JP6834676B2 - Analytical device and analytical method - Google Patents

Description

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

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

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

JP-A-2015-127691

On the surface of the sample analysis disc, track regions in which convex portions and concave portions are alternately arranged are formed. In the reaction region formed on the track region, fine particles are usually trapped in the protrusions and recesses. Therefore, in order to measure the total number of fine particles captured in the reaction region, it is necessary to scan the laser beam on the convex portion and the concave portion, and the measurement time for detecting the fine particles becomes long.

An analyzer that uses an optical disk device for sample detection performs servo control such as tracking control and focus control. Therefore, when scanning the laser beam against the concave portion, the laser beam is also irradiated to the convex portions on both adjacent sides. If the particles are trapped in the adjacent protrusions, the particles are detected. Further, the above fine particles are also detected when the laser beam is scanned against the adjacent recess. That is, since one fine particle is measured twice by crosstalk between tracks, it becomes a factor that deteriorates the quantification accuracy of the fine particles.

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

The present invention, in the track area of the disc sample analysis, a peripheral region which is the other of the one in which the target area and the concave portion and the convex portion of the concave and convex portions are alternately formed, the track the area has fine particles to label the target substance is captured, the only target area, and a track which the laser beam is scanned by being irradiated, the laser spot of the laser beam, the target area before and Symbol the laser beam is irradiated so as to include a second peripheral region is a peripheral region of the other side adjacent to the first peripheral region and the target region is a peripheral region of one side adjacent to the target region , area including the laser spot, and the first laser spot located in a region including the front Symbol Target region before Symbol first peripheral region, and a pre-Symbol Target region before Symbol second peripheral area second is divided into a laser spot is located in a first light receiving region for receiving the laser light in the divided first laser spot as the first detection light, split second laser spots in an optical pickup having a second light receiving region for receiving the laser beam as the second detection light, first generate a received light level signal based on the received light level of the first detection light, the second A second light receiving level signal is generated based on the light receiving level of the detected light, the first light receiving level signal and the second light receiving level signal are added to generate a detection signal, and the first light receiving level is generated. A detection signal generation circuit that generates a difference signal by subtracting the second light receiving level signal from the signal, and a fine particle detection signal if the detection signal exceeds the first threshold value, and the difference signal is the second. If the threshold value of is exceeded, a measurement correction signal is generated, an exclusive logical sum of the fine particle detection signal and the measurement correction signal is logically calculated, and a fine particle measurement signal is generated when the exclusive logical sum is 1. Then, by counting the fine particle measurement signal, the number of fine particles that label the detection target substance captured in the target region and the number of fine particles that label the detection target substance captured in the peripheral region are obtained. providing analysis apparatus Ru and a logic operation circuit which measures the total number of.

Further, in the present invention, in the track region of the sample analysis disc, a target region which is one of the concave portion and the convex portion and a peripheral region which is the other of the concave portion and the convex portion are alternately formed. Fine particles labeling the substance to be detected are captured in the track region, and only the target region is a track scanned by irradiation with laser light, and the laser spot of the laser light is in front of the target region. irradiating the laser beam so as to include a second peripheral area is a peripheral region of the first peripheral area and the other side adjacent to the target region is a peripheral region of one side adjacent to the serial target region and includes the laser spot, and the first laser spot located in a region including the front Symbol Target region before Symbol first peripheral region, and a pre-Symbol Target region before Symbol second peripheral area It is divided into a second laser spot located in the region, the laser light at the divided first laser spot is received as the first detection light, and the laser light at the divided second laser spot is the second. It receives light as the second detection light, generates a first light reception level signal based on the light reception level of the first detection light, and generates a second light reception level signal based on the light reception level of the second detection light. Then, the first light receiving level signal and the second light receiving level signal are added to generate a detection signal, and the second light receiving level signal is subtracted from the first light receiving level signal to obtain a difference signal. If the detection signal exceeds the first threshold value, a fine particle detection signal is generated, if the difference signal exceeds the second threshold value, a measurement correction signal is generated, and the fine particle detection signal and the measurement are generated. The exclusive logical sum with the correction signal is logically calculated, a fine particle measurement signal is generated when the exclusive logical sum is 1, and the fine particle measurement signal is counted to capture the target region. providing minute析方method you measure the total number of the number of particles to label the detection target substance and the number of fine particles to label the target substance is captured in the peripheral region.

