Particle recovery device and particle recovery method

Abstract

To excellently recover a tangible component contained in a liquid sample of various densities.SOLUTION: A particles recovery device for recovering particles contained in a liquid sample includes: a flow cell having a flow channel in which the liquid sample flows; a density acquisition unit for acquiring density of the liquid sample; standing wave formation means for generating a standing wave by irradiating an ultrasonic wave in the flow channel; a control unit for determining a frequency of the ultrasonic wave that generates the standing wave in the flow channel based on the density acquired by the density acquisition unit to cause the standing wave formation means to irradiate an ultrasonic wave having the determined frequency; and recovery means for recovering the particles focused in the flow channel by the standing wave.SELECTED DRAWING: Figure 1

Description

[Technical field]

[0001] The present disclosure relates to a particle recovery device and a particle recovery method. [Background technology]

[0002] A flow channel filled with a liquid sample containing particles is irradiated with ultrasonic waves to form a node of a standing wave in the flow channel, and the particles focused at the node of the standing wave are collected.

[0003] For example, Patent Document 1 discloses a technology for a particle processing device that separates and recovers particle components by applying ultrasound to a flow path through which a solution containing a solvent component and a particle component flows, thereby generating a node of the sound pressure of a standing wave at a predetermined position in the flow path. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] Japanese Patent Application Publication No. 10-82723 Summary of the Invention [Problem to be solved by the invention]

[0005] In the field of clinical testing, for example, urinary sediment testing is performed to analyze the amount and type of formed elements, such as red blood cells and white blood cells, contained in a liquid sample such as urine to examine the health condition of a person who excretes urine. Because the amount of formed elements contained in urine is minute, it is desirable to obtain a concentrated solution with a high concentration of the formed elements in urine by recovering the formed elements in urine in a small amount of solvent, and then analyze the formed elements contained in the concentrated solution.

[0006] An object of the present disclosure is to effectively recover particles contained in a liquid sample. [Means for solving the problem]

[0007] In a liquid sample such as urine, the density and components of the liquid part of urine are diverse because the amount of urine excreted and the components excreted from the body into urine vary depending on the circumstances such as water intake, sweating, dietary restrictions, and the health condition of the person excreting the urine. The inventor irradiated ultrasonic waves of a single frequency into the flow path of a cell filled with a liquid sample such as urine to generate a standing wave with a node in the flow path, recovered the formed components focused at the node in a small amount of liquid to obtain a concentrated solution of the formed components, and measured the recovery rate of the formed components recovered in the concentrated solution. As a result, the inventor found that the frequency of ultrasonic waves at which the formed components can be successfully recovered differs depending on the density of the liquid part of the liquid sample.

[0008] The particle recovery device according to a first aspect of the present disclosure has been made based on the above discovery, and includes a flow cell having a flow path through which a liquid sample flows, a density acquisition unit that acquires the density of the liquid sample, a standing wave forming means that irradiates ultrasound into the flow path to generate standing waves, a control unit that determines the frequency of ultrasound that will generate standing waves in the flow path based on the density acquired by the density acquisition unit and causes the standing wave forming means to irradiate ultrasound of the determined frequency, and recovery means that recovers particles focused in the flow path by the standing waves.

[0009] A particle recovery device according to a first aspect of the present disclosure includes a standing wave forming means that irradiates an ultrasonic wave into a flow path to generate a standing wave within the flow path, and a control unit that determines the frequency of the ultrasonic wave based on the density of the liquid sample, thereby providing an apparatus that recovers particles contained in liquid samples of various densities with a high recovery rate.

[0010] A particle recovery method according to a second aspect of the present disclosure acquires the density of a liquid sample, determines the frequency of ultrasound that generates standing waves in a flow path through which the liquid sample flows based on the density of the liquid sample, irradiates ultrasound into the flow path, and recovers particles focused in the flow path by the standing waves generated by irradiating the ultrasound.

[0011] A particle recovery method according to a second aspect of the present disclosure provides a method for recovering particles contained in liquid samples having various densities, etc., with a high recovery rate by determining the frequency of ultrasound that generates standing waves in a flow path through which the liquid sample flows based on the density of the liquid sample. Effect of the Invention

[0012] According to the present disclosure, particles contained in liquid samples having a variety of densities and the like can be effectively recovered. [Brief description of the drawings]

[0013] [Figure 1] FIG. 1 is a diagram showing a configuration of a particle recovery device according to a first embodiment of the present disclosure. [Diagram 2] FIG. 2 is an enlarged view of an outlet of the particle recovery device according to the first embodiment of the present disclosure. [Diagram 3] FIG. 2 is a diagram of a flow cell according to a first embodiment of the present disclosure. [Figure 4] 1 is a diagram of particle recovery by a particle recovery device according to a first embodiment of the present disclosure. [Diagram 5] FIG. 4 is a flow diagram of an optimal frequency measurement procedure using the particle collection device according to the first embodiment of the present disclosure. [Figure 6] FIG. 4 is a diagram showing the change in recovery rate obtained by an optimal frequency measurement procedure using the particle recovery device according to the first embodiment of the present disclosure. [Figure 7] FIG. 2 is a flow diagram of a particle concentration procedure using the particle recovery device according to the first embodiment of the present disclosure. [Figure 8] 1 is a diagram showing a configuration of a modified example of a particle recovery device according to the first embodiment of the present disclosure. [Figure 9] 1 is a diagram showing a configuration of a modified example of a particle recovery device according to the first embodiment of the present disclosure. [Figure 10] FIG. 4 is a diagram showing the configuration of a particle recovery device according to a second embodiment of the present disclosure. [Figure 11] FIG. 11 is a flow diagram of a particle concentration procedure using a particle recovery device according to a second embodiment of the present disclosure. [Figure 12]FIG. 11 is a diagram showing a change in optimal frequency due to differences in density of a liquid sample using the particle recovery device according to the first embodiment of the present disclosure. [Figure 13] FIG. 11 is a diagram showing changes in optimal frequency due to differences in components of a liquid sample using the particle recovery device according to the first embodiment of the present disclosure. [Figure 14] FIG. 4 is a diagram showing a change in recovery rate due to differences in density of a liquid sample using the particle recovery device according to the first embodiment of the present disclosure. [Figure 15] FIG. 4 is a diagram showing changes in recovery rate due to differences in components of a liquid sample using the particle recovery device according to the first embodiment of the present disclosure. [Figure 16] 1 is a diagram showing a change in the reciprocal of focusing time due to differences in density of a liquid sample and voltage applied to a piezoelectric element using a particle recovery device according to a first embodiment of the present disclosure. FIG. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0014] First embodiment (composition) First, the configuration of a particle recovery device 10 according to a first embodiment of the present disclosure will be described.

[0015] As shown in Figures 1 to 4, a particle recovery device 10 according to a first embodiment of the present disclosure includes a flow cell 40, a support member 18 that supports the flow cell 40, a piezoelectric element 42 provided on a wall surface of the flow cell, an oscillator 16 that oscillates the piezoelectric element, a Spitz tube 12 that stores sample liquid 30 (an example of a "liquid sample containing particles" according to an embodiment of the present disclosure), an introduction path 14 that allows the sample liquid 30 to flow from the Spitz tube 12 into the flow cell 40, a first pump 20 and a second pump 22 that suck the sample liquid 30, a control unit 44, and a density measurement unit 60 serving as a density acquisition unit that measures the density of the sample liquid 30.

[0016] The sample liquid 30 is, for example, a bodily fluid collected from a living body containing particles such as epithelial cells, in particular a liquid such as human urine, and flows from a state stored in the Spitz tube 12 through the introduction path 14 into the flow cell 40.

[0017] The flow cell 40 is, for example, a substantially rectangular parallelepiped member supported by a support member 18, and has a circular hole-shaped flow path 50 that communicates from the upstream side to the downstream side in the longitudinal direction, as shown in Fig. 3. A piezoelectric element 42 is disposed on the wall surface of the flow cell.

[0018] The density measuring unit 60 is a device that measures the density or a physical property value correlated with density (hereinafter, density or a physical property value correlated with density will be simply referred to as "density") of the sample liquid 30 flowing through the introduction path 14 and into the flow cell 40. Physical property values ​​correlated with density include, for example, the specific gravity, osmotic pressure, electrical resistance, and refractive index of the sample liquid. In addition, when the sample liquid is urine, the creatinine concentration contained in the urine can be included. The density measuring unit 60 can be, for example, a specific gravity meter, an osmometer, an electrical resistance meter, a refractometer, or the like.

[0019] As an example, density measurement unit 60 is a refractometer provided in introduction path 14. The refractometer measures the refractive index of sample liquid 30 flowing in introduction path 14. The sample liquid 30 whose refractive index has been measured flows into a flow cell provided downstream of density measurement unit 60. The refractometer, which is density measurement unit 60, is connected to control unit 44, which will be described later, and the measured value of the refractive index of sample liquid 30 measured by the refractometer is transmitted to control unit 44.

[0020] The flow cell 40 is made of a hard material such as glass, for example, and is formed by cutting a circular hole in the center of a square prism block.

[0021] As described above, the upstream side of the flow channel 50 is the inlet port 52 through which the sample liquid 30 flows in from the introduction channel 14, and the downstream side of the flow channel 50 is the outlet port 54 through which the sample liquid 30 is discharged. In this embodiment, the direction from the inlet port 52 of the flow channel 50 to the outlet port 54 (the direction in which the sample liquid flows) is defined as the "flow direction."

