Particle sorting system, orifice component, and plate
The particle separation system addresses the challenge of aligning the cuvette flow path and the orifice in flow cytometry by using a controlled holding portion and positioning mechanism, resulting in improved alignment accuracy and reduced user burden.
Patent Information
- Application Number
- PCT/JP2024/030712
- Authority / Receiving Office
- WO · WO
- Patent Type
- Applications
- Current Assignee / Owner
- Priority Date
- 2024-05-02
- Filing Date
- 2024-08-28
- Publication Date
- 2025-03-20
AI Technical Summary
Existing flow cytometry systems face challenges in accurately aligning the cuvette flow path with the orifice, requiring manual effort and resulting in instability and increased user burden.
A particle separation system with a holding portion that positions a plate with an orifice, and a control unit that adjusts the position of the holding portion parallel to the discharge axis, allowing for precise alignment of the cuvette flow path and the orifice based on their shapes.
The system enables accurate and automated alignment of the cuvette flow path and the orifice, reducing user effort and improving the stability of the flow stream, thereby enhancing the overall performance of the particle separation process.
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Figure JP2024030712_20032025_PF_FP_ABST
Abstract
Description
Particle sorting system, orifice components and plates
[0001] The present technology relates to a particle sorting system, an orifice component, and a plate, and more particularly to a particle sorting system, an orifice component, and a plate that enable accurate alignment of a cuvette channel and an orifice.
[0002] Currently, a technology called flow cytometry is used to analyze and separate biological particles such as cells and microorganisms, as well as particles such as microbeads. Flow cytometry is a method for analyzing and separating particles by aligning particles in a liquid, irradiating them with light, and detecting the light emitted from each particle. The device used for this flow cytometry is called a flow cytometer (also called a "cell sorter").
[0003] In a flow cytometer, a vibration element is generally provided in a part of the flow path through which particles surrounded by sheath liquid flow, and this vibration element vibrates a part of the flow path, continuously breaking the liquid discharged from the discharge port of the flow path into droplets. Then, based on the detection signal obtained by irradiating light, the droplets containing the particles are given a positive (+) or negative (-) charge, or are left uncharged, and are split by a deflection plate depending on the charge state, and the target particles are collected in each collection container.
[0004] Among flow cytometers, there is a flow cell type device having a cuvette flow path through which a liquid containing particles flows. In the case of a flow cell type device, it is necessary to align the orifice with the cuvette flow path.
[0005] For example, Patent Document 1 discloses "a method for forming droplets from a jet of a flow cytometer, comprising: a. forming a nozzle volume; b. introducing a flow of sheath fluid into the nozzle volume; c. introducing a flow of a substance into the sheath fluid in the nozzle volume; d. providing an oscillator coupled to the nozzle volume and positioned not completely outside the nozzle volume; e. applying an AC voltage with an amplitude of less than 100 millivolts to the oscillator; f. causing the sheath fluid to flow out of the nozzle volume; and g. forming at least one droplet from the sheath fluid after causing the sheath fluid to flow out of the nozzle volume." However, in a flow cytometer that implements this method, the user must themselves fix the nozzle body to a cuvette using an O-ring and a fixing member.
[0006] Special Publication No. 10-507524
[0007] However, it is difficult to accurately align the cuvette flow channel and the orifice at the desired position. Although it is possible to fit the cuvette flow channel and the orifice together and seal them using an O-ring, it is difficult to accurately adjust the position in the direction of the flow of the liquid containing particles, and the influence of component tolerances cannot be ignored. Furthermore, aligning the cuvette flow channel and the orifice requires manual labor by the user, and performing accurate position adjustment every time places a heavy burden on the user.
[0008] Therefore, a main object of the present technology is to provide a technology that enables accurate alignment between a cuvette channel and an orifice.
[0009] This technology first provides a particle sorting system that includes a cuvette flow path through which a liquid containing particles flows, a holding unit that holds a plate that includes an orifice portion that ejects the liquid, and a control unit that controls the position of the holding unit to change to approximately parallel to the ejection axis, and in which the cuvette flow path and the plate can be positioned based on their respective shapes.
[0010] The present technology also provides an orifice component comprising a base member and an orifice portion through which a liquid containing particles flows, the orifice portion being formed at one end of the base member and extending in a direction approximately perpendicular to the base member.
[0011] Furthermore, the present technology also provides a plate comprising a base member and an orifice portion through which a liquid containing particles flows, the orifice portion being formed at one end of the base member and capable of being fitted with an orifice part extending in a direction substantially perpendicular to the base member.
[0012] 1A is a schematic diagram showing an example of an embodiment of the vicinity of the main channel P13 and orifice portion C2 of the cuvette channel P of the particle sorting system 100 according to the present technology. FIG. 1B is a schematic diagram showing an example of a first embodiment of the particle sorting system 100 according to the present technology. FIG. 1C is a schematic diagram showing an example of an embodiment of the holder 11. FIG. 1D is a diagram explaining the positioning (coarse adjustment) of the cuvette channel P and the orifice portion C2. FIG. 1E is a diagram explaining the positioning (fine adjustment) of the cuvette channel P and the orifice portion C2. FIG. 1F is a diagram explaining a state in which a relative tilt occurs between the stage S of the holder 11 and the cuvette channel P. FIG. 1G is a diagram explaining how the control unit 12 controls the step of aspirating the orifice portion C2 toward the cuvette channel P in addition to two-stage positioning. FIG. 1A is a diagram explaining the elevation height of the stage S (position of the potentiometer M2), and FIG. 1B is a diagram explaining the operating status of the suction (degassing pump). FIG. 1A is a plan view of a plate E including a closed orifice portion C3, and FIG. 1B is a partial enlarged view of FIG. 1A. 15A and 15B are diagrams illustrating cleaning (under normal and abnormal conditions) using a plate E including a closed orifice portion C3. FIG. 15B is a flowchart illustrating a flow at the start of sorting. FIG. 15C is a flowchart illustrating a flow during cleaning. FIG. 15D is a flowchart illustrating a flow at the completion of sorting or cleaning. FIG. 15C is a schematic diagram illustrating another example of a first embodiment of a particle sorting system 100 according to the present technology. FIG. 15A is a front view illustrating an example of a second embodiment of an orifice component C according to the present technology, and FIG. 15B is a rear view illustrating an example of a second embodiment of an orifice component C according to the present technology. FIG. 15A is a left side view illustrating an example of a second embodiment of an orifice component C according to the present technology, and FIG. 15B is a right side view illustrating an example of a second embodiment of an orifice component C according to the present technology. FIG. 15B is a plan view illustrating an example of a second embodiment of an orifice component C according to the present technology, and FIG. 15B is a bottom view illustrating an example of a second embodiment of an orifice component C according to the present technology. FIG. 15C is a perspective view illustrating an example of a second embodiment of an orifice component C according to the present technology. FIG. 15D is a cross-sectional view taken along line P-P in A of FIG. 15A. 10 is a partially enlarged view illustrating the state in which the orifice part C is attached to or detached from the plate E. FIG. 11 is a partially enlarged view illustrating the state in which the plate E is fitted to the orifice part C.1A is a perspective view showing an example of an embodiment of a plate E and an orifice component C; FIG. 1B is a diagram illustrating a state when the orifice component C is replaced; FIG. 1C is a diagram illustrating the orifice component C and the plate E in detail; FIG. 1D is a schematic diagram illustrating an example of an embodiment (another embodiment 1) different from that of FIG. 1 in the vicinity of a cuvette flow path P and an orifice portion C2; FIG. 1E is a schematic diagram illustrating an example of an embodiment (another embodiment 2) different from that of FIG. 1 in the vicinity of a cuvette flow path P and an orifice portion C2; FIG. 1F is a diagram illustrating a water-stopping shape; FIG. 1A is a partial enlarged view of the water-stopping shape when the water-stopping shape is a substantially annular convex shape, and FIG. 1B is a partial enlarged view of FIG. 1A; FIG. 1C is a diagram illustrating a gap between the orifice portion C2 and the cuvette flow path P; FIG. 1D is a diagram illustrating a taper angle difference between the cuvette flow path P and the orifice portion C2; FIG. 1E is a diagram illustrating a water-stop valve structure C6 in a closed orifice portion C3; FIG. 1A is a front view illustrating a modified example of a second embodiment of the orifice component C according to the present technology; and FIG. 1B is a rear view illustrating a modified example of the second embodiment of the orifice component C according to the present technology. 33A is a left side view showing a modified example of the second embodiment of the orifice component C according to the present technology, and B is a right side view showing a modified example of the second embodiment of the orifice component C according to the present technology. 33A is a plan view showing a modified example of the second embodiment of the orifice component C according to the present technology, and B is a bottom view showing a modified example of the second embodiment of the orifice component C according to the present technology. 33B is a perspective view showing a modified example of the second embodiment of the orifice component C according to the present technology. 33C is a cross-sectional view taken along line Q-Q in A of FIG. 33A. 33D is a perspective view showing a modified example of the embodiment of the plate E and the orifice component C, which is different from FIG. 23. 33A is a perspective view showing the embodiment of the closed orifice section C3 of FIG. 32, and B is a perspective view showing a modified example of the embodiment of the closed orifice section C3, which is different from FIG. 32.
[0013] Preferred embodiments for carrying out the present technology will be described below with reference to the drawings. The embodiments described below are examples of typical embodiments of the present technology, and should not be construed as narrowing the scope of the present technology. The description will be given in the following order: 1. 1. First embodiment (particle sorting system 100) (1) Cuvette flow path P (2) Holding unit 11 (3) Control unit 12 (3-1) Positioning of cuvette flow path P and orifice unit C2 (3-2) Replacing plate E including orifice unit C2 (3-3) Cleaning using plate E including closed orifice unit C3 (3-4) Others (3-5) Examples of control by control unit 12 [Control example 1] [Control example 2] [Control example 3] (3-6) Other embodiment 1 (3-7) Other embodiment 2 (4) Irradiation unit 13 (5) Detection unit 14 (6) Sorting control unit 15 (charging unit 15a, deflection plate 15b, collection container 15c) (7) Imaging unit 20 (8) Break-off control unit (9) Memory unit 17 (10) Display unit 18 (11) User interface 19 (12) Others Second embodiment (orifice part C) (1) base member C1 (2) orifice portion C2 (3) water stop mechanism C4 (4) closed orifice portion C3 (5) positioning mechanism C23 (6) tilt control mechanism C24 3. Third embodiment (plate E)
[0014] 1. First embodiment (particle sorting system 100)
[0015] Fig. 1 is a schematic diagram showing an example of an embodiment of the vicinity of the main channel P13 and orifice C2 of the cuvette channel P of a particle sorting system 100 according to the present technology, and Fig. 2 is a schematic diagram showing an example of a first embodiment of the particle sorting system 100 according to the present technology. Note that the holder 11 is omitted from Fig. 2. The particle sorting system 100 according to this embodiment has at least the cuvette channel P, the holder 11, and a controller 12, and may also have an irradiation unit 13, a detection unit 14, a sorting controller 15, and other components. Each component will be described below.