According to the analyzer and analysis method of the present invention, the influence of crosstalk between tracks can be suppressed, and fine particles can be measured accurately in a shorter time than before.

It is a block diagram which shows the analyzer of one Embodiment. It is a top view which shows the light receiving area of a photodetector. It is a top view which shows the relationship between the light receiving area of a photodetector and the detection light which irradiates the light receiving area. It is a figure which shows the relationship between the fine particle which is captured on the track region of the sample analysis disk, and the laser spot of the laser beam which irradiates the track region. It is a time chart which shows the relationship between a detection signal, a fine particle detection signal, a difference signal, and a measurement correction signal. It is a time chart which shows the relationship between a detection signal, a fine particle detection signal, a difference signal, and a measurement correction signal. It is a time chart which shows the relationship between a detection signal, a fine particle detection signal, a difference signal, and a measurement correction signal.

The analyzer of one 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 15a and 15b, and a light detector 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 a laser beam La having a wavelength of, for example, 405 nm. The collimator lens 12 makes the laser light La parallel light. The beam splitter 13 transmits the laser beam La. The objective lens 14 focuses the laser beam La on the track region 101 of the sample analysis disk 100 at a predetermined beam spot.

In the track region 101, concave portions 102 (target region) and convex portions 103 (peripheral region) 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 to the outer peripheral portion. The sample analysis disc 100 has a disk shape equivalent to that of an optical disc such as a Blu-ray disc (BD), a DVD, or a compact disc (CD).

The sample analysis disc 100 is made of, for example, a resin material such as a polycarbonate resin or a cycloolefin polymer generally used for optical discs. The sample analysis disc 100 is not limited to the above optical discs, and optical discs conforming to other forms or predetermined standards can also be used.

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

The laser light La is reflected in the track region 101 and is incident on the beam splitter 13 via the objective lens 14 as the detection light Lb. The beam splitter 13 reflects the detection light Lb toward the condenser lenses 15a and 15b. The condenser lenses 15a and 15b focus the detection light Lb toward the photodetector 30.

As shown in FIG. 2A, the photodetector 30 has 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, 34.

The photodetector 30 detects the light receiving level RL1 of the detected 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 receiving level RL2 of the detected 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 receiving level RL3 of the detected 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 receiving level RL4 of the detected 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 the light receiving level signal RS1 based on the light receiving level RL1. The detection signal generation circuit 21 generates the light receiving level signal RS2 based on the light receiving level RL2. The detection signal generation circuit 21 generates the light receiving level signal RS3 based on the light receiving level RL3. The detection signal generation circuit 21 generates the light receiving level signal RS4 based on the light receiving level RL4.

The detection signal generation circuit 21 adds the light receiving level signal RS1, the light receiving level signal RS2, the light receiving level signal RS3, and the light receiving level signal RS4 to generate a total signal (RS1 + RS2 + RS3 + RS4), and outputs the detection signal DS to the logical operation circuit 22. To do.

The detection signal generation circuit 21 adds the light receiving level signal RS1 and the light receiving level signal RS2 to generate an addition signal (RS1 + RS2), and adds the light receiving level signal RS3 and the light receiving level signal RS4 to generate an addition signal (RS3 + RS4). Generate. The detection signal generation circuit 21 subtracts the addition signal (RS3 + RS4) from the addition signal (RS1 + RS2) to generate a difference signal SS ((RS1 + RS2) − (RS3 + RS4)) and outputs it to the logical operation circuit 22.

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

An example of a method of measuring fine particles by logical operation of the exclusive OR of the fine particle detection signal BS and the measurement correction signal CS will be described with reference to FIGS. 3 to 6.

As shown in FIG. 3, recesses 102 and protrusions 103 are alternately formed in the track region 101 of the sample analysis disc 100. Hereinafter, a case where the recess 102 is a track TR and the laser beam La is scanned on the recess 102 will be described. In addition, in order to make the explanation easy to understand, the same components as those in FIG. 1 are designated by the same reference numerals.

