Information processing device, microparticle analyzer, method of extracting particle information, method of distinguishing particles, analysis method, information processing system, and program for extracting particle information

Abstract

With the present technology, a principal objective is taken to be providing technology for: recognizing, from a signal-strength versus measurement-time waveform in which a liquid in which particles are present has been measured as a measurement subject, an ideal range of particle information for the particles; and extracting said information. As a result of having conducted assiduous research, the present inventors found out that by establishing a center time in addition to a pre-extraction time, a post-extraction time, and a threshold, an ideal range of particle information for a single particle can be recognized from a waveform a waveform of signal-strength versus measurement-time wherein a liquid in which particles are present has been measured as a measurement subject, and the impact of size, shape and properties of particles present in the measurement-subject liquid can be reduced.

Description

Information processing device, microparticle analysis device, particle information extraction method, particle discrimination method, analysis method, information processing system, and particle information extraction program

[0001] The present technology relates to an information processing device, a microparticle analysis device, a particle information extraction method, a particle discrimination method, an analysis method, an information processing system, and a particle information extraction program. More specifically, the present technology relates to an information processing device, a microparticle analysis device, a particle information extraction method, a particle discrimination method, an analysis method, an information processing system, and a particle information extraction program for particle information that extracts particle information of particles from a waveform of signal intensity versus measurement time measured in a liquid containing particles.

[0002] 2. Description of the Related Art Conventionally, a method has been known in which particle information on particles is extracted from a waveform of signal intensity measured while a liquid containing particles is being measured.

[0003] For example, Patent Document 1 listed below discloses a method for performing multi-color measurement by correcting the fluorescence intensity of a signal intensity waveform having multiple peaks measured in an apparatus for measuring the characteristics of microparticles (e.g., a flow cytometer).

[0004] Japanese Patent Application Laid-Open No. 2011-232259

[0005] The main purpose of this technology is to provide a technology that identifies an appropriate range of particle information for a particle from the waveform of signal intensity versus measurement time when measuring a liquid containing particles, and extracts that information.

[0006] As a result of extensive research, the inventors have found that by setting a center time in addition to a pre-extraction time, post-extraction time, and threshold value, it is possible to identify an appropriate range of particle information for a single particle from the waveform of signal intensity versus measurement time measured with a liquid containing particles as the measurement target, and to reduce the effects of the size, shape, and quality of particles present in the liquid being measured.

[0007] That is, the present technology provides an information processing device that includes a receiving unit that acquires at least one of information about a sample containing microparticles in a microparticle analysis device or information about the measurement conditions of the sample, an extraction unit that extracts particle information about one particle from a waveform of signal intensity versus measurement time from microparticles contained in the sample measured by the microparticle analysis device, and an input unit that inputs mode selection information for selecting a mode for the extraction unit, wherein the extraction unit includes mode selection means for selecting between a normal extraction mode and at least one or more center time fixed extraction modes, and can select the center time fixed extraction mode based on the mode selection information input to the input unit. The center-time fixed extraction mode may use a preset pre-extraction time, post-extraction time, threshold, and center time to identify a point at which the signal intensity exceeds the threshold as an extraction start reference point, and identify an earlier ending point among a center-time end point at which the center time ends with the extraction start reference point as a starting point and a threshold drop point at which the signal intensity finally falls below the threshold within the center time with the extraction start reference point as a starting point as an extraction end reference point, and extract, as particle information for one particle, a waveform from an extraction start point that is obtained by tracing back the pre-extraction time from the extraction start reference point to an extraction end point at which the post-extraction time has elapsed from the extraction end reference point. The extractor may include center time determination means for adjusting and setting the center time so that the proportion of particle information extracted when the center time end point is identified as the extraction end reference point is 10% or less of the total number of extracted particle information. In the normal extraction mode, a point where the signal intensity exceeds the threshold is recognized as an extraction start reference point, a threshold drop point where the signal intensity becomes equal to or less than the threshold is recognized as an extraction end reference point, and a waveform from an extraction start point that is obtained by tracing back the pre-extraction time from the extraction start reference point to an extraction end point that is obtained by tracing back the post-extraction time from the extraction end reference point may be extracted as particle information for one particle. In this technology, the mode selection information may be input manually, by reading the measurement object, or by reading the measurement information.When the extraction unit of the information processing device of the present technology includes a mode selection means for selecting between a center-time fixed extraction mode and a normal extraction mode, the information processing device may further include a calculation means for calculating particle diameters from particle information, and when the average particle diameter of the particles is 10 μm or more, the mode selection means may select the center-time fixed extraction mode. The information processing device of the present technology may further include an analysis unit for analyzing the waveform of the extracted particle information. The present technology also provides a microparticle analysis device including the information processing device of the present technology.

[0008] Next, the present technology provides a particle information extraction method for extracting particle information from a waveform of signal intensity versus measurement time measured in a liquid containing particles, the method comprising: setting a pre-extraction time, a post-extraction time, a threshold, and a center time; identifying a point in the waveform at which the signal intensity exceeds the threshold as an extraction start reference point; identifying the earliest ending point among a center time end point starting from the extraction start reference point and a threshold drop point within the center time starting from the extraction start reference point at which the signal intensity falls below the threshold as an extraction end reference point; and extracting particle information for one particle from the waveform from the extraction start point, which is located back by the pre-extraction time from the extraction start reference point, to an extraction end point at which the post-extraction time has elapsed from the extraction end reference point. The center time may be set by adjusting the ratio of particle information extracted when the center time end point is identified as the extraction end reference point to the total number of extracted particle information, so that the ratio is 10% or less. The particle diameter of the particles related to the particle information extracted by this technology may be 10 μm or more, and the particles may contain a carrier such as a carrier. Furthermore, the liquid to be measured may have 10,000,000 particles or less per 100 μl of liquid. This technology also provides a particle discrimination method that discriminates particles based on the waveform shape of particle information extracted by executing the particle information extraction method of this technology. Furthermore, this technology also provides a method for analyzing the particle information extracted by executing the particle information extraction method of this technology.

[0009] Next, the present technology provides an information processing system comprising: a measurement system that measures a waveform of signal intensity versus measurement time using a liquid containing microparticles as a measurement object; a receiving system that acquires at least one of information about the measurement object from the measurement system or information about the measurement conditions of the measurement object; an extraction system that extracts particle information about a single particle from the waveform of signal intensity versus measurement time from microparticles contained in the sample measured by a microparticle analysis device; and an input system that inputs mode selection information for selecting a mode for the extraction system, wherein the extraction system comprises a mode selection means for selecting between a normal extraction mode and at least one or more fixed center time extraction modes, and the information processing system can select the fixed center time extraction mode based on the mode selection information input to the input system. The center-time fixed extraction mode uses a preset pre-extraction time, post-extraction time, threshold, and center time to identify a point at which the signal intensity exceeds the threshold as an extraction start reference point, and identifies the earlier ending point of a center time end point at which the center time ends with the extraction start reference point as a start point, or a threshold drop point within the center time with the extraction start reference point as a start point at which the signal intensity finally becomes equal to or less than the threshold as an extraction end reference point, and extracts, from the waveform, a waveform from an extraction start point that is backtracked by the pre-extraction time from the extraction start reference point to an extraction end point at which the post-extraction time has passed from the extraction end reference point as particle information for one particle.The present technology also provides a particle information extraction program that extracts particle information about particles from a waveform of signal intensity versus measurement time, measured using a liquid containing particles as a measurement target. The program uses a preset pre-extraction time, post-extraction time, threshold, and center time to identify a point in the waveform where the signal intensity exceeds the threshold as an extraction start reference point, and identifies the earliest ending point among the center time end point, starting from the extraction start reference point and the threshold drop point, where the signal intensity last becomes equal to or less than the threshold within the center time starting from the extraction start reference point, as an extraction end reference point. The program extracts particle information about a single particle from the waveform, starting from the extraction start point, which is located back by the pre-extraction time from the extraction start reference point, to the extraction end point, where the post-extraction time has passed from the extraction end reference point.

[0010] 1 shows an example of a flow diagram of a particle information extraction method (center time fixed extraction mode) of the present technology. 2 shows an example of a flow diagram of a normal particle information extraction method (normal extraction mode). 3 shows an image diagram of extracting particle information about particles having one peak as particle information using the normal extraction mode. 4 shows an image diagram of extracting particle information about particles having multiple peaks as particle information using the normal extraction mode. 5 shows an image diagram of extracting particle information about particles having multiple peaks as particle information using the center time fixed extraction mode. 6 shows an image diagram of a case where the center time is set shorter when extracting particle information about particles having multiple peaks as particle information using the center time fixed extraction mode. 7 shows an image diagram of a case where the center time is set even shorter when extracting particle information about particles having multiple peaks as particle information using the center time fixed extraction mode. 8 shows an image diagram of extracting particle information about particles having one peak as particle information using the center time fixed extraction mode. 9 shows an image diagram of extracting particle information about another particle having multiple peaks as particle information using the center time fixed extraction mode. 10 shows an image diagram of extracting particle information about another particle having multiple peaks as particle information using the center time fixed extraction mode. 1 shows an image diagram of a case where a short center time is set when particle information about particles having multiple peaks as particle information is extracted using a fixed center time extraction mode. FIG. 1 shows an image diagram of extracting particle information about particles having multiple peaks as particle information using a modified version of the fixed center time extraction mode. FIG. 1 shows an example of a flow diagram for setting the center time. FIG. 1 shows an image diagram illustrating the effect on the number of events when the center time is set short. FIG. 1 shows an image diagram illustrating the effect on the number of events when the center time is set sufficiently long. FIG. 1 shows an example of a waveform of signal intensity when particles consisting of only carriers are measured. FIG. 1 shows an example of a waveform of signal intensity when particles consisting of only cells are measured. FIG. 1 shows an example of a waveform of signal intensity when particles consisting of carriers carrying cells are measured. FIG. 1 shows an example of a waveform of signal intensity when other particles are measured. FIG. 2 is a diagram schematically showing an example of the overall configuration of an information processing device of the present technology. FIG. 2 is a diagram schematically showing the overall configuration of a biological sample analyzer.

