Microparticle sorting device and microparticle sorting method

Abstract

The main purpose of the present technology is to provide a fine particle sorting device and a fine particle sorting method capable of sorting target fine particles with high efficiency. The present technology provides a microparticle sorting apparatus and the like including: a channel structure including: a main channel through which a first liquid containing microparticles flows; a recovery channel through which particles to be recovered among the microparticles are recovered; and a connection channel connecting the main channel and the recovery channel, the control unit providing a pressure change in the recovery channel and recovering particles to be recovered through the recovery channel. The control unit provides a pressure change in a positive direction, generates a pressure vibration PVr in the recovery channel, and performs a recovery operation Cr for recovering particles to be recovered by the pressure change in a negative direction generated by the pressure vibration PVr.

Description

Technical Field

[0001] The present technology relates to a particle sorting device and a particle sorting method. Background Art

[0002] The particle sorting device can be used for the purpose of sorting and recovering specific particles from a sample. For example, the particle sorting device forms a sheath flow containing particles in a channel, and irradiates the particles in the sheath flow with light to detect fluorescence and / or scattered light emitted from the particles. Therefore, a group (population) of particles exhibiting predetermined optical properties is sorted and recovered. A flow cytometer, which is an example of a particle sorting device, sorts and recovers only a specific type of cells by optically identifying each cell labeled with a fluorescent dye.

[0003] Patent Documents 1 and 2 disclose a microchip type particle sorting device that forms a sheath flow in a main channel formed in a microchip to sort particles. The particle sorting device disclosed in Patent Documents 1 and 2 includes a branch channel communicating with the main channel and an actuator that generates negative pressure in the branch channel.

[0004] The particle sorting device disclosed in Patent Document 1 applies a voltage having a step waveform component of an undershoot waveform and a pulse waveform to an actuator. The particle sorting device disclosed in Patent Document 2 applies a driving waveform that is any one of a pulse waveform, a step waveform, or an undershoot step waveform to an actuator, and controls the application of the pulse waveform for the falling waveform portion and the rising waveform portion, respectively.

[0005] The particle sorting devices disclosed in Patent Documents 1 and 2 apply a descending drive waveform to an actuator so that the inside of a branch channel has a negative pressure. Thus, a flow is formed that leads from the main channel to the branch channel, and particles are brought from the main channel into the branch channel. In addition, these particle sorting devices apply an ascending drive waveform to an actuator to generate a positive pressure in the branch channel and return the inside of the branch channel to an initial state. That is, in these particle sorting devices, application of an ascending drive waveform is performed as a return operation of the actuator.

[0006] Reference List

[0007] Patent Literature

[0008] Patent Document 1: WO 2014 / 013802 A

[0009] Patent Document 2: Japanese Patent Application Publication No. 2014-039534 Summary of the invention

[0010] Problems to be solved by the present invention

[0011] The present inventors have considered that the operation time when the rising drive waveform is applied in the prior art particle sorting device is the time when the particles are not sorted and is a dead time from the viewpoint of sorting efficiency. The present inventors have considered that the particle sorting efficiency can be improved by reducing such dead time.

[0012] Therefore, a main object of the present technology is to provide a microparticle sorting device and a microparticle sorting method capable of sorting target microparticles with high efficiency.

[0013] Solution to the problem

[0014] In order to solve the above-mentioned problems, the present inventors have studied an apparatus capable of performing sorting at a specific time when microparticle sorting is not performed in a microparticle sorting apparatus in the related art, and as a result, have completed the present technology.

[0015] That is, the present technology provides a particle sorting device including a channel structure, the channel structure including: a main channel, through which a first liquid containing particles flows; a recovery channel, through which recovery target particles in the particles are recovered; and a connecting channel connecting the main channel and the recovery channel; and a control unit, which applies a pressure change in the recovery channel and recovers the recovery target particles into the recovery channel, wherein the control unit performs a recovery operation Cr of applying a pressure change in a positive direction to generate a pressure vibration PVr in the recovery channel and recovering the recovery target particles through a pressure change in a negative direction caused by the pressure vibration PVr.

[0016] The control unit may apply a pressure change in a negative direction in the recovery channel and perform a recovery operation Cf of recovering the recovery target particles through the pressure change in the negative direction.

[0017] The control unit may be configured to alternately perform the recycling operation Cf and the recycling operation Cr.

[0018] The particle sorting device may further include a particle detection unit that detects particles that have passed a predetermined position in the main channel, and the control unit may be configured to perform a recovery operation Cf or a recovery operation Cr according to an interval TIx of a time point when the particle detection unit has detected two consecutive particles.

[0019] The control unit may be configured to recover the particle detected earlier of the two consecutive particles through the recovery operation Cf, and to recover the particle detected later of the two consecutive particles through the recovery operation Cf if the interval TIx between the time points is shorter than a predetermined value.

[0020] The particle sorting device may further include a particle detection unit to detect particles that have passed through a predetermined position in the main channel, and the control unit may be configured to perform a recovery operation Cf after a time DTf from a time point when the particle detection unit detects the particles, and to perform a recovery operation Cr after a time DTr from a time point when the particle detection unit detects the particles.

[0021] The time DTf and the time DTr may be different from each other.

[0022] The time DTr may be shorter than the time DTf.

[0023] In a case where, after the control unit applies a pressure change in a positive direction, it takes time T2 for the liquid flow in a predetermined section in the channel structure to return to the state before the pressure change in the positive direction is applied, the time interval TIz from when the control unit applies the pressure change in the positive direction to when the control unit applies the next pressure change may be equal to or longer than time T2.

[0024] After the control unit applies a pressure change in the negative direction, if it takes time T1 for the liquid flow in a predetermined section in the channel structure to return to the state before the pressure change in the negative direction is applied, the time interval TIy from when the control unit applies the pressure change in the negative direction to when the control unit applies the next pressure change may be equal to or longer than time T1.

[0025] The particle sorting device may further include an actuator, and the control unit may apply the pressure change in the recovery channel by applying a driving waveform to the actuator.

[0026] The particle sorting device may further include an actuator, and the control unit may apply a pressure change in a positive direction by applying a rising driving waveform Wr to the actuator, and perform the recovery operation Cr.

[0027] The particle sorting device may further include an actuator, the control unit may apply a pressure change in a negative direction by applying a falling drive waveform Wf to the actuator and perform a recovery operation Cf, and the control unit may apply a pressure change in a positive direction by applying a rising drive waveform Wr to the actuator and perform a recovery operation Cr.

[0028] The rising driving waveform Wr may be a rising driving waveform Wfr having a falling waveform.

[0029] The diameter of the connecting channel may be equal to or greater than 60 μm.

[0030] The channel structure may further include a liquid supply channel connected to the connecting channel, so that a second liquid can be supplied, the second liquid can be immiscible with the first liquid, and in the recovery operation Cr, the control unit can recover an emulsion in which the first liquid containing the recovery target particles is contained in the second liquid.

[0031] The particle sorting device may further include a particle sorting microchip, and the particle sorting microchip may have a channel structure.

[0032] In addition, the present technology provides a particle sorting method, comprising: in a particle sorting device including a channel structure, a control step of applying a pressure change in a recovery channel, the channel structure comprising: a main channel, a first liquid containing particles flows through the main channel; a recovery channel, recovery target particles in the particles are recovered through the recovery channel; and a connecting channel, the connecting channel connecting the main channel and the recovery channel; and a recovery step of recovering the recovery target particles into the recovery channel, wherein the control step includes applying a pressure change in a positive direction to generate a pressure vibration PVr in the recovery channel, and the recovery step includes performing a recovery operation Cr, which recovers the recovery target particles through a pressure change in a negative direction caused by the pressure vibration PVr. BRIEF DESCRIPTION OF THE DRAWINGS

[0033] Figure 1 is a schematic diagram showing the configuration of the microparticle sorting apparatus according to the first embodiment.

[0034] Figure 2 This is an enlarged view of the particle sorting section.

[0035] Figure 3 : is a schematic diagram showing a state where the sample fluid and the sheath fluid form a laminar flow.

[0036] Figure 4 is a block diagram showing a functional configuration of the particle sorting apparatus according to the first embodiment.

[0037] Figure 5 is a plan view showing an example of a microparticle sorting microchip.

[0038] Figure 6 is a perspective view showing an example of a microparticle sorting microchip.

[0039] Figure 7 is along Figure 5 Cross-sectional view along line XX.

[0040] Figure 8 is a diagram showing an example of a driving waveform applied to an actuator.

[0041] Fig. 9: is a diagram showing analysis results in simulation regarding pressure changes in the pressure chamber and flow rate changes in the connecting channel.

[0042] Fig.10 It shows Figure 1 Schematic diagram of a portion of the channel structure shown in .

[0043] Fig.11 is a diagram showing the temporal relationship among an event signal in a particle detection unit, a piezoelectric driving voltage, and a flow velocity change in a connecting channel.

[0044] Fig.12 is a block diagram for describing the configuration of a control unit.

[0045] Fig.13 is a diagram for describing the waveform of an electrical signal read by an event detection circuit.

[0046] Fig.14 A conceptual diagram used to describe event packets.

[0047] Fig.15 is a diagram for describing gating on a histogram graph and a 2D graph.

[0048] Fig.16 is a schematic diagram for describing a pulse waveform including a falling drive waveform and a rising drive waveform.

[0049] Fig.17 is a first flow chart illustrating an example of an algorithm embodying a particulate recovery operation.

[0050] Fig.18 is a second flow chart illustrating an example of an algorithm embodying a particulate recovery operation.

[0051] Fig.19 is a timing diagram used to describe the particle recovery operation.

[0052] Fig. 20 is a timing chart for describing a comparative example.

[0053] Fig.21 is a timing chart for describing a modification of the particulate recovery operation.

[0054] Fig. 22 is a timing chart for describing a modification of the particulate recovery operation.

[0055] Fig.23 : is a flowchart showing the second process in the modification of the particulate recovery operation.

[0056] Fig.24 is an alternate plot photograph showing the emulsion created in the recycling channel by applying a falling drive waveform and a rising drive waveform.

[0057] Fig.25 is a diagram showing a rising driving waveform and a falling driving waveform.

[0058] Fig.26 : is a view showing the analysis result of simulating the change of the flow rate in the connection channel when the rising drive waveform and the rising drive waveform with a falling waveform are applied. DETAILED DESCRIPTION

[0059] Hereinafter, a preferred mode for carrying out the present technology will be described with reference to the accompanying drawings. The embodiments described below show representative embodiments of the present technology, and the scope of the present technology is not limited to these embodiments. The present technology will be described in the following order.

