WO2023032336A1

WO2023032336A1 - Detection system, suction system, and liquid suction method

Info

Publication number: WO2023032336A1
Application number: PCT/JP2022/016121
Authority: WO
Inventors: 克俊田原
Original assignee: ソニーグループ株式会社
Priority date: 2021-08-30
Filing date: 2022-03-30
Publication date: 2023-03-09

Abstract

Provided is a suction technology that makes it possible to detect a remaining amount of liquid by means of a simple structure and can be easily reset.　Provided is a detection system that has a suction system and a detection unit. The suction system comprises a suction unit that has a suction nozzle that suctions a liquid. The suction unit has a first conduction unit and a second conduction unit that is insulated from the first conduction unit. The detection unit detects information about a sample in the liquid suctioned by the suction unit. The detection system of the present technology makes it possible to detect the remaining amount of liquid before the liquid is completely gone from the suction system, i.e., before air is detected at the detection unit.

Description

Detection system, aspiration system, and liquid aspiration method

This technology relates to a detection system that detects a sample in liquid, an aspiration system that aspirates liquid, and a liquid aspiration method.

In recent years, in various detections and analyzes using liquid samples, the sample liquid is automatically aspirated and introduced into the device, and various detections and analyzes are performed in various devices. For example, in a flow cytometer that analyzes and fractionates microparticles such as cells and microorganisms, there is generally a hole in the center of the sample nozzle, through which the sample is sucked, and data from the sample is collected in the instrument. get.

In this way, as the technology for automatically sucking the sample liquid progressed, there were cases where the sample liquid ran out and air was sucked in as the measurement continued, causing problems in the measurement data and the measurement system of the device. .

On the other hand, for example, in Patent Document 1, based on information detected by a detection unit, a feature amount related to the number of detections in a certain time interval is specified, and based on a predetermined threshold value, it is determined that the feature amount is abnormal. A technique is disclosed for controlling to terminate the detection. Japanese Patent Laid-Open No. 2002-200001 discloses a detection device that automatically terminates detection when air is detected, using this technology.

International Publication No. 2018/047442 Pamphlet

As described above, in various detections and analyzes using a liquid sample, while the automatic suction technology of the sample liquid is progressing, as in the technology described in Patent Document 1, when an abnormality is detected such as when air is sucked Finally, techniques for terminating detection are being developed.

However, the detection of air in the detection unit means that the sample liquid has already disappeared from the sample container and sample tube, so recovery requires time and procedures.

As a method for detecting the remaining amount of sample in the sample container, for example, weight measurement of the sample is conceivable. There is a problem of compatibility with other mechanisms such as stirring.

Therefore, the main purpose of this technology is to provide a suction technology that can detect the remaining amount of liquid with a simple structure and is easy to restore.

In the present technology, first, a suction unit having a suction nozzle for sucking liquid is provided,
The suction part is
a first conductive portion;
a suction system comprising a second conductive portion insulated from the first conductive portion;
a detection unit that detects information about the sample in the liquid aspirated by the aspiration unit;
A detection system is provided, comprising:
Part or all of the suction nozzle of the detection system according to the present technology may be configured with the first conductive portion.
The upstream end of the second conductive portion of the detection system according to the present technology may be provided near the tip of the suction nozzle.
The second conductive portion of the detection system according to the present technology may be provided downstream of the first conductive portion.
An upstream end of the second conductive portion of the detection system according to the present technology may be provided at a maximum water level position of the container holding the liquid.
A detection system according to the present technology can include a processing unit that detects the amount of the liquid based on an energization signal from the first conductive unit or the second conductive unit.
The processing section of the detection system according to the present technology is provided downstream of the second conductive section having an upstream end near the tip of the suction nozzle and/or the first conductive section. It is possible to detect lack of liquid based on the energization signal from the second conductive portion.
The processing unit of the detection system according to the present technology detects excess liquid based on an energization signal from the second conductive unit having an upstream end at a position of the maximum appropriate water surface of the container holding the liquid. can do.
The processing unit of the detection system according to the present technology,
Based on an energization signal from the second conductive portion having an upstream end near the tip of the suction nozzle and/or from the second conductive portion provided downstream of the first conductive portion , detect the lack of fluid,
Excessive amount of liquid can be detected based on an energization signal from the second conductive section, the upstream end of which is provided at the maximum appropriate water surface position of the container holding the liquid.
The detection system according to the present technology can include a control unit that controls suction of the liquid based on information on the amount of the liquid detected by the processing unit.
The detection unit of the detection system according to the present technology can detect light from the sample.
The sample that can be detected by a detection system according to the present technology may be particles.
In this case, cells can be detected as particles.
The detection system according to the present technology can also include a sorting unit that sorts the particles.

In the present technology, next, a suction unit having a suction nozzle for sucking liquid is provided,
The suction part is
a first conductive portion;
An aspiration system is provided, comprising the first conductive portion and an insulated second conductive portion.

The present technology further provides a method of sucking liquid using a suction unit having a suction nozzle for sucking liquid, comprising:
The suction part is
a first conductive portion;
a second conductive portion insulated from the first conductive portion;
An energizing step of energizing the first conductive portion or the second conductive portion;
a liquid amount detection step of detecting the amount of the liquid based on an energization signal from the first conductive portion or the second conductive portion;
To provide a liquid suction method for performing
In the liquid suction method according to the present technology, it is also possible to perform a control step of controlling suction based on the amount of liquid detected in the detection step.

In the present technology, "upstream side" and "downstream side" mean the upstream side and downstream side with respect to the direction of liquid flow when the liquid is sucked.

In the present technology, "particles" can include a wide range of bio-related microparticles such as cells, microorganisms, and ribosomes, or synthetic particles such as latex particles, gel particles, and industrial particles.