[0011] Preferred embodiments of the present technology will be described below. However, the embodiments shown below are examples of typical embodiments of the present technology, and the present technology is not limited to only the preferred embodiments below and can be freely modified within the scope of the present technology.

[0012] [Method for extracting particle information] When measuring particles present in a liquid using a flow cell or the like having a measurement flow path, particle information about the particles is extracted, for example, from a graph of the waveform of the measurement results of the signal intensity of forward scattering (FSC) of light irradiated by the particles against the measurement time.

[0013] Here, the signal intensity waveform of the forward scattered light from the particles to be measured may differ in signal intensity level, shape, and pattern depending on the size and type of the particle, and a waveform relating to one particle may be recognized as a waveform relating to two particle information. Incorrectly recognizing the number of particle information pieces or the signal intensity waveform may result in errors in subsequent analysis or in particle identification results.

[0014] In the particle information extraction method according to the present technology, when particle information of a particle is extracted from a waveform of signal intensity versus measurement time measured in a liquid containing particles, a pre-extraction time (PreFetch), a post-extraction time (PostFetch), a threshold (Threshold), and a center time (SeekSpan) are set. By setting the center time, the present technology can suitably extract particle information about a single particle from the waveform. A more detailed explanation will be given below using the figures.

[0015] Fig. 1 is an example of a flow diagram of the particle information extraction method of the present technology, and Fig. 2 is an example of a flow diagram of a general particle information extraction method. As shown in these figures, the particle information extraction method of the present technology differs from the general particle information extraction method in that a center time is set in addition to a pre-extraction time, a post-extraction time, and a threshold value.

[0016] In Fig. 1, in order to easily understand the differences from the ordinary particle information extraction method shown in Fig. 2, the flow shows that the center time is set after the pre-extraction time, post-extraction time, and threshold value are set, but the center time may be set before the pre-extraction time, post-extraction time, and threshold value are set. Furthermore, there is no particular restriction on the order in which the pre-extraction time, post-extraction time, threshold value, and center time are set, and these items can be set in any order.

[0017] The pre-extraction time and post-extraction time can be set to any measurement time value greater than or equal to 0, for example, based on the waveform pattern of the change in signal strength detected on the vertical axis relative to the measurement time on the horizontal axis.

[0018] The threshold value can be set to any signal strength value equal to or greater than 0, for example, by referring to the waveform shape of the change in signal strength detected on the vertical axis against the measurement time on the horizontal axis.

[0019] The center time can be set to any measurement time value based on, for example, the waveform pattern of the change in signal strength detected on the vertical axis relative to the measurement time on the horizontal axis of interest. The center time may also be adjusted using a suitable setting method for the center time, which will be described later.

[0020] To extract a waveform relating to one particle from a graph of signal intensity versus measurement time, measured using a liquid containing particles as the measurement target, an extraction start reference point that serves as the reference for the start portion of the waveform relating to the particle information and an extraction end reference point that serves as the reference for the end portion of the waveform relating to the particle information are identified, and the waveform from the extraction start point, which is located back from the extraction start reference point by the pre-extraction time, to the extraction end point, which is located from the extraction end reference point by the elapse of the post-extraction time, is extracted as particle information for one particle.

[0021] A collection of information extracted as particle information for one particle is called an event, and the measurement time from the extraction start point to the extraction end point is called the measurement time length for one event, and is called Width.

[0022] The extraction start reference point is identified by the same procedure in the particle information extraction method of the present technology shown in the example of Fig. 1 and the ordinary particle information extraction method shown in the example of Fig. 2. Specifically, from a graph of the waveform of signal intensity versus measurement time, the point at which the signal intensity exceeds a set threshold (Cross Up) is identified as the extraction start reference point.

[0023] On the other hand, the determination of the extraction end reference point is performed using a procedure that differs between the particle information extraction method of this technology and the ordinary particle information extraction method.

[0024] In the ordinary particle information extraction method shown in the example of Fig. 2, as described above, a threshold cross-down point (cross-down) that appears after the identified extraction start reference point and at which the signal intensity falls below the set threshold is recognized as the extraction end reference point. In contrast, in the particle information extraction method of the present technology shown in the example of Fig. 1, as described above, the identified extraction start reference point is used as the start point and recognized as the extraction end reference point. For example, the center time end point at which the set center time ends and the last threshold cross-down point that appears within the center time starting from the extraction start reference point are recognized as the extraction end reference point, whichever ends earlier.

[0025] Below, we will explain in more detail the differences between the particle information extraction method of this technology and the ordinary particle information extraction method using an example of a graph of the waveform of signal intensity versus measurement time contained in measurement information measured using a liquid containing particles as the measurement target.

[0026] The measurement information from which particle information is extracted using this technology may be measurement information measured by a measuring device, such as a microparticle analyzer, that can measure a liquid containing particles as a measurement target, and transferred directly without being stored on a storage medium, or past measurement information stored on a storage medium may be used.

[0027] <Method for extracting normal particle information> In order to clarify the features of the method for extracting particle information of the present technology, we will first explain the procedure for extracting normal particle information from the waveform of signal intensity versus measurement time measured using a liquid containing particles as the measurement target, and the challenges involved.

[0028] FIG. 3 shows an image of particle information about particles having one peak as particle information extracted from a graph of the signal intensity waveform versus measurement time, obtained by measuring a liquid containing particles using a conventional particle information extraction method. The waveform shown in FIG. 3 shows the change in detected signal intensity on the vertical axis versus measurement time on the horizontal axis. Note that Auto Setup Beads (sold by Sony Biotechnology) were used as the particles in FIG. 3 . The signal intensity is the signal intensity measured by forward scattering (FSC / Forward Scatter) when light is irradiated onto the measurement object. Note that the signal intensity used in this technology is not limited to the signal intensity of forward scattering, but the signal intensity of the data used in this specification is the signal intensity of the forward scattering, unless otherwise specified.

[0029] In a typical particle information extraction method, a pre-extraction time, a post-extraction time, and a threshold value are set according to the flow shown in Fig. 2. In the waveform graph, the point where the signal intensity graph exceeds the threshold value (the Threshold line in Fig. 3) (Cross Up in Fig. 3) is the extraction start reference point. Thereafter, the point where the signal intensity graph falls below the threshold value (threshold drop point / Cross Down in Fig. 3) is the extraction end reference point.

[0030] Thereafter, using the certified extraction start reference point and extraction end reference point as described above, the width for one event is determined to be from the extraction start point (DSP / Data Start Point in FIG. 3 ) that is obtained by tracing back the pre-extraction time (PreFetch in FIG. 3 ) from the extraction start reference point to the extraction end point (DEP / Data End Point in FIG. 3 ) that is obtained by tracing back the post-extraction time (PostFetch in FIG. 3 ) from the extraction end reference point, and the waveform during this period is extracted as particle information for one particle.

[0031] Next, we will consider the case of extracting particle information about particles having multiple peaks as particle information from a graph of the signal intensity waveform versus measurement time, as shown in Figure 4. The waveform shown in Figure 4, like the case of Figure 3, shows the change in detected signal intensity on the vertical axis versus the measurement time on the horizontal axis. The waveform shown in Figure 4 represents the change in signal intensity detected for a single particle, and is used as particle information for a single particle that has been confirmed to have multiple peaks. As an example of particles with complex surface shapes, non-spherical beads were used as the particles in Figure 4.

[0032] In the waveform shown in FIG. 4, there are two points (Cross Up in FIG. 4) where the graph showing the signal strength exceeds a threshold (Threshold line in FIG. 4) and two points (Cross Down in FIG. 4) where the graph showing the signal strength is equal to or less than the threshold.

[0033] According to the procedure of a typical particle information extraction method, the first cross-up that appears is the extraction start reference point, and the first cross-down that appears thereafter is the extraction end reference point. As a result, the width for one event is defined as the period from the extraction start point (DSP in FIG. 4 ), which is calculated by tracing back the pre-extraction time (PreFetch in FIG. 4 ) from the extraction start reference point, to the extraction end point (DEP in FIG. 4 ), which is calculated by tracing back the post-extraction time (PostFetch in FIG. 4 ) from the extraction end reference point, and the waveform during this period is extracted as particle information for one particle. In other words, with a typical particle information extraction method, when particle information for one particle is detected as multiple peaks, there is a risk that it will be extracted as particle information for two particles. This may change the number of extracted events, potentially leading to erroneous analysis or discrimination based on the waveform of signal intensity versus measurement time.

[0034] <Method for extracting particle information according to the present technology> In consideration of the above points, the present technology sets a center time and identifies an extraction end reference point based on the center time, thereby suitably extracting particle information about one particle. This will be described in more detail with reference to FIG. 5 .

[0035] The waveform shown in FIG. 5 is the same as the waveform shown in FIG. 4, and shows the change in signal intensity detected for one particle over measurement time.

[0036] In the particle information extraction method of the present technology, the pre-extraction time, post-extraction time, threshold value, and center time are set according to the flow shown in Fig. 1. As mentioned above, there is no restriction on the order in which the pre-extraction time, post-extraction time, threshold value, and center time are set, and these items can be set in any order.