[0022] 2, a double pipe having an outer pipe 56 and an inner pipe 58 arranged at the center of the outer pipe 56 is connected to the outlet 54. The inner pipe 58 extends from the opening of the outer pipe 56 to the outside of the outer pipe 56. As an example, the double pipe is connected to the outlet 54 of the flow path 50 so that the inner pipe 58 is arranged along the central axis of the inner diameter of the flow path 50.

[0023] As shown in FIG. 2, the inner tube 58 is located on the central axis of the flow path 50 downstream of the portion where the piezoelectric element 42 of the flow path 50 contacts (downstream of the portion where the standing wave SW described later is generated), and opens toward the upstream side.

[0024] Here, the outer tube 56 is bent into an L-shape and is connected to the first pump 20. The inner tube 58 is connected to the second pump 22. As a result, by driving the first pump 20 and the second pump 22, it is possible to suck the sample liquid 30 stored in the Spitz tube 12 into the flow cell 40 and cause it to flow therein, and also to discharge the sample liquid 30 in the flow path 50 to the outside via the outer tube 56 and the inner tube 58 separately.

[0025] Furthermore, particles in the sample liquid 30 are collected after being discharged to the outside through the inner tube 58. That is, the first pump 20, the second pump 22, the outer tube 56, and the inner tube 58 constitute a "collection means" according to an embodiment of the present disclosure.

[0026] The first pump 20 and the second pump 22 are each capable of being driven independently, and it is preferable that the sample liquid 30 can be sucked from the Spitz tube 12 into the flow cell 40 by driving only the first pump 20 .

[0027] 2, the inner diameter of the outer tube 56 is approximately the same as the inner diameter of the flow path 50, and the inner diameter of the inner tube 58 is approximately half the inner diameter of the flow path 50. In other words, the internal cross-sectional area of ​​the inner tube 58 is approximately ¼ the internal cross-sectional area of ​​the outer tube 56. The diameter of the inner tube 58 is smaller than the wavelength of the ultrasonic waves generated by the piezoelectric element 42.

[0028] The piezoelectric element 42 is a member that expands and contracts in a predetermined direction when an AC voltage is supplied, and is provided in contact with one side of the flow cell 40 along the flow direction of the flow cell 40 .

[0029] The oscillator 16 supplies an AC voltage to the piezoelectric element 42 of the flow cell 40, thereby expanding and contracting the piezoelectric element 42 in the thickness direction (the direction toward the inner wall surface of the flow cell 40). As a result, ultrasonic waves, which are compressional waves traveling from the side surface of the flow cell 40 to which the piezoelectric element 42 is attached toward the inside of the flow cell 40, are transmitted to the inner wall surface of the flow cell 40, i.e., into the flow channel 50. In addition, as the generated ultrasonic waves are transmitted to the flow channel 50, the sample liquid 30 contained in the flow channel 50 is irradiated with the ultrasonic waves.

[0030] As shown in FIG. 4, the inner wall surface of the flow channel 50 on the side where the piezoelectric element 42 is provided is referred to as inner wall surface A, and the wall surface on the opposite side of the central axis to inner wall surface A is referred to as inner wall surface B.

[0031] As described above, the ultrasonic waves emitted from the piezoelectric element 42 are transmitted to the flow channel 50 through the wall surface of the flow cell 40, so that the ultrasonic waves (ultrasound A) are irradiated to the sample liquid 30 from the inner wall surface A side in the flow channel 50. The piezoelectric element 42, the inner wall surface A, and the oscillator 16 correspond to a first ultrasonic irradiation unit that irradiates the sample liquid 30 with ultrasonic waves.

[0032] Then, the ultrasonic wave (ultrasonic wave A) transmitted to the sample liquid 30 reaches the inner wall surface B side on the opposite side across the axial center of the flow channel 50.

[0033] At this time, part of the ultrasonic wave (ultrasonic wave A) that reaches inner wall surface B is reflected by inner wall surface B without passing through inner wall surface B. That is, part of the ultrasonic wave that reaches inner wall surface B travels again through sample liquid 30 toward inner wall surface A. In other words, piezoelectric element 42, inner wall surface B, and oscillator 16 correspond to a second ultrasonic wave irradiating unit that irradiates ultrasonic wave B, which has the same frequency and amplitude as ultrasonic wave A but travels in the opposite direction and overlaps with ultrasonic wave A. The second ultrasonic wave irradiating unit faces the first ultrasonic wave irradiating unit.

[0034] A part of the ultrasonic wave B that reaches the inner wall surface A again is reflected by the inner wall surface A without being transmitted through the inner wall surface A. That is, a part of the ultrasonic wave that reaches the inner wall surface A propagates through the sample liquid 30 and travels again toward the inner wall surface B.

[0035] Furthermore, since the piezoelectric element 42 continuously generates ultrasonic waves (ultrasonic waves A), the inside of the flow channel 50 described above is continuously irradiated with ultrasonic waves.

[0036] At this time, if the wavelengths of ultrasonic waves A and B satisfy the condition described in the following formula (1), the ultrasonic waves reflected on the inner wall surface A side and the inner wall surface B side overlap and are amplified, so that a standing wave SW is generated in a direction perpendicular to the flow direction inside the flow channel 50. Note that L is the inner diameter [m] of the flow channel 50, λ is the wavelength [m] of the ultrasonic waves, and n is any integer equal to or greater than 1.

[0037]

number

[0038] That is, the oscillator 16, the piezoelectric element 42, the inner wall surface A and the inner wall surface B are an example of a "standing wave forming means" according to an embodiment of the present disclosure.

[0039] The frequency of the AC voltage supplied from the oscillator 16 is equal to the frequency of the ultrasonic waves emitted from the piezoelectric element 42 to the sample liquid 30 in the flow path 50. In other words, by changing the frequency of the AC voltage supplied from the oscillator 16 to the piezoelectric element 42, it is possible to change the frequency of the ultrasonic waves emitted from the piezoelectric element 42.

[0040] In addition, there is a correspondence between the voltage value (amplitude) of the AC voltage supplied from the oscillator 16 and the amplitude of the ultrasonic waves emitted from the piezoelectric element 42, and by modulating the voltage value (amplitude) of the AC voltage supplied from the oscillator 16 to the piezoelectric element 42, it is possible to modulate the amplitude of the ultrasonic waves emitted from the piezoelectric element 42.

[0041] Here, the frequency and amplitude of the AC voltage supplied to the piezoelectric element 42 by the oscillator 16 is controlled by a waveform controller 46 included in a control unit 44, which will be described later.

[0042] The control unit 44 has, as an example, a storage unit 70, a waveform controller 46, a receiving unit 45 that receives a density value from the density measurement unit 60, and a waveform derivation unit 47. The receiving unit 45 receives the density value of the sample liquid 30 from the density measurement unit 60. In other words, the control unit 44 and the density measurement unit 60 are an example of a density acquisition unit that acquires the density of the sample liquid 30. The waveform derivation unit 47 determines the frequency and amplitude of the AC voltage that the oscillator 16 supplies to the piezoelectric element 42 based on the density value of the sample liquid 30 received by the receiving unit 45 and the correspondence between the density and frequency of the sample liquid 30 stored in the storage unit 70. Then, the waveform controller 46 controls the oscillator 16 so that the frequency and amplitude of the AC voltage determined by the waveform derivation unit 47 are supplied to the piezoelectric element 42.

[0043] The configuration of receiving unit 45 is not particularly limited, and it may be connected to density measurement unit 60 via a wire and receive the density value of sample liquid 30 from density measurement unit 60, or may be connected to density measurement unit 60 wirelessly and receive the density value of sample liquid 30 from density measurement unit 60. Also, control unit 44 may instruct density measurement unit 60 to transmit the density value to receiving unit 45, and density measurement unit 60 may transmit the density value to receiving unit 45 in accordance with the instruction from control unit 44.

[0044] Also, density measurement unit 60 may actively transmit the density value to receiving unit 45. Similarly, examples of waveform controller 46 and waveform derivation unit 47 include arithmetic devices or control devices such as microcontrollers or microprocessors.

[0045] (Generation of standing waves and particle concentration principle) As shown in FIG. 4(A), when sample liquid 30 is filled in flow path 50 and before ultrasonic waves are irradiated into flow path 50, the particles contained in sample liquid 30 are uniformly dispersed in sample liquid 30.

[0046] In this state, when an AC voltage is supplied to the piezoelectric element 42 and ultrasonic waves are generated from the piezoelectric element 42 , the ultrasonic waves travel along the wall surface of the flow cell 40 and are irradiated into the sample liquid 30 in the flow channel 50 .

[0047] Here, when the wavelength λ of the ultrasonic wave propagating through the sample liquid 30 is approximately half the diameter of the flow path 50, that is, when n=1 in the above-mentioned formula (1), a standing wave SW is generated in the sample liquid 30 in the radial direction of the flow path 50, as shown in Fig. 4(B). The inner wall surface A and the inner wall surface B become the free ends of the standing wave.

