JP2018165620A - Analyzer and analysis method - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an analyzer and an analysis method which inhibit influence due to crosstalk among trucks, and can measure fine particles in a short time compared with conventional ones.SOLUTION: An analyzer 1 comprises an optical pick-up 10 and a signal processing circuit 20. The signal processing circuit 20 generates received light level signals RS3, RS4 from detection light Lb3, Lb4 that the optical pick-up 10 has received, and generates received light level signals RS1, RS2 from detection light Lb1, Lb2. The signal processing circuit 20 adds the received light level signals RS3, RS4 and the received light level signals RS1, RS2 and generates a detection signal DS, and subtracts the received light level signals RS1, RS2 from the received light level signals RS3, RS4 and generates a difference signal SS. The signal processing circuit 20 generates a fine particle detection signal BS from the detection signal DS, generates a measurement correction signal CS from the difference signal SS, and generates a fine particle measurement signal HS when these exclusive OR become 1.SELECTED DRAWING: Figure 1

Description

  The present invention relates to an analyzer and an analysis method for analyzing biological materials such as antigens and antibodies.

  An immunoassay is known in which a specific antigen or antibody associated with a disease is detected as a biomarker to quantitatively analyze the effect of disease detection and treatment.

  In Patent Document 1, an antibody fixed in a reaction region on a sample analysis disk is bound to an antigen in a sample, the antigen is labeled with fine particles having an antibody, and laser light emitted from an optical pickup is scanned. Thus, an analyzer for detecting fine particles trapped in the reaction region is described. The analyzer described in Patent Document 1 uses an optical disk device for specimen detection.

Japanese Patent Laying-Open No. 2015-127691

  A track region in which convex portions and concave portions are alternately arranged is formed on the surface of the sample analysis disk. In the reaction region formed on the track region, fine particles are usually trapped in the convex and concave portions. Therefore, in order to measure the total number of fine particles trapped in the reaction region, it is necessary to scan the convex portions and the concave portions with laser light, and the measurement time for detecting the fine particles becomes long.

  In an analyzer using an optical disk device for specimen detection, servo control such as tracking control and focus control is performed. Therefore, when the laser beam is scanned with respect to the concave portion, the laser beam is also irradiated to the adjacent convex portions on both sides. When fine particles are captured by the adjacent convex portions, the fine particles are detected. Further, the fine particles are also detected when scanning the laser beam with respect to the adjacent concave portion. That is, one particle is measured twice due to crosstalk between tracks, which causes a deterioration in the quantitative accuracy of the particles.

  An object of the present invention is to provide an analysis apparatus and an analysis method capable of suppressing the influence of crosstalk between tracks and accurately measuring fine particles in a shorter time than conventional.

  In the present invention, the target region and the peripheral region are alternately formed, and the laser beam is applied to the track region in which the fine particles labeling the detection target substance are captured, and the laser spot of the laser beam is the first target region and the Irradiating so as to be located in a first irradiation region including a first peripheral region and a second peripheral region on both sides adjacent to the first target region, the laser spot is irradiated with the first target region and the first target region A first laser spot located in a region including the first peripheral region on one side adjacent to the first target region; and the other adjacent to the first target region and the first target region. The first laser beam is divided into a second laser spot located in a region including the second peripheral region on the side, and the laser beam divided into the first laser spot is received as first detection light Region and said second laser spot An optical pickup having a second light receiving region for receiving the divided laser light as a second detection light; and a first light reception level signal is generated based on a light reception level of the first detection light; A second light reception level signal is generated based on the light reception level of the second detection light, and a detection signal is generated by adding the first light reception level signal and the second light reception level signal, Subtracting the second received light level signal from the received light level signal to generate a difference signal, generating a particulate detection signal based on the detection signal, generating a measurement correction signal based on the difference signal, and detecting the particulate detection Provided is an analysis apparatus comprising: a signal processing circuit that performs a logical operation on an exclusive OR of a signal and the measurement correction signal and generates a fine particle measurement signal when the exclusive OR is 1. .

  In the present invention, the target region and the peripheral region are alternately formed, and the laser beam is applied to the track region where the fine particles for labeling the detection target substance are captured, and the laser spot of the laser beam is the first target region. And the first target region including both the first peripheral region and the second peripheral region on both sides adjacent to the first target region, and the laser spot is irradiated to the first target region And a first laser spot located in a region including the first peripheral region on one side adjacent to the first target region, and adjacent to the first target region and the first target region Splitting into a second laser spot located in a region including the second peripheral region on the other side, receiving the laser beam split into the first laser spot as a first detection light, Divided into second laser spots The user light is received as the second detection light, a first light reception level signal is generated based on the light reception level of the first detection light, and a second light is received based on the light reception level of the second detection light. A light reception level signal is generated, the first light reception level signal and the second light reception level signal are added to generate a detection signal, and the second light reception level signal is subtracted from the first light reception level signal. A difference signal is generated, a particle detection signal is generated based on the detection signal, a measurement correction signal is generated based on the difference signal, and an exclusive OR of the particle detection signal and the measurement correction signal is calculated. Provided is an analysis method characterized by performing a logical operation and generating a particle measurement signal when the exclusive OR becomes 1.

