Concentration measuring device

Abstract

This density measurement device comprises: a light source that emits light; a first optical system that is disposed on the light path of the light emitted from the light source, and that collects the light emitted from the light source; a tube body that is light transmitting, that is disposed, on the light path, at a position more on the rear-stage side than the focal position of the first optical system, and that parallelizes light which is incident on a lateral surface of the tube body, in a state where a fluid flows inside the tube body; and a detection unit that detects light which travelled through the tube body.

Description

[Technical Field]

[0001] The present disclosure relates to a concentration measurement device. [Background technology]

[0002] Conventionally, a concentration measuring device has been known that includes a resin tube, a light source that emits light toward the fluid in the resin tube, and a light receiving element that receives the light that passes through the resin tube, and that measures the concentration of the fluid using the Beer-Lambert law (see, for example, Patent Document 1). [Prior art documents] [Patent documents]

[0003] [Patent Document 1] Japanese Patent Application Publication No. 2016-223878 Summary of the Invention [Problem to be solved by the invention]

[0004] However, in the concentration measuring device described in Patent Document 1, the light emitted from the light source and passing through the resin tube is emitted in a diffused state, meaning that part of the light passing through the resin tube travels in a direction that does not reach the light receiving element and is not detected by the light receiving element. Therefore, in the concentration measuring device described in Patent Document 1, it may not be possible to ensure a sufficient amount of light to be detected by the light receiving element, resulting in a decrease in measurement accuracy.

[0005] Therefore, the present disclosure relates to a concentration measurement device that can improve measurement accuracy. [Means for solving the problem]

[0006] According to the present disclosure, there is provided a concentration measuring device comprising: a light source that emits light; a first optical system that is arranged on the optical path of the light emitted from the light source and that focuses the light emitted from the light source; a light-transmitting cylinder that is arranged at a position downstream of the focal position of the first optical system on the optical path and that collimates the light that enters the side surface while a fluid is flowing inside; and a detection unit that detects the light that passes through the cylinder. [Brief explanation of the drawings]

[0007] [Figure 1] 1 is a diagram illustrating a configuration of a concentration adjusting device according to a first embodiment of the present disclosure. [Figure 2] FIG. 2 is a diagram showing the configuration of a measuring device main body. [Figure 3] FIG. 10 shows a tube holder. [Figure 4] FIG. 10 shows a tube holder. [Figure 5] FIG. 1 is a diagram illustrating a method for calculating cell concentration. [Figure 6] FIG. 1 is a diagram illustrating a method for calculating cell concentration. [Figure 7] FIG. 1 is a diagram showing the configuration of a biological sample analyzer. [Figure 8] FIG. 10 is a diagram showing the configuration of a measurement device main body according to a second embodiment of the present disclosure. [Figure 9] FIG. 10 is a diagram showing a sixth lens. [Figure 10] FIG. 10 is a diagram showing the configuration of a measurement device main body according to a third embodiment of the present disclosure. [Figure 11] FIG. 10 is a diagram showing the configuration of a measurement device main body according to a fourth embodiment of the present disclosure. [Figure 12] FIG. 2 is a hardware configuration diagram illustrating an example of a computer that realizes the functions of a control device according to the embodiment. DETAILED DESCRIPTION OF THE INVENTION

[0008] Hereinafter, embodiments of the present disclosure will be described with reference to the drawings. Note that the present disclosure is not limited to the embodiments described below. Furthermore, in the drawings, the same parts are denoted by the same reference numerals.