Biologically relevant microparticles include chromosomes, ribosomes, mitochondria, and organelles that make up various cells. Cells include animal cells (eg, blood cells, etc.) and plant cells. Microorganisms include bacteria such as Escherichia coli, viruses such as tobacco mosaic virus, and fungi such as yeast. Furthermore, bio-related microparticles include bio-related macromolecules such as nucleic acids, proteins, and complexes thereof. Technical particles may also be, for example, organic or inorganic polymeric materials, metals, and the like. Organic polymeric materials include polystyrene, styrene-divinylbenzene, polymethyl methacrylate, and the like. Inorganic polymeric materials include glass, silica, magnetic materials, and the like. Metals include colloidal gold, aluminum, and the like. The shape of these fine particles is generally spherical, but in the present technology, they may be non-spherical, and their size, mass, etc. are not particularly limited.

1 is a block diagram showing an example of a detection system 1 according to the present technology; FIG. 1 is a front view showing a first embodiment of a suction system 11 according to the present technology; FIG. FIG. 3 is a cross-sectional view taken along the line AA of FIG. 2; It is a cross-sectional schematic diagram which shows the cross section of 1st Embodiment of the suction system 11 which concerns on this technique. It is a cross-sectional schematic diagram which shows the flow direction cross section of 1st Embodiment of the suction system 11 which concerns on this technique. 1 is an enlarged cross-sectional schematic diagram in which a section perpendicular to a flow direction of a first embodiment of a suction system 11 according to the present technology is enlarged; FIG. It is a cross-sectional schematic diagram which shows the flow direction cross section of 2nd Embodiment of the suction system 11 which concerns on this technique. It is a cross-sectional schematic diagram which shows the flow direction cross section of 3rd Embodiment of the suction system 11 which concerns on this technique. It is a cross-sectional schematic diagram which shows the flow direction cross section of 4th Embodiment of the suction system 11 which concerns on this technique. It is a cross-sectional schematic diagram which shows the flow direction cross section of 5th Embodiment of the suction system 11 which concerns on this technique. FIG. 11 is an enlarged cross-sectional schematic view of a suction system 11 according to a fifth embodiment of the present technology, in which a vertical cross section is enlarged with respect to the flow direction; It is a cross-sectional schematic diagram which shows the flow direction cross section of 6th Embodiment of the suction system 11 which concerns on this technique. FIG. 13 is an enlarged schematic diagram of a dashed circle portion in FIG. 12 ; It is a cross-sectional schematic diagram which shows the flow direction cross section of 7th Embodiment of the suction system 11 which concerns on this technique. FIG. 12 is a schematic cross-sectional view showing a flow direction cross section of an eighth embodiment of the suction system 11 according to the present technology; 1 is a conceptual diagram schematically showing a first embodiment of a detection system 1 according to the present technology; FIG. It is a conceptual diagram which shows typically 2nd Embodiment of the detection system 1 which concerns on this technique. FIG. 3 is a conceptual diagram schematically showing a third embodiment of a detection system 1 according to the present technology; FIG. 10 is a flow chart showing an example of a liquid suction control method using the liquid suction method according to the present technology; 4 is a drawing-substituting graph showing the results of Example 1. FIG. 7 is a drawing-substituting graph showing the results of Example 2. FIG.

Preferred embodiments for carrying out the present technology will be described below with reference to the drawings.
The embodiments described below are examples of representative embodiments of the present technology, and the scope of the present technology should not be interpreted narrowly. The description will be given in the following order.
1. Detection system 1
(1) Suction system 11
<First embodiment>
<Second embodiment>
<Third Embodiment>
<Fourth Embodiment>
<Fifth Embodiment>
<Sixth embodiment>
<Seventh embodiment>
<Eighth embodiment>
(2) Flow path P (P11, P12a, P12b, P13)
(3) Detector 12
(4) Processing unit 13
(5) Control unit 14
(6) Fractionation section 15
(7) Storage unit 16
(8) Display unit 17
(9) Input section 18
2. Liquid suction method

1. Detection system 1
FIG. 1 is a block diagram showing an example of a detection system 1 according to the present technology. A detection system 1 according to the present technology includes at least a suction system 11 and a detection unit 12 . Moreover, it is also possible to provide a channel P, a processing unit 13, a control unit 14, a sorting unit 15, a storage unit 16, a display unit 17, an input unit 18, and the like, as necessary.

In the example shown in FIG. 1, the suction system 11 is provided in the detection device, but the present technology is not limited to this form, and for example, a suction device may be provided separately from the detection device and connected to each other. is also possible. In the example shown in FIG. 1, the processing unit 13, the control unit 14, the sorting unit 15, the storage unit 16, the display unit 17, and the input unit 18 are included in the information processing apparatus. For example, it is also possible to use a detection device having an information processing function and to include some or all of these in the detection device. The detection system 1 will be described in detail below.

(1) Suction system 11
FIG. 2 is a front view showing the first embodiment of the suction system 11 according to the present technology, and FIG. 3 is a cross-sectional view taken along line AA. 2 and 3 show a tube t that connects the suction system 11 and the detection device and a liquid storage section C that stores the liquid L for convenience of explanation. , the tube t and the liquid containing portion C are not essential, and it is also possible to use tubes and containers provided in the detection device, and disposable tubes and containers. Although not shown, the suction system 11 may be provided with a pump, a pressurizing mechanism, and the like for suction.

FIG. 4 is a conceptual diagram showing an example of how the liquid L is reduced. 1 in FIG. 4 is a state in which the liquid L is abundant. 2 in FIG. 4 shows a state in which the liquid L is sucked and the height of the tip of the nozzle is the same as that of the liquid L. FIG. When the liquid L is further sucked, the liquid L and the tip of the nozzle are connected by surface tension, as indicated by 3 in FIG. When the liquid L is further sucked, as shown in 4 in FIG. 4, the surface tension between the liquid L and the tip of the nozzle is broken, leaving an arcuate droplet at the tip of the nozzle, and the droplet at the tip of the nozzle gradually becomes smaller. (See 5 in FIG. 4). Then, when the liquid L is further sucked, as indicated by 6 in FIG. 4, the droplets at the tip of the nozzle disappear and air is sucked.