  According to the analysis apparatus and the analysis method of the present invention, the influence of crosstalk between tracks can be suppressed, and fine particles can be measured with higher accuracy in a shorter time than in the past.

It is a block diagram which shows the analyzer of one Embodiment. It is a top view which shows the light reception area | region of a photodetector. It is a top view which shows the relationship between the light reception area | region of a photodetector, and the detection light irradiated to a light reception area | region. It is a figure which shows the relationship between the microparticles | fine-particles caught on the track area of the sample analysis disk, and the laser spot of the laser beam irradiated to a track area. It is a time chart which shows the relationship between a detection signal, particulate detection signal, a difference signal, and a measurement correction signal. It is a time chart which shows the relationship between a detection signal, particulate detection signal, a difference signal, and a measurement correction signal. It is a time chart which shows the relationship between a detection signal, particulate detection signal, a difference signal, and a measurement correction signal.

  An analyzer according to an embodiment will be described with reference to FIG. The analyzer 1 includes an optical pickup 10 and a signal processing circuit 20. The optical pickup 10 includes a laser light source 11, a collimator lens 12, a beam splitter 13, an objective lens 14, condenser lenses 15 a and 15 b, and a photodetector 30. The signal processing circuit 20 includes a detection signal generation circuit 21 and a logic operation circuit 22.

  The laser light source 11 emits laser light La having a wavelength of, for example, 405 nm. The collimator lens 12 makes the laser beam La parallel light. The beam splitter 13 transmits the laser light La. The objective lens 14 focuses the laser beam La on the track region 101 of the sample analysis disk 100 with a predetermined beam spot.

  In the track region 101, concave portions 102 (target regions) and convex portions 103 (peripheral regions) are alternately formed in the radial direction. The concave portion 102 and the convex portion 103 are formed in a spiral shape from the inner peripheral portion toward the outer peripheral portion. The sample analysis disc 100 has a disk shape equivalent to an optical disc such as a Blu-ray disc (BD), DVD, or compact disc (CD).

  The sample analysis disk 100 is made of, for example, a resin material such as polycarbonate resin or cycloolefin polymer generally used for optical disks. Note that the sample analysis disk 100 is not limited to the optical disk described above, and an optical disk conforming to another form or a predetermined standard may be used.

  The concave portion 102 in the track region 101 of the sample analysis disc 100 corresponds to a groove of the optical disc, and the convex portion 103 corresponds to a land. The track pitch corresponding to the pitch in the radial direction of the recesses 102 is, for example, 320 nm.

  The laser beam La is reflected by the track region 101 and enters the beam splitter 13 through the objective lens 14 as detection light Lb. The beam splitter 13 reflects the detection light Lb toward the condenser lenses 15a and 15b. The condensing lenses 15 a and 15 b collect the detection light Lb toward the photodetector 30.

  As shown in FIG. 2A, the photodetector 30 includes a light receiving region 31, a light receiving region 32, a light receiving region 33, and a light receiving region 34. The photodetector 30 is a quadrant photodiode in which the light receiving region is divided into four. The detection light Lb is incident on the light receiving regions 31, 32, 33, and 34.

  The light detector 30 detects the light reception level RL1 of the detection light Lb incident on the light receiving region 31, and outputs it to the detection signal generation circuit 21 of the signal processing circuit 20. The photodetector 30 detects the light reception level RL <b> 2 of the detection light Lb incident on the light receiving region 32 and outputs it to the detection signal generation circuit 21. The photodetector 30 detects the light reception level RL3 of the detection light Lb incident on the light receiving region 33 and outputs it to the detection signal generation circuit 21. The photodetector 30 detects the light reception level RL4 of the detection light Lb incident on the light receiving region 34 and outputs it to the detection signal generation circuit 21.

  The detection signal generation circuit 21 generates a light reception level signal RS1 based on the light reception level RL1. The detection signal generation circuit 21 generates a light reception level signal RS2 based on the light reception level RL2. The detection signal generation circuit 21 generates a light reception level signal RS3 based on the light reception level RL3. The detection signal generation circuit 21 generates a light reception level signal RS4 based on the light reception level RL4.