[0009] (First embodiment) [General configuration of concentration adjusting device] FIG. 1 is a diagram showing the configuration of a concentration adjusting device 1 according to a first embodiment of the present disclosure. The concentration adjusting device 1 is a device that adjusts the concentration of a fluid containing biological particles. Specifically, the concentration adjusting device 1 adjusts the concentration of the fluid to an appropriate concentration to be input into a biological sample analyzer 6100 (see FIG. 7). The concentration adjusting device 1 and the biological sample analyzer 6100 may be directly connected by a tube, and the fluid whose concentration has been adjusted by the concentration adjusting device may be input into the biological sample analyzer 6100 via the tube. Alternatively, the fluid whose concentration has been adjusted by the concentration adjusting device may be removed from the concentration adjusting device and input into the biological sample analyzer 6100. In the first embodiment, the biological sample analyzer 6100 is a device used for cell therapy, and its detailed configuration will be described later in "Configuration of the Biological Sample Analyzer." In the first embodiment, the fluid is a cell suspension stained with an antibody dye (labeled with a labeling substance). That is, the concentration adjusting device 1 aseptically adjusts the cell concentration in the cell suspension to an appropriate cell concentration to be input into a biological sample analyzing device 6100 (described below) without directly touching the cell suspension. As shown in Fig. 1, the concentration adjusting device 1 includes a cell suspension container 2, a hollow fiber module 3, a measuring device main body 4, a waste liquid container 5, a control device 6, pipes 71-75, pumps PO1-PO3, and valves V1-V3.

[0010] As shown in FIG. 1, the cell suspension container 2 is a container that contains a cell suspension L1. A pipe 71 is connected to the cell suspension container 2. Under the control of the control device 6, a valve V1 arranged on the pipe 71 is opened and a pump PO1 is driven, whereby the cell suspension L1 is supplied into the cell suspension container 2 through the pipe 71.

[0011] Furthermore, pipes 72 and 74 are connected to cell suspension container 2. Furthermore, cell suspension container 2 is arranged on a circular flow path of pipe 72 - hollow fiber module 3 - pipe 73 - measurement device main body 4 - pipe 74 - cell suspension container 2 - pipe 72. Then, under the control of control device 6, valve V2 arranged on pipe 73 and valve V3 arranged on pipe 74 are opened, and pump PO2 arranged on pipe 72 is driven, whereby cell suspension L1 in cell suspension container 2 circulates along the circular flow path.

[0012] As shown in Fig. 1, the hollow fiber module 3 includes a hollow fiber membrane 31 and an outer cylinder 32 that houses the hollow fiber membrane 31. Although Fig. 1 shows only one hollow fiber membrane 31 inside the outer cylinder 32, in reality, a plurality of hollow fiber membranes 31 are housed inside the outer cylinder 32. The hollow fiber membrane 31 is a straw-shaped membrane with a hollow interior, and has a large number of pores on its surface that are smaller than the cells in the cell suspension L1. These pores allow unbound antibody dyes and the like to pass through, but do not allow cells to pass through.

[0013] A pipe 75 is connected to this hollow fiber module 3. Under the control of the control device 6, a pump PO3 arranged on this pipe 75 is driven, causing the cell suspension L1 to flow through the hollow fiber membrane 31 along the annular flow path described above. As a result, unbound antibody dyes and the like in the cell suspension L1 are discharged to the outside of the hollow fiber membrane 31, while the cells in the cell suspension L1 remain inside the hollow fiber membrane 31. The unbound antibody dyes and the like discharged to the outside of the hollow fiber membrane 31 are discharged into the waste liquid container 5 via the pipe 75.

[0014] The measurement device main body 4 is a device for measuring the cell concentration in the cell suspension L1 that flows through the annular flow path described above. The detailed configuration of the measurement device main body 4 will be explained later in the section "Configuration of the measurement device main body."

[0015] The waste liquid container 5 is a container for storing waste liquid L2 such as unbound antibody dyes discharged to the outside of the hollow fiber membrane 31, as shown in FIG.

[0016] The control device 6 includes a controller such as a CPU (Central Processing Unit) or an MPU (Micro Processing Unit), or an integrated circuit such as an ASIC (Application Specific Integrated Circuit) or an FPGA (Field Programmable Gate Array). The control device 6 calculates the cell concentration in the cell suspension L1 based on the detection result of the measurement device main body 4, and adjusts the cell concentration by controlling the operation of the pumps PO1 to PO3 and the valves V1 to V3 as described above. That is, the control device 6 corresponds to a control unit according to the present disclosure. Furthermore, the measurement device main body 4 and the control device 6 correspond to a concentration measurement device 100 (FIG. 1) according to the present disclosure.

