JP6920887B2 - Optical measuring device and optical measuring method - Google Patents

Description

The present invention relates to an apparatus and a method for measuring the intensity of light generated in a sample in response to irradiation of the sample with light.

The sample can be analyzed by measuring the intensity of the light generated in the sample in response to the irradiation of the sample with light. Devices that perform such light measurement include a light source that outputs the irradiation light that is applied to the sample, a photodetector that detects the intensity of the generated light generated in the sample and outputs a detection signal, and the detection signal. A processing unit that outputs a digital value according to a value (analog value) is provided (see Patent Document 1).

The light generated in the sample in response to the light irradiation is fluorescence, transmitted light, reflected light, scattered light, or light generated by a non-linear optical phenomenon (for example, harmonic light or Raman scattered light). By detecting the fluorescence intensity, the concentration of the fluorescent substance contained in the sample can be measured. By detecting the intensity of transmitted light, the concentration of the sample can be measured. By detecting the intensity of scattered light, it is possible to measure the concentration and size of scattered substances contained in the sample. Further, the non-linearity of the sample can be measured by detecting the intensity of the light generated by the non-linear optical phenomenon.

Japanese Unexamined Patent Publication No. 2004-257901

When measuring the intensity of light generated in each of a plurality of samples in parallel, it is necessary to prepare as many devices including the above-mentioned light source, photodetector, and processing unit as the number of samples to be measured in parallel.

The present invention has been made to solve the above problems, and an object of the present invention is to provide an apparatus and a method capable of more easily measuring the intensity of light generated in each of a plurality of samples.

The optical measuring device of the present invention is a device that measures the intensity of light generated in each of a plurality of samples in response to irradiation of each of the plurality of samples with light, and (1) has a one-to-one correspondence with a plurality of samples. An irradiation unit that includes a plurality of light sources provided in the above and outputs irradiation light emitted from each light source to the corresponding samples over different irradiation periods, and (2) one-to-one with respect to a plurality of samples. A detection unit that includes a plurality of correspondingly provided light detectors, detects the intensity of the generated light generated in response to the irradiation of the irradiation light in the corresponding sample by each light detector, and outputs a detection signal. (3) It has an input terminal in which the detection signals output from each of the multiple light detectors are commonly input as analog values, and is input to the input terminal during the irradiation period when each light source of the irradiation unit outputs the irradiation light. It is provided with a processing unit that inputs an analog value to be generated and outputs a digital value corresponding to the analog value as a value indicating the intensity of generated light generated in a sample corresponding to the light source.

In one aspect of the optical measuring device of the present invention, the irradiation unit outputs irradiation light from each light source over different irradiation periods based on a synchronization signal indicating the irradiation period of each light source, and the processing unit performs this synchronization. It is preferable to perform conversion processing from an analog value to a digital value based on the signal. Further, it is preferable that the optical measuring device further includes a control unit that gives a synchronization signal to the control unit that outputs the synchronization signal to the irradiation unit and the processing unit.

In one aspect of the optical measuring device of the present invention, the processing unit digitally outputs a signal converter that outputs a voltage value corresponding to the value of the detection signal input to the input terminal and a voltage value output from the signal converter. It is preferable to include an AD converter that converts the value into a value and outputs the digital value. The signal converter preferably includes an integrator that has a capacitance unit that stores electric charges based on a detection signal input to the input terminal and outputs a voltage value corresponding to the amount of accumulated electric charges. Further, the signal converter includes the integrator which is the first integrator and the integrator which is the second integrator, and the first integrator and the second integrator include the irradiation periods of the plurality of light sources. It is preferable to input the detection signals alternately in synchronization with the above.

The light measurement method of the present invention is a method of measuring the intensity of light generated in each of a plurality of samples in response to irradiation of each of the plurality of samples with light, and (1) has a one-to-one correspondence with a plurality of samples. In the irradiation unit including a plurality of light sources provided in the above, a light irradiation step of outputting irradiation light emitted from each light source to a corresponding sample over different irradiation periods, and (2) a plurality of samples. On the other hand, in the detection unit including a plurality of light detectors provided in a one-to-one correspondence, each light detector detects the intensity of the generated light generated in response to the irradiation of the irradiation light in the corresponding sample and detects the detection signal. Each light source of the irradiation unit outputs the irradiation light in the processing unit that has a light detection step that outputs A signal processing step that inputs an analog value input to the input terminal during the irradiation period and outputs a digital value corresponding to this analog value as a value indicating the intensity of the generated light generated in the sample corresponding to the light source. And, including.

In one aspect of the light measurement method of the present invention, in the light irradiation step, irradiation light is output from each light source over different irradiation periods based on a synchronization signal indicating the irradiation period of each light source, and in the signal processing step, It is preferable to perform the conversion process from the analog value to the digital value based on the synchronization signal. Further, it is preferable to further include a synchronization step of outputting the synchronization signal to the irradiation unit and the processing unit.

In one aspect of the optical measurement method of the present invention, the signal processing step includes a signal conversion step that outputs a voltage value corresponding to the value of the detection signal input to the input terminal, and a signal conversion step that converts the output voltage value into a digital value. It is preferable to include an AD conversion step for outputting the digital value. In the signal conversion step, it is preferable to use an integrator to accumulate electric charges based on the detection signal input to the input terminal and output a voltage value according to the amount of the accumulated electric charges. Further, in the signal conversion step, it is preferable to use two integrators to alternately input detection signals in synchronization with the irradiation period of each of the plurality of light sources to accumulate charges.

