JP4665673B2 - Optical analyzer - Google Patents

Description

  The present invention relates to an optical analyzer for optically inspecting a biological, chemical, or biochemical liquid sample by using an optical scanning technique of an optical disk device.

  Conventionally, an optical analyzer that analyzes blood characteristics using an optical scanning technique of an optical disk device while using an analytical disk in which blood is collected as a liquid sample and rotating the analytical disk around an axis. There is. (For example, refer to Patent Document 1).

  As shown in the exploded perspective view of FIG. 10, this analysis disk 100 includes a base substrate 102 on which concentric or spiral tracks 101 are present, and a spacer substrate 103 on which blood is collected and transferred. The upper cover 104 in which blood inlets and air inlets are formed is bonded to these upper parts.

  The plan view of FIG. 11 is an enlarged view of the main part of the analysis disk 100. Note that the chamber for collecting blood and the flow path for transfer are schematically shown. The analysis disk 100 collects a certain amount of blood and separates the blood into a blood cell component and a plasma component, and is disposed outside the axial center with respect to the first chamber 200. It has the 2nd chamber 201 to which the plasma component isolate | separated in the chamber 200 is transferred, and the flow path 202 for a transfer which connects the 1st chamber 200 and the 2nd chamber 201. FIG.

  As an analysis operation using such an analysis disk, blood is filled from the injection port 204 formed in the first chamber 200 with a pipette or the like, and the blood is collected in the first chamber 200 for analysis. The disk 100 is rotated. Then, the blood is centrifuged in a state where it does not exceed the apex 202a of the transfer channel 202, that is, in a state where it is held in the first chamber 200.

  After the centrifugation, when the rotation of the analysis disk 100 is stopped, the centrifuged plasma component 111 is transferred to the entrance of the second chamber 201 through the transfer channel apex 202a by capillary action (shown in the figure). Status).

  When the analysis disk 100 is rotated again, the separated plasma component is transferred from the first chamber 200 to the second chamber 201 by centrifugal force and capillary action force. The second chamber 201 can hold a reagent 205 that develops color by reacting with a specific substance to be analyzed in plasma.

  After the transfer to the second chamber 201 is completed and a color reaction occurs, the laser beam is irradiated along the track 101 from the optical pickup disposed on the lower surface of the analysis disk 100 while rotating the analysis disk 100. As a result, the second chamber 201 is scanned. Then, by detecting the transmitted light obtained from the second chamber 201 with a photodetector arranged on the upper surface of the analysis disk 100, the amount of a specific substance in the plasma component that has reacted with the reagent can be detected. .

It should be noted that analysis of other substances in the plasma component is also possible by changing the type of reagent held in the second chamber. Furthermore, although the example in which the above-described analysis disk is composed of only the first to second chambers has been given, the present invention is not limited thereto, and more chambers may be provided connected to the second and subsequent chambers. Sometimes configured.
Japanese National Patent Publication No. 10-50497

  By the way, in the optical analyzer as described above, the plasma component centrifuged in the first chamber 200 must be transferred through the transfer channel 202 by a predetermined amount necessary for the analysis in the second chamber 201. I must.

  However, in the above-described analysis disk, when the blood cell component in the blood is extremely large or the blood cell component 112 is centrifuged in the first chamber 200 in a biased state, the transfer channel 202 is not provided. The blood cell component flows in, the transfer channel is clogged, and a necessary amount of plasma component may not be transferred to the second chamber 201 in some cases.

  The conventional optical analysis apparatus has a problem in that an accurate analysis result cannot be obtained because the analysis is continued without detecting such a problem even though such a problem has occurred. That is, when the amount of the plasma component is less than the required amount, the analysis reagent 205 held in a dry state in the second chamber 201 dissolves to form a concentrated reaction solution, which is higher than the analysis value originally obtained. The result will be obtained. In addition, when the amount of plasma component is small, the reagent 205 may not be sufficiently dissolved, and an error may be caused in reading of the amount of transmitted light by the photodetector.

  Further, in the above-described conventional optical analyzer, even if a necessary amount of plasma component is transferred to the second chamber, the reagent is not sufficiently dissolved and is thin when it remains undissolved. Since the reaction solution has a concentration, there is a problem that the analysis value becomes lower than the analysis value that should be originally obtained, or that the reagent interferes with optical detection, so that a highly accurate analysis cannot be performed.

  Therefore, the present invention solves the above-described problem, and an optical analysis capable of detecting whether a necessary amount of a liquid sample has been transferred to the second chamber and whether the reagent held in the second chamber has been dissolved properly. An object is to provide an apparatus.