[0016] (1) Cuvette flow path P
[0017] The cuvette flow path P allows at least a liquid containing particles to flow, and includes a main flow path P13. In this embodiment, the main flow path P13, where optical detection is performed, is configured so that particles contained in the sheath liquid are aligned in a substantially straight line, and as shown in FIG. 2, the particles are ejected outside the flow cell and then separated.
[0018] Specifically, a fluid containing sheath liquid and particles (hereinafter also referred to as "sample liquid") is first injected into a conical container through sheath liquid injection ports P12a, P12b and sample liquid injection port P11. The conical container is installed with its apex facing vertically downward, and a tube or the like for introducing sheath liquid is connected to the upper side. The top of the conical container is open, and a vibration element is attached and sealed with an O-ring. The sample liquid is injected vertically from above the container. The vibration element and piston are annular, and a pipe passes through their central hole. The conical container narrows at the bottom, and beyond that, a main channel (linear channel) P13 is connected to a cuvette channel P formed inside.
[0019] A laminar flow is formed within the conical vessel, with the sheath liquid surrounding the sample liquid. As the flow continues in the discharge direction, optical detection is performed in the main flow channel P13 by laser light irradiation. A removable nozzle outlet P131 is located at the end of the main flow channel P13, and as shown in FIG. 2, the main flow channel P13 slopes downward, narrowing continuously from the nozzle outlet P131 to the orifice C2. A vibration element attached directly above the conical vessel applies minute vibrations to the sheath liquid and sample liquid in the forward and backward directions relative to the flow. The liquid column ejected from the orifice C2 then advances vertically downward, expanding the neck formed at the same frequency as the vibration of the vibration element, until it breaks into droplets at the break-off point (BOP), located 10 to 20 mm from the orifice C2.
[0020] The vibration element applies vibrations to the liquid including the sheath liquid by supplying a driving voltage based on one or more frequencies. This allows the liquid to be continuously broken into droplets, generating a fluid stream (a flow of droplets D). The frequency may be in a frequency range specified by a user. The vibration element is not particularly limited, and any conventionally known element may be freely selected and used as appropriate, and specific examples include a piezoelectric element.
[0021] In the present technology, the term "particles" may broadly include biological particles such as cells, microorganisms, and ribosomes, as well as synthetic particles such as latex particles, gel particles, and industrial particles. In addition, in the present technology, the particles may be contained in a liquid sample, etc.
[0022] Bio-related particles may include chromosomes, ribosomes, mitochondria, organelles (cell organelles), and the like that make up various cells. Cells may include animal cells (e.g., blood cells) and plant cells. Microorganisms may include bacteria such as Escherichia coli, viruses such as tobacco mosaic virus, and fungi such as yeast. Bio-related particles may also include bio-related polymers such as nucleic acids, proteins, and complexes thereof. Industrial particles may be, for example, organic or inorganic polymer materials, metals, etc. Organic polymer materials may include polystyrene, styrene-divinylbenzene, polymethyl methacrylate, etc. Inorganic polymer materials may include glass, silica, magnetic materials, etc. Metals may include gold colloids, aluminum, etc.
[0023] In the present technology, the particles may be labeled with one or more dyes such as fluorescent dyes. In this case, examples of usable fluorescent dyes 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, and Brilliant Violet (BV421).
[0024] (2) Holding part 11
[0025] The holder 11 holds a plate E including an orifice C2 that ejects a fluid containing at least particles. The "orifice C2" and the "plate E" will be described later in "2. Second embodiment (orifice component C)" and "3. Third embodiment (plate E)."
[0026] The shape of the holder 11 is not particularly limited as long as it can hold the plate E, but it is preferable that the holder 11 has a shape that makes it easy to load the plate E. Specifically, examples of the shape include a substantially plate-like or substantially hemispherical shape having a surface that is substantially perpendicular to the ejection axis of the droplet D from the orifice portion C2.
[0027] 3 is a schematic diagram showing an example of an embodiment of the holder 11. The holder 11 can move in a direction substantially parallel to the ejection axis (of droplets D from the nozzle outlet P131) while holding the plate E, and this movement is controlled by a control unit 12, which will be described later. Specifically, the holder 11 has an elevation control mechanism including a motor M1, a potentiometer M2, a stage drive shaft M3, and a stage compression spring M4, and also has a stage S on which the plate E is placed. Note that the present technology is not limited to this configuration of the elevation control mechanism, and is not particularly limited as long as it can change the position of the stage S.
[0028] Specifically, as shown in FIG. 3A, when the stage S is raised, no spring force is applied (the spring is not compressed). Next, when the stage S is raised further, as shown in FIG. 3B, the orifice C2 and the nozzle outlet P131 of the cuvette flow path P are merely in contact with each other, and no spring force is applied. In this embodiment, the potentiometer M2 detects the position of the stage drive shaft M3, not the position of the stage S. Finally, when the stage S is raised further, as shown in FIG. 3C, the spring is compressed, and this force presses the orifice C2 and the nozzle outlet P131 together. Furthermore, the holder 11 may be moved in a desired direction, such as a direction substantially perpendicular to the ejection axis, as needed.
[0029] Furthermore, in this embodiment, one or more sensors may be provided to detect the position of the stage S. For example, a sensor may be provided to detect the upper end or lower end of the moved stage S, but the present technology is not limited to these. Furthermore, although not shown, the holder 11 may be provided with a structure such as a stopper that physically prevents the plate E from being pushed too far into the stage S when it is loaded, or the control unit 12 may issue a warning to the user by detecting this with the sensor 16 or the like.
[0030] (3) Control unit 12
[0031] The control unit 12 controls the position of the holding unit 11 to change the position substantially parallel to the ejection axis of the droplet D from the nozzle outlet P131. As will be described later, control other than the above-described control may be performed as necessary.
[0032] (3-1) Positioning of the cuvette flow path P and the orifice portion C2
[0033] As described above, in the prior art, it was difficult to align the cuvette flow path and the orifice with the desired fit accuracy due to mechanical play, component tolerances, and the like. However, in the present technology, the positioning of the holder 11 that holds the plate E including the orifice portion C2 is achieved by the above-described elevation control mechanism, and the control unit 12 can mechanically change the position to be approximately parallel to the ejection axis, eliminating the need for the user to perform the alignment themselves. Therefore, the alignment of the cuvette flow path P and the orifice portion C2 can be mechanically controlled, enabling highly accurate alignment. Furthermore, as a result, factors that cause instability in the flow stream can be eliminated, reducing the user's need to readjust the orifice position.
[0034] Specifically, in this embodiment, the cuvette flow path P and the plate E can be positioned based on their respective shapes. Specifically, when the control unit 12 raises the holding unit 11 substantially parallel to the discharge axis, the positioning is performed based on the engagement between a positioning pin P41 provided on the cuvette flow path P and an engagement unit E4 of the plate E.
[0035] FIG. 4 is an explanatory diagram illustrating the positioning (coarse adjustment) of the cuvette flow path P and the orifice portion C2. More specifically, as shown in FIGS. 4A to 4C, a positioning pin P41 for the plate E is provided on the cuvette holder P4 that holds the cuvette flow path P, and an engagement portion E4 for engaging with the positioning pin is provided on the plate E. The positioning pin P41 engages with the engagement portion, thereby determining the position of the plate E with respect to the cuvette flow path P. The shape of the engagement portion E4 is not particularly limited as long as the positioning pin P41 can be engaged with it, and can be appropriately designed to have a shape such as a through-hole, a hole, a holder, a groove, or the like. The number of positioning pins P41 is also not particularly limited and can be one or two or more. Accordingly, the number of engagement portions E4 is also not particularly limited as long as it is the same number as the positioning pins P41.
[0036] The control unit 12 can also control the positioning of the cuvette flow path P and the plate E in multiple stages. Specifically, two-stage positioning is possible: rough adjustment is performed based on the engagement between the positioning pin P41 provided on the cuvette flow path P side and the engagement portion E4 of the plate E, and then more accurate fine adjustment is performed, as described below.
[0037] 5A to 5C are explanatory diagrams illustrating the positioning (fine adjustment) of the cuvette flow path P and the orifice C2. More specifically, as shown in FIGS. 5A to 5C, the coarse adjustment is as described above, but the fine adjustment involves positioning based on the engagement between the lower end of the cuvette flow path P (= nozzle outlet P131) and the upper end of the orifice C2. In this case, the engagement is preferably based on a concave-convex shape, and more preferably, the nozzle outlet P131 functions as a concave portion and the orifice C2 functions as a convex portion. This allows for more accurate positioning.
[0038] In this case, it is preferable that the orifice C2 has a tapered shape C22 in part. Specifically, as shown in Fig. 20 (to be described later), it is preferable that the tapered shape C22 is continuously formed in a substantially annular shape so as to surround the connection portion (the connecting surface in Fig. 20) with the cuvette flow path P through which the particle-containing liquid flows. This tapered shape C22 allows the orifice C2 to be smoothly drawn into the recess formed in the nozzle outlet P131.
[0039] Furthermore, in this case, it is preferable that the orifice portion C2 is movable in at least one direction consisting of a direction substantially parallel to the discharge axis, a direction substantially perpendicular to the discharge axis, and a direction substantially rotating with respect to the discharge axis. As a result, even if some misalignment occurs during the fitting, the play of the orifice portion C2 with respect to the plate E can cover even a slight misalignment, and coupled with the tapered shape C22, smooth positioning (fitting) can be achieved without damaging the components.
[0040] As described above, in this embodiment, positioning is performed in two stages, coarse adjustment and fine adjustment, so that the positioning between the cuvette flow path P (particularly the nozzle outlet P131) and the orifice portion C2 can be performed more accurately than in the prior art. Furthermore, because the holding portion 11 is controlled by the control portion 12 and automatically moves in a direction approximately parallel to the ejection axis, the user does not need to perform positioning themselves, thereby improving usability. Note that, although the above example describes positioning in two stages, the present technology is not limited to this and may perform positioning in three or more stages.