The generated light may be fluorescence, transmitted light, reflected light, scattered light, or light generated by a nonlinear optical phenomenon.

According to the present invention, the intensity of light generated in each of a plurality of samples can be measured more easily.

FIG. 1 is a diagram showing an overall configuration of the optical measuring device 1 of the present embodiment. FIG. 2 is a diagram showing a main configuration of the optical measuring device 1 of the present embodiment. FIG. 3 is a timing chart showing an operation example of the optical measuring device 1 of the present embodiment. FIG. 4 is a timing chart showing another operation example of the optical measuring device 1 of the present embodiment. FIG. 5 is a diagram showing another configuration example of the signal converter 31 of the processing unit 30. FIG. 6 is a diagram showing still another configuration example of the signal converter 31 of the processing unit 30. FIG. 7 is a timing chart showing an operation example of the optical measuring device 1 when the signal converter 31B is used. FIG. 8 is a diagram showing another configuration example of the processing unit 30. FIG. 9 is a timing chart showing an operation example of the optical measuring device 1 when the processing unit 30A is used. FIG. 10 is a diagram showing a configuration of a modified example of the measurement optical system.

Hereinafter, embodiments for carrying out the present invention will be described in detail with reference to the accompanying drawings. In the description of the drawings, the same elements are designated by the same reference numerals, and duplicate description will be omitted. The present invention is not limited to these examples, and is indicated by the scope of claims, and is intended to include all modifications within the meaning and scope equivalent to the scope of claims.

The light measuring device or the light measuring method of the present invention measures the intensity of light generated in each of a plurality of samples in response to light irradiation, and the number of samples will be described as 3 in the following embodiments. N appearing below is each integer of 1 or more and 3 or less. Further, the light measuring device or the light measuring method of the present invention has the intensity of arbitrary light (fluorescence, transmitted light, reflected light, scattered light, or light generated by a nonlinear optical phenomenon) generated in a sample irradiated with light. However, in the following embodiment, the case of measuring the fluorescence intensity will be described.

FIG. 1 is a diagram showing an overall configuration of the optical measuring device 1 of the present embodiment. FIG. 2 is a diagram showing a main configuration of the optical measuring device 1 of the present embodiment. Optical measurement apparatus 1 is for measuring the intensity of fluorescence generated by the irradiation of the excitation light to the sample placed in each sample container 2 ₁ to 2 _3, irradiation unit 10, detecting unit 20, processing unit 30, It includes a control unit 40, an input unit 50, a display unit 60, and a storage unit 70.

Irradiation unit 10 includes a light source ₁₁ 1 to 11 ₃ and the excitation light transmission filter ₁₂ 1 to 12 ₃ which is provided to the sample vessels ₂ 1 to 2 ₃ to correspond one-to-one, also, the light source ₁₁ 1 to 11 ₃ Includes a light source drive circuit 13 for driving the light source. A light source drive circuit may be provided individually for each light source 11 _n.

Each light source 11 _n outputs light having a wavelength (or a band including this wavelength) that can excite the sample placed in the corresponding sample container 2 _n. Each light source _11n is, for example, an LED (light emitting diode), LD (laser diode) or SLD (superluminescent diode). A lens for increasing the directivity of light may be provided on the light output side of each light source 11 _n. The lens may be integral with the light source 11 _n, may be separate from the light source 11 _n.

Each excitation light transmission filter 12 _n is the corresponding light source 11 _n and optically connected, inputs the light output from the corresponding light source 11 _n. Each excitation light transmission filter 12 _n selectively transmits excitation light having a wavelength that excites the sample, and outputs the _{excitation light to the corresponding sample container 2 n.} Transmission wavelengths of the excitation light transmitting filter 12 _n, i.e., the excitation light wavelength is selected appropriately in accordance with the fluorescent substance contained in a sample placed in the sample container 2 _n. Each excitation light transmission filter 12 _n may be a good dielectric multilayer filter filter characteristics may be colored glass filters. The excitation light transmission filter 12 _n may block light having a wavelength of the detected generated light.

Light source drive circuit 13, the light source 11 _n and is electrically connected, by driving the respective light sources 11 _n emit light over a predetermined irradiation period. Each light source 11 _n is driven by a light source drive circuit 13 that receives an instruction from the control unit 40, and outputs excitation light that is irradiated to the _{corresponding sample container 2 n over different irradiation periods.} That is, of the light source 11 ₁ to 11 _3, if there one light source is outputting irradiation light, other light source does not output the illumination light.

Detector 20 includes an optical detector ₂₁ 1 to 21 ₃ and the fluorescence transmitting filter ₂₂ 1-22 ₃ provided to the sample vessels ₂ 1 to 2 ₃ correspond to one-to-one. For convenience of illustration, does not show the range of the detection unit 20 in FIG. 1 does not show fluorescence transmitting filter 22 _{1-22 3} in FIG.

Each fluorescence transmission filter 22 _n selectively transmits the fluorescence (generated light) generated in the sample according to the irradiation of the excitation light (irradiation light) to the sample placed in the corresponding sample container 2 _n. The fluorescence is output to the corresponding light detector 21 _n. Each fluorescence transmission filter 22 _n blocks light other than fluorescence (for example, light transmitted through the excitation light transmission filter 12 _n ). Transmission wavelength of each fluorescent transmission filter 22 _n is selected appropriately depending on the fluorescent material contained in the sample placed in the sample container 2 _n. Each fluorescence transmission filter 22 _n is to filter characteristic may be a good dielectric multilayer filter may be a colored glass filter.