In order to solve the above-mentioned problems, an optical analyzer according to the present invention includes a first chamber into which a liquid sample is introduced around an axis, and an outer side than the axis with respect to the first chamber. And a second chamber that is connected to the first chamber by a transfer flow path, and further holds a reagent that dissolves in the liquid sample inside the first chamber. An analysis disk having a third chamber arranged outside and connected to the second chamber by a transfer channel and holding the liquid sample mixed with the reagent is mounted, A laser light source for irradiating the disk with laser light, a photodetector for detecting transmitted light from the analysis disk irradiated by the laser light source, and the analysis disk And a rotary drive means for rotating the serial axis around the first of the analytical disc that introducing a liquid sample into the chamber, by rotating about the axis, the reagent in the second chamber And the liquid sample are mixed, the liquid sample mixed with the reagent is transferred to the third chamber , and the analysis disk is optically scanned to analyze the components in the liquid sample. In the analyzer
The reagent and the liquid sample are mixed in the second chamber by rotating the analysis disk of the liquid sample introduced into the first chamber, and the liquid sample mixed with the reagent is After the operation of transferring to the third chamber , the amount of transmitted light is detected in a plurality of spots that are present in a grid pattern in the vertical and horizontal directions in the region in which the reagent is held in the second chamber. And measuring the number of spots where the amount of the transmitted light is a predetermined threshold value to detect dissolution of the reagent in the liquid sample in the second chamber. is there.

According to the optical analyzer of the present invention, an accurate amount that the required amount of fluid sample is not reliably transferred to the second chamber or that the reagent held in the second chamber is not reliably dissolved. Therefore, in such a case, the analysis can be stopped, or a process for dissolving the reagent can be performed to improve the analysis accuracy.

  Embodiments of an optical analyzer according to the present invention will be described below in detail with reference to the drawings. In the following embodiment, an example of detecting whether or not an amount of liquid sample necessary for analysis has been properly transferred to the chamber will be described in Embodiment 1, and the reagent required for the analysis held in the chamber will be dissolved properly. An example of detecting whether or not the above has been performed will be described in the second embodiment.

(Embodiment 1)
The configuration of the optical analyzer according to Embodiment 1 of the present invention will be described with reference to FIG. The present optical analyzer irradiates the analysis disc 100 with laser light from the optical pickup 107 while rotating the analysis disc 100 in the direction of arrow C by the disc motor 106. The pickup 107 is screwed to a feed screw 109 driven by the traverse motor 108, and drives the traverse motor 108 so that the servo control circuit 110 follows and tracks the track based on the output of the pickup 107. The pickup 107 is moved in the radial direction.

  Note that the laser light is irradiated on the analysis disk not only by driving the traverse motor 108 but also by a tracking actuator (not shown) provided in the pickup 107 so that the optical path of the laser light is directed in the surface direction of the analysis disk 100. It is configured to accurately trace the track 101 while driving and controlling the position as necessary.

  The servo control circuit 110 detects the address information recorded on the track, and drives the disk motor 106 (CLV control) so that the linear velocity is constant. The above tracking operation is controlled by the CPU 123.

  Above the analysis disk 100, a photodetector 113 that detects the amount of transmitted light that has passed through the analysis disk 100 out of the laser light emitted from the optical pickup 107, an adjustment circuit 130 that adjusts the gain of the output of the photodetector 113, A / D converter 131 for A / D converting the output of adjustment circuit 130, transmitted light amount signal processing circuit 132 for processing A / D converted data, and memory for storing data obtained by transmitted light amount signal processing circuit 132 135, a CPU 133 for controlling them, and a display unit 134 for displaying the analyzed results.

  The flow path structure of the analysis disk used in this embodiment will be described. In this embodiment, an example of an optical analyzer using an analysis disk for analyzing triglyceride (TG) in blood collected from a human body will be described.

  FIG. 2 shows a plan view of the main part of the analysis disk. The analysis disk is connected from the axial center side by an injection port 117 for injecting blood using a collection tool such as a pipette or a syringe, and an injection port 117 and a transfer channel 118d. The first chamber 116a disposed in the first chamber 116a, the second chamber 116b connected to the first chamber 116a by the transfer flow path 118a, and disposed on the outer peripheral side from the first chamber 116a, and the second chamber 116b and the transfer channel 118b, and is connected to the third chamber 116c disposed on the outer peripheral side from the second chamber 116b, and the third chamber 116c and the transfer channel 118c, and is connected to the third chamber 116c. And a fourth chamber 120 disposed on the outer peripheral side.