  The detection signal generation circuit 21 adds the light reception level signal RS1, the light reception level signal RS2, the light reception level signal RS3, and the light reception level signal RS4 to generate a sum signal (RS1 + RS2 + RS3 + RS4), and outputs it as a detection signal DS to the logic operation circuit 22 To do.

  The detection signal generation circuit 21 adds the light reception level signal RS1 and the light reception level signal RS2 to generate an addition signal (RS1 + RS2), and adds the light reception level signal RS3 and the light reception level signal RS4 to generate an addition signal (RS3 + RS4). Generate. The detection signal generation circuit 21 generates a difference signal SS ((RS1 + RS2) − (RS3 + RS4)) by subtracting the addition signal (RS3 + RS4) from the addition signal (RS1 + RS2), and outputs the difference signal SS to the logic operation circuit 22.

  The logical operation circuit 22 generates a fine particle detection signal BS that is a pulse signal that becomes a high level during a period in which the signal level of the detection signal DS exceeds the threshold value. The logical operation circuit 22 generates a measurement correction signal CS that is a pulse signal that becomes a high level during a period in which the signal level of the difference signal SS exceeds the threshold value. The logical operation circuit 22 performs a logical operation of exclusive OR (BS XOR CS) of the particle detection signal BS and the measurement correction signal CS.

  An example of a method for measuring fine particles by a logical operation of exclusive OR of the fine particle detection signal BS and the measurement correction signal CS will be described with reference to FIGS.

  As shown in FIG. 3, concave portions 102 and convex portions 103 are alternately formed in the track region 101 of the sample analysis disk 100. Hereinafter, a case where the concave portion 102 is the track TR and the laser beam La is scanned on the concave portion 102 will be described. In order to make the description easy to understand, the same components as those in FIG.

  When the laser beam La is scanned on the track TR, in order to perform tracking control, the laser beam La includes a region (first step) in which the laser spot LS includes the concave portion 102 and the convex portions 103 on both sides adjacent to the concave portion 102. 1 irradiation region). When the convex portion 103 is the track TR and the laser beam La is scanned on the convex portion 103, the laser beam La has the laser spot LS at the convex portion 103 and the concave portions 102 on both sides adjacent to the convex portion 103. Irradiation so as to be located in a region including the second region (second irradiation region).

  The diameter of the laser spot LS is determined by 1.22 × the wavelength of the laser beam La ÷ the numerical aperture NA of the objective lens 14. As shown in FIG. 1, the laser beam La is reflected by the track region 101, and is condensed as the detection light Lb on the photodetector 30 through the objective lens 14, the beam splitter 13, and the condenser lenses 15a and 15b.

  As shown in FIG. 2B, the detection light Lb is incident on the light receiving regions 31, 32, 33, and 34 of the photodetector 30 after being divided into four. The detection light Lb that is divided and incident on the light receiving region 31 is divided into Lb1, the detection light Lb that is divided and incident on the light receiving region 32 is Lb2, the detection light Lb that is divided and incident on the light receiving region 33 is divided into Lb3, and the light receiving region 34 The incident detection light Lb is Lb4. Laser spots LS1, LS2, LS3, and LS4 shown in FIG. 3 correspond to Lb1, Lb2, Lb3, and Lb4 shown in FIG. 2B.

  As shown in FIG. 3, the laser beam La includes laser spots LS <b> 1 and LS <b> 2 including a recess 102 and a protrusion 103 (first protrusion) on one side (left side in FIG. 3) adjacent to the recess 102. Irradiated so as to be located in the region. Further, the laser beam La is positioned so that the laser spots LS3 and LS4 are located in a region including the concave portion 102 and the convex portion 103 (second convex portion) on the other side adjacent to the concave portion 102 (right side in FIG. 3). Is irradiated.

  The detection lights Lb1 and Lb2 generated by the laser spots LS1 and LS2 of the laser light La are incident on the light receiving regions 31 and 32 of the photodetector 30. The detection lights Lb3 and Lb4 generated by the laser spots LS3 and LS4 of the laser light La are incident on the light receiving regions 33 and 34 of the photodetector 30.

  Therefore, the laser beam La (laser spot LS) includes laser spots LS1 and LS2 (first laser spot) located in a region including the concave portion 102 and the convex portion 103 on one side adjacent to the concave portion 102, and the concave portion 102. And laser spots LS3 and LS4 (second laser spots) located in a region including the convex portion 103 on the other side adjacent to the concave portion 102. The laser beam La divided into the laser spots LS1 and LS2 enters the light receiving regions 31 and 32 (first light receiving region) as detection light Lb1 and Lb2 (first detection light), and is divided into laser spots LS3 and LS4. The laser beam La is incident on the light receiving regions 33 and 34 (second light receiving region) as detection light Lb3 and Lb4 (second detection light).