[0041] It is preferable that the control unit 12 controls the orifice C2 to be sucked toward the cuvette flow path P in response to the lifting of the holder. Specifically, a slight tilt may occur relative to the stage S of the holder 11 and the cuvette flow path P (see FIG. 6 ), which affects the posture of both during crimping. Therefore, in order to reduce the effect of the relative tilt, the cuvette flow path P and the orifice C2 are brought into contact with each other by suction (for example, air suction using a degassing pump), and then the control unit 12 controls the lifting of the holder 11 to finally crimp them together.
[0042] 6 is a diagram illustrating a state in which a relative tilt occurs between the stage S of the holder 11 and the cuvette flow path P. More specifically, as shown in FIG. 7, it is necessary to eliminate the relative tilt as much as possible, and the orifice C2 is first aligned with the cuvette flow path P by a suction operation.
[0043] 7 is a diagram illustrating how the control unit 12 controls the two-stage positioning and the process of aspirating the orifice C2 toward the cuvette flow path P. First, as shown in FIG. 7A, the holding unit 11 loads a plate E including the orifice C2 onto the stage S. Next, as shown in FIG. 7B, the stage S is raised and moved to the vicinity of the insertion position of the cuvette flow path P (=the nozzle outlet P131 having a recess). Next, as shown in FIG. 7C, the cuvette flow path P is fitted to the orifice C2 through two-stage positioning.
[0044] Next, as shown in FIG. 7D, the stage S is raised and moved to a position close to the nozzle outlet P131 of the cuvette flow path P. Here, FIG. 7D will be explained in detail, divided into sections a to c. First, as shown in FIG. 7A, the stage S is stopped just before the orifice portion C2 comes into close contact with the nozzle outlet P131. Next, as shown in FIG. 7B, the orifice portion C2 is sucked upward in a direction substantially parallel to the ejection axis (see the black arrow in FIG. 7B), and the orifice portion C2 is lifted, aligning the top surface of the orifice portion C2 with the bottom surface of the nozzle outlet P131. Then, as shown in FIG. 7C, the stage S is raised, and the top surface of the orifice portion C2 is pressed against the bottom surface of the nozzle outlet P131.
[0045] From the above, as shown in FIG. 7E, the suction operation is stopped, and the orifice portion C2 and the nozzle outlet P131 come into close contact with each other accurately.
[0046] FIG. 8A illustrates the elevation height (position of potentiometer M2) of stage S, and FIG. 8B illustrates the operating status of suction (degassing pump). Here, the elevation height (movement of stage S) and the on / off state of the degassing pump will be described with reference to FIG. 8 . First, the control unit 12, which has raised the stage S, temporarily stops the stage S just before the orifice C2 contacts the cuvette flow path P, as shown in FIG. 8A-a. It is preferable to stop the degassing pump at a position where it can sufficiently suction the orifice C2. Next, as shown in FIG. 8B-b, the degassing pump generates negative pressure, sucking the orifice C2 toward the cuvette flow path P. Then, while continuing suction, the stage S resumes its elevation under the control of the control unit 12 (see FIG. 8A-c), and stops its elevation when a predetermined pressure (e.g., 10 N to 50 N) is reached (see FIG. 8A-d). Finally, the degassing pump stops its operation after checking whether the crimping is properly completed, as shown in B-e of Fig. 8. By doing this, as described above, the orifice C2 is allowed to settle before the final crimping using the holding part 11 is possible.
[0047] (3-2) Replacement of plate E including orifice C2
[0048] In this embodiment, the plate E including the orifice portion can be replaced with a plate E including a closed orifice portion C3 for cleaning the inside of the cuvette, thereby enabling cleaning of the inside of the cuvette.
[0049] The positioning of the cuvette flow path P and the closed orifice portion C3 is the same as that explained in "(3-1) Positioning of the cuvette flow path P and the orifice portion C2" above, and therefore will not be explained here.
[0050] Here, the particle sorting system 100 according to this embodiment may have a sensor 16. Specifically, examples of the sensor include a plate presence / absence sensor that determines whether or not a plate E is present, a cleaning nozzle sensor that determines whether or not a cleaning nozzle is present, and a sensor that detects that the stage S has reached the upper end or the lower end of the holder 11 described above, but the present technology is not limited to these.
[0051] More specifically, the control unit 12 receives a signal from the plate presence / absence sensor and determines the presence or absence of the plate E. This prevents various flows controlled by the control unit 12 from proceeding while the plate E is not held by the holder 11.
[0052] The control unit 12 can also receive a signal from a cleaning nozzle sensor, determine whether it is a cleaning nozzle, and if it determines that it is a cleaning nozzle, control, for example, a degassing pump to clean the inside of the cuvette.
[0053] The method of discrimination by the sensor 16 is not particularly limited, and can be based on a portion of the shape of each plate E. Specifically, discrimination is performed by changing the presence or absence of a notch E5 between the plate E including the orifice portion C2 and the plate E including the closed orifice portion C3. More specifically, as shown in FIG. 9 , the plate E including the closed orifice portion C3 has a notch E5 detected by the cleaning nozzle sensor in a portion of the longitudinal direction of the main body E3 of the plate E. On the other hand, although not shown, the plate E including the orifice portion C2 is designed not to have a notch E5 detected by the cleaning nozzle sensor. Note that, although FIG. 9 shows the notch E5 as the shape detected by the cleaning nozzle sensor, the present technology is not limited thereto, and a hole, a through-hole, a protrusion, a groove, or the like may be used instead of the notch.
[0054] Additionally, when the control unit 12 determines that the holding unit 11 has reached the bottom end using a sensor, stopper component, or the like that detects that the stage S has reached the bottom end of the holding unit 11, it controls the plate E including the orifice portion C2 or the plate E including the closed orifice portion C3 to be in a removable state. Specifically, if the plate E including the orifice portion C2 or the plate E including the closed orifice portion C3 is removed by a user while the holding unit 11 is being raised or lowered, this could result in damage to various components or the occurrence of errors. For this reason, removal is possible only after the holding unit 11 has reached the bottom end, thereby preventing damage to the various components and the occurrence of errors.
[0055] The control unit 12 can change the pressure in the upward direction on the ejection axis of the holding unit 11 when the orifice unit C2 or the closed orifice unit C3 contacts the cuvette flow path P. Specifically, the pressure of the orifice unit C2 at the time of contact can be set to be higher than the pressure of the closed orifice unit C3. This makes it possible to more reliably achieve close contact between the orifice unit C2 and the nozzle outlet P131. Furthermore, it is not necessary for the pressures to be different between the two units; if necessary, the pressure of the orifice unit C2 at the time of contact may be set to be equal to the pressure of the closed orifice unit C3.
[0056] (3-3) Cleaning using plate E including closed orifice portion C3
[0057] In this embodiment, as described above in "(3-2) Replacing the plate E including the orifice portion C2," the plate E including the orifice portion C2 can be replaced with a plate E including a closed orifice portion C3, and when the plate E is replaced with the plate E including the closed orifice portion C3, the inside of the cuvette flow path P can be cleaned using the closed orifice portion C3. FIG. 10 is a diagram illustrating cleaning (under normal conditions and under abnormal conditions) using the plate E including the closed orifice portion C3. Cleaning using the plate E including the closed orifice portion C3 will be described below with reference to FIG. 10.
[0058] 10A to 10E are diagrams illustrating cleaning (normal operation) using a plate E including a closed orifice portion C3. First, as shown in FIG. 10A, a cleaning solution is sent to the cuvette flow path P. The waste liquid flows around the closed orifice portion C3, reaches the closed nozzle C31, and is then discharged. Next, as shown in FIG. 10B, the cuvette flow path P is soaked in a cleaning solution (cleaner solution). In this case, discharge from the closed nozzle C31 is also temporarily stopped. Next, as shown in FIG. 10C, pure water (including ultrapure water) or sheath liquid is sent. At this time, there is residue in the closed nozzle C31. Next, as shown in FIG. 10D, the cuvette flow path P is soaked in pure water or sheath liquid. In this case, discharge from the closed nozzle C31 is also temporarily stopped. 10C to 10D, the concentration of the residue can be reduced by repeating these steps once or twice or more as necessary. Finally, as shown in FIG. 10E, the inside of the cuvette flow path P is replaced with pure water or sheath liquid to complete the process.
[0059] Fig. 10F is a diagram illustrating cleaning (in an emergency) using a plate E including a closed orifice portion C3. Therefore, the cleaning method shown in Fig. 10 is not normally used, but is a method that is used when a blockage or the like occurs in the cuvette flow path P. Hereinafter, emergency cleaning using the plate E will be described with reference to Fig. 10.
[0060] First, as shown in Fig. 10F, pure water or sheath liquid is sent (backflowed) from the closed nozzle C31 to remove any blockages in the cuvette flow path P. After the backflow cleaning operation, the cuvette flow path P is always cleaned with a cleaning liquid (preferably a cleaning liquid containing a chemical) to eliminate the influence of the contaminated closed nozzle C31. Examples of the cleaning operation include the methods described above with reference to Figs. 10A to 10E.
[0061] (3-4) Other
[0062] The control unit 12 can also correct the detection values detected by the detection unit 14 and calculate the feature quantities of each particle. Specifically, it calculates feature quantities such as particle size, shape, and internal structure from the detection values of the received fluorescence and scattered light. It also makes a sorting decision based on the calculated feature quantities and the sorting conditions received from the user interface 19 (described later), and generates a sorting control signal. Specific types of particles are sorted and collected by controlling the charging unit 15a (described later) based on the sorting control signal.
[0063] Furthermore, the control unit 12 may be connected to an imaging element, a detection unit 14, etc., and perform analysis based on the image acquired by the imaging element, the signal detected by the detection unit 14, etc. Specifically, the control unit 12 analyzes or calculates data relating to the state of the droplet D based on the image acquired by the imaging element. Also, the BOP fluctuation amount; ΔBOP (difference in break-off position), etc. may be calculated from the data relating to the state of the droplet D.
[0064] The control unit 12 may be included in a housing in which the detection unit 14 and the like are provided, or may be located outside the housing. The control unit 12 may also be connected to each unit of the particle sorting system 100 via a network, either wired or wirelessly.
[0065] (3-5) Example of control by the control unit 12
[0066] An example of control by the control unit 12 will be described below with reference to a flowchart.
[0067] [Control Example 1]
[0068] FIG. 11 is a flowchart illustrating the flow at the start of sorting. In the flowchart shown on the left side of FIG. 11, sorting setup is first initiated (S101). Specifically, the user is notified of an instruction to insert plate E (S102). Specifically, the user is instructed to insert plate E on the display unit 18 using a GUI or the like. Next, for example, if a predetermined condition (e.g., detection by a sensor to confirm insertion of plate E) is met, a button such as "Next" becomes pressable (active), and the flow proceeds to the next step (S103). On the other hand, if the predetermined condition is not met, the user is again notified of an instruction to insert plate E (S102).