  Among these, the reagent required for analysis is held in a dry state in the second chamber 116b. For analysis of triglyceride, WST-9, NAD +, glycerol dehydrogenase, lipoprotein lipase, diaphorase can be used. The inlet 117 and the first to third chambers each have a capacity of 0.5 to 5 μL, and the fourth chamber is configured to have a volume of 0.5 to 1 μL. Can do.

  A series of operations for analyzing TG in the optical analyzer configured as described above will be described. First, an appropriate amount of blood for analysis, for example, 5 μl, is injected from the injection port 117. Then, the analysis disk 100 is mounted on the optical analyzer as shown in FIG. 1, and the spin-up process performed in the conventional optical disk apparatus is performed. By this process, the blood collected in the inlet 117 is transferred to the first chamber 116a.

  Thereafter, a separation process for separating the blood plasma component and the blood cell component is performed in the first chamber. Centrifugation is performed by rotating at about 6000 rpm for about 2 minutes. When the rotation of the analysis disk 100 is stopped after centrifugation, only the plasma component located on the inner peripheral side of the first chamber 116a is transferred by the capillary action of the transfer channel 118a as shown in FIG. It is transferred to the outlet 118a.

  After the rotation is stopped for about 90 seconds, when the analysis disk 100 is rotated again at about 3000 rpm, the plasma components transferred to the entrance of the second chamber 116b are immediately transferred to the second chamber 116b as shown in FIG. It flows into the chamber 116b. FIG. 4 shows a state where the analysis disk 100 is rotating. In this state, the reagent 119 previously held in the second chamber 116b is dissolved in the plasma component.

  The analysis disk 100 is rotated for about 5 seconds to dissolve the reagent 119 in the plasma component, and then the rotation is stopped. Then, the plasma component in which the reagent 119 is dissolved is transferred from the second chamber 116b to the outlet of the transfer channel 118b, that is, the inlet of the third chamber 116c by capillary action.

  After stopping the rotation for about 90 seconds, when the analysis disk 100 is rotated again at about 3000 rpm, the plasma component is transferred to the third chamber 116c as shown in FIG. Until the transfer from the second chamber 116b to the third chamber 116c, the reagent 119 dissolved in the plasma component and the substance in the plasma component unnecessary for the analysis of TG cause an agglutination reaction. Therefore, the aggregated material is centrifuged by rotating the analysis disk for about 5 seconds while being transferred to the third chamber 116c. Aggregates accumulate on the outer periphery of the third chamber 116c.

  When the rotation of the analysis disk 101 is stopped, the plasma component is transferred from the third chamber 116c to the outlet of the transfer channel 118c by capillary action. After stopping the rotation for about 45 seconds, when the analysis disk 101 is rotated again at about 3000 rpm, the plasma component is transferred to the fourth chamber 120 as shown in FIG. The plasma component in the fourth chamber 120 for analysis is irradiated with laser light, and the concentration of TG is calculated from the amount of transmitted light obtained by transmission.

  Here, the characteristic configuration of the present embodiment in the series of TG concentration measurements described above will be specifically described. In the present embodiment, it is monitored whether the plasma component after being centrifuged in the first chamber 116a is accurately transferred to the next second chamber 116b by an amount necessary for TG analysis. It is characterized by that.

  That is, as shown in FIG. 4, after the analysis disk 100 is rotated to transfer the plasma component from the first chamber 116a to the second chamber 116b, the plasma component is transferred from the first chamber 116a to the second chamber 116b. It is characterized by checking whether or not a sufficient amount has been transferred to the second chamber 116b.

  Specifically, while the analysis disk 100 is rotated for 5 seconds as described above, a laser beam is emitted from the optical pickup 107 at a predetermined position within the second chamber 116b in the radial direction from the axis. Irradiate. The predetermined position is a position at which accurate analysis is possible when the plasma component is filled to the lowest level, and the amount of transmitted light at a plurality of positions 902 in the circumferential direction is measured.

  The determination method is to measure the amount of transmitted light when plasma component is not introduced (usually, AD value in the range of 0 to 700) in advance, set this as a threshold value, and the value of transmitted light when plasma component is satisfied By comparing (usually, the range of AD values 901 to 1023), it is possible to detect whether or not the plasma component is filled in the second chamber 116b.