[0017] [Configuration of the measuring device body] FIG. 2 is a diagram showing the configuration of the measurement device main body 4. As shown in FIG. As shown in Figure 2, the measuring device main body 4 includes a light source 41, a first lens 421, a second lens 422, a tube TB, a tube holder 43, a third lens 44, a light shielding plate 45, a fourth lens 46, a fifth lens 47, and a detection unit 48.

[0018] The tube TB corresponds to the cylindrical body according to the present disclosure. That is, the tube TB is formed in a cylindrical shape and has optical transparency. Examples of the material of the tube TB include a resin material such as PVC (polyvinyl chloride). The tube TB constitutes a part of the annular flow path described above. That is, the cell suspension L1 flows through the tube TB. The light source 41 emits light toward the cell suspension L1 in the tube TB. In the first embodiment, the light source 41 emits light in a wavelength band of 700 nm or more.

[0019] As shown in FIG. 2, the first lens 421 is disposed downstream of the light path of the light source 41, and collimates the light emitted from the light source 41. As shown in FIG. 2, the second lens 422 is disposed downstream of the first lens 421 in the optical path, and focuses the parallel light passing through the first lens 421 at a position upstream of the tube TB in the optical path. The first and second lenses 421 and 422 described above correspond to the first optical system 42 (FIG. 2) according to the present disclosure.

[0020] 3 and 4 are views showing the tube holder 43. Specifically, Fig. 3 is a perspective view of the tube holder 43 as seen from the upstream side of the optical path, and Fig. 4 is a perspective view of the tube holder 43 as seen from the downstream side of the optical path. As shown in Fig. 2, the tube holder 43 is disposed downstream of the first optical system 42 in the optical path. As shown in Fig. 3 or 4, the tube holder 43 is a plate body having a substantially rectangular shape in a plan view, and is made of a light-blocking material that blocks light. The tube holder 43 holds the tube TB. The tube holder 43 is disposed in an orientation in which each plate surface is substantially perpendicular to the optical axis of the light emitted from the light source 41.

[0021] In this tube holder 43, a tube groove 431 extending linearly in the vertical direction in FIG. 3 or 4 is formed on the plate surface on the front side of the optical path. Further, the tube holder 43 has a through-hole 432 formed at approximately the center of the plate surface, penetrating each plate surface, and communicating with the tube groove 431. Furthermore, in the tube holder 43, circular recesses 433 and 434 are formed on each plate surface, with the through-hole 432 at the center. The tube TB is held by the tube holder 43 in a state where it is inserted into the tube groove 431. A part of the light passing through the tube TB passes through the through hole 432.

[0022] Here, the tube TB collimates light incident on its side surface while the cell suspension L1 is flowing inside. Specifically, in the first embodiment, the tube TB functions as an optical element (cylindrical lens) that collimates light that has passed through the first optical system 42 and that has passed through the tube TB in a plane perpendicular to the longitudinal direction of the tube TB. That is, the focal position of the tube TB (cylindrical lens) is set to the focusing position of the first optical system 42 (the focal position of the second lens 422).

[0023] 2, the light blocking plate 45 is disposed downstream of the tube holder 43 in the optical path. The light blocking plate 45 is a plate made of a light blocking material that blocks light. The light blocking plate 45 is disposed in such a position that each plate surface is substantially perpendicular to the optical axis of the light emitted from the light source 41. In the light blocking plate 45, an opening 451 is formed at the approximate center position, penetrating each plate surface, as shown in FIG.

[0024] 2, the third lens 44 is provided between the tube TB and the light blocking plate 45. This third lens 44 corresponds to the third optical system according to the present disclosure. That is, the third lens 44 focuses the parallel light passing through the tube TB onto the opening 451. 2, the fourth lens 46 is disposed downstream in the optical path from the light blocking plate 45. The fourth lens 46 collimates the light that has been collected by the third lens 44 and passed through the opening 451. 2, the fifth lens 47 is disposed downstream of the fourth lens 46 in the optical path. The fifth lens 47 focuses the light collimated by the fifth lens 47 onto the detection surface of the detection unit 48.