[0037] Next, according to the flow shown in FIG. 1, the point (SP in FIG. 5) where the graph showing the signal intensity exceeds the threshold (Threshold line in FIG. 5) in the waveform graph in FIG. 5 becomes the extraction start reference point.

[0038] Next, in the waveform graph of FIG. 5 , when the extraction start reference point identified above is used as the starting point and the center time end point (MP in FIG. 5 ) at which the center time (Seek Span in FIG. 5 ) ends is compared with the threshold drop point (Cross Down in FIG. 5 ) at which the signal intensity finally becomes equal to or lower than the threshold within the center time starting from the extraction start reference point, the last threshold drop point ends earlier, and therefore this last threshold drop point becomes the extraction end reference point (EP in FIG. 5 ).

[0039] Then, as described above, using the certified extraction start reference point and extraction end reference point, the width for one event is determined to be from the extraction start point (DSP in FIG. 5 ), which is calculated by going back a pre-extraction time (PreFetch in FIG. 5 ) from the extraction start reference point, to the extraction end point (DEP in FIG. 5 ), which is calculated by passing a post-extraction time (PostFetch in FIG. 5 ) from the extraction end reference point, and the waveform during this period is extracted as particle information for one particle.

[0040] When the particle information extraction method of the present technology is used, even when a liquid containing particles is measured as the measurement object and the waveform of the signal intensity detected for one particle versus measurement time has multiple peaks, it can be confirmed that the multiple peaks can be suitably extracted as particle information about one particle.

[0041] As in the example of Figure 5, when the last threshold drop point that appears within the center time is recognized as the extraction end reference point, the distance on the horizontal axis from the extraction start point to the extraction end point (the length of the measurement time for the target particle) varies depending on the position of the last threshold drop point that appears within the center time.

[0042] Fig. 6 is an image diagram of a case where the center time is set short when detecting particle information from a waveform with multiple peaks. The waveform shown in Fig. 6 is the same as the waveforms shown in Fig. 4 and Fig. 5, and shows the change in signal intensity detected for one particle over measurement time.

[0043] In the case of Fig. 6, the central time is set shorter than in the case of Fig. 5. For this reason, in the case of Fig. 6, the point (SP in Fig. 6) at which the graph showing the same signal intensity as in Fig. 5 exceeds the threshold value (Threshold line in Fig. 5) becomes the extraction start reference point, but because the central time is shorter than in Fig. 5, when the recognized extraction start reference point is used as the starting point and the central time end point (MP in Fig. 6) at which the central time (Seek Span in Fig. 6) ends is compared with the threshold drop point (Cross Down in Fig. 6) at which the signal intensity finally becomes equal to or lower than the threshold value within the central time starting from the extraction start reference point, the central time end point ends earlier, and so this central time end point becomes the extraction end reference point (EP in Fig. 6).

[0044] Then, as described above, using the certified extraction start reference point and extraction end reference point, the width for one event is determined to be from the extraction start point (DSP in FIG. 6 ), which is calculated by going back a pre-extraction time (PreFetch in FIG. 6 ) from the extraction start reference point, to the extraction end point (DEP in FIG. 6 ), which is calculated by passing a post-extraction time (PostFetch in FIG. 6 ) from the extraction end reference point, and the waveform during this period is extracted as particle information for one particle.

[0045] In addition, as in the example of Figure 6, when the center time end point is recognized as the extraction end reference point, the distance on the horizontal axis from the extraction start point to the extraction end point (the length of the measurement time for one event, i.e., Width) is the sum of the set center time, pre-extraction time, and post-extraction time, and is a fixed value.

[0046] In the example shown in Fig. 6, multiple peaks contained in the waveform can be extracted as particle information related to one particle, but when the central time end point is recognized as the extraction end reference point, there may be cases where all peaks related to one particle in the waveform cannot be extracted as particle information related to one particle. An example of this is shown in Fig. 7.

[0047] Figure 7 is an image diagram when the center time is set even shorter than the example shown in Figure 6. The waveforms shown in Figure 7 are the same as those shown in Figures 4 to 6, and show the change in signal intensity detected for one particle with respect to the measurement time.

[0048] In the example of Fig. 7, when particle information about one particle is extracted according to the flow shown in Fig. 1, the central time end point (MP in Fig. 7) at which the set central time (Seek Span in Fig. 7) ends becomes the extraction end reference point (EP in Fig. 7), as shown in Fig. 7. Based on this, in the same procedure as in the previous example, the period from the extraction start point (DSP in Fig. 7) to the extraction end point (DEP in Fig. 7) is set as the width for one event, and the waveform during this period is extracted as particle information about one particle.

[0049] However, as shown in Fig. 7, it can be seen that not all peaks relating to one particle contained in the waveform are included between the extraction start point and the extraction end point. In other words, the center time set in the example shown in Fig. 7 is too short to suitably extract particle information relating to one particle from the target waveform of signal intensity versus measurement time, and is therefore not an appropriate value for the set center time.

[0050] That is, when the ratio of events for which the horizontal distance (width) from the extraction start point to the extraction end point is calculated as a fixed value by recognizing the end point of the central time as the extraction end reference point relative to the total number of detected particle information (total number of events) is high, there is a risk that particle information relating to one particle cannot be extracted from the waveform in many cases because the set central time is too short, as in the example shown in FIG. 7 .

[0051] In other words, in this technology, the validity of the set center time value can be evaluated by using as an index the ratio of events for which the horizontal distance (width) from the extraction start point to the extraction end point is calculated as a fixed value to the total number of extracted particle information (total number of events).

[0052] The particle information extraction method of the present technology can also suitably extract particle information about particles that have one peak as particle information, an example of which is shown in FIG.

[0053] The waveform shown in FIG. 8 shows the change in signal intensity detected for one particle over measurement time, and is the same as the waveform shown in FIG.

[0054] In the example of Fig. 8, a central time (Seek Span in Fig. 8) is set according to the flow shown in Fig. 1, and the central time end point (MP in Fig. 8) at which the set central time ends is compared with the threshold drop point (Cross Down in Fig. 8) at which the signal strength finally falls below the threshold within the central time, starting from the extraction start reference point (SP in Fig. 8) at which the signal strength for the measurement time exceeds the threshold. In the case of Fig. 8, the last threshold drop point ended earlier, so this last threshold drop point becomes the extraction end reference point (EP in Fig. 8).

[0055] Then, as in the other examples, using the certified extraction start reference point and extraction end reference point, the width for one event is determined to be from the extraction start point (DSP in FIG. 8 ), which is calculated by going back a pre-extraction time (PreFetch in FIG. 8 ) from the extraction start reference point, to the extraction end point (DEP in FIG. 8 ), which is calculated by passing a post-extraction time (PostFetch in FIG. 8 ) from the extraction end reference point, and the waveform during this period is extracted as particle information for one particle.

[0056] From FIG. 8, it can be seen that the particle information extraction method of the present technology can suitably extract particle information even for particles having one peak as particle information.

[0057] Next, the particle information extraction method of the present technology can naturally suitably extract multiple peaks from a waveform different from the waveforms shown in Figures 4 to 7 as particle information related to one particle. An example is shown in Figure 9.

[0058] The waveform shown in FIG. 9 shows the change in signal intensity detected for one particle over measurement time, with lymphocytes in human peripheral blood being the measurement target.

[0059] According to the flow shown in Fig. 1, a central time (Seek Span in Fig. 9) is set, and the central time end point (MP in Fig. 9) at which the set central time ends is compared with the threshold drop point (Cross Down on the right side in Fig. 9) at which the signal strength finally falls below the threshold within the central time, starting from the extraction start reference point (SP in Fig. 9) at which the signal strength for the measurement time exceeds the threshold. In the case of Fig. 9, the last threshold drop point ended earlier, so this last threshold drop point becomes the extraction end reference point (EP in Fig. 9).

[0060] Then, as in the other examples, using the certified extraction start reference point and extraction end reference point, the width for one event is determined from the extraction start point (DSP in FIG. 9 ), which is calculated by tracing back the pre-extraction time (PreFetch in FIG. 9 ) from the extraction start reference point, to the extraction end point (DEP in FIG. 9 ), which is calculated by tracing back the post-extraction time (PostFetch in FIG. 9 ) from the extraction end reference point, and the waveform during this period is extracted as particle information for one particle. This confirms that multiple peaks can be suitably extracted as particle information for one particle from the waveform in FIG. 9 as well.

[0061] Furthermore, the example in Fig. 10 confirms that the particle information extraction method of the present technology can suitably extract multiple peaks from a waveform that exhibits a different shape from the above-mentioned example as particle information related to a single particle. Note that the waveform in Fig. 10 shows the change in signal intensity detected for a single particle over measurement time, using HeLa cells derived from human cervical cancer as the measurement target.

[0062] According to the flow shown in Fig. 1, a central time (Seek Span in Fig. 10) is set, and the central time end point (MP in Fig. 10) at which the set central time ends is compared with the threshold drop point (Cross Down on the right side in Fig. 10) at which the signal strength finally falls below the threshold within the central time, starting from the extraction start reference point (SP in Fig. 10) at which the signal strength for the measurement time exceeds the threshold. In the case of Fig. 10, the last threshold drop point ended earlier, so this last threshold drop point becomes the extraction end reference point (EP in Fig. 10).