When the laser light La is scanned on the track TR, in order to perform tracking control, the laser light La is a region in which the laser spot LS includes a concave portion 102 and convex portions 103 on both sides adjacent to the concave portion 102 (the first). It is irradiated so as to be located in the irradiation area of 1). When the convex portion 103 is a track TR and the laser light La is scanned on the convex portion 103, the laser light La has the laser spot LS with the convex portion 103 and the concave portions 102 on both sides adjacent to the convex portion 103. Is irradiated so as to be located in the region including (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 light La is reflected in the track region 101 and is focused as the detection light Lb on the photodetector 30 via 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 divided into four parts and incident on the light receiving regions 31, 32, 33, and 34 of the photodetector 30. The detection light Lb divided into the light receiving region 31 and incident is divided into Lb1, the detection light Lb divided into the light receiving region 32 and incident is Lb2, and the detection light Lb divided into the light receiving region 33 and incident is divided into Lb3 and the light receiving region 34. Let Lb4 be the detection light Lb that is incident. The 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 light La includes a concave portion 102 in which the laser spots LS1 and LS2 are adjacent to the concave portion 102, and a convex portion 103 (first convex portion) on one side (left side in FIG. 3) adjacent to the concave portion 102. It is irradiated so that it is located in the area. Further, the laser beam La is located in a region where the laser spots LS3 and LS4 include the concave portion 102 and the convex portion 103 (second convex portion) on the other side (right side in FIG. 3) adjacent to the concave portion 102. Is irradiated to.

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

The detection signal generation circuit 21 generates light-receiving level signals RS1 and RS2 (first light-receiving level signals) based on the light-receiving levels RL1 and RL2 of the detection lights Lb1 and Lb2, and the light-receiving levels RL3 and RL4 of the detection lights Lb3 and Lb4. The light receiving level signals RS3 and RS4 (second light receiving level signal) are generated based on the above.

FIG. 3 shows an example of a state in which the fine particles 40 labeling the substance to be detected are captured on the track region 101. In addition, in FIG. 3, in order to distinguish each concave portion 102 and each convex portion 103, each concave portion 102 is shown as concave portion 1021, 1022, 1023, and each convex portion 103 is shown as convex portion 1031, 1032, 1033, 1034. There is.

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

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

When the laser light La is scanned on the first track TR1, in order to perform tracking control, the laser light La has the laser spot LS having the concave portion 1021 and the convex portions 1031 and the convex portions 1032 on both sides adjacent to the concave portion 1021. It is irradiated so as to be located in the area including and. Assuming that the concave portion 1021 is the first concave portion, the convex portion 1031 is the first convex portion, and the convex portion 1032 is the second convex portion.

FIG. 4 is a time chart showing the relationship between 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 over the fine particles 40a, the light receiving levels RL1, RL2, RL3, and RL4 are lowered by the fine particles 40a at substantially the same level.

As a result, the signal levels of the light receiving level signals RS1, RS2, RS3, and RS4 are lowered at almost the same level, so that the signal level of the detection signal DSa with respect to the fine particles 40a is lowered, and the signal level of the difference signal SS is hardly changed.

The logical operation circuit 22 generates a fine particle detection signal BSa which is a pulse signal that becomes a high level during the period when 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 during which the signal level exceeds the threshold value means that when the laser beam La is scanned on the fine particles 40a, the light receiving level is lowered by the fine particles 40a, so that the signal level falls below the threshold value in FIGS. 4 to 6. The period of stay.

The logical operation circuit 22 executes the logical operation of the exclusive OR of the fine 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 logical operation flag, the fine particle detection signal BS is set to 1 because the fine particle detection signal BSa is generated, and the measurement correction signal CS is not generated to be set to 0. Logical operation is performed. As a result, the exclusive OR becomes 1, so that the logical operation circuit 22 generates the fine particle measurement signal HSa corresponding to the fine particle detection signal BSa. That is, the logical operation circuit 22 executes the logical operation of the exclusive OR of the fine particle detection signal BS and the measurement correction signal CS, and generates the fine particle measurement signal HS when the exclusive OR is 1.

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

The logical operation circuit 22 generates the fine particle detection signal BSe1 which is a pulse signal that becomes a high level during the period when 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 the logical operation of the exclusive OR of the fine particle detection signal BS and the measurement correction signal CS. The fine particle detection signal BS is logically calculated as 1 because the fine particle detection signal BSe1 is generated and 0 because the measurement correction signal CS is not generated. As a result, the exclusive OR becomes 1, so that the logical operation circuit 22 generates the fine particle measurement signal HSe corresponding to the fine 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 the fine particles 40b at substantially the same level.

As a result, the signal levels of the light receiving level signals RS1, RS2, RS3, and RS4 are lowered at almost the same level, so that the signal level of the detection signal DSb with respect to the fine particles 40a is lowered, and the signal level of the difference signal SS is hardly changed.