[0025] The detection unit 48 detects light passing through the cell suspension L1 in the tube TB (light passing through the fifth lens 47). In the first embodiment, the detection unit 48 is configured with a photodiode, and outputs a voltage corresponding to the amount of received light to the control device 6. Then, the control device 6 calculates the cell concentration in the cell suspension L1 based on the voltage.

[0026] [How to calculate cell concentration] Next, a method for calculating the cell concentration by the control device 6 will be described. 5 and 6 are diagrams for explaining the method of calculating the cell concentration. According to the Beer-Lambert law, it is known that the absorbance of the cell suspension L1 is proportional to the cell concentration. Furthermore, as shown in FIG. 5, the absorbance can be calculated based on the following formula (1) by measuring the amount of incident light P0 and the amount of transmitted light P1.

[0027]

number

[0028] Incidentally, although absorbance can be measured using equation (1), this method also causes the absorbance of the tube TB to be reflected in the measurement results. Therefore, the control device 6 defines the voltage detected by the detection unit 48 when a reference fluid L1, which serves as a reference and has a cell concentration of 0 (no cells), is placed in the tube TB and measured as V0, and defines the voltage detected by the detection unit 48 when a cell suspension L1, which is the measurement target and contains cells, is placed in the same tube TB and measured as V, and calculates the absorbance based on the following equation (2).

[0029]

number

[0030] Then, the control device 6 calculates the cell concentration in the cell suspension L1 by substituting the absorbance calculated by equation (2) into the relationship between the absorbance of the cell suspension L1 and the cell concentration (hereinafter referred to as the calibration curve (see equation (3) below)). The calibration curve is calculated in advance, for example, as shown below.

[0031] First, as shown in Table 1 below, eight types of cell suspensions L1 (samples No. 0 to No. 7) with different cell concentrations, including a cell suspension L1 (sample No. 0) with a cell concentration of 0, are prepared (step S1).

[0032] [Table 1]

[0033] Next, prepare eight tubes TB cut to approximately 10 cm, place the eight types of cell suspension L1 (samples No. 0 to No. 7) prepared in step S1 into the eight tubes TB, and seal both ends of each tube TB (step S2). Next, each tube TB (each tube TB containing eight types of cell suspension L1 (samples No. 0 to No. 7)) prepared in step S2 is placed in the measurement device main body 4, and the voltage value is measured by the detection unit 48 (step S3). The voltage values ​​measured in step S3 are as shown in Table 1.

[0034] Next, the absorbance of each sample No. 0 to No. 7 is calculated by substituting each voltage value measured in step S3 into equation (2) (step S4). The absorbances calculated in step S4 are as shown in Table 1. Then, as shown in FIG. 6, an approximate line (shown by a dashed line in FIG. 6) is calculated from the cell concentrations and absorbances of samples No. 0 to No. 7, and the approximate line is used as a calibration curve. In the above example, the calibration curve is expressed by the following formula (3).

[0035]

number

[0036] [Configuration of the biological sample analyzer] Next, the configuration of the biological sample analyzer 6100 will be described.

[0037] An example configuration of a biological sample analyzer according to the present disclosure is shown in Figure 7. The biological sample analyzer 6100 shown in Figure 7 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 sorting unit 6104 that sorts specific biological particles P from within the biological sample. An example of a biological sample analyzer 6100 that includes the sorting unit is a cell sorter.

[0038] (biological samples) 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., (particularly fluorescent dyes) and fluorescent dye-labeled antibodies, etc.). Note that the biological sample analyzer of the present disclosure may also analyze particles other than biological particles, such as beads for calibration purposes.

[0039] (flow path) 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, and in particular, 10 μm or more and 1 mm or less. The flow channel C and the flow channel structure including it may be made of a material such as plastic or glass.

[0040] 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 channel 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 channel structure in which flow channel C is formed, or so that the interrogation point of light is outside the flow channel structure. An example of the former is a configuration in which the light is irradiated onto flow channel C within a microchip or flow cell. In the latter, the light may be irradiated onto biological particles after they have left the flow channel structure (particularly its nozzle portion), and an example of this is a jet-in-air flow cytometer.