[0060] 1. First Embodiment (Microparticle Sorting Device)

[0061] 1-1. Overview

[0062] 1-2. Basic Configuration

[0063] 1-3. Detailed structure

[0064] 1-4. Simulation of pressure change and flow rate change

[0065] 1-5. Particle recovery operation

[0066] 1-5-1. Microparticle recovery operation process

[0067] 1-5-2. Configuration of control unit for performing particle recovery operation

[0068] 1-5-3. Algorithm for implementing particle recovery operation

[0069] 2. Second Embodiment (Emulsion Generating Device)

[0070] 2-1. Overview

[0071] 2-2. Configuration and operation

[0072] 3. Third embodiment (microparticle sorting method)

[0073] 4. Fourth embodiment (emulsion forming method)

[0074] 1. First Embodiment (Microparticle Sorting Device)

[0075] 1-1. Overview

[0076] A particle sorting device according to a first embodiment of the present technology includes a channel structure, which includes: a main channel, through which a first liquid including particles flows; a recovery channel, through which recovery target particles in the particles are recovered; and a connecting channel connecting the main channel and the recovery channel. The particle sorting device further includes a control unit, which applies a pressure change to the inside of the recovery channel and recovers the recovery target particles into the recovery channel. The control unit performs a recovery operation Cr of applying a pressure change in a positive direction to generate a pressure vibration PVr in the recovery channel, and recovering the recovery target particles through a pressure change in a negative direction caused by the pressure vibration PVr.

[0077] The particle sorting device according to the present embodiment uses the pressure vibration PVr generated by applying the pressure change in the positive direction in the recovery channel to sort the particles. Therefore, the dead time (time when the particles are not sorted) generated in the particle sorting device of the related art is reduced, and more efficient sorting becomes possible.

[0078] A channel structure including a main channel, a recovery channel, and a connection channel may be formed in, for example, a particle sorting microchip. That is, a particle sorting device according to the present embodiment may include a particle sorting microchip, and the particle sorting microchip may have a channel structure. Hereinafter, an example of the present embodiment will be described by taking a particle sorting device including a particle sorting microchip as an example with reference to the accompanying drawings.

[0079] 1-2. Basic Configuration

[0080] First, the basic configuration of the microparticle sorting apparatus according to the first embodiment will be described. Figure 1 1 is a schematic diagram showing the configuration of the particle sorting apparatus 100. The particle sorting apparatus 100 includes a particle sorting microchip 150 (hereinafter, also simply referred to as "microchip 150"). The microchip 150 can be attached to the particle sorting apparatus 100 in a replaceable manner.

[0081] The microchip 150 has a channel structure including: a main channel 155 through which a first liquid including microparticles flows; a recovery channel 159 through which recovery target particles among the microparticles are recovered; and a connection channel connecting the main channel 155 and the recovery channel 159. The connection channel is included in a particle sorting section 157 provided in the microparticle sorting microchip 150.

[0082] Figure 2 is an enlarged view of the particle sorting section 157. Figure 2As shown, the connecting channel 170 is provided between the main channel 155 and the recovery channel 159. In the particle sorting section 157, the recovery target particles are recovered into the recovery channel 159. Specifically, the control unit (details will be described later) performs a recovery step of recovering the recovery target particles into the recovery channel 159.

[0083] The microchip 150 can be manufactured by methods known in the art. For example, the microchip can be manufactured by bonding two substrates in which the above-mentioned channels are formed. The channels can be formed on both substrates, or can be formed on only one of the substrates. In order to make it easier to align when bonding the substrates, the channels can be formed in only one of the substrates.

[0084] As a material for forming the microchip 150, a material known in the art can be used. Examples include, but are not limited to, for example, polycarbonate, cycloolefin polymer, polypropylene, polydimethylsiloxane (PDMS), polymethyl methacrylate (PMMA), polyethylene, polystyrene, glass, and silicon. In particular, polymer materials such as polycarbonate, cycloolefin polymer, and polypropylene are particularly preferred because they have excellent processability and can manufacture microchips inexpensively using a molding device.

[0085] Reference again Figure 1 The particle sorting device 100 includes a light irradiation unit 101 , a particle detection unit 102 , and a control unit 103 .

[0086] The light irradiation unit 101 irradiates the microparticles flowing through the main channel 155 with light (e.g., excitation light). That is, the light irradiation unit 101 performs a light irradiation step of irradiating the microparticles flowing through the main channel 155 with light. The light irradiation unit 101 may include a light source that emits light and an objective lens that focuses the excitation light on the microparticles flowing through the detection area. The light source can be appropriately selected by those skilled in the art according to the purpose of the analysis, and may be, for example, a laser diode, an SHG laser, a solid-state laser, a gas laser, a high-brightness LED or a halogen lamp, or may be a combination of two or more thereof. The light irradiation unit 101 may also include other optical elements as needed in addition to the light source and the objective lens.

[0087] The particle detection unit 102 detects particles passing through a predetermined position in the main channel 155. That is, the particle detection unit 102 performs a particle detection step of detecting particles passing through a predetermined position in the main channel 155. More specifically, the particle detection unit 102 detects scattered light and / or fluorescence generated from particles by light irradiation of the light irradiation unit 101. The particle detection unit 102 may include a condenser lens that collects fluorescence and / or scattered light generated from particles, and a detector. As a detector, a PMT, a photodiode, a CCD, a CMOS, etc. can be used, but the detector is not limited thereto. In addition to the condenser lens and the detector, the particle detection unit 102 may also include other optical elements as needed. For example, the particle detection unit 102 may further include a spectroscopic unit. Examples of optical components constituting the spectroscopic unit may include, for example, a grating, a prism, and an optical filter. The spectroscopic unit may detect, for example, light having a wavelength that should be detected independently of light having another wavelength. The particle detection unit 102 may convert the detected light into an analog electrical signal by photoelectric conversion. The particle detection unit 102 transmits the analog electrical signal to the control unit 103.

[0088] The control unit 103 determines whether the microparticle is a recovery target particle based on the characteristics of the light detected by the particle detection unit 102. That is, the control unit 103 performs a determination step of determining whether the microparticle is a recovery target particle based on the characteristics of the light detected by the particle detection unit 102. More specifically, the control unit 103 processes the acquired analog electrical signal to generate information associated with information about the characteristics of the light. For example, the control unit 103 may determine based on scattered light such as forward scattered light, side scattered light, or back scattered light, determine based on fluorescence having the same or multiple wavelengths, or determine based on an image (e.g., a dark field image and / or a bright field image, etc.).

[0089] In addition, the control unit 103 operates to recover the microparticles based on the determination result. Specifically, the control unit 103 applies a pressure change to the inside of the recovery channel 159 based on the determination result in the determination step and recovers the recovery target particles into the recovery channel 159. That is, the control unit 103 performs a control step of applying a pressure change to the inside of the recovery channel 159 and a recovery step of recovering the recovery target particles into the recovery channel 159 based on the determination result in the determination step. Therefore, the flow in the microchip 150 is controlled, and as a result, the microparticles can be recovered.

[0090] 1-3. Detailed structure

[0091] Next, the detailed configuration of the particle sorting device 100 will be described. Figure 1As shown, the microchip 150 is provided with a sample fluid inlet 151 and a sheath fluid inlet 153. A sample fluid including a first liquid containing microparticles and a sheath fluid including only the first liquid not containing microparticles are introduced into a sample fluid channel 152 and a sheath fluid channel 154, respectively, from these inlets.

[0092] The microchip 150 has a channel structure in which a sample fluid channel 152 through which a sample fluid flows and a sheath fluid channel 154 through which a sheath fluid flows merge at a junction 162 to become a main channel 155. In the main channel 155, the sample fluid and the sheath fluid form a laminar flow.

[0093] Figure 3 Schematic diagram showing a state where the sample fluid and the sheath fluid form a laminar flow. Figure 3 As shown, the sample fluid channel 152 and the sheath fluid channel 154 merge at the junction 162 to form, for example, a laminar flow in which the sample fluid is surrounded by the sheath fluid. Preferably, in the laminar flow, the particles are substantially arranged in a row. As described above, the above-mentioned channel structure forms a laminar flow including particles flowing substantially in a line.

[0094] The above-mentioned laminar flow flows toward the particle sorting section 157 through the main channel 155. Preferably, the microparticles flow in a line in the main channel 155. Therefore, when a particle detection region 156 to be described below is irradiated with light, light generated by irradiating one microparticle with light and light generated by irradiating another microparticle with light can be easily distinguished from each other.

[0095] like Figure 1 and Figure 3 As shown, the microchip 150 has a particle detection area 156. Figure 1 As shown, in the particle detection area 156, the light irradiation unit 101 irradiates the microparticles flowing through the main channel 155 with light. The particle detection unit 102 detects the light generated by the light irradiation. The control unit 103 determines whether the microparticle is a recovery target particle based on the characteristics of the light detected by the particle detection unit 102. The control unit 103 applies a pressure change to the inside of the recovery channel 159 and recovers the recovery target particle based on the determination result.

[0096] Figure 4 1 is a block diagram showing the functional configuration of the particle sorting device 100. As described above, the particle sorting device 100 includes the light irradiation unit 101, the particle detection unit 102, and the control unit 103 as functional units. Figure 4 As shown, the particle sorting device 100 may further include an actuator 107. In this case, the control unit 103 may apply a pressure change to the recovery channel 159 (see FIG. 15A ) by applying a driving waveform to the actuator. Figure 1 ) inside. Details of the actuator 107 and the control unit 103 will be described later with reference to other drawings.

[0097] Reference again Figure 1 The channel structure of the microchip 150 includes: a main channel 155, through which the first liquid including microparticles flows; a recovery channel 159, through which recovery target particles among the microparticles are recovered; and a waste channel 158, through which non-recovery target particles are disposed. In the particle sorting section 157, only when the recovery target particles flow, a channel is formed from the main channel 155 through the connecting channel 170 (refer to Figure 2 ) enters the flow of the recovery channel 159, and the recovered target particles are recovered into the recovery channel 159.

[0098] Reference Figure 2 The particle sorting control in the particle sorting section 157 is described. Figure 2 As shown in FIG. 1A , the particle sorting section 157 includes a connecting channel 170 connecting the main channel 155 through which the particles P flow and the recovery channel 159. Figure 2 As shown in FIG. 1B , among the microparticles P, the recovery target particles Po flow into the recovery channel 159 through the connection channel 170. Figure 2 As shown in C, the particles Pw that are not the target of recovery flow into the waste channel 158.

[0099] In the particle sorting section 157, the laminar flow flowing through the main channel 155 flows into the waste channel 158. In the particle sorting section 157, only in the case where the recovery target particle Po flows, a flow entering the recovery channel 159 is formed, and the recovery target particle Po is recovered. When the recovery target particle Po is sucked into the recovery channel 159, the sample fluid forming the laminar flow or the sample fluid and the sheath fluid forming the laminar flow may also flow to the recovery channel 159.