[0069] Next, it is determined whether or not a cleaning nozzle (=closed orifice portion C3) is attached (S104). If a cleaning nozzle is attached, an alert is notified to the user (S105). Then, the user is prevented from proceeding to the subsequent flow, and the display unit 18 may display a message instructing the user to check again whether a cleaning nozzle is attached, or the user may be instructed by voice notification or the like to check again. After checking again, the user then starts over from S102.
[0070] On the other hand, if a cleaning nozzle is not attached, the control unit 12 receives an instruction to raise or lower the holder 11 (S106). The instruction to raise or lower the holder 11 may be switched to automatic raising or lowering, or may be initiated by a user instruction via the user interface 19. Since automatic raising or lowering may cause a user's fingers to get caught, it is preferable that the user issue an instruction to raise or lower the holder 11 after closing the exterior door.
[0071] Next, the control unit 12 starts raising and lowering the stage S (S107). Basically, the holder 11 rises, but may be stopped or lowered as necessary. Next, it is determined whether the height of the stage S (the position of the potentiometer M2) is at a predetermined position (S108). If the height is higher or lower than the predetermined position, the control unit 12 controls the holder 11 to make adjustments, and the process returns to S107. On the other hand, if the height is at the predetermined position, the control unit 12 stops raising and lowering the holder 11 (S109) and notifies each component of the particle sorting system 100 that the orifice C2 has been installed (S110). The completion of installation may be communicated to the user via the display unit 18 using a GUI or the like. This completes the sorting setup, allowing the system to proceed to the next step.
[0072] In the flowchart shown on the left side of Fig. 11, the two-stage positioning and suction operation is performed between S106 and S109. The two-stage positioning and suction operation will be described below with reference to the flowchart shown on the right side of Fig. 11.
[0073] In the flowchart shown on the right side of FIG. 11 , the first stage of lifting / lowering is initiated (S111). This corresponds to the "coarse adjustment" described above. Next, the control unit 12 determines whether the lift height of the stage S (the position of the potentiometer M2) is at a predetermined position (S112). If it is higher or lower than the predetermined position, the process returns to S111. On the other hand, if it is at the predetermined position, the control unit 12 stops the first stage of lifting / lowering (S113). Next, the control unit 12 starts a suction operation (S114). Basically, the suction operation starts when the stage S reaches a predetermined position in the design. There are several patterns for starting the suction operation, including a pattern in which the lifting / lowering is stopped, a pattern in which the suction operation is performed, and then the lifting / lowering is resumed, and a pattern in which the lifting / lowering is continued and the suction operation is started when the stage S reaches the predetermined position in the design.
[0074] Next, the control unit 12 determines whether a predetermined time has elapsed since the start of the suction operation using a timer or the like (S115). If the predetermined time has not elapsed, the process returns to S114 and the suction operation continues. On the other hand, if the predetermined time has elapsed, the control unit 12 stops the suction operation (S116). Note that in this embodiment, instead of determining based on the predetermined time in S115, the determination may be made based on the pressure measured by a pressure gauge or the like installed on the suction side.
[0075] Next, the second stage of lifting and lowering is started (S117). This corresponds to the "fine adjustment" described above. Next, the control unit 12 determines whether the lift height of the stage S (the position of the potentiometer M2) is at a predetermined position (S118). If it is not at the predetermined position, the process returns to S117. On the other hand, if it is at the predetermined position, the operations shown in S109 to S110 of the flowchart shown on the left side of FIG. 11 are performed.
[0076] [Control Example 2]
[0077] FIG. 12 is a flowchart illustrating the flow during washing. In the flowchart shown in FIG. 12, washing is first started (S201). Specifically, the user is notified of an instruction to insert plate E (S202). Specifically, the user is instructed to insert plate E on the display unit 18 using a GUI or the like. Next, for example, if a predetermined condition (e.g., detection by a sensor to confirm insertion of plate E) is met, a button such as "Next" becomes pressable (active), and the flow proceeds to the next step (S203). On the other hand, if the predetermined condition is not met, the user is again notified of an instruction to insert plate E (S202).
[0078] Next, it is determined whether a cleaning nozzle (= closed orifice portion C3) is attached (S204). If a cleaning nozzle is not attached, an alert is notified to the user (S205). The user is then prevented from proceeding to the subsequent flow, and the display unit 18 may display a message instructing the user to check again whether anything other than the cleaning nozzle is attached, or the user may be instructed by voice notification or the like to check again. After checking again, the user then starts over from S202.
[0079] On the other hand, if a cleaning nozzle is attached, the control unit 12 receives an instruction to raise or lower the holder 11 (S206). The instruction to raise or lower the holder 11 may be switched to automatic raising or lowering, or may be initiated by a user instruction via the user interface 19. If automatic raising or lowering is used, there is a risk that the user may get their fingers caught, so it is preferable that the user issue an instruction to raise or lower the holder 11 after closing the exterior door.
[0080] Next, the control unit 12 starts raising and lowering the stage S (S207). Basically, the stage S rises, but may be stopped, lowered, or otherwise moved as necessary. Next, it is determined whether the height of the stage S (the position of the potentiometer M2) is at a predetermined position (S208). If the height is higher or lower than the predetermined position, the control unit 12 controls the holder 11 to make adjustments, and the process returns to S207. On the other hand, if the height is at the predetermined position, the control unit 12 stops raising and lowering the holder 11 (S209) and notifies each component of the particle sorting system 100 that the closed orifice C3 has been installed (S210). The completion of installation may be communicated to the user via the display unit 18 using a GUI or the like. This completes the cleaning setup, allowing the process to proceed to the next step (e.g., starting the pump).
[0081] [Control Example 3]
[0082] FIG. 13 is a flowchart illustrating the flow when sorting or washing is completed. In the flowchart shown in FIG. 13, first, sorting or washing is completed (S301). Next, the control unit 12 receives a signal to start removing the plate E (S302). Next, the control unit 12 controls the stage S to start descending (S303). Basically, the stage S descends here, but may be stopped, raised, or other operations performed as necessary. Next, the control unit 12 determines whether the stage S has reached the bottom end (S304). Specifically, whether the stage S has reached the bottom end is determined using a sensor or the like that detects the bottom end of the stage S.
[0083] If the stage S has not reached the bottom end, the process returns to S303. On the other hand, if the stage S has reached the bottom end, the user is instructed to remove the plate E via the display unit 18 using a GUI or the like (S306). Then, removal of the plate E including the orifice portion C2 or the plate E including the closed orifice portion C3 is completed (S307).
[0084] (3-6) Other embodiment 1
[0085] FIG. 26 is a schematic diagram showing an example of an embodiment (another embodiment 1) different from FIG. 1 in the vicinity of the cuvette flow path P and the orifice portion C2. FIG. 26A is a diagram illustrating the mounting state, and FIGS. 26B and 26C are diagrams illustrating the mounting procedure. FIGS. 26A and 26B are side cross-sectional views of the cuvette flow path P and the orifice portion C2. In this embodiment, the orifice portion C2 is cylindrical, and positioning is performed by the top surface and outer peripheral surface of the cylinder. Next, after positioning, the holder 11 is raised and lowered to press the top surface of the orifice portion C2 against the bottom surface of the nozzle outlet P131. When press-fitting, positioning is performed by the convex portion of the cylindrical portion and the concave portion of the nozzle outlet P131.
[0086] 26C is a bottom cross-sectional view of the cuvette flow path P and the orifice C2. Specifically, in the first stage of positioning (coarse adjustment), the cuvette flow path P is positioned in the XY directions by the arcuate portion formed in the orifice C2 and the arcuate portion of the cuvette flow path P. Then, in the second stage of positioning, the cuvette flow path P is positioned (fine adjustment) by the cylindrical portion of the orifice C2 and the cylindrical portion of the cuvette flow path P. In terms of performing positioning in two stages, Alternative Embodiment 1 is based on the same technical idea as the above-described embodiment.
[0087] (3-7) Alternative Embodiment 2 FIG. 27 is a schematic diagram showing an example of an embodiment (alternative embodiment 2) different from that shown in FIG. 1 in the vicinity of the cuvette flow path P and the orifice portion C2. FIG. 27A is a diagram illustrating the mounting state, and FIGS. 27B and 27C are diagrams illustrating the mounting procedure. FIGS. 27A and 27B show side cross-sectional views of the cuvette flow path P and the orifice portion C2. In this embodiment, positioning is performed by forming an arc surface on the orifice portion C2 and forming a flat surface on the plate E. Next, after positioning, the holder 11 is raised and lowered to press the top surface of the orifice portion C2 against the bottom surface of the nozzle outlet P131. This embodiment is a mechanism for positioning using one plane and one arc, rather than three planes.
[0088] 27C is a bottom cross-sectional view of the cuvette flow path P and the orifice C2. Specifically, in the first stage of positioning (coarse adjustment), the cuvette flow path P is positioned in the XY directions by the arcuate portion formed in the orifice C2 and the arcuate portion of the cuvette flow path P. Then, in the second stage of positioning, the cuvette flow path P is positioned (fine adjustment) by the flat portion of the plate E and the flat portion of the cuvette flow path P. In terms of performing positioning in two stages, Alternative Embodiment 2 is based on the same technical idea as the above-described embodiment.
[0089] (4) Irradiation unit 13
[0090] Fig. 14 is a schematic diagram showing another example of the first embodiment of the particle sorting system 100 according to the present technology. Note that the holder 11 is omitted in Fig. 14. Each part will be described below.
[0091] The particle sorting system 100 according to this embodiment may include an irradiation unit 13. The irradiation unit 13 irradiates a part of the main flow path P13 through which the particle-containing liquid flows with laser light. Specifically, the irradiation unit 13 irradiates the particles that are flowed through the main flow path P13 in a state of being aligned substantially in a line at the center of the three-dimensional laminar flow with laser light.
[0092] As shown in Fig. 2, the irradiation unit 13 may include one or more light sources 131. When the irradiation unit 13 includes a plurality of light sources 131, the irradiation unit 13 may be configured to combine laser beams emitted from the plurality of light sources 131 and irradiate the particles with the combined laser beam. Furthermore, the irradiation unit 13 may be configured to irradiate the particles with laser beams from the plurality of light sources 131 at different positions in the flow direction of the liquid. In the present technology, the plurality of light sources 131 may emit laser beams having the same wavelength or different wavelengths.