The logical operation circuit 22 generates the fine particle detection signal BSb, which is a pulse signal that becomes a high level during the period when 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 the logical operation of the exclusive OR of the fine particle detection signal BS and the measurement correction signal CS. The fine particle detection signal BS is logically calculated as 1 because the fine particle detection signal BSb is generated and 0 because the measurement correction signal CS is not generated. As a result, the exclusive OR becomes 1, so that the logical operation circuit 22 generates the fine particle measurement signal HSb corresponding to the fine particle detection signal BSb.

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

When the laser light La is scanned on the second track TR2, in order to perform tracking control, the laser light La has the laser spot LS having the concave portion 1022 and the convex portions 1032 and the convex portion 1033 on both sides adjacent to the concave portion 1022. It is irradiated so as to be located in the area including and. Assuming that the concave portion 1022 is the first concave portion, the convex portion 1032 is the first convex portion, and the convex portion 1033 is the second convex portion.

FIG. 5 is a time chart showing the relationship between 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 over the fine particles 40c, the light receiving levels RL1, RL2, RL3, and RL4 are lowered by the fine particles 40c at substantially the same level.

As a result, the signal levels of the light receiving level signals RS1, RS2, RS3, and RS4 are lowered at almost the same level, so that the signal level of the detection signal DSc with respect to the fine particles 40c is lowered, and the signal level of the difference signal SS is hardly changed.

The logical operation circuit 22 generates the fine particle detection signal BSc, which is a pulse signal that becomes a high level during the period when 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 the logical operation of the exclusive OR of the fine particle detection signal BS and the measurement correction signal CS. The fine particle detection signal BS is logically calculated as 1 because the fine particle detection signal BSc is generated and 0 because the measurement correction signal CS is not generated. As a result, the exclusive OR becomes 1, so that the logical operation circuit 22 generates the fine particle measurement signal HSc.

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

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

The logical operation circuit 22 executes the logical operation of the exclusive OR of the fine particle detection signal BS and the measurement correction signal CS. The fine particle detection signal BS is logically calculated as 1 because the fine particle detection signal BSe2 is generated, and the measurement correction signal CS is logically operated as 1 because the measurement correction signal CSe is generated. As a result, the exclusive OR becomes 0, and the fine 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, 40g captured by the other convex portion 1033 adjacent to the second track TR2 (concave 1022), the light receiving level RL3, by the fine particles 40f, 40g RL4 decreases, and the light receiving levels RL1 and RL2 do not change. As a result, the signal levels of the light receiving level signals RS3 and RS4 are lowered, and the signal levels of the light receiving level signals RS1 and RS2 are not changed. Therefore, the signal level of the detection signal DSfg1 for the fine particles 40f and 40g is lowered, and the signal of the difference signal SSfg1 is lowered. The level goes up.

The logical operation circuit 22 generates the fine particle detection signal BSfg, which is a pulse signal that becomes a high level during the period when 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 the logical operation of the exclusive OR of the fine particle detection signal BS and the measurement correction signal CS. The fine particle detection signal BS is logically calculated 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, the exclusive OR becomes 1, so that the logical operation circuit 22 generates the fine particle measurement signal HSfg corresponding to the fine particle detection signal BSfg1.

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

When the laser light La is scanned on the third track TR3, in order to perform tracking control, the laser light La causes the laser spot LS to have a concave portion 1023 and a convex portion 1033 and a convex portion 1034 adjacent to the concave portion 1023. It is irradiated so that it is located in the including area. Assuming that the concave portion 1023 is the first concave portion, the convex portion 1033 is the first convex portion, and the convex portion 1034 is the second convex portion.

FIG. 6 is a time chart showing the relationship between 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 over the fine particles 40d, the light receiving levels RL1, RL2, RL3, and RL4 are lowered by the fine particles 40d at substantially the same level.

As a result, the signal levels of the light receiving level signals RS1, RS2, RS3, and RS4 are lowered at almost the same level, so that the signal level of the detection signal DSd with respect to the fine particles 40d is lowered, and the signal level of the difference signal SS is hardly changed.