[0100] In order to prevent the particles Pw that are not the recovery target from entering the recovery channel 159, as shown in FIG. Figure 2 As shown in A, the liquid supply channel 161 may be connected to the connecting channel 170. The liquid supply channel 161 is, for example, disposed in the up-down direction of the connecting channel 170 (so as to be substantially perpendicular to the axial direction of the connecting channel 170). Figure 2 In the case of the arrow X direction, the liquid supply channel 161 can be parallel to Figure 2155. The liquid supply channel 161 is configured to intersect the connecting channel 170 near the center thereof. The second liquid (liquid other than the first liquid containing particles) is introduced into the connecting channel 170 from the liquid supply channel 161. Therefore, the second liquid is supplied to the connecting channel 170 from the up and down directions. The second liquid supplied to the connecting channel 170 flows to both the main channel 155 and the recovery channel 159. Because a flow from the connecting channel 170 toward the main channel 155 is formed, the particles Pw that are not the recovery target are prevented from entering the recovery channel 159.

[0101] For example, by driving the actuator 107 (see Figure 4 ) performs recovery of the recovery target particles into the recovery channel 159. The actuator 107 may be, for example, an actuator using a pressure element such as a piezoelectric element.

[0102] In the following, reference will be made to Figures 5 to 7 The actuator 107 and the microparticle sorting microchip 150a (hereinafter, simply referred to as "microchip 150a") are described. Figure 5 and Figure 6 1 and 2 are a plan view and a perspective view of the microchip 150a, respectively. Figure 7 is along Figure 5 Cross-sectional view along line XX. Figures 5 to 7 The microchip 150a shown is Figure 1 The illustrated microchip 150 differs in that a pressure chamber 165 is depicted, but is otherwise identical.

[0103] like Figure 6 and Figure 7 As shown, the actuator 107 is arranged on the surface of the microchip 150a at a position corresponding to the recovery channel 159 so that the wall of the recovery channel 159 can be deformed. The actuator 107 is in contact with the surface of the microchip 150a.

[0104] For example, the recovery channel 159 may include a pressure chamber 165 which is a region where the inner space is enlarged. In this case, the actuator 107 may be arranged on the surface of the microchip 150a at a position corresponding to the pressure chamber 165.

[0105] The internal space of the pressure chamber 165 expands in the plane direction (the width direction of the recovery channel 159), such as Figure 5 and Figure 6 As shown, and also expands in the cross-sectional direction (the height direction of the recovery channel 159), as shown Figure 7 That is, the recovery channel 159 expands in the width direction and the height direction in the pressure chamber 165. In other words, the recovery channel 159 is formed so that its cross section is orthogonal to the flow direction of the sample fluid and the sheath fluid in the pressure chamber 165.

[0106] The actuator 107 deforms the recovery channel 159 (pressure chamber 165) by the expansion / contraction force generated according to the change of the applied driving voltage. Due to the deformation, the volume of the recovery channel 159 (pressure chamber 165) changes, and a pressure change is generated in the recovery channel 159 (pressure chamber 165). For example, when the actuator 107 contracts, the volume of the pressure chamber 165 increases, and the pressure in the pressure chamber 165 changes in the negative direction. For example, when the actuator 107 expands, the volume of the pressure chamber 165 decreases, and the pressure in the pressure chamber 165 changes in the positive direction.

[0107] In order to effectively transmit the expansion / contraction force of the actuator 107 to the recovery channel 159 (pressure chamber 165), preferably, the surface of the microchip 150a is recessed at a position corresponding to the pressure chamber 165, and the actuator 107 is arranged as follows: Figure 7 Therefore, the displacement plate 167 that contacts the actuator 107 and constitutes a part of the pressure chamber 165 can be thinned. When the displacement plate 167 is thin, the displacement plate 167 is easily displaced as the actuator 107 expands and contracts, so that the volume of the pressure chamber 165 can be easily changed.

[0108] In order to generate an extension / contraction force in the actuator 107, the control unit 103 (refer to Figure 4 ) applies a predetermined drive waveform to the actuator 107. Figure 8 1 is a diagram showing an example of a driving waveform applied to the actuator 107. Figure 8 As shown, the driving waveform may include a falling driving waveform Wf (falling slope) and a rising driving waveform Wr (rising slope).

[0109] For example, the control unit 103 applies the falling driving waveform Wf to the actuator 107. Figure 6 and Figure 7 The actuator 107 shown in FIG. 1 contracts, the pressure chamber 165 is deformed in a direction in which the volume increases, and a pressure change in a negative direction is generated in the pressure chamber 165. In addition, the control unit 103 applies a rising drive waveform Wr to the actuator 107, for example. Figure 6 and Figure 7 The actuator 107 shown in FIG. 1 is expanded, the pressure chamber 165 is deformed in a direction of volume reduction, and a pressure change in a positive direction is generated in the pressure chamber 165 .

[0110] As mentioned above, in Figure 8 The falling driving waveform Wf shown in FIG. 1 is applied to apply a pressure change in the negative direction immediately after the driving waveform is applied. Figure 8The rising driving waveform Wr shown in FIG. 1 is applied to apply a pressure change in the positive direction immediately after the driving waveform is applied. In the driving waveform, the driving height (voltage) of the falling waveform Wf, the driving height (voltage) of the rising driving waveform Wr, the driving voltage application time (falling slope) of the falling driving waveform Wf, the driving voltage application time (rising slope) of the rising driving waveform Wr, and the time interval Th (driving time interval Th) between the falling driving waveform Wf and the rising waveform Wr are used as control parameters.

[0111] 1-4. Simulation of pressure change and flow rate change

[0112] When plastic is used as the material of the microchip 150a and the falling drive waveform Wf and the rising drive waveform Wr are applied as the drive waveforms of the actuator 107 (piezoelectric actuator), simulations on pressure changes in the pressure chamber 165 and flow rate changes in the connecting channel 170 are performed. Fig. 9 is a diagram showing the analysis results in the simulation. Fig. 9 In the example, the left side (I) is the analysis result when the falling drive waveform Wf is applied. The right side (II) is the analysis result when the rising drive waveform Wr is applied. Fig. 9 , the upper stage (A) shows the piezoelectric driving voltage, the middle stage (B) shows the pressure change of the pressure chamber 165, and the lower stage (C) shows the flow rate change in the connecting channel 170. In the figure of the lower stage (C), with respect to the flow in the connecting channel 170, the upper direction of the lower stage (C) is the direction of the pressure chamber 165 (the direction of the recovery channel 159), and the lower direction of the lower stage (C) is the direction of the main channel 155.

[0113] When the falling driving waveform Wf is applied, the pressure chamber 165 is deformed in the direction of increasing volume. Fig. 9 As shown in (BI), a pressure change in the negative direction is immediately generated in the pressure chamber 165, and as shown in (CI), the flow in the connecting channel 170 is accelerated in the direction of the pressure chamber 165. At this time, due to the pressure change caused by the fluid suction, the inner wall surface of the channel is elastically deformed to generate elastic vibration. The elastic vibration causes a change in the volume of the pressure chamber 165 and causes pressure vibration in the pressure chamber 165. Due to the pressure vibration, a vibrating flow that alternately repeats the flow in the suction direction toward the recovery channel 159 and the flow in the discharge direction opposite to the suction direction is generated in the connecting channel 170. Therefore, in the case where the falling driving waveform Wf with a pressure change in the negative direction is applied to the pressure chamber 165, a vibrating flow toward the recovery channel 159 is generated immediately after the application, and then a vibrating flow toward the main channel 155 is generated. The vibrating flow toward the recovery channel 159 generated immediately after the application is indicated by the arrow F1 in (CI).

[0114] When the rising driving waveform Wr is applied, the pressure chamber 165 is deformed in a direction of decreasing volume. Fig. 9 As shown in (BII), a pressure change in the positive direction is immediately generated in the pressure chamber 165, and as shown in (CII), the flow in the connecting channel 170 is accelerated in the direction of the main channel 155. At this time, the inner wall surface of the channel is elastically deformed to cause elastic vibration. Pressure vibration is generated by elastic vibration. Vibration flow is generated by pressure vibration. The vibration characteristics of the vibration flow when the rising drive waveform Wr is applied are opposite to the vibration characteristics of the vibration flow generated when the falling drive waveform Wf is applied.

[0115] When the above-mentioned pressure change in the positive direction occurs immediately after the application of the rising drive waveform Wr, pressure vibration is generated due to the pressure change. Then, the pressure vibration causes a pressure change in the negative direction. A vibration flow toward the recovery channel 159 is generated by the pressure change in the negative direction. Therefore, in the case where the rising drive waveform Wr to which the pressure change in the positive direction is applied is applied in the pressure chamber 165, a vibration flow toward the main channel 155 is generated immediately after the application, and then a vibration flow toward the recovery channel 159 is generated. In (CII), arrow F2 indicates the vibration flow toward the recovery channel 159.

[0116] As mentioned above Fig. 9 As described above, a vibration flow to the recovery channel 159 is generated when each of the falling drive waveform Wf and the rising drive waveform Wr is applied. In order to generate these vibration flows more efficiently, the connection channel 170 (refer to Figure 7 ) is preferably equal to or greater than 60 μm. The connecting channel in the microchip generally used in the particle sorting device in the related art may be, for example, about 30 μm. For example, the diameter of the particles flowing through the connecting channel may be about 10 μm. On the other hand, the diameter of the connecting channel 170 in the present embodiment is preferably larger than that in the prior art. Therefore, the vibration flow (reference) toward the recovery channel 159 generated after the application of the rising drive waveform Wr can be increased. Fig. 9 The peak value of the flow rate of the arrow F2 in FIG. 1 is obtained. Therefore, the amount of liquid sucked in when the rising drive waveform Wr is applied can be increased, and the suction force of the particles can be increased. In the present embodiment, for example, the diameter of the particles flowing through the connecting channel 170 can be equal to or greater than 20 μm and equal to or less than 30 μm. As described above, the diameter of the particles can be greater than that in the prior art. The upper limit of the diameter of the connecting channel 170 can be, for example, equal to or less than 90 μm.

[0117] The element that can affect the suction force when the rising driving waveform Wr is applied is not limited to the diameter of the above-mentioned connection channel 170. For example, Figure 7 The dimensions of the pressure chamber 165 and / or recovery channel 159 shown and the properties of the liquid flowing in the microchip (eg, the kinematic viscosity and flow rate of the liquid) may also affect the above-mentioned suction force.