[0093] The type of laser light irradiated from the irradiation unit 13 is not particularly limited, and examples thereof include a semiconductor laser, an argon ion (Ar) laser, a helium-neon (He—Ne) laser, a dye laser, a krypton (Cr) laser, a solid-state laser that combines a semiconductor laser with a wavelength conversion optical element, etc. Two or more of these can also be used in combination.
[0094] 2, the irradiation unit 13 may include a light-guiding optical system 132 for guiding the laser light to a predetermined position. The light-guiding optical system may include optical components such as a beam splitter group, a mirror group, and an optical fiber. The light-guiding optical system 132 may also include a lens group for focusing the combined excitation light, such as an objective lens 1000 (see FIG. 1).
[0095] (5) Detection unit 14
[0096] The particle sorting system 100 according to this embodiment may include a detection unit 14. The detection unit 14 detects light generated by the irradiation of laser light by the above-described irradiation unit 13. Specifically, the detection unit 14 detects fluorescence and scattered light (e.g., forward scattered light, back scattered light, side scattered light, Rayleigh scattering, Mie scattering, etc.), which are light to be measured and generated from the particles by irradiating the particles with laser light.
[0097] The detection unit 14 may include at least one photodetector 141 that detects the measurement target light. The photodetector 141 may include one or more light-receiving elements and may have a light-receiving element array. Furthermore, the photodetector 141 may have one or more photodiodes, such as a photomultiplier tube (PMT), an avalanche photodiode (APD), or a multi-pixel photon counter (MPPC), as the light-receiving element. In this case, the photodetector 141 may be, for example, a PMT array in which two or more PMTs are arranged in a one-dimensional direction. Furthermore, the photodetector 141 may include an imaging element, such as a charge-coupled device (CCD) or a complementary metal-oxide-semiconductor (CMOS).
[0098] The detection unit 14 may include a signal processing unit such as an A / D converter that converts the electrical signal obtained by the photodetector 141 into optical data (digital signal). The optical data obtained by the conversion by the signal processing unit is transmitted to the above-mentioned control unit 12. Examples of the optical data include optical data including fluorescent light data, and more specifically, optical intensity data of light including fluorescent light (for example, feature amounts such as area, height, and width).
[0099] The detection unit 14 may also include a detection optical system 142 that allows light of a predetermined detection wavelength to reach a corresponding photodetector 141. The detection optical system 142 includes, for example, a spectroscopic unit such as a prism or a diffraction grating, and a wavelength separation unit such as a dichroic mirror or an optical filter.
[0100] (6) Preparation control unit 15 (charging unit 15a, deflection plate 15b, collection container 15c)
[0101] The particle sorting system 100 according to this embodiment may include a sorting control unit 15. The sorting control unit 15 includes a charging unit 15a, a deflection plate 15b, and a collection container 15c. The charging unit 15a applies an electric charge to the deflection plate 15b based on the optical data detected by the detection unit 14. Specifically, the charging unit 15a applies a charge signal to the deflection plate 15b as necessary, thereby applying a positive or negative electric charge to the desired droplets D.
[0102] The charging unit 15a may also correct the charge amount of the droplets D. Specifically, a correction voltage is applied to the charge signal, a process known as defanning. This prevents the zero-charge droplet group, i.e., the center stream, from spreading, allowing the collection container 15c to be narrower, thereby narrowing the deflection angle of the side streams. Furthermore, when sorting is performed frequently (e.g., when sorting with almost no intervening zero-charge droplets) or when charging is performed continuously in the same direction, the side streams are also affected by the charge of the droplets adjacent to the front, and defanning can be performed to prevent the side streams from splitting.
[0103] The deflection plates 15b control the direction of travel of desired droplets D based on the presence or absence of an electrical force and the magnitude of the force, and guide the droplets D to a predetermined collection container 15c. Specifically, the deflection plates 15b deflect the direction of travel of each droplet D in the fluid stream by an electrical force acting between the droplets D and the positive or negative charge applied thereto, and guide the droplets D to a predetermined collection container 15c. As shown in FIG. 2, the deflection plates 15b are arranged opposite each other across the fluid stream. There are no particular limitations on the deflection plates 15b, and conventionally known electrodes can be used. Different positive or negative voltages are applied to the deflection plates 15b, and when the charged droplets D pass through the electric field formed thereby, an electrical force (Coulomb force) is generated, and each droplet D is attracted toward one of the deflection plates 15b.
[0104] A plurality of collection containers 15c may be arranged in a substantially straight line in the opposing direction of the deflection plate 15b. The collection containers 15c are not particularly limited, and examples thereof include plastic tubes and glass tubes. The number of collection containers 15c is not particularly limited in the present technology. The collection containers 15c may be replaceably installed in a collection container container (not shown). Specifically, the collection containers 15c are arranged on a Z-axis stage (not shown) configured to be movable in a direction perpendicular to the discharge direction of the droplets D from the orifice portion C2 and the opposing direction of the deflection plate 15b.
[0105] (7) Imaging unit 20
[0106] The particle sorting system 100 according to this embodiment may include an imaging unit 20. The imaging unit 20 captures images of the liquid before it is broken into droplets and the droplets D in the BOP. Examples of the imaging unit 20 include a droplet camera such as a CCD camera or a CMOS sensor. The droplet camera 201 may be disposed between the orifice C2 and the deflection plate 15b at a position where it can capture an image of the droplets D. The droplet camera 201 may also adjust the focus of the captured image of the droplets D. Examples of the light source 202 that illuminates the image capture area in the droplet camera 201 include a strobe. The imaging unit 20 can also capture a phase image at a certain time, and can also capture the images continuously within a fixed period. The term "fixed period" as used herein is not particularly limited and may refer to one period or multiple periods. In the case of multiple periods, the periods may be continuous or discontinuous in time.
[0107] The image captured by the imaging unit 20 is displayed on the display unit 18 described later and can be used by the user to check the formation status of the droplets D (e.g., the size, shape, spacing, etc. of the droplets D). The strobe may be controlled by a break-off control unit described later, the control unit 12 described above, or the like. The strobe is composed of, for example, an LED for capturing images of the droplets D and a laser (e.g., a red laser light source) for capturing images of the particles, and can be switched by the break-off control unit described later depending on the purpose of capturing the images, etc. The specific structure of the strobe is not particularly limited, and for example, conventionally known circuits and / or elements can be used.
[0108] (8) Break-off control section
[0109] The particle sorting system 100 according to this embodiment may also have a breakoff control unit (not shown). The breakoff control unit controls the breakoff of the droplet D containing the target particle based on an image of the state of the droplet D containing the particle acquired by the imaging unit 20 described above. This control can be performed by the control unit 12 described above. Specifically, the drive voltage of the vibration element is adjusted based on the timing at which the droplet D containing the particle breaks off, as determined from multiple droplet observation images captured by the imaging unit 20, to control the coupling state between the droplet D and the liquid column and / or the distance between the droplet D and the liquid column, as well as the breakoff position of the droplet D, so as to maintain constant. This allows the droplet D to be adjusted by constantly applying feedback to the drive voltage, thereby preventing the droplet D from becoming unstable after sorting begins.
[0110] (9) Storage section 17
[0111] The particle sorting system 100 according to this embodiment may include a memory unit 17. The memory unit 17 stores various items, such as optical data detected by the detection unit 14, feature quantities of each particle calculated by the control unit 12, a sorting control signal generated, and sorting conditions input via the user interface 19. The memory unit 17 may be included in a housing in which the detection unit 14 and other components are provided, or may be located outside the housing. The memory unit 17 is not essential for the particle sorting system 100 according to this embodiment, and an external storage device (e.g., a hard disk) may be used. Alternatively, a configuration may be adopted in which the housing in which the detection unit 14 and other components are provided is connected to a network wirelessly or wired, thereby storing data on a server or cloud. Furthermore, the memory unit 17 may be connected to each component of the particle sorting system 100 via a network wirelessly or wired.
[0112] (10) Display section 18
[0113] The particle sorting system 100 according to this embodiment may have a display unit 18. The display unit 18 can display various items, for example, the feature quantities of each particle calculated by the control unit 12 as a histogram or the like. It may also display images captured by the imaging unit 20. The display unit 18 is not essential to the particle sorting system 100 according to this embodiment, and an external display device (e.g., a display, a monitor, a printer, a personal digital assistant, etc.) may be used. Furthermore, the display unit 18 may be connected to each component of the particle sorting system 100 via a network, either wirelessly or via a wire.
[0114] The display unit 18 may be, for example, a smart speaker, earphones, headphones, VR or AR goggles, smart glasses, a projector, etc., and these may be used in conjunction with the above-mentioned external display device or the display unit 18 within the housing.
[0115] (11) User Interface 19
[0116] The particle sorting system 100 according to this embodiment may have a user interface 19. The user interface 19 is a component for user operation. The user can input various data via the user interface 19, access each component of the particle sorting system 100, and control each component. Specifically, the user can set a region of interest for a histogram or the like displayed on the display unit 18 and determine sorting conditions, etc. via the user interface 19. The user interface 19 is not essential for the particle sorting system 100 according to this embodiment, and an external operating device (e.g., a mouse, keyboard, buttons, a touch panel, a personal digital assistant, etc.) may also be used. Furthermore, the user interface 19 may be connected to each component of the particle sorting system 100 via a network, either wired or wirelessly.
[0117] In addition, the user interface 19 may be, for example, a smart speaker, VR or AR goggles, smart glasses, etc., and may be used in conjunction with the above-mentioned external operating device or the user interface 19 within the housing.
[0118] (12) Other
[0119] The functions performed by each part of the particle sorting system 100 according to this embodiment can be stored as a program in a general-purpose computer, a control unit including a CPU, and hardware resources including a recording medium (e.g., non-volatile memory (e.g., USB memory), HDD, CD, etc.), and can be made to function. The functions can also be realized by a server or cloud connected via a network.
[0120] 2. Second embodiment (orifice part C)
[0121] 15 to 17 are six-sided views showing an example of a second embodiment of the orifice component C according to the present technology, and Fig. 18 and Fig. 19 are perspective views showing an example of the second embodiment of the orifice component C according to the present technology. Fig. 20 is a cross-sectional view taken along line P-P in A of Fig. 15. The orifice component C according to this embodiment has a base member C1 and an orifice portion C2 through which a liquid containing particles flows, and may have other portions, etc., as necessary.