[0048] In this case, as shown in FIG. 4B, a node N of the standing wave SW is generated on the central axis of the flow path 50, and an antinode AN of the standing wave SW is generated on the inner wall surface of the flow path 50, i.e., the inner wall surface A and the inner wall surface B. Then, the particles dispersed between the antinode AN and the node N of the standing wave SW move toward the position of the node N of the standing wave SW. As a result, the particles in the sample liquid 30 are focused at the position of the node N of the standing wave SW, and the particles in the sample liquid 30 are reduced, i.e., the concentration is reduced, in other places than the node N of the standing wave SW, so that the sample liquid 30 has a part (concentrated liquid) 34 where the particles are focused and a part (low concentration liquid) 32 where almost no particles are included. In other words, the density of the particles in the sample liquid 30 is biased depending on the position in the flow path 50, and the concentration (density) of the particles is high at the position where the node N of the standing wave SW exists, and the concentration (density) of the particles is low at positions other than the position where the node N exists.

[0049] 4(B), the particles do not immediately disperse throughout the sample liquid 30, but remain for a while at the position where the node N of the standing wave SW was present. Therefore, the sample liquid 30 remains separated into the concentrated liquid 34 and the low concentration liquid 32 inside the flow cell 40. In other words, the particle concentration (density) is high at the position where the node N of the standing wave SW was present, and the particle concentration (density) is low at positions other than the position where the node N was present.

[0050] Then, as shown in FIG. 4(C), when the first pump 20 and the second pump 22 are driven in a state in which the concentration (density) of particles in the sample liquid 30 is high at the position where the node N of the standing wave SW was present, the particles focused at the position of the node N are discharged as concentrated liquid 34 into the inner tube 58 provided downstream, and the low concentration liquid 32 is discharged into the outer tube 56.

[0051] In this way, the piezoelectric element 42 is vibrated so as to generate a standing wave SW in the radial direction of the flow channel 50 in the sample liquid 30, and the liquid in which the particles are concentrated is collected from the inner tube 58, thereby making it possible to concentrate the particles.

[0052] 4(C), when the particles in the sample liquid 30 are discharged by the first pump 20 and the second pump 22 from a state in which the particles are concentrated, it is preferable to discharge the sample liquid 30 in a state in which the flow of the sample liquid 30 is a laminar flow inside the flow path 50 in order to prevent the particles from being discharged from the outer tube 56 due to disturbance in the flow of the liquid. The sample liquid 30 may be collected while being irradiated with ultrasonic waves.

[0053] In addition, the discharge amount of the first pump 20 connected to the outer pipe 56 is greater than the discharge amount of the second pump 22 connected to the inner pipe 58. The ratio of the discharge amounts of the first pump 20 and the second pump 22 according to one embodiment of the present disclosure is desirably equal to the ratio of the cross-sectional areas of the diameters of the outer pipe 56 and the inner pipe 58.

[0054] (Determination of the first frequency) In the particle recovery device of this embodiment, an example of a procedure for determining an optimal frequency, which is an ultrasonic frequency that can satisfactorily recover particles in a sample liquid 30, will be shown as a procedure for measuring the sample liquids 30 of Samples 1 to 5. For each sample, the same human urine was used as a matrix, which is a standard component.

[0055] As the sample liquid 30 of sample 1, human epithelial cells, which are formed components in urine, were added as particles to urine prepared by mixing multiple urine samples from healthy individuals for averaging. The density of the sample liquid 30 of sample 1 was 1.01 g / cm 3 It was.

[0056] As the sample solution 30 of sample 2, glucose was added to sample 1 to make the density 1.02 g / cm 3 was prepared.

[0057] As sample solution 30 of sample 3, urea was added to sample 1 to make the density 1.02 g / cm 3 was prepared.

[0058] As sample solution 30 of sample 4, albumin was added to sample 1 to make the density 1.02 g / cm 3 was prepared.

[0059] As sample solution 30 of sample 5, glucose was added to sample 1 to make the density 1.05 g / cm 3 was prepared.

[0060] For sample solution 30 of sample 6, urea was added to sample 1 to make the density 1.05 g / cm 3 was prepared.

[0061] As sample solution 30 of sample 7, albumin was added to sample 1 to make the density 1.05 g / cm 3 was prepared.

[0062] Table 1 below summarizes the descriptions of Samples 1 to 7 above.

[0063] [Table 1]

[0064] Concentration rates were calculated for the sample liquid 30 of Sample 1 to Sample 7 by comparing the concentration of the solid components contained in the concentrated liquid 34 after the concentration procedure described below with the concentration of the solid components in the sample liquid 30 before the concentration procedure. Furthermore, the concentration rate was multiplied by the ratio of the flow rate of the concentrated liquid 34 to the flow rate of the sample liquid 30 to obtain a recovery rate. The recovery rate indicates the ratio (B / A) of the number of solid components (B) contained in the concentrated liquid 34 to the number of solid components (A) contained in the sample liquid 30 before the concentration procedure. In this embodiment, the flow rate of the concentrated liquid 34 is 20% of the flow rate of the sample liquid 30, so that if the recovery rate exceeds 20%, it can be said that concentration has been achieved. If the recovery rate exceeds 20%, it can be said that a standing wave SW with a node formed in the center of the flow path 50 is generated.

[0065] FIG. 5 is a flow diagram of the operation procedure of the particle collection device for measuring the frequency of the ultrasonic waves generated by the standing wave SW.

[0066] First, in a first step S11, the sample liquid 30 stored in the spitz tube 12 is caused to flow into the flow path 50 in the flow cell 40 by driving only the first pump 20 while the second pump 22 is stopped.

[0067] Next, in a second step S12, after the sample liquid 30 is caused to flow into the flow path 50, the first pump 20 is stopped and a predetermined time T1 is waited until the flow of the sample liquid 30 in the flow path 50 stops.

[0068] Next, in the third step S13, a constant AC voltage of 60 V is supplied from the oscillator 16 to the piezoelectric element 42 to vibrate the piezoelectric element 42, and ultrasonic waves of a constant frequency are irradiated onto the sample liquid 30 in the flow path 50 for a predetermined time T2 to generate a node N on the central axis of the flow cell 40.

[0069] Next, in a fourth step S14, the supply of AC voltage from the oscillator 16 to the piezoelectric element 42 is stopped, causing the piezoelectric element 42 to stop vibrating.

[0070] Next, in a fifth step S15, the first pump 20 and the second pump 22 are driven to discharge the sample liquid 30 from the flow path 50 by causing the concentrated liquid 34 to flow into the inner tube 58 and the low concentration liquid 32 to flow into the outer tube 56, as shown in Figure 4(C).

[0071] Here, in the third step S13, ultrasonic waves having frequencies of 330 kHz, 330.5 kHz, and 331 kHz were irradiated to sample 1, 330.5 kHz, 331 kHz, and 331.5 kHz to samples 2 to 4, 332.5 kHz, 333 kHz, and 333.5 kHz to sample 5 and sample 7, and 332.5 kHz, 333 kHz, 333.5 kHz, 334 kHz, and 334.5 kHz to sample 6.

[0072] FIG. 6 shows the results of measuring the recovery rate by subjecting the sample liquids 30 of Samples 1 to 7 to the above-mentioned concentration treatment, measuring and comparing the concentrations of formed components before and after the concentration treatment.

[0073] As shown in FIG. 6(A), the density is 1.01 g / cm 3 In the sample liquid 30 of sample 1, the recovery rate exceeded 20% at frequencies of 330 kHz, 330.5 kHz, and 331 kHz, so it can be said that a standing wave SW occurred. The recovery rate was improved most when the frequency of the irradiated ultrasonic waves was set to 330.5 kHz. It was also estimated that the recovery rate decreased when ultrasonic waves with a frequency of 331 kHz or higher were irradiated. In this way, by irradiating the sample liquid 30 of sample 1 with ultrasonic waves with a frequency of 330.5 kHz, the particles in the sample liquid 30 can be efficiently recovered.

[0074] Similarly, as shown in FIG. 6(B), the density is 1.02 g / cm 3In the sample liquid 30 of Sample 2, Sample 3, and Sample 4, the recovery rate exceeded 20% at frequencies of 330.5 kHz, 331 kHz, and 331.5 kHz, so it can be said that a standing wave SW occurred. The recovery rate was improved most when the frequency of the irradiated ultrasonic waves was set to 331 kHz. In this way, by irradiating the sample liquid 30 of Sample 2, Sample 3, and Sample 4 with ultrasonic waves of 331 kHz, which is higher than the frequency of 330.5 kHz at which the highest recovery rate was obtained in Sample 1, it is possible to efficiently recover particles in the sample liquid 30.

[0075] Similarly, as shown in FIG. 6C, in the sample liquid 30 of Sample 5 and Sample 7, whose density is 1.05 g / cm3, the recovery rate exceeds 20% at frequencies of 332.5 kHz, 333 kHz, and 333.5 kHz, so that it can be said that standing waves SW occurred. In the sample liquid 30 of Sample 6, whose density is 1.05 g / cm3, the recovery rate exceeds 20% at frequencies from 332.5 kHz to 334.5 kHz, so that it can be said that standing waves SW occurred. And, the recovery rate was most improved when the frequency of the irradiated ultrasonic wave was set to 333 kHz in Sample 5, 334 kHz in Sample 6, and 332.5 kHz in Sample 7. Thus, by irradiating the sample liquids of Sample 5, Sample 6, and Sample 7 with ultrasonic waves of 333 kHz, 334 kHz, and 332.5 kHz, which are higher than the frequency of 331 kHz at which the highest recovery rate is obtained in Samples 2 to 4, respectively, it is possible to efficiently recover particles in the sample liquid 30.