[0118] 1-5. Particle recovery operation

[0119] 1-5-1. Microparticle recovery operation process

[0120] The particle sorting device 100 according to the present embodiment uses a vibration flow (see Fig. 9 The particle sorting device 100 recovers particles by using the vibration flow (see arrow F2 in FIG. 1 ) generated immediately after the application of the rising driving waveform Wr and flowing to the recovery channel 159. Fig. 9 The arrow F1 in FIG. 1 and the vibration flow to the recovery channel 159 generated after applying the rising drive waveform Wr (refer to FIG. 1 ). Fig. 9 Arrow F2) in the figure is used to recover the particles.

[0121] Specifically, the control unit 103 applies a pressure change in the positive direction in the recovery channel 159 to generate a pressure vibration PVr in the recovery channel 159. The control unit 103 performs a recovery operation Cr of recovering the recovery target particles by the pressure change in the negative direction (specifically, the first pressure change in the negative direction) caused by the pressure vibration PVr. That is, the control step performed by the control unit 103 includes applying a pressure change in the positive direction in the recovery channel 159 and generating the pressure vibration PVr in the recovery channel. The recovery step performed by the control unit 103 includes performing a recovery operation Cr of recovering the recovery target particles by the pressure change in the negative direction (specifically, the first pressure change in the negative direction) caused by the pressure vibration PVr.

[0122] Preferably, the control unit 103 applies a pressure change in a positive direction in the recovery channel 159 by applying the rising drive waveform Wr to the actuator 107. Therefore, the control unit 103 generates a pressure vibration PVr in the recovery channel 159 and performs the above-described recovery operation Cr.

[0123] More specifically, the above-mentioned recovery operation Cr is an operation of recovering target particles through the vibration flow flowing to the recovery channel 159 caused by the pressure change in the negative direction caused by the pressure vibration PVr (specifically, the first pressure change in the negative direction).

[0124] In addition, the control unit 103 may apply a pressure change in the negative direction in the recovery channel 159 and perform a recovery operation Cf of recovering the recovery target particles by the pressure change in the negative direction. That is, the control step performed by the control unit 103 includes applying a pressure change in the negative direction in the recovery channel 159. In addition, the recovery step performed by the control unit 103 includes performing a recovery operation Cf of recovering the recovery target particles by the pressure change in the negative direction.

[0125] Preferably, the control unit 103 applies a pressure change in the negative direction in the recovery channel 159 by applying the falling drive waveform Wf to the actuator 107 , and performs the above-described recovery operation Cf.

[0126] More specifically, the above-described recovery operation Cf is an operation of recovering target particles by the vibration flow toward the recovery channel 159 generated immediately after the falling drive waveform Wf is applied.

[0127] In the particle sorting device 100, as an example, the control unit 103 may be configured to alternately perform the recovery operation Cf and the recovery operation Cr. Therefore, the number of failed recovery of target particles can be reduced and the recovery rate can be improved. Fig.19 and Fig. 20 The point of reducing the recovery failure by alternately performing the recovery operation Cf and the recovery operation Cr (ie, by alternately applying the falling driving waveform Wf and the rising driving waveform Wr) is described again.

[0128] The particle sorting device in the prior art performs the application of the rising drive waveform Wr as the return operation of the actuator. Therefore, the operation time when the rising drive waveform Wr is applied is a dead time in which the particles are not recovered. However, the particle sorting device 100 according to the present embodiment uses the application of the rising drive waveform Wr in the particle recovery operation. That is, the particle sorting device 100 according to the present embodiment can recover the recovery target particles during the operation time when the rising drive waveform Wr is applied. Therefore, the dead time in the prior art is reduced, and the recovery target particles can be effectively collected. That is, the target particles can be sorted with high efficiency.

[0129] Fig.10 It shows Figure 1 Schematic diagram of a portion of the channel structure shown in FIG. In order to accurately recover the target particle Po in the recovery channel 159, it is necessary to drive the actuator 107 at the optimal timing. Specifically, when the particle detection unit 102 (refer to FIG. 1 ) in the particle detection area 156 is Figure 1 ) detected Fig.10When the recovery target particle Po in the main channel 155 shown in FIG. 1 and then reaches the connecting port 169 of the connecting channel 170 (the portion where the connecting channel 170 and the main channel 155 are connected to each other), it is necessary to drive the actuator 107 to form a flow toward the recovery channel 159. In order to accurately recover the recovery target particle Po, it is necessary to optimize the time (recovery start time) from the detection of the particle to the application of the drive waveform to the actuator 107 by appropriately setting the application conditions of the drive waveform.

[0130] In the following, reference will be made to Fig.11 The relationship between the driving waveform and the recovery time in the case where particles can be recovered in driving both the falling driving waveform Wf and the rising driving waveform Wr is described. Fig.11 is a diagram showing the time relationship between the event signal in the particle detection unit 102, the piezoelectric drive voltage, and the flow rate change in the connection channel 170. Fig.11 In FIG. 1 , (I) on the left is a diagram showing the time relationship when the falling drive waveform Wf is applied. (II) on the right is a diagram showing the time relationship when the rising drive waveform Wr is applied. Fig.11 , the upper stage (A) shows the signal intensity, the middle stage (B) shows the piezoelectric driving voltage, and the lower stage (C) shows the flow rate change in the connecting channel 170. In the figure of the lower stage (C), with respect to the flow in the connecting channel 170, the upper direction of the lower stage (C) is the direction of the pressure chamber 165 (the direction of the recovery channel 159), and the lower direction of the lower stage (C) is the direction of the main channel 155.

[0131] The optimal recovery start time when the falling drive waveform Wf is applied is Fig.11 The time DTf shown in (B1) in FIG. After the time DTf from the signal detection of the particle detection unit 102, the application of the drive waveform is started, and immediately after the application, the flow rate in the connecting channel 170 is accelerated to the pressure chamber 165 side (in the suction direction). The target particles are recovered by the flow toward the pressure chamber 165.

[0132] On the other hand, if the time variation (CII) of the flow rate of the connecting passage 170 in the case of applying the rising drive waveform Wr is observed, when the rising drive waveform Wr is applied, the flow rate first accelerates toward the main passage 155, and then accelerates toward the pressure chamber 165 side. Therefore, when the rising drive waveform Wr is applied, it takes more time from the start of the application of the drive waveform to the generation of the flow to the pressure chamber 165 side compared to the application of the falling drive waveform Wf. Therefore, in the case of applying the rising drive waveform Wr to recover the recovery target particles, it is necessary to detect the timing of applying the drive waveform from the event in advance compared to the case of applying the falling drive waveform Wf. Assuming that the optimal recovery start time when the rising drive waveform Wr is applied is the time DTr, the time DTr is shorter than the time DTf, as shown in (BII). In order to recover the recovery target particles when the falling drive waveform Wf is applied and when the rising drive waveform Wr is applied, it is preferred to drive the actuator 107 at different recovery start times each time.

[0133] In order to drive the actuator 107 at the above timing, the control unit 103 may be configured to perform the above recovery operation Cf after the time DTf from the time point when the particle detection unit 102 detects the microparticle, and to perform the above recovery operation Cr after the time DTr from the time point when the particle detection unit 102 detects the microparticle. In this case, the time DTf and the time DTr may be different from each other, and preferably, the time DTr is shorter than the time DTf.

[0134] 1-5-2. Configuration of control unit for performing particle recovery operation

[0135] 1-5-2-1. Overall structure of the control unit

[0136] Figure 4 The control unit 103 shown controls the recovery operation of recovering the target particles by applying a driving voltage to the actuator 107. Fig.12 The overall configuration of the control unit 103 is described.

[0137] Fig.1223 is a diagram showing the configuration of the control unit 103. The control unit 103 includes a plurality of circuits 2302 to 2309 connected to a bus 2301. Specifically, the circuit denoted by reference numeral 2302 in the figure is an analog-to-digital conversion circuit 2302. The circuit denoted by reference numeral 2303 is an event detection circuit 2303. The circuit denoted by reference numeral 2304 is a recycling start time calculation circuit 2304. The circuit denoted by reference numeral 2305 is a gating circuit 2305. The circuit denoted by reference numeral 2306 is an output queue circuit 2306. The circuit denoted by reference numeral 2307 is an output timing generation circuit 2307. The circuit denoted by reference numeral 2308 is an output signal generation circuit 2308. The circuit denoted by reference numeral 2309 is a microprocessing unit (MPU) 2309. Note that the analog-to-digital conversion circuit 2302 is denoted as "A / D" in the figure.

[0138] The control unit 103 further includes a clock counter 2310. The clock counter 2310 is connected to the event detection circuit 2303, the recycling start time calculation circuit 2304, the gating circuit 2305, the output queue circuit 2306, the output timing generation circuit 2307 and the output signal generation circuit 2308.

[0139] The control unit 103 further includes an input / output interface circuit (PC I / O unit) 2311 for personal computer connection connected to the MPU 2309 and a control PC 2312 connected to the PC I / O unit 2311 .

[0140] The control unit 103 further includes a digital-analog conversion circuit 2313 connected to the output signal generating circuit 2308. It should be noted that the digital-analog conversion circuit 2313 is indicated as "D / A" in the drawings.

[0141] 1-5-2-2. Detailed configuration of the control unit

[0142] Then, reference will be made to Fig.12 The detailed configuration of the control unit 103 is described.

[0143] [Analog-to-digital conversion circuit]

[0144] The analog-to-digital conversion circuit 2302 is a circuit of the subsequent stage (output side) of the particle detection unit 102 (refer to Figure 4 ) and connected to the particle detection unit 102. In addition, a plurality of analog-digital conversion circuits 2302 are arranged. Here, the analog-digital conversion circuits 2302 may be arranged to correspond to the number of channels of the particle detection unit 102 ( Fig.12Ch) in order to correspond to each of the multiple light beams (wavelength regions) detected by the particle detection unit 102. Alternatively, the same number of analog-to-digital conversion circuits 2302 as the number of sensors of the particle detection unit 102 may be configured.

[0145] The electrical signal corresponding to each analog-digital conversion circuit 2302 output from the particle detection unit 102 is input to each analog-digital conversion circuit 2302. The electrical signal is an analog signal obtained by the particle detection unit 102 performing photoelectric conversion on the light (fluorescence and scattered light) detected by the particle detection unit 102. Then, each analog-digital conversion circuit 2302 converts each input electrical signal from an analog signal to a digital signal. In addition, each analog-digital conversion circuit 2302 outputs the electrical signal converted into a digital signal to the subsequent stage.

[0146] [Event detection circuit]

[0147] The event detection circuit 2303 is a circuit at a subsequent stage of each analog-to-digital conversion circuit 2302 , and is connected to each analog-to-digital conversion circuit 2302 .