  The detection signal generation circuit 21 generates light reception level signals RS1 and RS2 (first light reception level signals) based on the light reception levels RL1 and RL2 of the detection lights Lb1 and Lb2, and receives the light reception levels RL3 and RL4 of the detection lights Lb3 and Lb4. Based on the received light level signals RS3 and RS4 (second received light level signal).

  FIG. 3 shows an example of a state in which the fine particles 40 that label the detection target substance are captured on the track region 101. In FIG. 3, in order to distinguish the concave portions 102 and the convex portions 103, the concave portions 102 are illustrated as concave portions 1021, 1022, and 1023, and the convex portions 103 are illustrated as convex portions 1031, 1032, 1033, and 1034. Yes.

  Two fine particles 40a and 40b are captured in the recess 1021 corresponding to the first track TR1. One particle 40c is captured in the recess 1022 corresponding to the second track TR2. One particle 40d is captured in the recess 1023 corresponding to the third track TR3.

  The fine particles 40 are not captured by the convex portion 1031. One fine particle 40e is captured by the convex portion 1032 located between the first track TR1 and the second track TR2. Two fine particles 40f and 40g are connected and captured by the convex portion 1033 located between the second track TR2 and the third track TR3. The fine particles 40 are not captured by the convex portion 1034.

  When the laser beam La is scanned on the first track TR1, in order to perform tracking control, the laser spot LS includes a concave portion 1021 and convex portions 1031 and convex portions 1032 on both sides adjacent to the concave portion 1021. It irradiates so that it may be located in the field containing. When the concave portion 1021 is a first concave portion, the convex portion 1031 is a first convex portion, and the convex portion 1032 is a second convex portion.

  FIG. 4 is a time chart showing the relationship among the detection signal DS, the fine particle detection signal BS, the difference signal SS, and the measurement correction signal CS when the laser beam La is scanned on the first track TR1. When the laser beam La is scanned on the fine particles 40a, the light receiving levels RL1, RL2, RL3, and RL4 are lowered at substantially the same level by the fine particles 40a.

  As a result, the signal levels of the light reception level signals RS1, RS2, RS3, and RS4 decrease at substantially the same level, so that the signal level of the detection signal DSa with respect to the fine particles 40a decreases and the signal level of the difference signal SS hardly changes.

  The logical operation circuit 22 generates a fine particle detection signal BSa that is a pulse signal that becomes a high level during a period in which the signal level of the detection signal DSa exceeds the threshold value. Since the signal level of the difference signal SS hardly changes and does not exceed the threshold value, the measurement correction signal CS is not generated. Here, the period in which the signal level exceeds the threshold value is that when the laser beam La is scanned on the fine particle 40a, the light reception level is lowered by the fine particle 40a, and therefore the signal level is below the threshold value in FIGS. This is the period of time.

  The logical operation circuit 22 executes a logical operation of exclusive OR of the particle detection signal BS and the measurement correction signal CS. If the high level is set to 1 and the low level is set to 0 as the logic operation flag, the particle detection signal BSa is generated as the particle detection signal BS, so that the particle detection signal BSa is 1, and the measurement correction signal CS is not generated. Logical operation is performed. As a result, since the exclusive OR becomes 1, the logic operation circuit 22 generates the particle measurement signal HSa corresponding to the particle detection signal BSa. That is, the logical operation circuit 22 performs a logical operation of an exclusive OR of the particle detection signal BS and the measurement correction signal CS, and generates a particle measurement signal HS when the exclusive OR is 1.

  Next, when the laser beam La is scanned in the vicinity of the fine particle 40e captured by the convex portion 1032 adjacent to the first track TR1 (recessed portion 1021), the light receiving levels RL3 and RL4 are lowered by the fine particle 40e. Levels RL1 and RL2 do not change. As a result, the signal levels of the light reception level signals RS3 and RS4 are decreased, and the signal levels of the light reception level signals RS1 and RS2 are not changed. Therefore, the signal level of the detection signal DSe1 for the fine particles 40e is decreased, and the signal level of the difference signal SSe1 is To rise.

  The logical operation circuit 22 generates a fine particle detection signal BSe1 that is a pulse signal that becomes a high level during a period in which the signal level of the detection signal DSe1 exceeds the threshold value. Since the signal level of the difference signal SSe1 rises and does not exceed the threshold value, the measurement correction signal CS is not generated.