[0076] From this, it is understood that the above concentration process can generate standing waves SW for any of the sample liquids 30 of Sample 1 to Sample 7, and that it is possible to set the frequency of the ultrasonic waves that improves the recovery rate. In addition, it is understood that the ultrasonic frequencies that can efficiently recover particles in the sample liquid 30 are different for Samples 1 to 7, since the densities of the samples are different for each sample. In addition, the frequency that can effectively recover particles from a high-density sample tends to be higher than the frequency that can effectively recover particles from a low-density sample. From this, it is understood that there is a correlation between the density of a sample and the frequency that can effectively recover particles from the sample, and that particles contained in the sample can be effectively recovered by irradiating the sample with ultrasonic waves of a frequency according to the density of the sample.

[0077] Therefore, by irradiating sample liquids 30 having different densities, such as samples 1 to 7, with ultrasonic waves at frequencies corresponding to the respective densities, standing waves SW can be generated even when the densities of the sample liquids 30 are different.

[0078] Therefore, a first frequency is obtained that can effectively recover formed elements contained in a sample representative of each density of sample liquid 30. The first frequency is an ultrasonic frequency that generates a standing wave SW on the central axis of the flow path 50 containing the sample liquid 30 and can efficiently recover particles in the sample liquid 30. Then, a "density vs. frequency relationship" (to be described later) that is a correspondence relationship between the density and the first frequency is obtained, and the "density vs. frequency relationship" is stored in the storage unit 70.

[0079] Then, a second frequency is derived from the measured density value and the density-frequency relationship obtained by measuring the density of the sample liquid 30. The second frequency is presumed to be a frequency that allows good recovery of particles contained in the sample liquid 30. Then, the frequency of the ultrasonic waves to be irradiated to the sample liquid in the flow channel according to the first embodiment is determined.

[0080] The first frequency can be, for example, a median or average of frequencies obtained by preparing a plurality of sample liquids 30 exhibiting the same density and determining the frequency at which the formed components contained in the sample liquids 30 can be recovered with a high recovery rate. Alternatively, a plurality of sample liquids 30 can be mixed to prepare an averaged sample liquid, and the frequency at which the formed components contained in the averaged sample liquid can be recovered satisfactorily can be determined.

[0081] If the frequency of the ultrasonic wave is f [Hz], then f can be calculated by the following formula (2): where v is the speed of sound propagating through the sample liquid 30 [m / s].

[0082]

number

[0083] Then, by substituting equation (1) into equation (2) and transforming the equation, we obtain the following equation (3).

[0084]

number

[0085] Here, in the above-mentioned formula (3), n can take any integer value (n=1, 2, 3, etc.) as the so-called vibration mode. In other words, if the frequency f of the ultrasonic wave is set to a frequency where n is an integer value, it is possible to generate a standing wave SW in the flow path 50.

[0086] The number of nodes N in the standing wave SW is an integer value equal to n. For example, if the frequency f of the ultrasonic wave is set so that n is 2, the number of nodes N of the generated standing wave SW will be 2.

[0087] Furthermore, the position at which node N occurs is a position obtained by equally dividing the distance from inner wall surface A to inner wall surface B (the radial length of flow path 50) by n+1. For example, when n=1, node N occurs at a position 1 / 2 of the length from inner wall surface A to inner wall surface B. When n=2, node N occurs at a position 1 / 3 and a position 2 / 3 of the length from inner wall surface A to inner wall surface B.

[0088] In this manner, when n=1, the position of the node N of the standing wave SW in the particle recovery device 10 according to this embodiment is only on the central axis of the flow path 50, as shown in FIG. 4(B).

[0089] (Particle concentration procedure) Next, the particle concentrating method according to the first embodiment of the present disclosure will be described with reference to FIG.

[0090] FIG. 7 is a flow diagram of a particle concentration procedure according to the first embodiment of the present disclosure, and the procedure of the particle concentration process will be described with reference to this diagram.

[0091] First, in a first step S21, the first pump 20 alone is driven while the second pump 22 is stopped, thereby causing the sample liquid 30 stored in the Spitz tube 12 to flow into the density measurement unit 60. Then, the density measurement unit 60 measures the density of the sample liquid 30, and transmits the measured value of the density of the sample liquid 30 to the control unit 44.

[0092] Next, in a second step S22, the control unit 44 derives a second frequency for the sample liquid 30 based on the density value of the sample liquid 30 received from the density measurement unit 60 and the density vs. frequency relationship stored in the memory unit 70.

[0093] Next, in a third step S23, the first pump 20 alone is driven to cause the sample liquid 30 to flow into the flow path 50 in the flow cell 40.

[0094] Next, in a fourth step S24, after the sample liquid 30 is caused to flow into the flow path 50, the first pump 20 is stopped and the flow of the sample liquid 30 in the flow path 50 is waited for a predetermined time T1 until the flow of the sample liquid 30 in the flow path 50 stops.

[0095] Next, in a fifth step S25, an AC voltage is supplied from the oscillator 16 to the piezoelectric element 42 to vibrate the piezoelectric element 42, and the sample liquid 30 in the flow channel 50 is irradiated with the vibration (ultrasonic wave) of the second frequency derived in S22 for a predetermined time T2. A node N is generated on the central axis of the flow channel 50, and the particles in the flow channel 50 move to the position of the node N.

[0096] Next, a sixth step S26 is carried out. Since S26 is the same as S14, the explanation thereof will be omitted.

[0097] Next, the seventh step S27 is carried out. Since S27 is the same as S15, the explanation thereof will be omitted.

[0098] Next, in an eighth step S28, the amount of concentrated liquid discharged into the inner tube 58 is measured to confirm whether the amount of concentrated liquid obtained is appropriate for the intended use of the concentrated liquid. If the amount of concentrated liquid obtained is not sufficient at this point, the process returns to the third step S23, and if the amount of concentrated liquid obtained is sufficient, the concentration procedure is terminated.

[0099] (Action and Effects) By carrying out the particle concentration process according to the above-mentioned procedure, the following actions and effects are obtained.

[0100] First, according to the particle collection device 10 according to the first embodiment of the present disclosure, the control unit 44 derives the frequency (second frequency) of the ultrasonic waves to be irradiated into the flow path 50 from the density value of the sample liquid 30 measured by the density measurement unit 60 and the density-to-frequency relationship. The second frequency derived from the density value of the sample liquid 30 and the density-to-frequency relationship is presumed to be a frequency that exhibits a high collection rate. Then, the ultrasonic waves of the second frequency derived by the control unit 44 are irradiated from the ultrasonic irradiation unit to the sample liquid 30 in the flow path 50.

[0101] As a result, the particles dispersed in the sample liquid 30 are focused at the position of a node N of the standing wave SW.

[0102] Here, when multiple sample liquids 30 are prepared and the densities of the sample liquids 30 differ among the multiple sample liquids 30, the ultrasonic frequency at which particles in the sample liquids 30 can be efficiently recovered differs for each sample liquid 30.

[0103] However, the particle collection device 10 according to the first embodiment of the present disclosure measures the density of the sample liquid 30 by the density measuring unit 60. This measures the density for each sample liquid 30, and from the obtained density value of the sample liquid 30 and the density vs. frequency relationship stored in the storage unit 70, it is possible to determine the ultrasonic frequency at which the particles contained in the sample liquid 30 can be favorably collected.

[0104] In this way, according to the particle collection device 10 of the first embodiment of the present disclosure, even if multiple sample liquids 30 have different densities and therefore different frequencies at which particles can be efficiently collected from each sample liquid 30, the frequency of ultrasound to be irradiated into the flow path can be determined for each sample liquid 30, so that ultrasound of a frequency at which particles can be efficiently collected from the sample liquid 30 can be irradiated.

[0105] Therefore, even when particles are measured in a series of operations using a plurality of sample liquids 30, it is possible to concentrate the particles, thereby improving the work efficiency and stabilizing the recovery rate of formed components.

[0106] As described above, since the number of nodes N of the standing wave SW at the optimum frequency is set to 1, the particles are concentrated in the center of the flow channel 50 in the radial direction, which is the position of the node N.

[0107] Here, a double pipe including an outer pipe 56 and an inner pipe 58 arranged inside the outer pipe 56 along the central axis of the outer pipe 56 is connected to the outlet 54 of the particle collection device 10 according to one embodiment of the present disclosure, the outer pipe 56 being arranged coaxially with the flow path 50, and the inner pipe 58 being arranged on the central axis of the flow path 50.

[0108] Therefore, in the sample liquid 30 filled in the flow path 50, the concentrated liquid 34 easily flows into the inner tube 58, and the low concentration liquid 32 easily flows into the outer tube 56, thereby improving the efficiency of concentrating particles.

[0109] Furthermore, as described above, in the particle collection device 10 according to the first embodiment of the present disclosure, the sample liquid 30 is left stationary after flowing into the flow path 50, and vibration is applied to the sample liquid 30 while it is stored therein, thereby preventing the sample liquid 30 from flowing inside the flow path 50.

[0110] Therefore, when the sample liquid 30 is discharged from the flow path 50, the flow of the sample liquid 30 can be made into a laminar flow state so that the concentrated liquid 34 can easily flow into the inner tube 58 and the low concentration liquid 32 can easily flow into the outer tube 56. This can improve the efficiency of concentrating particles.

[0111] (Modification) In the above description, the density measuring unit 60 and the storage unit 70 are components of the particle collection device 10, but the configuration of the particle collection device 10 according to the first embodiment of the present disclosure is not limited to this.

