JP2016161371A - Cell suction system and tip folding determination method of suction tip in the same - Google Patents

Abstract

PROBLEM TO BE SOLVED: To easily detect folding of a tip of a suction tip without macroobservation.SOLUTION: A cell suction system with a sucker on which a suction tip is mounted includes: a pressure section for pressuring the inside of the suction tip; a pressure measurement section for measuring a pressure change inside the suction tip; and a determination section for determining folding of a tip of the mounted suction tip on the basis of the pressure change inside the suction tip.SELECTED DRAWING: Figure 1

Description

  The present invention relates to a cell suction system, and more particularly to a technique for determining tip breakage of a suction tip in a cell suction system.

  In life system research and the like, a specific cell is identified from many cells in a cell culture vessel, and the work of sucking the cell or its intracellular substance is frequently performed. For example, in a drug discovery process that discovers and designs new drugs, a drug discovery screening process is performed in which a drug exhibiting efficacy / activity is searched for from among a large number of candidate compounds. From the group of cells in the cell culture container to which the compound has been given, cells that exhibit a remarkably specific change are selected, the intracellular material or cells are aspirated, and analysis such as mass spectrometry is performed.

  Patent Document 1 discloses that an intracellular substance suction operation is performed using a suction tip called a nanospray ionization capillary while confirming cells to be sucked with a microscope.

  As shown in FIG. 4, for example, the suction tip 300 used for the intracellular substance suction operation is a special glass tube having a suction port 301, a mounting port 302, and the diameter of the tip of the suction port 301 is as follows. For example, it is formed with a thickness of about 0.1 μm to 100 μm.

  During the intracellular substance suction operation, the mounting port 302 of the suction tip 300 is mounted at the tip of the suction device. Then, while confirming the cells to be aspirated with a microscope, the aspiration tip 300 is moved manually or by a transporter, and the aspiration port 301 is inserted into the target cell. During the movement, the inside of the suction chip 300 is pressurized so that the suction port 301 does not suck the peripheral components including the cell culture solution in the cell culture container, and the pressure is applied after the suction port 301 reaches the target cell. And release the intracellular material.

Japanese Patent No. 5317983 Special table 2010-504086 gazette

  Since the suction tip 300 is a thin glass tube, it may be broken for some reason in the process from manufacture to actual use. However, in general, the suction tip 300 is so thin that it is difficult to see, so it is difficult to visually recognize that it is broken.

  For this reason, after attaching the suction tip 300 to the aspirator and moving it to the cell culture container, it is noticed that the suction tip 300 is broken only when the suction port 301 is detected by magnifying observation with a microscope. . In this case, it is necessary to discard the damaged suction tip 300, attach a new suction tip 300, re-moving the suction tip 300, and re-detect the suction port 301, which causes many return steps and causes a deterioration in tact time. Become. For this reason, it is desirable to detect the breakage of the tip of the suction tip 300 as easily as possible.

  Therefore, an object of the present invention is to easily detect the breakage of the tip of the suction tip without magnifying observation.

In order to solve the above problems, the cell aspiration system according to the first aspect of the present invention is a cell aspiration system including an aspirator to which an aspiration tip is attached, and a pressurizing unit that pressurizes the inside of the aspiration tip; A pressure measurement unit that measures a change in pressure in the suction tip and a determination unit that determines whether or not the tip of the attached suction tip is broken based on the pressure change in the suction tip.
Here, the determination unit can determine that the tip of the suction tip is broken when the pressure change amount within a reference time exceeds a reference value after pressurizing the suction tip.
Moreover, the said pressurization part and the said pressure measurement part can be provided in the said suction device.
In order to solve the above-mentioned problem, the tip breakage determination method of the suction tip in the cell suction system according to the second aspect of the present invention is a method of determining the tip breakage of the suction tip in the cell suction system including the suction device to which the suction tip is attached. A pressure step for pressurizing the inside of the suction tip, a pressure measuring step for measuring a pressure change in the suction tip, and a tip breakage determination of the attached suction tip based on the pressure change in the suction tip. And a determination step for performing.