[0148] The electrical signals output from each analog-to-digital conversion circuit 2302 are input to the event detection circuit 2303. Then, the event detection circuit 2303 uses a specific signal among the input electrical signals as a trigger signal for identifying the microparticles. That is, in the case where the value of the trigger signal satisfies a predetermined condition, the event detection circuit 2303 identifies each electrical signal detected from the microparticles. It should be noted that the trigger signal may be an electrical signal of light (e.g., forward scattered light) having the maximum intensity among the multiple light beams detected by the particle detection unit 102, but is not limited thereto.

[0149] In addition, if Fig.13 As shown, the event detection circuit 2303 reads the waveform of each input electrical signal and calculates the width, height and area of ​​the read waveform. Fig.14 As shown, the event detection circuit 2303 creates an event data packet using each value of the calculated waveform, etc., wherein each electrical signal is associated with a corresponding particle. An event data packet is an example of measurement data for a particle. The event detection circuit 2303 then outputs the created event data packet to a subsequent stage.

[0150] Here, the event data packet includes an item (hereinafter referred to as the first item) that completes data recording when the packet is created. In addition, after the packet is created, the event data packet includes an item (hereinafter referred to as the second item) that is updated with the processing related to the electrical signal corresponding to the packet.

[0151] The first item includes, for example, the following items.

[0152] The width, height and area of ​​the electrical signal waveform

[0153] The number of particles identified (event number)

[0154] The number of electrical signals used as trigger signals

[0155] ·Trigger signal detection time point

[0156] Note that the number of the electrical signal used as the trigger signal may be the channel number. In addition, the signal input from the clock counter 2310 may be used to record the detection time point of the trigger signal. The signal may be obtained by counting the clock signal from the clock generating circuit (not shown) input thereto by the clock counter 2310.

[0157] On the other hand, the second items include, for example, the following items.

[0158] The time when particles should be recovered

[0159] The first flag indicating whether to recycle particles

[0160] A second flag indicating whether to recycle particles

[0161] Note that the first flag is a flag set by the gating circuit 2305. On the other hand, the second flag is a flag set by the output queue circuit 2306. The first flag and the second flag are basically set to 1 or 0, and can be used to determine whether to recycle the corresponding particle. Further details of each flag will be described later.

[0162] [Recycling start time calculation circuit]

[0163] like Fig.12 As shown, the recycling start time calculation circuit 2304 is a circuit at a subsequent stage of the event detection circuit 2303 and is connected to the event detection circuit 2303.

[0164] The event data packet output from the event detection circuit 2303 is input to the recycling start time calculation circuit 2304. Then, based on the input event data packet, the recycling start time calculation circuit 2304 calculates the driving start time point of the actuator 107 to generate a flow toward the recycling channel 159 in the connection channel 170 when the microparticle (recycling target particle) has arrived at the communication port 169, as the time point of the microparticle included in the second item. The recycling start time calculation circuit 2304 calculates both the recycling start time point for recycling by applying the falling drive waveform Wf and the recycling start time point for recycling by applying the rising drive waveform Wr. The recycling start time point in each driving waveform calculated by calculation is recorded in the event data packet, and the recorded event data packet is output to the subsequent stage. The calculation of the recycling start time point can be performed by adding the predetermined time (delay time) from the microparticle detection to the application drive waveform to the detection time point of the trigger signal included in the first item. In addition, the recycling start time point can be calculated as a clock counter value.

[0165] [Gate circuit]

[0166] The strobe circuit 2305 is a circuit at a subsequent stage of the event detection circuit 2303 and is connected to the event detection circuit 2303 .

[0167] The event data packet output from the event detection circuit 2303 is input to the gating circuit 2305. Then, the gating circuit 2305 sets the first flag for the input event data packet. In addition, the gating circuit 2305 outputs the event data packet after setting the first flag to the subsequent stage.

[0168] The setting of the first mark may be performed based on a threshold value pre-set for a parameter of each electrical signal included in the event data packet. In this case, the threshold value may be at least one of the width, height, and area of ​​the waveform. Then, in the case where the parameter satisfies the threshold value, the value of the first mark may be set to a value (e.g., "1") indicating that the recovery of the particles is performed. On the other hand, in the case where the parameter does not satisfy the threshold value, the value of the first mark may be set to a value (e.g., "0") indicating that the recovery of the particles is not performed.

[0169] In addition, the threshold value can be a range preset by gating. Here, gating is a process of surrounding and specifying a range corresponding to the recovery target particles on a distribution map representing the characteristic distribution of the particles in the particle group. Gating is performed before the recovery operation of the recovery target particles begins. Note that the distribution map can be created by a graphical user interface (GUI) on the control PC 2312. In addition, gating can be performed by a gating circuit 2305.

[0170] Here, Fig.15A shows the result of gating a histogram as an example of a distribution diagram. In this histogram, the horizontal axis represents a parameter and the vertical axis represents the number of particles. The parameter in the figure is the area of ​​the waveform of the electrical signal corresponding to channel number 1 (Ch1), but other parameters can be used. Then, the rectangular box in the figure is a gate that specifies the range corresponding to the recovered target particles, and the range can be used as a threshold for setting the first mark.

[0171] on the other hand, Fig.15 FIG. 8B shows the result of gating on a two-dimensional (2D) graph as another example of a distribution graph. In the 2D graph, different parameters are assigned to the horizontal and vertical axes. Fig.15 The parameter on the horizontal axis in B is the area of ​​the waveform of the electric signal corresponding to channel number 2 (Ch2), and the parameter on the vertical axis is the area of ​​the waveform of the electric signal corresponding to channel number 3 (Ch3). However, parameters other than the areas of the waveforms of the two electric signals may be used. Then, the rectangular box in the figure is a gate that specifies the range corresponding to the recovered target particles, and the range can be used as a threshold for setting the first mark.

[0172] [Output Queue Circuit]

[0173] Reference again Fig.12 The output queue circuit 2306 is a circuit at a subsequent stage of the collection start time calculation circuit 2304 and the gate circuit 2305 , and is connected to the collection start time calculation circuit 2304 and the gate circuit 2305 .

[0174] The event data packet outputted from the recycling start time calculation circuit 2304 and the event data packet outputted from the gating circuit 2305 are inputted into the output queue circuit 2306. Then, the event data packet of two inputs indicating the same particle (that is, the same event number) is integrated (combined) into one event data packet by the output queue circuit 2306. In the integrated event data packet, both the delay time point and the first mark are written. Note that the integration of the event data packet can be performed by any one of the circuits 2304 and 2305 by the communication between the recycling start time calculation circuit 2304 and the gating circuit 2305. In addition, the recycling start time calculation circuit 2304 and the gating circuit 2305 can be connected in series.

[0175] In addition, the output queue circuit 2306 arranges the event data packets of different particles that are sequentially input according to the order of the earliest recycling start time point included in the event data packet. Here, the event data packets that are input to the output queue circuit 2306 and wait for the output of the driving waveform for recycling the corresponding particles are defined as "output queue". The output queue is updated in response to the input of a new event data packet to the output queue circuit 2306.

[0176] In addition, the output queue circuit 2306 determines whether to recycle particles corresponding to each event data packet according to the purity priority mode or the acquisition rate priority mode. It should be noted that the purity priority mode and the acquisition rate priority mode are operation modes of the control unit 103 that are selectively preset before the particle recycling operation starts. The setting of the mode can be performed by the control PC 2312 via different user interfaces.

[0177] Here, the purity priority mode is a mode in which, when the recovery target particles and the non-recovery target particles flow in a state close to each other and the possibility of both particles being captured together is high, the recovery target particles are intentionally regarded as "non-recovery target particles (non-acquisition)" to increase the purity of the captured particles. That is, when the purity priority mode is set, the recovery target particles close to the non-recovery target particles are not recovered and are discarded.

[0178] On the other hand, the acquisition rate priority mode is a mode in which, in a case where recovery target particles and non-recovery target particles flow in a state close to each other and there is a high possibility that the two particles are captured together, two particles are acquired and the number of acquired particles is increased even if the purity of the captured particles is reduced.

[0179] Then, the output queue circuit 2306 performs setting of the second flag based on the determination result of the presence or absence of recycling of the particle according to the set mode. At this time, in the case where it is determined that the recycling of the particle is performed, the output queue circuit 2306 can set the second flag to "1". On the other hand, in the case where it is determined that the recycling of the particle is not performed, the output queue circuit 2306 can set the second flag to "0". Note that the present invention is not limited to such a flag setting aspect.

[0180] In addition, the output queue circuit 2306 writes the application timing of the drive waveform to be applied to the actuator 107 to the memory. The memory can be a random access memory (RAM). In addition, the memory can be connected to the bus 2301, or can be built into the control unit 103 or the circuit of the control PC 2312. In addition, when writing out the application timing, the setting values ​​of the first tag and the second tag can be referenced. In this case, when the two tags are set to the values ​​indicating the execution of recycling, the application timing of the corresponding particles can be written to recycle. In addition, the drive waveform can be a drive voltage.

[0181] Here, when the pulse waveform Wp is applied as the driving waveform, the output queue circuit 2306 writes the application timing of the falling driving waveform Wf and the application timing of the rising driving waveform Wr into the memory. Fig.16As shown, the falling drive waveform Wf and the rising drive waveform Wr can be part of the pulse waveform Wp, the falling drive waveform Wf forms the front part of the pulse waveform Wp, and the rising drive waveform Wr forms the rear part of the pulse waveform Wp. In addition, the height (amplitude) of the falling drive waveform Wf is the same as the height of the rising drive waveform Wr.

[0182] The falling drive waveform Wf is applied to deform the pressure chamber 165 in the direction of increasing volume, and a pressure change is applied in the negative direction immediately after the application of the drive waveform. The force generated in the actuator by applying the falling drive waveform Wf may be to weaken the displacement plate 167 (refer to Figure 7 ) to increase the volume in pressure chamber 165. In the case where actuator 107 is a piezoelectric element, a drive waveform for reducing the drive voltage applied to the expanded piezoelectric element to cause the piezoelectric element to contract may be used.

[0183] On the other hand, the rising drive waveform Wr is applied to deform the pressure chamber 165 in the direction of volume reduction, and the pressure change in the positive direction is applied immediately after the application of the drive waveform. The force generated in the actuator by applying the rising drive waveform Wr can be used to enhance the displacement plate 167 (refer to Figure 7 ) to reduce the volume in pressure chamber 165. In the case where actuator 107 is a piezoelectric element, a drive waveform for increasing the drive voltage applied to the contracting piezoelectric element to expand the piezoelectric element may be used.