[0112] 8, the density measuring device 62 and the memory device 72 may be provided separately from the housing 24 that houses the support member 18, the oscillator 16, the first pump 20, the second pump 22, and the control unit 44. The density measuring device 62 and the memory device 72 are connected to the control unit 44. In this case as well, the introduction path 14 is connected to the spitz tube 12, and the sample liquid 30 stored in the spitz tube 12 flows through the introduction path 14 and is introduced into the flow cell 40.

[0113] Then, a density measuring device 62 provided in the middle of the introduction path 14 transmits the density value of the sample liquid 30 to the control unit 44 of the particle collection device 10. The control unit 44 receives the density value of the sample liquid 30 received from the density measuring device 62 and the density vs. frequency relationship from the storage device 72, and thereby determines the frequency of the ultrasonic waves.

[0114] Even in this case, the same effects as those of the particle recovery device 10 according to the first embodiment of the present disclosure can be obtained.

[0115] Further, for example, not only the frequency is determined according to the density of the sample liquid 30 as described above, but also the amplitude of the ultrasonic waves irradiated in S25 and the irradiation time T2 of the ultrasonic waves may be determined according to the density of the sample liquid 30.

[0116] Even when the sample liquid 30 is irradiated with ultrasonic waves of the second frequency, the recovery rate of the formed components contained in the high-density sample liquid 30 is lower than that of the low-density sample liquid 30. Therefore, the high-density sample liquid 30 is irradiated with ultrasonic waves having a larger amplitude than that of the low-density sample liquid 30, or the high-density sample liquid 30 is irradiated with ultrasonic waves for a longer time than that of the low-density sample liquid 30. As a result, particles from the sample liquids 30 with different densities can be recovered at a stable recovery rate.

[0117] As described above, the flow cell 40 is made of glass, for example, and therefore it is possible to observe formed elements contained in the sample liquid 30 flowing through the flow channel 50 through the flow cell 40. For this reason, as shown in Fig. 9, the particle collection device 10 according to the present disclosure may further include an image detector 80 for observing the inside of the flow channel 50 at a position where the flow cell 40 is viewed from the side.

[0118] In this case, the image detector 80 acquires the state of focusing of the particles in the flow channel 50 and transmits it to the control unit 44. This enables the control unit 44 to correct the ultrasonic frequency, the ultrasonic amplitude, or the predetermined time T2 in S25 of the concentration process procedure based on the state of focusing of the particles.

[0119] Furthermore, in the case where the control unit 44 has an input unit to which a density of the sample liquid 30 measured in advance is input, and the frequency is determined based on the input value of the density of the sample liquid 30, the particle collection device 10 may be configured not to have the density measurement unit 60. The input unit corresponds to the density acquisition unit.

[0120] The input unit is, for example, a button or a terminal that allows the operator of the particle collection device 10 to input the density to the control unit. For example, when the sample liquid 30 is urine, a portion of the subject's urine collected in a urine collection cup is dispensed into the Spitz tube 12, and a portion of the urine is left in the urine collection cup. The creatinine concentration in the urine, which correlates with the urine density, is measured by dipping a creatinine test paper into the urine remaining in the urine collection cup. The density can be input to the control unit 44 by inputting the measured value of the creatinine concentration into the input unit.

[0121] Furthermore, in the case where the frequency corresponding to the density of the sample liquid 30 is directly determined by an operator who operates the particle recovery device 10, the particle recovery device 10 may be configured without including the memory unit .

[0122] In the above description, the density measuring unit 60 measures the density of the sample liquid 30 from the volume and weight of the sample liquid 30, but this is not limiting and a value known to be correlated with density may be used. For example, the osmotic pressure, refractive index, electrical resistivity, creatinine concentration, etc. of the sample liquid 30 may be measured, and the obtained value may be used instead of the density in the above description.

[0123] In addition, by providing a pressurizing means such as a liquid delivery pump in the middle of the introduction path 14, the sample liquid 30 in the flow path 50 may be pressurized when the inflow of the sample liquid 30 into the flow path 50 is completed.

[0124] In this case, since the sample liquid 30 in the flow path 50 is pressurized by the pressurizing means during S25, it is possible to prevent cavitation from occurring in the sample liquid 30 filled in the flow path 50. This improves the particle concentration efficiency and prevents the particles from being destroyed.

[0125] In the present embodiment, the piezoelectric element 42 is provided on only one side of the flow direction of the flow cell 40, but this is not limiting. For example, the second piezoelectric element may be provided on the opposite side of the flow direction of the flow cell 40 to the piezoelectric element 42. In this case, the ultrasonic wave generated from the second piezoelectric element and irradiated into the flow channel 50 has the same frequency and amplitude as the ultrasonic wave generated from the piezoelectric element 42 and irradiated into the flow channel 50, and has the same phase at the central axis of the flow channel 50.

[0126] In the above-described particle recovery device 10, the diameter of the inner tube 58 is approximately half that of the outer tube 56, but the embodiment of the present disclosure is not limited to this. For example, by preparing various ratios of the diameter of the inner tube 58 to the diameter of the outer tube 56, the recovery rate of particles in the sample liquid 30 may be appropriately set.

[0127] In addition, the ratio of the discharge amounts of the sample liquid 30 by the first pump 20 and the second pump 22 is set to be equal to the ratio of the cross-sectional areas of the inner tube 58 and the outer tube 56, but the ratio of the discharge amounts of the sample liquid 30 by the first pump 20 and the second pump 22 in the particle collection device 10 according to an embodiment of the present disclosure is not limited to this. For example, the collection rate of particles in the sample liquid 30 may be appropriately set by varying the ratio of the discharge amounts of the sample liquid 30 by the first pump 20 and the second pump 22.

[0128] In the above-mentioned particle collection device 10, the predetermined number (the number of nodes N obtained by the standing wave SW) is set to 1, but the standing wave SW that the particle collection device 10 according to an embodiment of the present disclosure can have is not limited to this. For example, as shown in the above-mentioned formula (3), n may be an integer of 2 or more, and the frequency of the ultrasonic waves may be set so that the number of nodes N obtained by the standing wave SW is 2 or more (so-called high-order mode) to generate the standing wave SW. In this case, since the nodes N are also generated at positions off the center in the radial direction of the flow path 50, the diameter of the inner tube 58 may be changed to correspond to the position of the nodes N, and the discharge port 54 may be replaced by a double tube, and a multiple tube in which a larger number of tubes are connected coaxially may be used, and the inner tubes 58 may be disposed at positions corresponding to the positions where the nodes are generated.

[0129] In addition, although it is said that the particle recovery device 10 according to an embodiment of the present disclosure can concentrate particles in the sample liquid 30, depending on the density and physical properties of the sample liquid 30 and the particles, the particles may be concentrated at the antinode position rather than the node N position of the standing wave generated by the vibration of the piezoelectric element 42. In this case, the relationship between the first pump 20 and the second pump 22 and the outer tube 56 and the inner tube 58 described above may be reversed. That is, by making the low concentration liquid 32 on the inner tube 58 side and the concentrated liquid 34 on the outer tube 56 side, the particles can be concentrated.

[0130] In the above description, the flow cell 40 has a substantially rectangular parallelepiped shape as an example, but the embodiment of the present disclosure is not limited to this. For example, the flow cell 40 may have a cylindrical shape or a regular polygonal prism shape.

[0131] In addition, in the above description, the flow passage 50 is a circular hole, but the embodiment of the present disclosure is not limited to this. For example, the flow passage 50 may be a polygonal hole.

[0132] Second Embodiment Next, a particle recovery device 10 according to a second embodiment of the present disclosure will be described. Note that descriptions of the same configuration and the same principle as in the first embodiment will be omitted.

[0133] (composition) Fig. 10 is a diagram showing the configuration of particle collection according to the second embodiment of the present disclosure. As shown in Fig. 10, the particle collection device 10 according to the second embodiment of the present disclosure differs from the particle collection device 10 according to the first embodiment in the following respects. That is, the particle collection device 10 according to the second embodiment includes a component information acquisition unit 90 in the introduction path 14.

[0134] As an example, the component information acquisition unit 90 is provided midway through the inlet path 14, and measures the concentrations of multiple components contained in the sample liquid 30 that flows through the inlet path 14 and into the flow cell 40. Then, the component information acquisition unit 90 transmits the measured values ​​of the concentrations of the components in the sample liquid 30 to the control unit 44. That is, the control unit 44 according to the second embodiment receives the value of the density of the sample liquid 30 from the density measurement unit 60, and also receives the measured values ​​of the concentrations of the components contained in the sample liquid 30 from the component information acquisition unit 90.

[0135] The components measured by the component information acquisition unit 90 are components whose concentrations in the sample liquid 30 vary greatly depending on the individual sample liquids 30, and are components that affect the density of the sample liquid 30. The components measured by the component information acquisition unit 90 can be set appropriately depending on the type of sample liquid 30. When the sample liquid 30 is urine, the components measured by the component information acquisition unit 90 are, for example, glucose, urea, and albumin. Furthermore, the component information acquisition unit 90 can be a biosensor such as a glucose sensor.

[0136] Then, the frequency of the AC voltage that the oscillator 16 supplies to the piezoelectric element is determined based on the received density value of the sample liquid 30, the received concentration values ​​of the components contained in the sample liquid 30, and the correspondence between the density and frequency of each component measured by the component information acquisition unit stored in the memory unit 70.