[0063] Then, as in the other examples, using the certified extraction start reference point and extraction end reference point, the width for one event is determined from the extraction start point (DSP in FIG. 10 ), which is calculated by tracing back the pre-extraction time (PreFetch in FIG. 10 ) from the extraction start reference point, to the extraction end point (DEP in FIG. 10 ), which is calculated by tracing back the post-extraction time (PostFetch in FIG. 10 ) from the extraction end reference point, and the waveform during this period is extracted as particle information for one particle. This confirms that multiple peaks can be suitably extracted as particle information for one particle from the waveform in FIG. 10 as well.

[0064] Also, in the waveform shown in FIG. 10 , if the center time is set to be short and all peaks relating to one particle in the waveform cannot be extracted as particle information relating to one particle, the center time end point (MP in FIG. 11 ) that ends earlier than the last threshold drop point (Cross Down on the right side in FIG. 11 ) becomes the extraction end reference point (EP in FIG. 11 ).

[0065] 6 or 7, the proportion of events calculated with a fixed horizontal distance (width) from the extraction start point to the extraction end point relative to the total number of detected particle information (total number of events) increases. Therefore, even for particles showing the waveform shown in Fig. 10, it can be confirmed that the validity of the set center time value can be evaluated by using as an index the proportion of events calculated with a fixed horizontal distance (width) from the extraction start point to the extraction end point relative to the total number of extracted particle information (total number of events).

[0066] <Modification of the method for extracting particle information according to the present technology> Next, a modification of the method for extracting particle information according to the present technology will be described with reference to Fig. 12. The waveform shown in Fig. 12 is the same as the waveform shown in Fig. 4.

[0067] In the particle information extraction method according to this modification, the extraction start reference point is used as the start point, and the center time end point at which the center time ends is recognized as the extraction end reference point. In other respects, the method is the same as the particle information extraction method according to the present technology described above.

[0068] More specifically, in the waveform graph of FIG. 12, the point (SP in FIG. 12) where the graph showing the signal intensity exceeds the threshold (Threshold line in FIG. 12) is the extraction start reference point.

[0069] Next, in the waveform graph of FIG. 12, the extraction start reference point identified above is set as the starting point, and the central time end point (MP in FIG. 12) at which the central time (Seek Span in FIG. 12) ends is identified as the extraction end reference point (EP in FIG. 12).

[0070] Then, as described above, using the certified extraction start reference point and extraction end reference point, the width for one event is determined to be from the extraction start point (DSP in FIG. 12 ), which is calculated by going back a pre-extraction time (PreFetch in FIG. 12 ) from the extraction start reference point, to the extraction end point (DEP in FIG. 12 ), which is calculated by passing a post-extraction time (PostFetch in FIG. 12 ) from the extraction end reference point, and the waveform during this period is extracted as particle information for one particle.

[0071] <Setting the Center Time> This technology sets an appropriate center time and identifies an extraction end reference point based on that center time, thereby suitably extracting particle information about a single particle. For this reason, setting the center time is important. Below, we will explain a suitable method for setting the center time in the particle information extraction method of this technology.

[0072] 13 shows a flow diagram for setting the central time. First, in the first step S101, a central time (Seek Span) is provisionally set. For example, the central time can be provisionally set as a range that can include particle information about one particle from the waveform pattern of the change in signal intensity detected on the vertical axis relative to the measurement time on the horizontal axis.

[0073] Next, in a second step S102, events are acquired based on the set center time, and in a third step S103, the distribution of widths calculated for each acquired event is confirmed. The distribution of widths can be confirmed, for example, by a histogram.

[0074] As mentioned above, when the proportion of events for which the width is calculated as a fixed value is high by recognizing the center time end point as the extraction end reference point relative to the total number of extracted particle information (total number of events), the histogram showing the distribution of width will look, for example, as shown in Figure 14.

[0075] In the histogram shown in Fig. 14, the horizontal axis represents the width value (unit: clock) and the vertical axis represents the number of events. When the end point of the central time is recognized as the reference point for ending the extraction, the width becomes a fixed value and its value becomes maximum. In the example of Fig. 14, when the width is 200, the end point of the central time is recognized as the reference point for ending the extraction and the width becomes a fixed value.

[0076] 14, the number of events when the width is 200 is significantly higher than when the width is other than 200. In other words, the proportion of particle information detected by identifying the center time end point as the extraction end reference point is high relative to the total number of detected particle information (total number of events).

[0077] Here, when the Width in FIG. 14 is 200, for example, particle events that have a relationship like the waveform in FIG. 6 or particle events that have a relationship like the waveform in FIG. 7 are counted with respect to the set center time (Seek Span).

[0078] If the total number of detected particle information (total number of events) is taken as 100%, and the end point of the center time is recognized as the extraction end reference point and the proportion of detected particle information is defined as the saturation rate, if the saturation rate is sufficiently small, the set center time is recognized as a valid center time according to the flow of FIG. 13, and the setting is terminated.

[0079] On the other hand, if the ratio of particle information detected when the end point of the center time is recognized as the extraction end reference point to the total number of detected particle information (total number of events) is high and the saturation rate is large, the center time is reset to a longer value according to the flow of FIG. 13 .

[0080] The guideline for the value when resetting the center time is affected by the characteristics of the particles being measured in the target waveform, the flow velocity during measurement, etc., but for example, a value of 10 μs to 20 μs or the like can be set as the maximum value of the center time, and the value of the center time can be adjusted within this maximum range.

[0081] Thereafter, events are acquired again using the set center time, and the distribution of widths calculated for each acquired event is checked.

[0082] As shown in the flow chart of Fig. 13, the above process is repeated until the saturation rate reaches a sufficiently small value, which can be set to any value, such as 10% or less, 8% or less, 5% or less, or 3% or less.

[0083] When the saturation rate is sufficiently small, below the arbitrary value shown above, a histogram showing the distribution of widths may look like that shown in Figure 15. In the example of Figure 15, when width is 270, the center time end point is recognized as the extraction end reference point, and width becomes a fixed value. Note that the saturation rate in the case of Figure 15 is 0.96%.

[0084] In the histogram of FIG. 15, it can be seen that the number of events when the width is 270 is not significantly higher than when the width is other than 270, and the saturation rate is sufficiently small.

[0085] In the example shown in Fig. 15, the saturation rate is sufficiently small, so it is possible to preferably confirm the distribution of events with a width of less than 270. In this example, for example, it is possible to preferably confirm the distribution of particle events with multiple peaks in particle information, which has a relationship like the waveform in Fig. 5 with respect to the set center time (seek span), or particle events with one peak in particle information, which has a relationship like the waveform in Fig. 8.

[0086] According to the flow of FIG. 13, if the saturation rate becomes sufficiently small as in the example shown in FIG. 15, the set center time is recognized as a valid center time, and the setting is terminated.

[0087] <Measurement target> This technology is a method for extracting particle information, in which a liquid containing particles is measured as a measurement target, and particle information of the particles is extracted from the waveform of signal intensity versus measurement time. As described above, by setting a center time and extracting particle information based on that center time, it is possible to reduce the effects of the size, shape, and quality of particles present in the liquid being measured.

[0088] The liquid containing particles, which is the target of the present technology and is the measurement target related to the waveform, is not particularly limited. Therefore, as described above, whether a single particle information piece has a complex waveform or a simple waveform, particle information can be suitably extracted without being limited by the shape of the waveform of the particle information.

[0089] On the other hand, in the particle information extraction method of the present technology, the width (corresponding to the calculation interval) becomes longer depending on the set center time. Therefore, for example, when the particle concentration is high compared to the set center time, information on multiple events may overlap within the width range. Therefore, the particle information extraction method of the present technology may be used in combination with a normal particle information extraction method that does not set a center time, depending on the measurement target related to the target waveform.

[0090] In particular, it is anticipated that measurement targets that are preferably extracted using the particle information extraction method of the present technology are particles present in a liquid, such as particles with large diameters of 10 μm or more, 30 μm or more, or 50 μm or more.

[0091] Furthermore, it is preferable to use the particle information extraction method of the present technology when the particle information has a complex waveform due to the complex surface shape of particles present in the liquid. Examples of particles with complex surface shapes include carriers holding biological components such as cells, carriers (single carriers not holding biological components), and particles with no symmetry.

[0092] The carrier may hold one or more cells or a plurality of cells. Furthermore, a biological component (e.g., a cell or a cell-derived component (e.g., a secretion)) may be held on the carrier. Holding a biological component on the carrier includes, for example, a case where the biological component is captured on the carrier or a case where the biological component is encapsulated in the carrier. The carrier may be, for example, a carrier used for secretion analysis. Furthermore, a carrier encapsulating a biological component may be, for example, an emulsion. The emulsion may be a multiple emulsion. Examples of multiple emulsions include oil-in-water-in-oil ("o / w / o") and water-in-oil-in-water ("w / o / w") emulsions. Furthermore, the carrier may be in a form in which beads or the like hold the biological component. Such forms also include carriers such as carriers and charged particles.

[0093] The cells held on the carrier may include, for example, antibody-secreting cells and / or antibody-binding cells. The shape of the carrier is not particularly limited, and may have any particle shape such as a spherical, ellipsoidal, or rod-like shape.

[0094] Furthermore, the complex waveform of particle information may be due to the particle size and shape of the particles present in the liquid being measured, or may be due to multiple particles flowing close to each other. Therefore, the frequency with which particles pass through the detection unit may be reduced by adjusting the number of particles per unit volume of the liquid being measured to a certain number or less. For example, by adjusting the number of particles present in 100 μl of the liquid being measured to 10,000,000 or less, 10,000 or less, 1,000 or less, or 100 or less, it may be possible to avoid overlapping information from multiple events within the Width range.

