the reagent and the sample arranged in the housing;
A dispensing mechanism that dispenses the reagent and sample of the placement portion into the microchip;
A measuring unit for measuring the substance to be measured in the sample dispensed in the microchannel, having a transport mechanism unit in which the microchips are arranged at a predetermined pitch;
The measurement unit includes a dispensing station where the reagent and sample are dispensed onto the microchip by the dispensing mechanism unit, and a detection station that detects a measurement target substance in the sample dispensed onto the microchip. Are arranged in this order from the upstream side to the downstream side of the process so as to correspond to the predetermined pitch, and the microchip is predetermined in advance from the upstream side of the process to the downstream side relative to the stations. The clinical analyzer is configured so that the measurement of the measurement target substance is performed by moving at a pitch,
A clinical analyzer comprising a temperature adjustment unit capable of adjusting the temperature of the microchip in which the reagent and the sample are injected before the microchip is arranged in the detection station.   The temperature control unit is configured to change the microchip in a state where the reagent and the sample are injected from before the microchip is arranged to the detection station until the detection of the measurement target substance at the detection station is completed. 2. The clinical analyzer according to claim 1, wherein the temperature can be adjusted for a while.   The temperature control unit includes the microchip in a state where the reagent and the sample are injected, from when the microchip is disposed in the dispensing station until the detection of the measurement target substance in the detection station is completed. 2. The clinical analyzer according to claim 1, wherein the temperature can be adjusted for a while.   4. The temperature control unit according to claim 1, wherein only the microchip can be temperature-controlled before the microchip is placed in the dispensing station. 5. The clinical analyzer according to item 1.   The clinical analysis according to any one of claims 1 to 4, wherein the temperature control unit determines a target temperature for temperature control of the microchip in accordance with measurement contents measured in the measurement unit. apparatus.   6. The temperature control unit according to claim 1, wherein the temperature of the microchip in a state where the reagent and the sample are injected is individually controlled for each station. 6. Clinical analysis equipment.   6. The temperature control unit is configured to collectively control the temperature of the microchip in a state in which the reagent and the sample are injected, for a plurality of the stations. 6. The clinical analyzer described.   The introduction station for introducing the reagent and the sample by pressurization and / or inhalation into the microchannel of the microchip is disposed between the dispensing station and the detection station. The clinical analyzer according to any one of 1 to 7.   The clinical analyzer is configured to measure the measurement target substance by moving the microchip in one direction at a predetermined pitch from the upstream side to the downstream side of the process relative to each station. The clinical analyzer according to any one of claims 1 to 8, wherein   The clinical analyzer repeatedly circulates the microchip relative to each station from the upstream side to the downstream side of the process continuously at a predetermined pitch, and repeatedly measures the measurement target substance. The clinical analyzer according to any one of claims 1 to 8, wherein the clinical analyzer is configured as follows.   The clinical analyzer according to claim 10, wherein a desorption station for desorbing the microchip is disposed at an arbitrary position. The clinical analyzer according to claim 10 or 11, wherein the transport mechanism has a rotary table on which the microchip is arranged. 13. The clinical analyzer according to claim 12, wherein the number of each station and the number of the microchips mounted on the rotary table are the same.   The clinical analyzer according to claim 12 or 13, wherein a series of operations of one microchip is completed when the rotary table makes one rotation.   The clinical analysis apparatus according to claim 1, wherein the microchip includes a recording unit that records information on processing.

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