The logical operation circuit 22 generates the fine particle detection signal BSd, which is a pulse signal that becomes a high level during the period when 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 the logical operation of the exclusive OR of the fine particle detection signal BS and the measurement correction signal CS. The fine particle detection signal BS is logically calculated as 1 because the fine particle detection signal BSd is generated and 0 because the measurement correction signal CS is not generated. As a result, the exclusive OR becomes 1, so that the logical operation circuit 22 generates the fine 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 receiving levels RL1 and RL2 are raised by the fine particles 40f and 40g. It decreases and the light receiving levels RL3 and RL4 do not change. As a result, the signal levels of the light receiving level signals RS1 and RS2 are lowered, and the signal levels of the light receiving 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 lowered.

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

The logical operation circuit 22 executes the logical operation of the exclusive OR of the fine particle detection signal BS and the measurement correction signal CS. The fine particle detection signal BS is logically calculated as 1 because the fine particle detection signal BSfg2 is generated, and the measurement correction signal CS is logically operated as 1 because the measurement correction signal CSfg is generated. As a result, the exclusive OR becomes 0, and the fine 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 on the third track TR3. Specifically, the fine particle measurement signal HSd on the third track TR3 is counted, and the number of fine particles 40 when the laser beam La is scanned on the third track TR3 is determined to be 1 based on the count result.

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

Therefore, the logical operation circuit 22 determines that the total number of fine particles 40 captured on the track region 101 shown in FIG. 3 is 7. When the fine particle detection signal BS is counted as in the conventional case, the total number of fine particles 40 captured on the track region 101 shown in FIG. 3 is determined to be 10.

In this measurement error, the fine particles 40e are double-counted by inter-track crosstalk when the laser beam La is scanned on the first track TR1 and when the second track TR2 is scanned, and the laser beam La is second. This is because the fine particles 40f and 40g are double-counted by the inter-track crosstalk in the case where the track TR2 is scanned and the case where the third track TR3 is scanned.

As described above, the analyzer 1 and the analysis method of the present embodiment generate the measurement correction signal CS based on the difference signal SS, and measure with the fine particle detection signal BS generated based on the detection signal DS which is the total signal. The logical operation of the exclusive OR with the correction signal CS is executed. The analyzer 1 and the analysis method of the present embodiment generate the fine particle measurement signal HS when the exclusive OR is 1, and count the fine particle measurement signal HS to capture the fine particles 40 on the track region 101. To measure.

Therefore, according to the analyzer 1 and the analysis method of the present embodiment, by scanning only the recess 102 of the track region 101 with the laser beam La, the fine particles 40 captured in the recess 102 and one adjacent to the recess 102. The total number of fine particles 40 captured by the convex portion 103 on the side of the surface can be measured. Therefore, according to the analyzer 1 and the analysis method of the present embodiment, the influence of crosstalk between tracks can be suppressed, and fine particles can be measured accurately in a shorter time than before.

The present invention is not limited to the above-described embodiment, and various modifications can be made without departing from the gist of the present invention.

For example, the detection signal generation circuit 21 may generate a 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 particles 40 is inverted, for example, the fine particles 40e are counted when the laser beam La is scanned through the second track TR2 (recess 1022), and the first fine particles 40e are counted. It is not counted when the track TR1 (recess 1021) is scanned.

That is, the total number of fine particles 40 when the laser beam La is scanned through the first track TR1 corresponds to the total number of fine particles 40a and 40b captured in the concave portion 1021 and the total number of fine particles captured in the convex portion 1031. The total number of fine particles 40 when the laser beam La is scanned on the second track TR2 corresponds to the total number of fine particles 40c captured in the concave portion 1022 and the fine particles 40e captured in the convex portion 1032. The total number of fine particles 40 when the laser beam La is scanned through the third track TR3 corresponds to the total number of fine particles 40d captured in the concave portion 1023 and the fine particles 40f and 40g captured in 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 beam La is scanned only in the convex portion 103 of the track region 101, so that the fine particles 40 captured in the convex portion 103 and the concave portion 102 on one side adjacent to the convex portion 103 are captured. The total number of the fine particles 40 may be measured.

Specifically, for example, the convex portion 1032 is the first convex portion, the concave portion 1021 on one side adjacent to the convex portion 1032 is the first concave portion, and the concave portion 1022 on the other side is the second concave portion. The optical pickup 10 arranges the laser light La so that the laser spot LS is located in a second irradiation region including the first convex portion and the first and second concave portions on both sides adjacent to the first convex portion. Irradiate to.