[0095] Alternatively, the flow rate per unit time of the liquid to be measured flowing through the flow path of the microparticle analyzer may be adjusted to decrease the frequency at which particles pass through the detection unit, for example, by changing the sheath pressure or the orifice size.

[0096] Here, the biological component may be a component obtained from a living organism. Examples of biological components include, but are not limited to, biological particles, components contained in biological particles, and secretions secreted from biological particles. The biological component includes various components derived from a living organism.

[0097] The biological particle may be a biological particle, such as a cell, a microorganism, or a biologically-related particle. The biological particle may be a single particle or a group (particularly an aggregate) of multiple biological particles. The biological particle may be a microorganism, such as a cell, such as an animal cell (e.g., a blood cell) or a plant cell, a bacterium, such as Escherichia coli, a virus, such as tobacco mosaic virus, or a fungus, such as yeast.

[0098] Examples of components contained in the bioparticles include, but are not limited to, bioparticle components that make up cells, such as chromosomes, liposomes, mitochondria, and various organelles (cellular organelles), as well as biologically derived components such as biopolymers, such as nucleic acids, proteins, lipids, sugar chains, or complexes of these.

[0099] Examples of secreted products from the bioparticles include, but are not limited to, exosomes, microvesicles, and apoptotic bodies. Exosomes are membrane vesicles formed by the invagination of endosomes formed within cells by endocytosis, which are then released extracellularly. Common membrane proteins contained in exosomes include tetraspanins (e.g., CD9, CD63, CD81), integrins, and major histocompatibility complex (MHC) molecules.

[0100] [Method for Distinguishing Particles] Particles can also be distinguished based on the waveform shape of particle information extracted by executing the particle information extraction method of the present technology. An example of this will be described with reference to Figs. 16 to 18 .

[0101] Figures 16 to 18 are graphs each showing nine pieces of particle information extracted using this technology, with nine waveforms of the extracted particle information superimposed on each other. Figure 16 relates to a waveform when the particles present in the liquid are carriers that are independent carriers without cells or the like. The carriers used were the same non-spherical beads used as the particles in Figure 4. Figure 17 relates to a waveform when the particles present in the liquid are cells. Jurkat cells were used. Figure 18 relates to a waveform when the particles present in the liquid are carriers carrying cells. The cells used were the same Jurkat cells as used in Figure 17, and the carrier used was the same carrier as used in Figure 16.

[0102] In each of Figures 16 to 18, the waveforms of the nine pieces of particle information displayed in an overlapping manner vary, but the shapes of the nine extracted waveforms are similar, confirming that particle information can be suitably extracted using this technology.

[0103] Furthermore, for HeLa cells derived from human cervical cancer shown in the example of Figure 10, the waveform shape of the particle information extracted by executing the particle information extraction method of the present technology is compared with the method similar to that of Figures 16 to 18 described above, as shown in Figure 19, and it can be confirmed that particle information can be suitably extracted by the present technology.

[0104] Furthermore, based on the waveform shapes of the particle information shown in FIGS. 16 to 19, it is possible to determine whether particles present in a liquid are particles such as cells or carriers.

[0105] Furthermore, by combining identification techniques using compounds specific to biological components, such as the aforementioned barcode molecules, fluorescent materials, affinity molecules, or reagent molecules, it is possible to distinguish between carriers that do not carry cells and carriers that carry cells.

[0106] [Method for analyzing a measurement object] The particle information extracted by executing the particle information extraction method of the present technology can also be used to analyze a measurement object. For example, analysis of particle size, shape, quality, etc., can be achieved using the signal intensity of the waveform of the particle information (height in the vertical axis direction of the waveform) or the integrated value of the signal intensity of the waveform of the particle information (area), or analysis of biological components in the measurement object from the particle information. In this case, depending on the purpose of the analysis, the extracted particle information may be processed as necessary, as long as the effect of the present technology is not significantly impaired.

[0107] [Particle Information Detection Program] As described above, this technology can extract particle information from the waveform of signal intensity versus measurement time measured in a liquid containing particles, while reducing the effects of the size, shape, and quality of particles present in the liquid. It is also possible to construct a particle information extraction program that controls the process of extracting this particle information.

[0108] That is, the present technology can also be implemented as a particle information extraction program that extracts particle information about particles from a waveform of signal intensity versus measurement time measured in a liquid containing particles, using a preset pre-extraction time, post-extraction time, threshold, and center time, and identifies a point in the waveform where the signal intensity exceeds the threshold as an extraction start reference point, and identifies the extraction start reference point as a starting point and an extraction end reference point, and extracts particle information about a single particle from the waveform from an extraction start point that is backtracking from the extraction start reference point by the pre-extraction time to an extraction end point where the post-extraction time has elapsed from the extraction end reference point. Here, the extraction end reference point may be identified as the earlier of the center time end point at which the center time ends and the threshold drop point at which the signal intensity last becomes equal to or less than the threshold within the center time starting from the extraction start reference point.

[0109] By executing the particle information extraction program of this technology, the technology can suitably extract particle information of the particles from the waveform of signal intensity versus measurement time measured in a liquid containing particles. Note that the particle information extraction program of this technology may be combined with any program as needed, depending on the purpose of the program, as long as the desired physical properties are not impaired.

[0110] The particle information extraction program of the present technology can be stored as a program in hardware resources including, for example, a personal computer, a control unit including a CPU, and a recording medium (non-volatile memory (such as a USB memory), HDD, CD, etc.), and can be operated by the personal computer or the control unit.

[0111] [Information Processing Device] The present technology can also be implemented as an information processing device that executes the present technology.

[0112] 20 is a diagram schematically illustrating an example of the overall configuration of an information processing device according to the present technology. In the diagram, solid lines indicate components essential to the information processing device according to the present technology, and dotted lines indicate components that the information processing device according to the present technology optionally includes. Note that the configuration illustrated in FIG. 20 is an example of an information processing device according to the present technology, and may include components other than those illustrated in the diagram as long as the performance of the present technology is not impaired.

[0113] The information processing device of the present technology includes an extraction unit that extracts particle information of particles from a waveform of signal intensity with respect to measurement time included in measurement information obtained by measuring a liquid containing particles as a measurement target, and the extraction unit has a fixed center time extraction mode. Furthermore, the extraction unit may have a normal extraction mode.

[0114] The center-time fixed extraction mode is a setting for an information processing device of the present technology to realize the particle information extraction method of the present technology. That is, using a preset pre-extraction time, post-extraction time, threshold, and center time, a point at which the signal intensity exceeds the threshold is recognized as an extraction start reference point, and the extraction start reference point is recognized as a start point and an extraction end reference point. The waveform from the extraction start point, which is obtained by tracing back the pre-extraction time from the extraction start reference point, to the extraction end point, which is obtained by tracing back the post-extraction time from the extraction end reference point, may be extracted as particle information for one particle. Here, the extraction end reference point may be determined to be the earlier of the center-time end point at which the center time ends and the threshold drop point at which the signal intensity finally becomes equal to or less than the threshold within the center time starting from the extraction start reference point.

[0115] The center-time fixed extraction mode may have a plurality of center-time fixed extraction modes with different conditions in advance.

[0116] As with the particle information extraction method of the present technology, the pre-extraction time, post-extraction time, threshold value, and center time can be set to any desired values ​​by referring to the description in this specification.

[0117] The extraction unit of the information processing device of the present technology may include a center time determination means for executing the above-described preferred method for setting the center time. That is, the center time determination means adjusts and sets the center time so that the ratio of particle information extracted by identifying the end point of the center time as an extraction end reference point to the total number of extracted particle information is 10% or less.

[0118] In the normal extraction mode, the point at which the signal intensity exceeds the threshold is recognized as the extraction start reference point, and the threshold drop point at which the signal intensity becomes equal to or less than the threshold is recognized as the extraction end reference point. The waveform from the extraction start point, which is located back from the extraction start reference point by the pre-extraction time, to the extraction end point, which is located back from the extraction end reference point by the post-extraction time, is extracted as particle information for one particle.

[0119] The extraction unit of the information processing device of the present technology may include a mode selection means for selecting between a fixed center time extraction mode and a normal extraction mode. Here, the normal extraction mode is a mode for executing the normal particle information extraction method described above. By being able to select between the fixed center time extraction mode and the normal extraction mode, it is possible to select a mode according to the measurement target and effectively prevent information of multiple events from being included in the Width range.

[0120] <Input Unit> When the information processing device of the present technology includes a mode selection unit that selects between a center time fixed extraction mode and a normal extraction mode, the information processing device may further include an input unit that inputs mode selection information for selecting a mode. In this case, the mode selection unit selects between the center time fixed extraction mode and the normal extraction mode based on the mode selection information.

[0121] When the information processing device of the present technology is equipped with an input unit, the method of inputting mode selection information to the input unit is not particularly limited, but examples include manual input by a user, reading of the measurement target by the information processing device of the present technology, or reading of measurement information by the information processing device of the present technology.

[0122] Reading the measurement target can be, for example, detecting the nozzle shape of the measurement target, detecting the liquid by sending a liquid equipped with an identification means, or reading an identification number assigned to a container or the like of the liquid to be measured, where particles are present. The identification number used can be any means used as an identification number, such as a barcode or a two-dimensional barcode (QR Code (registered trademark)). The reading can be performed by the information processing device of the present technology, or by a device separate from the information processing device of the present technology that has a function for measuring the measurement target, and the results can be transferred to the information processing device of the present technology.