[0184] When the application timing of the falling drive waveform Wf and the rising drive waveform Wr is written to the memory as described above, the output queue circuit 2306 can write the recycling start time point included in the event data packet as the application timing of the falling drive waveform Wf and the application timing of the rising drive waveform Wr.

[0185] [Output timing generation circuit]

[0186] like Fig.12 As shown, the output timing generation circuit 2307 is connected to the output queue circuit 2306. The output timing generation circuit 2307 reads the recycling start time point of the event data packet arranged at the front of the output queue written to the RAM by the output queue circuit 2306 from the RAM. Then, the output timing generation circuit 2307 generates an output timing signal at the recycling start time by comparing the read recycling start time with the value of the signal from the clock counter 2310. Here, the output timing signal is a signal for allocating the output timing of the drive waveform. The output timing generation circuit 2307 outputs the generated output timing signal to the subsequent stage. In addition, after the output timing signal, the output timing generation circuit 2307 can send a completion signal to the output queue circuit 2306 to prompt the update of the output queue.

[0187] In the case where the drive waveform is a pulse waveform, the output timing generation circuit 2307 refers to the memory in which the application timing of the falling drive waveform Wf and the rising drive waveform Wr is written by the output queue circuit 2306. Then, the output timing generation circuit 2307 generates an output timing signal for each drive waveform by comparing the application timing of the falling drive waveform Wf and the rising drive waveform Wr in the memory with the value of the signal from the clock counter 2310. In addition, the output timing generation circuit 2307 outputs the generated output timing signal to the subsequent stage.

[0188] [Output signal generation circuit]

[0189] The output signal generating circuit 2308 is a circuit at a subsequent stage of the output timing generating circuit 2307 , and is connected to the output timing generating circuit 2307 .

[0190] The output timing signal output from the output timing generation circuit 2307 is input to the output signal generation circuit 2308. Then, the output signal generation circuit 2308 generates a drive waveform (output signal) corresponding to the input output timing signal, and outputs the drive waveform to the subsequent stage. In addition, the output signal generation circuit 2308 updates the step counter and the output state signal after outputting the drive waveform. Note that the output state signal is a signal indicating the state of waveform stop / output (enable / disable).

[0191] Here, the step counter indicates the stepwise output level of the drive waveform. In other words, the step counter indicates the change value from the reference value of the drive waveform that changes stepwise as the number of applications of the drive waveform increases. The output difference of each level difference of one stage of the step counter is constant. The step counter and the output state signal can be input to the output queue circuit 2306 or the output timing generation circuit 2307 and used for processing of each of the circuits 2306 and 2307.

[0192] When the driving waveform is a pulse waveform, the output signal generating circuit 2308 generates and outputs a falling driving waveform Wf and a rising driving waveform Wr, respectively.

[0193] [Digital to analog conversion circuit]

[0194] The driving waveform output from the output signal generating circuit 2308 is input to the digital-to-analog conversion circuit 2313. Then, the digital-to-analog conversion circuit 2313 converts the input driving waveform from a digital signal to an analog signal, and outputs the signal to the driving circuit of the actuator 31.

[0195] It should be noted that in Fig.12 The control unit 103 in the embodiment may be applied to apply a driving waveform other than a pulse waveform.

[0196] 1-5-3. Algorithm for implementing particle recovery operation

[0197] Reference Fig.17 and Fig.18 The flowchart of FIG. 1 depicts an example of an algorithm embodying a particle recovery operation. Fig.17 and Fig.18 is a flow chart primarily showing the operation of the output queue circuit. Fig.17 shows the overall operation, and Fig.18 Calculation of application timings of the falling drive waveform Wf and the rising drive waveform Wr is shown.

[0198] [Overall operation]

[0199] exist Fig.17 In the flowchart of , the following first to fourth processes are executed individually and in parallel.

[0200] [First treatment]

[0201] The first process will be described. First, in step S101-1, it is determined whether there is an input of an event (event data packet). For this determination, the event data packet input from the previous circuit (e.g., the recycling start time calculation circuit and the gating circuit) is used. And, in the case of obtaining a positive determination result in step S101-1 (step S101-1: "Yes"), the process proceeds to step S101-2, and in the case of obtaining a negative determination result in step S101-1 (step S101-1: "No"), step S101-1 is repeated.

[0202] Next, in step S101 - 2 , the output queue is updated by adding a new event determined as “there is input” in step S101 - 1 to the output queue.

[0203] Finally, in step S101-3, whether to recycle particles (acquisition / non-acquisition) is re-evaluated based on the output queue updated in step S101-2, and the process returns to step S101-1. Here, it is expressed as "re-evaluation" because the evaluation in this step corresponds to the process of re-evaluating the events already in the queue (events that have been evaluated and the second flag is set). In the case of purity priority, the events subsequently added to the queue can be close to the events previously added, so that the process of this step works effectively.

[0204] [Second Process]

[0205] In step S102, it is selected whether the next event to be acquired (recovery of target particles) is to be recovered by applying the falling drive waveform Wf or by applying the rising drive waveform Wr, and the recovery start time point of the selected drive waveform recorded in the event data packet is written to the memory.

[0206] Fig.18 The details of the selection of the drive waveform and the calculation of the application timing in step S102 are shown. Fig.18 In the flowchart of , in S111, it is determined whether the value of the step counter is 0. In the case of obtaining a positive determination result (step S111: Yes), the processing proceeds to steps S112 and S113, and in the case of obtaining a negative determination result (step S111: No), the processing proceeds to steps S114 and S115. The case of obtaining a positive determination result (that is, the case where the value of the step counter is 0) corresponds to the case where the value of the drive waveform is a reference value. The hold value of the drive waveform can be used. This corresponds to the state where the actuator applies the maximum value of the drive waveform. In the case where the value of the step counter is 0, the processing proceeds from the state of applying the maximum value of the drive waveform to applying the falling drive waveform Wf, and the step counter is updated by +1 level. On the other hand, in the case where the step counter is not 0, the processing proceeds to the application of the rising drive waveform Wr, and the step counter is updated by -1 level. In the case of the present algorithm (preferred aspect of the present technology), since the value of the step counter alternately adopts 0 and +1, the application of the falling drive waveform Wf and the application of the rising drive waveform Wr are alternately selected.

[0207] Here, T2 described in step S112 and T1 described in step S114 will be described. In the case of sorting and recovering target particles by driving the actuator, the flow is disturbed. Therefore, it is necessary to ensure the return time in the flow field until the moment of recovering the next target particle. In order to ensure the return time, the timing of the pressure change can be, for example, as follows.

[0208] The time until the flow returns after the application of the falling drive waveform Wf is defined as T1. More specifically, after the control unit 103 applies a pressure change in the negative direction, the time required for the flow of the liquid in the predetermined section in the channel structure to return to the state before the pressure change in the negative direction is applied is defined as T1. The time interval TIy from when the control unit 103 applies a pressure change in the negative direction to when the next pressure change is applied is preferably the same as or longer than time T1. In addition, the time until the flow returns after the application of the rising drive waveform Wr is defined as T2. More specifically, after the control unit 103 applies a pressure change in the positive direction, the time required for the flow of the liquid in the predetermined section in the channel structure to return to the state before the pressure change in the positive direction is applied is defined as T2. The time interval TIz from when the control unit 103 applies a pressure change in the positive direction to when the next pressure change is applied is preferably the same as or longer than time T2. Note that the times T1 and T2 can be values ​​obtained by adding the operation margin time of the circuit to the time required for the flow to return.

[0209] In the case of the present algorithm (preferred aspect of the present technology), the application of the falling drive waveform Wf and the application of the rising drive waveform Wr are performed alternately. Therefore, in the case where an affirmative determination is made in step S111 (step S111: Yes), since the value of the step counter is 0, and the processing proceeds to the application of the falling drive waveform Wf, only in the case where the time interval TIz from the previous acquisition event is equal to or longer than the time T2 (step S112: Yes), the processing proceeds to step S113 and the falling timing is written.

[0210] [Third Process]

[0211] The third process will be described. Fig.17 . In the case where the application of the falling drive waveform Wf is selected in the second processing (step S102), first, in step S103-1, the application timing of the falling drive waveform Wf of the event obtained by applying the falling drive waveform Wf is written into the memory. The written application timing is referenced by the output timing generation circuit. Subsequently, in step S103-2, it is determined whether the falling trigger output of the falling drive waveform Wf is completed. The falling trigger output is to output the output timing signal of the falling drive waveform Wf generated by the output timing generation circuit to the output signal generation circuit. Finally, in step S103-3, the output queue is updated by deleting the event of the falling trigger output completion from the output queue, and the processing returns to step S103-1.

[0212] [Fourth Process]

[0213] The fourth process will be described. In the case where the application of the rising drive waveform Wr is selected in the second process (step S102), first, in step S104-1, the application timing of the rising drive waveform Wr for the event obtained by applying the rising drive waveform Wr is written into the memory. The written application timing is referenced by the output timing generation circuit. Subsequently, in step S104-2, it is determined whether the rising trigger output of the rising drive waveform Wr is completed. The rising trigger output is an output timing signal of the rising drive waveform Wr generated by the output timing generation circuit and output to the output signal generation circuit. Finally, in step S104-3, the output queue is updated by deleting the event of the completed rising trigger output from the output queue, and the process returns to step S104-1.

[0214] According to a preferred aspect of the present technology, application Fig.19 The driving waveform (driving signal) is shown in the timing diagram. Fig.19 The event detection time point is shown in Fig.19 A in), fall time ( Fig.19 B in), rise time ( Fig.19 C in), driving signal ( Fig.19 D in ), and a symbol indicating success or failure in obtaining the recovered target particles ( Fig.19 In the case of sorting and recovering target particles by applying a falling drive waveform Wf, the falling drive waveform Wf is applied to the actuator after a specific time DTf from event detection. In the case of sorting and recovering target particles by applying a rising drive waveform Wr, the rising drive waveform Wr is applied to the actuator starting at a time DTr shorter than the time DTf from event detection. The application of the falling drive waveform Wf and the application of the rising drive waveform Wr are repeated alternately. When the drive waveform is applied in this manner, as shown in E in the figure, the success or failure of obtaining the recovery of the target particles at each timing of applying the drive waveform is successful (○).

[0215] As a comparative example of this embodiment, Fig. 20 An example of a driving waveform obtained in a particle sorting device in the related art, that is, a driving waveform obtained when only a basic pulse waveform is applied, is shown. The rising waveform included in the pulse waveform is applied for the return operation of the actuator and is not used to sort the recovered target particles. Fig. 20 In the comparative example shown in FIG. 1 , the next falling timing may arrive before the application of the previous pulse waveform ends (refer to Fig. 20 B and D in FIG. 1 ). However, in this case, as during the output of the previous pulse waveform, the next falling timing is logically suspended or ignored. Therefore, for events that are close to each other, acquisition failure (×) occurs, such as Fig. 20As shown in E.