  The AD value means a value obtained by converting the amount of transmitted light detected by the photodetector from a digital value to a digital value. In this embodiment, the value is digitally converted to binary 10 bits. Therefore, the transmitted light amount is represented by a digital value in a range where the minimum voltage value is 0 and the maximum voltage value is 1023.

  When it is determined that the necessary amount of plasma component has been transferred, the following steps are performed. If the amount of transmitted light does not exceed a predetermined threshold, the blood cell component is clogged, etc. It can be determined that is not sufficiently introduced into the second chamber. In this case, error processing is performed, for example, the fact that an analysis abnormality has occurred is displayed on the display unit 134, and further, the subsequent operation of the analyzer is stopped and the measurement can be terminated.

  Further, in order to examine whether or not a sufficient amount of plasma component has been transferred from the first chamber 116a to the second chamber 116b, it can also be performed by detecting the amount of blood remaining in the first chamber 116a.

  That is, the timing after performing the centrifugal separation operation in the first chamber and the operation of transferring the plasma component to the second chamber 116b, specifically, as shown in FIG. In a state where the rotation operation for moving to the chamber 116b is performed, a plurality of positions 903 in a predetermined radial direction are irradiated with laser light from the axial center of the first chamber 116a, and the amount of transmitted light is measured. The position in the radial direction 903 is a position where accurate analysis cannot be performed if the blood sample remains in this position.

  The method of discrimination is that the amount of transmitted light at a position 903 in a state where blood is not introduced is measured in advance, and this value and the transmission before and after performing the transfer operation of the plasma component from the first chamber to the second chamber. It can detect by comparing with the value of light quantity. Specifically, when a change is observed up to a value measured in advance after the transfer of the plasma component to the chamber 106b as compared with the value of the transmitted light amount before the transfer to the chamber 116b, the plasma component is accurately It is determined that the chamber 106b has been transferred to the next step. However, if the value of the amount of transmitted light does not change to a value measured in advance, it is determined that the plasma component is present in the chamber 116a and the chamber 106b is not sufficiently filled. Then, an error message is displayed on the display unit 134, and the operation of the analyzer can be stopped.

  As described above, according to the first embodiment, when a liquid sample is transferred from chamber to chamber, it is possible to detect whether or not an amount necessary for analysis has been transferred properly, and reliability of analysis accuracy. Can be improved.

  The information indicating the positions 902 and 903 may be written on the analysis disk, or information may be separately given to the memory 135.

(Embodiment 2)
Next, as Embodiment 2 of the present invention, an example will be described in which it is detected whether or not the reagent necessary for the analysis held in the chamber has been properly dissolved. The configurations of the optical analyzer and the analysis disk used in the present embodiment are the same as those described in the first embodiment, and different operations will be mainly described below.

  In the present embodiment, as shown in FIG. 7, it is detected whether or not the reagent 119 held in the second chamber 116b is properly dissolved by the transferred plasma component. Therefore, first, before the plasma component is transferred to the second chamber 116b, the amount of transmitted light (usually with an AD value of 0 to 700) in a plurality of positions 802 (20 spots in this case) in the region holding the reagent 119. Measure the range.

  Then, after the blood is held in the first chamber, the analysis disk 100 is rotated and the centrifugal separation operation is performed, and then the rotation and the rotation of the analysis disk are repeated, and the first chamber 116a is rotated to the first chamber 116a. The plasma component is transferred to the second chamber 116b (state shown in FIG. 8). The rotation of the analysis disk 100 is maintained in a state where the plasma component is transferred to the second chamber 116b, and the dissolution of the reagent 119 is promoted.

  After rotating the analysis disk 100 for a predetermined time, the amount of transmitted light is detected again at the plurality of positions 802 (20 spots). Usually, if the plasma component reacts with the reagent in the second chamber and can be surely dissolved, the amount of transmitted light is in the range of AD values 901 to 1023. Therefore, if the number of spots in which the amount of transmitted light (AD value 901 to 1023) is detected among a plurality of positions 802 (20 spots) is equal to or more than a predetermined number of spots (for example, 18 spots or more). It can be determined that the amount corresponds to the amount of reagent that can be accurately analyzed, and the reagent 119 can be determined to be dissolved in the plasma component by an amount that allows accurate analysis. After confirming the dissolution of the reagent 119, the rotation of the analysis disk 100 is stopped, and the rotation is repeated again to transfer the plasma component to the third chamber, and the next analysis step is performed.