As described above, in the conventional technology, an abnormality is detected by detecting air in the detection unit of the detection device. . On the other hand, if the suction system 11 according to the present technology is used, it is possible to detect the remaining amount of the liquid L before the liquid L completely disappears from the suction system 11, that is, before air is detected by the detection unit. can. Hereinafter, a method for detecting the remaining amount of the liquid L by the suction system 11 according to the present technology will be described in detail while showing each embodiment.

<First embodiment>
FIG. 5 is a schematic cross-sectional view showing a flow direction cross-section of the suction system 11 according to the first embodiment of the present technology, and is a cross-sectional view along the line AA in FIG. 3 for explaining the cross-sectional structure of the suction system 11. It is a schematic diagram of the enlarged width direction. FIG. 6 is an enlarged schematic cross-sectional view of the first embodiment of the suction system 11 according to the present technology in a direction perpendicular to the flow direction, and is an enlarged schematic cross-sectional view of the BB line cross section of FIG. .

The suction system 11 according to the present technology includes a suction section 111 having a suction nozzle N for sucking the liquid L. In addition, if necessary, a tube t for connecting to the detection device, a container (liquid storage portion C) containing the liquid L, a pump for suction (not shown), etc. One or two or more types of equipment can be freely provided.

The suction part 111 of the suction system 11 according to the present technology is characterized by including a first conductive part 1111 and a second conductive part 1112 . The first conductive portion 1111 and the second conductive portion 1112 are in a state of being insulated via an insulating portion 1113, for example.

The suction system 11 according to the first embodiment has a structure in which the suction nozzle N is composed of a first conductive portion 1111 and covered with a second conductive portion 1112 with an insulating portion 1113 interposed therebetween (FIG. 6). reference). The suction nozzle N, which is the first conductive portion 1111, is connected to Vcc via a resistor, and the second conductive portion 1112 is connected to Vout via a resistor.

When the liquid L is in the

states

1 and 2 of FIGS. Since a certain suction nozzle N is closed, the level of Vout becomes High. 4, the electrical connection between the first conductive portion 1111 and the second conductive portion 1112 is broken, that is, the suction nozzle whose circuit is the first conductive portion 1111 N is no longer closed, and the level of Vout becomes Low. Thus, the lack of the liquid L can be detected by the level of Vout before the liquid L is in the state of 6 in FIG. 4 described above, that is, before the suction nozzle N sucks air.

Since the suction system 11 according to the present technology can detect the state before the liquid L completely disappears from the suction system 11, recovery is very simple compared to the conventional technology.

In the suction system 11 according to the first embodiment shown in FIG. 5, the first conductive portion 1111 is connected to Vcc and the second conductive portion 1112 is connected to Vout, but the effect of the present technology can be obtained even in reverse. can. That is, it is possible to connect the first conductive portion 1111 to Vout and connect the second conductive portion 1112 to Vcc.

Vcc is preferably a temporally limited pressurization such as a pulse, considering the effect on the sample and the necessary detection frequency. For example, a pulse of 1-10 V and 3-30 μs at 0.5-2 times per second can be mentioned. The number of resistors may be 3 to 30 kΩ for R ₀ and 0.5 to 5 MΩ for R ₁ , but other constants may be used depending on the sensitivity of detection.

As for how the liquid L is reduced, in a general flow cytometer, the sample consumption is generally 240 μL/min (=4 μL/sec) or less, and in this case, the water droplets remaining at the tip of the sample nozzle are 10 μL or more. If there are, it takes 2.5 seconds to suck them out, so 0.5-2 detections per second is sufficient.

<Second embodiment>
FIG. 7 is a schematic cross-sectional view showing a flow direction cross section of the suction system 11 according to the second embodiment of the present technology. In the first embodiment shown in FIG. 5 and the second embodiment shown in FIG. 7, both the first conductive portion 1111 and the second conductive portion 1112 are located near the tip of the suction nozzle N, that is, the bottom surface of the liquid storage portion C. Although provided in the vicinity, in the suction system 11 according to the first embodiment shown in FIG. In contrast, in the suction system 11 according to the second embodiment shown in FIG. 7, the end of the suction portion 111 is raised downstream only to the end of the second conductive portion 1112 .

For example, in the configuration of the suction system 11 according to the first embodiment shown in FIG. 5, the energized state is canceled in any of the states 3 to 5 in FIG. If not, as in the suction system 11 according to the second embodiment shown in FIG. The lack of liquid can be detected before the suction nozzle N sucks air.

However, if the upstream end portion of the second conductive portion 1112 is raised too much, the level of Vout becomes Low with the liquid L remaining in the liquid containing portion C being large. On the other hand, like the suction system 11 according to the first embodiment shown in FIG. Since there is also an advantage that the liquid L in the storage portion C can be sucked to the limit, depending on the thickness of the insulating portion 1113, the viscosity of the liquid L, etc., the first conductive portion 1111, the second conductive portion 1112, and the insulation It is desirable to design the configuration of the upstream end of portion 1113 .

The second embodiment is the same as the first embodiment except for the shapes of the upstream end portions of the first conductive portion 1111, the second conductive portion 1112, and the insulating portion 1113, so the description is omitted here.

<Third Embodiment>
FIG. 8 is a schematic cross-sectional view showing a flow direction cross section of the suction system 11 according to the third embodiment of the present technology. In the suction system 11 according to the third embodiment, the upstream end portion of the second conductive portion 1112 is provided at the maximum appropriate water surface position of the container (liquid storage portion C) holding the liquid L.