[0137] The other configurations are similar to those of the particle recovery device 10 according to the first embodiment.

[0138] (Determining the optimum frequency) In the particle collection device 10 according to the second embodiment, the first frequency is obtained by the procedure shown in FIG. 5, similarly to the particle collection device 10 according to the first embodiment.

[0139] First, the density of sample liquid 30 and the concentrations of components contained in sample liquid 30 are measured, and the correspondence relationship between the density of sample liquid 30 and the first frequency obtained by the procedure for determining the first frequency according to the first embodiment, as shown in FIG. 13 described below, is stored in memory unit 70 as the “density versus frequency relationship” according to the second embodiment of the present disclosure.

[0140] Furthermore, in the procedure for measuring the frequency of the ultrasound irradiated to the sample liquid 30 according to the second embodiment, the component information acquisition unit 90 measures a first frequency that similarly shows a high recovery rate for multiple sample liquids 30 that contain the highest concentrations of each component being measured.

[0141] Then, for each type of component contained in sample liquid 30 at the highest concentration, the correspondence relationship between the density of sample liquid 30 and the first frequency is stored in memory unit 70.

[0142] Then, the optimal frequency according to the second embodiment is determined by deriving a second frequency from the density vs. frequency relationship created using a sample containing the component contained in the highest concentration in sample liquid 30, the measured density of sample liquid 30, and the measured concentrations of multiple components.

[0143] (Particle concentration procedure) Next, a particle concentrating method according to a second embodiment of the present disclosure will be described with appropriate reference to FIG.

[0144] FIG. 11 is a flow diagram of a particle concentration procedure according to the second embodiment of the present disclosure, and the procedure of the particle concentration process will be described with reference to this diagram.

[0145] First, in a first step S31, the first pump 20 alone is driven with the second pump 22 stopped, causing the sample liquid 30 stored in the Spitz tube 12 to flow into the density measurement unit 60 and the component information acquisition unit 90. Then, the density measurement unit 60 transmits the value of the density of the sample liquid 30 to the control unit 44, and the component information acquisition unit 90 transmits the concentration of the components contained in the sample liquid 30 to the control unit 44.

[0146] Next, in a second step S32, a second frequency for sample liquid 30 is derived based on the value of the density of sample liquid 30 received from density measurement unit 60 and the density vs. frequency relationship stored in storage unit .

[0147] The component contained in sample liquid 30 at the highest concentration is selected from among the components contained in sample liquid 30 received from component information acquisition unit 90, and a density vs. frequency relationship that was created using sample liquid 30 containing the same component as the selected component and stored in storage unit 70 is selected. Then, a second frequency is obtained based on the selected density vs. frequency relationship and the density value of sample liquid 30, and the frequency (second frequency) of the ultrasound to be irradiated to sample liquid 30 is determined.

[0148] Alternatively, the second frequency for each component is obtained from the "density vs. frequency relationship" for each component stored in memory unit 70 and the density value of sample liquid 30. By multiplying the obtained second frequency for each component by the ratio of the measured concentration of each component, a second frequency weighted by the concentration of each component is obtained, and the frequency of the ultrasound to be irradiated to sample liquid 30 can be determined.

[0149] In the particle concentration procedure according to the second embodiment, steps S33 to S39 are similar to steps S23 to S29 in the particle concentration procedure according to the first embodiment.

[0150] (Action and Effects) By carrying out the particle concentration process according to the above-mentioned procedure, the following actions and effects are obtained.

[0151] First, when multiple sample liquids 30 are prepared and the liquid properties such as density and viscosity of the sample liquids 30 are different among the multiple sample liquids 30, the ultrasonic frequency at which particles in the sample liquids 30 can be efficiently collected is different for each sample liquid 30. Specifically, the frequency at which particles in a high-density sample can be efficiently collected tends to be higher than the frequency at which particles in a low-density sample can be efficiently collected. However, even if the sample liquids 30 have the same density, if the concentrations of the components contained in the sample liquids 30 are different, the ultrasonic frequency at which particles in the sample liquids 30 can be efficiently collected also changes slightly.

[0152] Here, the particle collection device 10 according to the second embodiment of the present disclosure further includes a component information acquisition unit 90 in addition to the particle collection device 10 according to the first embodiment, and is therefore capable of acquiring the concentration of the components in the sample liquid 30.

[0153] Therefore, in the particle collection device 10 according to the second embodiment of the present disclosure, the concentration of a component contained in the sample liquid 30 is measured, a second frequency is derived from a density-to-frequency relationship created using a sample containing the measured component, the measured density value of the sample liquid 30, and the measured concentration of the component, and ultrasonic waves of the second frequency are irradiated to the sample liquid 30. Thus, the frequency of the ultrasonic waves to be irradiated to the sample liquid 30 can be determined.

[0154] As a result, the particle recovery device 10 of the second embodiment of the present disclosure is able to derive the optimal frequency for generating standing waves more accurately than the particle recovery device 10 of the first embodiment of the present disclosure, and is able to recover particles contained in the sample liquid 30.

[0155] Other functions and effects are similar to those of the particle recovery device 10 according to the first embodiment.

[0156] (Modification) In the above description, the particle recovery device 10 according to the second embodiment may further perform the following control.

[0157] In the particle collection device 10 according to the second embodiment, the amplitude of the ultrasonic waves irradiated to the sample liquid 30 may be adjusted according to the concentration of the component measured by the component information acquisition unit 90. For example, when the amplitude of the ultrasonic waves irradiated to the sample liquid 30 is reduced, the occurrence of cavitation in the flow path can be suppressed, and the destruction of particles can be prevented. When the amplitude of the ultrasonic waves irradiated to the sample liquid 30 is increased, the pressure due to the standing waves generated in the flow path increases, and the focusing of the particles can be accelerated.

[0158] Also, for example, the predetermined time T2 for irradiating the sample liquid 30 with ultrasonic waves may be adjusted depending on the type of the component measured at the highest concentration among the components measured by the component information acquisition unit 90. When the predetermined time T2 for irradiating the sample liquid 30 with ultrasonic waves is increased, the time for particles in the sample liquid 30 to focus increases, and the recovery rate can be improved. When the predetermined time T2 for irradiating the sample liquid 30 with ultrasonic waves is decreased, the time required for the particle recovery operation is reduced, and the efficiency of the particle recovery process can be improved.

[0159] Furthermore, the control unit 44 may have an input unit to which the previously measured concentrations of the components of the sample liquid 30 are input, and the control unit 44 may determine the frequency based on the input values ​​of the concentrations of the components of the sample liquid 30. In this case, the particle collection device 10 may be configured not to have the component information acquisition unit 90. The concentrations of the components contained in the sample liquid 30 may be measured, for example, using urine test strips.

[0160] In addition, if the operator operating the particle collection device 10 directly determines the frequency of the ultrasound to be irradiated to the sample liquid 30 based on the concentration of the components of the sample liquid 30, the particle collection device 10 may be configured not to have a memory unit 70.

[0161] Note that the modifications of the particle recovery device 10 according to the first embodiment of the present disclosure can also be applied to the particle recovery device 10 according to the second embodiment of the present disclosure. EXAMPLES

[0162] Next, the effects of the first embodiment of the present disclosure were verified from the results of various experiments shown below. The flow cell 40 used in the experiments had a longitudinal dimension of 100 mm, a transverse dimension (radial direction) of 16.9 mm on the long side and 10 mm on the short side, and the diameter of the flow channel 50 was 2.6 mm. The piezoelectric element 42 was disposed on one surface along the longitudinal direction of the short side of the flow cell 40 in the transverse direction.

[0163] As the sample liquid 30 of sample 8, human epithelial cells, which are particles of formed components, were added to urine prepared by mixing multiple urine samples from healthy individuals. The density of the sample liquid 30 of sample 8 was 1.02 g / cm 3 The above-mentioned items were used for Sample 5, Sample 6, and Sample 7. The details of Sample 8 are summarized in Table 2.

[0164] [Table 2]

[0165] (Experiment 1) In Experiment 1, the first frequency of each of the sample solutions 30 of Samples 1 to 7 was measured at intervals of 0.5 kHz to confirm the effect of the particle recovery method according to the first embodiment of the present disclosure.

[0166] FIG. 12 shows the results of measuring the first frequency at 0.5 kHz intervals for each of the sample liquids 30 of Samples 1 to 7 by the procedure shown in FIG. 5, and calculating the density (1.01 g / cm 3 , 1.02g / cm 3 and 1.05 g / cm 3 ) is a diagram showing the results using the median value of the first frequency for each frequency band.

[0167] More specifically, as shown in FIG. 6, the density is 1.01 g / cm 3 The recovery rate of formed components in sample 1 was measured by irradiating ultrasonic waves of 330 kHz, 330.5 kHz, and 331 kHz to sample 1, which shows a density of 1.01 g / cm. The highest recovery rate was observed at 330.5 kHz. 3 The first frequency of the sample solution 30 was set to 330.5 kHz, and is plotted in FIG.

[0168] Density is 1.02g / cm 3The recovery rates of formed components contained in Samples 2 to 4 were measured by irradiating ultrasonic waves of 330.5 kHz, 331 kHz, and 331.5 kHz to Samples 2 to 4, which showed the density of 1.02 g / cm. 3 The first frequency of the sample solution 30 was set to 331 kHz, and the result is plotted in FIG.

