EP-3913352-B1 - MICROPARTICLE ISOLATION DEVICE, MICROPARTICLE ISOLATION SYSTEM, DROPLET ISOLATION DEVICE, DROPLET CONTROL DEVICE, AND DROPLET CONTROL PROGRAM

Inventors

• OTSUKA, Fumitaka

Dates

Publication Date

20260506

Application Date

20191205

Claims (5)

1. A microparticle sorting device (1) comprising: a voltage supply unit (13) that supplies a drive voltage to a vibration element (V) that applies a vibration to an orifice (P3) that generates a fluid stream; a control unit (16) that controls a driving condition supplied to the vibration element on a basis of a relative relationship between a droplet (D) discharged from the orifice and a satellite droplet (SD) present between droplets, wherein the control unit controls the driving condition using, as an index, absorption easiness indicating absorption easiness of the satellite droplet relative to either a preceding droplet to the satellite droplet or a subsequent droplet to the satellite droplet such that a state in which the satellite droplet is absorbed by the preceding or subsequent droplet is maintained, and wherein the absorption easiness is calculated by using a first expression (Y1-Y0)/(Y2-Y0) or a second expression (Y2-Y1)/(Y2-Y0), wherein Y1 is a gravity center position of the satellite droplet and Y0 and Y2 are gravity center positions of the preceding and subsequent droplets respectively, wherein the first expression is used if the satellite droplet is absorbed by the preceding droplet and the second expression is used if the satellite droplet is absorbed by the subsequent droplet; and a sorting unit (14) that sorts the droplet containing microparticles on a basis of optical information detected from the microparticles flowing through a flow path (P).
2. The microparticle sorting device according to claim 1, wherein the driving condition is a frequency of the drive voltage.
3. The microparticle sorting device according to claim 1, wherein the driving condition is strength of the drive voltage.
4. A microparticle sorting method executed by a microparticle sorting device (1), the method comprising: supplying a drive voltage to a vibration element (V) that applies a vibration to an orifice (P3) that generates a fluid stream; controlling a driving condition supplied to the vibration element on a basis of a relative relationship between a droplet (D) discharged from the orifice and a satellite droplet (SD) present between droplets, wherein the control unit controls the driving condition using, as an index, absorption easiness indicating absorption easiness of the satellite droplet relative to either a preceding droplet to the satellite droplet or a subsequent droplet to the satellite droplet such that a state in which the satellite droplet is absorbed by the preceding or subsequent droplet is maintained, and wherein the absorption easiness is calculated by using a first expression (Y1-Y0)/(Y2-Y0) or a second expression (Y2-Y1)/(Y2-Y0), wherein Y1 is a gravity center position of the satellite droplet and Y0 and Y2 are gravity center positions of the preceding and subsequent droplets respectively, wherein the first expression is used if the satellite droplet is absorbed by the preceding droplet and the second expression is used if the satellite droplet is absorbed by the subsequent droplet; and sorting the droplet containing microparticles on a basis of optical information detected from the microparticles flowing through a flow path (P).
5. A microparticle sorting control program, that causes a microparticle sorting device (1): to execute a function of supplying a drive voltage to a vibration element (V) that applies a vibration to an orifice (P3) that generates a fluid stream, to execute a control function of controlling a driving condition supplied to the vibration element on a basis of a relative relationship between a droplet (D) discharged from the orifice and a satellite droplet (SD) present between droplets, wherein the control unit controls the driving condition using, as an index, absorption easiness indicating absorption easiness of the satellite droplet relative to either a preceding droplet to the satellite droplet or a subsequent droplet to the satellite droplet such that a state in which the satellite droplet is absorbed by the preceding or subsequent droplet is maintained, and wherein the absorption easiness is calculated by using a first expression (Y1-Y0)/(Y2-Y0) or a second expression (Y2-Y1)/(Y2-Y0), wherein Y1 is a gravity center position of the satellite droplet and Y0 and Y2 are gravity center positions of the preceding and subsequent droplets respectively, wherein the first expression is used if the satellite droplet is absorbed by the preceding droplet and the second expression is used if the satellite droplet is absorbed by the subsequent droplet, and to execute a function of sorting the droplet containing microparticles on a basis of optical information detected from the microparticles flowing through a flow path (P).