Each photodetector 21 _n is optically connected to a corresponding fluorescence transmission filter 22 _n and receives fluorescence transmitted through the fluorescence _{transmission filter 22 n.} Each photodetector 21 _n detects the intensity of the fluorescence received, and outputs a detection signal indicating the fluorescence intensity to the processing unit 30. Each photodetector 21 _n is, for example, a photodiode, an avalanche photodiode, a photomultiplier tube, or the like.

Light source 11 _1, the excitation light transmission filter 12 _1, sample container _{2 1,} and measuring optical system _{3 1} an optical system including a fluorescence transmitting filter 22 ₁ and the photodetector 21 _1. Light source 11 _2, the excitation light transmitting filter 12 _2, the sample container ₂ is _2, and the measurement optical system _{3 2} an optical system including a fluorescence transmitting filter 22 ₂ and the photodetector 21 _2. Further, the light source 11 _3, the excitation light transmitting filter 12 _3, the sample container _{2 3,} and the fluorescence transmitted through the filter 22 ₃ and the photodetector 21 ₃ measuring optical system _{3 3} an optical system including a. The measurement optical systems 3 _{1 to} 3 ₃ are arranged inside the dark box so that stray light from the outside does not enter. Further, the measurement optical systems 3 _{1 to} 3 ₃ are optically separated from each other, and the irradiation light and the generated light generated by a certain measurement optical system of _{the measurement optical systems 3 1 to} 3 _{3 are measured by the other two.} It is not received by the optical detector of the optical system.

Processor 30 includes an optical detector ₂₁ 1 to 21 ₃ and input terminals electrically connected. Its input terminal, an optical detector 21 ₁ to 21 ₃ detection signal output from each is input to the common as an analog value. The processing unit 30 inputs an analog value input to the input terminal during the irradiation period in which _{each light source 11 n} of the irradiation unit 10 outputs irradiation light (excitation light), and the processing unit 30 inputs a digital value corresponding to the analog value. It is output to the control unit 40 as a value indicating the intensity of the generated light (fluorescence) generated in the sample corresponding to the light source 11 _n. The details of the processing unit 30 will be described later.

The control unit 40, a light source drive circuit 13 and are electrically connected, emit light over a respective light source 11 ₁ to 11 ₃ in a predetermined irradiation period by controlling the light source driving circuit 13. The control unit 40 is electrically connected to the processing unit 30, controls the operation of the processing unit 30, and inputs a digital value output from the processing unit 30 to control the intensity of fluorescence generated in each sample. Obtain and analyze the sample based on this fluorescence intensity. The control unit 40 stores these digital values, fluorescence intensity, and analysis results in the storage unit 70. The control unit 40 includes a CPU that performs the above control and analysis, and is, for example, a computer such as a personal computer, a smart device, a microcomputer, or a cloud server. The connection between the control unit 40 and other components may be wireless as well as wired, and may include a connection by network communication.

The control unit 40 _{generates a synchronization signal indicating the irradiation period of each light source 11n} of the irradiation unit 10, and outputs this synchronization signal to the irradiation unit 10 and the processing unit 30, respectively. The light source drive circuit 13 of the irradiation unit 10 outputs irradiation light from _{each light source 11 n over different irradiation periods based on the synchronization signal output from the control unit 40.} The processing unit 30 performs conversion processing from an analog value to a digital value based on the synchronization signal output from the control unit 40. This synchronization signal may be a periodic clock signal or a trigger signal that directly indicates each operation timing. When the synchronization signal is a clock signal, each of the light source drive circuit 13 and the processing unit 30 counts the pulses of the clock signal and determines each operation timing in response to reaching a predetermined count value. The synchronization signal does not have to be output from the control unit 40, and one of the light source drive circuit 13 and the processing unit 30 may be generated and output to the other.

The input unit 50 is electrically connected to the control unit 40 and receives inputs such as measurement conditions, measurement start and measurement end. The input unit 50 is, for example, a keyboard, a mouse, a touch screen, or the like. The input unit 50 may transmit a simple on / off such as a momentary switch or an alternate switch to the control unit 40.

The display unit 60 is electrically connected to the control unit 40 and displays measurement conditions and measurement results. The display unit 60 is, for example, a liquid crystal display, an organic EL display, a touch screen, or the like. Further, the display unit 60 may display by turning on / off a light emitting element such as an LED.

The storage unit 70 is electrically connected to the control unit 40, and stores the fluorescence intensity and the analysis result output from the control unit 40. The storage unit 70 is, for example, an internal memory or an external storage.

Next, the configuration of a main part of the optical measuring device 1 of the present embodiment will be described with reference to FIG. Hereinafter, each photodetector 21 _n will be described as a photodiode. The cathode of each photodetector 21 _n is a ground potential, and the anode of _{each photodetector 21 n is common.} Each photodetector 21 _n generates a charge according to incidence of light, and outputs from the anode current corresponding to the electric charge as a detection signal to the processing unit 30. The amount of electric charge generated per unit time in each photodetector 21 _n is a current value (analog value) according to the intensity of the received light.

The processing unit 30 includes a signal converter 31 and an AD converter 33. Signal converter 31 comprises a photodetector ₂₁ 1 to 21 ₃ input terminal T to be respective anodes electrically connected. Its input terminal T, photodetector 21 ₁ to 21 ₃ current value output from the respective (detection signal) is input to the common as an analog value. _{The signal converter 31 inputs an analog value input to the input terminal T during the irradiation period in which each light source 11 n} of the irradiation unit 10 outputs the irradiation light (excitation light), and responds to the input analog value. Outputs the voltage value. The AD converter 33 is electrically connected to the signal converter 31 and inputs a voltage value output from the signal converter 31. The AD converter 33 converts the input voltage value (analog value) into a digital value, and outputs the digital value as a value indicating the intensity of the generated light (fluorescence) generated in the sample corresponding _{to the light source 11 n.} ..