[0122] FIG. 21 is a partially enlarged view illustrating the mounting and removal of the orifice part C from the plate E. As shown in FIG. 21, the orifice part C according to this embodiment can be removed from the plate E, and the orifice part C can be disposed of as a single unit. This meets the demands of cell sorters, such as changing the shape of the orifice depending on the particle size and replacing the orifice in response to clogging, etc. This also contributes to preventing contamination and improving usability. Additionally, since only the miniaturized orifice part C needs to be disposed of, it also contributes to reducing manufacturing costs. Each part will be described below.
[0123] (1) Base member C1
[0124] An orifice portion C2 is formed at one end of the base member C1, and as shown in Figures 15 to 17, the orifice portion C2 is formed so as to extend in a substantially vertical direction relative to the base member C1, with the base member C1 being substantially horizontal.
[0125] The base member C1 and the orifice portion C2 may be formed as separate members and then integrated, or may be integrally molded. In this embodiment, however, they are preferably integrally molded to improve manufacturing efficiency. If integrally molded, the base member C1 and the orifice portion C2 are preferably formed from resin. If they are formed as separate members, for example, at least the top surface of the orifice portion C2 may be formed from a material with a high Young's modulus, such as ceramic, and the rest may be formed from the resin.
[0126] Preferred resins include general-purpose plastics such as polyethylene (PE), polypropylene (PP), polystyrene (PS), polyvinyl chloride (PVC), ABS resin, and polymethyl methacrylate (PMMA); engineering plastics such as polycarbonate (PC), polyacetal (POM), and modified polyphenylene ether (PPE); and optical plastics such as cycloolefin polymer (COP) and cyclic olefin copolymer (COC). The use of these resins improves the moldability of the water-stopping mechanism C4 (described below) and enables it to be crushed at a desired pressure (e.g., 10 to 30 N). These resins may also contain various powders of carbon, metal, or the like, or various fibers.
[0127] Furthermore, even if the orifice part C2 is an orifice part C formed with a water-stopping mechanism C4 described below, by integrally molding it with a resin that will collapse under a desired pressure, that is, that will undergo plastic deformation due to the pressing force when attaching the orifice part C2, the water-stopping shape will be destroyed after one use, and the orifice part C can be distributed as a disposable product. The "water-stopping mechanism C4" and "water-stopping shape" will be described below in "(4) Water-stopping mechanism C4".
[0128] (2) Orifice portion C2
[0129] As shown in Fig. 20 , the orifice portion C2 has an orifice flow path C21 formed therein. Liquid is discharged to the outside through the orifice flow path C21. The shape of the orifice portion C2 is not particularly limited as long as the orifice flow path C21 is formed therein and extends in a direction substantially perpendicular to the base member C1, but as described above, it is preferable that the orifice portion C2 has a tapered shape C22 in part. Specifically, as shown in Fig. 20 and other figures, it is preferable that the tapered shape C22 is continuously formed in a substantially annular shape so as to surround the connection portion (the connecting surface in Fig. 20 and other figures) with the cuvette flow path P through which the liquid containing particles flows.
[0130] As described above, the orifice portion C2 is preferably movable in at least one direction consisting of a direction substantially parallel to the discharge axis, a direction substantially perpendicular to the discharge axis, and a direction substantially rotating relative to the discharge axis. This allows the orifice portion C2 to move to compensate for any slight misalignment that may occur when the nozzle outlet P131 is mated with the nozzle outlet P131, and coupled with the tapered shape C22, allows for smooth positioning (mating) without damaging the components.
[0131] (3) Water stop mechanism C4
[0132] The orifice part C according to this embodiment may further include a water-stopping mechanism C4 that prevents leakage of the liquid containing particles from the connection between the cuvette flow path P through which the liquid flows and the orifice part C2.
[0133] In the past, if the O-ring did not fit properly into the orifice fitting when replacing the orifice, the watertight function could not be maintained, resulting in leakage inside the device. Therefore, every time the orifice was replaced or installed, the user had to check, using a microscope or similar device, for scratches or foreign objects in the O-ring, which can be as small as 1 mm in diameter. If foreign objects were found, they had to be removed with tweezers without damaging the O-ring, subjected to ultrasonic cleaning, and then reattached while checking under a microscope or similar device. Furthermore, depending on the size of the particles, the orifice had to be removed and reattached.
[0134] However, due to the device's configuration, liquid containing particles flows from the cuvette flow path in the direction of gravity, so a water-stop mechanism is required between the cuvette flow path and the orifice. Therefore, the use of an O-ring was essential in conventional technology. Despite this, there were cases where the O-ring came off or remained in the cuvette during use, resulting in poor usability in conventional technology. On the other hand, there are also types in which the orifice and O-ring are bonded with resin or other adhesive, but repeated cleaning reduces the adhesive's ability to adhere, eventually causing the O-ring to come off. For these reasons, orifice replacement has been a very time-consuming process for users.
[0135] In contrast, by using the water-stopping mechanism C4 in this embodiment, it is possible to provide an orifice structure that prevents liquid leakage from the connection part and allows stable droplet formation for a long period of time even under specified conditions such as a constant pressure, and it is also possible to reduce the effort required for users to replace the orifice.
[0136] The water-stopping mechanism C4 is preferably formed in a part of the orifice portion C2. The water-stopping mechanism C4 formed in a part of the orifice portion C2 may be an O-ring as long as it can perform the water-stopping function, but in this case, it is preferable that the O-ring is fixed to a part of the orifice portion C2 in advance. This saves the user the trouble of attaching the O-ring. Furthermore, as will be described later, it may be an integrally molded "water-stopping shape." The water-stopping shape will be described later.
[0137] The water-stopping mechanism C4 is preferably formed on the connecting surface of the orifice C2 with the cuvette flow path P. Specifically, it is preferably formed on the top surface of the orifice C2. This allows the orifice C2 and the cuvette flow path P to be pressed together by the pressure caused by the rising of the holding part 11, eliminating the need for the user to perform the work themselves and avoiding complication of the work.
[0138] The water-stopping mechanism C4 is preferably formed on the connecting surface and is based on a shape integrally molded with the orifice portion C2. Specifically, an integrally molded water-stopping shape can be used. This is expected to have the following advantages: The user does not need to check the connection status of the orifice portion C2 and the O-ring using a microscope or the like every time. It also eliminates the need for the O-ring to be cleaned (removed with tweezers, cleaned, and reattached). Furthermore, by making the orifice portion C2 with the water-stopping shape disposable, the orifice can be replaced without worrying about scratches, foreign matter, or adhesion between the orifice and the O-ring. Therefore, an orifice replacement mechanism can be provided that significantly shortens and improves the user's work process for orifice replacement (improving ease of use).
[0139] FIG. 28 is a diagram illustrating the water-stopping shape. FIG. 28A is a perspective view showing an example of an embodiment of the orifice portion C2, FIG. 28B is a perspective cross-sectional view of FIG. 28A, and FIG. 28C is a cross-sectional view of FIG. 28A. In this way, the orifice portion C2 has a water-stopping shape on the connection surface with the cuvette. By making the water-stopping shape fine enough to deform when the orifice portion C2 is crimped to the cuvette flow path P, an O-ring is no longer required to stop water from entering the orifice, eliminating the disadvantages of using an O-ring. Disadvantages of using an O-ring include the possibility that the O-ring may come off and be left behind when the orifice is removed, leading to equipment malfunctions; the O-ring may bend inside the cuvette, causing deterioration in droplet performance; and small O-rings (e.g., those with a diameter of approximately 1 mm) are difficult to assemble, resulting in increased parts costs.
[0140] The water-stopping shape may be a substantially circular convex shape as shown in Fig. 28, or may be a substantially elliptical convex shape or a polygonal convex shape such as a triangle or a square. Also, it does not necessarily have to be a continuous shape, and may be partially discontinuous or entirely discontinuous (for example, a collection of convex portions arranged in a substantially circular ring shape). In this embodiment, a substantially circular convex shape as shown in Fig. 28 is preferable.
[0141] Fig. 29A is a partial enlarged view of the water-stopping shape when the water-stopping shape is a substantially annular convex shape, and Fig. 29B is a partial enlarged view of Fig. 29A. In Fig. 29A, L1 is the seal diameter, which is the central diameter of the circumference that is crushed by water-stopping, and is determined according to the diameter of the orifice portion C2. Specifically, when the diameter of the orifice portion C2 is 2.79 mm, the seal diameter is preferably 0.7 to 2.0 mm, and the outer diameter ratio is preferably about 0.2 to 0.7, although the present technology is not limited to these.
[0142] In Figure 29B, L3 is the seal base width, which is the width of the base of the seal. The larger the width, the smaller the gap when crushed, improving droplet performance. On the other hand, the smaller the width, the easier it is to crush, improving water-stopping robustness. The seal base width is determined according to the seal diameter L1. Specifically, when the seal diameter is 0.8 mm, the seal diameter ratio is preferably 0.01 to 0.5, and more preferably 0.05 to 0.1, but the present technology is not limited to these values.
[0143] 29A, L2 is the diameter of the trapezoidal portion, which is the diameter of the surface that is closest to the cuvette flow path P. The larger the trapezoidal portion diameter, the closer it is to the water-stopping portion, and the smaller the gap when crushed, improving droplet performance. The trapezoidal portion diameter is determined according to the seal diameter L1. Specifically, when the seal diameter is 0.8 mm, the seal diameter ratio is preferably 0.5 to 0.15, and more preferably 0.75 to 0.95, but the present technology is not limited to these.
[0144] FIG. 30 is a diagram illustrating the gap between the orifice portion C2 and the cuvette flow path P. The inventors of the present application discovered that a deformed shape for water blocking may be additionally provided on the connecting surface to ensure droplet performance. Specifically, the gap between the orifice portion C2 and the cuvette flow path P was reduced. More specifically, in general water blocking using tapered portion deformation, the gap is on the order of several millimeters, but this is designed to be on the order of several microns. It has been confirmed that the gap between the orifice portion C2 and the cuvette flow path P affects droplet performance.
[0145] 31 is a diagram illustrating the taper angle difference between the cuvette flow path P and the orifice C2. The taper angle difference is the taper difference between the cuvette flow path P into which the orifice C2 enters and the orifice C2. This difference causes the tapered portion of the orifice C2 to collapse and stop water from passing through, so it is preferable that the taper angle difference be within a predetermined range. Specifically, the taper angle difference is preferably 3 to 12 degrees, and more preferably 6 to 9 degrees, but is not limited to these in the present technology.
[0146] (4) Closed orifice section C3
[0147] The closed orifice portion C3 is the same as that described in "(3-2) Replacing the plate E including the orifice portion C2" and "(3-3) Cleaning using the plate E including the closed orifice portion C3" in "1. First embodiment (particle sorting system 100)." That is, it is used to clean the inside of the cuvette flow path P. Furthermore, an example of control by the control unit 12 using the closed orifice portion C3 is the same as that described in "Control Example 2" in "(3-5) Example of control by the control unit 12" in "1. First embodiment (particle sorting system 100)," and therefore will not be described here.