[0041] (Light irradiation part) 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 emitted from one or more different light sources to one irradiation point.

[0042] (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, and has, for example, a photodetector array. Each photodetector may include, as the light-receiving element, one or more PMTs (photomultiplier tubes) and / or photodiodes such as APDs and MPPCs. 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.

[0043] 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.

[0044] Furthermore, the detection unit 6102 may 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).

[0045] (Information Processing Department) 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 executes 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.

[0046] If the biological sample analyzer 6100 includes a fractionating unit 6104 (described below), the information processing unit 6103 can determine whether to sort the biological particles based on the optical data and / or morphological information. Then, the information processing unit 6103 can control the fractionating unit 6104 based on the result of this determination, and the fractionating unit 6104 can sort the biological particles.

[0047] The information processing unit 6103 may be configured to output various data (e.g., optical data or 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.

[0048] 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.

[0049] (Preparative separation section) 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 movement of the droplets with electrodes. The sorting method may also be a method of controlling the direction of movement of the bioparticles within the channel structure to perform sorting. The channel structure may be provided with a control mechanism using, for example, pressure (spray or suction) or electric charge. An example of such a channel structure is a chip (for example, the chip described in JP 2020-76736 A) having a channel structure in which a channel C branches into a recovery channel and a waste channel downstream, and specific bioparticles are recovered into the recovery channel.

[0050] [Effects of the first embodiment] According to the first embodiment described above, the following effects are achieved. In the concentration measuring device 4 according to the first embodiment, the first optical system 42 focuses the light emitted from the light source 41 at a position on the upstream side of the tube TB in the optical path. In other words, the tube TB is disposed at a position on the downstream side of the focal position of the first optical system 42. The tube TB functions as an optical element (cylindrical lens) that collimates the light that has passed through the first optical system 42 and is transmitted through the tube TB in a plane perpendicular to the longitudinal direction of the tube TB. Therefore, most of the light transmitted through the tube TB can be detected by the detection unit 48. That is, a sufficient amount of light can be detected by the detection unit 48, and the accuracy of measuring the cell concentration can be improved.

[0051] However, when the detection unit 48 detects scattering holes scattered in the cell suspension L1 in addition to the transmitted light that has passed through the tube TB (cell suspension L1), it is not possible to correctly calculate the absorbance. In the concentration measuring device 4 according to the first embodiment, the third lens 44 focuses the parallel light passing through the tube TB (cell suspension L1) onto the opening 451 of the light-shielding plate 45. Therefore, the transmitted light passes through the opening 451, while the scattered light is blocked by the light-shielding plate 45. Therefore, the detecting unit 48 can detect only the transmitted light, and the absorbance can be calculated correctly.

[0052] Incidentally, many of the antibody dyes in cell suspension L1 are excited to emit fluorescence by light in any of the wavelength bands (hereinafter referred to as excitation wavelengths) of around 405 nm, around 488 nm, around 561 nm, and around 638 nm. For this reason, if the concentration measurement device 4 is configured to emit light of the above-mentioned excitation wavelengths from the light source 41, the antibody dyes will fade and will not emit fluorescence even when irradiated with light of the above-mentioned excitation wavelengths in the biological sample analyzer 6100. In the concentration measuring device 4 according to the first embodiment, the light source 41 emits light in a wavelength band of 700 nm or more. Therefore, when the concentration measuring device 4 measures the cell concentration in the cell suspension L1, the antibody dye does not fade.

[0053] When measuring the cell concentration in the cell suspension L1, the red blood cells contained in the cell suspension L1 become a noise source, making it difficult to accurately measure the absorbance. In addition, the absorption coefficients of deoxygenated hemoglobin and oxygenated hemoglobin in red blood cells are relatively low at wavelengths of 700 nm or longer. In the concentration measuring device 4 according to the first embodiment, the light source 41 emits light in a wavelength band of 700 nm or more. This reduces the influence of red blood cells contained in the cell suspension L1 on the absorbance, making it possible to accurately measure the absorbance.