As shown in FIG. 2, the signal converter 31 may have an integrator configuration including an amplifier 311 and a capacitance unit 312 and a switch 313. The amplifier 311 has an inverting input terminal, a non-inverting input terminal, and an output terminal. The non-inverting input terminal of the amplifier 311 is set to the ground potential. Inverting input terminal of the amplifier 311, the light detector ₂₁ 1 to 21 ₃ of the detecting unit 20 are electrically connected to respective anode and. The output terminal of the amplifier 311 is electrically connected to the sample hold circuit 331 of the AD converter 33. The capacitance unit 312 and the switch 313 are connected in parallel to each other and are provided between the inverting input terminal and the output terminal of the amplifier 311.

In this signal converter 31, when the switch 313 is in the ON state, the charge accumulation of the capacitance unit 312 is initialized, and the voltage value of the output terminal of the amplifier 311 is also initialized. When the switch 313 is in the off state, electric charges are accumulated in the capacitance unit 312 based on the detection signal input to the inverting input terminal of the amplifier 311, and the charge corresponds to the amount of the electric charges stored in the capacitance unit 312. The voltage value is output from the output terminal of the amplifier 311. The voltage value output from the amplifier 311 is held by the sample hold circuit 331 of the AD converter 33. The voltage value held by the sample hold circuit 331 is output to the AD converter 33 and converted into a digital signal by the AD converter 33. The sample hold circuit does not have to be built in the AD converter 33. In this case, the sample hold circuit is electrically connected to each of the output terminal of the amplifier 311 and the AD converter 33. High-sensitivity photodetection can be performed by appropriately setting the length of the charge accumulation period and the capacitance value of the capacitance section 312 in the signal converter 31 having such an integrator configuration.

Next, an operation example of the optical measuring device 1 of the present embodiment and the optical measuring method of the present embodiment will be described. Optical measurement method of this embodiment uses the optical measuring apparatus 1, and measures the intensity of the fluorescence generated by the irradiation of the excitation light to the sample container 2 ₁ to 2 ₃ is placed in each sample.

FIG. 3 is a timing chart showing an operation example of the optical measuring device 1 of the present embodiment. This operation is performed based on the synchronization signal output from the control unit 40 in the synchronization step. This figure shows, in order from the top, the light source ₁₁ 1 to 11 ₃ of each output, an optical detector ₂₁ 1 to 21 ₃ of each output, the output of the output and the sample and hold circuit 331 of the signal converter 31 is shown. Further, although the operation for two cycles is shown in this figure, the same applies to the subsequent cycles.

In the light irradiation step, the light source 11 ₁ outputs the irradiation light in a period _{T 11} (time _t 10 _{~t 12),} in the period _{T 12} following the period _{T 11} (time _t 12 _{~t 14)} source 11 ₂ is irradiated outputting the light, the light source 11 ₃ outputs irradiation light in a period _{T 13} following the period _{T 12} (time _t 14 _{~t 20).} Further, the _{light source 11 1} outputs the irradiation light in the period T ₂₁ (time t _{20 to t 22 ) following this period T 13} , and the light source 11 in the period T ₂₂ (time t _{22 to t 24} ) _{following this period T 21. 2} outputs irradiation light, the light source 11 ₃ outputs irradiation light in a period _{T 23} following the period _{T 22} (time _t 24 _{~t 30).} The periods T ₁₁ , T ₁₂ , T ₁₃ , T ₂₁ , T ₂₂ , and T ₂₃ do not overlap each other. Thus, the light source ₁₁ 1 to 11 _3, and outputs the irradiation light (excitation light) over a different irradiation periods from each other.

In light detecting step, a light detector 21 ₁ to 21 _3, and outputs a detection signal having a value corresponding to the received light intensity by receiving different periods over to generate light (fluorescence) from each other. In other words, the optical detector 21 ₁ is receiving fluorescence period _{T 11,} the photodetector 21 ₂ receives the fluorescence period _{T 12,} the photodetector 21 ₃ receives fluorescence period _{T 13.} Further, the photodetector 21 ₁ receives the fluorescence period _{T 21,} the photodetector 21 ₂ receives the fluorescence period _{T 22,} the photodetector 21 ₃ receives fluorescence period _{T 23.} Detection signals output from the optical detectors ₂₁ 1 to 21 ₃ is input in common to the input terminal T of the signal converter 31 (inverting input terminal of the amplifier 311).

In the signal processing step, the switch 313 of the signal converter 31 is turned on at the initial _{stage of each of the periods T 11} , T ₁₂ , T ₁₃ , T ₂₁ , T ₂₂ , and T 23, and the charge accumulation of the capacitance unit 312 is initialized. , The voltage value of the output terminal of the amplifier 311 is also initialized. After initialization, the switch 313 of the signal converter 31 is turned off, and the electric charge is accumulated in the capacitance section 312 based on the detection signal input to the inverting input terminal of the amplifier 311 and is accumulated in the capacitance section 312. A voltage value corresponding to the amount of electric charge is output from the output terminal of the amplifier 311 (signal conversion step). In each of the periods T ₁₁ , T ₁₂ , T ₁₃ , T ₂₁ , T ₂₂ , and T ₂₃ , the rate of increase of the voltage value output from the signal converter 31 is the detection signal input to the input terminal T of the signal converter 31. It corresponds to the value of, and corresponds to the intensity of the fluorescence received by each photodetector.