[0216] 1-5-3-1. Algorithm Variations

[0217] Next, a variation of the above algorithm will be described. In this variation, the processing content of the second processing of the output queue circuit is different from that of the above algorithm. Fig.21 Two adjacent events shown in part A of . In the case where the previous event in segment A is sorted by applying the falling drive waveform Wf and the subsequent event is sorted by applying the rising drive waveform Wr according to the above algorithm, the time from event detection to the start of the recovery operation is shorter in the rising drive waveform Wr than in the falling drive waveform Wf, and therefore the interval of the sorting drive timing is less than the event interval. Here, the event interval is TIx. That is, the interval between the time points when the particle detection unit 102 detects two consecutive particles is TIx. Moreover, (time DTf)-(time DTr)+(time T1) is set to time T3 (that is, T3=DTf-DTr+T1). In the case where the interval TIx between the above-mentioned time points is equal to or less than T3 (that is, in the case of TIx≤T3), the respective sorting drive timings become close to each other or are reversed, and the sorting by applying the rising drive waveform Wr of the next event fails. As a result, the acquisition rate of the recovered target particles is reduced. In order to avoid this situation, as Fig. 22 As shown, in the case where events close to each other occur as in region A, the falling driving waveform Wf is continuously applied to perform sorting. Therefore, sorting failure caused by the sorting drive timings of the falling driving waveform Wf and the rising driving waveform Wr being close to or opposite to each other can be avoided, and the acquisition rate of recovered target particles can be further improved.

[0218] Fig.231 is a flowchart showing the second processing in this modification. In the case where the step counter is 0 in step S141 (step S141: Yes), the processing proceeds to steps S142 and S143, and proceeds to writing the falling time. In the case where the step counter is not 0 in step S141 (step S141: No), the processing proceeds to step S144. In step S144, in the case where the value of the step counter is the maximum (negative determination in step S144) (step S144: No), the processing proceeds to steps S148 and S149, and proceeds to writing of the rising timing. In the case where the value of the step counter is less than the maximum value (max) in step S144 (step S144: Yes), in step S145, the previous acquisition execution is the falling drive waveform Wf (step S145: Yes), and in step S146, the timing of the previous acquisition execution is equal to or less than time T3 (step S146: Yes), the processing proceeds to step S143, and the writing of the falling timing is performed. That is, in this case, application of the falling drive waveform Wf is performed continuously with the previous acquisition execution.

[0219] On the other hand, in the case where a negative determination is obtained in step S145 (step S145: No), the process proceeds from step S147 to step S149, and the writing of the rise time is performed. In the case where a negative determination is obtained in step S146 (step S146: No), the process proceeds from step S148 to step S149, and the writing of the rise time is performed. In addition, in the present modification, the application of the falling drive waveform Wf or the application of the rising drive waveform Wr is selected by the flowchart, and the selection of the application of the falling drive waveform Wf is continuously performed by the value of the step counter, the drive waveform of the previous acquisition execution event, and the time interval from the previous acquisition execution event.

[0220] As an example of a particle sorting device implemented by the above-described present modification, the control unit 103 may be configured to perform a recovery operation Cf or a recovery operation Cr according to the interval TIx between the time points when the particle detection unit 102 has detected two consecutive particles. In addition, the control unit 103 may be configured to recover the particle detected earlier of the two consecutive particles through the recovery operation Cf, and to recover the particle detected later of the two consecutive particles through the recovery operation Cf in the case where the interval TIx between the time points is shorter than a predetermined value. The case where the interval TIx between the time points is shorter than the predetermined value may be, for example, a case where the interval TIx between the time points is equal to or shorter than the time T3 (i.e., in the case where TIx≤T3).

[0221] 2. Second Embodiment (Emulsion Generating Device)

[0222] 2-1. Overview

[0223] The particle sorting device according to the second embodiment of the present technology also provides a particle sorting device for recovering an emulsion containing recovery target particles. In the particle sorting device according to the second embodiment, the above-mentioned channel structure further includes a liquid supply channel, which is connected to the connecting channel so as to be able to supply a second liquid. The second liquid is immiscible with the above-mentioned first liquid. In the recovery operation Cr, the particle sorting part recovers an emulsion of the first liquid containing the recovery target particles contained in the second liquid. Therefore, the particle sorting device according to this embodiment can be an emulsion generating device.

[0224] 2-2. Configuration and operation

[0225] The configuration and operation of the particle sorting device according to the second embodiment will be described focusing on the differences from the particle sorting device according to the first embodiment. Configurations that are the same or equivalent to those of the first embodiment are denoted by the same reference numerals. Configurations and operations that are not described may be the same as those of the first embodiment described in 1. As described above.

[0226] The particle sorting device according to this embodiment includes Figure 3 15. In the particle sorting section 157, a liquid supply channel 161 is connected to a connecting channel 170 to be able to supply a second liquid. The second liquid is immiscible with a first liquid containing microparticles. In the connecting channel 170 included in the particle sorting section 157, an emulsion is formed in which the first liquid containing the recovery target particles is contained in the second liquid. Specifically, an emulsion containing the recovery target particles and an emulsion not containing the recovery target particles are formed. The emulsion containing the recovery target particles is recovered in the recovery channel 159.

[0227] One of the first liquid and the second liquid used in the present embodiment may be, for example, a hydrophilic liquid, and the other may be a hydrophobic liquid. That is, as an example, the first liquid may be a hydrophilic liquid, and the second liquid may be a hydrophobic liquid. In this case, an emulsion containing a hydrophobic liquid as a dispersion medium and a hydrophilic liquid as a dispersion body may be formed in the particle sorting section 157. As another example, the first liquid may be a hydrophobic liquid, and the second liquid may be a hydrophilic liquid. In this case, an emulsion containing a hydrophilic liquid as a dispersion medium and a hydrophobic liquid as a dispersion body may be formed in the particle sorting section 157.

[0228] In this embodiment, the control unit 103 recovers the emulsion containing the recovery target particles in the above recovery operation Cr. That is, the recovery step performed by the control unit 103 may include recovering the emulsion containing the recovery target particles in the above recovery operation Cr.

[0229] Preferably, the control unit 103 recovers the emulsion containing the recovery target particles in the above recovery operation Cf. That is, preferably, the recovery step performed by the control unit 103 may include recovering the emulsion containing the recovery target particles in the above recovery operation Cf.

[0230] In this embodiment, Fig.24 The emulsion generated in the recovery channel by applying the falling drive waveform Wf and the rising drive waveform Wr is shown in FIG. Fig.24 In the figure shown in place of photographs A and B, A shows the emulsion when the falling drive waveform Wf is applied, and B shows the emulsion when the rising drive waveform Wr is applied. As shown in the figure, an emulsion containing microparticles can be generated by applying each of the falling drive waveform Wf and the rising drive waveform Wr. Therefore, the generation of unnecessary emulsion containing no microparticles is reduced, and the emulsion containing microparticles can be generated efficiently. It should be noted that, like the technology in the prior art, in the case where the application of the rising drive waveform Wr is performed as the return operation of the actuator, the emulsion generated when the rising drive waveform Wr is applied is an unnecessary emulsion containing no microparticles.

[0231] In the particle separation device according to this embodiment, when performing the following steps: Figure 8 In the case of application of the falling drive waveform Wf and the rising drive waveform Wr shown, the size of the emulsion generated when the falling drive waveform Wf is applied is slightly different from the size of the emulsion generated when the rising drive waveform Wr is applied, and the size of the emulsion when the rising drive waveform Wr is applied is smaller than the size of the emulsion when the falling drive waveform Wf is applied. This is because the flow toward the recovery channel due to the vibration flow when the rising drive waveform Wr is applied is weaker than the flow toward the recovery channel generated immediately after the falling drive waveform Wf is applied. Therefore, in order to further make the size of the emulsion when the falling drive waveform Wf and the rising drive waveform Wr are applied uniform, it is preferable to apply the following Fig.25 The rising drive waveform shown in .

[0232] Fig.25 The rising driving waveform in the embodiment includes the second falling waveform w1, the flat waveform w2 and the rising waveform w3 in time sequence. In this specification, Fig.25 The rising driving waveform in is referred to as “the rising driving waveform Wfr with a falling waveform”.

[0233] Fig.26The analysis results of simulating the flow velocity change in the connecting channel when the rising drive waveform Wr is applied and the flow velocity change in the connecting channel when the rising drive waveform Wfr with a falling waveform is applied are shown. It can be seen that the peak value of the flow velocity in the direction of the pressure chamber increases when the rising drive waveform Wfr with a falling waveform is applied compared to when the rising drive waveform Wr is applied. Therefore, by applying the rising drive waveform Wfr with a falling waveform, the size of the emulsion can be increased by increasing the suction amount of the first liquid from the main channel. Therefore, the unevenness of the emulsion generated when the falling drive waveform Wf is applied and when the rising drive waveform Wr is applied can be reduced, and an emulsion with a constant quality can be more accurately generated.

[0234] Furthermore, the present invention is not limited to the second embodiment, and the rising drive waveform Wfr having a falling waveform may be adopted in the first embodiment. That is, in the first embodiment, the rising drive waveform may be the rising drive waveform Wfr having a falling waveform.

[0235] When the rising driving waveform Wfr having a falling waveform is applied, the suction amount of the first liquid from the main channel can be increased compared to when the rising driving waveform Wr is applied. Therefore, the difference between the suction amount when the falling driving waveform Wf is applied and the suction amount when the rising driving waveform Wr is applied can be reduced, and the sorting of the microparticles can be performed more stably.

[0236] 3. Third embodiment (microparticle sorting method)

[0237] The present technology also provides a particle sorting method performed in a particle sorting device according to the first embodiment. In the particle sorting device according to the first embodiment, the particle sorting method includes a control step of applying a pressure change in a recovery channel and a recovery step of recovering target particles into the recovery channel. In the particle sorting method, the control step includes applying a pressure change in a positive direction and generating a pressure vibration PVr in the recovery channel. The recovery step includes performing a recovery operation Cr, which recovers the recovery target particles through the pressure change in a negative direction caused by the pressure vibration PVr.

[0238] The microparticle sorting apparatus used in the microparticle sorting method according to the present technology is the same as the apparatus described in 1. As described above, and the description thereof also applies to the microparticle sorting method according to the present technology.

[0239] 4. Fourth embodiment (emulsion forming method)

[0240] The present technology also provides an emulsion generation method performed in the emulsion generation device according to the second embodiment. The emulsion generation method includes a recovery step of recovering the emulsion containing recovery target particles.