[0169] Density is 1.05g / cm 3 Samples 5 and 7 were irradiated with ultrasonic waves of 332.5 kHz, 333 kHz, and 333.5 kHz to measure the recovery rate of formed components contained in samples 5 and 7.

[0170] Density is 1.05g / cm 3 For sample 6, which shows a density of 1.05 g / cm3, the recovery rate of formed components was measured when ultrasonic waves of 334 kHz and 334.5 kHz were applied. The highest recovery rate was observed at 333 kHz for sample 5, 334 kHz for sample 6, and 332.5 kHz for sample 7. The median frequency of 333 kHz, which showed the highest recovery rate for samples 5, 6, and 7, was used as the density of 1.05 g / cm3. 3 The first frequency of the sample solution 30 is plotted in FIG.

[0171] In this experiment, the density was 1.02 g / cm 3 The first frequency of each of the sample liquids 30, which are different in components, is measured, and the median value obtained is 1.02 g / cm 3 is the first frequency of the sample liquid 30, and the density is 1.02 g / cm 3 A first frequency of the averaged sample liquid is calculated based on the density of the sample liquid 30. 3 The first frequency of the sample liquid 30 is 1.05 g / cm 3 The first frequency of the sample liquid 30 can be obtained in a similar manner.

[0172] It can be seen from Fig. 12 that the optimum frequency of each plot point increases as the density increases. That is, it can be seen from Fig. 12 that the optimum frequency changes depending on the density of the sample liquid 30.

[0173] As shown in FIG. 12, the relationship between density and optimal frequency, that is, the density vs. frequency relationship, can be obtained by interpolating between the plotted points. In the example shown in FIG. 12, the density is expressed as ρ(g / cm 3 ), and the frequency is f (kHz), then f = 63.462ρ + 266.35, as shown by the dotted line in Figure 12.

[0174] By storing the density vs. frequency relationship thus obtained in the memory unit 70 of the particle collection device 10 according to the first embodiment of the present disclosure, even when particles contained in an unknown sample liquid 30 are focused and collected, the control unit 44 can determine the second frequency based on the density vs. frequency relationship stored in the memory unit 70. Note that, although a correlation equation between density and the first frequency is used as the density vs. frequency relationship in this experiment, a lookup table comparing density and the first frequency may also be used.

[0175] 13 shows the relationship between the density and the first frequency of sample liquid 30 for each of the various components (glucose, urea, and albumin) added to the sample liquids of Samples 2 to 7. That is, Fig. 13(A) shows the relationship between the density and the first frequency of sample liquid 30 of Samples 2 and 5 in which the component contained in the sample liquid at the highest concentration is glucose, Fig. 13(B) shows the relationship between the density and the first frequency of sample liquid 30 of Samples 3 and 6 in which the component contained in the sample liquid at the highest concentration is urea, and Fig. 13(C) shows the relationship between the density and the first frequency of sample liquid 30 of Samples 4 and 7 in which the component contained in the sample liquid at the highest concentration is albumin.

[0176] From Fig. 13, it can be seen that, as in Fig. 12, the first frequency of each plot point increases as the density increases, but the slope of the plot points, i.e., the density vs. frequency relationship, differs for each component. Therefore, from Figs. 13(A) to (C), it can be seen that even if the density of sample solution 30 is approximately the same, the first frequency changes depending on the components contained therein. In the example shown in Figs. 13(A) to (C), the frequency of sample solution 30 to which glucose has been added is f G (kHz), and the frequency of the sample solution 30 containing urea is f B (kHz), and the frequency of the sample solution 30 containing albumin is f A (kHz), then, as shown by the dotted line in Figure 13(A), G =66.667ρ+263, as shown by the dotted line in Figure 13(B) B =100ρ+229, as shown by the dotted line in Figure 13(C), A =50ρ+280.

[0177] In this way, the correspondence relationship between the density of the sample liquid 30 and the first frequency for each component contained in the sample liquid 30 (for each component measured by the component information acquisition unit 90) is stored in advance in the memory unit 70 of the particle recovery device 10 according to the first embodiment of the present disclosure. Then, the component information acquisition unit 90 reads out from the memory unit the correspondence relationship between the density and the first frequency for the component that exhibits the highest measured concentration value among the measured concentration values ​​of the components detected. The second frequency is derived using the read-out correspondence relationship and the density acquired by the density acquisition unit. As a result, even when particles of an unknown sample liquid 30 are focused and recovered, it can be said that the control unit 44 can determine the optimal frequency based on the density-frequency relationship stored in the memory unit 70 for each component.

[0178] 13(A) to 13(C), the slopes are different for each component. Therefore, the control unit 44 may weight the concentrations of the components contained in the unknown sample liquid 30 based on the density vs. frequency relationships for each component described above to correct the frequency. This makes it possible to determine the frequency of the ultrasonic waves that generate the standing wave SW for the unknown sample liquid 30 with higher accuracy.

[0179] (Experiment 2) In Experiment 2, the recovery rates were measured using the sample liquids 30 of Samples 1 to 7, and the effects of the particle recovery method according to the first embodiment of the present disclosure were confirmed.

[0180] FIG. 14 shows the recovery rate of each of the sample solutions 30 of Samples 1 to 7 measured by irradiating them with the first frequency obtained in the above-mentioned Experiment 1 in the procedure shown in FIG. 5. 3 , 1.02g / cm 3 and 1.05 g / cm 3 ) is used. More specifically, the results are shown for the median recovery rate for each 1.01 g / cm 3 The plotted point is the recovery rate of sample 1 in sample solution 30, which is 1.02 g / cm 3 The plotted point is the recovery rate of sample 2, sample solution 30, which is 1.05 g / cm 3 The plotted point indicates the recovery rate of sample solution 30 of sample 5.

[0181] It can be seen from Fig. 14 that the recovery rate of each plot point decreases as the density increases. That is, it can be seen from Fig. 14 that the recovery rate changes depending on the density of the sample liquid 30.

[0182] As shown in FIG. 14, the relationship between density and recovery rate can be obtained as a linear function by interpolating between the plotted points. In the example shown in FIG. 14, density is expressed as ρ(g / cm 3 ), and the recovery rate is C (%), then C = -699.23ρ + 775.28, as shown by the dotted line in Figure 14.

[0183] By storing the correspondence relationship between the density of sample liquid 30 and the recovery rate obtained in this manner in the memory unit 70 of the particle recovery device 10 according to the first embodiment of the present disclosure, the control unit 44 can determine the recovery rate based on the correspondence relationship stored in the memory unit 70, even when particles contained in an unknown sample liquid 30 are focused and recovered.

[0184] In addition, when recovering particles from sample liquid 30 whose recovery rate decreases, i.e., sample liquid 30 with a high density, measures such as increasing the amount of sample liquid 30 introduced or increasing the specified time T2 for ultrasonic irradiation may be taken to compensate for the reduced recovery rate.

[0185] 15 shows the relationship between the density of sample liquid 30 and the recovery rate for each of the added components (glucose, urea, and albumin) in the sample liquids of Samples 2 to 7. That is, FIG. 15(A) shows the results for sample liquid 30 of Samples 2 and 5, FIG. 15(B) shows the results for sample liquid 30 of Samples 3 and 6, and FIG. 15(C) shows the results for sample liquid 30 of Samples 4 and 7.

[0186] From Fig. 15, it can be seen that, as in Fig. 14, the recovery rate of each plot point decreases as the density increases, but the slope of the plot points, i.e., the correspondence between density and recovery rate, differs for each component. Therefore, from Figs. 15(A) to (C), it can be seen that the recovery rate changes depending on the components contained in the sample solution 30. In the example shown in Figs. 15(A) to (C), the recovery rate of the sample solution 30 to which glucose has been added is C G (%), and the recovery rate of sample solution 30 to which urea was added is C B (%), and the recovery rate of sample solution 30 to which albumin was added is C A (%), as shown by the dotted line in Figure 15(A), G =-113.33ρ+163.6, as shown by the dotted line in Figure 15(B) C B =-453.33ρ+523.6, as shown by the dotted line in Figure 15(C) A =-466.67ρ+522.6.

[0187] By storing the correspondence relationship between the density of the sample liquid 30 and the recovery rate obtained in this manner in the memory unit 70 of the particle recovery device 10 according to the first embodiment of the present disclosure, the control unit 44 can determine the recovery rate based on the correspondence relationship stored in the memory unit 70, even when particles of an unknown sample liquid 30 are focused and recovered.

[0188] 15(A) to (C), the slope is different for each component. Therefore, the control unit 44 may estimate the recovery rate based on the concentration measurement values ​​of each component acquired by the component information acquisition unit 90, the density measurement value of the sample liquid 30 acquired by the density acquisition unit, and the above-mentioned correspondence relationship between density and recovery rate. This makes it possible to more reliably take the above-mentioned measures for the unknown sample liquid 30 and recover particles in the sample liquid 30.

[0189] (Experiment 3) In Experiment 3, the sample liquids 30 of Sample 5 and Sample 8 were used to measure the influence of the amplitude of the irradiated ultrasonic waves, and the effect of the particle recovery method according to the first embodiment of the present disclosure was confirmed.