  According to the present invention, it is possible to easily detect breakage of the tip of the suction tip without magnifying observation.

It is a figure which shows typically the structure of the cell suction system which concerns on this embodiment. It is a figure which shows the example of a time-dependent change of the pressure in a chip | tip after pressurization in the normal suction chip | tip without a tear, and the pre-break generation | occurrence | production suction tip with a tear. It is a flowchart explaining operation | movement of the cell suction system which concerns on this embodiment. It is a figure which shows the example of the suction chip used for intracellular substance suction operation | work.

  Embodiments of the present invention will be described with reference to the drawings. FIG. 1 is a diagram schematically showing a configuration of a cell aspiration system 100 according to the present embodiment. The cell suction system 100 is a system that supports the work of sucking intracellular substances or one or a plurality of cells using the suction tip 10.

  As shown in the figure, a cell aspiration system 100 includes an aspirator 120 that attaches the aspiration chip 10 to aspirate intracellular components, a transport unit 130 that moves the aspirator 120, and a control unit that controls each part and performs signal processing. 140, a microscope 150, a confocal scanner 160, and a camera 170. A cell 200 as a sample is stored in a cell culture vessel 210 together with a cell culture solution 220.

  The microscope 150 includes an objective lens 151, an imaging lens 152, and an illumination 153, and acquires an enlarged image in the placed cell culture vessel 210. The illumination 153 is used as a light source for acquiring a bright field image of the sample or illuminating the suction tip 10. At this time, a ring shape surrounding the suction tip 10 is formed so that the tip of the suction tip 10 can be easily recognized.

  The confocal scanner 160 includes a pinhole disk array 161, a microlens array disk 162, a dichroic mirror 163, a band pass filter 164, and a relay lens 165, and acquires a confocal image of a sample by combining with the microscope 150. . The confocal image is captured by the camera 170 and input to the control unit 140. Therefore, the microscope 150, the confocal scanner 160, and the camera 170 constitute a confocal microscope system. However, the configuration of the optical system such as the microscope 150 and the confocal scanner 160 is not limited to the example shown in the figure. For example, the confocal scanner 160 may be omitted.

  At the time of the intracellular substance suction operation, the suction tip 10 is attached to the tip of the suction device 120. Then, while confirming the cells 200 to be sucked with the confocal microscope system, the suction tip 10 is moved by the transport unit 130, and the suction port of the suction tip 10 is inserted into the target cells. During the movement, the inside of the suction tip 10 is pressurized so that the suction port does not suck the peripheral components including the cell culture solution 220 in the cell culture vessel 210, and is added after the suction port reaches the target cell 200. Release pressure and aspirate intracellular material.

  For this reason, the aspirator 120 is provided with a pressurizing unit 121 for pressurizing the inside of the suction tip 10. The pressurization state of the pressurizing unit 121 is controlled by the control unit 140.

  By the way, when the inside of the suction tip 10 is pressurized, if the tip of the suction tip 10 is bent, the air leaks from the ruptured portion, and the pressure inside the suction tip 10 rapidly decreases. FIG. 2 shows an example of a change over time of the pressure in the chip after pressurization in the normal suction tip 10 without tearing and the suction tip 10 in which the broken tip is broken. This figure also shows that the internal pressure of the suction tip 10 without tearing gradually decreases after pressurization, whereas the internal pressure of the suction tip 10 with tearing decreases rapidly after pressurization.

  For this reason, it is possible to detect the breakage of the tip of the suction tip 10 by measuring the change over time in the pressure inside the tip after pressurization. Therefore, in the cell aspiration system 100 of the present embodiment, the pressure measuring unit 122 is provided in the aspirator 120, and the change with time in the pressure in the chip after pressurization is measured. A tip break determination unit 141 that determines whether the suction tip 10 is bent based on the measurement result of the pressure measurement unit 122 is provided in the control unit 140.