[0123] Reading measurement information can be realized by a method in which an information processing device of the present technology reads measurement information obtained by measuring a measurement object, a method in which an information processing device of the present technology receives measurement information from a device other than the information processing device of the present technology that has the function of measuring a measurement object using any transmission / reception means, and the information processing device of the present technology reads the received measurement information, or a method in which a device other than the information processing device of the present technology that has the function of measuring a measurement object reads the results from the measurement information and transfers them to the information processing device of the present technology.

[0124] <Calculation Means> When the information processing device of the present technology includes a mode selection means for selecting between a center time fixed extraction mode and a normal extraction mode, the information processing device of the present technology may further include a calculation means for calculating particle diameters from the particle information. By including the calculation means, the information processing device of the present technology can suitably read the measurement information and select a suitable detection mode.

[0125] In other words, when the particles have an average particle size larger than a certain size, based on the average particle size of the particles present in the liquid being measured calculated by the calculation means, the mode selection means can select the center time fixed extraction mode, which can more effectively avoid information from multiple events being included overlapping within the Width range.

[0126] The calculation means calculates the average particle size of the particles using, for example, the strength of the signal intensity of the waveform of the particle information (height in the vertical axis direction of the waveform) or the integrated value (area) of the signal intensity of the waveform of the particle information as an index.

[0127] The average particle size that is determined to be a particle with a certain size or larger will be affected by the shape and concentration of the particles present in the liquid being measured, but values ​​such as 10 μm or larger, 30 μm or larger, or 50 μm or larger may be used.

[0128] When the mode selection means of the information processing device of the present technology selects a mode, the information processing device of the present technology may change parameters related to the measurement conditions of the microparticle analyzer according to the selected mode. For example, the flow rate of the flow path in the microparticle sorting device may be controlled in a fixed center time extraction mode. The flow rate may be controlled by, for example, changing the sheath pressure or the orifice size. When changing these parameters, the change may be made by any method, such as manual setting by the user, reading the measurement target by the information processing device of the present technology, or reading the measurement information by the information processing device of the present technology.

[0129] <Analysis Unit> The information processing device of the present technology may further include an analysis unit that analyzes the waveform of the extracted particle information. By including the analysis unit, for example, it is possible to analyze biological components in the measurement target. Furthermore, the analysis unit can process and use the extracted particle information depending on the purpose of the analysis, within a range that does not significantly impair the effects of the present technology.

[0130] In the information processing device of the present technology, the waveform of the signal intensity versus measurement time from which the extraction unit extracts particle information of particles may be, for example, measurement information of a liquid containing particles measured by a microparticle analysis device described below.

[0131] <Receiving Unit> The information processing device of the present technology may further include a receiving unit that receives the waveform. By including the receiving unit, for example, measurement information from a microparticle analysis device can be efficiently received, and the information processing device of the present technology can read the measurement information. Furthermore, if the information processing device of the present technology includes an input unit, including the receiving unit can efficiently input mode selection information to the input unit.

[0132] <Other Configurations> The information processing device of the present technology may include other configurations in addition to the above-described configurations as needed, as long as the desired physical properties are not impaired. Examples of the other configurations include a storage unit that stores measurement information and the like, a calculation unit, and the like.

[0133] In the information processing device of the present technology, the above-mentioned components can be realized by any method. For example, each component can be incorporated into a processing device such as a personal computer, or can be stored as a program in a hardware resource such as a control unit including a CPU and a recording medium (non-volatile memory (USB memory, etc.), HDD, CD, etc.), and can be operated by the processing device or control unit of the personal computer. Each of the above-mentioned components can be provided in a single processing device, or can be distributed among multiple processing devices.

[0134] [Information Processing System] As described above, when a system is constructed by combining a plurality of processing devices such as personal computers, the present technology is executed as the entire system.

[0135] That is, the present technology can also be implemented as an information processing system that includes a measurement system for measuring a waveform of signal intensity versus measurement time in a liquid containing particles as a measurement target, a receiving system for receiving the waveform from the measurement system, and an extraction system for extracting particle information about the particles from the waveform, wherein the extraction system uses a predetermined pre-extraction time, post-extraction time, threshold, and center time to identify a point at which the signal intensity exceeds the threshold as an extraction start reference point, and identifies the extraction start reference point as an extraction end reference point, and extracts particle information about a single particle from the waveform from an extraction start point that is obtained by tracing back the pre-extraction time from the extraction start reference point to an extraction end point that is obtained by tracing back the post-extraction time from the extraction end reference point. Here, the extraction end reference point may be identified as the earlier of the center time end point at which the center time ends and the threshold drop point at which the signal intensity last becomes equal to or less than the threshold within the center time starting from the extraction start reference point.

[0136] The information processing device of the present technology and each processing device that constitutes the information processing system can be implemented as a finished product, but can also be implemented in a form incorporated into a measuring device that can measure a liquid containing particles as a measurement target, such as a microparticle analyzer.

[0137] <Microparticle analysis device> As described above, the information processing device of the present technology can be incorporated into a microparticle analysis device and implemented as a microparticle analysis device equipped with the information processing device of the present technology. Below, a biological sample analysis device will be described as an example of a microparticle analysis device. Note that in the biological sample analysis device, the present technology can be implemented by being incorporated into, for example, an information processing unit or the like.

[0138] An example configuration of a biological sample analyzer according to the present disclosure is shown in Figure 21. The biological sample analyzer 6100 shown in Figure 21 includes a light irradiation unit 6101 that irradiates light onto a biological sample S flowing through a flow path C, a detection unit 6102 that detects light generated by irradiating the biological sample S with light, and an information processing unit 6103 that processes information related to the light detected by the detection unit. Examples of the biological sample analyzer 6100 include a flow cytometer and an imaging cytometer. The biological sample analyzer 6100 may also include a fractionation unit 6104 that separates specific biological particles P from within the biological sample. An example of a biological sample analyzer 6100 that includes the fractionation unit is a cell sorter.

[0139] (Biological Sample) The biological sample S may be a liquid sample containing biological particles. The biological particles may be, for example, cells or non-cellular biological particles. The cells may be living cells, and more specific examples include blood cells such as red blood cells and white blood cells, and reproductive cells such as sperm and fertilized eggs. The cells may be directly collected from a specimen such as whole blood, or may be cultured cells obtained after culturing. Examples of the non-cellular biological particles include extracellular vesicles, particularly exosomes and microvesicles. The biological particles may be labeled with one or more labeling substances (e.g., dyes (particularly fluorescent dyes) and fluorescent dye-labeled antibodies). Note that the biological sample analyzer of the present disclosure may also analyze particles other than biological particles, such as beads for calibration purposes.

[0140] (Flow Channel) The flow channel C is configured to allow the biological sample S to flow. In particular, the flow channel C can be configured to form a flow in which biological particles contained in the biological sample are aligned in a substantially straight line. The flow channel structure including the flow channel C may be designed to form a laminar flow. In particular, the flow channel structure is designed to form a laminar flow in which the flow of the biological sample (sample flow) is surrounded by the flow of sheath liquid. The design of the flow channel structure may be appropriately selected by those skilled in the art, and a known design may be adopted. The flow channel C may be formed in a flow channel structure such as a microchip (a chip having flow channels on the order of micrometers) or a flow cell. The width of the flow channel C may be 1 mm or less, particularly 10 μm or more and 1 mm or less. The flow channel C and the flow channel structure including it may be formed from a material such as plastic or glass.

[0141] The biological sample analyzer of the present disclosure is configured so that light from light irradiation unit 6101 is irradiated onto the biological sample flowing within flow path C, and particularly onto biological particles within the biological sample. The biological sample analyzer of the present disclosure may be configured so that the interrogation point of light on the biological sample is within the flow path structure in which flow path C is formed, or so that the interrogation point of light is outside the flow path structure. An example of the former is a configuration in which the light is irradiated onto flow path C within a microchip or flow cell. In the latter, the light may be irradiated onto biological particles after they have left the flow path structure (particularly its nozzle portion), and an example of this is a jet-in-air flow cytometer.

[0142] (Light Irradiation Unit) The light irradiation unit 6101 includes a light source unit that emits light and a light-guiding optical system that guides the light to an irradiation point. The light source unit includes one or more light sources. The type of light source is, for example, a laser light source or an LED. The wavelength of the light emitted from each light source may be any of ultraviolet light, visible light, and infrared light. The light-guiding optical system includes optical components such as a beam splitter group, a mirror group, or an optical fiber. The light-guiding optical system may also include a lens group for focusing light, such as an objective lens. There may be one or more irradiation points where the light intersects with the biological sample. The light irradiation unit 6101 may be configured to focus light irradiated from one or more different light sources onto one irradiation point.

[0143] (Detection Unit) The detection unit 6102 includes at least one photodetector that detects light generated by irradiating the bioparticles with light. The detected light is, for example, fluorescence or scattered light (e.g., one or more of forward scattered light, back scattered light, and side scattered light). Each photodetector includes one or more light-receiving elements, for example, a photodetector array. Each photodetector may include one or more PMTs (photomultiplier tubes) and / or photodiodes such as APDs and MPPCs as light-receiving elements. The photodetector includes, for example, a PMT array in which multiple PMTs are arranged in a one-dimensional direction. The detection unit 6102 may also include an imaging element such as a CCD or CMOS. The detection unit 6102 can acquire images of the bioparticles (e.g., bright-field images, dark-field images, and fluorescence images) using the imaging element.