If too much liquid L is put into the liquid storage part C due to an operation such as stirring, it may spill out. Therefore, in the suction system 11 according to the third embodiment, the upstream end portion of the second conductive portion 1112 is provided at the maximum appropriate water surface position of the container (liquid storage portion C) that holds the liquid L, thereby Excess liquid in part C can be detected.

When the liquid L is filled up to the position exceeding the upstream end of the second conductive portion 1112, the first conductive portion 1111 and the second conductive portion 1112 are electrically connected through the liquid L, that is, , the circuit is closed to the suction nozzle N, which is the first conductive part 1111, so the level of Vout becomes High. On the other hand, as in the example shown in FIG. 8, when the water surface of the liquid L is below the upstream end of the second conductive portion 1112, the electrical connection between the first conductive portion 1111 and the second conductive portion 1112 is broken. state, that is, the circuit is no longer closed to the suction nozzle N, which is the first conductive portion 1111, and the level of Vout becomes Low. In this way, the position of the water surface of the liquid L can be detected from the level of Vout, and an excess of the liquid L can be detected.

The third embodiment is the same as the first embodiment except that the upstream end of the second conductive part 1112 is provided at the maximum appropriate water surface position of the container (liquid storage part C) holding the liquid L. Since it is the same, the explanation is omitted here.

<Fourth Embodiment>
FIG. 9 is a schematic cross-sectional view showing a flow direction cross section of the suction system 11 according to the fourth embodiment of the present technology. A suction system 11 according to the fourth embodiment is a modification of the third embodiment shown in FIG. 8 described above. In the suction system 11 according to the third embodiment shown in FIG. 8, the upstream end of the second conductive portion 1112 and the upstream end of the insulating portion 1113 are at the same height, but the fourth embodiment shown in FIG. The suction system 11 according to the embodiment has a configuration in which the upstream end of the insulating portion 1113 extends further downward than the upstream end of the second conductive portion 1112 .

For example, the suction system 11 according to the fourth embodiment shown in FIG. , the upstream end of the insulating portion 1113 is preferably extended below the upstream end of the second conductive portion 1112 .

Other configurations of the fourth embodiment are the same as those of the third embodiment, so the description is omitted here.

<Fifth Embodiment>
FIG. 10 is a schematic cross-sectional view showing a flow direction cross section of the suction system 11 according to the fifth embodiment of the present technology. FIG. 11 is an enlarged schematic cross-sectional view of the fifth embodiment of the suction system 11 according to the present technology, in which the cross section perpendicular to the flow direction is enlarged. The suction system 11 according to the fifth embodiment has a configuration in which the first embodiment shown in FIG. 5 described above and the third embodiment shown in FIG. 8 described above are combined. That is, the suction system 11 according to the fifth embodiment includes both the second conductive portion 1112a for detecting the lack of the liquid L and the second conductive portion 1112b for detecting the excess of the liquid L. ing.

Note that the upstream end portion of the second conductive portion 1112a for detecting the loss of the liquid L from the liquid containing portion C is the upstream side of the insulating portion 1113a, as in the second embodiment shown in FIG. It is also possible to provide side edges and steps.

Further, the upstream end of the second conductive portion 1112b for detecting excess liquid L is separated from the upstream end of the insulating portion 1113b by a step, as in the fourth embodiment shown in FIG. It is also possible to provide

Detection of lack of liquid L using the second conductive part 1112a is the same as in the first embodiment, and detection of excess liquid L using the second conductive part 1112b is the same as in the third embodiment. . Also, other structures are the same as those in the first and third embodiments, and thus descriptions thereof are omitted here.

<Sixth embodiment>
FIG. 12 is a schematic cross-sectional view showing a flow direction cross section of the suction system 11 according to the sixth embodiment of the present technology. In the suction system 11 according to the sixth embodiment, the second conductive portion 1112 is provided downstream of the suction nozzle N, which is the first conductive portion 1111, via the insulating portion 1113. As shown in FIG. In the suction system 11 according to the sixth embodiment, lack of the liquid L can be detected before air is detected by the detection section. The principle will be described with reference to FIG.

FIG. 13 is an enlarged schematic diagram of the dashed circle portion in FIG. 13, that is, when the insulating portion 1113 is filled with the liquid L, the state in which the first conductive portion 1111 and the second conductive portion 1112 are electrically connected through the liquid L, that is, the circuit is closed to the suction nozzle N, which is the first conductive portion 1111, the level of Vout becomes High. Next, in the state of 2 in FIG. 13, that is, when air begins to enter the insulating portion 1113, the electrical connection between the first conductive portion 1111 and the second conductive portion 1112 is broken, that is, the circuit is closed to the first conductive portion. The suction nozzle N, which is 1111, is no longer closed, and the level of Vout becomes Low. In this way, the lack of liquid L can be detected by the level of Vout in state 3 of FIG. 13, ie, before air enters tube t.

In the suction system 11 according to the sixth embodiment, since the second conductive portion 1112 is provided downstream of the suction nozzle N, which is the first conductive portion 1111, the liquid L in the suction nozzle N is depleted. Then, the lack of the liquid L is detected, so the liquid L in the suction nozzle N is also detected by the detection unit 12, which will be described later. Therefore, the liquid L can be sucked to the limit. As a result, for example, when the liquid L in the suction nozzle N contains a rare specimen, and when it is desired to advance the liquid L to the detection stage until the end, like the suction system 11 according to the sixth embodiment, It is preferable to provide the second conductive portion 1112 on the downstream side of the suction nozzle N, which is the first conductive portion 1111 .

In the suction system 11 according to the sixth embodiment, as in the first embodiment shown in FIG. 5, it is also possible to connect the first conductive portion 1111 to Vout and connect the second conductive portion 1112 to Vcc. be.