  However, here, among a plurality of positions 802 (20 spots), the number of spots where the amount of transmitted light (AD value 901 to 1023) is detected is equal to or greater than a predetermined number of spots (for example, 18 spots). If not, it can be determined that it does not correspond to the amount of reagent that can be accurately analyzed, and it is determined that the reagent has not yet been dissolved in an amount that allows accurate analysis, and the rotational operation of the analysis disk 100 is further extended. If the amount of transmitted light does not exceed a predetermined threshold even after performing this extension operation, an analysis error is displayed and the subsequent analysis can be stopped.

  In order to detect whether or not the reagent is properly dissolved, after transferring the plasma component from the second chamber 116b to the third chamber 116c, the undissolved reagent 119 remains in the second chamber 116b. Whether it is not detected can be detected.

  That is, as shown in FIG. 9, after transferring the plasma component to the third chamber 116c, the amount of transmitted light at a plurality of positions 802 (20 spots) held by the reagent 119 is detected. Usually, if the plasma component reacts with the reagent in the second chamber and can be surely dissolved, the amount of transmitted light is in the range of AD values 701 to 900. Among a plurality of positions 802 (20 spots), the number of spots where the amount of transmitted light (AD values 701 to 900) is detected is equal to or greater than a predetermined number of spots (for example, 18 spots). Then, it can be determined that the amount corresponds to the amount of reagent that can be accurately analyzed, and it can be determined that the reagent has been properly dissolved.

  Further, in the case where the reagent 119 is dissolved in the plasma component to cause a color reaction, the degree of coloration in the second chamber 116b or the third chamber is greater than a predetermined value. Sometimes it can be determined that the reagent has dissolved.

  Further, instead of detecting whether or not the reagent 119 is dissolved, it is possible to adopt a configuration in which the shape of the reagent is detected from transmitted light and it is determined whether or not the reagent is dissolved.

Configuration diagram of an optical analyzer according to Embodiment 1 of the present invention Plan view of the main part of the analysis disk used in the same embodiment Plan view of the main part of the analysis disk used in the same embodiment Plan view of the main part of the analysis disk used in the same embodiment Plan view of the main part of the analysis disk used in the same embodiment Plan view of the main part of the analysis disk used in the same embodiment The principal part top view of the analysis disk used in Embodiment 2 of this invention Plan view of the main part of the analysis disk used in the same embodiment Plan view of the main part of the analysis disk used in the same embodiment Disassembled perspective view of analysis disc Plan view of relevant parts showing a conventional analytical disk

Explanation of symbols

DESCRIPTION OF SYMBOLS 100 Analysis disc 101 Track 102 Base substrate 103 Spacer substrate 104 Cover disc 106 Disc motor 107 Pick up 108 Traverse motor 109 Feed screw 110 Servo control circuit 111 Plasma component 112 Blood cell component 113 Photo detector (PD)
114 Unnecessary aggregate 116a First chamber 116b Second chamber 116c Third chamber 117 Inlet port 118a, 118b, 118c, 118d Transfer channel 119 Analytical reagent 120 Fourth chamber

Claims (2)

A first chamber into which a liquid sample is introduced around an axis, and is disposed outside the axis with respect to the first chamber, and is connected to the first chamber by a transfer channel. And a second chamber in which a reagent that dissolves in the liquid sample is held, and an outer side of the axis with respect to the second chamber, and the second chamber and the flow for transfer. A laser light source mounted with an analysis disk having a third chamber for holding the liquid sample mixed with the reagent connected by a path, and irradiating the analysis disk with laser light; and the laser light source A detector for detecting the transmitted light from the analysis disk irradiated by the light source, and a rotation drive means for rotating the analysis disk about the axis. Said analysis disk of introducing the liquid sample into the first chamber, by rotating about the axis, wherein the liquid sample and the second chamber by the reagents are mixed, the liquid mixed with the reagent In the analyzer in which the sample transfers the liquid sample to the third chamber , and the analysis disk is optically scanned to analyze the components in the liquid sample.
The reagent and the liquid sample are mixed in the second chamber by rotating the analysis disk of the liquid sample introduced into the first chamber, and the liquid sample mixed with the reagent is After the operation of transferring to the third chamber , the amount of transmitted light is detected in a plurality of spots that are present in a grid pattern in the vertical and horizontal directions in the region in which the reagent is held in the second chamber. And measuring the number of spots at which the amount of transmitted light has reached a predetermined threshold value to detect dissolution of the reagent in the liquid sample in the second chamber. apparatus. Instead of detecting the amount of transmitted light in the region holding the reagent, the shape of the reagent is detected from the transmitted light to determine whether the reagent is dissolved or not. Item 4. The optical analyzer according to Item 1 .

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