[0144] The detection unit 6102 includes a detection optical system that allows light of a predetermined detection wavelength to reach a corresponding photodetector. The detection optical system includes a spectroscopic unit such as a prism or a diffraction grating, or a wavelength separation unit such as a dichroic mirror or an optical filter. The detection optical system is configured to, for example, disperse light generated by irradiating bioparticles with light, and detect the dispersed light using a plurality of photodetectors, the number of which is greater than the number of fluorescent dyes with which the bioparticles are labeled. A flow cytometer that includes such a detection optical system is called a spectral flow cytometer. The detection optical system is also configured to, for example, separate light corresponding to the fluorescent wavelength range of a specific fluorescent dye from the light generated by irradiating bioparticles with light, and detect the separated light using a corresponding photodetector.

[0145] The detection unit 6102 may also include a signal processing unit that converts the electrical signal obtained by the photodetector into a digital signal. The signal processing unit may include an A / D converter as a device that performs the conversion. The digital signal obtained by the conversion by the signal processing unit may be transmitted to the information processing unit 6103. The digital signal may be handled by the information processing unit 6103 as data related to light (hereinafter also referred to as "light data"). The light data may be light data including, for example, fluorescent light data. More specifically, the light data may be light intensity data, and the light intensity may be light intensity data of light including fluorescent light (which may include feature quantities such as area, height, and width).

[0146] (Information Processing Unit) The information processing unit 6103 includes, for example, a processing unit that processes various data (e.g., optical data) and a storage unit that stores various data. When the processing unit acquires optical data corresponding to a fluorescent dye from the detection unit 6102, the processing unit may perform fluorescence spillover correction (compensation processing) on ​​the light intensity data. Furthermore, in the case of a spectral flow cytometer, the processing unit performs fluorescence separation processing on the optical data to acquire light intensity data corresponding to the fluorescent dye. The fluorescence separation processing may be performed, for example, according to the unmixing method described in Japanese Patent Application Laid-Open No. 2011-232259. When the detection unit 6102 includes an image sensor, the processing unit may acquire morphological information of bioparticles based on images acquired by the image sensor. The storage unit may be configured to store the acquired optical data. The storage unit may further be configured to store spectral reference data used in the unmixing processing.

[0147] If the biological sample analyzer 6100 includes a fractionating unit 6104 (described below), the information processing unit 6103 can determine whether to fractionate bioparticles based on the optical data and / or morphological information. The information processing unit 6103 can then control the fractionating unit 6104 based on the result of this determination, allowing the fractionating unit 6104 to fractionate the bioparticles.

[0148] The information processing unit 6103 may be configured to output various data (e.g., optical data and images). For example, the information processing unit 6103 may output various data (e.g., two-dimensional plots, spectral plots, etc.) generated based on the optical data. The information processing unit 6103 may also be configured to accept input of various data, such as accepting gating processing on a plot by a user. The information processing unit 6103 may include an output unit (e.g., a display, etc.) or an input unit (e.g., a keyboard, etc.) for executing the output or input.

[0149] The information processing unit 6103 may be configured as a general-purpose computer, for example, as an information processing device including a CPU, RAM, and ROM. The information processing unit 6103 may be included in a housing that includes the light irradiation unit 6101 and the detection unit 6102, or may be located outside the housing. Furthermore, various processes or functions performed by the information processing unit 6103 may be realized by a server computer or a cloud connected via a network.

[0150] (Sorting unit) The sorting unit 6104 sorts the bioparticles according to the determination result by the information processing unit 6103. The sorting method may be a method of generating droplets containing bioparticles by vibration, applying an electric charge to the droplets to be sorted, and controlling the direction of travel of the droplets using electrodes. The sorting method may also be a method of controlling the direction of travel of the bioparticles within the flow channel structure to perform sorting. The flow channel structure is provided with, for example, a control mechanism using pressure (spray or suction) or electric charge. An example of such a flow channel structure is a chip (for example, the chip described in JP 2020-76736 A) having a flow channel structure in which a flow channel C branches downstream into a recovery flow channel and a waste flow channel, and specific bioparticles are recovered into the recovery flow channel.

[0151] The present technology may have the following configuration: [1] An information processing device comprising: a receiving unit that acquires at least one of information about a sample containing microparticles in a microparticle analysis device or information about measurement conditions for the sample, an extracting unit that extracts particle information about one particle from a waveform of signal intensity versus measurement time from a microparticle contained in the sample measured by the microparticle analysis device, and an input unit that inputs mode selection information for selecting a mode for the extracting unit, wherein the extracting unit comprises mode selection means that selects between a normal extraction mode and at least one or more center-time fixed extraction modes, and is capable of selecting the center-time fixed extraction mode based on the mode selection information input to the input unit. [2] The information processing device according to [1], wherein the center-time fixed extraction mode uses a preset pre-extraction time, post-extraction time, threshold, and center time to identify a point at which the signal intensity exceeds the threshold as an extraction start reference point, and identify the earlier of a center-time end point at which the center time ends with the extraction start reference point as a starting point and a threshold drop point at which the signal intensity finally becomes equal to or less than the threshold within the center time with the extraction start reference point as a starting point as an extraction end reference point, and extracts, as particle information for one particle, a waveform from an extraction start point that is backtracking from the extraction start reference point by the pre-extraction time to an extraction end point at which the post-extraction time has elapsed from the extraction end reference point. [3] The information processing device according to [2], wherein the extraction unit includes center time determination means for adjusting and setting the center time so that a ratio of particle information extracted by identifying the center time end point as the extraction end reference point to a total number of extracted particle information is 10% or less. [4] The information processing device according to any one of [1] to [3], wherein the normal extraction mode recognizes a point where the signal intensity exceeds the threshold as an extraction start reference point, recognizes a threshold drop point where the signal intensity becomes equal to or less than the threshold as an extraction end reference point, and extracts, as particle information for one particle, a waveform from an extraction start point that is located back from the extraction start reference point by the pre-extraction time, to an extraction end point that is located back from the extraction end reference point by the post-extraction time.[5] The information processing device according to any one of [1] to [4], wherein the mode selection information is input manually, by reading the measurement target, or by reading the measurement information. [6] The information processing device according to any one of [1] to [5], wherein the extraction unit further comprises a calculation unit that calculates particle diameters from the particle information, and wherein the mode selection unit selects a center time fixed extraction mode when the average particle diameter of the particles is 10 μm or more. [7] The information processing device according to any one of [1] to [6], further comprising an analysis unit that analyzes the waveform of the extracted particle information. [8] A microparticle analysis device comprising the information processing device according to any one of [1] to [7]. [9] An information processing system comprising: a measurement system that measures a waveform of signal intensity versus measurement time using a liquid containing microparticles as a measurement object; a receiving system that acquires at least one of information about the measurement object from the measurement system or information about the measurement conditions of the measurement object; an extraction system that extracts particle information about one particle from the waveform of signal intensity versus measurement time from microparticles contained in the sample measured by a microparticle analyzer; and an input system that inputs mode selection information for selecting a mode of the extraction system, wherein the extraction system comprises mode selection means that selects between a normal extraction mode and at least one or more center time fixed extraction modes, and the center time fixed extraction mode can be selected based on the mode selection information input to the input system.

[10] The information processing system described in [9], wherein the center-time fixed extraction mode uses a pre-extraction time, post-extraction time, threshold, and center time that are set in advance, to identify a point at which the signal intensity exceeds the threshold as an extraction start reference point, and to identify the earlier ending point among a center-time end point at which the center time ends with the extraction start reference point as a start point and a threshold drop point at which the signal intensity finally becomes equal to or less than the threshold within the center time with the extraction start reference point as a start point, and to extract, as particle information for one particle, a waveform from an extraction start point that is back by the pre-extraction time from the extraction start reference point to an extraction end point at which the post-extraction time has passed from the extraction end reference point.

[11] An information processing apparatus comprising: an extraction unit that extracts particle information of a particle from a waveform of signal intensity versus measurement time included in measurement information obtained by measuring a liquid containing particles as a measurement target; the extraction unit has a center-time fixed extraction mode; and the center-time fixed extraction mode uses a preset pre-extraction time, post-extraction time, threshold, and center time to identify a point at which the signal intensity exceeds the threshold as an extraction start reference point; and identify the earliest ending point among a center-time end point at which the center time ends with the extraction start reference point as a start point, and a threshold drop point at which the signal intensity finally becomes equal to or less than the threshold within the center time with the extraction start reference point as a start point, and extracts, as particle information for one particle, waveforms from an extraction start point that is backtracking from the extraction start reference point by the pre-extraction time, to an extraction end point from the extraction end reference point at which the post-extraction time has passed.

[12] The information processing device according to

[11] , wherein the extraction unit comprises a center time determination means for adjusting and setting the center time so that the ratio of particle information extracted by recognizing a center time end point as an extraction end reference point to the total number of extracted particle information is 10% or less.

[13] The information processing device according to

[11] or

[12] , wherein the extraction unit comprises a mode selection means for selecting between the center time fixed extraction mode and a normal extraction mode, wherein the normal extraction mode recognizes a point at which the signal intensity exceeds the threshold as an extraction start reference point, and recognizes a threshold drop point at which the signal intensity becomes equal to or less than the threshold as an extraction end reference point, and extracts, as particle information for one particle, a waveform from an extraction start point that is obtained by tracing back the pre-extraction time from the extraction start reference point to an extraction end point at which the post-extraction time has elapsed from the extraction end reference point.

[14] The information processing device according to

[13] , further comprising an input unit for inputting mode selection information for selecting a mode, and selecting the center time fixed extraction mode or the normal extraction mode based on the mode selection information.

[15] The information processing device according to

[14] , wherein the mode selection information is input manually, by reading the measurement object, or by reading the measurement information.

[16] The information processing device according to any one of

[13] to

[15] , wherein the extraction unit further comprises a calculation unit that calculates particle diameters from the particle information, and wherein the mode selection unit selects a center time fixed extraction mode when the average particle diameter of the particles is 10 μm or more.