[0148] FIG. 32 is a diagram illustrating the stop valve structure C6 in the closed orifice portion C3. In the above-described "Control Example 2," cleaning liquid, pure water, and the like flow from the cuvette flow path P. To prevent these liquids from entering unintended locations, the closed orifice portion C3 preferably includes a stop valve structure C6. Specifically, as shown in FIGS. 32A and 32B, the stop valve structure C6 may be implemented by placing an O-ring at the base of the closed orifice portion C3. Furthermore, the shape of the base of the closed orifice portion C3 may center the closed orifice portion C3 in the reaction force direction of the O-ring.
[0149] Also, as shown in Fig. 32B, two stop valve structures C6 may be provided. On the other hand, as shown in Fig. 32C, if the O-ring is formed too large, the O-ring will hit the bottom surface of the cuvette flow path P, making centering impossible. Therefore, it is preferable to set the diameter of the O-ring so that it does not hit the bottom surface of the cuvette flow path P. Specifically, it is preferable to use the stop valve structure C6 shown in Fig. 32A and B.
[0150] Fig. 40A is a perspective view showing the embodiment of the closed orifice portion C3 shown in Fig. 32, and Fig. 40B is a perspective view showing a modified example of the embodiment of the closed orifice portion C3 different from Fig. 32. Note that Figs. 40A and 40B omit the stop valve structure C6.
[0151] In A of Fig. 40, the top surface is flat, whereas the closed orifice section C3 shown in B of Fig. 40 has two concave shapes C32 on the top surface. By shifting the position and shape of the top surface of the closed orifice section C3 from line symmetry in this way, the water flow that hits the top surface of the closed orifice section C3 is divided into upward and horizontal directions, eliminating the circulation area and generating a circumferential flow, which is expected to improve the cleaning effect. Note that in the embodiment shown in B of Fig. 40, the top surface of the closed orifice section C3 has two concave shapes C32, but the present technology is not limited to this and may have, for example, a plurality of concave or convex shapes, an S-shaped groove, or the like.
[0152] Furthermore, in the embodiment shown in Fig. 40B, the closed orifice portion C3 shown in Fig. 40A has two drainage holes C33, whereas the embodiment shown in Fig. 40B has four drainage holes C33. This can promote drainage more than when there are two drainage holes C33.
[0153] 33 to 35 are six-sided views showing a modified example of the second embodiment of the orifice component C according to the present technology, and Fig. 36 and Fig. 37 are perspective views showing a modified example of the second embodiment of the orifice component C according to the present technology. Fig. 38 is a cross-sectional view taken along line QQ in A in Fig. 33. The outer wall of the orifice portion C2 of the orifice component C according to the present technology can be provided with a positioning mechanism C23 for determining the position of the orifice channel C21 relative to the cuvette channel P of the particle sorting system 100.
[0154] If the orifice channel C21 is inclined relative to the cuvette channel P of the particle sorting system 100, there is a concern that the particle sorting accuracy may decrease. Therefore, it is desirable that the cuvette channel P and the orifice channel C21 of the particle sorting system 100 are positioned coaxially. In this technology, by providing a positioning mechanism C23 on the outer wall of the orifice section C2, it is possible to prevent the orifice channel C21 from being inclined relative to the cuvette channel P of the particle sorting system 100, and further improve the particle sorting accuracy.
[0155] The shape of the positioning mechanism C23 is not particularly limited, and any shape can be adopted as long as it can coaxially position the cuvette channel P and the orifice channel C21 of the particle sorting system 100. For example, as in the modified example of the second embodiment shown in Figures 33 to 37, the outer wall of the orifice section C2 is provided with a convex rib structure that is approximately parallel to the orifice channel C21, and, for example, although not shown, a concave rib structure is provided on the inner wall of a recess formed in the nozzle outlet P131 of the particle sorting system 100 (see Figures 3 and 4, etc.), and these rib structures are fitted together, thereby allowing the cuvette channel P and the orifice channel C21 of the particle sorting system 100 to be positioned coaxially. Note that, although not shown, the rib structure provided on the outer wall of the orifice section C2 can also be concave, and a convex rib structure can be provided on the inner wall of the recess formed in the nozzle outlet P131 of the particle sorting system 100, and fitted together.
[0156] 33 to 37, the outer wall of the orifice portion C2 is provided with a positioning mechanism C23 having a four-rib structure, but the number of ribs is not limited, and a positioning mechanism C23 having one or more rib structures can be used. From the viewpoint of preventing tilting, two or more ribs are preferable, and three or more ribs are more preferable. Furthermore, from the viewpoint of ease of manufacturing the orifice part C, eight or less ribs are preferable, seven or less ribs are more preferable, and six or less ribs are even more preferable.
[0157] When the orifice portion C2 described above has a tapered shape C22, it is preferable to provide the positioning mechanism C23 closer to the base member C1 than the tapered shape C22. In other words, it is preferable not to provide the positioning mechanism C23 in the tapered shape C22 portion. With this configuration, the tapered shape C22 allows for smooth retraction into the recess formed in the nozzle outlet P131, and after retraction, the positioning mechanism C23 can accurately position the cuvette channel P and the orifice channel C21 of the particle sorting system 100 coaxially.
[0158] 33 to 37, the outer wall of the orifice portion C2 is provided with a positioning mechanism C23 having a rib structure that continues from below the tapered shape C22 to the base member C1, but the positioning mechanism C23 does not necessarily have to be a continuous shape and may be partially discontinuous. Furthermore, the positioning mechanism C23 does not necessarily have to extend from below the tapered shape C22 to the base member C1, and although not shown, it may be discontinued at, for example, 1 / 3 or 1 / 2 of the height from the base member C1.
[0159] (6) Tilt Control Mechanism C24 A tilt control mechanism C24 can be provided on the top surface (connection surface on the nozzle outlet P131 side of the particle sorting system 100) of the orifice portion C2 of the orifice component C according to the present technology. After the orifice component C is installed in the particle sorting system 100, the aforementioned water stop mechanism C4 can prevent liquid leakage from the connection portion between the cuvette channel P and the orifice portion C2. However, if the orifice component C itself is tilted, the aforementioned water stop mechanism C4 may not be able to prevent liquid leakage. Therefore, in the present technology, by providing the tilt control mechanism C24 on the top surface (connection surface on the nozzle outlet P131 side of the particle sorting system 100) of the orifice portion C2, it is possible to more reliably prevent liquid leakage from the connection portion between the cuvette channel P and the orifice portion C2.
[0160] The shape of the tilt control mechanism C24 is not particularly limited, and any shape can be adopted as long as it can control the tilt after the orifice part C is installed in the particle sorting system 100. For example, as in the modified example of the second embodiment shown in Figures 33 to 38, the top surface of the orifice part C2 (the connection surface on the nozzle outlet P131 side of the particle sorting system 100) can have a substantially circular convex shape that contacts the inner bottom surface of the recess formed in the nozzle outlet P131 of the particle sorting system 100. Alternatively, it may have a substantially elliptical convex shape or a polygonal convex shape such as a triangle or a square. Furthermore, it does not necessarily have to be a continuous shape, and may be partially discontinuous or entirely discontinuous (for example, a collection of convex parts arranged in a substantially circular ring shape).
[0161] 3. Third embodiment (Plate E)
[0162] As described above, Fig. 21 is a partially enlarged view illustrating the state in which the orifice part C is attached to or detached from the plate E, and Fig. 22 is a partially enlarged view illustrating the state in which the plate E is fitted to the orifice part C. Fig. 23 is a perspective view showing an example of an embodiment of the plate E and the orifice part C, and Fig. 24 is a view illustrating the state when the orifice part C is replaced. The plate E according to this embodiment can be fitted to the orifice part C described above, and may have other parts, etc., as necessary. Each part will be described below.
[0163] As described above, the orifice part C can be detached from the plate E as shown in FIGS. 21 and 22, and once fitted, the orifice part C can be disposable, while the plate E according to this embodiment can be reused.
[0164] Figure 24 is a diagram illustrating the state when replacing the orifice part C. As described above, the orifice part C is disposable on its own, and therefore can be supplied and distributed in units of orifice part C. Furthermore, as shown in Figure 24B, after replacement, the orifice part C2 is provided with a retractable backlash for two-stage lifting and lowering, thereby enabling the above-mentioned two-stage positioning. This allows the orifice part C to be made smaller.
[0165] In addition, in the present technology, not only the orifice part C alone but also the plate E alone or the orifice part C and the plate E fitted together may be distributed.
[0166] Examples of materials for forming the plate E include resins. Examples of resins include, but are not limited to, cyclic olefins, polycarbonates, polymethyl methacrylate resins (PMMA), polyethylene, polystyrene, polypropylene, and polydimethylsiloxane (PDMS). Furthermore, various powders of carbon, metals, and the like, and various fibers may be added to these resins.
[0167] When fitting the orifice part C to the plate E, it is preferable to insert the orifice part C in the longitudinal direction of the plate E (the longitudinal direction of the main body E3 of the plate E: see FIG. 23) to fit the orifice part C. This makes it easier for the user to fit the orifice part C, improving usability.
[0168] The orifice part C and the plate E can be fitted together, for example, by using a pressing part E1 that presses the orifice part C against the plate E and a fixing part E2 that fixes the orifice part C. Specifically, the orifice part C is first inserted between the pressing part E1 and the plate E (see FIG. 21). Next, after the insertion, the orifice part C is fixed to the plate E by using the fixing part E2 to fix the orifice part C inserted between the pressing part E1 and the plate E.
[0169] Examples of materials for forming the pressing portion E1 and the fixing portion E2 include, but are not limited to, stainless steel alloy, titanium alloy, and metallic glass. FIG. 25 is a diagram illustrating the orifice part C and the plate E in detail. In the embodiment shown in FIG. 25 , the pressing portion E1, which presses the disposable orifice part C, is formed of, for example, a wire-cut stainless steel alloy, and the main body E3 is formed of the resin described above. The fixing portion E2 is designed so that the user can disassemble it for cleaning when stubborn salting or other deposits accumulate. Meanwhile, minor salting or other deposits can be removed by ultrasonic cleaning without disassembly.