  The logical operation circuit 22 executes a logical operation of exclusive OR of the particle detection signal BS and the measurement correction signal CS. The particle detection signal BS is logically calculated as 1 because the particle detection signal BSe1 is generated, and is 0 because the measurement correction signal CS is not generated. As a result, since the exclusive OR becomes 1, the logic operation circuit 22 generates the particle measurement signal HSe corresponding to the particle detection signal BSe1.

  Next, when the laser beam La is scanned on the fine particles 40b, the light receiving levels RL1, RL2, RL3, and RL4 are lowered by substantially the same level by the fine particles 40b.

  As a result, the signal levels of the light reception level signals RS1, RS2, RS3, and RS4 decrease at substantially the same level, so that the signal level of the detection signal DSb for the fine particles 40a decreases and the signal level of the difference signal SS hardly changes.

  The logical operation circuit 22 generates a fine particle detection signal BSb that is a pulse signal that becomes a high level during a period in which the signal level of the detection signal DSb exceeds the threshold value. Since the signal level of the difference signal SS hardly changes and does not exceed the threshold value, the measurement correction signal CS is not generated.

  The logical operation circuit 22 executes a logical operation of exclusive OR of the particle detection signal BS and the measurement correction signal CS. The particle detection signal BS is logically calculated as 1 because the particle detection signal BSb is generated, and is 0 because the measurement correction signal CS is not generated. As a result, since the exclusive OR becomes 1, the logic operation circuit 22 generates the particle measurement signal HSb corresponding to the particle detection signal BSb.

  The logical operation circuit 22 counts the fine particle measurement signal HS in the first track TR1. Specifically, the fine particle measurement signals HSa, HSe, HSb in the first track TR1 are counted, and the number of fine particles 40 when the laser light La is scanned on the first track TR1 based on the count result is 3 Is determined. The total number of the fine particles 40 when the laser beam La is scanned on the first track TR1 corresponds to the total number of the fine particles 40a and 40b captured by the concave portion 1021 and the fine particles 40e captured by the convex portion 1032.

  When the laser beam La is scanned on the second track TR2, in order to perform tracking control, the laser spot LS includes a concave portion 1022 and convex portions 1032 and convex portions 1033 on both sides adjacent to the concave portion 1022. It irradiates so that it may be located in the field containing. When the concave portion 1022 is a first concave portion, the convex portion 1032 is a first convex portion, and the convex portion 1033 is a second convex portion.

  FIG. 5 is a time chart showing the relationship among the detection signal DS, the fine particle detection signal BS, the difference signal SS, and the measurement correction signal CS when the laser beam La is scanned on the second track TR2. When the laser beam La is scanned on the fine particle 40c, the light receiving levels RL1, RL2, RL3, and RL4 are lowered at substantially the same level by the fine particle 40c.

  As a result, the signal levels of the light reception level signals RS1, RS2, RS3, and RS4 decrease at substantially the same level, so that the signal level of the detection signal DSc for the fine particles 40c decreases and the signal level of the difference signal SS hardly changes.

  The logical operation circuit 22 generates a fine particle detection signal BSc that is a pulse signal that becomes a high level during a period in which the signal level of the detection signal DSc exceeds the threshold value. Since the signal level of the difference signal SS hardly changes and does not exceed the threshold value, the measurement correction signal CS is not generated.

  The logical operation circuit 22 executes a logical operation of exclusive OR of the particle detection signal BS and the measurement correction signal CS. The particle detection signal BS is logically calculated as 1 because the particle detection signal BSc is generated, and is 0 because the measurement correction signal CS is not generated. As a result, since the exclusive OR becomes 1, the logic operation circuit 22 generates the particle measurement signal HSc.

  Next, when the laser beam La is scanned in the vicinity of the fine particles 40e captured by one convex portion 1032 adjacent to the second track TR2 (recessed portion 1022), the light receiving levels RL1 and RL2 are decreased by the fine particles 40e. The received light levels RL3 and RL4 do not change. As a result, the signal levels of the light reception level signals RS1 and RS2 are decreased, and the signal levels of the light reception level signals RS3 and RS4 are not changed. Therefore, the signal levels of the detection signal DSe2 and the difference signal SSe2 for the fine particles 40e are decreased.

  The logical operation circuit 22 generates the fine particle detection signal BSe2, which is a pulse signal that becomes high level during the period when the signal level of the detection signal DSe2 exceeds the threshold value. The logical operation circuit 22 generates a measurement correction signal CSe that is a pulse signal that becomes a high level during a period in which the signal level of the difference signal SSe2 exceeds the threshold value.