[0054] Incidentally, when measuring the optical characteristics of the cell suspension L1 through the tube TB, it is difficult to accurately measure the optical characteristics due to individual differences in the tube TB (variations in the inner diameter and wall thickness of the tube TB). In the concentration measuring device 4 according to the first embodiment, the voltage detected by the detecting unit 48 when a reference fluid L1 having a cell concentration of 0 (containing no cells) is placed in a tube TB and measured is defined as V0, and the voltage detected by the detecting unit 48 when a cell suspension L1 to be measured containing cells is placed in the same tube TB and measured is defined as V, and the absorbance is calculated based on equation (2). This allows individual differences between tubes TB to be cancelled out, making it possible to accurately measure the absorbance and cell concentration of the cell suspension L1 to be measured.

[0055] (Second embodiment) Next, a second embodiment will be described. In the following, the same components as those in the first embodiment described above are denoted by the same reference numerals, and detailed description thereof will be omitted or simplified. FIG. 8 is a diagram showing the configuration of a measurement device main body 4A according to the second embodiment of the present disclosure. As shown in FIG. 8, a measurement device main body 4A according to the second embodiment is configured by adding a sixth lens 49 to the measurement device main body 4 described in the first embodiment.

[0056] FIG. 9 is a diagram showing the sixth lens 49. As shown in FIG. 8, the sixth lens 49 is disposed between the tube holder 43 and the third lens 44. This sixth lens 49 corresponds to the second optical system according to the present disclosure. That is, the sixth lens 49 functions as an optical element (cylindrical lens) that collimates the light that has passed through the tube TB within a plane including the longitudinal direction of the tube TB.

[0057] [Effects of the second embodiment] The measurement device main body 4A according to the second embodiment includes a sixth lens 49 that collimates the light that has passed through the tube TB in a plane that includes the longitudinal direction of the tube TB. Therefore, by using the tube TB and the sixth lens 49, each functioning as a cylindrical lens, in combination, more of the light passing through the tube TB can be detected by the detection unit 48. In other words, the amount of light detected by the detection unit 48 can be more satisfactorily ensured, and the accuracy of measuring the cell concentration can be further improved.

[0058] (Third embodiment) Next, a third embodiment will be described. In the following, the same components as those in the first embodiment described above are denoted by the same reference numerals, and detailed description thereof will be omitted or simplified. FIG. 10 is a diagram showing the configuration of a measurement device main body 4B according to the third embodiment of the present disclosure. 10, in a measurement device main body 4B according to the third embodiment, the fourth and fifth lenses 46, 47 are omitted from the measurement device main body 4 described in the first embodiment. A light shielding plate 45 is disposed in contact with a detection unit 48.

[0059] [Effects of the third embodiment] A measurement device main body 4B according to the third embodiment does not include the fourth and fifth lenses 46 and 47. This simplifies the configuration of the measurement device main body 4B.

[0060] (Fourth embodiment) Next, a fourth embodiment will be described. In the following, the same components as those in the second embodiment described above are denoted by the same reference numerals, and detailed description thereof will be omitted or simplified. FIG. 11 is a diagram showing the configuration of a measurement device main body 4C according to the fourth embodiment of the present disclosure. 11, a measurement device body 4C according to the fourth embodiment is different from the measurement device body 4A described in the second embodiment in that the fourth and fifth lenses 46 and 47 are omitted. A light shielding plate 45 is disposed in contact with a detection unit 48.

[0061] [Effects of the fourth embodiment] A measurement device main body 4C according to the fourth embodiment does not include the fourth and fifth lenses 46 and 47. This simplifies the configuration of the measurement device main body 4C.

[0062] (Other embodiments) Up to this point, the embodiments for carrying out the present disclosure have been described, but the present disclosure should not be limited to only the first to fourth embodiments described above. In the first to fourth embodiments described above, the concentration adjusting device 1 is configured to adjust the cell concentration in the cell suspension L1 in a sterile manner, but this is not limiting and the cell concentration may be adjusted in a non-sterile manner. Furthermore, the configuration of the concentration adjusting device 1 is merely an example, and other configurations may be adopted.