[0170] FIG. 25B shows the mating portion between the orifice part C and the plate E as viewed from the back. The a in FIG. 25B is the first contact surface where the orifice part C and the plate E come into contact. The b in FIG. 25B shows the shape where the orifice part C snaps into the plate E. The c in FIG. 25B is the gap between the outer shapes that sets the amount of play required for the orifice part C2. Additionally, the d in FIG. 25B is the second contact surface where the orifice part C and the plate E come into contact. The moment can be absorbed by the deflection of the plate E.
[0171] 25B indicates a portion that functions as a latch. Also, 25Bf indicates a portion of the fixing portion E2 formed of a stainless steel alloy or the like, as viewed from the back side. For example, an E-type retaining ring (E-ring) can be used, but the present technology is not limited to this. An E-type retaining ring is a ring-shaped retaining ring that has a circumferential groove cut into the discharge shaft and is inserted from the radial direction (i.e., a direction at 90 degrees relative to the discharge shaft) to secure the retaining component.
[0172] 21 to 25, the plate E and the orifice part C are fitted together via the pressing part E1 and the fixing part E2, but the method of fitting the plate E and the orifice part C is not limited to this, and for example, as in the modified example shown in Fig. 39, a structure in which the orifice part C is directly fitted to the main body E3 of the plate E may be used. By using a structure in which the orifice part C is directly fitted to the main body E3 of the plate E, the number of parts can be reduced, which not only simplifies the manufacture of the orifice part C but also contributes to cost reduction.
[0173] The present technology can also employ the following configurations. [1] A particle sorting system comprising: a cuvette flow path through which a liquid containing particles flows; a holder for holding a plate including an orifice portion for ejecting the liquid; and a control unit for controlling the holder to change its position substantially parallel to an ejection axis, wherein the cuvette flow path and the plate can be positioned based on their respective shapes. [2] The particle sorting system according to [1], wherein the orifice portion is detachable from the plate. [3] The particle sorting system according to [1] or [2], wherein the orifice portion is disposable. [4] The particle sorting system according to any one of [1] to [3], wherein the orifice portion has a tapered portion in part. [5] The particle sorting system according to any one of [1] to [4], wherein the orifice portion is movable in at least one direction consisting of a substantially parallel direction, a substantially perpendicular direction, and a substantially rotational direction relative to the ejection axis. [6] The particle sorting system according to any one of [1] to [5], wherein the orifice unit further has a water stop mechanism that prevents leakage of the liquid containing the particles from a connection between the orifice unit and a cuvette flow path through which the liquid flows. [7] The particle sorting system according to [6], wherein the water stop mechanism is formed in a part of the orifice unit. [8] The particle sorting system according to [7], wherein the water stop mechanism is formed on a connection surface of the orifice unit with the cuvette. [9] The particle sorting system according to [8], wherein the water stop mechanism is formed on the connection surface and is based on a shape that is integrally molded with the orifice unit.
[10] The particle sorting system according to any one of [1] to [9], wherein the control unit controls the positioning of the cuvette flow path and the plate in multiple stages.
[11] The particle sorting system according to any one of [1] to
[10] , wherein the positioning is based on engagement between a positioning pin provided on the cuvette flow path and an engagement portion of the plate.
[12] The particle sorting system according to
[11] , wherein the positioning is based on a fitting between a lower end of the cuvette channel and an upper end of the orifice portion.
[13] The particle sorting system according to
[12] , wherein the fitting is based on a concave-convex shape.
[14] The particle sorting system according to any one of [1] to
[13] , wherein the plate including the orifice portion is replaceable with a plate including a closed orifice portion that cleans the inside of the cuvette flow path.
[15] The particle sorting system according to any one of [1] to
[14] , wherein the control unit receives a signal from a plate presence / absence sensor and determines whether the plate is present or absent.
[16] The particle sorting system according to any one of [1] to
[15] , wherein the control unit receives a signal from a washing nozzle sensor and determines whether the nozzle is a washing nozzle, and if it determines that the nozzle is a washing nozzle, controls to clean the inside of the cuvette flow path.
[17] The particle sorting system according to
[16] , wherein the determination is made based on a part of the shape of the plate.
[18] The particle sorting system according to
[12] , wherein the control unit controls to suck the orifice portion toward the cuvette flow path in response to the lifting of the holder.
[19] The particle sorting system according to
[14] , wherein the control unit controls the plate including the orifice unit or the plate including the closed orifice unit to be in a removable state when it is determined that the holder has reached the lower end.
[20] The particle sorting system according to
[14] , wherein the control unit changes the upward pressure on the discharge axis of the holder when the orifice unit or the closed orifice unit abuts against the cuvette flow path.
[21] An orifice component comprising: a base member; and an orifice unit through which a liquid containing particles flows, the orifice unit being formed at one end of the base member and extending in a direction approximately perpendicular to the base member.
[22] The orifice component according to
[21] , which is disposable.
[23] The orifice component according to
[21] or
[22] , wherein the orifice unit has a tapered shape in part.
[24] The orifice part according to any one of
[21] to
[23] , wherein the orifice part is movable in at least one direction of a group consisting of a substantially parallel direction, a substantially perpendicular direction, and a substantially rotational direction with respect to the discharge axis.
[25] The orifice part according to any one of
[21] to
[24] , wherein the base member and the orifice part are integrally molded.
[26] The orifice component according to any one of
[21] to
[25] , further comprising a water-stopping mechanism for preventing leakage of a particle-containing liquid from a connection between the orifice and a cuvette flow path through which the liquid flows.
[27] The orifice component according to
[26] , wherein the water-stopping mechanism is formed in a part of the orifice.
[28] The orifice component according to
[27] , wherein the water-stopping mechanism is formed on a connection surface of the orifice component with the cuvette flow path.
[29] The orifice component according to
[28] , wherein the water-stopping mechanism is formed on the connection surface and is based on a shape integrally molded with the orifice component.
[30] A plate comprising a base member and an orifice component through which a particle-containing liquid flows, the orifice component being formed on one end of the base member and extending in a direction substantially perpendicular to the base member, and being engageable with the orifice component.
[31] The plate according to
[30] , which is inserted in the longitudinal direction of the plate and the orifice part is fitted in place.
[32] The plate according to
[31] , which has a pressing part that presses the orifice part against the plate and a fixing part that fixes the orifice part.
[33] The plate according to
[32] , which is inserted between the pressing part and the plate.
[34] The plate according to
[33] , which, after the insertion, is fixed to the orifice part by the fixing part.
[0174] 100: Particle sorting system 11: Holder 12: Controller 13: Irradiation unit 14: Detector 15: Sorting controller 15a: Charging unit 15b: Deflection plate 15c: Collection container 16: Sensor 17: Memory unit 18: Display unit 19: User interface 20: Imaging unit 201: Droplet camera 202: Light source 1000: Objective lens P: Cuvette flow path P11: Sample liquid injection port P12a, P12b: Sheath liquid injection port P13: Main flow path P131: Nozzle outlet P4: Cuvette holder P41: Positioning pin D: Droplet BOP: Break-off point C: Orifice part C1: Base member C2: Orifice part C22: Tapered shape C23: Positioning mechanism C24: Tilt control mechanism C3: Closed orifice part C31: Closed nozzle C32: Concave shape C33: Drain hole C4: Water stop mechanism C6: Water stop valve structure E: Plate E1: Pressing part E2: Fixing part E3: (Plate) main body E4: Engagement part E5: Notch part S: Stage
Claims
1. A particle sorting system comprising: a cuvette flow path through which a liquid containing particles flows; a holder that holds a plate including an orifice portion that ejects the liquid; and a control unit that controls the position of the holder to change approximately parallel to an ejection axis, wherein the cuvette flow path and the plate can be positioned based on their respective shapes.
2. The particle sorting system according to claim 1, wherein the orifice portion is detachable from the plate.
3. The particle sorting system according to claim 1, wherein the orifice portion is disposable.
4. The particle sorting system according to claim 1, wherein the orifice portion has a tapered portion.
5. The particle sorting system according to claim 1, wherein the orifice portion is movable in at least one of the group consisting of a substantially parallel direction, a substantially perpendicular direction, and a substantially rotational direction relative to the discharge axis.
6. A particle sorting system as described in claim 1, wherein the orifice portion further has a water-stopping mechanism for preventing leakage of the liquid containing the particles from a connection between the orifice portion and a cuvette flow path through which the liquid flows.
7. The particle sorting system according to claim 6, wherein the water-stopping mechanism is formed in a part of the orifice portion.
8. The particle sorting system according to claim 1, wherein the control unit controls the positioning of the cuvette flow path and the plate in multiple stages.
9. A particle sorting system as described in claim 1, wherein the positioning is based on engagement between a positioning pin provided on the cuvette flow path side and an engagement portion of the plate.
10. The particle sorting system of claim 1, wherein the positioning is based on the engagement of a lower end of the cuvette flow channel with an upper end of the orifice portion.
11. The particle sorting system of claim 10, wherein the interlocking is based on a concave-convex shape.
12. The particle sorting system according to claim 1, wherein the plate including the orifice portion is replaceable with a plate including a closed orifice portion that performs cleaning inside the cuvette flow path.
13. The particle sorting system according to claim 1, wherein the control unit receives a signal from a plate presence / absence sensor and determines whether the plate is present or not.
14. The particle sorting system of claim 1, wherein the control unit receives a signal from a cleaning nozzle sensor, determines whether it is a cleaning nozzle, and if it determines that it is a cleaning nozzle, controls to clean the inside of the cuvette flow path.
15. The particle sorting system of claim 14, wherein the discrimination is based in part on a shape of the plate.
16. The particle sorting system according to claim 1, wherein the control unit controls the orifice unit to suck the liquid toward the cuvette flow path in response to the lifting of the holding unit.
17. A particle sorting system as described in claim 12, wherein the control unit controls the plate including the orifice portion or the plate including the closed orifice portion to be in a removable state when it determines that the holding portion has reached the lower end.
18. A particle sorting system as described in claim 12, wherein the control unit changes the upward pressure in the ejection axis of the holding unit when the orifice unit or the closed orifice unit abuts against the cuvette flow path.
19. An orifice component comprising: a base member; and an orifice portion through which a liquid containing particles flows, the orifice portion being formed at one end of the base member and extending in a direction approximately perpendicular to the base member.
20. A plate comprising a base member and an orifice portion through which a liquid containing particles flows, the orifice portion being engageable with an orifice part formed at one end of the base member and extending in a direction approximately perpendicular to the base member.
Citation Information
Patent Citations
High-speed flow cytometer droplet formation system
JP1998507524A
Flow cytometer and cell sorter
JP2011232033A
Nozzle, carrier, nozzle assembly, and sample processor
WO2022156791A1
Cited By
Orifice part for flow cytometer
USD1097840S