  The logical operation circuit 22 executes a logical operation of exclusive OR of the particle detection signal BS and the measurement correction signal CS. The particle detection signal BS is logically operated as 1 because the particle detection signal BSe2 is generated, and the measurement correction signal CS is 1 as the measurement correction signal CSe is generated. As a result, the exclusive OR becomes 0 and the particle measurement signal HS is not generated. That is, the fine particle detection signal BSe2 is not counted.

  Next, when the laser beam La is scanned in the vicinity of the fine particles 40f and 40g captured by the other convex portion 1033 adjacent to the second track TR2 (recessed portion 1022), the light receiving level RL3 is detected by the fine particles 40f and 40g. RL4 decreases and the light reception levels RL1 and RL2 do not change. As a result, the signal levels of the light reception level signals RS3 and RS4 are lowered, and the signal levels of the light reception level signals RS1 and RS2 are not changed. Therefore, the signal level of the detection signal DSfg1 with respect to the fine particles 40f and 40g is lowered. Level rises.

  The logical operation circuit 22 generates a fine particle detection signal BSfg that is a pulse signal that becomes a high level during a period in which the signal level of the detection signal DSfg exceeds the threshold value. Since the signal level of the difference signal SSfg1 rises and does not exceed the threshold value, the measurement correction signal CS is not generated.

  The logical operation circuit 22 executes a logical operation of exclusive OR of the particle detection signal BS and the measurement correction signal CS. The fine particle detection signal BS is logically operated as 1 because the fine particle detection signal BSfg1 is generated, and 0 because the measurement correction signal CS is not generated. As a result, since the exclusive OR becomes 1, the logic operation circuit 22 generates the particle measurement signal HSfg corresponding to the particle detection signal BSfg1.

  The logical operation circuit 22 counts the particle measurement signal HS in the second track TR2. Specifically, the fine particle measurement signals HSc and HSfg in the second track TR2 are counted, and based on the count result, the number of the fine particles 40 when the laser light La is scanned on the second track TR2 is determined to be 3. To do. The logical operation circuit 22 determines that the number of the fine particles 40 is 2 based on the pulse width of the fine particle measurement signal HSfg. The total number of the fine particles 40 when the laser beam La is scanned on the second track TR2 corresponds to the total number of the fine particles 40c captured by the concave portion 1022 and the fine particles 40f and 40g captured by the convex portion 1033.

  When the laser beam La is scanned on the third track TR3, in order to perform tracking control, the laser spot LS includes a concave portion 1023, a convex portion 1033 and a convex portion 1034 adjacent to the concave portion 1023. Irradiation is carried out so that it may be located in the area | region to include. When the concave portion 1023 is a first concave portion, the convex portion 1033 is a first convex portion, and the convex portion 1034 is a second convex portion.

  FIG. 6 is a time chart showing the relationship among the detection signal DS, the fine particle detection signal BS, the difference signal SS, and the measurement correction signal CS when the laser beam La is scanned on the third track TR3. When the laser beam La is scanned on the fine particle 40d, the light receiving levels RL1, RL2, RL3, and RL4 are lowered at substantially the same level by the fine particle 40d.

  As a result, the signal levels of the light reception level signals RS1, RS2, RS3, and RS4 decrease at substantially the same level, so that the signal level of the detection signal DSd for the fine particles 40d decreases and the signal level of the difference signal SS hardly changes.

  The logical operation circuit 22 generates a fine particle detection signal BSd that is a pulse signal that becomes a high level during a period in which the signal level of the detection signal DSd exceeds the threshold value. Since the signal level of the difference signal SS hardly changes and does not exceed the threshold value, the measurement correction signal CS is not generated.

  The logical operation circuit 22 executes a logical operation of exclusive OR of the particle detection signal BS and the measurement correction signal CS. The particle detection signal BS is logically calculated as 1 because the particle detection signal BSd is generated, and 0 as the measurement correction signal CS is not generated. As a result, since the exclusive OR becomes 1, the logic operation circuit 22 generates the particle measurement signal HSd.

  Next, when the laser beam La is scanned in the vicinity of the fine particles 40f and 40g captured by the convex portion 1033 adjacent to the third track TR3 (concave portion 1023), the light reception levels RL1 and RL2 are caused by the fine particles 40f and 40g. The light reception levels RL3 and RL4 do not change. As a result, the signal levels of the light reception level signals RS1 and RS2 are decreased, and the signal levels of the light reception level signals RS3 and RS4 are not changed, so that the signal levels of the detection signal DSfg2 and the difference signal SSfg2 for the fine particles 40f and 40g are decreased.