[0241] The emulsion generating apparatus used in the emulsion generating method according to the present technology is the same as the apparatus described in 2. The above and its description also apply to the emulsion generating method according to the present technology.

[0242] The present technology may also take the following configurations. [1]

[0244] A particle sorting device, comprising:

[0245] The channel structure includes: a main channel through which a first liquid containing microparticles flows; a recovery channel through which recovery target particles in the microparticles are recovered; and a connecting channel connecting the main channel and the recovery channel; and

[0246] A control unit applies a pressure change in the recycling channel and recycles the target particles into the recycling channel,

[0247] Here, the control unit performs a recovery operation Cr of applying a pressure change in a positive direction to generate a pressure vibration PVr in the recovery channel and recovering the recovery target particles through the pressure change in a negative direction caused by the pressure vibration PVr. [2]

[0249] According to the particle sorting device of [1],

[0250] Here, the control unit applies a pressure change in a negative direction in the recovery channel and performs a recovery operation Cf of recovering the recovery target particles through the pressure change in the negative direction. [3]

[0252] According to the particle sorting device of [2],

[0253] The control unit is configured to perform the recycling operation Cf and the recycling operation Cr alternately. [4]

[0255] The particle sorting device according to [2] or [3] further comprises:

[0256] A particle detection unit detects particles that have passed through a predetermined position in the main channel,

[0257] Therein, the control unit is configured to perform the recovery operation Cf or the recovery operation Cr according to the interval TIx of the time point when the particle detection unit has detected two consecutive particles. [5]

[0259] According to the particle sorting device of [4],

[0260] The control unit is configured to recycle the particle detected earlier of two consecutive particles through the recycle operation Cf, and to recycle the particle detected later of two consecutive particles through the recycle operation Cf when the interval TIx between the time points is shorter than a predetermined value. [6]

[0262] The particle sorting device according to any one of [2] to [5], further comprising:

[0263] A particle detection unit detects particles that have passed through a predetermined position in the main channel,

[0264] The control unit is configured to perform the recovery operation Cf after a time DTf from a time point when the particle detection unit detects the particle, and to perform the recovery operation Cr after a time DTr from a time point when the particle detection unit detects the particle. [7]

[0266] According to the particle sorting device of [6],

[0267] Here, the time DTf and the time DTr are different from each other. [8]

[0269] The particle sorting device according to [6] or [7],

[0270] Among them, the time DTr is shorter than the time DTf. [9]

[0272] The particle sorting device according to any one of [1] to [8],

[0273] In which, after the control unit applies a pressure change in a positive direction, it takes time T2 for the liquid flow in a predetermined section in the channel structure to return to the state before the pressure change in the positive direction is applied, and the time interval TIz from when the control unit applies the pressure change in the positive direction to when the control unit applies the next pressure change is equal to or longer than time T2.

[10]

[0275] The particle sorting device according to any one of [2] to [8],

[0276] In which, after the control unit applies a pressure change in the negative direction, it takes time T1 for the liquid flow in a predetermined section in the channel structure to return to the state before the pressure change in the negative direction is applied, and the time interval TIy from when the control unit applies the pressure change in the negative direction to when the control unit applies the next pressure change is equal to or longer than time T1.

[11]

[0278] The particle sorting device according to any one of [1] to

[10] , further comprising:

[0279] Actuator,

[0280] Therein, the control unit applies a pressure change in the recovery channel by applying a drive waveform to the actuator.

[12]

[0282] The particle sorting device according to any one of [1] to

[11] , further comprising:

[0283] Actuator,

[0284] Here, the control unit applies a pressure change in a positive direction by applying the rising driving waveform Wr to the actuator, and performs a recovery operation Cr.

[13]

[0286] The particle sorting device according to any one of [2] to [8], further comprising:

[0287] Actuator,

[0288] wherein the control unit applies a pressure change in a negative direction by applying a falling drive waveform Wf to the actuator and performs a recovery operation Cf, and

[0289] The control unit applies a pressure change in the positive direction by applying the rising driving waveform Wr to the actuator, and performs the recovery operation Cr.

[14]

[0291] The particle sorting device according to

[12] or

[13] ,

[0292] Here, the rising driving waveform Wr is a rising driving waveform Wfr having a falling waveform.

[15]

[0294] The particle sorting device according to any one of [1] to

[14] ,

[0295] Wherein, the diameter of the connecting channel is equal to or greater than 60 μm.

[16]

[0297] The particle sorting device according to any one of [1] to

[15] ,

[0298] Wherein, the channel structure further comprises a liquid supply channel connected to the connecting channel so as to be able to supply the second liquid,

[0299] the second liquid is immiscible with the first liquid, and

[0300] In the recovery operation Cr, the control unit recovers an emulsion in which the first liquid containing the recovery target particles is contained in the second liquid.

[17]

[0302] The particle sorting device according to any one of [1] to

[16] , further comprising:

[0303] Microparticle sorting microchip,

[0304] Among them, the particle sorting microchip has a channel structure.

[18]

[0306] A particle sorting method, comprising:

[0307] In a particle sorting device including a channel structure, the channel structure includes: a main channel, through which a first liquid containing particles flows; a recovery channel, through which recovery target particles in the particles are recovered; and a connecting channel connecting the main channel and the recovery channel.

[0308] a controlling step of applying a pressure change in the recycling channel; and

[0309] The recycling step is to recycle the target particles into the recycling channel.

[0310] wherein the controlling step comprises applying a pressure change in a positive direction to generate a pressure oscillation PVr in the recovery channel, and

[0311] The recovery step includes performing a recovery operation Cr of recovering target particles through a pressure change in a negative direction caused by the pressure vibration PVr.

[0312] Reference Symbols List

[0313] 100 Particle Sorting Device

[0314] 101 Light irradiation unit

[0315] 102 Particle Detection Unit

[0316] 103 Control Unit

[0317] 107 Actuator

[0318] 109 Second light irradiation unit

[0319] 150, 150a Microparticle Sorting Microchip

[0320] 155 Main Channel

[0321] 156 Particle Detection Area

[0322] 157 Particle Sorting Unit

[0323] 158 Waste Channel

[0324] 159 Recycling Channel

[0325] 165 Pressure Chamber

[0326] 170 connection channels.

Claims

1. A particle sorting device, comprising: The channel structure comprises: a main channel through which a first liquid containing microparticles flows; a recovery channel through which recovery target particles in the microparticles are recovered; and a connecting channel connecting the main channel and the recovery channel; and a control unit that applies a pressure change in the recycling channel and recycles the recycling target particles into the recycling channel, The control unit applies the pressure change in a positive direction to generate a pressure vibration PVr in the recovery channel, and performs a recovery operation Cr of recovering the recovery target particles through the pressure change in a negative direction caused by the pressure vibration PVr.

2. The particle sorting device according to claim 1, in, The control unit applies the pressure change in the negative direction in the recovery channel, and performs a recovery operation Cf of recovering the recovery target particles by the pressure change in the negative direction.

3. The particle sorting device according to claim 2, in, The control unit is configured to alternately perform the recycling operation Cf and the recycling operation Cr.

4. The particle sorting device according to claim 2, further comprising: a particle detection unit for detecting the particles that have passed through a predetermined position in the main channel, The control unit is configured to perform the recycling operation Cf or the recycling operation Cr according to an interval TIx between time points when the particle detection unit has detected two consecutive particles.

5. The particle sorting device according to claim 4, in, The control unit is configured to recover the particle detected earlier of the two consecutive particles through the recovery operation Cf, and to recover the particle detected later of the two consecutive particles through the recovery operation Cf if the interval TIx between the time points is shorter than a predetermined value.

6. The particle sorting device according to claim 2, further comprising: a particle detection unit for detecting the particles that have passed through a predetermined position in the main channel, The control unit is configured to perform the recovery operation Cf after a time DTf from a time point when the particle detection unit detects the particle, and to perform the recovery operation Cr after a time DTr from a time point when the particle detection unit detects the particle.

7. The particle sorting device according to claim 6, in, The time DTf and the time DTr are different from each other.

8. The particle sorting device according to claim 6, in, The time DTr is shorter than the time DTf.

9. The particle sorting device according to claim 1, in, After the control unit applies the pressure change in the positive direction, when it takes time T2 for the liquid in a predetermined section in the channel structure to flow back to the state before the pressure change in the positive direction is applied, the time interval TIz from when the control unit applies the pressure change in the positive direction to when the control unit applies the next pressure change is equal to or longer than time T2.

10. The particle sorting device according to claim 2, in, After the control unit applies the pressure change in the negative direction, when it takes time T1 for the liquid in a predetermined section in the channel structure to flow back to the state before the pressure change in the negative direction is applied, the time interval TIy from when the control unit applies the pressure change in the negative direction to when the control unit applies the next pressure change is equal to or longer than time T1.

11. The particle sorting device according to claim 1, further comprising: Actuator, Wherein, the control unit applies the pressure change in the recovery channel by applying a driving waveform to the actuator.

12. The particle sorting device according to claim 1, further comprising: Actuator, Here, the control unit applies the pressure change in a positive direction by applying a rising driving waveform Wr to the actuator, and performs the recovery operation Cr.

13. The particle sorting device according to claim 2, further comprising: Actuator, wherein the control unit applies the pressure change in the negative direction by applying a falling drive waveform Wf to the actuator and performs the recovery operation Cf, and the control unit applies the pressure change in the positive direction by applying a rising drive waveform Wr to the actuator and performs the recovery operation Cr.

14. The particle sorting device according to claim 12, in, The rising driving waveform Wr is a rising driving waveform Wfr having a falling waveform.

15. The particle sorting device according to claim 1, in, The connecting channel has a diameter equal to or greater than 60 μm.

16. The particle sorting device according to claim 1, in, The channel structure further includes a liquid supply channel connected to the connection channel so as to be able to supply a second liquid, The second liquid is immiscible with the first liquid, and In the recovery operation Cr, the control unit recovers an emulsion in which the first liquid containing the recovery target particles is contained in the second liquid.

17. The particle sorting device according to claim 1, further comprising: Microparticle sorting microchip, Wherein, the particle sorting microchip has the channel structure.

18. A method for sorting particles, comprising: In a particle sorting device including a channel structure, the channel structure includes: a main channel through which a first liquid containing particles flows; a recovery channel through which recovery target particles in the particles are recovered; and a connecting channel connecting the main channel and the recovery channel. a controlling step of applying a pressure change in the recycling channel; and a recovery step, recovering the target particles into the recovery channel, wherein the controlling step comprises applying a pressure change in a positive direction to generate a pressure oscillation PVr in the recovery channel, and The recovery step includes performing a recovery operation Cr of recovering the recovery target particles through a pressure change in a negative direction caused by the pressure vibration PVr.

Images