The laser spot LS includes the 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, and the first convex portion. It is divided into second laser spots LS3 and LS4 located in a region including a 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 light La divided into the second laser spots LS3 and LS4 as the second detection lights 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 the laser beam La scans only the recess 102.

A two-segment 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. A more optimum value may be set according to the size of the diameter and the wavelength of the laser light La used or the numerical aperture of the objective lens 14. In the case of a detection system in which the signal level caused by the fine particles captured in the track region is detected as a high value with respect to the signal level in which the fine particles are not captured in the track region, the signal exceeds the threshold value. On the other hand, the logical operation flag may be set to 1.

1 Analyzer 10 Optical pickup 20 Signal processing circuit 31, 32 Light receiving area (first light receiving area)
33,34 Light receiving area (second light receiving area)
40 Fine particles 101 Track area 102 Recess (target area)
103 Convex part (peripheral area)
La laser light LS laser spot Lb detection light RS light receiving level signal DS detection signal SS difference signal BS fine particle detection signal CS measurement correction signal HS fine particle measurement signal

Claims (2)

In the track region of the sample analysis disc, a target region, which is one of the concave portion and the convex portion, and a peripheral region, which is the other of the concave portion and the convex portion , are alternately formed, and the detection is performed in the track region. Fine particles that label the target substance are captured ,
The only target region, and tracks the laser beam is scanned by being irradiated, the laser spot of the laser beam, the first is a peripheral region of one side adjacent to the target region before and Symbol Target region the laser beam is irradiated so as to include the peripheral region and a second peripheral area is a peripheral region of the other side adjacent to the target region of the laser spot, before Symbol target region before Symbol first a first laser spot located in a region including the peripheral area of the previous SL divided into a second laser spots located in a region including the Target region before Symbol second peripheral area, divided a first light receiving region for receiving the laser beam as a first detection light in the first laser spot, a second light that receives the laser light in the divided second laser spot as the second detection light An optical pickup with an area and
A first light receiving level signal is generated based on the light receiving level of the first detected light, a second light receiving level signal is generated based on the light receiving level of the second detected light, and the first light receiving level is generated. A detection signal generation circuit that adds the signal and the second light receiving level signal to generate a detection signal, and subtracts the second light receiving level signal from the first light receiving level signal to generate a difference signal.
If the detection signal exceeds the first threshold value, a fine particle detection signal is generated, if the difference signal exceeds the second threshold value, a measurement correction signal is generated, and the fine particle detection signal and the measurement correction signal The exclusive logical sum of is logically calculated, a fine particle measurement signal is generated when the exclusive logical sum is 1, and the fine particle measurement signal is counted to capture the detection target substance in the target region. A logic calculation circuit that measures the total number of the number of fine particles that label the substance and the number of fine particles that label the detection target substance captured in the peripheral region .
Analysis device Ru equipped with. In the track region of the sample analysis disc, a target region, which is one of the concave portion and the convex portion, and a peripheral region, which is the other of the concave portion and the convex portion , are alternately formed, and the detection is performed in the track region. Fine particles that label the target substance are captured ,
Only the target region, and tracks the laser beam is scanned by being irradiated, the first laser spot of the laser beam is a peripheral region of one side adjacent to the target region before and Symbol Target region The laser beam is irradiated so as to include the peripheral region and the second peripheral region which is the peripheral region on the other side adjacent to the target region.
Said laser spot, the region including a first laser spot located in a region including the front Symbol Target region before Symbol first peripheral region, and a pre-Symbol Target region before Symbol second peripheral area Divided into a second laser spot located
The laser light at the divided first laser spot is received as the first detection light, and the laser light is received.
The laser light at the divided second laser spot is received as the second detection light, and the laser light is received.
A first light receiving level signal is generated based on the light receiving level of the first detected light.
A second light receiving level signal is generated based on the light receiving level of the second detected light.
The first light receiving level signal and the second light receiving level signal are added to generate a detection signal.
The difference signal is generated by subtracting the second light receiving level signal from the first light receiving level signal.
If the detection signal exceeds the first threshold value, a fine particle detection signal is generated.
If the difference signal exceeds the second threshold value, a measurement correction signal is generated.
The exclusive OR of the fine particle detection signal and the measurement correction signal is logically calculated.
When the exclusive OR is 1, a fine particle measurement signal is generated .
By counting the fine particle measurement signal, the total number of fine particles that label the detection target substance captured in the target region and the number of fine particles that label the detection target substance captured in the peripheral region. To measure
Minute析方method.

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