  The logical operation circuit 22 generates the fine particle detection signal BSfg2, which is a pulse signal that becomes high level during the period when the signal level of the detection signal DSfg2 exceeds the threshold value. The logical operation circuit 22 generates a measurement correction signal CSfg, which is a pulse signal that becomes a high level during a period in which the signal level of the difference signal SSfg2 exceeds the threshold value.

  The logical operation circuit 22 executes a logical operation of exclusive OR of the particle detection signal BS and the measurement correction signal CS. The particle detection signal BS is logically operated as 1 because the particle detection signal BSfg2 is generated, and the measurement correction signal CS is 1 as the measurement correction signal CSfg is generated. As a result, the exclusive OR becomes 0 and the particle measurement signal HS is not generated. That is, the fine particle detection signal BSfg2 is not counted.

  The logical operation circuit 22 counts the fine particle measurement signal HS in the third track TR3. Specifically, the fine particle measurement signal HSd in the third track TR3 is counted, and based on the count result, the number of fine particles 40 when the laser light La is scanned on the third track TR3 is determined to be 1.

  The total number of the fine particles 40 when the laser beam La is scanned on the third track TR3 corresponds to the total number of the fine particles 40d captured by the concave portion 1023 and the fine particles captured by the convex portion 1034.

  Accordingly, the logical operation circuit 22 determines that the total number of the fine particles 40 captured on the track area 101 shown in FIG. When the fine particle detection signal BS is counted as in the prior art, the total number of fine particles 40 captured on the track area 101 shown in FIG.

  This measurement error is caused when the laser beam La is scanned on the first track TR1 and when the laser beam La is scanned on the second track TR2, the fine particles 40e are double counted due to crosstalk between the tracks, and the laser beam La is second This is because the fine particles 40f and 40g are double-counted by crosstalk between tracks when the track TR2 is scanned and when the third track TR3 is scanned.

  As described above, the analysis apparatus 1 and the analysis method of the present embodiment generate the measurement correction signal CS based on the difference signal SS, and measure the particle detection signal BS generated based on the detection signal DS that is a total signal. A logical operation of exclusive OR with the correction signal CS is executed. In the analysis apparatus 1 and the analysis method of the present embodiment, the particle 40 captured on the track region 101 is generated by generating the particle measurement signal HS when the exclusive OR is 1, and counting the particle measurement signal HS. Measure.

  Therefore, according to the analysis apparatus 1 and the analysis method of the present embodiment, the laser beam La scans only the concave portion 102 of the track region 101, so that the fine particles 40 captured in the concave portion 102 and the one adjacent to the concave portion 102 It is possible to measure the total number of fine particles 40 captured by the convex portion 103 on the second side. Therefore, according to the analysis apparatus 1 and the analysis method of the present embodiment, the influence of the crosstalk between tracks can be suppressed, and the fine particles can be measured with higher accuracy in a shorter time than in the past.

  In addition, this invention is not limited to embodiment mentioned above, In the range which does not deviate from the summary of this invention, it can change variously.

  For example, the detection signal generation circuit 21 may generate the difference signal SS ((RS3 + RS4) − (RS1 + RS2)) by subtracting the addition signal (RS1 + RS2) from the addition signal (RS3 + RS4). In this case, since the change in the signal level of the difference signal SS with respect to the fine particle 40 is inverted, for example, the fine particle 40e is counted when the laser beam La is scanned on the second track TR2 (recess 1022), and the first When the track TR1 (recess 1021) is scanned, it is not counted.

  That is, the total number of fine particles 40 when the laser beam La is scanned on the first track TR1 corresponds to the total number of fine particles 40a and 40b captured by the concave portion 1021 and the fine particles captured by the convex portion 1031. The total number of the fine particles 40 when the laser beam La scans the second track TR2 corresponds to the total number of the fine particles 40c captured by the concave portion 1022 and the fine particles 40e captured by the convex portion 1032. The total number of the fine particles 40 when the laser beam La is scanned on the third track TR3 corresponds to the total number of the fine particles 40d captured by the concave portion 1023 and the fine particles 40f and 40g captured by the convex portion 1033.

  The convex portion 103 may be the target region and the concave portion 102 may be the peripheral region. That is, the laser light La is scanned only on the convex portion 103 of the track region 101, thereby being captured by the fine particles 40 captured by the convex portion 103 and the concave portion 102 on one side adjacent to the convex portion 103. The total number of fine particles 40 may be measured.

  Specifically, for example, the convex portion 1032 is a first convex portion, the concave portion 1021 on one side adjacent to the convex portion 1032 is a first concave portion, and the concave portion 1022 on the other side is a second concave portion. In the optical pickup 10, the laser beam La is positioned in a second irradiation region where the laser spot LS includes the first convex portion and the first and second concave portions on both sides adjacent to the first convex portion. Irradiate.