Description

TECHNICAL FIELD The present technology relates to a microparticle sorting device, a microparticle sorting system, a droplet sorting device, a droplet control device, and a droplet control program. More specifically, this relates to a technology of sorting and recovering a droplet containing specific particles and the like. BACKGROUND ART An optical measurement method using flow cytometry (flow cytometer) is conventionally used for analyzing bio-related microparticles such as cells, microorganisms, and liposomes. The flow cytometer is a device that irradiates particles flowing through a flow path formed in a flow cell, a microchip and the like with light, and detects fluorescence or scattered light emitted from each particle to analyze. Some flow cytometers have a function of sorting to recover only particles having specific characteristics on the basis of an analysis result, and a device that especially sorts the cells is called as a "cell sorter". In the cell sorter, in general, a vibration element and the like applies a vibration to the flow cell or microchip to make fluid discharged from the flow path thereof droplets (refer to Patent Documents 1 and 2). The droplet separated from the fluid is charged with a positive (+) or negative (-) charge, then a travel direction thereof is changed by a deflection plate and the like, and the droplet is recovered in a predetermined container and the like. In contrast, a device such as the cell sorter that sorts the droplet tends to have unstable sorting performance due to an effect and the like of temperature change, hydraulic pressure fluctuation, and differential pressure due to change in sheath pressure. Therefore, in order to stabilize the sorting performance, a microparticle sorting device that controls a drive voltage of a voltage supply unit by imaging the fluid and droplet discharged from an orifice of the flow cell or microchip and detecting the droplet from the image is conventionally proposed (refer to Patent Document 3). Furthermore, Patent Document 4 discloses a technology of stably forming a droplet by providing, on a droplet sorting device, a detection unit that detects a state of a droplet discharged from an orifice that generates a fluid stream and a satellite droplet present between the droplets, and a control unit that controls a frequency of a drive voltage supplied to a vibration element that applies a vibration to the orifice on the basis of a position in which the satellite droplet is present. CITATION LIST PATENT DOCUMENT Patent Document 1: Japanese Unexamined Patent Publication No. 2007-532874Patent Document 2: Japanese Patent Application Laid-Open No. 2010-190680Patent Document 3: International Publication No. 2013/145905Patent Document 4: Japanese Patent Application Laid-Open No. 2016-57286US 2017/0241899 A1 relates to a droplet sorting device, a droplet sorting method, and a program, and more specifically relates to a technology of separating and collecting droplets including specific particles and the like. SUMMARY OF THE INVENTION PROBLEMS TO BE SOLVED BY THE INVENTION Although a sorting performance in a microparticle sorting technology is improved day by day by the above-described conventional technology, it is also a fact that a droplet forming technology that is less susceptible to environmental fluctuation such as temperature change and has excellent robustness is expected. Therefore, a principal object of the present technology is to provide a droplet forming technology capable of stably sorting a droplet. SOLUTIONS TO PROBLEMS The invention is defined by the appended claims. In the present technology, "microparticles" broadly include bio-related microparticles such as cells, microorganisms, and liposomes, synthetic particles such as latex particles, gel particles, and industrial particles or the like. The bio-related microparticles include chromosomes forming various cells, liposomes, mitochondria, organelles (cell organelles) and the like. The cells include animal cells (such as blood cells) and plant cells. The microorganisms include bacteria such as Escherichia coli, viruses such as tobacco mosaic virus, fungi such as yeast and the like. Moreover, the bio-related microparticles may also include bio-related polymers such as nucleic acids, proteins, and complexes thereof. Furthermore, the industrial particles may be, for example, an organic or inorganic polymer material, metal or the like. The organic polymer material includes polystyrene, styrene/divinylbenzene, polymethyl methacrylate and the like. The inorganic polymer material includes glass, silica, a magnetic material and the like. The metal includes gold colloid, aluminum and the like. In general, shapes of the microparticles are generally spherical, but they may be non-spherical, and its size, mass and the like are also not especially limited. BRIEF DESCRIPTION OF DRAWINGS Fig. 1 is a schematic conceptual diagram schematically illustrating a microparticle sorting device 1