At the end of each of the periods T ₁₁ , T ₁₂ , T ₁₃ , T ₂₁ , T ₂₂ , and T ₂₃ , the voltage value (analog value) output from the signal converter 31 is held by the sample hold circuit 331 of the AD converter 33. , Is output from the sample hold circuit 331 over a certain period of time. Then, it is converted into a digital value by the AD converter 33, and the digital value is output from the AD converter 33 (AD conversion step). The digital value output from the AD converter 33 is transferred to the control unit 40.

Periods T ₁₁ , T ₁₂ , T ₁₃ , T ₂₁ , T ₂₂ , and T ₂₃ each need only be a time during which an increase in the voltage value output from the signal converter 31 can be observed with a sufficient SN ratio. For example, it is preferably 1 millisecond to 1 minute. For example, if each period is 3 seconds, the measurement time of one cycle in which the measurement is performed once for each of the three samples is 9 seconds.

In the period T _11, T ₂₁ of the light source 11 ₁ is outputting irradiation light, the fluorescence is generated by putting obtained sample in the sample container 2 _1, the detection signal output from the photodetector 21 ₁ that has received the fluorescence Is input to the processing unit 30, and the value of the detection signal is converted into a digital value. In the period T _12, T ₂₂ of the light source 11 ₂ is outputting irradiation light, the fluorescence is generated by putting obtained sample in the sample container 2 _2, detection signals outputted from the photodetector 21 ₂ having received the fluorescence Is input to the processing unit 30, and the value of the detection signal is converted into a digital value. Further, in the period T _13, T ₂₃ of the light source 11 ₃ is outputting irradiation light, the fluorescence is generated by putting obtained sample in the sample container 2 _3, output from the photodetector 21 ₃ that has received its fluorescence The detection signal is input to the processing unit 30, and the value of the detection signal is converted into a digital value.

The signal processing of the processing unit 30 including the signal converter 31 and the AD converter 33 is performed in synchronization with the irradiation light output of _{each light source 11n.} Control unit 40, by controlling synchronously the signal processing of the processing unit 30 and the irradiation light output of each light source 11 _n to each other, the intensity of fluorescence digital value output from the processing unit 30 has occurred in any sample It is possible to grasp whether it represents. Therefore, the intensity of light generated in each of the three samples can be measured. Further, since one processing unit 30 may be provided for each of the _{three measurement optical systems 3 1 to 33, the apparatus configuration can be simplified.}

FIG. 4 is a timing chart showing another operation example of the optical measuring device 1 of the present embodiment. This operation is also performed based on the synchronization signal output from the control unit 40. Also this figure shows, in order from the top, the light source ₁₁ 1 to 11 ₃ of each output, each output optical detectors ₂₁ 1 to 21 _3, the output of the output and the AD converter 33 of the signal converter 31 is shown. Further, although the operation for two cycles is shown in this figure, the same applies to the subsequent cycles.

The period _{T 11} (time _t 10 _{~t 11)} the light source 11 ₁ outputs the irradiation light source 11 ₂ outputs irradiation light in a period _{T 12} after this period _{T 11} (time _t 12 _{~t 13)} , the light source 11 ₃ outputs irradiation light in a period _{T 13} after this period _{T 12} (time _t 14 _{~t 15).} Further, the light source 11 ₁ outputs the irradiation light in the period T ₂₁ (time t _{20 to t 21 ) after this period T 13} , and in the period T ₂₂ (time t _{22 to t 23} ) _{after this period T 21.} light source 11 ₂ outputs irradiation light, the light source 11 ₃ outputs the irradiation light to the period _{T 23} after this period _{T 22} (time _t 24 _{~t 25).} The periods T ₁₁ , T ₁₂ , T ₁₃ , T ₂₁ , T ₂₂ , and T ₂₃ do not overlap each other. Thus, the light source ₁₁ 1 to 11 _3, and outputs the irradiation light (excitation light) over a different irradiation periods from each other.

In this operation example, the waiting period between the _{irradiation period T 11} and the next irradiation period T _{12 (time t 11 to t 12} ) and the waiting period between the irradiation period T ₁₂ and the next irradiation period T ₁₃ (time). t _{13 to t 14} ), waiting period between irradiation period T ₁₃ and next irradiation period T _{21 (time t 15 to t 20} ), waiting period between irradiation period T ₂₁ and next irradiation period T ₂₂ (Times t _{21 to t 22} ), waiting period between irradiation period T ₂₂ and next irradiation period T _{23 (time t 23 to t 24} ) and waiting period between irradiation period T ₂₃ and next irradiation period. At (time _t 25 _{~t 30),} both light sources ₁₁ 1 to 11 ₃ does not output the illumination light (excitation light). During these waiting periods, the digital value output from the AD converter 33 is transferred to the control unit 40.

In this operation example, for example, the light source 11 after the period _{T 11 1} to output the illumination light (excitation light) (time _t 10 _{~t 11)} is completed, delayed fluorescence from the sample corresponding to the light source 11 ₁ is generated even, the waiting period occurrence of the delayed fluorescence since (time _t 11 _{~t 12)} disappear among the light emitted from the light source 11 ₂ in the next period _{T 12} (time _t 12 _{~t 13)} (excitation light) Irradiation does not affect the detection of fluorescence generated in the sample.