<Seventh embodiment>
FIG. 14 is a schematic cross-sectional view showing a flow direction cross section of the suction system 11 according to the seventh embodiment of the present technology. The suction system 11 according to the seventh embodiment has a configuration in which the first embodiment shown in FIG. 5 described above and the sixth embodiment shown in FIG. 12 described above are combined. That is, the suction system 11 according to the seventh embodiment includes the second conductive portion 1112a for detecting loss of the liquid L from the liquid storage portion C and the second conductive portion 1112a for detecting loss of the liquid L from the suction nozzle N. and a second conductive portion 1112b are provided.

Further, although not shown, the suction system 11 according to the seventh embodiment includes a second conductive part for detecting excess liquid L according to the third embodiment shown in FIG. 8 or the fourth embodiment shown in FIG. A portion 1112 may also be included.

Detection of loss of the liquid L from the liquid containing portion C using the second conductive portion 1112a is the same as in the first embodiment, and loss of the liquid L from the suction nozzle N using the second conductive portion 1112b. is the same as in the sixth embodiment. Further, since other structures are the same as those of the first and sixth embodiments, descriptions thereof are omitted here.

<Eighth Embodiment>
FIG. 15 is a schematic cross-sectional view showing a flow direction cross section of the suction system 11 according to the eighth embodiment of the present technology. In the first to seventh embodiments described above, the suction nozzle N was formed of the first conductive portion 1111, but the suction nozzle N of the suction system 11 according to the eighth embodiment has conductivity. It is made up of materials that do not In the suction system 11 according to the eighth embodiment, a first conductive portion 1111 is provided downstream of the suction nozzle N, and a second conductive portion 1112 is provided downstream of the first conductive portion 1111 via an insulating portion 1113. .

In the suction system 11 according to the eighth embodiment, the loss of the liquid L can be detected at the stage when air begins to enter the insulating portion 1113 . Since the principle of detection of lack of liquid L is the same as that of the suction system 11 according to the sixth embodiment, the explanation is omitted here.

In the suction system 11 according to the eighth embodiment, as in the first embodiment shown in FIG. 5, it is also possible to connect the first conductive portion 1111 to Vout and connect the second conductive portion 1112 to Vcc. be.

(2) Flow path P (P11, P12a, P12b, P13)
The liquid L sucked by the suction system 11 described above is sent to the detection section 12, which will be described later, and the sample in the liquid L is detected. The detection of the sample can be performed in a state where the liquid L containing the sample is caused to flow through the channel P, as exemplified in the detection system 1 according to the first embodiment shown in FIG. 16, for example.

The flow path P can pass a fluid composed of a sample flow (liquid L) containing a sample and a sheath flow that flows so as to enclose the sample flow. This channel P may be provided in advance in the detection system 1 according to the present technology, but it is also possible to install a disposable chip T or the like provided with the channel P in the detection system 1 and perform detection. is.

The form of the flow path P is also not particularly limited and can be freely designed. For example, not only the flow path P formed in the chip T of two-dimensional or three-dimensional plastic, glass, or the like as shown in FIG. can also be used in the detection system 1 according to the present technology.

Further, the channel width, channel depth, and channel cross-sectional shape of the channel P are not particularly limited as long as they can form a laminar flow, and can be designed freely. For example, a microchannel with a channel width of 1 mm or less can also be used in the detection system 1 . In particular, a microchannel having a channel width of about 10 μm or more and 1 mm or less can be suitably used for the present technology.

The method of sending the liquid L is not particularly limited, and it can be made to flow through the channel P according to the form of the channel P to be used. For example, the case of the channel P formed in the chip T shown in FIG. 16 will be described. The liquid L containing the sample is introduced into the sample liquid channel P11, and the sheath liquid is introduced into the two sheath liquid channels P12a and P12b. The sample liquid flow path P11 and the sheath liquid flow paths P12a and P12b merge to form a main flow path P13. The sample liquid laminar flow sent in the sample liquid channel P11 and the sheath liquid laminar flows sent in the sheath liquid channels P12a and P12b join in the main channel P13, and the sample liquid laminar flow A sheath flow sandwiched by the sheath liquid laminar flow can be formed.

The sample that flows through the channel P can be labeled with one or more dyes such as fluorescent dyes. In this case, fluorescent dyes that can be used in this technology include Cascade Blue, Pacific Blue, Fluorescein isothiocyanate (FITC), Phycoerythrin (PE), Propidium iodide (PI), Texas red (TR), Peridinin chlorophyll protein (PerCP ), Allophycocyanin (APC), 4',6-Diamidino-2-phenylindole (DAPI), Cy3, Cy5, Cy7, Brilliant Violet (BV421) and the like.

(3) Detector 12
The detection unit 12 detects measurement target light generated from the sample by light irradiation emitted from the light source 121 . The detection unit 12 detects the characteristics of the sample flowing through the main flow path P13. Although the characteristic detection is not particularly limited, for example, in the case of optical detection, by irradiating a sample such as particles that are arranged in a row in the center of the three-dimensional laminar flow in the main flow path P13 and sent, Scattered light and fluorescence generated from the sample are detected by the detector 12 .

In this light irradiation and detection, in addition to the laser light source, an irradiation system such as a condenser lens, a dichroic mirror, and a band-pass filter that collects and irradiates the laser to the cells may be configured. The detection system is composed of, for example, a PMT (photomultiplier tube), an area imaging device such as a CCD or a CMOS device, or the like.

The light to be measured detected by the detection system of the detection unit 12 is light generated from the sample by irradiation with the measurement light. Specifically, for example, it is forward scattered light, side scattered light, scattered light such as Rayleigh scattering and Mie scattering. These light beams to be measured are converted into electrical signals, output to a processing unit 13, a control unit 14, a sorting unit 15, a storage unit 16, a display unit 17 and the like, which will be described later, and used to determine the optical properties of particles.