  FIG. 4 is a flowchart for explaining the operation of the cell suction system 100 having the above configuration. When performing the intracellular substance aspiration operation, first, the aspiration tip 10 is attached to the tip of the aspirator 120 (S101).

  Then, the pressurizing unit 121 pressurizes the inside of the suction chip 10 (S102), and the pressure measuring unit 122 measures a change with time in the chip internal pressure after pressurization (S103).

  The tip break determination unit 141 determines that the tip break has occurred (S110) when the pressure in the chip after pressurization has rapidly decreased (S104: Yes). For example, by setting the reference time and the allowable pressure change amount in advance, it can be determined whether or not the pressure in the chip after pressurization is drastically reduced. The determination result that the tip is broken is notified to the user, for example, by displaying that fact or outputting an alarm.

  By this notification, the user can immediately replace the suction tip 10 in which the tip is broken (S111). As described above, in the cell suction system 100 of the present embodiment, the tip break of the suction tip 10 can be easily detected without performing magnified observation at an early stage after the suction tip 10 is mounted. It is possible to prevent the deterioration of the tact time when the tip break occurs.

  On the other hand, when the pressure in the chip after pressurization does not decrease rapidly (S104: No), the suction chip 10 is moved to the vicinity of the target cell by the transport unit 130, assuming that the tip is not broken ( S105). Then, magnified observation is performed to detect the suction port and the target cell (S106), and the suction port of the suction tip 10 is inserted into the target cell.

  In this state, the pressurized state in the suction tip 10 is released (S107), and the intracellular substance is sucked (S108). After the suction, the suction tip 10 is removed at a predetermined position (S109), and the intracellular substance suction work is finished. The sucked intracellular substance can be accurately analyzed using, for example, a mass spectrometer.

As described above, according to the cell suction system 100 of the present embodiment, the tip break is determined based on the change with time in the tip pressure, so that the tip break of the suction tip 10 can be easily detected without performing magnified observation. It is possible to measure the change in the pressure in the tip over time for determining the tip breakage not only when the suction tip 10 is mounted, but also during the movement of the suction tip 10, and suction by contact during movement, etc. The breakage of the chip 10 may be detectable.

DESCRIPTION OF SYMBOLS 10 ... Suction chip, 100 ... Cell suction system, 120 ... Aspirator, 121 ... Pressure part, 122 ... Pressure measurement part, 130 ... Conveyance part, 140 ... Control part, 141 ... Determination part, 150 ... Microscope, 151 ... Objective Lens, 152 ... Imaging lens, 153 ... Illumination, 160 ... Confocal scanner, 161 ... Pinhole disk array, 162 ... Microlens array disk, 163 ... Dichroic mirror, 164 ... Band-pass filter, 165 ... Relay lens, 170 ... Camera 200 ... cell 210 ... cell culture vessel 220 ... cell culture solution

Claims (4)

A cell aspiration system comprising an aspirator with a suction tip,
A pressurizing unit for pressurizing the inside of the suction tip;
A pressure measuring unit for measuring a pressure change in the suction tip;
A cell aspiration system comprising: a determination unit configured to determine whether the attached suction tip is broken based on a pressure change in the suction tip.   The determination unit determines that a tip break of the suction tip has occurred when a pressure change amount within a reference time exceeds a reference value after pressurizing the inside of the suction tip. A cell aspiration system according to claim 1.   The cell aspiration system according to claim 1 or 2, wherein the pressurizing unit and the pressure measuring unit are provided in the aspirator. A method for determining the tip break of a suction tip in a cell suction system equipped with a suction device to which a suction tip is attached,
A pressurizing step for pressurizing the inside of the suction tip;
A pressure measuring step for measuring a pressure change in the suction tip;
Based on the pressure change in the suction tip, a determination step for determining the tip breakage of the attached suction tip;
A method for determining breakage of the tip of a suction tip in a cell suction system.