[0063] (Hardware configuration) The control device 6 according to the above-described embodiment, its modifications, and application examples can be realized by, for example, a computer 1000 configured as shown in Fig. 12. Fig. 12 is a hardware configuration diagram showing an example of the computer 1000 that realizes the functions of the control device 6. The computer 1000 has a CPU 1100, a RAM 1200, a ROM (Read Only Memory) 1300, an HDD (Hard Disk Drive) 1400, a communication interface 1500, and an input / output interface 1600. The components of the computer 1000 are connected by a bus 1050.

[0064] The CPU 1100 operates and controls each unit based on programs stored in the ROM 1300 or the HDD 1400. For example, the CPU 1100 loads the programs stored in the ROM 1300 or the HDD 1400 into the RAM 1200 and executes processing corresponding to the various programs.

[0065] The ROM 1300 stores boot programs such as a BIOS (Basic Input Output System) that is executed by the CPU 1100 when the computer 1000 is started up, and programs that depend on the hardware of the computer 1000 .

[0066] HDD 1400 is a computer-readable recording medium that non-temporarily records programs executed by CPU 1100 and data used by such programs. Specifically, HDD 1400 is a recording medium that records programs for executing the operations according to the present disclosure, which are examples of program data 1450.

[0067] The communication interface 1500 is an interface for connecting the computer 1000 to an external network 1550 (e.g., the Internet). For example, the CPU 1100 receives data from other devices and transmits data generated by the CPU 1100 to other devices via the communication interface 1500.

[0068] The input / output interface 1600 is an interface for connecting the input / output device 1650 and the computer 1000. For example, the CPU 1100 receives data from an input device such as a keyboard or a mouse via the input / output interface 1600. The CPU 1100 also transmits data to an output device such as a display, a speaker, or a printer via the input / output interface 1600. The input / output interface 1600 may also function as a media interface for reading programs and the like recorded on a predetermined recording medium. Examples of media include optical recording media such as a DVD (Digital Versatile Disc) or a PD (Phase Change Rewritable Disk), magneto-optical recording media such as an MO (Magneto-Optical disk), tape media, magnetic recording media, and semiconductor memories.

[0069] For example, when the computer 1000 functions as the control device 6 according to the above-described embodiment, the CPU 1100 of the computer 1000 executes a program loaded onto the RAM 1200, thereby realizing the functions of the control device 6. The HDD 1400 stores programs and the like according to the present disclosure. The CPU 1100 reads and executes program data 1450 from the HDD 1400, but as another example, the CPU 1100 may obtain these programs from another device via an external network 1550.

[0070] The information processing unit 6103 that constitutes the biological sample analyzer 6100 can also be realized with a hardware configuration similar to that of the computer 1000 described above.

[0071] Furthermore, the effects described herein are merely descriptive or exemplary and are not limiting. In other words, the technology according to the present disclosure may achieve other effects that will be apparent to those skilled in the art from the description of this specification, in addition to or in place of the above-described effects.