Note that the detection unit 12 may magnetically or electrically detect cell characteristics. In this case, for example, microelectrodes are arranged to face the main flow path P13 of the chip T, and the resistance value, capacitance value (capacitance value), inductance value, impedance, change value of the electric field between the electrodes, or magnetization , magnetic field change, magnetic field change, etc. can be measured.

(4) Processing unit 13
The processing unit 13 detects the amount of the liquid L based on the energization signal from the first conductive unit 1111 or the second conductive unit 1112 .

Specifically, when using the suction system 11 according to the first embodiment shown in FIG. 5, the second embodiment shown in FIG. 7, and the sixth to eighth embodiments shown in FIGS. Based on the energization signal from the second conductive part 1112 provided with the upstream end near the tip of the suction nozzle N and/or the second conductive part 1112 provided downstream of the first conductive part 1111 , to detect the lack of fluid.

Further, when using the suction system 11 according to the third embodiment shown in FIG. 8 and the fourth embodiment shown in FIG. Based on the energization signal from the second conductive part 1112 provided with the side end, excess liquid is detected.

Further, when using the suction system 11 according to the fifth embodiment shown in FIG. based on the energization signal from the second conductive part 1112 whose upstream end is provided at the maximum appropriate water surface position of the liquid storage part C holding the liquid L. Detect excess.

The processing unit 13 can also be connected to the detection unit 12 and analyze detection signals obtained from samples detected by the detection unit 12 . For example, the processing unit 13 can correct the light detection value received from the detection unit 12 and calculate the feature amount of each sample. Specifically, a feature amount indicating the size, shape, internal structure, etc. of the sample is calculated from the detected values of the received fluorescence, forward scattered light, and backscattered light. Further, it is also possible to perform fractionation determination based on the calculated feature quantity and the fractionation conditions received in advance from the input unit 18 and generate a fractionation control signal.

(5) Control unit 14
The controller 14 controls the suction of the liquid L based on the amount information of the liquid L detected by the processor 13 . Specifically, control is performed to stop the suction of the liquid L when the lack or excess of the liquid L is detected. By stopping the suction of the liquid L when the lack of the liquid L is detected, the suction of air to the detection section can be prevented. Further, by stopping the suction of the liquid L when an excess of the liquid L is detected, it is possible to prevent the outflow of the liquid L due to stirring of the liquid L or the like.

In addition, when the lack or excess of the liquid L is detected and the suction of the liquid L is stopped, it is displayed on the display unit 17 described later, or automatically sent to a preset contact such as e-mail or telephone. It is also possible to contact

(6) Fractionation unit 15
The detection system 1 according to the present technology can include a sorting unit 15 for sorting samples. In the detection system 1 according to the present technology, the fractionation unit 15 is not essential, and may be a device for detecting the sample in the liquid L. However, based on the information detected by the detection unit 12 described above, the sample can also be fractionated.

The fractionation unit 15 fractionates the sample based on the information about the sample in the liquid L detected by the detection unit 12 . For example, in the sorting section 15, particles can be sorted downstream of the channel P based on the analysis results of the size, shape, internal structure, etc. of the sample analyzed from the optical data. Hereinafter, the fractionation method will be described separately for each embodiment.

For example, in the detection system 1 according to the first embodiment shown in FIG. 16 and the detection system 1 according to the second embodiment shown in FIG. By applying vibration to the whole or part of the path P13, droplets D are generated at a predetermined point (break-off point BOP) of the liquid column coming out of the ejection port O of the main path P13. In this case, the vibrating element 151 to be used is not particularly limited, and a known one can be freely selected and used. One example is a piezo vibration element. In addition, by adjusting the amount of liquid supplied to the sample liquid flow path P11, the sheath liquid flow paths P12a and P12b, and the main flow path P13, the diameter of the ejection port, the vibration frequency of the vibration element 151, and the like, the droplet size can be adjusted. It can be adjusted to generate droplets containing aliquots of the sample.

Next, based on the analysis results of the size, shape, internal structure, etc. of the sample analyzed based on the information on the sample in the liquid L detected by the detection unit 12, positive or negative charges are applied. Then, the charged droplets are changed in a desired direction by

counter electrodes

152a and 152b to which a voltage is applied, and collected into

collection containers

153a, 153b and 153c.

Further, for example, in the embodiment shown in FIG. 18, downstream of the main flow path P13 formed in the substrate T, there are provided three branch flow paths, namely, the fractionation flow path P14 and the waste flow paths P15a and P15b. A sample to be fractionated that has been determined to satisfy the characteristics is taken into the fractionation channel P14, and a sample that is not to be fractionated that has been determined to not satisfy the predetermined characteristics is not taken into the fractionation channel P14. , the two waste flow paths P15a and P15b, so that the liquid can be sorted.

The sample to be sorted can be taken into the sorting channel P14 using a known method. This can be done by generating pressure and using this negative pressure to suck the sample liquid and the sheath liquid containing the sample to be sorted into the sorting channel P14. In addition, although not shown, by controlling or changing the laminar flow direction using a valve electromagnetic force, a fluid stream (gas or liquid), or the like, the sample to be fractionated is taken into the fractionation channel P14. It is also possible to

In the detection system 1 according to the third embodiment shown in FIG. 18, the sample liquid reservoir B1 is provided in the sample liquid flow path P11, the sheath liquid reservoir B2 is provided in the sheath liquid flow paths P12a and P12b, and the fractionation flow path P14 is divided. By connecting the liquid collecting portion B3 and the waste liquid storing portion B4 to the waste flow paths P15a and P15b, a completely closed sorting device can be formed. For example, when the sample to be fractionated is cells or the like for use in cell preparations or the like, in order to maintain a sterile environment and prevent contamination, the detection system 1 according to the third embodiment shown in FIG. It is preferable to design to be a completely closed type such as

In this way, the suction system 11 according to the present technology can also be used for the completely closed detection system 1.