Next, another configuration example of the signal converter 31 of the processing unit 30 and another configuration example of the processing unit 30 will be described.

FIG. 5 is a diagram showing another configuration example of the signal converter 31 of the processing unit 30. The signal converter 31A of another configuration example shown in this figure is an integrator configuration including an amplifier 311, a capacitance unit 312, and switches 314 to 318. The amplifier 311 has an inverting input terminal, a non-inverting input terminal, and an output terminal. The non-inverting input terminal of the amplifier 311 is set to the ground potential. Switch 314 is provided between the inverting input terminal of the photodetector ₂₁ 1 to 21 _3, respectively the anode and the amplifier 311 of the detection unit 20. The switch 315 is provided between the inverting input terminal and the non-inverting input terminal of the amplifier 311. One end of the capacitance unit 312 is connected to the inverting input terminal of the amplifier 311. The other end of the capacitance unit 312 is connected to the output terminal of the amplifier 311 via the switch 316, and the reference potential Vref is input via the switch 317. The switch 318 is provided between the output terminal of the amplifier 311 and the sample hold circuit 331.

In this signal converter 31A, when the switches 314 and 316 are in the off state and the switches 315 and 317 are in the on state, the voltage between both ends of the capacitance unit 312 is initialized to Vref. When the switches 314 and 316 are on and the switches 315 and 317 are off, electric charges are accumulated in the capacitance section 312 based on the detection signal input to the inverting input terminal of the amplifier 311 and the capacitance is accumulated. A voltage value corresponding to the amount of electric charge stored in the unit 312 is output from the output terminal of the amplifier 311. When the switch 314 turns off, the charge accumulation in the capacitance portion 312 ends. When the switch 318 is in the ON state, the voltage value output from the output terminal of the amplifier 311 is held by the sample hold circuit 331 and is output from the sample hold circuit 331 to the AD converter 33 for a certain period of time.

FIG. 6 is a diagram showing still another configuration example of the signal converter 31 of the processing unit 30. The signal converter 31B of still another configuration example shown in this figure is a configuration of a current-voltage converter including an amplifier 311 and a resistor 319. The amplifier 311 has an inverting input terminal, a non-inverting input terminal, and an output terminal. The non-inverting input terminal of the amplifier 311 is set to the ground potential. The resistor 319 is provided between the inverting input terminal and the output terminal of the amplifier 311. In this signal converter 31B, a voltage value corresponding to the current value of the detection signal input to the inverting input terminal of the amplifier 311 is output from the output terminal.

FIG. 7 is a timing chart showing an operation example of the optical measuring device 1 when the signal converter 31B is used. This operation is also performed based on the synchronization signal output from the control unit 40. Also this figure shows, in order from the top, the light source ₁₁ 1 to 11 ₃ of each output, an optical detector ₂₁ 1 to 21 ₃ of each output, the output of the output and the sample and hold circuit 331 of the signal converter 31B is shown. Further, although the operation for two cycles is shown in this figure, the same applies to the subsequent cycles.

Light source ₁₁ 1 to 11 ₃ each output and the photodetector ₂₁ 1 to 21 ₃ of each output in the operation example shown in FIG. 7 is the same as that of the operation example shown in FIG. In the operation example shown in FIG. 7, the voltage value output from the output terminal of the signal converter 31B is the voltage value of the signal converter 31B in each of _{the periods T 11} , T ₁₂ , T ₁₃ , T ₂₁ , T ₂₂ and T _23. This corresponds to the current value of the detection signal input to the inverting input terminal of the amplifier 311. If the input current value of the signal converter 31B is constant in each period, the output voltage value of the signal converter 31B is also constant. In this case, the voltage value (analog value) output from the signal converter 31B at an arbitrary timing within each period is held by the sample hold circuit 331, and is output from the sample hold circuit 331 to the AD converter 33 over a certain period of time. Will be done. After that, the AD converter 33 converts the voltage value output from the sample hold circuit 331 into a digital value, and the digital value is output from the AD converter 33. The digital value output from the AD converter 33 is transferred to the control unit 40.

FIG. 8 is a diagram showing another configuration example of the processing unit 30. The processing unit 30A of another configuration example shown in this figure includes a signal converter 31, a signal converter 32, an AD converter 33, a switch 34, and a switch 35.

The signal converter 31 has an integrator configuration including an amplifier 311, a capacitance unit 312 and a switch 313, similar to that shown in FIG. The signal converter 32 also has an integrator configuration including an amplifier 321 and a capacitance unit 322 and a switch 323.

The switch 34 selects either one of the input terminal T1 of the signal converter 31 (the inverting input terminal of the amplifier 311) and the input terminal T2 of the signal converter 32 (the inverting input terminal of the amplifier 321), and selects one of them. electrically connecting the input terminal and the optical detector 21 ₁ to 21 ₃ of each anode of the detecting section 20. The switch 35 selects either one of the output terminal of the signal converter 31 (output terminal of the amplifier 311) and the output terminal of the signal converter 32 (output terminal of the amplifier 321), and sets the selected output terminal. It is electrically connected to the sample hold circuit 331. The connection state of the switch 34 and the switch 35 is controlled by the control unit 40.

FIG. 9 is a timing chart showing an operation example of the optical measuring device 1 when the processing unit 30A is used. This operation is also performed based on the synchronization signal output from the control unit 40. This figure shows, in order from the top, the light source ₁₁ 1 to 11 ₃ of each output, the connection state of the switch 34, the connection state of the switch 35, operation of the signal converter 31, the operation and the AD converter 33 of the signal converter 32 The operation is shown.