[0072] The following configurations also fall within the technical scope of the present disclosure. (1) a light source that emits light; a first optical system that is provided on an optical path of the light emitted from the light source and that collects the light emitted from the light source; a light-transmitting cylinder that is disposed at a position downstream of a focal position of the first optical system on the optical path and that collimates the light that has entered a side surface while a fluid is flowing inside; and a detection unit that detects light passing through the cylindrical body; A concentration measuring device comprising: (2) The concentration measuring device according to (1), wherein the cylinder has a cylindrical shape and collimates the light passing through the cylinder in a plane perpendicular to the longitudinal direction of the cylinder. (3) The concentration measuring device described in (1) or (2) further comprises a second optical system provided between the cylinder and the detection unit, which collimates the light passing through the cylinder in a plane including the longitudinal direction of the cylinder. (4) a light blocking plate provided between the cylindrical body and the detection unit and having an opening penetrating from the front to the back; a third optical system provided between the cylindrical body and the light blocking plate, the third optical system focusing the light passing through the cylindrical body onto the opening; The concentration measuring device according to any one of (1) to (3) above, further comprising: (5) The concentration measuring device according to (4), wherein the light blocking plate is disposed in contact with the upstream side of the optical path of the detecting unit. (6) The concentration measuring device according to any one of (1) to (5), wherein the fluid is a fluid containing biological particles. (7) The concentration measuring device according to (6), wherein the fluid is a cell suspension stained with an antibody dye. (8) The concentration measuring device according to any one of (1) to (7), wherein the light source emits light in a wavelength band of 700 nm or more. (9) a control unit that calculates the concentration of the fluid from the absorbance of the fluid using the Beer-Lambert law; The control unit calculates the absorbance from a detection result obtained by the detection unit of light passing through the cylindrical body when a reference fluid having a concentration of 0 is flowing through the cylindrical body, and a detection result obtained by the detection unit of light passing through the cylindrical body when the fluid to be measured is flowing through the cylindrical body. [Explanation of symbols]

[0073] 1 Concentration adjustment device 2. Cell suspension container 3 Hollow fiber module 4, 4A to 4C Measuring device body 5 Waste container 6. Control device 31 Hollow fiber membrane 32 outer cylinder 41 Light source 42 First Optical System 43 Tube holder 44 The Third Lens 45 Shade 46 The Fourth Lens 47 The Fifth Lens 48 Detector 49 The Sixth Lens 71~75 Piping 100 Concentration measuring device 421 First Lens 422 Second Lens 431 Tube groove 432 Through hole 433,434 recess 451 Opening 1000 computers 1050 Bus 1100 CPU 1200 RAM 1300 ROM 1400 HDD 1450 Program Data 1500 Communication Interface 1550 External Network 1600 Input / Output Interface 1650 input / output device 6100 Biological sample analyzer 6101 Light irradiation unit 6102 Detector 6103 Information Processing Department 6104 Preparative separation section C flow path L1 cell suspension L2 waste liquid P bioparticles PO1~PO3 pump S Biological samples TB Tube V1~V3 valves

Claims

1. a light source that emits light; a first optical system that is provided on an optical path of the light emitted from the light source and that collects the light emitted from the light source; a light-transmitting cylinder that is disposed at a position downstream of a focal position of the first optical system on the optical path and that collimates the light that has entered a side surface while a fluid is flowing inside; and a detection unit that detects light passing through the cylindrical body; A concentration measuring device comprising:

2. 2. The concentration measuring device according to claim 1, wherein the cylinder has a cylindrical shape and collimates the light passing through the cylinder in a plane perpendicular to the longitudinal direction of the cylinder.

3. The concentration measuring device according to claim 1 , further comprising a second optical system provided between the cylinder and the detection unit, which collimates the light passing through the cylinder in a plane including the longitudinal direction of the cylinder.

4. a light blocking plate provided between the cylindrical body and the detection unit and having an opening penetrating from the front to the back; a third optical system provided between the cylindrical body and the light blocking plate, the third optical system concentrating the light passing through the cylindrical body onto the opening; The concentration measuring device according to claim 1 , further comprising:

5. 5. The concentration measuring device according to claim 4, wherein the light blocking plate is disposed in contact with the upstream side of the optical path of the detecting unit.

6. 2. The concentration measuring device according to claim 1, wherein the fluid contains biological particles.

7. 7. The concentration measuring device according to claim 6, wherein the fluid is a cell suspension stained with an antibody dye.

8. 2. The concentration measuring device according to claim 1, wherein the light source emits light in a wavelength band of 700 nm or more.

9. A control unit is further provided that calculates the concentration of the fluid from the absorbance of the fluid using the Beer-Lambert law; The control unit calculates the absorbance from the detection result of the detection unit detecting light passing through the cylinder when a reference fluid with a concentration of 0 is flowing through the cylinder, and the detection result of the detection unit detecting light passing through the cylinder when the fluid to be measured is flowing through the cylinder.

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