(7) Storage unit 16
The detection system 1 according to the present technology can include a storage unit 16 that stores various data. The storage unit 16 can store, for example, information on samples detected by the detection unit 12, records of information processing in the processing unit 13, and all other items related to detection.

Also, in the present technology, the storage unit 16 can be provided in a cloud environment. In that case, it is also possible for each user to share various information recorded in the storage unit 16 on the cloud via the network.

Note that the storage unit 16 is not essential in the present technology, and various data can be stored using an external storage device or the like.

(8) Display unit 17
The detection system 1 according to the present technology can include a display unit 17 that displays various types of information. The display unit 17 can display all items related to detection, such as sample information detected by the detection unit 12 and various data processed by the processing unit 13 .

In the present technology, the display unit 17 is not essential, and an external display device may be connected. As the display unit 17, for example, a display, a printer, or the like can be used.

(9) Input section 18
The detection system 1 according to the present technology can include an input unit 18 that is a part operated by a user. A user can access and control each part through the input part 18 .

In the present technology, the input unit 18 is not essential, and an external operating device may be connected. For example, a mouse, a keyboard, or the like can be used as the input unit 18 .

2. Liquid Suction Method The liquid suction method according to the present technology includes an energization step of energizing the first conductive portion 1111 or the second conductive portion 1112 using the suction system 11 according to the present technology described above, and Alternatively, a liquid amount detection step of detecting the amount of the liquid L based on the energization signal from the second conductive portion 1112 is performed.

In the liquid suction method according to the present technology, it is possible to perform a control process for controlling suction based on the amount of liquid detected in the detection process. A specific example of the control process will be described with reference to the flowchart of FIG.

First, using the suction system 11 according to the third embodiment shown in FIG. 8 or the fourth embodiment shown in FIG. Based on the energization signal from the provided second conductive part 1112, it is detected whether or not the amount of the liquid L is less than the specified amount. When an excess of the liquid L is detected, an error is issued and the suction is terminated. If excess liquid L is not detected, aspiration is initiated and sample detection in liquid L is performed.

In parallel with the sample detection work, the remaining amount of the liquid L is detected. Specifically, using the suction system 11 according to the first embodiment shown in FIG. 5, the second embodiment shown in FIG. 7, or the sixth to eighth embodiments shown in FIGS. Based on the energization signal from the second conductive portion 1112 provided with the upstream end near the portion and/or the second conductive portion 1112 provided downstream of the first conductive portion 1111, the lack of the liquid L is detected. detect loss.

When the lack of liquid L is detected, an error is issued and the suction is terminated. When the lack of the liquid L is not detected, the detection is terminated if the number of events acquired in the detection exceeds the set number, and further detection is performed if the set number is not exceeded.

The present invention will be described in further detail below based on examples. It should be noted that the examples described below are examples of typical examples of the present invention, and the scope of the present invention should not be interpreted narrowly.

In Example 1, liquid loss from the tip of the suction nozzle N was detected using the suction system 11 according to the first embodiment shown in FIG. Specifically, SUS is used for the suction nozzle N, which is the first conductive part 1111, an insulating sheet is wrapped around it, and a copper plate is wrapped around it as the second conductive part 1112, and the circuit shown in FIG. 5 is applied. and verified it. The results are shown in the graph of FIG. In the graph of FIG. 20, Event Rate is the number of samples detected by the laser spot per second, Vout is the High/Low level of the technique, and Sample Aspirate Pressure is the pressure at which the nozzle aspirates the sample.

As shown in the graph of FIG. 20, the sample suction pressure becomes unstable from 59 seconds onwards, so it can be seen that air begins to enter the laser spot from this point. Going back even further, Vout goes Low at 22 seconds, which is 37 seconds earlier than when air started to enter at the laser spot.

Also, the Event Rate drops once and then rises, but the time when the Event Rate drops once is thought to be just before the connection between the sample solution and the sample solution at the tip of the suction nozzle N is broken. Also, the reason why the Event Rate increases after that is that although the sample is taken in at the same pressure, air enters the inside of the sample line from the tip of the suction nozzle N, and the load gradually decreases. This is probably because the amount of sample sucked per unit time increases.

From the above results, the timing at which Vout becomes Low indicates any of the states 3 to 5 in FIG. .

In Example 2, the lack of liquid from the suction nozzle N was detected using the suction system 11 according to the sixth embodiment shown in FIG. Specifically, SUS is used for the suction nozzle N, which is the first conductive portion 1111, a short sample line with a slightly thick inner diameter is connected to facilitate the passage of electricity, and a short second conductive portion 1112 is further connected thereon. , and a conventional sample line were connected to it, and the circuit shown in FIG. 12 was applied for actual verification. The results are shown in the graph of FIG. In the graph of FIG. 21, Event Rate is the number of samples per second detected by the laser spot, Vout is the high/low level of the technique, and sample suction pressure is the pressure at which the nozzle sucks up the sample.

As shown in the graph of FIG. 21, air enters the laser spot at 115 seconds due to the unstable sample suction pressure. On the other hand, Vout became Low at 109 seconds, 6 seconds before the air entered the laser spot, and at that stage it was possible to detect that the sample had run out. Do you get it.