[0190] In experiment 3, for the sample solutions 30 of samples 5 and 8, the frequency of the ultrasonic waves to be irradiated was set to the optimum frequency obtained in experiment 1 described above, and the change in focusing efficiency was confirmed by changing the amplitude of the ultrasonic waves in the procedure shown in Fig. 5. More specifically, the amplitude of the ultrasonic waves was controlled by changing the AC voltage supplied from the oscillator 16 to the piezoelectric element 42 between 50V and 80V, and the collection efficiency at each voltage value was measured.

[0191] Here, the focusing efficiency is derived using the reciprocal of the time (focusing time) taken for the formed components contained in the sample liquid 30 of the samples 5 and 8 filled in the flow channel 50 to be focused at the center inside the flow channel 50 after the start of ultrasonic irradiation of the flow cell 40. In other words, the greater the reciprocal of the focusing time, the shorter the concentration time, and therefore the higher the efficiency.

[0192] 16A and 16B are diagrams showing the results of the inverse of the focusing time obtained, in which (A) shows the results for the sample liquid 30 of Sample 8, and (B) shows the results for the sample liquid 30 of Sample 5.

[0193] 16(A) and 16(B), at each plot point, the reciprocal of the focusing time increases as the voltage supplied from the oscillator 16 to the piezoelectric element 42, i.e., the amplitude of the ultrasonic wave, increases, but when the density increases, the reciprocal of the focusing time decreases. Therefore, it can be seen that when the density increases, the focusing efficiency decreases.

[0194] As shown in Figures 16(A) and 16(B), by interpolating between the plotted points, a linear relationship between the voltage and the inverse of the focusing time could be obtained. In the example shown in Figures 16(A) and 16(B), if the inverse of the focusing time of sample 8 is R2 (1 / s), the inverse of the focusing time of sample 5 is R6 (1 / s), and the voltage supplied to the piezoelectric element 42 is E (V), then R2 = 0.0278E-1.0143 as shown by the dotted line in Figure 16(A) and R6 = 0.0225E-0.9169 as shown by the dotted line in Figure 15(B), respectively.

[0195] By storing the correspondence between the ultrasonic amplitude (the voltage value of the AC voltage supplied to the piezoelectric element 42) and the focusing time relative to the density of the sample liquid 30 obtained in this manner in the memory unit 70 of the particle recovery device 10 according to the first embodiment of the present disclosure, the control unit 44 can adjust the focusing time based on the correspondence stored in the memory unit 70, even when particles contained in an unknown sample liquid 30 are focused and recovered.

[0196] As can be seen from FIG. 16, when recovering particles from sample liquid 30 with a low density, in other words, when recovering particles from sample liquid 30 with a high focusing efficiency, measures may be taken to reduce the predetermined time T2 for irradiating ultrasound for focusing.

[0197] As a result, when particles contained in the sample liquid 30 having a low density are collected, the time for which ultrasonic waves are irradiated can be shortened, and it can be said that the efficiency of the work of collecting the particles can be improved.

[0198] Furthermore, as can be seen from FIG. 16, when recovering particles of sample liquid 30 having a low density, in other words when recovering particles of sample liquid 30 having a high focusing efficiency, measures may be taken to reduce the amplitude of the AC voltage supplied from oscillator 16 to piezoelectric element 42, i.e., the amplitude of the ultrasound irradiated to sample liquid 30.

[0199] As a result, when recovering particles contained in the sample liquid 30 with low density, it is possible to suppress the occurrence of cavitation in the flow channel 50 and prevent the destruction of the particles by reducing the amplitude of the irradiated ultrasound.

[0200] The above describes an embodiment of the present disclosure with reference to the attached drawings. However, it is clear that a person with ordinary knowledge in the technical field to which the present disclosure pertains can conceive of various modifications or applications within the scope of the technical ideas described in the claims, and it is understood that these also naturally fall within the technical scope of the present disclosure. [Industrial Applicability]

[0201] The particle collection apparatus according to the present disclosure can be used, for example, in an analytical instrument for liquids containing particles, and the particle collection method according to the present disclosure can be used, for example, in the operating procedures of an analytical instrument for liquids containing particles. [Explanation of symbols]

[0202] 10 Particle collection device 12 Spitz tube 14 Introductory path 16 Oscillators 18 Support member 20 First Pump 22 Second Pump 24 Case 30 Sample liquid (an example of a liquid sample) 32 Low concentration liquid 34 Concentrate 40 Flow Cell 42 Piezoelectric element (an example of a standing wave forming means) 44 Control section 45 Receiving section 46 Waveform Controller 47 Waveform derivation section 50 Flow Path 52 Intake port 54 Outlet 56 Outer tube 58 Inner tube 60 Density measurement section 62 Density measuring device 70 Storage section 72 Storage device 80 Image Detector 90 Component information acquisition section SW standing wave A Inner wall surface B Inner wall surface N section

Claims

1. A particle recovery device for recovering particles contained in a liquid sample, comprising: a flow cell having a flow path through which the liquid sample flows; a density acquisition unit for acquiring a density of the liquid sample; a standing wave generating means for generating a standing wave by irradiating an ultrasonic wave into the flow path; a control unit that determines a frequency of ultrasonic waves that generate a standing wave in the flow channel based on the density acquired by the density acquisition unit, and causes the standing wave forming means to irradiate ultrasonic waves of the determined frequency; a collecting means for collecting the particles focused in the flow path by the standing wave; A particle recovery device comprising:

2. the density acquisition unit acquires the density of the liquid sample from a density measurement device that is connected to the particle recovery device and measures the density of the liquid sample. The particle recovery device of claim 1 .

3. The density acquisition unit is a density measurement unit that measures the density of the liquid portion of the liquid sample to acquire the density of the liquid portion of the liquid sample. The particle recovery device of claim 1 .

4. The control unit further includes a memory unit that stores a density-to-frequency relationship that is a correspondence relationship between the density of the liquid sample in the flow channel and the frequency of the ultrasonic wave that generates a standing wave in the liquid sample, and determines a frequency of the ultrasonic wave based on a value of the density of the liquid sample and a frequency derived from the density-to-frequency relationship stored in the memory unit. A particle recovery device according to any one of claims 1 to 3.

5. The control unit adjusts the amplitude of the ultrasonic wave based on the density acquired by the density acquisition unit. A particle recovery device according to any one of claims 1 to 4.

6. The control unit determines a length of time for irradiating the ultrasonic wave based on the density acquired by the density acquisition unit. A particle recovery device according to any one of claims 1 to 5.

7. The particle recovery device further includes a component information acquisition unit that acquires concentrations of a plurality of components contained in the liquid sample in the flow path, The storage unit stores a density vs. frequency relationship for each of the plurality of components; the control unit determines a frequency of the ultrasonic wave based on the concentrations of the components contained in the liquid sample acquired by the component information acquisition unit, the density of the liquid sample, and the multiple density-to-frequency relationships. The particle recovery device of claim 4.

8. The control unit adjusts the amplitude of the ultrasonic waves based on the values ​​of the component concentrations and the density of the liquid sample acquired by the component information acquisition unit. The particle recovery device of claim 7.

9. The control unit determines a time length for irradiating the ultrasonic wave based on the values ​​of the component concentrations and the density of the liquid sample acquired by the component information acquisition unit. The particle recovery device according to claim 7 or 8.

10. a direction in which the standing wave is generated is perpendicular to a flow direction of the liquid sample in the flow channel, The recovery means is a double pipe having an inner pipe and an outer pipe with the same axial center on the downstream side of the flow direction. A particle recovery device according to any one of claims 1 to 9.

11. In the recovery means, the internal cross-sectional area of ​​the inner tube is ¼ or less of the internal cross-sectional area of ​​the outer tube. The particle recovery device of claim 10.

12. The liquid sample filling the flow path is pressurized by a pressurizing means. the standing wave forming means irradiates the ultrasonic wave while the liquid sample is pressurized inside the flow channel by the pressurizing means. A particle recovery device according to any one of claims 1 to 11.

13. the standing wave generating means generates the standing wave while the liquid sample is stored in the flow channel. A particle recovery device according to any one of claims 1 to 12.

14. The number of nodes of the standing wave is 1. A particle recovery device according to any one of claims 1 to 13.

15. A method for recovering particles contained in a liquid sample, comprising the steps of: Obtaining a density of the liquid sample; determining a frequency of an ultrasonic wave that generates a standing wave in a flow path through which the liquid sample flows, based on the density of the liquid sample; The ultrasonic wave is applied to the inside of the flow channel, The particles focused in the flow channel by a standing wave generated by irradiating the ultrasonic wave are collected. Particle recovery method.

16. measuring concentrations of a plurality of components contained in the liquid sample, and determining a frequency of ultrasonic waves to be irradiated into the flow channel based on a correspondence relationship between the concentrations of the plurality of components, the density of the liquid sample, the density of the liquid sample for each of the components, and a frequency of ultrasonic waves that generates a standing wave in the liquid sample; The method for recovering particles according to claim 15.

17. adjusting the amplitude of the ultrasonic wave based on the concentration and the density of the component contained in the liquid sample; The method for recovering particles according to claim 16.

18. determining a duration of the ultrasonic irradiation based on the concentration and density of a component contained in the liquid sample; The method for recovering particles according to claim 16 or 17.

19. The liquid sample is a body fluid collected from a living body. The method for recovering particles according to any one of claims 15 to 18.

20. The body fluid is urine. The method for recovering particles according to claim 19.

21. The number of nodes of the standing wave is 1. The method for recovering particles according to any one of claims 15 to 20.

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