During the period T ₁₁ (time t _{10 to t 12} ), the light source 11 ₁ outputs the irradiation light, the photodetector 21 ₁ receives the fluorescence, and the switch 34 causes the input terminal T 1 of the signal converter 31 to be each photodetector. It is connected to 21 _n. At the beginning of this period T ₁₁ , the switch 313 of the signal converter 31 is turned on, the charge accumulation of the capacitance unit 312 is initialized, and the voltage value of the output terminal of the amplifier 311 is also initialized. After initialization, the switch 313 of the signal converter 31 is turned off, and the electric charge is accumulated in the capacitance section 312 based on the detection signal input to the inverting input terminal of the amplifier 311 and is accumulated in the capacitance section 312. A voltage value corresponding to the amount of electric charge is output from the output terminal of the amplifier 311.

During the period T ₁₂ (time t _{12 to t 14} ) following this period T ₁₁ , the input terminal T1 of the signal converter 31 is _{disconnected from each photodetector 21 n} by the switch 34, and the output voltage value of the signal converter 31 is set. Is confirmed. Further, during this period T ₁₂ , the output terminal of the signal converter 31 is connected to the sample hold circuit 331 by the switch 35, and the output voltage value of the signal converter 31 is held by the sample hold circuit 331. During this period T ₁₂ , the AD converter 33 performs the AD conversion process and outputs the digital value to the control unit 40. Digital value output at this time are those corresponding to the detection signal value of the photodetector 21 _1.

Further, in a period _{T 12,} the light source 11 ₂ outputs irradiation light, the light detector 21 ₂ is receiving fluorescence, input terminal T2 of the signal converter 32 is connected to the light detectors 21 _n by the switch 34 .. At the beginning of this period T ₁₂ , the switch 323 of the signal converter 32 is turned on, the charge accumulation of the capacitance unit 322 is initialized, and the voltage value of the output terminal of the amplifier 321 is also initialized. After initialization, the switch 323 of the signal converter 32 is turned off, and the electric charge is accumulated in the capacitance section 322 based on the detection signal input to the inverting input terminal of the amplifier 321 and is accumulated in the capacitance section 322. A voltage value corresponding to the amount of electric charge is output from the output terminal of the amplifier 321.

During the period T ₁₃ (time t _{14 to t 20} ) following this period T ₁₂ , the input terminal T2 of the signal converter 32 is _{disconnected from each photodetector 21 n} by the switch 34, and the output voltage value of the signal converter 32 is changed. Is confirmed. Further, during this period T ₁₃ , the output terminal of the signal converter 32 is connected to the sample hold circuit 331 by the switch 35, and the output voltage value of the signal converter 32 is held by the sample hold circuit 331. During this period T ₁₃ , AD conversion processing is performed by the AD converter 33, and the digital value is output to the control unit 40. Digital value output at this time are those corresponding to the detection signal value of the light detector 21 _2.

Further, in a period _{T 13,} the light source 11 ₃ outputs irradiation light, the light detector 21 ₃ receives the fluorescence, an input terminal T1 of the signal converter 31 is connected to the light detectors 21 _n by the switch 34 .. At the beginning of this period T ₁₃ , the switch 313 of the signal converter 31 is turned on, the charge accumulation of the capacitance unit 312 is initialized, and the voltage value of the output terminal of the amplifier 311 is also initialized. After initialization, the switch 313 of the signal converter 31 is turned off, and the electric charge is accumulated in the capacitance section 312 based on the detection signal input to the inverting input terminal of the amplifier 311 and is accumulated in the capacitance section 312. A voltage value corresponding to the amount of electric charge is output from the output terminal of the amplifier 311.

During the period T ₂₁ (time t _{20 to t 22} ) following this period T ₁₃ , the input terminal T1 of the signal converter 31 is _{disconnected from each photodetector 21 n} by the switch 34, and the output voltage value of the signal converter 31 is set. Is confirmed. Further, during this period T ₂₁ , the output terminal of the signal converter 31 is connected to the sample hold circuit 331 by the switch 35, and the output voltage value of the signal converter 31 is held by the sample hold circuit 331. During this period T ₂₁ , AD conversion processing is performed by the AD converter 33, and the digital value is output to the control unit 40. Digital value output at this time are those corresponding to the detection signal value of the photodetector 21 _3.

Subsequent operations are the same. In this configuration example, the two signal converters 31 and 32 alternately input detection signals to accumulate charges in synchronization with the irradiation period of each of _{the light sources 11 1 to} 11 _3. During the period when one signal converter inputs the detection signal and stores the charge, the AD converter 33 digitally sets the output voltage value of the other signal converter that stores the charge in the previous period. And output the digital value. Therefore, even while the AD converter 33 converts the output voltage value of one signal converter into a digital signal, the charge can be accumulated by the other signal converter.

The present invention is not limited to the above embodiment, and various modifications are possible. The number of measurement optical systems including a light source, a photodetector, and the like is set to 3 in the above embodiment, but may be 2 or 4 or more. Although the generated light generated in the sample irradiated with light is fluorescent in the above embodiment, it may be transmitted light, reflected light, scattered light, or light generated by a nonlinear optical phenomenon. A filter that selectively transmits light of a specific wavelength among the light output from the light source and a filter that selectively transmits light of a specific wavelength among the light generated by the sample may be provided as necessary.