[17] The information processing device according to any one of

[11] to

[16] , further comprising an analysis unit that analyzes the waveform of the extracted particle information.

[18] The information processing device according to any one of

[11] to

[17] , wherein the waveform is measured by a microparticle analysis device.

[19] The information processing device according to any one of

[11] to

[18] , further comprising a receiving unit that receives the waveform.

[20] A microparticle analysis device comprising the information processing device according to any one of

[11] to

[19] .

[21] A method for extracting particle information from a waveform of signal intensity versus measurement time measured in a liquid containing particles, the method comprising: setting a pre-extraction time, a post-extraction time, a threshold, and a center time; identifying a point in the waveform at which the signal intensity exceeds the threshold as an extraction start reference point; identifying an earlier ending point among a center time end point starting from the extraction start reference point and a threshold drop point at which the signal intensity last becomes equal to or less than the threshold within the center time starting from the extraction start reference point as an extraction end reference point; and extracting, as particle information for one particle, a waveform from an extraction start point that is backtracking by the pre-extraction time from the extraction start reference point to an extraction end point at which the post-extraction time has elapsed.

[22] The method for extracting particle information according to

[21] , wherein the center time is set by adjusting the ratio of particle information extracted using the center time end point as the extraction end reference point to the total number of extracted particle information.

[23] The particle information extraction method according to

[21] or

[22] , wherein the particle diameter is 10 μm or more.

[24] The particle information extraction method according to any one of

[21] to

[23] , wherein the particle includes a carrier.

[25] The particle information extraction method according to

[24] , wherein the carrier is a support.

[26] The method for extracting particle information according to any one of

[21] to

[25] , wherein the number of particles in 100 μL of the liquid is 10,000,000 or less.

[27] A method for distinguishing particles, which distinguishes particles based on the waveform shape of particle information extracted by carrying out the method for extracting particle information according to any one of

[21] to

[26] .

[28] A method for analyzing the measurement object, which analyzes the particle information extracted by carrying out the method for extracting particle information according to any one of

[21] to

[26] .

[29] An information processing system comprising: a measurement system that measures a waveform of signal intensity versus measurement time using a liquid containing particles as a measurement target; a receiving system that receives the waveform from the measurement system; and an extraction system that extracts particle information about the particle from the waveform, wherein the extraction system uses a preset pre-extraction time, post-extraction time, threshold, and center time to identify a point at which the signal intensity exceeds the threshold as an extraction start reference point, and identify the earliest ending point among a center time end point at which the center time, starting from the extraction start reference point, ends and a threshold drop point within the center time, starting from the extraction start reference point, at which the signal intensity finally becomes equal to or less than the threshold, as an extraction end reference point, and extracts, as particle information about one particle, a waveform from an extraction start point that is backtracked by the pre-extraction time from the extraction start reference point to an extraction end point at which the post-extraction time has passed from the extraction end reference point.

[29] A particle information extraction program that extracts particle information of particles from a waveform of signal intensity versus measurement time, measured using a liquid containing particles as a measurement target, the program using a preset pre-extraction time, post-extraction time, threshold, and center time to identify a point in the waveform at which the signal intensity exceeds the threshold as an extraction start reference point, identify the earliest ending point among the center time end point, starting from the extraction start reference point, and the threshold drop point, within the center time starting from the extraction start reference point, at which the signal intensity finally becomes equal to or less than the threshold, as an extraction end reference point, and extract, as particle information for one particle, a waveform from the extraction start point that is backtracking from the extraction start reference point by the pre-extraction time, to the extraction end point from the extraction end reference point at which the post-extraction time has passed.

[0152] 100 Support 102, 102-1, 102-2, 102-3, 102-4 Opening 103, 103-1, 103-2, 103-3 Cavity 104 Inner surface of cavity 105 Capture part 60 Container 80 Particle (bioparticle)

Claims

1. An information processing device comprising: a receiving unit that acquires at least one of information relating to a sample containing microparticles in a microparticle analysis device or information relating to the measurement conditions of the sample; an extraction unit that extracts particle information for one particle from a waveform of signal intensity versus measurement time from a microparticle contained in the sample measured by the microparticle analysis device; and an input unit that inputs mode selection information for selecting a mode of the extraction unit, wherein the extraction unit has a mode selection means for selecting between a normal extraction mode and at least one or more center time fixed extraction modes, and is capable of selecting the center time fixed extraction mode based on the mode selection information input to the input unit.

2. The information processing device of claim 1, wherein the center time fixed extraction mode uses preset pre-extraction time, post-extraction time, threshold, and center time to identify the point at which the signal intensity exceeds the threshold as an extraction start reference point, and identify the earlier of the center time end point at which the center time ends with the extraction start reference point as a starting point and the threshold drop point at which the signal intensity finally becomes equal to or below the threshold within the center time with the extraction start reference point as a starting point, and extracts the waveform from the extraction start point that is back by the pre-extraction time from the extraction start reference point to the extraction end point at which the post-extraction time has passed from the extraction end reference point as particle information for one particle.

3. The information processing device according to claim 2, wherein the extraction unit is provided with a central time determination means for adjusting and setting the central time so that the proportion of particle information extracted by recognizing an end point of the central time as an extraction end reference point relative to the total number of extracted particle information is 10% or less.

4. The information processing device of claim 1, wherein the normal extraction mode recognizes the point where the signal intensity exceeds the threshold as an extraction start reference point, recognizes the threshold drop point where the signal intensity falls below the threshold as an extraction end reference point, and extracts the waveform from an extraction start point that is back from the extraction start reference point by the pre-extraction time to an extraction end point that is back from the extraction end reference point by the post-extraction time as particle information for one particle.

5. The information processing device according to claim 1, wherein the mode selection information is input manually, by reading the measurement object, or by reading the measurement information.

6. The information processing device according to claim 1, wherein the extraction unit further comprises a calculation means for calculating particle diameters from the particle information, and when the average particle diameter of the particles is 10 μm or more, the mode selection means selects a center time fixed extraction mode.

7. The information processing device according to claim 1, further comprising an analysis unit that analyzes the waveform of the extracted particle information.

8. A microparticle analysis device comprising the information processing device according to claim 1.

9. A method for extracting particle information, in which a liquid containing particles is used as a measurement target, and particle information of the particles is extracted from a waveform of signal intensity versus measurement time, the method comprising: setting a pre-extraction time, a post-extraction time, a threshold, and a central time; recognizing a point in the waveform at which the signal intensity exceeds the threshold as an extraction start reference point; recognizing an earlier ending point among a central time end point starting from the extraction start reference point and an threshold drop point at which the signal intensity finally becomes equal to or below the threshold within the central time starting from the extraction start reference point as an extraction end reference point; and extracting, from the waveform, a waveform from an extraction start point that is backdating the pre-extraction time from the extraction start reference point to an extraction end point at which the post-extraction time has passed from the extraction end reference point as particle information for one particle.

10. The method for extracting particle information according to claim 9, wherein the central time is set by adjusting the ratio of particle information extracted by recognizing an end point of the central time as an extraction end reference point to 10% or less of the total number of extracted particle information.

11. The method for extracting particle information according to claim 9, wherein the particle diameter is 10 μm or more.

12. The method for extracting particle information according to claim 9, wherein the particles include a carrier.

13. The method for extracting particle information according to claim 11, wherein the number of particles in 100 μl of the liquid is 10,000,000 or less.

14. A particle discrimination method for discriminating particles based on the waveform shape of particle information extracted by carrying out the particle information extraction method according to claim 9.

15. A method for analyzing a measurement object, comprising carrying out the method for extracting particle information according to claim 9 and analyzing the extracted particle information.

16. An information processing system comprising: a measurement system which measures a waveform of signal intensity versus measurement time using a liquid containing microparticles as a measurement object; a receiving system which acquires at least one of information about the measurement object from said measurement system or information about the measurement conditions of said measurement object; an extraction system which extracts particle information about one particle from the waveform of signal intensity versus measurement time from microparticles contained in the sample measured by a microparticle analysis device; and an input system which inputs mode selection information for selecting a mode of said extraction system, said extraction system comprising mode selection means for selecting between a normal extraction mode and at least one or more center time fixed extraction modes, and which is capable of selecting the center time fixed extraction mode based on the mode selection information input to said input system.

17. The information processing system of claim 16, wherein the center time fixed extraction mode uses preset pre-extraction time, post-extraction time, threshold, and center time to identify the point at which the signal intensity exceeds the threshold as an extraction start reference point, and identifies the earlier of the center time end point at which the center time ends with the extraction start reference point as a starting point, and the threshold drop point at which the signal intensity finally becomes equal to or below the threshold within the center time with the extraction start reference point as a starting point, as an extraction end reference point, and extracts the waveform from the extraction start point that is back by the pre-extraction time from the extraction start reference point to the extraction end point at which the post-extraction time has passed from the extraction end reference point as particle information for one particle.

18. A particle information extraction program for extracting particle information of particles from a waveform of signal intensity versus measurement time measured in a liquid containing particles, the program using preset pre-extraction times, post-extraction times, thresholds, and center times to identify a point in the waveform at which the signal intensity exceeds the threshold as an extraction start reference point, and to identify the earlier of the center time end point, starting from the extraction start reference point and the threshold drop point, at which the signal intensity finally falls below the threshold within the center time starting from the extraction start reference point, as an extraction end reference point, and to extract particle information for one particle from the waveform from an extraction start point that is backdating the pre-extraction time from the extraction start reference point to an extraction end point at which the post-extraction time has passed from the extraction end reference point.

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