Note that the present technology can also have the following configuration.
(1)
A suction unit having a suction nozzle for sucking liquid,
The suction part is
a first conductive portion;
a suction system comprising a second conductive portion insulated from the first conductive portion;
a detection unit that detects information about the sample in the liquid aspirated by the aspiration unit;
a detection system.
(2)
The detection system according to (1), wherein part or all of the suction nozzle is composed of the first conductive portion.
(3)
The detection system according to (1) or (2), wherein the upstream end of the second conductive portion is provided near the tip of the suction nozzle.
(4)
The detection system according to any one of (1) to (3), wherein the second conductive section is provided downstream of the first conductive section.
(5)
The detection system according to any one of (1) to (4), wherein the upstream end portion of the second conductive portion is provided at the maximum appropriate water surface position of the container holding the liquid.
(6)
The detection system according to any one of (1) to (5), further comprising a processing section that detects the amount of the liquid based on an energization signal from the first conductive section or the second conductive section.
(7)
The processing section includes the second conductive section having an upstream end near the tip of the suction nozzle and/or the second conductive section provided downstream of the first conductive section. The detection system according to (6), which detects lack of liquid based on the energization signal of.
(8)
(6) or ( The detection system according to 7).
(9)
The processing unit is
Based on an energization signal from the second conductive portion having an upstream end near the tip of the suction nozzle and/or from the second conductive portion provided downstream of the first conductive portion , detect the lack of fluid,
any one of (6) to (8), wherein an excess of the liquid is detected based on an energization signal from the second conductive section having an upstream end provided at a water surface position of the maximum appropriate amount of the container holding the liquid. The detection system described in .
(10)
The detection system according to any one of (6) to (9), further comprising a control unit that controls suction of the liquid based on information on the amount of the liquid detected by the processing unit.
(11)
The detection system according to any one of (1) to (10), wherein the detection unit detects light from the sample.
(12)
The detection system according to any one of (1) to (11), wherein the sample is a particle.
(13)
The detection system according to (12), which has a sorting section that sorts the particles.
(14)
The detection system according to (12) or (13), wherein the particles are cells.
(15)
A suction part having a suction nozzle for sucking liquid is provided,
The suction part is
a first conductive portion;
A suction system comprising a second conductive portion insulated from the first conductive portion.
(16)
A method for sucking liquid using a suction unit having a suction nozzle for sucking liquid,
The suction part is
a first conductive portion;
a second conductive portion insulated from the first conductive portion;
An energizing step of energizing the first conductive portion or the second conductive portion;
a liquid amount detection step of detecting the amount of the liquid based on an energization signal from the first conductive portion or the second conductive portion;
the liquid aspiration method.
(17)
The liquid suction method according to (16), wherein a control step of controlling suction is performed based on the amount of liquid detected in the liquid amount detection step.

Detection system: 1
Suction system: 11
Liquid: L
Suction part: 111
First conductive part: 1111
Second conductive part: 1112
Insulator: 1113
Suction nozzle: N
Flow path: P
Sample liquid flow path: P11
Sheath liquid flow path: P12a, P12b
Main flow path: P13
Preparative flow path: P14
Waste channel: P15a, P15b
Detector: 12
Light source: 121
Processing unit: 13
Control unit: 14
Preparative section: 15
Vibration element: 151
Counter electrodes: 152a, 152b
Collection containers: 153a, 153b, 153c
Sample liquid reservoir: B1
Sheath liquid reservoir: B2
Preparative liquid reservoir: B3
Waste liquid reservoir: B4
Storage unit: 16
Display part: 17
Input part: 18

Claims

A suction unit having a suction nozzle for sucking liquid,
The suction part is
a first conductive portion;
a suction system comprising a second conductive portion insulated from the first conductive portion;
a detection unit that detects information about the sample in the liquid aspirated by the aspiration unit;
a detection system.
The detection system according to claim 1, wherein part or all of said suction nozzle consists of said first conductive portion.
　The detection system according to claim 1, wherein the upstream end of the second conductive part is provided near the tip of the suction nozzle.
The detection system according to claim 1, wherein said second conductive portion is provided downstream of said first conductive portion.
　The detection system according to claim 1, wherein the upstream end of the second conductive part is provided at the maximum appropriate water surface position of the container holding the liquid.
The detection system according to claim 1, comprising a processing section that detects the amount of the liquid based on the energization signal from the first conductive section or the second conductive section.
The processing section includes the second conductive section having an upstream end near the tip of the suction nozzle and/or the second conductive section provided downstream of the first conductive section. 7. The detection system according to claim 6, which detects lack of liquid based on the energization signal of the.
7. The processing unit according to claim 6, wherein the processing unit detects excess liquid based on an energization signal from the second conductive unit, the upstream end of which is provided at the maximum appropriate water surface position of the container holding the liquid. detection system.
The processing unit is
Based on an energization signal from the second conductive portion having an upstream end near the tip of the suction nozzle and/or from the second conductive portion provided downstream of the first conductive portion , detect the lack of fluid,
7. The detection system according to claim 6, wherein an excess of liquid is detected based on an energization signal from said second conductive part having an upstream end at a water level position of the maximum appropriate amount of said liquid holding container.
The detection system according to claim 6, comprising a control unit that controls suction of the liquid based on information on the amount of the liquid detected by the processing unit.
The detection system according to claim 1, wherein the detection unit detects light from the sample.
The detection system according to claim 1, wherein the sample is a particle.
The detection system according to claim 12, comprising a sorting section that sorts the particles.
The detection system according to claim 12, wherein the particles are cells.
A suction unit having a suction nozzle for sucking liquid,
The suction part is
a first conductive portion;
A suction system comprising a second conductive portion insulated from the first conductive portion.
A method for sucking liquid using a suction unit having a suction nozzle for sucking liquid,
The suction part is
a first conductive portion;
a second conductive portion insulated from the first conductive portion;
An energizing step of energizing the first conductive portion or the second conductive portion;
a liquid amount detection step of detecting the amount of the liquid based on an energization signal from the first conductive portion or the second conductive portion;
the liquid aspiration method.
The liquid suction method according to claim 16, wherein a control step for controlling suction is performed based on the amount of liquid detected in the liquid amount detection step.