The arrangement and configuration of the light source, the sample container, the photodetector, and other optical systems in the measurement optical system are not limited to the above embodiments. For example, the irradiation light may be guided by an optical fiber from the light source to the sample container, or the generated light may be guided by an optical fiber from the sample container to the optical detector. Further, as shown in FIG. 10, in the measurement optical system 3 _{n including the light source 11 n} and the photodetector 21 _n , a fluorescence transmission filter 22 _n is inserted between the sample container 2 _n and the photodetector 21 _n. In addition, lenses 23 _n and 24 _n may be provided. The fluorescence transmission filter 22 _n is preferably provided between the lens 23 _n and the lens 24 _n. In this configuration example, by the lens 23 _n, 24 _n for selectively guided to the photodetector 21 _n fluorescence generated in the specimen is provided, excitation light or light detectors scattered light 21 It is possible to suppress the incident on _n.

1 ... _{Photodetector, 2 1} to 2 ₃ ... Sample container, 3 _{1 to} 3 ₃ ... Measurement optical system, 10 ... Irradiation unit, 11 _{1 to} 11 ₃ ... Light source, 12 _{1 to} 12 ₃ ... Excitation light transmission filter, 13 ... light source drive circuit, 20 ... detector, ₂₁ 1 to 21 3 _... photodetector, ₂₂ 1-22 3 _... fluorescence transmitting filter, 30, 30A ... processing unit, 31 and 31A, 31B, 32 ... signal converter, 33 ... AD converter, 40 ... control unit, 50 ... input unit, 60 ... display unit, 70 ... storage unit.

Claims (11)

A device that measures the intensity of light generated in each of the plurality of samples in response to the irradiation of each of the plurality of samples with light.
An irradiation unit that includes a plurality of light sources provided on a one-to-one basis for the plurality of samples and outputs irradiation light emitted from each light source to the corresponding samples over different irradiation periods.
It includes a plurality of photodetectors provided on a one-to-one basis for the plurality of samples, and each photodetector detects the intensity of the generated light generated in response to the irradiation of the irradiation light in the corresponding sample. And a detector that outputs a detection signal
It has an input terminal in which detection signals output from each of the plurality of light detectors are commonly input as analog values, and is connected to the input terminal during an irradiation period in which each light source of the irradiation unit outputs the irradiation light. A processing unit that inputs an input analog value and outputs a digital value corresponding to the analog value as a value indicating the intensity of the generated light generated in the sample corresponding to the light source.
Bei to give a,
The irradiation unit outputs the irradiation light from each light source over different irradiation periods based on a synchronization signal indicating the irradiation period of each light source.
The processing unit performs conversion processing from an analog value to a digital value based on the synchronization signal.
Optical measuring device. A control unit that outputs the synchronization signal to the irradiation unit and the processing unit is further provided.
The optical measuring device according to claim 1. The processing unit has a signal converter that outputs a voltage value corresponding to the value of the detection signal input to the input terminal, and a signal converter that converts the voltage value output from the signal converter into a digital value and converts the digital value into a digital value. Including the AD converter to output,
The optical measuring device according to claim 1 or 2. The signal converter has a capacitance unit that stores electric charges based on a detection signal input to the input terminal, and includes an integrator that outputs a voltage value according to the amount of accumulated electric charges.
The optical measuring device according to claim 3. The signal converter includes the integrator which is the first integrator and the integrator which is the second integrator.
The first integrator and the second integrator alternately input the detection signal in synchronization with the irradiation period of each of the plurality of light sources.
The optical measuring device according to claim 4. It is a method of measuring the intensity of light generated in each of the plurality of samples in response to the irradiation of each of the plurality of samples with light.
In an irradiation unit including a plurality of light sources provided on a one-to-one basis for the plurality of samples, light irradiation is performed to output irradiation light emitted from each light source to the corresponding samples over different irradiation periods. Steps and
In the detection unit including a plurality of photodetectors provided in a one-to-one correspondence with the plurality of samples, the intensity of the generated light generated in response to the irradiation of the irradiation light in the corresponding sample by each photodetector. A light detection step that detects and outputs a detection signal,
In a processing unit having an input terminal in which detection signals output from each of the plurality of light detectors are commonly input as analog values, the input is made during the irradiation period in which each light source of the irradiation unit outputs the irradiation light. A signal processing step in which an analog value input to a terminal is input and a digital value corresponding to the analog value is output as a value indicating the intensity of generated light generated in a sample corresponding to the light source.
Only including,
In the light irradiation step, the irradiation light is output from each light source over different irradiation periods based on the synchronization signal indicating the irradiation period of each light source.
In the signal processing step, conversion processing from an analog value to a digital value is performed based on the synchronization signal.
Optical measurement method. A synchronization step of outputting the synchronization signal to the irradiation unit and the processing unit is further included.
The optical measurement method according to claim 6. The signal processing step includes a signal conversion step that outputs a voltage value corresponding to the value of the detection signal input to the input terminal, and an AD that converts the output voltage value into a digital value and outputs the digital value. Including conversion steps,
The optical measurement method according to claim 6 or 7. In the signal conversion step, an integrator is used to accumulate electric charges based on the detection signal input to the input terminal, and a voltage value corresponding to the accumulated electric charge is output.
The optical measurement method according to claim 8. In the signal conversion step, the two integrators are used to alternately input the detection signals in synchronization with the irradiation period of each of the plurality of light sources to accumulate charges.
The optical measurement method according to claim 9. The generated light is light generated by fluorescence, transmitted light, reflected light, scattered light, or a nonlinear optical phenomenon.
The optical measurement method according to any one of claims 6 to 10.

Images