  The laser spot LS includes first laser spots LS1 and LS2 located in a region including the first convex portion and the first concave portion on one side adjacent to the first convex portion, the first convex portion, The laser beam is divided into second laser spots LS3 and LS4 located in a region including the second concave portion on the other side adjacent to the first convex portion.

  The light receiving regions 31 and 32 receive the laser light La divided into the first laser spots LS1 and LS2 as the first detection lights Lb1 and Lb2. The light receiving regions 33 and 34 receive the laser beam La divided into the second laser spots LS3 and LS4 as the second detection beams Lb3 and Lb4.

  The method of measuring the fine particles 40 by the logical operation of the exclusive OR of the fine particle detection signal BS and the measurement correction signal CS by the signal processing circuit 20 is the same as the case where only the concave portion 102 is scanned with the laser beam La.

  A two-divided photodiode may be used as the photodetector 30. In this case, one light receiving area corresponds to the light receiving areas 31 and 32, and the other light receiving area corresponds to the light receiving areas 33 and 34.

  The threshold value of the detection signal DS and the difference signal SS is set to an intermediate value between the signal level when the fine particles are not captured in the track region and the signal level caused by the fine particles captured in the track region. You may set to a more optimal value according to the magnitude | size of a diameter, the wavelength of the laser beam La used, or the numerical aperture of the objective lens 14. FIG. In the case of a detection system in which the signal level caused by the fine particles captured in the track area is detected as a high value with respect to the signal level where the fine particles are not captured in the track area, the signal exceeds the threshold value. On the other hand, the logical operation flag may be set to 1.

DESCRIPTION OF SYMBOLS 1 Analyzer 10 Optical pick-up 20 Signal processing circuit 31, 32 Light-receiving area (1st light-receiving area)
33, 34 Light receiving area (second light receiving area)
40 Fine particles 101 Track area 102 Concavity (target area)
103 Convex (peripheral area)
La laser beam LS laser spot Lb detection beam RS received light level signal DS detection signal SS difference signal BS particle detection signal CS measurement correction signal HS particle measurement signal

Claims (2)

The target region and the peripheral region are alternately formed, and the laser beam is applied to the track region where the fine particles for labeling the detection target substance are captured. The laser spot of the laser beam is the first target region and the first target region. Irradiating to include a first peripheral region and a second peripheral region on both sides adjacent to the region, the laser spot is irradiated on one side adjacent to the first target region and the first target region A region including a first laser spot located in a region including the first peripheral region, the first target region and the second peripheral region on the other side adjacent to the first target region Is divided into a second laser spot and a first light receiving region for receiving the laser light divided into the first laser spot as a first detection light, and the second laser spot. The second detection light An optical pickup having a second light receiving region to the light receiving,
A first received light level signal is generated based on the received light level of the first detected light, a second received light level signal is generated based on the received light level of the second detected light, and the first received light level. A detection signal is generated by adding a signal and the second received light level signal, a difference signal is generated by subtracting the second received light level signal from the first received light level signal, and based on the detected signal The particle detection signal is generated, a measurement correction signal is generated based on the difference signal, an exclusive OR of the particle detection signal and the measurement correction signal is logically calculated, and the exclusive OR becomes 1. A signal processing circuit for generating a particle measurement signal in a case;
An analysis apparatus comprising: The target region and the peripheral region are alternately formed, and the laser beam is applied to the track region where the fine particles for labeling the detection target substance are captured. The laser spot of the laser beam is the first target region and the first target region. Irradiate so as to be located in the first irradiation region including the first peripheral region and the second peripheral region on both sides adjacent to the region,
A first laser spot located in a region including the first target region and the first peripheral region on one side adjacent to the first target region; and the first target. A second laser spot located in a region including a region and the second peripheral region on the other side adjacent to the first target region;
Receiving the laser light divided into the first laser spots as first detection light;
Receiving the laser light divided into the second laser spots as second detection light;
Generating a first received light level signal based on the received light level of the first detection light;
Generating a second received light level signal based on the received light level of the second detection light;
Adding the first received light level signal and the second received light level signal to generate a detection signal;
Subtracting the second received light level signal from the first received light level signal to generate a difference signal;
Generate a particulate detection signal based on the detection signal,
Generate a measurement correction signal based on the difference signal,
Logical operation of an exclusive OR of the particle detection signal and the measurement correction signal;
A fine particle measurement signal is generated when the exclusive OR is 1, An analysis method characterized by:

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